ZrOCl2 · 8H2O as an Efficient Reagent for the Solvent‐Free Synthesis of 3,4‐Dihydropyrimidin‐2‐(1H)‐ones

ZrOCl₂ · 8H₂O, a commercially available reagent, can be used for the promotion of the synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones under solvent‐free reaction conditions. All reactions were performed at 90°C in good to high yields.     

Two‐Step Novel Synthesis of 2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐4,7‐diphenyloxepine‐3‐carbonitrile and 5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐6‐phenyl‐2H‐pyran‐3‐carbonitrile

Starting from indan‐1,3‐dione, a novel two‐step synthesis of the oxepine derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction conditions is described.     

Novel Approach to 3‐Methyl‐1H‐quinoxalin‐2‐ones

A novel approach to the synthesis of 3‐methyl‐1H‐quinoxalin‐2‐ones has been described. These compounds were regioselectively prepared by starting from substituted phenylamines and α‐chloropropionyl chloride through the efficient procedures of acylation, nitration, reduction, intramolecular alkylation, and oxidation.     

KHSO4 · H2O/SiO2‐Catalyzed,One‐Pot,Solvent‐Free Synthesis of Pyrazolines,Tetrahydrocarbozoles and Indoles using Microwave Irradiation

A new high‐yielding, operationally simple, solvent‐free, and mild method for preparation of pyrazolines, tetrahydrocarbazoles, and indoles has been developed using KHSO₄ · H₂O impregnated on SiO₂. The reactions have been probed under microwave irradiation (MWI), and ultrasonic and thermal conditions, employing different solid supports. The data revealed that KHSO₄ · H₂O impregnated on SiO₂ under MWI provides the best yields in a shorter time under solvent‐free reaction conditions.     

Novel Synthetic Route of (2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic Acid

(2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic acid, a key intermediate of Fidarestat, was synthesized from natural chiral pool D‐mannitol. Its structure was confirmed by optical analyses, elemental analyses, and IR, ¹H NMR, and ESI‐MS spectra.     

Facile Synthesis of 2‐Alkylthio‐5,5‐dimethyl‐4H‐imidazol‐4‐ones

The isothiocyanate 3, obtained from aza‐Wittig reaction of iminophosphorane 2 with CS₂, reacts with phenylhydrazine to give thiosemicarbazide 4. Reactions of 4 with alkyl halides in the presence of K₂CO₃ directly provided 2‐alkylthio‐4H‐imidazol‐4‐ones 6 in good yields.     

CeCl3 · 7H2O‐KI‐Catalyzed,Environmentally Friendly Synthesis of N,N′‐Disubstituted Ureas in Water Under Microwave Irradiation

N,N′‐Disubstituted ureas were efficiently synthesized by reactions of urea with a variety of amines in water under microwave irradiation using CeCl₃ · 7H₂O‐KI as catalyst. This protocol has advantages of not using toxic phosgene and hazardous organic solvents, high reaction rate, high yield, and a simple workup procedure.     

Facile Synthesis of 2‐Alkylthio‐3‐alkyl‐5‐phenylmethylidene‐4H‐imidazol‐4‐ones

2‐Alkylthio‐3‐alkyl‐5‐phenylmethylidene‐4H‐imidazol‐4‐ones 6 were synthesized by N‐alkylation and S‐alkylation of 2‐thioxo‐5‐phenylmethylidene‐4‐imidazolidinone 5, which was obtained via cyclization of vinyl isothiocyanate 4 with excess ammonium hydroxide (28% NH₃ in water).     

Facile One‐Pot Synthesis of 4‐Hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic Acid 1,1‐Dioxide

We report a convenient synthesis of 4‐hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic acid‐1,1‐dioxide (6a) prepared in a novel one‐pot reaction. The synthesis involves two transformations starting from 2‐methyl‐2H‐1,2‐benzothiazin‐4‐(3H)‐one 1,1‐dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One‐pot synthesis of an important intermediate, saccharin‐N‐methane sulfonic acid (4), is also described.     

Catalytic Oxidative Cyclocondensation of o‐Aminophenols to 2‐Amino‐3H‐phenoxazin‐3‐ones

The catalytic oxidative cyclocondensation of the o‐aminophenols 1a–f was investigated. The oxidants used were air/laccase, H₂O₂/horseradish peroxidase, H₂O₂/ebselen (3), and TBHP/diphenyl diselenide 4. The products obtained were 2‐amino‐3H‐phenoxazin‐3‐one—questiomycin A, its derivative 2b, and cinnabarinic acid and actinocin (2c,d). Substrates with methyl groups at 4 and 5 positions of benzene ring were converted to different dihydrophenoxazinones 2g,h. Compounds having chlorine atoms at the same positions underwent oxidation to planar phenoxa-zinones 2e,f with elimination of one hydrochloride molecule.     

Convenient Synthesis of Substituted 5‐(Hydroxymethyl)‐8‐methyl‐3‐(4‐phenylquinazolin‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones

Abstract

Interaction of 2‐imino‐2H‐pyrano[2,3‐c]pyridin‐3‐carboxamide with substituted 2‐aminobenzophenones proceeds via recyclization mechanism leading to substituted 3‐(4‐arylquinazolyn‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones. Their reaction with acetic anhydride affords the O‐acylation products.     

Synthesis of 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzofuro[3,2‐ d ] pyrimidin‐4(1H)‐ones

With the purpose of searching for new biologically active compounds, a method of synthesis of new heterocyclic systems [3‐alkyl(aryl)‐2‐thioxo‐2,3‐dihydro‐1H‐benzofuro[3,2‐d]pyrimidin‐4(1H)‐ones] has been developed. The method is based on the interaction of ethyl 3‐isothiocyanato‐1‐benzofurane‐2‐carboxylate in 2‐propanol with amines in the presence of an equimolecular quantity of triethylamine.     

One‐Pot Synthesis of 2‐(1‐Alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐quinoxaline Derivatives using Molecular Iodine

The title compound (5) has been prepared in one pot by refluxing 1‐(1‐alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐ethanone (1) with substituted o‐phenylenediamine (2) in ethanol in the presence of iodine. Alternatively, 5 could also be prepared by treating 2‐bromo‐1‐(1‐ alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐ethanone (3A) with 2 in refluxing ethanol. The formation of 5 from 1 and 2 probably occurs through the intermediacy of 3B (i.e., 3, X=I) and 4.     

Convenient Synthesis of Some Substituted 5‐Oxonitriles under Aqueous Conditions: Synthesis of 3,4‐Dihydro‐2H‐pyrrole‐2‐carbonitriles

Michael additions of [(diphenylmethylene)amino]acetonitrile (1) to α,β‐unsaturated ketones (chalkones) (2) under aqueous conditions allow for the highly diastereoselective synthesis of substituted 2‐amino‐5‐oxonitriles (3). Selective removal of diphenylmethylene protecting group, followed by in situ cyclization, gives 3,5‐diaryl‐3,4‐dihydro‐2H‐pyrrole‐2‐carbonitriles (4).     

Synthesis of 7‐Sulfamoyl‐substituted 2‐Oxo‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepines

Sulfochlorination of 2‐оxo‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepine led to regioselective formation of the corresponding 7‐chlorosulfonyl derivative. Starting from this reagent, a large number of substituted 2‐oxo‐7‐sulfamoyl‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepines were obtained. This approach is amenable to combinatorial production of the title compounds, which possess promising therapeutic potential.     

Efficient Synthesis of Trialkyl (E)‐3‐{3‐Oxo‐2‐3,4‐dihydro‐2‐(1H)‐quinoxalinylidene}‐prop‐1‐ene‐1,2,3‐tricarboxylates

The reaction of dialkyl acetylenedicarboxylates with alkyl 2‐[3‐oxo‐3,4‐dihydro‐2(1H)‐quinoxadinylidene]ethanoates in the presence of triphenylphosphine leads to trialkyl (E)‐3‐{3‐oxo‐2‐3,4‐dihydro‐2‐(1H)‐quinoxalinylidene}‐prop‐1‐ene‐1,2,3‐tricarboxylates in good yields.     

New Synthesis of 2‐Polyfluoroalkyl Substituted 1,4,5,6‐Tetrahydro‐pyrimidines and 4,5,6,7‐Tetrahydro‐1H‐1,3‐diazepines

A new efficient method for the preparation of 2‐polyfluoroalkyl substituted 1,4,5,6‐tetrahydropyrimidines and 4,5,6,7‐tetrahydro‐1H‐1,3‐diazepines by the reaction of polyfluoroalkanethiocarboxylic acids amides and 1,3‐propylenediamine or 1,4‐buthylenediamine is presented.     

Microwave‐Assisted One‐Pot Synthesis of 2‐(Substituted phenyl)‐1H‐benzimidazole Derivatives

A series of 2‐(substituted phenyl)‐1H‐benzimidazole derivatives with various 5‐and 6‐position substituents (‐H, ‐CH₃, ‐CF₃) were synthesized via microwave irradiation using a short synthetic route and Na₂S₂O₅ as oxidant. This simple, fast, and efficient preparation of benzimidazole derivatives has been developed using readily available and inexpensive reagents (aldehydes and 1,2‐phenylenediamines) under solvent‐free conditions.     

Synthesis of Tetrahydro‐2(1H)quinazolinones,Cyclopenta[d]‐2(1H)pyrimidinones,and Their Thioxo Analogs from 2‐Trifluoroacetyl‐1‐methoxycycloalkenes

A series of six (8)‐alkyl‐4‐trifluoromethyl‐5,6,7,8‐tetrahydro‐2(1H)quinazolinones, 4‐trifluoromethyl‐cyclopenta[d]‐2(1H)pyrimidinones, and their thioxo analogs from the reaction of five β‐alkoxyvinyl trifluoromethyl ketones, derived from alkylated cyclohexanones and cyclopentanone with urea and thiourea, is reported. The reactions were carried out in a single step in propan‐2‐ol as solvent and boron trifluoride diethyl etherate as catalyst in 18–65% yield.