DE1114804B - Process for the preparation of N-arylsulfonyl-N'-alkyl-ureas - Google Patents

Description

The patent application relates to a process for the preparation of N-arylsulfonyl-N'-alkyl ureas, in where the alkyl contains 2 to 8 carbon atoms. Such ureas have been known for a long time (See British Patents 808 073,808 072,808071; Austrian patent specification 196 413; Swiss patents 331 999 to 332 007).

According to these patents, it is also known to react such N-arylsulfonyl-N'-alkyl ureas of N-arylsulfonylureas with alkylamines to produce (see, for example, Swiss patent 332 005).

Checking the examples in Swiss patent 332 005 using the model of N-p-tosyl-N-n-butyl urea results in a yield of 2.5% when working without a diluent when working with o-dichlorobenzene as a diluent a yield of 5%

It is understandable that such yields make industrial application of this process impossible. It was therefore later proposed to convert N-arylsulfonyl-N'-acylureas into their salts with amines and ^{to heat the salts obtained to temperatures above 100 °} C. (cf. Austrian patent 195 436 and German patent 1 043 318). Better yields can already be achieved with this process; but it has the disadvantage that it has one step more than the simple transamidation process.

In example 3 of patent specification 9,688 of the Office for Invention and Patents in the Soviet Zone of Occupation In Germany, the turnover of p-acetylaminobenzenesulfonylurea with aniline in Acetone described in the presence of glacial acetic acid. If the specified conditions are strictly observed 57% of the desired end product is obtained in an impure state. After two recrystallizations 40% pure product is obtained from acetonitrile.

It has been found that N-arylsulfonyl-N'-alkyl-ureas can be obtained in the simplest manner and with very good yields if the reaction of an arylsulfonylurea with an alkylamine in a ketone with an approximate boiling point of 90 to 12O ⁰ C, preferably 100 to 120 ^° C. and a molar ratio of sulfonylurea to alkylamine of 1: 1.2 and if it is ensured that the ammonia split off is removed from the reaction mixture as quickly and completely as possible.

As an advantageous solvents are aliphatic ketones, within from 100 to 12O ⁰ C

Method of manufacture
of N-arylsulfonyl-N'-alkyl ureas

Applicant:

Cilag-Chemie Aktiengesellschaft,
Schaffhausen (Switzerland)

Representative: Dipl.-Chem. Dr. A. Ullrich

and Dipl.-Chem. Dr. T. Ullrich, patent attorneys,

Heidelberg, Bismarckstrasse 17th

Claimed priority:
Switzerland of April 7, 1959 (No. 71 640)

DipL-Chem. Robert EgIi, Schaffhausen (Switzerland),
has been named as the inventor

boiling, proven. The possibility of being reactive Influence of the aliphatic ketones on the intermediate formation of ketimines

; C = N -alkyl

R '

(R = lower alkyl radicals) cannot be ruled out, but has not been proven.

It is advantageous to choose such a ketone as a solvent that is little or practical in water is insoluble. After the transamidation has ended, the N-arylsulfonyl-N'-alkylurea formed can namely be brought into solution by adding alkali lye in the aqueous phase, while the ketone, that contains various impurities, separates.

An additional purification of the end product is achieved in this way.

As ketones, which correspond to the above conditions, are mentioned: methyl isobutyl ketone, Methyl n-propyl ketone, methyl sec-butyl ketone, dietetic

ethyl ketone and ethyl isopropyl ketone.

A mixture of different ketones can also be used, e.g. B. a higher and a lower

109 708/418

Claims (1)

3 4 boiling ketone, and so the boiling point is 35 minutes, the evolution of ammonia has ended. set the desired height. . The now clear solution is cooled to 20 ° C and then . stirred with 700 ecm 4% sodium hydroxide solution. the Example 1 aqueous layer is separated and the ketone layer N-tosyl-N'-n-butyl urea 5 is extracted once with 70 ecm of water. The United Approach aqueous solutions are mixed with 10% sulfur 214.0 g of p-toluenesulfonylurea acid blunted to pH 8.7, with 4 g of carboraffin-C 800.0 g = 1000 ecm of methyl isobutyl ketone are stirred and the whole is filtered. The filtrate is under 80.3 g · butylamine stirring in a mixture of 700 ecm of methanol and 80.0 g = 100 ecm acetone 10 350 g 10% sulfuric acid added dropwise. The p-toluenesulfonylurea is added to the mixture. The final pn value is 3.2 and the period of dropping was added methyl isobutyl ketone ünd.Acetön and about _^3/4 hour. The whole thing is still being stirred to do this, with stirring within 15 to 30 minutes, 15 minutes and sucks off the crystal pulp. To let the butylamine run in. washing with water and drying in the air It is formed by increasing the temperature from 15 to 15 drying cabinet one receives 165 g, that is 85% of the 20 ⁰ C a thick, but still stirrable pulp. One theory, on Np-chlorobenzenesulfonyl-N'-n-propyl- stirs about ¹ J ₂ . up to 1 hour and then heated urea with a melting point of 129 ⁰ C. rapidly to the boil, whereupon NH ₃ evolution occurs. The evolution of NH ₃ and thus the reaction are described in Example 3
accelerated by cooking as intensively as possible and 20 by fractionators. After everything has gone into solution in the same way as in the previous examples (what the almost complete Re- described, 150 g of Np-tosylurea shows action and, depending on the type of refluxing, 35 g of ethylamine (dissolved in 200 ecm of methyl isobutyl- 30 minutes to 2 hours), about ketone) and 1200 ecm of methyl isobutyl ketone as a solution are boiled for 10 to 20 minutes and then quickly reduced after boiling for 3 hours and the usual cooling. Now the light yellow reaction solution is well worked with 148 g of Np-tosyl-N'-ethyl-urea (that is 1000 g of 4% sodium hydroxide solution and the aqueous 87% of theory) with a melting point of 141 to 142 ^° C. The sodium salt solution is separated off . One extracts the ketone layer twice with 50 ecm of water each time. Example 4
The combined aqueous solutions are possible Lent immediately with good stirring with about heating, 150 g p-tosyl barnstoff with 100 g-octyl-120 g / 0% H ₂ SO ₄ blunted to pn 8.5 to 9 and amine in 700ccm methyl isobutyl ketone filtered for 30 minutes with 5 g carboraffin-C. to boiling and works according to the instructions of The coal is washed with 150 ecm of water. Example 1 gives 176 g of N-p-tosyl-N'-n-octyl-The filtrate is now allowed to melt with stirring into a mixture of 800 g of methanol in the course of 2 hours point 101 to 102 ° C. shrinks and 500 g 10% ^e r H ₂ SO _4. One can convert in the same way: p-tosyl- after adding about one tenth of the amount of urea with n-propylamine, isopropylamine, amylamine, be vaccinated. After cooling to 15 to 20 ° C, isoamylamine, heptylamine. Instead of p-tosyl adjusted to pH 3 to 3.5 and still V ₂ to 1 hour 40 urea can also p-Methoxybenzenesulfonylur- stirred further. Then the crystalline product, p-isopropylbenzenesulfonylurea, p-fluoro sucked off or centrifuged off and benzenesulfonylurea used well with water for the reaction washed. The easily consumable, white product will be
dried in an air drying cabinet at 40 to 60 ° C. Yield 45 PATENT CLAIMS:
at ³ _{l reflux for 1} hour 243 g = 90% of theory 1. Process for the preparation of N-arylsulfonyl- F. corr. 127 to 128 ° C N'-alkyl ureas by reacting an N-aryl at 2V ₂ hours back sulfonyl urea with an alkylamine in one flow boiling 230 g = 85% of theory 50 solvent, characterized in that one F. corr. 126 to 127 ° C the reaction in a molar ratio of 1: 1.2 . in a ketone of approximate boiling point Example 2 _{γοη 9Q to 12} o ⁰ c, preferably 100 to 120 ⁰ C, and Np-chlorobenzenesulfonyl-N'-n- _{propylurea with the} fastest possible removal of the Approach 55 makes split ammonia. 164.3 g of N-p-chlorobenzenesulfonylurea 2. The method according to claim 1, characterized in that 45.5 g of n-propylamine - shows that a ketone is used that is found in 800.0 ecm of methyl isobutyl ketone water is little or practically insoluble. The N-p-chlorobenzenesulfonylurea is under Stirring registered in the methyl isobutyl ketone. 60 Publications considered: Then the n-propylamine is allowed to run in, patent No. 9,688 of the Office for Invention whereby a thick, but still stirrable crystal pulp and patent system in the Soviet occupation zone arises. Now one heats with constant stirring to the Germany; Boiling, ammonia escaping vigorously. According to British patent specification No. 604 259. © 109 708/418 10.61