Diploma Thesis: Basicity and Transmission of Substituent Effects in 4-Substituted 1,2,3,4-Tetrahydroquinolines, Chelyabinsk State University, Russia, 1990.

Abstract

Derivatives of 1,2,3,4-tetrahydroquinolines (1) attract much interest due to (i) their structure combining both aromatic and heteroatomic rings, and (ii) their pharmacological activity.  In addition, 1,2,3,4-tetrahydroquinoline system poses some interesting questions about substituent effect transmission.  The semi-chair heterocycle in 1 is flexible and two stereoisomers of 1 (1a and 1b) with axial and equatorial substituents in positions 2, 3 and 4 are in equilibrium.

In the present work we concentrated on the effect of the substituents in position 4.  A series of mono-4- (I) and di-4,4'-substituted (II) 2,6-dimethy-1,2,3,4-tetrahydroquinolines was synthesized:

Basicity (K_a) of both axial and equatorial isomers of compounds I and II was measured by potentiometric titration in methanol.  Results of there measurements were analysed using two-parameter Taft equation as follows:

                                       logK_a = logK_aº + ρ_axσ_ax + ρ_eqσ_eq,

where ρ is sensitivity coefficient and σ is inductive substituent constant, indexes ax and eq correspond to axial and equatorial substituent positions.

Analysis of the sensitivity coefficients obtained by this method revealed that:

1.  Substituent effect is transmitted via both the aliphatic three-carbon chain and the aromatic ring, the latter contributing ca. 75% of the transmission.

2.  Axial substituents in position 4 transmit their effect via the aromatic ring to a greater extent compared to eqatorial substituents in position 4.

3.  Substituent effect transmission viaa the three-carbon chain is not dependant on the position (axial or equatorial) of the 4-substituent.