N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

The availability and application of direct, functional group-compatible C–H activation methods for late-stage modification of small-molecule bioactives and other valuable materials remains an ongoing challenge in organic synthesis. In the current study, we demonstrate that a LED-activated, photoredox-mediated, Pd(OAc)2-catalyzed C–H arylation, employing a phenyldiazonium aryl source and either tris(2,2′-bipyridine)ruthenium(II) or (2,2′-bipyridine)bis[3,5-di-fluoro-2-[5-(trifluoromethyl)-2-pyridinyl-kN][phenyl-kC]iridium(III) as photoredox initiator, may successfully produce unprecedented mono- and bis-phenyl derivatives of functionality-rich 2,6-diphenylpyrimidine substrates at room temperature. The series of 19 substrates employed herein, which share the biologically-relevant 4-methyl-2,6-diphenylpyrimidine-5-carboxylate scaffold, were generated via a synthetic route involving (3-component) Biginelli condensation, oxidative dehydrogenation of the obtained 3,4-dihydropyrimidin-2(1H)-one to 2-hydroxypyrimidine, O-sulfonylation, and Suzuki-Miyaura C–C cross-coupling. Submission of these substrates to pyrimidine-N-atom-directed C–H arylation conditions led to regioselective phenylation at the ortho site(s) of the pyrimidine-C2-connected phenyl ring, revealing substituent-dependent electronic and steric effects. A focused library of 18 mono- and 10 bis-phenyl derivatives was generated. Its members exhibit interesting 3D and peripheral substitution features that render them promising for evaluation in drug discovery efforts.

Ag2O/GO/TiO2 Composite Nanostructure: an efficient heterogeneous catalyst for one pot synthesis of Bis (dihydropyrimidinone) and tetrahydro-4H-chromenes derivatives

The simple and efficient synthesis reaction was used for preparing Bis (dihydropyrimidinone) derivatives through Biginelli condensation reaction of terephthalic aldehyde, 1, 3-dicarbonyl compounds and (thio) urea or guanidine and tetrahydro-4H-chromenes via one pot condensation of aromatic aldehydes, malononitrile and dimedone with Ag2O/GO/TiO2 composite nanostructures as a catalyst. The structural functionalities and morphological observations of catalyst were obtained using characterization techniques of field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transfer infrared (FT-IR) spectroscopy and transmission electron microscope (TEM). The structures of Bis (dihydropyrimidinone) and tetrahydro-4H-chromenes confirmed by FT- IR, NMR and mass spectroscopy. Excellent yields of the products, simple reaction process and simple work-up are attractive features of these effective synthesis methods.

Effect of Different Solvents on Biginelli Reaction Using Layered Double Hyroxide (LDH) As an Ecofriendly Catalyst

A simple and efficient method of the 3,4- dihydropyrimidin-2(1H)-ones/thiones synthesis in good to high yield is described. It consists in a one-pot three-component Biginelli condensation using Layered double hydroxide (LDH) as catalyst. The effect of different solvents on the yields of final product also been studied. Highly polar solvent as well as highly non-polar gives less yields in presence of LDH catalyst.

Aiding the versatility of simple ammonium ionic liquid by the synthesis of bioactive 1,2,3,4-tetrahydropyrimidine, 2-aminothiazole and quinazolinones derivatives.

Simple ammonium ionic liquids [ILs] are the efficient, green, environment friendly catalyst in promoting Biginelli condensation reaction, Hantzsch reaction and Niementowski reaction to afford 1,2,3,4-tetrahydropyrimidine, 2-aminothiazole and quinazolinone derivatives respectively...

Ag2O/GO/TiO2 Composite Nanostructure: An Efficient Heterogeneous Catalyst for one Pot Synthesis of Bis (Dihydropyrimidinone) and Tetrahydro-4H-chromenes Derivatives

The simple and efficient synthesis reaction was used for preparing Bis (dihydropyrimidinone) derivatives through Biginelli condensation reaction of terephthalic aldehyde, 1, 3-dicarbonyl compounds and (thio) urea or guanidine and tetrahydro-4H-chromenes via one pot condensation of aromatic aldehydes, malononitrile and dimedone with Ag2O/GO/TiO2 composite nanostructures as a catalyst. The structural functionalities and morphological observations of catalyst were obtained using characterization techniques of field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transfer infrared (FT-IR) spectroscopy and transmission electron microscope (TEM). The structures of Bis (dihydropyrimidinone) and tetrahydro-4H-chromenes confirmed by FT- IR, NMR and mass spectroscopy. Excellent yields of the products, simple reaction process and simple work-up are attractive features of these effective synthesis methods.

Ultrasound Assisted One-Pot Synthesis of Tetrahydropyrimidne Deriva-tives through Biginelli Condensation: A Catalyst Free Green Chemistry Approach

: The chemical applications of ultrasound, "sonochemistry", has become an exciting new field of research during the past decade as it can increase reactivities by nearly a million fold. Owing to the increasing use of Green technology approach, due to its various merits over Classical methodology and as a need for sustainable Chemistry, this reaction has received renewed interest for preparing tetrahydropyrimidine (THPM) through Biginelii condensation in an environmentally thoughtful manner with improved yields. The classical reaction has been modified in the recent past with/without various catalysts and several structural variants in different solvents to synthesize a large number of Biginelli type compounds due to its diverse pharmacological properties. We reported ultrasound assisted one-pot catalyst free procedure for the synthesis of 6-Aryl substituted-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-Carbonitrile from various aromatic aldehydes, ethyl cyano-acetate and urea under a basic condition with affording isolated yield up to 99% within a reaction time of 5-20 min under mild condition. The synthesized products were characterized by MP, IR, NMR and Mass spectroscopies.

Fast and Efficient One-Pot Three-Component Synthesis of Some 1,2,3,4- Tetrahydro-6-methyl-N-phenyl-5-pyrimidinecarboxamide Derivatives via Biginelli Condensation Reaction

Tetrahydropyrimidine (THPM) synthesis has an enormous importance in organic chemistry and especially in pharmaceutical applications. Pyrimidines are the most active class of N-containing heterocyclic compounds and have different biological properties. The heterocyclic ring system with a thio group occupy a unique position in medicinal chemistry. This type of compounds play an important role in synthetic drugs and in biological processes. Dihydropyrimidinethione derivatives occur widely in nature. Several modifications of THPM-5-carboxamides have attracted considerable interest of medicinal chemists due to their pharmacological and therapeutic properties. A series of 1,2,3,4-tetrahydro- 2-pyrimidinone/thione derivatives bearing a phenylcarbamoyl group at C-5 position were synthesized by one-pot three-component Biginelli condensation reaction. The reaction of acetoacetanilide as the 1,3-dicarbonyl component with various aromatic aldehydes and urea/thiourea in the presence of a catalytic amount of p-toluenesulfonic acid monohydrate (PTSA·H2O) or concentrated HCl as an efficient catalyst leads to Biginelli compounds. We have prepared eight THPM 5-carboxamide derivatives, four of them are new compounds. Their structures were confirmed by spectroscopic techniques and elemental analysis. These compounds have potential applications in organic synthesis and medicinal chemistry. We have synthesized a series of THPM-5-carboxamides by simple and efficient threecomponent Biginelli condensation reaction. Significant benefits of the present procedure include: a) application of inexpensive, non-toxic, environmentally friendly and easily available catalysts, b) the reactions are easy to carry out without high temperature and the workup is very simple, c) the required reaction times are relatively short (30-80 min with HCl and 8-24 h with PTSA·H2O), d) compatibility with various functional groups, e) the products are isolated in good to excellent yields (50-95%).

Synthesis of Dihydropyrimidinones (DHPMs) and Hexahydro Xanthene Catalyzed by 1,4-Diazabicyclo [2.2.2] Octane Triflate Under Solvent-Free Condition

Objective:DABCO salts were evaluated as catalysts for the Biginelli reaction between 4- methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4 hours.Methods:DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol) were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel (hexane/ethyl acetate (1:2)) to give pure desired product.Results:Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73 mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo [2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures. Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4- dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.Conclusion:In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction was performed at moderate temperature under solvent-free conditions.