Heteroadamantanes and their derivatives. 6. Synthesis and mass-spectrometric investigation of 5-mono- and 5,6-disubtituted 6-oxo-1,3-diazaadamantanes

The corresponding 5-mono- and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes were obtained with high yields by the condensation of mono- and ,'-disubstituted acetones with hexamethylenetetramine in the presence of glacial acetic acid, and their structures were confirmed by IR and PMR spectra. The behavior of the compounds under electron impact was studied, and the main fragmentation paths of their molecules were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1679–1685, December, 1985.     

Heteroadamantanes and their derivatives

6-Cyano-1,3-diazaadamantan-6-ols and- 9-cyano-3,6-diazahomoadamantan-9-ols, whose reaction with ammonia forms the corresponding 6-cyano-6-amino-1,3-diazaand 9-cyano-9-amino-3,6-diazahomoadamantanes, were prepared by the exchange reaction of 1,3-diazaadamantan-6-ones and 3,6-diazahomoadamantan-9-ones with acetone cyanohydrin. When heated with ammonium carbonate, spirohydantoins were directly obtained from the former compounds and from the initial ketones by Bucherer—Bergs synthesis.See [1] for Communication 15.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 648–652, May, 1992.     

Heteroadamantanes and their derivatives

5,7,-Dinitro-6,6-dimethyl-1,3-diazaadamantane was synthesized by condensation of 1,3-dinitro-2,2-dimethyl-propane with hexamethylenetetramine. Like the previously prepared 5,7-dinitro-1,3-diazaadamantane, it is converted into the corresponding diamino derivative with hydrazine hydrate in the presence of a nickel catalyst, and the diamino compounds gave the 5,7-dibromo derivatives on treatment with sodium nitrite in conc. HBr. The latter were converted to 6,6-dimethyl-1,3-diazaadamantane and 1,3-diazaadamantane on treatment with hydrazine hydrate in the presence of nickel catalyst in ethanol.For Communication 18 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–233, February, 1993.     

Heteroadamantanes and their derivatives

1-p-nitrophenyl-3,6-diazahomoadamantane and 1-p-nitrophenyl-3,6-diazahomoadamantan-9-one were obtained by nitration of 1-phenyl-3,6-diazahomoadamantane and 1-phenyl-3,6-diazahomoadamantan-9-one with a mixture of potassium nitrate and sulfuric acid; 1-p-nitrophenyl-3,6-diazahomoadamantan-9-one was reduced with sodium borohydride to 1-p-nitrophenyl-3,6-diazahomoadamantan-9-ol. It was found that the nitro groups of these nitrophenyldiazahomoadamantanes were reduced to amino groups by heating with hydrazine hydrate without a catalyst. 1-p-Aminophenyl-3,6-diazahomoadamantan-9-one was obtained by reduction of nitrophenyl-azahomoadamantanone with tin in sulfuric acid, and 9-amino-1-p-aminophenyl-3,6-diazahomo-adamantane was obtained by reduction of its oxime with a nickel—aluminum alloy in water—base medium.See [1] for 17.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1257–1261, September, 1992.     

Heteroadamantanes and their derivatives. 7. Synthesis and mass-spectrometric study of functional derivatives of 5-mono- and 5,7-disubstituted 1,3-diazaadamantanes

The chemical behavior of the carbonyl group of 5-mono and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes was studied. The structures of the functional derivatives obtained were confirmed by IR and ¹H and ¹³C NMR spectral data. The behavior of the compounds under the influence of electron impact was studied, and the principal pathways of fragmentation of their molecules were ascertained.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 647–653, May, 1989.     

Heteroadamantanes and their derivatives 26. Synthesis of derivatives of hydroxybenzyldiazahomoadamantane

Summary 1-(4-Hydroxy-3-nitrobenzyl)-3,6-diazahomoadamantan-9-one was obtained by the nitration of hydroxybenzyldiazahomoadamantanone. The behavior of the carbonyl group of this ketone and of its nitro derivative has been studied. The structures of the functional derivatives obtained were confirmed by data of IR, PMR, and mass spectra.For part 25 see [1].M. V. Lomonosov Moscow State Academy of Fine Chemical Technology, Moscow 117571. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 391–394, March, 1995.Original article submitted December 29, 1994.     

Heteroadamantanes and their derivatives. 4. Synthesis of 1,3,5-triazaadamantane

Reduction of 7-nitro-1,3,5-triazaadamantane with hydrazine hydrate in the presence of Raney nickel gave 7-hydroxyamino- and 7-amino-1,3,5-triazaadamantane, from which 7-chloro-, 7-bromo-, and 7-thiocyanato-1,3,5-triazaadamantanes were synthesized by substitutive deamination. Desulfurization of 7-thiocyanato-1,3,5-triazaadamantane in the presence of Raney nickel gave 1,3,5-triazaadamantane.For Communication 3, see [1].Translated from Khitniya Geterotsiklicheskikh Soedinenii, No. 6, pp. 837–840, June, 1985.     

Microwave-assisted synthesis of 5-aryl-3-hydroxy-2-oxindole derivatives and evaluation of their antiglaucomic activity

A set of new 5-aryl-3-hydroxy-2-oxindoles was synthesized by decarboxylative condensation of the corresponding 5-aryl-substituted isatins with malonic or cyanoacetic acids under microwave irradiation. The antiglaucomic activity of the obtained compounds was evaluated. The most water soluble compounds can reduce the intraocular pressure (IOP) up to 2 Torr.     

Heteroadamantanes and their derivatives. 23. Reduction of nitroaryl derivatives of 3,6-diazahomoadamantane

It has been found that nitroaryl derivatives of diazahomoadamantane can be reduced selectively by hydrazine. New data are presented on the noncatalytic reduction of p-nitrophenyldiazahomoadamantane by hydrazine hydrate.For Communication 22 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1405–1408, October, 1993.     

Heteroadamantanes and their derivatives. 14. Synthesis of 3,6-diazahomoadamantan-9-ols and their acetates

The reduction of 3,6-diazahomoadamantan-9-ones with metal hydrides gave 3,6-diazahomoadamantan-9-ols, which were convened to acetates by the action of acetic anhydride. The effect of the substituents in the nodal positions on the rates of reduction and acylation is demonstrated.See [1] for Communication 13.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 804–809, June, 1991.     

Heteroadamantanes and their derivatives. 13. Synthesis of 1-azaadamantane and some derivatives of it

3,5,7-Tribromo-1-azaadamantane is made by the action of sodium nitrite on 3,5,7-triamino-1-azaadamantane in concentrated hydrobromic acid. The reduction of this compound with hydrazine hydrate in the presence of a nickel catalyst gives 1-azaadamantane.For Communication 12, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1083–1085, August, 1990.     

The synthesis of 5- and 6-hydroxy-2-methylisoquinuclidine

The reduction of the isomeric 5,6-epoxy-2-carboethoxyisoquinuclidines with lithium aluminum hydride afforded 5- and 6-hydroxy-2-methylisoquinuclidine. Contrary to expectation essentially single epimers were obtained for each alcohol.     

Heteroadamantanes and their derivatives. 10. Hydrolysis of 7-bromo-1,3,5-triazaadamantane

Potentiometric titration was used to determine the rate constants of hydrolysis of 7-bromo-1,3,5-triazaadamantane at 50 and 80C. It was shown that the rate of this reaction is significantly lower than the rate of hydrolysis of 1-bromoadamantane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 543–545, April, 1990.     

A convenient stereoselective synthesis of 5-hydroxy-3-oxoesters and 3-hydroxy-5-oxoesters

A biocatalytic approach was employed for the asymmetric reduction of sterically demanding ketones to prepare 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates. Screening a collection of microorganisms led to the identification of stereocomplementary microbial strains that provide access to both enantiomers of 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). Moreover, the application of Saccharomyces cerevisiae gave two diastereomers of 3,5-dihydroxy-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). The applicability of the identified strains was demonstrated by transforming the obtained dihydroxy ester into the chemically valuable lactone (4S,6R)-tetrahydro-4-hydroxy-6-phenyl-pyran-2-one.     

Carboxyketenes from 4-hydroxy-1,3-oxazin-6-ones and Meldrum's acid derivatives

New 4-hydroxy-1,3-oxazin-6-ones 8 and 16 were prepared from chlorocarbonyl(phenyl)ketene and amides. The flash vacuum thermolysis (FVT) reactions of these compounds and the 4-methoxy derivative 17 were investigated by Ar matrix isolation IR spectroscopy and online mass spectrometry including MS/MS analysis. Carboxy(phenyl)ketene 10 is formed as the major product by thermal fragmentation of 4-hydroxy-1,3-oxazin-6-one 8. This takes place via the unstable 6-hydroxy tautomer 9. Another tautomer, the 5H-isomer 12, leads to the formation of benzoyl isocyanate 13 as a minor product together with phenylketene 14. Carboxy(phenyl)ketene 10 remains detectable at high FVT temperatures but undergoes thermal decarboxylation to phenylketene 14. The same carboxy(phenyl)ketene 10 is also produced in significant amounts by FVT of 5-phenyl-Meldrum's acid 18 via the unstable enol tautomer 19. A small amount of the unsubstituted carboxyketene 20 is observable on FVT of Meldrum's acid 1 itself.     

N-Methylmorpholinium 4-aryl-5-cyano-3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates: synthesis and properties

Reactions of aromatic aldehydes with cyanothioacetamide and dimethyl malonate in the presence ofN-methylmorpholine affordedN-methylmorpholinium 4-aryl-5-cyano-3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates. The latter were used to synthesize substituted 6-(alkylthio)-2-oxo-1,2,3,4-tetrahydropyridines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 485–487, March, 2000.     

Heteroadamantanes and their derivatives. 21. Synthesis of thioureas of the 3,6-diazahomoadamantane series

Unsubstituted and phenyl-substituted thioureas were obtained by the action of benzoyl isothiocyanate and phenyl isothiocyanate on amino-substituted diazahomoadamantanes.For Communication 20 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 814–817, June, 1993.     

Studies on pyrazines. 4.. The synthesis of 2-hydroxy-6-phenylpyrazine and its derivatives

This report describes a new method for the preparation of 2-hydroxy-6-phenylpyrazine ( 1 ). Amino acetal 5 was converted to glycyl amino acetal 7 by two steps in excellent yield. Cycliza-tion of 7 to 1 was accomplished in 33% yield by refluxing in acetic acid followed by oxidation with manganese dioxide. Compound 1 was also prepared by hydrolysis of amino- and methoxy-pyrazines 3 and 15 , derived from 2-hydroxy-5-phenylpyrazine ( 2 ) and the 2-amino homologue 4 , respectively, and by decarboxylation of 2-hydroxy-5-phenylpyrazinecarboxylic acid ( 19 ).