Halogenation of Thioureas

The reaction of substituted thioureas with carbonyl chloride is perhaps the most useful synthetic method for chloroformamidines. Thus, alkyl 

N-p-Toluenesulfonyl-N -n-butylchloroformamidine ( ). To a solution of 20 g (0.07 mole) of l-p-toluenesulfonyl-3-n-butylthiourea in 150 ml of carbon tetrachloride dropwise and with stirring a solution of 7 g (0.07 mole) of phosgene in carbon tetrachloride is added. After stirring for 90 min at room temperature the precipitated N-p-toluenesulfonyl-N -n-butylchloro-formamidine (17.9 g 88.6%), m.p. 90-95°C is collected by filtration. 

In contrast, the reaction of 1-arenesulfony 1-3-aryIthioureas (V, R = R = aryl), with carbonyl chloride affords the four-membered ring 1,3-thiazetidine-2-ones (IX) almost exclusively ( ). The compounds (IX) are also formed as minor by-products in the reaction of aliphatic and aromatic 1,3-disubstituted thioureas with carbonyl chloride ( ). 

The reaction of thioureas with carbonyl chloride can be conducted at room temperature in an inert diluent, preferentially in a solvent, in which the starting thiourea is soluble. Suitable solvents are benzene, chlorobenzene, ethylene dichloride, dioxane, etc. If by-products are formed, they are easily separated with diethyl ether, in which the salt-like chloroforma-midine hydrochlorides are completely insoluble. Sometimes it is possible to isolate the initial reaction product X, especially if a nonpolar solvent is being used, which retards the elimination of carbonyl sulfide ( ). 

The use of an excess of carbonyl chloride in the reaction with di-substituted thioureas has to be avoided, because the chloroformamidine hydrochlorides eliminate hydrogen chloride and the generated carbodi-imides add carbonyl chloride to afford chloroformamidine-N-carbonyl chlorides XI 

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