A method for the selective reduction of aldehydes of variously substituted furans to methyl groups without metal catalysts and hydrogen

Abstract

The present invention relates to a 5-methyl substituted furan compound of general formula (I) and a method for preparing the same. In particular, the present invention relates to a method for preparing a methyl substituted furan compound from different aldehyde substituted furan compounds without metal catalyst and hydrogen, atom-economical, highly selective and low-cost.

Description

Technical Field

[0001] The present invention relates to 5-methyl substituted furan compounds of general formula (I) and a method for their preparation:

[0002]

[0003] wherein

[0004] R 1 is selected from the group consisting of: hydrogen, hydroxymethyl, methyl, alkyl, hydroxy, aldehyde, halide, ester, carboxylic acid, amide, amine, substituted amine, alkoxy / ether bond, sulfur derivative, phosphorus derivative, and any aryl and heteroaryl functional groups; and R 2 and R 3 can be selected from the group consisting of: hydrogen, alkyl, and aryl.

[0005] More specifically, the present invention relates to a new protocol for a "metal-free method for the selective reduction of aldehydes of differently substituted furans to methyl". The present invention has developed a metal-free catalyst-free, hydrogen-free, atom-economical, highly selective, and low-cost method for the preparation of methyl-substituted furan compounds from differently aldehyde-substituted furan compounds. The steps of this method are easy to scale up and can achieve high purity without cumbersome purification steps.

[0006] The present invention specifically relates to methods for the preparation of 5-methylfurfuryl alcohol (5-MFA), 2,5-dimethylfuran (DMF), and 5-methylfuran from the corresponding aldehyde compounds, which have great uses as biofuels and for other applications.

[0007] The present invention also relates to methyl-substituted furan compounds of general formula (I), which can be used as intermediates / final products in the production of biofuels, fragrances, food additives, drugs, resins, and biopolymer synthesis.

[0008] The present invention also relates to a convenient, inexpensive, effective, and scalable method for the synthesis of methyl-substituted furan compounds of general formula (I). Background Art

[0009] In recent decades, the production of biomass-derived biofuels has become a hot topic and an important issue. Increasingly, the depletion of fossil resources and greenhouse gas emissions have forced the research community to use renewable resources as raw materials for biofuel production. Biomass resources (lignocellulose, cellulose, starch, fructose, glucose, sucrose, etc.) have been considered renewable resources for the production of energy and fine bulk chemicals because these resources are widely available in nature. In this article, 5-hydroxymethylfurfural (HMF) is considered a platform molecule; it is derived from biomass (Mika, L.T., Csefalvay, E. and Nemeth, A., Chem. Rev., 2018, 118, (2), 505-613), which is a key intermediate for the production of various fine chemicals and biofuels).

[0010] The reduction of 5-HMF gives 2,5-dimethylfuran (DMF), which is a promising biofuel derived from 5-HMF and directly from biomass. Due to high processing costs and scale-up problems, the industrial-scale production of biofuels still requires a high degree of scientific intervention. In this regard, 5-methylfurfural methanol (5-MFA) is envisioned as an important intermediate (Thananatthanachon, T. and Rauchfuss, B.T., Angew. Chem., 2010, 49, 6616-6618) that undergoes hydrogenolysis to give dimethylfuran (biofuel). Nishimura et al. have reported the hydrogenation of 5-HMF to 2,5-DMF using a Pd-Au / C catalyst via the 5-MFA intermediate. Under these conditions, the yield of 5-MFA produced is very low (Nishimura, S.; Ikeda, N. and Ebitani, K., Catalysis Today, 2014, 232, 89-98). 5-Chlorofuran-2-carbaldehyde has also been reported as a precursor for the synthesis of 5-MFA using Zr-benzylphosphonate (GC quantitative yield 98%) (Li, H.; Fang, Z.; He, J. and Yang, S., ChemSusChem, 2017, 10, 681-686). In addition, 5-MFA also plays an important role in the synthesis of 2,5-DMF using Cu / g-Al 2 O 3 and molecular hydrogen (as a hydrogen source). The role of water in Cu / g-Al 2 O 3The influence was discovered, and it was found that in the absence of water, the main hydrogenolysis products of 5-HMF are 5-MFA and 2,5-DMF (Liu, Y.; Mellmer, A. M.; Alonso, M. D. and Dumesic, A. J., ChemSusChem, 2015, 8, 3983-3986). Continuing this development, various heterogeneous catalytic methods (such as ruthenium catalysts supported on zirconia (Ru(OH) x / ZrO 2 )) have also been applied in various alcohol solvents to hydrogenate 5-HMF to 2,5-BHMF with high selectivity, and it was observed that in the presence of 2-propanol and tert-butanol, 5-MFA is formed as a by-product (Han, J.; Kim, H. Y.; Jnag, S. H.; Hwang, Y. S.; Jegal, J.; Kim, W. J. and Lee, S. Y., RSC Adv., 2016, 6, 93394-93397). Subsequently, Cu(50)-SiO 2Nanocomposites have also been developed for the synthesis of DHMF from 5-HMF. It has been reported that 5-MFA (2%) forms together with DHMF (Upare, P.P.; Hwang, K.Y. and Hwang, W.D., Green Chem., 2018, 20, 879-885). The maximum yield of 5-MFA (19%) was obtained by using Ru-Sn / ZnO (Upare, P.P.; Hwang, W.D.; Hwang, K.Y.; Lee, H.U.; Hong, Y.D. and Chang, S.J., Green Chem., 2015, 17, 3310-3313). Fu et al. also screened nickel supported on perovskite-type oxides and observed that 5-MFA (38.5%) forms together with other hydrogenolysis products of 5-HMF (Chen, Y.M.; Chen, B.C.; Zada, B. and Fu, Y., Green Chem., 2016, 18, 3858-3866). Chatterjee et al. attempted another method for the synthesis of BHMF from 5-HMF, which was carried out by hydrogenation in an aqueous medium under mild reaction conditions at a hydrogen pressure of 0.8 MPa using the catalyst Pt / MCM-41 without any additives. It was observed that 5-MFA (GC yield 90%) was produced only when the substrate was methylfurfural and BHMF, and an increase in the reaction time from the standard conditions (2 h to 6 h) favored the formation of 5-MFA (Chatterjee, M.; Ishizaka, T. and Kawanami, H., Green Chem., 2014, 16, 4734-4739). Recently, Hu et al. catalytically transferred hydrogenated 5-methylfurfural to 5-methylfurfuryl alcohol at 140 °C using N-alkylzirconium phosphate nanohybrids (ZrPN), with a GC quantitative yield of up to 99%. (Li, H.; He, J.; Riisager, A.; Saravanamurugan, S.; Song, B. and Yang, S. ACS Catal. 2016, 6, 7722-7727). Another CTH method using NiO nanoparticles was carried out, and a yield of 93% of 5-MFA was observed from 5-methylfurfural at a high temperature of 180 °C (He, J.; Schill, L.; Yang, S. and Riisager, A., ACS Sustainable Chem. Eng., 2018, 6, 17220-17229). Zhao et al. recently also reported that in the absence of external gas, by using CuO / Cu 2 O·SiO 2Synthesis of 2-methylfuran (MF) via selective deoxygenation of aqueous furfural over a layered copper silicate precursor at a site (Li, B.; Li, L.; Sun, H. and Zhao, C. ACS Sustainable Chem. Eng., 2018, 6, 12096 - 12103). Zhu et al. reported that a Cu-based catalyst supported on SiO 2 converted furfural to 2-MF with a high yield of 89% (Dong, F.; Zhu, Y. L.; Zheng, H. Y.; Zhu, Y. F.; Li, X. Q. and Li, Y. W. J. Mol. Catal. A: Chem. 2015, 398, 140 - 148). A mixed catalytic method using a Cu-Zn-Al catalyst and cyclohexanol (used as a hydrogen donor) was also used for the synthesis of 2-MF from furfural, with a selectivity of 87% at 250 °C (Zheng, H. Y.; Zhu, Y. L.; Bai, Z. Q.; Huang, L.; Xiang, H. W. and Li, Y. W. Green Chem. 2006, 8(1), 107 - 109).

[0011] As a continuation of the prior art, the object of the present invention is to develop a very simple method for preparing methyl-substituted furan compounds from different aldehyde-substituted furan compounds. The present invention specifically relates to methods for preparing 5-methylfurfural alcohol (5-MFA), 2,5-dimethylfuran (DMF), and 2-methylfuran from the corresponding aldehyde compounds, which compounds have great utility as biofuels and for other applications.

[0012] Purpose of the Invention

[0013] The main object of the present invention is to provide 5-methyl-substituted furan compounds of general formula (I):

[0014]

[0015] Another object of the present invention is to develop a metal- and hydrogen-free, highly selective and cost-effective method for synthesizing 5-MFA and DMF from 5-HMF and 2,5-diformylfuran (DFF) or 5-methylfuran-2-carboxaldehyde following a convenient method that has wide applications in the fields of biofuels, food additives, pharmaceuticals, etc., and overcomes the disadvantages detailed.

[0016] Another object of the present invention is to develop an atom-economical and high-yield method that forms very few by-products and does not require cumbersome purification.

[0017] Another object of the present invention is to develop a milder and more effective method suitable for scale-up conversion.

[0018] Another object of the present invention is to develop a scalable method for the production of biofuels or biofuel candidates, which utilizes low-cost saccharide-based biomass and follows a stepwise approach from 5-HMF or its aldehyde-substituted derivatives.

[0019] Another object of the present invention is to apply the same strategy to reduce aldehyde groups linked to molecules of a similar type.

[0020] Another object of the present invention is to produce high-value biochemicals (5-MFA, DMF, etc.) using non-edible and low-cost cellulose / saccharide compounds as raw materials for biofuels, food additives, fragrances, and pharmaceutical applications.

[0021] Another object of the present invention is to produce 2-(ethoxymethyl)-5-methylfuran (EMMF) using 5-MFA for biofuel / biodiesel and other commercial applications.

[0022] Another object of the present invention is to develop a method for the production of low-cost 2,5-dimethylfuran (DMF) for use in biofuels and the synthesis of commercially important molecules / products. SUMMARY OF THE INVENTION

[0023] In one embodiment, the present invention provides a method for preparing a 5-methyl-substituted furan of general formula (I):

[0024]

[0025] wherein

[0026] R 1 is selected from the group consisting of hydrogen, hydroxymethyl, methyl, alkyl, hydroxy, aldehyde, halide, ester, carboxylic acid, amide, amine, substituted amine, alkoxy / ether bond, sulfur derivative, phosphorus derivative, and aryl and heteroaryl functional groups; and R 2 and R 3 are independently selected from the group consisting of hydrogen, alkyl, and aryl.

[0027] In another embodiment, the present invention provides a cost-effective, atom-economical, highly selective, and high-yield method for preparing a 5-methyl-substituted furan compound of general formula (I) from low-cost saccharide compounds (e.g., bagasse, straw, corncobs, other cellulose raw materials, cellulose, starch, polysaccharide, glucose, and fructose) via 5-HMF and its corresponding products, and minimizing by-product formation to avoid expensive purification processes.

[0028] In another embodiment, the present invention provides a one-pot method for preparing a 5-methyl-substituted furan of general formula (I).

[0029] In another embodiment, the present invention provides a metal - and hydrogen - free, highly selective and cost - effective method for preparing 5 - methyl - substituted furans of general formula (I).

[0030] In another embodiment, the present invention provides a method for preparing 5 - methyl - substituted furans of general formula (I), which comprises:

[0031] i) Reacting an amine compound and an inorganic base with a substituted furan - aldehyde of formula (II) in a suitable solvent to in - situ generate the corresponding imine:

[0032]

[0033] ii) Reducing the in - situ generated imine of step (i) to a methyl - substituted furan of general formula (I) in a suitable solvent under basic conditions;

[0034] iii) Isolating the methyl - substituted furan of general formula (I); and

[0035] iv) Optionally, purifying the isolated methyl - substituted furan of general formula (I).

[0036] In another embodiment, the present invention provides a method for preparing 5 - methylfurfuryl alcohol (5 - MFA) of formula (1),

[0037]

[0038] which comprises:

[0039] i) Reacting an amine compound and an inorganic base with 5 - hydroxymethylfurfural (HMF) in a suitable solvent to in - situ generate the corresponding imine;

[0040] ii) Reducing the in - situ generated imine of step (i) to 5 - MFA of formula (1) in a suitable solvent under basic conditions;

[0041] iii) Isolating 5 - MFA of formula (1); and

[0042] iv) Optionally, purifying the isolated 5 - MFA.

[0043] In another embodiment, the present invention provides a method for preparing 2,5 - dimethylfuran of formula (IV),

[0044]

[0045] which comprises the following steps:

[0046] i) Reacting an amine compound and an inorganic base with 2,5 - diformylfuran in a solvent to in - situ generate the corresponding diimine;

[0047] ii) Reducing the in-situ generated diimine of step (i) in a solvent under basic conditions to obtain 2,5-dimethylfuran of formula (IV);

[0048] iii) Separating 2,5-dimethylfuran of formula (IV); and

[0049] iv) Optionally, purifying the separated 2,5-dimethylfuran of formula (IV).

[0050] In yet another embodiment, the present invention provides a method for preparing 2-(ethoxymethyl)-5-methylfuran (EMMF) of formula (V) from 5-methylfurfural methanol (5-MFA) of formula (III)

[0051]

[0052] Thus, the method involves a combination of inorganic bases under milder solvent conditions without metals to avoid unwanted reactions and meet the desired conditions for successful conversion. Detailed Description

[0053] The present invention provides a "metal-free method for selectively reducing aldehydes of different substituted furans to methyl groups", which includes the following in-situ steps: hydrazone of a carbonyl compound, and further decomposition in the presence of a strong base to obtain a 5-methyl-substituted furan compound of general formula (I):

[0054]

[0055] Wherein

[0056] R 1 is selected from the group consisting of: hydrogen, hydroxymethyl, methyl, alkyl, hydroxy, formyl, halide, ester, carboxyl, nitro, amide, amino, substituted amino, alkoxy, ether, sulfur derivative, phosphorus derivative, and aryl and heteroaryl functional groups; and R 2 and R 3 can be selected from the group consisting of: hydrogen, alkyl, and aryl.

[0057] Compared with the prior art methods, the present invention provides a metal-free and hydrogen-free reduction method for the direct conversion of 5-HMF and di / monoformyl furan to the corresponding 5-MFA and DMF, which has a good yield.

[0058] In this study, the difficult and hitherto untried Wolff-Kishner reduction method was carried out at a rather low temperature for the selective conversion of 5-aldehyde-substituted furan compounds to 5-methyl-substituted furan compounds of general formula (I), which has a good yield and negligible by-product formation.

[0059] Furthermore, the method is carried out under normal reflux conditions and does not require an expensive autoclave system.

[0060] It was found that the improved synthesis method has high selectivity, high yield and is suitable for large-scale production of 5-MFA in very good yield.

[0061] The entire improved system also limits the formation of unwanted by-products, over-reduction and polymerization.

[0062] In one embodiment, the present invention provides a method for preparing a 5-methyl-substituted furan of general formula (I):

[0063]

[0064] wherein

[0065] R 1 is selected from the group consisting of: hydrogen, hydroxymethyl, methyl, alkyl, hydroxy, aldehyde, halide, ester, carboxylic acid, amide, amine, substituted amine, alkoxy / ether bond, sulfur derivative, phosphorus derivative, and aryl and heteroaryl functional groups;

[0066] R 2 and R 3 can be selected from the group consisting of: hydrogen, alkyl and aryl; the method comprising the steps of:

[0067] i) reacting an amine compound and an inorganic base with a substituted furan aldehyde of formula (II) in a solvent to in-situ obtain the corresponding imine compound:

[0068]

[0069] ii) reducing the in-situ generated imine of step (i) in a solvent under basic conditions to obtain a 5-methyl-substituted furan of general formula (I);

[0070] iii) separating the methyl-substituted furan of general formula (I); and

[0071] iv) optionally, purifying the separated methyl-substituted furan of general formula (I).

[0072] In another embodiment, the alkyl is methyl.

[0073] In another embodiment, the present invention provides a cost-effective, atom-economic, highly selective and high-yield method for preparing a 5-methyl-substituted furan compound of general formula (I) from low-cost saccharide compounds (e.g., bagasse, rice straw, corncob, other cellulose raw materials, cellulose, starch, polysaccharide, glucose and fructose) via 5-HMF and its corresponding products, and minimizing by-product formation to avoid expensive purification processes.

[0074] In another embodiment, the present invention provides a one-pot method for preparing 5-methyl-substituted furans of general formula (I).

[0075] In another embodiment, the present invention provides a metal- and hydrogen-free, highly selective and cost-effective method for preparing 5-methyl-substituted furans of general formula (I).

[0076] In another embodiment, the present invention provides a method for preparing 5-methylfurfuryl alcohol (5-MFA) of formula (1).

[0077]

[0078] It comprises:

[0079] i) reacting an amine compound and an inorganic base with 5-hydroxymethylfurfural (HMF) in a suitable solvent to in-situ generate the corresponding imine;

[0080] ii) reducing the in-situ generated imine in step (i) to 5-MFA of formula (1) in a suitable solvent under basic conditions;

[0081] iii) separating 5-MFA of formula (III); and

[0082] iv) optionally, purifying the separated 5-MFA of formula (III).

[0083] 5-HMF has been used as a major structural unit, which is generated from carbohydrate compounds, for the construction of 5-MFA.

[0084] The alcohol group of 5-HMF was not found to be reactive and ended with the major 5-MFA product and 2,5-diformylfuran or monoformylfuran, both of which were successfully converted to DMF as the major product under this method.

[0085] In another embodiment, the final product of formula (I) or formula (III) or formula (IV) is separated by an extraction method using a suitable extraction solvent.

[0086] Suitable extraction solvents include but are not limited to alkyl ketones, ethyl acetate, dichloromethane, chloroform, THF, diethyl ether, etc. and mixtures thereof.

[0087] In order to obtain a high yield and purity of the final product of formula (I) or formula (III) or formula (IV), distillation is carried out under variable pressure and temperature conditions.

[0088] This method follows the traditional Wolff-Kishner reduction method, which has not been explored in aldehyde-substituted furan compounds of general formula (II).

[0089] Amine compounds include, but are not limited to, hydrazine hydrate, hydrazine hydrochloride, aryl-substituted hydrazine / alkyl-substituted hydrazine / hydroxy-substituted hydrazine, and such groups of any diamine compounds further extended, and the diamine compounds have an imine-forming tendency and follow a similar Wolff-Kishner reduction method, etc. Preferably, the inorganic base is a strong inorganic base.

[0090] Inorganic bases include, but are not limited to, inorganic bases such as alkali metal alkoxides, alkali metal hydroxides, and alkali metal hydrides. Most preferably, the alkali metal is K, Na, and Cs. Alkali metal alkoxides are selected from the group consisting of: KO t Bu, NaO t Bu, KOEt, NaOEt, KOMe, and NaOMe. Alkali metal hydroxides are selected from the group consisting of: NaOH and KOH; and the alkali metal hydride is NaH.

[0091] Most preferably, the inorganic base is selected from the group consisting of: KO t Bu, NaO t Bu, KOEt, NaOEt, KOMe, NaOMe, NaOH, KOH, and NaH.

[0092] Preferably, the suitable solvent is an alcoholic organic solvent.

[0093] The alcoholic organic solvent is a protic alcohol with a variable boiling point and has a proton transfer ability under strong basic conditions to reduce the imine formed in situ from the carbonyl group to an alkyl carbon.

[0094] Alcoholic organic solvents include, but are not limited to, alkyl alcohols, cycloalkyl alcohols, etc.

[0095] Preferably, the alkyl or cycloalkyl alcohol solvent is selected from the group consisting of: methanol, ethanol, isopropyl alcohol, n-butanol, 2-butanol, tert-butanol, or a mixture thereof. Most preferably, the alcohol solvent is 2-butanol and ethanol.

[0096] The separation step iii) of the above method is carried out by an extraction method using a solvent selected from the group consisting of: alkyl ketones, ethyl acetate, dichloromethane, chloroform, THF, diethyl ether, or a mixture thereof.

[0097] In another embodiment of the present invention, methyl furfuryl alcohol (5-MFA) of formula (III) is further reacted in the presence of aluminum trichloride and ethanol to obtain 2-(ethoxymethyl)-5-methylfuran (EMMF) of formula (V)

[0098]

[0099] Depending on the different bases and solvents used in this transformation, the suitable temperature for the reaction can vary between 80 and 180 °C. Preferably, the reaction is carried out at a temperature in the range of 120 to 140 °C to obtain the highest yield and low by-product formation.

[0100] The reaction time can be selected from 2 - 6 hours or until the reaction is complete.

[0101] To expand the scope of the present method, different 5 - aldehyde - substituted furan compounds have been successfully used to produce 5 - methyl - substituted furans conforming to the general formula (I).

[0102] In method development, different hydrazine analogues, inorganic bases, and alcohol solvents have been used for the selective formation of compounds conforming to the general formula (I).

[0103] The present method for preparing the desired 5 - methyl - substituted furan of formula (I) in a highly selective manner involves using an amine compound to selectively form an imine with the aldehyde group of the substituted furan compound of formula (II). Under alcohol solvent conditions, the base specifically reduces the carbonyl group through proton transfer by generating nitrogen as one of the by - products.

[0104] Preferably, the molar concentration / ratio of the reactants is: aldehyde - substituted furan (1 equivalent), amine compound (1 - 3 equivalents), inorganic base (0.5 - 4 equivalents).

[0105] The purification method is selected from any suitable method known in the art, including but not limited to chromatographic techniques, distillation, crystallization, etc.

[0106] Preferably, purification is carried out by solvent extraction, fractional distillation, and then other purification techniques can be carried out.

[0107] In yet another embodiment, the present invention provides a method for preparing 2 - (ethoxymethyl) - 5 - methylfuran (EMMF) of formula (V) from 5 - methylfurfuryl alcohol (5 - MFA) of formula (III)

[0108]

[0109] In this method, optimized reagents, substrates, solvents, and reaction conditions work together importantly to produce the desired compound of general formula (I) with minimized by - product formation.

[0110] Furthermore, the present method is applicable to the scale - up production of 5 - methyl - substituted furan compounds of general formula (I) from different aldehyde - substituted furan compounds; these compounds can be used as raw materials for biofuels and other commercially valuable products.

[0111] The 5 - MFA prepared by the scale - up method as a raw material chemical can be further used as a precursor for the production of biofuels (such as 2,5 - dimethylfuran (2,5 - DMF)) and other important biochemicals (Scheme 1).

[0112]

[0113] Scheme 1. 5-MFA produced from 5-HMF is a platform compound for the production of biofuels and other important biochemicals.

[0114] List of abbreviations:

[0115] HMF: 5-hydroxymethylfurfural

[0116] DMF: 2,5-dimethylfuran

[0117] 5-MFA: 5-methylfurfural methanol

[0118] MF: 2-methylfuran

[0119] EMMF: 2-(ethoxymethyl)-5-methylfuran

[0120] THF: tetrahydrofuran

[0121] GC-MS: gas chromatography / mass spectrometry

[0122] NMR: nuclear magnetic resonance

[0123] TLC: thin layer chromatography

[0124] Materials and methods used in the experiments:

[0125] All raw materials and solvents used were purchased from commercial suppliers. For example, hydrazine hydrate and its analogs were purchased from Thomas Baker and Sigma, bases were purchased from Avra, solvents were purchased from CDH and SDFine. 5-HMF was used and prepared through our own patent (Application No.: 201811023331), and other starting materials were purchased from Sigma and TCI.

[0126] Embodiment

[0127] General experimental procedure:

[0128] Add a base (0.5 - 2.0 equivalents) and an alcohol solvent to a dried round-bottom flask (500 mL). Heat the reaction mixture in the temperature range of 120 °C to 140 °C until the base is completely dissolved. In another round-bottom flask, add 5-HMF (1.0 equivalent) and 2-butanol together, and then gradually add hydrazine hydrate (1 - 3 equivalents) dropwise under gentle stirring. Gradually add the 5-HMF mixture to the pre-dissolved alkaline solution and reflux at 120 - 130 °C for 2 - 6 hours. Monitor the progress of the reaction by TLC. After the reaction is completed, extract the mixture with ethyl acetate / ether, and use Na 2 SO 4Dry, and then remove the solvent by distillation under vacuum at 100 - 110 °C to obtain the crude product 5-MFA, which is further purified by vacuum distillation to obtain 5-MFA with a yield of 50 - 70% and a selectivity > 90%. The product is further analyzed by GC-MS and NMR( 1 H and 13 C).

[0129]

[0130] Scheme 2. Synthesis of 5-methyl-substituted furan from 5-aldehyde-substituted furan

[0131] 1. Experimental procedure for the synthesis of 5-MFA from 5-HMF:

[0132] Add KO t Bu (106.8 g, 0.95 mol) and 2-butanol (1 L) to a dry batch reactor (15 L). Heat the reaction mixture, stir, and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add 5-HMF (100.0 g, 0.79 mol) and 2-butanol (300 mL) together, and then gradually add hydrazine hydrate (78.0 mL, 1.58 mol) dropwise with gentle stirring. Gradually add the 5-HMF mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 6 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, extract the mixture with ethyl acetate / ether, and dry it with Na 2 SO 4 Dry, and then remove the solvent by distillation under vacuum at 100 - 110 °C to obtain 5-MFA, 45.15 g, with a yield of 51%. The crude product is further analyzed by GC-MS and NMR. 1 H NMR (300 MHz, CDCl 3 ) δ 6.15 (d, 1H, J = 3 Hz), 5.91 (d, 1H, J = 3 Hz), 4.52 (s, 2H), 2.29 (s, 3H); 13 C NMR (300 MHz, CDCl 3 ) δ 152.31, 152.30, 108.67, 106.19, 57.35, 13.48; GC-MS [M] + = 112

[0133]

[0134] Scheme 3. Synthesis of 5-MFA from 5-HMF

[0135] 2. Experimental procedure for the synthesis of 5-MFA from 5-HMF:

[0136] Add sodium tert-butoxide NaO t Bu (18.2 g, 0.19 mol) and 2-butanol (25 mL) to a dried round-bottom flask (500 mL). Heat the reaction mixture, stir, and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add HMF (20 g, 0.15 mmol) and 2-butanol (15 mL) together, and then gradually add hydrazine hydrate (11.6 mL, 0.23 mol) dropwise with gentle stirring. Gradually add the 5-HMF mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 6 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, extract the mixture with ethyl acetate / ether, dry it with Na 2 SO 4 dry, and then remove the solvent by distillation at 100 - 110 °C to obtain the crude product 5-MFA, which is further purified by vacuum distillation to obtain 5-MFA, 9.0 g, with a yield of 50.5%. Further analyze the distilled reaction residue by GC-MS and NMR. The spectral data are the same as those described for Compound III in Scheme 2.

[0137]

[0138] Scheme 4. Synthesis of 5-MFA from 5-HMF

[0139] 3. Experimental procedure for the synthesis of 5-MFA from 5-HMF:

[0140] Add KOH (3.3 g, 0.05 mol) and 2-butanol (10 mL) to a dried round-bottom flask (250 mL). Heat the reaction mixture, stir, and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add HMF (5.0 g, 0.03 mol) and 2-butanol (10 mL) together, and then gradually add hydrazine hydrate (2.9 mL, 0.05 mol) dropwise with gentle stirring. Gradually add the 5-HMF mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 6 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, extract the mixture with ethyl acetate / ether, dry it with Na 2 SO 4 dry, and then remove the solvent by distillation at 100 - 110 °C to obtain the crude product 5-MFA, which is further purified by vacuum distillation to obtain 5-MFA, 1.1 g, with a yield of 25%. Further analyze the distilled reaction residue by GC-MS and NMR. The spectral data are the same as those described for Compound III in Scheme 2.

[0141]

[0142] Scheme 5. Synthesis of 5-MFA from 5-HMF

[0143] 4. Experimental procedure for the synthesis of 2-methylfuran from 2-furaldehyde:

[0144] Add KO t Bu (1.1 g, 0.010 mol) and 2-butanol (3 mL) to a dried round-bottom flask (100 mL). Heat the reaction mixture, stir, and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add 2-furaldehyde (1.0 g, 0.01 mol) and 2-butanol (3 mL) together, and then add hydrazine hydrate (1.02 mL, 0.020 mol) dropwise with gentle stirring. Gradually add the 2-furaldehyde mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 6 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, analyze the mixture by GC-MS. Further analyze the product by GC-MS and compare it with the standard.

[0145]

[0146] Scheme 6. Synthesis of 2-methylfuran from 2-furaldehyde

[0147] 5. Experimental procedure for the synthesis of 2,5-dimethylfuran (DMF) from 2,5-diformylfuran:

[0148] Add KO t Bu (45.0 mg, 0.403 mmol) and 2-butanol (1.5 mL) to a dried round-bottom flask (100 mL). Heat the reaction mixture, stir, and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add 2,5-diformylfuran (100 mg, 0.806 mmol) and 2-butanol (3 mL) together, and then add hydrazine hydrate (79 μL, 1.612 mmol) dropwise with gentle stirring. Gradually add the 2,5-diformylfuran mixture to the pre-dissolved basic solution and reflux at 130 °C for 3 - 5 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, analyze the mixture by GC-MS. Further analyze the product by GC-MS and compare it with the standard.

[0149]

[0150] Scheme 7. Synthesis of 2,5-dimethylfuran from 2,5-diformylfuran

[0151] 6. Experimental procedure for the synthesis of 2-ethyl-5-methylfuran from 5-ethylfuran-2-carbaldehyde:

[0152] Add KO tBu (45.0 mg, 0.403 mmol) and 2-butanol (1.5 mL). Heat the reaction mixture, stir and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add 5-ethylfuran-2-carbaldehyde (100 mg, 0.805 mmol) and 2-butanol (3 mL) together, and then add hydrazine hydrate (79 μL, 1.611 mmol) dropwise under gentle stirring. Gradually add the 5-ethylfuran-2-carbaldehyde mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 5 h. Monitor the reaction progress by TLC. After the reaction is complete, analyze the mixture by GC-MS and compare it with the standard.

[0153]

[0154] Scheme 8. Synthesis of 2-ethyl-5-methylfuran from 5-ethylfuran-2-carbaldehyde.

[0155] 7. Experimental procedure for the synthesis of 4,5-dimethylfuran-2-carbaldehyde:

[0156] Add KO t Bu (45.0 mg, 0.403 mmol) and 2-butanol (1.5 mL). Heat the reaction mixture, stir and reflux at 130 °C until the base is completely dissolved. In another round-bottom flask, add 4,5-dimethylfuran-2-carbaldehyde (100 mg, 0.806 mmol) and 2-butanol (3 mL) together, and then add hydrazine hydrate (79 μL, 1.612 mmol) dropwise under gentle stirring. Gradually add the 4,5-dimethylfuran-2-carbaldehyde mixture to the pre-dissolved basic solution and reflux at 120 - 130 °C for 3 - 5 h. Monitor the reaction progress by TLC. After the reaction is complete, analyze the mixture by GC-MS and compare it with the standard.

[0157]

[0158] Scheme 9. Synthesis of 2,3,5-trimethylfuran from 4,5-dimethylfuran-2-carbaldehyde

[0159] 8. Experimental procedure for the synthesis of 2-(ethoxymethyl)-5-methylfuran (EMMF) from 5-MFA:

[0160] Add 5-MFA (100 mg, 0.8919 mmol) and ethanol (2 mL) to a dried round-bottom flask (100 mL), and then add aluminum chloride (3.56 mg, 0.0267 mmol). Heat and stir the reaction mixture under reflux at 90 °C for 4 - 12 hours. Monitor the progress of the reaction by TLC. After the reaction is complete, neutralize the reaction mixture with sodium bicarbonate, and then extract with ether / ethyl acetate. Dry the extract of the reaction over sodium sulfate and concentrate it under vacuum to obtain the desired product compound V with an approximate quantitative conversion rate. Further analyze the product by GC-MS and compare it with the standard.

[0161]

[0162] Scheme 10. Synthesis of EMMF from 5-MFA

[0163] The main advantages of the present invention are as follows:

[0164] 1. A simple, atom-economical and cost-effective method for preparing 5-methyl-substituted furans from 5-aldehyde-substituted furans has been developed.

[0165] 2. In this method, hydrogen and metals are not used, it is easy to scale up, and high yields can be achieved without cumbersome purification.

[0166] 3. No over-reduction is found in this method, and the product is easily separated by solvent extraction and distillation.

[0167] 4. A autoclave system is not required and the reaction is carried out under reflux conditions, thus reducing the risk.

[0168] 5. This method can be applied to the production of high-demand platform compounds 5-MFA, 2,5-DMF and other 5-methyl-substituted furan compounds at low cost, for use as biofuels and other applications.

[0169] 6. 5-MFA is a very good choice for the production of 2,5-DMF following an energy-saving process.

[0170] 7. The etherification of 5-MFA can be completed with different alkyl alcohols under milder acidic conditions, which has great applications in biofuels and biodiesels.

Claims

1. A method for preparing 5-methylfuranmethanol (5-MFA) of formula (III), The method comprises the following steps: i) adding 106.8 g of potassium tert-butoxide and 1 L of 2-butanol to a dried batch reactor to obtain a reaction mixture; ii) heating the reaction mixture obtained in step i) at 130° C. to obtain a pre-dissolved alkaline solution; iii) adding 100.0 g of 5-hydroxymethylfurfural (5-HMF) and 300 mL of 2-butanol to another round-bottom flask, and then adding 78.0 mL of hydrazine hydrate dropwise to obtain a 5-HMF mixture; iv) adding the 5-HMF mixture obtained in step iii) to the pre-dissolved alkaline solution obtained in step ii) and reflux at 120-130° C. for 3-6 hours to obtain a mixture; v) The mixture obtained in step iv) is extracted with ethyl acetate or diethyl ether and dried over Na2SO4, and then the solvent is removed by vacuum distillation at 100-110°C to obtain 5-MFA of formula (III).

2. A method for preparing 2,5-dimethylfuran of formula (IV), The method comprises the following steps: i) adding 45.0 mg of potassium tert-butoxide and 1.5 mL of 2-butanol to a dried round-bottom flask to obtain a reaction mixture; ii) heating the reaction mixture obtained in step i) at 130° C. to obtain a pre-dissolved alkaline solution; iii) adding 100 mg of 2,5-diformylfuran and 3 mL of 2-butanol to another round-bottom flask, and then adding 79 μL of hydrazine hydrate dropwise to obtain a 2,5-diformylfuran mixture; iv) adding the 2,5-diformylfuran mixture obtained in step iii) to the pre-dissolved alkaline solution obtained in step ii) and monitoring the progress of the reaction to obtain 2,5-dimethylfuran of formula (IV).

3. A method for preparing 2-methylfuran, The method comprises the following steps: i) adding 1.1 g of potassium tert-butoxide and 3 mL of 2-butanol to a dried round-bottom flask to obtain a reaction mixture; ii) heating the reaction mixture obtained in step i) at 130° C. to obtain a pre-dissolved alkaline solution; iii) adding 1.0 g of 2-furancarboxaldehyde and 3 mL of 2-butanol to another round-bottom flask, and then adding 1.02 mL of hydrazine hydrate dropwise to obtain a 2-furancarboxaldehyde mixture; iv) adding the 2-furancarboxaldehyde mixture obtained in step iii) to the pre-dissolved alkaline solution obtained in step ii) and monitoring the progress of the reaction to obtain 2-methylfuran.

4. A method for preparing 2-(ethoxymethyl)-5-methylfuran of formula (V), wherein on the basis of the method of claim 1, 5-methylfuranmethanol (5-MFA) of formula (III) is further reacted in the presence of aluminum chloride and ethanol to obtain 2-(ethoxymethyl)-5-methylfuran of formula (V)

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