DE1620101A1 - Process for the preparation of 3-trihalomethyl-5-alkoxy-1,2,4-thiadiazole compounds - Google Patents

Description

"Process for the preparation of 3-trihalomethyl-5-alkoxy-1,2,4-thiadiazole compounds" priority: July 28, 1965, V.St.A., application no .; 475 551 The invention relates to a new process for the preparation of 3-trihalomethyl-5-alkoxy-1,2,4-thiadiazole compounds of the general formula in which X is a fluorine or chlorine atom and R is a lower alkyl group with 1 to 4 carbon atoms, which is characterized in that a trihaloacetamidine, optionally in the presence of an acid acceptor, is condensed with a lower alkylthiocarbonic acid chloride in an inert solvent and the N- Trihalogeniminoacetyl-O-alkylthiocarbamate, optionally after previous isolation, treated with chlorine or bromine, the process according to the invention proceeds according to the following reaction equation: Both stages of the process according to the invention are carried out in the presence of an inert solvent. This solvent is preferably the same in both stages. The use of the same solvent in both reaction stages makes it possible to carry out the second stage of the shaping according to the invention without isolating the N-trihalogeniminoacetyl-O-alkylthiocarbamate formed as an intermediate product. If necessary, however, this new intermediate product can be separated off from the reaction mixture of the first stage, purified if necessary and dissolved in the same or a different inert solvent in which the second reaction stage is carried out.

Suitable inert solvents for the process according to the invention are e.g. aliphatic hydrocarbons, chlorinated hydrocarbons, ether and esters of up to 6 carbon atoms. Specific examples of solvents are pantane, hexane, cyclohexane, petroleum ether and other lower aliphatic hydrocarbons with up to 6 carbon atoms; Carbon tetrachloride, methyl acetate, ethyl acetate, Isopropyl acetate, dimethyl ether, methyl ethyl ether, diethyl ether and diisopropyl ether.

The first stage of threading according to the invention is preferred carried out in the presence of an organic amine as an acid acceptor. Preferably are used as organic amines tert-amides or amines, their substituents lower alkyl or acyl groups, cycloaliphatic or aromatic groups with S or fewer carbon atoms are examples of this are pyridine H-methylpyrrolidine, Dimethylaniline, diphenylamine, methylformamide, dimethylacetamide, methyl diethylamine, Trimethylamine and triethylamine, the trihalogeno-cetamidine used can also be used as an acid acceptor to serve. In this case, it is used in molar excess. The hydrochloride with the acid acceptor precipitates out of the solvent and can be filtered off or be spun off when the intermediate product N # N-trihaloiminoacetyl formed -O -alkylthiocarbamate is separated off, the solvent can be removed from the intermediate product are distilled off. The residue is purified by recrystallization.

If the trihaloacetamidine is used as an acid acceptor, it becomes preferably iK1 an amount ratio of 2 moles per mole of alkyl thiocarbonic acid chloride used. The formed hydrochloride of the Tribslo @ enacei @@ dina is separated and by treatment with a Base regenerated again. Using a tertiary amine as acid acceptor are preferably the tertiary amine, the Trihaloacetamidine and the alkylthiocarbonic acid chloride in equimolar proportions used.

The second stage of the process of the invention is preferred carried out using the reaction mixture obtained in the first stage, from which the hydrochloride of the acid acceptor was separated. You can do that too Separate N-trihalogeniminoacetyl-O-alkylthiocarbamate formed as an intermediate and dissolve in the same or a different inert solvent.

The solution of the intermediate product is with liquid, gaseous or Chlorine or bromine dissolved in a solvent, preferably in stoichiometric Quantities, brought to the implementation ge, as in the above reaction equation is explained.

You can use more or less chlorine or bromine, but you will best yields achieved when the amount used is not significantly above the theoretical Amount lies.

If the halogen is used in a tube, the solvent can the same or a different solvent than that used to dissolve the intermediate Solvent used, carbon tetrachloride is particularly suitable for dissolution the halogens, because there are no by-products and the yields are excellent After the addition of the halogen, the reaction mixture is used to separate off the solvent distilled.

The desired thiadiazole remains. It can be used for cleaning in The reactions described above can be distilled in a vacuum Temperature range from about 0 to 50 ° C, preferably at a temperature of about 15 to 30 ° C.

The examples illustrate the invention.

Example 1 12.5 g (0.1 mol) of ethylthiocarbonic acid chloride in 100 ml Ether are added dropwise with stirring to a solution of 32D3 g (0.2 mol) of trichloroacetamidine given in 240 ml of ether at room temperature.

18.8 g (95 yv of theory) of trichloroacetamidine hydrochloride fall from the solution which are filtered off. The filtrate is evaporated to dryness. The residue is recrystallized from high-boiling petroleum ether. 19.9 g (80% of the Theory) N-tricloriminoacetyl-O-ethylthiocarbamate with a melting point of 99 to 1010C was obtained.

C5H7Cl3N2OS (249.6); Calculated: C 24.06; H 2.83; C1 42.62; N 11.23S12.85 gefa: C, 24.26; R 295; C1 42.60; N 11.59; S12.87 Example 2 A solution of 6.4 g (0.04 mol) bromine in 50 ml ethyl acetate is added dropwise to a stirred solution of 10 g (0.04 mol) of N-trichloriminoacetyl-O-ethylthiocarbamate in 150 ml of ethyl acetate given at 15 to 17 ° C. When the addition of the bromine solution is complete, the reaction mixture is Filtered and the filtrate evaporated to dryness. The crude 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole is distilled in vacuo. Yield 8.0 g (81% of theory) of pure product from Boiling point 77 ° C 0.1 torr. The IR spectrum of the product is an authentic one Sample identical to Example 3 A small excess of chlorine gas, determined with a Flow meter, is slowly immersed in a stirred solution of 5 g. For 2 hours (0.02 mol) N-Trichloriminoacetyl-O-ethylthiocarbamet in 100 ml of ethyl acetate at 15 initiated to up to 200C. The reaction mixture is filtered and the ethyl acetate distilled off. The residue is distilled in vacuo. 3.9 g (79 X the Theory) 3-trichloromethyl-5-ethoxy-1, 2,4-thiadiazole obtained.

Example 4 A solution of 6.25 g (0.05 mol) of ethylthiocarbonic acid chloride in 50 ml of ether is added dropwise with stirring to a solution of 8.1 g (0.05 mol) Trichloroacetamidine and 5.0 g (0.05 mol) of tri-ethylamine in 100 ml of ether at 200C. After stirring for 15 minutes at room temperature, the precipitated triethylamine hydrochloride becomes filtered off and the filtrate evaporated to dryness.

The brown residue is washed with 50 ml of hexane. It will be 7.8 g crude product obtained. After recrystallization from petroleum ether (bp 65 to 1100C) pure N-trichloriminoacetyl-O-ethylthiocarbamate with a melting point of 99 to 1000C is obtained. The yield is 6.7 g (53.5 ffi of theory).

Example 5 Chlorine gas is slowly poured into a stirred solution of 6 g of N-trichloroiminoacetyl-O-ethylthiocarbamate initiated in 150 ml of ethyl ether.

The yellow solution will turn colorless after 10 minutes, but will still be Chlorine absorbed. After a further 10 minutes, the mixture obtained is filtered and the solvent evaporated. The liquid residue is distilled in vacuo. There are 2.9 g of a first run (chlorinated ether) and 4.8 g (80.5% of theory) 3-Trichloromethyl-5-ethoxy-1,2,4-thiadiazole was obtained.

Example 6 A solution of 12.5 g (0.1 mol) of ethylthiocarbonic acid chloride in 100 ml of ether slowly becomes a stirred solution of 32.3 g (0.2 mol) of trichloroacetamidine added dropwise into 240 ml of ether at room temperature. The yellow slurry is 15 minutes stirred, then refluxed for a further 15 minutes and finally filtered. This gives the theoretical amount of trichloroacetamidine hydrochloride4 It is then poured into the filtrate at a moderate speed for 2G minutes introduced chlorine gas with ice cooling. The reaction mixture is filtered and the Solvent distilled off under reduced pressure. The liquid residue will fractionally distilled. There are 13.2 g (53% of theory) of 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole obtain.

Example 7 The procedure of Example 6 is repeated using an equivalent amount of trifluoroacetamidine instead of the trichloroacetamidine. Man receives the 3Tri in a satisfactory yield fluoromethyl-5-ethoxy-1,2,4-thiadiazole.

Example 8 The procedure of Example 6 is repeated using an equivalent amount of n-butylthiocarbonic acid chloride instead of ethylthiocarbonic acid chloride. 3-Trichloromethyl-5-n-butoxy-1,2,4-thiadiazole is obtained in a satisfactory yield.

Example 9 One. Solution of 5.0 g (0.04 mol) of ethylthiocarbonic acid chloride in 30 ml of ethyl acetate slowly becomes a solution of 12> 9 g (0.08 mol) of trichloroacetamidine given in 100 ml of ethyl acetate at 20 ° C.

The mixture is stirred for 30 minutes at room temperature and the precipitated Trichloroacetamidine hydrochloride (7.2 g; 91% of theory) is filtered off. The filtrate it is evaporated to dryness, there are 8.2 g (82% of theory) of N-trichloroiminoacetyl-O-ethylthiocarbamate obtained from m.p. 98 to 1000C without recrystallization. Example 10 A solution of 5.0 g (0.04 mol) of ethylthiocarbonic acid chloride in 30 ml of high-boiling petroleum ether (Bp. 65 to 110 ° C) slowly becomes a solution of 12.9 g (0.08 mol) of trichloroacetamidine added to 100 ml of petroleum ether at 20 ° C. After stirring for 30 minutes at room temperature the reaction mixture is used to separate the insoluble N-trichloriminoacethyl-O-ethylthiocarbamate and trichloroacetamidine hydrochloride filtered off. The trichlorac.tamidine hydrochloride is washed out of the solid mixture with water.

The yield of dried N-trichloroiminoacetyl-O-ethylthiocarbamate is 6.1 g (61% of theory).

Example 11 Chlorine gas is poured into a stirred suspension of for 30 minutes 12.5 g of N-trichloroiminoacetyl-O-ethylthiocarbamate in 250 ml of carbon tetrachloride initiated under ice cooling. The reaction mixture is filtered and the filtrate evaporated. The residue is distilled in vacuo. 10.5 g (84% of the Theory) colorless and pure 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole obtained.

Practically no forerun or residue is obtained.

Example 12 Chlorine gas is added to a slurry of 5 g of N-trichloroiminoacetyl-O-ethylthiocarbamate introduced in 100 ml of petroleum ether (bp 65 to 110 ° C) for 30 minutes with ice cooling The chlorination is accompanied by occasional light phenomena. After filtering off The solvent is evaporated off the mixture and the residue is distilled. 27 g (54 e of theory) of 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole are obtained.

Example 13 A solution of 12> 5 g (0.1 mol) of ethylthiocarbonic acid chloride in 100 ml of ethyl acetate is slowly added to a stirred solution of 32.3 g (0.2 mol) Trichloroacetamidine added to 240 ml of ethyl acetate at room temperature. The mixture is filtered. This is the theoretical amount of trichloroacetamidine hydrochloride Obtained through the filtrate is at a moderate speed for 20 minutes and chlorine gas passed under ice cooling. The reaction mixture will filtered, the solvent was distilled off under reduced pressure and the liquid The residue is distilled in vacuo. There are 15.5 g (62% of theory) of 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole received, claims

Claims (1)

Patent claims 10 Process for the preparation of 3-trihalogenmethyl-5-alkoxy-1,2,4-thiadiazole compounds of the general formula in which X denotes a fluorine or chlorine atom and R denotes a lower alkyl group having 1 to 4 carbon atoms, characterized in that a trihaloacetamidine, optionally in the presence of an acid acceptor, is condensed with a lower alkylthiocarbonyl chloride and the N-trihaloimioacetyl-Oalkylthiocarbamate formed , if necessary after previous isolation, treated in an inert solvent with chlorine or bromine, 2. Process according to claim 1, characterized in that an aliphatic hydrocarbon, a chlorinated hydrocarbon, an ether or ester with up to 6 carbon atoms is used as the inert solvent according to claim 1, characterized in that either the trihaloacetamidine or triethylamine used is used as the acid-binding agent.