Peter Wuts (https://petergmwuts.com), André Stoller and Bryce Assink helped us understand this reaction sequence that looks as if it is a deoxygenation reaction. Peter, André and Bryce are long time loyal readers of the PTC Tip of the Month newsletter who participated in our 2-day course “Industrial Phase-Transfer Catalysis” in the early 2000’s.
Tetrabutylammonium bromide is used as the phase-transfer catalyst to “deoxygenate” in very high yield a [1,3]oxathiol-2-one using dibromomethane (also used as solvent) and base.
Our loyal readers pointed out that of the [1,3]oxathiol-2-one is a cyclic monothiocarbonate and as such it is sensitive to hydrolysis, especially in the presence of base. Once the carbonyl is attacked and the ring opened, the sulfide anion reacts with dibromomethane to form the bromomethyl thioether. After decarboxylation of the newly formed carbonate anion, the remaining phenoxide oxygen attacks the bromomethyl group to close the ring.
In other words, the ring is not directly “deoxygenated.” In fact, the methylene carbon in the 1,3-oxathiolane ring is sourced from the dibromomethane.
Please be aware that when PTC-NaOH conditions are used in the presence of dichloromethane, formaldehyde can be formed which is a safety concern. Under such conditions, dichloromethane is hydrolyzed to chloromethanol that liberates HCl to form formaldehyde. In this case, since 5M NaOH was used as base, it likely was not strong enough to form formaldehyde from dibromomethane.
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!).
Hi Marc,
Not 100% sure but I think that NaOH is used to hydrolyze the benzo[d][1,3]oxathiol-2-one to the hydroxythiophenol, while CH2Br2 acts as the source of the methylene bridge (either through double alkylation or formaldehyde generaation).
Thanks for these posts!
Take care,
Raphael
It seems to me that the simplest route would be the hydrolysis of the cyclic ester to the disodium salt of the thiophenolic and the phenolic groups. The thiophenolate is the more nucleophilic moiety which would attack the methylene bromide and the secondary attack by the phenolate would effect ring closure. I hope this helps. Tom Schlaf
Retired Process Chemist
Hello Marc,
how about a simple two-step process: at first the oxathiolone is hydrolysed by the base to the ortho hydroxy-thiophenol, which is in the second step alkylated to the product.
Best regards
Timo