Synthesis of 3,1-Benzoxazines from N-Substituted ortho-(Cycloalk-1-enyl or alk-2-en-2-yl)anilines

New derivatives of 3,1-benzoxazine have been synthesized by the cyclization of RCO-substituted at the nitrogen atom (R = OEt, Me, NH₂) ortho-(cycloalk-1-enyl or alken-1-yl)anilines under mild conditions.     

Oxidation of N-acyl-2-(cycloalk-1-enyl)anilines with ozone and hydrogen peroxide

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH₄ gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me₂S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H₂O₂ in HCOOH affords -(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H₂O₂ in the presence of Na₂WO₄ and H₃PO₄ gives 3,1-benzooxazine in high yield.     

Cyclization of ortho-(alk-2-enyl)anilines under the action of iodine

The reaction of ortho-(cyclohex-2-enyl)aniline with I₂ in nonpolar and polar solvents affords predominantly 1-iodohexahydrocarbazole and azatricyclotridecatriene, respectively. Under analogous conditions, 4-methyl-2-(1-methylbut-2-en-1-yl)aniline undergoes cyclization to form exclusively products with quinoline structures regardless of the solvent used.     

Chemistry of naphthazarin derivatives 13. Conformational analysis of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones by quantum chemistry methods

The molecular structures of various conformers of 2-hydroxy-1,4-naphthoquinone; 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones; 2,5,8-trihydroxy-1,4-naphthoquinone; and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4-naphthoquinones were studied by density functional theory (B3LYP/6-31(d), B3LYP/6-31(d, p)) and ab initio (MP2/6-31G, MP2/6-31(d)) methods. The strengths of the intramolecular hydrogen bonds formed by the β-hydroxy group with the O atom at C(1) and with the double bond π-electrons of the alkenyl substituents in the quinonoid rings were estimated. The compounds studied mainly exist as rotamers with the former-type hydrogen bonds. The splitting of the quinonoid bands of the stretching vibrations of the β-hydroxy group in the IR spectra of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4-naphthoquinones in hexane solutions is due to the existence of rotamers formed upon internal rotation of the alkenyl substituent. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1667–1673, October, 2006.     

Intramolecular cyclization ofortho-(cyclohex-2-enyl)anilines. Modified synthesis of ellipticine

It was found that the reactions of arylamines with 3-bromocyclohexene afforded hydrocarbazole compounds in 64–78% yields. A modified procedure for the synthesis of antitumor alkaloid ellipticine was proposed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2144–2149, November, 1999.     

Amidines: synthesis from o-alkenylanilines and cyclization in polyphosphoric acid

Condensation of 2-[(E)-pent-3-en-2-yl]-4-, 2-[(E)-pent-2-en-2-yl]-4-, or 2-(cyclopent-1-enyl)-6-methylaniline with 1-chloro-1-(N-methylimino)- or 1-chloro-1-(N-phenylimino)ethane affords the corresponding amidines. Cyclization of the N-methylimino derivatives in polyphosphoric acid gives 3,4-dihydroquinazolines in high yields.     

Synthesis of indolines and tetrahydroquinolines fromortho-(alk-2-enyl)anilines

Intramolecular cyclization ofo-alkenylanilines was studied. Heating ofo-(cyclopent-2-en-1-yl) arylammonium chlorides at 200–220 °C yields cyclopenta[b]indolines as the main reaction products. Cyclization of 4-methyl-2-(pent-3-en-2-yl)aniline under the same conditions gave a mixture of indolines and tetrahydroquinolines. An alk-1-enylarylamine containing a vinylic double bond does not form cyclization products on the nitrogen atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 975–978, May, 1999.     

Chemistry of naphthazarin derivatives. 12. Synthesis and investigation of prototropic tautomerism of 3-(alk-1-enyl)-2-hydroxynaphthazarins

Substituted 3-(alk-1-enyl)-2-hydroxynaphthazarins were synthesized. According to data from IR spectroscopy, these compounds exist in organic aprotic solvents as mixtures of tautomeric 1,4-naphthoquinonoid forms. The compositions of tautomeric mixtures were quantitatively determined. The effects of the structure of the alkenyl substituent and the polarity of the solvent on the tautomeric equilibrium were qualitatively estimated.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2519–2525, November, 2004.     

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.     

Synthesis of 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane) from 6-(cyclopent-1-enyl)-2-methylaniline

The reaction of 6-(cyclopent-1-enyl)-N-ethoxycarbonyl-2-methylaniline with Br₂ or its reaction with NH₃ followed by the reaction with Br₂ afforded 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane), respectively.     

An unexpected reaction of 2-(cyclopent-2-enyl)aniline hydrochloride with dimethyldioxirane

An unusual direction of the reaction of 2-(cyclopent-2-enyl)aniline hydrochloride with dimethyldioxirane was found: the formation of two isomeric products,viz., 3- and 6-chloro-2-(cyclopent-2-enyl)anilines, was observed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1654–1655, August, 1998.     

A facile synthesis of 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones by the reaction of 1,1-dimethylethyl 2-isocyanobenzoates with N,N-dialkyliminium iodides

A convenient synthetic approach to 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones has been developed. Thus, 1,1-dimethylethyl 2-isocyanobenzoates, which can be readily prepared from 2-nitrobenzoic acids by a simple four-step sequence, react with N,N-dialkyliminium iodides without using any catalysts under mild conditions to give the desired products in generally fair-to-good yields.     

A facile synthesis of 2-(N-alkylamino)-pyrimidin-4-one derivatives

Substituted 2-(N-alkylamino)-pyrimidin-4-ones were synthesized from N-alkyl β-amino acid esters starting with guanidinylation using Pbf-activated thiourea. The six-membered pyrimidinones were obtained in good yields via intramolecular cyclization during TFA cleavage of the Pbf protecting group.     

Convenient and efficient stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates using iron(III) or indium(III) chloride

The stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates has been achieved efficiently and in high yields and in short reaction times from Baylis-Hillman adducts, 3-hydroxy-2-methylene-alkanoates, by treatment with FeCl₃ or InCl₃ at room temperature.     

A facile protocol for the synthesis of mono-N-methyl anilines via formimidate intermediates

A general procedure for the preparation of mono-N-methyl anilines has been developed with excellent yields. This protocol relies on a NaBH₃(OAc) reduction of formimidate intermediates that are quantitatively generated by treatment of primary substituted anilines with triethyl orthoformate under the catalysis of MCM-41-SO₃H mesoporous zeolite. The newly developed procedure was facile, efficient, and environmentally benign.     

Synthesis of 2-oxazolidinones from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol

A series of isomeric 2-oxazolidinones has been synthesized from (1S, 2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 579–584, April, 2006.     

Synthesis ofN-(3-azido-2-nitroxypropyl)-,N-(2,3-diazidopropyl)-, andN-(2-azido-3-methoxypropyl)-N-alkylnitramines

N-(3-Azido-2-nitroxypropyl)-N-alkylnitramines andN-(2,3-diazidopropyl)-N-alkylnitramines were prepared by nitration and azidation ofN-alkyl-N-(2-hydroxy-3-chloropropyl)sulfamates andN-(3-azido-2-hydroxypropyl)-N-alkylsulfamates. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 206–208, January, 1999.     

Synthesis of partially saturated N-substituted 4H-3,1-benzothiazine-2(1H)-thiones

Summary Acid-catalyzed reaction of 2-arylidenecyclohexanones1 with N-substituted dithiocarbamic acids2 gave open-chain addition products3 and4. Dehydration of3 and4 afforded only one of the three possible isomeric N-substituted 4H-3,1-benzothiazine-2(1H)-thiones5 and6.

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Synthese von partiell gesättigten N-substituierten 4H-3,1-Benzothiazin-2-(1H)-thionen

Zusammenfassung Die säurekatalysierte Reaktion von 2-Arylidencyclohexanonen1 mit N-substituierten Dithiocarbaminsäure2 ergab die offenkettigen Additionsprodukte3 und4. Die Dehydratation von3 und4 führte ausschließlich zu einem der drei möglichen N-substituierten 4H-3,1-Benzothiazin-2(1H)-thion-Isomeren5 und6.

     

Quantum chemical study of the transformation of 2-(N-alkylamino)-3-(indol-1-yl)-and 2-(N-alkylamino)-3-(indol-3-yl)maleimides by protic acids: Tandem hydride transfer/cyclization mechanism

The geometric parameters, the charge distribution, and the energetics of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides and their conjugated acids were studied by density functional theory calculations at the B3LYP/6-31G(d) level. The mechanism of the tandem hydride transfer/cyclization sequence, which occurs after protonation of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides, was analyzed. The investigation of the potential energy surface for the tandem hydride transfer/cyclization of the iminium cation that formed upon protonation revealed that the hydride transfer followed by intramolecular cyclization at position 7 of the indole fragment in N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)maleimide is the preferable process, unlike alternative intramolecular cyclization involving the cationic center at the C(2) atom of the indole fragment and the benzene ring of the N-ethylaniline fragment of the indoleninium cation in N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimide. A study of the key intermediates of the assumed reaction mechanism demonstrated that these intermediates are actually stationary points on the potential energy surface (minima and transition states). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2069–2073, December, 2006.     

A new method for the synthesis of 3-aryl-6-(2-pyrrolyl)pyridazines

A new method for the synthesis of 3-halo-6-(N-tosyl-2-pyrrolyl)pyridazine 7 was developed. Suzuki cross-coupling reactions of 7 with arylboronic acids and in situ de-tosylation gave a variety of novel 3-aryl-6-(2-pyrrolyl)pyridazines. It found that protection of the pyrrolyl moiety was necessary for efficient coupling reaction.