(328b) Mechanistic Details and Process Implications of Azide Mediated Conversion Route of Carboxylic Acid to Isocyanate | AIChE

(328b) Mechanistic Details and Process Implications of Azide Mediated Conversion Route of Carboxylic Acid to Isocyanate

Mechanistic Details and
Process Implications of Azide Mediated Conversion Route of Carboxylic Acid to
Isocyanate

Anuj A. Verma,
Herbert Ogutu, Yuanyuan Li, Ann M. Czyzewski, Su Yu, & Xiu C. Wang

Process Research
& Development, AbbVie Inc., North Chicago, IL

The conversion of a
carboxylic acid to an isocyanate via the Curtius rearrangement is a
commercially attractive route in the pharmaceutical and chemical industries.
Traditionally, the carboxylic acid is converted to acyl azide at 20°C by using
diphenyl phosphoryl azide (DPPA) as the azide source. The acyl azide is
subsequently heated to enable Curtius rearrangement to form isocyanate. A
safety concern is identified in handling a pot of acyl azide across scales of
operation and it is desired to minimize the inventory of that azide. Herein, we
describe a process which minimizes that inventory. The process synthesis was
accomplished by developing a generalized azide chemistry/reaction engineering
platform (attached to Curtius reactions) to critically evaluate and identify
optimal processes which are inherently safe at different scales of operation.
The platform involves a detailed mechanistic understanding of product formation
along-with impurity generation, and represents a step above traditional kinetic
modeling by elucidating optimal reagent selection rules in addition to traditional
reaction engineering solutions to reduce impurity generation and increase the
product formation rate.

AbbVie contributed to
the design, research, and interpretation of data, writing, reviewing, and
approving the publication.  Anuj A. Verma, Herbert Ogutu, Yuanyuan Li, Ann
M. Czyzewski, Su Yu, and Xiu C. Wang are AbbVie employees who worked on this
project.