Single step process for the synthesis of furan derivatives from carbohydrates

Abstract

The present invention discloses a single step process for the synthesis of furan derivative from carbohydrate comprises stirring the reaction mixture of carbohydrate in solvent in presence of catalyst at temperature in the range of 170 to 190° C. for the period in the range of 23 to 25 hrs to afford corresponding furan derivative.

Claims

1. A single step, single pot process for the synthesis of a furan derivative from a carbohydrate comprises stirring the reaction mixture of the carbohydrate in solvent in presence of a catalyst at temperature in the range of 170 to 190° C. for a period in the range of 23 to 25 hrs. to afford the corresponding furan derivative comprising 2,5-di(formyl)furan or 5-((methylthio)methyl)-2-furfural.

2. The process as claimed in claim 1, wherein said carbohydrate is selected from fructose, glucose or sucrose.

3. The process as claimed in claim 1, wherein said catalyst is selected from Sulfuric acid or Sn-Mont.

4. The process as claimed in claim 1, wherein said solvent is selected from dimethyl sulfoxide, N,N-dimethylformamide, water, 1-butyl-3-methylimidazolium chloride or combination thereof.

5. The process as claimed in claim 1, wherein the yield of said furan derivative is in the range of 30 to 60%.

6. The process as claimed in claim 1, wherein the yield of said furan derivative is in the range of 30 to 50%.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

(2) In line with the above objectives, the present invention provides a single step, single pot process for the synthesis of furan derivatives selected from 2,5-di(formyl)furan (DFF) and 5-((methylthio)methyl)-2-furfural (MTMF) from carbohydrates.

(3) In an embodiment, the present invention provide a single step, single pot process for the synthesis of furan derivative from carbohydrate comprises stirring the reaction mixture of carbohydrate in solvent in presence of catalyst at temperature in the range of 170 to 190° C. for the period in the range of 23 to 25 hrs to afford corresponding furan derivative.

(4) The carbohydrate is selected from fructose, glucose or sucrose.

(5) The furan derivative is selected from 2,5-di(formyl)furan (DFF) or 5-((methylthio)methyl)-2-furfural (MTMF).

(6) The catalyst is selected from Sulfuric acid (H.sub.2SO.sub.4) or Sn-Mont (Tin hydroxide nanoparticles-embedded montmorillonite).

(7) The solvent is selected from Dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), water, 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]) or combination thereof.

(8) The yield of corresponding furan derivative is in the range of 30 to 60%, preferably 30 to 50%.

(9) The 2,5-di(formyl)furan and 5-((methylthio)methyl)-2-furfural are produced directly from carbohydrates (e.g. fructose, glucose and sucrose) in one-pot process with single solvent (DMSO) system. 2,5-di(formyl)furan is produced in high yield (33-48%) from carbohydrates using catalytic amount of concentrated H.sub.2SO.sub.4 (10 mol %). While, 5-((methylthio)methyl)-2-furfural is produced in good to moderate yield (36-45%) from carbohydrates using Sn-Mont catalyst.

(10) The process for the synthesis of furan derivative is depicted in scheme 1 below:

(11) ##STR00001##

(12) The results are presented in Table 1 shows distribution of dehydration products on different acid catalysts using glucose. Initially, dehydration of glucose is started with the Sn-Mont catalyst at 150° C. in DMSO. After 24 h, glucose is consumed completely with 38% yield of HMF (Table 1, entry 1). Next experiment is performed at 170° C., the product distribution is 19% HMF and 21% MTMF [5-((methylthio)methyl)-2-furfural] (Table 1, entry 2). Interestingly, selectivity to MTMF is increased at 180° C. with 36% yield (Table 1, entry 3). DMSO decomposes at high temperature (180° C.) on Sn-Mont to polysulfides which helped to convert HMF to MTMF. In presence of SnCl.sub.4.5H.sub.2O, dehydration followed by chlorination of glucose is facilitating to the 5-(chloromethyl)furfural (Table 1, entry 6). Amberlyst-15 and heteropoly acid (H.sub.3PW.sub.12O.sub.40) are found ineffective for this reaction (Table 1, entry 7, 8). Interestingly, in presence of conc. H.sub.2SO.sub.4 glucose is directly converted to DFF in 33% yield. Under experimental conditions DMSO behaves as an oxidation agent as well as reaction medium (Table 1, entry 9).

(13) TABLE-US-00001 TABLE 1 Catalyst optimization for thermal dehydration of glucose in DMSO .sup.a T t Conv. Yield (%) .sup.b Entry Catalyst Loading (° C.) (h) (%) HMF MTMF DFF 1 Sn-Mont 0.2 g 150 24 100 38 0 0 2 Sn-Mont 0.2 g 170 24 100 19 21 0 3 Sn-Mont 0.2 g 180 24 100 06 36 trace 4 Sn-Mont 0.2 g 180 12 100 30 06 trace 5 Mont 0.2 g 180 24 61 09 07 0 6 SnCl.sub.4•5H.sub.2O 10 mol % 180 24 100 09 (12).sup.c 0 0 7 Amberlyst-15 0.2 g 180 24 71 07 0 0 8 H.sub.3PW.sub.12O.sub.40 10 mol % 180 24 80 09 06 08 9 H.sub.2SO.sub.4 10 mol % 180 24 100 0 0 33 10 — — 180 24 00 0 0 0 .sup.a Reaction conditions: Glucose (0.5 g, 0.277 mmol), DMSO (10 mL), catalyst. .sup.b yields reported on HPLC, .sup.cyield of 5-(chloromethyl)-2-furfural

(14) The result in table 2 shows dehydration of fructose and sucrose. In DMSO, fructose and sucrose are heated at 180° C. with Sn-Mont, MTMF is produced in 45% and 40%, respectively (Table 2, entry 1 and 2). Similarly, with concentrated H.sub.2SO.sub.4 fructose and sucrose are transformed into DFF with 48% and 39%, respectively (Table 2, entry 3 and 4).

(15) TABLE-US-00002 TABLE 2 One-pot synthesis of 2,5-diformylfuran and 5-((methylthio)methyl)- 2-furfural from carbohydrates in DMSO .sup.a Conversion Yield (%) .sup.b Entry Substrates Catalyst Loading (%) MTMF DFF HMF 1 Fructose Sn-Mont 0.2 g 100 45 2 06 2 Sucrose >99 40 2 04 3 Fructose H.sub.2SO.sub.4 10 mol % 100 0 48 Trace 4 Sucrose >99 0 39 Trace .sup.a Reaction conditions: Carbohydrate (0.5 g), DMSO (10 mL), catalyst, 180° C., 24 h. .sup.b yields reported on HPLC.

(16) Following examples are given by way of illustration therefore should not be construed to limit the scope of the invention.

EXAMPLES

Example 1: Preparation of Sn-Mont

(17) Into an aqueous solution of SnCl.sub.4.5H.sub.2O (0.3 M, 80 mL), montmorillonite (5 g) was added lot wise under stirring at room temperature. After complete addition of montmorillonite, mixture was stirred further for 4 h. Then mixture was filtered, residue was washed with plenty of water (millipore water) until neutral filtrate. Residue was dried in oven at 110° C. for 24 h, ground in mortar pestle and kept in glass bottle.

Example 2: General Procedure for Synthesis of DFF from Carbohydrates

(18) A solution of carbohydrates (fructose/glucose/sucrose, 10 g) in DMSO (10 mL) was heated at 180° C. for 24 h, under stirring in the presence of conc. H.sub.2SO.sub.4 (0.54 g or 0.3 mL, 10 mol %). Because small quantities of Me.sub.2SO.sub.2 and Me.sub.2S (Unpleasant odour) were produced during the reaction, the outgoing gas was bubbled through bleach (NaOCl) to oxidize the Me.sub.2S and fully destroy the odour. The reaction was monitored by quantitative HPLC analysis with an external standard. Once the highest yield of DFF was achieved, the reaction mixture was cooled to room temperature. Diluted with dichloromethane (300 mL), washed with saturated solution of NaHCO.sub.3 (1×100 mL) and water (2×100 mL). Separated organic phase was evaporated and passed through silica (60-120 mesh size). The yield of pure DFF as a yellow crystalline solid was 2.88 g (42% calculated on fructose used), 1.84 g (27% calculated on glucose used) and 2.24 g (31% calculated on sucrose used).

(19) .sup.1H NMR (200 MHz, CDCl.sub.3), δ ppm 7.4 (s, 2H, furan H), 9.8 (s, 2H, CHO); .sup.13C NMR (50 MHz, CDCl.sub.3) δ ppm 119.19 (s, 2CH) 154.19 (s, 2C) 179.18 (s, 2CHO).

Example 3: General Procedure for Synthesis of MTMF from Carbohydrates

(20) A solution of carbohydrates (fructose/glucose/sucrose, 10 g) in DMSO (10 mL) was heated at 180° C. for 24 h, under stirring in the presence of Sn-Mont (4 g). Because small quantities of decomposition products of DMSO (Unpleasant odour) were produced during the reaction, the outgoing gas was bubbled through bleach (NaOCl) to oxidize the Me.sub.2S and fully destroy the odour. The reaction was monitored by quantitative HPLC analysis with an external standard. Once the highest yield of MTMF was achieved, the reaction mixture was cooled to room temperature and filtered to separate the catalyst. Catalyst bed was washed with dichloromethane (300 mL) further mother liquor was washed with water (2×100 mL). Separated organic phase was evaporated and passed through silica (60-120 mesh size). The yield of pure MTMF as a brown crystalline solid was 3.29 g (38% calculated on fructose used), 2.42 g (28% calculated on glucose used) and 3.0 g (33% calculated on sucrose used).

(21) .sup.1H NMR (200 MHz, CDCl.sub.3) δ ppm 2.15 (s, 3H) 3.74 (s, 2H) 6.44-6.45 (d, J=3.54 Hz, 1H) 7.20-7.22 (d, J=3.54 Hz, 1H) 9.58 (s, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3) δ ppm 15.81 (s, CH.sub.3) 30.38 (s, CH.sub.2) 110.23 (s, CH) 122.56 (s, CH) 152.41 (s, C) 159.31 (s, C) 177.30 (s, CHO).

Example 4: Analysis of DFF and MTMF

(22) TLC analysis was performed using Merck 5554 aluminium-backed silica plates, and the compounds were visualized under UV light (254 nm). Conversion of carbohydrates was calculated by using Agilent HPLC (column: Hi-Plex USP L17, detector: RI and mobile phase: millipore water with 0.6 mL/min flow). Yield of dehydration product of carbohydrates calculated by using Agilent HPLC (column: Poroshell 120 EC-C18, 2.7 μm, detector: UV and mobile phase: 0.1% acetic acid in millipore water:acetonitrile (85:15) with 0.6 mL/min flow). Pure products were characterized and confirmed by .sup.1H-NMR and .sup.13C-NMR using CDCl.sub.3 (0.01%, TMS) as solvent on 200 MHz frequency Bruker instrument. The products were also confirmed using QP-Ultra 2010 GC-MS Shimadzu instrument, RTX-5 column, helium as carrier gas, EI mode and ionization source temperature 200° C.

Example 5: Thermal Dehydration of Glucose Over Different Acidic Catalysts

(23) Initially, dehydration of glucose was started with the Sn-Mont catalyst at 150 in DMSO. After 24 h, glucose was consumed completely with 38% yield of HMF (Table 1, entry 1). Next experiment was performed at 170° C., the product distribution was 19% HMF and 21% MTMF [5-((methylthio)methyl)-2-furfural](Table 1, entry 2). Interestingly, selectivity to MTMF was increased at 180 with 36% yield (Table 1, entry 3). Presence of Lewis acid and Brønsted acid sites are unique features of Sn-Mont which facilitates the glucose isomerisation to fructose on its Lewis acid sites and dehydration of in-situ formed fructose to HMF on its Brønsted acid sites. DMSO decomposes at high temperature (180° C.) on Sn-Mont to polysulfides which helped to convert HMF to MTMF. In presence of SnCl.sub.4.5H.sub.2O, dehydration followed by chlorination of glucose was facilitating to the 5-(chloromethyl)furfural (Table 1, entry 6). Amberlyst-1 and heteropoly acid (H.sub.3PW.sub.12O.sub.40) were found ineffective for this reaction (Table 1, entry 7, 8). Interestingly, in presence of conc. H.sub.2SO.sub.4 glucose was directly converted to DFF in 33% yield. Under experimental conditions DMSO behaves as an oxidation agent as well as reaction medium (Table 1, entry 9).

(24) TABLE-US-00003 TABLE 1 Catalyst optimization for thermal dehydration of glucose in DMSO .sup.a T t Conv. Yield (%) .sup.b Entry Catalyst Loading (° C.) (h) (%) HMF MTMF DFF 1 Sn-Mont 0.2 g 150 24 100 38 0 0 2 Sn-Mont 0.2 g 170 24 100 19 21 0 3 Sn-Mont 0.2 g 180 24 100 06 36 trace 4 Sn-Mont 0.2 g 180 12 100 30 06 trace 5 Mont 0.2 g 180 24 61 09 07 0 6 SnCl.sub.4•5H.sub.2O 10 mol % 180 24 100 09 (12).sup.c 0 0 7 Amberlyst-15 0.2 g 180 24 71 07 0 0 8 H.sub.3PW.sub.12O.sub.40 10 mol % 180 24 80 09 06 08 9 H.sub.2SO.sub.4 10 mol % 180 24 100 0 0 33 10 — — 180 24 00 0 0 0 .sup.a Reaction conditions: Glucose (0.5 g, 0.277 mmol), DMSO (10 mL), catalyst. .sup.b yields reported on HPLC, .sup.cyield of 5-(chloromethyl)-2-furfural

Example 6: Thermal Dehydration of Fructose and Sucrose

(25) In DMSO, fructose and sucrose were heated at 180° C. with Sn-Mont, MTMF was produced in 45% and 40%, respectively (Table 2, entry 1 and 2). Similarly, with concentrated H.sub.2SO.sub.4 fructose and sucrose were transformed into DFF with 48% and 39%, respectively (Table 2, entry 3 and 4).

(26) TABLE-US-00004 TABLE 2 One-pot synthesis of 2,5-diformylfuran and 5-((methylthio)methyl)- 2-furfural from carbohydrates in DMSO .sup.a Conversion Yield (%) .sup.b Entry Substrates Catalyst Loading (%) MTMF DFF HMF 1 Fructose Sn-Mont 0.2 g 100 45 2 06 2 Sucrose >99 40 2 04 3 Fructose H.sub.2SO.sub.4 10 mol % 100 0 48 Trace 4 Sucrose >99 0 39 Trace .sup.a Reaction conditions: Carbohydrate (0.5 g), DMSO (10 mL), catalyst, 180° C., 24 h. .sup.b yields reported on HPLC.

Example 7: Parameter Study for the Glucose Conversion to DFF Over H.SUB.2.SO.SUB.4

(27) a) Dehydration of Glucose with H.sub.2SO.sub.4 (10 Mol %) in Different Solvents:

(28) The basic criterion for the solvent selection is that glucose should soluble in selected solvents. Therefore some solvent such as N,N-dimethylformamide (DMF), H.sub.2O and 1-Butyl-3-methylimidazolium chloride [Bmim] [Cl] were chosen for glucose dehydration reaction. When glucose was dissolved in DMF and 10 mol % H.sub.2SO.sub.4 subsequently heated at 180° C. for 24 h. Levulinic acid (09%) was formed along with excess humin after complete consumption of glucose (Table 3, entry 1). On the other hand, under experimental conditions in presence of water, HMF (09%) and levulinic acid (21%) were formed after full glucose conversion (Table 3, entry 2). In presence of 1-Butyl-3-methylimidazolium chloride ([Bmim][Cl]) DFF was not formed at all (Table 3, entry 3). Thus from above experiments it is concluded that, other than DMSO all other solvents were not suitable for the production of DFF from glucose.

(29) TABLE-US-00005 TABLE 3 Dehydration of glucose with H.sub.2 SO.sub.4 (10 mol %) in different solvents .sup.[a] Yield Entry Solvents Conversion HMF DFF LA 1 DMF 100 00 00 09 2 H.sub.2O 100 09 00 21 3 [Bmim][Cl] (3 mL) 100 19 00 09 .sup.[a] Reaction conditions: glucose (0.5 g), H.sub.2SO.sub.4, solvent (10 mL), 180° C., 24 h. LA = Levulinic acid. DMF = N,N-dimethylformamide, [Bmim][Cl] = 1-Butyl-3-methylimidazolium chloride

(30) b) Dehydration of Glucose with Different Concentrations of H.sub.2SO.sub.4 in DMSO

(31) In the catalyst optimisation study different concentration (5, 15, 20 mol %) of H.sub.2SO.sub.4 (Table 4) is screened. With 5 mol % of H.sub.2SO.sub.4, glucose was consumed completely with 07% of HMF and 29% DFF (Table 4, entry 1). While using 15 mol % of H.sub.2SO.sub.4, DFF was produced in 31% yield (Table 4, entry 2). On the other hand, in presence of 20 mol % of H.sub.2SO.sub.4, DFF yield was dropped to 28% (Table 4, entry 3). Higher catalyst concentration than 10 mol % has induced negative effect on DFF yield due to excess humin formation.

(32) TABLE-US-00006 TABLE 4 Dehydration of glucose with different concentrations of H.sub.2SO.sub.4 in DMSO Yield Entry Concentration of H.sub.2SO.sub.4 Conversion HMF DFF 1  5 mol % 100 07 29 2 15 mol % 100 00 31 3 20 mol % 100 00 28 .sup.[a]Reaction conditions: glucose (0.5 g), H.sub.2SO.sub.4, DMSO (10 mL), 180° C., 24 h.

(33) c) Dehydration of Glucose with H.sub.2SO.sub.4 (10 Mol %) in DMSO at Different Temperature

(34) The range of temperatures from 160-190° C. is studied in Table 5. At 160° C., product distribution was 32% HMF and 06% DFF with complete conversion of glucose (Table 5, entry 1). While increasing temperature to 170° C., DFF yield was increased to 17% (Table 5, entry 2). However, at 190° C. DFF was obtained in 31% yield which was comparable to the result obtained at 180° C.

(35) TABLE-US-00007 TABLE 5 Dehydration of glucose with H.sub.2SO.sub.4 (10 mol %) in DMSO at different Yield (%) Entry Temperature (° C.) Conversion (%) HMF DFF 1 160 100 32 06 2 170 100 21 17 3 190 100 00 31 .sup.[a]Reaction conditions: glucose (0.5 g), H.sub.2SO.sub.4, DMSO (10 mL), 160-190° C., 24 h.

Example 8: Parameter Study for the Glucose Conversion to MTMF Over Sn-Mont

(36) a) Dehydration of Glucose with Different Sn-Mont Loading in DMSO

(37) Effect of Sn-Mont loading was studied for the MTMF production and results are presented in Table 6. When lower than 0.2 g loading of Sn-Mont was used, conversion of glucose wasn't reached to 100% (Table 6, entry 1 and 2). While, more than 0.2 g loading of Sn-Mont was used, MTMF was formed in 38% yield which is comparable to the results obtained with 0.2 g Sn-Mont loading (Table 6, entry 1 and 2). Thus 0.2 g loading was found optimum loading and same amount was used for further experiment.

(38) TABLE-US-00008 TABLE 6 Dehydration of glucose with different Sn-Mont loading in DMSO .sup.[a] Yield (%) Entry Sn-Mont loading (g) Conversion (%) HMF MTMF 1 0.1 69 17 05 2 0.15 90 19 12 3 0.250 100 00 38 .sup.[a] Reaction conditions: glucose (0.5 g), Sn-Mont, DMSO (10 mL), 180° C., 24 h.

(39) b) Dehydration of Glucose with Sn-Mont in DMSO at Different Temperature

(40) Dehydration of glucose was studied over Sn-Mont at different temperature (160-190° C.) in DMSO solvent (Table 7). At 160° C., product distribution was 30% of HMF and 08% of MTMF (Table 7, entry 1). While at 170° C., product distribution was 19% of HMF and 19% of MTMF (Table 7, entry 2). However, at 190° C., MTMF was obtained in 36% yield which was comparable to the result obtained at 180° C.

(41) TABLE-US-00009 TABLE 7 Dehydration of glucose with Sn-Mont in DMSO at different temperature .sup.[a] Yield (%) Entry Temperature (° C.) Conversion (%) HMF MTMF 1 160 100 30 08 2 170 100 19 19 3 190 100 00 36 .sup.[a] Reaction conditions: glucose (0.5 g), Sn-Mont, DMSO (10 mL), 160-190° C., 24 h.

ADVANTAGES OF THE INVENTION

(42) 1) Single step, single catalyst, single solvent, one-pot process

(43) 2) Simple and cost effective process

(44) 3) No external 02 required in DFF production.

(45) 4) No external source of S is required in MTMF production.

(46) 5) No use of external oxygen pressure

(47) 6) Isolation of furfural (HMF) is not required.