1911 Encyclopædia Britannica/Quinoline

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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 homologies 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-amino-benzaldehyde with acetaldehyde in the presence of aqueous caustic soda (P. Friedlander 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 an hydride of ortho-aminohydrocinnamic acid), the chlorinated compound first formed being then reduced by hydriodic acid (A. Baeyer):

C6H4Langle.svg CH2 – CH2 → C6H4Langle.svg CH=C·Cl → C6H4Langle.svg 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). Quinoline.jpg 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 homologies 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 aldehyde's, 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 aldehyde's 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.

Hexagon, point up.jpgHexagon, point up.jpgN

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, C¢H5-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):

C6H4Langle.svg CH2 – CO or C6H4Langle.svg CH=C(OH) → C6H4Langle.svg CH = C·Cl → C6H4Langle.svg CH=CH
| | | |  .

It is also formed from isobenzalphthalide by the action of ammonia, followed by phosphorus oxychlorxde and reduction of the chlorinated product (S. Gabriel),

C6H4Langle.svg CH = C·C6H5 →C6H4Langle.svg CH = C·C6H5 →C6H4Langle.svg CH = C·C6H5 →C6H4Langle.svg 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).