Reaction #1833

Reaction equation

toluene

paraformaldehyde

Methylmagnesium chloride

p-cresol

→

product

Yield 18.0%

2-Hydroxy-5-methylbenzaldehyde

Yield 18.0%

Solvents

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Otherthe exothermic reaction
2. 2
   TemperatureThe reaction mixture was heated
3. 3
   Temperatureat reflux for 18 hours
4. 4
   Temperaturecooled
5. 5
   Washwashed with 200 mL of 2N aqueous hydrochloric acid and 200 mL of water
6. 6
   OtherThe organic layer was removed
7. 7
   Filtrationfiltered through Celite
8. 8
   Dryingdried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Othersolvents removed under vacuum
11. 11
    OtherCrystallization of the crude residue from cold hexanes

Procedure

Methylmagnesium chloride solution in tetrahydrofuran (100 mL, 3.0M, 300 mmol) at room temperature was treated dropwise over 30 minutes with a solution of 32.3 g (300 mmol) of p-cresol in 30 mL of tetrahydrofuran. An additional 70 mL of tetrahydrofuran was added to moderate the exothermic reaction. The mixture was aged at room temperature for 2 hours then treated with 400 mL of toluene, 41mg of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and 23 g of paraformaldehyde. The reaction mixture was heated at reflux for 18 hours, then cooled and washed with 200 mL of 2N aqueous hydrochloric acid and 200 mL of water. The organic layer was removed, filtered through Celite, dried over magnesium sulfate, filtered and solvents removed under vacuum. Crystallization of the crude residue from cold hexanes gave 7.4 g (54 mmol, 18%) of the product. The mother liquors were further purified by column chromatography on silica gel, eluting with methylene chloride, to give an additional 17.5 g (128 mmol, 43%) of the product. 1H NMR (200 MHz,CDCl3): 2.33 (s,3H), 6.89 (d,10 Hz,1H), 7.33 (m,2H), 9.83 (s,1H), 10.80 (s,1H).

Source