CS232998B1 - Process for the treatment of 1,2-diphenyl-3,5-dioxo-474,4-dimethyl-3-ovxopentyl-pyrazolidine from mother liquors and wash liquors after crystallization - Google Patents

Abstract

Method of processing 1,2-diphenyl-3,5-dioxo-4-(4,4-dimethyl-3-oxopentyl)pyrazolidine (Tribuzon) from mother liquors after crystallization. Production of pharmaceutical substances with antirheumatic, antiphlogistic and uricosuric effects. The technological procedure according to the invention increases the yield of the reaction process while maintaining the quality of the product. The purpose is achieved when the distillation residue obtained by distilling off the crystallization solvents after refining, formed by a suspension of Tribuzon, or its salt, is added to the reaction mixture after alkylation of 1,2-diphenyl-3,5-dioxopyrazolidine with Mannich's base of pinecoline and is processed normally with the main proportion. In the chemistry of related heterocyclic compounds. ^,CO-N-C,HR (CH.)7CCOCH,CH,CH I 0 5 Tribuzon J J xCO-N-CgH5

Description

The invention relates to a process for the treatment of 1,2-diphenyl-3,5-dioxo-4- (4,4-dimethyl-3-oxopentyl) pyrazolidine (Tribuzone) from the mother liquors after crystallization.

Tribuzone is an important drug with anti-rheumatic and anti-inflammatory effects. The basic preparation procedure is alkylation of 1,2-diphenyl-3,5-dioxopyrazolidine with pinacolin Mannich base. The reaction is carried out in an environment of organic solvents from higher temperatures in the presence of alkali alcoholates (U.S. Pat. No. 113,604, U.S. Pat. No. 136,647). A disadvantage of these basic processes is the formation of significant amounts of by-products and thus the need for multiple purification operations to obtain suitable products for the preparation of dosage forms. Higher-purity products can be obtained by the process of AO No. 2,196 e, in particular by carrying out the reaction in a reducing environment according to the author's certificate No. 229,493.

The crude Tribuzone can be crystallized using organic solvents, preferably using lower aliphatic alcohols, e.g. addition of reducing agents to reduce oxidation reactions at higher temperatures.

Isolation of the product from the mother liquors after crystallization and purification of the product thus obtained is very difficult and problematic. Derivatives of 1,2-diphenyl-3,5-di-axopyrezolidine are substances subject to undesirable conversions at elevated temperatures, e.g. when the mother liquors are concentrated. In addition, the mother liquor product contains by-products contained in the raw Tribuzon. Cleaning the product obtained from the mother liquors is laborious and reduces the production capacity of the plant.

Recently, a process for utilizing Tribuzone from mother liquors after crystallization has been elaborated, in which, simultaneously with the desired methanol recovery, the distillation residue is treated under the current process for preparing Labor Tribunon without labor and new equipment while increasing process efficiency.

The essence of the procedure is the distillation of mother liquors and washing liquors after event. adjusting the pH with an alkaline agent, preferably calcium hydroxide. A distillation residue consisting of a Tribuzon suspension event. its salts are added to the reaction mixture after alkylation of 1,2-diphenyl-3,5-dioxopyrazolidine by the mannich base of pinacoline and processed with the major part of the technology. The purity of the product thus obtained is suitable for further processing into a pure substance. This process is advantageous to be used in combination with the raw Tribuzon process according to euthoric certificate No 229 793, as this process guarantees a higher product quality.

The higher economic effect can be documented by the fact that the yield of the crude product is increased by min. 6% essentially using the same technology with the same equipment at this stage.

The recovery of methanol by distillation is an essential process both from an economic and environmental point of view.

The exemplary embodiment is illustrative but not limiting.

Exemplary embodiment

To a butannic solution of sodium butylate prepared by dissolving 6.5 g of sodium (0.283 mol) in 330.0 ml of n-butanol at 20 ° to 30 ° C was added sequentially 2.0 g of zinc powder, 70.3 g of 1,2-diphenyl. -3,5-di. oxopyrazolidine (0.279 mol) and 41.0 g of 2,2 ' -dimethyl-5-dimethylamino-3-pentanone (0.261 mol) were heated to boiling and boiled for 3 hours.

After cooling to 110 ° C, 100.0 ml is added. toluene and, after cooling to 60 ° C, about 75.0 ml of the distillate obtained from the mother and wash liquors of Tribuzon.

The distillation residue is obtained by partial evaporation of the crystallization solvent, after crystallization of 97.3 g of tribonone crude, from the mother liquors and washings after the event. prior adjustment of the pH to 7 to 10 with calcium hydroxide.

EŽ at 45 50 ° C, the reaction mixture is combined with the distillation residue acidified with 64.0 ml hydrochloric acid, the resulting suspension was cooled to 0 C. ^N, the product is suction filtered, washed with methanol, water e then dried at 50-60 ° C.

97.3 to 97.8 g of 1,2-diphenyl-3,5-dioxo-4- (4,4-dimethyl-3-oxopentyl) pyrazolidine are obtained. The product is almost white, mp 144.0-146.0 ° C (uncorrected on glass).

Claims (1)

SUBJECT OF THE INVENTION A process for the treatment of 1,2-diphenyl-3,5-dioxo-4- (4,4-dimethyl-3-oxopentyl) pyrazolidine from the mother liquors and washings after crystallization and after optionally crystallization. adjusting their pH, characterized in that the distillation residue after recovery of the crystallization solvent is added to the reaction mixture after alkylation of the 1,2-diphenyl-3,5-dioxopyrazolidine sodium salt with pinacoline Mannich base and worked up together with the main reaction product.