Organic Syntheses, CV 3, 200
Submitted by C. G. Overberger, J. H. Saunders, R. E. Allen, and Robert Gander.
Checked by Arthur C. Cope and Theodore T. Foster.
1. Procedure
A
dry 2-l. three-necked round-bottomed flask is equipped with a
sealed stirrer, a
500-ml. dropping funnel (Note
1), and an
efficient reflux condenser attached to a
calcium chloride tube. In the flask are placed
29.1 g. (1.2 gram atoms) of magnesium turnings, a crystal of
iodine, and about
50 ml. of dry ether. A solution of
229 g. (1.2 moles) of m-bromochlorobenzene (Note
2) in
850 ml. of dry ether is added with stirring at a rate which maintains rapid refluxing. The reaction begins after
20–50 ml. of the ether solution is added (Note
3), and the addition requires 1–3 hours. The mixture is stirred and heated on the
steam bath under reflux for 1 hour after all the
m-bromochlorobenzene has been added.
A cooled solution of
60 g. (1.365 moles) of freshly distilled acetaldehyde in 200 ml. of dry ether (Note
4) is added through the dropping funnel during 2–3.5 hours, as rapidly as the condenser capacity permits. The mixture is stirred and heated under reflux for 1 hour after the addition is completed.
The reaction mixture is cooled in ice, and the addition compound is decomposed by adding dropwise with stirring
185 ml. of a 25% solution of ammonium chloride in water (Note
5). The
ether solution becomes clear, and the salts separate as a cake. The
ether solution is decanted, combined with
150 ml. of ether that has been used to rinse the salt cake, and dried over anhydrous
magnesium sulfate. After removal of the
ether the product is distilled under reduced pressure to give
154.5–164.5 g. (
82.5–88%) of
m-chlorophenylmethylcarbinol boiling at
99–104°/4 mm.;
nD25 1.5405 (Note
6).
2. Notes
1. It is convenient to use a Hershberg stirrer with a rubber slip seal protected from
ether vapor with a
short water-cooled condenser. The dropping funnel may be connected to the flask through an extension tube to prevent clogging, which occurs if the Grignard reagent comes in contact with the
acetaldehyde in the tip of the funnel.
3. If the reaction does not begin spontaneously, the mixture should be heated under reflux until the reaction starts before more than
50 ml. of the m-bromochlorobenzene solution is added.
5. The submitters state that the complex may be decomposed by pouring the reaction mixture onto 1 kg. of crushed ice to which
50 ml. of concentrated sulfuric acid has been added. The
ether layer is separated, combined with two
100-ml. ether extracts of the aqueous layer, and washed with three 250-ml. portions of water, one
250-ml. portion of 10% sodium carbonate solution, and finally with 250 ml. of water.
6. The same general method (including the procedure of (Note
5)) has been used by the submitters to prepare the following substituted phenylmethylcarbinols:
An alternative preparation of similar carbinols, consisting in the reaction of
methylmagnesium iodide with a substituted
benzaldehyde, is advantageous when the aromatic aldehyde is available. The following carbinols have been prepared by the submitters in that way:
|
Aldehyde |
Carbinol |
Boiling Point |
% Yield |
|
p-Chlorobenzaldehyde [Heyden Chemical Corporation; Org. Syntheses Coll. Vol. 2, 133 (1943)] |
p-Chlorophenylmethylcarbinol |
98–100°/4.5 mm. |
59 |
o-Chlorobenzaldehyde (Heyden Chemical Corporation) |
o-Chlorophenylmethylcarbinol |
94°/4 mm. |
69 |
o-Bromobenzaldehyde |
o-Bromophenylmethylcarbinol |
102–105°/2–3 mm. |
73 |
m-Bromobenzaldehyde |
m-Bromophenylmethylcarbinol |
105–110°/2–3 mm. |
74 |
p-Bromobenzaldehyde [Org. Syntheses Coll. Vol. 2, 89, 442 (1943)] |
p-Bromophenylmethylcarbinol |
90°/1 mm. |
64 |
2,3-Dichlorobenzaldehyde |
2,3-Dichlorophenylmethylcarbinol |
112–113°/2 mm. m.p. 55–57° |
76 |
2,4-Dichlorobenzaldehyde (Heyden Chemical Corporation) |
2,4-Dichlorophenylmethylcarbinol |
125–126°/7 mm. |
62 |
2,6-Dichlorobenzaldehyde (Eastman Kodak Company) |
2,6-Dichlorophenylmethylcarbinol |
104–107°/2.5 mm. |
89 |
3,5-Dichlorobenzaldehyde |
3,5-Dichlorophenylmethylcarbinol |
126°/4 mm. |
69 |
3,4-Dichlorobenzaldehyde (Heyden Chemical Corporation) |
3,4-Dichlorophenylmethylcarbinol |
125–130°/3–4 mm. |
73 |
|
3. Discussion
This preparation is referenced from:
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
acetaldehyde (75-07-0)
sulfuric acid (7664-93-9)
ether (60-29-7)
ammonium chloride (12125-02-9)
magnesium turnings (7439-95-4)
sodium carbonate (497-19-8)
benzaldehyde (100-52-7)
iodine (7553-56-2)
methylmagnesium iodide (917-64-6)
magnesium sulfate (7487-88-9)
COPPER CHROMITE
2,3-Dichlorobenzaldehyde (6334-18-5)
2,3-Dichlorophenylmethylcarbinol
2,4-Dichlorobenzaldehyde (874-42-0)
2,4-Dichlorophenylmethylcarbinol (81156-68-5)
2,6-Dichlorobenzaldehyde (83-38-5)
2,6-Dichlorophenylmethylcarbinol
3,5-Dichlorobenzaldehyde (10203-08-4)
3,5-Dichlorophenylmethylcarbinol
3,4-Dichlorobenzaldehyde (6287-38-3)
3,4-Dichlorophenylmethylcarbinol
m-Bromobenzaldehyde (3132-99-8)
m-Chlorobenzaldehyde (587-04-2)
p-Chlorobenzaldehyde (104-88-1)
p-Bromobenzaldehyde (1122-91-4)
o-chlorobenzaldehyde (89-98-5)
m-bromochlorobenzene (108-37-2)
m-Chlorophenylmethylcarbinol (5182-44-5)
Benzyl alcohol, m-chloro-α-methyl- (6939-95-3)
m-Trifluoromethylphenylmethylcarbinol (455-01-6)
m-Methylphenylmethylcarbinol (1875-89-4)
m-tert-Butylphenylmethylcarbinol
p-Chlorophenylmethylcarbinol (1875-88-3)
o-Chlorophenylmethylcarbinol (19819-95-5)
o-Bromobenzaldehyde (6630-33-7)
o-Bromophenylmethylcarbinol (1074-16-4)
m-Bromophenylmethylcarbinol (28229-69-8)
p-Bromophenylmethylcarbinol (4654-39-1)
m-chloroacetophenone (99-02-5)
paraldehyde (123-53-7)
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