Multi‐component Reactions,Solvent‐free Synthesis of Substituted Pyrano‐pyridopyrimidine under Different Conditions Using ZnO Nanoparticles

2‐Amino‐4‐(4‐substitutedphenyl)‐5‐oxo‐4H,5H‐pyrano[2,3‐d]pyrido[1,2‐a]pyrimidine‐3‐carbonitrile‐derivatives 2–12 were synthesized via multi‐component condensation reactions of different aromatic aldehydes, 3H‐pyrido[1,2‐a]pyrimidine‐2,4‐dione 1 , and malononitrile by using ZnO nanoparticles as green chemistry, environmentally friendly catalyst under solvent‐free conditions. The present work creates a variety of biologically active heterocyclic compounds in excellent yield and a short time. The structures of all synthesized compounds were elucidated with the elemental analyses, IR, ¹H NMR, and mass spectral data.     

Microwave assisted,sequential two-step,one-pot synthesis of novel imidazo[1,2-a]pyrimidine containing tri/tetrasubstituted imidazole derivatives

A series of novel imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives (1-10) has been synthesized via sequential two-step, one-pot, multicomponent reaction using imidazo[1,2- a ]pyrimidine-2-carbaldehyde, benzil, primary amines, and ammonium acetate catalyzed by p -toluenesulfonic acid under microwave-assisted conditions. The results showed that target compounds can be obtained from a wide range of primary amines bearing different functional groups with moderate to good yields (46%-80%) under optimum reaction conditions. This method provides a green protocol for imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives due to ethyl alcohol as a green solvent, microwave irradiation as a greener heating method and one-pot multicomponent reaction as a green technique. The synthesized compounds have been elucidated using various spectroscopic tools such as FT-IR, ¹H NMR, ¹³ C NMR, and MS.     

One‐pot New Barbituric Acid Derivatives Derived from the Reaction of Barbituric Acids with BrCN and Ketones

Reaction of cyclic β‐dicarbonyl compounds such as pyrimidine‐(1H,3H,5H)‐2,4,6‐trione (BA), 1,3‐dimethyl pyrimidine‐(1H,3H,5H)‐2,4,6‐trione (DMBA) and 2‐thioxo‐pyrimidine‐(1H,3H,5H)‐4,6‐dione (TBA) with cyanogen bromide in acetone and 2‐butanone in the presence of triethylamine afforded a new class of stable heterocyclic spiro[furo[2,3‐d]pyrimidine‐6,5′‐pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)‐pentaones (dimeric forms of barbiturate) at 0 °C and ambient temperature. Structure elucidation was carried out by X‐ray crystallographic, ¹H NMR, ¹³C NMR, two dimensional NMR, FT‐IR spectra, mass spectrometry and elemental analysis. The mechanism of product formation is discussed. The reaction of DMBA with cyanogen bromide in the presence of triethylamine also afforded trimeric form of barbiturate of uracil derivatives in good yield. The reaction of selected acyclic β‐dicarbonyl compounds with cyanogen bromide in the presence of triethylamine in acetone and/or diethyl ether has also been investigated under the same condition. Diethyl malonate and ethyl cyanoacetate brominated and also ethyl acetocetate both brominated and cyanated on active methylene via cyanogen bromide.     

Synthesis,reactions, and biological study of some new thienopyrimidine derivatives as antimicrobial and anti‐inflammatory agents

Pyrimidine and thienopyrimidine derivatives play a very important role in organic chemistry because of their wide applications as bioactive compounds with multiple biological activities. However, a literature survey revealed that the merger of different groups in the thieno[2,3‐d]pyrimidine heterocyclic ring enhances its antibacterial, antifungal and anti‐inflammatory activities. This encouraged us to prepare a new series of thieno[2,3‐d]pyrimidine heterocyclic compounds and to test them as antimicrobial and anti‐inflammatory agents. These compounds have shown remarkable activity toward fungi, bacteria, and inflammation. Thus, these compounds have been prepared by the chloroacylation of 5‐amino‐4‐phenyl‐2‐(p‐tolylamino)thieno[2,3‐d] pyrimidine‐6‐carboxamide ( 4 ) using chloroacetyl chloride under neat condition to afford the target compound ( 6 ), which was used as precursor for the synthesis of a number of bioactive compounds. Thus reaction of the chloromethylpyrimidine derivative ( 6 ) with triphenylphosphine in dry benzene gave the corresponding ((4‐oxo‐9‐phenyl‐7‐(p‐tolylamino)‐3,4‐dihydropyrimido[4′,5′:4,5]thieno[2,3‐d]pyrimidin‐2‐yl)methyl) triphenylphosphonium chloride ( 7 ). Compounds 8a – 8c and 9a – 9c were obtained by the reaction of 7 with some selected aromatic aldehydes and ketones in methanol and sodium methoxide under Wittig reaction condition. The structures of the all new synthesized compounds were established on the basis of their analytical and spectral data (IR, ¹H NMR, ¹³C NMR, and MS).     

New environmentally friendly solvent free synthesis of dihydropyrimidinones catalysed by N-butyl-N,N-dimethyl-α-phenylethylammonium bromide

N-Butyl-N,N-dimethyl-α-phenylethylammonium bromide catalyzes efficiently the three component condensation reaction of an aromatic aldehyde, a β-keto ester and urea/thiourea under solvent free conditions at 100°C to afford the corresponding dihydropyrimidinone in high yield.     

Regio- and diastereoselective synthesis of new functionalized indolo[2,3-b]indole-pyrimidine based on C–N bond formation via a four-component reaction

A facile and diastereoselective synthetic procedure has been designed for the preparation of new substituted indolo[2,3-b]indole (IDID) moiety at position-5 of the pyrimidine ring by a one-pot four-component reaction of dimedone, aniline and substituted derivatives, barbituric acid/thiobarbituric acid and isatin under mild conditions. This method proceeds rely on a CsbndN bond formation under catalyst-free conditions affording a range of skeletally diversity 5-indolo[3,2-b]indole-pyrimidine-based heterocycles. 5-Indolo[2,3-b]indol-pyrimidine-2,4,6-trione and 5-indolo[2,3-b]indol-2-thioxo-pyrimidine-4,6-dione were obtained in EtOH solvent in high yield, short reaction time and diastereoselectivity. The structural diversities of the synthesized compounds have been confirmed spectroscopically, by IR ¹H- and ¹³C NMR, EI-MS spectra and elemental analyses which agree with the proposed structures.     

Green approach for the synthesis of 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol 3‐yl)methylene)‐1H‐pyrazole‐5(4H)‐ones and their DNA Cleavage,antioxidant, and antimicrobial activities

3‐Methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones (5a‐i) was prepared by the condensation reaction of different 3‐formyl‐2‐phenylindole derivatives (2a‐i) and 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one in quantitative yield by applying various green synthetic methods as grinding, microwave irradiation using different catalysts under solvent‐free mild reaction conditions with high product yields. The structures of the synthesized compounds were characterized on the basis of elemental analysis, infrared, ¹HNMR, ¹³C NMR, and mass spectral data. The synthesized compounds were screened for free radical scavenging, antimicrobial, and DNA cleavage activities. Most of the tested compounds belonging to the 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones series exhibited promising activities.     

Synthesis of 12‐aryl‐12H‐benzo[i][1,3]‐dioxolo[4,5‐b]xanthene‐6,11‐diones using silica sulfuric acid as an efficient and versatile catalyst under solvent‐free conditions

Some novel 12‐aryl‐12H‐benzo[i][1,3]‐dioxolo[4,5‐b]xanthene‐6,11‐diones can be rapidly and efficiently synthesized in excellent yields by condensing a variety of aldehydes with 3,4‐methylenedioxyphenol and 2‐hydroxy‐1,4‐naphthoquinone in the presence of a catalytic amount of silica sulfuric acid under solvent‐free conditions. The simple experimental procedure, solvent‐free reaction conditions, utilization of an inexpensive and readily available catalyst, short period of conversion, and excellent yields are the advantages of the present method. Furthermore, the catalyst can be recycled and reused three times without significant loss of activity. The structures of the novel compounds are confirmed by IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. J. Heterocyclic Chem., 2011.     

TiO2–SiO2 Catalyzed Eco‐friendly Synthesis and Antioxidant Activity of Benzopyrano[2,3‐d]pyrimidine Derivatives

A cost‐effective and eco‐friendly synthesis of benzopyrano[2,3‐d ]pyrimidine derivatives has been developed via three component one‐pot tandem approach by condensing different salicylaldehydes and secondary amines with malononitrile in the presence of TiO₂–SiO₂ catalyst at 80°C under solvent‐free conditions. Mild experimental conditions, reusability of the catalyst, and cost effectiveness are the merits of this procedure. Compounds 4g , 4h , and 4i bearing 2‐OMe group on the hydroxyphenyl group linked to the central carbon present in between the two nitrogen atoms of the pyrimidine ring were found to exhibit good antioxidant activity while other compounds have moderate antioxidant activity.     

Zwitterionic Salts from the Reaction of Symmetrical and Unsymmetrical (thio)Barbituric Acids with 2‐Pyridinecarbaldehyde under Solvent‐free Condition

A simple and efficient synthesis for the preparation of unusual charge‐separated pyridinium (thio)barbiturate zwitterion derivatives was achieved via a one‐pot reaction of (thio)barbituric acid derivatives and 2‐pyridinecarbaldehyde under solvent‐free condition and also in methanol under refluxing. The structure of the compounds was confirmed by ¹H NMR, ¹³C NMR, FT‐IR, mass and X‐ray analysis. The mechanism of the formation is discussed. Instead, no related pyridinium zwitterion was afforded from the reaction between dimedone and 2‐pyridinecarbaldehyde under the same conditions and its xanthene derivative was obtained.     

An Efficient Synthesis of Highly Optically Active 4-Substituted-2（5H）-furanones from Chiral 3-Bromo-2（5H）-furanone

Highly optically active 4-substituted-2(5H)-furanones 6a-6j were obtained in good yields with de≥98% by the tandem Michael addition/elimination reaction of chiral 3-bromo-2(SH)-furanone (4a), which was conveniently prepared starting from 2-furaldehyde under mild conditions. The products were identified on the basis of their satisfactory elemental analysis and spectroscopic data of IR, UV, ^1H NMR, ^13C NMR and mass spectra. The stereochemistry and absolute configuration of this type of compounds were established by the X-ray crystallographic study. The reaction provided a short and efficient synthesis of the interesting highly optically active 4-subsdtuted-2(5H)-furanones containing an active pyrimidine and a purine base group.     

A microwave‐assisted solid‐state synthesis and characterization of diheterocyclic thioureas

In this study, a number of new diheterocyclic thioureas have been synthesized under microwave irradiation coupled with solvent‐free condition, which proves to be simple and efficient. The structures of the prepared compounds are characterized by elemental analysis, IR, ¹H NMR, and ¹³C NMR spectra. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:148–151, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20193     

Stereoselective synthesis of new dihydropyrimidinone glycoconjugates #

Stereoselective synthesis of dihydropyrimidinone glycoconjugates in high yields, from different sugar aldehydes, by a three‐component coupling (Biginelli) reaction is reported. In this new method, HC1 generated ‘in situ’ from2,4,6‐trichloro[l,3,5]triazine(TCT; 10 mol%), was used under mild and solvent free reaction conditions.     

Unequivocal total assignment of 13C and 1H NMR spectra of some pyrido[1,2‐a]pyrimidine derivatives by 2D‐NMR

We report the total assignments of the ¹³C and ¹H NMR spectra of some 4‐methyl‐2‐oxo‐(2H)‐pyrido[1,2‐a]pyrimidine and 2‐methyl‐4‐oxo‐(4H)‐pyrido[1,2‐a]pyrimidine derivatives. The products were characterized by ¹H and ¹³C NMR and reported data for similar compounds. No comparative data for the two sets of isomeric compounds with respect to ¹³C and ¹H NMR have been reported to date. We made some detailed studies of the 2D NMR spectra of these compounds and observed that assignments made for non‐protonated carbon atoms by us and those reported in the literature for similar compounds need correction. The revised assignments were made on the basis of heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) techniques. Copyright © 2003 John Wiley & Sons, Ltd.     

Identification of a Unique Cationic Impurity in Preladenant™ Using Accurate MS and NMR

High resolution MS, 1D, and 2D NMR were used to determine the structure of a unique cationic impurity generated during the synthesis of Preladenant? H/D exchange experiments were performed by both MS and NMR to confirm the acidic nature of the cationic dihydroimidazole proton. The presence of three exchangeable protons was established by MS experiments and the disappearance of the C11 proton in ¹H‐NMR spectrum on equilibration with D₂O confirmed the acidic nature of the cationic dihydroimidazole proton. A piperazine ring contraction mechanism is proposed for the formation of the cationic dihydroimidazole.     

Synthesis,molecular docking studies,and absorption,distribution, metabolism,and excretion prediction of novel sulfonamide derivatives as antibacterial agents

A series of novel sulfonamide‐amide derivatives were synthesized from 3‐(2,4 dichlorophenylamino)‐3‐oxopropane‐1‐sulfonylchloride and a variety of amines under solvent‐free conditions at room temperature. 3‐(2,4‐dichlorophenylamino)‐3‐oxopropane‐1 sulfonylchloride was synthesized in four steps starting from 2,4‐dichloroaniline and chloropropanoic acid in good yield and purity. The synthesized compounds were screened for their in vitro antibacterial activity against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213). Molecular docking of sulfonamide derivatives into S. aureus tyrosyl‐tRNA synthetase (TyrRS)‐active site was also performed and among these, 5m and 5g tightly fit the active sites that might be inhibitors of TyrRS for further investigations. Also in the silico metabolism profile, drug‐like properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) of the title compounds were calculated by the preADMET server.     

Peroxide/Potassium Iodide Redox Systems for in situ Oxyiodination of Organic Compounds under Liquid‐Phase and Solvent‐Free Conditions

Iodination of certain aromatic amines and phenols are triggered by the oxidation of KI by peroxy compounds such as tert‐butyl hydroperoxide (^tBuOOH) under liquid‐phase and solvent‐free conditions by grinding the reactants in a mortar with a pestle. The reactions afforded corresponding iodo derivatives in good yield with high regioselectivity (Table 1).     

A Greener Approach Synthesis and Docking Studies of Perimidine Derivatives as Potential Anticancer Agents

Microwave solvent‐free technique was employed to the synthesis of series of 2‐(1H‐perimidin‐2(3H)‐ylidene) derivatives, 4‐(1H‐perimidin‐2‐yl)‐1H‐pyrazole‐3‐carboxamides, pyrrolo[1,2‐a]perimidin‐10‐ones, and 8H‐[1,2,4]triazolo[4,3‐a]perimidine. Compared with conventional method, the obvious feature of microwave method is higher in chemical yield, faster reaction rate, and cleaner reaction condition. The structures of the synthesized compounds were confirmed based on their elemental analyses and spectroscopic data (FT‐IR, ¹H‐NMR, ¹⁹F‐NMR, ¹³C‐NMR, and LC‐MS/MS). Some of the synthesized compounds exhibit anticancer potential against the growth of both the human breast (MCF‐7) and the liver carcinoma (HepG2) tumor cells. The most active cytotoxic perimidine derivatives were docked against topoisomerase II to investigate their binding and DNA intercalating activity against the protein crystal structure.     

Three‐Step Synthesis of Novel 2‐Aryl‐3‐benzamidobenzofurans: Regiospecific Reactions Catalyzed by Molybdate Sulfuric Acid

A solvent‐free and synthetic pathway to novel benzofuran derivatives, starting from oxidation of phenyl ketones to arylglyoxals in three steps was developed. The molybdate sulfuric acid catalyzed the reaction of arylglyoxals with benzamide and phenols to afford 2‐aryl‐3‐benzamidobenzofurans in high yield. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR, and ¹³C NMR spectral data. The present methodology offers several advantages such as non‐hazardous reaction condition, simple operation, and work‐up procedure.     

Silica‐Supported P2O5 as an Efficient Heterogeneous Catalyst for the One Pot Synthesis of 3‐Amino‐imidazo[2,1‐b](1,3)benzothiazole under Green Conditions

The new approach involving the solid supported catalyst for the formation of C–N bond followed by cyclization has been reported. In this work we have reported a facile, efficient, and environment‐friendly protocol for the synthesis of some new 3‐amino‐imidazo[2,1‐b](1,3)benzothiazole derivatives by one‐pot condensation of 2‐aminobenzothiazole, indole‐3‐carbaldehyde, and aryl isocyanide in the presence of silica‐supported P₂O₅ as a heterogeneous solid acid catalyst. The reaction was performed using conventional method under green conditions. The present approach offers the advantages of simple methodology, inexpensive acid catalyst, short reaction time, easy work up with excellent yield, simple purification and use of green solvent. All the newly synthesized compounds were characterized in details using physical and chemical techniques such as melting point, ¹H NMR, ¹³C NMR, and FTIR spectroscopy.