Investigations on 2,3′-Biquinoline. 17. Regioselectivity of the Halogenation of 2,3′-Biquinoline Derivatives

Abstract

It is known that the halogenation of quinoline in strongly acidic medium occurs at position 5 and 8 forming a 1:1 ratio of isomers. It is thought that such an orientation is a consequence of the deactivation of the pyridine ring due to protonation [2,3].In the case of less strong acid the quinoline is initially substituted at position 3 and then at position 6 and 8 and this arises from its initial conversion to the quinolinium cation which reacts with a nucleophile at position 2 to form a 1,2-dihydroquinoline. Subsequent addition of the electrophile occurs at position 3 etc [2, 3].2,3'-Biquinoline was of interest as a model compound for the investigation of electrophilic substitution in quinolines because, as a result of its asymmetry, a monoprotonation principally at one of the nitrogen atoms might be expected. In this case the reaction of a first kind would occur on a nonprotonated quinoline fragment and permit an evaluation of the regioselectivity of the electrophilic substitution in the quinoline free base and in the second kind on the other ring.We have previously shown [4] that the 2,3'-biquinoline 1 is nitrated by potassium nitrate in sulphuric acid on the 2-quinoline fragment and this agrees with a direction of monoprotonation of 2,3'-biquinoline at the nitrogen atom in position 1'. With the above in mind the halogenation of 2,3'-biquinoline in the presence of acid would be expected to occur in the 2-quinoline fragment at positions 5 and 8. In fact, treatment of compound 1 with bromine or chlorine in sulphuric acid in the presence of Ag 2 SO 4 gives a mixture of the 8-halo-2,3'-biquinoline 2, the 5-halo-2,3'-biquinoline 3, and the 5,8-dihalo-2,3'-biquinoline 4 in the ratio 2:1:4 (from 1 H NMR spectroscopic data).

The investigation in 2,3'-biquinoline series 26.* Regioselective nitration of 1'-alkyl-1',4'-dihydro-2,3'-biquinolin-4'-ones and 1'-alkyl-1',2'-dihydro-2,3'-biquinolin-2'-ones

“…We showed previously [4] that nitration of 2,3'-biquinolines is effected at positions 5 and 8, which is explained by the direction of their monoprotonation to position 1'. The direction of halogenation depends on the acidity of the medium and is effected at positions 5 and 8 in strongly acidic media and at position 6' in weakly acidic media [5]. It might have been expected that the direction of nitration of 1'-alkyl- 2,3'-biquinolin-4'-ones 1 and 1'-alkyl-1',2'-dihydro-2,3'-biquinolin-2'-ones 9 will also be changed depending on the acidity of the medium.…”