1911 Encyclopædia Britannica/Pyridine

PYRIDINE, C₅H₅N, an organic base, discovered by T. Anderson (Trans. Roy. Soc. Edin., 1851, 20, p. 251) in bone oil. It is also found among the distillation products of bituminous coal, lignite, and various shales, and has been detected in fusel oil and crude petroleum. It is a decomposition product of various alkaloids (nicotine, sparteine, cinchonine, &c.), being formed when they are strongly heated either alone or with zinc dust. It may be s nthetically prepared by distilling allyl ethyl amine over heated lead oxide (W. Königs, Ber., 1879, 12, p. 2341) by passing a mixture of acetylene and hydrocyanic acid through a red-hot tube (W. Ramsay, Ber., 1877, 10, p. 736); by heating pyrrol with sodium methylate and methylene iodide to 200° C. (M. Dennstedt and J. Zimmermann, Ber., 1885, 18, p. 3316), by heating isoamyl nitrate with phosphorus pent oxide (E. T. Chapman and M. H. Smith, Ann., 1868, Suppl. 6, p. 329); and by heating piperidine in acetic acid solution with silver acetate (J. Tafel, Ber., 1892, 25, p. 1619). The amount of pyridine produced in most of these processes is very small, and the best source for its preparation is the “ light-oil ” fraction of the coal-tar distillate. The basic constituents are removed by dilute sulphuric acid, the acid layer removed, and the bases liberated by alkali, separated, dried, and fractionally distilled.

Pyridine is a colourless liquid of a distinctly unpleasant, penetrating odour. It boils at 114.5° C., and is miscible with water in all proportions. It is a tertiary base, and combines readily with the alkyl halides to form pyridinium salts. Nascent hydrogen reduces it to piperidine, C₅H₁₁N (see below), whilst hydriodic acid above 300° C. reduces it to n-pentane (A. W. Hofmann, Ber., 1883, 16, p. 590). It is a very stable compound, chromic and nitric acids being without action upon it, whilst the halogens only yield substitution derivatives with difficulty. It reacts with sulphuric acid only at high temperatures, yielding a sulphonic acid. It forms addition compounds with mercuric and auric chlorides. On the constitution of the pyridine nucleus, see Körner, Gior. dell' acad. di Palermo, 1869, and C. Riedel, Ber., 1883, 16, p. 1609. As regards the isomerism of the pyridine substitution products, three mono-derivatives are known, the different positions being indicated by the Greek I letters a., 13 and 'y, as shown in the inset formula. This B 4 A' formula also allows of the existence of six di-deriva-B

tives, six tri-derivatives, three tetra- and one penta- f derivative, when the substituent groups are identi“ N °' cal; all of which are in agreement with known facts.

The three monochlorpyridines are known, the a. and 'y compounds resulting from the action of phosphorus pentachloride on the corres onding oxypyridines, and the B compound from the action of cliloroform on potassium pyrrol. ez-Aminopyridine, C5H4N -N Hg, is formed by heating 5-amino pyridine-2-carboxylic acid. It is a crystalline solid which melts at 56° C. and boils at 204° C. It can only be diazotized in the presence of concentrated sulphuric acid, and even then the free diazonium sulphate is not stable, readily passing in the presence of water to u.-oxypyridine. /S-Aminopyridine is obtained by heating H-pyridyl urethane with fuming hydrochloric acid until no more carbon dioxide is liberated (T. Curtius and E. Mohr, Bef., 1898, 31, p. 249§), or by the action of bromine and caustic soda on the amide of nicotinic acid (F. Pollak, Monats., 1895, 16, p. 54). It melts at 64° C. and boils at 250-252° C. The aminopyridines are readily soluble in water, and resemble the aliphatic amines in their general chemical pro erties. V The oxypyridines may be prepared by distilling the corresponding oxypyridine carboxylic acids with lime, or by fusing the pyridine carboxylic acids with caustic potash. The mono-oxypyridmes are easily soluble in water and possess only feeble basic properties. The 5 compound is hydroxylic in character, whilst the a. and fy derivatives behave frequently as if they possess the tautomeric ketostructure, yielding according to the conditions of the experiment either N- or 0-ethers (H. v. Pechmann, Bef., 1895, 28, p.,1624), thus corresponding to the formulae CH CH C-OH CO

HC('§ CH HC(|CH HC(§ CH HC' ICH

HC /C-OH HC:co HC' / CH HC CH

N/ NH D(hha.-oxypyridine

a.-pyridone ~/-oxypyridine 'Y-Pyridone The homologies of pyridine may be synthesized in various ways. One of the most important is the so-called “ colliding " synthesis of A. Hantzsch (Ann., 1882, 215, p. 1; Bef., 1882, 15, p. 2914) which consists in the condensation of two molecules of aceto-acetic ester with one of an aldehyde and one of ammonia:- Roc-cn R'-cHo c -con Roc-c-cHR'~c-con cn.-co”+ NH, + did-cfia " cial-c-NH-C-cni The resulting dihydro-compound is then oxidized with nitrous acid, the ester hydrolysed and the resulting acid heated with lime; carbon dioxide is eliminated land axgrisuppxtituted pyridine of the type is o tain . e reaction is ap arentl a R C/CH C(CH )N general one for all aldehyde's. Onllhe cori/rse CH C(CH)/ of the reaction see also C. Beyer, Bef., 1891, “ 24, p. 1662, and E. Knoevenagel, Bef., 1898, 3I, tQ. 73%. In this) reacttionhthe péopoations aédphyméledand agetoace ic es er may e in erc an e an a.-y isu s 1 u e ri mes are then obtained. Of the other methods for preparin pyridine homologies 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 pyridine's (Ber., 1883, 16, p. 1410 seq.; Ann., 1888, 247, p. 1). S. Ruhemann prepared -y-substituted dioxypyridines by condensing alkyl-dicarboxy-glutaconic esters with ammonia.

1 . 1 R'O C'C:CR-CH-CO R' H Q:CR -C H M. Scholtz (Ben, 1895, 28, p. 1726) prepared aa- methylphenylpyridine by distilling cmnamenylidene acetoxime, C, H¢CH:CH-CH:CH-C(:N~OH)-CH, = Cs§ 5%' § , H, € § H, +H, o The 1-5 dike tones of the type inset, when heated with ammonia, also yield pyridine derivatives. Alkyl pyridine's -CO CO- are also obtained by heating aldehyde C:CH~CH ammonias alone or with aldehyde's and -CO CO- ketones (A. v. Baeyer, Ann., 1870, 155, pp. 281, 294; ]. Pochl, Bef., 1887, 20, p. 722).

The subjoined table shows the chief homologies of pyridine:- Position

Name. Formula. of Sub- Remarks.

stituent.

Picolines C5H4(CH3)N a. Liquid, b.p. 1290. Oxiizes to picolinic acid.

Condenses readily

with aldehyde's.

B Liquid, b.p. 143°. Oxidizes

to nicotinic acid.

Does not condense

L witl: alldehydes. O

7 iqui, .p. 14 -I 5 .

Lutidines C5H4(C2H5)N a., /3, 'y, Three isomer; 4 All liquids. The B compound

is a decomposition

product of

cinchonine, quinine,

strychnine and brucme.

C¢, H3(CH3)¢N aa'ba-pg aB' Fiye d isomers. All 3 ', 'y. iqui s.

Callidines C5H4(C;H1)N a, ;3. Liquids. The a compound is a decomposition

product of conine.

Both contain the normal

propyl group.

a, 7. Contpining the isopropy

group.

C5H;(CHa)(C2H5)N a.'o., ;f§ , Liquids. 57|

C, H2(CH3)3N wa' Liquid, b. . 171-172°. Prepared) by the

Hantzsch synthesis.

1, WB' Found in coal-tar.

Pyridine carboxylic acids are usually prepared by oxidizing the homologies of the base; they also result as decomposition products of various alkaloids. The more important are shown in the table.

Position

Name. Formula. of Sub- Remarks.

stituent.

Picolinic C5H4(CO2H)N a M.p. 137°. Easil soluacid. ble in water. hfellow

coloration with

FeSO4. Position of

carboxyl group determined

by synthesis

from a-naphthylamine

(Z. Skraup and

A. Cobenzl, Monats.,

18831 4. p- 436).

Nicotinic C5H4(CO2H)N B M.p. 228-229 . An oxiacid. dation product of

nicotine, hydras tine

and berberine. Constitution

determined

by synthesis from

/S-naphthylamine

(Skraup).

Quinolinic C5H, (COzH)2N ad M.p. 192-195° with deacid. composition into nicotinic

acid. Formed

by oxidation of

quinoline.

Cincho- C5H;(CO2H)2N /Sy M.p. 258-259°. Formed meronic by oxidation of quinacid.

ine, cinchonine, and

b C H (CO H) N Moi isoquinolinet 1

a-Car o- 5 1 2 3 aBy . .249»250°. rystacincho- lizes with 1%H2O. An

meronic oxidation product of

acid. cinchonine, quinine

and papaverine.

Berbero- C5H2(CO¢H), N a-yd' M.p. 243°. An oxidanic tion product of ber|

acid. berine. Gives a red

coloration with

FeSO4. Boiling with

glacial acetic acid

gives cinchomeronic

acid.

Trigonelline, C7i-l1NO2, the methyl betaine of nicotinic acid, was discovered in 1885 by E. Iahns (Ber., 1885, 18, p. 2518), and is found in the seeds of Triganella and Strophanthus hispidus. It is very soluble in water. With baryta it yields methyl amine, and when heated with concentrated hydrochloric acid, to 260° C. it yields methyl chloride and nicotinic acid. It was synthesized by A. Hantzsch (Ber., 1886, 19, p. 631) by condensing methyl iodide and potassium nicotinate at 150 C. the resulting iodide being then decomposed by moist silver oxide. A. Pictet (Ben, 1897, 30, p. 2117) obtained it by oxidizing nicotine methyl hydroxide with potassium permanganate. Apophyllenic acid, CgH1NO4-HZO, the methyl betaine of cinchomeronic acid, was synthesized by W. Roser (Ama, 1886, 234, p. 118).

Piperidine or hexa-hydro pyridine, C51-IHN, 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 trim ethylene cyanide (A. Ladenburg) and by the action of alkalis on e-chl0ramylamine, Cl(CH2)5-NH2 (S. Gabriel, Bef., 1892, 25, p. 421). It is also produced in the electrolytic oxidation of N-nitroso piperidine in sulphuric acid solution (F. B. Ahrens, Bef., 1898, 31, p. 2275). It is aliquid which boils at 105-106° C., and possesses an ammonia cal 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 I8O° 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, Bef., 1904, 37, p. 3228). A. W. Hofmann (Ben. 1881, 14, p. 660), by a process of exhaustive methylation and distillation, obtained the unsaturated hydrocarbon piperylene, CH2:CH-Cl-I2-Cl-I: CHL from piperidine (see also A. Ladenburg, Ann., 1894- 279, 11344)-Cf.H11N(+CH;,

I)1> C5HmN(CH;,)2I (+AgOH) -5 C5H10N(CHa)2~OH (distil)L

CsHeN(CHsMOH?-('i'AgOH)CsHsN(CHs)al@(°i'CHal)CsH9N(CHa)2 (distil) (L

Csl'is'i'N(CHs)a+H2O

], v. Braun (Ben, I9O.¥; 37, p. 2915) showed that benzoyl pi eridine, when heated wit phosphorus pentachloride to 200° in sealed tubes, yields benzonitrile, and pentamethylene dichloride, thus leading to a simple method of preparing pentamethylene compounds. At 125-130° C. the compound C6H5C-Cl:N(CH¢)5-Cl is obtained; this with water yields benzoylamidochloramylamine C5H5CONH(CH2)5Cl, which when heated with hydrochloric acid tc 170-180° C. furnishes e-chloramylamine, NH¢(CH2)5Cl. a-Propy1piperidine is the alkaloid conine (g.'v.).