N-Aminomethylation

Similar isomerization reactions were observed in CDCI3 solutions of N-( -aminomethyl)-l,2,4-triazoles and -tetrazoles (90T633). As for the analogous benzotriazoles, these reactions are-intermolecular and slow at 20°C in the NMR time scale. 

The reaction of 2,5-dimercapto-l,3,4-thiadiazolidine 34 with dialkylamines under Mannich reaction conditions gave N,S-aminomethylated thiadiazoles in 69-70% yields (Equation 24) <1998CHE1431>. With urea, thiourea, semicarbi-zide, or thiosemicarbazide, thiadiazolidine 34 gave N,N-aminomethylated thiadiazoles in 89-98% yields (Equation 25). 

N-Heterocyclic substrates are the most used for Mannich reactions, usually in acetic acid as a solvent, but methyleneinunonium salts in acetonitrile are also frequently employed as reagents. Such conditions appear adequate to overcome the chemoselectivity problem posed by the formation of the undesired N-aminomethylated product. Apart from rare exceptions, the rules genoally followed are as follows ... 

Examples of synthesis following path b arc given by the formation of benzopyrazine derivative starting from N-aminomethyl-isatine and by the preparation of pyiridazine derivative 318 (Fig. 122) from aminomethyl-y-ketoearboxyacid and hydrazine. In this... 

Paris, J.. Couqucict, J., and Tronchc, P N-Aminomethylation en scric thiazolique Application a quciques amino-2-bcn7.othia/olcs. Bull. Soc. Chim. Fr.. 672, 1973. 

The second NH group in 103 (R = Me, Et R = Ph, cyclohexenyl) did not undergo further aminomethylation. The reaction led only to N-aminomethyl product 104 (R = Me, Et R = Ph, cyclohexenyl). This was explained by the formation of the lactim form, which renders the other hydrogen inaccessible to a second condensation reaction owing to the stabilization of the lactim moiety by an intermolecular hydrogen bond.25... 

N-Aminomethylation with prim. ar. amines of dicarboxylic acid imides... 

N-Aminomethyl compounds from N-chlorides via insertion of 1 G-atom s. 20, 314 NCI NCHgN <... 

Thiobenzamide has been reported to undergo a Mannich-type reaction on simultaneous treatment with aldehydes and arylsulphinic acids, yielding the compounds (267). 2-, 3-, and 4-thiocarbamoylpyridines similarly gave the N-(aminomethyl)thioamides (268) by reaction with a variety of amines in the presence of formaldehyde. A new stereospecific synthesis of 5,6-di-hydro-4H-l,3-thiazines (269) depends on the reaction of thioamides with aldehydes and alkenes it was considered likely that (270) is an intermediate in this reaction. 

---