QUINOLINE (Benzopyridine), C9H7N, an organic base first obtained from coal-tar in 1834 by F. Runge (Pogg. Ann.,
1834, 31, p. 68), and later by C. Gerhardt by the distillation of
cinchonine, quinine and other alkaloids with caustic potash
(Ann., 1842, 42, p. 310; 44, p. 279). It also occurs with
pyridine and its homologues in bone-oil. It may be prepared
by distilling cinchoninic acid with lime; by the reduction of
ortho-aminocinnamic aldehyde (A. Baeyer and V. Drewson, Ber.,
1883, 16, p. 2207); by passing the vapour of allyl aniline
over heated lead oxide; by the condensation of ortho-aminobenzaldehyde
with acetaldehyde in the presence of aqueous
caustic soda (P. Friedländer and C. F. Gohring, Ber.,
1882, 15, p. 2572; 1883, 16, p. 1833); by the action of orthotoluidine
on glyoxal at 150° C. (V. Kulisch, Monats., 1894,
15, p. 276); by the action of phosphorus pentachloride on
hydrocarbostyril (the inner anhydride of ortho-aminohydrocinnamic
acid), the chlorinated compound first formed being then
reduced by hydriodic acid (A. Baeyer):
C6H4 |
CH2 – CH2 |
→ C6H4 |
CH=C·Cl |
→ C6H4 |
CH=CH
|
| |
| |
| ;
|
NH – CO |
N=C·Cl |
N= CH
|
and by the so-called “Skraup” reaction, which consists in
oxidizing a mixture of aniline, glycerin and concentrated
sulphuric acid, with nitrobenzene (Z. Skraup, Monats., 1880,
1, p. 316; 1881, 2, p. 141). This reaction is a very violent
one, and its mechanism may probably be explained as
follows: The glycerin is first converted into acrolein,
which combines with the aniline to form acrolein-aniline,
and this product is then oxidized by the nitrobenzene:
C3H8O3→9C3H4O(+C6H5NH2)→C6H5N:CH·CH2→C9H7N.
The nitrobenzene may be replaced by arsenic acid, when the
reaction proceeds much more quietly and a cleaner product is
obtained (C. A. Knueppel, Ber., 1896, 29, p. 703). The Skraup
reaction is a perfectly general one for primary amino-compounds;
the halogen-, nitro- and oxy-anilines (amino phenols) react
similarly, as do also the toluidines, naphthylamines, aminoanthracene,
meta- and para-phenylene diamines, and ortho- and
γ-aminoquinoline.
Quinoline is a colourless liquid with a smell resembling that
of pyridine. It boils at 238° C. and is very hygroscopic. It
is a tertiary base and forms well-defined salts. It is almost
insoluble in water, but dissolves readily in the common organic
solvents. It combines readily with the alkyl halides. H.
Decker (Ber., 1905, 38, p. 1144) has found that many ortho substituted
quinolines will not combine with methyl iodide owing to
steric hindrance, but the difficulty can be overcome in most cases
by using methyl sulphate and heating the reaction components
to 1000 C. for half an hour. Nitric acid and chromic acid have
little action on quinoline, but alkaline potassium permanganate
oxidizes it to carbon dioxide, ammonia, oxalic, and quinolinic
acids (S. Hoogewerif and W. A. v. Dorp, Rec. Pays Bas, 1882,
1, p. 107).
Bleaching powder oxidizes it to chlorcarbostyril.
It is reduced by the action of zinc and ammonia
to di-and tetra-hydroquinolines. A hexahydro- and
a decahydroquinoline have been obtained
by heating tetrahydroquinoline with hydriodic
acid and phosphorus to high temperatures
(E. Bamberger, Bar., 1890, 23, p. 1138). Numerous substitution
products of quinoline are known, and the positions in the
molecule are generally designated in accordance with the
scheme shown in the inset formula: the letters o, m, p, a,
standing for ortho-, meta-, para-, and ana-.
The oxyquinolines possess a certain importance owing to their
relationship to the alkaloids. Those with the hydroxyl group in
the benzene nucleus are prepared from the amino phenols by the
Skraup reaction. Only two are known containing the hydroxyl
group in the pyridine nucleus, namely, carbostyril (α-oxyquinoline),
which is formed by the reduction of ortho-aminocinnamic acid with
ammonium sulphide (L. Chiozza, Ann., 1852, 83, p. 118) or with
ferrous sulphate and baryta, and kynurine (γ-oxyquinoline), which is
obtained by the action of nitrous acid on γ-aminoquinoline (A.
Claus and H. Howitz, Jour. prak. Chem., 1894, 158, p. 232). It is
also formed by the condensation of anthranilic acid with acetaldehyde
(S. Niementowski, Bef., 1895, 28, p. 2811). They are both
crystalline solids, the former melting when anhydrous at 199–200°,
and the latter at 52° C.
Of the homologues of quinoline, the most important are quinaldine,
lepidine, γ-phenylquinoline, and flavoline. Quinaldine
(α-methylquinoline) is present in coal-tar; it may be prepared
by condensing aniline with par aldehyde and concentrated hydrochloric
acid (O. Doebner and W. v. Miller, Ber., 1881, 14, pp. 2812
et seq.). The reaction is a perfectly general one, for the aniline
may be replaced by other aromatic amines and the aldehyde by
other aldehydes, and so a large number of quinoline homologies
may be prepared in this way. Quinaldine may also be obtained by
condensing ortho-aminobenzaldehyde with acetone in presence
of caustic soda (P. Friedlander, loc. cit.). It is a colourless
liquid which boils at 247° C. The –CH3 group is very reactive,
condensing readily with aldehydes and with phthalic an hydride.
Potassium permanganate oxidizes it to acetylanthranilic acid,
HOOC(I)·C6H4·(2)NH·COCH3, while chromic acid oxidizes it to
quinaldic acid (quinoline-α-carboxylic acid). Lepidine(γ-methylquinoline)
was first obtained by distilling cinchonine with caustic potash.
It may be prepared synthetically by condensing ortho-amino ace top hen one
with par aldehyde and caustic soda (L. Knorr, Ann., 1886,
236, p. 69) or from aniline, acetone, formaldehyde and hydrochloric
acid (C. Beyer, Jour. prak. Chem., 1885, 140, p. 125). It may also
be prepared by condensing αγ-dimethylquinoline and formaldehyde,
the resulting α-ethanollepidine, C9H5·CH3N(CH2·CH2·OH),
breaks down on. heating and forms lepidine (W. Konigs and A.
Mengel, Bef., 1904, 37, p. 1322). It is a colourless liquid which
boils at 255° C. Chromic acid oxidizes it to cinchoninic aci d
(see below), whilst potassium permanganate oxidizes it to lepidimc
acid (γ-methylquinolinic acid) and cinchomeronic acid (see Pyridine).
γ-Phenylquinoline, which is probably the parent substance
of the cinchona alkaloids, is prepared by heating γ-phenylquinsldic
acid, the oxidation product of the γ-phenylquinaldine, which
results from the action of alcoholic potash on a mixture of orthoaminobenzophenone
and acetone (W. Konigs and R. Geigy, Ber.,
1885, 18, p. 2400), or by the action of sulphuric acid on Lenzoylacetone
anilide (C. Beyer, Bef., 1887, 20, p. 1767). It crystallizes
in needles which melt at 61° C. Flavoline (α-phenyl-γ-methyb
quinoline) is formed on heating tlavenol (see below) with excess of
zinc dust, or by heating molecular proportions of ortho-amino ace top hen one
and ace top hen one, in dilute alcoholic solution, with
a small quantity of 10% caustic soda solution (O. Fischer, Bef.,
1886, 19, p. 1037). Closely related to flavoline is flavaniline or
(α)-para-aminophenyl-γ-methylquinoline, which is formed when
acetanilide and anhydrous zinc chloride are heated together for
many hours at 250–270° C. (O. Fischer and C. Rudolph, Bef., 1882,
15, p. 1500), or by heating ortho- and para-amino ace top hen one
with zinc chloride to 90° C. (O. Fischer, Bef., 1886, 19, p. 1038).
It crystallizes from benzene in prisms; which melt at 97° C. Sodium
nitrite in the presence of excess of acid converts it into the corresponding
hydroxylic compound flavenol.
The oxy derivatives of the quinoline homologies are best obtained
from the aniline derivatives of, β-ketonic acids. At 110° C.
aniline and acetoacetic ester condense to form anilido-acetoacetic
ester, CH3CO·CH2·CO·NH·C6H5, which is converted by concentrated
acids into a-oxy—y-methylquinoline (L. Knorr, Ann., 1886, 236, p. 73).
On the other hand, at about 240° C., the amine and ester react
to form β-anilidocrotonic ester, CH3C(NHC6H5) : CH·COOC2H5,
which yields γ-oxy-α-methylquinoline (M. Conrad and L. Limpach,
Ber., 1887, 20, p. 947).
Numerous carboxylic acids of quinoline are known, the most
important of which are quinaldic, cinchoninic and acridinic acids.
Quinaldic acid (quinoline-α-carboxylic acid) is produced when
quinaldine is oxidized by chromic acid. It crystallizes in needles,
which contain two molecules of water of crystallization, and melt
at 156° C. When heated above the melting-point it loses carbon
dioxide and yields quinoline. Alkaline potassium perrranganate
oxidizes it to pyridine tricarboxylic acid (2·3·6). Cinchoninic
acid (quinoline-γ-carboxylic acid) is formed when 'cinchonine is
oxidized by nitric acid, or by the oxidation of lepidine. It crystallizes
from water in needles or prisms and in the anhydrous
state melts at 253–254° C. Potassium permanganate oxidizes it to
pyridine tricarboxylic acid (2·3·4). Acridinic acid (quinoline-a/3dicarboxylic
acid) is formed when acridine is oxidized by potassium
permanganate (C. Graebe and H. Caro, Ber., 1880, 13, p. 100).
It crystallizes in needles, which are easily soluble in alcohol, and when
heated above 130° C. lose carbon dioxide and leave a residue of
quinoline-B-carboxylic acid.
N
|
Isoquinoline.
|
Isoquinoline, isomeric with quinoline, was first discovered in
coal-tar in 1885 by S. Hoogewerif and W. A. v. Dorp (Rec. Pays
Bas, 1885, 4, 125); its formula is shown in the
inset. It may be separated from the quinoline which
accompanies it by means of the difference in the
solubility of the sulphates of the two compounds, N
isoquinoline sulphate being much less soluble than
quinoline sulphate. It may be prepared by passing
the vapour of benzylidene ethyl amine through a red-hot tube
(A. Pictet and S. Popovici, Ber., 1892, 25, p. 733); by the action
of concentrated sulphuric acid on benzyl amino-acetaldehyde,
C6H5·CH2·NH·CH2-CHO (E. Fischer), or on benzylidene aminoacetal,
CGHBCH: N - CH2 - CH(OC2H5)2 (C. Pomeranz, Monats.,
1892, 14, p. 116); by heating cinnamenyl aldoxime with phosphorus
pent oxide to 70° C. (E. Bamberger, Ber., 1894, 27, p, 1955),
C6H5CH: CH-CH: NOH → [C6H5CH: CH~NH~COH]→C9H7N;
by the action of hydriodic acid on the oxydichlorisoquinoline
formed when phosphorus pentachloride reacts with hippuric acid;
by the distillation of homophthalimide over zinc dust (M. Le Blanc,
Ber., 1888, 21, p. 2299), or by treatment with phosphorus oxychloride
followed by the reduction of the resulting dichlorisoquingiline
with hydriodic acid (S. Gabriel, Ber., 1886, 19, pp. 1655,
2355):
C6H4 |
CH2 – CO |
or C6H4 |
CH=C(OH) |
→ C6H4 |
CH = C·Cl |
→ C6H4 |
CH=CH
|
| |
| |
| |
| .
|
CO – NH |
C(OH):N |
C·Cl=N |
CH=N
|
It is also formed from isobenzalphthalide by the action of ammonia,
followed by phosphorus oxychlorxde and reduction of the chlorinated
product (S. Gabriel),
C6H4 |
CH = C·C6H5 |
→C6H4 |
CH = C·C6H5 |
→C6H4 |
CH = C·C6H5 |
→C6H4 |
CH = C·C6H5
|
| |
| |
| |
| ;
|
CO – O |
CO – NH |
CCl = N |
CH = N
|
and from isocoumarin carboxylic acid by conversion into isocarbostyril
on heating, and subsequent reduction by distillation with
zinc dust (E. Bamberger, Ber., 1892, 25, p. 1138). It melts at
22–23° C. and boils at 240° C., and behaves in most respects similarly
to quinoline. By oxidation with alkaline potassium permanganate
it yields phthalic acid and cinchomeronic acid. Reduction by means
of tin and hydrochloric acid gives a tetra hydro derivative.
Numerous derivatives of isoquinoline are obtained in the decomposition
of various vegetable alkaloids. Papaverine on fusion with alkalis yields a dimethoxyisoquinoline, whilst hydrohydrastinine,
hydrocotarnine and the salts of cotarnine may be considered
as derivatives of reduced isoquinolines (see Opium).