氧化铝催化的芳香胺参加的Mannich反应—β-芳胺基苯丙酮的新合成法

Mannich反应是一类重要的有机化学反应,典型的Mannich反应是在酸催化下进行的。近年来,一些固体催化剂如AgNO_3、Cu_2X_2(X=C1、Br、I)、 CuCl_2、CuBr_2、Cu(OAC)_2等也被用于一些特殊的Mannich反应中,但有关报道不多。Al_2O_3作为Man-nich反应的催化剂未见文献报道。 1982年,陈光旭、徐秀娟等采用HCl-EtOH作催化剂,首次实现了芳香胺作为胺组分与甲醛和酮直接进行的Mannich反应,合成了一系列β-芳胺基酮:     

芳香酮与芳香醛及芳香胺的Mannich反应

醛、酮与芳香醛及芳香胺的 Mannich 反应,文献[1]曾报道在 HCl-EtOH 溶液中苯乙酮及甲醛与芳香胺的 Mannich 反应。本文在此基     

对-甲苯乙酮与芳香醛和芳香胺的Mannich反应

Mannich反应是合成新化合物的重要方法 [1] ,其对应的产物 Mannich碱常常具有广泛的生物活性 [2 ] .文献报道 ,对 -甲苯乙酮的 Mannich碱具有抑癌 [3]和麻醉拮抗 [4 ]等生物活性 ,但是文献中对 -甲苯乙酮 Mannich碱的合成却是从胺交换法 [5] 、酮交换法 [6] 、查耳酮与胺的 Michael加成[7] 、Schiff碱与酮的缩合 [8～ 14 ] 、β-内酰胺与有机锂的亲核裂解 [15] 等间接方法得到的 .即使是从直接法合成 ,一般也是甲醛参与的 Mannich反应 .虽然芳香醛和芳香胺同时参与的 Mannich反应已有报道 [16] ,但对 -甲苯乙酮与芳香醛和芳香胺直接进行…     

超声辅助负载碘催化Mannich反应的研究

以芳香醛、苯乙酮和芳香胺为原料，乙醇作溶剂，使用蒙脱土负载碘催化Mannich反应，合成了β-氨基羰基衍生物（4a~4h），收率89.9%~98.5%，其结构经¹H NMR和IR确证。催化剂循环使用3次，4a收率70.4%     

黄芩苷元的Mannich反应

利用天然产物黄芩苷元（baicalein)在A环8－位碳上进行Mannich反应，合成 了11个新的Mannich碱化合物。反应温和，产物易纯化，收率达80％以上。同时考 察了伯胺与甲醛配比为1：2时，产物为二氢苯并E嗪类化合物和黄芩苷元A环上5－ ，6－，7－位羟基对8－位氢进行Mannich反应活性的影响。并对Mannich碱化合物 2b和2j进行盐酸成盐4b和4j，初步考察了它们的溶解度与黄芩苷元的差别。     

间硝基苯甲醛或间氯苯甲醛与芳香胺和芳香酮的Mannich反应

间硝基苯甲醛或间氯苯甲醛与芳香胺和芳香酮在20~25℃和催化量的浓盐酸催化下能直接进行Mannich反应, 用一步合成法合成15个1-芳基-3-芳胺基(3-硝基苯基)丙酮。产率为68~87%。产物结构经元素分析, IR, ^1H NMR, MS鉴定。本文还讨论了反应的适宜条件。     

苯骈咪唑-N-Mannich碱与苯乙酮的交换反应

Mannich反应是在有机合成中广泛采用的反应,是甲醛与胺及含有活性氢的分子(如甲基酮等)发生缩合反应,是制备β-胺基酮类的方便方法.但一般认为芳香胺不能参加这个反应,因此,可先制成脂肪胺的Mannich碱,然后用芳香胺交换来制备β-芳胺基酮^[1-5].     

M(OTf)_3催化N－烷氧羰基吡咯或噻吩醛和盐酸伯胺的新颖Mannich反应

三氟甲磺酸盐M(OTf)_3 (M = Sc, Y, Ln)在水相中能较好地催化N－烷氧羰基 吡咯或噻吩与甲醛和盐酸伯胺的新颖的Mannich反应，其中Y(OTf)_3催化效果最佳 。该反应具有条件温和，收率较高和原子经济性等优点，为N－烷氧羰基吡咯和噻 吩类Mannich碱的合成提供了一种新方法，同时该反应以水为主要溶剂溶剂，符合 当今绿色化学的发展趋势。     

芳香胺参加的Mannich反应——3-芳氨基-3-苯基-1-(4-溴苯基)丙酮的合成

文献报道过芳香胺与苯甲醛生成的Schiff碱可在少量相应的芳香胺盐酸盐或浓盐酸催化下制备Mannich碱(Ⅰ),所用的Schiff碱系事先合成,且产率较低(15-68.9％)。本文报导用4-溴苯乙酮、苯甲醛和芳香胺在少量浓盐酸催化下能直接发生Mannich反应,     

M(OTf)_3催化N－烷氧羰基吡咯或噻吩醛和盐酸伯胺的新颖Mannich反应

三氟甲磺酸盐M(OTf)_3 (M = Sc, Y, Ln)在水相中能较好地催化N－烷氧羰基 吡咯或噻吩与甲醛和盐酸伯胺的新颖的Mannich反应,其中Y(OTf)_3催化效果最佳 。该反应具有条件温和,收率较高和原子经济性等优点,为N－烷氧羰基吡咯和噻 吩类Mannich碱的合成提供了一种新方法,同时该反应以水为主要溶剂溶剂,符合 当今绿色化学的发展趋势。     

COMBINATORIAL SYNTHESIS OF MANNICH BASES IN SOLUTION/POLYMER REAGENT WORKUP

1.INTRODUCTIONCombinatorialsynthesisisapowerfultoolforpreparationanddiscoveryofdrugleads[1].However,becauseofthelackofefficientanalyticalmeanstocharacterizetheintermediatesandsmallamountofbyproductsonthepolymersupportsproducedinsolid-phasesynthesis,manychemistshaveturnedtheirintereststosolution-phasemethodsforlibrarygenerationinsteadofsolid-phasesynthesis[2].Buttheconventionalseparationtechniquescannotmeettherequirementtopurifyeveryproductofasolution-phaselibrary,thusthesolid-phasescavenge…     

类Mannich反应合成2,5-二苯基-3,3-二取代-2,3-二氢-1,4,2-氧氮磷杂环戊烯-2-氧化物

本文报道了以苯甲酰胺,醛(或酮)苯基二氯化膦为原料进行的Mannich反应,其产物经部分水解合成了α-(N-苯甲酰氨基)二取代甲基苯基膦酸(Ⅰ),此化合物脱水关环得2,5-二苯基-3,3-二取代-2,3-二氢-1,4,2-氧氮磷杂环戊烯-2-氧化物(Ⅱ).经¹HNMR及元素分析证明了Ⅰ和Ⅱ的结构,并对反应机理进行了探讨。     

Theoretical Studies on the Mechanism of Mannich Reaction Involving Iminium Salt as Potential Mannich Reagent(1)——Use Acetaldehyde as Pseudo-acid Component

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A New Investigation of Mannich Reaction

Mannich reaction is widely used for the synthesis of many kinds of compounds1. In the synthesis of the derivatives of styryl ketonic Mannich bases, a one-pot method is used, in which ketone, secondary-amine hydrochloride, paraformaldehyde are refluxed together in alcohol2,3. In most cases the normal Mannich product MA is obtained. But when certain amine is used as the reactant, a side-product IM, instead of MA is obtained. MS and 1HNMR data indicate that compound IM is a new type of Man…     

Parallel synthesis of an indole-based library via an iterative Mannich reaction sequence

A library of 1,3-disubstituted indoles has been prepared via an iterative Mannich reaction sequence. The first Mannich reaction with secondary amines and formaldehyde preferentially yields 3-aminomethyl indoles, while the second Mannich reaction introduces an additional aminomethyl group at the N1-position of the indole ring. A library of 25 substituted indoles has thus been prepared in moderate to good yields with purity.     

Synthesis of 2([Methyl-5-[(E)-2-aryl-1-ethenyl]-4-isoxazolyl]imino)-1,3-thiazolan-4-ones and Their Mannich Bases

Isoxazolyl chloroacetamides (2) were obtained from 4-amino-3-methyl-5-styrylisoxazoles (1) on reaction with chloroacetyl chloride. Cyclocondensation of 2 with NH₄SCN yielded 2([-methyl-5-(E)-2-aryl-1-ethenyl]-4-isoxazolylimino)-1,3-thiazolan-4-ones(3). Mannich reaction of 3 with formaldehyde and secondary amines gave isoxazolyl thiazolidinone Mannich bases (4 and 5).     

Chemoselective aminomethylation of bifunctional substrates: carbonyl versus phenolic hydroxyl,carbonyl versus pyrazole and pyrrole versus phenolic hydroxyl as competing activating groups

Chemoselectivity in the Mannich reaction for three different types of bifunctional substrates has been investigated. 1-Hydroxy-2-naphthalenylethanone affords either phenolic Mannich bases at high pH (free amines), or ketonic Mannich bases at low pH (amine hydrochlorides), whereas the use of N,N-dimethylmethyleneiminium chloride as a preformed dimethylaminomethylation reagent gave the phenolic Mannich base. 1-Aryl-3-(1H-pyrazol-1-yl)-1-propanones undergo aminomethylation at position 4 of the pyrazole ring, and not at the methylene group α to the carbonyl function, regardless of the reaction conditions. 4-(2,5-Dimethyl-1H-pyrrol-1-yl)phenol is aminomethylated chemoselectively on the pyrrole ring under mild reaction conditions.     

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.