CARTIGNY DAMIEN (CN)
CENTRE NAT RECH SCIENT (FR)
| WO2010018570A1 | 2010-02-18 |
| US20130245276A1 | 2013-09-19 | |||
| US20130331580A1 | 2013-12-12 |
SEBASTIAN IMM.: "An Efficient and General Synthesis of Primary Amines by Ruthenium- Catalyzed Amination of Secondary Alcohols with Ammonia", ANGEW. CHEM. INT. ED., vol. 49, no. 44, 2 August 2010 (2010-08-02), pages 8126 - 8129, XP002669003
SEBASTIAN IMM.: "Improved Ruthenium-Catalyzed Amination of Alcohols with Ammonia: Synthesis of Diamines and Amino Esters", ANGEW. CHEM. INT. ED., vol. 50, 5 July 2011 (2011-07-05), pages 7599 - 7603, XP002664616
| Claims 1. A process for preparing an annine compound, the process comprising: reacting ammonia with a compound having at least one hydroxyl functional group [Compound (H)], in an aqueous medium and in the presence of a catalyst system comprising at least one transition metal [Metal (T)] and a donor ligand [Ligand (D)], wherein the Ligand (D) comprises at least one hydrophilic group. 2. The process of Claim 1 , wherein the hydrophilic group is selected from: - ionic groups selected from carboxyl group, sulfonic acid group, phosphoric acid group and ammonium group; and - nonionic hydrophilic groups selected from polyol group, carbohydrate group, and polyether group. 3. The process of Claim 1 or 2, wherein the Compound (H) is selected from primary, secondary and tertiary alcohols. 4. The process of Claim 3, wherein the Compound (H) is of the general formula (I): Ra_CH2— OH (I), where Ra is selected from the group hydrogen, unsubstituted or substituted Ci- C3o-alkyl, C3-Cio-cycloalkyl, C3-Cio-heterocyclyl comprising at least one heteroatom selected from N, O and S, Cs-Ci4-aryl and Cs-Ci4-heteroaryl comprising at least one heteroatom selected from N, O and S, wherein the substitution is selected from the group consisting of: F, CI, Br, OH, OR4, CN, NH2, NHR4, N(R4)2, Ci-Cio-alkyl, Cs-Cio-cycloalkyl, Cs-Cio-heterocyclyl comprising at least one heteroatom selected from N, O and S, Cs-Ci4-aryl and C5-Ci4-heteroaryl comprising at least one heteroatom selected from N, O and S, wherein R4 is selected from Ci-Cio-alkyl and Cs-C-m-aryl. 5. The process of Claim 1 or 2, wherein the Compound (H) is selected from a group consisting of: benzyl alcohol, ethylene glycol, glycerol, triethanolamine, and monoaminoethanol. 6. The process of any of the preceding claims, wherein the Metal (T) is chosen from the group consisting of Ru, Rh, Ir, Pd, Pt, Au, Ag and Pd, and preferably from the group of Ru, Ir, and Pd. 7. The process of any of the preceding claims, wherein the catalyst system contains at least one Metal (T)-based compound selected from the group of: [Ru(p-cymene)CI2]2, [Ru(benzene)CI2]2, [Ru(CO)2CI2]2, [Ru(CO)3CI2]2, [Ru(CO)CIH(PPh3)3], [Ru(COD)(allyl)], [RuCI3 H2O], [Ru(acetylacetonate)3], [Ru(DMSO)4CI2], [Ru(PPh3)3(CO)(H)CI], [Ru(PPh3)3(CO)CI2], [Ru(PPh3)3(CO)(H)2], [Ru(PPh3)3CI2], [Ru(cyclopentadienyl)(PPh3)2CI], [Ru(cyclopentadienyl)(CO)2CI], [Ru(cyclopentadienyl)(CO)2H], [Ru(cyclopentadienyl)(CO)2]2, [Ru(pentamethylcyclopentadienyl)(CO)2CI], [Ru(penta- methylcylcopentadienyl)(CO)2H], [Ru(pentamethylcyclopentadienyl)(CO)2]2, [Ru(indenyl)(CO)2CI], [Ru(indenyl)(CO)2H], [Ru(indenyl)(CO)2]2, ruthenocene, [Ru(binap)CI2], [Ru(bipyridine)2CI2-2H2O], [Ru(COD)CI2]2, [Ru(pentamethylcyclo-pentadienyl)(COD)CI], [Ru3(CO)i2] , [Ru(tetraphenylhydroxycyclopentadienyl)(CO)2H], [Ru(PMe3)4(H)2], [Ru(PEt3)4(H)2], [Ru(PnPr3)4(H)2], [Ru(PnBu3)4(H)2], [Ru(PnOctyl3)4(H)2], [lrCI3-H2O], KlrCU, K3lrCI6, [lr(Cp*)CI2]2, [lr(Cp*)(NH3)2]l2, [lr(COD)CI]2, [lr(cyclooctene)2CI]2, [lr(ethene)2CI]2, [lr(cyclopentadienyl)CI2]2, [lr(pentamethylcyclopentadienyl)CI2]2, [lr(cylopentadienyl)(CO)2], [lr(pentamethylcyclopentadienyl)(CO)2], [lr(PPh3)2(CO)(H)], [lr(PPh3)2(CO)(CI)], [lr(PPh3)3(CI)], [Pt(cod)CI2]2 and Pd(NTf2)2. 8. The process of Claim 7, wherein the catalyst system contains at least one Metal (T)-based compound selected from the group of: [Ru(p-cymene)CI2]2, [Ru3(CO)i2] , [Pt(cod)CI2]2, [lr(Cp*)CI2]2, [lr(Cp*)(NH3)2]l2, and Pd(NTf2)2. 9. The process of any of the preceding claims, wherein the Ligand (D) is chosen from a group consisting of phosphor donor ligands, oxygen donor ligands, nitrogen donor ligands and sulfur donor ligands. 10. The process of any of the preceding claims, wherein the Ligand (D) is chosen from SulfoXantphos ligand and 3,3',3"-Phosphanetriyltris(benzenesulfonic acid) trisodium salt (abbreviated as TPPTS). 1 1. The process of any of the preceding claims, wherein the reaction between the ammonia and the Compound (H) occurs at a temperature of from 20 to 250°C, preferably from 100 to 200°C, and more preferably from 150 to 200°C. 12. The process of any of the preceding claims, wherein pressure of the reaction between ammonia and the Compound (H) is controlled to be within the range of 0.1 to 10 MPa, preferably from 0.2 to 5 MPa, and more preferably from 0.2 to 3 MPa. 13. The process of any of the preceding claims, wherein the reaction time between the ammonia and the Compound (H) is from 15 minutes to 15 hours, preferably from 30 minutes to 5 hours, more preferably from 30 minutes to 1 hour. 14. The process of any of the preceding claims, wherein the reaction between ammonia and the Compound (H) is carried out under microwave irradiation. |
CATALYZED AMINATION OF ALCOHOLS IN AQUEOUS MEDIUM
Technical Field
[0001] The present invention pertains to a catalytic process for preparing annine compounds from alcohol compounds, and more particularly, to a catalytic process for the direct amination of alcohol compounds by means of ammonia in an aqueous medium.
Background Art
[0002] For chemical industry and numerous biological processes, amines are of great importance and find use in a wide range of applications, notably including agrochemicals, pharmaceuticals and food additives.
[0003] Among the various known procedures for manufacturing amines, the
reaction between ammonia and alcohols is of special industrial interest, as ammonia and various alcohol compounds are readily available chemical materials with relatively low cost, and are obtainable from renewable resources. Further advantageously, the amination reaction of alcohols generates water as the only by-product, which is far more environmental friendly than the salt by-products resulted from amination of alkyl or aryl halides.
[0004] Nevertheless, in the related study and literatures published, the reaction of ammonia and alcohol to generate selected amine compounds has only been described for limited number of process conditions, predominantly over a heterogeneous catalyst system and applicable for only a few alcohols. The challenges faced in most heterogeneously catalyzed processes include multiple factors: firstly, many metal complex catalysts are prone to be deactivated by ammonia; secondly, high selectivity to primary amines has been hard to achieve since they are more nucleophilic than ammonia, leading to undesired side-product formation (including higher amines, alkenes and alkanes); thirdly, the catalyzed gas-phase reaction normally requires high temperatures (up to 400°C) and high pressures (up to 300 bars), thus raising the mechanical requirements of the reaction vessels.
[0005] In comparison, homogeneously catalyzed alcohol amination processes generally utilize significant lower temperature (generally from 100 to 150°C) and give better product selectivity, as in the below-discussed examples.
[0006] In 2008, Gunanathan and Milstein reported the first selective synthesis of primary amines from alcohols using ammonia gas in toluene and in water (Scheme 1 and Scheme 2), in GUNANATHAN, C, et al. Selective
Synthesis of Primary Amines Directly from Alcohols and Ammonia. Angew. Chem., Int. Ed.. 2008, no.47, p.8661.
Scheme 1
Λ Ru-cat. (0.1 mol%) ^ R-^ 0H + NH 3 . R^N H 2
Water, 1 35 °C, 18-36 h
(7.5 atm) 90-100% conversion
55-92% yield
R = Ph, 4-MePh, Bz, n-hexyl, /7-pentyl
Scheme 2
Two years later, Beller et al. reported an alternative process to synthesize primary amines, by reacting secondary alcohols with ammonia in the presence of a catalyst system made of [Ru3(CO)i2] and CataCXium PCy, as illustrated in Scheme 3 below and detailed in IMM, S., et al. Eine effiziente und allgemeine Synthese primarer Amine durch Ruthenium- katalysierte Aminierung sekundarer Alkohole mit Ammoniak. Angewandte Chemie. 2010, vol.122, p.8303.
CataCXiu m PCy
Scheme 3
Meanwhile, another catalyzed process to synthesize primary amines from ammonia and secondary alcohols (see Scheme 4) was reported by Vogt et al., which relied on the catalytic activity of a pincer-type Ruthenium complex and avoided use of a base, according to VOGT, D., et al. Direkte Aminierung von sekundaren Alkoholen mit Ammoniak. Angewandte Chemie. 2010, vol.122, p.8307.
NH 2
) A1 -
n = 1 , 2, 4 R 1 , R 2 = Me, Et, n-butyl,
n-pentyl, n- exyl, P
Scheme 4 Disadvantageously, however, the above two homogeneously catalyzed processes both used gaseous or liquid ammonia as the reactant, which requires elevated reaction pressure and hence high-pressure vessel to facilitate. In an effort to circumvent this shortcoming, Yamaguchi and his co-workers reported different catalyzed processes for alcohol amination, notably using aqueous ammonia as the amination agent. Specifically, as described in YAMAGUCHI, R., et al. Multialkylation of aqueous ammonia with alcohols catalyzed by water-soluble Cp * lr-ammine complexes. J. Am. Chem. Sec. 2010, vol.132, p.15108. , di- or tri-alkylation of amine may be respectively obtained by reacting secondary or primary alcohols with aqueous ammonia, in the presence of an Iridium complex catalyst (see Scheme 5 and Scheme 6).
R = H, 4-Me, 4-OMe, 4-CI, 4-Br, R = n-C 5 H 1 1 , n-C 7 H 15 , /-PrCH 2 CH 2
3-Br, 2- Br, 4-CF 3 , 4-C0 2 Me, 4-Ph r-BuCH 2 , Bz, Bz-CH 2 , EtOCH 2 , Ph
Scheme 5
84-86% yield 63-89% yield
(3 examples) (4 examples)
n = 1 ,2, 3 R = n-C 6 H 13 , Ph, Bz, BzCH 2
Scheme 6
More recently, Ohshima and Mashima reported another alcohol amination process using aqueous ammonia as the amination agent, which relies on a Platinum-based catalyst system ( MASHIMA, K., et al. Platinum-Catalyzed Direct Amination of Allylic Alcohols with Aqueous Ammonia: Selective Synthesis of Primary Allylamines. Angew. Chem., Int. Ed.. 2012, vol.51 , p.150. ). Particularly, according to their study, aqueous ammonia could react with allylic alcohols using a catalyst system of a [Pt(cod)Cl2] complex with a DPEphos ligand (Scheme 7), and medium-to-high product yields were observed. Nevertheless, such reaction notably needed very long reaction period (normally from 24 to 65 hours) to approach completion, posing a definite challenge for industrial scale-up application.
68-70% yield 61-78% yield 66% yield (5 examples) (9 examples)
R1 = 4-MePh, 4-MeOPh, 2- eOPh, R = Me, Ph, 4-MeOPh , furanyl, thiophenyl
1 -naphtyl,2-naphtyl R 2 = Me, Ph, 3-FPh, 4-FPh , 4-CF 3 Ph
R 3 = H , Me
Scheme 7
[001 1] In view of the shortcoming of the prior art processes set forth above, it is therefore an object of the present invention to provide an improved process for producing amines from reacting ammonia with alcohols, which uses an effective homogenous catalyst system to greatly shorten reaction time while providing satisfactory conversation rate and product selectivity.
Summary of invention
[0012] The present application provides a process for preparing an amine
compound, the process comprising: reacting ammonia with a compound having at least one hydroxyl functional group [Compound (H)], in an aqueous medium and in the presence of a catalyst system comprising at least one transition metal [Metal (T)] and a donor ligand [Ligand (D)], wherein the Ligand (D) comprises at least one hydrophilic group.
[0013] Advantageously, the process of the present invention allows amination of alcohols by ammonia in an aqueous medium, and employs an effective catalyst system which helps obtain the desired amine product with a high selectivity in a short reaction time. Further, compared to the prior art processes, the invented alcohol amination process uses comparatively low catalyst loading and significantly increases the overall reactant conversion rate.
[0014] For the purpose of the present invention, the term "aqueous medium" refers to a medium which contains liquid water, for at least 50 molar percent and preferably at least 80 molar percent of the totality of the medium. Specifically, the aqueous medium according to the present invention may be a homogeneous or heterogeneous medium, such as a biphasic or multiphasic system comprising an aqueous phase.
[0015] In certain embodiment of the invention, the aqueous medium notably
comprises between 1 to 40 molar percent of a non-water solvent that optionally contains water-soluble component(s), and said non-water solvent may be selected from a group of:
- polar protic solvents, such as isopropanol, methanol, ethanol, and acetic acid;
- polar aprotic solvents, such as dimethyl sulfoxide (DMSO), acetone, and acetonitrile; and
- apolar solvents, such as tetrahydrofuran, dioxane, diethylether,
diisopropyl ether, cyclohexane, toluene, benzene, xylene, octane, hexane, heptane, 1 ,4-dioxane, tert-butyl methyl ether (MTBE), mesitylene, diglyme and 1 ,2-dimethoxyethane.
[0016] As one starting material of the present process invention, the ammonia used may be in an aqueous or gaseous form. As used herein, aqueous ammonia is understood to include dissolved ammonia, ammonium hydroxide, and ammonium ion in a water solution.
[0017] As another starting material of the present process invention, the
compound (H) is preferably an alcohol having at least one hydroxyl functional group (-OH) connected to a carbon atom.
[0018] Suitable compounds (H) include practically all alcohols which satisfy the prerequisites specified above, and the alcohols may be straight-chain, branched or cyclic. Optionally, the alcohols can carry substituents which exhibit inert behaviour under the amination reaction conditions, for example alkoxy, alkenyloxy, alkenyloxy, alkylamino, dialkylamino and halogens (F, CI, Br, I).
[0019] According to the present invention, compounds (H) are preferably selected from aliphatic alcohols and notably include primary, secondary and tertiary alcohols.
[0020] As used herein, the term "aliphatic alcohol" is intended to mean any
alcohol in which the hydroxyl functional group(s) is not attached directly to an aromatic ring, and includes within its scope alcohols which contain an aromatic structure, for example benzene ring, provided that the hydroxyl group is not phenolic.
[0021] As used herein, a "primary alcohol" refers to an organic compound having at least one primary hydroxyl group of the formula (-CH2-OH), a
"secondary alcohol" refers to an organic compound having at least one secondary hydroxyl group of the formula R 1 R 2 CH(OH), and a "tertiary alcohol" refers to an organic compound having at least one tertiary hydroxyl group of the formula R 1 R 2 R 3 C(OH), where none of R 1 , R 2 and R 3 is hydrogen.
[0022] Suitable alcohols for compounds (H) are, for example, those of the general formula (I):
Ra_CH 2 — OH (I),
where R a is selected from the group of hydrogen, unsubstituted or substituted Ci-C3o-alkyl, C3-Cio-cycloalkyl, C3-Cio-heterocyclyl comprising at least one heteroatom selected from N, O and S, Cs-Ci 4 -aryl and Cs-Ci 4 - heteroaryl comprising at least one heteroatom selected from N, O and S, and wherein the substitution is selected from the group consisting of: F, CI, Br, OH, OR 4 , CN, NH 2 , NHR 4 or N(R 4 ) 2 , Ci-Cio-alkyl, C 3 -Cio-cycloalkyl, C 3 - Cio-heterocyclyl comprising at least one heteroatom selected from N, O and S, C5-Ci 4 -aryl and Cs-Ci 4 -heteroaryl comprising at least one
heteroatom selected from N, O and S, wherein R 4 is selected from C1-C10- alkyl and Cs-C-m-aryl.
[0023] Preferred example of compounds (H) include: methanol, ethanol, n- propanol, n-butanol, isobutanol, n-pentanol, n-hexanol, n-heptanol, n- octanol, n-nonanol, 2-ethylhexanol, tridecanol, stearyl alcohol, palmityl alcohol, benzyl alcohol, 2-phenylethanol, 2-(p-methoxyphenyl)ethanol, 2- (3,4-dimethoxyphenyl)ethanol, allyl alcohol, propargyl alcohol, 2- hydroxymethyl-furan, lactic acid, serine, 1 ,2-ethanediol (ethylene glycol), 1 ,2-propanediol (1 ,2-propylene glycol), 1 ,3-propanediol (1 ,3-propylene glycol), 1 ,4-butanediol (1 ,4-butylene glycol), 1 ,2-butanediol (1 ,2-butylene glycol), 2,3-butanediol, 2-methyl-1 ,3-propanediol, 2,2-dimethyl-1 ,3- propanediol (neopentyl glycol), 1 ,5-pentanediol, 1 ,2-pentanediol, 1 ,6- hexanediol, 1 ,2-hexanediol, 1 ,7-heptanediol, 1 ,2-heptanediol, 1 ,8- octanediol, 1 ,2-octanediol, 1 ,9-nonanediol, 1 ,2-nonanediol, 1 ,10- decanediol, 2,4-dimethyl-2,5-hexanediol, hydroxypivalic acid neopentyl glycol ester, diethylene glycol, triethylene glycol, 2-butene-1 ,4-diol, 2- butyne-1 ,4-diol, polyethylene glycols, polypropylene glycols, such as 1 ,2- polypropylene glycol and 1 ,3-polypropylene glycol, polytetrahydrofuran, diethanolannine, 1 ,4-bis(2-hydroxyethyl)piperazine, diisopropanolannine, N- butyldiethanolamine, 2,5-(dimethanol)-furan, 1 ,4- bis(hydroxymethyl)cyclohexane, N-methyldiethanolamine, glycerol, trimethylolpropane, triethanolamine, 2,2-bis(hydroxymethyl)-1 ,3- propanediol (pentaerythritol), sorbitol, inositol, sugars and polymers with primary hydroxyl groups (-CH2-OH) such as, for example, glucose, mannose, fructose, ribose, deoxyribose, galactose, N-acetylglucosamine, fucose, rhamnose, sucrose, lactose, cellobiose, maltose and amylose, cellulose, starch and xanthan.
[0024] Another preferred group of compounds (H) are alkanolamines having at least one primary hydroxyl group (-CH2-OH). Examples of alkanolamines which can be used as compounds (H) are monoaminoethanol, 3- aminopropan-1 -ol, 2-aminopropan-1 -ol, 4-aminobutan-1-ol, 2-aminobutan- 1-ol, 3-aminobutan-1 -ol, 5-aminopentan-1 -ol, 2-aminopentan-1 -ol, 6- aminohexan-1 -ol, 2-aminohexan-1 -ol, 7-aminoheptan-1 -ol, 2- aminoheptan-1 -ol, 8-aminooctan-1 -ol, 2-aminooctan-1-ol, N-(2- hydroxyethyl)aniline, N-(2-aminoethyl)ethanolamine, 1 -(2- hydroxyethyl)piperazine, 2-(2-aminoethoxy)ethanol, N-butylethanolamine, N-ethylethanolamine, N-methylethanolamine, N,N-dimethylethanolamine, N-(2-hydroxyethyl)-1 ,3-propanediamine, 3-(2-hydroxyethyl)amino-1- propanol, 3-dimethylamino-1 -propanol, Ν,Ν-dibutylethanolamine, N,N- dimethylisopropylamine and N,N-diethylethanolamine.
[0025] Preference is given to alkanolamines which have at least one primary
hydroxyl group (-CH2-OH) and at least primary amino group of the formula (-CH2-NH2).
[0026] Particular preferred compounds (H) include: benzyl alcohol, ethylene
glycol, glycerol, triethanolamine, and monoaminoethanol. [0027] As aforementioned, the catalyst system used in the process of the present invention comprises at least one transition metal [Metal (T)] and a donor ligand [Ligand (D)].
[0028] Preferably, the catalyst system used in the process of the present
invention is a homogenous catalyst. For the purpose of the present invention, a "homogenous catalyst" means that the catalytically active part of the catalyst is at least partly present in solution in the aqueous medium. Preferably, at least 50 molar percent of the catalyst system of the present invention is present in the solution in the aqueous medium.
[0029] The Metal (T) comprised in the catalyst system is generally chosen from the group consisting of: Ru, Rh, Ir, Pd, Pt, Au, Ag and Pd, preferably from the group of Ru, Ir, and Pd.
[0030] Notably, the Metal (T)-based compounds used in the catalyst system may be selected from the group of: [Ru(p-cymene)Cl2]2, [Ru(benzene)Cl2]2, [Ru(CO) 2 CI 2 ] 2 , [Ru(CO) 3 CI 2 ] 2 , [Ru(CO)CIH(PPh 3 ) 3 ], [Ru(COD)(allyl)],
[RuCI 3 H 2 O], [Ru(acetylacetonate) 3 ], [Ru(DMSO) CI 2 ],
[Ru(PPh 3 ) 3 (CO)(H)CI], [Ru(PPh 3 ) 3 (CO)CI 2 ], [Ru(PPh 3 ) 3 (CO)(H) 2 ],
[Ru(PPh 3 ) 3 CI 2 ], [Ru(cyclopentadienyl)(PPh 3 ) 2 CI],
[Ru(cyclopentadienyl)(CO) 2 CI], [Ru(cyclopentadienyl)(CO) 2 H],
[Ru(cyclopentadienyl)(CO)2]2, [Ru(pentamethylcyclopentadienyl)(CO)2CI], [Ru(penta-methylcylcopentadienyl)(CO)2H],
[Ru(pentamethylcyclopentadienyl)(CO)2]2, [Ru(indenyl)(CO)2CI],
[Ru(indenyl)(CO) 2 H], [Ru(indenyl)(CO) 2 ]2, ruthenocene, [Ru(binap)CI 2 ], [Ru(bipyndine) 2 Cl2-2H 2 O], [Ru(COD)CI 2 ]2, [Ru(pentamethylcyclo- pentadienyl)(COD)CI], [Ru 3 (CO)i 2 ],
[Ru(tetraphenylhydroxycyclopentadienyl)(CO)2H], [Ru(PMe 3 ) 4 (H) 2 ],
[Ru(PEt 3 ) 4 (H) 2 ], [Ru(PnPr 3 ) 4 (H) 2 ], [Ru(PnBu 3 ) 4 (H) 2 ], [Ru(PnOctyl 3 ) 4 (H) 2 ], [lrCI 3 -H 2 O], KlrCU, K 3 lrCI 6 , [lr(Cp * )CI 2 ] 2 , [lr(Cp * )(NH 3 ) 2 ]l 2 , [lr(COD)CI] 2 , [lr(cyclooctene)2CI]2, [lr(ethene)2CI]2, [lr(cyclopentadienyl)Cl2]2,
[lr(pentamethylcyclopentadienyl)Cl2]2, [lr(cylopentadienyl)(CO)2],
[lr(pentamethylcyclopentadienyl)(CO) 2 ], [lr(PPh 3 ) 2 (CO)(H)],
[lr(PPh 3 ) 2 (CO)(CI)], [lr(PPh 3 ) 3 (CI)], [Pt(cod)CI 2 ] 2 and Pd(NTf 2 ) 2 . [0031] Preferred Metal (T)-based compounds in the above group include: [Ru(p- cymene)CI 2 ]2, [Ru 3 (CO)i 2 ], [Pt(cod)CI 2 ] 2 , [lr(Cp * )CI 2 ] 2 , [lr(Cp * )(NH 3 ) 2 ]l 2 , and Pd(NTf 2 ) 2 .
[0032] Generally, at least one hydrophilic group is comprised in the Ligand (D) to cause it to partition into the aqueous medium while providing the necessary steric and electronic properties to ensure a desired catalyst stability, activity, and selectivity.
[0033] The term "hydrophilic group", as used herein, refers to an ionic group
(such as carboxyl group, sulfonic acid group, phosphoric acid group, or ammonium group), or a nonionic hydrophilic group (such as polyol group, carbohydrate group, or polyether group). Design and the selection of said hydrophilic group for the Ligand (D) can find reference in
SHAUGHNESSY/K.H.. Hydrophilic Ligands and Their Application in Aqueous-Phase Metal-Catalyzed Reactions. Chem. rev.. 2009, vol.109, p.643-710.
[0034] Specifically, the hydrophilic group of the Ligand (D) may be selected from the group consisting of:
- SO3X, CO 2 Y, and OZ, wherein X, Y, and Z are each independently hydrogen or a cation selected from H + , NH 4 + , K + , Li + , and Na + ;
- alkyl polyether group having 2 to 30 carbon atoms; and
- NR 1 R 2 , N + R 1 R 2 R 3 , PR R 2 , and P + R R 2 R 3 , wherein R 1 , R 2 and R 3 are each independently selected from hydrogen, alkyl, (C3 - C6) allyl, vinyl, cycloalkyl, phenyl, benzyl, and phenethyl.
[0035] The Ligand (D) is notably chosen from a group consisting of phosphor donor ligands, oxygen donor ligands, nitrogen donor ligands and sulfur donor ligands.
[0036] Preferred examples of Ligand (D) include SulfoXantphos ligand, and
3,3',3"-Phosphanetriyltris(benzenesulfonic acid) trisodium salt
(abbreviated as TPPTS).
[0037] Generally, in the process of the present invention, the catalyst system is used with an amount of from 0.1 to 5000 ppm by weight, based on the total aqueous medium. [0038] Moreover, in the process of the present invention, the annination reaction generally occurs at a temperature of from 20 to 250°C, preferably from 100 to 200°C, and more preferably from 150 to 200°C. The absolute pressure of said reaction is generally controlled to be within the range of 0.1 to 10 MPa, preferably from 0.2 to 5 MPa, and more preferably from 0.2 to 3 MPa, which can be either the autogenous pressure of the solvent at the reaction temperature or the pressure of a gas such as nitrogen, argon, or hydrogen.
[0039] The average reaction time is generally from 15 minutes to 15 hours,
preferably from 30 minutes to 5 hours, more preferably from 30 minutes to 1 hour.
[0040] In the amination reaction of the present invention, the ammonia can be
used in stoichiometric, substoichiometric or superstoichiometric amounts based on the hydroxyl groups of the Compound (H). In a preferred embodiment, the ammonia is used in an amount from 1 - to 250-fold, preferably from 1 - to 100-fold, in particular in from 2- to 15-fold, molar excess per mole of hydroxyl groups in the Compound (H).
[0041] To carry out the amination reaction, the reactants of ammonia and the
Compound (H), together with the catalyst system and optionally with one or more solvents are introduced into a reactor containing an aqueous medium. The introduction of reactants, catalyst, and the optional solvent(s) may be carried out simultaneously or separately. The amination reaction can be carried out continuously, in the semibatch mode, in the batch mode, admixed in product as solvent or without admixing in a single pass.
[0042] It is in principle possible to use all reactors which are basically suitable for gas/liquid reactions at the given temperature and the given pressure for the catalytic process of the invention.
[0043] Preferably, the amination reaction in the process of the present invention is carried out under microwave irradiation.
[0044] The microwave irradiation according to the invention can be carried out using commercially available microwave synthesizers, such as Biotage® Initiator Microwave Synthesizer available from Biotage AB.
[0045] The microwave irradiation is generally in the range of 50-1000 W,
preferably in the range of 100 to 500 W, for a period of 1 -120 min. [0046] Any excess ammonia present, any solvent present, the catalyst and the water co-product are removed from the reaction output. The excess ammonia, the catalyst, any solvent and any un-reacted Compound (H) can be recirculated to the amination reaction.
[0047] If the amination reaction is carried out in one or more solvents, the one or more solvents can be miscible with the amination product and be separated off by distillation after the reaction. It is also possible to use solvents which have a miscibility gap with the amination products or the starting materials. Suitable solvents for this purpose are, for example, toluene, benzene, xylenes, alkanes such as hexanes, heptanes and octanes and acyclic or cyclic ethers such as diethyl ether, tetrahydrofuran, tert-amylalcohol and dioxane. As a result of suitable choice of the Ligand (D), the catalyst system of the present invention can preferentially dissolve in the solvent phase, i.e. in the phase not comprising product. The ligand (D) can also be selected so that the catalyst system dissolves in the amination product. In this case, the amination product can be separated from the catalyst by distillation.
[0048] If used, the one or more solvents can also be miscible with the starting materials and the product under the reaction conditions and only form a second liquid phase comprising the major part of the catalyst system after cooling. As solvents which display this property, mention may be made by way of example of toluene, benzene, xylenes, alkanes such as hexanes, heptanes and octanes. The used catalyst can then be separated off together with the solvent and be reused. The product phase can also be admixed with water in this variant. The proportion of the catalyst comprised in the product can be subsequently separated off by means of suitable absorbents such as polyacrylic acid and salts thereof, sulfonated polystyrenes and salts thereof, activated carbons, montmorillonites, bentonites and zeolites or else be left in the product.
[0049] The amination reaction can also be carried out in a two-phase system. In the case of the two-phase reaction, suitable nonpolar solvents are, in particular, toluene, benzene, xylenes, alkanes such as hexanes, heptanes and octanes in combination with non-polar ligand (D), as a result of which the catalyst accumulates in the nonpolar phase. In this embodiment, in which the amination product and the water co-product
of reaction and any unreacted starting materials form a second phase enriched with these compounds, the major part of the catalyst system can be separated off from the product phase by simple phase separation and be reused.
[0050] It can also be advantageous for the water co-product formed in the
reaction to be removed continuously from the reaction mixture. The water co-product of reaction can be separated off from the reaction mixture directly by distillation or as azeotrope with addition of a suitable solvent (entrainer) and using a water separator or be removed by addition of water-withdrawing auxiliaries.
Description of embodiments
[0051] The following examples are provided to illustrate preferred embodiments of the invention and are not intended to restrict the scope thereof.
[0052] Materials
SulfoXantphos was synthesized according to the route described in MUL, W. P., et al. New, Highly Efficient Work-Up Protocol for Sulfonated
Diphosphines. Adv. Synth. Catal. . 2002, vol.344, p.293.
TPPTS was obtained from commercial sources (CAS number: 63995-70-0) Examples
[0053] Example 1 Amination process using ruthenium sulfoxantphos catalyst
In a 5ml_ glass vial (from Biotage AB), 81 mg (0.075 mmol) of benzyl alcohol was mixed with 1 gram of 28 wt % aqueous ammonia (10 equiv. to benzyl alcohol) and 1 .75 ml of water, using a magnetic stirrer, and with the addition of catalyst including [Ru( -cymene)Cl2]2 (5 mol%) and
SulfoXantphos ligand (20 mol%). The vial was then heated under microwave irradiation in a Biotage® Initiator Microwave Synthesizer, under a temperature of 180°C and for a period of 30-45 minutes. The crude product was then washed with a saturated aqueous solution of NaHCO3 extracted with ethyl acetate, dried with magnesium sulfate, and concentrated under reduced pressure. The formation of benzylamine was confirmed, and the reactant conversion rate and product selectivity both exceeded 95%.
SulfoXantphos
[0054] Example 2 Amination process using iridium sulfoxantphos catalyst
Identical procedure in Example 1 was followed, except changing the metal salt to [lr(Cp*)(NH3)2]l2- The formation of AAbenzylaniline was confirmed, and the reactant conversion rate and product selectivity were 72% and 62%, respectively.
[0055] Example 3 Amination process using palladium sulfoxantphos catalyst
Identical procedure in Example 1 was followed, except changing the metal salt to Pd(NTf2)2. The formation of AAbenzylaniline was confirmed, and the reactant conversion rate and product selectivity were 72% and 62%, respectively.
[0056] Example 4 Amination process using ruthenium TPPTS catalyst
Identical procedure in Example 1 was followed, except changing the donor ligand to TPPTS. The formation of AAbenzylaniline was confirmed, and the reactant conversion rate and product selectivity were 72% and 62%, respectively.
[0057] Comparative Example 1 Amination process in the absence of catalyst
Identical procedure in Example 1 was followed, without using any metal salt or donor ligand in the reaction mixture. Both the reactant conversation rate and the selectivity to AAbenzylaniline were lower than 1 %.
[0058] Comparative Examples 2-3 Amination process without metal salt catalyst
Identical procedure in Examples 1 -4 was followed, without using any metal salt in the reaction mixture. Both the reactant conversation rate and the selectivity to AAbenzylaniline were barely detectable (see Table 1 ).
[0059] Comparative Examples 4-7 Amination process without donor ligand
Identical procedure in Examples 1 -4 was followed, without using any donar ligand in the reaction mixture. Both the reactant conversation rate and the selectivity to AAbenzylaniline were barely detectable (see Table 1 ).
Table 1
1 The conversion rate of benzyl alcohol reactant
2 The selectivity towards /V-benzylaniline