Synthesis of some new N,N''-diaryisubstituted methylene-bis-dihydro-2H-1,3-benzoxazines

The synthesis of a new series of six-membered N,N'-diarylsubstituted methylene-bis-dihydro-2H-1,3-benzoxazines (Sa-e) was achieved in excellent yields by Mannich-type condensation of N,N'-diarylsubstituted methylene-bis-o-hydroxybenzyl amines (4a-e) with formaldehyde in chloroform at reflux. These amines (4a-e) were obtained by the reduction of N,N'-diarylsubstituted methylene-bis-o-hydroxybenzyl imines (3a-e) with NaBH4, which inturn were obtained by the condensation of methylene-bis-salicylaldehyde (2) with various substituted arylamines.     

Synthesis of 2-phenylethynyl-1,3-dioxanes and their hydrolysis

2-Phenylethynyl substituted 1,3-dioxanes were obtained by the reaction of 1,3-dioxanium salts with an lotsich reagent. It was shown that they are readily hydrolyzed with the formation of a-acerylenic ketones. A simple new method is proposed for the synthesis of the latter without isolating the intermediate 1,3-dioxanes using the reaction of 4 substituted 2-methyl(phenyl, furyl)-1,3-dioxanium salts with hydroxymethyl- and phenylethynylmagnesium bromide as examples.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 193–197, February, 1996.     

Nouvelle voie d'acces aux dihydro-3,4-2H-benzoxazines-1,3

3,4-Dihydro-2H-1,3-benzoxazines were prepared from primary amines and dihalocompounds by a method which can lead to compounds dissymetrically substituted in positions 2 and 4.     

A novel dilithiation approach to 3,4-dihydro-2H-1,3-benzothiazines, 3,4-Dihydro-2H-1,3-benzoxazines,and 2,3,4,5-tetrahydro-1,3-benzothiazepines

3,4-Dihydro-2H-1,3-benzothiazines 4, 3,4-dihydro-2H-1,3-benzoxazines 9, and 2,3,4,5-tetrahydro-1,3-benzothiazepines 6 were synthesized by directed ortho-lithiation of thiophenols and phenols and by side-chain lithiation of substituted thiophenols, respectively, in one-pot by reacting with N,N-bis[(benzotriazol-1-yl)methyl]amines 3 as 1,3-biselectrophile synthons.     

SnCl4-Catalyzed Aza-Acetalization of Aromatic Aldehydes: Synthesis of Aryl Substituted 3,4-Dihydro-2H-1,3-benzoxazines

Stannic tetrachloride was an efficient Lewis acid catalyst for the aza-acetalization of aromatic aldehydes with o-arylaminomethyl phenols, and a series of novel aryl substituted 3,4-dihydro-2H-1,3-benzoxazines were prepared in good yields under mild conditions. SnCl₄ was a more efficient catalyst for the reaction than p-toluenesulfonic acid, sulfuric acid, and aluminium chloride.     

Construction of functionalized 2,3-dihydro-1,4-benzoxazines via [5 + 1] annulations of 2-halo-1,3-dicarbonyl compounds with imines

A series of functionalized 2,3-dihydro-1,4-benzoxazines were obtained in moderate to excellent yields via domino [5 + 1] annulations of 2-halo-1,3-dicarbonyl compounds 2 with imines 1 under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized tetracyclic-1,4-benzoxazines which contain two new heterocyclic rings and one quaternary carbon center has also been developed.     

Synthesis of substituted salicylamines and dihydro-2H-1,3-benzoxazines

Phenols were converted to their magnesium salts with the MgCl₂-Et₃N base system and subsequently reacted with Eschenmoser's salt, affording N,N-dimethyl substituted benzylamines in high to excellent yields. A series of mono N-substituted benzylamines were prepared in one-pot syntheses by ortho-formylation of phenols to corresponding salicylaldehydes, which in turn reacted with amines to imines. The imines were subsequently reduced to mono N-substituted benzylamines. Some of these benzylamines were further converted, without work-up, to mono N-substituted dihydro-2H-1,3-benzoxazines.     

A Facile and Efficient Synthesis of 4‐Arylidene‐2‐phenyl‐5(4H)‐oxazolones and Their Antimicrobial Evaluation against Selected Human and Phytopathogens

A simple and convenient method has been developed for the synthesis of a series of 2‐(4‐substituted phenyl)‐4‐(substituted arylidene)‐1,3‐oxazol‐5‐ones ( 5a–j ) via reactions of hippuric acid with differently substituted aromatic aldehydes ( 4a–j ) in sodium acetate, potassium acetate, calcium acetate, and ammonium acetate, respectively, which were tested for their efficiency as catalysts in both conventional and microwave‐assisted synthetic methods in presence of 4 Å zeolites. The title compounds were evaluated for their antimicrobial properties against selected human pathogens (bacterial and fungal) and phytopathogens (fungal) and were compared with standard drugs. The results of the study are reported.     

Synthesis of phenyl-substituted 2H-3,4-dihydro-3-aminomethyl-1,4-benzoxazines. Intermediates for 1H-2,3,3a,4-tetrahydroimidazo[5,1-c][1,4]benzoxazin-1-one derivatives. Part II

The synthesis of 2H-3, 4-dihydro-3-aminomethyl-1, 4-benzoxazines substituted by one phenyl group in the 2, 3 or α-position is reported. The two diastereoisomers of the 2-phenyl-derivative were independently synthesized from ethyl trans-3-phenylglycidate by a stereospecific route. A previous attempt at the synthesis of these same compounds gave rise to an unexpected aliphatic-aromatic ketone rearrangement.     

Synthesis of the 1,3-oxathiolanes using asymmetrically oxiranes

An efficient synthesis of 1,3-oxathiolane-2-imin derivatives is described via one-pot reaction between arylisothiocyanats, asymmetrically substituted oxiranes and catalytic amount of methanol.The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of this method.     

Studies of 4H-3,1-benzoxazines. 14. Structure and some properties of 2-[2-hydroxyphenyl(naphthyl)]-1,2-dihydro-4H-3,1-benzoxazines

It has been shown that the condensation of tertiary aminophenylcarbinols with 2-hydroxybenz(naphth)aldehydes gives the corresponding 1,2-dihydrobenzoxazines and their structural Schiff base isomers. The reaction of 2-[2-hydroxyphenyl(naphthyl)]-1,2-dihydro-4H-3,1-benzoxazines with aliphatic aldehydes gives substituted 3,1-benzoxazino[1,2-c][1,3]benz(naphth)oxazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1230–1241, August, 2006.     

Enantiopure 1,4-benzoxazines via 1,2-cyclic sulfamidates. Synthesis of levofloxacin

1,2-Cyclic sulfamidates undergo efficient and regiospecific nucleophilic cleavage with 2-bromophenols (and related anilines and thiophenols), followed by Pd(0)-mediated amination to provide an entry to substituted and enantiomerically pure 1,4-benzoxazines (and quinoxalines and 1,4-benzothiazines). This chemistry provides a short and efficient entry to (3S)-3-methyl-1,4-benzoxazine 19, a late stage intermediate in the synthesis of levofloxacin.     

三组分串联反应一锅合成多环稠合的1,5-苯并二氮杂䓬化合物

以取代的邻苯二胺、1,3-环戊二酮或1,3-环己二酮(5,5-二甲基-1,3-环己二酮)、2,3-二羰基化合物为原料,无水乙醇为溶剂,对甲苯磺酸为催化剂,经2~5 h串联反应一锅合成43种新颖的1,5-苯并二氮杂?化合物,产率最高可达95%.该反应序列首先通过两次的亲核加成-脱水反应过程,形成分子内亚胺和烯胺结构的活性中间体,然后再经分子内的碳碳偶联环合-质子转移等过程,生成多环稠合的1,5-苯并二氮杂?目标化合物,实现了在一个反应体系中形成一个二氮杂七元环和四个新化学键(两个C—N,一个C=C,一个C—C).该方法操作简单,反应便捷,对环境友好,产率高,为1,5-苯并二氮杂?化合物的合成提供绿色环保,高效简便的合成思路.     

Studies of benzoxazines 16*. Synthesis and reactivity of 2,4-substituted 4H-3,1-benzoxazines

A novel method has been developed for preparation of substituted 4H-3,1-benzoxazines via formation of tetrafluoroborates. The substitution of halogen in 2-(α-haloalkyl)-4,4-diphenyl-4H-3,1-benzoxazines by NH and SH nucleophiles was performed. The effect of electrophilic substitution in the annelated aromatic ring in a series of 2,4-substituted 4H-3,1-benzoxazines has been studied.     

Synthesis of substituted 4-(3-alkyl-1,2,4-oxadiazol-5-ylmethyl)-3,4-dihydro-2H-1,4-benzoxazines and 4-(1H-benzimidazol-2-ylmethyl)-3,4-dihydro-2H-1,4-benzoxazines

Substituted 2H-1,4-benzoxazines were synthesized from substituted 2-amino phenols and 1,2-dibromoethane using K₂CO₃ in good to excellent yields. The cyclized products were further reacted with alkyl bromides to obtain the desired N-substituted 3,4-dihydro-2H-1,4-benzoxazines.     

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.     

Mannich反应合成3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪及其杀菌活性

以取代苯酚、多聚甲醛和取代苯胺为原料,在无催化剂的条件下,通过Mannich缩合反应合成了一系列新型3,6(8)-二取代-2,4-二氢-1,3-苯并噁嗪类化合物。 结果表明,取代苯酚和取代苯胺的取代基为供电子基时,合成产物的产率高于吸电子取代基的。 产物的结构用1H NMR、13C NMR、IR和MS等进行了表征。 初步测试了目标化合物的杀菌活性,部分化合物具有较好的杀菌活性。 当浓度为25 mg/L时,化合物4j和4d对菌核病菌的抑制率分别为86.1％和81.5％,化合物4i对灰霉病菌的抑制率为81.6％。     

Synthesis of 4H-3,1-benzoxazines, quinazolin-2-ones, and quinoline-4-ones by palladium-catalyzed oxidative carbonylation of 2-ethynylaniline derivatives

An effective and straightforward approach to the synthesis of 4H-3,1-benzoxazines 3 and 4, quinazolin-2-ones 5, and quinoline-4-one derivatives 6 and 7 is provided by palladium-catalyzed cyclization-alkoxycarbonylation of variously substituted 2-(trimethylsilanyl)ethynylaniline amide or urea derivatives 2. Reactions are carried out in 7:1 MeCN/MeOH at 65 or 75 degrees C in the presence of catalytic amounts of 10% Pd/C in conjunction with Bu(4)NI and KF and under 2.4 MPa of a 3:1 mixture of CO and air. Anti and syn 6-exo-dig cyclization modes account for the formation of the two stereoisomers. Isomerization of the vinylpalladium intermediate may occur as well. Formation of a double carbonylation product 7r and of a gem-dimethoxycarbonylation product 6s, whose structures have been determined by X-ray diffraction analysis, is justified through an unusual type of rearrangement.     

Synthesis of 4‐hydroxyquinolin‐2(1H)‐one analogues and 2‐substituted quinolone derivatives

A versatile synthetic method for preparing 4‐hydroxyquinolone and 2‐substituted quinolone compounds from simple benzoic acid derivatives was demonstrated. The synthetic strategies involve the use of well known ethyl acetoacetate synthesis, malonic ester synthesis and reductive cyclization. The key intermediates were keto esters 4a‐e , which could be transformed to 4‐hydroxyquinolones 5a,b or 2‐substituted quinolone ethyl esters 6a‐c depending on the reaction conditions. 4‐Hydroxyquinolone analogues were prepared and investigated for N‐methyl‐D‐aspartate (NMDA) activity in vitro. Among these derivatives, 6,7‐difluoro‐3‐nitro‐4‐hydroxyquinolin‐2(1H)‐one ( 9 ) exhibited moderate activity.     

A facile approach for the synthesis of novel xanthene derivatives with Vilsmeier–Haack reagent

Chemistry of Heterocyclic Compounds - A series of new derivatives of formylxanthenes have been synthesized via the reaction of substituted 1,3-benzoxazines with Vilsmeier–Haack reagent. It...