A new strategy for solid phase synthesis of a secondary amide library using sulfonamide linker via radical traceless cleavage

Juntao Luo, Wenqiang Huang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A new strategy for solid phase synthesis of a secondary amide library using sulfonamide linker via radical traceless cleavage is reported. Polystyrylsulfonyl chloride (1) reacted with primary amines to afford polystyryl-supported N-alkyl sulfonamides (2), which were acylated with acid chlorides and followed by radical cleavage with TiCl4/Zn to afford secondary amides. It was interestingly found that the products released from acyl alkanesulfonamide resins are closely dependent on the substituents of benzene rings of alkyl or acyl groups on the resins. When the substituent on benzene ring of N-benzyl group of sulfonamides is an electron rich MeO-group, the products released from sulfonamide resins are dependent on the substitution position on benzene ring: para-MeO- to yield 1,2-bis (p-methoxylphenyl)ethane and N - p-methoxylbenzyl benzamide (30: 1); ortho-MeO- to give 1,2-bis (o-methoxylphenyl)ethane and N - o-methoxylbenzyl benzamide (1:15); and meta-MeO- only to release N - m-methoxylbenzyl benzamide. Neither N-benzoyl sulfonamide resins on benzene ring with electron-drawing para-O2N-, nor the one with electron-donating para-H2N- could release any amide product, while the N-benzoyl sulfonamide resins on benzene ring with para-acetamido group released para-acetamidobenzamides. The conjugation effect to stabilize the radical groups in the radical cleaving process was observed.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalMolecular Diversity
Volume6
Issue number1
DOIs
StatePublished - 2003
Externally publishedYes

Keywords

  • Acyl alkanesulfonamide resins
  • Radical traceless cleavage
  • Secondary amides
  • Solid phase organic synthesis

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry

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