A scalable, metal-, azide- and halogen-free method for the preparation of triazoles

Peter R. Clark; Glynn D.  Williams; Jerome F.  Hayes; Nicholas C. O. Tomkinson

doi:10.1002/anie.201915944

A scalable, metal-, azide- and halogen-free method for the preparation of triazoles

Peter R. Clark, Glynn D. Williams, Jerome F. Hayes, Nicholas C. O. Tomkinson

Pure And Applied Chemistry

Research output: Contribution to journal › Article

Abstract

A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

Original language	English
Pages (from-to)	6740-6744
Number of pages	5
Journal	Angewandte Chemie International Edition
Volume	59
Issue number	17
Early online date	15 Jan 2020
DOIs	https://doi.org/10.1002/anie.201915944
Publication status	Published - 20 Apr 2020

Keywords

1,2,3-triazole
azide-free
α-ketoacetals
amines
heterocycles

Access to Document

10.1002/anie.201915944

Embargoed Document

Clark-etal-ACIE-2020-A-scalable-metal-azide-and-halogen-free-method-for-the-preparation-of-triazoles
Accepted author manuscript, 780 KB
Embargo ends: 15/01/21

Fingerprint Dive into the research topics of 'A scalable, metal-, azide- and halogen-free method for the preparation of triazoles'. Together they form a unique fingerprint.

Profiles

Nick Tomkinson

nicholas.tomkinson@strath.ac.uk

Pure And Applied Chemistry - Professor

Person: Academic

Projects

1 Active

PP: Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation

Murphy, J. & Bell, J.

1/01/19 → 31/12/23

Project: Research

Cite this

Clark, P. R., Williams, G. D., Hayes, J. F., & Tomkinson, N. C. O. (2020). A scalable, metal-, azide- and halogen-free method for the preparation of triazoles. Angewandte Chemie International Edition, 59(17), 6740-6744. https://doi.org/10.1002/anie.201915944

@article{2be46a19dfb14ff3b95ae801748830cb,

title = "A scalable, metal-, azide- and halogen-free method for the preparation of triazoles",

abstract = "A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.",

keywords = "1,2,3-triazole, azide-free, α-ketoacetals, amines, heterocycles",

author = "Clark, {Peter R.} and Williams, {Glynn D.} and Hayes, {Jerome F.} and Tomkinson, {Nicholas C. O.}",

year = "2020",

month = "4",

day = "20",

doi = "10.1002/anie.201915944",

language = "English",

volume = "59",

pages = "6740--6744",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

number = "17",

}

TY - JOUR

T1 - A scalable, metal-, azide- and halogen-free method for the preparation of triazoles

AU - Clark, Peter R.

AU - Williams, Glynn D.

AU - Hayes, Jerome F.

AU - Tomkinson, Nicholas C. O.

PY - 2020/4/20

Y1 - 2020/4/20

N2 - A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

AB - A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

KW - 1,2,3-triazole

KW - azide-free

KW - α-ketoacetals

KW - amines

KW - heterocycles

U2 - 10.1002/anie.201915944

DO - 10.1002/anie.201915944

M3 - Article

VL - 59

SP - 6740

EP - 6744

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 17

ER -