Réaction #1833

Équation de réaction

toluene

paraformaldehyde

Methylmagnesium chloride

p-cresol

→

product

Rendement 18.0%

2-Hydroxy-5-methylbenzaldehyde

Rendement 18.0%

Solvants

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autrethe exothermic reaction
2. 2
   TempératureThe reaction mixture was heated
3. 3
   Températureat reflux for 18 hours
4. 4
   Températurecooled
5. 5
   Lavagewashed with 200 mL of 2N aqueous hydrochloric acid and 200 mL of water
6. 6
   AutreThe organic layer was removed
7. 7
   Filtrationfiltered through Celite
8. 8
   Séchagedried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Autresolvents removed under vacuum
11. 11
    AutreCrystallization of the crude residue from cold hexanes

Mode opératoire

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