Oxidation reactions of azines.

Oxidative coupling and unusual hydroxymethylation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the presence of dicyanomethane

“…In our recent work 1,2 on the oxidative transformation of the notorious neurotoxin THP 1 3 and its analogues we have discovered a novel C sp 3 -C sp 3 coupling reaction between tetrahydropyridines and compounds containing an activated methyl group such as acetone, methyl aryl ketones and nitromethane. In the presence of potassium permanganate the THP nucleus in this unusual reaction is attacked by the CH acid at the allylamine position 2 leading to the formation of 2-R-methylideneTHP.…”

“…The presence of the double bond in the hydroxymethyl derivative 4 raises the possibility of oxodihydroxylating this THP system using a one-pot protocol recently elaborated in our laboratory. 6 However, the attempted polyfunctionalization of 4 yielded only an intermediate 2-oxo-5-hydroxymethylTHP 5 (50%) and 4-phenylpyridine 6 (10%) (Scheme 3). The formation of the latter presents, to our knowledge, the first example of the oxidative elimination of two groups (methyl and hydroxymethyl) from the THP ring, thus achieving total aromatization under such mild conditions.…”

Cascade and stepwise oxidation of 4-phenyl- and 4-(γ-pyridyl)tetrahydropyridines

“…4 Compound 3a was obtained by hydroxylation of 2a in aqueous MeCN (2a:KMnO 4 = 1:1.5) at 0 °C, 1.5 h; yield 54%, mp 117 °C. 2 The yield of 3a was increased to 76% at 20 °C, 2 h. One-pot oxodihydroxylation of 1a in aqueous MeCN (1a:KMnO 4 = 1:1.5) at 20 °C, 2 h gave 3a in 76% yield. 2 Compound 3b was prepared by hydroxylation of 2b in aqueous MeCN (2b:KMnO 4 = 1:1.5) at 0 °C, 2 h; yield 45%, mp 220-222 °C.…”

“…2 The yield of 3a was increased to 76% at 20 °C, 2 h. One-pot oxodihydroxylation of 1a in aqueous MeCN (1a:KMnO 4 = 1:1.5) at 20 °C, 2 h gave 3a in 76% yield. 2 Compound 3b was prepared by hydroxylation of 2b in aqueous MeCN (2b:KMnO 4 = 1:1.5) at 0 °C, 2 h; yield 45%, mp 220-222 °C. 3 One-pot oxodihydroxylation of 1b in aqueous MeCN (1b:KMnO 4 = 1:1.5) at 20 °C yielded 65% of 3b in 2 h. 3 Compound 4a was obtained from one-pot oxidation of 1a•HCl in acetone (1a•HCl:KMnO 4 = 1:1.5) at 20 °C, 2 h; yield 85%, colourless oil, R f 0.73 in acetone.…”

“…It was therefore established that oxidation of 4-pyridyl-THP 1b into 2b and 4b proceeded well, though with lower yields (27% and 58%, respectively) in comparison with the analogous reactions of 4-phenylTHP. 2,4 The lactams 2a,b were readily hydroxylated at < 0 °C (in contrast to the inert 4-aryl THP 1 1 ) into the cis-diol lactams 3a,b with yields 54% and 45%, respectively. However, at room temperature the yield of 3a was increased to 76%.…”