N-substituted Lactams Research Articles

Ruthenium-catalyzed synthesis of N-substituted lactams by acceptorless dehydrogenative coupling of diols with primary amines.

Herein, we report the first example of synthesis of N-substituted lactams via an acceptorless dehydrogenative coupling of diols with primary amines in one step, which was enabled by combining Ru3(CO)12 with a hybrid N-heterocyclic carbene-phosphine-phosphine ligand as the catalyst.

ChemInform Abstract: Iridium‐Catalyzed Single‐Step N‐Substituted Lactam Synthesis from Lactones and Amines.

Catalytic lactam synthesis was achieved directly from lactones and amines using an Ir catalyst. Three sequential transformations—aminolysis of lactone, N-alkylation of amine with hydroxyamide, and intramolecular transamidation of aminoamide—afforded the corresponding N-substituted lactams.

Iridium-catalyzed single-step N-substituted lactam synthesis from lactones and amines.

Catalytic lactam synthesis was achieved directly from lactones and amines using an Ir catalyst. Three sequential transformations—aminolysis of lactone, N-alkylation of amine with hydroxyamide, and intramolecular transamidation of aminoamide—afforded the corresponding N-substituted lactams.

ChemInform Abstract: Highly Efficient and Versatile Synthesis of Lactams and N‐Heterocycles via Al(OTf)3‐Catalyzed Cascade Cyclization and Ionic Hydrogenation Reactions.

The discovery and development of an efficient and versatile method for the synthesis of N-substituted lactams is described. Pyrrolindinones, piperidones, and structurally related heterocycles were formed by Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions of corresponding nitrogen substituted ketoamides in good yields.

Highly Efficient and Versatile Synthesis of Lactams and N-Heterocycles via Al(OTf)3-Catalyzed Cascade Cyclization and Ionic Hydrogenation Reactions

The discovery and development of an efficient and versatile method for the synthesis of N-substituted lactams is described. Pyrrolindinones, piperidones, and structurally related heterocycles were formed by Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions of corresponding nitrogen substituted ketoamides in good yields.

FeCl3-Catalyzed Cascade Cyclization in One Pot: Synthesis of Ring-Fused Tetrahydroquinoline Derivatives from Arylamines and N-Substituted Lactams

Multiple cross-dehydrogenative-coupling reactions catalyzed by FeCl3 in one pot were developed. Arylamines and N-substituted lactams were reacted, and ring-fused tetrahydroquinoline derivatives were formed by two C-C bonds and one C-N bond formation as well as one C-N bond cleavage. The lactams were also used as solvent.

Moisture compatible and recyclable indium (III) chloride catalyzed and microwave assisted efficient route to substituted 1H-quinolin-2-ones

An efficient three component synthesis of highly functionalized 4-methyl-1H-quinolin-2-ones in one-pot from readily available coumarin, hydrazine and isatin catalyzed by a recyclable and moisture compatible InCl3 under microwave irradiation has been developed. The synthesis involves a InCl3 catalyzed dehydrative nucleophilic substitution on the lactone moiety of coumarin by the isatin hydrazone resulting in the formation of N-substituted lactams, 6substituted-4-methyl-1-(2-oxo-1,2-dihydroindol-3-ylidenamino)-1H-quinolin-2-ones. The coumarin based transformation into substituted 1H-quinolin-2-ones proceeded smoothly with quantitative yields at ambient temperature.

Viehes Salt in a Novel One Pot Synthesis of Azolo[1,2-a]Pyrimidines

We have developed a practical procedure for the synthesis of polyfunctional azolo[1,5- a]pyrimidines via the reactive species generated in situ from N-substituted lactams and Viehes salt. The described protocol allowed for the introduction of three elements of diversity into the targeted molecules, including substituents originating from the i) nucleophile input, ii) lactam ring and iii) nucleophilic aromatic displacement (SNAr) of the NMe2 group with amines. A short reaction sequence, good yields of title compounds (55-81%), as well as their ready isolation, and purification are the distinct advantages of the reported protocol.

Novel synthesis of sterically hindered N-substituted lactams from imides

An efficient and practical synthesis of sterically hindered N-substituted lactams has been developed starting from simple starting materials. The stereochemistry of the synthetically useful N, N acetal intermediate has been established.

Novel one pot synthesis of azolo[1,5- a]pyridines from Viehe’s salts

We have developed a practical procedure for the synthesis of polyfunctional azolo[1,5- a]pyridines via the reactive species generated in situ from N-substituted lactams and Viehe’s salt. The reaction is regioselective with respect to the nucleophilic addition of bis-anions derived from methyl azolyl acetates. The described protocol allowed for the introduction of three elements of diversity into the targeted molecules, including substituents originating from the (i) nucleophile input, (ii) lactam ring, and (iii) nucleophilic aromatic displacement (S NAr) of the NMe 2 group with amines. A short reaction sequence, good yields of title compounds (44–69%), as well as their ready isolation, and purification are the distinct advantages of the reported protocol.

Viehe′s Salt in a Novel One Pot Synthesis of Pyrimidines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Viehe’s salt in a novel one pot synthesis of pyrimidines

A series of pyrimidine derivatives are synthesized from N-substituted lactams, and Viehe’s salt. A short reaction sequence, good yields of the targeted heterocyclic compounds (44–67%), as well as their convenient isolation and purification are the distinct advantages of the reported protocol.

Synthesis and the Keto‐enol Equilibrium of 2‐Acyl Lactams.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and the keto-enol equilibrium of 2-acyl lactams

Condensation of N-substituted lactams with carboxylic acid esters was studied. A wide range of substituted 2-acyl lactams with different ring sizes were synthesized. The structure of 2-acyl lactams (primarily, the ring size) was found to influence the keto-enol tautomerism.

Computational studies on the enantioselectivity of α-chymotrypsin towards β-carbomethoxy-γ-lactams

In our previous work, racemic β-carbomethoxy-γ-lactams were subjected to enzymatic hydrolysis in the presence of α-chymotrypsin. The hydrolysis of three N-substituted lactams proved to be highly enantioselective, whereas an unsubstituted lactam was recovered in racemic form. Thus, in this paper we applied several molecular modeling protocols to explain the substrate specificity and the enantioselectivity of this enzyme. The adopted procedures involved accurate docking experiments of both enantiomers of each lactam to the protein active site, whose 3-D structure was obtained from X-ray crystallographic data, followed by extensive conformational and energetic analysis of the computer-generated complexes. The results obtained fully account for the experimental evidences on the enantioselective hydrolysis of these interesting, potential drugs by α-chymotrypsin.

Influence of N-substituted lactams on acyclic free radical based hydrogen transfer

anti Relative stereochemistry is achieved in the hydrogen-transfer reaction of a lactam adjacent to the carbon-centered radical. The sense of diastereoselectivity is reversed using N-substituted lactams, and optimal results favoring syn reduced products are obtained with an α-methylbenzyl group and a Boc group.

Biocatalytic Production of Chiral Pharmaceutical Intermediates

Biocatalytic production of several key chiral intermediates in the synthesis of anti-inflammatory, anti-viral and anti-leukaemic agents is described. These include (i) a nucleoside oxidase from Stenotrophomonas maltophilia to oxidise unnatural purine nucleosides, (ii) a serine-type protease from an alkalophilic Bacillus sp. to resolve racemic N-substituted lactams, and (iii) a co-immobilised uridine phosphorylase and purine nucleoside phosphorylase preparation from recombinant E. coli strains that catalyse base transfer reactions.

On the activating anionic polymerization of ε-caprolactam in bulk caused by bis carbamyl derivatives

Abstract The anionic polymerisation of e-caprolactam (e-CL) in the presence of bifunctional N-substituted biscarcarbamyl lactams: hexamethylen-dicarbamyl-dicaprolactam (C-X), and 1-isocyanat 3,3,5 trimethyl-5 methyl cyclohexyl-carbamyl-caprolactam (C-I) was studied. They accelerated the polymerization process and did not cause its poisoning. The kinetics of the polymerization in the presence of both additives was investigated and the activating energy were determined. Their activating effect was compared with the most widely used acylcaprolactam (AL). The different action of C-X C-I were explained by their structural difference.

Origins of diastereoselectivity in the alkylation of N-substituted lactams and amides derived from optically active aminoalcohols

The origins of diastereoselectivity in the alkylation of lactams 1a and 1b and amides 6a and 6b are discussed. A rigid intermediate in which the pyramidalized amide nitrogen chelated the alkoxide lithium cation is invoked. Further experiments conducted with different substrates are in agreement with the proposed model. Furthermore this model can explain the differences observed previously between ephedrine and pseudoephedrine amide alkylation.

Improvement of the Synthesis of Chiral Non-Racemic Bicyclic Lactams in the Piperidin-2-ones Series

Abstract Bicyclic lactams 8 have been prepared in enantiomerically pure form from the corresponding amino esters 5 and glutaric anhydride. The key step is the reduction of imides 7 in methanol. Selective reduction of 8 furnished N-substituted lactams 9.