Beta-amino Carbonyl Compounds Research Articles

Synthesis of Some New Amino Carbonyl Compounds by Mannich Reaction

Beta-aminocarbonyl compounds are important intermediates produced from Mannich condensation. In this research, benzaldehyde, para-hydroxy acetophenone or para-nitro acetophenone were reacted with a various of primary aromatic amines to give compounds (1-7) and (8-14), respectively. The chemical formulas of the synthesized compounds were confirmed by conducting some physical and spectroscopic measurements, such as, melting points, IR and H1-NMR spectrum. After testing the biological activity of some of the synthesized compounds (8,10,11,13) using Gram-positive (Streptococcus, and Staphylococcus aureus), Gram-negative (Klebsiella spp., and Escherichia coli) bacteria, as well as yeast strains, were chosen for this investigation (candidan albicans). Isolated bacteria were identified using standard methods of isolation and identification, including direct assays and culture on various media. Some theoretical tests have also been carried out such as SwissADME and cardioToxCSM prediction on all prepared compounds to predict their activity in terms of pharmacokinetic properties (ADME) and also predict their cardiotoxicity on some heart functions such as arrhythmia, cardiac failure, heart block, hERG toxicity, Hypertension (HT), and Myocardial Infarction (MI).
 
 Keywords: Secondary amines, aldehyde, Mannich condensation, antimicrobial activity.

One-pot Preparation of ?–amino Carbonyl Compounds by Mannich Reaction Using MgO/ZrO2 as Effective and Reusable Catalyst

A new one-pot and efficient three-component condensation of aldehyde, ketones, and amines in the presence of MgO/ZrO2 as an inexpensive and effective catalyst for the synthesis of beta-amino carbonyl compounds by Mannich reaction is described. The present methodology offers several advantages, such as good yields, Short reaction times and a recyclable catalyst with a very easy work up.

Chemoselective Synthesis of Substituted Imines, Secondary Amines, and β‐Amino Carbonyl Compounds from Nitroaromatics through Cascade Reactions on Gold Catalysts

Substituted imines, alpha,beta-unsaturated imines, substituted secondary amines, and beta-amino carbonyl compounds have been synthesized by means of new cascade reactions with mono- or bifunctional gold-based solid catalysts under mild reaction conditions. The related synthetic route involves the hydrogenation of a nitroaromatic compound in the presence of a second reactant such as an aldehyde, alpha,beta-unsaturated carbonyl compound, or alkyne, which circumvents an ex situ reduction process for producing the aromatic amine. The process is shown to be highly selective towards other competing groups, such as double bonds, carbonyls, halogens, nitriles, or cinnamates, and thereby allows the synthesis of different substituted nitrogenated compounds. For the preparation of imines, substituted anilines are formed and condensed in situ with aldehydes to provide the final product through two tandem reactions. High chemoselectivity is observed, for instance, when double bonds or halides are present within the reactants. In addition, we show that the Au/TiO2 system is also able to catalyze the chemoselective hydrogenation of imines, so that secondary amines can be prepared directly through a three-step cascade reaction by starting from nitroaromatic compounds and aldehydes. On the other hand, Au/TiO2 can also be used as a bifunctional catalyst to obtain substituted beta-amino carbonyl compounds from nitroaromatics and alpha,beta-unsaturated carbonyl compounds. Whereas gold sites promote the in situ formation of anilines, the intrinsic acidity of Ti species on the support surface accelerates the subsequent Michael addition. Finally, two gold-catalyzed reactions, that is, the hydrogenation of nitro groups and a hydroamination, have been coupled to synthesize additional substituted imines from nitroaromatic compounds and alkynes.

Direct anti‐Selective Catalytic Asymmetric Mannich‐Type Reactions of α‐Ketoanilides for the Synthesis of γ‐Amino Amides and Azetidine‐2‐amides

Breaking with convention: A homodinuclear nickel complex derived from a biphenyldiamine-based Schiff base catalyzed an anti-selective Mannich-type reaction of alpha-ketoanilides (see scheme) to afford unique building blocks for the synthesis of azetidine-2-amides and alpha-hydroxy gamma-amino amides. This approach stands in contrast to conventional Mannich-type reactions for the synthesis of beta-amino carbonyl compounds. o-Ns = o-nitrobenzenesulfonyl.

PdII‐Catalyzed Asymmetric Addition Reactions of 1,3‐Dicarbonyl Compounds: Mannich‐Type Reactions with N‐Boc Imines and Three‐Component Aminomethylation

This paper describes catalytic asymmetric Mannich-type reactions of beta-ketoesters and malonates using chiral palladium complexes. Although readily enolizable, carbonyl compounds are attractive substrates, the use of such compounds as nucleophiles in Mannich-type reactions has not been extensively investigated. In the presence of chiral Pd aqua complexes (2.5 mol %), beta-ketoesters reacted with various N-Boc imines (Boc=tert-butoxycarbonyl) to afford the desired beta-aminocarbonyl compounds in good yield with high to excellent stereoselectivity (up to 96:4 d.r., 95-99 % ee in most cases). In these reactions, construction of highly crowded vicinal quaternary and tertiary carbon centers was achieved in one step. A chiral Pd enolate is considered to be the key intermediate. To elucidate the stereoselectivity observed in the reaction, possible transition-state models are discussed, taking into account steric and stereoelectronic effects. Furthermore, this catalytic system was applied to the Mannich-type reaction of malonates with N-Boc imine as well as one-pot classical aminomethylation of beta-ketoesters using benzylamine salt and formalin. The reactions proceeded smoothly, and the corresponding Mannich products were obtained in high yield with moderate to good enantioselectivity.

Lewis Base Catalyzed Mannich‐Type Reactions between Trimethylsilyl Enol Ethers and Aldimines

Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.

Highly Efficient One-Pot Three-Component Mannich Reaction in Water Catalyzed by Heteropoly Acids

[reaction: see text] Heteropoly 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 beta-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.

Lithium Heptadecafluorooctanesulfonate Catalyzed Mannich‐Type and aza‐Diels—Alder Reactions in Supercritical Carbon Dioxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Multiple component reactions: an efficient nickel-catalyzed Reformatsky-type reaction and its application in the parallel synthesis of beta-amino carbonyl libraries.

Multiple-component condensations (MCC) where three or more reactants combine to afford a new core structure possessing the molecular features of its composite building blocks is a powerful method for the preparation of molecular diversity. We have developed an efficient, nickel-catalyzed, Reformatsky-type three-component condensation (3CC) reaction that affords beta-amino carbonyl compounds. The scope of the reaction is demonstrated both in the gram and microscale settings; 15 beta-amino esters, amides, and a ketone were prepared efficiently at the mmol scale, and a library of 64 beta-amino carbonyl compounds was generated at the micromol scale.

The proline-catalyzed direct asymmetric three-component Mannich reaction: scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols.

We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide beta-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.

Lewis acid promoted highly stereoselective rearrangement of 2,3-aziridino alcohols: a new efficient approach to beta-amino carbonyl compounds.

A new Lewis acid promoted rearrangement reaction of 2,3-aziridino alcohols was discovered, which involved the highly stereoselective construction of a diastereogenic quaternary carbon center and efficient formation of beta-amino carbonyl compounds in excellent yields. A wide variety of Lewis acids were proved to be effective for the reaction, and a possible reaction mechanism was also discussed.

Asymmetric steering of the Mannich reaction with phthaloyl amino acids

Mannich-type reactions are powerful methods for the efficient synthesis of beta-amino carbonyl compounds that are valuable intermediates for the construction of natural products, beta-peptides, and peptidomimetics. For the efficient steric steering of Mannich reactions a method was developed that consists in the treatment of imines with N-protected amino acid chlorides to give N-acyliminiumion intermediates that are subsequently attacked with silylketene acetals. The reactions are run best at room temperature and in the absence of any Lewis acid. The highest stereoselectivity is observed if N,N-phthaloyl tert-leucine is employed as chiral auxiliary and if N-aryl,C-aryl Schiffs bases are used that carry two ortho-substituents in either aromatic ring. Under these conditions the Mannich adducts are formed in preparatively useful yields and with excellent stereoselectivity (diastereomer ratio in general >99:1). The chiral auxiliary group is readily removed by 1) cleavage of the phthaloyl imide via reduction with NaBH4 and acid hydrolysis followed by 2) Edman degradation.