Interaction of aminoazoles with Meldrum’s acid and dialkyl ketones or cyclohexanone

Interaction of 3-amino-5-methylpyrazole, 3-amino-5-methylthio-, and 3,5-diamino-1,2,4-triazole with Meldrum’s acid, acetone, ethyl methyl ketone, and cyclohexanone leads to alkyl-substituted pyrazolo[3,4-b]pyridin-6-ones and 1,2,4-triazolo[1,5-a]pyrimidin-7-ones respectively. The structure of 5,5-dimethyl-2-methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidin-7-one was demonstrated by an X-ray structural investigation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 595–601, April, 2007.     

Reaction of arylidene derivatives of Meldrum's acid with 3-amino-1,2,4-triazole

The condensation of arylidene derivatives of Meldrum's acid with 3-amino-1,2,4-triazole in nitrobenzene leads to 4,5,6,7-tetrahydro-1,2,4-triazolo [1,5-a]pyrimidin-5-ones. In DMF the reaction proceeds with the formation of arylsubstituted N-(2H-1,2,4-triazol-3-yl)-3-(2H-1,2,4-triazol-3-ylamino)propionamides. Ukrainian Research Institute for the Pharmacotherapy of Endocrine Diseases, Kharkov 310002. Kharkov State University, Kharkov 310077, Ukraine     

Studies on Pyrazine Derivatives. 39. Synthesis,Reactions, and Tuberculostatic Activity of 3-Pyrazinyl-1,2,4-triazolo[4,3-<Emphasis Type="Italic">a</Emphasis>]-1,3-diazacycloalkanes

In the reactions of S,S-dimethyldithiocarbamate pyrazinoylhydrazone with diamines some 3-pyrazinyl-1,2,4-triazolo[4,3-a]-1,3-diazacycloalkanes were obtained, and the mechanism of their formation was proposed. The products were acylated, hydroxyalkylated, and aminomethylated. Their tuberculostatic activity was tested in vitro.__________Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–237, February, 2005.     

2-amino-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines: Synthesis and reactions with electrophilic reagents

The hydrogenation of 2-amino-5-R-7-R′-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines with NaBH₄ led to the formation of 2-amino-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidines. Acylation, sulfonylation, and alkylation of these compounds depending on conditions and the reagent character occur at the amino group, atoms N³ or N⁴. The treatment with alkali of 2-amino-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo-[1,5-a]pyrimidinium bromide resulted in 2-amino-3-benzyl-5-R-7-R′-3,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidine, similar reaction of 2-acetamido-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidinium bromide gave a mesoionic product of a hydrogen elimination from the amide nitrogen atom.     

Reaction Between 5-Isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione and <Emphasis Type="Italic">tert</Emphasis>-Butyl Isocyanide in the Presence of Primary or Secondary Amines

Summary. 5-Isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione (the condensation product of Meldrums acid and acetone) reacts smoothly with tert-butyl isocyanide in the presence of primary or secondary amines to produce N-tert-butyl-2,2-dimethylbutyramide derivatives and/or 1-tert-butyl-4,4-dimethyl-2,5-dioxopyrrolidine-3-carboxamides in good yields.     

Three component condensation of 3-amino-1,2,4-triazole with carbonyl compounds. A new synthesis of 1,2,4-triazolo[1,5-a]pyrimidines

Three component condensation of 3-amino-1,2,4-triazole with an aromatic aldehyde and ketone gives 1,2,4-triazolo[1,5-a]-pyrimidines. An x-ray structural investigation of 5-phenyl-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]benzo[h]quinazoline was undertaken in order to determine the course of this reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 481–485, April, 1993.     

Fluoroalkyl-containing lithium β-diketonates in the synthesis of 1,2,4-triazolo[1,5-a]pyrimidines

Cyclocondensation of fluorine-containing lithium -diketonates with 3-amino-1,2,4-triazoles afforded 7-fluoromethyl-1,2,4-triazolo[1,5-a]pyrimidines.     

Reactions with heterocyclic amidines,VII: Synthesis of some new pyrazolo[1,5-c]-1,2,4-triazines,pyrazolo[1,5-a]-1,3,5-triazines and pyrazolo[1,5-a]pyrimidines

Diazotised 5-amino-3-methyl-4-phenyloyrazole (1) reacted with active methylene reagents and with -naphthol to yield the pyrazolo[1,5-c)-1,2,4-triazine derivatives2a-e and5. Compound1 reacted with benzoyl isothiocyanate and with phenyl isothiocyanate to yield the corresponding pyrazol-5-ylthiourea derivatives6a, b. 5a was converted into the thiourea derivative8 by the action of acids or alkalies. A synthesis of 2-methyl-3-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidin-5-one from the reaction of -phenylacetoactonitrile (3-oxo-2-phenyl-butyric nitrile) and -cyanoethylhydrazine is reported.

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Reaktionen mit heterocyclischen Amidinen, VII: Synthese einiger neuer Pyrazolo[1,5-c]-1,2,4-triazine, Pyrazolo[1,5-a]-1,3,5-triazine und Pyrazolo[1,5-a]pyrimidine

Zusammenfassung Diazotiertes 5-Amino-3-methyl-4-phenylpyrazol (1) reagiert mit einer aktiven Methylenkomponente und -Naphthol zu den Pyrazolo[1,5-c]-1,2,4-triazin-Derivaten2a-e und5. 1 ergibt mit Benzoylisothiocyanat und Phenylisothiocyanat die entsprechenden Pyrazol-5-yl-thioharnstoffe6a, b. 5a wurde mittels Säure oder Base in das Thioharnstoffderivat8 umgewandelt. Es wird über eine Synthese von 2-Methyl-3-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidin-5-on aus -Phenylacetoacetonitril (3-Oxo-2-phenyl-butyronitril) und -Cyanoethylhydrazin berichtet.

     

On the Synthesis of 3-Acetyl-1-aryl-1,4,5,6-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazepin-7-ones by Reaction of Nitrilimines with 3-Aminopropanoic Acid

Summary. Nitrilimines were prepared from N-arylhydrazono chlorides and reacted with -alanine yielding the corresponding amidrazones, which were treated with 1,1-carbonyldiimidazole in THF affording the hitherto unknown 3-acetyl-1-aryl-1,4,5,6-tetrahydro-1,2,4-triazepin-7-ones.     

Microwave-assisted three-component synthesis of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]-pyrimidine-6-carboxamides and their selective reduction

Multicomponent reactions (MCRs) and microwave-assisted organic synthesis (MAOS) have been used as key methods for the synthesis of fused dihydropyrimidine derivatives. The three-component condensation of 3-amino-5-alkylthio-1,2,4-triazoles with aromatic aldehydes and acetoacetamides under microwave irradiation was developed as a rapid and efficient solution-phase method for the high-yielding preparation of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamide libraries. In addition, the selective reduction of the formed dihydrotriazolopyrimidines to trans-trans-2-alkylthio-7-aryl-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamides was established. The described synthetic protocols provide rapid access to novel and diversely substituted dihydroazolopyrimidine libraries.     

Effect of ‘Transannular Transmission’ in Dibenzo-18-Crown-6

The effect of the nature of the substituent in the monosubstituted derivatives of dibenzo-18-crown-6 on the reactivity and direction of the electrophilic substitution reaction of the unsubstituted benzene ring has been determined. This transfer is carried out via the macrocycle and therefore is called transannular transmission. The possible mechanism of this transmission is discussed.     

Imine-enamine tautomerization of dihydroazolopyrimidines 4. Synthesis and tautomerization of 5-(2-hydroxyphenyl)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines

The condensation of 3-amino-1,2,4-triazole with 2-hydroxychalcones gives 7-aryl-5-(2-hydroxyphenyl)-4,7(6,7)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. Both tautomeric forms were isolated for a number of these compounds. PMR spectroscopy was used to show that the enamine form is predominant in DMSO in contrast to the case in CHCl₃.For Communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1353–1356, October, 1993.     

Imine-enamine tautomerism of dihydroazolopyrimidines. 3. 5-Aryl-substituted 4,7(6,7)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines

5-Aryl-substituted 4,7(6,7)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines were obtained by condensation of 3-amino-1,2,4-triazole with -dimethylaminopropiophenone hydrochlorides or crotophenone. The effect of steric and electronic factors on the position of the imine-enamine equilibrium in solutions of the synthesized substances is examined. 5-Phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyriniidine was subjected to x-ray diffraction analysis.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1539–1544, November, 1991.     

On triazoles XIX: The reaction of 5-amino-1,2,4-triazoles with functionalized acetoacetic esters

Summary Different functionalized alkyl 3-oxo-butyrates (2) were reacted with 5-amino-3-Q-1H-1,2,4-triazoles (1) to yield3 and4 type 1,2,4-triazolo[1,5-a]pyrimidinones. In case of2 (R ¹=methyl,R ²=1-ethoxycarbonylethyl,R ³=ethyl) beside the corresponding derivative4 the unexpected 5,6-dihydro-6,8-dimethyl-7-ethoxycarbonyl-3-methylthio-1,2,4-triazolo[4,3-a]-1,3-diazepin-5(9H)-one (7) was isolated, representing a novel ring system.

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Über Triazole, 19. Mitt.: Die Reaktion von 5-Amino-1,2,4-triazolen mit funktionalisierten Acetoessigestern

Zusammenfassung Verschiedene funktionalisierte 3-Oxo-buttersäurealkylester (2) wurden mit 5-Amino-3-Q-1H-1,2,4-triazolen (1) umgesetzt, wobei 1,2,4-Triazolo[1,5-a]pyrimidinone der Typen3 und4 erhalten wurden. Im Fall von2 (R ¹=Methyl,R ²=1-Ethoxycarbonylethyl,R ³=Ethyl) wurde neben dem erwarteten Derivat4 das unerwartete 5,6-Dihydro-6,8-dimethyl-7-ethoxycarbonyl-3-me-thylthio-1,2,4-triazolo[4,3-a]-1,3-diazepin-5(9H)-on (7) isoliert, welches ein neues Ringsystem darstellt.

     

Imine-enamine tautomerism of dihydroazolopyrimidines 5. Steric effects and the tautomeric equilibrium for dihydro-1,2,4-triazolo[1,5-a]pyrimidines

The reaction of 3-amino-1,2,4-triazole with -dimethylaminopropiophenones or unsaturated ketones gives 5,7-disubstituted 4,7(6,7)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. An increase in the bulk of the substituent at C₍₇₎ in the bicyclic system leads to relative stabilization of the enamine tautomer of these compounds. An x-ray diffraction structural analysis of 7-tert-butyl-5-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine showed that the introduction of a tert-butyl group into the dihydropyrimidine ring leads to significant loss of planarity of this system.For Communication 4, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1357–1363, October, 1993.     

Zum Reaktionsmechanismus von Glutaraldehyd mit Proteinen

The interaction of glutaraldehyde with model aliphatic amines was studied in order to understand the crosslinking reaction of glutaraldehyde with proteins. The reaction in organic solvents gave N-alkyl-1,4-dihydropyridines and N,N-dialkyl-1,5-diiminopentanes. The isolated products are new or were previously described by us for the first time¹. Hydration of the reaction products led to stable N-alkylpiperidines and N,N-dialkyl-1,5-diaminopentanes. In aqueous solution the reaction depends on thepH: at apH above 7, N-alkyl-1,4-dihydropyridines and at apH below 7, polymers were obtained. For the crosslinking reaction of proteins with glutaraldehyde the following mechanism is proposed: Monomeric glutaraldehyde reacts with the protein to give intermediate N-alkyl-2,6-dihydroxypiperidines. Intramolecular dehydration leads to the corresponding N-alkyl-1,4-dihydropyridines. Condensation of the cyclic monohydrate of glutaraldehyde and N-alkyl-2,6-dihydroxypiperidines gives linear polymeric crosslinks containing -oxo-N-alkylpiperidine units.

Lubig R., Dissertation, RWTH Aachen, 1974.     

Synthesis of a Calix[4]arene Containing 'Hard' and 'Soft' Metal Ion Binding Sites

Co-receptor 1,3-calix[4]-di(aza-benzo)crown-crown-6 (1-H) designed with one calix[4]arene in a 1,3-alternate conformation and hard and soft metal ion binding sites has been prepared according to three pathways (A-C). Pathway B, consisting of two different 1 + 1 condensations with ditosylate derivatives, was shown to be the most efficient.     

Synthesis of 3-thienyl-substituted isothiazolines-2 and 1,2,4-thiadiazoles based on nitrile sulfides of the thiophene series

The reaction of substituted - and -thienylcarboxamides with chlorocarbonylsulfenyl chloride gave 5-thienylsubstituted 1,3,4-oxathiazol-2-ones. Decarboxylation of the latter by heating in o-dichlorobenzene generated in situ - and -thienylnitrile sulfides, which in the presence of dipolarophiles [dimethyl fumarate, N-phenylmaleinimide, chloro(trichloro)acetonitrile] give the corresponding 3-thienyl-substituted ²-isothiazolines and 5-chloromethyl(trichloromethyl)-1,2,4-thiadiazoles.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1892–1897, August, 1992.     

Synthesis of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]indole-2-thione and 1,5,6,10b-Tetrahydroimidazo[2,1-<Emphasis Type="Italic">a</Emphasis>]-isoquinoline-2(3H)-thione derivatives

Thionation of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one derivative with Lawessons reagent in boiling toluene afforded 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole-2-thione derivative. Alkylation of the latter with ethyl iodide in DMF in the presence of a strong base gave 2-ethylthio-9,9,9a-trimethyl-9,9a-dihydro-3H-imidazo[1,2-a]indole. 1,5,6,10b-Tetrahydroimidazo[2,1-a]isoquinoline-2(3H)-thiones were synthesized by thionation of the corresponding carbonyl substrates.Published in Khimiya Geterotsiklicheskikh Soedinenii, No 11, pp. 1695–1700, November, 2004.     

Partially Hydrogenated Aromatic Substituted Tetrazolo[1,5-a]pyrimidines

By treating 5-aminotetrazole with aromatic ,-unsaturated ketones or with Mannich base hydrochlorides there have been synthesized aromatic substituted 4,7-dihydrotetrazolo[1,5-a]-pyrimidines. They can be reduced to the corresponding 4,5,6,7-tetrahydro derivatives by the action of NaBH₄. The high thermodynamic stability of the 4,7-dihydrotetrazolo[1,5-a]pyrimidines when compared with the 4,5-dihydro isomers has been revealed. Reaction of 5-aminotetrazole both with cyclohexanone as well as with 2-cyclohexylidenecyclohexanone leads to formation of 9,9-pentamethylene-4,5,6,7,8,9-hexahydrotetrazolo[5,1-b]quinazoline, the structure of which was demonstrated using X-ray crystallography.