Method for preparing pyrrole and furan compounds from N-acetylglucosamine

Abstract

The invention discloses a method for preparing pyrrole and furan compounds from a marine waste biomass chitin monomer-N-acetylglucosamine. The method comprises the following steps: in a salt-containing water system, catalyzing N-acetylglucosamine to perform reverse aldol reaction by using a composite valence molybdenum catalyst, and further reacting with beta-diketone compounds to obtain pyrrole and furan compounds at the same time. The introduction of the inorganic salt can promote the dehydration process and improve the distribution ratio of the pyrrole compound in an organic phase, so that high-yield preparation of the pyrrole compound from N-acetylglucosamine is realized. The invention develops a new way for efficiently preparing pyrrole and furan compounds under mild conditions by utilizing marine waste biomass renewable resources.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for preparing pyrrole and furan compounds from N-acetylglucosamine. Background Art

[0002] N-Acetyl-D-Glucosamine (NAG) molecular formula C8H 15 NO6, molecular weight 221.21, is an acetyl derivative of glucosamine and a constituent unit of the polysaccharide chitin in marine crustaceans. Chitin is the second largest biopolymer in nature after cellulose and is an important component of the shells of many lower animals, such as about 15% to 30% in shrimp shells and about 15% to 20% in crab shells. It is also a component of the cell membrane of lower plants and fungi, and also exists in a series of organisms such as fungi, green algae, yeast, squid, sponges, mollusks, nematodes, arthropods, etc.

[0003] In the traditional industrial field, there is a complete scheme for extracting chitosan from marine waste biomass. The main steps include demineralization, deproteinization and decolorization. The obtained chitosan can be further degraded to obtain NAG or glucosamine. The utilization of NAG is currently focused on hydrogenation to prepare amino alcohols, oxidation to prepare amino sugar acids, two-molecule cyclization to prepare deoxyfructosazine, and thermal decomposition to obtain a series of compounds such as pyrrole, pyrazine or pyridine. Kerton developed a method for preparing 3-acetylamino-5-acetylfuran (3A5AF) by dehydration using NAG as a raw material, and derived a series of furanamine compounds for drug synthesis (ChemSusChem, 2012, 5(9): 1767-7); Cao Fei et al. used NAG as a raw material and obtained a new, unsubstituted 3-acetylaminofuran (3AF) compound through a reverse aldol-dehydration reaction, and applied it to the synthesis of dantrolene analogs of anesthetic drugs (ChemSusChem 2023, e202300133). The preparation of these compounds fully utilizes the nitrogen contained in NAG.

[0004] Pyrrole is a five-membered nitrogen heterocyclic compound with unique electronic and steric properties. It is an intermediate for various bioactive substances, natural products, drugs, and fragrances, as well as an important precursor for functional materials. For example, the pyrrole ring is a key structural unit of important biological molecules such as chlorophyll, heme, and porphyrin-like cofactors (such as heme b, chlorophyll a, and vitamin B12); the pyrrole ring is also commonly found in natural products and candidate drugs, and its derivatives are used in antifungal, analgesic, antitumor, and antiviral fields. It is also widely used in the synthesis of pesticides and fragrances. In addition, polypyrrole is a highly efficient conductive polymer that can be used for electrode materials, electromagnetic shielding materials, and gas separation membrane materials. It has a wide range of application value in the fields of energy, optoelectronic devices, sensors, and molecular wires.

[0005]

[0006] So far, the method for preparing pyrrole compounds is mainly cyclization reaction. Among them, the classic pyrrole ring synthesis includes Knorr method, Paal-Knorr method, Hantzsch method, Van Leusen reaction and Barton-Zard reaction (Formula 1). These methods can be divided into two categories: one is to construct the pyrrole ring through the condensation reaction of carbonyl compounds (such as aminoketones, dicarbonyl compounds or halogenated ketones) and amines; the other is to form the pyrrole ring through the condensation cyclization of enamine active intermediates or isocyanate with nitroolefins. Except for the synthesis of 2,5-disubstituted pyrroles by Paal-Knorr reaction of some easily available dicarbonyl compounds, other pyrrole ring syntheses have the limitations of difficult raw materials and harsh reaction conditions. In recent years, many methods such as new catalysts and multi-component one-pot methods have been developed for pyrrole synthesis, but these methods still need to be further expanded. For example: The advantage of Van Leusen reaction is that it can directly obtain unsubstituted pyrrole and the yield is very high, but the high yield needs to be carried out at a low temperature of -80 degrees, which is not easy to operate and has high energy consumption. The selection of different synthetic routes is mainly based on factors such as the position and quantity of substituents on the pyrrole ring, the difficulty of raw material synthesis, and atom economy. There is still huge room for further development of new and greener pyrrole ring synthesis technologies.

[0007] Considering that the pyrrole ring is a nitrogen-containing heterocyclic ring, its nitrogen element can be derived from nitrogen-containing biomass, such as chitin, amino acids, and amino groups of raw materials, thereby solving the problem of raw materials for preparing pyrrole. As early as the 1980s, heterocyclic compounds such as pyrazine, pyrrole, and pyridine were discovered in the pyrolysis reaction of chitin. GAO et al. pyrolyzed chitin at 300°C, and indeed detected pyrrole, pyrazine, and pyridine compounds in the pyrolysis products. Chen et al. also used the pyrolysis method to generate furfural from cellulose glucose, and then exchanged furfural with ammonia to generate pyrrole (Formula 2). In this specific method, ammonia promotes the dealdehyde grouping of cellulose pyrolysis product FF to generate furan, and then furan undergoes a ring-opening reaction, allowing the C2 amino group to connect to the C5 position to form a ring, and the O atom is removed in the form of hydroxyl by dehydration to form pyrrole. Li et al. reported in 2011 that a possible mechanism of a cascade reaction involving carbon cation intermediates was proposed under the catalysis of InCl3. The amino sugars (D-glucosamine and D-galactosamine) and 1,3-dicarbonyl compounds were condensed in one pot in water to synthesize C-pyrrolidinyl glycosides. Another example: Professor David Milstein's research group at the Weizmann Institute in Israel (Angew. Chem. Int. Ed., 2016, 55, 14373-14377) reported the use of simple, alcohols obtained by enzymatic hydrolysis of lignocellulose, and then pyrrole compounds were obtained by Co-catalyzed dehydrogenation and coupling with amines, with more friendly reaction conditions.

[0008] However, the preparation conditions of the PNNH-Co chelate catalyst used in it are still relatively difficult.

[0009] Summary of the invention

[0010] The present invention provides a method for preparing pyrrole and furan compounds from N-acetylglucosamine. In the method, in a salt water system, a composite valence molybdenum catalyst is used to catalyze a reverse aldol reaction to generate an intermediate N-acetylglucosamine and erythrose / threose, and then the intermediate reacts with a β-diketone compound under mild conditions to form pyrrole (1) and furan (2) compounds through a condensation-dehydration reaction.

[0011]

[0012] In the present invention, we have established a method for preparing pyrrole and furan compounds from N-acetylglucosamine, which mainly utilizes the retro-aldol reaction of NAG to form active N-acetylglucosamine and erythrose, which react with dicarbonyl compounds in situ to undergo condensation-dehydration reaction to form pyrrole and furan compounds (Formula 3).

[0013]

[0014] The technical solution adopted by the present invention is:

[0015] A method for preparing pyrrole and furan compounds from N-acetylglucosamine, wherein in a salt water system, complex valence molybdenum is used as a catalyst, N-acetylglucosamine and β-diketone compounds are added to react under mild conditions to obtain a pyrrole compound (1), and the reaction also co-produces a furan compound (2).

[0016] When acetylacetone is selected as the in-situ capture agent β-diketone compound, its pyrrole product is N-acetyl-2-methyl-3-acetylpyrrole (3), and its furan product is 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) (4).

[0017]

[0018] The composite valence molybdenum catalyst mainly refers to IV, V and VI valence composite catalysts obtained by reducing VI valence molybdenum. VI valence molybdenum raw materials include but are not limited to molybdic acid, molybdenum trioxide, magnesium molybdate, ammonium molybdate, phosphomolybdic acid, etc., preferably molybdic acid, molybdenum trioxide or sodium molybdate, wherein the composite valence molybdenum catalyst prepared from molybdic acid as raw material has the best effect. The composite valence molybdenum catalyst in the reaction: the dosage of N-acetylglucosamine is optimized to 0.5-1.0.

[0019] The β-diketone compounds include but are not limited to the following two categories: acetylacetone (I) and ethyl acetoacetate (II), the former including acetylacetone, 2,4-hexanedione, benzoylacetone, dibenzoylmethane, 1,3-indandione, 1,3-cycloheptanedione, 2,4-piperidinedione, 1,3-cyclopentanedione, methyl acetylacetonate, etc.; the latter including ethyl acetoacetate, ethyl formyl acetate, ethyl aminoacetoacetate, ethyl chloroacetoacetate, ethyl benzoylacetate, etc. The present invention preferably uses acetylacetone, ethyl acetoacetate, ethyl 4-chloroacetoacetate, ethyl aminoacetoacetate, 2,5-hexanedione, 2,4-piperidinedione, 1,3-cyclopentanedione, among which acetylacetone has the best effect.

[0020]

[0021] The salt water system includes, but is not limited to, sodium chloride, calcium chloride, sodium bromide, potassium chloride, lithium chloride, lithium bromide, magnesium chloride, sodium carbonate, sodium bicarbonate, calcium sulfate, etc. Preferably, chloride salts or bromide salts are used, among which sodium chloride, magnesium chloride and lithium bromide are the best.

[0022] The reaction conditions are: reaction temperature 60-120°C, reaction time 1-4h, preferably 80-100°C, reaction time 1-3.5h. The concentration of molybdenum-containing catalyst is 0.5-1.5mmol. The salt-containing water system, preferably chloride salt and bromide salt, has a concentration of 5wt.%-30wt.%. More preferably, a 15% LiBr salt water system is selected.

[0023] The molar ratio of the reaction substrate N-acetylglucosamine to the β-diketone compound is 1:1-1:20, preferably 1:3-1:8.

[0024] The raw material source of the present invention, N-acetylglucosamine, comes from marine waste biomass.

[0025] In one embodiment of the present invention, 2.5 mL of water, 2.5 mL of acetylacetone, 220 mg of N-acetylglucosamine, 60 mg of a complex valence molybdenum catalyst, and 15 wt.% of lithium bromide are used. After the reaction, the organic phase is separated to obtain a pyrrole compound, and the aqueous phase is separated to obtain a furan compound. Under the optimal conditions, the reaction temperature is 90° C. and the reaction time is 3 h. The yields of the pyrrole compound and the furan compound are 95% and 74%, respectively.

[0026] Beneficial effects: Compared with the existing pyrrole synthesis method, which has the problems of difficult raw material acquisition and harsh reaction conditions, the raw material source N-acetylglucosamine of the present invention comes from marine waste biomass; the whole reaction process is simple and the yield is high; two heterocyclic compounds pyrrole and furan are obtained at the same time, which is an optimal process route for high-value utilization of marine waste biomass. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The effect of molybdate types on the yield of pyrrole compounds;

[0029] Figure 2 The effect of salt types on the yield of pyrrole compounds;

[0030] Figure 3 Effect of salt concentration on the yield of pyrrole compounds;

[0031] Figure 4 Effect of molybdic acid content on the yield of pyrrole compounds;

[0032] Figure 5 The effect of reaction temperature on the yield of pyrrole and furan compounds;

[0033] Figure 6 Single crystal of the pyrrole product N-acetyl-2-methyl-3-acetylpyrrole;

[0034] Figure 7Pyrrole product N-acetyl-2-methyl-3-acetylpyrrole 1 H NMR;

[0035] Figure 8 Pyrrole product N-acetyl-2-methyl-3-acetylpyrrole 13 C NMR;

[0036] Fig. 9 MS of the pyrrole product N-acetyl-2-methyl-3-acetylpyrrole;

[0037] Fig.10 Furan product 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) 1 H NMR;

[0038] Fig.11 Furan product 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) 13 C NMR;

[0039] Fig.12 Furan product 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) MS;

[0040] Fig.13 MS of the pyrrole product of the reaction of N-acetylglucosamine with 1,3-cyclohexanedione;

[0041] Fig.14 MS of the pyrrole product of the reaction of N-acetylglucosamine with 1,3-indandione;

[0042] Fig.15 MS of the pyrrole product of the reaction of N-acetylglucosamine with 1,3-cyclopentanedione;

[0043] Fig.16 MS of the pyrrole product of the reaction of N-acetylglucosamine with 2,4-hexanedione;

[0044] Fig.17 MS of the pyrrole product of the reaction of N-acetylglucosamine with methyl acetylacetonate;

[0045] Fig.18 MS of the pyrrole product of the reaction of N-acetylglucosamine with ethyl acetoacetate;

[0046] Fig.19 MS of the pyrrole product of the reaction of N-acetylglucosamine with ethyl 4-chloroacetoacetate;

[0047] Fig. 20 MS of the pyrrole product from the reaction of N-acetylglucosamine with ethyl carbamoyl acetate. DETAILED DESCRIPTION

[0048] The present invention can be better understood according to the following examples. However, the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0049] General experimental method:

[0050] 1) Preparation of composite valence molybdenum catalyst:

[0051] Add water, VI valence molybdenum raw materials, such as molybdic acid, molybdenum trioxide, magnesium molybdate, ammonium molybdate, phosphomolybdic acid, etc., and reducing agent vitamin C into a pressure-resistant tube, wherein the ratio of VI valence molybdenum raw materials to reducing agent is 1:5, and react at 60-80°C for 1-2h. Add acetylacetone dropwise and stir for 30min. Separate the organic phase, remove acetylacetone by vacuum distillation to obtain a gray-green composite valence molybdenum catalyst. XPS is used to characterize the composite valence molybdenum catalyst, which has a mixed type of molybdenum valence IV, V and VI valence.

[0052] 2) Preparation of pyrrole and furan compounds from N-acetylglucosamine:

[0053] In a salt water system, a composite valence molybdenum catalyst is used to catalyze the reverse aldol reaction of N-acetylglucosamine. The generated active intermediates N-acetylglucosamine and erythrose are captured in situ by the β-diketone compound acetylacetone, and react under mild conditions to obtain pyrrole and furan compounds. The specific performance is:

[0054] Add 2.5 mL of water, 2.5 mL of acetylacetone, 220 mg of N-acetylglucosamine, 60 mg of complex valence molybdenum catalyst, 15 wt.% of lithium bromide into a pressure tube, and react at 120°C for 2 h. After the reaction, put it in ice water for rapid cooling. Take the organic phase to determine the content of pyrrole compounds by gas chromatography, and take the aqueous phase to determine the content of furan compounds by high performance liquid chromatography.

[0055] 3) Isolation of pyrrole compound: After the reaction is completed, separate the organic phase (10 mL), add 150 mL of 10% copper acetate solution, stir evenly and react for 3-5 hours, filter the precipitate (blue-green, copper acetylacetonate); extract the aqueous phase with ethyl acetate 2-3 times, add anhydrous sodium sulfate and dry overnight, evaporate the ethyl acetate to obtain a crude pyrrole compound. If further purification is required, column chromatography is used to further separate the target product.

[0056] 4) Separation of furan compounds: After the reaction is completed, separate the aqueous phase (10 mL), add 10 mL of 10% copper acetate solution, stir evenly and react for 3-5 hours, filter the precipitate (blue-green, copper acetylacetonate); further concentrate the aqueous phase to dryness to obtain a crude furan compound. If further purification is required, column chromatography is used to further separate the target product.

[0057] Product characterization and detection methods:

[0058] Characterization of pyrrole compounds: The product N-acetyl-2-methyl-3-acetylpyrrole was characterized by HRMS, 1 H and 13 C NMR characterization: HRMS (ESI, C 13 NH) m / z:166.1(M+H + ), see the attached Figure 1-4 .

[0059] Characterization of furan compounds: The product 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) was characterized by HRMS, 1 H and 13 C NMR characterization, HRMS (ESI, C 13 NH) m / z:185(M+H + ) See attached for details Figure 5-7 .

[0060] The detection of the pyrrole product N-acetyl-2-methyl-3-acetylpyrrole was performed by GC. The reaction product samples in the organic phase were analyzed by a Shimadzu gas chromatograph (GC-2010Plus) equipped with a Restek Rtx-VMS capillary. The specific conditions were that 1 μL of sample was injected into the gas chromatography column with a split ratio of 49:1. The carrier gas was helium with a flow rate of 1 mL / min-1. The initial oven temperature started at 40°C and was maintained for 5 minutes. The temperature was increased to 240°C at a rate of 7.5°C / min. The temperature was maintained at 240°C for 15 minutes.

[0061] The furan product 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran was detected by HPLC (Dionex, Sunnyvale, CA). The specific conditions were: using a Sinochrom ODS-BP 5μm C18 column and a 254nm ultraviolet (UV) detector for detection, a mobile phase of 17% CH3CN / H2O, a flow rate of 0.6mL min-1, and a column oven set at 30°C.

[0062] Detection of N-acetylglucosamine: The lower aqueous phase of the reaction solution was detected by HPLC (Dionex ICS-3000, Sunnyvale, CA). The specific conditions were to use an integrated amperometric detector and a CarboPac PA1 guard column and analytical column (Dionex, Sunnyvale, CA) to quantify acetylglucosamine to determine whether the reaction was complete. The mobile phase was 0.005 Mmol H2SO4, and the flow rate was 0.6 mL / min. The column oven was set to 30°C.

[0063] Product yield calculation method:

[0064] The yield of pyrrole compound is calculated according to the following equation:

[0065]

[0066] The yield of furan compounds is calculated according to the following equation:

[0067]

[0068] Example 1: Effect of catalyst type on reaction progress

[0069] We selected acetylacetone as a diketone compound to explore the optimal reaction conditions for preparing pyrrole and furan compounds as an in-situ capture agent. In the present invention, a catalyst needs to be added to catalyze the reverse aldol reaction of N-acetylglucosamine, thereby obtaining active N-acetylglucosamine and erythrose, which undergo condensation reaction with acetylacetone in situ, and then dehydrate to produce pyrrole and furan compounds. It can be seen that the reverse aldol reaction of N-acetylglucosamine is the key to preparing pyrrole and furan compounds, and it is extremely important to screen out an efficient reverse aldol catalyst.

[0070] This example adopts the single factor analysis method, selects four VI valence molybdenum raw materials, such as molybdic acid, molybdenum trioxide, sodium molybdate, phosphomolybdic acid and vitamin C as reducing agents to prepare a composite valence molybdenum catalyst, and the reaction conditions are: 70℃ reaction for 1.5h. The specific conditions for preparing pyrrole and furan compounds from N-acetylglucosamine are: 2.5mL of water (pressure tube); 2.5mL of acetylacetone (pressure tube); reaction temperature 100℃; reaction time 1h; N-acetylglucosamine dosage is 220mg; composite valence molybdenum catalyst dosage is 60mg. At the same time, we choose not to add catalyst and IV valence molybdenum dioxide as catalyst for comparative experiments. Since the reverse aldol reaction produces equal proportions of N-acetylglucosamine and erythrose, and condenses with acetylacetone, theoretically, pyrrole and furan compounds are produced in equal proportions. Therefore, after the reaction is completed, we take the upper organic phase and determine the content of pyrrole compounds by gas chromatography to determine the efficiency of the catalyst.

[0071] Depend on Figure 1 It can be seen that when the blank control group experiment is conducted without adding the composite valence molybdenum catalyst, the retro-aldol reaction will not occur. Although N-acetylglucosamine is consumed during the reaction, the presence of pyrrole compounds is not detected in the organic phase. After adding the above four composite valence molybdenum catalysts, there is a certain retro-aldol catalytic effect, and the yield of pyrrole compounds is between 7-39%. Among them, the catalytic effect of the composite valence molybdenum catalyst prepared with molybdic acid as the VI valence molybdenum raw material is much better than other catalysts, and the yield of pyrrole compounds can reach 39% under the reaction conditions. When IV valence molybdenum dioxide is used as a catalyst, the presence of pyrrole compounds can also be detected in small amounts, with a yield of less than 3%. Subsequent studies will be conducted on composite valence molybdenum catalysts derived from molybdic acid.

[0072] Example 2: The effect of salt type on the reaction

[0073] During the reaction, we observed that the partitioning effect between the reaction water and the organic phase was not good. Here, we considered introducing inorganic salts into the reaction water phase. On the one hand, the addition of inorganic salts can promote the dehydration reaction and reduce the formation of by-product dihydropyrrole compounds; on the other hand, the addition of inorganic salts can increase the distribution ratio of pyrrole compounds in the organic phase and promote rapid phase separation between the water and organic phases.

[0074] This example adopts single factor analysis, with no salt added as the blank control group, and selects five typical chloride and bromide salts, including sodium chloride, lithium bromide, magnesium chloride, calcium chloride, and potassium chloride. The reaction conditions are: 2.5 ml of water (pressure tube); 2.5 ml of acetylacetone (pressure tube); reaction temperature 120 ° C; reaction time 2h; acetylglucosamine dosage 220 mg; molybdic acid-derived composite valence molybdenum catalyst dosage 60 mg; salt concentration is 10wt.%. Similarly, we determine the promotion effect of inorganic salts by measuring the content of pyrrole compounds in the upper organic phase by gas chromatography.

[0075] Depend on Figure 2 It can be seen that after adding inorganic salts, the yield of pyrrole compounds in some reactions was slightly improved. Among them, lithium bromide had the best promotion effect, and the yield of pyrrole products reached 48%. This shows that lithium bromide does promote the formation of pyrrole compounds.

[0076] Example 3: The effect of salt concentration on the reaction

[0077] In Example 2, we introduced inorganic salts to find their promoting effect on the reaction, and further considered the effect of salt concentration in order to further improve the yield. Therefore, we selected the above two salts with better effects, lithium bromide and magnesium chloride, for comparative study.

[0078] By using the single factor analysis method, lithium bromide and magnesium chloride were selected to react under the same reaction conditions. The reaction conditions are: 2.5 ml of water (pressure tube); 2.5 ml of acetylacetone (pressure tube); reaction temperature 120°C; reaction time 2h; 220 mg of acetylglucosamine; 60 mg of complex valence molybdenum catalyst; salt concentration 5-30wt.%. Similarly, we determined the promotion effect of inorganic salts by measuring the content of pyrrole compounds in the upper organic phase by gas chromatography.

[0079] Depend on Figure 3 It can be seen that: no matter at what concentration, the promoting effect of lithium bromide as an inorganic salt is better than that of magnesium chloride as an inorganic salt. As the concentration of inorganic salt increases, the promoting effect on pyrrole compounds becomes more obvious. However, after exceeding 15wt.%, its promoting effect decreases. Considering the salt type and its concentration comprehensively, when 15% LiBr is selected, the effect is the best, and the yield of pyrrole compounds is as high as 65%.

[0080] Example 4: Study on the effect of molybdic acid concentration on yield

[0081] After completing Examples 1-3, we determined that the complex-valence molybdenum catalyst derived from molybdic acid was the optimal catalyst and 15 wt% LiBr was the optimal salt, and then continued to consider the effect of the catalyst dosage to optimize the reaction.

[0082] The single factor analysis method was used to change the amount of the complex valence molybdenum catalyst from molybdic acid. The reaction conditions were: 2.5 ml of water (pressure tube); 2.5 ml of acetylacetone (pressure tube); reaction temperature 120°C; reaction time 2 hours; 220 mg of acetylglucosamine; 15 wt.% lithium bromide concentration; 30-90 mg of the complex valence molybdenum catalyst from molybdic acid. Similarly, we determined the effect of the catalyst by measuring the content of pyrrole compounds in the upper organic phase by gas chromatography.

[0083] Depend on Figure 4 It can be seen that the increase in the amount of complex-valence molybdenum catalyst derived from molybdic acid does not show a certain regularity in the effect on the formation of pyrrole compounds. When the amount of molybdic acid is 60 mg, the highest yield of pyrrole compounds is 65%.

[0084] Example 5: Effect of reaction temperature and time on the yield of pyrrole compounds

[0085] After determining the optimal raw materials, raw material ratios, catalysts and their concentrations, we explored the temperature and time in this example. First, using the single factor analysis method, we chose different temperatures to react under the same 2h conditions. The reaction conditions are: 2.5ml of water (pressure-resistant tube); 2.5ml of acetylacetone (pressure-resistant tube); reaction time 2h; 220mg of acetylglucosamine; 60mg of complex valence molybdenum catalyst from molybdic acid; 15wt.% lithium bromide, and the reaction temperature is between 80-120°C. Considering that the formation of the two products, pyrrole compounds and furan compounds, has a certain correlation with temperature, here, after the reaction is completed, we take the organic phase to determine the content of pyrrole compounds on gas chromatography, and take the aqueous phase to determine the content of furan compounds on high performance liquid chromatography, and calculate the yields of the two products at the same time, and get Table 1.

[0086] Table 1: Yields of pyrrole and furan compounds at different temperatures

[0087]

[0088] As can be seen from Table 1, the yields of pyrrole compounds and furan compounds are low when the reaction temperature is low (80°C) and high (120°C); while the yields of the two products are acceptable at 90°C, 100°C, and 110°C. Since the yields of the two compounds may be different at different reaction times, we preferred 90°C, 100°C, and 110°C to investigate the product yields at different times. The specific results are shown in Figure 5 .

[0089] Depend on Figure 5 The data show that: with the extension of reaction time, the yields of pyrrole and furan compounds increased; at different temperatures, the growth trend was different. Under the optimal conditions, the reaction temperature was 90 ° C and the reaction time was 3h, the yields of pyrrole and furan compounds were 95% and 74% respectively.

[0090] Example 6: Reaction adaptability of diketone compounds

[0091] Under the above reaction conditions, we expanded the types of diketone compounds. Different diketone compounds were used to replace acetylacetone as in-situ capture agents, and N-acetylglucosamine / erythrose obtained by the reverse aldol reaction of N-acetylglucosamine catalyzed by a complex valence molybdenum catalyst derived from molybdic acid was subjected to a condensation reaction to form different pyrrole and furan compounds.

[0092] This example uses single factor analysis to select eight dicarbonyl compounds, including 5-methyl-1,3-cyclohexanedione, 1,3-indanedione, 1,3-cyclopentanedione, 2,4-hexanedione, methyl acetylacetonate, ethyl acetoacetate, ethyl 4-chloroacetoacetate, and ethyl carbamoyl acetate. The specific conditions for the reaction are: 220 mg of N-acetylglucosamine; 60 mg of the complex valence molybdenum catalyst from molybdic acid; 2.5 ml of water (pressure-resistant tube); the dicarbonyl compound is added at a molar ratio of 3:1 to N-acetylglucosamine; the reaction temperature is 120°C; the reaction time is 2 hours. After the reaction is completed, sampling is performed for mass spectrometry.

[0093] As shown in Table 2, the reaction results of different diketone compounds with N-acetylglucosamine show differences. Here, some reactions that can detect the target pyrrole compounds by mass spectrometry are listed. The structure of the pyrrole compound is shown in Table 2, and its mass spectrometry detection is detailed in Figure 13-20 .

[0094] Table 2: Preparation of pyrrole compounds from different β-diketones

[0095]

[0096]

Claims

1. A method for preparing pyrrole and furan compounds from N-acetylglucosamine, It is characterized in that In a salt water system, using complex valence molybdenum as a catalyst, adding N-acetylglucosamine and β-diketone compounds to react under mild conditions to obtain a pyrrole compound (1), and the reaction also co-produces a furan compound (2); 2. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The composite valence molybdenum catalyst refers to a composite catalyst of IV, V and VI valence states obtained by reducing VI valence molybdenum; the VI valence molybdenum raw materials include but are not limited to molybdic acid, molybdenum trioxide, magnesium molybdate, ammonium molybdate, and phosphomolybdic acid.

3. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The β-diketone compounds include but are not limited to the following two categories: acetylacetones and ethyl acetoacetates. The acetylacetones include acetylacetone, 2,4-hexanedione, benzoylacetone, dibenzoylmethane, 1,3-indandione, 1,3-cycloheptanedione, 2,4-piperidinedione, 1,3-cyclopentanedione, and methyl acetylacetonate; the ethyl acetoacetates include ethyl acetoacetate, ethyl formyl acetate, ethyl aminoacetoacetate, ethyl chloroacetoacetate, and ethyl benzoyl acetate.

4. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The salt water system includes, but is not limited to, sodium chloride, calcium chloride, sodium bromide, potassium chloride, lithium chloride, lithium bromide, magnesium chloride, sodium carbonate, sodium bicarbonate, and calcium sulfate.

5. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The mild conditions are reaction temperature of 80-120° C. and reaction time of 1-3.5 h.

6. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The molar ratio of N-acetylglucosamine to β-diketone compounds is 1:1-1:20, preferably 1:3-1:

8.

7. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The composite valence molybdenum catalyst: the dosage of N-acetylglucosamine is 0.5-1.

0.

8. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 1, It is characterized in that The β-diketone compound is acetylacetone, its pyrrole product is N-acetyl-2-methyl-3-acetylpyrrole (3), and its furan product is 5-(1,2-dihydroxyethyl)-2-methyl-3-acetylfuran (DMAF) (4); 9. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 3, It is characterized in that The β-diketone compound is preferably acetylacetone, ethyl acetoacetate, 2,5-hexanedione, 2,4-piperidinedione, or 1,3-cyclopentanedione.

10. A method for preparing pyrrole and furan compounds from N-acetylglucosamine according to claim 4, It is characterized in that The salt in the salt water system is preferably chloride salt or bromide salt, and the salt concentration is 5wt.%-30wt.%.

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