Hexamethyl guanidinium chloride (HMG Cl) performed the best out of 19 phase-transfer catalysts, including thermally stable tetraphenyl phosphonium salts. This was for the high temperature fluoride chloride halex exchange shown in the diagram.

We usually see hexaethyl guanidinium chloride (HEG Cl) used for high temperature PTC reactions. HEG Cl was not reported at all in this patent. We speculate that the fluoride ion may act as a base and cause side reactions at the beta-hydrogen of the ethyl group of HEG Cl. Since HMG Cl has no beta-hydrogens, perhaps HMG Cl may be better for high-temperature fluoride-chloride halex reactions than HEG Cl.

If your company needs help in choosing the best phase-transfer catalyst to reduce cost and/or optimize performance of your commercial process, now contact Marc Halpern of PTC Organics to benefit from the most highly specialized expertise in industrial phase-transfer catalysis.

Quaternary ammonium molybdate salts have been used for epoxidation and other oxidations using hydrogen peroxide. US Patent 10,590,364 (17-Mar-2020 assigned to Vanderbilt Chemicals) describes quaternary ammonium molybdate salts that contain sulfur that are useful as additives in lubricants and greases for friction reduction, wear reduction, and/or extreme pressure performance. The composition of these salts is [R4N]2 [Mo2S8O2].

The procedure is laid out in the patent and involves reacting ammonium heptamolybdate, sulfur dissolved in aqueous ammonium sulfide for 16 hours then adding quat bromide dropwise or portionwise plus post-reaction time and workup.

The quat salts prepared, isolated and characterized include tetramethylammonium, tetraethylammonium, tetrabutylammonium, tetraoctyalammonium, hexadecyl trimethyl ammonium, methyl trioctylammonium and ditallow dimethyl ammonium.

If your company needs help to choose a phase-transfer catalysis for the development or optimization of a commercial PTC application, contact Marc Halpern of PTC Organics for highly specialized expertise in industrial phase-transfer catalysis.

Tetrabutylammonium salts are sometimes used as phase-transfer agents without being phase-transfer catalysts.

Several tetrabutylammonium oxo-sulfoxy carbamate salts were synthesized as described in a patent this month:  Abe, T.; Furuuchi, T.; Sakamaki, Y.; Inamura, S.; Morinaka, A.; (Meiji Seika Pharma) US Patent 10,556,905, 11-Feb-2020.

The tetrabutylammonium oxo-sulfoxy carbamate salts were prepared from tetrabutylammonium hydrogen sulfate which were then extracted into methylene chloride or ethyl acetate, then isolated and reacted further. Example 112 shows the synthesis of a complex tetrabutylammonium salt on a 0.1 mole scale.

There are many commercial quats that are used in the textile industry that may be low cost alternatives to the more classical quaternary ammonium phase-transfer catalysts. A quick search of such quat salts shows many quat containing 2-hydroxyethyl and 2-hydroxypropyl quats such as the one shown here.

These quat salts often have one or two 2-hydroxyalkyl groups, one methyl group or benzyl group and one or two vegetable oil based alkyl chains or derivatives.

The 2-hydroxyalkyl quats have been reported in the patent literature to be effective phase-transfer catalysts for certain PTC aldol condensations, borohydride reductions and dehydrohalogenations.

A variety of tetrabutylammonium salts with a heterocyclic anion (or other N-anions) as the counteranion, were used to as initiators for the anionic polymerization of butyl acrylate, methyl methacrylate and acrylonitrile in THF (in an old US Patent 5,494,983 cited in a patent that issued this month).

Yields of 95%-100% and dispersities in the range of 1.1 to 1.2 were obtained with TBA carbazolide. Higher dispersities (>1.6) were observed when using toluene and NMP as the solvent.

In comparison, the use of sodium carbazolide made from sodium hydride and carbazole in THF gave much lower yield (49%) of polybutyl acrylate and much broader molecular weight distribution (D = 3.8).

Cocoalkyl benzyl bis[beta-hydroxypropyl] ammonium chloride might not seem like a mainstream phase-transfer catalyst but it was reported for one of the largest commercial PTC processes in history, namely the dehydrochlorination of dichlorobutane to chloroprene, monomer for synthetic rubber. US Patent 4,418,232 describes the use of this phase-transfer catalyst at a level of 1,115 ppm in a continuous process that produce chloroprene in 99.2% yield with only 0.8 mole% NaOH. Example 2 in the patent describes a throughput of 16 tons per hour.

This patent is taught in great detail by Mac Halpern in the 2-day course “Industrial Phase-Transfer Catalysis.”

The composition of cocoalkyl is typically about C18 10%, C16 10-20%, C14 20-30%, C12 40-50%  and C10 10%.

Quaternary ammonium cations containing beta-hydroxypropyl and beta-hydroxyethyl groups are known to be used in PTC aldol condensation, PTC borohydride reduction and PTC dehydrohalogenation.

Merial is a company that specializes in veterinary compounds. This October 2019 patent describes the chiral addition of hydroxylamine to alkenes to form chiral isoxazolines. The inventors screened 16 chiral phase-transfer catalysts and they found that for this reaction, quinine derivatized with tribenzyloxybenzyl chloride provided higher enantiomeric excess (99.1% S) than other chiral quats, including trialkoxybenzyl quininium quats (89.0% S for triethoxybenzyl and 86.4% S for trimethoxybenzyl).

One of the poor performing chiral quats was anthracenylmethyl quininium chloride (only 62% S: 38% R). More importantly, when the chiral hydroxyl was capped with an allyl group, the product was racemic! These results are in contrast to other chiral PTC reactions in which anthracenylmethyl cinchona alkaloids work well and O-allyl chiral quats work well.

The procedure for preparing the chiral quat was described on a scale using 1.5 kg quinine. The quininium quat was prepared in toluene as the solvent at 60-65 deg C and 12 hours reaction time.

This patent illustrates the need to screen a variety of chiral quats to best match the specific 3 points of chiral recognition for each different substrate.

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.

Tetramethylammonium isobutyrate was synthesized in order to esterify the isobutyrate with an alkyl chloride in a solvent-free and water-free system, though the reaction was not catalytic in TMA salt.

TMA isobutyrate was easily synthesized by mixing isobutyric acid with exactly 1.0 equivalent tetramethylammonium hydroxide (25% aqueous), removing the water first by reduced pressure, then by azeotropic drying with toluene to form the quat salt as an amber liquid.

It is interesting to note that the reaction reported prior to the one that used TMA isobutyrate, was a PTC nucleophilic substitution between the methyl mercaptide anion and a chloroformate using 1 mole% tetrabutylammonium hydrogen sulfate. It used 15% aqueous sodium methyl mercaptide which has been used in many PTC-mercaptide reactions. PTC excels in performing reactions with water-sensitive chloroformates in the presence of water under well-chosen PTC conditions, that we teach in the 2-day course “Industrial Phase-Transfer Catalysis.”

We find it interesting that the inventors decided to make the quat isobutyrate salt to perform this reaction and not use more classical PTC conditions, especially since they demonstrated knowledge of high-performance PTC methodology in the preceding reaction.

If you want to learn more about choosing the optimal conditions for PTC esterifications, bring the 2-day course “Industrial Phase-Transfer Catalysis” in-house to your company site and benefit from MANY low-cos high-performance green chemistry processes using phase-transfer catalysis.

Methyl tributyl ammonium methyl sulfate, “MTBA MS” was reported this month in US Patent 10,370,767. It was used as a conducting salt in an electrochemical process for the reductive coupling of an aromatic vinyl compound (e.g., styrene)  and a carbonyl compound (e.g., acetone).

MTBA MS is presumably made by the reaction of tributylamine with dimethylsulfate with no waste, especially if there is no need to hydrolyze the methylsulfate to hydrogen sulfate. One may speculate that MTBA hydrogen sulfate would be a good phase-transfer catalyst for PTC T-reactions and would likely be less expensive than tetrabutylammonium hydrogen sulfate.

In the 2-day PTC course “Industrial Phase-Transfer Catalysis“, we teach why methyl tributyl ammonium salts delier high performance for PTC T-Reactions. Now register here for the rare public PTC course in Prague.

Adogen 464 is a registered trademark of Evonik and is essentially the same material as Aliquat 336 (registered trademark of BASF) which represents methyl tricaprylylammonium chloride. This material has an effective molecular weight of 432 g/mole since the “caprylyl” alkyl groups are a 2:1 molar mixture of octyl to decyl groups. As we teach in our 2-day PTC course, Adogen 464 has an effective C# of 27 and an effective q-value of 1.34.

The patent shown in the figure that issued this month used Adogen 464 for an etherification. Since Adogen 464 has an average of 27 carbon atoms, it distributes nearly exclusively into the toluene phase. This is important for workup. More hydrophilic quaternary ammonium phase-transfer catalysts, such as tetrabutylammonium, would distribute significantly into both the organic and aqueous phases. That affects aqueous waste treatment.

In this patent, tosylate was the leaving group. Tosylate is sometimes a catalyst poison in PTC systems. As we teach in our 2-day PTC course, in cases such as this one, tosylate does not bind irreversibly to the organophilic quat since it is competing for association with the anion of 7-hydroxy-4-(4-bromo-2-fluoroanilino)-6-methoxyquinazoline that contains many carbon atoms, more than tosylate.

If you want to learn how to choose a phase-transfer catalyst like an expert, now register for the public PTC course to be conducted in Prague in October 2019 or bring our highly valuable 2-day PTC course in-house to your company.