3.4- Dihydropyrimidin-2 -ones oxidation

Steady-state analysis of DPD in addition to crystal strucmres ° has led to the proposal of a two-site ping-pong mechanism, in which NADPH binds and reduces FAD at one end of the protein. The reducing equivalents are passed to the FMN at the other end of the protein via the Fe-S clusters. The reduced FMN reacts with the pyrimidine forming dihydropyrimidine and oxidized FMN. Here, we will focus on the pyrimidine reaction. 

Bahrami K, Khodaei MM, Farrokhi A (2009) Highly efficient solvent-free synthesis of dihydropyrimidinones catalyzed by zinc oxide. Synth Commun 39 1801-1808 74. Gross GA, Wurziger H, Schober A (2006) Solid-phase synthesis of 4,6-diaryl-3,4-dihydro-pyrimidine-2(lH)-one-5-carboxylic acid amide derivatives a Biginelli three-component-condensation protocol based on immobilized beta-ketoamides. J Comb Chem 8 153-155 Desai B, Dallinger D, Kappe CO (2006) Microwave-assisted solution phase synthesis of dihydropyrimidine C5 amides and esters. Tetrahedron 62 4651 664 Kumar A, Maurya RA (2007) An efficient bakers yeast catalyzed synthesis of 3,4-dihydro-pyrimidin-2-(lH)-ones. Tetrahedron Lett 48 4569-4571 77. Zalavadiya P, Tala S, Akbari J, Joshi H (2009) Multi-component synthesis of dihydropyrimidines by iodine catalyst at ambient temperature and in-vitro anti mycobacterial activity. Arch Pharm 342 469-475... 

Oxidation of 3,4-dihydropyrimidin-2(l //)-oncs (DHPMs) with ceric ammonium nitrate (CAN) in acetic acid resulted in ethyl 2,4-dioxo-6-phenyltetrahydropyrimidin-5-carboxylates as the major product. However, DHPMs undergo a regioselective oxidation with CAN in the presence of sodium hydrogencarbonate in neutral aqueous acetone solution to yield ethyl 6-meihyl-4-aryl(alkyl)pyrimidin-2(l //)-one-5-carboxylates. A mechanism involving a nitrolic acid intermediate has been suggested.72... 

Nanosized sulfated tin oxide (STO) particles dispersed in the micropores of Al-pillared clay (STO/Al-P), were used by Mishra and co-workers [91] as an environmentally benign, recyclable and efficient catalyst for the solvent-free synthesis of 3,4-dihydropyrimidin-2(l//)-ones 42 using a domestic microwave oven. The protocol offers advantages in terms of simple experimentation, reusable catalyst, excellent yields, short reaction times, and preclusion of toxic solvents (Scheme 31). 

After the first reported example starting from alcohols [58], Yadav and coworkers developed a new one-pot oxidation methodology of aromatic alcohols 49 using a Brpnsted acidic ionic liquid [Hmim]HSO catalyst with NaNOj followed by their condensation with urea and dicarbonyl compounds in the same vessel at 80°C, giving access to 3,4-dihydropyrimidin-2(17/)-ones 51 with moderate to high yield (55-97%) (Scheme 9.18) [59]. 

The three-component condensation of aldehydes, p-ketoesters, and urea has been carried out in water using ceria (cerium oxide, CeO,) NPs supported on poly(4vp-co-dvb) as a catalyst for the preparation of 3,4-dihydropyrimidin-2(l//)-ones in good yields [97] (Scheme 5.43). 

The ability of bismuth(III) nitrate pentahydrate as effective catalyst in the Biginelli reaction was reported, while the oxidative property of this salt has been also investigated. By combining both of these characteristics, the authors developed a convenient alternative method for the Biginelli reaction. The direct synthesis of 3,4-dihydropyrimidin-2(lH)-ones by three-component condensation in one pot, using benzyl halides in place of aldehydes in the presence of bismuth nitrate pentahydrate in tetrabutylammonium fluoride (TBAF), afforded the products in good to excellent yields. Some chemoselectivity was observed, the aliphatic halides gave less than 30% of the respective dihydropyrimidinones under the present reaction conditions (Equation 12) [33a]. 

Hydroxylations of fatty acids by cytochrome P450119 compound increase in rate with chain length and show no intermolecular KE in buffer. With glycerol, the rate of reaction of lauric acid increases, and a KIE is observed. Reversible formation of a non-reactive complex of a fatty acid with the cytochrome and its isomerization to a reactive one is proposed. A tandem oxidative cyclocondensation process is reported for the synthesis of 3,4-dihydropyrimidin-2(l//)-one or -thione derivatives from primary aryl alcohols, -keto esters, and urea or thiourea in the presence of aluminium nitrate nonahydrate as oxidant catalyst. ... 

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