A patent application published three days ago (Yogendra, S. et al, Covestro, US Patent Application Publication 2024/0025753, 25-Jan-2024) describes what appears to be a practical setup to produce phosgene on a lab scale. This method might avoid the need to purchase and store hazardous phosgene in cylinders and might enable producing just enough phosgene needed for a specific use. This batchwise on-demand lab scale production of phosgene achieves the advantages of the large scale continuous on-demand industrial production of phosgene in the right quantity shortly before use with a short residence time to minimize storage and handling of excess hazardous phosgene. Large scale phosgene production uses porous activated carbon as the catalyst.
The concept in this patent application publication is to use a catalytic amount of a quaternary ammonium chloride, combine it with chlorine to form a quat polychloride and then react it with an excess of carbon monoxide. The reaction is performed at ambient temperature and near atmospheric pressure. This reaction may not be considered phase-transfer catalysis.
The inventors described two methods, one with solvent and one without solvent.
In one system, 3.5 mole% methyl triethyl ammonium chloride was used as the catalyst and chlorobenzene as the solvent. In this case, quantitative conversion of the chlorine to phosgene was achieved using a molar ratio of carbon monoxide to chlorine of 1.6.
In a second system, 40 mole% tetraethyl ammonium chloride was used as the catalyst without a solvent in a tubular reactor. In this case, a molar ratio of carbon monoxide to chlorine of 5.8 was used.
Dioctadecyl dimethyl ammonium triazolide was found to be an excellent ionic liquid for the capture of carbon dioxide used together with alcohols, especially 2-ethyl hexanol.
This system delivers several advantages that include effective absorption of carbon dioxide at attractive temperatures, effective desorption of carbon dioxide at practical temperatures and avoidance of volatile alcohols and amines used in other carbon dioxide absorption/desorption systems.
In this patent application published four days ago, four examples use 18-crown-6 to dietherify magnolol with allyl bromide derivatives. The yields are in the tight range of 82.4% to 86.2%.
The inventors used tetrabutylammonium bromide in DMF with allyl chloride in only one example and they obtained a yield of 77.1%. They performed the reaction at 100 deg C which might decompose the quat catalyst. The reaction with TBAB was run for 4 hours and they used the same weight of quat salt as they did crown ether in the other examples, but that was only 8.2 mole% TBAB.
We are surprised that the use of TBAB was an afterthought after using the much more expensive crown ether for this simple straightforward etherification.
These reactions were performed on an 80 gram scale. Why did the inventors choose to use crown ether instead of standard inexpensive PTC quat salts for these routine etherifications? We don’t know.
We are also surprised that water-miscible solvents were used for all five of these etherifications instead of using a non-polar water-immiscible solvent that would simplify workup by water washing instead of filtration and distilling off the solvent. This is especially surprising since the workup after the O-allylation and before the radical addition of thioacetic acetic in the next reaction step, included three water washes followed by extraction with trichloromethane. Wouldn’t it have been easier to use a water-immiscible non-polar solvent?
Had the inventors taken our 2-day course “Industrial Phase-Transfer Catalysis”, they would not have chosen 18-crown-6 as the phase-transfer catalyst and they would have chosen a much better solvent for workup. They didn’t benefit from the PTC course, but you should!
Four years ago, we highlighted a patent that used tetrabutylammonium acetate to capture carbon dioxide (see http://phasetransfercatalysis.com/ptc_catalyst/tetrabutylammonium-acetate-for-co2-capture/). This month a patent application was published (https://www.freepatentsonline.com/20230330624.pdf) entitled “Use Of Carboxylate Compound As Absorbent For Capturing Carbon Dioxide.”
Ideally, a quat carboxylate compound forms a “conjugate” with carbon dioxide that has appropriate hydrophilicity to be soluble in water at normal temperature, and can be precipitated from water after absorbing carbon dioxide. When the quat carboxylate compound forms the “conjugate” it should be stable to water after absorbing carbon dioxide.
This patent application publication published this month compares the effectiveness of the following quat salts: tributylhexyl phosphonium 2-ethylhexanoate, tetrabutyl phosphonium 2-ethylhexanoate, tributyloctyl phosphonium 2-ethylhexanoate, tributyldecadecyl phosphonium 2-ethylhexanoate, tributyldodecyl phosphonium 2-ethylhexanoate, tributyltetradecyl phosphonium 2-ethylhexanoate, tributylhexadecyl phosphonium 2-ethylhexanoate, tetrabutylammonium 2-ethylhexanoate, triethylbutylammonium 2-ethylhexanoate, tributylhexyl ammonium 2-ethylhexanoate, tributylhexyl phosphonium 2,2-dimethylbutyrate, tributylhexyl phosphonium 2-propylpentanoate, tributylhexyl phosphonium 2,2-dimethylhexanoate, tributylhexyl phosphonium 2-propylhexanoate, tributylhexyl phosphonium 2-ethylheptanoate, tributylhexyl phosphonium cyclohexyl formate and tributylhexyl phosphonium n-octanoate.
Carbon dioxide absorption with these quat salts ranged from about 10 mole% to 110 mole%. The highest performing quat salt was tributyloctyl phosphonium 2-ethylhexanoate.
The procedure was as follows: 2 mmol of quat salt and 40 mmol of water (0.72 g) were added in a glass bottle, a carbon dioxide balloon was connected to make the solution in carbon dioxide at one atmosphere. After stirring at 25° C. for 12 hours, the system was divided into an organic phase and an aqueous phase. The balloon was taken off and the gas carbon dioxide on the upper part of the solution in the bottle was replaced with air, then titrated with sodium hydroxide solution (0.2 w%), phenolphthalein was used as the indicator, and the carbon dioxide absorption amount was 2.2 mmol for tributyloctyl phosphonium 2-ethylhexanoate and 0.22 mmol for tributylhexyl phosphonium 2,2-dimethylbutyrate.
Acetate salts are used as catalysts to cyclize isocyanates into trimeric isocyanurates. Tetrabutylammonium acetate is sometimes used to facilitate the solubility of the acetate in the organic isocyanate, such as hexamethylene diisocyanate (HDI), for the cyclic trimerization reaction shown in the diagram. The tetrabutylammonium acetate is introduced as a 10% solution in 2-ethylhexanol.
The mechanism for the acetate-catalyzed isocyanuration reaction for aromatic isocyanates is described at https://www.sciencedirect.com/org/science/article/pii/S0022326321027389#f0015
We typically see the use of hexaalkyl guanidinium salts for high-temperature PTC applications performed a 120 deg C and higher. The reaction shown in the diagram was performed at 75 deg C and uses tetraethyl dibutyl guanidinium chloride (TEDBG Cl). Why?
Initially, the inventors used the classical tetrabutylammonium bromide (TBAB) for this S-alkylation and the reaction indeed did work with 91.5% monomer content after workup which degraded slightly to 90.7% monomer content after 3 months of storage. However, there was residual TBAB in the product that decomposed to result in 0.54% tributylamine in the product and that impurity constitutes a significant disadvantage.
In contrast, when the more stable tetraethyl dibutyl guanidinium chloride (TEDBG Cl) was used, there was obviously no residual tributylamine contaminating the product, bis(triethoxysilylpropyl)disulfide, and only 6 ppm residual TEDBG Cl was present in the product. The monomer content was 94.7% immediately after workup and degradation after 3 months of storage was minimal to 94.4% monomer in the product.
In our 2-day course “Industrial Phase-Transfer Catalysis,” we teach a session on separating the phase-transfer catalyst from the product and we show certain cases for minimizing waste while minimizing residual phase-transfer catalyst in the product.
The diagram shows an electrochemical process to form a useful dibenzocycloheptenone product. Several quaternary ammonium perchlorates were cited as electrolytes for this reaction. Tetraethyl ammonium perchlorate was used in several examples.
Sodium benzenesulfinate (PhSO2-Na+, not PhSO3- Na+ sulfonate) oxidizes at the anode to the benzensulfonate radical which in turn adds to the triple bond carbon alpha to the carbonyl to form an alkenyl radical that ring closes to form the seven membered ring in the product shown (dibenzocycloheptenone) after additional movement of electrons and loss of a proton.
It is interesting to note that the molar amount of the tetraethylammonium perchlorate is enough to oxidize the sulfinate to the sulfonate radical without the electrolytic cell, It makes one wonder if it would be worthwhile to try the oxidation with the quat perchlorate and see if the electrolytic setup is even necessary. For now, we assume that the quat ion pair is acting as an electrolyte in this system and not as an oxidizing reagent.
Tetrabutyl phosphonium chloride is used as a phase-transfer catalyst when working at temperatures at which the much less expensive tetrabutyl ammonium bromide is not stable, as long as no strong base is present (such as NaOH). These temperatures are often in the range of about 100 deg C to about 150 deg C, more often 100 deg C to 120 deg C.
PTC esterifications using alkyl halides (not benzyl halides) are often performed at temperatures in the range of 80 deg to 120 deg C, so tetraalkyl phosphonium quats are considered for these applications. When PTC applications are performed at higher temperatures at which tetraalkyl phosphonium quats are not stable due to decomposition by nucleophilic displacement, tetraaryl phosphonium quats (e.g., tetraphenyl phosphonium chloride) are often considered.
Tetraalkyl phosphonium quats such as tetrabutyl phosphonium are not at all stable in the presence of NaOH. PTC-NaOH conditions are used in the most common PTC applications. For these reasons, tetrabutyl phosphonium chloride has a rather narrow range of utility for non-NaOH PTC applications mostly performed at about 100 deg C to 120 deg C.
In the reaction shown in the diagram, tetrabutyl phosphonium was an appropriate choice. In another example described in this publication, the inventors performed an esterification of methacrylic acid at lower temperature (80 deg to 90 deg C) using a more reactive alkylating agent and they successfully used tetrabutyl ammonium bromide for that lower temperature esterification.
Another interesting and very important detail is that PTC is often used in reactions of water-sensitive compounds and that includes alkoxysilanes. In these cases, careful attention is paid to the water content. In this publication the potassium methacrylate salt was dried by azeotropic distillation before adding the water-sensitive 3-chloropropyldimethylethoxysilane reactant.
PTC Organics has helped companies develop and patent PTC applications using water-sensitive reactants and products, including alkoxysilanes. See for example: http://phasetransfercatalysis.com/ptc_tip/important-effect-of-water-on-profit-in-solid-liquid-ptc-esterification/.
Now contact Marc Halpern of PTC Organics when you need to achieve low-cost high-performance green chemistry for water-sensitive applications.
Tetrabutylammonium bromide (TBAB) is produced commercially in high yield by the straightforward reaction of tributylamine and butyl bromide when performed in the right solvent. From time to time, users of quaternary ammonium phase-transfer catalysts consider producing the quat salts themselves since the quaternization of the trialkylamine with an alkyl bromide or chloride is usually simple and reliable.
The challenge is obtaining the trialkylamine because not many producers are willing or have the capability to produce the trialkylamine that usually uses a toxic nickel catalyst. In the case of tributylamine, n-butyl alcohol and ammonia can react under the action of a catalyst to prepare tri-n-butylamine. According to the inventors of the patent CN116023269A (Shandong Tongcheng Medicine Co Ltd), the product of the method to produce tributylamine contains n-butylamine, di-n-butylamine and tri-n-butylamine, and the selectivity of the tri-n-butylamine is not as good as desired. If n-butyraldehyde and di-n-butylamine are adopted to react to generate enamine, and then reductive amination is carried out to obtain tri-n-butylamine, the problem of low selectivity of the tri-n-butylamine can be avoided, and the obtained product tri-n-butylamine has high yield and high purity.
The reductive amination is still not trivial to perform because it uses nickel tetracarbonyl as the catalyst, and hydrogen at 20-25 ATM (2.0-2.5 MPa). The solvent is toluene. The yield and selectivity are very good.
The abstract of the patent is as follows: “The invention discloses a synthesis method of tetrabutylammonium bromide, which takes n-butyraldehyde, di-n-butylamine and n-bromobutane as raw materials, hydrogen as a reducing agent and nickel tetracarbonyl as a catalyst, and sequentially performs serial reactions of enamine, reductive amination and quaternary amination, so that tetrabutylammonium bromide is generated by a one-pot method, the yield is 93-98%, and the product purity is 99.7-99.9%. The method has the advantages of convenient operation, simple raw materials and reagents, easy separation and purification of products and higher reaction yield.”
Quaternary ammonium carboxylate salts are produced and isolated to be used directly in applications or to diagnose factors for successful phase-transfer catalysis reactions.
In US Patent 11,636,986 (25-Apr-2023), the carboxylate salts of L-proline were formed with tetrabutylammonium and tetraethylammonium as electrolytes in “supercondensers” that have the capacity to store high content of electrical charge.
The procedure described is a neutralization of L-proline (a carboxylic acid) with a molar equivalent amount of either tetrabutylammonium hydroxide or tetraethylammonium hydroxide. The quat hydroxides were used as 40% aqueous solution and the proline was also prepared as an aqueous solution. The two aqueous solutions were combined.
We find it surprising that the aqueous mixture of quat hydroxide and proline was heated to 60 deg C for 2 hours before isolating the quat-prolinate salt. Since this is a simple neutralization of a carboxylic acid with hydroxide in water, the energy of activation should be as trivial as adding sodium hydroxide to acetic acid to form sodium acetate. We would expect the neutralization to be nearly instantaneous at room temperature.
In this case, the quat-prolinate salt required drying. After the neutralization, the water from the solution evaporated under reduced pressure to maintain the temperature no higher than 80 deg C (presumably to avoid decomposition of the quat), then the residue dissolved in acetonitrile, dried with magnesium sulfate and the acetonitrile was evaporated to produce the dry quat-prolinate salt.
When your process development program requires optimal choice of quaternary ammonium salts to achieve low-cost high-performance green processes using phase-transfer catalysis, contact Marc Halpern of PTC Organics to explore consulting to benefit from highly specialized expertise in industrial phase-transfer catalysis.
