Dornow, Alfred; Neuse, Eberhard published an article in 1951, the title of the article was The reaction of amidines with β-dicarbonyl compounds.Application In Synthesis of 2-Amino-6-methylnicotinamide And the article contains the following content:
cf. C.A. 34, 6629.3.-β-Dicarbonyl compounds react with RO2CCH2C(:NH)OR (Ia) via an amidine derivative, RCOCH2CR’:C(CO2R)C(:NH)N:C(OR)CH2CO2R, to form pyridine derivatives This reaction is studied further. MeCOCHNaCHO (23 g.) and 30 g. H2NCOCH2C(:NH)NH2.HCl (I) are refluxed in 80 cc. absolute EtOH 12 h. and the hot filtered solution is cooled, giving 56% 2-amino-6-methylnicotinamide (II), long needles, m. 220° [picrate, yellow leaflets, m. 253-4° (decomposition)]. Refluxing 1 g. II with concentrated HCl 10 h. and neutralizing the mixture with NH4OH give 100% free acid, m. 296°. Treating 0.35 g. II in 20 cc. dilute H2SO4 with 0.45 g. NaNO2 and warming the mixture on a water bath give 2-hydroxy-6-methylnicotinic acid, m. 227° (decomposition), which, decarboxylated, gives 6-methyl-2-pyridone, m. 157°. Refluxing 17.5 g. PhCOCHNaCHO and 13.5 g. I in 50 cc. absolute EtOH and 30 g. anhydrous KOAc 2 h., distilling off the solvent, extracting the residue with H2O, and refluxing the residue several hrs. with concentrated HCl give 11.6 g. 2-amino-6-phenylnicotinic acid-HCl, sintering at 219-20°, m. 240° (decomposition); free acid (III), m. 243° [picrate, m. 189-90° (decomposition)]. Only in 1 experiment was the amide, thick yellowish crystals, m. 220-1°, obtained; it shows strong blue fluorescence in alc. solution [picrate, yellow needles, m. 229-30° (decomposition)]. Diazotization of 0.22 g. III in 20 cc. dilute H2SO4 with 0.3 g. NaNO2 and boiling the mixture give 2-hydroxy-6-phenylnicotinic acid, m. 304° (decomposition), which, heated above its m.p., gives 6-phenyl-2-pyridone, m. 197°. Condensation of 20 g. EtCOCHNaCHO (IV) with 22 g. I in 100 cc. 50% MeOH gives 66% 2-amino-5,6-dimethylnicotinamide (V), fine yellowish crystals, m. 230-1° [picrate, m. 269-70° (decomposition)]. Diazotization of 2.5 g. V with 1.7 g. NaNO2 and boiling the mixture give 59% 2-hydroxy-5,6-dimethylnicotinic acid (VI) needles, m. 306° (decomposition) (cf. Barat, C.A. 26, 2979), also obtained on saponification of the cyanopyridone obtained on condensation of NCCH2CONH2 with IV. Heating VI above its m.p. gives 5,6-dimethyl-2-pyridone, m. 205-6°. Keeping 6.95 g. I in 50 cc. N NaOH with 5.1 cc. Ac2CH2 overnight at 20° gives 60% 2-amino-4,6-dimethylnicotinamide, m. 156.5°; from the aqueous mother liquor a compound, m. 295-300°, is isolated. 2-Hydroxy-4,6-dimethylnicotinic acid, prepared in 60% yield like VI, m. 254°. Refluxing 15 g. I 24 h. in 100 cc. EtOH containing 2.3 g. Na with 16 g. BzCH2COMe gives 21% 2-amino-4-methyl-6-phenylnicotinamide, yellowish crystals, m. 227°; from the mother liquor some CH2(CONH2)2, m. 166°, is isolated. Adding 11 g. EtO2CCH2C(:NH)OEt.HCl to 40 cc. satd Na2CO3 overlayered with ether and heating the residue of the dried ether solution with 5 g. BzCH2COMe 16 h. on a water bath give 52% Et 2-amino-4-methyl-6-phenylnicotinate (VII), cubelike crystals, m. 129°; its alc. solution fluoresces strongly blue [HCl salt, m. 205° (decomposition)]. Refluxing 1.1 g. VII 8 h. with 10 cc. concentrated HCl gives 90% HCl salt (VIII) of the free acid, needles, m. 171-2° (decomposition), from which, with NH4OH and AcOH, the free acid, m. 267° (decomposition), is obtained. Treating 0.9 g. VIII in dilute H2SO4, with 0.5 g. NaNO2 with warming gives 90% 2-hydroxy-4-methyl-6-phenylnicotinic acid (IX), crystals from AcOH, m. 278°, which is also obtained in 92% yield from the acid amide, m. 227°. Treating 0.9 g. VII in 15 cc. warm AcOH with 0.3 g. NaNO2 and boiling the mixture give 78% Et ester (X) of IX, broad leaflets, m. 163°; its aqueous solution shows weak bluish fluorescence. Heating 0.4 g. IX 10 min. at 300-5° gives 62% 4-methyl-6-phenyl-2-pyridone, m. 180°, which is also formed on heating IX or X with 80% H2SO4 or concentrated HCl. Refluxing 27.3 g. I and 29.5 g. 2-hydroxymethylenecyclohexanone (XI) 2 h. in 100 cc. absolute MeOH and keeping the mixture 12 h. in the cold give 51% 2-amino-5,6,7,8-tetrahydro-3-quinolinecarboxamide (XII), needles, m. 224-5°, soluble in concentrated H2SO4 with strong blue-violet fluorescence [picrate, yellow needles, m. 259-60° (decomposition)]. Refluxing Ia (R = Et) from 200 g. HCl salt 30 h. with 52 g. XI on a water bath gives 20 g. Et 2-amino-5,6,7,8-tetrahydro-3-quinolinecarboxylate (XIII), m. 127°. Distillation of the residue of the mother liquor gives addnl. XIII, b12 185°, bringing the total yield to 36%. XIII dissolves in concentrated H2SO4 or EtOH with strong blue-violet fluorescence [picrate, yellow needles, m. 212-13° (decomposition)]. Refluxing 5 g. XIII 10 h. with 30 cc. concentrated HCl gives 70% HCl salt of the acid, m. 232-4° (decomposition); free acid (XIV), needles from AcOH, m. 291-2° (decomposition), also obtained on refluxing 0.9 g. XII 10 h. with 20 cc. concentrated HCl. 2-OH analog (XV) of XIV, m. 268-9° (decomposition). Heating 0.15 g. XV 15 min. above its m.p. gives 5,6,7,8-tetrahydro-2-quinolone, needles, m. 201°. Treating 18 g. BzCH2C(:NH)OEt. HCl (XVI) in ether with 10 g. Na2CO3 in 100 cc. H2O, adding 3.1 g. Ac2CH2 to the dried ether solution, evaporating the ether, heating the residue 15 h. at 140-150°, and acidifying the mixture with concentrated HCl give 50% 4,6-dimethyl-2-phenacylpyrimidine-HCl (XVII), crystals from 6 N HCl, m. 201° (free base, yellow leaflets, m. 74°; picrate, yellow needles, m. 203°). Treating 1 g. XVII in 30 cc. 3 N HCl at 40-5° with 0.5 g. NaNO2 in 10 cc. H2O gives 80% 2-(α-isonitrosophenacyl) derivative (XVIII), leaflets, m. 212°. Hydrogenation of 0.8 g. XVIII in 200 cc. absolute EtOH with 0.15 g. PtO2 gives 4,6-dimethyl-2-(β-hydroxy-α-aminophenethyl)pyrimidine, which is converted into its picrate, m. 175-80° (decomposition). Refluxing 2 g. CHCCHO with BzCH2C(:NH)OEt from 25 g. XVI gives 54% 2-phenacylpyrimidine, m. 150°. The experimental process involved the reaction of 2-Amino-6-methylnicotinamide(cas: 100524-09-2).Application In Synthesis of 2-Amino-6-methylnicotinamide
2-Amino-6-methylnicotinamide(cas:100524-09-2) belongs to amides. Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis. Application In Synthesis of 2-Amino-6-methylnicotinamide
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics