Reaction #4064

Reaction equation

N-methylformanilide

1,4-difluorobenzene

n-butyllithium

sulfuric acid

→

product

Yield 77.6%

2,5-Difluorobenzaldehyde

Yield 77.6%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Otherremained below -55° C
2. 2
   workup.STIRRINGThe mixture was stirred for 1 hr at -50° C.
3. 3
   Temperatureto warm to -30° C. over 15 mins
4. 4
   Extractionextracted three times with hexane
5. 5
   WashThe extracts were washed once with 1N sulfuric acid, once with saturated sodium chloride solution
6. 6
   Concentrationconcentrated to an oil
7. 7
   workup.DISTILLATIONDistillation at 64°-65° C. (20 mm)

Procedure

To a stirred solution of 194.5 g (1.70 mol) of 1,4-difluorobenzene in 2 of dry tetrahydrofuran at -60° C. was added dropwise over 45 mins 1.70 mol (2.2 M in hexane) of n-butyllithium at a rate such that the temperature remained below -55° C. The reaction mixture was stirred for 45 mins at below -50° C. and 1.5 hr at -50° to -45° C. The solution was then cooled to -60° C. and a solution to 230 g of N-methylformanilide in 300 ml of tetrahydrofuran was added dropwise over 30 mins. The mixture was stirred for 1 hr at -50° C. and allowed to warm to -30° C. over 15 mins. The mixture was then poured into ice water, neutralized (pH 6-7) with 10% sulfuric acid and extracted three times with hexane. The extracts were washed once with 1N sulfuric acid, once with saturated sodium chloride solution and concentrated to an oil. Distillation at 64°-65° C. (20 mm) provided 187.5 g (77.5%) of product.

Source