SU1313851A1 - Method for producing 1-aminocyclopropane-1-carboxylic acid - Google Patents

Abstract

The invention relates to amino acids, in particular to the preparation of 1-aminocyclopropane-1-carboxylic acid (ACC), which is used as a phytohormone plant growth regulator. The increase in ACC output is achieved using a specific sequence of process steps. The preparation of ACC is carried out by the alkylation of malonic acid diethyl ester with 1,2-dibromoethanol in dimethylformamide in the presence of potassium carbonate. The resulting cyclopropane-1,4-dicarboxylic ester is subjected to alkaline saponification followed by ammonolysis to give cyclopropane-1,1-dicarboxylic acid monoamide, which is then treated with KOH and sodium hybromide to give the desired ACC. The method allows to increase. the output of the ACC from 33 to 55%. (L JS X) 00 ate

Description

The invention relates to organic chemistry, specifically to the preparation of 1-aminocyclopropane-1-carboxylic acid, which is used as a phytohormone plant growth regulator.

The aim of the invention is to increase the yield of the target product by carrying out, in a certain sequence of alkylation, alkaline saponification of ammonolysis, the treatment of sodium hypobromide.

Example 1. A mixture of 27.3 g (0.17 mol) of malonic acid diethyl ester, 39.6 g (0.21 mol) of 1,2-dibromoethane, 60 g (0.43 mol) and 300 ml of DMF is stirred at for 10 hours. The reaction mixture is cooled, filtered, 300 ml of water are added to the filtrate and the aqueous phase is extracted with 3 to 30 ml of sulfuric ether and 5.30 ml of ethyl acetate. The organic phase is dried with sodium sulfate, the desiccant is separated, the solvent is distilled off, and the remaining mobile liquid is distilled, and the fraction with boiling point is collected. Yub C (20 mm Hg). 28.62 g (0.15 mol), (90%) of cyclopropane-1,1-dicarboxylic acid diethyl ether are obtained.

Calculated,%: C 58.00, H 7.53.

C, H, 0,

Found,%: C 57.77, H 7.60, According to 1.4320.

To a solution of 20 g (0.11 mol) of diethyl cyclopropane-1, dicarboxylic acid in 150 ml of ethyl alcohol is added a solution of 8.45 g

ten

15

After that, 12.3 g (0.31 mol) of NaOH is added to the reaction mixture and the temperature is raised to 80 ° C over 30 minutes. The solution is cooled to room temperature, 7 ml of a 36% sodium bisulfite solution are added and the salt is neutralized. acid to pH 6. The target amino acid is isolated by column chromatography using KU-2 sulfonic cation exchanger according to a conventional method. 6.1 g (0.06 mol) of 1-aminocyclopropan-1- are obtained. carboxylic acid with a yield of 55% in terms of diethyl ether malon20

Howl acid, mp., 246-248 ° C (decomposition).

Example 2. Obtaining the target product with stepwise separation of intermediate compounds.

1. A mixture of 27.3 g (0.17 mol) of malonic acid diethyl ester,

39.6 g (0.21 mol) of 1,2-dibromoethane, 60 g (0.43 mol) of CgSOe and 300 ml of dimethylformamide are stirred at 90-95 ° C

25 for 10 hours. Reaction mixture

cooled, filtered, 300 ml of water was added to the filtrate and the aqueous phase was extracted with 3x30 ml of ether and 530 ml of ethyl acetate. Organic phase

30 are combined, dried, the solvents are distilled off, and the residue is distilled, collecting the fraction with so b.p. 108 ° C (20 mm Hg). 28.62 g (0.15 mol, 90%) of cyclopropane-1,1-di-35-carboxylic acid diethyl ether are obtained.

2. To a solution of 20.4 g (0.11 mol) of diethyl cyclopropane-1,1-dicarboxylic acid in 150 ml of ethyl alcohol is added a solution. 8.45 g

(0.15 mol) KOH in 50 ml of H, 0 and transfer-40 (0.15 mol) KOH in 50 ml of water and re-.

stir the solution for 36 hours at room temperature. Ethyl alcohol is then distilled off, the aqueous phase is extracted with ether, acidified with HCl 1 to pH 1 and the organic layer formed is decanted, and the aqueous phase is extracted with ethyl acetate. After decanting and extracting with ethyl acetate, the organic phases are combined, the mixture is distilled off at room temperature for 36 hours. The alcohol is then distilled off, the aqueous phase is washed with ether, ml, HC1 is acidified to a pH of 1 and the resulting organic layer is decanted. the aqueous phase is extracted with 3: 25 ml of ethyl acetate. Organic. the phase after decantation and the ethyl acetate extract are combined, the ethyl acetate is distilled off. The residue is dissolved in ethyl acetate, and the remaining product, with alcohol, is saturated at the scientific research institute with monoethyl ether and cooled with ammonia and left at room temperature. After 48 hours, ethyl alcohol and ammonia are distilled off, and the residue is washed with ether and mixed with sodium hypobromide solution prepared from 14.1 g (0.35 mol) of NaOH and g (0.075 mol) of bromine and cooled to -5 ° C. .

cyclopropane-1,1-dicarboxylic acid is used in further transformations. Yield 15.46 g (89.3%).

3. 14.22 g of monoethyl, cyclopropane-1, 1-carboxylic acid ester is dissolved in ethyl alcohol and the solution is desiccated while cooling with ammonia.

After that, 12.3 g (0.31 mol) of NaOH is added to the reaction mixture and the temperature is raised to 80 ° C over 30 minutes. The solution is cooled to room temperature, 7 ml of a 36% sodium bisulfite solution are added and the salt is neutralized. acid to pH 6. The target amino acid is isolated by column chromatography using KU-2 sulfonic cation exchanger according to a conventional method. 6.1 g (0.06 mol) of 1-aminocyclopropan-1- are obtained. carboxylic acid with a yield of 55% in terms of diethyl ether malono

Howl acid, mp., 246-248 ° C (decomposition).

Example 2. Obtaining the target product with stepwise separation of intermediate compounds.

1. A mixture of 27.3 g (0.17 mol) of malonic acid diethyl ester,

39.6 g (0.21 mol) of 1,2-dibromoethane, 60 g (0.43 mol) of CgSOe and 300 ml of dimethylformamide are stirred at 90-95 ° C

for 10 h. The reaction mixture

cooled, filtered, 300 ml of water was added to the filtrate and the aqueous phase was extracted with 3x30 ml of ether and 530 ml of ethyl acetate. Organic phase

combined, dried, the solvents were distilled off, and the residue was distilled, collecting the fraction with bp. 108 ° C (20 mm Hg). 28.62 g (0.15 mol, 90%) of diethyl cyclopropane-1,1-dicarboxylic acid are obtained.

2. To a solution of 20.4 g (0.11 mol) of diethyl cyclopropane-1,1-dicarboxylic acid in 150 ml of ethyl alcohol is added a solution. 8.45 g

(0.15 mol) KOH in 50 ml of water and re-.

acetate, and the remaining product, which is a monoethyl ether

cyclopropane-1,1-dicarboxylic acid is used in further transformations. Yield 15.46 g (89.3%).

3. 14.22 g of monoethyl, cyclopropane-1, 1-carboxylic acid ester is dissolved in ethyl alcohol and the solution is desiccated while cooling with ammonia.

313

After 48 hours, the volatiles were distilled off, and the resulting crystalline substance, which is the ammonium salt of mono amnd cyclopropane-1,1-dicarboxylic acid, was washed with ethyl acetate, ether, and dried in vacuo. Yield 10.95 g (83.3%).

4. 10.95 g (0.075 mol) of the product p. D are dissolved in 60 ml of water and mixed with 20 ml of 15% NaOH solution. The reaction mixture is vacuumed and mixed with a cooled solution of sodium gipobromide, prepared from 16.0 g (0.4 mol) of NaOH and 13.26 g (0.083 mol) of bromine. Most of this, another 10.0 g (0.25 mol) of NaOH is added to the reaction mixture and the temperature is raised to 80 ° C. The solution is then cooled, 10 ml of a 36% sodium bisulfite solution are added and neutralized. The target amino acid was selected by ion exchange chromatography using KU-2 sulfonic cation exchanger according to a conventional method. Yield 5.48 g (72.4%). M.p. 246-248 ° C (decomposition).

The total yield based on the starting malonic acid diethyl ester of Example 2 is 48.5%:

For convenience, a 25% ammonia solution can be used instead of saturating the cyclopropane-1-dicarboxylic acid monoethyl ether with ammonia.

Editor M.Kelemes Order 2179/25

Compiled by V. Odintsova

Tehred A. Kravchuk Proof-reader I. Erdeyi

Circulation 372Subscribe

VNIIPI USSR State Committee

for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5

Production and printing company, Uzhgbrod, ul. Project, 4

14

As can be seen from the above examples, the proposed method allows to increase the yield of the target product from 33 to 55% and to simplify the process by

avoiding the use of alcohol trv sodium and methanol, which requires increased precaution. At the same time, the yield increases as during the process without isolating

intermediate products, and with the selection.

Claims (1)

Invention Formula J5 SP of 1-aminocyclopropane-1-carboxylic acid by alkylation of malonic acid diethyl ester with 1,2-dibromoethane in dimethylformamide in the presence of potassium carbonate using ammonolysis, treatment with caustic potassium and bromine-containing compound, the fact that, in order to increase the code of the target product, obtained after alkylation of diethyl cyclopropane-1,1-dicarboxylic acid ester is subjected to alkaline saponification, subsequent ammonolysis with the preparation of cyclopropane-1,130 dicarboxylic acid monoamide you, which is then treated with sodium gipobromidom to give the desired product.