(S)-3-(3,4-二甲氧基苯基)-2-甲基丙氨酸衍生的手性咪唑啉酮催化剂合成新方法

以(S)-3-(3,4-二甲氧基苯基)-2-甲基丙氨酸盐酸盐为原料,针对其合成咪唑啉酮催化剂过程中反应条件苛刻和反应时间长等问题,重新设计了一条合成路线,并考察了温度、原料摩尔比和反应时间等对合成收率的影响。新合成路线中,合成关键中间体(S)-3-(3,4-二甲氧基苯基)-2-甲基丙氨酸甲酰胺7的反应时间由9 d缩短至7 h,不需剧毒的NaCN催化,收率达到98%。     

2,3-二羟甲基-2,3-二硝基-1,4-丁二醇四硝酸酯的合成、晶体结构及性能研究

以硝基甲烷为起始原料,经缩合、环化、氧化耦合、脱缩酮及硝化等5步反应合成了2,3-二羟甲基-2,3-二硝基-1,4-丁二醇四硝酸酯(BHDBT),总收率为36.1％,并采用核磁共振谱、红外光谱以及元素分析等进行了结构表征.用浓盐酸代替氯化氢气体,改进了关键中间体2,3-二羟甲基-2,3-二硝基-1,4-丁二醇(BHDB)的合成方法,并确定最佳反应条件为:刀(浓盐酸):n(BDND)=1.1∶1,反应温度55℃,时间4h,收率为94.8％.首次发现了BHDB和BHDBT的亚甲基质子具有磁不等价性,并从理论上分析其产生的原因.培养了BHDBT单晶,四元衍射晶体结构解析表明:BHDBT属于单斜晶系,空间群P2(1)/n,晶胞参数:a=0.81944(11) nm,b=2.3365(3) nm,c=0.85838(11) nm,a=90°,β=113.501(2)°,y=90°,V=1.5072(3) nm3,Z=4,Dc=1.852 g·cm-3,μ=0.189 mm-1,F(000)=856.BHDBT熔点为86.37℃,分解峰温度为185.79℃(DSC),摩擦感度为100％ (3.92 MPa,90°),特性落高H50为10.0 cm(5 kg).     

一种高分子紫外光吸收剂的合成研究

以2-(2-羟基-5-甲基苯基)苯并三唑、聚缩醛和哌嗪为原料,在乙二醇二甲醚溶剂中,经Mannich反应合成1,4-二[2-(2-羟基-5-甲基苯基)苯并三氮唑]哌嗪,确定了较佳缩合工艺条件。考察了物料配比、反应温度和时间对反应收率的影响,并经过正交实验,确定了反应的最佳工艺条件:在乙二醇二甲醚溶剂中,反应温度95℃,反应时间为24 h,n(2-(2-羟基-5-甲基苯基)苯并三唑)/n(HCHO)/n(哌嗪)=1.0∶1.5∶0.7,产品收率为82%,纯度98%(HPLC面积归一化法)。产品结构经IR、MS和1H-NMR表征。     

铜催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应合成手性膦酰化2,3-二氢呋喃

手性2,3-二氢呋喃衍生物是一类重要的杂环化合物,广泛存在于天然产物和生物活性分子中.它们也经常被用于手性四氢呋喃化合物的不对称合成.因此,人们发展了很多合成手性2,3-二氢呋喃化合物的方法,如有机小分子催化的多米诺迈克尔-烷基化反应、“中断的”Feist-Bénary反应或改进的 Feist-Bénary反应.此外,过渡金属催化的手性2,3-二氢呋喃的不对称合成在近些年引起了人们的极大关注. Ozawa等通过 Pd-催化2,3-二氢呋喃的动力拆分方法获得了手性2-芳基-2,3-二氢呋喃. Evans发展了一种 Sc-催化联烯硅和乙醛酸乙酯的[3+2]环加成反应合成手性2,3-二氢呋喃的方法.最近, Fu和 Tang等发展了 Cu催化烯酮和重氮化合物的[4+1]环加成反应合成手性2,3-二氢呋喃的方法.在 Nishibayashi和 van Maarseveen的开创性工作之后, Cu催化的不对称炔丙基转化反应取得了很大的进展.最近,我们发展了一类新的三齿手性 P,N,N-配体,在 Cu催化不对称炔丙基取代、脱羧炔丙基取代、[3+2]、[3+3]和[4+2]环加成反应中表现出优秀的对映和非对映选择性.其中,我们发现采用 Cu催化炔丙醇酯和β-酮酯的[3+2]环加成反应,能高对映选择性地获得手性2,3-二氢呋喃.我们设想,采用β-羰基膦酸酯代替β-酮酯,通过这种 Cu催化[3+2]环加成反应,将可以合成一类具有重要生物活性的手性膦酰化2,3-二氢呋喃化合物.基于这种设想,本文使用手性 P,N,N-配体,通过 Cu催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应,以很好的收率和最高92% ee的对映选择性获得了一系列光学活性的膦酰化2,3-二氢呋喃化合物.我们以炔丙醇酯1a与β-羰基膦酸酯2a为标准底物,优化了反应条件,考察了配体、Cu盐、碱和反应温度等对反应收率和对映选择性的影响.我们确定了最佳的反应条件：以4b为配体,以 Cu(OTf)2为铜盐,以t-BuOK为碱,以 MeOH为溶剂,–20oC反应24 h.在此条件下,我们对β-羰基磷酸酯2的适用范围进行了考察.结果表明,各种苯基取代的β-羰膦磷酸酯均能得到很好的收率和对映选择性.苯环上取代基的空间效应对反应的对映选择性影响不大,但对反应收率影响较大,与相应3-取代或4-取代底物相比较,2-取代的底物获得的收率较低.苯环对位取代基的电子效应对反应的影响不大,给电子基或吸电子基的底物,均得到了较好的收率和对映选择性.杂环取代的底物同样适用于该反应,以90%的收率和89% ee的对映选择性获得了相应的[3+2]环加成产物.对于烷基底物,虽然反应的产率略低,但是得到了高达92% ee的产物.此外,我们对炔丙醇酯底物的适用范围也进行了考察.结果表明,该体系对于各种取代的炔丙醇酯底物均可以获得较高的收率和良好的对映选择性.总之,本文发展了一种铜催化炔丙醇酯与β-羰基膦酸酯的不对称[3+2]环加成反应的方法,成功合成了手性膦酰化2,3-二氢呋喃化合物.通过使用一个结构刚性的酮亚胺三齿 P,N,N-配体,以很好的收率和最高92% ee的对映选择性获得了一系列光学活性的膦酰化2,3-二氢呋喃化合物.     

2,3-二取代-5-羟基苯并呋喃衍生物的合成

用1,4-环己二酮与联二酮的缩合反应首次合成了4个未见文献报道的标题化合物,结构经IR,1H NMR,MS和元素分析等测试确证,并对反应条件进行了初步探讨.结果表明,以LiCl作为催化剂,用1,3-二甲基-2-咪唑啉酮(DMI)为溶剂,于200℃反应1 h时收率最高.     

Et_3N·Mo(CO)_5催化取代2,3-二氢呋喃衍生物的合成

利用McDonald方法,制备了2-戊基-、2-(对-甲基)苯基-以及2-甲基-2-苯基-取代2,3-二氢呋喃化合物.实验表明,此种方法反应条件温和,后处理简单,适用范围广,可用以合成大量环内烯醇醚.     

2,3-二甲基-2-异丙基-丁酸的合成

二异丙基酮与MeMgBr反应制备2,3,4-三甲基-3-戊醇;再经Koch-Haaf羧化反应合成了2,3-二甲基-2-异丙基-丁酸,总收率51%,其结构经NMR,IR和GC-MS确证.     

2-甲基-6-(3-甲基-2-丁烯基)对苯二醌的合成

以邻甲基苯酚为原料,与1-氯-2-甲基-2-丁烯反应生成2-甲基-6-(3-甲基-2-丁烯基)苯酚,然后催化氧化得到目标产物2-甲基-6-(3-甲基-2-丁烯基)对苯二醌。该合成路线简单,易于操作,最终收率51%。     

“一锅法”合成2-氨基-N,3-二甲基-5-卤代苯甲酰胺

报道了从3-甲基-2-氨基苯甲酸出发一锅三步合成2-氨基-N,3-二甲基-5-卤代苯甲酰胺的方法.3-甲基-2-氨基苯甲酸(1)与固体光气反应生成中间体8-甲基-2H-3,1-苯并噁嗪-2,4(1H)-二酮(2),化合物2与甲胺水溶液发生胺解反应生成2-氨基-N,3-二甲基苯甲酰胺(3),3再与氯代丁二酰亚胺(NCS)、溴代丁二酰亚胺(NBS)或碘代丁二酰亚胺(NIS)发生芳香亲电取代反应生成目标产物2-氨基-N,3-二甲基-5-卤代苯甲酰胺(4～6).整个反应过程不需分离中间产品,最终产物经减压浓缩除去有机溶剂后,直接从水中析出针状晶体,总收率达到87%～94%,较文献报道的分步法收率提高30%以上.该方法工艺操作简单、反应条件温和、反应时间短、收率高,是一条环境友好的绿色合成路线.     

在氯化亚锡存在下2,3-二甲基-2-丁烯与乙酐的催化酰化反应

一种新的催化剂,SnCl2·2H2O,已用于2,3-二甲基-2-丁烯与乙酐的酰化反应来制备高产率的3,3,4-三甲基-4-戊烯-2-酮 (TMP). 发现SnCl2·2H2O是室温下2,3-二甲基-2-丁烯与乙酐进行酰化反应的有效催化剂. 考察了催化剂用量、乙酐用量、反应时间和溶剂的加入等因素对该酰化反应的影响. 发现当催化剂/2,3-二甲基-2-丁烯摩尔比在0.30/1和 0.60/1之间、反应时间为2 h时,所得酰化产品的产率最高. 该酰化反应进行到完全所需的时间取决于催化剂用量和乙酐用量. 在需要加入溶剂的情况下,二氯甲烷或氯仿是一种合适的溶剂.     

Reaction of 2-chloro-3-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone with cyclic amines (piperidine,morpholine, and pyrrolidine)

It was shown that the reaction of 2-chloro-3-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone with piperidine in the absence of a solvent gives not only a product of replacement of the chlorine atom by a piperidino group, 3-(4-N,N-dimethylaminoanilino)-2-piperidino-1,4-naphthoquinone, but also 2-(4-N,N-dimethylaminoanilino)-1,4-naphthoquinone and 2-(4-N,N-dimethylaminoanilino-2-piperidino)-1,4-naphthoquinone. The latter compounds are the only reaction products formed in dimethyl sulfoxide. The reaction with morpholine occurs in a similar way, whereas that with pyrrolidine gives only a product of replacement of the chlorine atom by hydrogen.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2451–2454, December, 1995.     

Reaction of 2,3-Dichloro-1,4-naphthoquinone with Some Active Methylene Compounds in Different Basic Media

Reaction of 2,3-dichloro-1,4-naphthoquinone with some active methylene compounds, such as malononitrile and cyanoacetamide, under various basic conditions has been investigated. A mechanism for these reactions is proposed.     

Synthesis and Crystal Structure of 2,3-Bis(dinitrofluoromethyl)-1,4-dioxane

For the first time the dinitromethyl group was modified to dinitrofluoromethyl group in the series of aliphatic polynitro compounds in the case of the reaction of 1,1,4,4-tetranitro-2,3-butanediol diacetate with ammonium fluoroxysulfate in the presence of sodium bicarbonate and ethylene glycol. Previously unknown 2,3-bis(dinitrofluoromethyl)-1,4-dioxane was synthesized. Its structure was determined by X-ray diffraction analysis.     

Reaction of 2-bromomethyl-1,3-thiaselenole with thiourea: en route to the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines

The regioselective reaction of 2-bromomethyl-1,3-thiaselenole 1 with thiourea is accompanied by rearrangement, expanding the ring to afford the corresponding six-membered isothiuronium salt, 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide 2, a synthon of the 2,3-dihydro-1,4-thiaselenin-2-ylthiolate anion. The latter was used for the synthesis of the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines 3a–g, bis(2,3-dihydro-1,4-thiaselenin-2-yl) disulfide 5 and 1,6-bis(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)hexane 6.     

Synthesis of Mixed Aryl 2,3-Diarylsulphanyl-1,4-naphthoquinones

The reaction of 2-arylsulphanyl-1,4-napththoquinone with aromatic thiols and sodium dithionate leads to bis-2,3-(arylsulphanyl)naphthalene-1,4-diols in high yield. Corresponding oxidized products, namely 2,3-diarylsulphanyl-1,4-naphthoquinones, are prepared in near quantitative yield by a copper(II)-catalyzed aerial oxidation reaction of bis-2,3-(arylsulphanyl)naphthalene-1,4-diols under mild condition.     

Preparation of Pseudo-Arsonolipids: Dl-2,3-Diacyloxybutane-1,4-Bis(Arsonic Acids)

Abstract

The title pseudo-arsonolipid with palmitoyl side chain has been prepared in ～70% yield from its parent DL-2,3-dihydroxybutane-1,4-bis(arsonic acid) after reduction of the As(V) to As(III) by thiophenol, acylation with palmitoyl chloride in the presence of pyridine and catalytic amounts of 4-(dimethylamino)pyridine, and reoxidation of As(III) to As(V) by hydrogen peroxide. In CDCl₃/CD₃OD esterification of the –AsO₃H₂ groups was detected by ¹H NMR.     

Synthesis of some NH- and NH,S- substituted 1,4-quinones

A series of NH-substituted-1,4-quinones, possessing one, two, three or not chlorine, were synthesized by the reaction between different quinones (p-chloranil (1), p-toluquinone (2), or 2,3-dichloro-1,4-naphthoquinone (3)) and (-)-cis-myrtanylamine (5) via nucleophilic reactions. Moreover, 2-bromo-1,4-naphthoquinone (4) was reacted with 2-(methylthio)ethylamine (11) to produce amino-substituted naphthoquinones (12 and 13), bearing with bromine and not bromine. In addition, 2-bromo-1,4-naphthoquinone (4) was reacted with 4′-aminodibenzo-18-crown-6 (14) and 4′-aminobenzo-18-crown-6 (16) to yield crown-containing 1,4-naphthoquinones (15 and 17), respectively. New compounds were characterized, providing ¹H NMR, ¹³C NMR, FTIR, MS-ESI, UV/Vis and elemental analysis.     

Synthesis of 2,5-bis(2-aminothiazol-5-yl)-3,6-dichloro-1,4-benzoquinones

A series of 2-(2-aminothiazol-5-yl)-3,6-dichloro-5-diethylaminoethenyl-1,4-benzoquinones was synthesized from 2-(2-aminothiazol-5-yl)-3,5,6-trichloro-1,4-benzoquinones using acetaldehyde and diethylamine in toluene solution. Refluxing these compounds with substituted thioureas in acetonitrile in the presence of hydrochloric acid gives the corresponding 2,5-bis(2-aminothiazol-5-yl)-3,6-dichlorohydroquinones which can be oxidized to the target products with ferric chloride in aqueous DMF.Riga Technical University, Riga LV-1048, LatviaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 835–839, June, 2000     

Synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives via a one-pot,three-component reaction under catalyst-free conditions

A concise, facile and straightforward synthetic method has been described for the synthesis of 2-(3-amino-2-oxoindolin-3-yl)-3-hydroxynaphthalene-1,4-dione derivatives by a one-pot, three-component reaction of isatins, 2-hydroxy-1,4-naphthoquinone and ammonium acetate under catalyst-free conditions in ethanol. This protocol becomes highly efficient due to its mild reaction conditions, operational simplicity, and overall good to excellent yields (80–99%).