SU681057A1 - Process for the preparation of 4-methyl-5-propoxyoxazol - Google Patents

Description

which solvent (3). When implementing this method, it is necessary to work with large quantities of hydrogen cyanide.

Methods are also known for the preparation of 4-methyl 5-alkoxy oxazoles by decarboxylation of an acidic oxazole chain. One of the methods is that 4-methyl-5-alkoxy-oxazole-2-carboxylic acid is heated to 50-200 ° C with or without an organic solvent, and COORj COORi

CH-COOR

СН-СЯ-COOR I I TOTCOCOOR

TOf, where R and RI are lower alkyl. Thus, the process itself is a two-step process, with the initial product for it also being obtained in two stages using a poisonous substance, phosgene. Another method is that decar is subjected to boxing 5-alkoxioxazole-4-acetic acid, which is previously obtained from aspartic acid 6. Asparaginic acid is esterified and dicersed with phosgene deacidium. The resulting 5-alkoxyoxazole-4-acetic acid ester was then sulphate the resulting carboxylic acid decarboxylated. Decarboxylation is carried out in the presence of compounds of the general formula H A-C-B, where A and B are electron-withdrawing substituents. They are taken in a molar ratio of the starting material of 0.1-0.5. The yield is 36-85%, and when using agents such as diethyl or dimethyl fumarate or fumarodinitrile as a catalyst, the cohesive product is contaminated with these compounds in an amount of 2-20%. The following catalysts do not contaminate the final alkoxioxazole: trais-dibenzyl acetylene, trans-bsalcetophenone, bms-tosylsulphenylethypene, dibenzyl fumarate. However, given the industrial application of these compounds are difficult to access. The closest to the proposed technical essence is the method of obtaining 4-megsh-5-alkoxoxazopes by cyclization of the alkyl ester of o-isocyanopropionic acid at ISO-ISOC (7. This method is simple in technological design, the starting alkyl esters of a-isocyanopropionic acid are obtained by dehydration

The sweat is obtained previously by alkaline hydrolysis of the corresponding ester (41.

However, the starting 4-metsh-1-5-alkoxy-oxazole-2-carboxylic acid ester is obtained by a two-step method: by reacting alanyl ester with a P1-gelev diester followed by treating the resulting alkoxyalylalanine ester with such a dehydrating agent as phosgene in the presence of a base 5.

Reaction scheme;

OR

3} - J

lf

0 COOR

1 corresponding esters of N-formylalanine. However, the yield of the target product is low (5-28%). The aim of the invention is to increase the yield of the target product. The proposed method for the preparation of 4-methyl-5-propoxyoxazole is that the propyl ester of isocyanopropionic acid is subjected to thermal cyclization, preferably at 135-i80 ° C in an aprotic nucleophilic solvent. As an aprotic nucleophilic solvent, N N-dimethylformamide, hexamethylphosphoric triamide (hexametal), acetonitrile, triethyl phosphate, and the like can be used. Such solvents can form donor-acceptor complexes with the isonitrile group of a-isocyanpropanoic acid propyl ester. As a result of complexation, the isomerization of o-isocyanopropionic acid propyl ester into o-cyano propionic acid propyl ester is minimized. In addition, dilution of a-isocyanopropionic acid propyl ester reduces the amount and quantity of by-products: resinous substances and d-amer of a-isocyanopropionic acid dimer. The optimum amount of solvent is two or more (about 4) equivalents. The yield of 4-methyl-5-propoxy-oxazole is determined by gas-liquid chromatography. 4-Methsl-5-propoxy-oxazole is obtained from the reaction mixture by vacuum distillation or by distillation with steam. Example 1. Obtaining propyl ester of o-isociophosphionic acid. To a solution of 49.9 g of N-formyl-o-alanine propyl ether and 153 ml of triethylamine v.250 ml of anhydrous chloroform are added dropwise at O-3C and stirring with p & 28.7 ml of phosphorus oxychloride in 50 ml of hls form in for 1.5 hours. Hold at 20 ° C for 3 hours, cool to 5 ° C, wash with 5% aqueous ammonia (2 times 150 ml) and dry with sodium sulfate. The solvent is removed and the residue is distilled in vacuo. Yield 36.7 g (83%) t.kip. 81-82 ° С110 mm Hg Art. Found,%: C 59.41; H 7.78; N 9.96. C7H ,, N02, Calculated.%: C 59.56; H 7.85; N 9.92. IR Spectrum (CCC) cm: 2120 (isonitrile group), 1745 (ester group). Example 2. Obtaining 4-methyl-5-propoxyoxazole. Ampoule containing 0.48 g of a-isocyanopropionic acid hfopyl ester and 4 equivalents of solvent (acetoiitrile, N, N-dimethylformamide, hexametapol, triethyl phosphate) is purged with nitrogen, sealed and placed in a thermostat at 135-180 ° C. The optimum cyclization time is at 135 ° C for 20 hours, at 4 hours. The yield of 4-methyl-5-1-fopoxy oxazole is determined by gas chromatography. The results of cyclization of a-isogshanpropionic acid propyl ester are shown in the table.