Amidine synthesis

Keimg et al. describes the optimization of 2-imino-piperazines using Lewis acids to catalyze the multicomponent a-amino amidine synthesis to make piperazines 39 (Scheme 6) [26]. A, Af -(jimethylethylenediamine 36 was used with an aldehyde 37 and isocyanide 38 in methanol with scandium (III) trifluoromethane sulfonate (Sc(OTf)3) as a catalyst to obtain the piperazine 39 in 57% yield. 

Keung W, Bakir F, Patron AP, Rogers D, Priest CD, Darmohusodo V (2004) Novel alpha-amino amidine synthesis via scandium(III) triflate mediated 3CC Ugi condensation reaction. Tetrahedron Lett 45(4) 733-737... 

The early antimicrobial compounds such as lucosit (219 R = Me) and globucid (219 R = Et) can be prepared by treatment of the 2-amino-l,3,4-thiadiazole with (V-acetylsulfonyl chloride in pyridine followed by deacetylation. A more recent antimicrobial compound (224) can be efficiently synthesized by the route shown in Scheme 35. The thiadiazole (220) is obtained by the usual cyclization procedure and then oximated to (221). Dehydration and the Pinner amidine synthesis followed by treatment with aminoacetaldehyde dimethyl acetal yields (222). Sulfuric acid cyclization furnishes the thiadiazoloimidazole derivative (223) which is further methylated, acetylated, nitrated and hydrolyzed to the desired (224) <69JHC(6)835). 

Since alkoxymethyleneiminium salts with nearly any substitution pattern are easy to prepare, this amidine synthesis has attained widespread application. Thus N-unsubstituted, IV-monosub-stituted and lV,A(-disubstituted alkoxymethyleneiminium salts (138) have been transformed to amidinium salts (137) by treatment with ammonia,primary and secondary amines and amine deri-vatives. ... 

The action of ammonia, primary and secondary amines on alkoxymethyleneiminium salts or alkylmercaptomethyleneiminium salts affords amidinium salts. Provided the educts are chosen in such a manner that the substitution pattern of the resulting amidinium salts does not exceed that of A/jV.AT -trisubstituted salts, the amidines can be released from the salts by addition of bases (see also Section 2.7.2.5.3). Very often the alkoxymethyleneiminium salts were prepared in situ and reacted without further purification with the amino compound to give the desired amidine. This amidine synthesis is of special synthetic interest, since it was stated that formamidines, derived from alicyclic amines, e.g. (306 equation 164), which are simple to obtain by this method, are readily transformed to reactive carbanions. Heterocycles, e.g. (307 equation 165), containing amidine structures, are accessible by reaction of appropriate difunctional compounds with iminium salts. ... 

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