CN100537513C - Preparation technology of monomethyl fumarate - Google Patents

Abstract

The monomethyl fumerate preparing process features that maleic anhydride is first alcoholized and ring-opening esterified with methanol into monomethyl maleate; and monomethyl maleate is then positioning reacted in non-polar solvent with hydrogen halide as catalyst to produce monomethyl fumerate. The present invention has simple preparation process, short production period of 1-2 hr, high yield up to 85-90 % and high production efficiency.

Description

Preparation technology of monomethyl fumarate

technical field

The invention relates to a preparation process of monomethyl fumarate as a high-efficiency broad-spectrum anti-mold and fungicide for grain, food and feed.

technical background

Monomethyl fumarate is also called monomethyl fumarate, the English name is: mono-methylfurmarate, MMF for short, MMF can widely and effectively inhibit the growth of mold in the environment, and the bacteria and yeasts that can be inhibited reach 30 A variety of them, especially aflatoxin has a strong inhibitory effect. At the same time, the antibacterial property of MMF is not affected by the pH value. Compared with dimethyl fumarate DMF, if the same anti-mold effect is to be achieved, the consumption of MMF is only three-fifths of the consumption of DMF. In addition, MMF is far less toxic and irritating than DMF. Therefore, MMF is an ideal anti-mildew, fungicide and anti-moth agent for grain, food and feed.

At present, the preparation method of MMF has the following two ways: one is the fumaric acid method, that is, using fumaric acid (fumaric acid, fumaric acid) as raw material, reacting with methanol under the catalysis of concentrated sulfuric acid or _BF3 . Another kind of approach is to be raw material with maleic anhydride (being called dehydrated malic anhydride again, or maleic anhydride), and its route comprises two kinds again, and the steps of two kinds of routes are respectively as follows:

First, maleic anhydride → maleic acid → fumaric acid → monomethyl fumarate (ie monomethyl fumarate).

Another route is maleic anhydride → monomethyl maleate → monomethyl fumarate.

Fumaric acid does not exist much in nature. It is produced from maleic acid aqueous solution catalyzed by thiourea, or fermented from molasses, but the vast majority of fumaric acid is converted from maleic anhydride. Therefore, the starting material for preparing monomethyl fumarate directly from fumaric acid is still maleic anhydride.

In the existing synthetic method of monomethyl fumarate, the production cycle is all long. For example, Zhong Guoqing and Zeng Renquan of Southwest University Rongchang Campus reported ["Fine Chemical Industry" 2002.19 (6) 343-345] using benzene as a solvent and hydrochloric acid-pyridine as a composite catalyst. The reaction time will be 3h and the yield will be 83%; When Chemical Co., Ltd. synthesizes monomethyl fumarate, the first step takes 1.5-5 hours to react; the second step uses hydrochloric acid as a catalyst in the presence of no solvent, and it takes 20-60 hours. As a solvent, it takes 3-8 hours, and the yield is about 95%.

Contents of the invention

For solving the above problems, the purpose of this invention is to provide a kind of preparation technology of monomethyl fumarate, and its reaction time is short, and yield is higher, and production efficiency improves greatly.

The object of the present invention is achieved like this: a kind of preparation technology of monomethyl fumarate is characterized in that: at first maleic anhydride alcohol is decomposed and esterified into monomethyl maleic acid by methanol, Then use hydrogen halide as a catalyst to react monomethyl maleate in a non-polar solvent to generate monomethyl fumarate.

The preparation process of the monomethyl fumarate of the present invention is simple, the production cycle is short, the reaction can be completed in only 1-2 hours, the yield is high, up to 85-90%, and the production efficiency is greatly improved.

Detailed ways

The present invention uses maleic anhydride as a raw material, undergoes methanolysis and ring-opening esterification into monomethyl maleate, and then undergoes transposition to generate monomethyl fumarate. The reaction formula is as follows:

Analyzing the structure of maleic anhydride (I), there are two carbonyl groups in the molecule, so it is easy to carry out alcohololysis ring-opening and methyl esterification in the presence of methanol to obtain monomethyl maleate (II), This step reaction is very fast and exothermic, so the reaction only needs to be heated to initiate the reaction and can continue. In order to completely methylate the maleic anhydride, a feed molar ratio of maleic anhydride:methanol=1:1.05-1.1 is used. In step ②, the molar ratio of maleic anhydride to catalyst is 1:0.25-0.4, and the reaction temperature is 80-95°C. In the process of transposition of monomethyl maleate (II) to monomethyl fumarate (III), since the double bond cannot rotate freely, the reaction process of the transposition process is firstly carbon-carbon The double bond breaks and then forms a carbon-carbon σ-bond. Only the σ-bond can be rotated. The carboxylic acid group -COOH and carboxylate methyl ester group on the same side in the monomethyl maleate molecule- Due to the steric effect of COOCH ₃ , once the double bond is broken, the two groups immediately rotate to the opposite side through the σ-bond, thus completing the transformation from monomethyl maleate to fumarate monoester process. Here, the breaking of the carbon-carbon double bond is achieved by the addition of the double bond to the hydrogen halide rather than the addition of the hydrogen halide acid, which can also react with the double bond to a certain extent, but the hydrogen halide The water of acid can hinder this reaction, so reaction time can be very long when making catalyzer with concentrated hydrochloric acid, therefore adopts to feed hydrogen chloride gas as catalyzer in the present invention. The product monomethyl fumarate is a lipid compound with weak polarity. When monomethyl maleate is converted into monomethyl fumarate of trans structure, if it is Substance is used as solvent, and according to the principle of mutual solubility of similars, the time required for the crystallization of the product from the solvent must be longer. If a non-polar substance is used as the dispersion solvent, the product can be precipitated from the solvent in the form of crystals very quickly. Therefore, the present invention The use of non-polar substances, such as petroleum ether, as a solvent for the transposition reaction can greatly shorten the reaction time.

With maleic anhydride:methanol=1:1.05-1.1 feeding molar ratio, methanol decomposes maleic anhydride and esterifies maleic anhydride into monomethyl maleic acid, the reaction temperature is 45-90°C, and the time is 30-60min, then use petroleum ether as the reaction dispersion solvent, pass through HCl, the molar ratio of maleic anhydride and HCl is 1:0.25-0.4, and catalyze the transposition of maleic acid monomethyl ester into fumadiene Acid monomethyl ester, that is, monomethyl fumarate, the reaction temperature is 80-95°C, and the reaction time is 30-60min.

Example

98 grams (1 mol) of maleic anhydride and 35.2 grams of methanol were heated to 50° C. under stirring, and the maleic anhydride began to dissolve. Since this reaction is an exothermic reaction, the heating can be stopped during the reaction, and the temperature can rise to 90°C. Start timing at 50°C, add 100ml of petroleum ether after 30min, feed HCl, stir and react at 80-95°C for 0.5-1h, control the flow of HCl so that the molar ratio of maleic anhydride to HCl fed is 1: 0.3, filtered and dried to obtain the crude product of monomethyl fumarate, which was recrystallized with aqueous ethanol solution, filtered and dried to obtain white crystals of monomethyl fumarate with a melting point of 142-144°C and a yield of 85-90 %.

Claims (7)

1. a preparation technology of monomethyl fumarate, it is characterized in that comprising the following steps: 1. maleic anhydride alcohol is decomposed ring-opening esterification to monomethyl maleate by methanol; 2. with hydrogen halide As a catalyst, make monomethyl maleate react in a non-polar solvent, and transposition generates monomethyl fumarate. 2. The preparation process of monomethyl fumarate according to claim 1, characterized in that: the molar ratio of maleic anhydride and methanol in the step ① is 1: 1.05-1.1. 3. The preparation process of monomethyl fumarate according to claim 1, characterized in that: the reaction temperature of maleic anhydride and methanol in the step ① is 45-90°C. 4. The preparation process of monomethyl fumarate according to claim 1, characterized in that: the molar ratio of the maleic anhydride to the catalyst is 1: 0.25-0.4. 5. the preparation technology of monomethyl fumarate according to claim 1, is characterized in that: the catalyzer in described step 2. is hydrogen chloride. 6. the preparation technology of monomethyl fumarate according to claim 1, is characterized in that: the nonpolar solvent in described step 2. is sherwood oil. 7. The preparation process of monomethyl fumarate according to claim 1, characterized in that: the reaction temperature in the step ② is 80-95°C.