Benzaldehyde → 2-[(E)-Benzylidene]cyclohexanone

Temperature

98 °C

Into an inert 100 gallon reactor, there is drawn 29.3 kg of cyclohexanone from a grounded drum on a weight scale. The reactor is vented with nitrogen and then 28.5 kg of benzaldehyde is added. Then 125 liters of deionized water is metered into the above mixture. The vessel is closed and `reinerted` with nitrogen. To the resulting reactor contents there is added, from a grounded drum on a weight scale, a 50 percent (w/v) solution of sodium hydroxide in water solution, (10.6 kg), while stirring the mixture. The resulting mixture is stirred and heated to reflux (about 98° C.). under an atmosphere of nitrogen. The mixture is held at reflux temperature for about three hours and then stirred and cooled overnight. The resulting cooled reaction mixture is extracted once with a 198 liter batch of methylene chloride, separating the aqueous layer, and then again with 132 liters of methylene chloride, neutralizing and discarding the aqueous layer. The combined methylene chloride liquid layers are washed with 284 liters of water and then with 284 liters of water containing 50 ml of acetic acid. After aqueous layer separation, the methylene chloride liquid layer is dried over sodium sulfate with stirring. The resulting dried methylene chloride layer is concentrated to an oil using 35° C. jacket water temperature and jet vacuum procedures. The (E)-2-(benzylidene)cyclohexanone is crystallized by dissolving the oily residue in 60 liters of Skellysolve® B and seeding with authentic material and cooling the vessel overnight by circulating a cooled water/methanol mixture through the reactor jacket. The pale yellow crystals are collected on a 24-inch filter, washed with Skellysolve® B, and recrystallized from 75 gallons of Skellysolve® B by heating to 50° C. to effect dissolution and then cooling the tank contents to 0° C. Alternatively, we have used isopropanol in this crystallization step with approximately equal effectiveness in terms of quality of the crystalline intermediate (E)-2-(benzylidene)cyclohexanone. The crystalline intermediate is dried in a vacuum oven at room temperature to give about 16.4 kg (33 percent yield) of the (E)-2-(benzylidene)cyclohexanone, m.p. 47°-54° C. (Lit. m.p. 54° C.). TLC analysis (silica gel GF; 5 percent ethyl acetate in Skellysolve® B developer) indicates the presence of a small amount of a less polar impurity, identified as ##STR10## on the basis of isolation and melting point.

1. customInto an inert 100 gallon reactor, there is drawn
2. customThe vessel is closed
3. additionTo the resulting reactor contents there is added, from a grounded drum on a weight scale
4. temperatureheated
5. temperatureat reflux temperature for about three hours
6. stirringstirred
7. temperaturecooled overnight
8. temperatureThe resulting cooled
9. customreaction mixture
10. extractionis extracted once with a 198 liter batch of methylene chloride
11. customseparating the aqueous layer
12. washThe combined methylene chloride liquid layers are washed with 284 liters of water
13. customAfter aqueous layer separation
14. dry with materialthe methylene chloride liquid layer is dried over sodium sulfate
15. stirringwith stirring
16. concentrationThe resulting dried methylene chloride layer is concentrated to an oil
17. customusing 35° C.
18. customThe (E)-2-(benzylidene)cyclohexanone is crystallized
19. dissolutionby dissolving the oily residue in 60 liters of Skellysolve® B
20. temperaturecooling the vessel overnight
21. customThe pale yellow crystals are collected on a 24-inch
22. filtrationfilter
23. washwashed with Skellysolve® B
24. customrecrystallized from 75 gallons of Skellysolve® B
25. temperatureby heating to 50° C.
26. dissolutiondissolution
27. temperaturecooling the tank contents to 0° C
28. customin this crystallization step with approximately equal effectiveness in terms of quality of the crystalline intermediate (E)-2-(benzylidene)cyclohexanone
29. customThe crystalline intermediate is dried in a vacuum oven at room temperature

ORD record

ord-f1e055e467674c94980878091f592687

Source dataset

uspto-grants-1987_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04652559