IE45712B1 - A process for the preparation of substituted n, n-dialkyl-thiocarbamic acid s-benzyl esters - Google Patents

Description

The invention relates to a novel process for preparing the per se known substituted thiocarbamic acid S-benzyl esters of the general formula I R1 RZ II · c — (i) wherein represents an alkyl group having 1—4 carbon atoms, R represents an alkyl group having 1 to 4 carbon atoms or a cyclohexyl group or r’ and R2 together form a polymethylene group having 4 to 6 carbon atoms R3 and R4 the same or different represent hydrogen or chlorine or 10 alkyl, alkoxy or alkylthio groups having 1 to 4 carbon atoms.

The thiocarbamic acid S-benzyl esters prepared by the novel process are well known herbicidal substances. In the British Patent Specification No. 1,287,131 compounds are disclosed, wherein a (Cj—Cg) alkoxy group and optionally one of the following substituents are attached to the phenyl-ring: halogen, nitro-group, alkyl-group having 1 to 5 carbon atoms.

British Patent Specifcation No. 1,356,306 discloses benzylthiocarbamates, wherein the nitrogen atom is substituted by two secondary-butyl groups.

The known methods directed to the preparation thereof are as follows: German Offenlegungsschrift (DE-OS) Nos. 2,019,491 and 1,955,892 disclose a first method wherein an appropriate dialkylamine is reacted in the presence of an acid binding substance with phosgene (carbonyl chloride) and - 2 4 3 7 13 the thus formed carbamyl chloride is reacted in an organic solvent medium under anhydrous conditions with sodium benzyl thiol ate which latter can be obtained through the reaction of a-substituted benzylthiol and metallic sodium.

German Offenlegungsschrift (DE-OS) Nos. 1,817,662 and 2,110,228, and French Patent Specifications Nos. 1,328,112 and 2,078,724 disclose a second method, wherein suitable benzylthiol is reacted in an organic solvent in the presence of an organic base, e.g. dialkylaniline, with phosgene and the thus obtained benzyl thio carbonyl chloride is reacted in the presence of an acid binding base with a suitable amine to obtain the desired thiocarbamic acid 3-cenzyl ester. A method is described in British Patent Specifcation No. i ,259,472 for manufacturing Ν,Ν-disubstituted - S - benzyl - thiocarbamates of the general formula I by condensation of phosgene with a S-benzyl mercaptan and reacting the obtained benzylthiocarbamic acid chloride with a secondary amine in the presence of a base capable of combining with the liberated hydrogen chloride.

A further method starts with a solution of an appropriate dialkylamine and carbonyl sulfide (CGS) is introduced into the solution, under cooling, thus forming a dialkyl ammonium salt of the appropriate dialkyl-thiocarbamic acid, which is reacted thereafter with a substituted benzyl chloride to obtain the desired thiocarbamic acid S-benzyl ester. This method is described in Soviet. Patent Specifcation No. 201,380 and in French Patent Specification No. 2,078,723.

The known methods referred to have several disadvantages.

In the first three methods dangerous gaseous phosgene has to be - 3 4S71S used under anhydrous circumstances. The phosgene, however, easily hydrplyzes ant| the hydrochloric acid formed causes corrosion.

Therefore very strict security measures and caution are necessary and the equipment has to be manufactured from corrosion-resistant structural material. The commercial-scale use of metallic sodium on the other hand, requires a closed technological system and a special technique. The fourth method has not found acceptance on a commercial scale due tp the complicated method of preparation of carbonyl sulfide.

There is, however, a need to develop a simplified and more 10 advantageous method for the preparation of the compounds mentioned above.

It has been found, surprisingly, that thiocarbamic acid S-benzyl esters can be prepared under very advantageous conditions of preparation and sometimes with an improved yield if suitable thiocarbamic acid O-alkyl esters are reacted with substituted benzyl chlorides.

According to the present invention a thiocarbamic acid O-alkyl ester of the general formula II (Ry and Rz as before) R' S \ il N_C_OR> / R’ (II) and a benzyl chloride of the general formula III (Rg and R^ as before) Cl— CHZ (III) - 4 4 5 712 are reacted in the presence of or without an inert organic solvent, and if desired in the presence of a divalent metal halogenide, especially chloride, catalyst, and optionally heating, thus forming a thiocarbanric acid S-benzyl ester of the general formula I and simultaneously splitting off an alkyl chloride of the general formula IV R5—-Cl (IV) In the general formulae II and IV, R represents an alkyl-group having 1 to 3 carbon atoms. A suitable rate of reaction can be obtained without using a catalyst in a temperature range of 170 to 180°C, If, however, a divalent metal halogenide, particularly chloride, is used as a catalyst in an amount of 3 to 7 weight % based on the reaction mixture,then the reaction takes place about 100°C over 2 to 3 hours. The reaction can be carried out by reacting directly the appropriate components or a surplus of benzyl chloride can be used as a solvent. As a suitable solvent, toluene may also be used, with or without a catalyst.

In the course of the reaction there is no substantial decomposition and no side reactions occur; the formed products are generally pale yellow. The alkyl chloride liberated during the reaction e.g. ethyl chloride boils out of the reaction mixture. On finishing the reaction a viscous substance corresponding to 7 to 10 weight % of the starting substances separates and can be isolated or can be filtered at the end of the reaction after treatment with activated carbon. The crude product or a solution thereof is preferably washed after separation with water and dried. - 5 I The purity of the obtained crude product is, on the basis of gas chromatography analysis, more than 90%; it is therefore directly suitable for the manufacture of plant protecting compositions. Using this, method distillation of products having high boiling point can be avoided. Ν,Ν-diethyl-thiocarbamic acid - S - (4 - chlorobenzyl) - ester, which is one of the most important herbicides used in the cultivation of rice, has a purity, when prepared by the present process, amounting to 973! which corresponds in this case, calculated on the weight of the crude product to a yield of 88%. In contrast thereto this compound could be prepared according to prior art methods with a yield of only about 78 to 79.5%. (German Offenlegungsschrift Nos. 2,019,491 and 1,817,662).

If this reaction is carried out in an organic solvent such as toluene, then the obtained reaction mixture can be used directly after a simple purification process (such as treatment with activated carbon, filtration, aqueous washing and drying) as starting material to prepare emulsifiable concentrates (EC) for plant protection.

The substituted thiocarbamic acid 0-alkyl ester serving as a starting substance is a known compound. The preparation of this compound is disclosed e.g. in US Patent Specification No. 3,224,863.

In the present process benzyl chlorides are used as starting substances whereas in the known methods the benzyl thiols serving as starting materials have to be prepared beforehand from the appropriate benzyl chlorides.

/ With the help of the present process the major disadvantages of the methods hitherto known can be eliminated or reduced. The novel - 6 45718 method does not require phosgene as a reaction component, the corrosion problem due to formation of hydrochloric acid is avoided, complicated security measures can be obviated, the equipment can be made from cheaper structural materials and the conditions of the synthesis are generally not so severe as with known methods'. In this way the technological process can be greatly simplified and the investment and maintenance costs can be reduced.

The yield of the claimed process is about 80 to 90?.

Although such a yield can be obtained with known methods as well, the above-mentioned other advantages of the present process cannot be attained. ihe following Examples serve to illustrate the claimed process without limiting the scope of the invention: Example 1 Ν,Ν-diethyl thiocarbamic acid - S - (4-chlorobenzyl) - ester. 80.5g. (0.5 moles) of Ν,Ν-diethyl-thiocarbamic acid - 0 - ethyl ester was dissolved in 170ml. of toluene and to this solution 80.5g. (0.5 moles) of 4 - chloro-benzyl-chloride and 7.5g. of anhydrous zinc chloride were added and thereafter refluxed for 3 hours. During the reaction ethyl chloride was formed which was removed by boiling off from the reaction mixture. Before finishing the refluxing of the mixture, 6g. of activated carbon was added to the reaction mixture, which was cooled and filtered. The toluene was distilled in vacuo using a water bath having a temperature of 80°C. 117.5g. of a pale yellow product was obtained, the yield amounting to 91?. The purity of the product was 97? on the basis of gas chromatography analysis. The yield calculated - 7 4 3 71» on the pure product was therefore 88%. The raw product was fractionated in vacuo. The weight of the main run amounted to 10.98g. The yield was 86%. The boiling point of the product at 2 torr was 150—152°C.

Example 2 Ν,Ν-diethyl-thiocarbamic acid - S-benzyl ester 32.2g. (0.2 moles) of Ν,Ν-diethyl-thiocarbamic acid -0 - ethyl ester and 38.8g. (34.4 ml. corresponding to 0.3 moles) of benzyl chloride were refluxed for two hours. The ethyl chloride which formed during the reaction was removed by boiling off from the reaction mixture. The reaction mixture was distilled in vacuo formed by a water jet pump and surplus benzyl chloride was recovered. The distillation residue was fractionated and 38.4g. of the desired product was obtained. Yield: 86% Boiling point at 1.5mm./Hg: 132—134°C.

Example 3 Ν,Ν-dipropyl- thiocarbamic acid - S - benzyl ester 75.6g.(0.4 moles) of Ν,Ν-dipropyl-thiocarbamic acid - 0 ethyl ester was dissolved in 100 ml. of toluene. To the resulting solution 52.5g. (0.4 moles) of benzyl chloride and 2.5g. of anhydrous zinc chloride were added and the mixture was refluxed for 3 hours; thereafter the mixture was treated with activated carbon and filtered, and the filtrate was washed twice with 50 ml. of water. After washing the mixture was dried over magnesium sulfate and was evaporated. The residue was distilled at or under 2 mm./Hg. at 128—130°C. 77.2 g. of the desired product was obtained. Yield: 77% . - 8 4 3712 Example 4 Ν,Ν-pentamethylene-thiocarbamic acid - S - benzyl ester 51.9g. (0.3 moles of N ,Ν-pentamethylene-thiocarbamic acid -0- ethyl ester was dissolved in 140ml. of tolueneand to this solution 38.0g. (34.4 ml. corresponding to 0.3 moles) of benzyl chloride and 6g. of zinc chloride were added. The mixture was refluxed for 3 hours. After refluxing 5g. of activated carbon was added to the reaction mixture and filtered. The filtrate was washed twice with 80ml. of water, dried over anhydrous sodium sulfate and evaporated. The residue was distilled on 2mm./Hg. at 131 — 134°C. 571.g of the desired product was obtained. Yield: 81%.

Example 5 (i,N-di ethyl-thiocarbanric acid - S - (4-chl orobenzyl)-ester 64.6g (0.4 moles of Ν,Ν-diethyl-thiocarbanric acid 0-ethyl ester was dissolved in 120ml. toluene and to this solution 64.4g. (0.4 moles) of 4-chlorobenzyl chloride and 4.5g. of ferrous chloride were added. The reaction mixture was refluxed for 2 hours. Thereafter the mixture was treated with 5g, of activated carbon, then filtered. The toluene was distilled off in vacuo using as a heating source a water bath having a temperature of 80°C. 72.4g. of yellowish brown oil was obtained which was purified by vacuum distillation. The weight of the main run was 70.8g. Yield: 68%. Boiling point: at 2mm./Hg. 150—152°C.

Example 6 The process was carried out similarly to the previous Example with the difference that 4.5g. cf cupric chloride was added as catalyst to the reaction mixture. The weight of the main run obtained by vacuum - 9 distillation amounted to 76.5g. Yield: 75%.

Example'7 The process was carried out similarly to Example 5 with the one difference that 4.0g. of stannous chloride was added as catalyst to the reaction mixture. The weight of the main run obtained by vacuum distillation amounted to 67.8g. Yield: 66.5%.

Example 8 The process was carried out similarly to Example 5 with the difference that 5.0g. of barium chloride was added as catalyst to the reaction misture. The weight of the main run obtained by vacuum distillation amounted to 61.2g. Yield: 60%.

Example 9 8.5g. (0.5 moles) Ν,Ν-diethyl-thiocarbamic acid S-ethylester and 80.5g. (0.5 moles) of 4-chlorobenzyl chloride were added to a f round bottom flask equipped with a reflux condenser and a thermometer.

As catalyst 1.6g. of cadmium chloride was added. The reaction mixture was refluxed for one hour at 120—130°C, the ethyl chloride formed boiling off vigorously from the reaction mixture. At the end of the reaction the cadmium chloride was filtered from the mixture. The obtained raw product was a pale yellow oil, weighing 122.8g. Yield: 95%.

Claims (3)

1. CLAIMS:1. A process for the preparation of substituted Ν,Ν-dialkyl thiocarbamic acid S-benzyl esters of the general formula I 5 wherein represents an alkyl group having 1--4 carbon atoms, o R represents en alkyl group having 1 to 4 carbon atoms or a cyclohexyl group or 1 2 R and R together form a polymethylene group having 4 to 6 10 carbon atoms, Ο Λ R and R the same or different represent hydrogen or chlorine or alkyl, alkoxy or alkylthio groups having 1 to 4 carbon atoms, characterized by reacting a thiocarbamic acid 0-alkyl ester of the general formula II 12 5 wherein R and R are the same as above and R represents an alkyl group having 1 to 3 carbon atoms, if desired in the presence of a divalent metal halogenide catalyst and an inert organic solvent, with a benzyl 43712 chloride of the general formula III Cl (in) 3 4 wherein R , R are the same as above.

2. A process for the preparation of an ester of the general formula I, substantially as herein described in any one of the Examples.

3. An ester of the general formula I, when prepared by the process of claim 1 or 2.