NL8105930A - PROCESS FOR THE PREPARATION OF CYANANACETYL HYDRAZONES OF 2-FORMYLGUINOXALINE-1,4-DIOXIDES. - Google Patents

Description

Br / Bl / lh / 109

Process for preparing cyanoacetylhydrazones from 2-formylguinoxaline-1,4-dioxides.

The invention relates to a process for the preparation of cyanoacetylhydrazones of 2-forraylguinoxalin-1,4-dioxides of the general formula 1, wherein R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms.

The preparation of this compound is described in Czechoslovakian Author Certificate No. 195,508 or also in U.S. Patent No. 4,225,604 or in British Patent No. 1,580,998, by conversion of 10 2-formylguinoxaline-1,4- dioxides of the general formula 2 wherein R 1 has the above meaning or by reacting functionally modified derivatives thereof, for example the acetal, with cyanoacetylhydrazide of the formula 3.

The compounds have excellent effect as growth promoters for pets, yet they can nevertheless also be used in combination with other drugs, such as, for example, sulfonamide to prevent or treat salmonalosis and dysentery in pigs and other pets. Its toxicity is about 20 times less than the toxicity of known growth stimulants which are derived from guinoxalin 1,4-dioxide, while the unwanted side effects are also markedly less. The 2-formylguinoxaline-1,4-dioxides of general formula 2 are prepared according to known methods described in the literature. According to one of these methods, benzofurazan-1-oxide of the formula IV is reacted with a β-ketoaldehyde of the formula 5, wherein R 1 has the above meaning, or with functionally modified derivatives thereof, for example acetals, in a inert organic solvent or diluent in the presence of a basic catalyst.

It has now been found that both of the above steps, that is, the preparation of 2-formylguinoxaline-1,4-8105930-* * * -2-dioxides or the functionally modified derivatives thereof of the general formula II and the preparation of the cyanoacetylhydrazones of 2-formylguinoxaline-1,4-dioxides of the formula 1 in water or in a mixture of water and organic or inorganic solvents! can be carried out, both ....... steps can be combined and carried out in one reaction vessel without isolating the intermediate. The final product with a high purity is obtained in a yield of .75-85%, based on the benzofurazan-1-oxide used as starting material, while the purity is the same as if the intermediate of the formula II is isolated. This yield is 5-10% higher than if the 2-formylguinoxalin 1,4-dioxide or its functionally modified derivative, such as, for example, the acetal, is isolated from the reaction medium, because these compounds are cooled even when cooled. are partially soluble in the reaction medium and isolation of the dissolved portion using resins is not economical. On the other hand, when the reaction with cyanoacetylhydrazine is carried out directly without isolation in the reaction mixture, all the 2-formylguinoxaline-1,4-dioxide present reacts with the general formula 2, or the functionally modified derivative thereof, because the reaction takes place almost quantitatively and the final product is practically insoluble in water. The process according to the present invention is therefore much more advantageous from a technological, economic and safety point of view than the hitherto known methods of preparation.

The combination of both reactions in 1 step is carried out according to the invention in such a way that the benzofuraztan-1-oxide of the formula 4 is reacted with the <-ketoaldehyde of the formula 5- in the presence of the basic reacting catalyst in water or in a mixture of water with an organic or inorganic solvent or diluent and after the condensation has taken place, on the one hand the o-nitroaniline present in the crude benzofurazan-1-oxide and the unreacted benzofurazan-1-oxide on the other hand <-ketoaldehyde from the reaction- 8 1 0 5 930 ------------------------- * · '-3- mixture removed by steam distillation, after which a excess of an organic ororganic acid and cyanoacetylhydrazine are added to the reaction mixture and the separated final product, for example, for suction, is isolated and washed with water.

The condensation of the benzofurazan 1-oxide of the formula 4 with the © (-ketoaldehyde of the formula 5 is preferably carried out in water in the process according to the invention. The benzofurazan-1-oxide has an explosive in an anhydrous state. For reasons of character and for safety reasons it is therefore preferable to use the still wet product for the reaction as obtained after the oxidation of o-nitroaniline with sodium hypochlorite and after washing with water. Aqueous ammonia is used as the basic reacting catalyst, although other catalysts mentioned in the literature can also be used for this type of conversion The amount of catalyst varies from a catalytic amount to several times the equivalent amount. action component to the other and the addition of catalyst is not critical and add this can be performed in any order. This condensation is carried out at a temperature of 0 ° C to the boiling point of the reaction medium used, preferably at 30-80 ° C. The reaction time depends on the temperature, the carbon to aldehyde used and the concentration of the reaction coraponte n and varies from about 1 hour to several days. The reaction mixture is added to it; subjected to steam distillation that the condensation has ended. The o-nitroaniline present in the crude benzofurazan 1-oxide, unreacted benzofurazan-1-oxide, o-ketoaldehyde and ammonia used as catalyst are removed from the reaction mixture. From the distillate, 3-7% of benzofurazan-1-oxide is obtained by suction based on the amount used in the conversion.

An organic or inorganic acid which is economically advantageous can be used to acidify the reaction mixture, such as formic acid, acetic acid, hydrochloric acid, sulfuric acid or a mixture thereof. Acidification can take place to neutral, weakly acidic or to strongly acidic reaction.

The reaction with cyanoacetylhydrazine of the formula III is carried out in such a way that the cyanoacetylhydrazine is added in an equivalent amount or in a slight excess to the neutral or acidic reaction mixture, which is optionally treated with activated carbon or another purifying agent. The reaction already takes place at a sufficient speed at room temperature, but can, however, be carried out at both a lower and a higher temperature, for example at the boiling point of the reaction mixture.

The reaction time depends on the starting materials used, the reaction medium, the pH and the temperature and is from several minutes to 24 hours. Suitable auxiliaries and water-miscible solvents can be added to the reaction medium to obtain the final product in the desired particle size.

An embodiment of the invention is further elucidated by means of the following example without limiting the scope of the invention.

Example I

Moist benzofurazan 1-oxide, containing 23 g (0.17 mol) benzofurazan-1-oxide, 7 ml of water and 31 ml of concentrated aqueous ammonia are heated to 50 ° C with stirring, then 7.1 ml of methylglyoxaldimethylacetal is then added and then 7.1 ml (together 28.4 ml of methylglyoxal dimethyl acetal) are added three more times for 1 hour each time and the mixture is stirred for an additional 11 hours at 50 ° C. A descending cooler is then connected to the reaction vessel, after which steam is introduced into the reaction mixture until about 200 ml of distillate is collected. The residue obtained after the steam distillation is cooled to room temperature, after which 100 ml of concentrated hydrochloric acid are added and 35 g of activated resin charcoal are added, the mixture is stirred at room temperature for 30 minutes and then filtered. After this, a solution of 18 g of cyanoacetylhydrazine in 65 ml of water is added with stirring to the mixture * 8105930. * s -5- and stirred for an additional 3 hours. The separated precipitate is filtered off with suction and washed with water until it no longer reacts acidically. The product is purified by boiling with 400 ml of ethanol, followed by suction and drying.

The yield is 35 g of pure cyanoacetylhydrazone of 2-formylguinoxaline-1,4-dioxide, which is 76%, based on the benzphurazan-1-oxide used in the reaction. 1.0 g of benzo-furazan-1-oxide is recovered from the distillate of the steam distillation.

* 11. 4 8105930

Claims (4)

A process for the preparation of cyanoacetylhydra zones of 2-formylguinoxaline-1,4-dioxides of the general formula 1, wherein R 1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, by reacting a 5-or-ketoaldehyde of the formula 5, wherein R 1 has the above meaning or with a furationally modified derivative thereof, such as an acetal, with benzofurazan-1-oxide of the formula 4 in an inert solvent or in a mixture thereof in the presence of a basic catalyst and then IQ reaction with cyanoacetylhydrazine of the formula 3, characterized in that the reaction of the benzofurazan-1-oxide with the or-ketoaldehyde is carried out in water, undesired components and impurities are removed from the reaction mixture by steam distillation and an organic inorganic acid and cyanoacetylhydrazine in the reaction vessel of the 2-formylguinoxaline-1,4-dioxide of the general formula 2, wherein ΈΓ has the above meaning or added to its furonially modified derivative and the separated final product is isolated. 20 .2. Process according to claim 1, characterized in that the basic catalyst used is preferably aqueous ammonia. 3. Process according to claims 1 and 2, characterized in that o-nitroaniline, benzofurazan-1-oxide, © (-keto-25-aldehyde or its furionally modified derivative, such as an acetal, and ammonia are removed from the reaction mixture by steam distillation before acidifying the reaction mixture and before adding the cyanoacetylhydrazine. 4. Process according to claims 1-3, characterized in that the acidification of the reaction mixture is carried out with an economically favorable acid, preferably with hydrochloric acid, formic acid or acetic acid. 8105930