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.
About Marc Halpern
Dr. Halpern is founder and president of PTC Organics, Inc., the only company dedicated exclusively to developing low-cost high-performance green chemistry processes for the manufacture of organic chemicals using Phase Transfer Catalysis. Dr. Halpern has innovated PTC breakthroughs for pharmaceuticals, agrochemicals, petrochemicals, monomers, polymers, flavors & fragrances, dyes & pigments and solvents. Dr. Halpern has provided PTC services on-site at more than 260 industrial process R&D departments in 37 countries and has helped chemical companies save > $200 million. Dr. Halpern co-authored five books including the best-selling “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives” and has presented the 2-day course “Practical Phase-Transfer Catalysis” at 50 locations in the US, Europe and Asia.
Dr. Halpern founded the journal “Industrial Phase-Transfer Catalysis” and “The PTC Tip of the Month” enjoyed by 2,100 qualified subscribers, now beyond 130 issues. In 2014, Dr. Halpern is celebrating his 30th year in the chemical industry, including serving as a process chemist at Dow Chemical, a supervisor of process chemistry at ICI, Director of R&D at Sybron Chemicals and founder and president of PTC Organics Inc. (15 years) and PTC Communications Inc. (20 years). Dr. Halpern also co-founded PTC Interface Inc. in 1989 and PTC Value Recovery Inc. in 1999. His academic breakthroughs include the PTC pKa Guidelines, the q-value for quat accessibility and he has achieved industrial PTC breakthroughs for a dozen strong base reactions as well as esterifications, transesterifications, epoxidations and chloromethylations plus contributed to more than 100 other industrial PTC process development projects.
Dr. Halpern has dedicated his adult life to his family and to phase-transfer catalysis (in that order!).
