den Hertog, H. J.; Schogt, J. C. M.; de Bruyn, J.; de Klerk, A. published the artcile< Derivatives of pyridine and quinoline. LXXXIII. Chloropyridines>, Recommanded Product: 2,3,4,6-Tetrachloropyridine, the main research area is .
2,4,5-Trichloropyridine has been synthesized, 6 other chloropyridines reëxamd., and the m. ps. and b. ps. of 19 chloropyridines determined Nicotinic acid (5 g.) divided in 2 tubes was shaken 4 h. at 250-70° with 42 g. PCl5 and 20 g. POCl3; steam distillation gave an oil and a precipitate which was refluxed 1 h. with 20 mL. 80% H2SO4, diluted with H2O, made basic, and steam-distilled; various fractions m. above 65° [cf. Seyfferth, J. prakt. Chem. 34, 241(1886)], and from the last fraction 2,3,5,6-tetrachloropyridine, m. 90-0.5°, was isolated. 3-Bromo-2,4-dihydroxypyridine (I) (5 g.) and 25 mL. 48% HBr heated 3 h. at 200° in 2 sealed tubes gave, after adding H2O and allowing to stand, 0.5 g. I and from the mother liquor 3.1 g. 5-bromo-2,4-dihydroxypyridine, m. 226.5-7.5°; 1 g. heated 2 h. at 200° with 10 mL. 38% HCl gave 3-chloro-2,4-dihydroxypyridine, decompose about 310°. Et 2,4-dihydroxy-5-pyridinecarboxylate (II) (3 g.) heated 2.5 h. at 115-20° with 18 g. POCl3 gave on steam distillation 90% of the 2,4-di-Cl compound (III), m. 31.5-2°. Saponification with an equivalent amount of dilute NaOH for 0.5 h. gave 80% 2,4-dichloro-5-pyridinecarboxylic acid “”hydrate”” (IV), m. 198° after liquefying at 155° and resolidifying, which could not be dehydrated by recrystallization from EtOH, C6H6, or ligroin, or by sublimation. IV (10 g.) and 10-15 g. POCl3 warmed to 100°, treated gradually with 30 g. PCl5, heated at 140° 0.5 h., evaporated under a vacuum, and the residue dissolved in C6H6 and saturated with NH3 gave 85% 2,4-dichloro-5-pyridinecarboxylic acid, m. 152-3° (from H2O). III (1.7 g.) in 2-3 mL. EtOH with 0.45 g. (NH2)2.H2O let stand 15 min. and a few ml. H2O added gave Et 2-chloro-4-hydrazino-5-pyridinecarboxylate, m. 147-8°; 1 g. suspended in 30 mL. boiling H2O treated dropwise with 35 mL. 10% CuSO4 solution, refluxed 2.5 h., and steam-distilled gave 45-50% Et 2-chloro-5-pyridinecarboxylate (V), saponified to the acid, m. 195° (decomposition) (amide, m. 211°). V (0.25 g.) heated 4 h. at 110° in a sealed tube with 0.1 g. Na in 6 mL. MeOH, diluted with H2O, acidified, and evaporated halfway gave 2-methoxy-5-pyridinecarboxylic acid, m. 171.5-2.5° (from H2O). 2,4-Dichloro-5-pyridinecarboxylic acid (4 g.) and 2 mL. POCl3 warmed to 100°, treated with 13 g. PCl5, warmed 0.5 h. at 140°, evaporated under a vacuum, taken up in C6H6, and saturated with NH3 gave 95% nitrile, m. 136-7°; 0.5 g. with 0.5 mL. Br in 50 mL. 7% KOH at room temperature for a few hrs., then a few hrs. at 70°, acidified, made basic, and extracted with Et2O gave 30-40% 2,4-dichloro-5-aminopyridine (VI), m. 80-1° (from ligroin). VI (0.5 g.) in 10 mL. 38% HCl in an ice-salt bath treated with 1.05 g. NaNO2 in 3 mL. H2O, then with 2.2 g. Cu powder, and steam-distilled gave 40-50% 2,4,5-trichloropyridine (VII), m. 8.5-9° (from aqueous EtOH). Heating 0.1 g. VII 4 h. at 160° with 2 mL. NH4OH (d. 0.9) gave 2,5-dichloro-4-aminopyridine, m. 119-20°; 0.02 g. in 0.5 mL. 38% HCl treated with 0.08 g. H2O2 and evaporated gave 2,3,5-trichloro-4-aminopyridine, m. 147°. NaNO2 with 1 g. 2-chloro-3-aminopyridine gave 0.5 g. 2,3-dichloropyridine, m. 66.5-7°, which with concentrated NH4OH at 190° 36 h. gave 2-amino-3-chloropyridine (VIII), m. 61.5-2°. Heating 0.7 g. 2,4-dihydroxypyridine (IX) with 4 mL. POCl3 2.5 h. at 130-40° gave on making basic, steam-distilling, and extracting with Et2O 60-5% 2,4-di-Cl compound, m. -1 to 0°, b760 189-90°; 0.6 g. with 16 mL. NH4OH heated at 170-80° 4.5 h., made basic, extracted with Et2O, evaporated, and the residue fractionally extracted with 20 mL. ligroin gave 0.05 g. 2-amino-4-chloropyridine, m. 129-30° (picrate, m. 236-43°); after an addnl. extraction with 35 mL. ligroin giving 0.1 g. crystals, 0.1 g. residue remained from which 4-amino-2-chloropyridine, m. 91-1.5°, could be isolated by crystallization 4-Nitraminopyridine (1.8 g.) with 11 mL. 38% HCl heated 10 h. at 100°, made alk., and steam-distilled gave in the 1st fraction (20 mL.) a little 4-chloro- (soluble in dilute HCl), and 10% 3,4,5-trichloropyridine, m. 71.5-2.5°. The 2nd fraction (100 mL.) gave (0.4 g. 4-amino-3,5-dichloropyridine (X), m. 159.5-60.5°. Koenigs, Mields, and Gurlt (C.A. 19, 70) suggested that X was 3,4-dichloropyridine (XII). However, the structure of X was indicated by its isolation in 55-60% yield from 4-aminopyridine by chlorination with HC1 and also from 4-amino-3-chloropyridine (XI). Reduction of 4-chloro-3-nitropyridine with Fe powder and AcOH gave 70% 3-amino-4-chloropyridine, m. 59.5-60.5° (N-Ac derivative, m. 113-13.5°; picrate, m. 181-1.5°); diazotization as before gave XII, m. 23-3.5°, b760 182-3°. XII heated 10 h. at 190° with NH4OH gave XI, m. 60.5-1.5° [picrate, m. 227-9° (decomposition)]; 0.2 g. XII with 0.04 g. Na in 2 mL. EtOH heated 4 h. at 160° gave a residue of 0.175 g. oily 3-chloro-4-ethoxypyridine (picrate, m. 159.5-60°; picrolonate, m. 202-3°). II with HCl and H2O2 gave 70% Et 2,4-dihydroxy-3-chloro-5-pyridinecarboxylate,m. 257-8°; POCl3 then gave 60% Et 2,3,4-trichloro-5-pyridinecarboxylate, m. 34°, 0.07 g. of which was boiled 1.5 h. with 4 mL. 1% NaOH and the Ag salt heated to 230° in a stream of CO2 with distillation, giving 2,3,4-trichloropyridine (XIII), m. 45-6°. IX with HCl and H2O2 gave 3-chloro-2,4-dihydroxypyridine (XIV), decompose about 310°; 0.2 g. I with 5 mL. 38% HCl at 200° 3 h. also gave XIV which was converted to XIII. Et 3-bromo-2,4-dihydroxy-5-pyridinecarboxylate with HCl, then POCl3, gave XIII. 2-Amino-3-chloro-4-bromopyridine (0.14 g.) in 50 mL. EtOH with 0.1 g. NaOH and 10 mg. Pd-Norit catalyst gave impure 2-amino-3-chloropyridine (impure picrate, m. 232-3°). XIII with NH4OH gave by filtration and extraction with ligroin 2-amino-3,4-dichloropyridine, m. 93-5° (picrate, m. 234.5-7°); the crystals less soluble in ligroin were 2,3-dichloro-4-aminopyridine (XV), m. 153.5-4.5° (picrate, m. 198.5-9.5°). XV with HCl and H2O2 gave 2,3,5-trichloro-4-aminopyridine, m. 150-2°. 2,6-Dichloro-4-aminopyridine (XVI) diazotized gave 85% 2,4,6-trichloropyridine (XVII), m. 32.5-3°, b760 217.5-18.5°. XVII with NH4OH gave 2-amino-4,6-dichloro-pyridine (most soluble in ligroin), m. 112.5°, and XVI, m. 170.3°. XVII with NaOMe as before gave 70-5% 2,4,6-trimethoxypyridine, m. 47-8°, which was converted to the 3,5-di-Cl derivative, m. 95.5-6°. 2,4-Dichloro-3-nitropyridine, prepared in 75% yield from IX, was reduced with Fe and AcOH, giving 85-90% 3-amino compound (XVIII), m. 69-9.5° (N-Ac derivative, m. 161-2°). XVIII (0.75 g.) in 15 mL. AcOH saturated with HCl was mixed with 0.7 mL. 30% aqueous H2O2 in 3.3 mL. AcOH, heated 0.5 h. at 80°, and poured into NaOH and Na2SO3 in H2O, giving 3-amino-2,4,6-trichloropyridine (XIX), m. 77.5-8°, and XVIII. Diazotization of XIX gave 75% 2,3,4,6-tetrachloropyridine (XX), m. 37.5-8°, b760 248-9.5°. XVI chlorinated as for XVIII gave 4-amino-2,3,6-trichloropyridine, m. 160-0.5°, which was converted to XX. The substance m. 74-5° [Sell and Dootson, J. Chem. Soc. 73,432(1898)] obtained by the chlorination of pyridine was therefore not XX.
Recueil des Travaux Chimiques des Pays-Bas et de la Belgique published new progress about 14121-36-9. 14121-36-9 belongs to class pyridine-derivatives, and the molecular formula is C5HCl4N, Recommanded Product: 2,3,4,6-Tetrachloropyridine.