SU580827A3 - Method of preparing c1-c8 dialkyl esters of malonic acid - Google Patents

Description

one

The invention relates to a process for the preparation of dialonic alkyl esters of malonic acid with a carbon number of 1-8 in the alkyl radical, which are widely used in organic synthesis, in particular, for the preparation of pharmaceutical preparations.

A known method for producing malonic acid dialkyl esters by reacting the corresponding chloro or bromoacetic acid alkyl ester with carbon monoxide in the presence of an organic base (dicyclohexylamine) and stoichiometric amounts of cobalt sodium tetracarbonyl as a catalyst at a temperature of 1-3 atm for 3 hours. products 10-80% 1.

The disadvantage of this method is the relatively low yield of the target products. The method is also complicated by the need to use a special catalyst, natricocobaltetracarbonyl, which is obtained by reducing dicobaltoctacarbonyl with subsequent neutralization of the resulting unstable hydroteracarbonyl with a base. Thus, to implement the known

The process ultimately requires at least 2 moles of the basic agent per 1 mole of the starting chloro or bromoacetic acid ester.

In order to increase the yield of the target products, in the proposed method, as a carbonyl compound of cobalt, dicobaltoctacarbonyl is used with a molar ratio of the latter to the alkyl ester of the corresponding acid 1: 2-1; 500. The reaction is carried out at a temperature of 50-150 ° C and pressure of .0.8 -130 atm. The reaction time is 5-6 hours.

The process is carried out in the presence of at least 1 mol of monobasic or 0.5 mol of dibasic base, as which alkali or alkaline earth metal salts such as carbonates, bicarbonates, acetates, secondary and tertiary phosphates, alkaline earth metals oxides, in particular, can be used. magnesium oxide, calcium oxide, and tertiary amines (triethylamine).

The catalyst, dicobaltcarbonyl, is used as an individual substance or as solutions in suitable organic solvents (ethers, cyclic ethers, alcohols, ketones, lower acetic acid esters). as a starting monohalogenoacetic acid ester, ethers of unbranched or branched alcohols with the number of carbon atoms of 1-8 chloro or bromoacetic acid are used. The proposed method provides a higher yield of the desired product (36-97.5%). The method also allows a more stable catalyst to be used, which excludes the use of an additional mole of basic reagent. The catalyst used is more accessible than the catalyst according to the known method. Example 1. Preparation of malonic acid ethyl ester 30 g COj (CO) g and 80 g (2 mol) KgO together with 400 ml of ethanol in a 1 l autoclave and under 5 atm. heated to 55c. 245 g (2 mol) of ethyl chloroacetic acid in 200 ml of ethanol are added over 3 hours, CO is added to the autoclave every 30 minutes, the pressure is brought to 5 atm, the reaction mixture is kept at 55 ° C for 2 hours. At the end of the reaction, water is added, acidified with sulfuric acid and extracted with ether. By distillation, 23 g of chloroacetic acid ethyl ester and 181 g of malonic acid diethyl ester are obtained. Yield 62.5%. Example 2. Malonic acid dimethyl ester is obtained under the conditions of Example 1 using 400 ml of methanol and 160 g (1.15 mol) of KjjCOj. The process is carried out under a pressure of 50 atm for 3.5 hours, maintaining the pressure through the supply of compressed carbon monoxide, and (2 mol) of chloroacetic acid methyl ester in 200 ml of SNOH is added. At the end of the reaction, the reaction mixture was sucked off from the precipitated salt and distilled off. 16.6 g of methyl acetic acid ester and 238 g of malonic acid dimethyl ester are obtained. The yield is 97.5%. Example 3. Obtaining dimethyl ester of malonic acid. The reaction is carried out in the conditions of example 2 using 60 g (1.1 mol) CaO as the basic agent. 32 g of methyl chloroacetic acid ester and 154 g of malonic “islota dimethyl ester are obtained. Yield 68.5%. Example 4. Obtaining dimethyl ester of malonic acid. The reaction is carried out under the conditions of Example 2 with the use of 108 g (1 mol) of chloroacetic acid methyl ester, 10 g of COjf (CO) and 180 g (1.1 mol) of WasHPO as the basic means and methanol. At the end of the reaction, 1 g of chloroacetic acid methyl ester is isolated. Yield 49%, Example 5. Preparation of malonic acid dimethyl ester. The reaction is carried out under the conditions of example 4, using 82 g (0.5 mol) as the main agent, after the completion of the reaction. 1.5 g of chloroacetic acid methyl ester and 98.5 g of malonic c-acid dimethyl ester are recovered. Yield 76%. Example 6. Obtaining dimethyl ester of malonic acid. The reaction is carried out under the conditions of example 4 with the use of 112 g of triethylamine as the basic agent, after the completion of the reaction 8 g of methyl chloroacetic acid ester and 81.5 g of masonic carboxylic acid dimethyl ester are isolated. Yield 67%. Example 7. Obtaining di-2-ethylhexyl ester of malonic acid. The reaction is carried out under the conditions of example 2. 340 g (1.65 mol) of chloroacetic acid 2-ethylhexyl ester are reacted with 130 g (0.93 mol) of Kj, COj, 700 ml of 2-ethylhexanol and 25 g of Cc3j (CO) g. 347 g of malonic acid di-2-ethylhexyl ester were isolated. Yield 66%. Example 8. Obtaining dimethyl ester of malonic acid. The reaction is carried out under the conditions of example 2 using 216 g of chloroacetic acid methyl ester, 20 g of Co2 (CO) g and 60 g of CaO as the basic agent in methanol, after the completion of the reaction, 33 g of chloroacetic acid methyl ester (15%) and 131 g of dimethyl malonic ester 59.5%. Example 9. Getting dimethyl ether. Malonic acid. The reaction was carried out under the conditions of Example 2, but using 5 g and at the reaction temperature, upon completion of the reaction, 38 g of methyl chloroacetic acid ester and 180 g of malonic acid dimethyl ester are obtained. The yield is 83.5%. Example 10. Getting diethyl ether malonovy acid. The reaction was carried out under the conditions of Example 2 using 83.5 g of bromoacetic acid ethyl ester, In g CO2 (CO) CI 80 t K2COzV as the main product and ethanol, 57 g of malonic acid diethyl ester was obtained. Yield 71%. Example 11. Preparation of Malonic Acid Diethyl Ester The reaction is perforated under the conditions of Example 2, but using 250 g of ethyl chloroacetic acid, 10 g of COj (CO) g and 106 g of NajCOj as the main product, 141 g (56%) of ethyl chloroacetate are obtained after the reaction. 90 g of malonic acid diethyl ester.

Example 12. Obtaining dimethyl ester of malonic acid.

150 ml of a 10% solution of Co, (CO) in acetic acid methyl ester in 150 ml of methanol are fed into a round bottom flask. Then, while stirring for 30 minutes, CO is passed through with an overpressure of 600 mm Hg. and heat up. 108 g (1 mol) of chloroacetic acid methyl ester are added dropwise over 3 hours and 40 mol of MgO are added in portions, by continuously passing CO. Then it is stirred for another 2 hours until the end of CO absorption. Water was added to the reaction mixture, acidified with sulfuric acid and extracted with ether. After removal of the ether, 46 g of malonic acid dimethyl ester (yield 36%) and 4.6 g of chloroacetic acid methyl ester were isolated.

Example 13. Obtaining dimethyl ether malonic acid.

Under the conditions specified in example 9, but using 10 g of Co (CO) dissolved in 150 ml of methanol, 70 g (0.5 mol) and 108 g (1 mol) of chloroacetic acid methyl ester are used as the basic agent. The mixture is reacted with sb.

The reaction mixture was separated from the separated salt and distilled off first with meth (nol, and then the target product. 44.5 g of chloroacetic acid methyl ester and 46 g of malonic acid dimethyl ester were isolated (yield 59.2%).

Claims (3)

1. A method for producing the C | -C dialkyl esters of malonic acid by reacting the corresponding chloroyl 1-bromoacetic acid ester with carbon monoxide in a solvent medium in the presence of a catalyst based on the carbonyl cobalt compound and the main agent when heated, followed by separation of the target product, characterized in that increasing the yield of the target product, as a carbonyl cobalt compound, use dicobaltoctaarbonyl, the process is carried out at a molar ratio of likobaltoctcarbonyl to the end chloro- or bromoacetic acid 1, 2-1: 500 at 50-150 ° С. 2. Method POP.1, distinguished by the fact that the process is carried out at a pressure of the Research Institute 0.8-130 at. Sources of information taken into account in the examination: 1 .P. 3.HecK, D. 3.Bhe6Pow Car-boxyaPky Pa1 (oi Reaclioiis by cobaPl SOGoiu Eaie Jo MC5, B5,17,1963, pp.2779-2782.