A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Hydrolysis of 7,7-Substituted Derivatives of 3-tert-Butyl-3,4-dihydro-2H-thiazolo-[3,2-a][1,3,5]triazin-6(7H)-one

Alkaline hydrolysis of 3-tert-butyl-7,7-bis(hydroxymethyl)-3,4-dihydro-2H-thiazolo[3,2-a][1,3,5]-triazin-6(7H)-one can occur in three directions: with cleavage of the tetrahydrotriazine ring, with cleavage of the thiazolidine ring, and also with opening of both rings. Depending on the process conditions, either the hydrolysis product corresponding to the first direction or the hydrolytic decomposition products corresponding to the second and third directions can be obtained in preparative quantities. Hydrolysis of 3,3′-di-tert-butyl-3′,4′-dihydro-2′ H-spiro[(perhydro-1,3-oxazine)-5,7′-thiazolo[3,2-a][1,3,5]triazin]-6′-one in (NH₄)₂CO₃ solution occurs in two steps: in the first step, cleavage of the tetrahydrotriazine ring occurs; and in the second step, opening of the perhydrooxazine ring occurs. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1089–1097, July, 2005.     

Reactions of 3-hydroxy-1,2-dihydroquinazolin-4-ones with aldehydes

The reactions of 3-hydroxy-2-(2-hydroxyalkyl)- [or (2-hydroxyaryl)]-1,2-dihydro-quinazolin-4-ones with formaldehyde or acetaldehyde afford 1,3-oxazino[3,4-a]quinazolin-4-one derivatives. The reactions with other aldehydes RCHO and 3-hydroxy-2-R′-1,2-dihydroquinazolin-4-ones can give 3-hydroxy-2-R-1,2-dihydroquinazolin-4-ones, 2-substituted quinazolin-4-ones, or dianthranilide. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2523–2526, December, 1998.     

Reactions of cyclic 1,3-dicarbonyl compounds with 1,2(1,4)-dihydro-1-methyl-2(4)-methylene-N-heterocycles. A new access to 6,12-methano-dibenz[d,g]-[1,3]oxazocinones

Summary The enamine-type methylene-N-heterocycles1–5 react with cyclic 2-ethoxymethylene-1,3-dicarbonyl compounds6 to give 2-[2-(hetarylidene)ethylidene]-1,3-dicarbonyl compounds7–14. The result of the reactions between 1,2-dihydro-1-methyl-2-methylene-quinoline (1a) and cyclic 1,3-dicarbonyl compounds depends on the nature of the dihydro intermediatesA/B. Dehydrogenation of keton intermediatesA results in 2-(1,2-dimethyl-4(1H)-quinolylidene)-1,3-dicarbonyl compounds17–21. Enol intermediatesB with 6-membered dicarbonyl ring form 6,12-methano-dibenz-[d,g][1,3]oxazocinones22–25.¹H NMR spectra and X-ray structure analysis prove the structure of23.

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Reaktionen cyclischer 1,3-Dicarbonylverbindungen mit 1,2(1,4)-Dihydro-1-methyl-2(4)-methylen-N-heterocyclen. Ein neuer Zugang zu 6,12-Methano- dibenz[d,g][1,3]oxazocinonen

Zusammenfassung Aufgrund ihres Enamincharakters reagieren die Methylen-N-heterocyclen1–5 mit cyclischen 2-Ethoxymethylen-1,3-dicarbonylverbindungen6 zu den 2-[2-(Hetaryliden)ethyliden]-1,3-dicarbonylverbindungen7–14. Das Ergebnis der Reaktionen zwischen 1,2-Dihydro-1-methyl-2-methylen-chinolin (1a) und cyclischen 1,3-Dicarbonylverbindungen hängt von der Natur der zwischenzeitlich entstehenden DihydroverbindungenA/B ab. Die Intermediat-KetoneA gehen durch Dehydrierung während der Reaktion in die 2-(1,2-Dimethyl-4(1H)chinolyliden)-1,3-dicarbonylverbindungen17–21 über. Die Intermediat-EnoleB mit sechsgliedrigem Dicarbonylring bilden in intramolekularer Reaktion die 6,12-Methano-dibenz[d,g][1,3]oxazocinone22–25, deren Struktur am Beispiel der Verbindung23 durch¹H-NMR sowie durch Röntgenkristallstrukturanalyse bewiesen wird.

     

Study of the Products of Iodocyclization of 4-Allyl-5-phenyl-1,2,4-triazole-3-thione

The interaction of 4-allyl-5-phenyl-1,2,4-triazole-3-thione with iodine proceeds with the formation of a mixture of 6-iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole and 6-iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine. The structures of the cyclization products obtained were established on the basis of the ¹H NMR spectra of their dehydroiodinated derivatives. 6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole, 3-phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine, and 3-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3-thiazine are formed on eliminating HI from the cyclization products.     

Intramolecular cyclization ofN-acetyl-6-(cyclopent-1-enyl)-2-methylaniline

N-Acetyl-6-(cyclopent-1-enyl)-2-methylaniline underwent intramolecular cyclization in the presence of HCl in CH₂Cl₂ at 20°C to form 2,8-dimethylspiro[cyclopentane-1,4′-4′H-3,1-benzooxazine] in quantitative yield. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 398–400, February, 1999.     

Reactions of 2-(4,5-dihydro-3-furyl)-1,3-diphenyl-1,3-diaza-2λ<Superscript>3</Superscript>-phospholidine and 4,5-dihydro-3-furylphosphonous diamides with nitrile imines

Reactions of 2-(4,5-dihydro-3-furyl)-1,3-diphenyl-1,3-diaza-2λ³-phospholidine (1) with nitrile imines are multistep processes involving cleavage of one P-N bond of the diazaphospholidine ring to form substituted 5-(2-chloroethyl)-4-(N,N′-diphenylethylenediamino)-1,4-dihydro-1,2,4λ⁵-diazaphosphorines 4 as final products. Analogs of phospholidine 1, namely, 4,5-dihydro-3-furylphosphonous dipiperidide and dimorpholide, react with C,N-diphenylnitrile imine with retention of both P-N bonds to give 5-(2-hydroxyethyl)-1,2,4-diazaphosphorinium chlorides. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1590–1593, July, 2005.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Synthesis and fungicidal activities of 1-[(2,2-diaryl-1,3-dioxolan-4-yl)methyl]-1H-azoles

Ketalization of benzophenones with epichlorohydrin or 3-chloropropane-1,2-diol gave 2,2-diaryl-4-chloromethyl-1,3-dioxolanes, which were used to alkylate sodium salts of imid-azole or 1,2,4-triazole. The resulting 1-[(2,2-diaryl-1,3-dioxolan-4-yl)methyl]-1H-azoles exhibit high fungicidal activities. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 940–944, May, 2007.     

Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones from various 2-dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3-oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step “one pot” synthesis under controlled microwave irradiation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–417, February, 2008.     

Syntheses of angular condensed ring systems combining a benzodiazepinic,or benzothiazepinic,and a coumarinic moiety

Summary The title compounds were prepared via intermediates resulting from reactions of 3-formyl-4-hydroxycoumarin (1) witho-phenylenediamine,o-aminophenol, ando-aminothiophenol, respectively. Intramolecular ring closures were effected between the free hydroxy and amino or thiol groups.

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Synthese von kondensierten Heterocyclen, die ein Benzodiazepin oder Benzothiazepin angular mit dem Coumarinsystem verknüpfen

Zusammenfassung Die Titelsubstanzen werden über Zwischenverbindungen erhalten, die aus der Reaktion von 3-Formyl-4-hydroxycoumarin (1) mito-Phenylendiamin,o-Aminophenol undo-Aminothiophenol enstehen. Der Ringschluß erfolgt über die freie Hydroxylgruppe und der Amino- bzw. Thiolgruppe.

     

Direct diastereoselective introduction of l-menthol residue into 1,2,4-triazin-5(4H)-one

The reaction of 3-phenyl-1,2,4-triazin-5(4H)-one (1) with l-menthol in the presence of aliphatic acid anhydrides results in (6S)- and (6R)-1-acyl-6-(l-menth-3-yl)-1,6-dyhydro-3-phenyl-1,2,4-triazin-5(4H)-ones. The reaction is diastereoselective with predominant formation of (6S)-isomers. The reaction diastereoselectivity increases with enhancement of the steric hindrance in the vicinity of the reaction center of the azine.     

The behavior of <Emphasis Type="Italic">p</Emphasis>-bis{3-[N-(3-chloro-buten-2-yl)pyrrolidinio(piperidinio or morpholinio)]propyn-1-yl}benzene dichlorides in an aqueous base medium

In aqueous base medium p-bis{3-[N-(3-chlorobuten-2-yl)pyrrolidinio (piperidinio or morpholinio)]-propyn-1-yl}benzene dichlorides undergo a two-way dehydrochlorination-cyclization reaction to form benzo[5,6-a:5′,6′-c]bis(2,2-tetramethylene- or -2,2-pentamethylene-4-methylisoindolinium) and benzo-[5,6-a:5′,6′-c]bisspiro(4-methylisoindoline-2,4′-morpholinium) dichlorides. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 546–549, April, 2009.     

Synthesis of 4-thia analogues of isoquinoline alkaloids

Summary (±)-4-Thiacarnegin (3) was synthesized by reaction of 6,7-dimethoxy-3-methyl-2H-1,3-benzothiazinium iodide (2) with methyl magnesium iodide, thereby opening a new synthetic route to 4-substituted dihydro-2H-1,3-benzothiazines. Compound3 was also obtained by reduction of 6,7-dimethoxy-3,4-dimethyl-2H-1,3-benzothiazinium iodide (5). In a similar way, reduction of the quaternary salts9 a–c afforded the (±)-4-thia analogues of cryptostilin-I, -II and -III (10 a–c). The isomers of the former compounds (12 a–c) were also synthesized by reduction of the 4H-1,3-benzothiazinium salts11 a–c.

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Synthese von 4-Thiaanalogen von Alkaloiden mit Isochinolingerüst

Zusammenfassung Aus 6,7-Dimethoxy-3-methyl-2H-1,3-benzothiaziniumjodid (2) wurde mit Methylmagnesiumjodid (±)-Thiacarnegin (3) dargestellt. Diese Reaktion bietet ein neues Verfahren für die Synthese von 4-substituierten Dihydro-2H-1,3-benzothiazinen.3 wurde auch durch Reduktion von 6,7-Dimethoxy-3,4-dimethyl-2H-1,3-benzothiaziniumjodid (5) erhalten. Die Reduktion der quartären Ammoniumsalze9 a–c ergab ebenfalls die Cryptostillin I-, II-, III-(±)-4-thiaanalogen Verbindungen (10 a–c). Reduktion der 4H-1,3-Benzothiazinium-Salze11 a–c lieferte die entsprechenden Isomeren12 a–c der obengenannten Verbindungen.

     

Reaction of 2-(4,5-dihydrofur-3-yl)-1,3-diphenyl-1,3-diaza-2-2λ3-phospholidine withC,N-diphenylnitriliminewithC,N-diphenylnitrilimine

The reaction of 2-(4,5-dihydrofur-3-yl)-1,3-diphenyl-1,3-diaza-2λ³-phospholidine withC,N-diphenylnitrilimine is a multistage process, in the course of which the 1,2,4-diazaphosphorine ring is formed and both rings of the initial organophosphorus compound are cleaved. 5-(2-Chloroethyl)-4-(N,N′-diphenylethylenediamino)-1,3-diphenyl-1,4-dihydro-1, 2,4λ⁵-diazaphosphorine was obtained as the final product. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 125–128, January, 2000.     

Oxalylation of the 3-oxo-<Emphasis Type="Italic">N</Emphasis>-phenyl-3-R-propanethioamides

Oxalylation of 3-oxo-N-phenyl-3-R-propanethioamides in aprotic solvents in the temperature range from −40°C to +20°C results in 4-acyl-5-phenylamino-2,3-dihydrothiophene-2,3-diones and 2-(2-oxo-2-R-ethylidene)-3-phenyl-1,3-thiazolidine-4,5-diones, while in the presence of potassium carbonate, potassium 4-acyl-2,3-dioxo-1-phenyl-2,3-dihydro-1H-pyrrole-5-thiolates are formed.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 757-760, March, 2005.     

[3,4]-annulated pyrroles 1. Polynuclear heterocyclic systems based on pyrrolo[3,4-d]pyrimidine-2,4-dione

The intramolecular electrophilic substitution in 6-functionalized 1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-diones was used for the synthesis of pyrimido[4′,5′:3,4]-pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione, pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,2,4]benzo-triazine-8,10(7H,9H)-dione, and 2H-pyrimido[4′,5′:3,4]pyrrolo[1,2-a]indole-2,4,11(1H, 3H)-trione derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2180–2185, December, 2006.     

Synthesis of 2-acetyl-3-methyl-4H-1,4-benzothiazine and its derivatives

Summary 2-Aminothiophenol (1) reacts with 3-chloro-2,4-pentanedione (2) in the presence of pyridine to form 2-acetyl-3-methyl-4H-1,4-benzothiazine (3) in high yields. Reaction of3 with hydrazine gives 4-(2-aminophenylthio)-3,5-dimethylpyrazole (5). Condensation of3 with 4-nitrobenzaldehyde yields the corresponding Schiff base7. Hydroxylamine with benzothiazine3 affords 3,9a-dimethyl-3a, 9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazine (8).

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Synthese von 2-Acetyl-3-methyl-4H-1, 4-benzothiazin und seinen Derivaten

Zusammenfassung 2-Aminothiophenol (1) reagiert mit 3-Chlor-2,4-pentandion (2) in Anwesenheit von Pyridin unter Bildung von 2-Acetyl-3-methyl-4H-1,4-benzothiazin (3) in sehr hoher Ausbeute. Benzothiazin3 kondensiert mit Hydrazin zu 4-(2-Aminophenylthio)-3,5-dimethylpyrazol (5), dessen Aminogruppe reagiert mit 4-Nitrobenzaldehyd zu einer Schiffschen Base (7), die spektroskopisch charakterisiert wurde. Benzothiazin3 mit Hydroxylamin ergibt 3,9a-Dimethyl-3a,9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazin (8). Die Stereochemie der letztgenannten Verbindung wurde ermittelt.

     

Synthese und Reaktionsverhalten von 6-sec-Amino-1,3-thiazin-2-thionen

The title compounds3 have been prepared by ring transformation reactions of the isomeric 2-sec-amino-1,3-thiazine-6-thiones1 via ring-opening products2 and by special cyclocondensation reactions with thiocarboxamides8, and with iminium salts10, starting from 2,2-dichlorovinyl ketones6 in all cases. The pathways differ specifically in scope and limitations. On the other hand the intermediates2 react with alkylating agents to 2,6-di-sec-amino-1,3-thiazinium salts4, which are also available via alkylation of3 to 2-methylthio-1,3-thiazinium salts11 and aminolysis. Moreover,11 serve as useful precursors for other 1,3-thiazine derivatives by nucleophilic methylthio displacement (examples12).