CsOH/γ-Al₂O₃: a heterogeneous reusable basic catalyst for one-pot synthesis of 2-amino-4,6-diaryl pyrimidines

Abstract

Pyrimidine derivatives were synthesized in one pot using a novel heterogeneous reusable catalyst, and complete characterization of catalyst was performed.

Polysubstituted Pyrimidines as Potent Inhibitors of Prostaglandin E2 Production: Increasing Aqueous Solubility

“…Analogues of compound 1 (Figure 1) bearing a hydrophilic aliphatic chain (instead of lipophilic 5‐butyl group) were designed and 10 target molecules were selected for the synthesis, based on calculated log P values (see SI) using Virtual Computational Chemistry Laboratory (VCCLAB) [16] . The synthetic route started from compound 2 (Scheme 1), which was prepared in a 69 % yield from acetophenone and p ‐anisaldehyde using the one‐pot assembly reported by Nimkar and co‐workers [17] . Compound 2 was brominated using bromine in chloroform to give 5‐bromopyrimidine derivative 3 (67 %), which was subsequently converted into 5‐cyanopyrimidine derivative 4 (by reaction with zinc cyanide in a 28 % yield) and into 5‐(1‐ethoxyvinyl)pyrimidine derivative 5 (via the Heck reaction with ethyl vinyl ether in a 61 % yield).…”

“…Compound 17 was prepared in analogous way to compound 14 . Pyrimidine 18 (Scheme 3) was prepared in a 73 % yield from acetophenone and 4‐(benzyloxy)benzaldehyde by the one‐pot assembly [17] . Bromination of compound 18 with bromine in chloroform gave 5‐bromopyrimidine derivative 19 quantitatively.…”

“…[16] The synthetic route started from compound 2 (Scheme 1), which was prepared in a 69 % yield from acetophenone and p-anisaldehyde using the one-pot assembly reported by Nimkar and coworkers. [17] Compound 2 was brominated using bromine in chloroform to give 5-bromopyrimidine derivative 3 (67 %), which was subsequently converted into 5-cyanopyrimidine derivative 4 (by reaction with zinc cyanide in a 28 % yield) and into 5-(1-ethoxyvinyl)pyrimidine derivative 5 (via the Heck reaction with ethyl vinyl ether in a 61 % yield). 5-Vinylpyrimidine 6, the key intermediate for further modifications, was obtained in a 58 % yield by the Suzuki-Miyaura coupling reaction of 5-bromopyrimidine 3 with pinacol vinyl boronate.…”

“…Pyrimidine 18 (Scheme 3) was prepared in a 73 % yield from acetophenone and 4-(benzyloxy)benzaldehyde by the one-pot assembly. [17] Bromination of compound 18 with bromine in chloroform gave 5-bromopyrimidine derivative 19 quantitatively. 5-Vinylpyrimidine 20 was obtained in a 35 % yield by the Suzuki-Miyaura coupling of compound 19 with pinacol vinyl boronate.…”

One‐potandtwo‐potmethods for chalcone derived pyrimidines synthesis and applications

“…Pyrimidopyrimidine is one of the unexpected side products (63% yield) formed and gave a low yield of the target product pyrimidin-2-one (34%) from the reaction of bromo-substituted ketonic or aldehyde derivatives in acidic condition. [162] In conventional method, side product and yield can be improved by adopting heterogeneous catalyst (KOH/γ-Al [163] and ionic liquids (i.e., [nbpy]AlCl 4 , [nbpy]FeCl 4 , [bmim] FeCl 4 ), among all CsOH/γ-Al 2 O 3 and Bi(TFA)3-[nbpy] FeCl 4 protocol formed higher yield, 60%-96% with minimal workup. [164] In 2008, inexpensive sulfamic acid and trimethylsilyl chloride-based one-pot reaction has been conducted under 1-6 h reflux in different solvents systems (ethanol, chloroform, water, acetonitrile) and solvent-free conditions at 45-70 C. The solvent-free condition at 70 C was able to produce 15%-95% yield compared to the reaction in different solvents conditions (22%-89%).…”