CS219751B1 - Process for preparing alkyl 3-methylquinoxaline-1,4-dioxide-2-carboxylic acid esters - Google Patents

Abstract

The invention relates to a method for preparing alkyl esters of 3-methyl-quinoxaline-1,4-dioxide-2-carboxylic acid by condensation of benzofurazan-1-oxide with alkyl ester of acetoacetic acid in an organic solvent in the presence of a catalytic amount of sodium carbonate.

Description

(54) A process for the preparation of 3-methylquinoxaline-1,4-dioxide-2-carboxylic acid alkyl esters

2

The invention relates to a process for the preparation of 3-methyl-quinoxaline-1,4-dioxide-2-carboxylic acid alkyl esters by condensation of benzofurazan-1-oxide with an acetic acid alkyl ester in an organic solvent in the presence of a catalytic amount of sodium carbonate.

The present invention relates to a process for the preparation of 3-methylquinoxaline-1,4-dioxide-2-carboxylic acid alkyl esters of the formula

N = COOR (I) wherein R represents an alkyl radical of 1 to 4 carbon atoms. These substances are important for their antibacterial effects or serve as intermediates in the synthesis of other quinoxaline-1,4-dioxide derivatives which are used, for example, as agents against pathogenic microorganisms, livestock stimulators, etc.

Existing methods for the preparation of 3-methylquinoline-1,4-dioxide-2-carboxylic acid esters involve the condensation of benzofurazan-1-oxide with acetic acid esters in the presence of basic catalysts. The highest yields of the condenser (about 80% of theory) were achieved by using a high excess of ocetoacetate, with simultaneous solvent function, under catalysis with morpholine. However, this process is less advantageous than the more commonly used preparation in conventional organic solvents due to the cost and difficult recovery / alkyl esters of acetic acid. The course and yield of the reaction of benzofuran-1-oxide with alkyl esters of acetic acid depends primarily on the choice and amount of the catalyst. An overview of the yields obtained with the use of a plurality of basic catalysts, for example some inorganic and organic bases, is given in German Patent Specification 2,215,320. Calcium hydroxide was found to be the optimum of the catalysts used, yields being around 70 percent of theory. Also, the results reported in other publications indicate that none of the catalysts used yielded better yields than calcium hydroxide. The disadvantage of using calcium hydroxide is, in particular, the fact that the reaction heat evolution with strongly exothermic condensation of benzofurazan-1-oxide with acetic acid alkyl esters is particularly rapid at the start of the reaction and in large-scale preparation and cooling.

The disadvantages of the prior art are eliminated by a process for the preparation of 3-methylquinoxaline-1,4-dioxide-2-carboxylic acid alkyl esters by condensation of benzofuran-1-oxide with an alkyl ester of C1 to C4 acetic acid in an organic solvent in the presence of a basic catalyst. sodium carbonate is used as the catalyst at a molar ratio of benzofurazan-1-oxide, alkyl acetates of acetic acid and sodium carbonate of 1: 1 to 1.5: 0.02 to 0.1.

The advantage of this process is to achieve yields at least equal to those obtained with calcium hydroxide, the product obtained is of higher purity, better filterability and when carrying out the preparation on a larger scale, the whole amount of reagents and catalysts can be submitted simultaneously without the risk of uncontrolled reaction. the advantage resulting from the nature of the catalyst used is the lower application of side reactions, in particular the decomposition of acetacetate, which, in addition to its lower consumption, also has a beneficial effect on solvent recovery from the mother liquor. The synthesis can be carried out in most common solvents, alcohols being particularly preferred.

In order to further elucidate the invention, the following examples are given: Example 1

A 201 L double-jacket reaction vessel with bottom outlet was charged with 10 L of ethanol, 2.722 kg of benzofurazan-1-oxide (20 mol), 2.863 kg of ethyl acetate (22 mol) and 106 g of sodium carbonate (1.0 mol), mixture The reaction mixture was then cooled to 15 ° C, the product was filtered off, washed with 2 L of ethanol and dried at a maximum of 50 ° C. methyl quinoxaline-1,4-dioxide-2-carboxylic acid is 3.922 kg, i.e. 79% of theory, m.p. 136-137 [deg.] C. EXAMPLE 2

Dissolve 554 g (4 gmol) of 100% benzofuran-1-oxide in 2 l of absolute ethanol, heat to 60 ° C, add 31.8 g (0.3 gmol) of anhydrous soda and add 652 g over 3 hours (5 gmol) ethyl acetate. The temperature was maintained at 60 ° C for an additional 6 hours. It is then cooled to 20 [deg.] C., the product is filtered off and washed with 500 ml of ethanol. The product obtained is well filtered and chromatographically pure. Yield: 766 g of ethyl 3-methylquinoxaline-1,4-dioxide-2-carboxylic acid ethyl ester of 98.9% purity, 75.5% of theory. M.p. 136-137 ° C.

Claims (1)

OBJECT OF THE INVENTION A process for the preparation of alkyl esters of 3-carbon carbonate by reacting benzofuran-1-oxide with -methyl-quinoxaline-1,4-dioxide-2-carboxylic acid with an alkyl acetic acid ester of the formula I wherein R is an alkyl radical of 1 to 4. wherein R is as defined above, in an organic solvent environment in the presence of a basic catalyst, characterized in that sodium carbonate is used as the catalyst at molar ratios of benzofurazan-1-oxide, alkyl esters of acetic acid and sodium carbonate of 1: 1 to 1.5: 0.02 to 0.1.