Phase-transfer catalysis works very well for N-alkylation of heterocycles that are not very organophilic, such as triazoles. This is due to the ability of the phase-transfer catalyst to impart enough organophilicity to the ion pair with the N-anion to be soluble in the organic phase. In the patent described here, the combination of PTC with the use of a polar solvent is effective to achieve high yield of the N-alkylation.
The N-H is very acidic and only needs potassium carbonate as the base for deprotonation. The use of iodide as a co-catalyst to form the reactive iodoethyl carbamate in-situ also helps the reaction. We speculate that optimization of this reaction would result in using a much lower excess of the bromoethyl carbamate.
If you need to improve the yield, selectivity, cycle time or achieve other process performance improvement of a challenging N-alkylation, now contact Marc Halpern of PTC Organics to integrate highly specialized expertise in industrial PTC-base reactions with your process development program.
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!).
