DE637260C - Process for the preparation of pyrazolone capsules - Google Patents

Description

Process for the preparation of pyrazolone derivatives The invention relates to a process for the preparation of pyrazolone derivatives of the general Formula i-R-3-methylpyrazol-5-one, in which R is phenyl or substituted phenyl means. A particularly characteristic representative of these compounds is i-phenyl-3-methylpyrazol-5-one, which is used in the chemical industry for various purposes ".

The procedure generally consists in the action of diketene to a hydrazine of the general formula R N H - N H2, in which R is phenyl or substituted Means phenyl.

The previous processes for the preparation of such pyrazolone compounds are based on a condensation reaction between acetoacetate and hydrazines. In this way, z. B. from phenylhydrazine with exit per i mole of water and i Mol. Ethyl alcohol i-phenyl-3-methylpyrazol-5-one shown. According to the Literature (cf. H e n 1 e, »Instructions f. D. Org. Prep. Pract. (T igo9, p. 164) become here, with the exclusion of the mother liquor, yields of 78% and including the same received up to 9o ° 1o of theory. There is also already an implementation between Phenylhydrazine and diketene have been described in the literature (see Chick` and Wilsmore, Journal of the Chemical Society - 93 [19081, p.948), but in this publication it is stated that 1 mole of diketene reacts with z mole of hydrazine. The one here The resulting compound was called the phenylhydrazone phenylhydrazide of acetoacetic acid recognized. There is no indication of the conditions under which a Pyrazol-5-one compound can be produced from diketene and phenylhydrazine.

The process according to the invention is based on the knowledge that, under properly chosen conditions, equimolecular amounts of phenylhydrazine and diketene can be converted to i-phenyl-3-methylpyrazol-5-one. It has also been found that this reaction is generally applicable to the preparation of pyrazol-5-one compounds of the formula iR-3-methylpyrazol-5-one, where R denotes phenyl or substituted phenyl, by adding any hydrazine, RN HN H2, in which R denotes the aromatic radical desired in the end product, reacts with equimolecular amounts of diketene. The reaction is carried out in the presence of a solvent at a higher temperature, preferably about 80 to 85 ° C., and the water formed is expediently continuously removed from the reaction mixture. Suitable solvents have proven to be such. B. benzene and töluene; when using the latter, reduced pressure is necessary to remove the toluene-water mixture. During the process an intermediate product is formed; however, it is not necessary to separate it. This process not only opens up a new way of achieving the position of the pyrazolones, but also has the advantage over the known processes that no alcohol diluted by the water that is split off at the same time does not have to be worked up. The yields are just as high as in the known process. In the preparation of i-phenyl-3-methylpyrazolone, a yield of 85 % of the theoretical yield was achieved, and further pyrazolone can also be obtained from the mother liquor.

Example i 549 (1/2 mol.) Phenylhydrazine were dissolved in 30o cc of benzene and. -in: Filled into a round-bottom flask equipped with a stirrer, dropping funnel and thermometer, which had a short-necked approach for distilling off the benzene-water mixture. The benzene solution was heated to a boil, then 42 g (1/2 mole) of diketene was added dropwise over a period of. a / 2 hour added. During this time, benzene and water were continuously distilled off; Within 10 minutes of adding all of the diketene, two thirds of the original amount of benzene "was removed from the reaction vessel. No or very little diketene could be detected in the distillate. The reaction mixture was then stirred until the temperature had dropped to 60 ° C The mother liquor was filtered off and the crystalline pyrazolone was washed three times with ether 128 ° C. and was recognized as z-phenyl-3-methylpyrazol-5-one. Example a- "The procedure was similar to that in Example i, but using toluene as the solvent. A condenser was used for the distillation of the toluene-water mixture and the pressure was reduced so as not to let the temperature rise above 85.degree. The yield and properties of the product were the same as described in Example i. Example 3 With other aromatic hydrazines, which were reacted in equimolecular amounts and under similar reaction conditions, as explained in Example i, the following three pyrazolones were obtained: From 2,4-dinitrophenylhydrazine (80% 2-aps yield 1- (2 ', 4'-dinitrophenyl) -3-methyl- azol-5-one with a melting point of * = o = - .. 'in -Tolylhydrazine gave with a yield of 73 to 74 / o i- (3'-methylphenyl) -3-methylpyrazol-5-one with a melting point of iog to i ia ° C, p-tolylhydrazine with a yield of 57 to 58 ° / o i- (4'-methylphenyl) -3-methylpyrazol-5-one with a melting point of 128 to z3a ° C.

Example 4 20 g of 2,4-dinitrophenylhydrazine were distributed in 50 cc of toluene; Then the mixture was heated to 110 ° C. or the boiling point of the solvent and 8.5 g of diketene were added. After a certain time, the color of the distributed solid gradually changed from deep red to yellow, indicating that the diketene was beginning to react with the dinitrophenylhydrazine. After six hours of warming, the solution was filtered off while still hot and the insoluble residue was washed out with ether. A yield of 21 g (corresponding to 80 ° 1) of I- (2 ', 4'-dinitrophenyl) -3-methylpyrazol-5-one was achieved. Example 5 Phenylhydrazine and diketene were exposed in equimolecular amounts. For this purpose, 54 g of phenylhydrazine were dissolved in 300 cc of benzene and the solution was kept at a temperature of about 45.degree. At this temperature, 21 g of diketene were added, whereupon the reaction mixture was heated to distill off the water formed. After about 100 cc of the benzene-water mixture had been removed, the addition of the diketene was continued and the temperature of the solution was kept at about 80 ° so that the water formed could be continuously distilled off. The total amount of diketene supplied was 4a g. The yield of pyrazolone obtained by crystallization from the reaction mixture was 82% of that theoretically possible. The amount of benzene-water mixture distilled off during the addition of the second portion of diketene was about 100 cc.

For example, 6,549 phenylhydrazine were added to 50 cc of ethyl acetate. The mixture was maintained at a temperature which was about 45 ° C initially the implementation fluctuated up to about 80 ° C, during which time 45 g of diketene Mixture were incorporated. One obtained by crystallization from to the Reaction mixture 47 g of pyrazolone, corresponding to a yield of 54 ° / a of the theoretical. 'Example 7'. The procedure was as in Example16, j @ =. but as a solvent a mixture of -5o cc of ethyl acetate and 10 cc of ethyl alcohol is used. The yield of pyrazolone was 41 g, corresponding to 45% of the theoretical.

The same amounts of phenylhydrazine and diketene were as above described, brought to implementation in a mixture, which zoo ccm of di-n-butyl ether contained as a solvent. A yield of 3 μg of pyrazolone was achieved, correspondingly 36 ° @ o of the theoretical amount.

Although the best yields were achieved at a temperature of about 80 to 85 ° C., temperatures of about 45 ° and 10 ° C. were also used. If the temperature is below 80 ° C, it will take a considerable amount of time to complete the reaction. As has been found, no significant amounts of pyrazolone are formed at temperatures below 40 ° C. For the better yield, the constant removal of the water from the reaction mixture is also desirable, but not necessary to maintain the reaction. agile.

Claims (3)

PATENT CLAIMS: i. Process for the production of pyrazolone derivatives, characterized in that equimolecular amounts of a hydrazine of the composition R-NH-NH2, where R denotes phenyl or substituted phenyl, in an inert Solvents, especially benzene or toluene, as solvents at temperatures Diketene is slowly added above 40 ° C. and the reaction product is crystallized wins. 2. The method according to claim i, characterized in that the during the reaction formed water is constantly distilled off together with the solvent. ' 3. The method according to claim i and 2, characterized in that one is at a Working temperature from 8o to 85 °.