Dr. Daniel R. Henton
- 1979 – 2004
The Dow Chemical Company
Department: Pharmaceuticals Process Research
Description: Synthesis, process development, and scale-up of developmental and commercial pharmaceutical bulk substances and intermediates. Synthesis of kilogram quantities of air and water sensitive polyolefin and chiral hydrogenation catalysts. Experienced in solution phase peptide synthesis, synthesis of numerous heterocyclic compounds, and carbohydrate chemistry. Developed and implemented several enzymatic processes, used at a 30-100 gal scale for production of chiral intermediates. Supported multiple steps in a commercial plant manufacturing multi-ton quantities of bulk fexofenadine hydrochloride.
- 2004 – 2013
The Dow Chemical Company
Department: Core R&D (Engineering & Process Science)
Description: Synthesis of, process development for, and scale-up of pharmaceuticals, fine chemicals, and intermediates for use in surfactants, polyurethanes, and polymer additives. Led development effort to convert inexpensive sugars to useful furans. Conducted hydroformylation chemistry on a variety of substrates at a lab and pilot plant scale.
- Ph.D - The Ohio State University, 1979
- B.Sc. - University of Missouri - St. Louis, 1975
- Fexofenadine hydrochloride. Developed and optimized the last three steps of the seven step commercial process to prepare the active ingredient in Allegra at a lab scale. Teamed with an engineering staff, implemented the process in 1000 gal – 5000 gal reactors, going from lab scale to commercial production in less than nine months. Involved in all aspects of developing a CGMP process for production of a pharmaceutical, from writing the chemistry section of the NDA, reviewing and writing batch production records, to troubleshooting the process as it was implemented on a large scale. Later, provided support for all steps of the commercial process, helping to implement recycle and reprocessing procedures for solvents and many key intermediates.
- Conversion of sugars to furanics. Led development effort to define a process to convert simple sugars (glucose, fructose) to hydroxymethylfurfural (HMF) in a semi-batch/continuous manner. Parameters considered were sugar concentration, temperature, pressure, residence time (flow rate), materials of construction, use of a co-solvent, added salts, and acid concentration. Explored expedient synthesis options for the production of furan-2,5-dicarboxylic acid (FDA) from a variety of precursors at the laboratory scale. Production of useful quantities of FDA by alternative processes was accomplished in parallel to the development of the semi-batch process from fructose via the intermediacy of HMF. Developed HPLC procedures for monitoring the conversion of the sugars to HMF using an RI detector.
- Led effort to build NMR expertise. Initiated acquisition of a Bruker 300 MHz NMR spectrometer for our department, led site design and installation effort. Initiated and installed upgraded capabilities several times, moving to a multinuclear capability (Avance QNP console & probe). Implemented procedures and created 1D and 2D experiment templates to allow efficient use of the NMR in a multi-user (50+ users) environment. Responsible for NMR maintenance for >20 years.
- Operation of modern GC and HPLC equipment, using Agilent, Perkin Elmer, and EZChrom software.
- Have used a variety of HPLC detectors: variable wavelength UV-VIS, diode array, RI, and ELSD.
- Familiar with the use of IR, UV-VIS, and NMR spectrometers and data interpretation from them.
- Familiar with the operation and use of a polarimeter. Have built and used a potentiostat, run cyclic voltammetry experiments, and conducted both oxidative and reductive electrochemical syntheses.
- Proficient in the use of conventional glassware, distillation equipment, and high pressure equipment from Autoclave Engineers and Parr.
- Have helped install and have regularly used glove boxes from MBraun and Vacuum Atmosperes.
- American Chemical Society
- Organic Section, ACS
- Michigan Scientists Organization Award for “Excellence in Science” 2001
- Development Scientists Organization Award for “Excellence in Technical Development” (Cramer Award), 1997
- Eastman Kodak Research Fellowship, 1979
- American Institute of Chemists Gold Medal Award, 1975
- Henton, D. R.; Goralski, C. T., “Preparation of d,l-Glaucine 1.5 Phosphate from Papaverine Hydrochloride” Midwest Pharmaceutical Process Chemistry Consortium Meeting, 10/8/99
- Horgan, S. W.; Burkhouse, D. W.; Cregge, R. J.; Freund, D. W.; LeTourneau, M.; Margolin;A; Webster, M. E.; Henton, D. R.; Barton, K. P.; Clouse, R. C.; DesJardin, M. A.; Donaldson, R. E.; Fetner, N. J.; Goralski, C. T.; Heinrich, G. P.; Hoops, J. F.; Keaten, R. T.; McConnell, J. R.; Nitz, M. A.; and Stolz-Dunn, S. K, “Process Development in the Synthesis of the ACE Intermediate MDL 28,726” Organic Process Research and Development, 3(4), 241-247 (1999).
- Goralski, C. T.; Hasha, D. L.; Henton, D. R.; Peet, N. P., "Isoquinoline Alkaloids 3. Synthesis of the 6-Ethyl and 6-Butyl Analogs of D,L-6-Methyl-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-4h-dibenzo(de,g)quinoline 1.5 phosphate (D,L-Glaucine 1.5 Phosphate) Org. Process Res. Dev., 1(4), 273-279 (1997).
- Goralski, C. T.; Hasha, D. L.; Krauss, R. C.; Williams, B. M.; Henton, D. R., "Isoquinoline Alkaloids 2. Preparation of D,L-Glaucine 1.5 Phosphate from D,L-Laudanosoline Hydrobromide" Org. Process Res. Dev., 1(4), 273-279 (1997).
- Henton, D. R.; McCarty, F. J.; Tripp, S. I.; DeWitt, J. E.; “Process for Preparing Anhydrous and Hydrate of Antihistamine Piperidine Derivatives (Polymorphs and Pseudomorphs)”, PCT Int. Appl., 57 pp., CA 124:202030 (1996).
- Henton, D. R., “Method for Converting Aminoguanidine Bicarbonate to Aminoguanidine Hydrochloride” International Technology Disclosures, 9(8), #089101, p.2, Aug. 25, 1991.
- Goralski, C. T.; Krauss, R. C.; Williams, B. M.; Henton, D. R.; and Brown, D. T., "Isoquinoline Alkaloids 1. An Efficient Preparation of d,1-Laudanosoline Hydrobromide" Ind. Eng. Chem. Res., 28(2), 221-224 (1989).
- Henton, D. R.; Goralski, C. T.; Heeschen, J. P.; Nyquist, R. A.; Pfeiffer, C. D., "d,1-6a-13C-Glaucine 1.5 Phosphate," J. Labelled Compds. and Radiopharm., 27(3), 297-307 (1989).
- Henton, D. R.; McCreery, R. L.; Swenton, J. S., "Anodic Oxidation of 1,4-Dimethoxy Aromatic Compounds. A facile Route to Functionalized Quinone Bisketals," J. Org. Chem., 45, 369-378 (1980).
- Henton, D. R.; Chenard, B. L.; Swenton, J. S. "Anodic Oxidation as a General Route to Benzoquinone Bis- and Mono-acetals," J. Chem. Soc., Chem. Commun., 326-327 (1979).
- Henton, D. R.; Swenton, J. S. "The Formation of Functionalized Quinone Bisketals by Anodic Methoxylation of Substituted 1,4-Dimethoxy Aromatics" Abstracts, Eleventh Central Regional meeting of the ACS, Columbus, OH (May 7-9, 1979).
- Manning, M. J.; Henton, D. R.; Swenton, J. S. "Anodic Oxidation as a Synthetic Expedient to Naphthoquinone Mono- and Bis-ketals," Tetrahedron Letters, 1679-1682 (1977).
- Jonathan C. Evans, Christian T. Goralski, Daniel R. Henton, Cynthia L. Rand, Paul C. Vosejpka, Process for the preparation of Epsilon-1-amino-2-(fluoromethylene)-4-(p-fluorophenyl)butane and novel intermediate thereof. U.S. Patent number 5,679,854, issued Oct 21, 1997. (also EP0872465 A3, Dec. 22, 1999).
- Daniel R. Henton, Frederick J. McCarty, Susan I. Tripp, Jill E. DeWitt, Methods of treating allergic reactions using hydrated forms of antihistaminic piperidine derivatives. US Patent number 7,666,881, issued Feb 23, 2010.
- Michael A. Gonzalez, Daniel R. Henton, David C. Molzahn, Process for selective, partial, substantially solvent-free, oxidation of methane to methanol and/or a methanol derivative with a heterogeneous catalyst and sulfur trioxide. US Patent number 8,242,300 issued Aug 14, 2012.