Amidines, reaction with carbon dioxide

The apparently quite broad structural requirements for anticonvulsant activity, noted earlier in this chapter, extend to yet another class of five-membered heterocycles that include an imide function. Imidazo-2,4-diones, better known as hydan-toins, have comprised some of the most widely used drugs for treating severe motor and psychomotor epileptic seizures. The general reaction used to prepare this heterocyclic system involves the treatment of a carbonyl compound with ammonium carbonate and potassium cyanide. The first step in the complex sequence can be visualized as the addition of the elements of ammonia and hydrogen cyanide to give an a-aminonitrile (88-2). Addition of ammonia to the cyano group would then lead to an amidine (88-3). Carbon dioxide or carbonate ion present in the reaction... 

Aromatic amines hardly react with carbon dioxide because of their poorer basicity/nucleophilicity [12]. However, in the presence of suitable auxiliary strong bases (B), such as amidines or pentaalkylguanidine superbases, carbamate salts (BH)02CNRAr (R = H, alkyl) can be generated in solution, as revealed by spectroscopic and reactivity data [13]. It has been shown that even tributylamine may be effective if a suitable alkah metal salt is present in the reaction mixture in the latter case, the IV-arylcarbamate has been isolated as an alkali salt (3.10) [14, 15]. 

Meyer and Wagner reported that 4-quinazolones can also be formed by heating isatoic anhydride with amidines. They found that reaction of isatoic anhydride 38 with W,iV -diaryl formamides or W,A -diaryl acetamides 44 proceeded smoothly at moderate temperatures (120-140 °C) to give 45 along with the evolution of carbon dioxide. 

Methylenecyclopropanes have been carboxylated with gaseous carbon dioxide in the presence of a stoichiometric amount of nickel(O) complexes [150]. Depending on the polarity of the reaction solvent and the nature of amine ligand (amidine or guanidine base), several reactions pathways have been observed, which may involve either oxidative coupling of CO2 with the C-C double bond of the substrate (see Sect. 5.3) or opening of the three-membered ring and further reaction with the heterocumulene. 

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