Reacción #343937

Ecuación de reacción

1-fluoro-2-methyl-4-(3,3,5,5-tetramethyl-1-cyclohexen-1-yl)benzene

1,3,5-trioxane

sulfuric acid

→

2-(4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde

Disolventes

acetic-acid

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe batch was heated to 106°-110° C. for 11/4 hours
2. 2
   Otropartitioned between 100 ml of water and 200 ml of heptane
3. 3
   workup.ADDITIONwas added
4. 4
   workup.ADDITIONA solution of 96 g of 85% potassium hydroxide in 100 ml of water was then added
5. 5
   Temperaturathe reaction mixture was heated to 68°-72° C. for 13/4 hours
6. 6
   TemperaturaThe batch was then cooled to 30° C.
7. 7
   Otroto separate
8. 8
   Concentraciónthe top layer was concentrated in vacuo until 25% of the total volume
9. 9
   workup.DISTILLATIONwas distilled off
10. 10
    workup.ADDITIONThe remaining solution was diluted with 100 ml of heptane and 182 g of triethylamine
11. 11
    workup.ADDITIONTo the resulting mixture, a solution of 324 g of sulfur trioxide/pyridine complex in 535 g of dimethyl sulfoxide and 78.3 g of triethylamine was added at 30°-35° C
12. 12
    Temperaturacooled to about 20° C.
13. 13
    Otroquenched with 600 g of iced water
14. 14
    Otroto separate
15. 15
    workup.ADDITIONThe top layer was diluted with 100 ml of methanol and 50% sodium hydroxide solution (90 g)
16. 16
    workup.ADDITIONwas added
17. 17
    workup.STIRRINGThe reaction mixture was stirred for 11/2 hours at 30°-34° C
18. 18
    workup.ADDITIONWater (100 ml) was added
19. 19
    Otroto separate at room temperature
20. 20
    Concentraciónthe top solution was concentrated in vacuo
21. 21
    Otroto remove the solvent
22. 22
    workup.DISSOLUTIONThe residue was dissolved in 200 ml of ethanol
23. 23
    Temperaturathe solution was cooled to about 3° C.
24. 24
    Otroto crystallize overnight
25. 25
    FiltraciónThe solids were filtered off
26. 26
    Lavadowashed with 80 ml of cold ethanol
27. 27
    Otrodried to constant weight

Procedimiento

To a mixture of 200 g of glacial acetic-acid, 200 g of 1-fluoro-2-methyl-4-(3,3,5,5-tetramethyl-1-cyclohexen-1-yl)benzene and 35.4 g of 1,3,5-trioxane, a catalytic quantity (4.0 g) of concentrated sulfuric acid was added and the batch was heated to 106°-110° C. for 11/4 hours. The mixture was then cooled to 30° C. and partitioned between 100 ml of water and 200 ml of heptane. The bottom layer was discarded and to the remaining solution 100 ml of methanol was added. A solution of 96 g of 85% potassium hydroxide in 100 ml of water was then added and the reaction mixture was heated to 68°-72° C. for 13/4 hours. The batch was then cooled to 30° C. and the phases were allowed to separate. The bottom layer was discarded and the top layer was concentrated in vacuo until 25% of the total volume was distilled off. The remaining solution was diluted with 100 ml of heptane and 182 g of triethylamine. To the resulting mixture, a solution of 324 g of sulfur trioxide/pyridine complex in 535 g of dimethyl sulfoxide and 78.3 g of triethylamine was added at 30°-35° C. The batch was stirred at 30°-35° C. for 1/2 hour, then cooled to about 20° C. and quenched with 600 g of iced water. The phases were allowed to separate and the bottom layer was discarded. The top layer was diluted with 100 ml of methanol and 50% sodium hydroxide solution (90 g) was added. The reaction mixture was stirred for 11/2 hours at 30°-34° C. Water (100 ml) was added and the phases were allowed to separate at room temperature. The bottom layer was discarded and the top solution was concentrated in vacuo to remove the solvent. The residue was dissolved in 200 ml of ethanol, the solution was cooled to about 3° C., seeded and the product was allowed to crystallize overnight. The solids were filtered off, washed with 80 ml of cold ethanol and dried to constant weight. Yield: 100 g of 2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde; m.p. 50.5°-51.5° C.

Fuente