Unexpected One‐pot Synthesis of Novel 2‐Aminopyrimidine‐4‐ones under Microwave Irradiation

One‐pot, three‐component condensation of guanidine, ethylbenzoylacetate and various aromatic aldehydes in the presence of NaHCO₃ have been investigated by microwave irradiation. The aromatic aldehydes bearing electron‐withdrawing groups undergo condensation with guanidine and ethylbenzoyl‐acetate to afford ethyl‐2‐amino‐4‐aryl‐1,4‐dihydro‐6‐phenylpyrimidine‐5‐carboxylate derivatives via Biginelli reaction. However, reaction of the aromatic aldehydes having electron‐releasing groups with guanidine and ethylbenzoylacetate did not give the corresponding dihydropyrimidines. Instead, novel 2‐amino‐5‐benzoyl‐5,6‐dihydro‐6‐arylpyrimidine‐4(3H)‐ones were obtained via an unexpected mechanism.     

An efficient and facile ultrasonic‐accelerated one‐pot synthesis of N‐acetyl‐2‐aryl‐1, 2‐dihydro‐(4H)‐3,1‐benzoxazin‐4‐ones

An application of ultrasonic irradiation in the one‐pot synthesis of N‐acetyl‐2‐aryl‐1,2‐dihydro‐(4H)‐3,1‐benzoxazin‐4‐ones from the condensation reaction between aromatic aldehydes and anthranilic acid in the presence of excess amount of acetic anhydride has been explored. The reactions proceed smoothly under mild and solvent‐free conditions at room temperature in the absence of any catalyst to afford the products in good to excellent yields. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:106–113, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20663     

Green Biginelli‐type Reaction: Solvent‐free Synthesis of 5‐unsubstituted 3,4‐dihydropyrimdin‐2(1H)‐ones

The Biginelli‐type compounds, 5‐unsubstituted 3,4‐dihydropyrimdin‐2(1H)‐ones were synthesized by a one‐pot three‐component condensation of aromatic aldehydes, aromatic ketones and urea in the presence of SnCl₄ · 5H₂O under solvent‐free conditions. The advantages of this method are short reaction time (4–10 min), excellent yields (74–97%), inexpensive catalyst and solvent‐free conditions. A plausible mechanism was proposed.     

Diastereoselective Synthesis of Functionalized Tetrahydropyrimidin‐2‐thiones via ZnCl2 Promoted One‐pot Reactions

In the presence of zinc chloride, the in situ generated β‐enamino ester from the reaction of morpholine, piperidine and pyrrolidine with methyl propiolate reacted, with aromatic aldehydes and thiourea in ethanol resulting in the functionalized tetrahydropyrimidin‐2‐thiones in satisfactory yields and with good diastereoselectivity. When aromatic aldehydes bearing electron‐withdrawing group were used in the reaction, the 4‐hydroxytetrahydropyrimidin‐2‐thione derivatives were obtained as the main product.     

Domino‐Hydroformylation/Aldol Condensation Catalysis: Highly Selective Synthesis of α,β‐Unsaturated Aldehydes from Olefins

A general and highly chemo‐, regio‐, and stereoselective synthesis of α,β‐unsaturated aldehydes by a domino hydroformylation/aldol condensation reaction has been developed. A variety of olefins and aromatic aldehydes were efficiently converted into various substituted α,β‐unsaturated aldehydes in good to excellent yields in the presence of a rhodium phosphine/acid–base catalyst system. In view of the easy availability of the substrates, the high atom‐efficiency, the excellent selectivity, and the mild conditions, this method is expected to complement current methodologies for the preparation of α,β‐unsaturated aldehydes.     

Synthesis of Functionalized Thiophenes by Four‐component Reactions of 1,3‐Thiazolidinedione,Aromatic Aldehydes,Cyanoacetamide and Cyclic Secondary Amines

The polysubstituted thiophene derivatives were conveniently prepared by the four‐component reactions of 1,3‐thiazolidinedione, aromatic aldehydes, cyanoacetamide and cyclic secondary amines such as pyrrolidine, morpholine and piperidine. The reaction mechanism is believed to involve domino reactions of Knoevenagel condensation, Michael addition, ring‐opening and recyclization of 1,3‐thiazolidinedione.     

Synthesis,characterization, antibacterial and antifungal activity of 2‐(aryl)‐3‐(3‐((8‐hydroxyquinolin‐5‐yl)diazenyl)phenyl)thiazolidin‐4‐ones

5‐((3‐Aminophenyl)diazenyl)quinolin‐8‐ol ( 1 ) was synthesized by diazotization reaction and coupled with 8‐hydroxyquinoline moiety. This amine on facile condensation with aromatic aldehydes in presence of glacial acetic acid and ethanol affords anils ( 2 ). These anils on cyclocondensation reaction with thioglycolic acid (i.e., mercaptoacetic acid) yield the titled compound ( 3 ). The structure of the newly synthesized anils ( 2 ) and thiazolidinones ( 3 ) has been confirmed by elemental analysis and spectral analysis. The titled compounds have been screened against different bacterial and fungal strains. J. Heterocyclic Chem., (2011).     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

Solvent‐free condensation of aromatic aldehydes and 2,3‐dimethyl‐1‐phenyl‐3‐pyrazolin‐5‐one by p‐toruenesulfonic acid

Solvent‐free condensation easily occurred by mixing aromatic aldehydes and 2,3‐dimethyl‐1‐phenyl‐3‐pyrazoline‐5‐one (antipyrine) in the presence of p‐toluenesulfonic acid as a solid acid catalyst at room temperature to give the corresponding disubstituted products as sole products in high yields.     

Green Approach to the Design of Functionalized Medicinally Privileged 4‐Aryl‐1,4‐dihydropyrano[2,3‐c]‐pyrazole‐5‐carbonitrile Scaffold

“On water” multicomponent condensation of aromatic aldehydes, malononitrile, and 3‐methyl‐2‐pyrazoline‐5‐one in the presence of sodium hydroxide as catalyst leads to 6‐amino‐3‐methyl‐4‐aryl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐carbonitriles in 85–98% yields.     

Kinetics of the Reaction between Aromatic Aldehydes and 1,5‐Diamino‐4,8‐Dihydroxypyridazino[4,5‐d]Pyridazine

Kinetic studies were performed to investigate the mechanism of Schiff base formation in the reaction between aromatic aldehydes and 1,5‐diamino‐4,8‐dihydroxypyridazino[4,5‐d]pyridazine (DDPP). The studies were conducted at different temperatures with ethanol as solvent and acetic acid as catalyst. It is proposed that the first step involves the reaction of the aldehyde with a solvated proton (i.e. specific acid catalysis). Depending on the acidity of the medium, free or mono‐protonated (DDPP) at tacks the carbonyl group to form a carbinol‐amine inter mediate which then de hydrates to form the product. Plot of ΔH^# versus ΔS^# for the reaction gave a good straight line with isokinetic temperature of 343.15 K. Good linear relationship was obtained from the plot of log k against σ° values. The rate law derived from the proposed mechanism is in agreement with the experimental data and observations. The effects of meta and para substituents of benzaldehyde toward reactivity have been studied.     

Synthesis of 2H‐Indazolo[2,1‐b]Phthalazine‐1,6,11(13H)‐Trione Derivatives Using Wet Cyanuric Chloride under Solvent‐Free Condition

A simple and facile synthesis of 2H‐indazolo[2,1‐b]phthalazine‐1,6,11(13H)‐trione derivatives has been accomplished by a three‐component condensation reaction of dimedone, aromatic aldehydes and phthalhydrazide under solvent‐free conditions in the presence of wet cyanuric chloride as a catalyst.     

Organic Electrosynthesis as a New Facile and Green Method for One‐pot Synthesis of Nanosized Particles of Octahydro‐imidazo[1,2‐a]quinolin‐6‐one Derivatives via a Multicomponent Reaction

Organic electrosynthesis as a new facile and green method was applied for one‐pot synthesis of octahydro‐imidazo[1,2‐a]quinolin‐6‐one derivatives, via a three component condensation of a dimedone, an aldehyde and 2‐(nitromethylene)imidazolidine in propanol in an undivided cell in the presence of sodium bromide as an electrolyte at room temperature. In this study, the anion of dimedone that was produced on the cathode reacted with aromatic aldehydes through the Knoevenagel reaction and then the product condensed with 2‐(nitromethylene)imidazolidine that resulted in a highly efficient formation of octahydro‐imidazo[1,2‐a]quinolin‐6‐one with 50–96% substance yields.     

Synthesis of 10‐substituted 3,6‐Diphenyl‐9‐aryl‐3,4,6,7,9,10‐hexahydro‐acridine‐1,8(2H,5H)‐dione Derivatives and Biological Activities

A series of novel 10‐substituted 3,6‐diphenyl‐9‐aryl‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione derivatives 2 were synthesized by condensation of compounds 1 with amines, which the compounds 1 were synthesized by 5‐phenylcyclohexane‐1,3‐dione and aromatic aldehydes according to Knoevenagel, Michael, and cyclization reactions in the presence of a very small amount of l‐proline as catalyzed at room temperature. The structures of all the synthesized compounds were characterized by IR, 1H NMR, and MS. In addition, the molecular structures of compound 1a have been determined by single‐crystal X‐ray diffraction analysis.     

Spectrophotometric Determination and Kinetic Studies of Condensation of Aromatic Aldehydes with 2-Thiobarbituric Acid

The condensation reaction of 2-thiobarbituric acid with aromatic aldehydes in ethanol has been investigated spectrophotometrically at 30-50°;C. The reaction was catalyzed by HCl solutions. The reaction follows overall second order kinetics, first order each in reactant. Activation parameters have been calculated from the dependence of the rate constants on temperature. The rate of condensation increases with the presence of electron donating groups on the aromatic ring of the aldehyde. The rate-determining step involves dehydration of the aldol intermediate. Based on this reaction, determination of 13 aromatic aldehydes in a concentration range of 0.149-76 mu;g/ml is proposed.     

Synthesis of 1‐(Cyclohexylamino)‐2‐(aryl)pyrrolo[1,2‐a]quinoline‐3‐carbonitrile Derivatives Using a Mild,Four‐Component Reaction

1‐(Cyclohexylamino)‐2‐(aryl)pyrrolo[1,2‐a]quinoline‐3‐carbonitrile derivatives were synthesized in an efficient method from four‐component condensation reaction between cyclohexyl isocyanide, quinoline, malononitrile, and aromatic aldehydes in the presence of a catalytic amount of titanium dioxide (TiO₂) in CH₂Cl₂ at ambient temperature in good yields. Silica gel column chromatography was employed for HCN elimination and then 1, 3 hydrogen shift was led to form final products 5a , 5b , 5c , 5d , 5e .     

A Facile and Efficient Solid Supported,One‐Pot Synthesis of Functionalized Piperidine Derivatives Catalyzed by Amberlite IRA400‐Cl Resin/I2/KI via Multicomponent Reaction

A facile and efficient one‐pot, solid supported synthesis of functionalized piperidine derivatives catalyzed by Amberlite IRA400‐Cl resin/I₂/KI via a multicomponent reaction of various aldehydes, aromatic amines, and 1,3‐dicarbonyl compounds has been achieved. The reaction has been carried out in a one‐pot reaction and Amberlite resin as a solid supported catalyst at room temperature. Shorter reaction time, easy workup, yield, and mild reaction condition make the novel synthetic strategy both practical and attractive.     

An Efficient One-pot Synthesis of β-Amino/β-Acetamido Carbonyl Compounds via ZrCl4-catalyzed Mannich-type Reaction

Zirconium(IV) chloride catalyzed efficient one-pot synthesis of β-amino/β-acetamido carbonyl compounds at room temperature is described. In the presence of ZrCl4, the three-component Mannich-type reaction via a variety of in situ generated aldimines, with various ketones, aromatic aldehydes and aromatic amines in ethanol, led to the formation of β-amino carbonyl compounds and the four-component Mannich-type reaction of aromatic aldehydes with various ketones, acetonitrile and acetyl chloride resulted in the corresponding β-acetamido carbonyl compounds in high to excellent yields. This methodology has also been applied towards the synthesis of dimeric β-amino/β-acetamido carbonyl compounds.     

Indium triflate‐catalyzed one‐pot synthesis of 14‐alkyl or aryl‐14H‐dibenzo[a,j]xanthenes in water

A mild, efficient, and environment friendly method has been developed for the synthesis of 14‐alkyl or aryl‐14H‐dibenzo[a, j]xanthenes by condensation of 2‐naphthol and aldehydes in the presence of a catalytic amount of indium(III) triflate (2 mol%) in water at 100°C. Different types of aromatic and aliphatic aldehydes are used in the reaction, and in all cases the products synthesized in moderate to excellent yields. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:232–234, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20539     

Melamine Trisulfunic Acid: An Efficient and Recyclable Solid Acid Catalyst for the Synthesis of 4,4′‐(Arylmethylene)‐bis‐(1H‐pyrazol‐5‐ols)

Melamine trisulfunic acid is employed as a recyclable catalyst for the condensation reaction of aromatic aldehydes with 3‐methyl‐l‐phenyl‐2‐pyrazolin‐5‐one. This condensation reaction was performed in ethanol under refluxing conditions giving 4,4′‐(arylmethylene)‐bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ols) in 80‐96% yields.