sh.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Ring forming reactions of imines of 2-aminobenzaldehyde and related compounds
Södertörn University, Avdelning Naturvetenskap. Karolinska Institutet.
Södertörn University, Avdelning Naturvetenskap. Karolinska Institutet.
2003 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 1, no 2, 367-372 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 1, no 2, 367-372 p.
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:sh:diva-15590DOI: 10.1039/b209505jISI: 000181557300019PubMedID: 12929432ScopusID: 2-s2.0-0041317250OAI: oai:DiVA.org:sh-15590DiVA: diva2:504993
Available from: 2012-02-22 Created: 2012-02-21 Last updated: 2017-02-15Bibliographically approved
In thesis
1. Synthesis of heterocycles from anthranilic acid and its derivatives
Open this publication in new window or tab >>Synthesis of heterocycles from anthranilic acid and its derivatives
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Anthranilic acid (2-aminobenzoic acid, Aa) is the biochemical precursor to the amino acid tryptophan, as well as a catabolic product of tryptophan in animals. It is also integrated into many alkaloids isolated from plants. Aa is produced industrially for production of dyestuffs and pharmaceuticals. The dissertation gives a historical background and a short review on the reactivity of Aa. The synthesis of several types of nitrogen heterocycles from Aa is discussed. Treatment of anthranilonitrile (2-aminobenzonitrile, a derivative of Aa) with organomagnesium compounds gave deprotonation and addition to the nitrile triple bond to form amine-imine complexed dianions. Capture of these intermediate with acyl halides normally gave aromatic quinazolines, a type of heterocyclic compounds that is considered to be highly interesting as scaffolds for development of new drugs. When the acyl halide was a tertiary 2-haloacyl halide, the reaction instead gave 1,4-benzodiazepine-3-ones via rearrangement. These compounds are isomeric to the common benzodiazepine drugs (such as diazepam, Valium®) which are 1,4-benzodiazepine-2-ones. Capture of the dianions with aldehydes or ketones, led to 1,2-dihydroquinazolines. Unsubstituted imine anions could be formed by treatment of anthranilonitrile with diisobutylaluminium hydride. Also in this case capture with aldehydes gave 1,2-dihydroquinazolines. Several different dicarboxylic acid derivatives of Aa were treated with dehydrating reagents, and the resulting products were more or less complex 1,3-benzoxazinones, one of which required X-ray crystallography confirm its structure. During the work on preparation of N-substituted derivatives of Aa, necessary for synthesis of 1,4-benzodiazepine-3,5-diones, it was noted that many of the obtained products were in fact not N-substituted, but O-substituted. This challenged the established notion that Aa reacts nucleophilically at the N-terminal under most conditions. Several grave errors in the recent literature were revealed. In 1976 researchers from the group that originally developed the common benzodiazepine drugs published a retraction of a claim of synthesis of a benzodiazepine by Gärtner in 1904. They found that the method actually gave a 6-membered ring system, not a 7-membered 1,4-benzodiazepine-3,5-dione as originally claimed. Because the 1,4-benzodiazepine skeleton is highly interesting as a scaffold for development of new drugs, a few publications on synthesis of this target has appeared. However, repetition of several of the described syntheses failed to yield the poorly described products. Studies on how to ring close N-carbamoyl derivatives of Aa were undertaken. It became clear that Umpolung of the substrates by N-derivatisation was a necessary prerequisite for ring closure. The introduction of the N-nitroso group was developed to this end, leading to N1-nitroso substituted 1,4-benzodiazepine-3,5-diones. The nitroso group could be removed after ring closure. Heating of one of these compounds induced a ring contraction rearrangement. A proposed mechanism involves elimination of HNO (nitrosyl) and proton mediated loss of CO.

Place, publisher, year, edition, pages
Stockholm: Karolinska Instiutet, 2004. 47 p.
National Category
Organic Chemistry
Identifiers
urn:nbn:se:sh:diva-32065 (URN)91-7349-913-7 (ISBN)
Public defence
2004-05-28, Hörsalen, plan 4, NOVUM, Hälsovägen 7-9, Huddinge, 10:00 (English)
Opponent
Supervisors
Available from: 2017-02-15 Created: 2017-02-15 Last updated: 2017-02-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Wiklund, PerBergman, Jan
By organisation
Avdelning Naturvetenskap
In the same journal
Organic and biomolecular chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 35 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf