Pyridine

Pyridine, C 5 H 5 N, 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 synthetically prepared by distilling allyl ethylamine over heated lead oxide (W. Kdnigs, 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 pentoxide (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 K6rner, 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, letters a, s and y, as shown in the inset formula. This o ¢ ? formula also allows of the existence of six di-derivatives, six tri-derivatives, three tetraand one penta 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 corresponding oxypyridines, and the 1 3 compound from the action of chloroform on potassium pyrrol. a-Aminopyridine, C5H4NNH2, is formed by heating 5-aminopyridine-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 a-oxypyridine. #-Aminopyridine  is obtained by heating a-pyridyl urethane with fuming hydrochloric acid until no more carbon dioxide is liberated (T. Curtius and E. Mohr, Ber., 18 9 8, 3 1, p. 2 493), 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 properties.

CH

| 

CH 

| 

C.OH 

| 

CO  
  
---|---|---|---  
  
HC/CH

| 

HC /Q CH

| 

HC" CH

| 

HC CH  
  
HCkjCOH

| 

HCUCO

| 

HCU CH

| 

HC /  
  
| 

NH

| | 

NH   
  
a -oxypyridine

| 

a -pyridone

| 

y -oxypyridine

| 

y -pyridone  
  
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-oxypyridines are easily soluble in water and possess only feeble basic properties. The /3 compound is hydroxylic in character, whilst the a and -y 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, Ber., 1895, 28, p. 1624), thus corresponding to the formulae The homologues of pyridine may be synthesized in various ways. One of the most important is the so-called "collidine" synthesis of A. Hantzsch (Ann., 1882, 215, p. I; Ber., 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: RO 2 CCH 2 R'CHO CH 2 CO 2 R RO 2 CCCHR'CC02R CH 3 CO + NH 3 + COCH 3 -' CH3C-NH-CCH3 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(CH3) 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, 3 1, p. 73 8. 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 y-substituted dioxypyridines by condensing alkyl-dicarboxy-glutaconic esters with ammonia.

(R'02C)2C:CR CH(C02R')2-> R'O 2 C C:CR CH C02R' H C:CRC H OCNH. CO HOC:N-C OH M. Scholtz (Ber., 1895, 28, p. 1726) prepared aamethylphenylpyridine by distilling cinnamenylidene acetoxime, CRH5CH:CHCH:CHC(:NOH)CH3= H C CH:CH H20 C 5 H 5. C N :CCH3m The 1 . 5 diketones of the type inset, when heated with ammonia, also yield pyridine derivatives. Alkyl pyridines -CO /COare also obtained by heating aldehyde ? C:CHCH< ammonias alone or with aldehydes and -CO CO - ketones (A. v. Baeyer, Ann., 1870, 155, pp. 281, 294; J. Plochl, Ber., 1887, 20, p. 722).

Name.

| 

Formula.

| 

Position

of Sub-

stituent.

| 

Remarks.  
  
---|---|---|---  
  
Picolines 

| 

C5H4(CH3)N

| 

a 

| 

Liquid, b.p. 129°. Oxi-

dizes to picolinic acid.  
  
| | | 

Condenses readily

with aldehydes.  
  
| | 

0

| 

Liquid, b.p. 143°. Oxi-

dizes to nicotinic acid.  
  
| | 

y

| 

Does not condense

with aldehydes.

Liquid, b.p. 144-145°.  
  
Lutidines 

| 

C5H4(C2H5)N

| 

a, 13, y, 

| 

Three isomers. All

liquids. The, com-

pound is a decompo-

sition product of

cinchonine, quinine,

strychnine and bru-

cine.  
  
| 

C5H3(CH3)2N

| 

aa', ay, a6 

00', ay.

| 

Five isomers. All

liquids.  
  
Collidines 

| 

Cal 4(C3H7)N

| 

a, 13. 

| 

Liquids. The a com-

pound is a decomposi-

tion product of conine.  
  
| | 

a, y. 

| 

Both contain the nor-

mal propyl group.

Containing the isopro-

pyl group.  
  
| 

C 5 H3(CH3)(C2H5)N

| 

a'a, y/3, 

ay, a(3'

| 

Liquids.  
  
| 

C,H 2 (CH 3) 3 N

| 

aya' 

| 

Liquid, b.p. 171-172°.  
  
| | | 

Prepared by the  
  
| | 

a 7 l3'

| 

Hantzsch synthesis.

Found in coal-tar.  
  
The subjoined table shows the chief homologues of pyridine: 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

of Sub-

stituent.

| 

Remarks.  
  
---|---|---|---  
  
Picolinic

acid.

| 

C5H4(C02H)N

| 

a

| 

M.p. 137°. Easily solu-

ble in water. Yellow

coloration with  
  
| | | 

FeSO 4. Position of

carboxyl group deter-

mined by synthesis

from a-naphthyl -

amine (Z. Skraup and  
  
| | | 

A. Cobenzl, Monats., 

1883, 4, p. 436).  
  
Nicotinic

acid.

| 

C 5 H 4 (CO 2 H)N

| 

0

| 

M.p. 228-229°. An oxi-

dation product of

nicotine, hydrastine

and berberine. Con-

stitution determined

by synthesis from  
  
| | | 

0-naphthylami n e  
  
| | | 

(Skraup).  
  
Quinolinic

acid.

| 

C5H3(C02H)2N

| 

aß

| 

M.p. 192-195° with de-

composition into nico-

tinic acid. Formed

by oxidation of

quinoline.  
  
Cincho-

meronic

acid.

| 

C5H3(C02H)2N

| 

ay 

| 

M.p. 258-259°. Formed

by oxidation of quin-

ine, cinchonine, and

of isoquinoline.  
  
a-Carbo-

cincho-

meronic

acid.

| 

C5H2(C02H)3N

| 

aay

| 

M .p. 249-250°. Crystal-

lizes with I ZH 2 O. An

oxidation product of

cinchonine, quinine

and papaverine.  
  
Berbero-

nic

acid.

| 

C5H2(C02H)3N

| 

ay/3'

| 

M.p. 243°. An oxida-

tion product of ber-

berine. Gives a red

coloration with  
  
| | | 

FeSO 4. Boiling with

glacial acetic acid

gives cinchomeronic  
  
| | | 

. acid.  
  
Trigonelline, C7H7N02, 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 260° 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, C8H7N04H20, the methyl betaine of cinchomeronic acid, was synthesized by W. Roser (Ann., 1886, 234, p. 118).

Piperidine or hexa-hydropyridine, C 5 H 11 N, 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)5NH2 (S. Gabriel, Ber., 1892, 2 5, p. 421). 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. 660), by a process of exhaustive methylation and distillation, obtained the unsaturated hydrocarbon piperylene, CH 2 :CHCH 2 CH: CH2, from piperidine (see also A. Ladenburg, Ann., (18 94, 2 79, P. 344).

C5H11N(+CH31) --> C5HioN(CH3)21 (+AgOH) -- C5H10N(CH3)2.OH (distil) C 5 HiN(CH3)3. OH -(-i-AgOH)C5H9N(CH3)31E-(-f-CH31)C5H9N(CH3)2 (distil) C1H3+N(CH3)3+H20 J. v. Braun (Ber., 1904, 37, p. 2915) showed that benzoyl piperidine, when heated with phosphorus pentachloride to 200° 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 C6H5CCl:N(CH2)5CI is obtained; this with water yields benzoylamidochloramylamine, C 6 H 5 CONH(Ch 2) 5 C1, which when heated with hydrochloric acid to 170-180° C. furnishes e-chloramylamine, NH 2 (CH 2) 5 C1. a-Propylpiperidine is the alkaloid conine.