1,4-Sorbitan is a useful compound for the production of certain prostaglandin analogues and Polysorbate 80 used an emulsifier and in excipient applications. 1,4-Sorbitan can be made by the acid-catalyzed dehydration of D-Sorbitol but challenges include low conversion of the Sorbitol and selectivity to avoid a second dehydration to the Isosorbide shown in the reaction diagram.
A previous report in the patent literature cited the use of toluene sulfonic acid as the acid catalyst in the presence of tetrabutylammonium bromide, however yield, purity, conversion and analytical were not reported. So, the inventors of this Lonza patent repeated the procedure in the previous report and compared the results to the new procedure they invented.
The use of 0.85 mole% toluene sulfonic acid and 1.8 mole% TBAB at a temperature of 110 C (molten reaction mixture at 90 C) at reduced pressure, presumably to remove the water, gave the product 1,4-Sorbitan after 6 hours and workup with ethanol and isopropanol to yield an isolated precipitate in 52.6% yield and 97% purity. Comparative examples gave low yield, higher levels of the double dehydrated isosorbide and lower conversion of D-Sorbitol.
We welcome suggestions and speculations from our readership about the potential role of the TBAB in this dehydration reaction. Is it possible that a secondary bromide intermediate is formed after protonation of the alcohol and dehydration to the carbocation and somehow that leads to selective mono-dehydration or desired stereochemistry?
We invite you to contact Marc Halpern of PTC Organics with your thoughts and please let us know if you authorize us to cite your name and company affiliation if we publish your input.
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!).
