Amidine and amine

Amidine and amine groups may be joined together to form this triazepinone ring by heating the compound with methanolic sulphuric add for 3h. The reactant is obtained by stirring isatoic anhydride (review of reactions [3008]) with an amidrazone (formally, a hydrazone of a carboxamide). 

It has been found that DTBP cross-linking substantially increased the salt stability of the complexes. The salt stabilization is reversed upon the addition of DTT, which cleaves the bifunctional reagent, indicating that it is not due to the conversion of the amines to amidines and is dependent upon the cross-linking. Similar results were achieved with other polycations, including poly(allylamine), and histone HI. 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

Amidines and sulfonamides have also been used as linkers for primary or secondary aliphatic amines (Entries 4, 5, and 7, Table 3.23). These derivatives are stable under basic and acidic reaction conditions and can only be cleaved by strong nucleophiles. Phenylalanine amides can be hydrolyzed by treatment with certain enzymes (Entry 8, Table 3.23), and can therefore be used for linking amines to supports compatible with enzyme-mediated reactions (CPG, some polyacrylamides, macroporous polystyrene, etc.). 

Amidines and guanidines are slightly more basic than aliphatic amines, and steri-cally crowded amidines (e.g. DBU) or guanidines are often used to mediate dehydro-halogenations. Conditions can, however, sometimes be found which lead to the N-alkylation of these organic bases (Scheme 6.30). Identification of appropriate conditions for such reactions is mostly empirical, because small changes can have important but unforeseeable effects on the selectivity of a reaction (compare, e.g., the first and second reactions in Scheme 6.30). If the reactivity of a given substrate is too low, its nucleophilicity can be enhanced by deprotonation. 

It effects a synthesis of amidines from simple carboxylic acids and amines ... 

Monoamines, primary diamines and secondary amines react with nitriles to give amidines, cyclic amidines and pyrimidines, respectively, in the presence of Yb(OTF)3 as a catalyst. Reaction of ammonia with acetonitrile is shown below. 

The formation of amidines from lactim ethers and amines proceeds readily with high yields,8, >18,21,70-70 e.g., in the synthesis of imidazo-[l,2-6]azepine derivatives reported by Stolle et al.77 (Scheme 9), and in the preparation of the pyrimido[l,2-a]-azepine derivative (Scheme 10).70... 

The proposed mechanism for the addition of terminal alkynes and amines to carbodiimides is shown in Figure 8.40. The organolanthanide alkynyl or amide formed in situ is the active intermediate, and the key step is the hydrolysis of a lanthanide amidinate or guanidinate species. 

The reduction of amides [176] to alcohols proceeds through a g m-amino alcohol, which loses either ammonia (or amine), forming an aldehyde, or water, forming an inline the aldehyde is then reduced to the alcohol, whereas the imine forms an amine on reduction. The intermediate gem-amino alcohol, is also formed in the reduction of oxaziridines (Chapter 18) [177], and a similar gem-diamine during the reduction of amidines to amines [68]. 

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. ... 

Nitrilium salts add amines and amine derivatives readily to give amidinium salts (151 equation 89). Alkaline work-up procedures often give the free amidines rather than the amidinium salts as the products. In these studies primary and secondary amines -and amino acids have been used. 

The reaction of chlorodiphenoxymethane with dimethylamine yields the amide acetal (459 equation 214). Dialkoxymethyl groups can be transferred by means of dialkoxyalkyltriethylammonium tetraflu-oroborate (460 equation 215) to primary amines and amides, amidines, secondary amines and amides once or twice to give amide acetals (461) and (462) Azodiazoles, e.g. (463) and (464) (Scheme 85), add to ketene dimethylacetal to give lactam acetals. ... 

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