PTC Tip of the Month, PTC Training PT Catalyst of the Month, PTC Reaction of the Month,
of the Month - When
to Use PTC For Route Selection
PTC is most often considered during development when trying to achieve the highest reaction performance after the identity of the target reaction has been set in stone (sometimes even after many years of commercial production). However, do not overlook the crucial importance PTC can play during route selection. We are aware of one case in which a key step in a pharmaceutical sequence suffered from a 35% yield loss due to a competing reaction and resulted in a non-competitive route. We are confident in this case that the selectivity and isolated yield could have been improved to > 90% during route selection, if highly specialized expertise in PTC would have been applied to this reaction just at the right time during development. You all know how crucial decisions can be for the long term impact of a project when the decisions are made during route selection. You will do yourself a great favor by properly considering PTC during route selection when any of the following challenges are encountered: need higher selectivity, need higher yield, need more acceptable solvent system, need to use less expensive/less hazardous strong base or need to reduce excess of an expensive reactant. Click here for list of > 30 PTC reaction categories.
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Top PTC Resources
Training - Save
$100 with early registration by March 1
The 2-day course "Practical Phase-Transfer Catalysis" will be conducted in the US in May 2004. Click here for agenda. Click here for registration or contact us by E-mail, website, telephone (+1 856-222-1146) or fax (+1 856-222-1124).
May 3-4, 2004 - Mt. Laurel, New Jersey (near PTC Organics) Early registration - save $100
May 2004 - Midland, Michigan
date to be announced - for details call +1 856-222-1146
Anytime - private in-house course (optional Opportunity Identification Session under secrecy agreement)
Catalyst of the Month - Tetraphenyl
High thermal stability in a variety of PTC applications...it is not readily susceptible to classic quat decomposition pathways such as Hofmann elimination, nucleophilic substitution or phosphine oxide decomposition.
Expensive; not soluble in all organic solvents
Reactivity Parameters (Contact PTC Organics for explanation)
C# = 24, note: phenyl groups are not as organophilic as hexyl groups, however
phosphorous imparts higher organophilicity than nitrogen; Accessibility q-value =
Availability, Samples and Quotes from Competitors
Request samples and quotes from: Dishman Pharmaceuticals & Chemicals (click on link)
PTC Reaction of the Month - Selective
Deprotection of Alcohols
Professor Crouch of Dickinson College has published interesting papers describing using PTC to achieve selective deprotection of alcohols by desilylation and deacetylation. A number of primary and secondary esters were hydrolyzed using powdered NaOH in THF at r.t. in isolated yields mostly in the range of 75-95% for aliphatic alcohols. High yields for deprotection of O-acetylated phenols require inert atmosphere (argon). Alkyl silyl ethers are stable under the PTC/NaOH conditions which deprotect acetyl ethers. Aryl silyl ethers are deprotected under the same conditions. Crouch, R.; Burger, J.; Zietek, K.; Cadwallader, A.; Bedison, J.; Smielewska, M.; Synlett, 2003, 991
Production Costs Too High?
Increase Yield: Could a 5-10% yield increase significantly increase profit (e.g., is your current yield < 88%)?
Reduce Cycle Time: Does your current process take > 8 hours? Want to eliminate isolation of intermediates?
Replace Strong Base with NaOH: Are you using alkoxides (e.g., methylate, t-butoxide), Na hydride, Na amide?
Improve Selectivity: Do you need to improve product assay or simplify workup? Too much hydrolysis?
Reduce Excess Reactants: Are you using > 10% excess of any expensive and/or hazardous reactant?
Replace Solvent for Easier Workup: Are you using DMSO, NMP, DMF, DMAC or undesirable solvent?
Increase Reactor Volume Efficiency: Does solvent and/or water take up > 50% of your reactor volume?
Other Challenges: Competing with China and India? Too much waste? Working with water-sensitive compounds?
If you answered "Yes" to even one question above and your reaction type is one of 35 on the PTC Reaction list, then Phase-Transfer Catalysis may help you achieve BREAKTHROUGH process improvement and improve profit margin and competitiveness.
INQUIRY: Contact Marc Halpern at PTC Organics by E-mail, website, telephone (+1 856-222-1146) or fax (+1 856-222-1124) to inquire about using PTC to improve process performance. As the world leader in industrial phase-transfer catalysis, PTC Organics offers PTC Breakthrough Process Screening for rapid and highly effective evaluation of breakthrough high-performance low-cost phase-transfer catalysis processes.
- Meet PTC Organics
Informex 2004 - January 19-22, 2004 in Las Vegas, Nevada, USA. PTC Organics booth # will be 2206.
2-Day PTC Course - public PTC courses in May 2004. Register early and save $100.
PTC Organics is a member of SOCMA
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performing any PTC reactions read this important message
Organic chemical reactions are inherently dangerous. Moreover, phase-transfer catalysis may provide rate and other enhancements which can intensify associated hazards. Under no circumstances should anyone perform any procedure on any scale based in whole or in part on any of the contents of this information provided here before thoroughly establishing safe operating procedures and performing a full and competent hazardous operations analysis with the participation of qualified technical personal trained in chemical, engineering, safety, industrial hygiene and environmental disciplines and sciences.
The list of PTC Tip of the Month subscribers will not be sold, rented or transferred and will be used only by PTC Communications, Inc. and PTC Organics, Inc. to provide information related to Phase-Transfer Catalysis. PTC Communications, Inc. reserves the right to distribute the PTC Tip of the Month to selected industrial chemists, engineers and managers.
PTC Tip of the Month #16 - January 2004
Copyright 2004 PTC Communications, Inc.
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