3- 2- pyrimidon-4-ones

In the IR spectra of six-membered heterocycles containing one or more carbonyl groups in the ring (pyridin-2- and -4-ones, the pyrones, and pyrimidones) one of the higher frequency bands in the 1700-1500 cm-1 region can usually be... 

Chlorination of 2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one with NCS in a mixture of AcOH and TFA at room temperature for 72 h yielded a 3-chloro-2-hydroxy derivative (95JMC4687). Bromination of 2-chloro-4//-pyrido[l, 2-n]pyrimidone with Br2 in a mixture of CH2CI2 and pyridine at room temperature for 15 min gave a 3-bromo derivative (00BMC751). 

Extension of this work by studying the reaction of 3-methyl-5-nitro-pyrimidin-4(3//)-one with -X-arylketones in the presence of ammonium acetate surprisingly revealed the formation of a mixture of 4-arylpyrimidines and 6-arylpyridin-2(l//)-ones (00JCS(P1)27). The ratio between pyridine and pyrimidine formation is dependent on the substituent X. With electron-donating substituents the formation of the pyridin-2(l//)-ones is favored, with electron-attracting substituents the formation of the pyrimidine derivatives (Scheme 21) In the formation of the 6-arylpyridin-2(l//)-ones the C-4- C-5-C-6 part of the pyrimidone-4 is the building block in the construction of the pyridine ring. Therefore, the pyrimidone can be considered as an activated o -nitroformylacetic acid (Scheme 21). 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

The carbonyl groups that participate in the alkyne-addition process have not been limited to those that can form enol tautomers. For example, amides have been used as nucleophiles in a one-pot reaction sequence for the preparation of 2,3-disubstituted furanopyridones using Pd catalysis (Equation (96)).343 Furopyridines have also been obtained from the reaction of iodopyridones with alkynes under Pd catalysis,344 and alkynyl pyrimidones have been converted into 2-substituted furanopyrimidones under the influence of an AgN03 catalyst.345... 

Synthesis of primidolol (65) can be carried out by a convergent scheme. One branch consists in application of the usual scheme to o-cresol (62) ring opening of the intermediate oxirane with ammonia leads to the primary amine (63). The side chain fragment (64) can be prepared by alkylation of pyrimidone (63) with ethylene dibromide to afford Alkylation of ami noalcohol with halide ... 

The synthesis of the module is provided in Scheme 10.5 (Kushner et al. 2007). Double alkylation of ethyl acetoacetate followed by guanidine condensation afforded alkenyl-pyrimidone intermediate 24 (Kushner et al. 2007). Isocyanate 25 was coupled to pyrimidone 24 to yield 26. Upon dimerization in DCM, RCM effectively cyclized the two UPy units (Mohr et al. 1997 Week et al. 1999). A one-pot reduction and deprotection through hydrogenation using Pearlman s catalyst gave diol module 27. Finally, capping 27 with 2-isocyanatoethyl methacrylate at both ends provided the UPy sacrificial cross-linker 28, which was thoroughly characterized by H- and C-NMR, Fourier transform IR (FTIR), and mass spectrometry. 

The thiocarbonyl group is a highly reactive dipolarophile and in general this group dominates the reactivity of nonenolisable exocyclic thioketones as illustrated for the systems shown 5-methylene-2-thioxo-l,3-thiazolinin-4-one (260) (161), pyrimidone-2- and -4-thiones (261, 262) (134), pyrazolo[l,5,4-e/][l,5]benzodi-azepin-6-thione (263) (162). 2-Thiono-4-imidazolidinone (264) also gave a C=S cycloadduct as expected but, in the case of the analogue 265 with an additional exocyclic methylene group, the latter proved to be more reactive (163). 

Hydrazines and hydroxylamines do not form pyrimidones with l,3-oxazin-4-ones instead the nucleophile attacks at C-2, opening the ring and effecting ring contraction through intramolecular attack by a lone pair of electrons of the introduced group upon the carbonyl function formerly at position 4 in the parent heterocycle (Scheme 13) (78CPB1825). 

In this sequence, substitution by 1 mol of dimethylamine first replaces the benzylmercaptan leading to 5-acetyl-2-dimethylamino-6//-l,3-thiazine (197). The thiazine then undergoes attack by dimethylamine excess at C-6, leading to the thiourea (198). The benzylmercaptan liberated in the first reaction may act as a nucleophile (BzS",H2NMe2+), and a different thiourea substituted by dimethylamino and benzylthio groups is obtained. The action of pyrrolidine on 1,3-thiazine-4-ones (194) can be seen as a Michael addition followed by elimination of H2S. In acidic media, the linear compound obtained is cyclized to the pyrimidone (200) (Scheme 80)... 

In an aqueous buffered medium, over the pH range 1-12, pyrimidone-2 exhibits a single one-electron wave. Preparative electrolysis, at a potential corresponding to the initial limiting current, led to formation of an insoluble product, isolated as a white amorphous powder, and shown by various physico-chemical criteria to correspond to a dimer consisting of two molecules of reduced pyrimidone-2. This was further confirmed by H NMR spectroscopy, which also established the structure of the product as 6,6 (or 4,4 )-bis-(3,6(4)-dihydropyrimidone-2), shown in Scheme 2, below. The structure of the dimer reduction product, and its solid state conformation, were subsequently further established by X-ray diffraction (see Sect. III.3.). 

In aqueous 0.1 M (CH3)4NBr, pyrimidone-2 was found to exhibit two reduction waves of equal height, with E1/2 values of —0.75 V and —1.55 V for waves I and II, respectively 1,2). (Fig. 1) Preparative electrolysis under these conditions at the potential of wave I resulted in formation of the same dimer reduction product as in aqueous buffered medium. By contrast, electrolysis on wave II led to formation of two products, one of which was identical with that formed on wave I. The other, readily soluble in aqueous medium, was identified as 3,6-dihydropyrimidone-2, identical with that synthesized chemically and described earlier by Skaric75). 

The foregoing is of obvious significance in relation to the photochemical behaviour of cyclobutane photodimers of natural pyrimidines such as uracil (III, Scheme 1), thymine, cytosine12,76). Photodissociation of such photodimers to the parent monomers, which proceed with quantum yields ranging from 0.5 to nearly unity, has, indeed, been employed as one of the criteria for identification of such dimers. The validity of this criterion is now, in the light of the behaviour of the dimer electroreduction product of pyrimidone-2, at best somewhat restricted, notwithstanding that the quantum yields for photodissociation of the latter are lower. 

This compound, like the parent pyrimidone-2, is predominantly in the keto form in aqueous medium and, in the pH range 2-9, exhibits, like pyrimidone-2, a one-electron polarographic wave. In more alkaline media (pH 9-12), a second wave is observed at more negative potentials. 

Chromatography of the electrolysis products formed in acid medium demonstrated that the major one was the photodissociable dimer 6,6 -6w-(3,6-dihydropyrimidone-2) (70%), accompanied by 3,6-dihydropyrimidone-2 (15 %) and about 15 % of a product not fully identified, but the UV absorption spectrum of which was consistent with its being a 1 1 adduct of cytosine and reduced pyrimidone-2 84). 

From the foregoing it is clear that in acid medium there is a three-electron reduction involving elimination of ammonia, followed by one-electron reduction of the resulting pyrimidone-2. 

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