DE1468388C - Process for the preparation of N aryl thiocarbamates - Google Patents

Description

Ar ₁ -NC-Cl + HO-Ar ₂
H ₃ CS

'Ar ₁ -NCO-Ar ₂ H, 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 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 l ^l / ₂ hours, heated under reflux, 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%.

i 468 388

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 ... N4.28%;
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

Cl

-ό

CH, to 105

to 106

to 142

up to 125

-OCH ₃ to 109

115.5 to 116

to 108

C ₁₉ H ₁₇ NOS

CgH ₁₇ NOS

C ₁₉ H ₁₇ NOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₉ H ₁₇ NO ₂ S

4.56

4.56

4.56

4.28

4.28

4.28

4.34

4.30

4.45

4.26

3.95

3.90

4.21

3.93

continuation

connection

Ar,

Cl

Cl

Cl-

CH ₃

CH ₃

/ X

Ar ₂

// X

Br

(T)

Va /

(Y)

VA /

141 to 142

147

131

110 to 111

118 to 119

127 to 128

110.5 to 111.5

117 to 118

110 to 111 formula

C _1R H,, BrNOS

CH ₁₇ NOS

C _1R H _1S NOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₈ H ₁₄ ClNOS

C ₁₉ H ₁₇ NOS

C ₁₉ H ₁₇ NOS

C ₁₉ H ₁₇ NOS

N-Ana! Yse (%) calculated found

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

By the method of the invention can be prepared J Arylthiocarbamate are the reeling-in German 55 \ __ writing thiocarbamic acid-O-aryl esters described 1,067,425 on the above-mentioned fields of application consider as apparent from the following embodiments.

Comparative tests were carried out using 60 representative representatives of the invention Compounds produced in comparison to the most effective Jaus der German Auslegeschrift 1067425 known compounds of the formulas

<f V-CH ₂ -NH-CO-

^w Il

OCH,

(CH ₂ ) ₂ —NH-C —O-

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 wherein Ar _{1 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
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, H, C 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 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 HC — Ar ₂ , in which Ar _{2 has the meaning given above.} The procedure is according to the following reaction scheme: Sponge infections of the human skin and for the protection of living plants against sponges and bacteria are useful. The N-aryl-thiocarbamates not previously described are made 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 10O ⁰ 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 made by the conversion of bis (N-substituted thiocarbamoyl) disulfide with chlorine or by reaction of a secondary amine 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