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.     

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.     

13C NMR spectra of some N-substituted 1,2-dihydro-3,1-benzoxazin-4-ones

The natural abundance ¹³C NMR spectra of a series of hitherto unknown l-atyl-methyl-1,2-dihydro-3,1-benzoxazin-4-ones have been recorded. The assignments of the various resonances have been made from chemical shift arguments, by the analysis of the fine splittings caused by one-bond and long-range couplings and also by comparison with model compounds.     

Ring-chain tautomerism of the novel 2-ferrocenyl-2,4-dihydro-1H-3,1-benzoxazine

The synthesis and the study of the spectroscopic and electrochemical properties as well as the solution behavior of the novel 2-ferrocenyl-2,4-dihydro-1H-3,1-benzoxazine (1a) are described. NMR studies reveal the existence of a tautomeric equilibria between the cyclic (1a) and the open-chain form (2a). Electrochemical studies based on cyclic voltametry and 57Fe Mossbauer spectroscopy as well as a comparative study of the ring-chain tautomerism of 1a and that of 2-phenyl-2,4-dihydro-1H-3,1-benzoxazine (3a) are also reported.     

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.     

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.     

硒催化2-氨基苄醇氧化羰基化合成1,4-二氢-2H-3,1-苯并噁嗪-2-酮

1,4-二氢-2H-3,1-苯并噁嗪-2-酮作为一种重要的母体骨架广泛存在于生物活性化合物中。此外,在有机合成中它可作为经受热脱羧生成氮杂-邻二亚甲基苯的有效工具。文献报道的合成1,4-二氢-2H-3,1-苯并噁嗪-2-酮的方法有：2-氨基苄醇与光气或其替代物反应,钯或硫催化的2-氨基苄醇与 CO的羰基化反应,钯或硒催化的2-硝基苄醇与 CO的羰基化反应,钯催化的2-叠氮基苄醇直接羰基化反应或2-叠氮基苄醇的氮杂-维悌希(aza-Wittig)/杂累积多烯调节的环合反应,苯并呋喃酮的胺解-霍夫曼重排反应,硼氢化锂还原1,2-二氢-3,1-苯并噁嗪-2,4-二酮,以及2-羟甲基苯基氨基甲酸酯的分子内亲核取代反应。上述合成方法存在原料毒性高或成本高且来源不便、原子经济性低、有腐蚀性废物或 CO2排放、CO利用率低、催化剂昂贵且难以循环使用、反应步骤较多等缺陷,因此发展绿色、高效、经济的合成新途径具有重要意义。本文采用廉价易得的非金属硒作催化剂,用 CO作羰基化试剂, O2作氧化剂,通过硒催化2-氨基苄醇的氧化羰基化反应直接合成了目标产物1,4-二氢-2H-3,1-苯并噁嗪-2-酮。通过考察反应时间、反应温度、催化剂硒的用量、助催化剂种类及用量、CO和 O2的比例及溶剂种类等影响因素,得到了优化的反应条件,目标产物收率最高可达87%。实验证实,该 Se/CO催化体系具有相转移催化功能。反应前硒以粉末形式存在于反应体系中,为多相体系;反应开始后,硒粉参与羰基化反应形成可溶活性化合物,从而成为均相体系;反应完成后硒粉经氧化可重新从反应介质中沉淀析出,又变为多相体系。因此,该体系既实现了高效的均相催化反应,又便于催化剂分离回收,且回收的硒可重复使用,其催化活性基本保持不变。结合相关文献,我们提出了该反应的机理：在助催化剂三乙胺存在下,硒首先与 CO反应原位生成羰基硒,然后羰基硒先后接受2-氨基苄醇中氨基和羟基的亲核进攻生成目标产物,同时释放出硒化氢,硒化氢再被 O2氧化为硒,从而进入下一轮催化循环反应。总之,我们成功开发出一条绿色、高效、经济的1,4-二氢-2H-3,1-苯并噁嗪-2-酮合成新途径。用廉价易得且能循环使用的硒替代贵金属钯作催化剂,用 CO替代剧毒光气或其衍生物作羰基化试剂, O2作氧化剂,硒催化的2-氨基苄醇氧化羰基化反应可顺利进行,以87%的良好收率得到目标产物,具有成本低、原子经济性高、CO利用率高、步骤简短、无腐蚀性废物或温室气体 CO2排放、无光气使用及环境相对友好等优点。     

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.     

Photoinduzierte bildung von 8bH-3,4-dihydro-1-(4-methylphenyl)-diazirino[3,1-a]isochinolin

Photolysis of 3,4-Dihydro-isoquinolinium-2-(4-methylphenylimide) $\text{2}$ gives under valence tautomerism the relevant aryl-substituted condensed diaziridin $\text{3}$. The process is thermally reversible.     

A Simple Indirect Route for the Synthesis of N-Alkyl-4-imino-1,4-dihydro-2H-3,1-benzoxazin-2-ones

Summary. Novel N-alkyl-4-imino-1,4-dihydro-2H-3,1-benzoxazin-2-ones were synthesized in a single step by Baeyer–Villiger oxidation of N-alkyl-3-imino-2-indolinone derivatives in high yields. The structures of the products were determined by spectral data and by X-ray diffraction. Besides their novel structures, these compounds may have important biological activities and industrial applications.     

One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-lithiophenyl isothiocyanates with aldehydes or ketones

An efficient one-pot method for the synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-dihydro-3,1-benzoxazine-2-thiones has been developed. Treatment of 2-bromophenyl isothiocyantes with butyllithium in THF at −78 °C generates 2-lithiophenyl isothiocyanates, which are allowed to react with various carbonyl compounds, including aldehydes, ketones, and butanolide, to give the corresponding desired products in moderate to good yields.     

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.     

Novel heterocycles. 13 Synthesis of 5,6-dihydro-1H-3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione

The synthesis of 5,6-dihydro-1H,3H-pyrrolo[3,2,1-ij][3,1]benzoxazine-1,3-dione ( 2a ), a new ring system, from N-acetylindoline is described.     

An efficient approach for the synthesis of N-Phenylcarboxamido-2-aryl-1,2-dihydro-(4H)-3,1-benzoxazine-4-ones

An efficient synthesis of N-phenylcarboxamodo-2-aryl-1,2-dihydro-(4H)-3,1-benzoxazin-4-ones is described by cyclization reaction of some 2-(benzylidene-amino)-benzoic acids with phenyl isocyanate under reflux conditions in CHCl₃. Higher yields of the products were produced in high purity with simple work-up.     

One-pot synthesis of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-isothiocyanatobenzoates with organolithiums

An efficient one-pot procedure for the preparation of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones from 2-isothiocyanatobenzoates has been developed. Thus, 2-isothiocyanatobenzoates were reacted with organolithiums including lithium enolates of acetates and tertiary acetamides in THF at −78 °C to give the desired products in generally good yields.     

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2-thioxo-1,2-dihydro-4H-3,1-benzothazin-4-one

The title compound was prepared and converted to 2-hydrazinyl-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one which was utilized to synthesize fused heterocyclic systems, namely benzotriazolothiazinone derivatives, as well as, nonfused heterocyclic systems such as pyrazolyl-benzothiazinones, benzothiazinylpyridazine and imidazolylbenzothiazinone derivatives via reaction with formamide, acetic acid, ethyl cyanoacetate, maleic anhydride and benzaldehyde followed by treatment with glycine, respectively. All compounds have been structurally characterized by means of IR, MS, and ¹H-NMR spectra. The synthesized compounds were evaluated in vitro for their antiproliferative activity against HePG-2 and MCF-7 cell lines. 2H-Benzo[d][1,3]thiazine-2,4(1H)-dithione and 2-thioxo-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one were the most potent against the two cancer cells compared to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.     

The copper(II) acetate complex with 2-(2-Hydroxyphenyl)-4,4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine

The Cu(II) acetate complex with 2-(2-hydroxyphenyl)-4,4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine (L) was synthesized for the first time and structurally studied by X-ray diffraction. The complex crystallizes as two crystallographically independent centrosymmetric binuclear molecules [Cu₂(μ-L)₂Ac₂] of similar structure, where L occurs as azomethin tautomeric form. The ligand performs tridentate chelate-bridging function. Each Cu atom exhibits extended tetragonal-pyramidal coordination by two O atoms and the N atom of one ligand L in the equatorial plane and by the O atom of the second ligand L in the axial position. The fourth equatorial position in the metal coordination polyhedron is occupied by the O atom of monodentate terminal acetate group.     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.