Takata, Toshihiro published an article in 1962, the title of the article was Synthesis of methylpyridine and 1,8-naphthyridine derivatives.Safety of 3-Methylpyridine-2,6-diamine And the article contains the following content:
When a mixture of 43 g. α,α’-dimethylglutaronitrile (I) and 30 g. NaNH2 in 258 ml. HCONH2 was kept for 2 days, filtered, and washed with PrOH and EtOAc, 41 g. α,α’-dimethylglutarimidine (II), m. 209-10° (decomposition) (absolute EtOH), was obtained. Similarly α-methylglutaronitrile gave 70% of α-methylglutarimidine (III), m. 154-5° (decomposition) (absolute EtOH). Reduction of 7 g. II in 100 ml. absolute EtOH was carried out with 98 g. Na and excess EtOH. Steam distillation of the product and evaporation of the acidified distillate and basification with NaOH gave 4.6 g. 3,5-dimethylpiperidine (IV), b. 144°, d20 0.8532, n20D 1.4560; picrate m. 184°. Reduction of III gave 3-methylpiperidine (V), b. 125-6°, d20 0.8570, n20D 1.4506; picrate m. 105°. Dehydrogenation of 0.5 g. IV with 0.2 g. of a Pd catalyst gave 0.35 g. 3,5-dimethylpyridine (VI), b. 168-71°, d20 0.9096, n20D 1.4501; picrate m. 242-3° (decomposition). 3-Methylpyridine (VII) was obtained similarly from V; picrate m. 149-50°. Dehydrogenation of 1 g. II in 4 ml. Ph2O at 300° for 11 hrs. with Pd catalyst gave 0.3 g. 2,6-diamino-3,5-dimethylpyridine (VIII), m. 186-7° (C6H6). VIII was acetylated with Ac2O in a sealed tube at 170° for 1 hr. to give the tetraacetyl derivative (IX), m. 149° (C6H6). Acetylation of VIII at 95° for 1 hr. gave the diacetyl derivative (X), m. 197°. 2,6-Diamino-3-methylpyridine (XI), m. 156-7°, was obtained in 30% yield by the dehydrogenation of III with Pd catalyst. Treatment of 12.2 g. VII with 16 g. NaNH2 in 16 g. Tetralin at 150-3° for 4 hrs. and at 198-200° for 17 hrs. and pouring the mixture into H2O and extraction with C6H6 and evaporation gave 2.5 g. XI. Acetylation of XI with Ac2O at 170-180° for 3 hrs. gave the triacetyl derivative, m. 142-4°. Acetylation of XI with Ac2O at 90-100° for 1 hr. gave the diacetyl derivative, m. 220-1°. Treatment of 2,4,6-tricyano-n-heptane (XII) with NaNH2 as before gave 3,6-dihydro-2,7-diiminooctahydro-1,8-naphthyridine (XIII), m. 222-4° (decomposition), in 87% yield and 1,3,5-tricyanohexane (XIV) gave 3-methyl-2,7-diiminooctahydro-1,8-naphthyridine (XV), m. 204-6° (decomposition), in 65% yield, while 1,3,5-tricyanopentane (XVI) gave 2,7-diiminooctahydro-1,8-naphthyridine (XVII) in 82% yield. A solution of 1.5 g. XIII in 240 ml. amyl alcohol was reduced with 21 g. Na at 130-40°. Working up as for IV gave 1 g. 3,6-dimethyldecahydro-1,8-naphthyridine (XVIII), m. 162-3° (C6H6); dipicrate m. 213° (decomposition). Similar reductions of 7 g. XV in 800 ml. amyl alcohol and 98 g. Na gave 4 g. 3-methyldecahydro-1,8-naphthyridine (XIX), m. 116-17° [dipicrate m. 205° (decomposition)] and of 1.2 g. XVII with 17 g. Na gave 0.9 g. decahydro-1,8-naphthyridine (XX), m. 116-17° (dipicrate m. 195°). Dehydrogenation of XVIII with a Pd catalyst in Ph2O gave 3,6-dimethyl-1,8-naphthyridine (XXI), m. 191-2° (petr. ether) in 71% yield; picrate m. 210-11° (decomposition). To a mixture of 320 g. CH2(CO2Et)2 (XXII) and 280 g. CH2:CMeCN was added a solution of 11 g. Na in 80 g. EtOH and the mixture stirred at 30-50° for 8 hrs. and at 80-90° for 2 hrs. Addition of HCl, and distillation of the product gave 338 g. α,α’-dimethyl-γ,-γ-dicarbethoxypimelonitrile (XXIII), b2 175°. γ,γ-Dicarbethoxypimeronitrile (XXIV), m. 60-2°, was obtained in 76% yield from 187 g. XXII, and 123 g. acrylonitrile and 10.6 ml. of 30% KOH in aqueous MeOH at room temperature for 2 hrs. XXIII (115 g.) was hydrolyzed with 55 g. KOH in 500 ml. absolute EtOH for a few days at room temperature Addition of water, acidification, and extraction with EtOAc gave α,α’-dimethyl-γ,γ-dicarboxypimelonitrile (XXV), m. 134-6° (decomposition). Similarly XXIV gave the corresponding diacid (XXVI), m. 158°. The K salt of XXV (47.1 g.) in 50% aqueous EtOH was treated with H at 100 atm. below 60° in the presence of 19 g. Raney Ni catalyst and the mixture was concentrated, acidified, and heated at 200° for 3 hrs. Addition of NaOEt in EtOH gave 20 g. 3-(β-methyl-ω-aminopropyl)-5-methyl-2-piperidone (XXVII); picrate m. 184-6°. Pyrolysis of 0.7 g. XXVII at 300° gave after purification as the hydrochloride and basification, 3,6-dimethyltetrahydro-1,8-naphthyridine (XXVIII), m. 110-11°; monopicrate m. 256°. Dehydrogenation of 0.11 g. XXVIII in 2 ml. Ph2O at 250-80° for 20 hrs. in the presence of Pd catalyst gave XXI. Reduction of XXVIII with Na in amyl alcohol gave XVIII. Reduction of 28 g. K salt of XXVI with Raney Ni as for XXV gave 13 g. 3-(ω-aminopropyl)-2-piperidone (XXIX); picrate m. 207°. Pyrolysis of XXIX gave hexahydro-1,8-naphthyridine; picrate m. 228-30°. The experimental process involved the reaction of 3-Methylpyridine-2,6-diamine(cas: 51566-22-4).Safety of 3-Methylpyridine-2,6-diamine
3-Methylpyridine-2,6-diamine(cas:51566-22-4) belongs to pyridine-derivatives. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Safety of 3-Methylpyridine-2,6-diamine