Synthesis of Derivatives of Quinoline.

Abstract

depending upon the amount of cobalt present. If cobalt be absent, the precipitate will be a pale green, and will remain so upon standing.It will, therefore, be evident that by this test, which is practically instantaneous and requires no manipulation, it is possible in one operation. carried on in a test-tube, to detect both elements, even if either element be in exceedingly small amount, in a great excess of the other, the test for cobalt being probably as delicate as any hitherto proposed (with the exception of \-ogel's test, outlined above, which requires the use of ammonium sulphocyanide, amyl alcohol and ether), while that for the detection of nickel is considerably more delicate than anything hitherto proposed for this purpose.For use in ordinary qualitative analysis in college laboratories where nickel-free cobalt salts are not supplied to students, the test may be modified in one of two ways in order to slightly decrease its delicacy. ( I ) T"ne students may be told that unless the change of color is retarded over a minute nickel may be regarded as absent, or ( 2 ) by using, instead of a gS sodium hydroxide solution, a IOX or I j K solution, when the delicacy is so decreased as to give practically no reaction for nickel in ordinary cobalt salt solutions. I desire to express my sincere thanks to Dr. J. F. Snell for the valuable advice he has rendered during the progress of this work. THE best method for the synthetical preparation of quinoline and its derivatives is that of Skraup,' which consists in heating an aromatic amine with glycerin, an aromatic nitro compound (usually nitrobenzene), and sulphuric acid. A quinoline ring is formed by the combining of the aromatic amine and the glycerin with loss of water and hydrogen. The nitro compound serves as an oxidizing agent, and is itself reduced to an amine from which quinolines are also formed, sometimes making mixtures that are difficult to separate.

Selectivity in the hydrogenation of 6- and 8-substituted-quinolines

“…This was refluxed with anhydrous glycerol (234 g) and As,O, (111 g), and concentrated H,SO, (217 g) was slowly added. The reaction was carried out and the crude product isolated as described for ( 2) and (3)., Crude (4) was then heated with an excess of acetic anhydride on a boiling water bath for 2 h. The mixture was then poured onto ice-water-HC1, extracted with ether, the aqueous solution was basified with 50% NaOH solution and extracted repeatedly with light petroleum. The solvent was distilled off and the residue was distilled (b.p.…”

“…. 3,4,4a,5,6,7,0.4 mol) was treated by the above procedure. After distillation in a Kugelrohr apparatus 72 g of a mixture of equal amounts of ( 6) and (34), plus a small amount of ( 20), was obtained.…”

“…When the scope of this change in behaviour towards hydrogenation of quinoline was investigated,,b a number of questions remained unanswered. The yield of 5,6,7,8tetrahydro-product in the case of 6-methylquinoline (2) was somewhat lower, and the yield in the case of 8methylquinoline (3) was considerably lower than for the parent compound (1).2b In consideration of the synthetic potential of the procedure it was interesting to determine the influence of other substituents at C-6 or C-8; i.e. if diminished yields of the 5,6,7,8-tetrahydro-product could be linked to the electron-donating properties of the substituents, and if the difference between 6and 8-substitution was a general phenomenon with possibly steric reasons.…”

“…(1) and related phenyl-substituted or -condensed pyridines it was generally accepted that saturation takes place at the pyridine ring to give, in the case of (I), 1,2,3,4-te trahydroquinoline, with further hydrogenation leading to the fully saturated systems. Only recently it has been shown that this only applies to hydrogenation in neutral or weakly acidic medium, whereas in strong acid (12~-HCl, 12~-H,So,, or CF,CO,H) the reaction leads to the 5,6,7,8-tetrahydro-, and then (less easily) to mainly cis-decahydro-products.…”

SOME NITRO DERIVATIVES OF 2,4- AND 2,6-DIMETHYLQUINOLINE1

“…1) indicates that the material obtained by Roberts and Turner was the eutectic mixture containing two moles of the 8-nitro derivative (I) to one of 6-nitro (11). Early attempts to prepare 8-nitro-2,6-dimethylquinoline by the Doebnervon Miller reaction on 3-nitrol-aminotoluene gave only about 1% yields (2). The modified procedure of Mills, Harris, and Lambourne (3) gave a 25% yield of the desired product, isolated as white crystals, m.p.…”