Preparation of 2,5,6-trihydroxy-3-hexenoic acid and 2,5-dihydroxy-3-pentenoic acid and esters thereof from C6 and C5 sugars

Abstract

Preparation of 2,5,6-trihydroxy-3-hexenoic acid and 2,5-dihydroxy-3-pentenoic acid and esters thereof from C6 and C5 sugars in the presence of a Lewis Acid material, wherein the yield of the 2,5,6-trihydroxy-3-hexenoic acid or 2,5-dihydroxy-3-pentenoic acid or esters thereof exceeds 15%. The process including the steps of contacting a saccharide composition including one or more C6 and/or C5 saccharide units with a Lewis Acid material; and recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof.

Claims

1. A process for the preparation of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof of the formula
R′—HC═CH—CHOH—COOR  (I) wherein R is selected from the group consisting of —H and C.sub.1-C.sub.8-alkyl; and R′ is hydroxymethyl or 1,2-dihydroxyethyl; the process comprising the steps of: a. contacting a saccharide composition comprising one or more C6 and/or C5 saccharide units with a Lewis Acid material; and b. recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof, wherein the Lewis Acid material comprises a framework structure and an active metal, wherein the process results in a yield of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof above 15%, and a yield of methyl lactate below 30%, wherein a concentration of alkali metal ions present in an environment of the Lewis Acid material is kept at a concentration of less than 0.13 mM or at an amount of less than 0.5 wt % of a catalyst composition, wherein the process is conducted under continuous conditions.

2. The process according to claim 1, wherein the esters of 2,5,6-trihydroxy-3-hexenoic acid or 2,5-dihydroxy-3-pentenoic acid are 2,5,6-trihydroxy-3-hexenoic acid methyl ester and 2,5-dihydroxy-3-pentenoic acid methyl ester.

3. The process according to claim 1, wherein the saccharide composition comprises one or more C6 and/or C5 saccharide units selected from the group consisting of sucrose, xylose, mannose, tagatose, galactose, glucose, fructose, arabinose, inulin, amylopectin and sugar syrup.

4. The process according to claim 1, wherein the saccharide composition contains at least 10% by weight of saccharide units.

5. The process according to claim 1, wherein the saccharide composition comprises a polar solvent.

6. The process according to claim 5, wherein the saccharide composition comprises one or more solvents selected from the group consisting methanol, ethanol, DMSO and water.

7. The process according to claim 1, wherein any alkali metal ion present in the saccharide composition is present in a concentration of less than 0.3 mM.

8. The process according to claim 1, wherein the Lewis acid material contains less than 0.5 wt % of alkali metal ion.

9. The process according to claim 1, wherein the Lewis Acid material is Sn-BEA.

10. The process according to claim 1, wherein the Lewis Acid material is Sn-MCM-41.

11. The process according to claim 1, wherein the saccharide composition is contacted with the Lewis Acid material at a temperature of from 30 to 190° C.

12. The process according to claim 11, wherein the temperature is from 80 to 170° C.

13. The process according to claim 1, wherein the saccharide composition is contacted with the Lewis Acid material for a period of at least 10 seconds.

14. The process according to claim 1, wherein the weight hourly space velocity is between 0.005 and 10 h.sup.−1.

15. A process for the preparation of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof of the formula
R′—HC═CH—CHOH—COOR  (I) wherein R is selected from the group consisting of —H and C.sub.1-C.sub.8-alkyl; and R′ is hydroxymethyl or 1,2-dihydroxyethyl; the process comprising the steps of: a. contacting a saccharide composition comprising one or more C6 and/or C5 saccharide units with a Lewis Acid material; and b. recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof, wherein the Lewis Acid material comprises a framework structure and an active metal, wherein the process results in a yield of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof above 15%, wherein a concentration of alkali metal ions present in an environment of the Lewis Acid material is kept at a concentration of less than 0.13 mM or at an amount of less than 0.5 wt % of a catalyst composition, wherein the process is conducted under continuous conditions, wherein the alpha-hydroxy-beta-ene-acids or esters thereof are subjected to a derivatization selected from acylation, silylation, alkylation, hydrolysis, hydrogenation, and amidation.

16. The process according to claim 1, wherein step b) includes a purification of the alpha-hydroxy-beta-ene-acids or esters thereof.

17. The process according to claim 1, wherein the concentration of alkali metal ions present in the environment of the Lewis Acid material is kept at a concentration of less than 0.13 mM.

18. A process for the preparation of alpha-hydroxy-beta-ene-acids or esters thereof of the formula
R′—HC═CH—CHOH—COOR  (I) wherein R is selected from the group consisting of —H and C.sub.1-C.sub.8-alkyl; and R′ is hydroxymethyl or 1,2-dihydroxyethyl; the process comprising the steps of: a. contacting a saccharide composition comprising one or more C6 and/or C5 saccharide units with a Lewis Acid material; and b. recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof, wherein the Lewis Acid material is a tin catalyst, wherein the process results in a yield of alpha-hydroxy-beta-ene-acids or esters thereof above 15%, and a yield of methyl lactate below 30%, wherein a concentration of alkali metal ions present in an environment of the Lewis Acid material is kept at a concentration of less than 0.13 mM or at an amount of less than 0.5 wt % of a catalyst composition, wherein the process is conducted under continuous conditions.

19. A process for the preparation of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof of the formula
R′—HC═CH—CHOH—COOR  (I) wherein R is selected from the group consisting of —H and C.sub.1-C.sub.8-alkyl; and R′ is hydroxymethyl or 1,2-dihydroxyethyl; the process comprising the steps of: a. contacting a saccharide composition comprising one or more C6 and/or C5 saccharide units with a Lewis Acid material; and b. recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof, wherein the Lewis Acid material is tin salt selected from the group consisting of tin chloride (SnCl.sub.4 and SnCl.sub.2), tin fluoride (SnF.sub.4 and SnF.sub.2), tin bromide (SnBr.sub.4 and SnBr.sub.2), tin iodide (Snl.sub.4 and Snl.sub.2), tin acetylacetonate (SnC.sub.10H.sub.14O.sub.4), tin pyrophosphate (Sn.sub.2P.sub.2O.sub.7), tin acetate (Sn(CH.sub.3 CO.sub.2).sub.4 and Sn(CH.sub.3 CO.sub.2).sub.2), tin oxalate (Sn(C.sub.2O.sub.4).sub.2 and SnC.sub.2O.sub.4), tin triflate ((CF.sub.3 SO.sub.3).sub.2 Sn and (CF.sub.3 SO.sub.3).sub.4 Sn)) and mixtures thereof, wherein the process results in a yield of 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or esters thereof above 15%, and a yield of methyl lactate below 30%, wherein a concentration of alkali metal ions present in an environment of the Lewis Acid material is kept at a concentration of less than 0.13 mM or at an amount of less than 0.5 wt % of a catalyst composition, wherein the process is conducted under continuous conditions.

20. The process according to claim 19, wherein the alpha-hydroxy-beta-ene-acids or esters thereof are subjected to a derivatization selected from the group consisting of acylation, silylation, alkylation, hydrolysis, hydrogenation, and amidation.

Description

EXAMPLES

(1) Preparation of Sn-BEA

(2) A. Process for the Preparation of Sn-BEA Via a Direct Synthesis Method (HF Route).

(3) Sn-Beta zeolites were synthesized by modifying the route described by Valencia et al. [U.S. Pat. No. 6,306,364 B1] In a typical synthesis procedure, 30.6 g f tetraethyl orthosilicate (TEOS, Aldrich, 98%) was added to 33.1 g of tetraethylammonium hydroxide (TEAOH, Sigma-Aldrich, 35% in water) under careful stirring and forming a two-phase solution. After stirring for .sup.˜60 min, one phase is obtained and tin(IV) chloride pentahydrate (SnCl4.5H.sub.2O, Aldrich, 98%) dissolved in 2.0 mL of demineralized water was added drop wise. Stirring was maintained for several hours to allow ethanol formed from the hydrolysis of TEOS to evaporate. Finally, 3.1 g hydrofluoric acid (HF, Fluka, 47-51%) in 1.6 g of demineralized water was added to the gel, yielding a solid with the molar composition; 1.0Si:0.005Sn:0.02Cl.sup.−:0.55TEA.sup.+:0.55F:7.5H.sub.2O. All samples were then homogenized and transferred to a Teflon-container placed in a stainless steel autoclave and subsequently placed at 140° C. for 14 days. The solid was recovered by filtration and washed with demineralized water, followed by drying overnight at 80° C. in air. The organic template contained within the material was removed by heating the sample at 2° C./min to 550° C. in static air, and this temperature was maintained for 6 h.

(4) B. Process of Preparing Sn-BEA Via a Post-Treatment Method.

(5) Sn/Beta (Si/Sn=125) was prepared according to the procedure described in ChemSusChem 2015, 8, 613-617. Commercial zeolite Beta, viz. (Zeolyst, Si/Al 12.5, NH4.sup.+ form) is calcined at 550° C. for 6 h to obtain the H.sup.+ form and treated with 10 g of concentrated nitric acid (HNO.sub.3, Sigma-Aldrich, ≥65%) per gram of zeolite Beta powder for 12 h at 80° C. The resulting solid is filtered, washed with ample water and calcined at 550° C. for 6 h using a ramp of 2° C./min to obtain the dealuminated Beta. This solid is impregnated by incipient wetness methodology with a Si/Sn ratio of 125. For this purpose, tin(II) chloride (0.128 g, Sigma-Aldrich, 98%) is dissolved in 5.75 mL water and added to the dealuminated 5 g of Beta. After the impregnation process, the samples are dried 12 h at 110° C. and calcined again at 550° C. for 6 h.

(6) C. Process of Preparing Sn-MCM-41

(7) The ordered mesoporous stannosilicate, Sn-MCM-41, was prepared according to the route described in Green Chemistry, 2011, 13, 1175-1181. In a typical synthesis, 26.4 g of tetraethylammonium silicate (TMAS, Aldrich, 15-20 wt % in water, ≥99.99%) was slowly added to a solution of 13.0 g of hexadecyltrimethylammonium bromide (CTABr, Sigma, ≥99.0%) dissolved in 38.0 g of water, and the mixture was allowed to stir for approx. 1 hour. At this point, SnC1.sub.4.5H.sub.2O and hydrochloric acid (HCl, Sigma-Aldrich, min. 37%) in 2.1 g of water were added dropwise to the solution and allowed to stir for 1.5 h. To this solution 12.2 g of TEOS was added and stirred for 3 h, leading to a gel composition of 1.0Si:0.005Sn:0.44CTABn0.27TMA:0.08Cl.sup.−:46H.sub.2O. The samples were then transferred to a Teflon-lined container placed in a stainless steel autoclave and placed in a pre-heated oven at 140° C. for 15 h. The solid was recovered by filtration, washed with ample water and then dried overnight at 80° C. The material was finalized by calcination, where the sample was heated to 550° C. at 2° C./min in static air and maintaining this temperature for 6 h.

Example 1

(8) a. In a typical reaction, 0.150 g of alkali-free Sn-Beta zeolite (Si/Sn=150), 0.45 g of sugar and 15.0 g of anhydrous methanol (15.0 g, Sigma-Aldrich, >99.8%) is added to a stainless steel pressure vessel (40 cc, Swagelok). The reactor is closed and placed in a preheated oil bath at 160° C. under stirring at 700 rpm and allowed to react for 20 hours. After reaction the vessel is rapidly cooled by submerging the reactor in cold water. The sugar derivative was identified by GC-MS (Agilent 6890 with a Phenomenex Zebron ZB-5 column equipped with an Agilent 5973 mass selective detector). b. Alternatively, 4.0 g of anhydrous methanol (Sigma-Aldrich, >99.8%), 0.36 g sugar (Sigma-Aldrich, >99%) and the desired amount of alkali-free Sn-Beta were added to a 5 mL glass microwave vial (Biotage). The reaction vessel was heated to 160° C. while stirred at 600 rpm for 2 hours in a Biotage Initiator+ microwave synthesizer. After cooling, samples were filtered and subsequently analyzed. In relevant reactions, alkali salt was added by replacing the appropriate portion of the methanol solvent with a 1 mM standard solution of K2CO3 (Sigma-Aldrich, 99.0%) in methanol to obtain the required concentration.

(9) Anhydrous tin(IV) chloride (Sigma Aldrich, St. Louis, Mo., USA) was dissolved in d6-DMSO (Sigma Aldrich) to a final concentration of 10% (w/v). Carbohydrates including glucose, fructose, ribose, arabinose, inulin, xylan and amylopectin (starch) (all from Sigma Aldrich, Megazymes (Bray, Ireland) Carbosynth (Compton, UK)) were dissolved in d6-DMSO at concentrations corresponding to 0.3-1 M saccharide monomer (30-100 mg/500 μl final volume) in 1.5 ml Eppendorf safelock tubes. Water (D20) was added to a final volume ratio (v/v) of 0, 5, 10, 15 or 20%. Anhydrous tin(IV) chloride was added from the stock solution, typically to a final carbohydrate:catalyst molar ratio of 10:1. Reaction mixtures containing carbohydrate in d6-DMSO with 10-vol % catalyst and defined water fraction were incubated while shaking at 600 rpm at 99° C. for 20 hours in an Eppendorf Thermomixer. Samples were transferred to 5 mm NMR sample tubes after the reaction and immediately analyzed at 30° C. by 1H and 13C NMR spectroscopy. The samples had some miscoloring due to humin formation, but remained transparent (albeit slightly colored) throughout the experiments with the best THA yields. Yields were estimated by comparing the 13C NMR signal integrals of a substrate solution with the signal integrals? of the product mixture (both normalized to the d6-DMSO signal) and by integrating the signals not overlapping the hydroxyl-region of an 1H NMR spectrum, which includes lactate and lactate oligomer methyl groups, 3-deoxy compound methylene groups and THA olefin as well as HMF furan hydrogen signals. Lactate molar fractions were divided by a factor of two when deriving the yields as % molC from C6 sugars. In situ experiments were performed by transferring the reaction mixtures from the 1.5 ml Eppendorf safelock tubes directly to NMR tubes followed by heating the NMR tubes in the spectrometer to the desired temperature. The reaction progress was then followed by pseudo-2D spectra containing series of 1H or 13C NMR spectra. For signal identification, homo- and heteronuclear assignment spectra were recorded for glucose- and xylose derived? reaction mixtures. All spectra were recorded on a Bruker (Fallanden, Switzerland) Avance II 800 MHz spectrometer equipped with a TCI Z-gradient CryoProbe and an 18.7 T magnet (Oxford Magnet Technology, Oxford, U.K.) or on a Bruker Avance III 600 MHz spectrometer equipped with a room temperature smart probe. NMR spectra were recorded, processed and analyzed with Bruker Topspin 2.1 or Bruker Topspin 3.0.

Examples 2-3

(10) Example 1b was followed where the temperature of the process was increased to 170° C. and decreased to 14° C., respectively. The catalyst used is Sn-Beta (Si/Sn=150) according to method A.

(11) TABLE-US-00001 TABLE 1 Yield of 2,5,6-trihydroxy-3-hexenoic acid methyl ester (THM) from a C6 sugar (glucose) at varying process temperatures. Example Temperature (° C.) Yield (%) 1 140 12 2 160 14.5 3 170 17.3

(12) As seen in Table 1, increasing the temperature provides increasing yields.

Examples 4-6

(13) Example 1a was followed where the starting material was xylose instead of glucose at 160° C., and different catalysts were used.

(14) TABLE-US-00002 TABLE 2 Yield of 2,5-dihydroxy-3-pentenoic acid methyl ester (DPM) from a C5 sugar (xylose) with different catalysts. Example Catalyst Yield (%) 4 Method A (Si/Sn = 200) 27.5 5 Method A (Si/Sn = 150) 24.5 6 Method B (Si/Sn = 125) 18.1

(15) As seen in Table 2, method A for the preparation of the catalyst provides increased yields under the conditions given.

Examples 7-10

(16) Example 1b was followed where the starting material was xylose at 160° C. and different initial concentrations in wt % of xylose in the reaction composition.

(17) TABLE-US-00003 TABLE 3 Yield of 2,5-dihydroxy-3-pentenoic acid methyl ester (DPM) at 160° C. Catalyst used is Sn-Beta (Si/Sn = 150) according to method A. Example Xylose concentration wt % Yield DPM (%) 7 4.3 26 8 8.3 32 9 15 30 10 23 30

(18) As observed in Table 3, it seems that at a higher xylose concentration results in increased yields of DPM until a threshold yield of DPM is achieved at a xylose concentration of around 7 wt % and possibly with a little peak around 8-9 wt %. This fact is surprising since sugar experiments are typically conducted in concentrations below 5 g/L. It is especially interesting to note that a concentration as high as 30 g/L produces DPM in a comparable yield as the lower concentrations. It is unusual to obtain high yields of products when using high concentrations of saccharides.

Examples 11-16

(19) Example 1b was followed where the starting material was xylose at 160° C., and different amounts of catalyst leading to different catalyst to substrate ratios were used.

(20) TABLE-US-00004 TABLE 4 Yield of 2,5-dihydroxy-3-pentenoic acid methyl ester (DPM) and methyl lactate (ML), xylose concentration 9 wt %. Catalyst used is Sn-Beta (Si/Sn = 150) according to method A. Mass ratio Example catalyst/substrate DPM Yield (%) ML Yield (%) 11 0 0 1 12 0.125 15 25 13 0.25 23 24 14 0.5 32 15 15 0.75 30 15 16 1 30 14

(21) As shown in Table 4, when the ratio of catalyst/substrate is 0.5 then the highest yield of DPM was obtained. Accordingly, the yield of DPM can be optimized by adjusting the ratio of catalyst/substrate. It is very interesting to note that the yield of ML decreased concomitantly with the increase in DPM. This change in selectivity of the catalyst when different amounts of catalyst were used is very surprising and has not been reported earlier. In order to obtain a high yield of DPM, the ratio of catalyst/substrate should be above 0.25.

Examples 17-24

(22) Example 1b was followed where the starting material was xylose at 160° C., and different concentrations of alkali metal ion (K.sub.2CO.sub.3) in methanol were used.

(23) TABLE-US-00005 TABLE 5 Yield of 2,5-dihydroxy-3-pentenoic acid methyl ester (DPM) and methyl lactate (ML), xylose concentration 9 wt %. Catalyst used is Sn-Beta (Si/Sn = 150) according to method A. Concentration of K.sub.2CO.sub.3 in Example methanol (mM) DPM Yield (%) ML Yield (%) 17 0 32 13 18 0.05 21 27 19 0.1 14 34 20 0.15 11 34 21 0.25 8 35 22 0.5 4 29 23 0.75 2 23 24 1 2 16

(24) As seen in Table 5, the concentration of alkali metal ion has an effect on the yield of DPM. As exemplified here for the case of K.sub.2CO.sub.3, a concentration of alkali metal ion below 0.1 mM led to DPM yields above 20%. ML yield must be kept below 30%. Therefore DPM is the main product found in the reaction mixture.

Examples 25-30

(25) Example 1a was followed where the starting materials were other sugars (instead of glucose) at 160° C. Catalyst used is Sn-Beta (Si/Sn=125) according to method B.

(26) TABLE-US-00006 TABLE 6 Yield of 2,5,6-trihydroxy-3-hexenoic acid methyl ester (THM) from different sugars. Catalyst used is Sn-Beta (Si/Sn = 125) according to method B. Example Sugar Yield (%) 25 Fructose 17.8 26 Mannose 14.7 27 Sorbose 17.3 28 Galactose 11.5 29 Tagatose 9.0 30 Sucrose 15.3

(27) As seen in Table 6, all the tested C6 monosaccharides and disaccharides produce THM.

Examples 31-33

(28) Example 1 was followed at 160° C. and different catalysts were used, said catalysts being prepared according to examples B and C.

(29) TABLE-US-00007 TABLE 7 Yield of 2,5,6-trihydroxy-3-hexenoic acid methyl ester (THM) from different catalysts Example Catalyst Yield (%) 31 Method A (Si/Sn = 125) 16.1 32 Method B (Si/Sn = 125) 13.8 33 Method C (Si/Sn = 125) 17.7

(30) As seen in Table 7, method C for the preparation of the catalyst is preferred.

Examples 34-38

(31) Example 1c was followed at 90° C. and different amounts of water were added in DMSO.

(32) TABLE-US-00008 TABLE 8 Yield of 2,5,6-trihydroxy-3-hexenoic acid (THA) with different amounts of water Example Water (wt %) THA Yield (%) HMF Yield (%) 34 0 20 42 35 5 47 32 36 10 49 25 37 15 48 22 38 20 43 20

(33) As seen in Table 8, the presence of 5-15 wt % of water in the solvent mixture is preferred.

Examples 39-44

(34) Example 1c was followed at 90° C. and 2,5-dihydroxy-3-pentenoic acid from different sugars in DMSO.

(35) TABLE-US-00009 TABLE 9 Yield of 2,5,6-trihydroxy-3-hexenoic acid (THA) and 2,5-dihydroxy-3-pentenoic acid (DPA) from different sugars Example Sugar THA Yield (%) DPA Yield (%) 39 Glucose 49 — 40 Sucrose 44 — 41 Fructose 44 — 42 Xylose — 49 43 Arabinose — 48 44 Inulin 42 —

Example 45

(36) Production, purification and identification of 2,5,6-trihydroxy-3-hexenoic acid methyl ester (THM) and 2,5-dihydroxy-3-pentenoic acid methyl ester (DPM)

(37) Production and Purification of 2,5,6-Trihydroxy-3-Hexenoic Acid Methyl Ester (THM)

(38) Post-treated Sn-Beta (3 g), Glucose (12 g, Sigma-Aldrich, >99.0%) and methanol (200 g, Sigma-Aldrich, >99.8%) were added to the Teflon liner of a 1 L autoclave reactor (Autoclave Engineers). The reactor was sealed and heated to 160° C. while stirred at 450 rpm for 16 hours. The reaction mixture was then cooled and filtered and resulted in the crude reaction mixture. The crude reaction mixture was concentrated under reduced pressure at 40° C. 2.1 g of the concentrate was dissolved in methanol, evaporated onto Celite and purified by flash column chromatography (silica gel 15 40 Mesh, CH.sub.2Cl.sub.2->20:1 CH.sub.2Cl.sub.2:MeOH) affording 0.30 g of pure THM.

(39) Production and Purification of 2,5-Dihydroxy-3-Pentenoic Acid Methyl Ester (DPM)

(40) Post-treated Sn-Beta (7.5 g), Xylose (30 g, Sigma-Aldrich, >99%), demineralized water (3 g) and methanol (300 g, Sigma-Aldrich, >99.8%) were added to the Teflon liner of a 1 L autoclave reactor (Autoclave Engineers). The reactor was sealed and heated to 160° C. while stirred at 450 rpm for 16 hours. The reaction mixture was then cooled and filtered and resulted in a crude reaction mixture including 15-20% DPM. The crude reaction mixture was concentrated under reduced pressure. The concentrate was dissolved in methanol, evaporated onto Celite and purified by dry column vacuum chromatography (silica gel 60 (15-40 μm), heptane->ethyl acetate), affording DPM of >94% purity (GC-MS).

(41) Analysis and Identification

(42) NMR experiments were recorded on a Bruker Ascend 400 spectrometer, 1H-NMR was recorded at 400 MHz and 13C-NMR was recorded at 100 MHz. The chemical shifts are given in ppm relative to the residual solvent signals, and the chemical shifts are reported downfield to TMS. HRMS was recorded on an LC-TOF (ES).

2,5,6-trihydroxy-3-hexenoic Acid Methyl Ester (THM)

(43) 1H-NMR (400 MHz, CD.sub.3OD): δ (ppm) 5.93 (dd, J=15.3, 4.3 Hz, 1H), 5.88 (dd, J=15.3, 4.1 Hz, 1H), 4.69 (d, J=4.1 Hz, 1H), 4.14 (ddd, J=6.7, 4.7, 4.1 Hz, 1H), 3.73 (s, 3H), 3.51 (dd, J=10.9, 4.7 Hz, 1H) 3.45 (dd, J=10.9, 6.7 Hz, 1H). .sup.13C-NMR (100 MHz, CD3OD): δ (ppm) 174.6, 133.8, 129.4, 73.4, 72.2, 67.0, 52.6. HRMS (ESI+) m/z calculated for C.sub.7H.sub.12O.sub.5 [M+Na]+: 199.0577; found: 199.0572.

2,5-dihydroxy-3-pentenoic Acid Methyl Ester (DPM)

(44) .sup.1H NMR (400 MHz, CD.sub.3OD) δ 5.89 (dtd, J=15.5, 5.0, 1.4 Hz, 1H), 5.72 (ddt, J=15.5, 5.7, 1.7 Hz, 1H), 4.76 (s, 4H), 4.58 (ddt, J=5.7, 1.4, 1.4 Hz, 1H), 3.99 (ddd, J=5.0, 1.6, 1.4 Hz, 2H), 3.63 (s, 3H), 3.21 (p, J=3.3, 1.6 Hz, 1H). .sup.13C NMR (101 MHz, CD.sub.3OD) δ 173.2, 132.2, 126.8, 70.9, 61.3, 51.2

EMBODIMENTS

(45) 1. A process for the preparation of alpha-hydroxy-beta-ene-acids or esters thereof of the formula
R′—HC═CH—CHOH—COOR  (I) wherein R is selected from the group consisting of —H and C.sub.1-C.sub.8-alkyl; and R′ is hydroxymethyl or 1,2-dihydroxyethyl;
the process comprising the steps of: a. contacting a saccharide composition comprising one or more C6 and/or C5 saccharide units with a Lewis Acid material; and b. recovering 2,5,6-trihydroxy-3-hexenoic acid and/or 2,5-dihydroxy-3-pentenoic acid or the esters thereof.

(46) 2. The process according to embodiment 1, wherein the esters of 2,5,6-trihydroxy-3-hexenoic acid or 2,5-dihydroxy-3-pentenoic acid are 2,5,6-trihydroxy-3-hexenoic acid methyl ester and 2,5-dihydroxy-3-pentenoic acid methyl ester.

(47) 3. The process according to any one of embodiments 1 or 2, wherein the saccharide composition comprises one or more C6 and/or C5 saccharide units selected from the group consisting of sucrose, xylose, mannose, tagatose, galactose, glucose, fructose, arabinose, inulin, amylopectin and sugar syrup.

(48) 4. The process according to any one of embodiments 1 to 3 wherein the saccharide composition contains at least 10% by weight of saccharide units.

(49) 5. The process according to any one of embodiments 1-4, wherein the saccharide composition comprises a polar solvent.

(50) 6. The process according to embodiment 5, wherein the saccharide composition comprises one or more solvents selected from the group consisting methanol, ethanol, DMSO and water.

(51) 7. The process according to any one of embodiments 1 to 6, wherein any alkali metal ion present in the saccharide composition is present in a concentration of less than 0.3 mM.

(52) 8. The process according to any one of embodiments 1 to 6, wherein the concentration of alkali metal ion in the saccharide composition is less than 0.3 mM.

(53) 9. The process according to any one of embodiments 1 to 8, wherein the Lewis acid material contains less than 0.5 wt % of alkali metal ion.

(54) 10. The process according to any one of embodiments 1 to 9, wherein the Lewis Acid material is Sn-BEA.

(55) 11. The process according to any one of embodiments 1 to 10, wherein the Lewis Acid material is Sn-MCM-41.

(56) 12. The process according to any one of embodiments 1 to 11, wherein the Lewis Acid material is tin salt, such as tin chloride (SnCl4 and SnCl2), tin fluoride (SnF4 and SnF2), tin bromide (SnBr4 and SnBr2), tin iodide (SnI4 and SnI2), tin acetylacetonate (SnC10H14O4), tin pyrophosphate (Sn2P2O7), tin acetate (Sn(CH3CO2)4 and Sn(CH3CO2)2), tin oxalate (Sn(C204)2 and SnC2O4), tin triflate ((CF3SO3)2Sn and (CF3SO3)4Sn)).

(57) 13. The process according to any one of embodiments 1 to 12, wherein the saccharide composition is contacted with the Lewis Acid material at a temperature of from 30 to 190° C.

(58) 14. The process according to embodiment 13, wherein the temperature is from 80 to 170° C.

(59) 15. The process according to any one of embodiments 1 to 14, wherein the saccharide composition is contacted with the Lewis Acid material for a period of at least 10 seconds.

(60) 16. The process according to any one of embodiments 1 to 15, wherein the process is conducted under continuous conditions.

(61) 17. The process according to embodiment 16, wherein the weight hourly space velocity is between 0.005 and 10 h.sup.−1.

(62) 18. The process according to any one of embodiments 1 to 17, wherein the alpha-hydroxy-beta-ene-acids or esters thereof are subjected to a derivatization selected from acylation, silylation, alkylation, hydrolysis, hydrogenation, amidation.

(63) 19. The process according to any one of embodiments 1 to 18, wherein step b) includes a purification of the alpha-hydroxy-beta-ene-acids or esters or derivatives thereof.

(64) 20. The process according to embodiment 19 wherein the purification includes evaporating the solvent under reduced pressure.

(65) 21. The process according to any one of embodiments 19 or 20, wherein the purification includes purifying the alpha-hydroxy-beta-ene-acids or esters or derivatives thereof by column chromatography.

(66) 22. The process according to any one of embodiments 19 or 20, wherein the purification includes purifying the alpha-hydroxy-beta-ene-acids or esters or derivatives thereof by distillation.

(67) 23. The process according to any one of embodiments 19 or 20, wherein the purification includes purifying the alpha-hydroxy-beta-ene-acids or esters or derivatives thereof by crystallization.