DE1082248B - Process for the production of substituted urea compounds - Google Patents

Description

Process for the preparation of substituted urea compounds The present invention relates to a method for producing substituted urea compounds.

It has been found that certain substituted urea compounds a marked effectiveness in combating and treating coccidiosis, a contagious poultry disease.

The substituted urea compounds can be prepared by adding a compound of the structural formula in which R 'denotes hydrogen or alkyl, with a methyl halide, dimethyl sulfate or an allyl halide in the presence of a strong base to form a compound of the structural formula converts, in which R 'has the above meaning and R is methyl or allyl.

4,4'-Dinitrocarbanilide is suspended in the process according to the invention in acetone, adds potassium hydroxide at room temperature and sets the mixture with it a methylating agent such as methyl iodide or dimethyl sulfate to give N, N'-dimethyl-4,4'-dinitrocarbamide around.

N, N'-diallyl-4,4'-dinitrocarbanilide can be prepared in the same way by reacting 4,4'-dinitrocarbanilide with potassium hydroxide and allyl bromide or Making allyl iodide.

Various dinitrocarbanilides, among others Nicarbazin used. Nicarbazin is the trade name for the Complex: compound of 4,4'-dinitrocarbanilide and 2-hydroxy-4,6-dimethylpyrimidine.

The experiments were carried out as follows: groups of ten each Chickens 2 weeks old were fed a mash feed which was 0.01% of the active ingredient contained in an even distribution. 24 hours after the start of the During feeding, each hen hen was inoculated with 50,000 cocysts of Eimeria tenella.

The experiment was completed after the appropriate types of feed Had been fed for 7 days after vaccination. They were as shown in the table listed Get results. The count of cocysts (i.e. the number of Parasites of the cultivar Eimeria tenella) took place by killing the animals and infecting them Organs were examined microscopically.

Active ingredients used: 1. N-methyl-4,4'-dinitrocarbanilide.

2. N, N'-dimethyl4,4'-dinitrocarbanilide.

3. N-ethyl-4,4'-dinitrocarbanilide.

4. Nicarbazin.

Test results % of% Ge Connection% Dying Cocyst- Binding in the freedom number.106 Feed increase number. 10 1 01 10 62 22 2 0.01 0 85 10 3 0.01 20 50 18 4 0.01 I 0 79 0.1 The dimethyl derivative is a stronger active ingredient against coccidiosis than the monomethyl and monoethyl derivative. The mortality rate is 0:10:20. The number of cocysts is considerably lower for the dimethyl derivative than for the other two derivatives.

The weight gain which is aimed at at the same time to under To achieve, among other things, a better survival of the test animals, shows a clear one Superiority for the dimethyl derivative.

The mortality of the test animals, which with the dimethyl derivative treated as an active ingredient is equivalent to that of nicarbazin.

The values for the number of cocysts are lower for nicarbazin. The comparison with the mortality evaluating makes it clear, however, that a decrease the number of cocysts is practically not below the value achieved by the dimethyl derivative is required. A major gain in the administration of the dimethyl derivative compared to feed containing nicarbazin lies in the higher weight gain. One Weight gain of 7901, for Nicarbazin a weight gain of 8501, for the dimethyl derivative opposite.

The following examples are intended to illustrate the invention.

Example 1 Preparation of N, N'-dimeth-yl-4,4'-dinitrocarbanilide HH CH3 CH3 02N O, N- NCN- 2K0H $ 2CHaJAcetone 0 -NQ ON 1¼) 0 96.6 g (0.32 mol) of 4,4'-dinitrocarbanilide were suspended in 900 cc of acetone. Then, 112 grams (2 moles) of potassium hydroxide (8501 grade) was quickly added to the slurry with stirring at room temperature. The slurry turned reddish brown and, after a few minutes, dark green. About 5 minutes after the potassium hydroxide was added, 10.5 cc (1.28 moles) of methyl iodide was added.

The slurry was refluxed for 1 hour and 15 minutes touched. During the reflux condenser, the supernatant phase became progressive clearer and took on a deeper color, an amber liquid towards the end and a heavy, steel-gray insoluble residue (mostly from excess Consisting of potassium hydroxide) remained. The hot muddy reaction mixture was filtered off with suction and the filter cake was washed three times with 400 cc of acetone each time. the The combined acetone filtrates were allowed to evaporate for approximately 16 hours at room temperature. The remaining crystal mass of N, N'-dimethyl-4,4'-dinitrocarbanilide became good with water, 6N hydrochloric acid (to remove p-nitroaniline and its N-methylated Derivatives) water, ethanol and finally mixed with ether are considering the poor solubility of the product in water, ethanol and Ether is not decisive at room temperature. The crystals of N, N'-Dimethyl-4,4'-dinitrocarbanilide melted to a clear one at 156.5-157.5 ° C yellow liquid. N, N'-Dimethyl-4,4'-dinitrocarbanilide can be derived from various Solvents recrystallize well. For example, there was 12.1 g of N, N'-dimethyl4,4'-dinitrocarbanilide dissolved in 175 cc of boiling ethyl acetate, and the mixture was at room temperature ditched. The N, N ~ dimethyl-4,4'-dinitrocarbanilide thus obtained showed a Melting point from 156.5 to 157.5 ° C.

The infrared spectrum of N, N'-dimethyl-4,4'-dinitrocarbanilide was characterized by an "abnormal urea carbonyl band" at 6.02 Ca. The C = O bond of the dinitrocarbanilide appears at 5.75 Il. Absorption of the N, N'-dimethyl-4,4'-dinitrocarbanilide, dissolved in ethanol, in the ultraviolet: maximum 3400 Â; EOI, = 1250.

Yield: 84%.

Example 2 Preparation of N, N'-dimethyl-4,4'-dinitrocarbanilide One Slurry of 30.2 g (0.1 mole) 4,4'-dinitrocarbanilide and 13.4 g (0.22 mole) powdered Potassium hydroxide was added at room temperature with stirring over 30 minutes 37.8 g (0.3 mol) of dimethyl sulfate were added. The slurry was stirred Heated for 2 hours on the reflux condenser and then Eltriert hot. The one during evaporation Crystals obtained from the acetone filtrate were poured onto a funnel with water, ethanol and finally washed with ether. The dry N, N'-dimethyl-4,4'-dinitrocarbanilide thus obtained weighed 18.35 g; F. = 149 to 151 "C. When mixed with one prepared according to Example 1 The sample showed no lowering of the melting point.

Example 3 Preparation of N, N'-diallyl-4,4'-dinitrocarbanilide A mixture of 400 cc of acetone, 15.8 g (0.24 mol) of powdered potassium hydroxide (of 850 purity) and 18.12 g (0.02 mol) of dry, powdered 4,4'-dinitrocarbanilide was prepared. The brightly colored slurry was admixed with 24.2 g (0.2 mol) of allyl bromide in one shot with stirring. The reaction mixture was refluxed with stirring for 11/2 hours and then filtered using vacuum. 2.6 g (14.40%) of dinitrocarbanilide were recovered from the insoluble filter cake. After the acetone had been removed from the filtrate, a crystalline precipitate contaminated with a yellow oil remained. After stirring the mass with ether, filtering and recrystallizing the crystalline cake from methanol, pale yellow crystals of N, N'-diallyl-4,4'-dinitrocarbanilide were obtained; F. = 109 to 109.5 ° C.

Yield: 85.6%.

Claims (3)

PATENT CLAIMS: 1. Process for the production of substituted urea compounds of the general formula in which R 'denotes hydrogen or alkyl and R denotes methyl or allyl, characterized in that a compound of the general formula in which R 'has the above meaning, reacts with a methyl halide, dimethyl sulfate or an allyl halide in the presence of a strong base. 2. The method according to claim 1, characterized in that one for Preparation of N, N'-dimethyl-4,4'-dmitrocarbanilide 4,4'-dinitrocarbanilide in the presence of potassium hydroxide with methyl iodide or dimethyl sulfate. 3. The method according to claim 1, characterized in that one for Preparation of N, N'-diallyl-4,4-dinitrocarbanilide 4,4'-dinitrocarbanilide in the presence of potassium hydroxide reacts with allyl bromide. References considered: Science, 122 (1955), p. 244.