B. Frank Gupton
VCU
John Monnier
USC
Steve Fong
VCU
Planning Grant Workshop
University of South Carolina, Columbia, SC
June 16, 2014

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.

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

Demonstrate the feasibility of flow reactor technology to carry out these types reactions using heterogeneous oxidation catalysts and
O
2 as an oxidant.
T
1
Oxidation
Aldehydes from Alcohols
O
2
Catalyst 1
O
2
T
2
O
2
NH
2
R
T
1 Oxidation
Catalyst 1
Oxidation
Catalyst 2
T
2
NH
2
R
Oxidation
Catalyst 2
Amides from Aldehydes and Amines
Amides from Alcohols and Amines

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


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

 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

 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
 Three Years
 $60,000 Year 1
$60,000 Year 2