Synthesis, NMR analysis and applications ..
For the synthesis of parabanic acid and its derivatives, see: Murray (1957, 1963); Ulrichan & Sayigh (1965); Richter (1984); Orazi (1977); Zarzyka-Niemiec & Lubczak (2004). For biological applications of parabanic acid and its derivatives, see: Ishii (1991); Kotani (1997); Sato (2011). For the synthesis, characterization and biological studies of the title compound, see: Xia (2011). For general background to crystallographic studies of compounds having biological activity from our research group, see: Fernandes (2010, 2011); Loughzail (2011). For the synthesis of a precursor molecule, see: Talhi (2011).
A reinvestigation of parabanic acidЦformaldehyde polymerization
From the old literature we emphasize a handful of descriptions reporting the synthesis of parabanic acid (imidazolidine-2,4,5-trione, 1, Fig. 1) and derivatives. Among the reported synthetic methodologies, this heterocyclic compound can be prepared by the condensation of urea with diethyl oxalate in an ethanolic solution of sodium ethoxide (Murray, 1957; 1963). The synthesis of 1,3-disubstituted parabanic acid derivatives have been reported in a similar fashion, starting from 1,3-dialkylureas and following different pathways. The reaction of oxalyl chloride with 1,3-dialkylureas affords the 1,3-disubstituted parabanic skeleton upon In other cases, the action of oxalyl chloride on has led to 2,2-dichloro-1,3-disubstituted imidazolidine-4,5-diones, which produced the parabanic structure after hydrolysis (Ulrichan & Sayigh, 1965). Furthermore, 3-substituted-5,5-dichlorooxazolidine-2,4-diones were obtained from the reaction of alkyl, aryl, and benzyl with oxalyl chloride, giving in high yields the corresponding imidazolidine-2,4,5-triones after treatment with aniline (Richter , 1984). The selectivity of the direct mono- and di--substitution of parabanic acid has also been discussed in the literature (Orazi , 1977; Zarzyka-Niemiec & Lubczak, 2004). Concerning biological applications, several novel patented forms of parabanic acid derivatives and salts have shown interesting activities such as human AMPK activating, blood glucose-lowering and lipid-lowering activities. In this context, several therapeutic agents containing these compounds as the active principle are, for example, useful drugs in the treatment of diabetic complications (Sato , 2011; Kotani , 1997; Ishii , 1991). In the present study, we describe the of 1,3-dicyclohexylparabanic acid (3) (Fig. 1) (Ulrichan & Sayigh, 1965) which has been isolated a completely different procedure which consists of an oxidative cleavage of the C2'—C5 single bond of 1,3-dicyclohexyl-(3-oxo-2,3-dihydrobenzofuran-2-yl)imidazolidine-2,4-dione (2) (Fig. 1), previously prepared in a two-step reaction involving the action of dicyclohexylcarbodiimide (DCC) on chromone-2-carboxylic acid (Talhi , unpublished data).
In the course of our systematic work on the subject we have focused on the synthesis of the low molecular weight products of addition of oxiranes to parabanic acid, i.e.