Perhaps the more experienced readers of the PTC Reaction of the Month can comment on the mechanisms of the two reactions shown in the diagram.
The first goal of this patent was to provide an industrially useful process for the production of the nitroso compound by reacting chloronitrobenzene with anisidine in the presence of base and a tertiary alcohol. The inventors achieved this while avoiding disadvantages of prior art including avoiding a large excess anisidine and avoiding extremely low temperature.
The secondary goal of this patent was to produce the quinoxaline compound from the nitroso intermediate by reaction with dialkyl malonate and hydrolysis of the ester.
It is not clear why the inventors used only 75 mole% of dimethyl malonate when using TBAB as the phase-transfer catalyst and KOH as the base. Higher isolated yields were obtained in the other examples in the patent that used 1.0 equivalent of dimethyl or diethyl malonate without PTC. Higher yields were also obtained when using lithium amide as the base instead of NaH as base in the first step to form the nitroso intermediate. We would have liked to see the result when using lithium amide as the base in the first step and a full equivalent of dimethyl malonate with TBAB in the second step.
In any case, I have never seen the addition of malonate to a nitroso group and thought it would be noteworthy for the PTC Reaction of the Month.
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!).
