The reaction sequence described in this patent includes multiple PTC steps.
In this first step the phase-transfer catalyst transfers and activates the inorganic sulfide nucleophile to perform nucleophilic aromatic substitution of the chloride on the electron deficient ring. The reaction proceeds at 70-75 deg C. Then butyl chloride is added and this nucleophilic aliphatic substitution is also catalyzed by PTC for this S-alkylation.
According to the inventors, the next step is the formation of the 2-(butylsulfoxy)benzonitrile from the sulfide by either oxidizing agent or halogenating agent. Subsequently, treatment with acid forms the cyclic 1,2-benzisothiazolin-3-one which also liberates butyl chloride.
It should be noted that PTC is able to associate with acids, such as HCl, by hydrogen bonding of the acid to the halide of QX. The complex QX-HCl then transfers the acid from a concentrated aqueous phase into an organic solvent such as chlorobenzene, where the acid-promoted reaction proceeds.
Overall, the yield of 90% is very good for the multi-reaction sequence and phase-transfer catalysis plays a key role in several of these reactions.
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!).
