N-Methyl-N-nitroso-p-toluenesulfonamide [Precursor to Diazomethane]

Typical Procedure: (methyl esterification of 4-methoxybenzoic acid): Feed A [KOH (0.6 M in CH₃OH/H₂O 1:1)] and feed B [N-methyl-N-nitroso-p-toluenesulfonamide (0.3 M in CH₃OH, 2 eq.)] are pumped into a T-mixer by two syringe pumps at flow rates of 200 µL/min each. The combined mixture goes through the inner tube of the tube-in-tube reactor [(inner; 0.8 mm inner diameter, 1 mm out diameter) (outer; 1.59 mm i.d., 3.2 mm o.d.) (4 m length)]. The mixture leaving the inner tube is quenched into conc. AcOH. Feed C [4-methoxybenzoic acid (1.5 mmol, 0.15 M in THF)] is pumped into the outer tube of the reactor at a flow rate of 200 µL/min. The mixture leaving the inner tube is quenched into conc. AcOH. The product stream from the outer tube of the reactor is collected in a storage vessel containing 2 mL AcOH to decompose any unreacted CH₂N₂. The collected product is concentrated under vacuum and extracted with Et₂O and saturated NaHCO₃ aqueous solution. The organic phase is dried over MgSO₄ and the solvent is then removed under vacuum to give methyl 4-methoxybenzoate (247 mg, yield 99%) as a white solid.

Typical Procedure:A reaction and distillation apparatus is assembled by connecting an addition funnel and condenser to a 100 mL long-neck distillation flask. Two in series receiving flasks are connected to the apparatus with the second flask containing an induction tube. A solution containing 6 g potassium hydroxide in 10 mL water, and a solution containing 35 mL carbitol (diethylene glycol monoethyl ether) and 10 mL of ether are placed in the distillation flask. 20~30 mL ether is placed in the second receiving flask making sure the induction tube is immersed into the ether. Both receiving flasks are cooled to 0 °C. A solution containing N-methyl-N-nitroso-p-toluenesulfonamide (21.5 g, 0.1 mol) in 140 mL ether is placed in the addition funnel. Heat the distillation flask to 70 °C in a warm water bath. As the ether begins to boil, start adding the N-methyl-N-nitroso-p-toluenesulfonamide solution dropwise over a 20 minute period. Swirl distillation flask from time to time. About 3 g of diazomethane (0.07 mol) is dissolved in ether distillate. The reagent should be used at once without storing it. *Note: Diazomethane is explosive and highly toxic. Wear protective gloves, protecting goggles, protective mask and work in a well ventilated fume hood. Also place a safety shield in front of distillation apparatus. Diazomethane may explode upon contact with ground glass joints or other scratched glass surfaces, so avoid handling or preparing this compound with such surfaces. Ordinarily, diazomethane is used as a solution in ether. *We have TMS diazomethane (T1146) available. This reagent is analogous in reactivity to diazomethane, but less explosive and less toxic. Please consider using this reagent prior to preparing diazomethane.