Imination of N‐methylpyridinium salts by liquid ammonia‐potassium permanganate. A new synthesis of nudiflorine

Abstract

Reaction of substituted 1‐methyl(benzyl)pyridinium salts (1) with liquid ammonia/potassium permanganate leads to introduction of the imino group at the carbon adjacent to the nitrogen. The regiospecificity of the reaction strongly depends on substituent X: at C‐6 for X = H, CONH2, C6H5 and at C‐2 for X = CH3. 3‐Aminocarbonyl‐1‐t‐butylpyridinium iodide (5) on treatment with liquid ammonia/potassium permanganate exclusively gives the 4‐imino compound 8; 1H nmr spectroscopy shows that 5 in liquid ammonia gives a mixture of the σ‐adducts 4‐amino‐1,4‐dihydro‐ and 6‐amino‐1,6‐dihydro‐3‐pyridinecarbonamide (6 and 7). Surprisingly, an oxodemethylation reaction is observed on treatment of 3‐aminocarbonyl‐1,6‐dimethylpyridinium iodide (13) with liquid ammonia/potassium permanganate, 1,6‐dihydro‐1‐methyl‐6‐oxo‐3‐pyridinecarboxamide (14) being obtained. This compound can easily be converted by phosphorus oxychloride into the alkaloid nudiflorine (15).

Regioselective Oxidation of 3-Substituted Pyridinium Salts

“…The synthesis of chiral 1H-pyridin-2-ones is useful, because the starting material is easily obtained and the regioselectivities of the reactions can attain high values depending on the substituent at position 3. [1, 2,3,4,5,6,7,8]. In a preliminary communication [9], we reported the oxidation of 3-(methyl and ethyl) pyridinium salts, where in all cases, the oxidation at the 2-position in the starting material was favored.…”

Reactions of 4-(trihalomethyl)quinazolines with aliphatic amines. Role of the halogen atom and of the amine on the reaction pattern

“…A white crystalline solid separated and was identified as propylamine hydrobromide (0.17 g). The residue was subjected to column chromatography (silica gel, 3:2 and 3:7 benzene/ethyl acetate), and two products were obtained: the first one (0.06 g) was identified as 4-(dibromomethyl)quinazoline1 2345 (9) (yield 30%), and the second one (0.1 g) [mp 54-56 °C; NMR (CD3COCD3) 1.00 (pseudotriplet, 3 H, CONHCH2CH2C//3), 1.72 (pseudosextet, 2 H, CONHCH2Gif2CH3), 2.95 (s, 1 , NH), 3.43 (pseudoquartet, 2 H, CONHC/i2CH2CH3), 7.50-8.00 (m, 3 H, H6-H8), 9.10-9.30 (m, 2 H, H2-H5); mass spectrum caled for C12H13N30 (M+) m/e 215.105854, found 215.1053] was identified as N-propyl-4-quinazolinecarboxamide (7) (yield 68%).…”

“…For steric reasons N-tert-butylpyridinium salts also gave addition at the 4-position in quaternary salts. 7 The -adducts are easily oxidized by potassium permanganate to the corresponding /V-alkyl-2-(4)-imino derivatives,8 and therefore this amination-oxidation reaction forms an interesting new synthetic tool for the preparation of iV-alkyl-2-iminoazines. The facile replacement of the ring hydrogen in azinium salts (SNH reactions8) by the imino group prompted us to look into the possibility of S^H replacement reactions by other nucleophilic species.…”

Pyrrole, pyrrolidine, piperidine, pyridine, and azepine alkaloids

“…Four new bases of this subgroup have been isolated. Acanthothamine, occurring in the stems of the Mexican plant Acanthothamnus aphyllus, has been formulated as (43), largely from spectral data.44 Mayteine is found in the root of Maytenus guianensis, an Amazonian tree. It has been assigned structure (44) on similar evidence.45 Triptofordinines A-1 and A-2, two new alkaloids of this family from Tripterygium wilfordii, have been assigned structures ( 45) and ( 46) respectively, largely as a result of a detailed two-dimensional n.m.r.…”