Methylpyridine Derivatives Ethyl

CHLOROCYCLOBUTANE, 51, 106 Mesitylene, cyanation, 50, 54 METHALATION OF 2-METHYLPYRIDINE DERIVATIVES ETHYL 6-METHYL-PYRIDINE-2-ACETATE, 52, 75 Metalation, directed, 53, 59 Methallyl alcohol, with phenyl-mercuric acetate to yield 2-methyl-3-phenylpropional-dehyde, 51, 17 METHALLYLBENZENE, 52, 115 7r-Methallylnickel bromide, 52, 115... 

METALATION OF 2-METHYLPYRIDINE DERIVATIVES ETHYL 6-METHYLPYRIDINE-2-ACETATE... 

Seidel28 cyclized compounds (32) derived from the amides (31) with dimethylformamide dimethyl acetal to the 3-substituted 2-oxo-2H-pyrido-[l,2- ]pyrimidines (33) by heating in acetic anhydride. On this basis he corrected the conclusion of Antaki,29 who had assumed that by reacting 2-amino-4-methylpyridine and ethyl ethoxymethylenecyanoacetate, the 2-oxo-2//-pyrido[l,2-a]pyrimidine (33 R = 8-Me, R1 = OEt) was produced. The product was in fact the 4-oxo isomer (36 R = 8-Me, R1 = H, R2 = COOEt). 

From 2-amino-6-methylpyridine and ethyl 3-aminocrotonate the expected 2,6-dimethyl-4-oxo-4//-pyrido[l,2-a]pyrimidine was not obtained, but instead a urea derivative is formed.36 Ethyl acetoacetate has also been replaced... 

Important commercial alkylpyridine compounds are a-picoline (2), Ppicoline (3), y-picoline (4), 2,6-lutidine (5), 3,5-lutidine (6), 5-ethyl-2-methylpyridine (7), and 2,4,6-coUidine (8). In general, the alkylpyridines serve as precursors of many other substituted pyridines used in commerce. These further substituted pyridine compounds derived from alkylpyridines are in turn often used as intermediates in the manufacture of commercially usehil final products. 

Meroquinenine, CgHjjOaN (meroquinene), formed by the oxidation of all four alkaloids and of cinchoninone or quininone and by the hydrolysis of quinenine or cinchenine (p. 489), crystallises from methyl alcohol in needles, m.p. 223-4° (dee.), [ajp -f- 27-5° (H2O). It gives a nitrosoamine, m.p. 67°, and a monoacetyl derivative, m.p. 110°, and can be esterified the ethyl ester hydrochloride has m.p. 165°. When oxidised by chromic acid it yields formic and cincboloiponic acids. On reduction with zinc dust and hydriodic acid, it adds on two atoms of hydrogen forming cincholoipon, CgH jOaN, and when heated with hydrochloric acid at 250-60° gives 3-ethyl-4-methylpyridine ()3-collidine). 

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

Ethyl pyridine-2-acetate and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with w-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

Okamoto et al. prepared the pyrido[l,2-c<]pyrimidines (142 R = H, Me) by heating 2-aminopyridines with ethyl 3-chloropropionimidate hydrochloride in ethanol or acetonitrile. In the case of 2-aminopyridine and 2-amino-4-methylpyridine, not only 142 (R = H, 8-Me) but also the 2-imino derivatives were isolated, which on treatment with acid were transformed to 2-oxopyrido[l,2-c<] pyrimidines (142). With 2-amino-6-methylpyridine or... 

Cyclocondensation of 2-amino-3-methylpyridine and allenephospho-nates 284 by stirring the reaction mixture in the absence of a solvent at 35-40°C for 48 hours afforded 4-methylene-3,4-dihydro-2//-pyrido[l,2-alpyrimidines 285 (90DOK619 91IZV473). The ethyl derivatives 285 (R = Et) were obtained as E and Z geometric mixtures. 

Pyridine is a colorless liquid mp, -42°C bp, 115°C) with a sharp, penetrating odor that can perhaps best be described as terrible. It is an aromatic compound in which an N atom is part of a six-membered ring. The most important derivatives of pyridine are the mono-, di-, and trimethyl derivatives the 2-vinyl and 4-vinyl derivatives 5-ethyl-2-methylpyridine (MEP) and piperidine, also called hexahydropyridine (below) ... 

Pyridine and its derivatives. The most unique pyridine derivative isolated from processed food is l,lt,5,6-tetrahydro-2-ace-topyridine. This compound was prepared by roasting proline and dihydroxyacetone at 92°C in presence of sodium bisulfate, and exhibited a strong odor reminiscent of freshly backed soda crackers (82). 2-Ethylpyridine and 2-pentylpyridine were reported in volatile flavor components of shallow fried (83). Pyridine, 2-methylpyridine, 3-methylpyridine, 2-ethylpyridine, 3-ethylpyri-dine, 5-ethyl-2-methylpyridine, 2-butylpyridine, 2-acetylpyridine, 2-pentylpyridine, 2-hexylpyridine, 3-pentylpyridine, 5-methyl-2-pentylpyridine, and 5-ethyl-2-pentylpyridine were identified in the volatiles of roasted lamb fat (8H). 2,5-Dimethylpyridine and... 

Dehydrogenation of the lactone acid (XVII) with palladium-charcoal yielded 2-ethylnaphthalene and under the same conditions the acid X afforded 2-ethyl-3-methylnaphthalene. The formation of these two hydrocarbons disproved the earlier hypotheses that the carbonyl group of himbacine was attached to a tertiary carbon atom and that the ethyl groups of 2-ethyl-6-methylpyridine and 2-ethyl-3-methylnaphthalene, isolated from the selenium dehydrogenation of himbacine, were derived from the same structure in the alkaloid. Moreover, since the results of the Hofmann degradation and the oxidation experiments had shown that the 6-(l,2-dimethylpiperidyl)-vinyl group was attached to a decalin residue by reason of the formation of the C-13 ketones, it only remained to establish the point of attachment. For this purpose the carboxyl group... 

In a follow-up study [34] it was discovered that the condensation of cyanothioacetamide with ethyl 2-ethoxymethylene-3-oxobutanoate in the presence of piperidine in fact gave a 41 % yield of 3-cyano-5-ethoxycarbonyl-6-methylpyridine-2(l//)-thione (III.92), and not the isomeric 4-methyl derivative as previously thought [32]. Methylation of (III.92) (Mel-KjCOj-DMF) followed by reduction (LiAlH4-Et20), methoxymethylation, and oxidation with w-chlorobenzoic acid led to the alcohol (III.98) (50%), the ether (Ill.lOO)... 

Ethyl-2-picotine. 4-Ethyl-2-methylpyridine a-methyl-7-ethylpyridine 4 -ethyl -a -picoline a-collidine. C,-H N mol wt 121.18. C 79,29%, H 9.15%, N 11.56%. Prepd from 2-picoline and acetic anhydride in the presence of zinc dust H. Maier-Bode, 1. Altpeter, Das Pyridin und Seine Derivate (Halle, 1934) p 54 Ger. pat. 390,333. 

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