JV-Imines, heteroaromatic

It has become increasingly apparent that heteroaromatic jV-imines I and their protonated compounds JV-aminoazonium salts 2 are highly useful as synthetic intermediates, particularly in preparative heterocyclic chemistry. 

Although aspects of the chemistry of the heteroaromatic jV-imines have been reviewed several times,1 4 recent significant developments in this field... 

In general, the reaction of heteroaromatic JV-imines with a,/ -unsaturated carbonyl compounds gives cycloaddition products as described later (Section IV,C). However, in some cases they can act as nucleophiles. Thus, pyridine N-ethoxycarbonylimine, in the presence of silicic acid, reacts with fumarate, maleic anhydride, (V-phenylmaleimide, p-benzoquinone, and a-naphthoquinone to give the corresponding enamines in good yields (Eq. 23).176 Pyridine JV-imine also reacts with dimethyl maleate to give dimethyl aminofumarate.164... 

Since Huisgen et al. first demonstrated the 1,3-dipolar character of pyridine N-imine in 1962,182 the 1,3-dipolar cycloaddition reactions of the heteroaromatic JV-imines have been explored extensively. The reactivity stems from the azomethine structure of the JV-imines.183 The cycloaddition of a variety of activated alkynes and alkenes to the JV-imines yields fused dihydro-pyrazoles and tetrahydropyrazoles, respectively. However, the aromaticity of the heteroaromatic ring is destroyed at this stage, so that such primary cycloadducts usually undergo further reaction to achieve stabilization in various ways as shown in Scheme 4 (i) aromatization, (ii) hydrogen transfer, (iii) rearomatization by rearrangement, and (iv) rearomatization by N—N... 

Amine Ar-imines are derived formally from tertiary amines by replacing the free pair of electrons by an imino group. Aliphatic, aromatic, or heteroaromatic compounds are obtained according to the nature of the amine. Heteroaromatic JV-imines are derived from heterocyclic compounds containing an azomethine nitrogen atom in the molecule. 

The synthesis of heteroaromatic iV-imines by way of ring opening of JV-(2,4-dinitrophenyl)pyridinium chlorides or pyrylium salts with hydrazine derivatives followed by recyclization has been known for many years. In particular, the latter procedure was the first method to be discovered for preparing pyridine iV-imines.70... 

Since the JV-imines are generally unstable, the reaction is usually carried out by treating the JV-aminoazonium salts with base in the presence of 1,3-dipolarophiles. The versatility of this reaction is demonstrated by application to a wide range of the six-membered heteroaromatic N-imines which include substituted pyridine JV-imines,187 di-JV-imines of 2,2 -bipyridyl and... 

The stereochemistry of the 1,3-dipolar cycloaddition of the heteroaromatic iV-imines has been investigated in some detail by using the reaction of phenanthridine N-benzoylimine with a series of activated olefins such as JV-methylmaleimide, maleic anhydride, diethyl maleate, methyl acrylate, methyl methacrylate, and methyl trans-crotonate (e.g., Eq. 30).202 The adducts from the former three have the all-cis stereochemistry. These results are rationalized in terms of secondary molecular orbital interactions. With acrylates such stereospecificity is lost, suggesting that this effect is of lesser importance in these cases (see Table II). 

Sec. IV.F] jV-imines and tv-aminoazonium salts 8. Five-Membered Heteroaromatic N -Substituted N-Imines... 

The major reaction of five-membered heteroaromatic N-imines (1-alkyl-l, 2,4-triazole 4-acylimines254 and 4-arylimines,255 2-phenylbenzotriazole 1-cyanoimine,97 thiazole JV-acetylimine,239 and 1-alkybenzimidazole 3-acylimines122) is N—N bond fission, with a few exceptions. In the case of 1-methylbenzimidazole JV-ethoxycarbony limine, a 1,2-migration of the ethoxycarbonylamino group has been observed.122... 

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