Halogenation of Complex Compounds to enable Drug Diversification and Novel Small Molecules

Web Published:

Princeton Docket # 10-2624/2706-1

At the present time there are few, if any, ways to incorporate halogen atoms selectively into complex compounds. Halogenated organic compounds play a central role in organic chemistry, affording important components of a variety of biologically active molecules as well as pharmacologically active reagents. Alkyl chlorides also find widespread use as intermediates in organic synthesis, as in cross coupling reactions.

Based on research and expertise in metalloporphyrin chemistry, researchers in the Department of Chemistry, Princeton University have discovered a novel method for using metalloporphyrins as effective catalysts for the incorporation of halogen atoms such as chlorine, bromine and fluorine into a wide variety of compounds. Utilizing inexpensive sodium hypochlorite as the chlorine source, a manganese porphyrin mediated chemoselective and regioselective chlorination reaction has been developed to achieve such halogenations. The development of metalloporphyrin ¿catalyzed incorporation of halogen into unactivated hydrocarbons could provide a significant new avenue for late stage drug diversification. Further the realization of such a process could provide insight into the mechanism of halogenations enzymes such as chloroperoxidase, a heme containing chlorinating enzyme and Syr3, a non-heme Fe(II) α ¿ketoglutarate-dependent halogenase.


- Clean, fast, and inexpensive

- Easily scaled to commercial use


- Drug diversification

- Novel, small molecule generation

- Generation of biologically active molecules


Liu,W.; Groves, J.T. ¿ Manganese Prophyrins Catalyze Selective C-H Bond Halogenations¿, J. Am Chem. Soc., 2010, 132, 12847-12849.

Intellectual Property & Development Status

The reference cited above describes several examples of using a manganese porphyrin mediated aliphatic C-H bond chlorination using sodium hypochlorite as the chlorine source, to produce alkyl chlorides as the major products with only trace amounts of oxygenation products. Substrates with strong C-H bonds, such as neopentane can also be chlorinated with moderate yield. Chlorination of a diagnostic substrate, norcarene afforded rearranged products indicating a long-lived carbon radical intermediate. Moreover, regioselective chlorination was achieved by using a hindered catalyst. Patent protection is pending.

The Inventor

Professor John T Groves, Professor of Chemistry

Professor Groves major thrust of research is at the interface of organic, inorganic, and biological chemistry. Many biochemical transformations as well as important synthetic and industrial processes are catalyzed by metals. Current efforts focus on the design of new, biomimetic catalysts and the molecular mechanisms of these processes, the design and assembly of large scale membrane-protein-small molecule constructs, studies of host-pathogen interactions related to iron acquisition by small molecule siderophores and molecular probes of the role of peroxynitrite in biological systems. Professor Groves is the recipient of many accolades, including recent awards of the 2010 Hans Fischer Career Award in Prophyrin Chemistry and the 2010 Remsen Award. He also was one of two people selected to receive the 2008 Grand Prix de la Fondation de la Maison de la Chimie, for his work with cytochrome P450 enzymes and model metalloporphyrin catalysts.


Laurie Tzodikov

Princeton University Office of Technology Licensing ¿ (609) 258-7256¿ tzodikov@princeton.edu

PU #10-2624

Patent Information:
For Information, Contact:
Prabhpreet Gill
Licensing Associate
Princeton University
John (Jay) Groves
Wei Liu
drug discovery
platform technology
small molecule