3-氨基吲唑、炔醛和NIS串联环化反应合成碘化嘧啶并[1,2-b]-吲唑

本文开发了一种在无需外加添加剂的条件下合成碘代嘧啶并[1,2-b]-吲唑类化合物的方法。经研究发现,3-氨基吲唑、炔醛和碘代丁二酰亚胺在二氯甲烷中室温条件下发生直接串联环化反应,以中等至良好的产率得到碘代嘧啶并[1,2-b]-吲唑类化合物。该反应有较好的底物适应性,并具有绿色环境友好和操作简便等优点。     

选择性合成双[噻吩并[2,3-d]嘧啶-4(3H)-酮]

以2-氨基-4-三氟甲基-5-甲基-噻吩-3-羧酸乙酯(1)为起始原料制得膦亚胺2.在碳酸钾的催化下,膦亚胺2与芳基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上2,2’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]3;膦亚胺2与烷基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上3,3’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]4.化合物3的核磁共振氢谱表明关环反应在嘧啶环的2,2’位;化合物4的核磁共振氢谱表明关环反应在嘧啶环的3,3’位.对合成反应机理的推导及目标产物核磁共振氢谱数据的分析解释了此合成反应的选择性.     

亚胺不对称催化还原的量子化学研究

对手性噁唑硼烷催化亚胺不对称还原反应进行了量子化学研究. 对反应中间体和过渡态进行了B3LYP/6-31G(d)全优化. 噁唑硼烷对亚胺还原的催化作用是显著的. 还原反应经历了催化剂-硼烷加合物、催化剂-硼烷-亚胺加合物、催化剂-氨基硼烷加合物的生成, 以及催化剂-氨基硼烷加合物的离解并再生催化剂等过程. 还原反应的速度控制步骤是噁唑硼烷-氨基硼烷加合物的离解. 理论预测的还原产物是与实验吻合的R-手性胺.     

桥连的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]的合成

2-氨基-4-三氟甲基-5-甲基-噻吩-3-羧酸乙酯(1)与三苯基膦、六氯乙烷及三乙胺反应,以84％的产率得到膦亚胺2.在碳酸钾的催化下,膦业胺2与芳基异氰酸酯和双官能亲核试剂的串联氮杂Wittig反应制得新型桥连的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]3,产率为58％～82％.所有产物结构经IR,1HNMR,MS表征和元素分析确证.     

4-取代-2-氨基嘧啶衍生物的合成

含乙酰基的芳杂环类化合物分别与过量40%~50%的N,N-二甲基甲酰胺-二甲基缩醛（DMF-DMA）在回流温度下进行反应,得到相应的中间产物3-(二甲氨基)-1-（取代）-2-丙烯-1-酮,收率为71.2%~85.2%。 所得中间产物在乙醇介质中,在乙醇钠存在下与盐酸胍回流反应5～7 h,制备了14个4-取代-2-氨基嘧啶类化合物,收率达66.6%~86.1%,产物经核磁、质谱、元素分析等进行了表征。     

3-次苄基6-氟-硫色满酮与3-氨基-1,2,4-三氮唑的环缩合反应研究

本文考察了溶剂、温度、反应时间和7-芳基等对3-次苄基6-氟-硫色满酮与3-氨基-1,2,4-三氮唑的环缩合反应的影响。实验结果表明在环缩合反应中同时生成了并四环的二氢嘧啶和嘧啶。而且高温时,并四环二氢嘧啶可以在没有脱氢剂的条件下直接脱氢生成嘧啶。文中合成的化合物结构经氢核磁共振谱、质谱、元素分析和X-射线单晶衍射确证。并对同时生成并四环二氢嘧啶和嘧啶的环缩合反应的机理进行了探讨。     

利用串联的氮杂Wittig反应方便合成3-[取代吡啶(噻唑)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮及其除草活性

用串联的氮杂Wittig关环反应合成了一系列3-[取代吡啶(嘧啶)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮.膦亚胺4和芳基异氰酸酯发生氮杂Wittig反应生成碳二亚胺5,继而在乙醇钠催化下与各种脂肪伯胺关环,以较好的收率得到目标产物7.初步生物活性测试结果表明:该系列部分化合物在100 mg/L的浓度下对双子叶植物油菜显示出较好的除草活性.     

杂环光化学——Ⅱ.核酸碱基衍生物与碳-碳叁键光环合加成反应的初步研究

碳-碳双键间的[2 2]光环合加成反应已有大量报道。但是,有关叁键参加的光环合加成反应报道则很少。近年来,核酸碱基及其衍生物的光化学引起了很多学者的兴趣。Itoh等研究了1,3-二甲基脲嘧啶和1,3-二甲基胸腺嘧啶与丁炔二酸二甲酯的光反应,得到了[2 2 2]的环加成产物。樊美公等报道了1,3-二甲基6-氮杂胸腺嘧啶与烯烃的光环合加成反应,确证了该反应发生在激发三线态,并合成了一些含有氮杂环丁烷结构的化合物。本文报道1,3-二甲基脲嘧啶和1,3-二甲基-6-氮杂胸腺嘧啶与丁炔二酸二甲酯和丙炔醇的反应。其中首次实现了碳-碳叁键和碳-氮双键间的光环合加成反应。合成了含有环丁烷、环丁烯、氮杂环丁烯和氮杂环丁烷结构的六个双环化合物和一个四环化合物。     

苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物的合成

在乙醇钠的催化下,4-[(三苯基膦叶立德)氨基]-2,3-二氢-3-苯基-2-硫代噻唑-5-羧酸乙酯(膦亚胺1)与芳香基二异氰酸酯和亲核试剂的双氮杂Wittig反应制得苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物,产率为56%～92%.产物结构经IR,1H NMR,MS和元素分析确证.     

TiO2光催化降解胸腺嘧啶的动力学和机理

考察了用于降解来自嘧啶家族的一种核酸—胸腺嘧啶(C5H6N2O2)的高级氧化过程。结果发现,在光催化剂TiO2作用下,胸腺嘧啶的光降解进行得很快,且在紫外光照射和水溶液中时更为明显。研究了胸腺嘧啶在TiO2催化剂上的吸附、降解动力学、以及pH值对光催化降解胸腺嘧啶性能的影响。另外,考察了胸腺嘧啶降解产物的矿化;比较和讨论了在光催化过程中胸腺嘧啶的消失和矿化速率。同时还研究了氮的矿化,确立了中间产物的识别方法。最后,采用电子密度计算提出了在紫外光照射下TiO2催化剂上胸腺嘧啶降解的可能化学途径。     

Utility of 2‐Acetyl Benzofuran for the Synthesis of New Heterocycles as Potential Anticancer Agents

A novel series of benzofuran derivatives containing thiazole, thiadiazine, and pyridotriazolopyrimidine were synthesized starting from 1‐(benzofuran‐2‐yl)‐3‐(1H –indol‐3‐yl)prop‐2‐en‐1‐one. Also, triazolopyrimidine derivatives were prepared from the reaction of 2‐acetylbenzofuran and pyrazole‐4‐carbaldehyde with 2‐thiobarbutyric acid and reaction of the product with hydrazonoyl halides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analyses, spectral data, and alternative synthetic routes whenever possible. Anticancer activity against 60 different human tumor cell lines representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney was validated by the U.S. National Cancer Institute using a two‐stage process. The results revealed that pyrazoline‐1‐thiocarbohydrazide 4b , triazolopyrimidine 20d , and pyrimidine thione 25 have promising antitumor activity against most cell lines.     

Redox‐Neutral Rhodium‐Catalyzed CH Functionalization of Arylamine N‐Oxides with Diazo Compounds: Primary C(sp3)H/C(sp2)H Activation and Oxygen‐Atom Transfer

An unprecedented rhodium(III)‐catalyzed regioselective redox‐neutral annulation reaction of 1‐naphthylamine N‐oxides with diazo compounds was developed to afford various biologically important 1H‐benzo[g]indolines. This coupling reaction proceeds under mild reaction conditions and does not require external oxidants. The only by‐products are dinitrogen and water. More significantly, this reaction represents the first example of dual functiaonalization of unactivated a primary C(sp³)? H bond and C(sp²)? H bond with diazocarbonyl compounds. DFT calculations revealed that an intermediate iminium is most likely involved in the catalytic cycle. Moreover, a rhodium(III)‐catalyzed coupling of readily available tertiary aniline N‐oxides with α‐diazomalonates was also developed under external oxidant‐free conditions to access various aminomandelic acid derivatives by an O‐atom‐transfer reaction.     

Redox‐Neutral Rhodium‐Catalyzed C?H Functionalization of Arylamine N‐Oxides with Diazo Compounds: Primary C(sp3)?H/C(sp2)?H Activation and Oxygen‐Atom Transfer

An unprecedented rhodium(III)‐catalyzed regioselective redox‐neutral annulation reaction of 1‐naphthylamine N‐oxides with diazo compounds was developed to afford various biologically important 1H‐benzo[g]indolines. This coupling reaction proceeds under mild reaction conditions and does not require external oxidants. The only by‐products are dinitrogen and water. More significantly, this reaction represents the first example of dual functiaonalization of unactivated a primary C(sp³) H bond and C(sp²) H bond with diazocarbonyl compounds. DFT calculations revealed that an intermediate iminium is most likely involved in the catalytic cycle. Moreover, a rhodium(III)‐catalyzed coupling of readily available tertiary aniline N‐oxides with α‐diazomalonates was also developed under external oxidant‐free conditions to access various aminomandelic acid derivatives by an O‐atom‐transfer reaction.     

Gold‐Catalyzed Highly Selective Photoredox C(sp2)−H Difluoroalkylation and Perfluoroalkylation of Hydrazones

The first gold‐catalyzed photoredox C(sp²)?H difluoroalkylation and perfluoroalkylation of hydrazones with readily available R_F?Br reagents is reported. The resulting gem‐difluoromethylated and perfluoroalkylated hydrazones are highly functionalized, versatile molecules. A mild reduction of the coupling products can efficiently produce gem‐difluoromethylated β‐amino phosphonic acids and β‐amino acid derivatives. In mechanistic studies, a difluoroalkyl radical intermediate was detected by an EPR spin‐trapping experiment, indicating that a gold‐catalyzed radical pathway is operating.     

An Efficient Synthesis of Pyrrolo[1,2‐a]quinazoline Derivatives in Ionic Liquid Catalyzed by Iodine

A mild, green, and facile method for the synthesis of 2,3,3a,4‐tetrahydropyrrolo[1,2‐a]quinazoline‐1,5‐dione derivatives is described in high yields by using ionic liquids as green media. The method involves the reaction of 2‐aminobenzamides with 4‐oxopentanoic acid or 4‐aryl‐4‐oxo‐butanoic acid catalyzed by iodine and has the advantages of mild reaction conditions, high yields, one‐pot, operational simplicity, and environmentally benign.     

Synthesis of Isoindolo[2,1‐a]quinazoline Derivatives in Ionic Liquid Catalyzed by Iodine

A mild, green, and facile method for the synthesis of 6,6a‐dihydroisoindolo[2,1‐a]quinazoline‐5,11‐dione derivatives is described in high yields using ionic liquids as green media. The method involves the reaction of 2‐aminobenzamides with 2‐formylbenzoic acid catalyzed by iodine and provides a new alkaloid library with potential activity for biomedical screening.     

A Straightforward Synthesis of 2‐[1‐Alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic Acid Derivatives via Domino Michael Addition?Cyclization Reaction

A new and efficient synthesis of 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives by a one‐pot three‐component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4‐dihydro‐3‐methylidenefuran‐2,5‐dione) is reported. The reaction was performed without catalyst and under solvent‐free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition? cyclization reaction is proposed (Scheme 2).     

The role of benzoic acid in proline‐catalyzed asymmetric michael addition: A density functional theory study

In asymmetric Michael addition between ketones and nitroolefins catalyzed by L ‐proline, we observed that it was benzoic acid or its derivatives rather than other proton acid that could accelerate the reaction greatly, and different benzoic acid derivatives brought different yields. To explain the experimental phenomena, a density functional theory study was performed to elucidate the mechanism of proline‐catalyzed asymmetric Michael addition with benzoic acid. The results of the theoretical calculation at the level of B3LYP/6‐311+G(2df,p)//B3LYP/6‐31G(d) demonstrated that benzoic acid played two major roles in the formation of nitroalkane: assisting proton transfer and activating the nitro group. In the stage of enamine formation from imine, the energy profiles of benzoic acid derivatives were also calculated to investigate the reasons why different benzoic acid derivatives caused different yields. The results demonstrated that the pK_a value was the major factor for p‐substituted benzoic acid derivatives to improve the yields, whereas for m/o‐substituted benzoic acid derivatives, both pK_a value and electronic and steric effects could significantly increase the yields. The calculated results would be very helpful for understanding the reaction mechanism of Michael addition and provide some insights into the selection of efficient additives for similar experiments. © 2012 Wiley Periodicals, Inc.     

RhodiumIII/SilverI Relay Catalyzed C—H Aminomethylation with Imine Equivalents and Lewis Acid Catalyzed [4+2] Cycloaddition of Indoles with Triarylhexahydrotriazine†

A Rh^III/Ag^I relay‐catalyzed C(sp²)—H coupling of indoles with triarylhexahydrotriazine (THT) is reported in this context. Upon merging Rh^III‐catalyzed C(sp²)—H bond activation and silver promoted THT dissociation, an efficient indole's C3 aminomethylation protocol is uncovered, providing C3 aminomethyl indoles in good yields and exhibiting potential applications for the synthesis of complicated bioactive compounds. We revealed the C3‐selectivity of this reaction through a detailed mechanistic investigation. Meanwhile, during the examination of the reaction conditions, we discovered another [4+2] cycloaddition pathway to afford tetrahydro‐indolo[3,2‐c]quinoline scaffold products via silver or Lewis acid catalysis.     

1,3‐O‐Transposition or Trisubstituted Z‐Enol Ester? A Comparative Study of Reactions of Ynones

Ynones are useful substrates for transition‐metal‐mediated synthesis. The Au^I‐catalyzed 1,3‐O‐transposition is an important reaction of ynones. Recently, an efficient Cu^I‐catalyzed synthesis of trisubstituted Z‐enol esters via interrupting the traditional 1,3‐O‐transposition reaction of ynones was reported by Zhu's group. Herein, density functional theory studies disclosed that the hydrogen bond formed by carboxylic acid plays an important role for the reactivity and selectivity in this novel reaction. A qualitative rule was also found to explain the substituent effect in the ynone substrate, and this is consistent with experiments. The Au^I‐catalyst and Cu^I‐catalyst were further compared to interpret the essential cause of why the Au^I‐catalyst prefers the 1,3‐O‐transpostion reaction. These conclusions might be helpful for the rational design of reactions of ynones.