一篇化学文献的翻译

Highly Efficient One-Pot Three-Component Mannich Reaction in Water Catalyzed by Heteropoly AcidsNajmodin Azizi, Lalleh Torkiyan, and Mohammad R. SaidiDepartment of Chemistry, Sharif University of Technology, P.O. Box 11465-9516, Tehran 11365, Iran Org. Lett., 2006, 8 (10), pp 20792082DOI: 10.1021/ol060498vPublication Date (Web): April 20, 2006Copyright 2006 American Chemical SocietyAbstractHeteropoly acids efficiently catalyzed the one-pot, three-component Mannich reaction of ketones with aromatic aldehydes and different amines in water at ambient temperature and afforded the corresponding -amino carbonyl compounds in good to excellent yields and with moderate diastereoselectivity. This method provides a novel and improved modification of the three-component Mannich reaction in terms of mild reaction conditions and clean reaction profiles, using very a small quantity of catalyst and a simple workup procedure. Carrying out organic reactions in water has become highly desirable in recent years to meet environmental considerations.The use of water as a sole medium for organic reactions would greatly contribute to the development of environmentally friendly processes. Indeed, industry prefers to use water as a solvent rather than toxic organic solvents. In this context, in recent years, much attention has been focused on Lewis acid catalyzed organic reactions in water. Heteropoly acids (HPAs) are environmentally benign and economically feasible solid catalysts that offer several advantages.Therefore, organic reactions that exploit heteropoly acid catalysts in water could prove ideal for industrial synthetic organic chemistry applications, provided that the catalysts show high catalytic activity in water. Mannich reactions are among the most important carboncarbon bond forming reactions in organic synthesis.They provide amino carbonyl compounds, which are important synthetic intermediates for various pharmaceuticals and natural products.The increasing popularity of the Mannich reaction has been fueled by the ubiquitous nature of nitrogen-containing compounds in drugs and natural products.However, the classical Mannich reaction is plagued by a number of serious disadvantages and has limited applications. Therefore, numerous modern versions of the Mannich reaction have been developed to overcome the drawbacks of the classical method. In general, the improved methodology relies on the two-component system using preformed electrophiles, such as imines, and stable nucleophiles, such as enolates, enol ethers, and enamines.But the preferable route is the use of a one-pot three-component strategy that allows for a wide range of structural variations. In this context, recent developments of asymmetric synthesis, using a three-component protocol, have made the Mannich reaction very valuable. However, despite the diverse synthetic routes so far developed for the asymmetric Mannich reaction, only a few one-pot procedures on the use of unmodified aldehydes or ketones in water have been reported in the literature. Furthermore, most of the reported Mannich reactions in water have been carried out in the presence of surfactants such as SDS. Unfortunately, normal-phase separation is difficult during workup due to the formation of emulsions because of the SDS.There is increasing interest in developing environmentally benign reactions and atom-economic catalytic processes that employ unmodified ketones, amines, and aldehydes for Mannich-type reaction in recent years. In continuation of our studies on the new variants, of one-pot, three-component Mannich-type reactions for aminoalkylation of aldehydes with different nucleophiles, and our ongoing green organic chemistry program that uses water as a reaction medium, performs organic transformations under solvent-free conditions, herein we describe a mild, convenient, and simple procedure for effecting the one-pot, three-component reaction of an aldehyde, an amine, and a ketone for the preparation of -amino carbonyl compounds in water using a heteropoly acid catalyst. Initially, the three-component Mannich reaction of 4-chlorobenzaldehyde (3.0 mmol), aniline (3.1 mmol), and the cyclohexanone (5 mmol) was examined (Scheme 1). Scheme 1. Direct Mannich Reaction Catalyzed by Heteropoly Acids in Different Solvents As a preliminary study, several Lewis acids and solvents were screened in the model reaction. The results of extensive Lewis acid and solvent screening and optimization are shown in a table in the Supporting Information. Heteropoly acids (HPAs) catalyze Mannich reactions in organic solvents such as acetonitrile, 1,2-dichloroethane, methanol, ethanol, toluene and mixtures of toluene/water and gave the desired products in low yield with the foramtion of aldol side products. Among the screened solvent systems, water was the solvent of choice, since in this solvent the Mannich-type reactions proceeded smoothly and afforded the desired adducts in high yields at room temperature. Consequently, we conclude that the HPAs are much more reactive in water than in other organic solvents. At room temperature, the Mannich reaction proceeded to completion affording the Mannich adduct in good to excellent yield and relatively good diastereoselectivity. Addition of surfactants such as sodium dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB) was not effective, and they did not improve diastereoselectivity. The reaction in pure water without using any catalyst gave a low yield of the product. Furthermore, we were excited to find that only 0.12 mol % of the catalyst gave good yields at room temperature. In the some cases, even 0.06 mol % of HPA was sufficient for the completion of the reaction. Furthermore, simple workup in water opened the route for an entirely green highly efficient one-pot Mannich reaction in water. In addition, H3PMo12O40 has been compared with H3PW12O40, and we found the same results for both heteropoly acids in this reaction in water. Encouraged by the remarkable results obtained with the above reaction conditions, and in order to show the generality and scope of this new protocol, we used various aldehydes and amines and the results. Table 2 clearly demonstrates that HPAs are excellent catalysts for Mannich reactions in water. Thus, a variety of aromatic aldehydes, including electron-withdrawing and electron-donating groups, were tested using our new method in water in the presence of H3PW12O40 or H3PMo12O40. The results are shown in Table 2. Generally, excellent yields of -amino ketones were obtained for a variety of aldehydes including those bearing an electron-withdrawing group. Furthermore, several electron-rich aromatic aldehydes led to the desired products in good yield. However, under the same reaction conditions aliphatic aldehydes, such as isobutyaldehyde, gave a mixture, due to enamine formation; the desired product was obtained in low yield (Table 2, entry 22). The scope of our method was extended to other amines. In the case of amines having an electron-donating group, such as 4-isopropylaniline, the corresponding amino ketones were obtained in good yields. Furthermore, amines with electron-withdrawing groups, such as 4-chloroaniline and 3,4-dichloroaniline, gave the desired product in good yields. The high yield, simple reaction protocol, and originality of this novel process prompted us to use other ketones under these conditions (Table 1). Thus, the three-component coupling reactions were carried out with acyclic ketones such as 2-butanone and acetophenone. The expected products were obtained in moderate yields under these conditions. Acyclic ketones were less reactive than cyclohexanone and needed much more catalyst to afford the desired products (Table 1). Table 1. HPA-Catalyzed Three-Component Mannich Reactiona(5mmol), acetophenone (3 mmol), and H3PW12O40 (0.02 g).bYield of isolated aReaction conditions: aldehyde (3 mmol), amine (3.1 mmol), 2-butanone products.cSyn/anti ratio.dSyn/anti ratio was determined by 1H NMR analysis of crude products.Table 2. One-Pot, Three-Component Direct Mannich Reactiona aReaction conditions: aldehyde (3 mmol), amine (3.1 mmol), and cyclohexanone (5 mmol) were successively added to a solution of catalyst (10 mg) in water (5 mL) placed in a test tube, and the reaction mixture was vigorous stirred at room temperature for 316 h.bYields of isolated products.cDiastereomeric ratio mearsured by 1H NMR spectroscopy analysis of the crude reaction mixture.The regioselectivity was determined by 1H and 13C NMR spectroscopy and by comparison with known compounds reported in the literature.8 In general, anti selectivity was observed in the reaction of cyclohexanone and 2-butanone. Despite of the low solubility of aldehydes, ketones, and amines in water, the heteropoly acid-catalyzed Mannich reactions still proceed efficiently at ambient temperature. The reaction might take place at the interface of organic materials with water in the heterogeneous system. It was found that vigorous stirring was required for the success of these reactions. The possibility of recycling the catalyst was examined. For this reason, the reaction of 4-chlorobenzaldehyde, aniline and cyclohexanone in water at room temperature in the presence of H3PW12O40 was studied. When the reaction was complete, ethyl acetate was added and organic materials were extracted and the aqueous solution was saved for the next reaction. When the same reaction was carried out in this solution, containing the used catalyst, low yields (ca. 60%) of the product were obtained. Another characteristic feature of the present protocol is the high chemoselectivity of cyclohexanone toward aldimines, prepared in situ from the reaction of aldehydes and amines, in preference to aldehydes as shown in Scheme 2. Although conventional Lewis acids activate aldehydes preferentially, in this media, aldehydes do not undergo aldol reaction by means of HPAs in water. The high chemoselectivity is rationalized by considering the higher basicity of nitrogen over oxygen. A related phenomenon was recently reported in the reactivity between aldimines and aldehydes by the use of proline, HBF4, and dibutyltin dimethoxide.11 Scheme 2. Aldole and Mannich Reaction in Water In conclusion, this procedure offers several advantages including low loading of catalyst, improved yields, clean reaction, use of unmodified ketones, which make it a useful and attractive strategy for the multicomponent reactions of combinational chemistry. In addition, a very easy workup has been realized that does not require organic solvents. When the products are solid and insoluble in water, the pure products can be obtained directly by filtration and washing the filtrate with water and by crystallization from ethanol or diethyl ether. No extraction or separation by column chromatography is necessary in some cases. Current efforts in our research group are attempting to expand the application of heteropoly acids in water for other reactions. AcknowledgmentWe are grateful to the Research Council of Sharif University of Technology for financial support. We thank “Volkswagen-Stiftung, Federal Republic of Germany” for financial support toward the purchase of chemicals. We also thank Professor J. Ipaktschi (University of Giessen) for his valuable advice and suggestions. 翻译稿杂多酸高效催化三组分共混曼尼希反应Najmodin艾则孜， Lalleh Torkiyan ，穆罕默德R 赛迪*谢里夫理工大学化学系，PO 11465-9516箱，伊朗，德黑兰11365ORG 。 Lett ， 2006年， 8（10） ，PP 2079-2082DOI ： 10.1021/ol060498v出版日期（网络） ： 2006年4月20日版权所有 2006年美国化学学会摘要 杂多酸能高效催化酮，芳香醛与不同胺类在环境温度下水中的三组分共混曼尼希反应，并且给予相应的 -氨基羰基化合物以优良的产量和温和的非对映选择性。这种方法使用非常少量的催化剂和一个简单的检验所程序，给三组分的曼尼希反应在反应条件的温和性和反应型材的干净性上提供了一个新的和改进的修改。为满足对环境的考虑，开展在水中的有机反应在近年来已变得非常可取。水作为有机反应的唯一媒介的使用，将大大推动环保进程的发展。事实上，业内人士更倾向于使用水作为溶剂，而不是有毒的有机溶剂。在此背景下，近年来，路易斯酸催化水中的有机反应受到了更多的关注。杂多酸（ HPAs）提供了多种优势，是对环境无害的和经济上可行的固体催化剂。因此，利用杂多酸催化剂在水中进行的有机反应证明了工业有机合成化学应用的理想选择，提供了催化剂在水中的高催化活性。曼尼希反应是有机合成反应中最重要的碳-碳键形成的反应的一种。它们为各种药品和天然产品提供了重要的合成中间体，即 -氨基羰基化合物。曼尼希反应的日益普及推动了普遍存在的含氮化合物在药物和天然产物的性质。然而，经典的曼尼希反应被一系列严重的弊端所困扰，并且只有有限的应用。因此，众多的现代版本的曼尼希反应已开发，以克服传统方法的弊端。在一般情况下，改进的方法依赖于使用预制的亲电试剂，如亚胺和稳定的亲核试剂，如烯醇，烯醚，烯胺的双组分系统。但更好的途径是使用三组分共混的战略，它允许广泛的结构性的变化。在此背景下，使用三组分不对称合成最近的发展已经使曼尼希反应非常宝贵。然而，尽管不对称的曼尼希反应到目前为止已开发了各种不同的合成路线，但只有为数不多的使用未修改的醛或酮在水中的共混程序已被文献报道。此外，大部分的被报道的在水中进行的曼尼希反应已被证实了表面活性剂如SDS的存在。不幸的是，由于SDS导致乳剂的形成，正常的相分离在工作中非常困难。在开发环境的良性反应和原子经济的催化过程中用未修改的酮，胺和醛的曼尼希型反应近年来有越来越多的利益。作为我们研究的新变种，即醛和不同的亲核试剂反应生成氨烷基化物的三组分共混反应和我们正在进行的使用水作为反应介质的绿色有机化学程序的延续，在无溶剂条件下进行有机转换，这里我们描述一个温和，方便，程序简单的以杂多酸作为催化剂在水中进行的醛，胺，酮制备 -氨基羰基化合物的三组分共混反应。4 - 氯苯甲醛（3.0mmol），苯胺（3.1mmol）和环己酮（5mmol）进行的三组分反应首先被研究。方案1 直接在不同溶剂中进行的杂多酸催化的曼尼希反应作为一个初步的研究，在模拟反应中对几种路易斯酸和溶剂进行了筛选。广泛的路易斯酸和溶剂的筛选和优化的结果显示在一个表格中。杂多酸催化在有机溶剂如乙腈， 1,2 - 二氯乙烷，甲醇，乙醇，甲苯，甲苯/水的混合物中进行的曼尼希反应，由于副产品的生成使所要产品产量低。在筛选溶剂体系中，水是被选择的溶剂，因为在此溶剂下曼尼希反应能顺利地进行，并且在室温下使所需的产物有一个高的产量。因此我们得出的结论是比起其它有机溶剂，杂多酸在水中更具有活性。在室温下，曼尼希反应能不断给予曼尼希加合物以良好的产量和相对较好的非对映选择性。添加表面活性剂，如十二烷基硫酸钠（ SDS ）或十六烷基三甲基溴化铵（CTAB）不是有效的，他们并没有提高非对映选择性。在不使用任何催化剂的纯水中进行的反应的产品产量比较低。此外，我们高兴地发现，在室温下只有0.12 mol的催化剂就给了良好的收益。在某些情况下，甚至0.06 mol %的杂多酸催化剂就能使反应非常有效地完成。此外，仅仅是研究水中的反应为一个在水中进行的完全绿色高效共混曼尼希反应已找到了反应路线。此外，H3PMo12O40已与H3PW12O40作了对比，并且对于在水中进行的这个反应，我们发现这两种杂多酸有相同的结果。在上述反应条件下取得了显着的成果感到鼓舞，并以显示这一新协议的通用性和范围，我们使用了各种醛，胺和