Grignard solutions

If reaction does not occur when a little allyl bromide is first introduced, further addition must be discontinued until the reaction has commenced. Remove 2-3 ml. of the Grignard solution with a dropper pipette, add about 0-5 ml. of allyl bromide and warm gently to start the reaction after this has reacted well, add the solution to the main portion of the Grignard reagent. 

D. a-Allyl- -bromoelhyl ethyl ether. The same apparatus is used as in the preparation of allylmagnesium bromide. The flask is charged with an amount of the Grignard solution (part C) equivalent to 2.78 moles of allylmagnesium bromide (or chloride) and cooled in an ice bath. A solution of 580 g. (2.5 moles) of o , 3-dibromoethyl ethyl ether (part B) in an equal volume of anhydrous ether is added slowly with stirring over a period of 3-4 hours. The mixture is allowed to stand overnight and is then hydrolyzed with 75 ml. of 20% acetic acid followed by 500 ml. of water. The ether layer is separated, washed with four 100-ml. portions of 10% aqueous sodium bicarbonate solution followed by four 100-ml. portions of saturated aqueous sodium chloride solution, dried over 100 g. of anhydrous calcimn sulfate, and distilled under reduced pressure. The yield of colorless a-allyl-/3-bromoethyl ethyl ether is 370-396 g. (77-82% based on the a, 3-dibromoethyl ethyl ether), b.p. 72-75°/21 mm., 1.4600-1.4606. 

A solution of 85.8 g (0.2 moles) of 3/ -acetoxy-27-norchoIest-5-en-25-one in 500 ml of anhydrous thiophen-free benzene is added to a Grignard solution prepared from 24.3 g (1 g-atom) of magnesium and 149 g (1.05 moles) of freshly distilled methyl iodide in 575 ml of anhydrous ether. The mixture is refluxed for 3 hr and allowed to stand overnight. After cooling to 5° the complex is decomposed by the slow addition of 200 ml of ice water and 400 ml of 50% acetic acid solution, and steam distilled until no more oil passes over. The residual product is filtered, washed with water and dried at 80°. Crystallization from methanol gives 70 g (87%) of cholest-5-ene-3)5,25-diol mp 179.5-181°. The analytical sample melts at 181.5-182.5° [a]o —39° (CHCI3). 

A Grignard solution is prepared from 1.35 g (56 mg-atoms) magnesium, 3.7 ml (8.4 g, 59 mmoles) methyl iodide and 47 ml dry ether. After addition of 80 ml of dry tetrahydrofuran the solvent is removed by distillation until the boiling point reaches 62°. Additions of 0.27 g (2.7 mmoles) of cuprous... 

A suitable laboratory method is to shift the Schlenk equilibrium in a Grignard solution (p. 132) by adding dioxan to precipitate the... 

A Grignard solution is prepared by introducing methyl chloride into a boiling suspension of 36 g of magnesium in 1,000 cc of absolute ether until all the magnesium has reacted. 

A) Preparation of p-Hydroxy-p -Methoxybemhydrylidenecyclohexane To a Grignard solution prepared from 110 g of magnesium (4.5 mols) and 840 g of p-bromoanisole (4.5 mols) in one liter of anhydrous ether, there was added dropwise with vigorous agitation 307 g of p-hydroxyphenyl cyclohexyl ketone (1.5 mols) dissolved in one liter of anhydrous ether. Upon completion of the addition the reaction mixture was refluxed for 2.5 hours with agitation, and was then cooled. Thereupon 15 mols of ammonium chloride dissolved in 3 liters of water were added. The ethereal layer was separated, washed with water, dried over anhydrous sodium sulfate and distilled. Yield 370 g. BP 180° to 190°C at 0.1 mm. The substance was recrystallized from a mixture of carbon tetrachloride and petroleum ether. MP 145° to 146°C. 

Rundle and co-worker performed x-ray diffraction studies on solid phenylmag-nesium bromide dietherate and on ethylmagnesium bromide dietherate, which they obtained by cooling ordinary ethereal Grignard solutions until the solids crystallized. They found that the structures were monomeric ... 

To the Grignard solution, 75 g. (71.5 cc., 0.5 mole) of ethyl benzoate (Org. Syn. 10, 51) in 200 cc. of dry benzene (Note 2) is added at such a rate that the mixture refluxes gently. The flask is cooled in a pan of cold water during the addition, which requires about an hour. After the addition is complete, the mixture is refluxed for an hour on a steam bath. The reaction mixture is cooled in an ice-salt bath and then poured slowly, with constant stirring, into a mixture of 1.5 kg. of cracked ice and 50 cc. of concentrated sulfuric acid. The mixture is stirred at intervals until all the solid which separates at the benzene-water interface has dissolved. If necessary, 50 g. of ammonium chloride is added to facilitate the decomposition of the magnesium salt, and additional benzene may be added if the amount present... 

Mix 294g (1.6M) 1,3,5-trichlorobenzene, 184g (3.4M) Na methoxide and 450g (3 3M) diglyme and reflux at 162° C for 42 hours. Cool to room temperature, filter and distill the solvent to get 70% yield of l-Cl-3,5-dimethoxybenzene (I). 43.2g (I) in 540 ml tetrahydrofuran is added dropwise to 7.3g Mg, a small crystal of iodine and a few drops of ethyl bromide (under nitrogen if possible) over Vi hour while the mixture is heated to 75° C. Reflux 2 hours and cool to room temperature to obtain the Grignard solution. 

Add 34.0g (0.27M) (II) in tetrahydrofuran to the Grignard solution of (I) over Vi hour, heat 6 hours at 60° C and hydrolyze with 1600 ml 50% sulfuric acid, keeping the temperature below 40° C. Evaporate in vacuum the solvent and add another 400 ml 50% sulfuric acid. Heat 1 hour at 95-100° C, cool, add ether, separate the aqueous layer and extract with ether. Dry and evaporate in vacuum the combined ether layers to get 71% yield 2-(3,5- dimethoxybenzoyl) heptane (HI) (can distill 133-8/0.2), which can be demethylated as described for the preparation of (VII) below and possibly used to synthesize an active THC analog (as can IV, V, or VI). 

Ethyl benzoate (15 g.) mixed with 15 c.c. of absolute ether is dropped into a Grignard solution prepared as just described from 6-4 g. of magnesium and 40 g. of bromobenzene. The conditions are the same as those observed in the preceding preparation at the end the solution is boiled for half an hour and worked up as before. Colourless prisms of triphenylcarbinol, melting point 162°, are obtained by recrystallising the solid residue from hot alcohol. Yield over 20 g. For further information about this important alcohol see p. 355. 

While the Grignard solution is being refluxed, the dropping funnel is charged with bis(tributyltin) oxide (371 g, 0.62 mol) (Note 1) in 150 mL of anhydrous ether. After the reflux, heating is stopped and the bis(tri-butyltin) oxide solution is added at such a rate as to maintain a reaction temperature of 36-38°C. The addition requires approximately 1 hr. After the addition is complete, the reaction mixture is refluxed for 1.5 hr and then stirred overnight at room temperature. 

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