TY - JOUR
T1 - Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles
AU - Fletcher, James T.
AU - Hanson, Matthew D.
AU - Christensen, Joseph A.
AU - Villa, Eric M.
N1 - Funding Information:
This publication was made possible by grants from the National Institute for General Medical Science (NIGMS, 5P20GM103427), a component of the National Institutes of Health (NIH), and its contents are the sole responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. JAC acknowledges Creighton University’s Baumann Family Scholarship for financial support.
Publisher Copyright:
© 2018 Fletcher et al.
PY - 2018/8/10
Y1 - 2018/8/10
N2 - The 1-substituted-4-imino-1,2,3-triazole motif is an established component of coordination compounds and bioactive molecules, but depending on the substituent identity, it can be inherently unstable due to Dimroth rearrangements. This study examined parameters governing the ring-degenerate rearrangement reactions of 1-substituted-4-imino-1,2,3-triazoles, expanding on trends first observed by L’abbé et al. The efficiency of condensation between 4-formyltriazole and amine reactants as well as the propensity of imine products towards rearrangement was each strongly influenced by the substituent identity. It was observed that unsymmetrical condensation reactions conducted at 70 °C produced up to four imine products via a dynamic equilibrium of condensation, rearrangement and hydrolysis steps. Kinetic studies utilizing 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde with varying amines showed rearrangement rates sensitive to both steric and electronic factors. Such measurements were facilitated by a high throughput colorimetric assay to directly monitor the generation of a 4-nitroaniline byproduct.
AB - The 1-substituted-4-imino-1,2,3-triazole motif is an established component of coordination compounds and bioactive molecules, but depending on the substituent identity, it can be inherently unstable due to Dimroth rearrangements. This study examined parameters governing the ring-degenerate rearrangement reactions of 1-substituted-4-imino-1,2,3-triazoles, expanding on trends first observed by L’abbé et al. The efficiency of condensation between 4-formyltriazole and amine reactants as well as the propensity of imine products towards rearrangement was each strongly influenced by the substituent identity. It was observed that unsymmetrical condensation reactions conducted at 70 °C produced up to four imine products via a dynamic equilibrium of condensation, rearrangement and hydrolysis steps. Kinetic studies utilizing 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde with varying amines showed rearrangement rates sensitive to both steric and electronic factors. Such measurements were facilitated by a high throughput colorimetric assay to directly monitor the generation of a 4-nitroaniline byproduct.
UR - http://www.scopus.com/inward/record.url?scp=85052207557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052207557&partnerID=8YFLogxK
U2 - 10.3762/bjoc.14.184
DO - 10.3762/bjoc.14.184
M3 - Article
AN - SCOPUS:85052207557
VL - 14
SP - 2098
EP - 2105
JO - Beilstein Journal of Organic Chemistry
JF - Beilstein Journal of Organic Chemistry
SN - 1860-5397
ER -