JV- imines

V-Imiue substituent has S chirality. b jV-Imine substituent has R chirality. c Total yields were in the range 82-95%. 

Metal complexes of the 1,4-diaza-1,3-butadiene ligands [RN=C(R )C(R")=NR = R-DAB R, R" ] have recently been surveyed by van Koten and Vrieze.111,112 Therefore we will refer extensively to these reviews and to some key references and we will discuss here the main points and new results. The discussion will be restricted to the above ligands, with passing mention of complexes of 2-pyridinecarbaldehyde-JV-imines, which are discussed in Chapter 13.2. 

Thiazole-jV-imines (36) are reported553 to give (37) with DM AD, but the possibility of rearrangement was not considered. In the case of the imide derived from 38 the product is stated to be 39,663 and here rearrangement is less likely to have taken place. 

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... 

H-NMR spectroscopy has been used to particular advantage in determining the pKa value of the unisolable pyridine AT- unsubstituted JV-imine which has a very high pKa value (13.4).8... 

JV-Aminoazonium salts and JV-imines are deaminated by nitrous acid to give the parent heterocycles.44,149... 

Early reports indicate that N-aminopyridinium salts react with aromatic aldehydes in the presence of base to give nitriles as the major products.1 Completely different reaction courses emerge when the l-methyl-3-amino-benzimidazolium salt 23 and 2-methyl-3-aminobenzothiazolium salt 25 are allowed to react with benzaldehyde under the similar conditions, affording a benzaldehyde phenylhydrazone 24151 and a 2,3-dihydro-1,3,4-benzothia-diazine 26,152 respectively likely reaction pathways are suggested in Eqs. (16) and (17). Benzo[c]cinnoline JV-imine reacts with p-anisaldehyde to give the bis-lV-imine 27.44... 

Reaction of pyridine JV-imines with 2H-azirines gives pyrido[l,2-h]triazine derivatives 38.162,163 Substituted pyridine, quinoline, and isoquinoline JV-imines react in an analogous manner. Although, in principle, two modes of cycloaddition are feasible with 3-substituted pyridine JV-imines, the reaction of the 3-methyl derivative involves cycloaddition at the more hindered site. 

On the other hand, the reaction of pyridine JV-imines bearing an electron-withdrawing group (CN and C02Me) at the 3-position gives exclusively inverse orientation to the less hindered position, which is in contrast to the course of the 1,3-dipolar cycloaddition of the same pyridine N-imines with ethyl propiolate (Section IV,C,1). 

Diphenylcyclopropenone and its thione are well known as highly electrophilic carbonyl compounds, which react with pyridine /V-acylimines to give l,3-oxazin-6-ones 39,46 166 and -6-thiones,46 respectively. The reaction of pyridine JV-imine with the cyclopropenone in methanol gives methyl 3-aminoacrylate 40.167 It is likely that these reactions involve ketene intermediates which are intercepted either by internal nucleophiles or by the solvent. Benzo[c]cinnoline JV-acylimines also give the oxazinones 39, whereas the Al-benzimidoylimines give stable 1 1 adducts as a result of a difference in the preferred site of attack by the electrophilic cyclopropenone (Eq. 22).168... 

Another interesting difference in reactivity has been observed when pyridine JV-imine is allowed to react with methylphenylcyclopropenone in methanol to give 3//-pyrido[l,2-b]pyridazin-3-one 42 in addition to ethyl 3-aminoacrylate.169,170 If the reaction is carried out in aprotic solvent, 42 is formed in fairly good yield. In some cases, 4,4a-dihydro intermediates 41 are isolated. In principle, two isomeric pyridopyridazinones may be formed by the cycloaddition of 3-methylpyridine JV-imine however, the cycloaddition occurs predominantly at the sterically less hindered site. By comparison, the reactions of the same JV-imine with 2//-azirines (Section IV,A,6) and with ethyl propiolate (Section IV,C,1) take place predominantly at the more hindered site. 

Possible pathways to the pyridopyridazinones are shown in Scheme 3. One route (path a) involves initial 1,3-dipolar cycloaddition of the JV-imine with the cyclopropenone and subsequent opening of the cyclopropanone ring with transfer of the amino hydrogen to afford 41. An alternate route (path b) is very similar to that proposed for the reaction with 2//-azirines (Section IV,A,6). 

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... 

Pyridine JV-imines react with cyanide ion to give s-triazolo[l,5-a]pyridine, obtained from 1,3-dipolar cycloaddition of initially formed 4-cyanopyridines with pyridine JV-imines (Section IV,C,1).138 Quinoline JV-imine gives 4-cyanoquinoline, 2,4-dicyanoquinoline, 4-cyanoquinaldamide, and a 1,3-dipolar cycloaddition product, depending on the solvent used.14... 

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... 

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... 

An interesting rearrangement has been observed in the reaction of pyridine JV-imines with triarylketeneimines an initial 1,3-dipolar cycloaddition is followed by a [l,5]-sigmatropic rearrangement with the subsequent loss of hydrogens, leading to the formation of lH-pyrrolo[3,2-h]pyridines 67 (Eq. 29).192... 

Pyridazine JV-acetylimine reacts with benzyne to give 1 1 cycloadduct 70, which has been shown to be a precursor of a variety of heterocyclic compounds.194 The same JV-imine undergoes 1,3-dipolar cycloaddition with perhalocyclopropenes to give tricyclic adducts 71,195 the structure being established by X-ray crystallography. 

The most important and general types of reaction that occur when an JV -substituted JV-imine is heated are (i) a 67t-electrocyclic reaction of 1,5-dipoles 208 (intramolecular 1,5-cyclization) and (ii) N—N bond fission. The reaction courses are highly dependent upon the nature of the substituent on the imino nitrogen. 

Pyridine JV-imine reacts with a pyrylium salt at room temperature, giving pyrazolo[l,5-a]pyridine 92.210 It is suggested that this reaction involves an unisolable [Pg.113]

Sec. IV.E] jV-IMINES AND A-AMINOAZONIUM SALTS 3. Isoquinoline N-Imines and Related Fused Pyridine N-Imines... 

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

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. 

Other bis azo compounds give y-triazole JV-imines as intermediates. Thus, photolysis of sydnones (58) 94-97 and of 2,5-disubstituted tetrazoles98-99 gives w-triazoles (62). These reactions probably involve the primary formation of nitrilimines (60) which dimerize to the bis azoethylene derivatives (61) which in turn cyclize to form the v-triazole IV-imines. These, under the reaction conditions, cleave at the exocyclic N-N bond (see Section IV,F). 

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