Aromatic Allylation via Diazotization; Application in synthesis of heterocyclic compounds

Research output: ThesisDoctoral Thesis (compilation)

Abstract

A new method for allylation of aromatic systems has been developed. A number of arylamines were converted via diazotization to the corresponding allylaromatic compounds using tert-butyl nitrite and an excess of allylic bromides with complete regioselectivity. Electron-withdrawing groups, in the aromatic moiety, were necessary to obtain good yields. The convenient experimental procedure allowed the synthesis of allyl-3,5-dinitrobenzene at a large scale. In addition, a new allylation-bromocyclization reaction was demonstrated. This result initiated the development of a new method to obtain fused heterocycles via iodocyclization. A number of tetrazoles and imidazole derivatives were prepared in good to excellent yields. The cyclization of some of the substrates deviated from Baldwin’s cyclization rules i.e. exo-selectivity. The obtained fused heterocyclic compounds were useful substrates for further derivatization. Furthermore, a method to obtain fused tetrazole derivatives from allylic bromides, generated in the allylation reaction, was developed. This new tandem reaction comprises a cycloaddition between a nitrile and trimethylsilyl azide induced by dibutyltin oxide followed by a intramolecular N-alkylation. These heterocyclic derivatives, incorporating a exomethylene functionality, were used in the parallel synthesis of a small library of amines. The fused tetrazole derivatives have structural similarities with Bengamides, a group of natural products possessing interesting pharmacological properties. This motivated the development of an analogue of Bengamide A, based on a fused tetrazole derivative. Key-intermediates of the analogue have been prepared.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Centre for Analysis and Synthesis
Supervisors/Advisors
  • [unknown], [unknown], Supervisor, External person
Award date2003 Sep 5
Publisher
Print ISBNs91-628-5767-3
Publication statusPublished - 2003

Bibliographical note

Defence details

Date: 2003-09-05
Time: 10:30
Place: Kemicentrum sal B

External reviewer(s)

Name: Renaud, Philippe
Title: Prof.
Affiliation: [unknown]

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Article: This thesis is based on the following papers and appendices.

Article: List of papersPaper IEk F.; Axelsson O.; Wistrand L-G.; Frejd T.Aromatic Allylation via Diazotization: Metal-Free C-C Bond FormationJ. Org. Chem. 2002, 67, 6376-6381.Paper IIEk F.; Wistrand L-G.; Frejd T.Aromatic Allylation via Diazotization; Variation of the Allylic Moiety and a Short Route to a Benzazepine DerivativeJ. Org. Chem. 2003, 68, 1911-1918.

Article: Paper IIIEk F.; Wistrand L-G.; Frejd T.Synthesis of Fused Tetrazole- and Imidazole Derivatives via IodocyclizationTetrahedron 2003. In press.

Article: Paper IVEk F.; Manner S.; Wistrand L-G.; Frejd T.Synthesis of Fused Tetrazole Derivatives via a Tandem Cycloaddition and N-alkylation ReactionSubmitted.

Article: Appendices

Article: Appendix IExperimental part of the synthesis of 2-allyl-5-nitropyridine.Excerpt from patent; Ek, F.; Wistrand, L. G. Preparation of allylic aromatic compounds by reaction of aromatic amines with a nitrite and an allylic olefin. EP 1013636, 2000, p 11.

Article: Appendix IIExperimental part of the attempted synthesis of a Bengamide analogue.



The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)

Subject classification (UKÄ)

  • Organic Chemistry

Keywords

  • Bengamide analogue.
  • parallel synthesis
  • trimethylsilyl azide
  • cycloaddition
  • imidazole
  • fused tetrazole derivatives
  • iodocyclization
  • benzazepine
  • tert-butyl nitrite
  • allylic bromide
  • aromatic allylation
  • diazotization
  • Organic chemistry
  • Organisk kemi

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