The preparation of 3-fluoroisonicotinic acid and related compounds was written by Roe, Arthur;Seligman, Robert B.. And the article was included in Journal of Organic Chemistry in 1955.Computed Properties of C6H6FN This article mentions the following:
To study the effect of a F atom adjacent to the CO2H group on the antituberculostatic activity of isonicotinic acid hydrazide, 3-fluoroisonicotinic acid (I) and some related compounds are prepared 2-Amino-4-picoline (50 g.) is converted by the method of Hawkins and Roe (C.A. 44,628i) into the nitramine and allowed to rearrange to 3- and 5-nitro-2-amino-4-picoline, which are hydrolyzed to a mixture (II), m. 159°, of 3-(III) and 5-nitro-2-hydroxy-4-picoline (IV). Warming 2.5 g. IV 2.5 hrs. with 20 cc. POCl3 gives 60.7% 2-chloro-5-nitro-4-picoline (V), b5 91.2°, m. 38.5-9.5°. Similarly, III gives 2-chloro-3-nitro-4-picoline (VI), m. 52-2.9°. Treating II with POCl3 gives a mixture of V and VI which (25 g.) is hydrogenated in 20 cc. AcOH in the presence of 0.5 g. NaOAc and 10% Pd-C at 65 lb. H pressure, the mixture evaporated in vacuo, and the residue made strongly alk. and extracted with Et2O, giving 89.5% 3-amino-4-picoline (VII), m. 104-5° (picrate, m. 177-8°). VII is converted by a modified Schiemann reaction into 4-picoline-3-diazonium fluoborate which, decomposed in boiling petr. ether (b.p. 60-90°), gives 68% 3-fluoro-4-picoline (VIII), b748 135.6°, nD27.5 1.4795 (picrate, yellow plates, m. 129-30°). Adding dropwise (3.5 hrs.) 48 g. KMnO4 in H2O to 17 g. VIII in 1 l. refluxing H2O, steam distilling the mixture to remove any unchanged VIII, evaporating the filtered solution until crystallization sets in, and acidifying it with HCl gives 45% I, m. 256-7° (decomposition and sublimation). Refluxing 2 g. I 1.5 hrs. with 20 cc. SOCl2, distilling off the excess SOCl2, and refluxing the residue 1 hr. with EtOH gives Et 3-fluoroisonicotinate-HCl (IX.HCl), from which 83.4% IX, b752 215°, is obtained (picrate, long yellow needles, m. 109-10°). Refluxing 2 g. IX 5.5 hrs. with 1.5 cc. 85% N2H4.H2O and 20 cc. 95% EtOH and distilling off the EtOH gives 92% I hydrazide, fine needles, m. 146.8-7.8°. IX.HCl refluxed with N2H4.H2O 36 hrs. forms 3-hydroxyisonicotinic acid hydrazide. In the experiment, the researchers used many compounds, for example, 3-Fluoro-4-methylpyridine (cas: 399-88-2Computed Properties of C6H6FN).
3-Fluoro-4-methylpyridine (cas: 399-88-2) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Computed Properties of C6H6FN