Continuous Catalytic Oxidation in Pharmaceutical Processing
B. Frank GuptonVCU
John Monnier
USC
Steve FongVCU
Center for Rational Catalyst SynthesisPlanning Grant Workshop
University of South Carolina, Columbia, SCJune 16, 2014
Project TitleResearch 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 RelevanceThe 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 AgentsPoor Atom EconomyReaction Selectivity and Process ControlProduct PurificationExtreme Reaction Conditions
Examples:Swern Oxidation
Tempo Oxidation
H
HHO
HOCOCl2, DMSO
Et3N, CH2Cl2-780C
H
HOHC
OHC
1.5 eq. TEMPO
MeCN, 7 hr.
OH O
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.
OH
O2
CHOOxidation
Catalyst 1
T1
Aldehydes from Alcohols
Amides from Aldehydes and Amines
OH
O2
Oxidation
Catalyst 1
Oxidation
Catalyst 2
NH2R
T1 T2
Amides from Alcohols and Amines
O NHR
NH2R
O2
CHO
O NHR
T2Oxidation
Catalyst 2
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
Duration of Project and Proposed BudgetDuration of Project and Proposed Budget
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