Chloroformamidinium salts

The chloroformamidinium salts are utilized in the synthesis of heterocyclic compounds. 

The required pentaalkyl guanidines were easily prepared through phosgenation of the appropriate urea to give the corresponding chloroformamidinium salt which reacts with an excess of amine to yield the expected guanidine (Ref. 37). 

An analogous methodology can be seen in the proposal to use chloroformamidinium salts as dehydrating agents. A A A /V -Tetramethylchloroformamidinium chloride, used as the condensation agent, is easily available by the reaction of A A A A -tetramethylurea and oxalyl dichloiide. The reaction of carboxylic acids (equation 33) can be achieved at -30 C in the presence of tiiethylamine. Thus, for instance, 2-furoic acid, cinnamic acid and crotonic acid yield e anhydrides in 84%, 83% and 83%, respectively. 

The reagent (1) reacts with secondary amides (16) in refluxing chloroform to give chloroformamidinium salts (17) in high yield (85-95 %).6 These salts can be hydrolyzed first to N-(l -chloroalkenyl)ureas (18) and then to N-acylureas (19). Dehydrochlorination of (18) with potassium r-butoxide gives the hitherto unknown ethynylureas (20). 

The loss of two molecules of HCl (often at room temperature) from the chloroformamidinium salts results in the formation of carbodiimides, RN=C=NR [2087,2087a]. The use of an excess of COClj should therefore be avoided, since carbodiimides themselves can react with phosgene to give chloroformamidine-iV-carbonyl chlorides, see Section 10.2.8. Indeed, in early work [2189a], diarylthioureas were found to react with an excess of COClj to form cyclic compounds ... 

Reaction of thioureas with phosgene is usually performed at room temperature in an inert solvent (such as benzene, chlorobenzene or 1,2-dichloroethane) in which the thiourea is soluble. By-products, if formed, are readily separated with ethoxyethane in which the chloroformamidinium chloride salts are insoluble. 

---