Mechanisms of the oxidations of NAD(P)H model Hantzsch 1,4-dihydropyridines by nitric oxide and its donor N-methyl-N-nitrosotoluene-p-sulfonamide.
4-Substituted derivatives of Hantzsch 1,4-dihydropyridine were treated by nitric oxide (NO) or its donor N-methyl-N-nitrosotoluene-p-sulfonamide (MNTS) to give the corresponding pyridine derivatives. When the 4-substituted group was methyl, ethyl, n-propyl, and aryl groups, it was preserved, but when the group was isopropyl or benzyl one, it was lost. 2,3-Dichloro-5, 6-dicyano-1,4-benzoquinone (DDQ) was used in place of NO and MNTS to react with the 4-substituted Hantzsch 1,4-dihydropyridines, no the corresponding 4-dealkyl Hantzsch pyridines were obtained from all the reactions. 1-Benzyl-1,4-dihydronicotinamide (BNAH), a close analogue of Hantzsch 1,4-dihydropyridine (HEH), was used instead of HEH to react with either of NO and MNTS, no reactions were observed for 3 days. Replacement of HEH by N-d-HEH and HEH-4,4-d(2) to react with NO, MNTS and DDQ gave the observed kinetic isotope effects of 3.1 and 1.4 for NO, 1.1 and 1.3 for MNTS, and 1.1 and 2.1 for DDQ, respectively. When p-dinitrobenzene, an electron-transfer inhibitor, was added into the title reaction systems, no remarkable inhibitory effect was observed. These results indicated that the oxidation of HEH by NO was initiated by hydrogen transfer from the N(1)-position to give the corresponding aminyl radical, which then underwent homolytic cleavage to become the final aromatized product (A). But the reaction of HEH with MNTS was initiated by nitrosation to give the corresponding N-nitroso compound, which was subsequently subjected to two steps of homolytic cleavage to afford the aromatized Hantzsch pyridine A.
Zhu
X Q
XQ
Department of Chemistry, Nankai University, Tianjin 300071, China. xqzhu@nankai.edu.cn
Zhao
B J
BJ
Cheng
J P
JP
D018360:Crystallography, X-Ray; D004095:Dihydropyridines / Q000737:chemistry*; D007700:Kinetics; D009249:NADP / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000737:chemistry*; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000737:chemistry*
D004095:Dihydropyridines; D020030:Nitric Oxide Donors; D013449:Sulfonamides; D009569:Nitric Oxide; D009249:NADP; C418734:N-methyl-N-nitrosotoluene-p-sulfonamide