IL26100A - Process for the manufacture of 3-trihalomethyl-5-alkoxy-1,2,4-thiadiazoles and intermediates therefor - Google Patents

Description

PE0CS33 FOR IHB Off JSiOVfili This invention relates to for the manufacture of by means of novel thlocarbamates as The novel process of this invention involves two the first to form the novel Intermediate and the second to convert the intermediate to the The two reactions are carried out consecutively in the same or different reaction Particularly advantageously both steps are carried out in a single reaction medium and apparatus without isolation of the More particularly the two steps of the novel process of this invention consist in a first reaction of with lower thlocarbonate chloride in the presence of an agent to form a reaction mixture containing the novel Without or without isolation or separation of the it is contacted with chlorine or bromine introduced as liquid or in solution to convert the intermediate to the resulting and separating that product from the reaction The novel intermediates are thlocarbamates of the formula X fluorine or chlorine and R is lower alkyl of 1 to 4 Specific examples of these novel intermediates thiocarbamate thiocarbamate thiocarbamate These novel intermediates have the particular utility of reacting readily with chlorine or bromine to form which have known Both steps of the novel process of this invention are carried out in the presence of an inert reaction The reaction medium is though not the same in both Use of the same reaction medium in both steps permits carrying out the second step of the process without isolating the intermediate from the first reaction When the novel intermediate is suitably separated from the first reaction purified as necessary and redissolved in the same or different inert reaction medium in which the second reaction is carried Suitable inert reaction media for either or both steps of the process of this invention are aliphatic ethers having up to 6 carbon Particular examples of suitable reaction media include petroleum ether and other lower aliphatic hydrocarbons having up to 6 carbon carbon methyl ethyl acetate and isopropyl dimethyl methyl ethyl diethyl ether and he first reaction of the process of this invention is the reaction of trihaloacetamidine with lower alkyl thlocarbonat chloride to form alkyl thlocarbamat as shown in the following HCl II II H S carried out the presence of an inert reaction medium and a nitrogen base as The latter is suitably a tertiary amide or amine in which the substituents are lower lower cycloaliphatic or aromatic of 8 or less Examples include methyl and The agent is also suitably an additional mole of the trihaloacetamidine used as The chloride of the agent precipitates and forms a slurry of solid hydrochloride in the inert reaction The precipitated hydrochloride is suitably removed by any conventional for by filtration or The when is separated from the inert reaction The reaction medium may be distilled from the The residual intermediate is suitably for by crystallization from the same or a different When the trihaloacetamidine is the appropriately it is used in the ratio of two moles to one mole of alkyl thiocarbonate The resulting hydrochloride of the trihaloacetamidine is recovered and is converted to the base by treatment with alkali for When a tertiary amine is used as the appropriately the tertiary the the alkyl thiocarbonate chloride are used in substantially equimolar reaction mixture from which the hydrochloride of the binding agent has been the intermediate is separated and redissolved in the same or a different inert reaction medium from the one in which it was The solution of the intermediate is contacted with gaseous or dissolved chlorine or bromine preferably in substantially the stoichiometric proportions indicated by the following 2 More or less chlorine or bromine can be used but best yields are obtained when the proportion does not substantially exceed the theoretical When the halogen is introduced as a the solvent may be the same or different inert reaction medium from the one in the intermediate is Carbon tetrachloride is especially advantageous in the avoiding the formation of byproducts and resulting in excellent After the halogen is the reaction mixture is suitabl distilled to remove the reaction medium and to obtain the thiadiazole It may be distilled in vacuum if Both reactions of the process of the present tion are carried out in the temperature range of 0 to suitably at ambient EXAMPLE I A solution of ethyl thlocarbonate chloride in ether at ambient Trichloroacetamidin hydrochloride which precipitated was removed by filtration and the filtrate was evaporated to The residue was crystallized from high boiling petroleum ether to yield of batnate melting at for EXAMPLE II A solution of elemental bromine in ethyl acetate was added dropwlse to a stirred solution of thiocarbamate produced in Example I in ethyl acetate taining the temperature between and 17 When the additio of bromine was the reaction mixture was filtered and the filtrate was evaporated to The crude was vacuum distilled to yield of pure product boiling at The spectrum of the product was identical with that of an authentic sample of this known EXAMPLE III A slight excess of gaseous measured through a was slowly bubbled for two hours into a stirred solution of thiocarbamate in ethyl acetate at to EXAMPLE T V A solution of chloride in ether waa added with to a solution of trichloroacetamidine and triethylamine mo ether ing the temperature at 20 After stirring the resulting slurry for minutes at room triethylamine hydrochloride was by filtration and the filtrate was evaporated to brown solid was washed with 50 of hexane to give of crude Recrystallizatlon from petroleum produced pure g Ai v Gaseous was slowly paused into a stirred solution of g ethyl ether The yellow solution turned colorless after 10 minutes but chlorine continued to be After 10 more the mixture was filtered and the solvent The liquid distilled in vacuo to give of forerun and of EXAMPLE VI A solution of s chloride in ether was slowly added to a stirred solution of trichloroacetamidine 3 in 0 bient tem The ellow slurr was Next gaseous chlorine was passed through the at a moderate rate for 20 minutes with Ice The reaction mixture was filtered and the removed liquid residue was subjected to illation to give of EXAMPLE VII The procedure Example was repeated substituting an equivalent amount ot trlfluoroacetamldlne for the acetamidine to produce a satisfactory yield of EXAMPLE VIII The procedure of Example VI was repeated substituting an equivalent amoun of arbonate chloride for the ethyl chloride to produce a satisfactory yield of IX A solution chloride in ethyl added to a solution of in ethyl acetate at The for 30 minutes at room temperature and the precipitated hydrochloride removed by filtration and the filtrate was evaporated to The residual thlocarbamate amounted to and melted at without 7 slowly added a of trrlchloroacetamidine 9 ether 100 at After stirring for 30 minutes at room the reaction mixture was removing the insoluble thiocarbamate and trichloroacetamidine The trichloroacetamidine hydrochloride was washed from the solid mixture with The yield of dried residual thiocarbamate was EXAMPLE XI Gaseous chlorine was passed for 30 minutes into a stirred suspension of thiocarbamate in carbon tetrachloride 250 with The reaction mixture was filtered and the filtrate distilling the residue in vacuum to yield of colorless and pure There was virtually no forerun or EXAMPLE XII Gaseous chlorine was bubbled into a slurry of thiocarbamate in petroleum ether during 30 minutes with The was accompanied by occasional emissions of visible After the mixture was solvent was evaporated and the residue was distilled to yield 7 of 2 EXAMPLE XIII A solution of ethyl thiocarbonate was filtered to remove the theoretical amount of acetamidine Gaseous chlorine was passed through the filtrate at a moderate rate for 20 minutes with The reaction mixture was solvent was removed in vacuum and the liquid residue was vacuum distilled to yield of insufficientOCRQuality

Claims (1)

1. THE OF INVENTION WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE CLAIMED A DEFINED A3 Method of diazoles of the formula N where X is fluorine or chlorine and R lower of 1 to 4 carbons by a first step of contacting trihaloacetamidine with lower alkyl ocarbonate chloride in the presence of an agent in an aliphatic dialkyl ether having up to 6 carbons as reaction medium to form a first reaction mixture containing alkyl thiocarbamate and hydrochloride of the separating said hydrochloride from said first reaction in a second contacting said 0 alkyl thiocarbamate with chlorine or bromine aliphatic ether having up to 6 carbons to form a second reaction mixture containing thiadiazole and 3 from said second reaction Method according to claim 1 which said first step is conducted in ethyl ox t l a etate as reaction medium and in the presence of as Method according in which said second step is conducted in ethyl ether ethyl acetate reaction Method according to claim 1 in which the same reaction according to claim ia which ethyl ether ia the reaction medium in both thioearbamatea of the formula in which ia fluorine or chlorine and ia lower of 1 to Attorney for the Applicant a insufficientOCRQuality