Synthesis of 6-Bromomethyl-substituted Derivatives of Pyridin-2(1H)-ones and Their Reaction with Nucleophiles

Unexpected reaction on bromination of 3,4-dihydropyridin-2(1H)-ones with N-bromosuccinimide

“…To elucidate these properties in a series of derivatives of dihydropyridin2)1H)-ones, 3,4-dihydropyrdin-2(1H)-ones with lipophilic substituents in the pyridine ring were synthesized for the first time by condensation of esters 1 with benzylidenecyanacetamide (2 On bromination of 5-tetradecyloxycarbonyl-and 5-hexadecyloxycarbonyl-3,4-dihydropyridones 3 with N-bromosuccinimide, in contrast to 5-methoxycarbonyl-3,4-dihydropyridones [2] and their 5-unsubstituted analogs [3], the lipophilic tetrahydropyridones 5, containing a bromine atoms and a hydroxy group, not described in the literature, were formed instead of the expected bromo- Apparently the presence of water in the reaction mixture led to the formation of hypobromous acid (HOBr) from N-bromosuccinimide, which subsequently added to the double bond. The additive hydroxybromination in the 3,4-dihydropyridin-2(1H)-one series 3 was previously unknown.…”

“…According to [7], compounds 3 with J 34 < 0.5 Hz exist in the trans-form with Ph and CONH 2 in pseudoaxial positions. In the spectra of compounds 5 J 34 = 11.4-11.6 Hz shows that the groups Ph and CONH 2 Tetradecyl (2S,3S,4R,5R)-3-bromo-5-carbamoyl-2-hydroxy-2-methyl-6-oxo-4-phenylpiperidine-3-carboxylate (5a). N-Bromosuccinimide (0.21 g, 1.17 mmol) and benzoyl peroxide (0.02 g) were added to a suspension of amide 3a (0.5 g, 1.06 mmol) in ethanol (25 ml) and the mixture was stirred at room temperature.…”

Synthesis and self-assembly of novel fluorous cationic amphiphiles with a 3,4-dihydro-2(1H)-pyridone spacer

“…Although the 6-bromomethyl compound was not isolated its presence as intermediate was suggested by the subsequent lactonization producing g-lactone fused 3,4-dihydropyridones. Another report on the 6-methyl group bromination utilized bromine in chloroform and irradiation with a 500 W lamp [18], in this case only the crude compound was isolated and not further characterized. In our case the 6-methyl group was brominated by dissolving the dihydropyridone in chloroform and simple drop-wise addition of a bromine chloroform solution with stirring.…”

3,4-Dihydro-2(1H)-Pyridones as Building Blocks of Synthetic Relevance

“…In this context, DHPo's as the Milrinone and the Amrinone are drugs with cardiotonic activity successfully used to treat heart failure (Figure 1). [2] In addition, they and their derivatives have also been reported to possess antitumor [3], antibacterial [4] anti-HIV [5], and other biological activities [6][7][8][9]. These results encourage many research groups to search potentially active DHPo's analogs.…”

“…The synthesis of 3,4-DHPo derivatives has been important by the pass of time. Different synthetic procedures to synthesize its taking place in the last years, although the most reported use the multicomponent reaction (MCR-4CR) of Meldrum's acid (1), a βketoester derivative (2), and aromatic aldehydes (3) in the presence of ammonium acetate. Additionally, a broad range of techniques have been covered, from the conventional synthesis, through energy resources such as microwave, ultrasound and infrared assisted, until solid and liquid phase synthesis, and recently the chemoenzymatic assisted methodology applying to their asymmetric synthesis (Scheme 1).…”