Meso ionic compounds

D. Molecular Orbital Calculations. Pharmacological Activity of Meso-ionic Compounds Meso-ionic— Definition and Delineation... 

This list shows that the five-membered meso-ionic heterocycles related to the azomethine imine 1,3-dipole (43) comprise the largest group and that meso-ionic compounds related to the nitrosoimines (39), thionitrosoimines (41), and carbonyl imines (42) are not yet known. Clearly synthetic challenges still exist in the field of meso-ionic compounds. 

This second class of five-membered heterocyclic meso-ionic compounds is represented by the type formula 14 20. So far, only eight representatives (Table II) of type B have been described, whereas acceptable combinations of the groupings a, b, c, d, e, and f derived from suitably substituted carbon, nitrogen, oxygen, or sulfur atoms lead, in principle, to 84 possibilities. However, not all these 84 possible structures are necess y well based because valence tautomerism (see Section VI) might well be associated with thermodynamic preference for the acyclic covalent valence isomer (46) rather than the cyclic meso-ionic alternative (20). 

VI. The Valence Tautomerism of Five-Membered Meso-ionic Compounds of Type A and Type B... 

Polycyclic meso-ionic l,3-diazol-4-ones (93) are also known. These include Besthorn s Red (93a) which was first described in 1904. The discovery of Besthorn s Red and its subsequent formulation (93a) forms an interesting part of the history of meso-ionic compounds. "... 

Interest in the photochemistry of meso-ionic compounds is now developing, and an interesting result has been obtained by the photolysis of 5-amino-1,3-thiazolium salts (126, R = H). For example, irradiation of the salt 126, R = R = Ph, R = H, X = Cl, in aqueous solution yields the disulfide 130 (23%) and the keto amidine 131 (70%). It is proposed that this reaction involves a bicyclic intermediate (132). ... 

These meso-ionic compounds are often referred to as isosydnones (146). They are prepared from )V-acyl-iV-(alkyl or aryl)-hydrazines (147, X = 0) or their hydrochlorides and carbonyl chloride. " The isosyd-... 

This new class of meso-ionic compounds have been recently synthesized. -Methyl-iV-benzoylhydrazine (147, R = Me, R = Ph) and aryl isocyanide dichlorides (ArN=CCl2) yield 1,3,4-oxadiazolium chlorides (154, R = Me, R = Ph, R = Ar), which with diazomethane give the meso-ionic l,3,4-oxadiazol-2-imines (153) as yellow crystalline compounds. Subsequently this synthetic method has been extended by the use of acylisocyanide dichlorides. These reagents yield the 1,3,4-oxadiazol-2-imines 153, R = SO,R, and 153, R = COR. "... 

The existence of the isomeric meso-ionic compounds 156 and 162 has been recently established.The transformation 156 162, R = Me, R = Ph, is achieved by heating in ethanolic solution or with ethane-thiol in benzene this isomerization could well involve the betaine intermediate (163). ... 

Representatives of this novel class of meso-ionic compounds in which the exocyclic substituent f (see Table I) is a stabilized carbanionoid residue [-C(CN)C02Me or -C(CN)2l have been recently synthesized. Base-catalyzed (potassium carbonate or triethylamine) condensation of AT-acylhydrazines (147) with 3,3-dichloroacrylonitriles (165) yield the greenish-yellow meso-ionic l,3,4-oxadiazol-2-enes (164) directly. 

The A-methyl-A -arylazoaminoacetonitriles (194) and hydrogen chloride in ether yield the 1,2,3-triazolium chlorides (195). These salts (195) and base did not give the corresponding meso-ionic compounds (193, R = Me, R == Ar, R = R = H), but the corresponding J acetyl derivatives (193, R = Me, R = Ar, R = H, R = Ac) were produced either from the nitriles (194) and acetyl chloride or from the 1,2,3-triazolium chlorides (195) and acetic aidiydride, followed by treatment with ammonium hydroxide. ... 

Two general methods have been described for the synthesis of this new class of meso-ionic compounds (196). The most convenient method is by the treatment of 4-bromo-l,2,3-triazolium salts (197, X = Br) with sodium sulfide in dimethylformamide. Alternatively, N-methylation of the isomeric 4- or 5-alkylmercapto-1,2,3-triazoles 198 or 199 with methyl tosylate gave intermediate triazolium salts (197, X = SR, Y = Tos), which yielded meso-ionic l,2,3-triazole-4-thiones (196) by 5-dealkylation by heating with piperidine. 

A number of general methods for the synthesis of meso-ionic 1,2,4-triazol-3-ones are available. Sodium ethoxide-catalyzed cyclization of 1-benzoyl-l,4-diphenylsemicarbazide (201, R = R = R = Ph, X = O) yielded anhydro-3-hydroxy-1,4,5-triphenyl-1,2,4-triazolium hydroxide (200, R = R = R = Ph). A general route to meso-ionic 1,2,4-triazol-3-ones (200) is exemplified by the formation of the 1,4,5-triphenyl derivative (200, R = R = R = Ph) from A-amino-MA -diphenylbenzamidine (202, R = R = R = Ph) and phosgene. In contrast with this ready meso-ionic compound formation, the corresponding reaction of the iV-methylbenzamidine (202, R = Me, R = R = Ph) did not yield the meso-ionic 1,2,4-triazol-3-one (200, R = Me, R = R = Ph). The product was in fact 3,4-diphenyl-2-methyl-l,2,4-triazol-5-onium chloride (203), which on heating gave 3,4-diphenyl-1,2,4-triazol-5-one (204, R = Ph). The formation of the A-methyl derivative (200, R = Me, R = R = Ph, yield 79%) by heating the 7V-thiobenzoyl semicarbazide (201, R = Me, R = R = Ph, X = S) with potassium carbonate in methyl cyanide has been reported. Another synthesis of A-methyl derivatives (200, R = Me) involves methylation of 3-methyl-4-phenyl-l,2,4-triazol-5-one (204,... 

R = Me). This yields a mixture including the meso-ionic compound 200, = Me, R = Ph. The 1,3-dipolar cycloaddition of phenyl isocyanate to iV-phenylsydnone (205) yielding the meso-ionic 1,4-diphenyl-1,2,4-triazol-3-one (200, R = R = Ph, R = H) provides a comparatively rare example of the interconversion of one type of meso-ionic compound into another. 

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