Pyridine N-imines

The formation of pyridine IV-imines by an add-catalyzed rearrangement of some diazepinones and related compounds has been extensively investigated by Moore and co-workers (Eq. 9).115 The formation of pyridine N-imines from l/f-l,2-diazepines is also known (Eq. 10).68 69,116,117 Diels-Alder reactions of pyrazoles with dimethyl acetylenedicarboxylate, in the presence of BF3, have been reported to give IV-aminopyridinium salts (Eq. II).118 l,4-Dihydropyrido[l,2-a]-as-triazinium salts and their pyrimido derivatives undergo ring contraction in boiling aqueous acid, yielding 1-aminoimidazo[l,2-a]pyridinium and pyrimidinium salts, respectively (Eq. 

The ultraviolet (UV) absorption spectra of the heteroaromatic N-imines are dependent upon many factors, such as the nature of the parent heterocycles, substituents on the imino nitrogen, and solvent used. Usually pyridine N-acylimines show two intense absorption maxima at 230-235 and 330-360 nm in aprotic solvents such as dioxane, benzene, or chloroform, the latter band of which disappears by addition of acid.13,20,21,75,77 In protic solvents such as alcohol or water a hypsochromic shift and a hypochromic effect of the long-wavelength absorption are observed for example, pyridine N-benzoylimine shows a maximum at 352 nm (e 9700) in dioxane but at 313 nm (e 4650) in ethanol. 13,21 The long-wavelength absorption of pyridine N-ethoxycarbonylimine has been ascribed to a n-n transition on the basis of a Pariser-Parr-Pople (PPP) calculation and measurements of the absorption spectra of preoriented pyridine N-imines in polarized UV light.125... 

The complete analysis of H-NMR spectra of a series of N - and 3-substi-tuted pyridine N-imines has been reported.129 The chemical shifts (5) of the ring protons for pyridine N-imines decrease in the order H-2 (H-6) > H-4 > H-3 (H-5). A similar relationship is seen in the13C-NMR spectrum of pyridine Af-benzoylimine which indicates significant downfield shifts of C-2 (143.1 ppm) and C-4 (137.8 ppm) relative to C-3 (129.4 ppm), reflecting the electron density at these positions.130... 

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). 

The foregoing reaction is probably initiated by nucleophilic addition of the iY-imines to the 2H-azirines to form 36 which may undergo homo-1,5-dipolar cyclization or ring opening followed by cyclization of 1,6-dipoles 37. This novel heterocyclic system was first prepared by the reaction of pyridine N-imines with a-chlorocinnamates, in which azirine intermediates were postulated.164 As a variation, use of azirine intermediates generated in situ from acetophenone oxime O-tosylate or dimethylhydrazone methiodide under the Neber reaction conditions also produces the pyrido[l,2-/>]triazines... 

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... 

Quinoline N-Imines and Related Fused Pyridine N-Imines... 

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

Table I gives the proton signals of some pyridine N-imines. A clear difference in the chemical shift between H-2,6 and H-3,4,5 can be attributed partially to the different electron density at the carbon-atom in...

Unlike some aliphatic amine N-imines,6 heteroaromatic N-imines are always alkylated at the nitrogen atom of the imino group,11 1214 34 37 72 - 86 - 87 [Eq. (10)] although mesomerism also affords other points of attack (see Section III,A). The alkylation of unsubstituted pyridine N-imines with polynitrohalobenzenes yields N-(polynitroarylimines) (see Section II, A,4). 

Heterocyclic N-imines contain a quaternary azomethine group which can be attacked by hydroxyl ions, leading to ring-opening. Such reactivity is strongly dependent on the heterocycle. For instance, pyridine N-imines are rather stable to bases17 69 whereas the 1,2,4-triazole 4-imines react very easily.80 82-90 137 In this reaction, the open-chain formamide 96 is... 

The mechanism of attack of 1,3-dipolar reagents on fluoroalkenes can be considered to be either stepwise or concerted. Heteroaromatic N-imines react by a stepwise 1,3 addition to perfluoroalkenes and -alkynes to give fluorinated pyrazolo[l,5-a]pyridines [82JCS(P1)1593]. Pyridinium /-butoxycarbonylmethylide with fluoroalkenes gave pyrrolo[l,2-a]pyri-dines [86JCS(P 1) 1769] and indolizines (22) are obtained with pyridinium phenacylide [91JFC(51)407]. 

Pyridine, on the other hand, is more reactive than benzene towards nucleophilic aromatic substitution. This is effectively reaction towards the C=N imine function, as described above. Attack is... 

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

The —S—C—C=N— chelate ring is greatly weakened or does not tend to form for steric reasons and the electron-withdrawing effect of the metal ion coordinated to the nitrogen atom facilitates nucleophilic attack at the imine carbon atom. Similar observations have been made with bis (2-pyridinal) ethylenedi-imine... 

A recent example of this is a crystal structural analysis of the zinc complex of the inline derived from 2-pyridinealdehyde and cis,cis,cis-l,3,5-triaminocyclohexane which shows the metal to be in a trigonal prismatic environment (Zn—N (pyridine), 2.211-2.282 A Zn—N (imine), 2.142-2.167 A).320... 

A completely similar reaction occurs when Ru2(CO)6(R-Pyca R R2 ) (R-Pyca R R2 = 6-R NC5H3-2-C(R2) = NR with R = alkyl or aryl Rl = H, Me and R2 = H, Me) is reacted with excess pyridinimine.164 The facile reaction leads to the formation of Ru2(CO)5(APM) (APM — bis(/i-t-butylamino)(2-pyridyl)methane-N) (ref. 162, footnote). (The crystal structure of this compound shows two C—C-coupled pyridin-2-imines which bridge a non-bonding Ru2 metal pair. The... 

NMR studies have been carried out on Schiff bases derived from pyridoxal phosphate and amino acids, since they have been proposed as intermediates in many important biological reactions such as transamination, decarboxylation, etc.90 The pK.d values of a series of Schiff bases derived from pyridoxal phosphate and a-amino adds, most of which are fluorinated (Figure 11), have been derived from H and19F titration curves.91 The imine N atom was found to be more basic and more sensitive to the electron-withdrawing effect of fluorine than the pyridine N atom. Pyridoxal and its phosphate derivative are shown in Figure 12a. The Schiff base formation by condensation of both with octopamine (Figure 12b) in water or methanol solution was studied by 13C NMR. The enolimine form is favoured in methanol, while the ketoamine form predominates in water.92... 

Ni = double-bonded nitrogen in imines Nr-(CB) = pyridine N. NA = double-bonded nitrogen in azo compounds. 

Condensed 4-nitropyrazoles have been produced from pyridinium N-imines and l,l-bis(methylmercapto)-2-nitroethylene 2-methylthio-l-nitropyrazolo[l,5-a]pyridines (54) (40-60%) are so obtained.49 After the electrocyclic transformation, the intermediate 53 does not lose the elements of nitrous acid, but rather undergoes dehydrogenation to yield the observed products (Scheme 11). Isoquinolinium (V-imine gives 2-methylthio-l-nitro-pyrazolo[5,1 -a]isoquino ine similarly.49... 

Pyrolysis of pyridine imidoyl-N-imines 114 also produces carbodiimides 115 in yields of... 

In terms of ligand development, imino functionalised carbenes mimic the aU nitrogen donor ligands bis-imines (N,N) and bis-imino pyridines (N,N,N) [129] (see Figure 3.44) and can be seen as an extension of a series of somewhat older functionalised carbenes oxazoline functionalised NHC [133], pyrido functionalised NHC [134,135] and bis-carbene pyridines... 

The nomenclature for the N-imines is varied for example, C5H5N+ — N COPh is named variously as pyridine iV-(or l-)benzoylimine, pyridine JV-(or l-)benzoylimide, N-(or l-)benzoyliminopyridinium ylide (or betaine), 1-benzoylaminopyridinium hydroxide, inner salt (Chemical Abstracts), or iV-pyridiniobenzamidate (IUPAC rule). The iV-imine nomenclature will be used in this review. 

The N -substituted N-imines can be prepared by the reaction of the N-aminoazonium salts, in the presence or absence of base, with anhydrides or acyl halides,8,13-17,20,21,45,46 diketene,47 diethyl malonate,48 sulfonyl chloride,8,15,49,50 /i-halovinyl ketones and esters,51-54 diethyl ethoxymeth-ylenemalonate and related compounds,53,55-57 isocyanates,17,58 thioiso-cyanates,17,58 imidoyl chlorides and imidates,59,60 nitro acetate,8,61 and active halobenzenes.62,63 Some representative pyridine -(substituted imines) prepared in this way are shown in Scheme 1. 

Pyrylium salts also react with hydrazine and its derivatives to give the N-aminoazonium salts (Eq. 3), although the reaction takes other courses in some cases.50,70,80-93 The reaction involves the formation of intermediate hydrazones by nucleophilic attack at the a-position of pyrylium rings. The hydrazones undergo ring closure followed by dehydration. This method has been utilized for the preparation of highly substituted pyridine AT-imines. 

The positive ion mass spectra of pyridine Af -unsubstituted N-imines, generated within the ion source by pyrolysis of the corresponding hydrochlorides, have been investigated.133 The mass spectrum of pyridine AMmine contains peaks attributable to the loss of 15 (NH) and 16 (NH2) mass units from the molecular ion in a ratio of approximately 2.5 1, whereas introduction of a methyl group at the 2-position of the pyridine ring causes a significant change in the intensity ratio of the [M — NH]+ and [M — NH2] + ( 1 2.5). This can be attributed to the operation of a so-called ortho effect, as in the case of 2-alkylated pyridine N-oxides. 

The basicity of Af-imines depends upon the nature of the substituents on the imino nitrogen. Thus, pyridine AP-unsubstituted AT-imine (pKa 11.2,138 13.68) and Af-methylimine (pKR 12-13138) are very strong bases, whereas pyridine N-acylimines (pKa 3.2 for the N-benzoylimine8 and 3.6 for the AT-acetylimine138) and Af-nitroimine lpKa —4.6s) are weak bases. 

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