Transcript No Slide Title

Continuous Catalytic Oxidation in
Pharmaceutical Processing
B. Frank Gupton
VCU
John Monnier
USC
Steve Fong
VCU
Center for Rational Catalyst Synthesis
Planning Grant Workshop
University of South Carolina, Columbia, SC
June 16, 2014
Project Title
Research Team: Frank Gupton, John Monnier…
Overview: Continuous Catalytic Oxidation in Pharmaceutical
Processing Applications
Technical Information: Coupling intelligent catalyst design with
continuous process capabilities will provide an effective platform for
the safe, selective and efficient oxidation of alcohols.
Industrial Relevance
The ability to carry out the selective oxidation of highly
functionalized molecules continues to be a major challenge in
pharmaceutical process development.
Issues:
Cost of Oxidizing Agents
Poor Atom Economy
Reaction Selectivity and Process Control
Product Purification
Extreme Reaction Conditions
Examples:
Swern Oxidation
Tempo Oxidation
Goals of the Proposal
Demonstrate the feasibility of flow reactor technology to carry out
these types reactions using heterogeneous oxidation catalysts and
O2 as an oxidant.
T1
Oxidation
Aldehydes from Alcohols
O2
Catalyst 1
T2
Oxidation
Amides from Aldehydes and Amines
Catalyst 2
O2
NH2R
T1
O2
Oxidation
T2
Oxidation
Catalyst 1
Catalyst 2
NH2R
Amides from Alcohols and Amines
Proposed Hypothesis
Coupling intelligent catalyst design with continuous process
capabilities will provide an effective platform for the safe, selective
and efficient oxidation of alcohols.
Why Flow Chemistry:
• Heat transfer
• Mixing
•Reproducibility
- Regulatory impact
- Operational inefficiencies
•Safety
-Short residence times
- Small reactor volumes
•Chemistry
- Kinetically controlled reactions
•Cost
- Capital
- Operational
Research Methods/ Techniques
 Preparation of bimetallic oxidation
catalysts by electroless deposition
- Group 1B metals paired with
Group VIII metals
Use continuous flow reactors to evaluate
oxidation catalysts
- Thales Nano X-Cube
Employ factorial design of experiments
to evaluate critical process parameters
- Reaction conditions
- Throughput
- Catalyst half life
Outcomes/ Deliverables

A continuous oxidation unit will be developed which will allow for
the evaluation of the chemical diversity of oxidation reactions with a
aromatic and aliphatic alcohols.
 Establishment of optimal operating parameter by factorial design of
experiments
 Evaluation of preferred bimetallic catalyst system for oxidation under
continuous operations
 Results will be used to refine our computational model
 Analytical methods will be developed to measure product quality in real time

Detailed kinetics for oxidation catalysts for catalyst optimization
 Obtain detailed kinetics of oxidation reactions
 Optimize catalyst synthesis methodology based on kinetic results
Impact

Demonstration of viability for continuous catalytic oxidation of
aromatic and aliphatic alcohols with oxygen as an oxidizing
agent
 Reduction to practice of safe, cost effective and sustainable method for
using oxygen as an oxidizing agent in organic synthesis

Optimization of bimetallic catalysts
 Enhanced reaction performance under continuous flow conditions
Duration of Project and Proposed Budget

Three Years

$60,000 Year 1
$60,000 Year 2