DESCRIPTION

TRIAZOLE CATALYSTS AND METHODS OF MAKING AND

USING THE SAME

CROSS-REFERENCE TO RELATED APPLICATION The presently disclosed subject matter claims the benefit of U.S. Provisional Patent Application Serial No. 61/243,006, filed September 16, 2009, the disclosure of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The presently disclosed subject matter relates to triazole catalysts, to methods of synthesizing triazole catalysts, and to methods of using the catalysts in chemical reactions, such as, but not limited to, oxidation reactions.

ABBREVIATIONS

A Angstroms

°C degrees Celsius

Δ heat

ε molar absorptivity

μL· microliter

μΙΤΙθΙ micromoles

atm atmospheres

Bu butyl

CH ₄ methane

cm centimeter

CO carbon monoxide

CO ₂ carbon dioxide

Cu copper

CyH cyclohexane

CyO cyclooctane

DCC N,N-dicyclohexylcarbodiimide DFT density functional theory

DIEA diisopropylethylamine

DMA dimethylacetamide

DMF dimethyl formamide

DMSO dimethyl sulfoxide

EPR electron paramagnetic resonance eq molar equivalents

ESI-MS electrospray ionization mass

spectroscopy

EXAFS extended X-ray absorption fine

structure

Fe iron

FMOC fluorenylmethyloxycarbonyl

GC-MS gas chromatography-mass

spectrometry

HBTU 2-(1 H-benzotriazole-1-yl)-1 ,1 ,3,3- tetramethylaminium hexafluorophosphate

HMDS hexamethyldisilazane

H ₂ 0 ₂ hydrogen peroxide

HOBT hydroxybenzotriazole

HPLC high performance liquid

chromatography

hr hour

ICP-AES inductively coupled plasma-atomic emission spectroscopy

IR infrared

L liter

LMCT ligand-to-metal charge transfer

M molar

MeCN acetonitrile

mol moles

Mn manganese NAD nicotinamide adenine dinucleotide nm nanometer

NMP N-methyl pyrrolidine

NMR nuclear magnetic resonance

OTf triflate

PEG polyethylene glycol

PPh ₃ triphenyl phosphine

pMMO particulate methane

monooxygenase

rt room temperature

SAR structure-activity relationship

SEM scanning electron microscopy sMMO soluble methane monooxygenase tBu tert-butyl

TEM transmission electron microscopy

TEOS tetraethyl orthosilicate

THF tetrahydrofuran

TLC thin layer chromatography

TOF turnover frequency

TON turnover number

Tz triazole

UV-Vis ultraviolet-visible

xs excess

BACKGROUND

The selective low temperature oxidation of methane has been a longstanding challenge and has limited the use of methane to that of a primary energy source. Methods to transform methane to methanol, a useful chemical intermediate as well as an easily transportable and stored liquid fuel, would therefore significantly decrease reliance on petroleum as both a source of energy and chemical feedstocks. The conventional synthesis of methanol from methane is a multi-step process, typically requiring high temperatures (700°C) and pressures (200 - 300 atm). Therefore, methods to develop catalysts that operate under mild conditions, preventing overoxidations to HCHO, COx, etc., are highly sought.

In nature, methane oxidation is catalyzed by iron and copper enzymes, soluble and particulate methane monooxygenase (sMMO and pMMO, respectively), under physiological conditions. Efforts to develop functional models based upon MMOs have been met with limited success. Metalloenzymes perform oxidations under mild conditions using molecular oxygen as the oxidant and exhibit remarkable substrate specificity as well as regioselectivity and/or stereoselectivity. Advancements in the understanding of the function of these enzymes has been due in large part to the study of biomimetic catalysts (see Que and Tolman, Nature, 455, 333-340 (2008)) as well as the use of X-ray crystallography (see Balasubramanian and Rosenzweig, Accounts of Chemical Research, 40, 573-580 (2007); and Rosenzweig and Sazi ^' nsky, Current Opinion in Structural Biology, 16, 729- 735 (2006)), detailed spectroscopic characterizations and kinetic studies (see Mahapatra et al.. J. Am. Chem. Soc, 118, 11555-11574 (1996) and Nguyen et al. J. Am. Chem. Soc, 118, 12766-12776 (1996)), and improvements in theoretical modeling. See Yoshizawa and Shiota, J. Am. Chem. Soc, 128, 9873-9881 (2006) and Yoshizawa and Shiota, Inorganic Chem., 48, 838-845 (2009).

However, there is still an outstanding need in the art for oxidation and other types of catalysts that can be easily and economically prepared, which can operate under mild conditions (e.g., room temperature and atmospheric pressure), and which catalyze reactions with a high degree of specificity. In particular, there exists a need for catalysts that can catalyze reactions involving the transformation of renewable feedstocks, such as cellulose, lignocellulose and natural gas, into fuels, such as methanol and ethanol, and other valuable chemicals. Such catalysts could play a role in making petroleum fuel alternatives easy to produce and more economically attractive. SUMMARY

In some embodiments, the presently disclosed subject matter provides a method for oxidizing a hydrocarbon substrate to provide one or more oxidation products, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and contacting a hydrocarbon substrate with the catalyst, thereby oxidizing the substrate to provide the one or more oxidation products.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a 1 ,2,4-triazole ligand selected from the group comprising a 4- substituted-1 ,2,4-triazole, a 3-substituted-1,2,4-triazole, a 1-substituted- 1 ,2,4-triazole, a 3, 5-disubstituted-1 ,2,4-triazole, a 3,4, 5-trisubstituted-1 ,2,4- triazole, a bis-1 ,2,4-triazole, and a 1 ,2,4-triazole attached to a solid support. In some embodiments, the 1 ,2,4-triazole ligand is a bi-dentate, tri-dentate, or tetra-dentate ligand. In some embodiments, the 1 ,2,4-triazole ligand is a 4- substituted-1 ,2,4-triazole.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (I):

(I)

wherein: Ri and R ₃ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and R ₂ is selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, - NHC(=0)R ₄ , and -CH(COOH)R ₄ , wherein R is alkyl, aryl, aralkyl, or an amino acid side chain; or wherein one of Ri, R ₂ , and R ₃ is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, at least one of R-i, R ₂ , and R ₃ is aryl or substituted aryl. In some embodiments, the substituted aryl is a substituted 1 ,2,3-triazolyl group. In some embodiments, the substituted 1 ,2,3-triazolyl group has the structure:

wherein R ₅ is selected from hydroxy-substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl.

In some embodiments, R ₂ is NH ₂ , substituted phenyl, substituted pyridyl, or substituted benzyl. In some embodiments, the substituted phenyl, substituted pyridyl, or substituted benzyl is substituted with one or more substituents selected from the group comprising alkyl, hydroxy, halo, amino, nitro, aryl, aralkyl, carboxyl, and alkoxy.

In some embodiments, R ₂ is -L-X, wherein L is a linker moiety and X is silica gel or polystyrene.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (II):

wherein: L-i is a direct bond or alkylene; R ₆ and R ₇ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and each R ₈ is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or wherein two R ₈ groups are together alkylene; or wherein one of R ₆ and R ₇ or one Rs is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (III): (III)

wherein: L ₂ is a direct bond or alkylene; Rg and R-io are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyl, and substituted aralkyl; and each Rn is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyi, substituted alkyi, aryl, substituted aryl, aralkyl, and substituted aralkyl; or wherein two Rn groups are together alkylene; or wherein one of Rg and R10 or one R-n is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (IV):

wherein: L ₃ is a direct bond or alkylene; R13 and R14 are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyl, and substituted aralkyl; and each R12 is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyi, substituted alkyi, aryl, substituted aryl, aralkyl, and substituted aralkyl; or wherein two R12 groups are together alkylene; or wherein one of R ₁₃ and R14 or one R ₁₂ is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing one or more ligand selected from the group comprising:

In some embodiments, providing a 1 , 2,4-triazole ligand comprises providing a 1 , 2,4-triazole ligand attached to a solid support, wherein said l

In some embodiments, providing a 1 , 2,4-triazole ligand comprises providing a 1 , 2,4-triazole ligand attached to a solid support, wherein the solid support is mesoporous silica gel. In some embodiments, the mesoporous silica gel comprises pores having a diameter between about 20 and about 300 angstroms. In some embodiments, the mesoporous silica gel is Santa Barbara Amorphous type material (SBA)-15.

In some embodiments, the mesoporous silica gel comprises hexagonal pores. In some embodiments, one or more 1 ,2,4-triazole ligand is attached on a surface within a pore of the mesoporous silica gel. In some embodiments, one or more auxiliary ligands are attached on the surface within the pore of the mesoporous silica gel, thereby providing a bifunctional pore. In some embodiments, the one or more auxiliary ligands are each independently selected from the group comprising thiol, thioether, nitrile, aryl, substituted aryl, and carboxylic acid.

In some embodiments, forming the catalyst comprises: contacting the 1 ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and contacting the pre-catalyst with a peroxide in the presence of molecular oxygen. In some embodiments, contacting the 1 ,2,4-triazole ligand with the transition metal compound to form the pre-catalyst is performed in tetrahydrofuran (THF). In some embodiments, contacting the 1 ,2,4-triazole ligand with the transition metal compound to form the pre-catalyst is performed at a temperature of between about 20°C and about 80°C. In some embodiments, the temperature is between about 40°C and about 60°C.

In some embodiments, the transition metal compound comprises a transition metal ion selected from the group comprising iron(ll), iron(lll), copper(l), copper(ll), and manganese(ll). In some embodiments, the transition metal compound is selected from the group comprising CuCI ₂ ,

Cu(N0 ₃ ) ₂ , Cu(BF ₄ ) ₂ , Cu(OSO ₂ CF ₃ )2, CuC0 ₃ , Cu(CIO ₄ ) ₂ , Cu(MeCN) ₄ BF ₄ ,

FeCI ₂ , Fe(BF ₄ ) ₂ and hydrates thereof.

In some embodiments, the pre-catalyst is dissolved in acetonitrile prior to being contacted with the peroxide. In some embodiments, contacting the 1 ,2,4-triazole ligand with the transition metal compound is performed in acetonitrile. In some embodiments, the peroxide is hydrogen peroxide or ferf-butyl peroxide. In some embodiments, contacting the hydrocarbon substrate with the catalyst is performed in water, acetonitrile, or mixtures thereof. In some embodiments, contacting the hydrocarbon substrate with the catalyst is performed at a temperature of between about 0°C and about 25°C. In some embodiments, the temperature is about 20°C.

In some embodiments, the substrate is added directly to a solution in which the catalyst has been formed. In some embodiments, the hydrocarbon substrate is selected from the group comprising straight-chain alkanes, cyclic alkanes, substituted alkanes, straight-chain alkenes, cyclic alkenes, and substituted alkenes. In some embodiments, the hydrocarbon substrate is selected from the group comprising methane, octane, cyclohexane, cyclooctane, cyclohexene, cyclooctene, styrene, methyl cinnamate, and 1 ,2-diphenylethene.

In some embodiments, the hydrocarbon substrate is methane. In some embodiments, the methane is from natural gas. In some embodiments, the methane is provided at 1 atmosphere of pressure. In some embodiments, the one or more oxidation products are each selected from the group comprising methanol, formaldehyde, formic acid, ethanol, acetic acid, and acetaldehyde. In some embodiments, contacting methane with the catalyst selectively oxidizes the methane to one of the group comprising methanol, formaldehyde, acetaldehyde, and acetic acid.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (I):

(I)

wherein: Ri and R ₃ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and F¾ is selected from aryl and substituted aryl; and contacting methane with the catalyst selectively oxidizes methane to formaldehyde. In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (I):

(I)

wherein: Ri and R ₃ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and l¾ is selected from aralkyl and substituted aralkyl; and contacting methane with the catalyst selectively oxidizes methane to acetaldehyde.

In some embodiments, providing the 1 ,2,4-triazole ligand comprises providing a ligand of Formula (II):

wherein: l_i is a direct bond or alkylene; F<6 and R ₇ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; each R ₈ is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or wherein two R ₈ groups are together alkylene; and contacting methane with the catalyst selectively oxidizes methane to methanol. In some embodiments, contacting methane with the catalyst is performed in water.

In some embodiments, the catalyst is immobilized on a solid support material and contacting methane with the catalyst selectively oxidizes the methane to acetic acid or acetaldehyde. In some embodiments, the hydrocarbon substrate is an alkene and each of the one or more oxidation products is selected from the group consisting of cis-diols and epoxides. '

In some embodiments, greater than about 60% of the hydrocarbon substrate is oxidized. In some embodiments, greater than about 80% of the hydrocarbon substrate is oxidized.

In some embodiments, the presently disclosed subject matter provides a catalyst comprising a bis^-oxo) coordination complex, the Νβ(μ- oxo) coordination complex comprising at least two transition metal ions and at least two 1 ,2,4-triazole ligands. In some embodiments, the catalyst is a compound of Formula (V):

wherein: each M is a transition metal atom; R _15i R ₇ , R ₁₈ , and R ₂ o are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, and substituted aralkyi; and Ri ₆ and R19 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi substituted aralkyi - NHC(=0)R ₂ i and -CH(COOH)R ₂ i , wherein R ₂ i is alkyl, aryl, aralkyi, or an amino acid side chain; or wherein one or more of R-| ₅ , Ri ₆ , R17, R18, R19, and R20 is a group of the structure -L-X, wherein L is a linker moiety and X is a solid support material. In some embodiments, M is selected from the group comprising Fe, Cu, and Mn. In some embodiments, R16 and R19 are independently selected from the group comprising NH ₂ , aryl, substituted aryl, aralkyi, and substituted aralkyi. In some embodiments, R-ie and R19 are selected from the group comprising phenyl, substituted phenyl, benzyl, substituted benzyl, 1 ,2,3-triazolyl, and substituted 1 ,2,3-triazolyl. In some embodiments, the catalyst is a compound of Formula (VI):

(VI)

wherein: each l_ ₄ is independently a direct bond or alkylene; each M is a transition metal atom; R22, R23, R25, and R26 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; each R24 and R27 are independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or two R24 groups or two R27 groups are together alkylene; or wherein one or more of R22, R23, R24, R25, R26, and R27 is -L-X, wherein L is a linker moiety and X is a solid support material. In some embodiments, M is selected from the group comprising Fe, Cu, and Mn. In some embodiments, R22, R23, 25, and R26 are independently selected from the group comprising methyl and phenyl.

In some embodiments, at least one of the 1 ,2,4-triazole ligands is immobilized on a solid support material. In some embodiments, the solid support material is silica gel or polystyrene.

In some embodiments, the catalyst has a turnover number of greater than about 100. In some embodiments, the catalyst has a turnover number of about 10 ⁴ .

In some embodiments, the presently disclosed subject matter provides a pre-catalyst of the catalyst comprising a bis^-oxo) coordination complex, wherein the pre-catalyst is a compound of Formula (Va): (Va)

wherein: each M is a transition metal atom; each of Xi, X ₂ , X3, and X4 is selected from the group comprising halo, hydroxy, alkoxy, aryloxy, acyloxy, and aralkyoxy; R15, R17, R ₁₈ , and R ₂₀ are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, and substituted aralkyi; and R ₁₆ and R19 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi substituted aralkyi, -NHC(=0)R ₂ i, and -CH(COOH)R ₂ i, wherein R ₂ 1 is alkyl, aryl, aralkyi, or an amino acid side chain; or wherein one or more of Ri ₅ , R16, Ri ₇ , R18, R19, and R ₂ o is a group of the structure -L-X, wherein L is a linker moiety and X is a solid support material.

In some embodiments, the pre-catalyst is a compound of Formula

(Via):

(Via)

wherein: each L ₄ is independently a direct bond or alkylene; each M is a transition metal atom; each of X5, Χβ, Xz, and X ₈ is selected from the group consisting of halo, hydroxy, alkoxy, aryloxy, acyloxy, and aralkoxy; R ₂₂ , R23, R ₂₅ , and R ₂ 6 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, and substituted aralkyi; and each R ₂₄ and R ₂₇ are independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or wherein two R24 or two R ₂₇ are together alkylene; or wherein one or more of R22, R23, R24, R25, R26, and R27 is -L-X, wherein L is a linker moiety and X is a solid support material.

In some embodiments, the presently disclosed subject matter provides a method of preparing a catalyst comprising a 1 ,2,4-triazole ligand, the method comprising: providing a 1 ,2,4-triazole ligand; contacting the 1 ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and contacting the pre-catalyst with a peroxide in the presence of oxygen thereby forming the catalyst. In some embodiments, contacting the 1 ,2,4- triazole ligand with the transition metal compound is performed in a first non- polar solvent. In some embodiments, the first non-polar solvent is tetrahydrofuran (THF). In some embodiments, the pre-catalyst is not isolated prior to being contacted with the peroxide.

In some embodiments, the presently disclosed subject matter provides a method of degrading a cellulosic substrate, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and contacting the cellulosic substrate with the catalyst, thereby degrading the cellulosic substrate to form one or more degradation products. In some embodiments, at least one of the one or more degradation products is cellobiose or hydroxymethylfurfural. In some embodiments, degrading the cellulosic substrate degrades or removes lignin from the substrate.

In some embodiments, the presently disclosed subject matter provides a method of preparing an aminoalcohol, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4- triazole ligand and a transition metal ion; and contacting an olefin with the catalyst in the presence of a nitrogen source, thereby preparing an aminoalcohol. In some embodiments, the nitrogen source is chloramine-T. In some embodiments, the transition metal ion is copper.

In some embodiments, the presently disclosed subject matter provides a method of preparing an aziridine, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4- triazole ligand and a transition metal ion; and contacting an olefin with the catalyst in the presence of a nitrogen source, thereby preparing an aziridine. In some embodiments, the nitrogen source is selected from an organic azide and an iododinane. In some embodiments, the transition metal ion is selected from the group comprising copper, iron, cobalt, and nickel.

It is an object of the presently disclosed subject matter to provide catalysts comprising 1 ,2,4-triazole ligands and transition metal ions and methods of using the catalysts.

An object of the presently disclosed subject matter having been stated hereinabove, and which is achieved in whole or in part by the presently disclosed subject matter, other objects will become evident as the description proceeds when taken in connection with the accompanying drawings as best described hereinbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a drawing showing exemplary generic structures of 1 ,2,4- triazole ligands for use according to the presently disclosed subject matter.

Figure 2 is a drawing showing exemplary structures of 4-substituted- 1,2,4-triazole ligands for use according to the presently disclosed subject matter.

Figure 3 is a drawing showing exemplary structures of 3,5- disubstituted-1 ,2,4-triazole ligands for use according to the presently disclosed subject matter.

Figure 4 is a drawing showing exemplary structures of 3-substituted- linked-bis-1 ,2,4-triazole ligands for use according to the presently disclosed subject matter.

Figure 5 is a drawing showing exemplary structures of fused bis- 1 ,2,4-triazole ligands for use according to the presently disclosed subject matter.

Figure 6 is a drawing showing exemplary structures of 1 -substituted- 1 ,2,4-triazole ligands for use according to the presently disclosed subject matter. Figure 7 is a drawing showing exemplary structures of 3-(1 ,2,3- triazolyl-substituted)-1 ,2,4-triazole ligands for use according to the presently disclosed subject matter.

Figure 8 is a drawing showing exemplary solid support attached 1 ,2,4- triazole ligands for use according to the presently disclosed subject matter.

Figure 9 is a schematic drawing showing an exemplary method of synthesizing a solid support attached pre-catalyst comprising a 1 ,2,4-triazole ligand and a transition metal.

Figure 10 is a schematic drawing showing the activation of the pre- catalyst described in Figure 9 and the use of the active catalyst in the oxidation of methane to acetic acid.

Figure 11 is a schematic drawing showing the degradation of cellulose as catalyzed according to the presently disclosed subject matter.

Figure 12 is a schematic drawing showing a reaction in the synthesis of a solid support immobilized triazole ligand.

Figure 13 is a schematic drawing showing isotopic labeling studies that can be used to determine the nature of the catalytic oxidizing species of a di-copper catalyst of the presently disclosed subject matter. ¹⁸ 0 is indicated by the filled-in Os. On the right-hand side, a potential catalytic cycle is shown.

Figure 14 is a schematic drawing showing isotopic labeling studies that can be performed in an aqueous environment to determine the source of the oxygen atom(s) in the products of the methane oxidation reactions catalyzed by the presently disclosed catalysts. ¹⁸ O is indicated by the filled- in Os.

Figure 15 is a schematic drawing showing possible reactions involved in acetaldehyde formation during methane oxidation.

Figure 16A is a schematic drawing showing an exemplary synthetic route to a mono-dentate 3,4,5-substituted triazole (3,4,5-Tz) ligand of the presently disclosed subject matter. The diacylhydrazide shown on the left- hand side of the drawing is contacted with an aryl amine (ArNH ₂ ) in the presence of POCI ₃ in ortho-dichlorobenzene at 140 °C to form the triazole ligand. Figure 16B is a schematic drawing showing an exemplary synthetic route to a bi-dentate triazole ligand (α,ω -Tz ₂ ) of the presently disclosed subject matter. As shown in the upper part of the drawing, an acyl chloride is heated with an aryl amine (ArNH ₂ ) in a mixture of pyridine and toluene, and then contacted with Lawesson's reagent and hydrazine to form the intermediate shown in the upper right of the drawing. The intermediate is then condensed with a diacyl chloride in diethyl ether the presence of potassium carbonate to form the ligand.

Figure 17 is a schematic drawing showing (at the top) an exemplary synthetic route to a di-substituted triazole and exemplary tri- and tetra- dentate triazole-based ligands ( ^R" Tz ₂ NR, ^R Tz ₂ Py, ^R Tz ₂ NPy ^R , ^R Tz ₃ N, and ^R Tz ₃ N) of the presently disclosed subject matter. In the synthetic route, Ν,Ν-dimethylformamide-dimethyl acetal (DMF-DMA) is heated with a hydrazide in acetonitrile at 50 °C, followed by heating with an amine (R"- NH ₂ ) in acetic acid to form the di-substituted triazole.

Figure 18 is a schematic drawing showing an exemplary synthesis of triazole ligands immobilized on mesoporous silica (i.e., fusTz ₂ -surf and ^R Tz ₂ Py-surf) and ligands that could be immobilized on silica (i.e., 3,4,5-Tz- surf and ^R Tz ₂ NPy ^R -surf). Reagents for i-xi are as follows: i) is Pd(PPh ₃ ) ₂ CI ₂ , Cul, NEt ₃ , T S-alkyne; ii) is TBAF, THF; iii) is azide-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica, Cul, piperidine, NMP; iv) is NaN ₃ , Me ₂ CO, heat; v) is SnCI ₂ , MeOH; vi) is t-butyl lithium, -78 °C, carbon dioxide; vii) is azide-functionalized Santa Barbara Amorphous (SBA)- type mesoporous silica, DCC, DMF, followed by reaction with the product of step 1 of the reaction shown at the top of Figure 17; ix) is DiBAL, toluene, H ⁺ , NaBH(OAc) ₃ , and azide-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica; x) is NaBH(OAc) ₃ , NaOH; xii) is N ₂ H ₄ and heat, followed by reaction with the product of step 1 of the reaction shown at the top of Figure 17.

Figure 19A is a schematic drawing showing the synthesis of bifunctionalized silica according to the presently disclosed subject mattter. FG1 and FG2 represent different functional groups or ligands. Figure 19B is a schematic drawing showing a representative catalytic site within a bi-functionalized pore in mesoporous silica. The distances were determined via molecular mechanics calculations. The larger spheres in the center represent copper. The smaller spheres in the center represent oxidant, e.g., oxygen (0 ₂ ) or hydrogen peroxide (H ₂ O ₂ ).

Figure 20A is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are amine and a thiol or thioether. The R groups can be, for example, hydrogen, t- butoxycarbonyl (BOC), ethylamine (-CH ₂ CH ₂ NH ₂ ), or N,N- (diethylamine)ethylamine (-CH ₂ CH ₂ N(CH ₂ CH ₂ NH ₂ ). The R' groups can be, for example, hydrogen or alkyl (e.g., methyl).

Figure 20B is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are azide and a thiol or thioether. The R' groups can be, for example, hydrogen or alkyl (e.g., methyl).

Figure 20C is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are amine and nitrile. The R groups can be, for example, hydrogen, t-butoxycarbonyl (BOC), ethylamine (-CH ₂ CH ₂ NH ₂ ), or N,N-(diethylamine)ethylamine (- CH ₂ CH ₂ N(CH ₂ CH ₂ NH ₂ ).

Figure 20D is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are azide and nitrile.

Figure 20E is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are amine and aryl. The R groups can be, for example, hydrogen, t-butoxycarbonyl (BOC), ethylamine (-CH ₂ CH ₂ NH ₂ ), or N,N-(diethylamine)ethylamine (- CH ₂ CH ₂ N(CH ₂ CH ₂ NH ₂ ). The R" groups can be, for example, hydrogen or hydroxyl or another aryl group substituent.

Figure 20F is a schematic drawing showing a pore in an exemplary bi- functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are azide and aryl. The R" groups can be, for example, hydrogen or hydroxyl or another aryl group substituent.

Figure 20G is a schematic drawing showing a pore in an exemplary bi-functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the two functional groups present in the pore are amine and carboxylic acid. The R groups can be, for example, hydrogen, t- butoxycarbonyl (BOC), ethylamine (-CH ₂ CH ₂ NH ₂ ), or N,N- (diethylamine)ethylamine (-CH ₂ CH ₂ N(CH ₂ CH ₂ NH ₂ ).

Figure 20H is a schematic drawing showing a pore in an exemplary functionalized Santa Barbara Amorphous (SBA)-type mesoporous silica material, wherein the pore is functionalized with azide groups.

Figure 21 shows a schematic drawing of a possible mechanism for cyclohexane oxidation to cyclohexanol according to the presently disclosed subject matter.

DETAILED DESCRIPTION

The presently disclosed subject matter will now be described more fully hereinafter with reference to the accompanying examples, in which representative embodiments are shown. The presently disclosed subject matter can, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the embodiments to those skilled in the art.

All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. Throughout the specification and claims, a given chemical formula or name shall encompass all optical and stereoisomers, as well as racemic mixtures where such isomers and mixtures exist. I Definitions

While the following terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the presently disclosed subject matter belongs.

Although any methods, devices, and materials similar or equivalent to those described herein can be used in the practice or testing of the presently disclosed subject matter, representative methods, devices, and materials are now described.

Following long-standing patent law convention, the terms "a", "an", and "the" refer to "one or more" when used in this application, including the claims. Thus, for example, reference to "a metal ion" includes a plurality of such metal ions, and so forth.

Unless otherwise indicated, all numbers expressing quantities of size, number of metal ions, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently disclosed subject matter.

As used herein, the term "about", when referring to a value or to an amount of size, weight, concentration, or percentage is meant to encompass variations of, in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1 %, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed methods.

The term "and/or" when used to describe two or more activities, conditions, or outcomes refers to situations wherein both of the listed conditions are included or wherein only one of the two listed conditions are included.

The term "comprising", which is synonymous with "including," "containing," or "characterized by" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. "Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements can be added and still form a construct within the scope of the claim.

As used herein, the phrase "consisting of excludes any element, step, or ingredient not specified in the claim. When the phrase "consists of appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

As used herein, the phrase "consisting essentially of limits the scope of a claim to the specified materials or steps, plus those that do not materially affect the basic and novel characteristic(s) of the claimed subject matter.

With respect to the terms "comprising", "consisting of, and "consisting essentially of, where one of these three terms is used herein, the presently disclosed and claimed subject matter can include the use of either of the other two terms.

As used herein the term "alkyl" refers to Ci_ ₂ o inclusive, linear (i.e., "straight-chain"), branched, or cyclic, saturated or at least partially and in some cases fully unsaturated (i.e., alkenyl and alkynyl) hydrocarbon chains, including for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl, pentyl, hexyl, octyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, octenyl, butadienyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, and allenyl groups. "Branched" refers to an alkyl group in which a lower alkyl group, such as methyl, ethyl or propyl, is attached to a linear alkyl chain. "Lower alkyl" refers to an alkyl group having 1 to about 8 carbon atoms (i.e., a C-1-8 alkyl), e.g., 1 , 2, 3, 4, 5, 6, 7, or 8 carbon atoms. "Higher alkyl" refers to an alkyl group having about 10 to about 20 carbon atoms, e.g., 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. In certain embodiments, "alkyl" refers, in particular, to Ci _-8 straight-chain alkyls. In other embodiments, "alkyl" refers, in particular, to C _1-8 branched-chain alkyls.

Alkyl groups can optionally be substituted (a "substituted alkyl") with one or more alkyl group substituents, which can be the same or different. The term "alkyl group substituent" includes but is not limited to alkyl, substituted alkyl, halo, arylamino, acyl, hydroxyl, aryloxyl, alkoxyl, alkylthio, arylthio, aralkyloxyl, aralkylthio, carboxyl, alkoxycarbonyl, oxo, and cycloalkyl. There can be optionally inserted along the alkyl chain one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms, wherein the nitrogen substituent is hydrogen, lower alkyl (also referred to herein as "alkylaminoalkyl"), or aryl.

Thus, as used herein, the term "substituted alkyl" includes alkyl groups, as defined herein, in which one or more atoms or functional groups of the alkyl group are replaced with another atom or functional group, including for example, alkyl, substituted alkyl, halogen, aryl, substituted aryl, alkoxyl, hydroxyl, nitro, amino, alkylamino, dialkylamino, sulfate, and mercapto.

"Cyclic" and "cycloalkyl" refer to a non-aromatic mono- or multicyclic ring system of about 3 to about 10 carbon atoms, e.g., 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. The cycloalkyl group can be optionally partially unsaturated. The cycloalkyl group also can be optionally substituted with an alkyl group substituent as defined herein, oxo, and/or alkylene. There can be optionally inserted along the cyclic alkyl chain one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms, wherein the nitrogen substituent is hydrogen, alkyl, substituted alkyl, aryl, or substituted aryl, thus providing a heterocyclic group. Representative monocyclic cycloalkyl rings include cyclopentyl, cyclohexyl, and cycloheptyl. Multicyclic cycloalkyl rings include adamantyl, octahydronaphthyl, decalin, camphor, camphane, and noradamantyl.

The term "aryl" is used herein to refer to an aromatic substituent that can be a single aromatic ring, or multiple aromatic rings that are fused together, linked covalently, or linked to a common group, such as, but not limited to, a methylene or ethylene moiety. The term aryl can refer to both non-heterocyclic aryl groups and aryl groups wherein one or more of the carbon atom of an aromatic ring backbone has been replaced by a heteroatom. Thus, the term aryl includes heteroaryl groups, including, but not limited to, furan, thiophene, pyridine, pyrimidine, pyridazine, pyrazine, imidazole, benzimidazole, benzofuran, and triazole (e.g., 1 ,2,4-triazole and 1,2,3-triazole).

In some embodiments, the term aryl specifically refers to a non- heterocyclic aromatic group comprising between 6 and 26 carbon atoms in the ring structure or structures making up the aryl group backbone (i.e., the aromatic ring structure or structures excluding any aryl group substituents, as defined hereinbelow). For example, the aryl group can include monovalent radicals of benzene, biphenyl, naphthalene, anthracene, phenanthrene, chrysene, pyrene, tetracene, benzo[a]anthracene, dibenzo[a,j]anthracene, dibenzo[a,h]anthracene, dibenzo[a,c]anthracene, coronene, fluoranthene, benzo[a]pyrene, benzo[c]phenanthrene, benzo[b]fluoranthene], hexahelicine, and the like. Thus, aryl groups include, but are not limited to, phenyl and napthyl.

The aryl group can be optionally substituted (a "substituted aryl") with one or more aryl group substituents, which can be the same or different, wherein "aryl group substituent" includes alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, hydroxyl, alkoxyl, aryloxyl, aralkyloxyl, carboxyl, acyl, halo, nitro, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, acyloxyl, acylamino, aroylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, arylthio, alkylthio, alkylene, and -NR'R", wherein R' and R" can each be independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, and aralkyl.

Thus, as used herein, the term "substituted aryl" includes aryl groups, as defined herein, in which one or more atoms or functional groups of the aryl group are replaced with another atom or functional group, including for example, alkyl, substituted alkyl, halogen, aryl, substituted aryl, alkoxyl, hydroxyl, nitro, amino, alkylamino, dialkylamino, sulfate, and mercapto.

The term "heteroaryl" refers to any aryl group as defined hereinabove, wherein one or more carbon atoms of the aryl group ring backbone or backbones is replaced by a heteroatom. The heteroatom can be N, S, O, Si, or B. Typical nitrogen-containing heteroaryl groups include, but are not limited to, pyridinyl, triazolyl, imidazolyl, pyrimidinyl, pyridazinyl, triazinyl, indolyl, quinolinyl, and the like.

"Alkylene" refers to a straight or branched bivalent aliphatic hydrocarbon group having from 1 to about 20 carbon atoms, e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. The alkylene group can be straight, branched or cyclic. The alkylene group also can be unsaturated and/or substituted with one or more "alkyl group substituents." There can be optionally inserted along the alkylene group one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms (also referred to herein as "alkylaminoalkyl"), wherein the nitrogen substituent is alkyl as previously described. Exemplary alkylene groups include methylene (-CH ₂ -); ethylene (-CH2-CH2-); propylene (-(CH ₂ )3-); cyclohexylene (- C ₆ Hio-); -CH=CH— CH=CH-; -CH=CH-CH ₂ -; -(CH ₂ ) _q -N(RHCH ₂ )r-, wherein each of q and r is independently an integer from 0 to about 20, e.g., 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20, and R is hydrogen or lower alkyl; methylenedioxyl (-O-CH ₂ -0-); and ethylenedioxyl (-0-(CH ₂ ) ₂ -0-). An alkylene group can have about 2 to about 3 carbon atoms and can further have 6-20 carbons.

The term "arylene" refers to a bivalent aromatic hydrocarbon group. Exemplary arylene groups include, but are not limited to, phenylene, napthalene, biphenylene (i.e., -C6H4-C6H4-), and the like.

The terms "carboxy" and "carboxyl" refer to carboylic acid and carboxylate groups and to their alkyl, aryl, aralkyl, and nitrogen-containing derivatives (e.g., alkoxycarbonyl, aryloxycarbonyl, aralkyoxycarbonyl, carbamoyl, alkylcarbamoyl, and dialkylcarbamoyl).

The term "carboxylic acid" refers to the -C(=0)OH group. The term "carboxylate" refers to the deprotonated anion of a carboxylic acid (i.e., - C(=O)0 ^" ).

"Alkoxycarbonyl" refers to an alkyl-O-CO- group. Exemplary alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, butyloxycarbonyl, and f-butyloxycarbonyl. "Aryloxycarbonyl" refers to an aryl-O-CO- group. Exemplary aryloxycarbonyl groups include phenoxy- and naphthoxy-carbonyl.

"Aralkoxycarbonyl" refers to an aralkyl-O-CO- group. An exemplary aralkoxycarbonyl group is benzyloxycarbonyl.

"Carbamoyl" refers to an H ₂ N-CO- group.

"Alkylcarbamoyl" refers to a R'RN-CO- group wherein one of R and R' is hydrogen and the other of R and R' is alkyl and/or substituted alkyl as previously described.

"Dialkylcarbamoyl" refers to a R'RN-CO- group wherein each of R and R' is independently alkyl and/or substituted alkyl as previously described.

The terms "hydroxyl" and "hydroxy" refer to the -OH group.

As used herein, the term "acyl" refers to an aryl or alkyl carboxylic acid (i.e., R-C(=O)OH, wherein R is alkyl, substituted alkyl, aryl or substituted aryl) wherein the hydroxyl has been replaced with another substituent. Thus, an acyl group can be represented by the formula RC(=O)— , wherein R is an alkyl or an aryl group as defined herein. As such, the term "acyl" specifically includes arylacyl groups, such as an acetylfuran and a phenacyl group. Additional specific examples of acyl groups include, but are not limited to, acetyl (i.e., CH ₃ C(=O)-) and benzoyl (i.e., (C ₆ H ₅ C(=O)-).

"Alkoxy" and "alkoxyl" refer to an alkyl-O- group wherein alkyl is as previously described. The term "alkoxyl" as used herein can refer to, for example, methoxyl, ethoxyl, propoxyl, isopropoxyl, butoxyl, i-butoxyl, and pentoxyl. The term "oxyalkyl" can be used interchangably with "alkoxyl" or "alkoxy".

"Aryloxy" and "aryloxyl" refer to an aryl-O- group wherein the aryl group is as previously described, including a substituted aryl. The term "aryloxyl" as used herein can refer to phenyloxyl or hexyloxyl, and alkyl, substituted alkyl, halo, or alkoxyl substituted phenyloxyl or hexyloxyl.

"Aralkyl" refers to an aryl— alkyl— group wherein aryl and alkyl are as previously described, and included substituted aryl and substituted alkyl. Exemplary aralkyl groups include benzyl, phenylethyl, and naphthylmethyl. "Aralkyloxyl," "aralkoxyl" and "aralkoxy" refer to an aralkyl-O- group wherein the aralkyi group is as previously described. An exemplary aralkyloxyl group is benzyloxyl.

"Amino" refers to the -N(R)2 group wherein each R is independently H, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, or substituted aralkyi. In some embodiments, the amino group is -NH ₂ . In some embodiments, the amino group is an alkylamino group having the structure -NHR, wherein R is alkyl or substituted alkyl. In some embodiments, the amino group is. a dialkylamino group having the structure -N(R)2, wherein each R is alkyl or substituted alkyl. In some embodiments, the amino group is an arylamino group having the structure -N(R) ₂ , wherein each R is H, aryl, or substituted aryl.

"Acyloxyl" and "acyloxy" refer to an acyl-O- group wherein acyl is as previously described. Thus, for example, an acyloxy group can have the structure R-C(=0)-0- wherein R is alkyl, substituted alkyl, aryl or substituted aryl.

"Acylamino" refers to an acyl-NR'-group, wherein acyl is as previously described and R' is H or alkyl. For example, an acylamino group can have the structure R-C(=0)-NR'-, wherein R is alkyl, substituted alkyl, aryl, or substituted aryl.

The terms "halo", "halide", or "halogen" as used herein refer to fluoro (F), chloro (CI), bromo (Br), and iodo (I) groups.

The term "nitro" refers to the -NO ₂ group.

The term "cyano" refers to the -CN group, wherein the carbon and nitrogen atoms are joined by a triple bond.

The term "thio" refers to a compound described previously herein wherein a carbon or oxygen atom is replaced by a sulfur atom. In some embodiments, the thio compound is a thiol, having the structure RSH, wherein R is, for example, alkyl, aryl, or aralkyi.

The term "peroxide" refers to a compound comprising an oxygen- oxygen single bond. In some embodiments, the peroxide can comprise the group -O-O-H (i.e., "hydroperoxy"). Exemplary peroxides include, but are not limite to, hydrogen peroxide, ferf-butyl peroxide and perbenzoic acids. The term "azide" refers to compounds having the group N ₃ (i.e., - N=N ⁺ =N ^" ). An azide can have the general formula of RN ₃ , wherein R is an organic radical, such as, but not limited to, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, phosphoryl, phosphinyl, and phosphorodiamidic. Thus, an "organic azide" refers to compounds, for example, including aryl azides, alkyl azides, acyl azides, sulfonyl azides, phosphoryl azides, phosphinyl azides and phosphorodiamidic azides.

The term "silyl" refers to a group having a silicon (Si) atom. Thus, silyl groups include, but are not limited to trialkyl silyl groups (i.e., -SiR ₃ , wherein each R is an alkyl group, which can be the same or different), silyl halides (e.g., -Si(R) _n (X)m where m = 1-3, n = 1-2, R is alkyl or aryl, and X is halo) and silyl ethers (e.g., -SiR _n (OR) _m , where m = 1-3, n = 1-2, and each R is alkyl or aryl and can be the same or different).

A structure represented generally by a formula such as:

as used herein refers to a ring structure, for example, an aliphatic and/or aromatic cyclic compound comprising a substituent R group, wherein the R group can be present or absent, and when present, one or more R groups can each be substituted on one or more available carbon atoms of the ring structure. The presence or absence of the R group and number of R groups is determined by the value of the integer n. Each R group, if more than one, is substituted on an available carbon of the ring structure rather than on another R group. For example, the structure:

wherein n is an integer from 0 to 2 comprises compound groups including, but not limited to:

A structure represented by a formula such as:

represents a structure attached covalently or ionically to another (unshown) moiety at the wavy line. The unshown moiety can be a macromolecular moiety, for example, a polymer or other solid support material. In some embodiments, the shown structure and the unshown moiety can be attached via a functional group (e.g., -Si(OR)2- or other divalent silyl group, -0-, -NR-, or -S-) bonded via one or more ionic or covalent bonds to both the shown and unshown moiety. For example, the structure directly above shows a 4- (propyl)-1,2,4-triazole ligand immobilized on another moiety (e.g., a solid support material, such as silica gel) through a unshown functional group on the left-hand end of the propyl group. In some embodiments, the functional group bonded to both the shown and unshown moiety is included in the shown moiety and the shown and unshown moieties are attached via a direct bond or bonds.

When the term "independently" or "independently selected" is used, the substituents being referred to (e.g., R groups, such as groups Ri and R ₂ , or L groups), can be identical or different. For example, both Ri and R ₂ can be substituted alkyls, or Ri can be hydrogen and R ₂ can be a substituted alkyl, and the like.

A named "R," "Ar," "L," "M," or "X" group will generally have the structure that is recognized in the art as corresponding to a group having that name, unless specified otherwise herein. For the purposes of illustration, certain representative "R," "Ar," "L," "M," and "X" groups as set forth above are defined below. These definitions are intended to supplement and illustrate, not preclude, the definitions that would be apparent to one of ordinary skill in the art upon review of the present disclosure. A "heteroatom," as used herein, is an atom other than carbon. In some embodiments, the heteroatoms are selected from the group consisting of N, O, P, S, Si, B, Ge, Sn, and Se. In some embodiments of the presently disclosed subject matter, the heteroatoms are selected from one of N and O.

The term "stereoisomer" refers to molecules that are made up of the same atoms connected by the same sequence of bonds, but have different three dimensional structures. The term stereoisomer includes enantiomers, i.e., mirror image stereoisomers, cis-trans isomers, and diastereomers.

The term "chiral" refers to the stereochemical property of a molecule of being non-superimposible on its mirror image. A chiral molecule has no symmetry elements of the second kind, e.g., a mirror plane, a center of inversion, and a rotation-reflection axis. The two forms of a chiral molecule are known as enantiomers. An enantiomer can be designated as "R" or "S" depending upon the orientation of the substituents that are connected to the molecule's chiral center. An enantiomer can also be labelled "(+)" (or "d" for dextrorotatory) or "(-)" (or "I" for levorotatory) based upon the direction in which the molecule rotates a plane of polarized light. A collection containing equal amounts of the two enantiomeric forms of a chiral molecule is referred to as a racemic mixture or racemate.

The term "diastereomer" refers to non-enantiomeric isomers which arise when more than one stereocenter is present in a molecule.

The term "transition metal" refers to an element of Groups 3 to 12 of the Periodic Table of the Elements. Thus, transition metals include: scandium (Sc), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), technetium (Tc), ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), cadmium (Cd), hafnium (Hf), tantalum (Ta), tungsten (W), rhenium (Re), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), mercury (Hg), rutherfordium (Rf), dubnium (Db), seaborgium (Sg), bohrium (Bh), hassium (Hs), meitnerium (Mt), darmstadtium (Ds, formerly ununnillium), roentgenium (Rg, formerly unununium), or ununbium (Uub). In some embodiments the transition metal can also be a lanthanide or an actinide element. In some embodiments, the transition metal is an element of Period 4 of the Periodic Table of the Elements. In some embodiments, the transition metal is cobalt, iron, copper, manganese, or nickel. In some embodiments, the transition metal is copper or iron.

As used herein, the terms "ligand" or "chelating group" refer generally to chemical species, such as a molecule or ion, which interacts (e.g., binds) in some way with another species. Thus, the terms "ligand" or "chelating group" can refer to a molecule or ion that binds a metal ion (e.g., a transition metal ion) to form a "coordination complex." A ligand that binds to a metal ion at one site (e.g., through electon donation from one ligand atom or functional group) can be referred to as "mono-dentate." A ligand that binds to a metal ion at more than one site can be referred to as "multi-dentate" (e.g., bi-dentate, tri-dentate, tetra-dentate, etc.). In some embodiments, ligands can bind to more than one individual metal ion.

A "coordination complex" or "complex" is a chemical species or compound in which there is a coordinate bond between a metal ion and an electron pair donor or other type of electron donor. Thus, ligands for coordination complexes are generally electron donors, molecules or ions having unshared electron pairs or having π bonds that can donate electron density to a metal ion. Depending upon their exact structure, coordination complexes can be charged species. Thus, in some embodiments, the structure of a coordination complex can be shown in brackets (e.g., [coordination complex]) with a superscript variable outside the brackets (e.g., ^y ) which is an integer (e.g., -4, -3, -2, -1 , 0, +1 , +2, +3, +4) indicating the number of positive or negative charges associated with the complex. One or more counter ions can also be associated with the complex.

The terms "bonding" or "bonded" and variations thereof can refer to either covalent or non-covalent bonding. In some cases, the term "bonding" refers to bonding via a coordinate bond.

The term "coordinate bond" refers to an interaction between an electron donor and a coordination site on a metal ion resulting in an attractive force between the electron donor and the metal ion. The use of this term is not intended to be limiting, in so much as certain coordinate bonds also can be classified as have more or less covalent character (if not entirely covalent character) depending on the characteristics of the metal ion and the electron donor.

The term "linker" refers to a group that is bound (e.g., covalently) to two different groups. As used herein, a "linker" can refer to a group that is used as a tether between a solid support material and a catalyst coordination complex or to a group that serves as a tether between two 1 ,2,4-triazole rings. Thus, in some embodiments, the linker is a bivalent group situated between a 1 ,2,4-triazole ring and a solid support. In some embodiments, the linker includes an alkylene group, an arylene group, or combinations thereof.

The term "amino acid side chain" refers to a group that is the side chain of one of the 20 natural amino acids (i.e, glycine, proline, alanine, valine, leucine, isoleucine, methionine, cysteine, phenylalanine, tyrosine, tryptophan, histidine, lysine, arginine, glutamine, asparagine, glutamic acid, aspartic acid, serine, and threonine). Thus, the term "amino acid side chain" can refer to H, methyl, isopropyl, isobutyl, sec-butyl, -CH ₂ CH ₂ SCH ₃ , benzyl, - CH ₂ -indoyl, -CH ₂ OH, -CH(OH)CH ₃ , -CH ₂ SH, para-hydroxybenzyl, - CH ₂ C(=O)NH ₂ , -CH ₂ CH ₂ C(=0)NH ₂ , -CH ₂ C(=0)OH, -CH ₂ CH ₂ C(=0)OH, - CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(=NH)NH ₂ , and -CH ₂ -imidazoyl.

The term "catalyst" refers to a molecule or chemical species that changes the rate of a chemical reaction (e.g., a bond formation or a bond cleavage). In some embodiments, the term "catalyst" can refer to a transition metal complex (i.e., an unactivated or an activated transition metal complex). In some embodiments, the catalyst is used in conjunction with one or more co-catalysts, activators, or other reagents. Such co-catalysts, activators, and other reagents include, but are not limited to, oxidants and nitrogen sources (e.g., azides). In some embodiments, the catalyst is an oxidation catalyst, which catalyzes the oxidation of a hydrocarbon substrate. In some embodiments, the catalyst catalyzes the degradation of cellulosic materials. In some embodiments, the catalyst can control the stereochemistry of the molecule that is the product of the chemical reaction being catalyzed. The terms "pre-catalyst" and "unactivated catalyst" refer to chemical compounds (e.g., transition metal complexes) that catalyze reactions in the presence of activators (e.g., peroxides or other oxidants) or that can be reacted with an activator to form an activated catalyst.

The term "activated catalyst" refers to a chemical compound (e.g., a transition metal complex) that can catalyze a reaction in the absence of an activator.

The term "selectively catalyzes" refers to a catalyzed reaction wherein one product is favored over the other products or potential products of a reaction. Thus, the term "selectively oxidizes" refers to the catalysis of an oxidation reaction wherein one possible oxidation product is favored over the other(s). In some embodiments, "selectively oxidizes" refers to the catalysis of an oxidation reaction wherein one oxidiation product makes up 50% or more of the reaction products (e.g., based on the moles of products present). In some embodiments, the favored product of the selectively oxidized reaction makes up 75% or more of the reaction products (i.e., 80%, 85%, 90%, 95% or more). In some embodiments, a selectively oxidized or selectively catalyzed reaction refers to a reaction where a single product of several possible products is formed. In some embodiments, the favored product has a particular molecular formula. In some embodiments, the favored product is a particular stereoisomer of a compound of a particular molecular formula.

The term "Ci oxidation product" refers to a product of the oxidation of methane wherein the product comprises one carbon atom. Thus, Ci oxidation products can include methanol, formaldehyde, and formic acid.

The term "C ₂ oxidation product" refers to a product of the oxidation of methane (or another chemical oxidation reaction) wherein the product comprises two carbon atoms. Thus, C ₂ oxidation products can include ethanol, acetaldehyde, and acetic acid.

The term "hydrocarbon substrate" refers to compounds comprising hydrogen and carbon that can undergo a transformation catalyzed by a catalyst of the presently disclosed subject matter. In addition to hydrogen and carbon, hydrocarbon substrates can optionally include other atoms, including, but not limited to, nitrogen, oxygen, halogen, sulfur, and phosphorous. Typical hydrocarbon substrates include, but are not limited to, alkanes (e.g., straight chain, branched, cyclic, and substituted alkanes) and alkenes (e.g., straight chain, branched, cyclic, and substituted alkenes).

The term "alkane" refers to a hydrocarbon substrate or molecule comprising carbon and hydrogen atoms wherein the carbon atoms (minus those carbon atoms in aromatic substituents) are bonded to one another via carbon-carbon single bonds. Typical alkanes include, but are not limited to, methane, ethane, propane, butane, pentane, hexane, heptane, octane, cylohexane, cycloheptane, and mixtures thereof. Alkanes can be branched (e.g., isobutane) or cyclic (e.g., cyclohexane). Alkanes can also be substituted by one or more aryl, aralkyl, halo, nitro, cyano, amino, hydroxyl, acyl, or carboxy group. In some embodiments, the substituted alkane is an alkane having one or more aryl or aralkyl substitutents.

The terms "alkene" and "olefin" refer to a molecule comprising at least one carbon-carbon double bond, not including bonds in an aromatic ring. In some embodiments, "olefin" refers to C2-C20 -olefins. Suitable olefins also include cyclic olefins and conjugated and non-conjugated dienes. Alkenes can include one or more aryl, halo, nitro, cyano, amino, hydroxyl, acyl, or carboxyl substituents. Examples of olefins include, but are not limited to, ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, 4-methyl-1- pentene, butadiene, isoprene, cyclopentene, cyclohexene, cyclooctene, styrene, norbornene, 1-methylnorbornene, 5-methylnorbornene, and the like, and mixtures thereof.

The term "aprotic solvent" refers to organic solvents that do not contain a donatable hydrogen atom. Typical aprotic solvents include, but are not limited to, acetone, acetonitrile, benzene, butanone, butyronitrile, carbon tetrachloride, chlorobenzene, chloroform, 1 ,2-dichloroethane, dichloromethane, diethyl ether, dimethylacetamide (DMA), N,N- dimethylformamide (DMF), dimethylsulfoxide (DMSO), 1 ,4-dioxane, ethyl acetate, ethylene glycol dimethyl ether, hexane, /V-methylpyrrolidone (NMP), pyridine, tetrahydrofuran (THF), and toluene. Certain aprotic solvents are polar solvents. Examples of polar aprotic solvents include, but are not limited to, acetone, acetonitrile (MeCN), butanone, DMF and DMSO. Certain aprotic solvents are non-polar solvents. Examples of nonpolar, aprotic solvents include, but are not limited to, diethyl ether, THF, aliphatic hydrocarbons, such as hexane, cyclohexane, and pentane, aromatic hydrocarbons, such as benzene and toluene, and symmetrical halogenated hydrocarbons, such as carbon tetrachloride and dichloromethane.

The term "cellulosic" refers to a composition comprising cellulose. Thus, the term "cellulosic" includes lignocellulosic materials.

The term "cellulose" refers to a polysaccharide of β-glucose (i.e., glucan) comprising β-(1-4) glycosidic bonds.

The term "lignocellulosic" refers to a composition comprising both lignin and cellulose. In some embodiments, lignocellulosic material can comprise hemicellulose, a polysaccharide which can comprise saccharide monomers other than glucose. Typically, lignocellulosic materials comprise about 38-50% cellulose, 15-30% lignin, and 23-32% hemicellulose.

Lignocellulosic biomass include a variety of plants and plant materials, such as, but not limited to, papermaking sludge; wood, and wood- related materials, e.g., saw dust, or particle board, leaves, or trees, such as poplar trees; grasses, such as switchgrass and sudangrass; grass clippings; rice hulls; bagasse (e.g., sugar cane bagasse), jute; hemp; flax; bamboo; sisal; abaca; hays; straws; corn cobs; corn stover; whole plant corn, and coconut hair. In some embodiments, lignocellulosic biomass is selected from the group including, but not limited to, herbaceous material, agricultural residues, forestry residues, municipal solid wastes, waste paper, pulp and paper mill residues, or a combination thereof. In some embodiments, lignocellulosic biomass is selected from the group including, but not limited to, corn stover, straw, bagasse, miscanthus, sorghum residue, switch grass, water hyacinth, hardwood, hardwood, softwood, wood chips, and wood pulp.

"Lignin" is a polyphenols material comprised of phenyl propane units linked by ether and carbon-carbon bonds. Lignins can be highly branched and can also be crosslinked. Lignins can have significant structural variation that depends, at least in part, on the plant source involved. The term "hemicellulose" can refer polysaccharides comprising mainly sugars or combinations of sugars (e.g., xylose, mannose, etc). Thus, xylan (polymerized xylose) and mannan (polymerized mannose) are exemplary hemicelluloses. Hemicellulose can be highly branced. Hemicellulose can be chemically bonded to lignin and can further be randomly acetylated, which reduces enzymatic hydrolysis of the glycosidic bonds in hemicellulose.

JL Triazole Catalysts

In some embodiments, the presently disclosed subject matter provides transition metal catalysts and pre-catalysts comprising a 1 ,2,4- triazole ligand and a transition metal atom. In some embodiments, the catalyst and/or pre-catalyst comprise a coordination complex of one or more 1 ,2,4-triazole ligands and one or more transition metal atoms. Diverse libraries of 1 ,2,4-triazole ligands can be prepared to vary the stereoelectronic demands of coordination complexes prepared from the ligands.

In some embodiments, the catalysts and pre-catalysts can comprise coordination complexes that comprise two transition metal atoms and two 1 ,2,4-triazole ligands. In some embodiments, the active catalyst is a Νε-(μ- oxo) complex comprising the transition metal atoms and at least one 1 ,2,4- triazole ligand. In some embodiments, the exact structure of the active catalyst can vary depending upon whether the catalyst is dissolved in a solution or is present as a dry solid.

As described further hereinbelow, coordination complex catalysts comprising 1 ,2,4-triazole ligands can be used to oxidize alkyl, cycloalkyl and benzylic C-H bonds under mild conditions (e.g., at or below room temperature) in water and in organic solvents to provide alcohols, ketones, aldehydes, and carboxylic acids. See Scheme 1. In particular, the presently disclosed catalysts can be used to catalyze the oxidation of methane. Depending upon the particular structure of the 1 ,2,4-triazole ligand used in the catalyst and/or other reaction conditions (e.g., solvent), the catalysts can catalyze the oxidation of methane into one or more Ci or C ₂ oxidation product(s). In some embodiments, the ligand structure and/or other conditions can be controlled to selectively oxidize methane into methanol. Thus, by way of example and not limitation, the presently disclosed catalysts can be used in the biofuels industry to tranform natural gas into methanol for use a fuel.

Scheme 1. Catalytic Oxidation of Alkanes. In addition to catalyzing the oxidation of simple alkanes, the presently disclosed 1 ,2,4-triazole-containing catalyts can be used to catalyze the oxidation and functionalization of olefins, resulting in the formation of diols (e.g., cis-diols), epoxides, aminoalcohols, and aziridines. See Scheme 2. These products can be used as chiral intermediates in the synthesis of natural products and in the pharmaceutical and fine chemicals industry. In particular, cis-diols are potential precursors to pharmaceuticals; however, previous efforts to use these scaffolds have been thwarted by the toxicity of existing catalysts for their preparation. The presently disclosed catalysts, in contrast, can include non-toxic metal atoms, such as copper.

catalyst

nitrogen source

Scheme 2. Catalytic Reactions with Olefins. Additionally, the presently disclosed catalysts can catalzye the degradation of cellulose. As with the oxidation of methane from natural gas, the degradation of cellulose can be beneficial in the biofuels industry. For example, the presently disclosed catalysts can be used to catalyze the delignification and/or the degradation of Iignocellulosic materials into smaller molecules, such as cellobiose or hydroxymethylfurfural, which can easily be transformed into ethanol or other chemicals. The catalysts can also be used to catalyze other reactions, including, but not limited to, palladium-free Sonogashira couplings (i.e., couplings between terminal alkynes and aryl or vinyl halides) and in reactions involved in Click chemistry.

The presently disclosed triazole catalysts have good activity, including good turnover numbers (TONs) and turnover frequency (TOF). In some embodiments, the catalysts have TONs of greater than about 100. In some embodiments, the catalysts have TONs of about 10 ⁴ .

j]A 1 ,2.4-Triazole Ligands

Suitable ,2,4-triazole ligands for use in the presently disclosed subject matter include, but are not limited to, mono-substituted 1 ,2,4- triazoles (e.g., 4-substituted 1 ,2,4-triazoles, 3-substituted 1 ,2,4-triazoles, or 1-substituted 1,2,4-triazoles), di-substituted triazoles (e.g., 3,5-disubstituted 1 ,2,4-triazoles or 3,4-disubstituted 1 ,2,4-triazoles), trisubstituted triazoles (e.g., 3-,4-,5-trisubstituted 1 ,2,4-triazoles), bis-1 ,2,4-triazoles, and solid support-linked 1 ,2,4-triazole ligands. Generic structures of exemplary 1 ,2,4- triazole ligands for use according to the presently disclosed subject matter are shown in Figure 1.

Stucture GN-A in Figure 1 shows a generic 4-substituted 1 ,2,4- triazole, while structure GN-B is a generic 3,5-disubstituted 1 ,2,4-triazole. Structure GN-C is a 4-amino-3,5-substituted-1,2,4-triazole (i.e., a trisubstituted 1 ,2,4-triazole). In some embodiments, the 1 ,2,4-triazole is substituted by a 1 ,2,3-triazole group, for example, at the 3- or 4-position. See Structures GN-D and GN-E of Figure 1. In some embodiments, the 1 ,2,4-triazole is fused to another aromatic ring (e.g., benzene or pyrimidine). See Structures GN-F and GN-G of Figure 1. In some embodiments, two or more individual 1 ,2,4-triazole rings are part of one fused bis-1 ,2,4-triazole ligand. See Structures GN-H, GN-I, GN-J, GN-K, GN-L, GN-M, GN-N, and

GN-O of Figure 1. Individual 1 ,2,4-triazoles can also be covalently linked to one another via organic linker moieties (e.g., alkylene or arylene linkers), but not form a fused ring system. The linker moiety can be attached, for example, at the 3- or 4-position of the individual triazole rings.

As further shown in Figure 1 , the triazole ligands can be substituted with aryl or alkyl group substituents (e.g., with groups R, R', and R"). The ligands can also be substituted with linkers that attach or can be used to attach the ligands to a solid support material.

The aryl group substituents of the triazole ligands can be electron- donating or electron-withdrawing. For example, a group that donates more electron density onto the molecule to which it is attached relative to a hydrogen substituent is considered electron-donating. A group that withdraws more electron density from the molecule to which it is attached relative to a hydrogen substituent is electron-withdrawing. Representative electron-donating groups include, but are not limited to, alkyl, aryl, alkoxy, aryloxy, amino, alkylamino, arylamino, hydroxy, alkylthio, -SH, and -O-acyl. Representative electron-withdrawing groups include, but are not limited to, appropriately-substituted alkyl and aryl groups (such as haloalkyl groups), - N(alkyl)3 ⁺ , nitro, cyano, halo, carboxy, and acyl.

The nature of the groups attached to the 1 ,2,4-triazole ligand can be used to change the outcome (e.g., yield, product distribution) of the reactions catalyzed by the catalysts comprising the ligand. Numerous other examples of electron-donating and electron-withdrawing groups are well-known to those skilled in the art. See, e.g., Gordon et al„ The Chemist's Companion, New York, John Wiley & Sons, (1972). Further, electron-donating and electron-withdrawing groups can be identified through routine experimentation by, for example, substitution in a molecule and testing of any resultant inductive effects.

Different triazole ligands can have different "denticity." The triazole ligands can be mono-dentate or multi-dentate. Multi-dentate triazole ligands be, for example, bi-dentate (i.e., capable of bonding to a metal ion at two sites, via electon donation from two atoms or functional groups on the ligand), tri-dentate (i.e., capable of bonding to a metal ion at three sites), or tetra-dentate (i.e., capable of bonding to a metal ion at four sites). In some embodiments, the multi-dentate ligand can bond to a metal ion through electron donation from a nitrogen atom of two or more individual triazole groups (e.g., of a single fused ligand). In some embodiments, the multi- dentate ligand can bond to a metal ion through electron donation from a nitrogen atom of one or more individual triazole groups and via electron donation from another electron donating group that forms part of the ligand (e.g., an amino, heteroaryl, or carboxylate group).

The denticity of the triazole ligands can affect the structure of the activated metal complex catalyst formed with the ligand. For example, in some embodiments, the use of a bi- or tri-dentate ligand can generate a bis( -oxo) and/or a side on peroxo metal complex catalyst. In some embodiments, the use of a tetradentate ligand can favor formation of an end- on peroxo metal complex catalyst. In some embodiments, the electron- donating ability of the ligand can also influence formation of a bis( - oxo)metal complex catalyst.

Further, chelate size can play a role in the reactivity of the catalyst. Thus, for example, the length of the groups linking two triazole groups together into one ligand can be varied to alter the reactivity of the catalyst formed.

In some embodiments, the 1 ,2,4-triazole ligand is a 4-substituted 1 ,2,4-triazole. Exemplary 4-substituted 1 ,2,4-triazole ligands of the presently disclosed subject matter are shown in Figure 2. The substituent at the 4 position can be selected from the group including, but not limited to, alkyl, aryl, aralkyl, amino, halo, hydroxy, alkoxy, aryloxy, acyl or acylamino. In some embodiments, the substituent at the 4-position is phenyl, napthyl, benzyl or pyridyl (i.e., 2-pyridyl, 3-pyridyl, or 4-pyridyl). In some embodiments, the substituent at the 4-position is substituted aryl or substituted aralkyl, wherein the substituted aryl or substituted aralkyl is substituted by one or more substituents including, but not limited to, alkyl (e.g., methyl), aryl (e.g., phenyl), aralkyl (e.g., benzyl or methylpyridine), nitro, halo (e.g., F, CI, Br, or I), hydroxy, alkoxy (e.g., methoxy), and carboxyl (e.g., -COOH) groups.

In some embodiments, the triazole ligand is a 3,5-disubstituted 1,2,4 triazole or a 3,4,5-trisubstituted 1 ,2,4-triazole. Exemplary di- and tri- substituted 1 ,2,4-triazoles are illustrated in Figure 3. In some embodiments, the 1 ,2,4-triazole is substituted at the 3- and 5-positions by aryl, aralkyl, substituted aryl, or substituted aralkyl groups. Such groups can include, but are not limited to, phenyl, pyridyl (e.g., 2-pyridyl), 4-halophenyl (e.g., 4- chlorophenyl), and 4-alkoxyphenyl (e.g., 4-methoxyphenyl). In some embodiments, the 1 ,2,4-triazole includes a substituent on the nitrogen atom at the 4-position of the ring in addition to substituents at the 3- and 5- positions. In some embodiments, the nitrogen at the 4-position of the triazole ring is substituted by an amino group (e.g., -NH ₂ orarylamino).

In some embodiments, the 1,2,4-triazole ligand is a bis-1 ,2,4-triazole wherein two 1 ,2,4-triazole rings are linked via an alkylene or arylene linker. Exemplary linked bis-1 ,2,4-triazoles are shown in Figure 4. The linker can be attached to one or both of the individual 1 ,2,4-triazole rings at the 3- position. In some embodiments, the linker is attached to one of the individual 1 ,2,4-triazole rings at the 4-position. The linked bis-1 ,2,4-triazole ligand can comprise aryl group substituents at the triazole ring positions not directly attached to the linker. Such substituents can include any suitable aryl group substituent, including, but not limited to aryl and aralkyl. In some embodiments, the linked-bis-1 ,2,4-triazole is substituted by one or more benzyl or phenyl groups.

In some embodiments, the bis-1 ,2,4-triazole ligand is a fused system. Exemplary fused-bis-1 ,2,4-triazole ligands of the presently disclosed subject matter are shown in Figure 5. The fused ligand can include fused aromatic groups in addition to the two 1 ,2,4-triazole rings, including, but not limited to benzene, pyridine, and napthalene. The ligand can also include one or more aryl group substituent attached to the 1 ,2,4-triazole rings and/or to the fused aromatic groups. The aryl group substituents of the fused-bis-1 ,2,4-triazole ligand can include, but are not limited to, alkyl, substituted alkyl (e.g., carboxyl-substituted alkyl), aryl, and substituted aryl. In some embodiments, the 1 ,2,4-triazole ligand is a 1 -substituted 1 ,2,4-triazole. Exemplary 1 -substituted 1 ,2,4-triazoles are shown in Figure

6. The substituent at the -position can include, but is not limited to, alkyl, substituted alkyl, aralkyl, and substituted aralkyl. In some embodiments, the substituent is -CH(COOH)R, wherein R is an amino acid side chain.

In some embodiments, the 1 ,2,4-triazole ligand is a 3-substituted 1 ,2,4-triazole. Exemplary 3-substituted 1 ,2,4-triazoles are shown in Figure

7. In some embodiments, the substituent at the 3-position includes a 1 ,2,3- triazole or substituted 1 ,2,3-triazole. The substituents of the 1 ,2,3-triazole can include, but are not limited to, substituted alkyl (e.g., hydroxy-substituted alkyl), aryl, and aralkyl.

II.A.i. Supported Ligands

In some embodiments, the 1 ,2,4-triazole ligand is attached to a solid support material (such as, but not limited to, silica gel, polystyrene, a polyoxometallate, a zeolite, or a metal-organic framework) or includes a substituent that can interact with (either covalently or non-covalently) a solid support material. For instance, various silyl groups can react via condensation reactions to covalently bond to silica-based solid support materials (e.g. silica gel or glass beads). Other functional groups, (e.g., thio, amino, oxo, hydroxy, carboxy, alkene, etc.) can form coordinate bonds or ionic bonds to metal-containing solid support materials or ionic or covalent bonds to solid support materials comprising organic polymers or inorganic polymers. Thus, in some embodiments, the ligands can be used in the synthesis of heterogenous catalysts. Some examples of 1 ,2,4-triazoles attached to solid support materials are illustrated in Figure 8.

The use of heterogenous catalysts offers several advantages. For instance, the use of heterogenous catalysts can ease the separation of the products from the catalytic species, correspond to lower catalyst loadings, provide an inert reaction media, and, in most cases, provide a more easily regenerable catalyst. The surfaces of heterogeneous catalysts can also be tailored to act synergistically with organic ligands to stabilize active catalytic structures or transition states. See argelefsky et al., Chemical Society Reviews, 88, 1118-1126 (2008). The movement of solid support-bound ligands and other surface-bound groups can be restricted in pores in the solid support, allowing for the formation of aggregates (such as multicopper species) that are unfavorable in homogeneous solution due to competition with translational entropy.

In some embodiments, triazole ligands can be immobilized onto solid supports through covalent linkages, either directly or through organic linkers attached to groups on the surface of the support. In some embodiments, the solid support comprises silica. In particular, the use of mesoporous silica materials (e.g., Santa Barbara Amorphous (SBA)-type materials) as the solid support can provide highly dispersed active species due to their high surface areas (e.g., > 500 m ² g ^"1 ) and low substrate binding. See Yang et al.. J. Materials Chemistry, 19, 1945-1955 (2009). The relatively large pore sizes of mesoporous silica, especially the SBA type, ranges from 20 to 300 angstroms, allowing for large molecules, even proteins, to be immobilized within pores. Large pore size also allows mass transport through the materials, enabling reactions to occur within pores, followed by diffusion of reaction products into the bulk reaction medium.

Functionalization of the inner surface of pores in mesoporous materials can be accomplished by, for example, post-synthetic grafting with an organotrialkoxysilane (RSi(OR')3)- See Zhang et al., J. Am. Chem. Soc, 118, 9164-9171 (1996); and Mercier et al.. Advanced Materials, 9, 500-503 (2006). Alternatively, tetraethyl orthosilicate (TEOS) and an organotrialkoxysilane (RSi(OR')3) can be co-polymerized. In some embodiments, the co-polymerization can be performed in the presence of a structure-directing agent (such as a block co-polymer/surfactant), which allows control of the distribution and loading of functional groups R in the channel pores. See Macguarrie et al.. J. Materials Chemistry, 11 , 1843- 1849 (2001); Mori et al.. Chemistry of Materials. 13, 2173-2178 (2001); and Corriu et al.. Chem. Comm., 1116-1117 (2001). Accordingly, mesoporous silica surfaces can be functionalized with a large variety of functional groups.

In some embodiments, co-condensation can be used to synthesize mesoporous materials that contain two distinct types of functional groups. See Asefa et al.. J. Am. Chem. Soc, 123, 8520-8530 (2001); Mouawia et al.. New Journal of Chemistry, 30, 1077-1082 (2006); Mehdi et al.. J. Nanosci. Nanotech., 6, 377-381 (2006); Mouawia et al.. J. Materials Chem., 18, 4193- 4203 (2008); Cauda et al.. J. Am. Chem. Soc, 131 , 11361-11370 (2009); and Chen et al.. J. Phys. Chem. C, 113, 2855-2860 (2009).

The presence of two distinct types of groups (e.g., a triazole ligand or triazole ligand-based catalyst and another "auxiliary" group), within a pore can provide for cooperative effects. For example, according to the presently disclosed subject matter, an auxiliary group can coordinate to a transition metal ion as a supplemental ligand to the triazole or can be used to provide a more hydrophobic environment (e.g., to facilitate partitioning of non-polar substrates to the reaction center when the bulk reaction medium is aqueous).

A variety of factors can control functional group positioning, including the nature of the functional group, pore size, and synthetic conditions (e.g., temperature, solvent, salt effects, etc.). The synthesis of bifunctional mesoporous silicas can be accomplished by co-hydrolysis and co- polymerization of a ternary mixture of TEOS and two different organotriethoxysilanes. The co-hydrolysis/co-polymerization can be performed, if desired, in the presence of a structure-directing agent, such as Pluronic 123 (P123), a triblock copolymer, as shown in Figure 19A. Reaction stoichimoetries can be varied to control the pore size and distribution of functional groups within the pore. Functional groups can include, but are not limited to, amines, thiols, thioethers, azides, nitriles, aryls, substituted aryls, and the like. Figures 20A-20H show functional group combinations that can be present in the pores of functionalized and bi-functionalized silica materials prepared according to the presently disclosed subject matter. Figure 19B shows a representative catalytic site within a pore in a bi-functionalized silica. As shown in Figure 19B, triazole ligands can coordinate to copper ions and an oxidant to form an active catalyst, while, for example, aryl groups can be present to control sterics and the hydrophilic/hydrophobic nature of the reaction site.

The functionalized materials can be characterized by any suitable method known in the art. For example, the composition of the materials can be determined from elemental analysis. X-ray diffraction (XRD) measurements and/or transmission or scanning electron microscopy (TEM or SEM) can be used to characterize the surfaces. N ₂ physisorption studies can be used to calculate values of surface area and porosity. The surface areas can also be calculated by the Brunauer-Emmett-Teller (BET) method and the pore-diameter distribution can be evaluated by the Barret-Joyner- Halenda (BJH) method. The materials can be further analyzed by electron paramagnetic resonance (EPR) spectroscopy and ¹³ C and ²⁹ Si solid-state nuclear magnetic resonance (NMR) spectroscopy. Diffuse reflectance spectroscopy can be used to measure the absorption spectra of the materials.

ll.A.ii. Ligand Synthesis

1 ,2,4-Triazole ligands for use in the presently disclosed catalysts can be prepared via any suitable method. Representative methods of synthesizing 1 ,2,4-triazole ligands for use in the presently disclosed catalysts are illustrated below in Scheme 3. 4-Substituted 1 ,2,4-triazole 2 can be prepared by reacting dimethylformamide (DMF) first with thionyl chloride and then with hydrazine to form compound 1. Compound 1 can then be reacted with a primary amine. The amine can be chosen based on the final nitrogen substituent desired in triazole ligand 2. For instance, when methyl amine is used, the 4-substituted 1,2,4-triazole 2 is a 4-methyl-1,2,4-triazole. When an amino acid (or carboxy or side chain protected derivative thereof) is used as the amine, the 4-substituent of triazole 2 can be -CH(COOH)R', wherein R' is the side chain of the amino acid.

As also illustrated in Scheme 3, 3,5-disubstituted 1 ,2,4-triazoles 3 and

4 can be prepared by reacting a nitrile with hydrazine to form N-amino-1 ,2,4- triazole 3. If desired, the N-amino group of compound 3 can be removed by reaction with hypophosphorous acid (i.e., phosphinic acid) and sodium nitrite to provide 4-H-3,5-disubstituted 1 ,2,4-triazole 4. Alternatively, 4-H-3,5- disubstituted 1 ,2,4-triazole 4 can be synthesized by reacting an acyl halide with hexamethyldisilazane (HMDS) to form N-acyl amide 5 which can be cyclized with hydrazine to form the triazole. 3,5-Fused 1 ,2,4-triazole ligands such as bistl^^triazolo^.S-aiS^'-clquinoxaline 8 can be prepared by reacting diketobenzopiperazine 6 with thionyl chloride to form dichloride 7. Compound 6 is then reacted with an acyl hydrazide to form quinoxaline 8.

The syntheses illustrated in Scheme 3 offer a highly modular approach to providing ligands for the presently disclosed catalysts in that many amines, nitriles, or carboxylic acid derivatives can be used as starting materials, allowing for the tuning of both steric and electronic effects. The starting materials are generally inexpensive. Finally, the methods can be extended to solid-phase organic synthesis, allowing for the combinatorial generation of ligands and catalysts. See, e.g., Figure 9, where the reagent designated as 1, can be the same as 1 in Scheme 3.

Scheme 3. Exemplary Syntheses of 1 ,2,4-Triazole Ligands. In addition to the synthetic routes shown in Scheme 3, a further exemplary route to a 3,4,5-trisubstituted mono-dentate triazole is shown in Figure 16A. As shown in Figure 16A, the trisubstituted triazoles can be synthesized from diacylhydrazides and aryl amines (ArNH ₂ ) in the presence of POCI ₃ via synthetic methodology known in the art. See Chiraiac, C. I., Revue Roumaine de Chimie, 28, 977-980 (1983). A further exemplary synthetic route to an alkylene-tethered bi-dentate triazole ligand (α,ω-Τζ ₂ ) is provided in Figure 16B. As indicated in Figure 16B, an acyl chloride can be reacted with an aryl amine (ArNhk) in the presence of Lawesson's reagent (i.e., 2,4-bis(4-methoxyphenyl)-1 ,3,2,4-dithiadiphosphetane-2,4-disulfide; see Katritzkv et al.. J. Chem. Soc, Perkins Trans. I, 1961-1963 (1979)) and hydrazine, followed by condensation with a diacyl halide. See Spasov and Demirov, Chem. Ber., 101 , 4238-4240 (1968). Figure 17 shows general synthetic methodology for the preparation of tri- and tetra-dentate triazole ligands via the reaction of Ν,Ν-dimethylformamide-dimethyl acetal (DMF- DMA) with a hydrazide, followed by condensation with an amine. See Stocks et al.. Organic Letters, 6, 2969-2971 (2004).

By way of additional example, 3,5-substituted 1 ,2,4-triazoles can be prepared from the reaction of amides with acyl hydrazides. 1 ,2,4-Triazoles can also be prepared via the reaction of an imide with an alkyl hydrazine (i.e., "the Einhorn-Brunner reaction") or the reaction of an amide with hydrazine. One of skill in the art can readily appreciate additional methods of synthesizing 1 ,2,4-triazoles upon review of and for use in the presently disclosed subject matter.

Further synthetic routes to supported triazole ligands, for example in pores of mesoporous silica supports, are shown in Figure 18. In general, modification of an aryl halide to an alkyne (e.g., via Sonogashira coupling) a carboxylic acid (e.g., via lithium-halogen exchange), or an alkene (e.g., via a Heck reaction) can allow incorporation of multi-substituted 1 ,2,4-triazoles into silica supports.

IIAiii. Ligands of Formulas (I), (II). (Ill), and (IV)

In some embodiments, the 1 ,2,4-triazole ligand is a ligand of Formula

(I):

wherein:

i and R ₃ are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

R ₂ is selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, substituted aralkyi, -NHC(=0)R ₄ , and - CH(COOH)R ₄ , wherein R ₄ is alkyi, aryl, aralkyi, or an amino acid side chain; or

wherein one of R _{1 (} R ₂ , and R ₃ is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can bond (via a ionic, coordinate or covalent bond or bonds) with a solid support material.

Suitable solid support materials include, but are not limited to, polyolefins (e.g., polyethylene, polypropylene, polystyrene, etc.), polyacrylamides, polyacrylates, talc, glass, and silica (e.g., silica gel, mesoporous silica, or amorphous silica), functionalized silica, metals, metal oxides, metal-organic matrices, polyoxometallates, and zeolites. Suitable linker moieties include, but are not limited to, alkylene, arylene, aralkylene, and thio (e.g., alkylthiols), amino, oxo, hydroxy, carboxy, or silyl derivatives thereof (e.g., siloxy ethers or silyl halides). Linker moieties can be based on organic polymers, such as, but not limited to, polyethylene glycol (PEG).

Generally, at least one of Ri or R ₂ of the ligand of Formula (I) will be a group other than H. In some embodiments, at least one of Ri, R ₂ , and R3 is aryl or substituted aryl. In some embodiments, at least one of Ri, R ₂ , and R ₃ is alkyi or substituted alkyi.

In some embodiments, the ligand of Formula (I) is a 4-substituted 1 ,2,4-triazole and R ₂ is a substitutuent selected from the group comprising amino, aryl, substituted aryl, aralkyi and substituted aralkyi. In some embodiments, R ₂ is -NH ₂ or arylamino (e.g., phenylamino). The R ₂ group can also be acylamino, -NHC(=O)R ₄ (e.g., benzoylamino). In some embodiments, R ₂ is phenyl, pyridyl, substituted phenyl or substituted pyridyl. In some embodiments, the substituted phenyl or substituted pyridyl is a phenyl or pyridyl moiety substituted with an electron-withdrawing group, such as nitro (i.e., -NO ₂ ) or carboxy. In some embodiments, the phenyl or pyridyl moiety is substituted by an electron-donating group, including, but not limited to, alkyl, aryl, aralkyl, amino, hydroxy, or alkoxy. In some embodiments, the phenyl or pyridyl group is substituted by one or more halo groups. In some embodiments, F¾ is benzyl or substituted benzyl. In some embodiments, l¾ is methylpyridine, wherein the pyridine can optionally include one or more additional aryl group substituents.

In some embodiments, the 1 ,2,4-triazole ligand is substituted by at least one heteroaryl substitutent (e.g., triazolyl, pyridyl, etc). For example, in some embodiments, one or more of Ri, R ₂ , and R ₃ is 1,2,3-triazolyl or a substituted 1 ,2,3-triazolyl ligand. In some embodiments, the substituted 1 ,2,3-triazolyl group has the structure:

wherein R5 is selected from aryl, substituted aryl, aralkyl, and substituted aralkyl. In some embodiments, the aralkyl or substituted aralkyl is based on a heteroaryl group. In some embodiments, the heteroaryl group is a nitrogen-containing heteroaryl group, including but not limited to imidazole, benzimidazole, pyrazole, pyrazine, pyrimidine, pyridazine, pyridine, triazole, indole, and pyrrole.

In some embodiments, the 1 ,2,4-triazole ligand is a fused polycyclic ligand. For example, in some embodiments, a single fused-1 ,2,4-triazole ligand can include two or more 1 ,2,4-triazole rings. In some embodiments, the fused polycyclic ligand can be a bis[1 ,2,4]triazolo[4,3-a:3'4'-c]quinoxaline or other structure of Formula (II):

wherein:

Li is a direct bond or alkylene;

R ₆ and R ₇ are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

each R ₈ is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxy!, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; or

wherein two R ₈ groups are together alkylene; or

wherein one of R ₆ and R or one R ₈ is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material. In some embodiments, R ₆ and R ₇ are selected from the group comprising methyl and phenyl.

In some embodiments, l_i is a direct bond. In some embodiments, L-i is methylene or ethylene.

In some embodiments, two R ₈ groups are together alkylene, such that the benzene ring of the structure of Formula (II) is fused to another aromatic or non-aromatic ring. For example, when two Re groups are together - CH=CH-CH=CH-, the structure of Formula (II) can include a napthalene group. See for example, FB-F in Figure 5.

In some embodiments, the fused-1 ,2,4-triazole ligand includes two 1 ,2,4-triazole rings fused to a pyridine ring and has a structure of Formula (HI):

wherein:

L ₂ is a direct bond or alkylene;

R _g and F¼ are independently selected from the group comprising H, , alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

each Rii is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; or

wherein two Rn groups are together alkylene; or

wherein one of R ₉ and Ri ₀ or one R is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, the fused-1 ,2,4-triazole comprises a structure of Formula (IV):

wherein:

l_3 is a direct bond or alkylene;

Ri3 and R-| ₄ are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and each R-12 is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or

wherein two R12 groups are together alkylene; or

wherein one of R13 and R14 or one R12 is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, the 1 ,2,4-triazole ligand is selected from the

In some embodiments, the ligand is a 1 ,2,4-triazole attached to a solid support wherein the ligand is selected from the group including, but not limited to:

While any suitable solid support material can be used, in some embodiments, the solid support is a mesoporous silica gel. In some embodiments, the mesoporous silica gel comprises pores having a diameter between about 20 and about 300 angstroms (e.g., about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 angstroms). A variety of mesoporous silica gels are commercially available or can be prepared via methods known in the art. For instance, the mesoporous silica gel can be a SBA type material, such as, but not limited to SBA-15. In some embodiments, the pores of the mesoporous silica gel can be hexagonal.

In some embodiments, one or more 1 ,2,4-triazole ligand can be attached (e.g., covalently) to a surface within a pore. One or more auxiliary ligands can also be attached on the surface of the pore, thereby making the pore multifunctional (e.g., bi-functional, tri-functional, etc.). Auxiliary ligands can include, for example, thiol, thioether, nitrile, aryl, substituted aryl, and carboxylic acid. The auxiliary groups can be added during synthesis of the microporous silica gel, for example, along with functional groups that can be (a) reacted to form a covalent bond or bonds with a triazole ligand or (b) reacted with other reagents to form a triazole group.

If desired, some or all of the free hydroxyl groups on the surface of a silica support (e.g., a mesoporous silica) can be capped with hydrophobic groups (e.g., reacted with an alkyl halide or acyl halide to provide an alkoxy- terminatated or ester-terminated silica), for example, to alter suface hydrophobicity .

II.B. Catalysts

The 1 ,2,4-triazole ligand is complexed with a metal compound to form a catalyst. In some embodiments, complexation of the triazole ligand with a metal compound can take place in a suitable polar or non-polar solvent at room temperature or with mild heating (e.g., at a temperature of less than about 85°C or less than about 45°C).

In some embodiments, the ligand and the metal compound complex are contacted to form a pre-catalyst that can be further contacted with an additional activator compound to provide the final, active catalyst complex. For instance, the presently disclosed oxidation catalysts can be prepared by first complexing a 1 ,2,4-triazole ligand with a suitable metal compound, and then reacting that initial complex with a peroxide (e.g., hydrogen peroxide, tert-butyl hydroperoxide) or other oxidant.

Thus, in some embodiments, the presently disclosed subject matter provides a catalyst comprising one or more transition metal ions and one or more 1 ,2,4-triazole ligand. In some embodiments, the transition metal ion is a copper, iron or manganese ion. In some embodiments, the complex comprises two metal ions and two 1 ,2,4-triazole ligands.

In some embodiments, the catalyst is a bis^-oxo) complex. However, other species for the catalyst are also possible, including, but not limited to, a μ-1 ,2-ρβΓθχο complex, a μ-η ² :η ² -ρβΓ0Χ0 complex, an end-on η ¹ superoxo complex, a side-on η ² superoxo complex, a side-on η ² peroxo complex, and a end-on n ¹ hydroperoxo complex.

More particularly, in some embodiments, the catalyst species can be a coordination complex of Formula (V):

(V)

wherein:

each M is a transition metal atom;

Ri5, Ri7, Ri8, and R ₂ o are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and

Ri ₆ and R19 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl substituted aralkyl and -CH(COOH)R ₂ i , wherein R ₂ i is alkyl, aryl, aralkyl, or an amino acid side chain; or

wherein one or more of R15, R16, R17, R18, R19, and R20 is a group of the structure -L-X, wherein L is a linker moiety and X is a solid support material.

In some embodiments, each M is a Period 4 transition metal atom. In some embodiments, each is selected from the group including, but not limited to, Fe, Cu, and Mn. In some embodiments each M is the same. Thus, in some embodiments, the catalyst is a di-copper, di-iron, or di- manganese catalyst. Depending upon M, the compound of Formula (V) can be charged (e.g., 2+). The compound of Formula (V) can be provided with one or more counter ions.

In some embodiments, the catalyst is a compound of Formula (V) formed from a 4-substituted-1 ,2,4-triazole. In some embodiments, Ri ₆ and R-I9 are selected from the group including, but not limited to, NH ₂ , aryl, substituted aryl, aralkyl, and substituted aralkyl. In some embodiments, R16 and 'Ri9 are phenyl, pyridyl, substituted phenyl, substituted pyridyl, benzyl, or substituted benzyl. The substitued phenyl can be o-nitrophenyl or another substituted phenyl comprising one or more electron-withdrawing groups. In some embodiments, the substituted phenyl is substituted by one or more electron-donating groups.

In some embodiments, one or more of R15-R20 is a heteroaryl or substituted heteroaryl group, such as a nitrogen-containing heteroaryl group. In some embodiments the heteroaryl or substituted heteroaryl group includes a 1 ,2,3-triazolyl group. The 1 ,2,3-triazolyl group can have the formula:

wherein R ₅ is selected from aryl, substituted aryl, aralkyi, and substituted aralkyi. In some embodiments, the R ₅ aralkyi or substituted aralkyi is based on a heteroaryl group. In some embodiments, the heteroaryl or substituted heteroaryl group includes another nitrogen-containing heteroaryl group.

In some embodiments, the catalyst comprises a polycyclic fused 1 ,2,4-triazole ligand. For example, the catalyst can be a bis^-oxo) complex comprising two quinoxolane groups of Formula (II) (or two fused Iigands of Formulas (III) or (IV)), described above. Such catalysts can have a structure of Formula (VI):

(VI)

wherein:

each L.4 is independently a direct bond or alkylene;

each M is a transition metal atom;

R22, R23, R25, and R26 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

each R24 and R27 are independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyi, and substituted aralkyi; or two R24 or two R27 groups are together alkylene; or

wherein one or more of R22, R23, R24, R25, R26, and R27 is -L-X, wherein L is a linker moiety and X is a solid support material. In some embodiments, each M is a Period 4 transition metal atom. In some embodiments, each M is selected from the group including, but not limited to, Fe, Cu, and Mn. In some embodiments, each M is the same transition metal atom. In some embodiments, the catalyst of Formula (VI) is a di-copper, di-iron or di-manganese catalyst. The structure of Formula (VI) can be charged depending upon the nature of M. In some embodiments, the catalyst of Formula (VI) can be provided with one or more associated counter ions.

In some embodiments, each L ₄ is a direct bond. In some embodiments, F 2, R23, R25, and R ₂ 6 are independently alkyl or aryl. In some embodiments, R ₂ 2, R23, R25 _> and R ₂ 6 are independently selected from the group consisting of methyl and phenyl. In some embodiments, each R ₂₄ and each R ₂₇ is H.

In some embodiments, one or both of the phenylene rings in the structure of Formula (VI) can include a nitrogen atom in place of one of the carbons of the phenylene ring backbone.

The presently disclosed subject matter provides heterogenous catalysts wherein the catalyst is immobilized on a solid support material. In some embodiments, at least one of the 1,2,4-triazole ligands of the catalyst of Formula (V) or Formula (VI) is immobilized on a solid support material. The triazole ligand can be immobilized either via ionic or covalent interactions. In some embodiments, the triazole is linked to the solid support material via covalent bonds through a linker moiety (e.g., an alkylene group). In some embodiments, the solid support is silica (e.g., a mesoporous or amorphous silica) or a resinous polyolefin, such as polystyrene.

In some embodiments, the catalyst has a TON of greater than about 100. In some embodiments, the catalyst has a TON of about 0 ₄ .

In some embodiments, the activated catalyst is generated from a pre- catalyst comprising a coordination complex of the transition metal ion and the 1 ,2,4-triazole ligand. Such pre-catalysts can be more stable then the active catalyst. Thus, in some embodiments, the active catalyst is generated in situ during the catalyzed reaction (i.e., when the pre-catalyst is in contact with the reaction substrate) or just prior (e.g., about 1 , 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 150, or 180 minutes prior) to being contacted with its substrate.

Accordingly, in some embodiments, the presently disclosed subject matter provides a pre-catalyst compound comprising a transition metal ion and a 1 ,2,4-triazole ligand. In some embodiments, the pre-catalyst comprises two transition metal ions and two 1 ,2,4-triazole ligands.

In some embodiments, the pre-catalyst is a compound of Formula

(Va):

wherein:

each M is a transition metal atom;

each of Xi , X ₂ , X3, and X4 is selected from the group comprising halo, hydroxy, alkoxy, aryloxy, acyloxy, and aralkyoxy;

Ri5, R-I7, R18, and R ₂ o are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and

R16 and R19 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, -NHC(=0)R ₂ i , and -CH(COOH)R ₂ i , wherein R ₂ i is alkyl, aryl, aralkyl, or an amino acid side chain; or

wherein one or more of R-| _5l R ₁₆ , R17, R-ie, R19, and R ₂₀ is a group of the structure -L-X, wherein L is a linker moiety and X is a solid support material.

In some embodiments, each M is a Period 4 transition metal atom. In some embodiments, each M is selected from the group including, but not limited to, Fe, Cu, and Mn. In some embodiments, each M is the same. In some embodiments, Xi, X ₂ , X ₃ , and X ₄ are each halo. In some embodiments, X-i, X ₂ , X ₃ , and X4 are each CI. In some embodiments, the pre-catalyst includes a 4-substituted-1,2,4- triazole. In some embodiments, Ri ₆ and F½ are selected from the group including, but not limited to, NH ₂ , aryl, substituted aryl, aralkyi, and substituted aralkyi. In some embodiments, F½ and R ₁₉ are phenyl, pyridyl, substituted phenyl, substituted pyridyl, benzyl, or substituted benzyl. The substitued phenyl, pyridyl, or benzyl can be substituted by one or more electron-withdrawing or electron-dontating groups.

In some embodiments, one or more of R15-R20 is a heteroaryl or substituted heteroaryl group. In some embodiments the heteroaryl or substitued heteroaryl group includes a 1 ,2,3-triazolyl group. The 1 ,2,3- triazolyl group can have the formula:

wherein R5 is selected from aryl, substituted aryl, aralkyi, and substituted aralkyi. In some embodiments, the R ₅ aralkyi or substituted aralkyi is based on a heteroaryl group. In some embodiments, the R5 heteroaryl or substituted heteroaryl group includes another nitrogen-contianing heteroaryl group (e.g., imidazoyl or pyridyl).

In some embodiments, the pre-catalyst is a compound of Formula

(Via):

(Via)

wherein:

each l_4 is independently a direct bond or alkylene;

each M is a transition metal atom; each of X ₅ , X ₆ , X ₇ , and X ₈ is selected from the group comprising halo, hydroxy, alkoxy, aryloxy, acyloxy, and aralkoxy;

f¾2, R23, Ι¾5, and R ₂ 6 are independently selected from the group comprising H, amino, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; and

each R ₂₄ and R ₂ are independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, and substituted aralkyl; or two R24 or two R ₂₇ groups are together alkylene; or

wherein one or more of R ₂₂ , R ₂ 3, R ₂ 4, R25, 26, and R27 is -L-X, wherein L is a linker moiety and X is a solid support material.

In some embodiments, each M is a Period 4 transition metal atom. In some embodiments, each M is selected from the group including, but not limited to, Fe, Cu, and Mn. In some embodiments, each M is the same transition metal atom. In some embodiments, the pre-catalyst of Formula (Via) is a di-copper, di-iron or di-manganese pre-catalyst. In some embodiments, each L ₄ is a direct bond. In some embodiments, R ₂₂ , R23, R25, and R ₂₆ are alkyl or phenyl. In some embodiments, R ₂₂ , R ₂₃ , R ₂₅ , and R ₂₆ are independently selected from the group comprising methyl and phenyl. In some embodiments, each R ₂₄ and each R ₂₇ is H. In some embodiments, X ₅ , X ₆ , X ₇ , and X ₈ are each halo. In some embodiments, X ₅ , Χβ, X7, and Xs are each CI.

In some embodiments, one or both of the phenylene rings in the structure of Formula (Via) can include a nitrogen atom in place of one of the carbons of the phenylene ring backbone.

In some embodiments, the pre-catalyst is immobilized on a solid support material. For example, the pre-catalyst can be covalenty or ionically attached to the solid support material via a substituent on one of the 1 ,2,4- triazole ligands. In some embodiments, the solid support material is polystyrene or silica (e.g., amorphous silica or a mesoporous silica). In some embodiments, the presently disclosed subject matter provides a pre- catalyst comprising mesoporous silica, wherein pores within the silica are bi- functionalized with a combination of a triazole-containing group that can act as a mono- or multi-dentate (e.g., bi-, tri-, or tetra-dentate) metal ion ligand and an auxiliary group selected from, for example, a thiol, a thioether, a carboxylic acid, an alkyi group, a substituted alkyi group, an aryl group, a substituted aryl group, an amine, a nitrile, or an azide. Free hydroxyl groups on the surface of the pores in the silica support can be capped, if desired. II. C. Methods of Synthesizing Catalysts

In some embodiments, the presently disclosed subject matter provides a method of synthesizing a catalyst comprising a 1 ,2,4-triazole ligand. In some embodiments, the method comprises:

providing a 1 ,2,4-triazole ligand;

contacting the 1 ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and

contacting the pre-catalyst with a peroxide in the presence of oxygen thereby forming the catalyst.

The 1 ,2,4-triazole ligand can be selected from the group including, but not limited to, mono-substituted 1 ,2,4-triazoles (e.g., 4-substituted 1,2,4- triazoles, 3-substituted 1 ,2,4-triazoles, or 1-substituted 1 ,2,4-triazoles), di- substituted triazoles (e.g., 3,5-disubstituted 1,2,4-triazoles or 3,4- disubstituted 1 ,2,4-triazoles), trisubstituted triazoles (e.g., 3-,4-,5- trisubstituted 1 ,2,4-triazoles), bis-1,2,4-triazoles, and solid-support linked 1,2,4-triazole ligands. In some embodiments, the 1 ,2,4-triazole ligand is a compound of one of Formulas (I), (II), (III), or (IV).

In some embodiments, the transition metal compound comprises a transition metal from Period 4 of the Periodic Table (e.g., Cr, Mn, Fe, Co, Ni, Cu, or Zn). In some embodiments, the transition metal compound comprises a transition metal ion selected from the group including, but not limited to, Cu (e.g., copper (I) or copper (II)), Fe (e.g., iron (II) or iron (III)), and Mn (e.g., manganese (II)). The transition metal compound can be a metal halide or a hydrate thereof. In some embodiments, the transition metal compound is selected from the group including, but not limited to, CuCI ₂ , Cu(NO ₃ ) ₂ , Cu(BF ₄ ) ₂ , Cu(OS0 ₂ CF ₃ )2, CuC0 _3l Cu(CI0 ₄ ) ₂ , Cu(MeCN) ₄ BF ₄ , FeCI ₂ , Fe(BF ₄ ) ₂ and hydrates thereof. The 1 ,2,4-triazole ligand can be contacted with the transition metal compound in a polar or non-polar solvent. In some embodiments, the solvent is a non-polar solvent, such as, but not limited to, an ether (e.g., diethyl ether, dimethoxymethane, diethylene glycol, dimethyl ether, tetrahydrofuran (THF), dioxane, diisopropyl ether, tert-butyl methyl ether). In some embodiments, the non-polar solvent is THF. In some embodiments, the solvent is a polar solvent, such as, but not limited to, an alcohol (e.g., methanol, ethanol, propanol, butanol, etc.), water, or acetonitrile.

The 1 ,2,4-triazole ligand can be dissolved in the solvent, and then the transition metal compound can be added and the mixture stirred for a period of time. The period of time can be from about 1 hour to about 8 hours (e.g., about 1 , 2, 3, 4, 5, 6, 7, or 8 hours). Generally, the contacting is performed at ambient or only slightly elevated temperatures. In some embodiments, the temperature is between about room temperature (i.e., about 20°C) and about 80°C. In some embodiments, the temperature is between about 40°C and about 60°C.

After the reaction is complete, the pre-catalyst can be isolated prior to use. For example, the pre-catalyst can be obtained as a solid and separated off by filtration. The crude product can be freed of the solvent or the solvents and subsequently purified by methods known to those skilled in the art and matched to the respective product, e.g. by recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography. In some embodiments, the pre-catalyst can be isolated and stored for a period of time prior to being transformed into the active catalyst compound.

In some embodiments, the solvent is removed and the pre-catalyst is dissolved in a solvent suitable for the formation of the active catalyst species and/or for the reaction being catalyzed. This solvent can be referred to as a "reaction solvent." In some embodiments, the reaction solvent is acetonitrile, water, or combinations thereof. The reaction solvent can also include acetone, tert-butanol, or one or more additional solvents that are not readily oxidized under the reaction conditions. For non-oxidative reactions, such as aziridination, the reaction solvent can be a non-polar solvent, including, but not limited to aromatic solvents such as benzene and toluene. In some embodiments, the active catalyst species is formed in the presence of the substrate for the reaction being catalyzed. Thus, the substrate can be added directly into a solution in which the catalyst has been formed or will be formed.

In some embodiments, the pre-catalyst can be formed in situ just prior to use, in a solvent suitable for the formation of the active catalyst or for the reaction being catalyzed or in a solvent that is miscible with another solvent that can form a solvent mixture suitable for the formation of the active catalyst or for the reaction being catalyzed. In such embodiments, the pre- catalyst is not isolated prior to use. Thus, in some embodiments, contacting the 1 ,2,4-triazole ligand with the transition metal compound and contacting the pre-catalyst with a peroxide are both performed in the same solvent, in miscible solvents, and/or without isolating (e.g., drying or purifying) the pre- catalyst. In some embodiments, the substrate is present during the contacting with the peroxide (e.g., the substrate can be added to a solution comprising the pre-catalyst prior to contacting the pre-catalyst with a peroxide). In some embodiments, contacting the 1 ,2,4-triazole ligand with the transition metal compound and contacting the pre-catalyst with a peroxide both take place in a reaction mixture comprising acetonitrile.

Any suitable number of molar equivalents of activator compound can be used to contact the pre-catalyst to form the active catalyst. Suitable activators include, but are not limited to, peroxides (e.g., hydrogen peroxide, perbenzoic acids, or tert-butyl hydroperoxide), sodium hypochlorite, potassium persulfate, molecular oxygen, and hypervalent iodine reagents. When a peroxide is used to form the active catalyst species, usually, at least about two molar equivalents of peroxide are contacted to the pre-catalyst. In some embodiments, between about two and about 20 molar equivalents of the peroxide is contacted to the pre-catalyst. In some embodiments, the peroxide is a hydroperoxide, such as hydrogen peroxide or tert-butyl peroxide. In some embodiments, the peroxide is added to a solution comprising the pre-catalyst over a period of time to minimize disproportionation of the peroxide. III. Methods of Use

III.A. Methods of Oxidizing Hydrocarbons

In some embodiments, the presently disclosed subject matter provides a method of oxidizing a hydrocarbon. More particularly, the presently diclosed triazole-based catalysts can be used in methods that involve the oxidation of alkyl and benzylic C-H bonds and of carbon-carbon double bonds. The oxidation reactions can be catalyzed under mild conditions and provide a variety of products, including alcohols (including diols), ketones, aldehydes, epoxides and carboxylic acids.

In some embodiments, the presently disclosed subject matter provides a method for oxidizing a hydrocarbon substrate to provide one or more oxidation products, the method comprising:

providing a 1 ,2,4-triazole ligand;

forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and

contacting a hydrocarbon substrate with the catalyst, thereby oxidizing the substrate to provide the one or more oxidation products.

The 1 ,2,4-triazole ligand can be selected from the group including, but not limited to, mono-substituted 1 ,2,4-triazoles (e.g., 4-substituted 1 ,2,4- triazoles, 3-substituted 1 ,2,4-triazoles, or 1-substituted 1,2,4-triazoles), di- substituted triazoles (e.g., 3,5-disubstituted 1 ,2,4-triazoles or 3,4- disubstituted 1 ,2,4-triazoles), trisubstituted triazoles (e.g., 1 ,2,4-triazoles substituted at the 3, 4, and 5 positions), bis-1 ,2,4-triazoles, and solid-support linked 1,2,4-triazole ligands.

In some embodiments, the 1 ,2,4-triazole ligand is a 4-substituted triazole ligand. The 4-substituted triazole ligand can be any compound comprising a 1 ,2,4-triazole ring wherein the nitrogen at the 4 position is bonded to the two carbons of the triazole ring and at least one other group other than hydrogen. For example, the subsitutent can be alkyl, aryl, aralkyl, amino, halo, hydroxy, alkoxy, aryloxy, or acyl.

In some embodiments, the method comprises providing a 1 ,2,4- triazole ligand of Formula (I):

wherein:

Ri and R3 are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

R ₂ is selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, substituted aralkyi, -NHC(=0)R ₄ and - CH(COOH)R ₄ , wherein R ₄ is alkyi, aryl, aralkyi, or an amino acid side chain; or

wherein one of Ri, R ₂ , and R ₃ is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material.

In some embodiments, the ligand of Formula (I) is a 4-substituted 1 ,2,4-triazole and R ₂ is a substitutuent selected from the group including, but not limited to, NH ₂ , aryl, substituted aryl, aralkyi and substituted aralkyi. In some embodiments, R ₂ is phenyl, pyridyl, substituted phenyl, or substituted pyridyl. The substituted phenyl or substituted pyridyl is a phenyl or pyridyl moiety substituted with one or more electron-withdrawing or electron- dontating aryl group substituents, such as, but not limited to, nitro (i.e., - N0 ₂ ), alkyi (methyl), hydroxy, halo (e.g., CI or F), carboxy (e.g., -COOH), or alkoxy (e.g., methoxy). In some embodiments, R ₂ is benzyl or substituted benzyl.

In some embodiments, the 1 ,2,4-triazole ligand is substituted by at least one heteroaryl substitutent. For example, in some embodiments, one or more of Ri, R ₂ , and R ₃ is 1 ,2,3-triazolyl or a substituted 1 ,2,3-triazolyl ligand. In some embodiments, the substituted 1 ,2,3-triazolyl group has the structure:

wherein R5 is selected from aryl, substituted aryl, aralkyi, and substituted aralkyi. In some embodiments, the aralkyi or substituted aralkyi is based on a heteroaryl group. In some embodiments, the R5 heteroaryl group is a nitrogen-containing heteroaryl group, including but not limited to, imidazole, benzimidazole, pyrazole, pyrazine, pyrimidine, pyridazine, pyridine, triazole, indole, and pyrrole.

In some embodiments, the 1 ,2,4-triazole ligand is a fused polycyclic group. In some embodiments, the fused polycyclic group can be a bis[1 ,2,4]triazolo[4,3-a:3'4'-c]quinoxaline. In some embodiments, the fused polycyclic group can be a structure of Formula (II):

wherein:

Li is a direct bond or alkylene;

R6 and R ₇ are independently selected from the group comprising H, amino, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; and

each R ₈ is independently selected from the group comprising H, halo, amino, nitro, cyano, carboxy, acyl, hydroxyl, alkyi, substituted alkyi, aryl, substituted aryl, aralkyi, and substituted aralkyi; or

wherein two Re groups together are alkylene; or

wherein one of R ₆ and R ₇ or one Re is -L-X, wherein L is a linker moiety and X is a solid support material or a group that can interact covalently or ionically with a solid support material. In some embodiments, the 1 ,2,4-triazole ligand is a compound of Formula (III) or Formula (IV).

In some embodiments, the 1 ,2,4-triazole ligand is selected from the

In some embodiments, providing the 1 ,2,4-triazole ligand further comprises attaching the ligand to a solid support material. For example, in some embodiments, the 1 ,2,4-triazole ligand includes a silyl ether substituent which can be condensed with silica gel or glass. In some embodiments, the 1 ,2,4-triazole ligand includes an aryl halide, an aryl alkyne, an amino, a carboxylic acid or a hydroxyl group that can be reacted with an azide, amino, carboxylic acid, or hydroxyl group-functionalized silica to form a covalent bond or bonds. In some embodiments the 1 ,2,4-triazole ligand is a solid support attached 1,2,4-triazole ligand having a structure

In some embodiments, contacting the catalyst with the substrate comprises contacting the catalyst with the substrate in the presence of one or more activator(s) or co-catalyst(s). In some embodiments, the catalyst is an active catalyst and is reacted with the substrate in the absence of any such activator. In some embodiments, forming the catalyst comprises contacting the ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and contacting the pre-catalyst with a peroxide in the presence of molecular oxygen.

The 1,2,4-triazole ligand can be contacted with the transition metal compound in a non-polar solvent, such as an ether (e.g., diethyl ether, dimethoxymethane, diethylene glycol, dimethyl ether, tetrahydrofuran (THF), dioxane, diisopropyl ether, tert-butyl methyl ether). The 1 ,2,4-triazole ligand can be dissolved in the non-polar solvent, and then the transition metal compound can be added and the mixture stirred for a period of time. The period of time can be from about 1 hour to about 8 hours (e.g., about 1 , 2, 3, 4, 5, 6, 7, or 8 hours). In some embodiments, the non-polar solvent is THF. Generally, the contacting is performed at ambient or only slightly elevated temperatures. In some embodiments, the temperature is between about room temperature (i.e., about 20°C) and about 60°C. In some embodiments, the temperature is about 40°C.

After the reaction is complete, the pre-catalyst can be obtained as solid and separated off by filtration. The crude product can be freed of the solvent or the solvents and is subsequently purified by methods known to those skilled in the art and matched to the respective product, e.g. by recrystallization, distillation, sublimation, zone melting, melt crystallization or chromatography. In some embodiments, the pre-catalyst can be isolated and stored for a period of time prior to being transformed into the active catalyst compound.

In some embodiments, the transition metal compound comprises a transition metal from Period 4 of the Periodic Chart. In some embodiments, the transition metal is selected from the group including, but not limited to, Cu, Fe, and Mn. In some embodiments, the transition metal compound comprises a transition metal ion selected from the group including, but not limited to, iron(ll), iron(lll), copper(l), copper(ll), and manganese(ll). The transition metal compound can be a metal halide or a hydrate thereof. In some embodiments, the transition metal compound is selected from the group comprising CuCI ₂ , Cu(NO ₃ ) ₂ , Cu(BF ₄ )2, Cu(OS0 ₂ CF ₃ )2, CuC0 ₃ , Cu(CIO ₄ ) ₂ , Cu( eCN) ₄ BF ₄ , FeCI ₂ , Fe(BF ₄ ) ₂ and hydrates thereof.

In some embodiments, the non-polar solvent is removed and the pre- catalyst is dissolved in a suitable solvent for the formation of the active catalyst species and/or for the reaction being catalyzed. In some embodiments, the solvent is acetonitrile, water, or combinations thereof. In some embodiments, the pre-catalyst is not isolated and the 1 ,2,4-triazole ligand and the transition metal compound are contacted in a solvent suitable for or miscible with the solvent required for formation of the active catalyst species and/or for the reaction being catalyzed. In some embodiments, the active catalyst species is formed in the presence of the hydrocarbon substrate.

In some embodiments, at least about two molar equivalents of peroxide is contacted to the pre-catalyst. In some embodiments, between about two and about 20 molar equivalents of the peroxide is contacted to the pre-catalyst. Any suitable peroxide can be used. In some embodiments, the peroxide is a hydroperoxide, such as hydrogen peroxide or tert-butyl peroxide. In some embodiments, the peroxide is added to a solution comprising the pre-catalyst over a period of time to minimize disproportionation of the peroxide. The hydrocarbon substrate and the catalyst can be contacted in any suitable solvent. In some embodiments, the hydrocarbon substrate can be contacted with the catalyst in water, acetonitrile, or mixtures thereof. The hydrocarbon substrate and the catalyst can be contacted at any suitable temperature. Generally, the temperature will be below about 60°C or below about 40°C. In some embodiments, contacting the hydrocarbon substrate with the catalyst is performed at a temperature of between about 0°C and about 25°C (e.g., about 0, 5, 10, 15, 20, or 25°C). In some embodiments, the temperature is about 20°C (i.e., about room temperature).

The hydrocarbon substate can be an olefin or an alkane. The alkanes that can be oxidized by the presently disclosed method include straight- chain, branched, cyclic, and substituted alkanes. The alkanes can be aryl- substituted alkanes (e.g., phenyl substituted alkanes). The aryl-substituted alkanes can include a benzylic C-H group. The olefin substrates can be straight-chain, branched, cyclic or substituted alkenes. In some embodiments, the hydrocarbon substrate is selected from the group including, but not limited to, methane, octane, cyclohexane, cyclooctane, cyclohexene, cyclooctene, styrene, methyl cinnamate, and 1 ,2- diphenylethene.

The oxidations products can include alcohols, diols, ketones, aldehydes, epoxides, carboxylic acids and mixtures thereof. Depending upon the structure of the hydrocarbon substrate, the oxidation product or products can be chiral.

In some embodiments, the triazole ligand is chosen so that the catalyst selectivly oxidizes the hydrocarbon substrate to provide more of one particular oxidation product than another or to provide only a single oxidation product from among several possible products. For instance, catalysts comprising 4-substituted 1 ,2,4-triazoles can be used to favor the formation of alcohol products, while catalysts comprising 3, 5-disubstituted-1 ,2,4-triazoles can be used to favor production of ketone products. In some embodiments, the catalyst ligand is chosen to control the chirality of the oxidation product or products (e.g., of the alcohol product or products). In some embodiments, greater than about 60% (greater than about 60, 65, 70, 75, 80, 85, 90, or 95%) of the hydrocarbon substrate is oxidized. In some embodiments, greater than about 80% of the hydrocarbon substrate is oxidized.

The amount of catalyst or pre-catalyst used can be varied depending upon the catalyst activity (e.g., TON or TOF). In some embodiments, about 5 mol% of the pre-catalyst is provided based on the amount of substrate, however, higher amounts (e.g., about 10 mol%, 15, mol% or 20 mol %) or lower amount (e.g., 1 , 2, 3, or 4 mol%) can be used.

III.A.i. Oxidation of Methane

In some embodiments, the presently disclosed triazole catalysts can be used to oxidize methane. Methane is a highly abundant, low-cost carbon source that can be used as a feedstock for energy sources. Methane is the major component of natural gas and can be produced from the anaerobic decay of biomatter. Selective oxidation of methane can provide methanol or ethanol that can be used as fuel, as well as other useful chemicals (i.e., formaldehyde, formic acid, acetic acid, and acetaldehyde). Prior to the present disclosure, methane oxidation reactions have typically required high temperature (e.g., > 200°C) and high pressure (e.g., > 5 atm.) However, the presently disclosed catalysts can oxidize methane under mild conditions and with great selectivity. In some embodiments, the presently disclosed catalysts can oxidize methane to methanol at room temperature.

Accordingly, in some embodiments, the hydrocarbon substrate of the presently disclosed oxidation methods is methane and the presently disclosed subject matter provides a method of oxidizing methane comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and contacting methane with the catalyst, thereby oxidizing methane to provide the one or more oxidation products. In some embodiments, forming the catalyst comprises contacting the 1 ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and contacting the pre-catalyst with a peroxide in the presence of oxygen thereby forming the catalyst. In some embodiments, the pre-catalyst is contacted with the peroxide in the presence of methane. In some embodiments, the pre-catalyst is contacted with the peroxide prior to being contacted with methane.

In some embodiments, the methane can be provided from natural gas. The natural gas can be from a commercial natural gas field (such as those associated with oil fields), from swamps or landfills, or from the decay of sewage or manure.

The contacting of the methane with the catalyst can occur under ambient conditions. Thus, the methane can be provided to the catalyst at about 1 atm of pressure. The contacting can be performed in water, organic solvents (e.g., acetonitrile), or mixtures thereof.

In some embodiments, contacting the methane with the catalyst selectively oxidizes the methane to one of the group including, but not limited to, methanol, formaldehyde, acetaldehyde, and acetic acid. The selectivity can be varied depending upon the structure of the 1 ,2,4-triazole ligand provided and/or the nature of the solvent used. For instance, in some embodiments, the 1 ,2,4-triazole ligand provided is a ligand of Formula (I):

(I)

wherein R ₂ is selected from aryl and substituted aryl; and contacting methane with the catalyst selectively oxidizes the methane to formaldehyde. In some embodiments, the 1,2,4-triazole ligand provided is a ligand of Formula (I) wherein F½ is selected from aralkyl and substituted aralkyl; and contacting methane with the catalyst selectively oxidizes the methane to acetaldehyde.

In some embodiments, the 1 ,2,4-triazole ligand provided is a fused bis-1 ,2,4-triazole ligand of Formula (II):

and contacting methane with the catalyst selectively oxidizes the methane to methanol. In some embodiments, the 1 ,2,4-triazole ligand is a fused bis- 1 ,2,4-triazole ligand of Formula (III) or Formula (IV). In some embodiments, contacting methane with the catalyst is performed in water.

The use of heterogenous catalysts can lead to the selective oxidation of methane to C2 oxidation products. See Figure 10. In some embodiments, the catalyst is immobilized on a solid support material and contacting methane with the catalyst selectively oxidizes the methane to acetic acid or acetaldehyde.

III.A.ii. Oxidation of Alkenes

In some embodiments, the presently diclosed subject matter provides a method of oxidizing alkenes, wherein the method comprises: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and contacting an alkene with the catalyst, thereby oxidizing the substrate to provide the one or more oxidation products, such as, but not limited to, diols and epoxides.

In some embodiments, forming the catalyst comprises contacting the 1 ,2,4-triazole ligand with a transition metal compound to form a pre-catalyst; and contacting the pre-catalyst with a peroxide in the presence of oxygen thereby forming the catalyst. In some embodiments, the pre-catalyst is contacted with the peroxide (or other activator) in the presence of the alkene. In some embodiments, the pre-catalyst is contacted with the peroxide (or other activator) prior to being contacted with the alkene.

In some embodiments, the catalyst selectively oxidizes the alkene to form a cis-diol. In some embodiments, the catalyst selectively catalyzes the asymmetric epoxidation of an alkene. In some embodiments, the alkene is selected from the group including, but not limited to, cyclohexene, cyclooctene, styrene, methylcinnamate, and 1 ,2-diphenylethene.

III.B. Other Transformations of Alkenes

In addition to catalyzing the oxidation of alkenes to provide cis-diols or epoxides, the presently disclosed catalysts can also be used to catalyze additional alkene transformations. For example, the presently disclosed catalysts with nitrogen sources to effect the transformation of alkenes to aminoalcohols or aziridines. Suitable nitrogen sources include nitrene sources, such as, but not limited to chloramine-T; bromamine-T; organic azides of the formula RN ₃ (for example, where R is aryl or heteroaryl); and iodinane reagents, such as PhlNTs (i.e., [N-(p- toluenesulfonyl)imino]phenyliodinane).

In some embodiments, the presently disclosed subject matter provides a method of producing an aziridine, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4- triazole ligand and a transition metal ion; and contacting an alkene with the catalyst and a nitrogen source, thereby producing an aziridine. In some embodiments, the transition metal ion is selected from the group including, but not limited to, copper, iron, cobalt, and nickel. In some embodiments, the nitrogen source is an organic azide or an iodinane.

In some embodiments, the presently disclosed subject matter provides a method of producing an aminoalcohol, the method comprising: providing a 1 ,2,4-triazole ligand; forming a catalyst comprising the 1 ,2,4- triazole ligand and a transition metal ion, and contacting an alkene with the catalyst and a nitrogen source, thereby producing an aminoalcohol. In some embodiments, the alkene is styrene or trans-stilbene. In some embodiments, the nitrogen source is chloramine-T. In some embodiments, the transition metal ion is copper.

III.C. Degradation of Cellulosic Substrates

Cellulosic biomass from plant sources can provide an alternative fuel feedstock to both oil and natural gas. Efforts to degrade cellulosic materials, particularly lignocellulosic materials, to fermentable sugars (e.g., glucose) often involve the use of harsh chemical or mechanical pretreatment steps (e.g., pretreatment with acids or alkali at elevated temperatures) and/or digestion with large amounts of enzymes or microbes. Due to the number of steps, the specialized equipment that can be involved, and/or the costs associated with the enzymes or microbes, the degradation of cellulosic materials and fermentation of the resulting sugars is generally not cost- effective as compared to the the production of gasoline from oil, for example.

As shown in Figure 11, the presently disclosed catalysts can degrade cellulosic materials under mild conditions to provide more easily manipulate- able small molecules, such as, but not limited to, cellobiose and hydroxymethylfurfural. In some embodiments, the presently disclosed catalysts can be used to degrade lignocellulosic materials, wherein the degradation includes degrading or removing lignin from the material. Removal of lignin can allow for the remaining cellulose from the lignocellulosic material to be degraded more easily into fermentable and other small molecules.

Accordingly, in some embodiments, the presently disclosed subject matter provides a method of degrading a cellulosic substrate, the method comprising:

providing a cellulosic substrate;

providing a 1 ,2,4-triazole ligand;

forming a catalyst comprising the 1 ,2,4-triazole ligand and a transition metal ion; and

contacting the cellulosic substrate with the catalyst, thereby degrading the substrate to form one or more degradation products.

In some embodiments, the transition metal ion is an iron ion. Thus, in some embodiments, forming a catalyst comprises contacting the 1 ,2,4- triazole ligand with a iron compound, such as, but not limited to FeCI ₃ . In some embodiments, the cellulosic substrate is contacted with a catalyst that is a pre-catalyst of Formula (Va) or (Via) and about 10 equivalents of peroxide. In some embodiments, the substrate is contacted with the catalysts in an oxygen atmosphere (e.g., under 1 atm of oxygen). In some embodiments, the cellulosic substrate is contacted with the catalyst in the presence of one or more additional metal salts or redox mediators (e.g., NAD). In some embodiments, the cellulosic substrate is contacted with the catalyst in water, acetonitrile, or a mixture thereof. In some embodiments, the cellulosic substrate is contacted with the catalyst at room temperature. In some embodiments, the cellulosic substrate is contacted with the catalyst at a slightly elevated temperature (e.g., about 60, 50, 40, or 30 °C). In some embodiments, one of the one or more degradation products is cellobiose or hyd roxymethylf u rf u ral .

In some embodiments, the cellulosic substrate is a lignocellulosic substrate. In some embodiments, the cellulosic substrate is provided from a plant source, such as, the leaves, stalks, or other parts of an agricultural crop, such as corn, rice, wheat, barley, alfalfa, oats, sunflowers, sugar cane, hemp, and the like. The cellulosic substrate can also be provided from forestry residues, papermaking residues, municipal/residential wastes, or from various grasses (e.g., sudangrass) or grass clippings.

EXAMPLES

The following Examples have been included to illustrate modes of the presently disclosed subject matter. In light of the present disclosure and the general level of skill in the art, those of skill can appreciate that the following Examples are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter.

Examples 1 - 12 relate to methods of the presently disclosed subject matter for the synthesis of catalysts comprising ,2,4-triazole ligands, their characterization, and their use in catalyzing the oxidation of hydrocarbons and other reactions.

Example 1

Synthesis of 1 ,2,4-Triazole Catalysts

1 ,2,4-Triazole ligands A-F, shown in Scheme 4, were synthesized via methods such as those described hereinabove (see, e.g., Scheme 3). Catalysts containing ligands A-F were prepared by reacting the desired ligand with a metal-containing compound in a non-polar, aprotic solvent to form a pre-catalyst comprising two 1 ,2,4-triazole ligands and two metal atoms. The precatalyst was then reacted with two equivalents of a peroxide (e.g., hydrogen peroxide or tert-butyl peroxide) in a polar, aprotic solvent to rovide the active catalyst.

E F

Scheme 4. Exemplary 1 ,2,4-Triazole Ligands.

For example, as shown in Scheme 5, ligand A, B, C, or D was contacted with CuCI ₂ .H ₂ 0 in THF at 40 °C for between 2 to 8 hours to provide a di-copper precatalyst. Catalysts comprising ligands E and F were synthesized analogously.

The structure of the precatalyst was confirmed by electrospray ionization mass spectroscopy (ESI-MS). ESI-MS data suggests that copper (II) complexes coordinate two monodentate ligands per center and copper (I) complexes coordinate three monodentate ligands, as do iron (II) complexes. MS data on complexes bearing bidentate ligands shows that the ligand binds the metal 1 :1. The precatalyst comprising ligand B was also studied by X- band EPR in acetonitrile at room temperature. The spectrum suggests that in solution a tetragonal structure is formed. When H ₂ 0 ₂ is added to the EPR sample, a species that is EPR-silent results, suggesting that the copper (II) complex is oxidized to copper (III).

pre-catalyst

Scheme 5. Synthesis of Catalyst

Formation of the catalyst was followed by UV-Vis spectroscopy. The precatalyst was dissolved in acetonitrile. Two equivalents of H ₂ O ₂ was added, resulting in the immediate formation of a new band at 391-416 nm (ε ~ 1200 L mol ^"1 cm ^"1 ) depending upon the ligand. This transition is characteristic of a ligand-to-metal charge transfer (LMCT) band corresponding to an oxo-bridged species. See Cramer and Tolman, Accounts of Chemical Research, 40, 601-608 (2007); Aboelella et al., J. Am. Chem. Soc, 126, 16896-16911 (2004); and Teramae et al., J. Inorganic Biochem., 98, 746-757 (2004). The 391-416 nm LMCT band was long-lived (e.g., over 30 minutes) and under anaerobic conditions did not form. Instead, a blue-shifted LMCT band at 329-378 nm (ε ~ 400 L mol ^"1 cm ^"1 ) consistent with an r| ¹ -hydroperoxo species appeared. See Cramer and Tolman. Accounts of Chemical Research, 40, 601-608 (2007). Without being bound to any one theory, it is believed that the peroxide serves a role as a promoter to a reactive intermediate that can activate O ₂ to form a bis^- oxo) complex. The lifetime of the presently disclosed catalysts is unique, as bis^-oxo) complexes generally are stable only at low temperatures. See Aboelella et al, J. Am. Chem. Soc, 126, 16896-16911 (2004); and Teramae et al.. J. Inorganic Biochem., 98, 746-757 (2004). The addition of cyclohexene to a solution containing a catalyst and H ₂ O ₂ results in rapid bleaching of the LMCT band, suggesting that an oxygen originating from H ₂ O ₂ is involved in the oxidation.

Example 2

Oxidation of Cyclohexane

Initial screening of catalyst activity was performed using cyclohexane as a substrate. Copper pre-catalysts were prepared as described hereinabove in Example 1 using ligands C and D from Scheme 4 above, and ligands G- shown in Scheme 6, below. More specifically, 1 μηηοΙ of copper pre-catalyst was dissolved in 250 μΙ_ of acetonitrile followed by addition of H ₂ O ₂ and then cyclohexane. The oxidation reactions were allowed to proceed for 1 hour and then quenched with triphenylphosphine (PPh ₃ ). Following quenching, yields of cyclohexanol and cyclohexanone were determined by gas chromatography-mass spectroscopy (GC-MS). Data for the oxidation of cyclohexane is provided in Table 1. Total yield (i.e., "Total" in Table 1) represents all oxidation products, while TON is the turnover number defined as the ratio of moles of oxidized products to moles of catalyst.

G H I J

Scheme 6. Further Exemplary 1 ,2,4-Triazole Ligands.

Very high turnover numbers were observed for this set of catalysts. The most efficient copper catalysts for cyclohexane oxidation in the literature have conversions of 30% or less and require much higher oxidant loadings. See Kirillov et al.. Angewandte Chemie-lnternational Edition, 44, 4345-4349 (2005). In the study described by Kirillov et al., using the presently described definition of turnover number, the observed values are roughly two levels of magnitude lower than those for the presently disclosed catalysts. The present results further suggest that simple tuning of ligand substituents can provide selectivity for the degree of oxidation.

Table 1. Catalytic Oxidation of Cyclohexane.

Catalyst Yield [%]

Ligand n(catalyst) cyclohexanol cyclohexanone Total TON

G 2000 76.2 21.1 98.9 989

G 4000 74.6 21.1 99.4 994

G 6000 59.8 36.3 99.5 995

G 1000 34.2 13.3 47.8 478

H 2000 13.3 53.3 70.1 701

I 2000 55.1 35.6 91.3 913

-8^ J 2000 62.7 10.4 74.5 745

D 2000 28.7 61.6 90.8 908

C 2000 34.1 12.8 46.9 469

K 2000 23.4 60.7 87.8 878

L 2000 48.3 50.8 99.1 991

M 2000 48.9 41.1 90.6 906

Example 3

Oxidation of Octane

Catalyst activity was further assessed using octane as a substrate. Analogous to the reactions described in Example 2 for cyclohexane, 1 μηηοΙ of precatalyst was dissolved in 250 μΐ_ of acetonitrile followed by addition of H ₂ O ₂ and then octane. The oxidation reactions were allowed to proceed for 1 hour and then quenched by ΡΡΙ¾. Yields of octanols and octanones were determined by GC-MS. Data for the catalytic oxidation of octane with the presently disclosed catalysts is provided in Table 2. Total yield (i.e., "Total" in Table 2) represents all oxidation products, while TON is the turnover number defined as the ratio of moles of oxidized products to moles of catalyst. As indicated by the data in Table 2, the presently disclosed catalysts had high catalyst activity toward the oxidation of straight-chain alkanes.

Table 2. Catalytic Oxidation of Octane.

Example 4

Oxidation of Alkenes

Catalyst activity was assessed using various alkenes as the substrate and the dicopper precatalyst formed as described in Example 1 using ligand G from Scheme 6. Precatalyst was dissolved in acetonitrile in an amount to provide 10 mol % of catalyst. Hydrogen peroxide was added as a 10% solution in acetonitrile over a period of 30 minutes to minimize disproportionation of the peroxide. As described in Table 3, depending on the substrate, 30-91% of the hydrogen peroxide was converted into alkene oxidation products. Generally, reactions of this type occur only with high- oxidation state metal dioxo metal complexes and non-heme based iron catalysts. For the particular catalyst used in this study, more highly strained alkenes preferentially formed cis-diol products. The selectivity of diol/epoxide formation for cyclohexene and cylooctene was comparable to non-heme iron complexes previously described in the art. See Oldenburg et al., J. Am. Chem. Soc, 127, 15672-15673 (2005).

Table 3. Catalytic Oxidation of Olefins

Example 5

Homogeneous Phase Oxidation of Methane

Room temperature catalysis of the oxidation of methane was performed using the triazole-containing catalysts prepared in Example 1. Reactions were conducted under a balloon of CH ₄ with a catalyst concentration of 0.05 M. Hydrogen peroxide (20 equivalents based on catalyst) was incrementally added with CH ₄ gas.

Results are provided in Table 4. Ligand pD refers to the 4-phenyl- substituted version of ligand D. Selectivity of the various catalysts was determined by GC-MS analysis of the products. The % yields were determined after 1 hour of reaction by calibration of the GC-MS chromatographs with an internal standard and are based on the CH ₄ added. TON was the total TON defined as the ratio of moles of oxidation products to moles of catalyst.

As indicated in Table 4, catalysts comprising the quinoxaline ligands

E and F from Scheme 4 appear to mimic the activity of pMMO, having excellent selectivity for oxidizing methane to methanol. Methane oxidation catalyzed by these catalysts proceeded in high yield and with moderate TONs (~10 ² ). Catalysts comprising 4(aryl)-substituted 1 ,2,4- triazoles gave Ci oxidation products as well, but were selective for formaldehyde formation; whereas catalysts having 4-(benzyl)-substituted 1 ,2,4-triazole ligands gave C ₂ oxidation products. Reactions were conducted in water to exclude all carbon sources other than CH ₄ . While it is not desired to be bound by a particular mechanism/theory of operation, the data suggests that this ligand environment significantly alters the coordination sphere of the oxidizing species to favor oxidative condensation of CH ₄ and a Ci oxidation product. Confirmation of product distributions was accomplished by both GC-MS and 1 ³ C NMR spectroscopy. No attempts were made to quantify formation of CO or CO ₂ .

Table 4. Homogeneous Phase Catalysis of the Oxidation of Methane. ³

a catalysts are the di-copper catalysts comprising two of ligands A, B, C, D, E, or F from Scheme 4, or pD as indicated in the left-hand column. * indicates that the catalyst was prepared using Cu(MeCN) ₄ BF ₄ as the metal source. Example 6

In Situ Catalyst Generation and Screening

The effects of isolating the precatalyst prior to use was studied by generating catalysts in situ and comparing the catalytic effects of the in situ generated catalysts in cycloalkane oxidation reactions compared to the catalytic effects of catalysts isolated prior to use. The in situ generation involved assembling the catalyst starting materials (i.e., 1 ,2,4-triazole ligand and metal salt), allowing complexation to occur, and then proceeding with oxidation chemistry.

More specifically, in situ generation of copper and iron-based catalysts was performed using Cu(N0 ₃ ) ₂ -2.5H ₂ 0, Cu(OTf) ₂ or [Fe(H ₂ 0) ₆ ][BF ₄ ] ₂ as metal ion sources. A 0.2 M solution of Cu(NO ₃ ) ₂ -2.5H ₂ 0 or Cu(OTf) ₂ in acetonitrile and a 0.2 M solution of [Fe(H ₂ 0) ₆ ][BF ₄ ] ₂ in acetonitrile/water (6:1) were prepared for use as described below.

In a reaction vessel, either 83 prnol of the desired triazole ligand (for use in preparing copper catalyts) or 125 pmol of the desired triazole ligand (for use in preparing iron catalysts) was added. To this 250 pl_ (50 pmol) of the metal solution was added. The reaction mixtures were heated to 60 °C for 2 hours and allowed to cool to room temperature. Upon cooling, a solid precipitate had formed in most instances. A 5 μΐ_ aliquot was taken from the solution for analysis by mass spectrometry. The mass spectral data observed for the solids associated with the in situ formation of copper and iron precatalysts using a molar excess of 4-benzyl-1 ,2,4-triazole (ligand B from Scheme 4) as the 1 ,2,4-triazole was determined. For the reaction of the ligand with Cu(N0 ₃ ) ₂ ' 2.5 H ₂ 0 in acetonitrile, the following fragments were observed: [CuL ₂ ] ²⁺ (observed mass of 190.6), [CuL ₂ (MeCN)] ²⁺ (observed mass of 21 1.1), and [CuL(MeCN) (observed mass of 263.1). For the reaction of the ligand with FeCI ₂ ^■ 4 H ₂ 0 in acetonitrile, the following fragments were observed: [FeL ₂ ] ²⁺ (observed mass of 187.1), [FeL ₃ ] ²⁺ (observed mass 266.7), [FeL ₃ (MeCN)] ²⁺ (observed mass of 287.0), and [FeL ₃ (MeCN) ₂ ] ⁺ (observed mass of 615.3). To the reaction mixture was then added 1 mmol of substrate (cyclohexane (CyH) or cyclooctane (CyO)) that was diluted by a factor of two into feri-butyl alcohol to facilitate dissolution into the reaction medium. 5 mmol of 30% w/w solution of H ₂ O ₂ was then added in 5 increments over a period of 15 minutes. During the addition of H ₂ O ₂ , the reaction mixture homogenized and effervescence was observed. After a period of 1 hour, a 50 μΐ_ aliquot was extracted from the reaction mixture, diluted into 1 mL of diethyl ether, passed through a short plug of basic alumina, and analyzed by GC-MS.

The results of oxidations catalyzed by the in situ generated catalysts are shown in Table 5. In Table 5, the ligands used are identified using the codes provided in Figures 2 and 3. The metal salts are identified by the abbreviations provided in Table 6, below. Table 5. In S/fw-Generated Catalyst Screening.

% %

Liqand Metal Substrate Ketone Conversi

4-N MC4 CyO 29.96 38.53

4-N MC4 CyH 18.44 18.444

4-0 MC4 CyO 24.01 32.88

4-0 MC4 CyH 30.55 30.55

4-R MC4 CyO 28.16 38.16

4-R MC4 CyH 29.57 29.57

4-T MC2 CyO 38.63 44.57

4-T MC2 CyH 41.62 41.62

4-T MF2 CyO 29.31 33.47

4-T MF2 CyH 43.87 43.87

4-AB MC2 CyO 20.43 24.37

4-AB MC2 CyH 0 0

4-AB MC4 CyO 26.41 36.36

4-AB MC4 CyH 8.29 10.03

35-B MC2 CyO 1.68 16.91

35-B MC2 CyH 13.52 13.52

35-B MF2 CyO 17.81 19.11

35-B MF2 CyH 20.03 20.03 Table 6. Metal Salts.

Abbreviation Formula

MC1 CuCI ₂ -2H ₂ O

MC2 Cu(NO ₃ ) ₂ -2.5H ₂ O

MC3 Cu(BF ₄ ) ₂ -6H ₂ O

MC4 CuOTf ₂

MC5 CuCO ₃

MC6 Cu(CIO ₄ ) ₂ -6H ₂ O

MF1 FeCI ₂ -4H ₂ O

MF2 Fe(BF ₄ ) ₂ 6H ₂ O

For comparison, the oxidation reactions were also perfomed using isolated catalysts. Cycloalkane oxidation results using the isolated catalysts are provided in Table 7, below. The codes used to indicate the ligands in Table 7 correspond to those in Figures 2-5 and 7. Oxidation conditions were the same as those used with the in situ generated catalysts with the exception that one of the reactions using the catalyst formed from the ligand denoted by code 4-0 (i.e., 4-(2-hydroxyphenyl)-1 ,2,4-triazole) was allowed to proceed from 12 hours, as indicated in the notes in the right-hand column of Table 7

Table 7. Cycloalkane Oxidation using Isolated Catalysts.

% %

Ligand Metal Substrate Ketone Conversion Notes

4-A MC2 CyO 34.14 37.36

4-A MC2 CyH 43.99 43.99

4-D MC2 CyO 22.94 27.44

4-D MC2 CyH 18.93 21.43

4-D MC4 CyO 26.85 34.96

4-D MC4 CyH 15.85 15.85

4-E MC4 CyO 32.52 41.49

4-G MC2 CyO 40.17 49.39

4-G MC2 CyH 38.57 38.57

4-G MC4 CyO 38.91 48.71

4-G MC4 CyH 47.98 47.98

4-M MC2 CyO 31.05 42.77

4-M MC2 CyH 13.99 13.99

4-M MC4 CyO 44.71 66.55

4-M MC4 CyH 19.98 19.98

4-N MC2 CyO 24.33 34.41

4-N MC2 CyH 13.53 13.53

4-O MC2 CyO 34.67 49.55 4-0 MC2 CyH 17.74 17.74

4-0 MF1 CyO 24.31 27.73

4-0 MF1 CyO 35.03 66.38

4-P MC2 CyO 27.06 33.72

4-P MC2 CyH 17.42 17.42

4-P MC4 CyO 31.85 34.95

4-P MC4 CyH 24 30.3

4-Q MC2 CyO 22.81 26.03

4-Q MC2 CyH 16.14 16.41

4-Q MC4 CyO 26.88 41.51

4-R MC2 CyO 35.36 40.48

4-R MC2 CyH 38.61 38.61

4-R MC4 CyO 28.82 33.05

4-R MC4 CyH 29.77 29.77

4-S C2 CyO 17.51 19.2

4-S MC4 CyO 14.99 20.9

4-T MC2 CyO 29.07 34.63

4-T MC2 CyH 29.97 29.97

4-T MC4 CyO 31.56 42.42

4-T MC4 CyH 26.67 32.42

3T-A MC1 CyO 16.4 23.9

3T-A MC2 CyO 14.74 25.25

3T-B MC1 CyO 13.03 16.16

3T-C MC1 CyO 14.29 18.93

3T-D MC1 CyO 2.27 2.27

3T-E MC1 CyO 1.83 1.83

3L-A MC2 CyO 5.11 7.72

3L-B MF2 CyO 10.37 12.68

35-C MC4 CyO 21.07 31.74

35-C MC4 CyH 7.99 7.99

35-H MC2 CyO 36.02 71.91

35-H MC2 CyH 30.24 30.24

FB-A MC2 CyO 4.21 4.21

FB-A MC2 CyH 2.02 2.02

FB-A MC4 CyO 8.68 8.68

FB-A MC4 CyH 6.91 6.91

The results of the in situ screening study indicated that omitting the step of isolating the pre-catalyst did not greatly decrease catalytic activity. Only minor decreases in catalytic activity were observed. Without being bound to any one theory, these minor decreases in catalytic activity are attributed to the complexation reation of the ligand and metal salt not proceeding entirely to completion.

Example 7

Heterogenous Phase Catalyst Synthesis

Heterogenous catalysis offers several advantages of green chemistry: lower catalyst loadings, ease of separation of products from the catalytic species, inert reaction media, and, in most cases, the catalysts are more easily regenerated.

Support Activation and Pretreatment

Silica-supported catalysts of the presently disclosed subject matter were synthesized by first activating silica gel (C18 silica gel, Premium Rf, 40- 75 μητι, 60A from Sorbent Technologies, Inc., Atlanta, Georgia, United States of America). Silica gel activation and pretreatment was carried out according to previously described protocols: for Protocol A see Inorganica Chimica Acta, 360, 1083-1094 (2007); for Protocol B see Synthesis, 11 , 1635-1642 (2007).

Protocol A: 10g of silica gel was refluxed with 100 mL of 1.2 N HCI for 23 hours. The suspension was then allowed to cool to room temperature and then filtered. The filtered silica gel was washed with de-ionized water until neutral pH was achieved. The silica gel was then washed successively with methanol (30 mL), acetone (15 mL), dichloromethane (15 mL), toluene (15 mL), methanol (15 mL) and diethyl ether (30 mL) and was then air dried overnight. The dry silica gel was spread on a petri dish and further dried in oven at 160 °C for 24 hours. Finally, the silica gel was dried under vacuum overnight.

Protocol B: 10g of silica gel was suspended in 80 mL cone. H ₂ SO ₄ and 15 mL cone. HN0 ₃ . The mixture was then heated at 110 °C for 49.5 hours. The suspension was then allowed to cool to room temperature and then filtered. The filtered silica gel was washed with de-ionized water until neutral pH was achieved. The silica gel was then washed successively with methanol (20 mL), acetone (20 mL), dichloromethane (20 mL), toluene (20 mL), methanol (20 mL) and diethyl ether (20 mL). Silica gel was then air dried for 1 hour, followed by oven drying at 160 °C for 12 hours. The silica was then dried again under vacuum overnight.

Immobilization of Amines on Activated Silica Gel:

Immobilization of 3-Aminopropyltriethoxysilane Derivatives on Activated Silica Gel:

Activated Silica Gel i NH ₂

Scheme 7. Immobilization of 3-Aminopropyltriethoxysilane on Activated Silica Gel.

3-aminopropyltriethoxysilane (1 mmol) was added to a suspension of 1g of activated silica in toluene (10 mL). The reaction mixture was heated overnight at 90 °C and then allowed to cool to room temperature. The mixture was then filtered and the silica washed successively with 30 mL each of methanol, de-ionized water, methanol, dichloromethane, acetone and diethyl ether. The silica was then dried overnight under vacuum. The Kaiser test (i.e., ninhydrin staining) provided dark blue beads, confirming the presence of a free amine.

Immobilization of 3-(2-Aminoethylamine)propyltriethoxysilane on activated silica gel:

Activated Silica Gel

Toluene, 90 °C, Overnight ? ⁰

Scheme 8. Immobilization of 3-(2-Aminoethylamine)propyltriethoxysilane on Activated Silica Gel.

3-(2-Aminoethylamine)propyltriethoxysilane was added to a suspension of 1g silica in toluene (10 mL). The reaction mixture was heated overnight at 90 °C and allowed to cool to room temperature. The mixture was then filtered and silica washed successively with 30 mL each of methanol, de-ionized water, methanol, dichloromethane, acetone and diethyl ether. Silica was then dried overnight under vacuum. The Kaiser test provided dark blue beads, confirming the presence of a free amine. General Procedure for Triazole Formation on Silica Gel:

From Amines:

25 Hrs

Scheme 9. Triazole Formation on Silica Gel from Immobilized Amine.

3-Aminopropyl triethoxy silane immobilized on silica (0.7 mmol) and diazine reagent (1.4 mmol) were added to a 2:1 :1 mixture of toluene, n- butanol and acetic acid. The reaction mixture was heated at 70 °C for 25 hours. The reaction mixture was then cooled to room temperature and filtered. The solid compound was washed successively with methanol (40 mL), dichloromethane (40 mL), methanol (20 mL) and diethyl ether (20 mL). The silica was then air dried.

From Hydrazides:

Scheme 10. Triazole Formation on Silica Gel from Immobilized Hydrazide.

Silica immobilized hydrazide (1 eq.) was added to a solution of dimethyl formamide dimethyl acetal (1 eq.) and acetic acid (1 eq.) in acetonitrile. The reaction mixture was heated at 50 °C for 1 hour. Amine (1.1 eq.) was added and the reaction mixture was heated at 120 °C for additional 7 hours. The reaction mixture was then cooled to room temperature and filtered. The solid compound was washed successively with methanol (40 mL), dichloromethane (40 mL), methanol (20 mL) and diethyl ether (20 mL). Silica was then air dried. General Procedure for Complexation of Silica Immobilized Ligands with Metal:

Scheme 11. Complexation of Metal with Immobilized Ligand.

Silica immobilized triazole (1 eq) and metal (1.1 eq) were mixed together in tetrahydrofuran. The reaction mixture was heated at 75 °C for 2 hours. The reaction mixture was filtered and filtered silica was washed successively with methanol, acetone and diethyl ether. A color change depending on the metal used was observed.

General Procedure for Coupling Modified Amino Acids to Amino Propane Triethoxysilanes Immobilized on Silica

Scheme 12. Coupling Modified Amino Acid to Silica.

Modified amino acids were coupled to amino propane triethoxysilanes immobilized on silica using standard HOBT/HBTU coupling conditions. Modified amino acid (0.2 mmol) was dissolved in N-methyl pyrrolidine (2 ml_) and HOBT (0.3 mmol), HBTU (0.9 mmol) and DIEA (2.8 mmol) were added.

The reaction mixture was sonicated for 15 minutes until complete dissolution was observed. This solution was added to silica. This suspension was shaken for 6 hours. The reaction mixture was filtered and filtered silica was washed successively with methanol, dimethylformamide, dichloromethane, acetone and diethyl ether. The Kaiser test gave yellow beads indicating the absence of primary amine. General Procedure for Making Hydrazides on Silica Support: Scheme 13. Preparation of Hydrazide on Solid Support.

Silica immobilized modified amino acid (1 eq.) was added to a solution of hydrazine monohydrate (2.5 eq.) in methanol. The reaction mixture was heated at 70 °C for 12 hours and then cooled to room temperature and filtered. The solid compound was washed successively with methanol (40 ml_), dichloromethane (40mL), methanol (20 mL) and diethyl ether (20mL). The silica was then air dried.

Ligand Loading Assay:

Ligand loading of ligands with fluorenylmethyloxycarbonyl (Fmoc)- protected precursors was determined via an Fmoc assay as previously described. See Letters in Peptide Science, 9, 203-206, 2002. The solution of dibenzofulvene resulting from cleavage of the Fmoc protecting group by DBU was analyzed using UV-Vis spectroscopy. Theoretical ligand loading can also be calculated based upon the number of moles of amine used to functionalize the support surface.

Catalyst Formation:

Catalysts were prepared from the silica-supported ligands by exposing the ligands to a transition metal salt (e.g., CuCI ₂ · 2H ₂ 0 as shown in the lower part of Figure 9) or another transition metal salt, including but not limited to a salt listed in Table 6. (e.g., MC2 (Cu(NO ₃ ) ₂ · 2.5H ₂ 0)).

Ligand and Catalyst Characterization:

Silica-supported ligands were characterized by infrared (IR) spectroscopy (KBr pellet) and in some cases by solid state NMR and the FMOC assay. Characterization data of various supported triazole ligands shown in Figures 8 and 13 and of some of their precursors is as follows:

Ligand S-1 shown in Figure 8: IR (cm ^"1 ): 3200-3600(br), 3189 (s),

3100(s), 1640 (vs); other peaks: 2870 & 2930, 2100, 2130, 1600, 1580, 1550, 1500, 1320, 1250, 1200, 1000. Solid State NMR ( ¹³ C cross- polarization magic angle spinning (CPMAS)): 179.3 111.51 , 39.2 (all peaks very broad, spanning 10 ppm).

Ligand S-2 shown in Figure 8: IR(cm ^"1 ): 3200-3600 (br); other peaks: 3000, 2850, 1860, 1680, 1600, 1520, 1500, 1400, 1200, 1 100, 1000. Fmoc assay of protected precursor indicated loading to be 0.64 mmols/g.

Ligand S-3 shown in Figure 8: IR (cm ^"1 ): 3200-3600(br); other peaks: 3050, 2850, 1860, 1680, 1600, 1520, 1500, 1400, 1200, 1100, 1000, 950.

Ligand S-4 shown in Figure 8: IR (cm ^"1 ): 3200-3600(br), 3250 (s); other peaks: 3100, 3000, 2850, 1860, 1680, 1600, 1520, 1400, 1200.

Supported primary amine shown in Figure 12: IR (cm ^-1 ): 3200-

3600(br), 3400 (s); other peaks: 2930, 2870, 1600, 1320, 1200.

Fmoc-protected modified amino acid reagent shown in Figure 12: high-resolution mass spectrometry: calculated: 421.1875; observed: 421.1863; 1 H NMR: 10.9 (weak s), 8.6 (s, 2H), 8.0 (s, 1 H), 7.2-7.5 (m, 8H), 4.68 (d, 2H), 4.52 (t, 1 H), 4.40 (t, 1 H), 4.01 (t, 2H), 1.75 (m, 4H), 1.2 (m, 2H).

Fmoc-protected, supported product of reaction shown in Figure 12: IR (cm ^"1 ): 3200-3600(br); other peaks: 3000, 2850, 1860, 1680, 1600, 1520, 1500, 1400, 1200, 1100, 1000.

Further characterization of the ligand and/or catalyst can be accomplished by powder X-ray diffraction, scanning electron microscopy (SEM), and inductively coupled plasma-atomic emission spectroscopy (ICP- AES). In particular, ICP-AES can facilitate measure of metal (e.g., copper) loading.

Example 8

Heterogenous Phase Catalysis of Methane Oxidation Table 8 provides a summary of some representative results of heterogenous phase catalysis of the oxidation of methane with the catalyst prepared according to Figure 9 (i.e., the catalyst prepared from ligand S-1 of Figure 6 and metal salt MC1 from Table 6). No Ci oxidation products were observed. Thus, under certain conditions, the immobilized catalyst appears to favor oxidatively coupled products, with acetic acid being modestly preferred under aqueous conditions. Based upon mass balance, the loading of the catalyst was roughly 0.5 weight %. Assuming 0.5 weight % copper loading, the TON for the immobilized catalyst is of the order of about 10 ² .

Table 8. Heterogenous Catalysis of the Oxidation of Methane in Acetonitrile and Water.

Further methane oxidiation reactions were performed with various silica-supported catalysts using a procedure wherein the heterogenous catalyst (50 μιτιοΙ) was added to deionized water (200 μΙ_). 100 μΙ_ (~1 mmol) of 30% hydrogen peroxide was added to this solution. A balloon was filled with methane gas (~3 mmol) and attached to the reaction vessel using a syringe. The reaction was stirred at room temperature until all the methane gas was consumed. The reaction was then monitored by gas chromatography-mass spectroscopy (GCMS). Results from methane oxidation reactions performed according to this procedure are shown in Table 9, below. The ligand codes correspond to the codes provided in Figure 8. The metal code corresponds to the metal salts listed in Table 6, above. Percentage (%) conversion refers to % of methane that was directly converted to methanol. TON (turnover number) refers to the ratio of moles of methanol produced to moles of catalyst used. These oxidation reactions were performed with approximately 1 mmol of methane and the catalyst was still active at the end of the reaction, suggesting that the actual TONs are larger than those observed. The supported catalysts were also robust, showing leaching of less than 5% in between catalyst runs. Table 9. Silica-Supported Catalyst Screening.

%

Ligand Metal Substrate Conversion TON

S-1 MC1 Methane 10 30

S-1 MC2 Methane 9.8 29

S-1 MC3 Methane < 1 NA

S-1 MC4 Methane 1.5 4.5

S-1 MC5 Methane < 1 NA

S-2 MC1 Methane 1 3

S-2 MF2 Methane 1.5 4.5

S-3 MC1 Methane 1 3

S-3 MF2 Methane 9.0 27

S-4 MC1 Methane 1 3

S-4 MF2 Methane 1 3

The effects of catalyst loading on methane oxidation was also studied. For the data shown in Table 10, below, silica-immobilized catalysts were prepared as described above in Example 7 with differing theoretical loading, determined by the number of moles of amine used to functionalize the surface.

Table 10. Catalyst Loading Effects on Heterogenous Catalysis

% Catalyst

Ligand Metal Substrate Conversion Loading

S1 MC2 Methane 12 36 0.5 mmol/g S1 MC2 Methane 10 30 1 mmol/g S1 MC2 Methane 1.5 4.5 5 mmol/g

The effect of the metal salt on methane coversion catalyzed by silica- supported catalysts was also studied. The results are shown in Table 11. S1c denotes the S1 ligand in which the free OH bonds on the silica surface are capped with OMe (methoxy) groups. Table 11. Metal Salt Effects of Heterogenous Catalysis.

%

Ligand Metal Substrate Conversion TON

S1 MC1 Methane 10 30

S1 MC2 Methane 10 30

S1 MC3 Methane < 1 NA

S1 MC4 Methane 1.5 4.5

S1 MC6 Methane < 1 NA

S1c MC1 Methane 0 0

S1c MC2 Methane 0 0

S1c MF1 Methane 0 0

Example 9

Methane Oxidation using Catalysts Prepared from Fused Triazole Ligands The catalytic activity of catalysts prepared using the fused triazole ligands shown in Figure 5 were studied using the conditions described above in Example 8 for the solid-support catalysts, excepting that free fused catalysts were used. Results are provided in Table 12, below.

Table 12. Methane Oxidation using Fused Triazole Catalysts.

%

Ligand Metal Substrate Conversion TON Notes

FB-A MC1 Methane 16

FB-A MC2 Methane 12

methane added until MeOH

FB-A MC1 Methane 19 production ceased

FB-B MC1 Methane 13

FB-C MC1 Methane 8.5

FB-C MC2 Methane 9

FB-D MC1 Methane 2

FB-E MC1 Methane 18

FB-I MC2 Methane 6.6

FB-J MC2 Methane 5

Example 10

Degradation of Cellulose

Lignin derived from switchgrass was digested using triazole-based catalysts made from Fe'" (i.e., FeC ) in acetonitrile at 50 °C under 1 atm of molecular oxygen. More particularly, FeCI ₃ was heated at 80 °C in the presence of 3 equivalents of triazole ligand in ethanol for 2 hours. The precipitate was isolated and used in the lignin degradation studies. Within 4 hours at 50 °C under an atmosphere of molecular oxygen, 10 μιτιοΙ of catalyst was able to digest 100 mg of lignin completely.

Catalyst-assisted digestion was also performed on untreated switchgrass, and by HPLC the lignin degradation products from switchgrass showed similar spectral features and retention times when compared to when isolated lignin was used. The presence of hydroxymethylfurfural was also observed by mass-spectrometry, suggesting that degradation of cellulose is also occurring. The yields on mass consumption of switchgrass were as high as 28%. The use of additives, such as other transition metal salts (e.g. MnCI ₂ ) and redox mediators (e.g. NAD), provided digestion where the mass consumption was as high as 36%. Example 11

Structural and Spectroscopic Studies

The nature of 1 ,2,4-triazole synthesis allows a diverse ligand set to be readily constructed from commercially available amines or carboxylic acids (hydrazides). A variety of amino-silyl ethers are used in the development of heterogenous triazole-based catalysts. Structure-activity relationships (SAR) between triazole ligand stereoelectronics and product distributions are determined and used to develop additional catalysts that selectively catalyze the oxidation of methane into particular Ci or C ₂ oxidation products. In addition to methanol, Ci oxidation products such as formaldehyde (see Arena and Parmaliana. Accounts of Chemical Research, 36, 867-875 (2003)) and C ₂ oxidation products such as acetic acid (see Periana et al.. Science, 301 , 814-818 (2003)) are useful chemical feedstocks. SAR studies are further used to optimize future generations of catalysts from the standpoint of yield and TON. Reactions are also conducted over a broad temperature and pressure range to study the effects on selectivity and TON.

Given the thermal stability of the presently disclosed catalysts at room temperature, isolation and crystallographic characterization of the reactive species are done. For example, single-crystal X-ray crystallography is used to identify the pre-catalyst and active catalyst solid-state structures. ESI-MS is also a probe of structure, while high-resolution ESI-MS can provide details of metal oxidation state.

Experiments using isotopically labeled oxidants are conducted to identify the source of the putative oxidant. UV-Vis (see Henson et al.. J. Am. Chem. Soc, 121 , 10332-10345 (1999)) and resonance Raman (see Holland et al., J. Am. Chem. Soc, 122, 792-802 (2000)) spectroscopies are diagnostic of the mode of metal-dioxygen coordination. For example, spectroscopic experiments to probe the nature of the copper-oxygen species are conducted, and the use of H ₂ ¹⁸ O ₂ and ¹⁸ 0 ₂ allows for identification of the source of oxygen in activation of the pre-catalyst and subsequent oxidative steps as shown in Figure 13. For matters of simplicity, the latter two chemical equations in Figure 13 omit the redox equilibria that can be present. Electrochemical experiments are conducted to understand the redox chemistry of catalyst activation and cycle. These experiments are also used to correlate substituent effects of the triazole to the observed reactivity. See Hatcher et al.. Inorganic Chem., 45, 3004-3013 (2006).

Electron paramagnetic resonance (EPR) spectroscopy is used to study the catalyst solution-state structure, the effects of coordinating solvents, non-coordinating anions, and catalyst activation with both H ₂ O ₂ and O ₂ . Extended X-ray absorption fine structure (EXAFS) data is used to obtain precise information on the oxidation state(s) of the metal under reaction conditions as well as coordination of ligands. See Mahapatra et al., J. Am. Chem. Soc, 118, 11555-11574 (1996). Mixed-valence intermediates (see Yoshizawa and Shiota, Inorganic Chem., 48, 838-845 (2009); and York et al.. J. Am. Chem. Soc, 129, 7990-7999 (2007)) have recently been implicated in the catalytic cycle of pMMO and, without being bound to any one theory, it appears that complexes of ligands of Formula (II) adopt this electronic configuration, in view of their high degree of selectivity for methanol as an oxidation product, making EXAFS particularly useful for these studies. Example 12

Mechanistic Studies

There are several mechanistic studies that can shed light on how the triazole-based catalysts function. Kinetic isotope effect n/ko data, derived from the use of both CD ₄ and D ₂ 0, is used to identify the rate-determining step: C-H bond activation or C-0 bond formation. Small values of kn/ko can implicate C-H activation as the rate-determining step and these values can be correlated to the nature of ligand in a structure-activity relationship. Reactions discussed above in acetonitrile did show oxidation of solvent. Using CD ₃ CN, GC-MS analysis can be used to asses the extent of the parallel oxidation. Reaction kinetics provide a probe of the extent to which a free radical mechanism is operative. Without being bound to any one theory, it is unlikely that a radical mechanism contributes, as this would favor oxidation of MeCN. Oxygen- and carbon-centered radical traps (e.g., 2,2,6,6-tetramethylpiperidine-1 -oxyl (TEMPO), diphenylamine (Pha H), and 2,6-di-fe/f-butyl-4-methylphenol (BHT)) can also be used to study this effect.

As catalysis with the presently disclosed catalysts proceeds well in water, a series of labeling studies are conducted in a purely aqueous environment, eliminating complications. As observed above, the Ci and C ₂ products unambiguously arise from CH ₄ as this is the only source of carbon in the reaction. Shown in Figure 14 is a labelling study based upon a related iron system (see Sorokin et al., Chem. Comm., 2562-2564 (2008)) that uses ¹³ CH ₄ (to allow rapid screening by ¹³ C NMR), as well as to study the source of oxygen in the oxidized products. Using GC-MS, the relative concentrations of isotopomer oxygenates is used to monitor the oxidative pathway(s). The effects of acidic reaction media can also be examined to investigate to what extent protonation of peroxo or oxo species affects reactivity.

Similar labeling studies are done for C ₂ oxidative pathways. See Bar- Nahum et al., J. Am. Chem. Soc, 126, 10236-10237 (2004). The likely pathways in the production of acetaldehyde are shown in Figure 15, and pathways can be similarly constructed for acetic acid formation. Briefly, a reaction time course is constructed to observe formation of methanol and acetaldehyde. Concomitant formation suggests no induction period exists. As acetaldehyde can be formed by the coupling of methanol and formaldehyde, labeling studies using ¹³ CH ₃ OH to determine the presence of the ¹³ C label in acetaldehyde are done. Oxidation of ethanol with these catalysts and the determination of its presence as an intermediate are used to investigate pathway (b). Inhibition studies with CO are also conducted to rule out the unlikely occurrence of pathway (d). The most likely pathway, (c), originates from the oxidation of CH ₄ to HCHO via CH ₃ OH, followed by oxidative coupling to another CH ₄ molecule. Labeling studies analogous to those shown in Figure 14 can be utilized.

Detailed structural and mechanistic calculations at the level of density functional theory (DFT) can be conducted. Of note to such study is the use of spin-unrestricted methods that allow for symmetry breaking of spin states as traditional methods overestimate the spin-state splitting. Preliminary energy minimizations at the level of molecular mechanics have shown structural similarities between the bis(^-oxo) core in the copper-triazole catalysts when compared to a theoretical model of pMMO. Relevant distances, dCu-Cu and dO-O, are within 0.07A of those calculated in pMMO.

In addition, the ratio of alcohol/ketone (A/K) in the oxidation of cyclohexane can be used to provide information regarding the lifetime of alkyl radicals. An A/K ratio of 1 suggests that long-lived alkyl radicals, such as cyclohexyl radical, are trapped by O ₂ at a diffusion-controlled rate to form alkylperoxyl radicals. Recombination of these radicals results in formation of equimolar amounts of cyclohexanol and cyclohexanone. When A K is >1 , the HO- radicals formed by a metal-based oxidant react quickly to form the alcohol as the main product. See Gozzo, F., Journal of Molecular Catalysis A- Chemical, 171, 1-22 (2001); Kim et al.. J. Am. Chem. Soc, 118, 4373- 4379 (1996); and Menage et al.. J. Chem. Soc, Dalton Trans., 2081-2084 (1994). Radical chain autooxidation processes typically have A/K < 1. See Gozzo, F., Journal of Molecular Catalysis A- Chemical, 171 , 1-22 (2001).

Intermolecular competition studies of the oxidation of adamantane, which contains both secondary and tertiary C-H bonds, can be performed to provide details about the regioselectivity of the oxidants. The regioselectivity can be parameterized as a 3 2° ratio derived from the amount of 1- adamantanol divided by the amount of 2-adamantanol and 2-adamantanone and multipled by 3 to correct for the higher number of secondary C-H bonds. See Teramae et al., J. Inorganic Biochemistry, 98, 746-757 (2004). Nonselective oxidants, such as HO- typically give 3 2° ratios of 2, while milder oxidants give higher values. The nature of the oxidant can also be assessed by analyzing the retention of configuration in the oxidation of tertiary C-H bonds of cis-1 ,2-dimethylcyclohexane. See Kim et al., J. Am. Chem. Soc, 119, 5964-5965 (1997).

Example 13

Catalysis of Aziridination and Formation of Aminoalcohols from Alkenes Copper catalysts comprising 1 ,2,4-triazole ligands were used to catalyze the formation of aminoalcohols from styrene and trans-stilbene using chloramine-T as a nitrogen source in water. The catalysts were used in 5 mol% to give the aminohydroxylated product in yields of greater than about 70% as determined by HPLC.

Copper, iron, cobalt, and nickel 1 ,2,4-triazole catalysts were used to study the catalysis of aziridination reactions. The nitrogen source used for the aziridination reactions was either an organic azide (e.g., an aryl or heteroaryl azide) or an iododinane reagent (e.g., PhlNTs).

Example 14

Cvclohexane Oxidation with Additional Catalysts

In a fashion similar to that described in Example 2, but using only 20 equivalents of H ₂ O ₂ , copper catalysts prepared from ligands A-F from Scheme 4 and with a 4-phenyl-substituted version of ligand D (referred to hereinbelow as ligand pD) were used to catalyze the oxidation of cyclohexane. Results of cyclohexane oxidation reactions catalyzed by the presently disclosed catalysts for 1 hour are shown hereinbelow in Table

13. A/K is the ratio of cyclohexanol to cyclohexanone after treatment with

PP i ₃ . The percent yield (% Yield) is calculated based on calibration of

GC-MS chromatographs with an internal standard and are based on the amount of cyclohexane added as a starting material. A possible mechanism for the oxidation of cyclohexane according to the presently disclosed subject matter is presented in Figure 21.

Table 13. Further Catalytic Oxidations of Cyclohexane.

* indicates that Cu(MeCN) ₄ BF ₄ was used as the metal source.

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It will be understood that various details of the presently disclosed subject matter can be changed without departing from the scope of the presently disclosed subject matter. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.