Grignard addition to aldehyde via chlorobenzene metalation; Benzhydrol
Submitted May 11, 2012, published May 14, 2012
Ramesha Ramakrishna (email@example.com
A contribution from
Chlorobenzene -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
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
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.
e.g. Actual NMR spectra (as images or jdx files for interactive spectra), photographs of apparatus, TLC’s or crystals or videos. Please contact the ChemSpider team (ChemSpider-at-rsc.org) for help with this.
Keywords: addition, alcohols, aldehydes, alkyl/alkenyl/aryl halides, aromatics/arenes, chlorobenzene, Grignard, magnesium, nucleophilic