4H-3,1-benzoxazines. 2. Synthesis of 2,4-substituted 1,2-dihydro-4H-3,1-benzoxazines

The reactions of o-aminophenylcarbinols with carbonyl compounds have been studied. Optimum conditions have been developed for the synthesis of 2-(5-X-2-furyl)-1,2-dihydro-4H-3,1-benzoxazines. It was found that 2,2-disubstituted 1,2-dihydro-4H-3,1-benzoxazines are unstable and are converted upon heating in the presence of acylating agents to 4H-3,1-benzoxazines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 842–847, June, 1988.     

Synthesis and rearrangement of 4-imino-4H-3,1-benzoxazines

Summary N-Acylanthranilamides react with dibromotriphenylphosphorane in the presence of triethylamine as HBr captor to give 4-imino-4H-3,1-benzoxazines in good yields. If the reaction is carried out without acid acceptor, N-acetylanthranilamides yield 2-methyl-4-quinazolones, whereas N-benzoylanthranilamides give 2-phenyl-4-imino-4H-3,1-benzoxazines. It has also been found that 2-methyl-4-imino-4H-3,1-benzoxazines rearrange under the influence of HCl or HBr into the respective 2-methyl-4-quinazolones; 2-phenyl-4-imino-4H-3,1-benzoxazines, however, do not undergo such a rearrangement.

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Synthese und Umlagerung von 4-Imino-4H-3,1-benzoxazinen

Zusammenfassung Die Umsetzung von N-Acyl-anthranilsäure-amiden mit Triphenyldibromphosphoran in Gegenwart von Triethylamin als HBr-Akzeptor führt mit guten Ausbeuten zu 4-Imino-4H-3,1-benzoxazinen. Wird die Reaktion ohne säurebindendes Mittel durchgeführt, dann entstehen aus N-Acetyl-anthranilsäure-amiden 2-Methylchinazolone-4, jedoch erhält man aus N-Benzoylanthranilsäure-amiden 2-Phenyl-4-imino-4H-3,1-benzoxazine. 2-Methyl-4-imino-4H-3,1-benzoxazine erleiden unter dem Einfluß von HBr oder HCl eine Umlagerung in entsprechende 2-Methylchinazolone-4, während 2-Phenyl-4-imino-4H-3,1-benzoxazine zu einer solchen Umlagerung nicht befähigt sind.

     

4-Hydroxy-2-quinolones. 112. Reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with active methylene compounds

The reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with malononitrile in dry pyridine leads to 1-hydroxy-3,6-dioxo-4,6-dihydro-3H-pyrimido[1,2-a]quinoline-5-carbonitrile. Acetoacetic and cyanoacetic esters under analogous conditions form anilides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid while diethyl malonate gives N,N′-di-2-carboxyanilides of malonic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 2007.     

Studies of 4H-3,1-benzoxazines

Bromination of 2,4-substituted 1,2-dihydro-4H-benzoxazines with bromine in acetic acid was conducted. It was shown that either the corresponding 6,8-dibromo-1,2-hydrobenzoxazines or the products of their dehydrogenation — 6,8-dibromobenzoxazines, are primarily formed as a function of the structure of the dihydrobenzoxazine and the concentration of bromine in the reaction mixture. The structure of 6,8-dibromo-2-(5-nitrofuryl-2)-4, 4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine was investigated by XSA. A stacking interaction between the nitrofuran fragment of one molecule and the condensed benzene ring of the other was detected in the crystal.See [1] for Communication 12.Kuban State Technological University, Krasnodar 350072. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1391–1397, October, 1997.     

Investigation of 4H-3,1-benzoxazines

The alkylation and acylation of 2,4-disubstituted 1,2-dihydro-4H-3,1-benzoxazines were used to obtain N-methyl and N-acetyl derivatives of these compounds for the first time.¹H NMR was used to reveal several conformational features of these compounds relative to their donor—acceptor properties at positions 2, 3, and 4 of the heterocycle.Communication 11, see [2].Kuban State Technological University, 350072 Krasnodar. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 841–846, June, 1997.     

Research on 4H-3,1-benzoxazines. 8. Synthesis and properties of 4H-3,1-benzoxazinium chlorides

A mechanism for the acylation of substituted o-aminophenylcarbinols with carboxylic acid chlorides and the formation of 2-alkyl(aryl, furyl)-4H-3,1-benzoxaziniun chlorides is proposed. The nitration and introduction of a sulfur atom into the heterocyclic ring of the 4H-3,1-benzoxazinium salts were investigated.For communication 7 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 537–541, April, 1993.     

2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one: Synthesis and investigation of serine protease inactivation

Summary 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one was prepared by thermal treatment of 2-(3-benzoylthioureido)-4,5-dimethoxybenzoic acid and by benzoylation of 2-amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one. The inactivation of chymotrypsin and human leukozyte elastase by the title compound and 2-benzoylamino-4H-3,1-benzoxazin-4-one is reported.

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2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on: Synthese und Untersuchung der Inaktivierung von Serin-Proteasen

Zusammenfassung 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on wurde durch thermische Behandlung von 2-(3-Benzoylthioureido)-4,5-dimethoxybenzoesäure und durch Benzoylierung von 2-Amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on hergestellt. Über die Inaktivierung von Chymotrypsin und humaner Leukozyten-Elastase durch die Titelverbindung und 2-Benzoylamino-4H-3,1-benzoxazin-4-on wird berichtet.

     

Synthesis and structure of 1-substituted 1-Oxo-1,2-dihydro-4H-3,1-benzoxaphosphorins

1-X-1-Oxo-1,2-dihydro-4H-3,1-benzoxaphosphorins (X = CH₂Cl, Ph, and OH) were obtained by reacting ortho-(butoxymethoxymethyl)phenylmagnesium bromide with derivatives of chloromethylphosphonic and chloromethylphosphinic acids, followed by intramolecular alkylation. X-Ray diffraction was used to study the molecular and crystalline structure of one of these compounds (with X = OH).Institute of Physiologically Active Substances, Russian Academy of Sciences, 142432 Chernogolovka. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2174–2180, September, 1992.     

4H-3,1-benzoxazoles. 4. Examination of the formation of 1,2-dihydro-4h-3,1-benzoxazines using tagged atoms

A mechanism is proposed for the formation of 4,4-diphenyl-1,2-dihydro-4H-3,1-benzoxazines, which has been proved by introducing a ¹⁷O/¹⁸O isotopic label into the starting 2-aminophenyldiphenylmethanols and carbonyl compounds. ¹⁷O NMR and mass spectrometry show that the 3,1-benzoxazine ring contains the oxygen atom from the alcohol group in the starting 2-aminophenyldiphenylmethanol.For Communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1670–1673, December, 1988.     

Synthesis of 2-amino-4H-3,1-benzoxazines and 2-amino-4H-3,1-benzothiazines by the rearrangement of <Emphasis Type="Italic">o</Emphasis>-cyclopropylphenylureas and <Emphasis Type="Italic">o</Emphasis>-cyclopropylphenylthioureas

Syntheses are reported for 2-cyclopropylphenylureas and 2-cyclopropylphenylthioureas and the behavior of these compounds was studied under conditions for the acid-catalyzed opening of the cyclopropyl ring. Upon the action of concentrated sulfuric acid or trifluoroacetic acid, these ureas and thioureas can undergo rearrangement to the corresponding 3,1-benzoxazines and 3,1-benzothiazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 115–126, January, 2008.     

Synthesis of 1,2-dihydro-4H-3,1-benzoxazine derivatives via ZnCl2 catalyzed cyclocondensation reaction

A short and facile synthesis of a series of 1,2-dihydro-4H-3,1-benzoxazine derivatives was accomplished in moderate to good yields via the novel cyclocondensation of substituted o-aminobenzonitrile with aldehydes or ketones catalyzed by ZnCl₂.     

New Pathway to the Synthesis of Substituted 4H-3,1-Benzoxazines

The intramolecular rearrangement of N-acyl-2-cyclopropylanilines by the action of protic acids gives substituted 4H-3,1-benzoxazines. The reaction proceeds in high yield through the formation of benzoxazine precursors, namely, the corresponding 3,1-benzoxazinium ions, which are stable in acid solution. N-Acylamino-2-alkenylbenzenes, in which the double bond of the alkyl chain is conjugated with the benzene ring, are capable of undergoing a similar rearrangement.     

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.     

Effect of p-substitution on the spectroscopic properties of 1,2-dihydro-4H-2-phenyl-3,1-benzoxazines

A series of 1,2-dihydro-4H-2-phenyl-3,1-benzoxazines (I) were obtained by condensation of o-aminobenzyl alcohol and substituted benzaldehyde. The effect of p-substitution on their spectroscopic properties was investigated by uv and mass spectroscopy.     

4H-3,1-Benzoxazin-4-ones methoxy-substituted 2-(2-arenesulfonylaminophenyl)-4H-3,1-benzoxazin-4-ones

Methoxy-substituted 2-(2-tosylaminophenyl)-4H-3,1-benzoxazin-4-one and 2-phenyl-4H-3,1-benzoxazin-4-one were synthesized. Their UV, IR, and luminescence spectra were studied. The position of the methoxy group affects the strength of the intramolecular hydrogen bond (IHB). The luminescence properties of methoxy-substituted 2-(2-tosylaminophenyl)-4H-3,1-benzoxazin-4-ones are associated with the strength of the IHB. The luminescence maximum is shifted to the short-wave region with strengthening of the IHB, and the luminescence intensity increase simultaneously.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1028–1032, August, 1971.The authors thank Yu. S. Ryabokobylko and A. O. Zisman for measuring the absorption spectra in the IR and UV regions.     

Synthesis of cyclopropyl-substituted 4H-3,1-benzoxazines from 2-amino-phenyl cyclopropyl ketones and 2-cyclopropanoylaminoacylbenzenes

2- and 4-cyclopropyl- and 2,4-dicyclopropyl-substituted 4H-3,1-benzoxazines were synthesized by the intramolecular acid catalyzed heterocyclization of ortho-acylamino-substituted benzyl alcohols, obtained from 2-aminophenyl cyclopropyl ketones and 2-cyclopropanoylaminoacylbenzenes. Translated from Khimiya Geterotsicklicheskikh Soedinenii No. 2, 252-268, February, 2009.     

The Reaction of 2-Aminoethyl- and 3-Aminopropyl-substituted Heterocycles with 2-Formyl-1,3-cyclanediones and 4-Oxo-3,1-benzoxazines

The reaction of 2-formyl-1,3-cyclohexanedione, its 5,5-dimethyl, 5-phenyl and 5-(2-furyl) derivatives and of 2-formyl-1,3-indanedione and dehydroacetic acid with histamine, 3-(1-imidazolyl)propylamine, 3-(4-morpholyl)propylamine, 3-(2-pyrrolidon-1-yl)propylamine, 2-(1-piperazinyl)ethylamine, tryptamine, and 2-(aminomethyl)pyridine gave fifteen 2-aminomethylene derivatives. The reaction of these amines with 2-methyl-4-oxo-3,1-benzoxazine gave the 3-substituted 2-methyl-4(3H)-quinazolinones and with 4-oxo-2-phenyl-3,1-benzoxazine the monosubstituted N-benzoylanthranilic acid amides.     

Research on 4H-3,1-benzoxazines. 9. 2-Alkyl(aryl,furyl)-4H-3,1-benzoxazinium perchlorates and their transformations

A new method was developed for obtaining 4,4-diphenyl-4H-3,1-benzoxazinium Perchlorates by acylation of o-aminophenyldiphenylcarbinol with organic acids in the presence of perchloric acid. Weak CH acidity of the exocyclic methyl group of the corresponding perchlorate was observed.For communication 8 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–546, April, 1993.     

Synthesis of novel 1,3,4-benzotriazepine derivatives from 4-oxo-3,1-benzoxazine and 3,1-benzothiazine-2-carbonitriles

Synthesis of novel oxygen and sulfur containing 1,3,4-benzotriazepine derivatives was performed via 3,1-benzoxazine and 3,1-benzothiazine intermediates obtained from Appel's salt chemistry. We observed that the sulfur containing precursors reacted differently than their oxygenated congeners and, after rearrangement, afforded novel heterocyclic compounds (e.g., benzoxazin-4-thione and 2-cyano-1,3,4-triazepine).     

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.