Picolinates

Water 2-methylpiperidine Water 3-metliylpipericline Water 4-methylpiperidine Water P picoline Water aa-Iutidine Glycerol m-toluidine. ... 

The -picoline in the base recovered from the residual picoline - ZnCl, complexes is separated from the y-picoline by fractional freezing pure /8-picoline has m.p. —18 -2° and y-picoline has m.p. -f 3 -6°. 

If much liquid ammonia is lost during the preparation of the sodamide, the volume should be m e up to 500-600 ml. before adding the y picoline. 

Rcolinic acid Is readily prepared by the oxidation of a-picoline with potas-... 

A solution of sodamide in liquid ammonia (essentially the amide NHj ion) is a very powerful alkylation catalyst, enabling condensations to be carried out with ease and in good yield which are otherwise either impossible or proceed with difficulty and are accompanied by considerable by-products. Thus 3-alkylpjTidines, otherwise inaccessible, are easily prepared from 3-picoline (see 3-n-amylpyridine in Section V,20). Also benzyl cyanide (I) and cyclohexyX bromide give a- r/ohexylphenylacetonitrile (II) ... 

Another example illustrating the greater reactivity of organolithium compounds is the preparation of the otherwise difficultly accessible esters of 2-pyridyl-acetlc acid by the following series of reactions from a-picoline ... 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl and 2 4-dimethyl-dicarbethoxy-p3nrole (V,12-V,13) 2-amino- and 2 4 dimethyl-thiazole (V,15-V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylp3rridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanop3n idine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi-oxylepidine (V,29). 

The easier elimination of pyridine compared to quinoline-4 may be related to the pK value of 4-methylthiazole, which is between those of lepidine and 2-picoline (25. 55). This reaction explains also why a neutrodimethine cyanine is obtained with such good yields when reacting together a quaternary salt, ketomethylene, and o-ester in a basic medium. As the reaction proceeds, the trimethine cyanine is attacked by the ketomethylene. The resulting 2-methyl quaternary salt is transformed into trimethine cyanine, consuming the totality of the ketomethylene (1, p. 512 661). The mesosubstituted neutrodimethine cyanine is practically pure. 

Picoline 129 2-Methyl-thiazole 128 2-Methvl-selen azole 149... 

For the methyl-substituted compounds (322) the increase in AG and AHf values relative to the unsubstituted thiazole is interpreted as being mainly due to polar effects. Electron-donating methyl groups are expected to stabilize the thiazolium ion, that is to decrease its acid strength. From Table 1-51 it may be seen that there is an increase in AG and AH by about 1 kcal mole for each methyl group. Similar effects have been observed for picolines and lutidines (325). 

These results show that the measured values of H° are close to those calculated from the thiazole value and the increments. That compounds substituted ortho-ortho to nitrogen (2,4-dimethyI and 2,4,5-trimethyl-thiazole) also obey this rule shows that the methyl groups do not interact sterically (150). The same conclusion had been reached in the case of the picolines and lutidines (151). 

---