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.

A patent was just issued to Ultraclean Fuel with Gordon Gargano and Marc Halpern as the inventors that describes the large scale desulfurization of fossil fuel hydrocarbons to produce “ultralow sulfur diesel” (ULSD) and other ultralow sulfur hydrocarbon products that contain less than 10 ppm sulfur. These outstanding results require the use of a carefully selected phase-transfer catalyst, a phosphotungstate co-catalyst and hydrogen peroxide to oxidize covalently bound sulfur to sulfones. The sulfones are removed from the hydrocarbon stream to produce high quality desulfurized product. The patent reference is Gargano, G.; Halpern, M.; (Ultraclean Fuel Pty Ltd) US Patent 10,214,697, 26-Feb-2019.

Process equipment is described (Figures 4-6) that can process 1,500 barrels per day of high sulphur hydrocarbon feed (63,000 gallons) with the potential for 15,000 barrels per day (630,000 gallons).

This patent is a follow up to US Patent 9,441,169 by Gargano and Halpern.

The impressive breakthrough results are as follows:

“Transmix/Diesel feed containing a total sulphur level of 271 ppm was successfully desulphurised to a total sulphur level of 0 ppm according to ASTM D5623 standards and from 334 ppm to 2 ppm according to ASTM D5453 standards.”

“Transmix Diesel Hydrocarbon containing a total sulphur level of 407 ppm was successfully desulphurized to a total sulphur level of 9.2 ppm.”

“Refinery Diesel Hydrocarbon containing a total sulphur level of 3996 ppm was successfully desulphurized to a total sulphur level of 10 ppm.”

“Natural Gas Condensate containing a total sulphur level of 432 ppm was successfully desulphurized to a total sulphur level of 4.8 ppm.”

“Jet Fuel containing a total sulphur level of 1518 ppm was successfully desulphurized to a total sulphur level of 9 ppm.”

This patent is a good example of achieving a major process breakthrough by integrating the highly specialized expertise of Marc Halpern of PTC Organics with the highly specialized expertise of a company in their primary field of focus. Your company should similarly consider achieving major breakthrough process technology to achieve best in class competitive advantage.

Now contact Marc Halpern of PTC Organics to inquire about collaboration to improve your company’s profit and achieve low-cost high-performance green chemistry.