DE1468388B - Process for the preparation of N-arylthiocarbamates - Google Patents

Description

Example 2

Preparation of N-methyl-N- (l-naphthyl) -4-chlorophenyl thiocarbamate

A mixture of 12.8 grams of 4-chlorophenol, 23.5 grams N-methyl-N-O-naphthy-O-thiocarbamic acid chloride and 5.3 g of powdered sodium carbonate in 155 ecm of methyl ethyl ketone is refluxed for 2 hours heated. Then the solvent is distilled off, and there will be about the residue 200 ecm of cold water was added, whereby 28.0 g of white crystals are obtained. By recrystallization colorless, crystalline needles with a melting point of 115.5 to 116 ° C. are obtained from ethanol.

Analysis value for C ₁₈ H ₁₄ ClNOS:

Calculated ... N 4.28%;
found .... N 4.21%.

Example 3

Preparation of N-methyl-N- (1-naphthyl) -2-naphthyl-thiocarbamate

This product is made in a manner similar to that described in Example 2, but from 14.4 g of 2-naphthol, '23, 5 g of N-methyl-N- (l-naphthyl) thiocarbamic acid chloride, 8.4 g of sodium hydrogen carbonate and 150 ecm Received methyl ethyl ketone. The yield is 27.5 g. By recrystallization from methyl ethyl ketone colorless crystalline needles with a melting point of 147 ° C. are obtained.

Analysis value for C ₂₂ H ₁₇ NOS:
Calculated ... N 4.09%;
found N 3.80%.

The following table lists other similar ones to that described in the preceding examples Processes that can be established are listed:

Ar ₁ -NCO-Ar ₂ H ₃ CS

connection

Ar ₁

Ar,

F. ( ⁰ C) formula

N analysis (%)

calculated

found

CH,

Cl

104 to

CH,

105 to

141 to

124 to

-OH,

108 to

115.5 to

107 to CoH ₁₇ NOS

4.56

4.30

C ₁₉ H ₁₇ NOS

C ₁₉ H ₁₇ NOS

4.56

4.56

4.45

4.26

C ₁₈ H ₁₄ ClNOS

4.28

3.95

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₉ H ₁₇ NO ₂ S

4.28

4.28

4.34

3.90

4.21

3.93

continuation

connection

Ar,

Cl

Cl

Cl-

CH ₃

CH ₃

Ar,

Br

CC)

C (

(Y)

f. ro

141 to

147

131

110 to

118 to

127 to

110.5 to 111.5

117 to

110 to

formula

C ₁₈ H ₁₄ BrNOS

C ₂₂ H ₁₇ NOS

C ₁₈ H ₁₅ NOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C _ig H, ₇ NOS

C ₁₉ H ₁₇ NOS

Q ₉ H ₁₇ NOS

N analysis (%) found calculated

3.76

4.07

4.77

4.28

4.28

4.28

4.56

4.56

4.56

3.50

3.80

4.51

4.23 (

4.10

4.49

4.10

4.35

. 4.30

The / · \ which can be produced by the method of the invention

Arylthiocarbamates are those in the German interpretation 55 \ _ / ( ^CH 2) 2 ^NH <JO; Writing 1 067 425 described thiocarbamic acid O-aryl esters on the above

Think about the turning areas, as from the following ,

is apparent from the explanations. f

en statements. f \ (CH ₂ ) ₂ -NHC-O

There were comparative experiments using 60 N = / II

of representative representatives of the S

Compounds produced in comparison to the most effective compounds of the formulas known from German Auslegeschrift 1067425 / ■ \

6 ₅

OCH ₃

(CH ₂ ) ₂ - NH - C - O

CH ₇ -NH-CO

in terms of fungicidal activity both in vitro

as well as in vivo. In addition, many others became constitutionally and functionally similar investigated comparable known compounds with regard to their activity in the field mentioned.

In the in vitro activity test, solutions of the compounds to be examined were left on a suspension a culture of Trichophyton mentagrophytes, Species interdigitale. From the Experimental results show that only the compounds according to the invention are satisfactory Exhibited anti-Trichophyton activity.

Since the effectiveness in vitro does not say anything about whether these compounds also in vivo are effective, the compounds according to the invention and the known comparative compounds subjected to an in vivo activity test carried out on the skin of live guinea pigs. Trichophyton mentagrophytes, Species esteroides, was used as the test fungus in this experiment. the Compounds to be investigated were in the form of a 2% solution in the treatment of a Artificially induced surface trichophytosis in the back of guinea pigs was tested. Included it turns out that only the compounds according to the invention affect artificially produced dermatomycosis the guinea pigs were highly effective, while those from the German Auslegeschrift 1,067,425 known compounds were completely ineffective.

209 529/584

Claims (1)

Claim: Process for the preparation of N-aryl-thiocarbamates of the general formula Ar ₁ -NCO-Ar ₂ H ₃ CS where Ar ₁ door is 1-naphthyl, tolyl, phenyl or chlorophenyl and Ar _{2 is} 2-naphthyl, tolyl, chlorophenyl, methoxyphenyl or bromophenyl and at least one of the substituents Ar ₁ and Ar _{2 is} a naphthyl radical, characterized in that a compound the general formula Ar ₁ -NC-Cl I Il H ₃ CS in which Ar _{1 has} the meaning given above, is reacted in a manner known per se with a compound of the formula HO-Ar ₂ , in which Ar _{2 has the meaning given above.} The invention relates to a process for the preparation of the N-aryl-thiocarbamates, new and for a number of purposes with beneficial substances. The invention now relates to a process for the preparation of N-aryl-thiocarbamates of the general type formula Ar ₁ -N- C - O -Ar ₂ I Jl- H ₃ CS wherein Ar _{1 is} 1-naphthyl, tolyl, phenyl or chlorophenyl and Ar _{2 is} 2-naphthyl, tolyl, chlorophenyl, methoxyphenyl or bromophenyl, with the proviso that at least one of the substituents Ar ₁ and Ar _{2 is} a naphthyl radical, which thereby is characterized in that a compound of the general formula Ar ₁ -NC-Cl H ₃ CS in which Ar _{1 has} the meaning given above, is reacted in a manner known per se with a compound of the formula HC — Ar ₂ , in which Ar _{2 has the meaning given above.} The procedure is according to the following reaction scheme: Ar ₁ -NC-Cl + HO-Ar ₂
H ₃ CS -Ar ₁ -NCO-Ar ₂ H ₃ CS In the following, the details of the process for preparing the new compounds will be more practical Examples are described from which it can also be seen that these products are used for the treatment of Sponge infections of the human skin and for the protection of living plants against sponges and bacteria are useful. The so far not described N-aryl-thiocarbamates are prepared according to the method of the invention by conversion of N-substituted. Thiocarbamic acid chlorides in equimolar amounts made of phenol or naphthol. The reaction is stopped by using a suitable solvent, such as water, ethanol, methanol, acetone or chloroform, successfully completed as a reaction medium. The use of alkali metal hydrogen carbonates, alkali metal carbonates, alkali metal hydroxides, Alkaline earth metal hydroxides or tertiary amines as the hydrogen chloride acceptor is desirable. The reaction temperature is between 0 and 100 ° C and the reaction time between 10 and 120 minutes. If water is used as the reaction medium, the end product separates out at the end of the reaction away. If an organic solvent is used, the product becomes after the reaction has ended obtained as a solid residue by evaporation of the solvent. The reaction product is washed with water and recrystallized with a suitable one organic solvents such as acetone, alcohol, benzene or carbon tetrachloride. The N-substituted thiocarbamic acid chloride used as starting material for the reaction is obtained by reacting bis (N-substituted thiocarbamoyl) disulfide with chlorine or by reaction of a secondary amine made with thiophosgene. Laboratory tests have found that these can be prepared by the process of the invention N-Aryl-thiocarbamate very useful substances with specific, therapeutic effectiveness against microbial infections of the skin (such as trichophytia) 40. pose and furthermore as an agricultural Fungicide, ζ. B. suitable for the control of rice powdery mildew and bacterial powdery mildew, whereby they known similar compounds, for example the compounds in the German Auslegeschrift 1 067 425 are superior, as can be seen from the explanations below emerges. The following examples illustrate the process of the invention. « B e i s ρ i e 1 1 Production of N-methyl-N-phenyl-2-naphthyl-thiocarbamate 9.0 g of N-methyl-N-phenyl-thiocarbamic acid chloride are added with stirring to a mixture of 7.2 g of 2-naphthol, 2.0 g of sodium hydroxide, 50 ml of acetone and 5 ml of water. After completion of the addition, the mixture is heated X ¹ I ₂ hours under Rückfiußbedingungen, cooled and poured into about 100 cc of cold water, the final product precipitates in the form of white crystals. The yield is 12.4 g. Colorless crystalline needles with a melting point of 131 to 132 ° C. are obtained by recrystallization from ethanol. Analysis value for C ₁₈ H ₁₅ NOS: Calculated ... N 4.78%;
found .... N 4.51%.