Nickel Chloride Hexahydrate Catalyzed Multicomponent Biginelli's Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐Ones and Thiones

An efficient protocol is reported for the one‐pot three‐component Bignelli synthesis of a series of 3,4‐dihydropyrimidine‐2(1H )‐ones and thiones in good yields (66–90%) from the aldehydes (4‐benzyloxybenzaldehyde, 5‐bromovanilin, 4‐formyl‐1‐cyclohexene, and trans‐cinnamaldehyde), β‐keto esters (ethyl acetoacetate, allyl acetoacetate, and t‐butyl acetoacetate), and urea/thiourea in ethanol, using nickel chloride hexahydrate as a catalyst.     

Multicomponent Efficient Synthesis of New [1,2,4]Triazolo[3,4]thiadiazines

A series of novel triazolo thiadiazines were synthesized by a simple, highly efficient, one‐pot pseudo four component approach involving the condensation of 4‐amino‐5‐hydrazinyl‐4H‐1,2,4‐triazole‐3‐thiol ( 1 ), aromatic aldehydes ( 2 ), and various phenacyl bromides ( 3 ) with good yields. The structures of compounds were confirmed by analytical and spectral (IR, ¹H NMR, ¹³C NMR) data.     

An Efficient,Multicomponent, One‐pot Synthesis of Tetra Substituted Pyrans in Water

A new and environmentally benign multi‐component synthesis of tetra substituted 4H‐pyran derivatives is developed via the one‐pot reaction of an aromatic aldehyde, malononitrile, and 1,3‐diketone in the presence of NaOH with water as the solvent at RT. The reaction is efficient and affords excellent yields of the products.     

Synthesis,Anticancer Evaluation,and Molecular Docking Studies of Novel (4‐Hydroxy‐2‐Thioxo‐3,4‐Dihydro‐2H‐[1,3]Thiazin‐6‐Yl)‐Chromen‐2‐Ones via a Multicomponent Approach

A series of coumarin‐substituted 1,3‐thiazine‐2‐thione derivatives ( 4a–m ) were synthesized via the multicomponent reaction of 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehyde ( 1 ) carbon disulfide ( 2 ), and various primary amines ( 3 ), in presence of triethylamine and acetonitrile under stirring with good yields. The structures of all the synthesized compounds were characterized by analytical and spectral studies. Further, the synthesized compounds were screened for their in vitro antiproliferative activities against different cancer cell lines (A549, MDA‐MB‐231, MCF7, HeLa, and B16F10). Studies on the molecular interactions to recognize the hypothetical binding motif of the title compounds with the target Hsp 100 were carried out employing the Schrodinger software. Compounds 4a , 4c and 4m showed activity against all the five cell lines compared with the reference drug, and 4a exhibited the least IC₅₀ concentration of 7.56 ± 1.07 μg/mL against MCF7. This in vitro anticancer result was supported by in silico docking and in silico ADME (absorption, distribution, metabolism, and excretion) studies as well.     

Efficient [Cu(NHC)]‐Catalyzed Multicomponent Synthesis of Pyrroles

Efficient [Cu(NHC)]‐catalyzed syntheses of pyrroles via two and three‐component coupling methods are described. Various 1,2‐, 1,2,3‐, 1,2,3,5‐ and fully substituted pyrroles were readily accessible through a suitable choice of ketone, primary amine and diol in a three‐component reaction. The N‐unsubstituted pyrrole formation is also feasible through a two‐component reaction involving a β‐amino alcohol and a ketone.     

Multicomponent Reaction for Synthesis of Novel 2‐Tosyloxyphenylpyridines

2‐Tosyloxybenzaldehyde 1 was reacted with some active methylene compounds as 1:1 or 1:2 molar ratio under different basic conditions to afford the corresponding 2‐tosyloxyarylidenes 2–4 and/or 2‐tosyloxyphenylpyridine 5 , respectively. Multicomponent reaction of 2‐tosyloxyarylidene 2 and AcONH₄ with active methylene compounds namely: malononitrile, ethyl acetoacetate, ethyl benzoylacetate, 1,3‐benzothiazol‐2‐ylacetonitrile, acetophenones or 3‐acetylheterocycle derivatives in methanol gave 2‐tosyloxyphenylpyridine derivatives 8 – 17 , respectively. The structures of new compounds were elucidated by elemental and spectral analysis.     

One‐Pot Multicomponent Synthesis of β‐Amino Amides

Multicomponent reactions are excellent tools for rapid generation of small molecules with broad chemical diversity and molecular complexity. Herein, a novel one‐pot multicomponent synthesis of β‐amino amides from aldehydes, anilines, carboxylic acids and ynamides has been successfully developed. This process is practical and efficient to unravel synthetic utility and scalability. Moreover, an isotope labeling reaction was conducted to elucidate a plausible reaction mechanism.     

An Efficient Synthesis of 5,6‐Dimethoxy 1‐ and 2‐Naphthols via Teuber Reaction

Based on the oxidation of 1,5‐naphthalenediol ( 4 ) and 6‐bromo‐2‐naphthol ( 9 ) via Teuber reaction, an efficient synthesis of 5,6‐dimethoxy‐1‐naphthol ( 1 ) and 5,6‐dimethoxy‐2‐naphthol ( 2 ) was achieved with high overall yield (16% for 1 and 25% for 2 ). The key steps of the synthetic strategy involved the oxidation of naphthols ( 4 and 9 ) to the corresponding naphthoquinones ( 5 and 10 ) and the conversion of 5,6‐dimethoxy‐2‐naphthaldehyde to 5,6‐dimethoxy‐2‐naphthol formate through Baeyer‐Villiger oxidation‐rearrangement.     

An Expedient Stereoselective Synthesis of Spirocyclopropyl Oxindoles from Indolin‐2‐One/N‐Protected Indolin‐2‐Ones and Bromonitroalkenes

A direct and much simpler way was developed for the diastereoselective synthesis of spiro cyclopropan‐1,3′‐oxindoles from indolin‐2‐one/N‐protected indolin‐2‐ones and bromonitroalkene. The fused restrained cyclopropanes were obtained with high diastereomeric ratios (upto >99:1) and in reasonable to high isolated chemical yields (upto 94%).     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

Three‐Component Reaction of Pyrimidin‐2‐yl Sulfonates with Sodium Azide and Alkynes: An Efficient Approach to C2–Triazolo Functionalized Pyrimidines

Pyrimidin‐2‐yl sulfonate, as an efficient reaction partner, can be easily prepared from cheap commercial materials, reacted with sodium azide and alkynes to give C2‐triazolo functionalized pyrimidines in good yields under mild reaction conditions. This procedure eliminates the need to handle organic halides or organic azides, as they are generated in situ, making this already powerful click process even more user‐friendly and safe.     

An Efficient Synthesis of 4‐Naphthylpyrimidin‐2‐amine Derivatives under Solvent‐Free Conditions

A simple, efficient, and mild protocol for the synthesis of 4‐naphthylpyrimidin‐2‐amine derivatives under solvent‐free conditions by the reaction of aromatic aldehydes (or 1‐naphthaldehyde), 2‐acetylnaphthalene (or aromatic ketones), guanidine carbonate, and sodium hydroxide was reported. The advantages of this protocol include short reaction time, mild reaction conditions, easy workup, high yields, and environmental friendliness.     

2‐Cyano‐2‐isocyanoalkanoates in Multicomponent Reactions

The reactivity of 2‐cyano‐2‐isocyanoalkanoates 2 in multi‐component reactions was investigated, i.e., in the Passerini reaction and the Ugi‐four‐component condensation (see Schemes 2 and 3, resp.). Interestingly, the structure of the 2‐cyano‐2‐isocyanoalkanoates 2 strictly limited the possible starting materials. Only the combination of aliphatic aldehydes, halogenated acetic acid derivatives, and nonaromatic amines gave satisfactory results, i.e., provided depsidipeptides 5 (Tables 3 and 4) and depsitripeptides 9 (Tables 6), respectively. Some of the products of the multicomponent reactions were transformed into crystalline compounds by decarboxylation (see Scheme 4). After fractional crystallization, the molecular structure of one of the decarboxylated depsitripeptides, i.e., of 10 , was established by X‐ray crystallography.     

CuBr2‐Promoted Multicomponent Aerobic Reaction for the Synthesis of 1,2,3‐Triaroylindolizines

An efficient synthesis of 1,2,3‐triaroylindolizines has been developed via CuBr₂‐promoted reaction of three molecules of aromatic methyl ketones and one molecule of pyridine derivative. A wide range of methyl aryl ketones and methyl heteroaryl ketones took part in the reaction and generate 1,2,3‐triaroylindolizines in good yields. This protocol also features such advantages as mild reaction conditions and high atom economy and step economy.     

Synthesis and Antibacterial Activity of s‐Triazoles,s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazines and s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles of 5‐Methylisoxazole

The condensation of 4‐amino‐5‐mercapto‐3‐(5‐methylisoxazol‐3‐yl)‐1,2,4‐triazole with substituted phenacyl bromide, aldehydes, p‐bromophenylisothiocyanate, aromatic carboxylic acids and oxalic acid, is described. The antibacterial activity of representative compounds was evaluated.