Contents: PTC Tip of the Month, PTC Training PT Catalyst of the Month, PTC Reaction of the Month, Subscribe/Unsubscribe

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PTC Tip of the Month - Generics and PTC: A Perfect Fit & Strategic Opportunity

What is the #1 key to generic pharmaceuticals and agrochemicals? LOW COST! Phase-Transfer Catalysis provides low-cost and high-performance processes for thousands of reactions in 40 categories, almost all of which are extremely common in pharma and ag. Can PTC provide your company with a cost advantage, even in the US, Europe or Japan? YES. Although low cost is typically associated with low labor cost, even low labor cost can’t fully compensate for inefficient raw material usage and other process imperfections. Question: Do you think that a 95% yield using PTC and NaOH for a key intermediate produced in YOUR plant, could compete with an 80% yield using NaOMe without PTC for the same intermediate produced in China?  Reaction time may not be so important in China, but yield and raw material costs are!

Since 1998, NCE’s have drastically decreased in pharma (52 down to 17) and ag. Your company may have considered a strategic shift to generics - A RARE GROWTH MARKET – and then rejected generics due to low labor cost competition. You may want to reconsider, because regardless of your company’s status, PTC IS A PERFECT FIT FOR GENERICS, possibly providing the key competitive advantage. Generics require low cost organic chemical processes. PTC technology delivers low cost organic chemical processes. Any questions?

Please forward this PTC Tip of the Month to your colleagues and encourage them to subscribe

PTC Training - Save $100 with early registration by March 1

The 2-day course "Practical Phase-Transfer Catalysis" will be conducted in three locations in 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)

PT Catalyst of the Month - Benzyl Triethyl Ammonium Chloride ("BTEAC" or "TEBA")

Advantages
Inexpensive; high reactivity reported in many literature references by Makosza for PTC-NaOH applications; very easy catalyst separation by extraction into water. Also called "TEBA," this catalyst usually induces high enough reactivity for substrates with pKa 16-23 before decomposing. Historically, a popular catalyst in the 1960's and 1970's.
Disadvantages
Stability is quite low in the presence of strong base due to Hofmann elimination (3 susceptible ethyl groups) and stability is low in the presence of nucleophiles due to substitution of the benzyl group. In fact, you must be very aware of the possibility of forming benzylated impurities of your substrate. Very hygroscopic (makes a puddle in lab balances within ~ 30 seconds). Note: TEBA often works faster than it decomposes, so it may be OK.
Reactivity Parameters (Contact PTC Organics for explanation)

Organophilicity C# = 13; Accessibility q-value = 1.6; benzyl group behaves more like a butyl group for C# and q-value

Availability, Samples and Quotes from Competitors
Request samples and quotes from: Delta Finochem, Dishman Pharmaceuticals & Chemicals, Lion Akzo, Nehachem, SACHEM (click on link)

PTC Reaction of the Month - Answer to Etherification Challenge from October

Thank you to the readers who submitted the process improvements for the application below. You will receive your complimentary CD-ROM "The Best of Industrial Phase-Transfer Catalysis" shortly. The answers included (in order of importance): [1] do not purchase solid NaOMe, rather use a mixture of MeOH and NaOH to form NaOMe in-situ. The phase-transfer catalyst will selectively transfer and activate the methoxide over the hydroxide. [2] Use the minimum equivalents of in-situ methoxide (probably don't need 4 equiv). [3] Use less solvent, or no solvent if above b.p. of product or some excess MeOH as solvent. [4] Although catalyst loading is low, it was suggested to use a less expensive phase-transfer catalyst which is easier to separate from the product or possibly recycle (for cases with higher catalyst usage). 

Production Costs Too High? Competitive Market?

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. 

Conferences - 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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Before 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.

Policy
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 #15 - December 2003
Copyright 2003 PTC Communications, Inc.

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