Phase-transfer catalysis excels in azide reactions as we teach in our 2-day course “Industrial Phase-Transfer Catalysis“. An effective PTC-azide application was reported in a patent issued this month.
We speculate that four process parameters were chosen to enhance safety.
The first choice is the use of tetrabutylammonium cation as the phase-transfer catalyst. Since azide is a good nucleophile, and since certain quaternary ammonium cations are more likely than others to be attacked by good nucleophiles that liberates trialkylamine and an alkylated nucleophile, it is important to avoid using quats for azide reactions that contain methyl or ethyl groups since the formation of even small amounts of methyl azide or ethyl azide can be explosive.
The second choice is likely the reason that the inventors used some bicarbonate. Hydrazoic acid is also quite explosive and its formation must be avoided. The pKa of hydrazoic acid is 4.7. The pKb of bicarbonate is 6.4. So, if a small amount of hydrazoic acid would somehow be formed, the bicarbonate would neutralize it up to the amount of the equilibrium with bicarbonate.
The third choice may be the reason that the inventors chose to work under mild conditions at room temperature, even though the reaction time as long.
Quat iodide was probably chosen to co-catalyze the reaction by forming the alkyl iodide in situ, which likely reduced the energy of activation of the halide displacement enabling working at the lower milder temperature.
Azide reactions should only be performed after performing a hazardous operations analysis including safely measuring exotherm behavior (such as DSC) on extremely small samples.
Now contact Marc Halpern of PTC Organics to develop processes in which exotherms need to be controlled while achieving low-cost high-performance green chemistry.
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!).
