Potassium Carbonate In DMF Research Articles

Microwave Synthesized Hydrophilic 4‐Oxo‐2‐phenylquinazoline‐3(4H)–carboximidamide and –Carboxamide as Privileged Small Molecule Scaffolds with Anti‐HIV‐1 Activities

AbstractOpportunistic infections like tuberculosis (TB) are prevalent in HIV‐infected individuals. In an approach to introducing an industrial‐scale microwave‐assisted production of agents having both antiviral and antibacterial properties, a set of hydrophilic 2,3‐substituted quinazolinones, 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboximidamide (Qg) and 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboxamide (Qu), were afforded in encouraging yields. They were obtained by treating 2‐benzamidobenzoyl chloride with guanidine hydrochloride or urea in the presence of potassium carbonate in DMF. DFT calculations were employed for geometrical optimization and vibrational frequency analysis of the compounds. Free energies of solvation (ΔGsol) of Qg, and Qu calculated using DFT lend evidence in support of their hydrophilicity The anti‐HIV‐1 activities of the small‐molecule quinazolinone derivatives Qg and Qu were investigated. The synthons under in vitro conditions inhibit the entry of HIV in receptor cells with low cytotoxicity (EC50=50.53 nM for Qu and EC50=97.92 nM for Qg). The study identifies the antiviral properties of the two benzo‐fused pyrimidine derivatives, which were earlier reported to have antitubercular activity. Our findings indicate the scope for further synthetic explorations of these quinazolinone scaffolds that can lead to developing promising alternatives in drug design, pharmaceutics, and clinical research.

Synthesis of Novel Oxo Pyrimido Pyrimidine and Their Derivatives

Abstract: Pyrimidine derivatives are synthesized to possess various pharmacological and biological activities. In the present work, we have synthesized 3-(4-methoxyphenyl)-1-phenyl prop-2-en-1-one (1) (chalcone) by using 4-methoxybenzaldehyde and acetophenone in the presence of alcoholic KOH by Claisen-Schmidt condensation reaction. After purification and characterization by physical and spectral methods, The synthesized chalcone have been converted into 6-(4-methoxyphenyl)-4- phenyl-1,6-dihydropyrimidin-2-amine (2) by treating with guanidine nitrate in the presence of alcoholic KOH. The structure (2) has been characterized by spectral analysis. The synthesized compound (2) is further reacted with ethyl 2-cyano-3, 3-bis (methylthio)acrylate in the presence of catalytic amount of potassium carbonate in DMF under reflux condition to givenovel 2- (4-methoxyphenyl)-8-(methylthio)-6-oxo-4-phenyl-1,6,9,9a-tetrahydro-2H-pyrimido[1,2-a] pyrimidine-7-carbonitrile(3) in good yields. The compound (3) possesses replaceable methylthio (-SCH3) group at 8 position. The compound (3) is further reacted with various nucleophiles like substituted aromatic amines, aromatic phenols, hetryl amines and active methylene compounds to give 2-(4-methoxyphenyl)-8-substituted-6-oxo-4-phenyl-1,6,9,9a-tetrahydro-2H-pyrimido[1,2-a]pyrimidine-7-carbonitrile in good yields.

Synthesis of a novel iminopyrimidooxazine and their derivatives

We have synthesized 2-(4-chlorophenyl)-8-(methylthio)-6-imino-4-phenyl-2,6,9,9a-tetrahydropyrimido[2,1-b][1,3]oxazine-7-carbonitrile (3) by the reaction of 6-(4-chlorophenyl)-4-phenyl-6H[1,3]oxazin-2-amine (2) with 2-(bis (methylthio)methylene)malononitrile in the presence of catalytic amount of potassium carbonate in DMF under reflux condition. The aminooxazine was prepared by the reaction of chalcone (1) with urea in the presence of ethanol and sodium hydroxide under reflux condition. The synthesized compounds were characterized by spectral methods. The compound (3) possesses replaceable methylthio (-SCH3) group at 8 position. The compound (3) react with various nucleophiles like substituted aromatic amines, aromatic phenols, hetarylamines and active methylene compounds to give 2-(4-chlorophenyl)-8-(substituted)-6-imino-4-phenyl-2,6,9,9a-tetrahydropyrimido[2,1-b][1,3]oxazine-7-carbonitriles in good yields.

Synthesis and antiproliferative activity of new hybrids bearing neocryptolepine, acridine and α-aminophosphonate scaffolds

Synthesis of novel α-aminophosphonate hybrids 8a–f was accomplished by the reaction of 11-phenoxy-4-formylneocryptolepine 3, aminoalkylamino acridines 6a–f and diphenyl phosphite 7 in the presence of lithium perchlorate as Lewis acid catalyst in methanol. The starting aldehyde 3 was obtained by reaction of 11-chloroneocryptolpine 1 with 4-hydroxybenzaldehyde 2 in the presence of potassium carbonate in DMF, whereas 9-aminoalkylamino acridines 6a–f were synthesized by reaction of 9-chloroacridine 4 with appropriate diamines 5a–f. The structure of all synthesized hybrids was confirmed by spectroscopic methods and showed spectra in consistence with the expected structures. The antiproliferative activity of all synthesized hybrids was evaluated against HCT-116, MCF-7, HepG2 and A549 human cancer cell lines. The screened results proved that most of the reported compounds are potent, especially hybrid 8a, which displayed the highest activity against MCF-7, HepG2 and A549 cancer cell lines with IC50 8.2, 23.1 and 19.4 µM, respectively. This activity is significantly higher than the standard drug doxorubicin. Moreover, hybrid 8f showed most potent activity against HCT-116 cancer cell line with IC50 2.4 µM higher than the reference drug doxorubicin (IC50:10.90 µM).

Synthesis of Novel Pyrimido Pyrimidine and Their Derivatives

Chalcone derivatives were synthesis by the reaction of some 4-nitrobenzaldehyde derivatives with acotophenone then the product obtained E-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one. This product is chalcone is another react with guanidine nitrate. The hetrocyclic derivatives of guanidine nitrate respectively the final product have been characterized by elemental analysis. the product obtained is 1,6 dihydro 6(4-nitrophenyl) 4-phenylpyridine 2-amine. In present report novel pyrimidines were prepared from starting materials chalcone and guanidine nitrate. The resulting compound 1,6-dihydro-6-(4-nitrophenyl)-4 phenylpyrimidin 2 amine (2) was further reacted with 2 bis(methylthio)methylene malononitrile in the presence of catalytic amount of potassium carbonate in DMF under reflux condition that offered novel 4,6,9,9a-tetrahydro-4-imino-2-(methylthio)-8-(4-nitrophenyl) 6 phenyl 1H pyrimido[1,2 a]pyrimidine 3 carbonitrile (3). The synthesized compounds were characterized by spectral methods. The compound (3) possesses replaceable methylthio (-SCH3) group at 2 position. The compound (3) react with various nucleophiles like substituted aromatic amines, aromatic phenols, hetryl amines and active methylene compounds to give 4,6,9,9a-tetrahydro-4-imino-2-(methylthio)-8-(4-nitrophenyl)-6-phenyl-1H-pyrimido[1,2-a]pyrimidine-3-carbonitrile –carbonitrile in good yields.

Reactions of Ethyl 5-Methyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylate with Selected Bases

The reactions of 5-methyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylic acid ethyl ester with some bases have been studied. The opening of 1,2,3-thiadiazole ring under the action of potassium tert-butylate in tetrahydrofuran in the presence of methyl iodide has led to the corresponding 4-methylsulfanylethynylfuran derivative. Under the action of potassium carbonate in DMF with an excess of primary amines or morpholine, the starting thiadiazole has formed the corresponding thioamides of furylacetic acid. The reaction of ethyl 5-methyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylate with hydrazine hydrate has led to hydrazinolysis of the ester group without cleavage of the 1,2,3-thiadiazole ring.

Synthesis of Novel Pyrimido Thiazine and Their Derivatives

In present report novel thiazines were prepared from starting materials chalcone and thiourea. The resulting compound 6-(4-methoxyphenyl) 4-phenyl-6H-1, 3-thiazin-2-amine (2) was further reacted with ethyl 2-cyano-3, 3-bis (methylthio) acrylate in the presence of catalytic amount of potassium carbonate in DMF under reflux condition that offered novel 2-(4-methoxyphenyl) 8-(methylthio)-6-0xo-4-phenyl-4, 6, 9, 9a-tetrahydropyrimido [2, 1-b] [1, 3]-thiazine-7-carbonitrile (3). The synthesized compounds were characterized by spectral methods. The compound (3) possesses replaceable methylthio (-SCH₃) group at 8 position. The compound (3) react with various nucleophiles like substituted aromatic amines, aromatic phenols, hetryl amines and active methylene compounds to give 2-(4-methoxyphenyl)-8-substituted-6-oxo-4-phenyl-4, 6, 9, 9a-tetrahydropyrimido [2, 1-b] [1, 3] thiazine-7-carbonitrile in good yields.

Synthesis of the Derivatives of 4-(5-Aryl-3-methylfuran-3-yl)-1,2,3-thiadiazole and Functionalization of 5-Aryl-2- methylfuran via Reactions of Thiadiazole Ring

By arylation of 2-methyl-3-acetylfuran via the Gomberg–Bachmann reaction 5-(4-ethoxycarbonylphenyl)-, 5-(2-nitrophenyl), and 5-(4-nitrophenyl)-2-methyl-3-acetylfurans were synthesized. Carboethoxyhydrazones of 2-methyl-5-phenyl-3-acetylfuran and its phenyl-substituted analogs when treated with thionyl chloride form 4-(5-aryl-2-methylfuran-3-yl)-1,2,3-thiadiazoles by the Hurd–Mori reaction. Thermal stability of obtained compounds increases with the increase in electron-acceptor action of substituent in phenyl ring. Opening of thidiazole ring in the compounds synthesized under the action of potassium tert-butylate in THF in the presence of alkyl iodides leads to the corresponding alkylthioethynylfurans. Performing the reaction with potassium carbonate in DMF in the presence of excess morpholine permits the preparation of (2-methyl-5- arylfuran-3-yl)thioacetylmorpholides.

Synthesis of Novel 7‐methylene‐6,7‐dihyrobenzo[f]Benzo[4,5]Imidazo[1,2‐d][1,4]Oxazepines via Base‐mediated Regioselective Intramolecular Hydroamination

A versatile and transition metal‐free approach for the synthesis of new 7‐methylene‐6,7‐dihyrobenzo[f]benzo[4,5]imidazo[1,2‐d][1,4]oxazepines were developed by an efficient 7‐exo‐dig regioselective hydroamination of 2‐(2‐(prop‐2‐yn‐1‐yloxy)phenyl)‐1H‐benzo[d]imidazole in the presence of potassium carbonate in DMF at 90°C.

ChemInform Abstract: An Efficient Transformation of Furano‐Hydroxychalcones to Furanoflavones via Base Mediated Intramolecular Tandem O‐Arylation and C—O Bond Cleavage: A New Approach for the Synthesis of Furanoflavones.

AbstractA new approach for the synthesis of the natural furanoflavones lanceolatin B (IIa) and pongaglabrone (IIb) from corresponding furano‐hydroxychalcones (I) under mild, metal‐free conditions is given.

ChemInform Abstract: Facile Synthesis of 3‐N‐Alkyl Pyrimidin‐2,4‐diones from N‐Sulfonyloxy Maleimides and Amines.

Reaction of variously substituted N-trifluoromethanesulfonyloxy maleimides with primary amines in the presence of potassium carbonate in DMF at room temperature results in the formation of 3-N-alkyl pyrimidin-2,4-diones in good yield.

Synthesis, anti microbial screening and cytotoxic studies of some novel pyrazole analogs

ABSTRACT Objective: To synthesize novel pyrazole analogs and evaluate their antimicrobial, anthelmintic and cytotoxic activity. Method: Novel (Z)-1-(4-chlorophenyl)-2-(3,5-dimethyl-4-(substituited phenyldiazenyl)-1H-pyrazol-1-yl)ethanone derivatives were synthesized by conventional method using potassium carbonate in DMF, under reflux condition. The antibacterial study was carried out against gram positive and gram negative bacteria using ciprofloxacin and norfloxacin as standard drugs. Antifungal activity was compared against fluconazole and evaluated using Candida albicans (MTCC 227) and Aspergillus niger (NCIM 1056). Anthelmentic activity assay was carried out on Indian earthworm, Pheretima posthuma. In vitro cytotoxicity studies were also carried out using Dalton’s lymphoma ascites cells (DLA) and Ehrlich ascites carcinoma cells (EAC). Results: Results of antibacterial study indicated that the compound 22 showed most promising activity against both Gram-positive and Gram-negative organisms. Compound 21 and 24, exhibited relatively good inhibitory profile against Gram negative organism. In case of compounds 25,27-30 exhibited equally potent antifungal activity as that of the standard drug fluconazole. Moreover, compound 21-24,26 showed excellent activity against C. albicans and A.niger. The in vitro cytotoxicity results and anthelmintic reports indicated compound 22 exhibited promising activity among the tested analogs. Conclusion: These newly synthesized pyrazole analogs, especially 21, 22 and 24 are better scaffolds to develop as broad spectrum chemotherapeutic agents.

Facile Synthesis of 3-N-Alkyl Pyrimidin-2,4-diones from N-Sulfonyloxy Maleimides and Amines.

Reaction of variously substituted N-trifluoromethanesulfonyloxy maleimides with primary amines in the presence of potassium carbonate in DMF at room temperature results in the formation of 3-N-alkyl pyrimidin-2,4-diones in good yield.

ChemInform Abstract: Nickel(II) Complex Containing N‐(4,5‐Dihydrooxazol‐2‐yl)benzamide Ligands: Highly Efficient Catalyst for Heck Coupling Reactions.

Heck reaction catalyzed by Ni(II) containing N-(4,5-dihydrooxazol-2-yl) benzamide has been developed. The coupling of alkenes with aryl iodide or aryl bromide in the presence of potassium carbonate in DMF provides the corresponding products with moderate to good yields. This method possesses obvious advantages such as low-cost catalyst and simple experimental operation. Copyright © 2014 John Wiley & Sons, Ltd.

Nickel(II) complex containing N‐(4,5‐dihydrooxazol‐2‐yl)benzamide ligands: highly efficient catalyst for Heck coupling reactions

Heck reaction catalyzed by Ni(II) containing N‐(4,5‐dihydrooxazol‐2‐yl) benzamide has been developed. The coupling of alkenes with aryl iodide or aryl bromide in the presence of potassium carbonate in DMF provides the corresponding products with moderate to good yields. This method possesses obvious advantages such as low‐cost catalyst and simple experimental operation. Copyright © 2014 John Wiley & Sons, Ltd.

Facile microwave-assisted synthesis of substituted benzofuran derivatives

A series of benzofuran derivatives have been synthesized by use of a microwave-assisted process. Substituted or unsubstituted ο-hydroxyacetophenone and salicylaldehyde reacted with ethyl bromoacetate, ω-bromoacetophenone, or chloroacetone under the action of potassium carbonate in DMF to yield substituted benzofuran derivatives. Compared with conventional heating, this microwave-assisted synthetic process has the advantages of more convenient operation, shorter reaction time, and higher yield.

Antitermite activity of 7-alkoxycoumarins and related analogs against Coptotermes formosanus Shiraki

Twenty-three 7-alkoxycoumarins and related analogs were synthesized from 7-hydroxycoumarin by treatment with various alkyl/aryl/acyl halides and potassium carbonate in DMF. Their antifeedant and termiticidal activities against Coptotermes formosanus Shiraki were examined. Among the 23 compounds and control, 7-cyclohexyloxycoumarin (2k), exhibited the highest termiticidal activity in no-choice test, followed by 7-(4-nitrophenoxy)coumarin (2q), and 7-(2-butynyloxy)coumarin (2u) at 5 μmol/disc. On the other hand, all of 7-alkoxycoumarins showed antifeedant activity except 7-hexadecyloxycoumarin (2i) and 7-octadecyloxycoumarin (2j), while 7-ethoxycoumarin (2b) demonstrated the highest antifeedant activity. The results suggested that a presence of cyclohexyloxy and aryloxy groups at C-7 position of coumarin skeleton was found to be important for the termiticidal and antifeedant activities. Arylalkoxy groups having methoxy groups at benzene ring, alkenoxy, and alkynoxy groups led to analogs with good termiticidal activity, while the incorporation of alkoxy groups with longer alkyl chains tended to reduce both the termiticidal and antifeedant activities.

Synthetic Protocols Mutually Applicable to 4-Oxoquinolines and 4-Oxo-1,8-naphthyridines: Synthesis of 1-Aryl-2-substituted and 1-Aryl-3-fluoro-4-oxoquinolines and 4-Oxo-1,8-naphthyridines

We have achieved the synthesis of 1-aryl-2-substituted 4-oxoquinoline and 4-oxo-1,8-naphthyridine derivatives, which cannot be synthesized by known methods, via two useful synthons, 2-formyl-4-oxoquinoline and 2-methylsulfonyl-4-oxo-1,8-naphthyridine. We also succeeded in the synthesis of 1-aryl-3-fluoro-4-oxoquinoline by fluorocyclization of N-arylenaminone with Select-fluor ® and potassium carbonate in DMF in a one-pot procedure. To the best of our knowledge, this is the first synthesis of 3-fluoro-4-oxoquinoline derivatives. We confirmed that these protocols were mutually applicable to the synthesis of 4-oxoquinoline and 4-oxo-1,8-naphthyridine derivatives.

Simple and Efficient Synthesis of Novel Fused Bicyclic Heterocycles Pyrimido-Thiazine and Their Derivatives

We report simple and efficient synthesis of novel fused bicyclic heterocyclic compounds 3 using bis (methylthio) methylene malononitrile 1 and thiourea 2 with potassium carbonate in DMF at reflux condition. The molar ratios of these substrates are 2:1 for the preparation of 2,6-dihydro-2,6-diimino-4,8-bis(methylthio) pyrimido[2,1-b][1,3]thiazine- 3,7-dicarbonitrile. This newly synthesized pyrimido thiazine acts as bis-electrophilic species reacting with various nucleophiles yielding 2,6-dihydro-2,6-diimino-4,8-(disubstituted)-pyrimido[2,1-b][1,3]thiazine-3,7-dicarbonitrile in good yields.

Synthesis of 3-substituted benzo[ g]isoquinoline-5,10-diones: a convenient one-pot Sonogashira coupling/iminoannulation procedure

A series of 3-substituted 5,10-dimethoxybenzo[ g]isoquinolines were prepared by coupling of terminal alkynes with the tert-butylimine of 3-bromo-1,4-dimethoxy-2-naphthaldehyde in the presence of a Pd-catalyst and subsequent Cu-catalyzed cyclization of the intermediate 3-alkynyl-2-naphthylcarbaldehyde. A CAN-mediated oxidative demethylation yielded the corresponding 2-azaanthraquinones in excellent yields. Since this methodology proved to be limited to alkynes bearing aromatic groups, an alternative and more general Pd-catalyzed coupling procedure was developed, starting from 3-bromo-1,4-dimethoxy-2-naphthaldehyde. For more acidic terminal alkynes, like phenylacetylene, a combination of Pd(OAc) 2/P( t-Bu) 3/CuI (2/6/1) with potassium carbonate in DMF gave a complete conversion within 24 h. For less acidic acetylenes, 2 equiv of alkyne and caesium carbonate as a base were required in order to obtain complete conversion of the starting material within 24 h. These altered Sonogashira conditions also allowed the isolation of a benzo[ f]indenone as an interesting side product in case Bu 4NCl was added to the reaction mixture. The 3-alkynyl-1,4-dimethoxy-2-naphthaldehyde acquired after completion of the Pd-catalyzed coupling could be cyclized by adding a solution of ethanolic ammonia and an extra equivalent of potassium carbonate to the reaction mixture. As such, this consecutive one-pot coupling/iminoannulation procedure was a convenient alternative to the Larock isoquinoline procedure, enabling the isolation of a series of 3-substituted 5,10-dimethoxybenzo[ g]isoquinolines.