1-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). 

Pyrazole rings are formed from 2-alkylpyridine-Af-imines and acid chlorides under basic conditions. For example, the 1-aminopyridinium salt (336) gives first (337) but this is very reactive and is acetylated under the reaction conditions to (338 Scheme 95) (68JOC3766). The 2-hydroxymethylpyridine (339) shows similar reactions (Scheme 96) (73CPB2146). 

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. 

Hydroxylamine-O-sulfonic acid (aminyl hydrogen sulfate) has often proved superior to chloramine for amination the former is a stable crystalline substance that can be easily handled and weighed. It aminates primary279,280 and secondary amines280 to hydrazines, and tertiary amines to hydrazinium salts.28<> It is a stronger animating agent than chloramine as it converts pyridine into the 1-aminopyridinium salt, a reaction that cannot be carried out by chloramine.281 Other heterocycles, e.g., uracil,282 can also be converted into hydrazines by hydroxylamine-O-sulfonic acid. 

Pyrido[l,2-6T [l,3,4]thiadiazines are conveniently prepared from 1-aminopyridinium salts. Specifically (241) and (243) served as useful intermediates for the synthesis of (242) and (244), respectively (Equations (51) and (52)) <73CPB2146,85BCJ1432). 

Finally, a synthesis of 2i/-pyrido[l,2-Z>]-as-triazines was reported, exploiting an intercepted Neber rearrangement. For this reaction, the trimethylhydrazonium iodides (40) were treated with KO/-Bu to presumably form the intermediate azirines. Rather than hydrolyzing these intermediates, the azirines were instead intercepted with 1-aminopyridinium salts (39) to directly furnish the heterocyclic products (41) in moderate yields. 

Under certain conditions, nitienium ion could be used for direct aromatic amination. Takeuchi and coworkers reported a photolyses of 1-(Amino and aIkylamino)-2-methyM,6-diphenylpyridinium [105], 1-aminopyridinium salts, 2-aminoisoquinolinium salt and 1-aminoquinolinium salts for eflftcient nitrogenation of aromatic compounds in the aromatics-trifluoroactic acid [106]. The use of 1-aminoquinolinium perchlorate showed the highest reactivity in these photolyses, giving primary aryl amine in high yield (Scheme 2.9). The yields of arylamines were generally increased in the presence of a small amount of crown ether. Further... 

The other ring contraction involves cleavage of the pjo idine ring under very mild conditions. Diazotization of 3-aminopyridinium salts (R = alkyl, allyl, aryl) gives lH-triazole-4-acraldehyde derivatives. A possible mechanism for the reaction is shown in Scheme 27. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

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). 

Oxidation of 4-substituted A-aminopyridinium salts 119 with aqueous bromine yields either the l,l -azopyridinium salts 120 or 1-pyr-idiniopyridinium salts 121, depending upon the nature of the 4-substituent (77JCS(P1)1593) (Scheme 21). 

The nucleophilic displacement of halogens in aromatic compounds by fluorine is aided by utilizing an appropriate catalyst. Polymer-supported aminopyridinium salts have been found to be versatile catalysts for the synthesis of aryl fluorides. The advantage of the catalyst is that it can be recycled and used again. l-Chloro-4-nitrobenzene (3) is converted to l-fluoro-4-nitrobenzene (4) in 71 % isolated yield using this method. The catalyst used has the structure 5.91... 

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... 

The chemistry used in the preparation of pyrazolo[ 1,5-a]pyridines is influenced by the presence of the bridgehead nitrogen. Syntheses involve the almost exclusive use of /V-aminopyridinium salts and often require the generation of ylides. 

The application of these correlations to the reduction of 3- and 4-aminopyridinium salts to aminopiperidines19 and the conversion of p-phenanthroline to the dihydro-derivative20 will serve as illustrations. The reaction of l-methyl-3-benzylaminopyridinium iodide (24)... 

Carboxylic and sulfonic acid chlorides and anhydrides give acylamino- and sulfonamidopyridines 748 and 749. Evidence exists that initial products of the reaction, the corresponding A -acyl-2-aminopyridinium salts, are unstable and rapidly rearrange to the thermodynamically more stable 2-acylaminoderivatives. 

Although l-aIkyl-4-(dialkylamino)pyridinium salts are moderate catalysts for the nucleophilic displacement of chloride, for example, by fluoride ion. their application is limited by their expense. To enable the separation of the catalyst from the product and thus facilitate reuse, immobilized aminopyridinium salts on divinylbenzene cross-linked polystyrene gels of type 3 and 4 are used (see Table 12). The catalytic activities of 3 and 4 were the same after recycling, even after they were reused 8 limes. ... 

Table 12. Synthesis of Fluorinated Aromatics through Halogen Exchange Using Potassium Fluoride Catalyzed by Polymer-Supported Aminopyridinium Salts ...

Pyridinium-7V-(irnidoyI)imides 110, prepared from the base-catalyzed reaction of jV-aminopyridinium salts and JV-ethoxycarbonyl imidates, undergo initial intramolecular cycloaddition in refluxing xylene to afford unstable triazoline intermediates 111, which rearomatize to triazoles in a second step (77JOC443). 

A -Aminopyridinium salts reacted smoothly with 2-methyl-3-phenylcyclopropenone in di-chloromethane in the presence of triethylamine at 20 C to give the corresponding 2-methyl-4-phenyl-3//-pyrido[l,2-A]pyridazin-3-ones la-f in fairly good yield. 2,3-Dipropylcyclo-propenone reacted with pyridinium amide salts in methanol to give 2,4-dipropyl-3//-py-rido[l, 2-6]pyridazin-3-ones Ig-j under reflux conditions. ... 

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

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]. 

By the action of MSH, 2-(2-acylhydrazino)pyridines are transformed to A[-aminopyridinium salts. These cyclized to l-aminotriazolo[l,5-a]pyri-dinium salts (224) in acid. The latter compounds can also be obtained by the direct amination of the corresponding 2-R-triazolo[ 1,5-a]pyridines with MSH or TSH [76JCS(P 1)367]. The cyclic contraction in 1,2-dihydro-s-tetrazines discussed earlier suggest the intermediate formation of dihydrazine 223. 

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