Development of a Scalable and Sublimation-Free Route to MTAD

Zohaib R. Siddiqi, Chad N. Ungarean, Tanner W. Bingham, David Sarlah

Research output: Contribution to journalArticlepeer-review

Abstract

The cyclic azodicarbonyl 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) is a versatile and powerful reagent used mainly in cycloaddition chemistry. Though known for more than 50 years, its unsafe preparation, as well as purification by sublimation, hampered its widespread applicability on a larger scale. Herein we report a scalable and safe route to MTAD, which avoids the generation of methyl isocyanate. Moreover, we demonstrate that sublimation can be circumvented by the application of judicious oxidation conditions, followed by simple filtration. Overall, up to 25 g of MTAD was prepared in a single batch from commercial starting materials in three steps, with recrystallization serving as the only purification in the sequence. When employed in dearomative methodologies, the MTAD obtained by this protocol displayed synthetic efficiency equivalent to that of MTAD purified by sublimation.

Original languageEnglish (US)
Pages (from-to)2953-2959
Number of pages7
JournalOrganic Process Research and Development
Volume24
Issue number12
DOIs
StatePublished - Dec 18 2020

Keywords

  • 1,2,4-triazoline-3,5-dione
  • arenophile
  • dienophile
  • MTAD
  • urazole

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Development of a Scalable and Sublimation-Free Route to MTAD'. Together they form a unique fingerprint.

Cite this