A reaction sequence was reported this month that uses tetrabutylammonium nitrate and tetrabutylammonium azide as reagents (not phase-transfer catalysts). Tetrabutylammonium nitrate is known to displace triflates in both primary and secondary positions. The purpose of the first step shown in the diagram is to is to invert stereocenter of the secondary carbon bearing the triflate. The second step forms the triflate again with desired stereochemistry in preparation for another inversion in the third step to produce the azide with the right stereochemistry.
The patent describes other azide displacements sometimes using sodium azide. The patent also describes the use of tetrabutylammonium nitrite (not nitrate) as reagent for deprotection of a silyloxy group.
Please note that there are 2 errors in the procedures and diagrams. The diagram states that tetrabutylammonium nitrite was used when the reagent is tetrabutylammonium nitrate based on the procedure text, the molecular weight and the known use of tetrabutylammonium nitrate for this application. Another error appears in the procedure text that cites the amount of the second triflate starting material as 41.3 mmol when it actually was 3.72 mmol. The mass of the triflate, the yield of 86% and the amount of TBA azide are consistent with 3.72 mmol and not 41.3 mmol.
While the uses of these tetrabutylammonium salts are not catalytic, one could envision using the proper choice of the right tetrabutylammonium salts with the less expensive sodium salts to reduce the cost, if cost minimization is an important factor. In such cases, you should contact Marc Halpern of PTC Organics to optimize the choice of quaternary ammonium salts as phase-transfer catalysts.
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!).
