N-Aminopyridinium salt

The principal interest in N-aminopyridinium salts and their benzo analogues is related to the fact that they can provide access to the ylide-like pyridinium imines, e.g. (100), and benzo analogues (Scheme 87) (80YZ1). 

There are two routes to [l,2,4]triazolo[l,5-a]pyridines from N-aminopyridinium salts. In one, Ar-(2-pyridyl)hydrazides (34) are converted by MSH (mesitylsulfonylhydroxylamine) to AZ-aminopyridinium salts, and these cyclize on heating, giving 1-aminotriazolopyridinium salts C35).4 In the other, AZ-aminopyridinium salts are treated with AZ-ethoxycarbonylacet-imidate to give pyridinium ylides (36), which cyclize on heating, giving mixtures of triazolopyridines and imidazopyridines.47,48... 

From N-Aminopyridinium Salts Containing 2-Methylene Groups. 382... 

Ring-degenerate transformations of N-methyl- and N-aminopyridinium salts 78KGS867. 

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... 

The reaction of N-aminoazonium salts with aliphatic and aromatic aldehydes in the absence of base gives the Schiff base type compounds 28.151,153-156 Some aliphatic ketones also react with N-aminoazonium salts.40,155 Hexane-2,5-dione reacts with N-aminopyridinium perchlorate to give l-(l -pyrrolyl)pyridinium cation 29 together with some of the bisper-chlorate 30.157 Certain esters such as diethyl malonate and ethyl cyano-acetate react with N-aminopyridinium salts in the presence of base to give the corresponding N-acylimines 31.48 However, the reaction of ethyl aceto-acetate and acetylacetone with N-aminoazonium salts in the presence of base gives 1,3-dipolar cycloaddition products (Section IV,C,1).36,154,158 The reaction of ethyl acetoacetate with 1-alkyl-l,2,4-triazole 4-imine affords zwitterionic triazolo[4,3-/>]pyridazines 32.139,159... 

Ar-(2,4-Dinitrophenyl)pyridinium chlorides ( Zincke salts 10,25-2 15) are starting materials for another preparation of N-aminopyridinium salts. Zincke salts react with hydrazines, aryl hydrazines, acyl hydrazines, and semicarbazides to form 5-(2,4-dinitroanilino)-2,4-pentadienal hydra-zones and semicarbazones, respectively, by ring-opening.17,25,27-32 The recyclization of these compounds (16) with molar quantities of acids yields the quaternary salts 17 and 2,4-dinitroaniline. 

Reactions of anabasine with sodium, with methyl methacrylate, and with phosphorus acid derivatives have been investigated. Dehydrogenation of anabasine may be effected with N-aminopyridinium salts. A number of nitronicotine derivatives have been prepared. ... 

CHEC-i(5)847>. The most common methods are the oxidative cyclization of pyridylamidines or pyridylamidoximes, treatment of A -aminopyridinium salts with mesitylsulfonylhydroxylamine (MSH) and subsequent thermal cyclization to the 1-aminotriazolopyridinium salts, treatment of N-aminopyridinium salts with A -ethoxycarbonylacetimidate to give ylides which cyclize on heating, and the reaction between 1,2-diaminopyridinium salts and carboxylic acids (or their chlorides). 

Nitrenium ions and direct electrophilic aromatic amination (cyclic nitrenium ions, formation of N-heterocycles by intramolecular amination, N-aminopyridinium salts) 05ZOR487. 

Photolysis of aryl azides in acidic media leads to rapid protonation of the initially formed singlet nitrenes with formation of singlet nitrenium ions. Nitrenium ions are nitrogen-centered diradicals that are formally isoelectronic with carbenes. They have been in the focus of research for their role as ultimate carcinogen in the metaboHsm of certain aromatic amines." " Nitrenium ions can also be made by photolysis of 2,2-benzisoxazolium (anthranihum) salts" or by irradiation of N-aminopyridinium salts. 

Cyanides can react with 1-aminopyridinium salts to give 2-substituted triazolopyridines, possibly via the pyridinium ylide. With 1-aminopyridinium iodide and cyanide ion the intermediate 4-cyanopyridine reacts with the aminopyridinium salt to give 2-(4-pyridyl)triazolopyridine (45).51 When acetonitrile or benzonitrile are used, 2-methyl- and 2-phenyltriazolo-pyridines are obtained.58 60 The reaction is thought to involve a dipolar cycloaddition of the N- mi nopyridine with the nitrile, as shown in Eq. (4). 

Interesting versions of this reaction occur with hydrazine and with N-amino heterocycles. Thus, reactions of 2 with N-amino-I,2,4-triazole, hydrazine, and 2V-aminopyridinium salts produce compounds 292 and 293 [77JCS(PI)I428] and 294 [77JCS(PI)327]. Similar examples have been reported [85JCS(PI)I209]. 

This cyclization is another example of the synthetic value of 1-aminopyridinium salts (review [1870]) its base-catalysed reaction with acetophenone N,N-dimethylhydrazone methiodide without external heat leads to a new fused triazine ring. 2-Chtoroacrylic esters react similarly but in the presence of a weaker base two moles of the pyridinium salt react and an N—N bond is cleaved to supply the third nitrogen. 

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. 

However, iV-ammonium salts as well as the IV-imines possess further acidic hydrogen atoms. In 0.2 N NaOD, (V-aminopyridinium salts (14) exchanged their hydrogen atoms at the 2-, and 4-, and 6-positions for a D atom within the time the NMR spectra could be measured.17 For the 4-amino-s-triazolium salts (93) base catalysis is not needed for the hydrogen exchange.134 The ylid or nucleophilic carbene structures 94 and 95 are intermediates (see also Wanzlick135 and Quast and Hunig136) and can be intercepted by sulfur or ethyl acetoacetate.134... 

Salts of 3-[3-(phenylpropynoyloxy)propyl]-N-aminopyridinium (43) (Equation (5)) undergo dipolar addition to form tricyclic pyrazolo[l,5-a]pyridines (44) <83H(20)20i, 85JSC(P1)379>. N-Methoxycarbonylmethyl-3-[3-(phenylpropynoyloxy)propy]pyridinium salts undergo a similar dipolar addition to give indolizine derivatives. 

In addition to reactions with amines, Zincke salts also react with other nitrogen nucleophiles, such as hydroxylamine and hydrazine, providing various A -substituted pyridine derivatives, such as pyridine N-oxides 39 and 7V-aminopyridinium salts 40. 

Heating the crystalline salt 2-aminopyridinium propiolate (346) at 100 °C in the solid state led to a 10 9 mixture of 2/f-pyrido[l,2-n]pyrimidin-2-one and ( )-3-(2-imino-l,2-dihydro-l-pyridyl)acrylic acid (347). Analysis of differental scanning calorimetry data shows unambiguously that the reaction takes place in the solid state. An endothermic peak at 81.1 °C corresponds to a solid state reaction, and a peak at 122-123 °C is attributed to melting. The product ratio of 2//-pyrido[l, 2-n]pyrimidin-2-one and 347 is 1 2.5 at 60°C, and 1 1.4 at 80°C (94MI12). 

Aldehydes readily yield imines, cf (976), and aryldiazonium salts form aryl azides and pyridine, presumably via ArN = N- N-Py+. Nitrous acid and A-aminopyridinium cations yield pyridine and... 

I-Aminobenziinidazoles are useful intermediates, and their alkylation may occur at either NHj or the =N— atom. On heating with an iodoalkane, only the 3-quatemary salt is obtained. This is cyclized on heating with an anhydride and sodium carbonate a lower yield is obtained when the carbonate is replaced by pyridine. When a 2-hydroxymethyM-aminopyridinium chloride is heated with acetic anhydride, the JV.O-diacetate is foimnl but in the presence of a base, this reaction yields the pyrazolopyridine. 

Oxidation of iV-aminopyridinium, N-aminoquinolinium, and N-amino-isoquinolinium bromides with lead tetraacetate in acetic acid affords 1-acetamido-2-pyridone (139), l-acetamido-2-quinolone (140), and 2-ace-tamido-l-isoquinolone (141), respectively.42 A similar oxidation is reported to occur with 2-aminoimidazopyridinium salts.258 There is good evidence that the oxidation implicates the bromide ion.42... 

The earlier reviews described a number of synthetic approaches to this system. The most generally useful, however, were observed to be those starting with A -aminopyridinium derivatives and constructing the five-membered ring. The chemistry of A -aminoazonium salts, and heteroaromatic N-imines in general, has been reviewed <81AHC(29)73>. Syntheses reported since the publication of the first edition continue to reflect the above-mentioned observation. 

The salt bis(4-aminopyridinium) tetrachloropaUadate(II) is formed by a discrete PdCIj anion and two Np, protonated C5H7N2 cations withont appreciable Pd—N interactions (Figure 4.1). The geometry of Pd(II) ion is square planar (Pd-Cl(l),... 

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