Recyclization of 5-Amino- oxazoles as a Route to new Functionalized Heterocycles (Developments of V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine)

The recyclizations of 5-amino- and 5-hydrazine-1,3-oxazoles mainly with electron-withdrawing group in 4^th position are considered. The chemical behavior of these heterocycles is due to the presence of two hidden amide fragments; therefore, the recyclization processes include a stage of nucleophile attack on 2^nd or 5^th position of the oxazole cycle. When the nitrile group is present in 4^th position, it is often involved in the recyclization forming α-aminoazoles. 5-Amino/hydrazine-1,3-oxazoles undergo recyclization both in nucleophilic (amines, hydrazine, thionating agents) and electrophilic medium ((trifluoro)acetic acid, other acylating agents). The numerous types of functionalized heterocycles can be easily obtained with the usage of these recyclizations, such as the derivatives of 3-amino-6,7-dihydro-5H-pyrrolo[1,2–a]imidazole, imidazolidine-2,4-dione, 1H-pyrazole-3,4,5-triamine, 5,6-diamino-2,3-diphenylpyrimidin-4(3H)-one, 2-(2-R-7-oxo-5-(trifluoromethyl)oxazolo[5,4–d]pyrimidin-6(7H)-yl)acetic acid, 2-R-4-(5-R′-1,3,4-oxadiazol-2-yl)oxazol-5-amine, (amino(5-amino-1,3,4-thiadiazol-2-yl)methyl)phosphonate.     

Synthesis and Reaction of 4-Methyl-3,4-epithiotetrahydropyran with α-Amino Acids

4-Methyl-3,4-epithiotetrahydropyran was synthesized by the recyclization of 4-methyl-3,4-epoxytetrahydropyran by the action of thiourea. The product reacts with -amino acids in an alkaline medium with regioselective opening of the thiirane ring at the least substituted carbon atom.     

Recyclization of benzimidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazanium salts into 1-(2,3-epithiopropyl)benzimidazol-2-ones under the action of epichlorhydrin

It has been shown that the reaction of epichlorhydrin with 3-hydroxybenzimidazo[2,1-b]thiazanium salts leads to recyclization of the thiazanium ring with the formation of substituted 1-(2,3-epithiopropyl)benzimidazol-2-ones in high yield. The proposed method enables the introduction of functional groups unstable in alkaline medium into the structure of thiirane derivatives.     

Conversion of 4- and 5-hydroxyaminothiazolidine-2-thiones under the action of alkalis

5-Hydroxyaminothiazolidine-2-thiones are oxidized in an alkaline medium to 5-hydroxyiminothiazolidine-2-thiones or undergo recyclization to derivatives of imidazolidine-2-thiones, depending on their structure. 4-Hydroxyaminothiazolidine-2-thiones break down under analogous conditions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1143–1145, August, 1989.     

Study of the mechanism of recyclization of furans into thiophenes and selenophenes in conditions of acid catalysis. 4. study of the effect of the solvent and direction of reactions of hydrolysis and recyclization of 2,5-dimethylfuran

The kinetics of hydrolysis of 2,5-dimethylfuran and its recyclization into the corresponding thiophene were investigated in water-alcohol medium W R I and 50% ethyl alcohol in the presence of HCl. It was found that the rates of these reactions are a function of both the initial concentration of the acid component and the concentration of water in the alcohol. The rate of hydrolysis is a function of the dilution of the alcohol to a greater degree than the rate of recyclization.See [1] for Communication 3.Scientific-Research Institute of Chemistry at N. G. Chernyshevskii Saratov State University, Saratov 410026. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 624-628, May, 1995. Original article submitted January 30, 1995.     

Reactions involving the formation and recyclization of heterocycles

The reaction of 5-aryl-1,3,4-oxadiazole-2-thiones with hydrazine and hydrazides proceeds with recyclization of the oxadiazole ring to a triazole ring. Depending on the nature of the aryl residue, adducts of 5-aryl-1,3,4-oxadiazole-2-thiones with hydrazine can be isolated in a number of cases. 6-Aryl-2-methyldihydro-1,2,4,5-tetrazine-3-thiones are formed with methylhydrazine as a result of recyclization.See [1] for communication VIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 905–909, July, 1971.     

Synthesis of 4-(Hydroxymethyl)dihydroisoindolium Salts and Their Intramolecular Recyclization

The review discusses intramolecular cyclization of ammonium salts containing a 4-hydroxybut-2- yn-1-yl group in combination with various π⁴-fragments, as well as mechanisms of cyclization and intramolecular recyclization of the resulting 4-(hydroxymethyl)dihydroisoindolium salts and their fused analogs. The process is accompanied by neither ring expansion nor contraction, and a pharmacophoric 1,3-dihydrofuran ring is formed instead of dihydroisoindolium fragment. The effects of electronic and structural factors on the intramolecular cyclization and recyclization processes are considered.     

Study of the effect of annelation on the rearrangement of 1,2-dialkylpyridinium salts by the MO LCAO self-consistent field (SCF) method

The anhydro bases formed from 1,2-dialkylquinolinium (I), 1,2-dialkylisoquinolinium (II), and 2,3-dialkylisoquinolinium (III) salts were calculated within the framework of the π-electron approximation of the MO LCAO self-consistent field (SCF) method. It is shown that, in contrast to II and III, I does not undergo recyclization; annelation of the pyridine ring facilitates recyclization. The recyclization indexes are linked with the aromatic character of the pyridine ring and increase as the aromatic character decreases. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 381–386, March, 1980.     

Structure and ambiphilic reactivity of indolizines. 6. Scope of the isomerizational recyclization of indolizines

The behavior of substituted 6- and 8-nitroindolizines in the isomerizational recyclization reaction has been examined. A novel method of synthesis of 2-acyl-5- and 7-nitroindoles has been developed, by recyclization of 3-acyl-6- and 8-nitroindolizines. The scope of the isomerizational recyclization of indolizines for the synthesis of indoles has been established.For Communication 5, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 758–764, June, 1990.     

Reduction and alkaline hydrolysis of 5-oxoindeno[1,2-b]pyridinium salts

5,9b-Dihydro derivatives of indeno[1,2-b]pyridine were obtained by the reduction of the corresponding 1,2-dimethyl-4-aryl-5-oxoindeno[1,2-b]pyridinium perchlorates. 1,2-Dimethyl-3-ethoxycarbonyl-4-phenyl-5-oxoindeno[1,2-b]pyridinium perchlorate forms in alkaline medium with splitting, recyclization and deamination products.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp 86–89, January, 1987.     

Synthesis of a New Polyheterocyclic System — Pyrazolo[5′,1′:2,3]pyrimido[1,6-<Emphasis Type="Italic">a</Emphasis>]benzimidazole

Cyanoethylhydrazones of 2-aroylmethyl-1H-benzimidazoles undergo recyclization on reaction with trifluoroacetyl anhydride to give 3-aryl-1-cyanoethyl-5-(2-trfluoroacetaminoanilino)pyrazoles. The recyclization products may be cyclized with closing of the benzimidazole ring in two ways: with formation of 1-(5-pyrazolyl)benzimidazoles or 5,6-dihydroderivatives of a new polyheterocyclic system — pyrazolo[5′,1′: 2,3]pyrimido[1,6-a]benzimidazole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1685–1690, November, 2005.     

Recyclization of 2-vinylpyridinium quaternary salts

It is shown that in the reaction of 2-vinylpyridinium quaternary salts with methylammonium sulfite under isomerization recyclization conditions a water molecule adds initially to the double bond of the vinyl substituents, after which the resulting carbinols undergo recyclization to N-alkylaniline derivatives. The reaction is accompanied by a parallel process involving dealkylation of the pyridine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 229–232, February, 1982.     

Isomerizational recyclizat10n of pyridylethylated cyclanones. A new method for the synthesis of substituted polyhydroacridines and their analogs

Mixtures of cis and trans isomers of 1,2,3,4,9,10,9a,10a-octahydroacridines are formed in the recyclization of quaternary salts of pyridylethylated alicyclic ketones. The 1,2,3,4,9,10-hexahydro-1-acridone skeleton was obtained in the recyclization of the quaternary salt of pyridylethylated dimedone, whereas a noncyclic amino ketone was isolated from the products of recyclization of the quaternary salt of pyridylethylated camphor. The structures of the compounds obtained were confirmed by means of data from the IR, UV, and PMR spectra.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1374–1380, October, 1982.     

Synthesis of bicyclic Β-oxo nitrones: Derivatives of 6-azabicyclo[3.2.1] octane and their reactions with nucleophilic reagents

It was shown that the recyclization of enamino ketones (hydrogenated derivatives of benzimidazole), which proceeds in an acid medium, leads to 6-azabicyclo[3.2.1]-oct-6-en-8-ones. The reactions of these with nucleophilic reagents proceed primarily at the carbonyl group, while reactions with an excess of organometallic reagents with subsequent oxidation lead to stable nitroxide radicals (derivatives of 6-azabicyclo[3.2.1]octane).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 682–686, March, 1991.     

Recyclization of tosylamino derivatives of 2-aryl-5-benzylfuran to give indoles through two alternative pathways

The recyclization of derivatives of 2-aryl-5-benzylfuran containing a tosylamine fragment to give indoles has been studied. If the tosylamino group is in the ortho position of the aryl substituent, the recyclization proceeds such that the furan ring may be seen as a formal equivalent of a 1,3-diketone. If, on the other hand, the tosylamino group is in the ortho positions of both the aryl and benzyl substituents, the recyclization proceeds through a pathway, in which the furan ring acts as the equivalent of a 1,4-dicarbonyl compound. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 376-382, March, 2009.     

Transformations of sym-octahydroxanthene-1,8-diones and 1,8-dioxo-sym-octahydroxanthylium salts in recyclization under the influence of amines

The chemical behavior of 9-R-sym-octahydroxanthene-1,8-diones and salts based on them in recyclization reactions under the influence of amines was studied. The effect of the basicity of the amines on the direction of recyclization was established. A method is proposed for the single-stage synthesis of sym-octahydroacridine-1.8-dione oximes based on 1,8-dioxo-sym-octahydroxanthenes. Conditions were worked out for the oxidation of sym-octahydroxanthene-1,8-diones and N-R-decahydroacridinediones to the corresponding salts. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 32–38, January, 2006.     

Study of the mechanism of recyclization of furans into thiophenes and selenophenes in conditions of acid catalysis. 6. Experiments with labeled atoms. Quantum chemical calculations of intermediates of recyclization and hydrolysis

The reaction of 2-methyl-5-R-furans (R=Me, Bu, 2,2-pentyl-2-methylpentyl) with H₂ ¹⁸O was investigated. Furans and the corresponding 2,5-alkanediones containing the¹⁸O isotope were obtained. The general characteristics of the recyclization and isotope exchange reactions were established. A kinetic study of recyclization of 2,5-dimethylfuran with¹⁶O and¹⁸O into 2,5-dimethylthiophene was conducted. A reverse kinetic isotope effect was found. The schemes of the mechanisms of these processes were refined based on the experimental data and quantum-chemical calculations of the recyclization and hydrolysis intermediates.See [1] for Communication 5.Scientific-Research Institute of Chemistry, N. G. Chernyshevskii Saratov State University, Saratov 410026. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1035–1042, August, 1997.     

Synthesis and Oxidation of 1,3-Diamino- and 1-Amino-3-azidoindazoles

The amination of 3-amino- and 3-azidoindazoles by hydroxylamine-O-sulfonic acid in an alkaline medium yields previously unreported 1,3-diamino- and 1-amino-3-azidoindazoles. These products undergo slow autoxidation in chloroform solution to give 4-aminobenzo-1,2,3-triazine. The action of formic or acetic acid on 3-amino-1-benzylideneaminoindazole leads to recyclization and formation of 3-amino-2-benzylindazole, which is also formed in the catalytic hydrogenation of 1-benzylamino-3-nitro- and 1-benzylideneamino-3-nitroindazoles.     

Formation and recyclization of heterocycles

Thiorhodanine is recyclized to 1,2,4-triazole-3-thione by reaction with hydrazine. The intermediate recyclization products were identified. 4-Iminothiazolidone is recyclized to 1,2,4-triazol-3-one by reaction with hydrazine, 1,3-oxazolid-4-one-2-thione forms 2-hydrazonooxazolid-4-one by reaction with hydrazine in neutral solvents. The intermediate transformation products were isolated and indicate that the reaction proceeds as a recyclization of the starting oxazolidone under the influence of hydrazine.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 39–41, January, 1971.     

Recyclization of 2-imino-2H-1-benzopyrans by the action of nucleophilic reagents 4. Use of 2-(N-aroylhydrazono)coumarin-3-carboxamides for the synthesis of 3-(1,3,4-oxadiazol-2-yl)coumarins

A new method for the synthesis of 3-(1,3,4-oxadiazol-2-yl)coumarins is proposed. It is based on the recyclization of 2-(N-aroylhydrazono)coumarin-3-carboxamides, which are readily obtained by the reaction of 2-iminocoumarin-3-carboxamides with arenecarboxylic hydrazides in an acidic medium. Advantages of the given method over alternative synthetic schemes were shown. Proposals on the mechanism of reaction were made.For Communication 3, see [1].Ukrainian Pharmaceutical Academy, Khar'kov 310002. Khar'kov State University, Khar'kov 310077, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 190–193, February, 1999.