SU755779A1 - Method of preparing 2-semicarbazidoacetic acid - Google Patents

Description

The invention relates to an improved method for the preparation of 2-seven 'carbazidoacetic acid, which is used in the chemical and pharmaceutical industry for the synthesis of anti-5 bacterial medical drugs furadonin and furagin.

A known method for the preparation of 2-semi- 10 carbazido acetic acid, consists in the fact that monochloroacetic acid solution is gradually added to an excess of hydrazine hydrate in aqueous solution of caustic soda at 90 “100 ° C. Excess hydrazine hydrate is distilled off in vacuo in the presence of a non-volatile organic solvent, for example polypropylene glycol 400, and the sodium salt 20 of hydraine-acetic acid contained in the residual mass by the action of evimolar amounts of potassium cyanate and hydrochloric acid at pH 6.5—

7.5 is converted to the sodium salt of 2-semicarbazidoacetic acid. 2-Се-25 mikarbaeidoacetic acid from the solution is precipitated by acidification to the isoelectric point (pH = 2.4) [This method has several significant drawbacks: 30

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low yield of 2-semicarbazidoacetic acid (40% of theory);

the reaction between hydrazine hydrate, caustic soda and monochloroacetic acid is carried out at a relatively high temperature of 90-100 ° C. In view of this, when working at industrial plants, in some cases, there are "claps" in the reactor, which is associated with the rapid interaction of monochloroacetic acid with hot hydrazine vapor. This phenomenon is unacceptable, as it can lead to an explosion of the reactor. The implementation of the above reaction at a lower temperature adversely affects the yield of 2-semicarbazidoacetic acid. For example, reacting a hydrazine hydrate, sodium hydroxide and monochloroacetic acid at 20 ° C. (Instead of ^at 90-100 C in the known method), with hydrazine hydrate followed by distillation in vacuo using a conventional technique, provided only 20% yield of 2-semikarbaeidouksusnoy acids, ·

distilling off the hydrazine hydrate residues from the reaction mixture is associated with a number of difficulties. In practice, the mentioned operation is carried out by heating the dry residue in vacuum at 90 ° С in

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for several hours. This leads to partial decomposition of the reaction mass, which is unacceptable due to the explosion hazard of hydrazine derivatives. The need for complete distillation of hydrazine hydrate is related to the fact that the remains of the latter impede the normal course of the subsequent synthesis of 2-semicarbazidoacetic acid, since hydrazine readily reacts with potassium cyanate to form semicarbazide or diamide Ν, Ν ¹ -hydrazine dicarboxylic acid.

This undesirable process not only pollutes the reaction mixture with by-products, but also reduces the yield of 2-semicarbazidoacetic acid, since part of the potassium cyanate is spent on the formation of semicarbazide and diamide N, N ¹ -hydrazine dicarboxylic acid.

The use of nonvolatile * organic solvents in the distillation of hydra-, einehydrate *, for example polypropylene glycol 4 00, which is difficult to separate and purify, increases the cost of the process and increases the amount of unreacted waste,

lack of convenient analytical methods to control the end of complete distillation of hydrazine hydrate;

The aim of the invention is to increase the yield of the target product and increase process safety.

This goal is achieved by the described method of obtaining 2-semicar baedooacetic acid, consisting in the interaction of hydrazine hydrate, caustic soda and monochloroacetic acid. At 20–60 ° C, distilling off hydrazine hydrate under vacuum with continuous supply to the semi-liquid residue.

Distinctive features are the implementation of the interaction at 20-60 ° C and the distillation of hydrazine hydrate in vacuum with a continuous supply of water to the semi-liquid reaction residue.

Typically, the distillation of hydrazine hydrate is carried out at a temperature in the mass of 30– B ^ C and a residual pressure of 15–50 mm Hg.

Example 1. To 30.9 g (0.5 mol)

. 81% hydrazine hydrate added with stirring 6.8 g (0.166 mol) of 98% sodium hydroxide and stirred for 20 minutes. Then, with stirring, a solution (0.083 mol) of 98% monochloroacetic acid in 6 ml of water is added, maintaining the temperature at 20-25 ° C. After that, the reaction mixture is maintained at. within 2 hours. The excess hydrazine hydrate is distilled off in a stream of nitrogen to the water banner in a water jet vacuum (the residual pressure in the system is 15 -

 30 mm Hg, mass temperature 30-60 ° C).

At the end of the distillation of hydrazine hydratemide to the semi-liquid mass, 5,120 ml of water are added dropwise gradually from a dropping funnel while simultaneously continuing to distill the distillate in vacuum (residual pressure in the system 30 -

50 mmHg.). The rate of addition of water and the temperature in the mass regulate “O so that a semi-liquid boiling mass forms in the flask. In this case, the water evaporates, promotes the complete and rapid removal of hydrazine hydrate. The duration of this operation is about 1 hour. In order to accelerate the process to a semi-liquid mass, water pre-warmed to 40–50 ° C can be added dropwise to the flask. The amount of distillate is approximately 100 ml. The content of hydrazine hydrate in an aqueous 20 distillate can be easily controlled by titration with 0.1 n. iodine solution at pH 7.0-7.5.

The residue in the flask is dissolved in 20 ml of water (at 75–80 ° C) (cooled to 25–20 ° C and neutralized with hydrochloric acid to pH 7 (this consumes about 6–7 ml of 27.5% hydrochloric acid). 6 g of 20 (0.073 mol) of 98% potassium cyanate in 10 ml of water (potassium cyanate is dissolved at a temperature not higher than 20 ° C) are added dropwise to the resulting solution while stirring. At 25, the neutral solution becomes alkaline. additional amount of hydrochloric acid (consumption of 27.5% acid is about 2.5-4.0 ml). The reaction mixture is kept not less than 4 hours, check the solution solution again (must be 7), filter.When stirred and cooled (temperature not above 25 ° C), concentrated hydrochloric acid (35-38%) is slowly added to the filtrate to pH 2.0-2 , 5 (acid consumption about 8.0 mp). Mixed at 8 ° C for 5 h, the precipitated crystals are sucked off and dried at 50-60 ° C. The yield of 2-semicarbazidoacetic acid (mp. 166-167 ° C ) 7.15 g (64.8% of theory, calculated on the initial amount of monochloroacetic acid).

During the synthesis of 2-semicarbazidoacetic acid as described above, but when the mixture of hydrazine hydrate and caustic soda interacts with monochloroacetic acid at 6 ° C, the same yield of 2-semicarbazidoacetic acid was obtained (64.8% of theory), mp. 170–171 ° C.

Example 2. To a solution of 30.9 g. 60 (0.5 mol) of 81% hydrazine hydrateplate in 15 ml of isopropanol are added with stirring to 6.8 g (0.166 mol) of caustic soda. After dissolving the precipitate, a solution of 8 g (0.083 mol) is added with stirring over a period of 45 minutes

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monochloracetic acid in 6 ml of water, maintaining the temperature of 40-45 ° C. The reaction mixture is kept at the same temperature for 2 hours. The remaining operations — hydrazine hydrate distilling, neutralization, treatment with potassium cyanate — 5, and isolation of the target product are carried out according to the procedure described in example 1. Output 2-semicarbaeoacetic. acids (mp. 169-17 (g)

6.05 g (54.8% of theory). , θ

Example 3. To 30.9 g (0.5 mol) of 81% hydrazine hydrate added, with stirring, 3.4 g (0.083 mol) of caustic soda and stirred 20 Mits. Separately prepare a solution of 8 g (0.083 mol) of monochloroacetic acid in 10 ml of water, neutralize it with the addition of 4.5 g (0.042 mol) of anhydrous sodium carbonate and add with stirring during 1.4 to the mixture of hydrazine hydrate 20 and caustic soda, maintaining the temperature in the range of 40-50 ° C. The reaction mixture is kept at the same temperature for 2 hours. The remaining operations are carried out similarly to the indicated method (Example 1). The only difference is that, before distilling off the hydrazine hydrate, 4 ml of concentrated (35%) hydrochloric acid are added to the reaction mixture with stirring. The amount of added water during the distillation of hydrazine hydrate is 160 ml. The yield of 2-semicarbazidoacetic acid (mp. 162-164 "C) 7.36 g (66.7% of theory). 35

Example 4. To 30.9 g (0.5 mol) of 81% hydrazine hydrate added, 6.8 g (0.166 mol) of sodium hydroxide are added with stirring and stirred for 20 minutes.

Then, over 10 minutes, a solution of 7.8 g (0.083 mol) of chloroacetamide in 25 ml of hot water is added with stirring in 25 ml of hot water, maintaining the temperature in the flask at 40-50 ° C. After that, the reaction mixture is maintained at the same temperature for 2 hours. The remaining operations are carried out similarly to the indicated method (Example 1). The yield of 2-semicarbazidoacetic acid (mp. 154–156 ° C) is 6.02 g (54.5% of theory).

Thus, the method allows to increase the yield of the target product by 1.5 times, as well as to increase the safety of the process, since according to a known method, the distillation of hydrazine hydrate is carried out without solvents, by prolonged heating of the dry residue in vacuum at 90 ° C. This is unacceptable, since hydraine-acetic acid, which is formed in the first stage of the synthesis, can decompose under these conditions with an explosion.

Claims (2)

Claim 1. A method of producing 2-semicarbazidoacetic acid by reacting at elevated temperature hydrazine hydrate, caustic soda and monochloroacetic acid, followed by distilling off hydrazine hydrate in vacuum, treating the reaction products with potassium cyanate, and increasing the safety of the process, the interaction carried out at 20-60 ° C, and the distillation of hydrazine hydrate in vacuum with a continuous supply of water to the semi-liquid reaction residue. 2. The method according to π. 1, characterized in that the distillation of hydrazine hydrate is carried out at a temperature in the mass of 30-60 ° C and a residual pressure of 15-50 mm Hg.