As today is the last day of the decade of the 2010’s, it is interesting to reflect on changes we have seen over the past few decades in PTC process development. We would like to share here some general conclusions about trends we found in the segmentation of the PTC process development market, though we will not disclose proprietary details about our customer base. We will also share historical perspectives about PTC technology development in industry and academia.

The following discussion is based on qualitative observations as well as an analysis of internal data at PTC Organics regarding the segmentation of phase-transfer catalysis process technology development customers. We looked at the industries and the geographical location of our customers’ process development headquarters.

First, we have a qualitative idea of shifts in the market segments and location of PTC process development efforts that we observed by our market presence as the leader in PTC process development in the past quarter century. Personally, I have been a full-time industrial phase-transfer catalysis entrepreneur with PTC Organics Inc. (and its predecessor PTC Communications Inc.) since 1995 and I have seen structural changes in the organic chemical industry like many of you have seen. With PTC Organics Inc. (and previously PTC Communications Inc.), I have attended and/or exhibited at tradeshows such as Informex, CPhI and Chemspec in each of the past 25 years and I have witnessed the shifts in industrial organic chemical activity on a qualitative basis. In addition, we analyzed the sales of PTC Organics’ over the past 20 years since companies that actively develop PTC technology turn to PTC Organics Inc. to address their most challenging phase-transfer catalysis projects to achieve lower cost higher performance green chemistry. When companies invest real money in PTC technology development, that shows commitment to the technology.

Early Days of Phase-Transfer Catalysis

When I first entered phase-transfer catalysis in 1976, five years after Charles Starks’ classic paper in which he coined the term phase-transfer catalysis, the majority of the breakthrough work in PTC was published by researchers in the US and Europe, mostly by academics, though Starks was an industrial chemist himself and there were already industrial PTC processes in Europe.

The manufacture of tetrabutylammonium bromide (TBAB) started when DuPont had a commercial PTC process that needed TBAB and they turned to surfactant-quat producer, Hexcel in Zeeland, Michigan, to produce TBAB. Sachem (in Texas) were making high purity quats for a variety of applications (including tetramethyl ammonium hydroxide for the new semiconductor industry). In the early 1980’s, Sachem and Zeeland Chemicals were the main ammonium quat producers in the US for small quats with up to about 20 carbon atoms and Henkel and Witco were the producers of Aliquat ® 336 and Adogen ® 464 with an average of 27 carbon atoms. Cytec (Canada) made aliphatic quaternary phosphonium salts and still do. Parish Chemical was the first commercial producer of 18-crown-6 and dibenzo-18-croen-6 in the US. In Europe, Dynamit Nobel was the main producer of TBAB and related quats in the early days and Rhone Poulenc produced TDA-1 which was an excellent complexant phase-transfer catalyst. In 1988, Dishman in India became a major producer of quaternary ammonium phase-transfer catalysts and grew their business significantly over the next decade by aggressive marketing.

By the time I completed my Ph.D. work in phase-transfer catalyzed hydroxide ion reactions in 1983, PTC technology development in academia had a strong presence in the US, Germany, Israel, Sweden, Italy, Poland and India. When I started presenting industrial PTC lectures around the world in 1995, PTC was thriving in the global chemical industry with many commercial applications growing in all industrialized countries, notably adding Switzerland, Japan, the UK, the Netherlands, Austria and Spain that enjoyed strong growth using PTC to manufacture products in a wide variety of industries. Though not well known publicly, there was much industrial PTC growth in Russia, as Dr. Felix Sirovski shared in the journal Phase-Transfer Catalysis Communications in 1997. Dr. Sirovski wrote that the robustness of PTC technology for a very wide range of commercial applications was an excellent match for the chemical plants in Russia that did not always enjoy investment in plant maintenance that was common in the West.

In 1987, Catalytica commissioned a study about the past, present and future of industrial phase-transfer catalysis and gathered the experts, Charles Starks of Vista Chemical (formerly of DuPont and Conoco), the inventor of PTC and the extraction mechanism; Charles Liotta of Georgia Tech and top notch award winning consultant at companies such as DuPont and Milliken; Dan Brunelle of General Electric, inventor of many PTC patents for the manufacture of engineering thermoplastics and inventor of several thermally stable phase-transfer catalysts, Howard Alper of University of Ottawa who was the leader in transition-metal PTC technology and myself, Marc Halpern, then a process chemist at Dow Chemical that was already manufacturing hundreds of millions of dollars of polymers, agrochemicals and pharmaceuticals using phase-transfer catalysis. I authored the study sold by Catalytica that included a study of 125 PTC patents up to that point.

In 1994, Charles Starks, Charles Liotta and I published the authoritative 650-page book “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives.” A year later, I founded PTC Communications Inc. and in 1999, I founded PTC Organics Inc. and co-founded PTC Value Recovery Inc.

2000-2009

By the year 2000, I presented the lecture “Reducing Cost of Manufacture of Organic Chemicals Using Phase-Transfer Catalysis” at more than 100 industrial process R&D departments in North America, Europe and Asia. By the year 2000, it was clear that the penetration of phase-transfer catalysis reached every segment of the chemical industry, not just the classical pharmaceuticals and agrochemicals. A study on PTC published in 2019 by non-PTC experts still perceived (incorrectly) that pharma and agrochem were the major users of phase-transfer catalysts. PTC is a highly technical niche and it is hard for outsiders to understand the market by casual study.

In the first decade of the 2000’s, large industrial PTC processes were growing or newly commercialized for a wide variety of monomers, polymers, fragrances, solvent, petrochemical applications and environmental applications in addition to the classical pharma, agrochem and specialty/fine organic chemicals. During the decade of 2000-2009, the investment of chemical companies in PTC process development for non-pharma/non-agrochem products was 38% of the total.

In the decade of the 2000’s, Asia-Pacific countries (most notably Japan, India and China) had great growth in PTC applications in all industrial segments. One of the greatest breakthroughs in all of phase-transfer catalysis is the family of “Maruoka chiral phase-transfer catalysts” invented by Keiji Maruoka in Japan starting just before the year 2000 and grew in patented applications in the 2000’s.

2010-2019

In the decade ending today (Dec 31, 2019), PTC process development continued to grow in all industrial segments and in all geographies. In fact, PTC Organics had a great year in 2019 in terms of sales for process development and contract research in a surprisingly wide range of applications including petrochemicals, commodity chemicals and veterinary products.

In this decade, non-pharma/non-agrochem investment in PTC process development grew to 53% from 38% in the previous decade.

In this decade, investment in PTC process development was led by European companies, followed by Asia-Pacific. Investment in PTC process development in North America remains strong, but not as strong as in Europe and Asia-Pacific. This confirms the qualitative shifts we have seen at chemical industry tradeshows over the past 25 years.

There has been a great proliferation of manufacturers of phase-transfer catalysts in India and China in the past two decades. I visited a plant in China in 2007 that produced and had in inventory nearly 50 different quaternary ammonium and phosphonium phase-transfer catalysts (many specialty phosphonium salts are used in the manufacture of epoxy resins). These days, when we obtain quotations for quaternary ammonium salts, there are many sources for these compounds, though we often have to sort through who are the actual manufacturers and who are the distributors (visits to actual manufacturing facilities).

In 2019, I conducted my 56th 2-day course “Industrial Phase-Transfer Catalysis.” That will likely be the last public PTC course I will conduct though demand for the in-house PTC course remains solid as companies recognize that phase-transfer catalysis delivers low-cost high -performance green chemistry for a very wide variety of strong base reactions, nucleophilic substitutions, oxidations, reductions, acid-catalyzed reactions and other applications in almost every industry that produces organic chemicals and polymers.

I have enjoyed a fascinating 43.5 years in phase-transfer catalysis (so far!) providing PTC services on-site at nearly 300 process R&D departments in 39 countries. Amazingly, we are now involved in what may become the largest PTC process.

The growth of industrial phase-transfer catalysis continues. Make sure that your company is not left behind. Now contact Marc Halpern of PTC Organics to explore how your company can achieve low-cost high-performance green chemistry to improve your company’s profitability and process R&D efficiency.

Burdeniuc, J.; (EVONIK DEGUSSA) US Patent 10,472,459, 12-Nov-2019

Polyurethanes are formed by reacting isocyanates with polyols in the presence of catalysts and other additives (e.g., blowing agent for polyurethane foam). Amine catalysts are effective but they have the disadvantage of odor and emissions. Other catalysts include transition metals that can be expensive and toxic. The amine and transition metal catalysts can be replaced by an inexpensive alkali metal sulfite (produced by passing sulfur dioxide through an alkaline solution) that is not volatile. The challenge of bringing the inorganic sulfite anion into contact with the organic isocyanates and polyols is solved by using a quaternary ammonium phase-transfer catalyst.

The use of tetrabutylammonium chloride (TBAC) with potassium sulfite could be used to totally replace amine catalyst and transition metal catalyst. Under the same conditions cetyl trimethyl ammonium chloride did not work. Neither did the surfactant sodium dodecylbenzenesulfonate. This suggests that a true phase-transfer mechanism for the sulfite is at work, not just reducing interfacial tension to promote reaction at an interface.

Also tested was the use of a mixture of amine catalysts (including DABCO) typically used to produce polyurethane foam. The amount of amine catalyst could be reduced by 75% by using potassium sulfite with TBAC or the very inexpensive benzyl trimethyl ammonium chloride.

We speculate (without data; not mentioned in the patent) that the inventors used expensive TBAC rather than the much less expensive than TBAB due to the potential suppression of sulfite extraction by the bromide. Chloride typically enables 10 times more extraction of hydrophilic anions (such as sulfite) relative to bromide.

In 1989, I briefly served as a manager of isocyanate process research group at a major polyurethane company. One of the quality control methods used for making polyurethane foam was a “top of cup” rise test. The picture shows a typical test for rise of foam in a cup.

If your company wants to improve process performance for a reaction of any anion that is or may be reacted with an organic substrate, now contact Marc Halpern of PTC Organics to integrate highly specialized expertise in industrial phase-transfer catalysis with your commercial goals to achieve low-cost high-performance green chemistry.

Aliquat 336 (registered trademark of BASF) is a mixture of 4 quat salts, described at http://phasetransfer.com/WhatisAliquat336andAdogen464.pdf, of which 33% is methyl trioctyl ammonium chloride. Aliquat 336 has been reported to enhance the activity of palladium catalysts for Suzuki and other reactions, for more than 20 years.

The point of this PTC Tip of the Month is that if you are using a palladium catalyst for Suzuki coupling or other reactions, you should probably screen Aliquat 336 (after first making sure that the reaction can be done safely such as by running a DSC first to assure no uncontrollable exotherms) to determine if you can achieve advantage using this phase-transfer catalyst. Advantages may be in reaction performance such as control of molecular weight, advantageous reaction conditions, using a less expensive form of palladium (choice of ligands) or even using less of the expensive palladium catalyst.

To illustrate the use of Aliquat 336 in Pd catalyzed PTC reactions, following is a sampling of US Patents that have used the Aliquat 336-Pd combination over the past year.

US Patent 10,403,822 (Sep 2019): Synthesis of thienothiophene isoindigo-based polymer semiconductors
US Patent 10,392,395 (Aug 2019): Synthesis of 4,7-bis-(2-bromo-4-methylpyridin-6-yl)-2,1,3-benzothiadiazole
US Patent 10,364,316 (Jul 2019): Synthesis of 2,5-diphenyl p-xylene
US Patent 10,340,457 (Jul 2019): Synthesis of dithiopentalenes
US Patent 10,290,809 (May 2019): Synthesis of polymer between dithiofluorene and thiobenzimidazole and US Patent 10,059,796 (Aug 2018)
US Patent 10,276,799 (Apr 2019): Synthesis of Iridium phenyl-isoquinoline phenyl-triazole compounds
US Patent 10,273,329 (Apr 2019): Synthesis of carbazole-divinylbenzene copolymers
US Patent 10,199,577 (Feb 2019): Synthesis of triphenyl derivatives and US Patent 10,134,988 (Nov 2018)
US Patent 10,158,079 (Dec 2018): Synthesis of polymers of benzodithiophene
US Patent 10,005,886 (2018): Synthesis of dimethyl 2,2”,4,4”,6,6”-hexamethyl-p-terphenyl-3,3”-diester

If you want to achieve high-performance low-cost PTC processes with efficient utilization of constrained R&D resources, now contact Marc Halpern of PTC Organics to integrate the highly specialized expertise of PTC Organics in industrial phase-transfer catalysis with your company’s commercial goals.

A patent issued last week that describes a PTC-cyanide reaction to form a cyanohydrin and reminded us of a few common misconceptions that we have seen over the years that have resulted in nuisance plant operability problems in mild cases and cost companies tens of millions of dollars per year in lost yield in severe cases! We will teach how to overcome these three misconceptions in our 2-day course “Industrial Phase-Transfer Catalysis” to be conducted in Prague next month (now register here for public PTC course in Prague). We will highlight these issues in the free PTC webinar to be conducted later this week on September 11, 2019 (now register here for free PTC webinar on Sep 11, 2019).

The first myth believed by some is that it is necessary to dissolve all of the alkali metal cyanide salt in water in order to carry out a PTC-cyanide reaction. In 2001, we visited a plant to identify opportunities to improve the performance of several large volume processes that used PTC or should use PTC. One of the large scale processes used cyanide as an aqueous solution. We pointed out that there may be a cause-and-effect relationship between the long and costly reaction time and the use of too much water in the system that hydrates the cyanide anion and reduces its nucleophilicity. The plant operators explained that they needed to dissolve the cyanide in water to facilitate the reaction.

We then explained that a phase-transfer catalyst is able to extract the cyanide anion from the surface of solid NaCN or KCN if it has a thin film of saturated cyanide salt, called “the omega phase” (discovered by Prof. Charles Liotta), that can be formed and optimized using small amounts of water. When we optimize the amount of water, usually at relatively low levels and using solid-liquid PTC conditions, reactivity greatly increases and we can achieve an increase in plant capacity, of an EXISTING plant, without capital investment!

Be sure to register for the free PTC webinar that will be conducted on September 11, 2019, in which we will discuss the effect of hydration in PTC systems.

A second misconception is that cyanide can only act as a nucleophile.

In the late 1990’s we received a non-confidential inquiry from a company that was suffering from a 35% yield loss (!!!) in a process that produced several hundred tons per year of a secondary nitrile from a secondary alkyl halide. I spoke with the plant chemist and said that I speculate that the yield loss is due to the cyanide anion partially acting as a base in addition to its predominant activity as a nucleophile. He confirmed that indeed the major side reaction was dehydrohalogenation. I told him that the solution is very simple and that he should submit a request for a PTC Process Consulting Agreement to his management so we could work together and recover the wasted value of about 100 metric tons per year of product!

The company did not engage us and used the poor excuse that they were not very profitable and did not want to invest in consulting! I replied that they would be a lot more profitable if they produced an extra 100 tons per year with no additional cost. That is when we learned that the real reason for declining our offer was organizational resistance to change. That was my incentive to write the article “5 Reasons that Companies Miss Process Improvement and Profit Opportunities using Phase-Transfer Catalysis.”  Unfortunately, the content of the article is still true today and is waiting for a champion (maybe YOU?!) in each company to take the initiative to stop wasting money on inefficient processes. If you want to contact us, please use THIS form and not the outdated Email address shown in the article.

We learned that several years later, the company figured out how to reduce the dehydrohalogenation in the cyanide-halide displacement using phase-transfer catalysis. They literally wasted millions of dollars of lost profit (!!!) because they didn’t want to admit that the relatively inexpensive PTC Process Consulting could show them technology that their technical team did not know. Is your company wasting lost profit right now due to resistance to change?!

The third misperception is that cyanide reactions are best performed using polar solvents.

As we show on page 109 of our 2-day PTC course manual, the product literature of one of the DMSO producers writes “DMSO is the best solvent for reactions involving cyanide and azide nucleophiles”. On page 215 of our PTC course manual, we compare 8 crucial process performance parameters for using PTC versus using PTC for reactions such as cyanide and azide reactions.

As always, the bottom line is that expert choice of PTC process conditions for cyanide reactions, can result in millions of dollars of added profit, which also saves a lot of jobs (maybe even YOUR job). Now register for the 2-day PTC course in Prague to be held on October 15-16, 2019 or bring the 2-day PTC course in-house to your company site to save millions of dollars, euros, etc.

Phase-transfer catalysis excels in transferring and reacting all kinds of oxidizing agents including permanganate and dichromate. Permanganate has a very high affinity for quaternary ammonium cations that enhances the extractability of this anionic oxidant. The first publication that launched the field of PTC, authored by Charles Starks, explicitly cited the use of Aliquat 336 with potassium permanganate (taught on page 197 of our PTC course manual). Another of the earliest PTC publications in the 1970’s was entitled “Purple Benzene” to describe what happens when you mix a quaternary ammonium salt with potassium permanganate and benzene (yes…we used benzene as a solvent in the 70’s!).

We don’t often see patents recently that cite the use of PTC with permanganate, but this August 2019 patent shows the reaction in the diagram that oxidizes a geminal alkene to a ketone using bicarbonate for pH control. A full equivalent of tetrabutylammonium hydrogen sulfate was used instead of catalytic quantity and it is not clear why so much was chosen to be used by the inventors.

PTC-permanganate oxidation of alkenes can produce a variety of products including diols, aldehydes, ketones, carboxylic acids and hydroxy-ketones depending on [1] the structure of the substrate [2] the pH of the aqueous phase in liquid-liquid PTC-permanganate systems and [3] and whether using aqueous workup or dry workup for solid-liquid PTC-permanganate systems. For more details, contact Marc Halpern of PTC Organics to explore PTC consulting to achieve your company’s process development goals.

One challenge of the use of PTC-permanganate reactions for commercial applications is the formation of manganese dioxide precipitate that is difficult to filter as a finely divided solid.

A patent was issued this month that used tetrabutylammonium bromide as a bromide source that can be used to carefully control at will not only the initiation of the polymerization of propylene oxide or epichlorohydrin, but also control the ratio of repeating units to a cationic end group at only one side of the polymer. This is useful for preparing an effective dispersion of a nanocarbon material in an aqueous phase.

The inventors of the patent Hoang, T.; Ohta, K.; Hayano, S.; Tsunogae, Y.; (Zeon Corporation) US Patent 10,344,124, 09-Jul-2019, found that a nanocarbon material is more favorably and more stably dispersed in a polyether-based polymer that contains a cation on only one terminal side. Examples of such polyethers that contain a cation on one side are polypropylene oxide or polyepichlorohydrin that has an onium salt on one side that can be produced by reacting an amine or a nitrogen heterocycle with a polypropylene oxide or polyepichlorohydrin that has a bromide at only one end.

For this purpose, in one example the inventors polymerized propylene oxide in the presence of a carefully chosen amount of tetrabutylammonium bromide (TBAB) as an organic soluble bromide source (21.5:1 molar ratio of PO:TBAB), triethylaluminum as polymerization catalyst and toluene as the solvent at 0 C for 2 hours. When the reaction was complete, the inventors added isopropanol to terminate the reaction and obtain polypropylene oxide with an average of 20 PO units, having a bromomethyl group at the polymerization starting terminal and a hydroxyl group at the polymerization terminating terminal.

The polypropylene oxide with bromomethyl at one end and hydroxyl at the other end was quaternized with 1-methyl imidazole or butyl dimethyl amine.

In other examples, the inventors reduced the amount of TBAB which increased the number of PO repeating units to 50, 100 and 200 at will and by design, in order to test for the optimal chain length for the stable dispersion of the nanocarbon material.

While this application is not strictly phase-transfer catalysis, it does leverage the concept of controlling a reaction by using a phase-transfer agent to introduce an anion into a reaction phase in a specific well-controlled quantity to achieve desired performance targets.

In our 2-day PTC course, we show other examples of using TBAB to initiate nucleophilic reactions induced by bromide that star with ring opening. Now register for the public PTC course in Prague in October 2019 or bring the PTC course in-house to your company to improve your personal performance, your department’s performance and your company’s performance. The increased profit your company will achieve from low-cost high-performance green chemistry using phase-transfer catalysis, may save jobs, perhaps your job.

This PTC Tip of the Month has helped many of our customers save large amounts of money, mostly by reducing excess expensive and/or hazardous raw materials while maintaining high yield and high throughput. The diagram is taken from the group exercise on page 108 of the course manual of “Industrial Phase-Transfer Catalysis.”

This graph shows the disappearance of benzoyl chloride as a function of agitation speed (in a small lab reactor) for the reaction of aqueous sodium phenoxide with benzoyl chloride in the presence of tetrabutylammonium hydrogen sulfate.

At low rpm, this PTC reaction is transfer rate limited (“T-Reaction”). In the T-Reaction regime, more agitation increases mass transfer of the phenoxide from the aqueous phase into the organic phase and reactivity increases. At some point when increasing agitation efficiency, the rate of consumption of phenoxide in the organic phase by the intrinsic reaction is slower than the rate of phenoxide transfer. In other words, the rate determining step shifts from mass transfer (“T-Reaction”) to the intrinsic nucleophilic substitution in the organic phase (“I-Reaction”).

In the I-Reaction regime, further increase in agitation efficiency does NOT increase throughput since the rate determining step is not no longer limited by transfer.

The sharp increase in the disappearance of the benzoyl chloride at the right side of the graph represents non-catalyzed interfacial hydrolysis of the benzoyl chloride.

In other words, if you think that you must agitate 2 phases as much as possible and you have  water-sensitive reactant, all you are doing is causing you purchasing manager to waste money on more benzoyl chloride (in this case).

This exercise is taught in the 2-day PTC course to give you the ammunition to convince your engineers to reduce the agitation efficiency of your 2- or 3-phase PTC systems when you have water-sensitive reactants or products.

Now register for the 2-day course “Industrial Phase-Transfer Catalysis” in order to learn dozens of specialized PTC techniques, like this one, so you can improve your personal performance in process development and plant support. This rare public PTC course (most PTC courses are conducted in-house due to the obvious high value) will be conducted in Prague on October 15-16, 2019 and you can enjoy a 15% discount by registering and paying before June 30, 2019.

Still not sure if you want to attend? Examine the PTC course agenda and you will understand why this is such a powerful course that helps you improve profit performance and R&D efficiency!

This patent describes a high yield PTC C-alkylation performed under dilute liquid-liquid PTC conditions in a microreactor. A forced thin film microreactor (shown in the diagram at https://www.m-technique.co.jp/e/members/ulrea/kouzou.html) is different than many other microreactors.  In most microreactors used with phase-transfer catalysis, the two liquids (aqueous phase and organic phase) are fed into in a static channel. In contrast, in a forced thin film reactor, the two liquids (aqueous phase and organic phase) are fed into a narrowing channel in which part of the channel surface is static and the other part of the channel surface is rotating.

The advantage of the forced thin film microreactor is claimed to be scalability without having to add too many microreactors in series as is commonly done with static microreactors.

For reasons not explained, performance is better when the aqueous phase containing the phase-transfer catalyst and NaOH is agitated for 15 minutes in a “Clearmix preparation apparatus” before being contacted with the organic phase. This seems surprising since the aqueous phase is quite dilute and both the NaOH and TBAB should be dissolved homogeneously without much effort or time. However, the results speak for themselves.

When the aqueous phase is prepared with the Clearmix apparatus (Table 1: Examples 1, 6, 7), the yields are 88% to 97% whereas when the “aqueous solution, which was manually agitated, was used after it was visually confirmed that the reacting agent was dissolved” (Comparative Example 1), the yield was only 51%. In all of these cases, the microreactor in which the PTC reaction was performed was a forced thin film type operating at the same flow rates and same rotation speeds of the rotating surface.

This patent should be studied by those of you who are combining the powerful advantages of phase-transfer catalysis with the powerful advantages of microreactors.

As we teach in our 2-day course “Industrial Phase-Transfer Catalysis” hydration is often the #1 factor that determines the amount of profit generated by a commercial PTC processes. This Dow Corning patent by DePierro and Reisch that issued this month illustrates the high sensitivity of solid-liquid PTC processes to hydration in a narrow range of added water. It is very important to be aware of the sensitivity because too many development teams overlook this important impact on profit when they are not aware of this sensitivity and they either unnecessarily lose yield or experience high variability from batch to batch due to minor changes in moisture level of the solid reactant.

This sensitivity to hydration is sometimes so significant that we have even seen differences in yield, reaction rate, etc. of large scale commercial solid-liquid PTC reactions, between batches when the solid reactant was taken from the middle of a container versus the top of the container that was exposed more to atmospheric moisture.

You really need to be aware of the levels of all hydrogen-bonding species in solid-liquid PTC reactions.

In this case, solid potassium sorbate was reacted with chloropropyl trimethoxy silane (CPTMS) in the presence of 1.7 mole% tetrabutylammonium bromide phase-transfer catalyst, Isopar G as solvent and stabiliziers. The graph shows the yield of the esterified product and the filtration rate after the reaction (to separate KCl byproduct) at a constant level of 3300 ppm methanol. Again, we must be aware of the level of all hydrogen-bonding species.

The inventors were very smart to test the effect of water at various levels up to 0.35% to understand the dramatic impact on yield. The inventors did not report the effect of water on reaction rate though they did mention that the reaction rate varied between 5 hours and 10 hours depending on reaction conditions. “The time required to complete the reaction varied depending on methanol and water concentration as well as temperature.”

Again, we teach process chemists and plant support chemists how to squeeze more profit from commercial solid-liquid PTC processes in our 2-day PTC course or by conducting PTC Process Consulting and PTC Contract Research. Don’t let your company make less profit by hesitating to take our PTC training, PTC Process Consulting or PTC Contract Research. The return on investment when contracting for PTC Organics’ services is often thousands of percent.

Now contact Marc Halpern of PTC Organics to improve process performance and R&D efficiency. The job you save may be your own!

We need your help.

In the late 1970’s, I saw an abstract of a talk at a conference that claimed to use TDA-1 [Tris(3,6-dioxaheptyl)amine], a polyether, to complex with magnesium and improve a Grignard reaction. I never heard the presentation or saw any other reference to it. I let that abstract slip into the depths of my memory.

This month, a procedure was reported in the patent shown in the diagram that uses catalytic TBAB in this Grignard reaction. I am having a hard time speculating the role of the TBAB.

Our subscribers are more knowledgeable and more intelligent than I. I am asking your help to suggest explanations of why the inventors added TBAB to this reaction. I am assuming that is not something they would do if it worked without TBAB.

Please indicate whether we can or should publish your name and company when you submit your suggested explanations.

Now contact Marc Halpern of PTC Organics to help the PTC community understand this reaction.