Pyrylium ions with amines

The first step involves the formation of a pyridinium ion by reaction of a pyrylium ion with a primary amine the second step (dequaternization) has been studied more extensively than the first (amine + pyrylium). This important work on dequaternization deserves special mention because, besides the value for synthesis and understanding of steric acceleration, it sheds new light on the mechanism of aliphatic nucleophilic substitution (84CSR47). 

Pent-2-endial (glutaconic dialdehyde) undergoes cyclization with ammonia to give pyridine. It yields pyridine-1-oxide with hydroxylamine and A-substituted pyridinium ions with primary amines. With acids, the pyrylium ion is formed reversibly. Hence pyridine derivatives (see p 230) can also be obtained by reacting pyrylium ions with NH3 and primary amines. 

Scheme 6.15 Reaction of pyrylium ions with primary amines and hydroxide anion.

Pyrylium ions react with ammonia or primary amines to give pyridinium ions (see p. 447). ... 

Pyrylium cations form pyridines with ammonia and pyridinium salts with primary amines (B-82MI 505-02). For example, 2,4,6-triphenylpyrylium cation (261 Z=0) yields 2,4,6-triphenylpyridine with ammonia, the corresponding 1-methylpyridinium salt with methylamine, and pyridine 1-arylimines with phenylhydrazine. Xanthylium ions (210), where ring opening cannot readily occur, form adducts (262) with ammonia, amines, amides, ureas, sulfonamides and imides. Similar adducts (e.g. 263) are formed by benzo[( ]pyrylium ions. 

Pyrylium ions react with ammonia or primary amines to give pyridinium ions (see p. 498). Primary amines react with 1,4-diketones, with microwave irradiation, to give A -substituted pyrroles.Similar reactions in the presence of Montmorillo-nite KSF or by simply heating the components with tosic acid have been reported. 

The basis of a reusable colorimetric probe for cyanide ion in water is the opening of a polymer-bound pyrylium ring by the anion <05CC2790>. Oligomers derived from the reaction of a -phenylene-bis-4,4 -(2,6-diphenylpyrylium) salt with amines are rod-like and range in length from 2-9 nm <05JOC405>. 

However, secondary amines yield aniline derivatives 50 with pyrylium ions in analogy to the example 43 44 ... 

Benzene derivatives, for example, 46/47, are obtained from the 2,4,6-trimethyl-pyrylium ion on ring-opening with hydroxide ions or with secondary amines and re-cydization via intramolecular aldol condensations ... 

This is an Sn2 process, since inversion is found at R. Another good leaving group is NTS2 ditosylamines react quite well with acetate ion in dipolar aprotic solvents RNTs2 4- OAc — ROAc. Ordinary primary amines have been converted to acetates and benzoates by the Katritzky pyrylium-pyridinium method (p. 447). Quaternary ammonium salts can be cleaved by heating with AcO in an aprotic solvent. Oxonium ions can also be used as substrates RsO -f R COO —> R COOR R2O. 

Alkyl halides or sulfuric or sulfonic esters can be heated with sodium or potassium thiocyanate to give alkyl thiocyanates, though the attack by the analogous cyanate ion (10-66) gives exclusive N-alkylation. Primary amines can be converted to thiocyanates by the Katritzky pyrylium-pyridinium method (pp. 447, 489). "... 

In the context of mechanistic studies, the electrochemical behavior and reactions with nucleophiles of 4-chloro-2,6-diphenylpyrylium and 4-chloro(bromo)flavylium have been studied <1999CHE653>. The proposed mechanism for nucleophilic substitution in halogen-substituted pyrylium and flavylium salts passes through formation of a charge-transfer complex that is converted into an ion-radical pair by simple electron transfer. Heterocyclic cleavage of the C-halogen bond occurs at the stage of the radical or the adduct from the reaction of the pyrylium salt and the nucleophile. In this study, an amine nucleophile was used however, the data are likely relevant for other types of nucleophiles as well (Scheme 5). 

A positive charge facilitates attack by nucleophilic reagents at positions or to the heteroatom. Amines, hydroxide, alkoxide, sulfide, cyanide and borohydride ions, certain carbanions, and in some cases chloride ions react with pyridinium, pyrylium, and thiopyrylium cations under mild conditions to give initial adducts of types 12 and 13. 

Improved procedures for the Chichibabin amination of pyridine derivatives have been reported (83JAP(K)58-208266, 83USP4386209, 83USP4405790). A general method has been developed for the conversion of 2-aminopyri-dines into 2-pyridones via 2-cthoxycarbonyl-l-(2-pyridyl)pyridinium ions 15. The pyridinium ions 15 are easily made from the 2-aminopyridines 14 and the corresponding pyrylium salt 13. On treatment with aqueous sodium hydroxide, pyridinium ions 15 are converted into the l-(substituted-2-pyridyl-carbonyl)-2-pyridones 16, which are readily hydrolyzed to the 2-pyridones 17 and the picolinic acid 18 (83JCS(P1)2623). 

Certain pyrylium salts react with primary amines to undeigo a process of ring opening and closing, which results in the replacement of oxygen by nitrogen. This can be a useful approach to pyridinium ions, as found in Scheme 6.31. 

Addition of an ammonia source to pyrylium salts readily affords pyridine derivatives and provides a good method for the preparation of the pyridine moiety if the corresponding pyrylium salt is accessible. The carbon oxygen double bond present in the pyrylium salt is an oxonium ion however, owing to aromatic stabilization they are easily formed by a variety of methods. The reactivity of pyrylium salts toward nucleophiles makes them useful reagents for the preparation of structurally diverse heterocyclic compounds. Thus pyrylium salts afford pyridines by reaction with ammonia, pyridine-A -oxides by reaction with hydroxylamine and pyridinium salts by reaction with primary amines. 

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