Gardner, T. S. published the artcileSynthesis of compounds for chemotherapy of tuberculosis. VII. Pyridine N-oxides with sulfur-containing groups, Application of Piperidine-4-carbothioamide, the publication is Journal of Organic Chemistry (1957), 984-6, database is CAplus.
cf. C.A. 51, 3610b. A number of C5H5N derivatives containing a CSNH moiety were prepared Isonicotinamide 1-oxide (Ia) (147 g.) refluxed 0.5 h. with 1.5 kg. POCl3, the solution concentrated, poured on ice, and made alk., and the separated nitrile collected, the solution was extracted 5 times with CHCl3, the solids also extracted with CHCl3, and the combined extracts yielded 85 g. isonicotinonitrile 1-oxide (I), m. 229-30°. I (30 g.) in 300 mL. MeOH containing 30% NH3 by weight and the solution left 2 days saturated with H2S gave 12 g. thioisonicotinamide 1-oxide, m. 205-6° (H2O). Thioisonicotinamide-HCl, orange colored solid, m. 231-2°(alc.). Nicotinonitrile 1-oxide (II) was obtained in 55% yield from nicotinamide 1-oxide by refluxing 0.5 h. with POCl3. II (28 g.) in 300 mL. MeOH containing 20% NH3 left 18 h. with H2S gave 14 g. thionicotinamide 1-oxide, m. 161-4° (H2O). Picolinamide (70 g.) heated 6 h. at 80° in a solution of 100 g. 40% AcO2H and 300 mL. AcOH gave 51 g. picolinamide 1-oxide (III), m. 165-6° (MeOH). The investigation of the picolino-type N-oxide gave several anomalies. Thus P2S5 and K2S in C5H5N with III deoxygenated the N-oxide and gave only thiopicolinamide. A mixture of 70 g. diatomaceous earth and 150 g. P2O5 refluxed 4 h. with 25 g. III in 500 mL. PhMe, the gummy mixture filtered on a dry Hyflo bed, the residue treated with H2O and concentrated NH4OH and extracted with CHCl3, and the combined PhMe and CHCl3 solutions concentrated gave 5 g. picolinonitrile 1-oxide, m. 122-3° (Et2O). The reaction of refluxing POCl3 on III rapidly deoxygenated the compound to give 2-picolinonitrile. In contrast, more than 6 h. refluxing POCl3 was required to deoxygenate Ia to give isonicotinonitrile. 4-Aminopyridine 1-oxide-HCl (20 g.) refluxed 6 h. with 12.5 g. NH4SCN in 250 mL. alc. gave 20 g. 4-pyridylthiourea 1-oxide, m. 126-7° (Me2CO). 3-Bromopyridine 1-oxide-HCl (53.5 g.) in 100 mL. H2O neutralized with dilute NaOH and extracted with CHCl3 gave the free 3-bromopyridine 1-oxide which when refluxed 5 h. in 300 mL. alc. with 19 g. CS(NH2)2 gave 50 g. 2-(3′-pyridyl)-2-thiopseudourea 1′-oxide-HBr (IV), m. 145-7° (alc.). IV could not be decomposed to give 3-pyridinethiol 1-oxide using NaOH solution N-Ethylnicotinamide (60 g.) treated at 10-15° with 120 g. 40% AcO2H in AcOH and concentrated at 80° gave 35 g. N-ethylnicotinamide 1-oxide, m. 123-4°. 3,5-Dibromopyridine (42 g.), 80 g. 40% AcO2H in AcOH, and 300 mL. AcOH heated 3 h. at 80° and then 12 h. at 50° gave 30 g. 3,5-dibromopyridine 1-oxide (V), m. 143-4° (alc.). V (20 g.) refluxed 5 h. in 300 mL. alc. and 15 g. CS(NH2)2 gave 20 g. 2-(5′-bromo-3′-pyridyl)-2-thiopseudourea 1′-oxide-HBr, m. 162-3° (alc.). Thioisonicotinamide (Va) (25 g.) in 1 l. H2O treated with 30 mL. 37% HCHO, the pH adjusted to 7.5 by KOH solution, the mixture left 6 h., and the pH adjusted to 7 by HCO2H, and the mixture cooled to 4° gave 24 g. N,N’-methylenebis(thioisonicotinamide)-H2O (VI), m. 146-7° (H2O). VI was less active than the parent compound in tuberculosis in mice. The assignment of the linear structure was based on analyses and the fact that IR analyses gave none of the characteristic absorption bands for the triazine structure. Isonipecotamide (100 g.) in 450 g. POCl3 refluxed 2 h. and concentrated in vacuo and poured on ice gave 37 g. 4-cyanopiperidine (VII), b7 100°, n23D 1.4741. VII (35 g.) left 48 h. at 25° in 300 mL. 30% NH3 saturated with H2S gave 30 g. thioisonipecotamide (VIII), m. 173-4° (H2O). Attempts to convert the isonipecotamide to VIII using P2S5 failed with or without K2S and only Va was obtained in 25-40% yields. Va (50 g.) and 56 g. α-bromopropionic acid heated 6 h. in PhMe gave 25 g. 5-methyl-2-(4-pyridyl)-4(5H)-thiazolone-HBr, m. above 250° (alc.). Va (50 g.) refluxed in 250 mL. AcCH2Cl gave 11.5 g. 4-methyl-2-(4-pyridyl)thiazole-HCl, m. 219-20° (decomposition) (MeOH). Reduction of the C5H5N ring eliminated activity; N-oxidation reduced activity, and separation from the ring of the CSNH group eliminated activity as did also the conversion of the group into a ring system.
Journal of Organic Chemistry published new progress about 112401-09-9. 112401-09-9 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carbothioamide, and the molecular formula is C6H12N2S, Application of Piperidine-4-carbothioamide.
Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem