Pyrimidones molecules

Meijer et al. reported the self-aggregation behavior of a molecule in chloroform (Fig. 11.8) containing two units of 2-ureido-4-pyrimidone linked through a spacer (which self-associates in the DDAA-AADD pattern strongly with a dimerization constant >106 m ) [36], This compound formed viscous solutions in chloroform, and the viscosity observed was dependent on the concentration and temperature. 

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.). 

Evidence that the radical anion is indeed a stronger base than the dimer anion species is forthcoming from the observed higher reactivity between the former and a non-reduced molecule than between two molecules of the radical anion, plus the fact that only about 50 % of the pyrimidone-2 is reduced. The site of reduction, based on the pathway previously established for pyrimidone-2 in aqueous medium 2,74), is clearly the N(3) = C(4) bond, with dimerization via a 6,6 (or, because of symmetry, 4,4 ) linkage. However, the reduction products were not chemically identified. 

Both the foregoing photoadducts exhibit three diffusion-controlled polarographic waves in aqueous medium in the pH range 1-12 92). The first two waves are due to successive one-electron additions, followed by the third, a two-electron reduction step. The pH-dependence of the initial one-electron reduction wave was found to be similar to that for pyrimidone-2. Following electrolysis, at the crest of wave I, of either of the photoadducts, the two one-electron waves disappeared and the reduction products exhibited UV absorption spectra with a band at 375 nm. A similar absorption band is exhibited following sodium borohydride reduction of Cyt(5-4)Pyo, leading to a product identified as 5-(4-pyrimidin-2-one)-3,6-dihydrocytosine. Mass spectroscopy revealed that the products of reduction on wave I were dimers consisting of two molecules of reduced photoadducts 92). 

Intramolecular addition to aromatic systems also occurs and De Keukeleire and coworkers have described a fascinating example of such a process. In their example the pyrimidone unit adds to the 1,2-positions of a benzene ring. This reaction takes place in the molecule (170) and occurs with full chemo-, stereo-and regio-selectivity affording the single stable adduct identified as (171). Intramolecular addition is also reported for the pyrimidine derivative (172) which on irradiation at 300 nm in acetone/acetonitrile yields two adducts in a ratio of 4 1 of the general structure (173). The major isomer was isolated by transesterification and was identified as (174). This result is claimed to be the first synthesis of a cis-jy/i-furanoside (2+2)-cycloadduct. ... 

Irradiation of the pyrimidone (258) in methylamine-ether proceeds via ring closure to the tricyclic structure (259). Attack of methylamine on this molecule followed by ring opening (Scheme 18) affords the final product (260). Other examples of this process were reported. ... 

In the search for inhibitors of cell adhesion molecule expression in human endothelial cells, thieno[23-d]pyrimidin-4-one 36 was first subjected to a Krapcho dccarboethoxylation. The resultant pyrimidone was then converted to 4-chlorothieno[23-leaving group, new C-S and C-N bond formations were easily achieved by SnAf displacements to produce 38 <01JMC988>. Yields were not given for all compounds... 

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