2.6- Dichloronicotinic acid

Table 2 Site-selective Suzuki-Miyaura coupling of 2,6-dichloronicotinic acid...

When nicotinic acid is heated for 8 hours at 180° with thionyl chloride, a low yield of 5-chloronicotiriic acid is obtained.182 The orientation observed in this case suggests an electrophilic attack, perhaps on a complexed nicotinic acid chloride molecule (which would thus behave somewhat like a pyridine A-oxide). If the reaction is carried out at 150° and the reaction time lengthened to 50 hours, a 30% yield of 5,6-dichloronicotinic acid is obtained.182 Both mechanistic pathways may be involved here. Isonicotinic acid reacts with thionyl chloride at 180-220°, presumably by, way of an electrophilic attack since 3-chloro-and 3,5-dichloroisonicotinic acid are formed.182 Nicotinoyl chloride (from nicotinic acid and thionyl chloride—probably in the complexed form) gives an 87% yield of 5-bromonicotinic acid on reaction with bromine for 10 hours at 150-1700.185... 

LXXXIV) gives rise to 2 4-dichloronicotinic acid chloride (LXXXV) which is converted to the amide (LXXXVI) and this in turn with the aid of sodium methylate to 2 4-dimethoxy-3-cyanopyridine (LXXXVII). When this last compound is treated with methyl iodide a reaction takes place, probably through the intermediate formation of an unstable methio-... 

Dichloropyridine-3-carhoxylic acid (5,6-dichloronicotinic acid) [41667-95-2] M 192.0, m 160-161 , 164-168 , 168 , pK st(i) 0.5. Reciystallisation of the acid from H2O provides the monohydrate which becomes anhydrous (m 161-162 ) on heating at 100 . The acid chloride distils at 125 / 24mm, solidifies on cooling, and crystallises from petroleum ether with m 48-49 . The methyl ester has m 67-68 (from aqueous MeOH), and the amide forms colourless plates from aqueous EtOH with m 218-220 . [Rath Schiffmaim Justus Liebigs Ann Chem 487 133 1931, Meyer Graf Chem Ber 61 2212 1928, Beilstein 22 H 44, 22 II 36, 22 III/IV511,22/2 V80.]... 

The 2,6-dichloronicotinic ester shown below gives catalyst-variable selectivity in couplings with phenyl-boronic acid, but the chelating amide is more selective 9 1 compared to 2.5 1 for the ester. ... 

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