Even veteran PTC chemists should be surprised to see the name of this compound as a phase-transfer catalyst. The inventors were looking for a catalyst for chiral PTC that would be both effective to achieve high ee and high yield as well as be produced from inexpensive raw materials.
The term “pentanidium compounds” refers to alkylated salts of pentanidines that contain five nitrogen atoms in conjugation. The key starting material is one of the diasteromers of a simple material 1,2-diphenyl-1,2-diaminoethane which is subsequently converted to the chiral phase-transfer catalyst in five very simple steps that use rather inexpensive reactants. In fact, it appears that the most expensive reaction in the sequence is the simple N-alkylation of an imidazolidin-2-one that uses NaH/THF! As a PTC expert, it bothers me that such reactions that are obviously made for PTC use expensive and hazardous strong base. However as a PTC businessperson, this means that there is still so much opportunity to expand the use of PTC, even in obvious cases.
In any case, the pentanidium salt is effective for the chiral Michael addition described in the May 2014 PTC Reaction of the Month. It will be interesting to see if these pentanidium salts gain popularity for chiral PTC reactions.
If you’re looking for an organophilic quat, you can’t get much more than having octadecyl trioctyl phosphonium iodide (ODTOPI). It has a whopping C# of 42, a tiny q-value of 0.43 (the lowest I have ever seen in a commercial quat), a soft phosphorous central atom and iodide as the counteranion. The use of this catalyst was the subject of a dispute between two large companies in the 90’s and this is the most organophilic phase-transfer catalyst I have seen that is commercial. This phase-transfer catalyst was used in a patent featured in this month’s PTC Reaction of the Month.
Tetraethyl ammonium hydroxide (TEAH) is an interesting phase-transfer catalyst.
As we teach in Module 1 of our PTC course, with a q-value of 2.0, it is excellent for T-Reactions. In fact, in the publication Halpern, M.; Sasson, Y.; Rabinovitz, M.; Tetrahedron, 1982, 38, 3183, tetraethyl ammonium was found to be the best symmetrical quaternary ammonium phase-transfer catalyst of the nine examined (MUCH better than tetrabutyl ammonium!). Tetraethyl ammonium was the second best phase-transfer catalyst in that publication out of 19 examined with only methyl tributyl ammonium being more active.
With a C# of only 12, TEAH is usually ineffective for I-Reactions.
Some of you may be tempted to buy TEAH as a base since it contains both hydroxide and has a cation suitable for T-Reactions. However, as we teach in Module 1 of our PTC course, tetraethyl ammonium is the quat that is most sensitive to Hofmann Elimination. In other words, the combination of tetraethyl ammonium and hydroxide is almost designed for decomposition. Hofmann Elimination is the #1 mechanism of decomposition of phase-transfer catalysts under basic conditions.
You may get lucky and observe TEAH to be a great phase-transfer catalyst before it decomposes, but I would strongly recommend that you test any TEAH you may have in the lab or plant before using it. You might find a lot of unquaternized triethylamine, even if the certificate of analysis certifies that it was high quality TEAH when it was shipped.
Tetrabutyl ammonium perchlorate is used as an electrolyte but may potentially be used for oxidations described in GFS’s monograph on perchlorate chemistry. As always, before performing any PTC reaction, especially one containing perchlorate, a full hazardous operations analysis must be performed to assure safety and taking all appropriate precautions.
Tetrabutyl ammonium perchlorate is supplied by GFS Chemicals.
It is interesting to note that perchlorate is one of the anions with the highest affinity for quaternary ammonium cations. As a result, if you have an aqueous phase that contains small amounts of perchlorate in the presence of other anions, such as chloride and sulfate, the quaternary ammonium cation may be effective in selectively extracting the perchlorate from that aqueous phase. A potential application may be to clean up soil or groundwater in areas that have perchlorate contamination such as Superfund locations in the Pacific Southwest of the United States.
The chiral phase-transfer catalyst shown in the figure is called “Dibutyl Maruoka Catalyst”. This catalyst was reported by Ikunaka and Maruoka in an article “Asymmetric Phase-Transfer Catalysts for the Production of Non-Proteinogenic alpha-Amino Acids” in Asymmetric Catalysis on Industrial Scale, 2nd edition, Blaser, H. and Federsel, H. editors, Wiley-VCH Verlag (2010)
The dibutyl Maruoka catalyst is now available commercially in gram quantities up to 100 g. This catalyst is used at levels of 0.1 mole%.
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
Triethylamine is typically not considered a phase-transfer catalyst, but it can form quaternary ammonium phase-transfer catalysts in-situ by reaction with an alkylating that may already be present in the reaction matrix.
However, triethylamine will work best when the alkylating agent has no beta hydrogen atoms that can undergo elimination. Triethylamine will react with alkyl halides, ethyl and higher to dehydrohalogenate and counterproductively consume reactant.
In the PTC Reaction of the Month above, triethylamine reacts with dimethylsulfate to form a quat that will methylate well. Trialkylamines in general are good for forming in-situ phase-transfer catalysts with methyl groups, allyl groups and benzyl groups since they don’t have beta hydrogen atoms.
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
Benzyl trimethyl ammonium chloride (BTMAC) is one of the least expensive phase-transfer catalysts since it is made from commodity benzyl chloride and commodity trimethyl amine. Moreover, the process for making BTMAC is simply reacting an aqueous solution of trimethyl amine with benzyl chloride and stripping some water until it is 60% BTMAC and shipping everything in the reactor.
BTMAC almost never gives the highest reactivity in PTC systems since it has only 10 carbon atoms (C# is not high enough) and the accessibility of the positive charge on the nitrogen (q-value = 3.14) is so high that it makes tighter ion pairs more than almost any other quaternary ammonium phase-transfer catalyst. Nevertheless, BTMAC is used is some commodity polymer PTC reactions, because its low price combined with the rate enhancement it provides relative to not using PTC is simply worth the investment. BTMAC is toxic and must be handled with care.
Benzyl Trimethyl Ammonium Chloride is available from Dishman and Biosolutions
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
Directory for suppliers of 80 PTC’s
Tetrabutyl ammonium iodide is used primarily when you need both a phase-transfer catalyst AND a co-catalyst to activate an alkyl chloride or bromide alkylating agent. An example is shown in the PTC Reaction of the month above.
Iodide is a good nucleophile so the reaction of an alkyl chloride with iodide to form the alkyl iodide is often faster than the reaction of other nucleophiles with the alkyl chloride. Since iodide is also a good leaving group, the reaction of the nucleophile with the alkyl iodide is also often faster than the reaction of the nucleophile with the original alkyl chloride. The net result is that tetrabutyl ammonium iodide catalyzes many alkylations more than tetrabutyl ammonium hydrogen sulfate or tetrabutyl ammonium bromide.
However, iodide is expensive and the price of iodide fluctuates. Due to this fluctuation, the price of tetrabutyl ammonium iodide is usually set at the higher end of the range of iodide price since tetrabutyl ammonium iodide can sit in inventory for a long time. Many process chemists use tetrabutyl ammonium bromide together with 1 mole% KI, since KI is more likely to be bought at current market price. Due to hard-soft acid-base theory, a lipophilic quaternary ammonium cation prefers to associate with the polarizable “softer” iodide several orders of magnitude greater than with the more compact “harder” chloride anion (or bromide that has intermediate “softness”). So, it is usually less expensive to use a combination of tetrabutyl ammonium bromide with KI than it is to buy tetrabutyl ammonium iodide. If the cost of the iodide is not crucial, then it is more convenient to buy tetrabutyl ammonium iodide.
Tetrabutyl Ammonium Iodide is available from Dishman
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
Tetramethyl ammonium bromide, TMAB, is found from time to time to be an effective phase-transfer catalyst, though it is usually to hydrophilic to be effective for most PTC reactions.
The diagram shows a reaction for which TMAB performed better than several other quaternary ammonium phase-transfer catalysts, PEG’s and even 18-crown-6
Tetramethyl Ammonium Bromide is available from Dishman and Biosolutions
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
Let’s say that you want a phase-transfer catalyst that will do a great job in activating an anion, such as in a nucleophilic substitution, but you don’t want too many carbons and you want extra thermal stabiliity.
Tributyl Octyl Phosphonium Chloride might be an excellent choice because:
[1] the central atom is a phosphorous and not a nitrogen that will make a much looser ion pair between the quat cation and the anion thereby activating its nucleophilicity
[2] the phosphorous equivalent of the q-value will be only 0.89 due to the 3 butyl groups and one octyl group. In other words, the accessibility of the positive charge on the phosphorous will be low in the absence of a methyl group or ethyl groups that will result in a much looser ion pair and activate anion nucleophilicity
[3] the P-quat is more thermally stable than the corresponding N-quat, giving you flexibility in choosing reaction conditions to achieve higher performance
From an operational decision making standpoint, let’s say you use Aliquat 336 and you don’t get enough reactivity. In that case, you should screen Tributyl Octyl Phosphonium Chloride because this P-quat has a phosphorous instead of a nitrogen, the q-value is 0.89 instead of 1.34 and if you need to increase the reaction temperature, you may get an extra 50 deg C of functional temperature range above that to be often expected for Aliquat 336 for many nucleophilic substitutions. Tributyl Octyl Phosphonium Chloride also has only 20 carbon atoms versus and average of 27 for Aliquat 336.
You really should have a sample of Tributyl Octyl Phosphonium Chloride on your shelf!
Tributyl Octyl Phosphonium Chloride is available from Cytec
Need to learn more about which phase-transfer catalyst to choose for a specific PTC application? Contact Marc Halpern of PTC Organics by E-mail.
