Phase-Transfer Catalysis Overview
Saving $Millions$ in the Production of Organic Chemicals
Using Phase-Transfer Catalysis
Marc Halpern, Ph.D.
PTC Organics, Inc.
900 Briggs Road, Suite 145, Mt. Laurel, New Jersey 08054 USA
Scope, Benefits and Barriers of Commercial Phase-Transfer Catalysis Applications
Phase-Transfer Catalysis, "PTC," technology is used in the commercial manufacture of more than $10 billion per year of chemicals shown in Table 1.1 PTC technology is also used in pollution prevention, pollution treatment and the removal or destruction of impurities in waste and product streams. PTC technology is used in these applications, because it provides many compelling benefits, primarily related to reducing the cost of manufacture of organic chemicals and pollution prevention. The many significant and advantageous process performance achievements which are routinely realized by using PTC are shown in Step 1 of Table 2.2 With such a long list of highly desirable benefits achieved in commercial applications (usually multiple benefits are achieved in each application), it is no wonder that PTC technology is used in a wide variety of applications! Cost reduction and pollution prevention are the two most powerful driving forces in the chemical industry today, and they match precisely the strengths and benefits provided by Phase-Transfer Catalysis.
The scope of PTC technology is most appropriately addressed by considering the range of reactions to which PTC is applicable. The 1700 patents and 8000 publications on PTC fall into about 30 major reaction categories, most of which are shown in Step 2 of Table 2. This scope of application is extremely broad and is responsible for the commercial PTC applications found in the wide range of industries listed in Table 1.
Despite these great benefits and wide scope of application, many chemical companies are still NOT using PTC technology, mostly due to lack of awareness, lack of expertise, lack of applicability and/or organizational resistance to change (not-so-amusing anecdotes3,4). A detailed discussion of the five top reasons and excuses why companies miss great opportunities to improve profit and process performance using PTC, can be found in the PTC journal5 and also on the web at www.phasetransfer.com/missopty.htm and www.phasetransfer.com/excuse.htm.
Table 1: Commercial Chemical Production Benefiting from Phase-Transfer Catalysis
and a wide variety of other commodity, specialty and fine organic chemicals
Table 2: The 60-Second Phase-Transfer Catalysis Test2
Does your existing plant process or process in development meet any of the criteria in Steps 1 and 2?
STEP 1: mark all that apply
Desired Process Improvement
STEP 3: IF your new or existing process:
A full description of all of the benefits and opportunities to improve profit and process performance using PTC are described in Volume 2 Issue 16 of the journal "Phase-Transfer Catalysis Communications."
Phase-Transfer Catalysis is useful primarily for performing reaction between anions (and certain neutral molecules such as H2O2 and transition metal complexes such as RhCl3) and organic substrates. PTC is needed because many anions (in the form of their salts, such as NaCN) and neutral compounds are soluble in water and not in organic solvents, whereas the organic reactants are not usually soluble in water. The name phase-transfer catalysis does what it says...the catalyst acts as a shuttling agent by extracting the anion or neutral compound from the aqueous (or solid) phase into the organic reaction phase (or interfacial region) where the anion or neutral compound can freely react with the organic reactant already located in the organic phase. Reactivity is further enhanced, sometimes by orders of magnitude (!), because once the anion or neutral compound is in the organic phase, it has very little (if any) hydration or solvation associated with it, thereby greatly reducing the energy of activation. Since the catalyst is often a quaternary ammonium salt (e.g., tetrabutyl ammonium, [C4H9]4N+), also called the "quat" and symbolized by Q+, the ion pair Q+X- (X- being the anion to be reacted) is a much looser ion pair than say Na+X-. This looseness of the ion pair is a third key reason for enhanced reactivity, which will ultimately lead to increased productivity (reduced cycle time) in commercial processes. At the end of the reaction, an anionic leaving group is usually generated. This anionic leaving group is conveniently brought to the aqueous (or solid) phase by the shuttling catalyst, thus facilitating the separation of the waste material from the product. This mechanism is called the "extraction mechanism" of phase-transfer catalysis and is shown in Figure 1.7
Figure 1: The Extraction Mechanism (Starks, 1971)
The extraction mechanism easily accounts for the benefits of PTC which include: achieving high reactivity (reactants are in the same phase with less hydration in a loose ion pair); extreme flexibility in choosing or eliminating solvent (a properly chosen quaternary ammonium catalyst can extract almost any anion into almost any organic medium, including into the product or into one of the organic reactants resulting in a solvent-free process); reducing the excess of water-sensitive reactants (such as phosgene, benzoyl chloride, esters and dimethyl sulfate since they are protected in the bulk organic phase from the aqueous phase by interfacial tension); higher selectivity (lower energy of activation allows reduction of reaction temperature and time); the use of inexpensive and less hazardous bases (hydroxide is easily transferred and activated in nearly all organic solvents) and many other benefits.
There are hundreds of commercial applications of Phase-Transfer Catalysis and they were commercialized due to the competitive advantages which they truly provide. Following is a selection of applications which would offer clear commercial benefit. This is only a selection and is not intended to be comprehensive or even to represent the best commercial applications.
Continuous Dehydrohalogenation to Produce a Large Scale Monomer8
Productivity @ 16 tons/hr, yield @ 99.2% and NaOH usage @ only 0.8 mole % excess!
Outstanding Reduction of Excess Hazardous High Volume Raw Material9
Great improvement in safety and environmental by reducing
phosgene excess by 94%!
Thiolation (Methyl Mercaptan)10
High yield for > 40 triazines, reduced cycle time by eliminating unit operations;
no isolation of intermediates; achieved single solvent for 3 steps with low emissions.
High Yield Solvent-Free Hazardous Nucleophilic Displacement12
High yield, with no solvent; explosive reactant in small excess; scaled up.
Sulfur Removal from Diesel Fuel13
PTC is used in problem solving in real world applications. Legislation in the US and Europe reduced the permitted sulfur levels in diesel fuels by 84% during the past five years. PTC/H2O2 was used as part of a process to achieve excellent desulfurization of diesel oil. A key sulfur component of diesel oil is dibenzothiophene and was quantitatively oxidized using 0.5 wt% Aliquat‚ 336, 0.3 wt% phosphotungstic acid and 11% aq. H2O2 (6.4 wt% on a 100% basis) at 60oC. Since H2O2 is expensive, the PTC oxidative desulfurization (ODS) is preceded by hydrodesulfurization (HDS). HDS of gas oils to < 0.5wt% sulfur is difficult. Thus, sequential HDS followed by PTC ODS was used to achieve 0.005 wt% sulfur, which is an order of magnitude lower than US and European requirements.
Thioesterification for Lubricant14
Phase-transfer catalysis offers a variety of conceptual and practical advantages when performing carbonylations as described in reference.15 Among these advantages unique to PTC are the ability of quats to transfer the anionic forms of metal carbonyls to the organic phase, in which CO is about 10 times more soluble than in water, which further leads to less hydrolysis of CO to formate and esters to acids. For example, malonic esters can be made by PTC carbonylation of ethyl chloroacetate at 1 atm CO at 25oC in the presence of cobalt carbonyl.16 Ni(CN)2 was used for the PTC double carbonylation of alkynols, using PEG-400 as the phase-transfer catalyst, LaCl3 as an additional co-catalyst, toluene as the solvent, and 5.0 N NaOH as the optimum base concentration.17 Yields of ene-dicarboxylic acids were up to 97%. PTC carbonylation has also been used to convert alkyl halides to acids and esters, and aryl halides to aryl carboxylic acids.
High yield in short reaction time at room temperature;
inexpensive oxidizing agent/no transition metal with high selectivity (vs. over-oxidation)
Epoxidation21 & Chiral Epoxidation22
Yield increase of 19% vs previous DMSO process. 100% recycle of toluene solvent vs no recycle of DMSO with 40% less solvent taking up reactor space. 95% (!) less cyanide excess, 85% (!) less aqueous waste, 3 less workup unit operations and better controlled exotherm through agitation vs. stepwise cyanide addition
Eliminated very expensive hazardous organic strong base (LDA)
at very expensive very low temperature with 19% yield increase!
Multiple Michael addition to acrylates used for lubricants also reported
Chiral Alkylation25, 26
How to Identify Opportunities to Improve Profit and Process Performance Using PTC?
Take the 60-Second PTC Test! All you have to so is ask yourself, for every existing commercial process and every new process in development:  Do you want to achieve higher process performance according to ANY of the criteria shown in Step 1 of Table 2?  Is the reaction you are performing on the list in Step 2 of Table 2? If the answer is "yes" to BOTH questions, you should probably consider Phase-Transfer Catalysis for your process.
How to Actually Profit from Opportunities Using PTC?
You have two choices to realize profit by using PTC for commercial manufacturing processes:
Develop PTC processes in-house:
Specific departments in a handful of chemical companies have significant internal expertise in phase-transfer catalysis. These departments routinely consider PTC as a process option when developing new processes. When problems arise in existing non-PTC processes, these departments will often consider and implement retrofit of the existing process with PTC to achieve the desired high performance. The author is aware of only two cases (one of which was induced after training by the author) in which chemical companies established a temporary team to identify opportunities to increase profit and improve performance by incorporating PTC into existing processes and into processes in development. Both of these companies use PTC in multiple processes with great success.
Departments and chemical companies which have some, though limited, expertise in PTC can implement a cost effective PTC opportunity identification & evaluation program. PTC Organics, Inc. offers a "PTC Cost Savings Program," in which PTC Organics, Inc. conducts a review of selected company processes, under secrecy agreement, and identifies opportunities to increase profit and improve processes using PTC. The program usually begins internally within the company, by having a senior scientist or manager (who is familiar with a broad range of company processes for the manufacture of organic chemicals) apply the criteria of the 60-Second PTC Test (Table 2) to many commercial processes or processes in development. This stage usually requires an investment of up to an hour of time of the senior scientist or manager. Alternatively, PTC Organics, Inc. can perform the initial evaluation, though this requires greater disclosure (under secrecy agreement) of processes by the company seeking to achieve higher profit/performance. A senior manager in the company then approves which processes will be evaluated by PTC Organics, Inc. A Confidential Disclosure Agreement is executed. A joint review of the processes is conducted by personnel from both companies. PTC Organics, Inc. determines which processes have the highest probability of success and makes specific recommendations for process improvements. The companies agree on well-defined Criteria For Success upon which performance is measured. PTC Organics, Inc. performs process development in its Willingboro, NJ lab and PTC Organics works with your company to shepherd the advantageous PTC process from concept through development and scale up to commercialization. Mutual incentive for both companies is achieved by linking the compensation of PTC Organics, Inc. to performance or to a commercialization contingency.
Outsourcing PTC Development and/or Manufacture:
The trend toward increased outsourcing of manufacture is being applied to enjoying higher profit by outsourcing the development and manufacture of organic chemicals by Phase-Transfer Catalysis. PTC Organics, Inc. is the only company dedicated exclusively to developing high performance processes for the manufacture of organic chemicals using Phase-Transfer Catalysis technology, which is based on its leadership position in this technology. PTC Organics, Inc. has partnering arrangements with custom manufacturers in the US and Europe, whereby processes developed by PTC Organics can be transferred into commercial manufacture. Through these facilities, PTC Organics, Inc. provides organic chemicals and custom manufacturing at attractive prices and high quality.
Phase-Transfer Catalysis delivers high productivity, enhanced environmental performance, improved safety, better quality and increased plant operability in hundreds of commercial manufacturing processes for organic chemicals in dozens of reaction categories. The companies who use PTC do so because PTC provides high performance in real world applications, primarily in reducing cost of manufacture and pollution prevention. Enormous opportunity exists right now (!) to increase corporate profits and process performance by retrofitting existing non-PTC processes with PTC and by developing new processes using PTC. Companies can achieve higher performance using PTC by developing these processes and manufacturing in-house or by outsourcing the development and/or manufacture using PTC. Most companies are not even aware that they can gain short term benefit ("low hanging fruit") to long term benefit using PTC. As a result, much opportunity is being missed. Strategic alliances exist specifically for helping companies enhance performance by identifying, evaluating and commercializing opportunities using PTC. Is your company achieving all it can using Phase-Transfer Catalysis? Would you like to be a hero?
last modified 14-Jul-2001