Continuous Catalytic Oxidation in

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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
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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.
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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

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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.
Aldehydes from Alcohols
T2
Oxidation Catalyst 2
Amides from Aldehydes and Amines
O2
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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

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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

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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

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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