Cyanamides amidine synthesis

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles (206) is the reaction of amidines with trichloromethylsulfenyl chloride (see Equation (30)). 3-Halo derivatives (349) (X = Cl, Br, I) (Equation (57)) have been obtained in moderate yields from the corresponding amines (348) via the Sandmeyer-Gatterman reaction <84CHEC-I(6)463>. 3-Chloro-l,2,4-thiadiazolin-5-ones (350) and (351) can be prepared by reacting chlorocarbonylsulfenyl chloride with carbodiimides or cyanamides respectively (Scheme 79) <84CHEC-I(6)463>. 

The dimethylaminooxazolidone derivative thozalinone (40-3) is described as an antidepressant. The synthesis of this agent again uses a cyanamide, provided in this case as a preformed reagent. Thus, reaction of alkoxide from ethyl mandelate (40-1) with A,A-dimethylcyanamide leads to the amidine (40-2) by addition to the nitrile. Internal displacement of the ester ethoxide group closes the ring to an oxazo-lidinone, forming the product (40-3) [42]. 

Type D Syntheses [C—N—C—S—N], The synthesis of A -l,2,4-thiadiazolines from potassium methyl cyanoiminodithiocarbonate, MeS C(=NCN)SK, and A -chloro-amidines (see Vol. 3, p. 682) has been extended by the inclusion of other A -chloro-cyanamide derivatives, e.g. NH2C(=NCl)OR, as one of the reactants. In this case, condensation at 5 °C produces 2-alkoxyimidoyl-3-imino-5-methylthio-A -l,2,4-thiadiazolines in 41—79% yield. They are dealkylated to the amides by methanolic hydrogen chloride and readily undergo aminolysis to the amidines, iV-Chloro-guanidines and A -chloroguanylurethane may be used similarly in this general synthesis. ... 

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