TECHNICAL FIELD

001| The present invention relates to the synthesis L2 ₅ 5,6-hexaoetetrol (BTO), 1 ,4,5 hexanetriol, and 1,2,6 hexanetriol irora C6 sugar alcohols or R- giycosides.

BACKGROUND OF THE INVENTION

[0002] R-giycosides are known to he important intermediates for the production of fine chemicals, including sugar-based surfactants. Ordinarily, R- glycosides are prepared by Fischer glycoskiation of an R-aleohol with a sugar, which involves the acid catalyzed formation of a glycoside bond between the acetal or ketal carbon of the sugar and the hydroxy! group of the alcohol. The most common sugar is glucose. R-giycosides can also be prepared by acid catalyzed Fischer glycosidaiion of glucose residues in a polysaccharide such as starch or cellulose with an alcohol, which .results in. cleavage of the glycosidk bonds in the polysaccharide via substitution of the alcohol moieties forming the free glucoskies. Strong acids, elevated temperatures, and elevated pressures are typically needed. A mechanism compatible with milder conditions and utilizing a less expensive starting material, especially a starting material with otherwise limited applications, would be economically advantageous, especially on an industrial scale.

(0 03J Cellulose is a primary component of plant matter, is non-nutritive, and. is not widely utilized outside of the paper and textile industries. Cellulose can be converted to glucose through acid or enzymatic hydrolysis, however, hydrolysis is difficult due to the robust crystalline structure of cellulose. Known acid hydrolysis methods typically require concentrated sulfuric acid to achieve good yields of glucose. Unfortunately glucose in the presence of concentrated sulfuric acid can degrade to form hydroxymethylfurfural fi ^; I3vlF ^! ) which in turn can further polymerize into a tarry substance known as humins. The formation of HMF and tarry humins negatively impacts the yield of glucose and requires additional separation steps. Enzymatic hydrolysis methods known in the art are also impractical for industrial scale conversion of cellulose to glucose due to low reaction rates and expense and enzymes do no hydroiyze cellulose that has beers chemically modified.

|0004| Recently, Deng et al. reported the direct conversion of cellulose and methanol into methyl gl ^y cosides in the presence of an acid catalyst Deng et al., Acid-

Moderate Temperatures. 46 ("hem. Coram. 2668-70 (2010). Various dilute mineral and organic acids were tested, with sulfuric acid providing the best yield of methyl gl ^y cosides at 48%, eggin-type heteropolyacids were also tested, with H^PW^Oao yielding 53% methyl glucosides. However, the conversion of cellulose in ethanol in the presence of I-hPW^O^ resulted in a decreased yield of 42% ethyl glycosides. Solid acids were tested, with various forms of carbon hearing S<¾H groups giving the best yield of methyl glycosides at 61 %.

|0085] K ore recently, Dora et al, reported the catalytic conversion of cellulose into methyl gl ^y cosides over sulfonated carbon based catalysts. Dora et. al., Effective Cat cJ¾

Sulfonated Carbon Based Catalyst 120 Bioresource Technology 318 -21 (2012).

Carbon based catalysts containing SO ₃ H groups were synthesized and evaluated for the conversion of cellulose in methanol. Specifically, rnicrocrystalline cellulose was reacted with methanol id the sulfonated carbon, catalyst (50% by weight of the rnicrocrystalline cellulose) a.t temperatures from 175°C to 275°C. A maximum 92% yield of .methyl glucosides as obtained at a reaction time of 1.5 minutes at 275°C.

|00 6{ Tunning to sugar alcohols, here are currently no known processes for producing sugar alcohols (i.e. hexitols or pentitols such as sorbitol and xylitoi ) from alky I glycosides by h drogenation. Typically sugar alcohols are produced by heating unmodified sugars at elevated pressure in the presence of a hydrogenation catalyst

{0087] Recently, Fukuoka. et al reported that sugar alcohols could be prepared from cellulose using supported platinum or ruthenium catalysis, which showed high activity tor the conversion of cellulose into sugar alcohols with the choice of support material being important. Fukuoka et t. £ jgj&^

Alcohols. 1 18 Agnew. Chem. 5285-87 (2006), The mechanism involves the hydrolysis of cellulose to glucose followed by the reduction of glucose to sorbitol, and marxmtol. However the yields were at best around 30% conversion to sugar alcohols, and the reactions took place at an. elevated pressure of 5 MPa.

[0008] More recently, Verendel et al. reviewed one-ροί conversions of polysaccharides into small organic molecules under a variety of conditions. Verendel et al„ 11 Synthesis

] 649--?7 (201 1 ). Bydroiysis-by-hydrogenation of cellulose under acidic conditions and elevated pressure was disclosed as yielding up to 90% sorbitol, although these processes were categorized as "by no means simple.-' The direct hydrolysis-hydrogenation of starch, inulin. and polysaccharide hydrolysates to sugar alcohols by supported metals under hydrogen, without the addition of soluble acids was also disclosed. Ruthenium or platinum deposited on aluminas, a variety of metals supported on activated carbon, and zeolites were reported as suitable catalysts for cellulose degradation. The effect of transition-metal nanoclusters on the degradation of cellobiose was also disclosed, with acidic conditions yielding sorbitol. A different study looked at the conversion of cellulose with varying erystallinity into polyols over supported ruthenium catalysts, with ruthenium supported on carbon nanotubes giving the best yield of 73% hexitols.

[0009] There remains a need for cost-effective methods of producing sugar alcohols with high selectivity and through alternate pathways.

1««1»] On yet another subject, the molecule 1 ,2,5,6-hexanetetrol ΓΤΠΧΓ) is a useful intermediate in the formation of higher value chemicals. HTO and. other polyols having ferwer oxygen atoms than carbon atoms may be considered a "reduced polyols. ^" ' Corma et ah discloses generally that higher molecular weight polyols containing at least four carbon atoms can be used to manufacture polyesters, alk d resins, and

polyurethanes. Corma et al., Chemical Routes for the Transformation

Ctoicals, 107 Chem. Rev. 2443 (2007).

e0il Sorbitol hydrogenoiysss is known to produce HTO, although typically the reaction conditions are harsh and non-economical. US Patent No, 4,820,880 discloses the production of HTO involving heating a solution of a hexitol in. an organic solvent with hydrogen at an elevated temperature and pressure in the presence of a copper ohromite catalyst. Exemplary starting hexitols include sorbitol and mannitol. Water was found to adversely affect the reaction speed requiring the reaction to be performed in the absence of water and Instead using ethylene glycol raonomethyl ether or ethylene glycol monoethyl ether as the sole solvent which puts a solubility limit on the amount sorbitol that can. be reacted. Under such conditions the maximum

concentration of sorbitol that was shown to be useful was 9,4% wt/wt in ethylene glycol monomethyl ether, which provided a molar yield of about 28% HTO. In a similar reaction where the sorbitol concentration was reduced to about 2% wt/wi in glycol, monomethyl ether, the molar yield of HTO was 38% however the low concentration of reaeiants makes such a process uneconomical More recently, US Patent No. 6,8 1 ,085 discloses methods for the hydrogenohsis of 6-earhon. sugar alcohols, including sorbitol, involving reacting the starting material with hydrogen at a temperature of at least 1.21PC in the presence of a .rhenium-containing multi-metallic solid catalyst. Nickel and ruthenium, catalysts were disclosed as traditional catalysts for sorbitol hydrogcnolysis, however these catalyst predominantly produced lower level poiyois such as glycerol and propylene glycol and were not shown to detectably produce HTO or hexa.aetriois.

[0012] There remains a need tor improved cost-effective catalyst for producing HTO from sugar alcohols and a need tor alternative substrates other than sugar alcohols.

|0β13| On another background subject, the molecule 2,5

bis(nydroxymeth l)tetrahydroruran 2 _? 5«ϊ:ΓΜ ^' ΠΠ·'1 is typically prepared by the catalyzed reduction of HMF, This is impractical due to the expense of HMF, harsh reaction conditions, and poor yields. For example, US Patent No, 4,S20,880 discloses the conversion of HTO to 2,5-OMTHF in ethylene glycol monomethyl ether with hydrogen at a pressure of at least 50 atmospheres, in the presence of a copper chromite catalyst, at a temperature in. the range of I SiF'C to 23 °C.

{ ^' 0014] Overall, there is need in the art to devise economical methods for converting cellulose to alky! glycosides, for converting alky! glycosides to sugar alcohols, for converting sugar alcohols to HTO and other reduced poiyois, and for making useful derivatives of such reduced poiyois such as 2,5-HMTHF.

SUMMAR Y OF THE INVENTION

0015] The present disclosure provides, in one aspect, .methods of synthesizing R-glyeosides from acetyl cellulose pulp substantiall without, the formation of degradation products. These methods involve heating an acetyl cellulose pulp in the presence of an alcohol of the formula ROI L where R is a Cj- alky I group, and an acid catalyst selected from the group consisting of phosp onie acid and a sulfonic acid, for a time and at a temperature sufficient to form an R-glycoside fraction from the acetyl cellulose puip. in preferred practices the acetyl cellulose pulp is derived from a monocot species, for example, a species selected from the group consisting of grasses, corn stover, bamboo, wheat straw, barley straw, millet straw, sorghum straw, and rice straw. In exemplary embodiments the acid catalyst iss a sulfonic acid of the formula R ^' SO.-J i where is an alky! or cyc!oalkyl group.

| ^' 0θ.1.δ] In another aspect the present disclosure provides methods of synthesizing sugar alcohols from alky I glycosides. These methods include contacting a solution containing an R-glycoside with a hydrogenation catalyst for a time and at a temperature and a pressure sufficient to convert the -giycostde to a mixture comprising the sugar alcohol and ROH, where R is a€j-(¾ afkyl group. The hydrogenation catalyst may contain copper and/r ruthenium. When the hydrogenation catalyst comprises copper and the solution should contains less than 2 ppm sulfide anion and less than 1 ppm chloride anions. Exemplary ruthenium, catalysis are selected from the group consisting of ruthenium supported, on carbon, ruthenium supported on. a zeolite, ruthenium supported on TiCb, and ruthenium supported on Ab(>3.

|I1 17] In another aspect the foregoing method are combined providing a method of producing sugar alcohols from acety Uued cellulose puip that includes generating an R-glycoside from acetyl cellulose pulp as described above; and contacting the R-glycoside with a hydrogenation catalyst, as further described above..

| ^' 0 18| In another aspect the present disclosure provides methods of making a reduced sugar alcohol including at least one member selected from the group consisting of 1 AS hexanefriol, ,2,6-hexanetetrol , and 1,2,5,6 hexanetetro. These methods include contacting a solution comprising water and at least 20% wt wt of a starting compound selected from the group consisting of a€6 sugar alcohol and a R-glycoside of a C6 sugar, wherein R is a methyl or ethyl group, with hydrogen and a .Raney copper catalyst for a time and at a temperature and. pressure sufficient to produce a mixture containing one or more of the a reduced sugar alcohols with a combined selectively yield of at least 50% mol/moi. in most advantageous embodiments of these methods the reaction solution comprises 20-30% wt/wt water and 45-55% of a C2-C3 glycol. In an exemplary embodiment the solution comprises 20-30% wt/wt water and 50-55% wt/wt propylene glycol. These methods provide of a combined selectivity yield for ther reduced sugar alcohols of at least 70% mol/mol. One specific embodiment of these methods is a method of making .1 ,2,5 i-hexanetetrol. This specific embodiment- includes contacting a solution comprising 20-30% wt/wt water, 45-55% of propylene glycol and at least 20% wt wt of a starting compound selected from the group consisting of ^' C6 sugar alcohol and a R -glycoside of a 06 sugar, wherein R is a methyl or ethyl group, with hydrogen and a Raney copper catalyst for a time and at a temperature and pressure sufficient to produce a mixture containing the 1 ,2,5,6-hexaneietrol with a selectively yield of at least 35% wt/wt. hi most advantageous embodiments the selecti vity yield for 1 ,2,5,6-hexanetelrol is at least 40% wt/wt.

0019J In yet another aspect, there is provided methods of making

tetrahydrofuran derivatives such as 2 _> 5-bis(hydroxymethyl)tetrahydrof iran from the reduced sugar alcohol. In one embodiment these methods include contacting a mixture comprising 1 ,2,5,6-hexarseieirol with an acid catalyst selected from the group consisting of sulfuric acid, phosphonk acid carbonic acid and a water tolerant. non-Bronst.ed Lewis acid for a time and at a temperature and a pressure sufficient to convert the 1 ,2,5,6- hexanctetrol to 2,5 bis(hydroxy e hyl)tetrahydrofuran. In exemplary embodiments the non-Bronsted Lewis acid is a triiiate compound such as of bismuth riilate and scandium, inflate. In other exemplary embodiments the acid acatalyst is sulfuric acid. In a preferred embodiment the acid catalyst is pbsosphonie acid,

0020 In certain embodiments, the mixture further includes 1 ,4,5 hexanetriol and contacting with the acid catalyst further converts the 1 ,4,5 hexanetriol to 2~ hydroxyeihyi tetrahydrofuran. In certain embodiments the method includes making 2 hydroxyethyl tetrahydrofuran by contacting a mixture comprising 1,4,5 hexanetriol with the same type of acid catalysts. Further methods may further include separating the 2- hydroxyethyi tetrahydrofuran from the 2 _? 5-his(liydroxymeth>4,}tetrahydrofuran. In a -particular further embodiment the separated 2,5 bis(hydroxy e hyl) tetrahydrofuran is contacted with a rhenium oxide catalyst for a time and. a temperature sufficient to convert the 2,5-bis(hydroxymethyI)tetrahydrofuran to 1,6 hexanedioi. BRIEF DESCRIPTION OF THE DRAWINGS

[0( 2 Ij Figure 1 shows synthesis of R glycosides from acetylated cellulose over an acid catalyst in the presence of an R alcohol, and synthesis of sorbitol from R- giucosides via hydrogenolysls over a hydrogenation catalyst according to certain aspects of the invention.

{0022J Figure 2 shows synthesis of hexanetriols and 1 ,2,5.6 hexanetetrol via hydrogenolysls of sorbitol and/or a€6 R-glucoside over a Raney nickel catalyst according to other aspects of the invention, and sho ws synthesis of 2,5 (bydoxyrnethyl) teirahydroiurao from 1 ,2,5.6 hexanetetro!, and synthesis 2-hydroxyethyi.

tetrabydrofuran from 1 ,4,5 hexanetrioL each by contact with a non-Bronsted Lewis acid according to yet another aspect of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0023J Synthesis of R-glye sldes from Acetyl Cellulose Pulp. The present disclosure provides, in one aspect, methods of synthesizing R~gIyeosides from acetyl cellulose pulp in the presence of an alcohol and an acid catalyst. "R ^M as used genericaiiy in chemical formulae throughout the present disclosure represents an alky! moiety. Glycosides genericaiiy refer to a substance containing a glyeosidie bond (i.e. a type of covalent bond that joins a sugar molecule to another functional group, in this case an alkyl moiety), while giucosides genericaiiy refer to glycosides derived from glucose, (0024| The acetyl cellulose pulp most suitable for use in the methods of the present disclosure is derived from a raonocot species. Preferably, the monoeot species is selected fr nt the group consisting of grasses, corn sto ver, bamboo, wheat straw, bailey straw, millet straw, sorghum straw, and rice straw. More preferably ie monoeot species is corn stover. The acetyl cellulose pulp may he prepared by any method known in the industry. One non-limiting example of the preparation of an acetyl ated cellulose pulp, disclosed in WIPO Publication No. WO 201 /044042, involves treatment of

Hgnoeeila!osic biomass with a C .-C acid (i.e. an acid containing 1 or 2 carbon atoms) followed by washing with a Q-C-2 acid-mi scible organic solvent.

[01)25] The alcohols most suitable for use in the methods of the present disclosure are those containing between I and 4 carbon atoms: methanol, ethanof propane!, biuanol, and isomers thereof. The alcohol is preferably present in at least a 5: 1 weight ratio of alcohol to acetyl cellulose pulp

026] The acid catalyst most suitable for use in the methods of the present disclosure sulfonic acids of the formula RSO¾H or phsosphonic acid. Suitable, but non- exclusive examples of sulfonic acids include dmony!naphthaiene sulfonic acid, 6- aiBino-m-toluene8uiibnic acid (also known as 2-ammo~5-methylbenzene sulfonic acid), aikylbenzene sulfonic acids (sold as Calsoft® LAS-99, which is a linear a!kylbenzene sulfonic acid comprising a .minimum 97% of CIO-C 16 aikyl derivatives of

henzenesuiionie acid), branched dodecylbenzene sulfonic acid (sold as Caamulse® EM~ 99), and a ikyiaryl sulfonic acid (sold as Aristonie® acid). The acid catalyst may be homogeneous or heterogeneous. The acid, catalyst is preferably present in an amount of at least 0.5% by weight of the alcohol and for economic reasons, preferably not more thaii 4% by weight of the alcohol.

[0027] In a typical process the acetyl cellulose pulp is first washed in the alcohol, of choice, which is most typically methanol or ethanol, although any C C alcohol may be used. The washed acetyl cellulose pulp is combined with the alcohol and an acid catalyst in a reaction vessel and heated for a time and at a temperature sufficient to form an R-glyeoside fraction from the acetyl cellulose pulp. The reaction vessel is then cooled to room temperature. Typically the contents are filtered to remove residual unreacted pulp. The liquid fraction may be further subjected to standard separation methods such as liquid extraction or distillatio to yield a purified R~ glycoside fraction.

(β028] in the methods for synthesizing R-glycosides provided herein, reaction time and temperature can be varied. At temperatures above 250°€ degradation products negatively impact the yield ofR-glycosides. At temperatures below 150°€, the acetyl cellulose pulp is not substantially soiubilized and the yield of R-glycosides is also negatively impacted. The preferred reaction temperature is therefore 150~250°C. The range of reaction times in the methods provided herein is typically between 15 minutes and 45 minutes . Heating the acetyl cellulose pulp at these temperatures and times soiubilizes the acetyl cellulose pulp, solubiiizes hydrophobic sulfonic acid catalysts, and allows tor the formation of an R-glycoside fraction while avoiding the formation, of significant, amounts of degradation products such as HMF. [0029] Typically, the yield of R-giyeosides from these .methods is between 20% and 60% of the weight of the starting sugars in the acetyl cellulose pulp. Other side products of the methods may include !evoglucosan, levoimates, furfural s such as hydroxyrnethyl furfural (HMF). and. some soluble free sugars such, as dextrose.

(0030) Synthesis of Sugar Alcohols from R-glycosldes. The present disclosure provides, in another aspect, methods of synthesizing sugar alcohols from R- glycosid.es in the presence of hydrogen and a hydrogenation catalyst as depicted in Figure L An Sugar alcohols that can be synthesized by the present .methods include, but are not limited to, sorbitol, man toh idiiol, dnlchoi, talitol and 1 ,4-sorbitan.

{0O31J ^' The K~glycoslde can be obtained from a commercial, source or derived from any known method in the industry, in certain embodiments the R -glycoside is derived from acetyl cellulose pulp according to the previously described methods, and therefore the alkyl moiety of the R-giycoside preferably contains between 1 and 4 carbon atoms. Other catalysts such as various copper catalysts may also be useful.. When the hydrogenation catalyst is selected as one containing copper, the R-glycoside should contain minimal anions, specifically less than 2 ppm sulfide anions and less than 1 ppm chloride anions.

{0032} The hydrogenation catalyst is preferably acidic. Hydrogenation catalysis containing ruthenium, including but not limited to ruthenium supported on carbon, ruthenium supported on a zeolite, ruthenium supported on Ti<¾, and ruthenium supported on AbO j, particularly favor the synthesis of sugar alcohols. The

hydrogenation catalyst is preferably present in an amount of 0.5 -12.5% weight of the II·· glycoside, in exemplary practices using ruthenium on carbon the amount was about 5% by weight of the R-glyeoside.

[0033] The methods include combining the R-glyeoside., hydrogenation catalyst, and water in a reactor vessel. Air is removed from the reactor vessel and hydrogen is charged to a desired pressure at room temperature. The reactor is then heated to a temperature for a time sufficient to convert the R~glycoside to a mixture comprising a sugar alcohol. The temperature should he at least .1 S0°€ and the pressure at least 600 psi. Lower temperatures and pressures result in substantially reduced yield of the sugar alcohol. Suitable temperatures are between 160°€ and 220°C. Most typically the temperature should between between 1 0°C and 1 iPC, with a temperature 5 0 of about 1. SO ^' being most preferred. Suitable pressures are 600 ···· 1000 psi , with exemplary pressures being about 850 psi. The reaction lime is typically 2 - 4 hours.

[0034} Under preferred conditions the R-glycoskie conversion rate reaches nearly 100% with a molar conversion rate to sorbitol of at least 85% in certain non- limiting examples using purified -giycosides the molar conversion rate reached 97% or even 100%,

|0 3S| Synthesis of 1,2,S,6 uimne e nil ami hexanetrio . In another aspect the present disclosure provides methods of synthesizing a desired compound including at least one member selected from the group consisting of 1 ,4,5 hexanetriol, 1 ,2,5,6 hexanetetrol, and L2,6-hexanetriol, from a starting compound that is a€6 R-g!ycoside or€6 sugar alcohol present as at least 20% wt/wt in s solution comprising water by hydrogenation with .hydrogen in the presence of a Raney copper catalyst. The Raney copper catalyst may be obtained from a commercial source (e.g., R. Grace & Co, United States}- or prepared by methods known io those of ordinary ski ll in the art Typically the method of preparation of a Raney copper catalyst involves alkali treatment of a copper aluminum alloy to etch away aluminum front, a surface portion of the alloy.

[0036} Preferably, the Raney copper catalyst is deployed as a fixed bed in a reactor and is present at 5%-30% of the weight of the starting compound. In contrast to the copper ebrornite catalyst described in. US. 4,820.080 or other copper catalysts such as sponge copper (see Example 6) the reaction with Raney copper can be performed in the presence of water with nigh molar selectivity for . 1 ,2,5,6 hexanetetroh 1 ,4,5 hexanetriol and 1 ,2,6-hexanetriol , which permits the starting material to be dissolved to 50% wt/wt or more of the reaction mixture when water is the only solvent, with the combined selectivity for the desired compounds is at least 50% mol/mol.

|0037J Although in some embodiments water may be the only solvent, in particularly advantageous embodiments the solvent is a mixture of 20-30% wt/wt water and 45-55% wt/wt of a C2-C3 glycol In this case the starting material can be from 15% to 5% wt/wt of the reaction mixture, i the most advantageous embodiments the€2- C3 glycol is propylene glycol In preferred practices the starting material ( ^" C6 sugar alcohol or C6 alky! glycoside) is at least 20% wt/wt of the reaction, mixture. In exemplary embodiments the starting material is about 25% wt/wt of the reaction mixture. While not being bound by theory, it is believed the mixture of atrr and propylene glycol strikes an optimal balance of having enough water to solubiiize up 10 35% of the starting material while the presence of enough C2-C3 glycol permits more hydrogen to be solubilized in the reaction mixture and fxrrther prolonging the lifespand of the Rane copper catalyst. When the starting material is a C6 R-giycoside or C6 sugar alcohol _. , the reaction with Raney copper under these conditions has a high selectivity for HTO and 1 ,4,5 hexanetriol with these combined species accounting for over 60% and in most case over 70% of the molar yield. Typically the HTO itself accounts for at least 35% and more typically at least 40% of the molar yield from the starting material.

{0038] A first subset of the methods involves the synthesis of HTO from€6 R-glycosides in the presence of the Raney copper catalyst. The R- glycoside can be obtained from a commercial source or derived from any known method in the industry, in certain emobdi ents the R-glycoside is an ethyl gl ^y coside obtained from actylated celluslose pulp as previously described herein. The reaction, however, can use any R- g!ycoside where the R group is a CI to€4 alkyi group. Most preferably the R group is methyl or ethyl, with the most commonly available glycosides being methyl glucoside or ethyl glucoside.

10039] A second subset of the methods involves the synthesis of HTO from. C6 sugar alcohols in the presence of the same catalyst. The sugar alcohols can be obtained from a commercial source or derived from any know method in the industry. In certain embodiments the sugar alcohols may be obtained by hydrogenation of€6 sugars or C6 R-glycosides. For example, sorbitol is typically obtained by hydrogenation of glucose over a Raney nickel catalyst. Ethyi glucoss.de may be obtained hydrogenation of an acetyl cellulose pulp according to the methods previously described herein.

{0040] The methods include in one aspect, combining the R-glycoside or sugar alcohol with water and optionally and more preferably with the C2-C6 glycol in a reaction vessel preferably containing a fixed bed of Raney copper. Air is removed from the reactor vessel and hydrogen is charged to a specified pressure at room, temperature. The reactor is then heated to a temperature and for a time sufficient to convert the starting materials to-a mixture containing the desired materials, which in the case of€6 sugar alcohol or C6 R-glycoside will be a mixture of HTO and 1 ,4,5 hexanetriol Under the best, reaction conditions over 98% of the starting material is converted with a selectivity for HTO and 1 ,4,5 hexanetriol. being least 50% mol/rnol when only water is used or greater than 60% and even greater than 70% when a combination of water and €2 or c3 glycol such as propylene glycol is used as the solvent Under such conditions BTO is least 35% and more preferably at least 40% of the mo/nioi yield from the starting material.

f 0041 J In the methods for synthesizing BTO provided herein, the pressure, temperature, and reaction time can. be varied. Preferably the temperature is between !7S°C and 250°C. In exemplary embodiments the temperature 1 0°C - 215°C. The pressure is preferably between 500 psi and 2500 psi. In more typical, embodiments the pressure is between WO and 2000 psi. In. certain exemplary embodiments the pressure is about 1800 psi. In. a batch reactor, the reaction time is preferably between I hour and 4 hours, and more preferably is 3 hours. In a continuous reaction system the input stream of starting materials and the How rate of hydrogen are adjusted to obtain an optimal residence time of the starting materials in contact with the Raney copper catalyst, in typical laboratory scale examples, the hydrogen flow rate was 800- 1 00 miililiters/minute and the sorbitol solution flow rate was 0.25 milHlilers/minute obtaining an average residence time of 2 hours.

{0042 j in addition to the major hexanetr!ols discussed above, the same methods of hydrogenolysis of C6 sugars or R-giucosides produce other polyols, such as 1.2,5 hexanetriol„ 1 ,2 butanedio!, 1 ,2,3 buianetriol, propylene glycol, ethylene glycol and small amounts. Under conditions where HTO synthesis is optimum, such as in the presence of propylene glycol and water, 1.2 butan.ed.iol is the third major product ma ie after HTO and 1,4,5 hexanetriol.

{0043] Similarly, C5 sugar alcohols such as ribotol, xylite! and arahiiol, and -glycostdes may also be subject to hydrogenol sis over Raney nickel as provided herein, resulting in the production of 1 ,2.5 pentanetriol as the dominant product along with 1 ,2. bu.tanedi.ol, 1 ,2,4 butanetriol, glycerol, ethylene glycol and propylene glycol Erythriioi may also be reduced by hydrogenolysis over Raney nickel to form 1 ,2 buatnediol as the dominant product, along with 1,2,4 butatnetrioL 2,3 hutatanediol, propylene glycol arid ethylene glycol,

[0044] In ns oleesslar c e!k ½a of polyols > etralmf rof unm

derivatives An important use of BTO and the hexanetriols, particularly 1 ,4,5 hexanetrioi, is thai these molecules can readily undergo intermoleeular eyclization in the presence of an acid to form useful tetrahydrofuran (IliF) derivatives as shown in Figure 2. The cyelkation reaction is a dehydration, which releases a water molecule form the polyols. The two dominant polyois from Raney nickel catalyzed

hydrogenoiysis of a C6 sugar alcohol are HTO and 1 ,4,5 hexanetrioi. ΗΪΟ undergoes cyelkation to form 2 _; 5-bis(hydroxym.ethyl}recrahydrofuran (2,5 R THF) which is useful starting material for the preparation of polymers or 1.6 hexanedioi. Under the same conditions 1 ,4,5 hexanetriol undergoes cyelization to form 2~hydoxyethyi ietrahydyrofuran, which is a valuable solvent and useful in the pharmaceutical field. Advantageously, the acid catalyzed intramolecular cyelization of these compounds to their respective ΊΊ ΊΡ derivatives allows for easy separation of the THF derivatives from one another and from the starting sugar alcohols and hexane polyols that may remain unreacted.

JO04SJ As mentioned in preferred embodiments the acid catalyst is preferably selected from the group consisting of sulfuric acid, phsosphonic acid, carbonic acid or a water tolerant non-Bronsted Lewis acid, it was surprisingly discovered that phosphonic acid present as a homogenous catalyst works exceptionally well, while phosphoric acid does not work at ail under most conditions, ft may also be the case that heterogenous phosphonic acid catalysts uch as were used for formation of glycosides, may also be useful.

[0946] A water tolerant non-Bronsted Lewis acid is a molecular species that accepts electrons in the manner that hydrogen accept electrons in a Br nsted acid, but. uses an acceptor species other than hydrogen, and that is resistant to hydrolysis in the presence of water. Exemplary water tolerant non-Bronsted Lewis acids are trifiate compound exemplified herein by bismuth (111) trifiate and scandium (ill) trifiate. Other suitable inflates include, but are not limited to, silver (l) trifiate, zinc (II) inflate, gallium ( 111) trifiate,, neodymium (II I) trifiate, aluminum trifiate, indium (ill) trifiate, tin (11) trifiate, lanthanum (ill) trifiate, iron (11) trifiate, yttrium (ill) trifiate, thallium ⁽ !) trifiate, gadolinium (H I) trifiate, holmium (ill) trifiate, praseodymium (ΠΪ) trifiate, copper (11) trifiate, samarium (111) trifiate, ytterbium (ΪΙΪ) trifiate hydrate, and nickel (11) trifiate,. Other suitable water tolerant non-Bronsted Lewis acids include, but are not limited to. bismuth (III) chloride, indium chloride tetrahydrate, tin (U) chloride. S 4 aluminum chloride hexahydrate, silver (I) acetate, cadmium sulfate, lanthanum oxide, copper (i) chloride, copper (f l) chloride, lithium bromide, and ruthenium (III) chloride. Preferably the acid catalyst is present in the range of 0.05% to 5% mo 'rnol of the starting materials in the reaction mixture. Still another alternative acid catalyst is carbonic acid, which can be generated performing the reaction in water, under pressure and in the presence of carbon dioxide.

[0O47 The methods comprise combining HTO, any of the hexanetriols or a mixture of the same with or without any residual unreacted sugar alcohol or 6C R- glycoside with the acid catalyst. In one practice the HTO and the hexanetriols nay first be separated form one another, for example by distillation. In other practices the entire reaction mixture resulting from hydrogenolysis of the sugar alcohol or 6€ R -glycoside over Raney copper can be used and the subsequent THF derivative separated thereafter by distillation, In the case where the acid catalyst is sulfuric acid or a non-Bronsted Lewis acid compound, the reaction mixture is preferably placed under vacuum of less than 0.4 psl and heated for a time sufficient to convert the hexanetriols and the HTO to their respective tetrahydrofutan derivatives described above. When the reaction is done in the presence of carbonic acid, it performed under pressure, typical ly at least 625 psi.

[0048] In the methods provided herein, the temperature, pressure, and reaction time can be varied. When the acid catalyst, is not generated from€0% the temperature is preferably between 1 10°C and 150 ^ft C. in methods using sulfuric acid or tri Irate catalysts, the temperature, pressure, and reaction time can be varied. Preferably the temperature is between l.20°C and 1 50°C. Temperatures below 120°C fail to proxdde sufficient thermal energy to effectuate ring closure. Temperatures above 15 'C induce formation of unwanted side products. When a inflate, such as bismuth iriflate or scandium iriflate is used as the acid catalyst, the temperature is more preferably about.

1 ;>o°c.

[0049] Further, the acid catalyzed cyelkation preferably takes place under vacuum to facilitate removal of the water formed b the dehydration and subsequent recovery the desired THF derivative products. The vacuum is preferably within the pressure range of 3.0 to 6,0 psi Pressures below 3.0 psi rnay cause some of the desired THF derivatives having low boiling points and high vapor pressures to evaporate.

Pressures above 6.0 psi fail to remove the water formed during the reaction. Lower pressures such as less than 0.4 psi, or even 0.1 psi are useful for the subsequent recovery of THF derivatives with l wer vapor pressures and/or higher boiling points.

[0050] Suitable reaction times are 1 to 4 hours, In some embodiments the reactions are complete in less 1- 2 hours, and in some embodiments about 1 hour.

|005i] The non-Bronsted Lewis acid catalysts useful herein are all water tolerant Preferably the non-Bronsted Lewis acid catalyst is a metal inflate. Preferably the non-Bronsted Lewis acid catalyst is homogeneous, in particular embodiments, the non-Bronsted Lewis acid catalyst is selected from the group consisting of bismuth inflate and scandium inflate. The trifUue acid catalyst load is preferably between 0,5 mole percent and 5 mole percent based on the starting polyoi, and more preferably present in an amount of 1 mole percent based on the starting polyoi .materials.

(0052) In addition to the above compounds, other polyols obtained by Raney nickel catalyzed hydrogenation of C6 sugar alcohols or R-giucosides include, 1 ,2,6 hexanetriol, 1,2,5 hexane trio! and 1 ,2,4 hutanetrioL Acid catalyzed cydteation of these compound predominantly forms 1 -methanol tetrahydropyranol, 5~

meth ehabydrofuran 2-raethanol, and 3 -hydroxy teuahydroiuran, respectively.

[0853} f urther, a€5 sugar alcohols may also be reduced to .lower polyols over Raney nickel. When a€5 sugar alcohol is used, the dominant, reduced polyoi is 1 ,2,5 pentanetrioi. Acid catalyzed cycUxaikm of this compound predominantly forms tetrahydrofuran-2 methanol.

[0054] As shown in Table 1 below, clearly full conversion of the polyols to their cycli ed derivatives is possible. As demonstrated in Table 1 and by certain non- limiting examples, when nearly full conversion of the starting sugar alcohol was achieved, up to a 83% mol/rnol yield the cyclized ΤΉΡ derivatives can be obtained from their respective starting polyoi compounds. As used herein, ''nearly full conversion'" means at least 97% of the starting compound or compounds are consumed in the reaction. !6

Table 1

% conversion to cyclic derivatives

% cydixed total % products total %

cycfoed from conversion

products converted

products

1 ,2,5,6 hexanetetroL crude mixture 25% 17% 68,00%

1,2,5,6 hexanetetroL crude mixture 28% 21% 75.00% _o

.1 ,2,5,6 hexanetetroL pure 99% 62% 62,63%

1 ,2,5 pentanetrioL pure 6 % 50% 78.13%

1 ,2,4 butanetriol, pure 88% 76% 86,36%

1 ,2,5 hexanetrioi pure 100% 83% 83.00%

1 551 The 2,5 >is(hydroxymethyi} tetrahydrofuran and other TIW (and pyran) derivatives made from the polyols can be readily separated from one another and from imreacted polyols by distillation. The 2,5 >is{hydroxymeth.yi) tetrahydrofuran can be subsequently converted to 1,6 hexanediol via oxidation of the furan ring by contact with a rhenium oxide catalyst for a time and a temperature sufficient to convert the 2 _; 5- is(hyclroxyrrKithyl)tefxahydrofitran to 1,6 hexanediol,

Preferrably the rhenium oxide catalyst further includes silicon oxide.

[0O56J The examples that follow are provided to illustrate various aspects of the invention and are not intended to limit the invention in any way. One of ordinary skill in the art may use these examples as a guide to practice vario us aspects of the invention with different sources of acetyl cellulose pulp, different alcohols, different acid catalysts, different hydrogenaiion catalysts, different polyol mixtures, or different conditions without departing from the scope of the invention disclosed.

Example 1 : Preparation of eth l glycosides from aceytlated corn stover pulp { ^' 8057J Aeetylated corn stover pulp obtained by the method described in. PCT Publication No, WO 2013/044042 was washed with ethano!, filtered, oven dried, and ground. A 75 milliliter autoclave reactor was charged with 2 grams of the washed, ground pulp, 40 grams of denatured ethanol, and 0.2 grams of methanesulfonic acid. The reactor system was heated to 185 ^'" C. After the set temperature was reached, the reactor contents were held at IWC for 30 minutes. The reactor was cooled to room temperature and the contents were filtered. About 0.84 grams of dried, residual pulp was removed from 44, 14 grains of filtrate. The yield of ethyl glycosides in the filtrate as a weight percent of the sugars from the starting solubilized pulp was 34%.

Example 2: Preparation of methyl glycosides from aceytiated. corn stover pulp |0058j Acetylated corn stover pulp was washed with eth.an.ol» filtered, oven dried, and ground. A. 75 milliliter autoclave reactor was charged with 2 grains of the washed, ground pulp, 40 grams of methanol., and 0.2 grains o methanesulfonic acid. The reactor system was heated to 185°C. After the set temperature was reached, the reactor contents were held at 1 85°C for 30 minutes. The reactor was cooled to room temperature and the contents were filtered. About 0.93 grams of dried, residual pulp was retrieved from 44.72 grams of filtrate. The yield ofmonomethyl glycosides in. the filtrate as a molar percent of the starting sugars in the pulp was 45%.

Example 3: .Preparation of methyl glycosides from aceytiated corn stover pulp ··- various acids

|00S9| The procedure described in Example 2 was followed using various reaction times and temperatures and various acids resulting in the .molar yields of raonomethyl glucosides shown in Table 2. EM -99 is a branched dodeeylbenzene sulfonic acid (sold as Cafiraulse® EM-99), LAS-99 is alkvibenzene sulfonic acids (sold as Calsoft® LAS-99)., pTSA is para-toluene sulfonic acid, MSA is methanesulfonic acid.

I S

Example 4: Preparation of sorbitol from, methyl giueoside - lower temperature |0060| A mixture of 80,1 grams of methyl giueoside, 1 .1 grams of u/C, and 300 milliliters of water was added to an autoclave reactor luted with temperature and pressure controllers. Air was removed by bubbling hydrogen through the dip-tube 3 times. Hydrogen was charged at 850 psi at room temperature. The mixture was heated to 140°C and held, a that temperature for 3 hours. The reactor was cooled to room temperature and the remaining hydrogen was released. The reactor contents were filtered to remove the catalyst. The filtrate was evaporated under vacuum to obtain less than 5% yield of sorbitol and a large amount of unreached methyl giueoside. )

Example 5; Preparation of sorbitol from methyl giueoside ···· higher temperature {006.11 A. mixture of 80.1 grams of .meth l giueoside, 10.1 grams of Ru€, and 300 milliliters of water was added to an autoclave reactor fitted with temperature and pressure controllers. Air was removed by bubbling hydrogen through the dip-tube 3 times. Hydrogen was charged at 850 psi at room temperature. The mixture was heated to 165°C and held at that temperature for 3 hours. The reactor was cooled to room temperature and. the remaining hydrogen was released. The reactor contents were filtered to remove the catalyst. The filtrate was evaporated under vacuum to obtain 97% yield of sorbitol and a small amount, ofunreacied methyl giueoside. Example 6: Preparation of sorbitol from methyl giucoskle j ^' 0062] A mixture of 80. I grams of methyl glycoside, 10.1 grams of Ru C, and 300 milliliters of water was added to an autoclave reactor fitted, with temperature and pressure controllers. Air was removed by bubbling hydrogen through the dip-tube 3 times. Hydrogen was charged at 850 psi ai room temperature. The mixture was heated to 180°C and held at that temperature for 3 hours. The reactor was cooled to room temperature and the remaining hydrogen was released. The reactor contents were tillered to remove the catalyst The filtrate was evaporated under vacuum to obtain 100% yield of sorbitol

Example 7: Preparation of 1 ,2,5,6 hexanetetrol from methyl glycoside in water with sponge copper catalyst -· comparative example

[0063 A mixture of 80.1 grams of methyl giucoskle, 24.8 grams of sponge copper, and 300 milliliters of water was added to an autoclave reactor fitted with temperature and pressure controllers. Air was removed by bubbling hydrogen through a dip-tube 3 times, ϊ-fydrogen was charged at 850 psi at room temperature. The mixture was heated to 225°C and held at that temperature for 3 hours. The reactor was cooled to room temperature and the remaining hydrogen was released. The reactor contents were filtered to remove the catalyst. The filtrate was evaporated under vacuum to obtain 1.2,5.6- exanetetrol ( 15% wt/wt) and sorbitol (85% wt/wt).

Example 8: Preparation of 1 ,2,5.6 hexanetetrol from sorbitol in water with

Raney copper low pressure

}d064] A Raney copper catalyst was loaded into a fixed bed reactor system. The reactor was charged with hydrogen at 600 psi, and the hydrogen flow rate was maintained at 1000 milliiiters/mi ste. The reactor was heated to 225°C. A solution of \ 50% wt/wt. sorbitol and water was ted through the reactor system at a rate where LHSV : ^:: 0.5 The conversion of sorbitol was 98.5%, with a 5.8% weight yield of 1, 2,5,6- hexane!etrol Example 9: Preparation of 1 ,2,5.6 hexanetetroi from sorbitol in water with

Raney copper - high pressure

} 0065 J Raney copper catalyst was loaded into a fixed bed reactor system as in example 7. Hydrogen was charged at. 1.800 psL and the hydrogen flow rate was maintained at 1000 mi Ui liters/minute. The reactor was heated to 205°C- . Again a solution of 50% wt/wt sorbitol and water was led through the reactor system at a rate- where L.HSV - 0,5. The conversion of sorbitol was 73%, with a 28.8% selective weight yield of 1,,2,5,6-hexan.eietrol. Other polyols were present but not quantified. Example 10 Preparation of 1 ,2,5,6-hexanetetrol from sorbitol in water/propykme glycol with Raney copper

l©fl66J Solutions containing 25%wt wt sorbitol, about 25%wt/wt water and about 50% weight propylene glycol as shown in Table 3 were passed through a .Raney copper fixed bed reactor system as described in Examples 8 and 9 , at 2 HFC and a. pressure of 1800 psi. The resulting reaction mixture was analyzed for propylene glycol (PG ethylene glycol (EG) 1 ,2 hexanedio! ( 1.2-HDO), 1 ,2 butanedso! (L2-BDO). 1 ,2,6 hexanetriol ( ,3,6-HTO), 1,4,5 hexanetriol (1 A5-HTO) and 1 ,2,5,6 hexanetetroi (1 ,2,5,6-HTO) with the results shown in Table 4.

Table 3

Example i 1 : Conversion of 1,2,5.6 hexanetetrol to 2,5- bis{hydroxymeihyl)leirahydrofura.n with sulfuric acid

f806?] A. solution of 0.6 grams of concentrated sulfuric acid and 36 grams of 1.2,5,6- exaneietrol was reacted under vacuum ('-20 ion) at I20°C for 1 hour. The solution was cookd to room temperature and then neutralized by adding 50 milliliters of water and 2 grams of calcium carbonate. The solution was .filtered and then

concentrated under vacuum to obtain about a 96% yield of 2,5- bis(hydroxyTnethyOtc rabydrofaran.

Example 12: ("(inversion of i ,2.5,6 hexaneteirol to 2,5

bis(hydroxymetbyi)ie†rahydroiur&n with bismuth Inflate

|;0068j A solution of 1 10 milligrams of bismuth trifiate and 151.41 grams of a sorbitol, bydrogenolysis mixture containing 33% wt/wt 1 2,5,6~hexaneietro! was reacted under vacuum (less than 5 ton'} at 130 ^'5 C for 2 hours The solution was cooled to room temperature. A sample analyzed by high performance liquid chromatography (H.PLC) showed Ml conversion of the 1 ,2,5,6-hexanetetrol and indicated that 93.4% of the theoretical yield of 2.5"bis(hydroxymeihyI)tetrahydro†iiran was obtained.

Example J 3: Conversion of 1 ,2,5,6 hexane etrol to 2,5

bis(hydroxyrnethyl)letmhydrofuran with scandium triDate

[0069] A solutio of 89 milligrams of scandium trif!ate and 163,57 grams of a sorbitol hydrogenolysis mixture containing 33% wi/wt I..2,5,6-hexanetet.ro! was reacted under v cuum (less than 5 torr) at I30 ^C' C for 2 hours. The solution was cooled io room temperature. A sample analyzed by IIPLC showed foil conversion of the 1 ,2,5,6·· hexanetetrol and indicated that 91.3% of the theoretical yield of 2,5- bis(hydroxymethyi)tetra.hydrotnran was obtained.

Example 14: Conversion of 1 ,2,5,6 hexaneietro! to 2,5- his(hydroxymethyi)tetrahydrofaran with bismuth trilfate

|007 ] A mixture of 544 milligrams of 1,2,5,6 hex.an.etet.rol and 24 milligrams of bismuth inflate was reacted under vacuum (200 torr ) at 130°C for 2 hours. The resulting residue was cooled to room temperature. A sample analyzed by gas chromatography indicated that, the residue contained 1 .24% (by weight) of the starting hexane- 1 ,2,5,6-tef.rol and 61.34% (by weight) of the desired (ietrahydrofuran-2 ,5 diy!)di ethanol.

Example 14: Conversion of 1,2,5,6 hexanetetrol to 2,5- bisthydroxymethylitetrahydroturan with phsosphonie acid

|O07lj A three neck, 500 ml, round bottomed flask equipped with a. PT.FE coated magnetic stir bar was charged with 300 g of a mesophasic, oil-white oil comprised of -42 wt.% 1 ,2,5,6-hexaneteirol and 3.44 g ofphosphonic acid ([-EPO3, 5 mol% relative to ΗΊΌ). One neck was capped with a ground glass joint, the center with a sleeved thermowell adapter fitted with a thermocouple, and the last a short path condenser affixed to a dry-ice cooled 250 niL pear-shaped receiver. While vigorously stirring, the mixture was heated to 150°€ under vacuum (20 torr) for 4 hours. After this time, the vacuum was broken and residual light colored oil cooled, and weighed, furnishing 3.06 g, OC analysis indicated that. 95 mol% of the ΗΊΌ had been converted and the selectivity yield for 2,5-bis(hydrox neihyl.)t.eirahydrofuraii. was 88%- mol/mol. Example 16: Preparation of teirahydrofean-2~ methanol from 1,2,5 pentaneiiiol.

[(M 72J A mixture of 1.05 grams of pentane-l ,2,5-triol aid 5? milligrams of bismuth triflate was reacted under vacuum (200 torr) at 130°C for 2 hours. The resulting .residue was cooled to room temperature. A sample analyzed by gas chromatography indicated that the residue contained 36.24% (by weight) of the starting perit.an.e~ 1,2,5- trio! and 50.37% (by weight) of the desired (tetrahydrofuran-2-yl )meilianol.

Example 17: Preparation of 3- tetxahydtofuranol from 1 ,2,4 butanetrioi [0073] A mixture of 1.00 grams of 1 ,2,4 butanetrioi and 62 milligrams of bismuth triflate was reacted under vacuum (200 torr) at 130 ^'":: € for 2 hours. The resulting residue was cooled to room temperature. A sample analyzed by gas chromatography indicated Chat the residue contained 12.56% (by weight) of the starting butane- l ,2,4~triol and 76.35% (by weight) of the desired tetrahydroforan-3-ol .

Example 18: Preparation of S-raethy (teirahydroft-.ran-2- methanol from 1.2,5

hexaneirioi

00 4] A mixture of 81 7 milligrams ,2,5 hexanetriol and 40 milligrams of bismuth triflate was reacted under vacuum (200 to.fr) at Bi 'C for 2 hours. The resulting residue was cooled to room temperature, A sample analyzed by gas chromatography indicated that the starting hexane-! ,2,5-triol was completely converted and that the residue contained 75.47% (by weight} of the desired methyltetrahydrornran-2- methanoL Also produced at. a 7.42% weight yield was the isomer 2-methyl-4~ tetrahydropyranol.

Example 1.9 General analytical protocol for ring cyclization f ^' 75] Upon completion of the reactani dehydrative eyeiizations as described in examples 1 1 -18, a sample of the reaction mixture was withdrawn and diluted with enough wafer to produce a 1.-5 oig/m t solution. An aliquot of this was then subjected to high performance liquid chromatography (HPLC) for quantification using an Agilent 1200® series instrument and employing the following protocol: A 1.0 μΐ, sample was injected onto a 300 mm x 7.8 mm. BioRad® organic acid column that was pre- equilibrated wHh an 5 nM sulfuric acid mobile phase and flowed at a rate of 0.800 mL/min. The mobile phase was held isocratic and molecular targets eluting from the column at signature times determined by refractive index detection (RID). A quantitative method for each analyte was established prior to injection, applying linear regression analysis with correlation coefficients of at least 0.995,