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Synthesis of substituted 1,2,3,4-tetrahydroquinolines

Synthesis of substituted 1,2,3,4-tetrahydroquinolines
Synthesis of substituted 1,2,3,4-tetrahydroquinolines

This thesis generalises the earlier reported one pot synthesis of 1,2,3,4-tetrahydroquinoline derivatives formed in formal [4+ 2] cycloadditions of aromatic iminium ions, which behave as 2-azadiene equivalents, with electron rich alkenes including cyclopentadiene, styrenes and 3,4-dihydro-2H -pyran. The iminium ions, derived from a series of aromatic amines (aniline derivatives; 5-, 7- and 8-aminoquinolines; 5-aminoisoquinoline; 1,4-di and 1-aminoanthraquinones and 3,6-diaminoacridine) and aqueous formaldehyde with trifluoroacetic acid catalysis, led to a number of novel azaheterocycles each possessing a 1,2,3,4-tetrahydroquinoline nucleus, including three compounds possessing an 11-azasteroidal skeleton from reactions with cyclopentadiene.

3-Aminopyridine gave rise to [1,5]naphthyridine derivatives in an analogous fashion. Most reactions proceeded in good to excellent yields. The introduction includes a thorough review of the literature concerning related aromatic 2-azadienes, their reactions being viewed as examples of aza Diels-Alder cycloadditions.

Hence an overview of the aza Diels-Alder reaction as a ring-forming synthetic strategy is presented, focusing on applications to heterocyclic synthesis. Consideration is given to the mechanism of the reactions and a non-concerted mechanism is proposed, as evidenced by the isolation of intermediate γ-aminoalcohols (which can be cyclised to the 1,2,3,4-tetrahydroquinoline derivatives under the reaction conditions) and by the observation of side products including 1,3-oxazines, which arise from trapping of an intermediate carbocation.

Successful cyclisations of 3,6-diaminoacridine and o-phenylenediamine with cyclopentadiene and of 1,4-diaminoanthraquinone with styrene indicate the power of this approach for the easy and rapid synthesis of chiral diamines of potential importance in asymmetric synthesis. 2-Aminopyridine derivatives behaved instead as 1,3-diazadienes with cyclopentadiene and styrenes giving rise to pyrido[1,2-a]pyrimidine derivatives.

University of Southampton
Merriman, Glynn David
Merriman, Glynn David

Merriman, Glynn David (1993) Synthesis of substituted 1,2,3,4-tetrahydroquinolines. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This thesis generalises the earlier reported one pot synthesis of 1,2,3,4-tetrahydroquinoline derivatives formed in formal [4+ 2] cycloadditions of aromatic iminium ions, which behave as 2-azadiene equivalents, with electron rich alkenes including cyclopentadiene, styrenes and 3,4-dihydro-2H -pyran. The iminium ions, derived from a series of aromatic amines (aniline derivatives; 5-, 7- and 8-aminoquinolines; 5-aminoisoquinoline; 1,4-di and 1-aminoanthraquinones and 3,6-diaminoacridine) and aqueous formaldehyde with trifluoroacetic acid catalysis, led to a number of novel azaheterocycles each possessing a 1,2,3,4-tetrahydroquinoline nucleus, including three compounds possessing an 11-azasteroidal skeleton from reactions with cyclopentadiene.

3-Aminopyridine gave rise to [1,5]naphthyridine derivatives in an analogous fashion. Most reactions proceeded in good to excellent yields. The introduction includes a thorough review of the literature concerning related aromatic 2-azadienes, their reactions being viewed as examples of aza Diels-Alder cycloadditions.

Hence an overview of the aza Diels-Alder reaction as a ring-forming synthetic strategy is presented, focusing on applications to heterocyclic synthesis. Consideration is given to the mechanism of the reactions and a non-concerted mechanism is proposed, as evidenced by the isolation of intermediate γ-aminoalcohols (which can be cyclised to the 1,2,3,4-tetrahydroquinoline derivatives under the reaction conditions) and by the observation of side products including 1,3-oxazines, which arise from trapping of an intermediate carbocation.

Successful cyclisations of 3,6-diaminoacridine and o-phenylenediamine with cyclopentadiene and of 1,4-diaminoanthraquinone with styrene indicate the power of this approach for the easy and rapid synthesis of chiral diamines of potential importance in asymmetric synthesis. 2-Aminopyridine derivatives behaved instead as 1,3-diazadienes with cyclopentadiene and styrenes giving rise to pyrido[1,2-a]pyrimidine derivatives.

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Published date: 1993

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Local EPrints ID: 462415
URI: http://eprints.soton.ac.uk/id/eprint/462415
PURE UUID: 659ce114-7c59-47a9-8176-e52a8292e3ed

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Date deposited: 04 Jul 2022 19:07
Last modified: 04 Jul 2022 19:07

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Author: Glynn David Merriman

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