It is rare to see tetrabutylammonium azide reported in the literature but this week, it appeared twice in US Patent 9,422,314 (23-Aug-2016). In Scheme 21 of this patent, tetrabutylammonium azide was used in the conversion of a cyclic trans 1-azide 2-mesylate to a cis-bisazide. It is interesting that in the previous step, which was a ring opening of an epoxide to a trans azido alcohol followed by conversion to the trans azido mesylate, the inventors used sodium azide and polyethylene glycol and not tetrabutylammonium azide. One would think that they would have used the same azide (either sodium or tetrabutylammonium) for both steps. Perhaps the ring opening was easier than the displacement of the secondary mesylate. In Scheme 25 of the patent, the inventors used tetrabutylammonium azide to displace a secondary tosylate on an open alkyl chain.
Overall, we do not recommend storing quat azides in the lab since they can potentially form alkyl azides that are unstable and potentially explosive. One should particularly avoid using quaternary ammonium salts that contain methyl groups or ethyl groups in the presence of azide since the potential formation of methyl azide or ethyl azide are very dangerous.
Before using phase-transfer catalysis for any azide reaction, make sure to do proper safety testing, for example DSC analysis, to assure that even small scale reactions can be performed safely.
If you need help to choose the best phase-transfer catalyst to make sure you don’t leave unrealized wasted profit on the table, now contact Marc Halpern of PTC Organics Inc.
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!).
