Oxazolo[3,2-a]pyridinium and oxazolo[3,2-a]pyrimidinium salts in organic synthesis

The methods for the synthesis of oxazolo[3,2-a]pyridinium and oxazolo[3,2-a]pyrimidinium salts and their reactivities are reviewed. Both systems exhibit ambident properties in reactions with nucleophiles; depending on the substituents and the reagents, both the oxazole and azine rings can undergo opening and transformations. A number of new methodologies involving oxazolopyridinium and oxazolopyrimidinium salts for the design of functionalized oxazoles, imidazoles, fused pyrroles, and other heterocyclic systems are generalized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 831–848, April, 2008.     

2,3-Diphenyl-1,2,3-triazolo[1,5-a]pyrimidinium salts

2,3-Diphenyl-1,2,3-triazolo[1,5-a]pyrimidinium salts, the structure of which was confirmed by the PMR spectra, were obtained by condensation of 4-amino-1,5-diphenyl-1,2,3-triazole with -diketones and their analogs in trifluoroacetic acid. The corresponding 4-acylvinylaminotriazoles are formed by the action of alkali on these salts. It was established that the salts with a methyl group in the 7 position do not form polymethine dyes, whereas the 5,7-dimethyl derivative does gives dyes owing to the activity of the methyl group in the 5 position. The ability of the 5,7-dimethyl derivative to undergo cyanine condensations is explained by the betaine cationic structures of the salts obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1422–1424, October, 1978.     

Effect of bases on 1,3,4-thiadazolo[3,2-a] pyrimidinium salts

1,3,4-Thiadiazolo[3,2-a]pyrimidinium salts are converted by the action of bases to 2-thiocyanopyrimidines, which were also obtained from 2-amino-1,3,4-thiadiazole and -diketones, thus bypassing the step involving the isolation of the pyrimidinum salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1660–1661, December, 1974.     

1,3,4-Oxadiazolo[3,2-α]pyrimidinium salts

5-Amino-1,3,4-oxadiazolium perchlorates react with 1,3-carbonyl-functional compounds to give 1,3,4-oxadiazolo[3,2-α]pyrimidinium perchlorates. The latter are cleaved by both alkali and strong acid to give 1-amino-2-pyrimidinone or 5-amino-1,3,4-oxadiazole derivatives. The l,3,4-oxadiazolo[3,2-α]pyrimidinium perchlorates react with anailine and hydrazines to give sym-triazolo[1,5-α]pyrimidinium salts and with acetylacetone to give pyrazolo[1,5-α]pyrimidines.     

Oxazolo[3,2-a]pyridinium salts

The first synthesis of the aromatic oxazolo[3,2-a]pyridinium ring system has been accomplished by the cyclization of 1-acetonyl- or 1-phenacyl-2-pyridones. Through use of the analogous quinolones and 2-(p-bromophenacyl)-1-isoquinolone, benzologs of the new system have been prepared.     

Thiazolo [3,2-a] pyridinium salts

The sulfides formed by the reaction of α-halo ketones or α-halo acetals with 2-mercaptopyridine may be cyclized in good yield to form thiazolo[3, 2-a]pyridinium salts. The presence of chloro or nitro substituents on the pyridine ring does not interfere with the synthesis. Nitration of 3-methylthiazolo[3, 2-a]pyridinium perchlorate has been found to occur at position 8.     

Hexahydrobenzothiazolo[3,2-a]pyridinium salts

Salts of hexahydrobenzothiazolo[3,2-a]pyridine are obtained by exchange reactions. Anions are placed in the order [(NC)₂CCHC(CN)₂]- > ClO₄ ^–>I₃ ^–>Br^– according to the ability to displace each other. X-ray structural and spectroscopic studies establish the cis-attachment of the thiazolidine and cyclohexane rings in the hexahydrobenzothiazolo [3,2-a]pyridinium salts studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1682–1688, December, 1988.     

Synthese und Eigenschaften von Thiazolo[3,2-a]pyrimidinen und Thiazolo [3,2-a] pyrrolo [2,3-d]pyrimidinen

From the alkali-catalysed reaction of thiouracil with bromoacetaldehyde diethyl acetal three products are isolated in nearly the same quantity: 2-(2, 2-diethoxyethylthio)-uracil ( 2 ) and two cyclization products: 3 , a thiazolo[3, 2-a]pyrimidin-5-one, and 4 , athiazolo[3, 2-a]pyrimidin7-one. By warming with acid both 2 and 4 yield 3 . Rearrangement of 4 to 3 proceeds also by heating the hydrochloride. Similar cyclizations leading to thiazolo[3, 2-d]pyrrolo[2, 3-d]pyrimidin-5-ones are also described. Bromine substitutes 3 in position 6. The bromo derivative 6 on treatment with primary or secondary amines affords 7-amino compounds.     

Facile synthesis of novel 3-substituted pyrido[1,2-a]pyrimidinium salts using vinamidinium salts

Pyrido[1,2-a]pyrimidinium salt derivatives 2a–f were prepared in good yields by condensation of 2-aminopyridine with 2-substituted vinamidinium salt derivatives 1a–f. The purity and the structure of the synthetized compounds were ascertained by elemental analysis, mass spectrometry, infrared, and NMR (¹H and ¹³C 400?MHz) spectroscopy.     

Single-reactor synthesis of 2R-thio-5,7-dimethyl-1,3,4-thiadiazolo[3,2-a]pyrimidinium perchlorates

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1146–1147, August, 1993.     

Asymmetric polymethine dyes based on thiazolo[3,2-a]quinoxalinium salts

Asymmetric carbocyanine dyes, the solutions of which are characterized by the presence of several absorption bands in the visible and near-IR regions, were synthesized from 4,5-dimethyl-1-oxo-2-phenyl-1,5-dihydrothiazolo[3,2-a]quinoxalin-3-ium perchlorate. Their deep color is due both to a more effective length of the condensed heterocyclic system and to the strong interaction of the electronic transitions, localized on the polymethine chain and on the heterocyclic ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1113–1116, August, 1992.     

Mesoionic isoxazolo[2,3-a]pyrimidinediones and 1,3,4-oxadiazolo[3,2-a]pyrimidinediones as potential adenosine antagonists

Several derivatives of two novel mesoionic ring systems, i.e., isoxazolo[2,3-a]pyrimidinedione and 1,3,4-oxadiazolo[3,2-a]pyrimidinedione, were prepared for evaluation as adenosine antagonists. Whereas both ring systems are relatively stable when the 6-position (i.e., that position corresponding to the purine 1-position) is substituted by an alkyl group, neither ring system is stable when this position is unsubstituted. An example of a 6-unsubstituted non-mesoionic isoxazolopyrimidinedione exhibited similar behavior. As adenosine antagonists, the mesoionic compounds were found to be less potent than their previously evaluated mesoionic thiadiazolo[3,2-a]pyrimidinedione counterparts.     

Some chemical properties of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

We have studied the reaction of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with amines, alkylating reagents, and hydrogen peroxide. We have shown that the presence of an aryl substituent at the 2 position of [1,3-thiazino[3,2-a]benzimidazol-4-ones has a substantial effect on the direction of the reactions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 445–452, March, 2006.     

Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3

2-Hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 2a and 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one 2b, were obtained in high yields under mild conditions from the cyclization reactions of bis-(2,4,6-trichlorophenyl) malonate and 2-aminobenzothiazole or 2-aminothiazole, respectively. A new class of compounds, 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones, were synthesized via the microwave assisted radical addition of compounds 2a and 2b to various alkenes using manganese(III) acetate. A preliminary acetylcholine esterase (AchE) inhibition test of compound 4e showed excellent (92%) inhibitory potential, comparable with the standard drug Donapezil®.