The inventors of this patent describe two methods using phase-transfer catalyzed to produce the desired product.
The inventors first report (in Example 1b) a 2-step process which starts with the non-PTC chlorination of 5-bromo-3-methyl-1H-pyridazin-6-one using sodium hypochlorite to form the N-Cl compound as a fully isolated intermediate. In the second step, the inventors added 2 mole% tetrabutyl ammonium chloride and a catalytic amount of bis(4-tert-butylcyclohexyl)peroxydicarbonate to perform the coupling at the N-Cl group with the electron-rich 1,2-dimethoxybenzene. We would appreciate reader input to propose the mechanism of this reaction using catalytic peroxycarbonate. Does this generate chlorine radicals from the displaced chlorine?
In the second method, the inventors report (Example 1c), an alternative 1-pot method to the desired product 4-bromo-2-(3,4-dimethoxyphenyl)-6-methyl-pyridazin-3-one. The dimethoxybenzene is used as both reagent and partial solvent for the initial chlorination of some of the N-H starting material to the N-Cl intermediate that is NOT isolated. The phase-transfer catalyst is Aliquat 336 (registered trademark of BASF) and PTC is known to enhance reactions of hypochlorite at the proper controlled pH. Then several portions of the N-H starting material are added together with additional corresponding amount of sodium hypochlorite and 1.9 mole% of methyl ethyl ketone peroxide (in chlorobenzene) to perform most of the conversion to the desired product.
We are not sure why the inventors choose a tetrabutylammonium salt for the 2-step process versus the ore organophilic Aliquat 336 for the 1-pot process, but we speculate that it is related to the workup procedure which was different for the wo methods. It is common for workup procedures using Aliquat 336 to be different than workup procedures using tetrabutylammonium salts due to the fact that Aliquat 336 distributes into water less than 1% in the presence of organic solvents whereas tetrabutylammonium salts can usually be washed into water with a few water washes.
PTC was very good to me. I am now retired but worked with PTC with undergraduates at Texas Lutheran University. PTC was an excellent way to get undergrads involved in chemistry. As you know not much equipment is needed to get started and the kids can get quick results. PTC is /was a win-win situation.