CH8  .CO + NH3 + CO•CH3 CH3•C-NH-G.

CH3 The resulting dihydro-compound is then oxidized with nitrous acid, the ester hydrolysed and the resulting acid heated with lime; carbon dioxide is eliminated and a trisubstituted pyridine of the type CH C(CHI) is obtained . The reaction is apparently a R•C' \N general one for all aldehydes . On the course \CH :C(CH3)/ of the reaction see also C . Beyer, Ber., 1891, 24, p . 1662, and E . Knoevenagel, Ber., 1898, 31, p . 738 . In this reaction the proportions of aldehyde and acetoacetic ester may be interchanged and ay disubstituted pyridines are then obtained . Of the other methods for preparing pyridine homologues mention may be made of the discovery by A . Ladenburg that the pyridinium alkyl iodides rearrange themselves when strongly heated and yield a and y alkyl pyridines (Ber., 1883, 16, p . 1410 seq . ; Ann., 1888, 247, p .

I) . S . Ruhemann prepared 7-substituted dioxypyridines by condensing alkyl-dicarboxy-glutaconic

esters with ammonia . R'02C)2C:CR•CH(CO2R')2-,R'02Co.c CRH•NC•COH•CO2R'-HHOC:CRNC . On Of •C OH M . Scholtz (Ber., 1895, 28, p . 1726) prepared aa- methylphenylpyridine by distilling cinnamenylidene acetoxime, CSHSCH:CH•CH:CH•C(:N•OH).CH3= H C•CHc H2O CeHs•c•N :C•CHs-- The 1.5 diketones of the type inset, when heated with ammonia, also yield pyridine derivatives . Alkyl pyridines -CO\ /CO- are also obtained by heating aldehyde >C:CH•CH< ammonias alone or with aldehydes and -CO CO- ketones (A. v . Baeyer, Ann., 187o, 155, pp . 281, 294; J . Pldchl, Ber., 1S87, 20, p . subjoined table shows the chief homologues of pyridine: Name .

Formula . Position Remarks . of Sub- stituent . Picolines C5H4(CHa)N a Liqquid, b.p . 129° . Oxi- Lutidines CSH4(C2H5)N y dizes to picolinic acid . a, /3, y, Condenses readily with aldehydes . Liquid, b.p . 143° . Oxi- dizes to nicotinic acid . Does not condense with aldehydes . Liquid, b.p .

144-145° . Three isomers . All liquids . The /3 com-

pound is a decompo- sition product of cinchonine, quinine, strychnine and bru- cine . CSH3(CHa)2N aa', ay, a,B' Five isomers . All /3l3', /37. liquids . Collidines C5H4(CaH1)N a, P . Liquids . The a com- C5H3(CH3)(C2H5)N a, y. pound is a decomposi- CSH2(CHa)3N a'a, y(3, tionproductof conine . ay, a/3' Both contain the nor- aya' mal propyl group . ay/3' Containing the isopro- Lis.rou p . qu1id Liquid, b .

. 171-172° . Prepared by the Hantzsch

synthesis . Found in coal-tar . Pyridine carboxylic acids are usually prepared by oxidizing the homologues of the base; they also result as decomposition products of various alkaloids . The more important are shown in the table . Name . Formula . Position Remarks . of Sub- stituent . Picolinic C5H4(CO2H)N a M.p . 137° . Easily solu- acid .

ble in

water . Yellow coloration with FeSO4 . Position of carboxyl group deter- mined by synthesis from a-naphthyl- amine (Z . Skraup and A . Cobenzl, Monals., Nicotinic C5H4(CO2H)N p 1883, 4, p . X36) . acid . M.p . 228—229 . An oxi- dation product of nicotine, hydrastine Quinolinic C6H3(CO2H)2N a$ and berberine . Con- acid . C5H3(CO2H)2N py stitution determined Cincho- C6H2(CO2H)2N apy by synthesis from meronic C6H2(CO2H)3N ayf3' p-naphthylamine acid .

(Skraup) . a-

Carbo- M.p . 192—195° with de- cincho- composition into nico- meronic tinic acid . Formed acid . by oxidation of Berbero- quinoline . nic M.p . 258—2590 . Formed acid . by oxidation of quin- ine, cinchonine, and of isoquinoline . M.p . 249-250° . Crystal- hies with IIH2O .

An oxidation product of cinchonine, quinine and papaverine . M.p . 243° . An oxida- tion product of ber- berine . Gives a red coloration with FeSO4 . Boiling with glacial acetic acid gives cinchomeronic acid . Trigonelline, C7H7NO2, the methyl betaine of nicotinic acid, was discovered in 1885 by E . Jahns (Ber., 1885, 18, p . 2518), and is found in the seeds of Trigonella and

Strophanthus hispidus . It is very soluble in water . With baryta it yields methylamine, and when heated with concentrated hydrochloric acid, to 26o° C. it yields methyl chloride and nicotinic acid . It was synthesized by A .

Hantzsch (Ber., 1886, 19, p . 31) by condensing methyl iodide and

potassium nicotinate at 150° C. the resulting iodide being then decomposed by moist silver oxide . A . Pictet (Ber., 1897, 30, p . 2117) obtained it by oxidizing nicotine methyl hydroxide with potassium permanganate . Apophyllenic acid, C8H7NO4•H20, the methyl betaine of cinchomeronic acid, was synthesized by W . Roser (Ann., 1886, 234, p . 118) . Piperidine or hexa-hydropyridine, C6H21N, was first obtained in 1848 by distilling piperine with lime . It is formed in the hydrolysis of piperine by alcoholic potash, by the reduction of trimethylene cyanide (A . Ladenburg) and by the action of alkalis on e-chloramylamine, Cl(CH2)s•NH2 (S . Gabriel, Ber., 1892, 25, p .

42I) . It is also produced in the electrolytic oxidation of N-nitroso piperidine in sulphuric acid

solution (F . B . Ahrens, Ber., 1898, 31, p . 2275) . It is a liquid which boils at 105—106° C., and possesses an ammoniacal smell . It is readily soluble in water, alcohol and ether, and is a very powerful base . It is oxidized to pyridine by heating with concentrated sulphuric acid to 300° C., or with nitrobenzene to 250° C., or with silver acetate to 180° C . Being an imide it readily yields a nitroso derivative, and N-alkyl and acidyl derivatives . The piperidine ring is easily split . When heated with fuming hydriodic acid to 300° C. it yields normal pentane and ammonia, and hydrogen peroxide oxidizes it to glutarimide and to a piperidinium oxide or oxime (R . Wolffenstein, Ber., 1904, 37, p .

3228) . A . W .

Hofmann (Ber .. 1881, 14, p . 66o), by a process of exhaustive methylation and distillation, obtained the unsaturated hydrocarbon piperylene, C H2: C H • C H2 • CH : CH2, from piperidine (see also A . Ladenburg, Ann., 1894, 279, P . 344)- C6HnN(+CH3I) — C5HI0N(CH3)2I (+AgOH) —j C6H,6N(CH3)2.OH (distil) 1 CiH9N(CH3)3.OHE--(+AgOH)C5H9N(CH3)3I<—(-}CHsI)C6H9N(CHs)2 (distil) C1H2+N(CH3)3+H20 J. v . Braun (Bee., 1904, 37, p . 2915) showed that benzoyl piperidine, when heated with phosphorus pentachloride to 20o° C. in sealed tubes, yields benzonitrile, and pentamethylene dichloride, thus leading to a simple method of preparing pentamethylene compounds . At 125—130° C. the compound C6H2C•Cl:N(C112)s•G is obtained; this with water yields benzoylamidochloramylamine C6H5CONH(CH2)5Cl, which when heated with hydrochloric acid tc 17o—18o° C. furnishes e-chloramylamine, NH2(CH2)SCI. a-Propyl, piperidine is the alkaloid conine (q.v.) .