COMBINATORIAL SYNTHESIS OF MANNICH BASES IN SOLUTION／POLYMER REAGENT WORKUP

This paper describes a combinatorial synthesis the mannich bases in Solution through the Mannich reaction using 3 ketones,5 amines and formaldehyde in solution and hydrochloride as a catalyst and then using a macroporous quarterized ammonium resin(CO32-form)as a scavenge agent to remove the acid catalyst when the Mannich reaction is completed.It was found by GC/MS analysis that the symmetrical ketone,such as acetone,in the Mannich reaction mainly produces one Mannich base;while the asymmetrical ketone,such as 2-pentanone,gives two.     

温和条件下对甲基苯磺酸铝高效催化一锅法合成β-氨基酮衍生物

室温条件下,对甲基苯磺酸铝可有效催化芳香酮、芳香醛和芳香胺的Mannich反应,三组分"一锅法"合成了一系列β-氨基酮衍生物.考察了溶剂及反应条件对产率的影响.反应结束后,催化剂经简单相分离可回收并多次重复使用,催化活性无明显下降.产物结构经IR,~1H NMR,元素分析进行表征.     

Nafion-H?: A recyclable and diastereoselective solid acid catalyst for three-component mannich reaction

One-pot, three-component Mannich reactions of ketones, aldehydes and amines are efficiently catalyzed by heterogeneous Nafion-H? ambient temperature to give the corresponding ??-amino ketones compounds in good to excellent yields. The catalyst can be easily recovered and reused without any decrease of activity for at least four times. Diastereoselective products can be obtained in Mannich reaction of aliphatic ketone.     

Sulfonated poly(4-vinylpyridine) heteropolyacid salts:A reusable green solid catalyst for Mannich reaction

Sulfonated poly（4-vinylpyridine） heteropolyacid salts acted as a heterogeneous catalyst to effectively catalyze the one-pot synthesis of β-amino carbonyl compounds via the Mannich reaction between aromatic aldehydes, aromatic ketone, and aromatic amines. In addition, the catalyst could be easily recovered by the filtration and reused six times without significant loss of catalytic activity.     

温和条件下对甲基苯磺酸铝高效催化一锅法合成β-氨基酮衍生物

室温条件下, 对甲基苯磺酸铝可有效催化芳香酮、芳香醛和芳香胺的Mannich反应, 三组分“一锅法”合成了一系列β-氨基酮衍生物. 考察了溶剂及反应条件对产率的影响. 反应结束后, 催化剂经简单相分离可回收并多次重复使用, 催化活性无明显下降. 产物结构经IR, ¹H NMR, 元素分析进行表征.     

Base-catalyzed three-component direct Mannich reaction of enolizable ketones with high syn-selectivities

The three-component direct Mannich reaction between aldehydes, p-toluenesulfonamide, and enolizable ketones was achieved for the first time with organic bases as the catalysts. The corresponding N-tosylated β-aminoketones were obtained in high yields and good to excellent diastereoselectivities using TMG as the catalyst. Through reduction of the ketone group, the reaction product may be converted into β-aminol with excellent diastereoselectivity.     

Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines Benzo[e][1,2,3]oxathiazine 2,2‐Dioxides Catalyzed by Cinchona Alkaloid‐based Primary Amines

Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by such compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine benzo[e][1,2,3]oxathiazine 2,2‐dioxides could be successfully carried out utilizing a combination of cinchona alkaloid‐derived primary amines with trifluoroacetic acid (TFA); the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89–97 % ee and with various aryl methyl ketones in 85–98 % ee. Moreover, the aryl carbonyl of a Mannich product could be transformed to ketoxime, which further undergoes a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity.     

Efficient PhB(OH)2-catalyzed one-pot synthesis of 3-substituted isoindolin-1-ones and isobenzofuran-1(3H)-ones under solvent free conditions

An efficient and practical one-pot synthesis of 3-substituted isoindolin-1-ones and isobenzofuran-1(3H)-ones has been developed under solvent free-conditions using non-toxic and cheap phenylboronic acid as excellent catalyst. This strategy involves the sequential two-step Mannich/lactamization cascade reaction of inexpensive 2-formylbenzoic acid with primary amines and a wide variety of ketones, and an aldol/lactonization cascade reaction of 2-formylbenzoic acid with a broad range of ketones.     

Novel one-pot Cu-nanoparticles-catalyzed Mannich reaction

Recyclable heterogeneous Cu-nanoparticles efficiently catalyzed the one-pot three-component Mannich reaction of ketones, aromatic aldehydes and amines in methanol. This method provides a novel and improved method for obtaining β-amino carbonyl compounds in terms of good yield with little catalyst loading.     

PEG-OSO3H as an efficient and recyclable catalyst for the synthesis of β-amino carbonyl compounds via the Mannich reaction in PEG-H2O

Sulfuric acid-modified polyethylene glycol 6000（PEG-OSO₃H） was applied as an efficient and recyclable catalyst for the synthesis ofβ-amino carbonyl compounds via the Mannich reaction between aldehydes,aromatic ketones and aromatic amines at room temperature using PEG400-H₂O（1:1） as environment-friendly solvents.The reactions were completed in short times and mild reaction conditions with good to excellent yields.     

聚苯乙烯负载氯化铁催化一锅法合成β-氨基酮类衍生物

制备了聚苯乙烯负载型氯化铁催化剂(PS-FeCl3),并通过红外光谱、X射线衍射、扫描电子显微镜等技术手段进行了表征。 在PS-FeCl3催化下,以苯乙酮、芳醛和芳胺为原料,采用一锅法Mannich反应合成了一系列β-氨基酮衍生物。 制备的催化剂性能稳定,使用4次仍保持较高活性。     

基于乙酸为溶剂和催化剂的芳乙酮Mannich反应

采用乙酸作溶剂和催化剂, 将芳乙酮与甲醛和二级胺进行Mannich反应及热解反应, 并未得到预期的Mannich碱或α,β-不饱和酮(2), 而是以较高产率(65%~73%)生成了乙酸(2-芳甲酰基)烯丙酯(3a~3o). 通过核磁共振波谱、 高分辨质谱和红外光谱表征了化合物3a~3o的结构, 研究了此“异常”反应的发生条件, 并提出了可能的反应机理. 结果表明, 芳乙酮的特殊结构及反应中过量的乙酸是产生化合物3a~3o的决定因素.     

Synthsis of 4‐Piperidones via Multicomponent Double Mannich Reaction Catalyzed by I2

A multicomponent double Mannich reaction of amines, aldehydes and ketones was efficiently catalyzed by molecular iodine, producing a series of 4‐piperidones in a stereoselective way. A variety of amines, aldehydes and ketones were tolerated in this tandem process, including those with labile functinal groups. Further investigation of the reaction between alkyl‐imines and ketones showed that imines from amines and ketones were formed in situ and isomerized to enamine in the presence of molecular iodine to accelerate the corresponding Mannich addition.     

稀土甲基磺酸盐催化苯乙酮、芳香醛和芳香胺的Mannich反应

室温下,稀土甲基磺酸盐催化苯乙酮、芳香醛和芳香胺的Mannich反应,三组分"一锅法"合成了23种β-氨基酮衍生物(其中4种为新化合物),其结构经~1H NMR,IR和元素分析确证.比较了甲基磺酸镧、亚铈、镨、钕、镱的催化活性,结果表明其催化活性接近;催化剂可重复使用.     

Acyclic chiral amines and amino acids as inexpensive and readily tunable catalysts for the direct asymmetric three-component Mannich reaction

The direct three-component asymmetric Mannich reaction catalyzed by acyclic chiral amines or amino acids is presented. Simple acyclic chiral amines and amino acids--such as alanine-tetrazole (9), alanine, valine, and serine-catalyzed the three-component asymmetric Mannich reactions between unmodified ketones, p-anisidine, and aldehydes with high chemo- and stereoselectivity, furnishing the corresponding Mannich bases with up to >99 % ee. This study demonstrates that the whole range of amino acids in nature, as well as nonproteogenic amino acid derivatives, can be considered in the design and tuning of novel, inexpensive organocatalysts for the direct asymmetric Mannich reaction.     

Stereoselective Mannich reactions catalyzed by Tröger’s base derivatives in aqueous media

A Tröger’s base derivative (5,12-dimethyl-3,10-diphenyl-1,3,4,8,10,11-hexaazatetracyclo [6.6.1.0^2,6.0^9,13]pentadeca-2(6),4,9(13),11-tetraenes) was used as an efficient catalyst for the three-component Mannich reactions of aromatic aldehydes and aromatic amines with ketones in water at room temperature. This rapid reaction afforded the corresponding β-amino ketones in good yields with excellent stereoselectivity.     

Highly Stereoselective Synthesis of β-Amino Ketones via a Mannich Reaction Catalyzed by Cellulose Sulfuric Acid as a Biodegradable,Efficient, and Recyclable Heterogeneous Catalyst

The efficient use of cellulose sulfuric acid as a heterogeneous catalyst promotes three-component, one-pot Mannich reaction of various ketones, aromatic aldehydes, and aromatic amines in ethanol to make the corresponding β-amino ketones with high stereoselectivity in favor of the anti-isomer. This protocol has several advantages such as good yield, mild reaction conditions, no environmental hazards, and simple workup procedure.      

Covert Mannich Reaction via Carbon Transfer

1,3‐Dimethylbenzimidazolidine reacts with ketones, which can provide activating α hydrogens and primary or secondary amines under acidic conditions, to yield aminomethylation derivatives by a covert Mannich reaction.     

Homo- and heterogeneous organocatalysis: enantioselective Mannich addition of ketones to endocyclic carbon-nitrogen double bonds

The proline-catalyzed Mannich addition of ketones to chalkogenazines is reported. Yields and enantioselectivities of the corresponding products were good to excellent, using different types of organocatalysts. Furthermore the immobilization of hydroxyproline into a readily synthesized polystyrene-copolymer was accomplished. The catalytic performance of this heterogeneous catalyst was successfully demonstrated in the discussed Mannich reaction.     

Amide Ionic Liquids（AILs）/L-Proline Synergistic Catalyzed Asymmetric Mannich Reactions

IntroductionThe Mannich reaction is one of the most importantreactions for the formation of C—C bonds in the organicsynthetic chemistry, and this reaction has been widelyused for the synthesis of secondary and tertiary aminederivatives that is considered…