US2193788A - N-methylsulphites and n-methanesulphinic acid salts of 1-aryl-2, 3-dialkyl-4-alkylaminopyrazolones - Google Patents

Description

Patented Mar. 19, 194i) UNITED STATES.

N-METH'YLSULPHITES' AND N-METHANE- SULPHINICACID- SALTS F LABEL-2,3- DIALKYLA-ALKYLAMINOPYRAZOLONES Max Bockmiihl, Walter Krohs, Fritz Racke, and

Kurt Windisch, Frankfort on the Main- Hochst, Germany, asslgnors to Winthrop Chemical Company, Inc., New York, N. Y., a corporation'of New York No Drawing. Application .iuly '21, 1938, Serial PATE '9 No. 220,496. In Germany July 24, 1937 comm. (o1; 260-31 0)" wherein X stands for a branched alkyl radical, for instance for one of the following radicals:

The present invention relates to N-methylsulphites and N-methanesulphinic acidsalts of 1- aryl-2.3-dialkyli-alkylaminopyrazolones.

In U. S. Patent No. 1,426,348, and German Pat- 5 ents Nos. 476,643 and 476,663, also in U. S. Patent 2,078,440 in connection with German Patent No. 617,237 there is described inter alia the manufacture of N-methylsulphites and N-methane-. sulphinic acid salts of 1-aryl-2.3-dialkyl-4-alkyl- 1o aminopyrazolones. All the compounds obtain able by that manufacture are N-methylsulphites or N-methanesulphinic acid salts of secondary amines and the alkyl radical of which situated at the amino-nitrogen is straight, such as for instance methyl, ethyl and the like.

We have found that N-methylsulphites and N-methanesulphinic acid salts of 1-aryl-2.3-dialkyl-4-alkyl-aminopyrazolones which contain a branched aliphatic radical at the 4-nitrogenare compounds which, in comparison with the known compounds, have,in addition ,to' the antipyretic action, a narcotic action and therefore are suitable for the use as analgesics; the invention consists in the manufacture of these compounds 5 containing a branched aliphatic radical.

The compound may be made in various ways. For example theaminopyrazolones named are directly condensed with formaldehyde bisulphite or formaldehyde sulphoxylate. Instead of starting from formaldehyde bisulphite there may be used formaldehyde and bisulphite in a desired sequence. If the aminopyrazolones are first condensed with formaldehyde the methylene-biscompounds of the amines are formed which may then be transformed into the N-Inethylsulphites by the addition of a further quantity of formaldehyde and of bisulphite. Furthermore, the proc- ECH; Hi-Y cur-on:

-"-Y stands for a mem 'sisting of and Me standing for a 9. -oto Me metal of the group consisting NT OFFICE CHz-CH: v 1

her of the group conof alkali metals or alkaline earth metals, said compounds being white powders soluble in water with a neutral reaction to litmus paper and sol- I uble in methyl alcohol and ethyl alcohol. 7

The following examples serve to illustrate the invention but they are not intended to limit it thereto; the parts are by weight; parts by volume have the same ratio to parts by weight that i the litre has to the kilo:

(1) 1 phenyl 2.3 dimeth yl 4 isopropylamino-5-pyrazolone melting at C. is prepared by causing l-phenyl 2.3 dimethyl 4 aminopyrazolone to react with isopropylbromide.

lOO parts thereof are introduced into the reaction solution, heated to 50 (3., prepared from parts of a sodium bisulphite solution of 37.8

per cent. strength and 40 parts ofa formaldehyde solution of 30 per cent. strength. After the pyrazolone has dissolved, 300 parts of alcohol are added, the solution is mixed with animal charcoal and filtered and the sodium salts of 1 phenyl 2.3 dimethyl 5 pyrazolone 4 isopropylaminomethylsulphurous acid is precipi- (2) 16 parts of the sodum salt of 1-phenyl-' 2.3 dimethyl-5-pyrazolone4-amino methylsulphurous acid and 3 parts of sodium' carbonate are dissolved in 50 parts of water and the solution is heated to 40 C. with 10 parts of di-isopropylsulphate, while stirring, until thefevolution' of carbon dioxide has ceased. The solution is then evaporated under reduced pressure -so;.as to obtain a dry mass which is recrystallized from dilute alcohol. The compound is identical with that obtained as described in-Examplda, 1.

(3) 20 parts of 1-phenyl-2.3-dimethylA-isopropylamino-5-pyrazolone are dissolved in dilute alcohol and the solution is mixed with 8 parts of a formaldehyde solution of 30 per cent. strength. After the solution has been stirred for some time 22 parts of sodium bisulphite of 37.8 per cent. strength are added and the whole is further stirred for one hour at 10 C. After the solvent has been evaporated under reduced pressure and the residue has been recrystallized from dilute alcohol a compound is obtained which is identical with that of Example 1.

The same compound is obtained by adding first the solution of sodium bisulphite to the dilute alcoholic solution of the amine and then running in the formaldehyde solution at 40 C. while stirring.

(4) 10 parts of 2. formaldehyde solution of 30 per cent. strength are added to a solution of 20.3 parts of 1-phenyl-2.3-dirnethyl-4-amino-5-pyrazolone in 50 parts of water, the whole is stirred for some time and then mixed with 20 parts of di-isopropyl sulphate and 6 parts of sodium carbonate. After the solution has been stirred for some time at 40 C. 28 parts of a solution of sodium bisulphite of 37.8 per cent.- strength are added and the whole is further stirred for some time at the same temperature. By evapcrating the solvent under reduced pressure and recrystallizing the residue from dilute alcohol the same compound is obtained as in Example 1.

(5) 49 parts of 1-phenyl-2.3-dimethyl-4-isopropylamino-5-pyrazolone are dissolved in parts of dioxane, 76 parts by volume of a formal.- dehyde solution containing 395 grams of formaldehyde per liter are added and 12.5 parts of sulphur dioxide are introduced into the solution while cooling. After the introduction has been finished the reaction is allowed to proceed for 15 minutes at room temperature and 400 parts of dioxane are then added. The l-phenyl-2.3-dimethyl-5-pyrazolone-4-isopropylaminomethane sulphonic acid crystallizes which is filtered with suction and washed with dioxane and petroleum ether.

16 parts of this acid are introduced at 40 C. into a suspension of 2 parts of calcium carbonate in 15 parts of water. Dissolution occurs with evolution of carbon dioxide. The whole is filtered. alcohol is added, the mass is cooled and the calcium salt which precipitates is filtered with suction. It melts at C. with decomposition.

(6) By heating for 3 hours at 100 C. 1- phenyl-2.3-dimethyl 4 aminopyrazolone with 2-bromobutane in. an alcoholic solution the lpheny1-2.3-dimethyl .4 secondarybutylaminopyrazolone, melting at 78 C., is obtained.

-dimethyhS-pyrazolone-4l-secondary-butylaminomethanesulphonic acid Which precipitates is filteredwith suction.

8 parts of the acid so obtained are introduced into .a mixture of 2.4 parts of caustic soda solution of 30 per cent. strength and 10 parts of absolute alcohol.

After the mixture has been filtered: ether isadded, the whole is filtered with suction and the sodium salt of the l-phenyl- 2.3-edimethyl-5-pyrazolone 4 secondary-butyl aminomethylsulphurous acid is recrystallized from a'mixture of acetone and absolute alcohol. The product melts at 166 C. with decomposition.

.(7) 245 parts of l-phenyl-2.3-dimethyl-4iso- 'propylamino-5-pyrazolone are introduced at 0. into a solution of 15.2 parts of sodium formaldehyde sulphoxylate in 15 parts of water. After the Whole has dissolved the solution is evaporated to dryness under reduced pressure and the sodium salt of the 1-phenyl-2.3-dimethyl-5 pyrazolone 4 isopropylaminomethanesulphinic acid is recrystalized from dilute alcohol.

8) 1 phenyl 2.3-dimethy1-4-isobutylamino- 5-pyrazolone, melting at 71 C., is prepared by reducing a mixture of 1-phenyl2.3-dimethyl-4- amino-5-pyrazo1one and isobutylaldehyde. 55 parts thereof are introduced at 50 C. into a reaction solution of 55 parts prepared from a sodium bisulphite solution of 37.7 per cent. strengthand 20 parts of a formaldehyde solution of 30 per cent. strength. After the pyrazolone has dissolved the solution is evaporated to dryness under reducedpressure and the sodium salt of .the l-phenyl-2.3-dimethyl-5-pyrazolone4- isobutylaminomethylsulphurous acid thus obtainedis recrystallized from ethyl acetate. It melts at 170 C. If recrystallized from moist ethyl acetate a product containing water of crystallization is obtained. melting at 70 C. to 75 C.

We claim:

1. The compounds of the following formula:

CHr-Y wherein X stands for a branched unsubstituted lower alkyl hydrocarbon radical and Y stands for a member of the group consisting of II S-OMe and Me standing for a metal of the group consisting of alkali metals or alkaline earth metals. said compounds being White powders soluble in water with a neutral reaction to litmus paper and soluble in methyl alcohol and ethyl alcohol.

2. The compound of the following formula:

I o s 1 7 v5' CH; I 06 \N-CH; DOB-OHr-N-zC-CH; on

10 forming a white powder soluble in water with a neutral reaction to litmus paper and soluble in methyl alcoholand ethyl alcohol. v v 3. The compound'of thefollowing formula:

OH; o6 N-on; on-N-azz-cm 20 CE: (I?

GHr-O. S.O.Na

forming a white powder soluble in water witha neutralreaction to litmus paper and soluble in methyl alcohol and ethyl alcohol. V e

4. The compound of the following formula:-

forming a white powder soluble in water with a neutral reaction to litmus paper and'soluble 15 in methyl alcohol and ethyl alcohol.

--MAX BOCKMETHL,

. WALTER KROHS.

FRITZ RACKE. I v KURT WINDISCH.