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Grignard addition to aldehyde via chlorobenzene metalation; Benzhydrol

SyntheticPage 559
DOI: 10.1039/SP559
Submitted May 11, 2012, published May 14, 2012
Ramesha Ramakrishna (
A contribution from ramesha

			Reaction Scheme: <img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" />Grignard addition to aldehyde via chlorobenzene metalation<img src="/images/empty.gif" alt="" /><img src="/images/empty.gif" alt="" />

Chemicals Used

Chlorobenzene -commercial grade
Bromobenzene-commercial grade
Toluene -commercial grade
Tetrahydrofuran commercial grade
Benzaldehyde from D. D. Fine Chem, LR grade
Magnesium turnings commercial grade
Ammonium chloride commercial grade


Tetrahydrofuran (150 ml, commercial THF dried over 20% KOH just before use, moisture content by KF <0.10%) added to a clean dry three necked flask ( 1 Lt) carrying thermometer pocket and mechanical stirrer under nitrogen atmosphere. Magnesium turnings (14.5 g, 0.6 mol) added all at once. To this a small amount of iodine (~ 0.5-1 g) and ethyl bromide (2-3 mL, one can also use di-bromoethane) added without stirring and observed for initiation of the reaction. At this point one can see bubbles at the junction of magnesium where ethyl bromide is added. To this add about 3-5 mL of a mixture of Chlorobenzene ( 50 g, 0.45 mol) and bromobenzene (15 g, 0.10mol) in toluene (200 mL) added and observe the initiation ( sometimes slight warming of the flask is required). Once the initiation starts continue the addition of mixture of chlorobenzene and bromobenzene over period of 1 hr keeping the exothermic reaction. Do not try to cool the reaction. Keeps the exothermic reaction going by the way of addition of chlorobenzene and bromobenzene. After complete addition, reflux for 2 h under nitrogen atmosphere. Cool to about 5oC and add a mixture of Benzaldehyde (53 g, 0.5 mol) in dry toluene ( 200 mL) over a period of 45 min keeping the temperature below 8 oC. After complete addition, stir for 30 min below 8oC and remove cooling. Stir for 4 h, during which the temperature comes to room temperature. Quench the reaction mixture with aqueous ammonium chloride ( ~50 g in 150 mL water)and warm to about 50-60 oC for 30 min. Add water (200 mL) and separate water layer. Water wash the organic layer again and dry over sodium sulphate (~ 75 g). Distil the organic layer under vacuum to get benzhydrol as the only product (70 g, 95% yield ) . This is normally pure by NMR

Author's Comments

1. It is always difficult to initiate Grignard reaction with chloro substrates. Many a times Grignard reaction stops after 50% reaction if the chloro substrates is used. One can overcome this problem by using a mixture of chloro (80-90%) and bromo substrate (20-10%).

2. Normally bromobenzene is 3-4 times expensive than chlorobenzene. Because of higher molecular weight of bromo compounds one has to use more quantity for the reaction. Therefore using chloro substrate is economically more viable.

3. Magnesium can be dried at 70-80 ofor 2-3 h for better initiation.

4. THF can be dried with KOH, just before the reaction. About 20-25 g of KOH is added to 100 mL THF and stirred for 3-4 min. The THF thus obtained is decanted to the reaction flask.

5. Toluene can be dried by distilling 10-15% and cooling the remaining toluene under nitrogen. This would remove any water present as azeotrope.

6. This is a practical method which can be used for any ketones/carbonyl compound.


1H NMR (300 MHz): 7.50-7.20 (m, 10H), 5.83 (s, 1H), 2.20 (s,OH)

13C NMR (75 MHz): 142.00, 128.25, 127.30, 127.12, 79.92

Lead Reference


Other References

V. Grignard, Compt. Rend. 130, 1322 (1900); D. A. Shirley, Org. React. 8, 28-58 (1954), Preparation of Grignard reagents: Y. H. Lai, Synthesis 1981, 585-604. Mechanistic study: K. Maruyama, T. Katagiri, J. Phys. Org. Chem. 2, 205 (1989). Review of stereoselective addition of carbonyl compounds: D. M. Huryn, Comp. Org. Syn. 1, 49-75 (1991). General review: G. S. Silverman, P. E. Rakita in Kirk-Othmer Encyclopedia of Chemical Technology vol. 12 (Wiley-Interscience, New York, 4th ed., 1994) pp 768-786.

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Keywords: addition, alcohols, aldehydes, alkyl/alkenyl/aryl halides, aromatics/arenes, chlorobenzene, Grignard, magnesium, nucleophilic

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