Novel synthesis of spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives

A two-step procedure involving acid catalyzed ring opening of spirocyclic epoxides with 2-haloanilines and subsequent palladium-catalyzed intramolecular C–O bond formation to provide spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives is described.     

Catalyst free synthesis of 2-Aryl-2H-benzo[b][1,4]oxazines and 3-Aryl-2H-benzo[b][1,4]thiazin-2-ones: An ultrasonication-assisted strategy

An ultrasonication-assisted synthesis of 2-Aryl-2H-benzo[b][1,4]oxazines and 3-aryl-2H-benzo[b][1,4]thiazin-2-ones has been established by reacting phenacyl bromides with 2-aminophenol and 2-aminothiophenol, respectively. This approach fosters flexibility in generating a diverse range of 1,4-benzoxazines and 1,4-benzothiazinones under catalyst-free reaction conditions. Further scope toward the synthesis of rarely occurring bis-benzoxazine adduct has also been explored, which enabled us to propose the reaction mechanism.     

Solid-phase synthesis of 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine derivatives

We have developed an efficient solid-phase synthetic approach for the synthesis of 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine derivatives. The methodology is of value for high throughput synthesis of these potentially bioactive molecules.     

Convenient synthesis of 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]- and [2,3-b]-1,5-oxazocine-6-ones

A convenient and diversity-oriented method for synthesis of the novel 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]-1,5-oxazocine-6-one skeleton 1 and the very rarely described 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocine-6-one skeleton 2, featuring cyclization using nucleophilic aromatic substitution (S_NAr) and Suzuki coupling, is described.     

One-pot synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives using multi-component reactions

In this work, a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives have been synthesized using an aromatic 1,2-diamine, Meldrum's acid, an isocyanide, and an arylidene malononitrile (or an aldehyde and malononitrile instead of an arylidene malononitrile) in CH₂Cl₂ at ambient temperature. Synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine proceeded via four- and five-component reactions; while the synthesis of malonamide derivatives was performed using five- and six-component reactions. In addition, a new series of the malonamide derivatives have been prepared using an aldehyde, malononitrile, Meldrum's acid, an isocyanide, and two molecules of 1,4-diamine via a six-component reaction. These procedures provide alternative methods to the synthesis of a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives.     

Novel synthesis and reactions of 1,4,7-trimethyl-4,5,7,8-tetrahydro-6h-imidazo[4,5-e][1,4]diazepine-5,8-dione—a cyclic caffeine analog

The synthesis of a cyclic homolog of caffeine is reported. Its 2-nitro- and 2-amino derivatives were obtained for the first time. It was shown that the 2-bromo and 2-chloro substituted cyclic homologs react with nucleophiles under basically identical conditions. Whereas 8-bromocaffeine can give a normal Ullman reaction product via heating with powdered copper in ethylene glycol, the homolog gives only a reduction product and does not react with potassium thiocyanate or cyanide.A. V. Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Odessa 270080. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 824–827, June, 1988.     

A new synthesis of 2,3-dihydrobenzo[1,4]dioxine and 3,4-dihydro-2H-benzo[1,4]oxazine derivatives by tandem palladium-catalyzed oxidative aminocarbonylation-cyclization of 2-prop-2-ynyloxyphenols and 2-prop-2-ynyloxyanilines

2-[(Dialkylcarbamoyl)methylene]-2,3-dihydrobenzo[1,4]dioxine and 3-[(dialkylcarbamoyl)methylene]-3,4-dihydro-2H-benzo[1,4]oxazine derivatives (3 and 5, respectively) were synthesized for the first time starting from readily available 2-prop-2-ynyloxyphenols 1 and 2-prop-2-ynyloxyanilines 4, respectively, through tandem oxidative aminocarbonylation of the triple bond-intramolecular conjugate addition. Reactions were carried out in the presence of catalytic amounts of PdI2 in conjunction with an excess of KI in N,N-dimethylacetamide (DMA) as the solvent at 80-100 degrees C and under 20 atm (at 25 degrees C) of a 4:1 mixture of CO-air. The reaction showed a significant degree of stereoselectivity, the Z isomers being formed preferentially or exclusively. The configuration around the double bond of the major stereoisomers was unequivocally established by X-ray diffraction analysis.     

One-step synthesis of substituted 2-amino-5,6,7,8-tetrahydro-4H-benzo[b]pyrans. Molecular and crystal structure of 2-amino-3-(2-methoxyethoxycarbonyl)-4-(2-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran

Substituted 2-aminobenzo[b]pyrans were synthesized by three-component condensation of aromatic aldehydes, cyanoacetic acid derivatives, and cyclic 1,3-diketones. The molecular and crystal structure of 2-amino-3-(2-methoxyethoxycarbonyl)-4-(2-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran was established by X-ray diffraction analysis.     

Sequential C-N and C-O bond formation in a single pot: synthesis of 2H-benzo[b][1,4]oxazines from 2,5-dihydroxybenzaldehyde and amino acid precursors

Functionalized β-aryl alanine ester derivatives were found to undergo rapid C-N and C-O bond formation with quinol carbonyl compounds to afford 2H-benzo[b][1,4]oxazines in good to excellent yields. This unprecedented finding reported herein offers a straightforward, highly efficient, and rapid method for the synthesis of 2H-benzo[b][1,4]oxazines.     

A novel and convenient method for the synthesis of new derivatives of pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione

A novel methodology has been developed for the efficient synthesis of 1,4-pyridopyrrolodiazepine derivatives. The key reaction is the bromination under mild conditions by NBS of compounds resulting via peptide coupling of l-proline methyl ester with 3-aminopyridine-2-carboxylic acid 1, then intramolecular cyclization in the construction of 2-bromo-6a,7,8,9-tetrahydro-5H-pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione 4. This latter is then engaged in cross-coupling reactions to generate 1,4-pyridopyrrolodiazepines derivatives 5a-m, 6a-i, 7, and 8a-c. This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.     

DABCO-catalyzed multi-component domino reactions for green and efficient synthesis of novel 3-oxo-3H-benzo[a]pyrano[2, 3-c] phenazine-1-carboxylate and 3-(5-hydroxybenzo[a]phenazin-6-yl) acrylate derivatives in water

An efficient, convenient and environmentally benign procedure for the synthesis of novel 3-oxo-3H-benzo[a]pyrano[2,3-c]phenazine-1-carboxylate and 3-(5-hydroxybenzo[a]phenazin-6-yl)acrylate derivatives has been developed by domino three-component condensation reaction between 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamines and acetylenic esters in the presence of a catalytic amount of DABCO as an expedient, eco-friendly and reusable base catalyst in water. This green process produces biologically and pharmacologically significant heterocycles in a one-pot single operation and offers considerable advantages such as:operational simplicity, short reaction time, high yields, reusability of catalyst, absence of any tedious workup or purification and avoids hazardous reagents/solvents.     

An efficient and green method for the synthesis of [1,3]oxazine derivatives catalyzed by thiamine hydrochloride (VB1) in water

An efficient and convenient synthesis of 1,3-oxazine derivatives has been achieved by the one-pot, multicomponent condensation of α- or β-naphthol, an aniline and formaldehyde using thiamine hydrochloride (VB₁) as a versatile biodegradable and reusable catalyst in water as a universal solvent.     

Microwave-assisted controllable synthesis of 2-acylbenzothiazoles and bibenzo[b][1,4]thiazines from aryl methyl ketones and disulfanediyldianilines

A condition-controlled strategy for selectively synthesis of 2-acylbenzothiazoles and bibenzo[b][1,4]thiazines from aryl methyl ketones and disulfanediyldianilines was realized using I₂/DMSO or I₂/MeCN systems, respectively. The desired products were synthesized in only 15 min with moderate to excellent yields (50%-90%) under microwave-assisted, metal-free conditions. The strategy provides a great advantage for selective synthetic applications in the efficient synthesis of benzothiazoles and bibenzothiazines heterocycle compounds.     

p-TSA-catalyzed facile and efficient one-pot eco-friendly synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives in aqueous medium

A green and operationally simple approach for the synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives by a one-pot three-component reaction of 4-amino-3-methyl-5 styrylisoxazoles, aryl glyoxal monohydrates and 4-hydroxy-1-methyl-2-quinolinone using p-TSA as the catalyst in aqueous medium was developed. The protocol proves to be an efficient and an environmentally benign in terms of high yields, operational simplicity, clean reaction profile, compatibility with wide range of substrates, water as a solvent and easy purification.     

A facile synthesis of benzo[b][1,4]thiazepine derivatives by palladium acetate catalyzed reaction

The preparation of steroid/nonsteroid fused benzo[b][1,4]thiazepines and 2-arylsubstituted benzo[b][1,4]thiazepines is described from Pd(OAc)₂ catalyzed reaction of steroidal/nonsteroidal β-halovinyl aldehydes and 2-aminothiophenols in DMF under heating condition.     

Convenient Synthesis of Substituted Quinoxalines and 2H-Benzo[b][1,4]oxazines in Water

A facile and convenient synthesis method has been developed for substituted quinoxalines and 2H-benzo[b][1,4]oxazines from the reactions of α-bromoketones with benzene-1,2-diamine and 2-aminophenol, respectively, which were catalyzed by tetrabutylammonium bromide(TBAB) in aqueous basic media.     

Base-mediated one-pot synthesis of 3,4,5,6-tetrahydro-4-substituted benzo[h]quinazoline-2(1H)-thione derivatives and evaluation of their antioxidant activity

One-pot three-component Beginelli-like reactions of a ketone 1, an aryl aldehyde 2, and thiourea 3 in the presence of sodium hydroxide are described. In this reaction, 3,4,5,6-tertrahydro-4-substituted quinazoline-2(1H)-thione derivatives 4a–h were obtained in good yields (73–85%). The compound 4a has been characterized by single crystal X-ray analysis. All the synthesized compounds 4a–h and 5a–b were screened for their in vitro antioxidant activity. Compounds 4c, 4e, and 4h have exhibited an excellent than the standard ascorbic acid. Compounds 4d, 4f, and 4g have also shown good activity. Remaining compounds show moderate antioxidant activity.     

6-甲基-3-甲基丙烯酰氧乙基-3,4-2H-1,3-苯并噁嗪及其共聚物的合成

以6-甲基-3-羟乙基-3,4-2H-1,3-苯并噁嗪(MB-OH)和甲基丙烯酰氯为原料, 通过酯化反应合成了6-甲基-3-甲基丙烯酰氧乙基-3,4-2H-1,3-苯并噁嗪(MBEM). 采用自由基溶液聚合法, 以偶氮二异丁腈(AIBN)为引发剂, 以甲苯为溶剂, 以MBEM与N-苯基马来酰亚胺(NPMI)为单体, 合成了6-甲基-3-甲基丙烯酰氧乙基-3,4-2H-1,3-苯并噁嗪-co-N-苯基马来酰亚胺共聚物[P(MBEM-co-NPMI)]. 分别对MB-OH, MBEM, P(MBEM-co-NPMI)进行加热固化, 得到相应的交联聚合物PMB-OH, PMBEM和P[P(MBEM-co-NPMI)]. 对其结构、分子量和热性能进行了表征. 结果表明, PMB-OH, PMBEM, P[P(MBEM-co-NPMI)]的最大损耗因子tanδ_max对应的玻璃化转变温度(T_g)分别为92, 129和181℃, 最大损耗模量G"_max对应的T_g分别为56, 91和156℃. 在N₂气氛围下, PMB-OH, PMBEM, P[P(MBEM-co-NPMI)]失重5%的温度分别为257, 244和260℃; 失重10%的温度分别为280, 266和284℃; 800℃的残炭率分别为23.2%, 17.8%和14.0%. 表明P[P(MBEM-co-NPMI)]具有优异的耐热性能.     

Parallel solution-phase synthesis of 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives from 1,5-difluoro-2,4-dinitrobenzene

This paper discusses the synthesis of privileged structures 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives in a parallel solution-phase manner using 1,5-difluoro-2,4-dinitrobenzene. Each scaffold possesses four diversity points. A cheap and efficient oxidant, urea-hydrogen peroxide (UHP), was applied for the introduction of the sulfone group. The intramolecular cyclization to 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one was achieved by microwave assistance or the use of an inorganic base.