化学化工专业英语23 Grignard Synthesis of Triphenylmethanol

23 Grignard Synthesis of Triphenylmethanol

23. 1 Prelab Exercise

Prepare a flow sheet for the preparation of triphenylmethanol. Through know ledge of the physical properties of the solvents, reactants, and products, show how the products are purified. Indicate which layer in separation should contain the product. In 1912 Victor Grignard received the Nobel Prize in chemistry for his work on the reaction that bears his name, a carbon-carbon bond-forming reaction by which almost any alcohol may be formed from appropriate alkyl halides and carbonyl compounds. The Grignard reagent is easily formed by reaction of an alkyl halide, in particular a bromide, with magnesium metal in anhydrous ether. Although the reaction can be written and thought of as simply it appears that the structure of the material in solution is rather more complex. There is evidence that dialkylmagnesium is

R--Br 十 Mg 一→ R--Mg-Br

It appears that the structure of the material in solution is rather more complex. There is evidence that dialkylmagnesium is present.

And that the magnesium atoms, which have the capacity to accept two electron pairs from donor molecules to achieve a four-coordinated state, are solvated by the unshared pairs of electrons on ether:

The Grignard reagent is a strong base and a strong nucleophile. As a base it will react with all protons that are more acidic than those found on alkenes and alkanes. Thus Grignard reagents react readily with water, alcohols, amines, thiols, etc. , to regenerate the alkane:

The starting material for preparing the Grignard reagent can contain no acidic protons. The reactants and apparatus must all be completely dry; otherwise the reaction will not start. If proper precautions are taken, however, the reaction proceeds smoothly.

The magnesium metal, in the form of turnings, has a coat of oxide on the outside. A fresh surface can be exposed by crushing a piece under the absolutely dry ether in the presence of the organic halide. Reaction will begin at the exposed surface, as evidenced by a slight turbidity in the solution and evolution of bubbles. Once the exothermic reaction starts it proceeds easily, the magnesium dissolves, and a solution of the Grignard reagent is formed. The solution is often turbid and gray due to

impurities in the magnesium. The reagent is not isolated but reacted immediately with, most often,an appropriate carbonyl compound:

to give, in another exothermic reaction, the magnesium alkoxide. In a simple acid-base reaction this alkoxide is reacted with acidified ice water to give the covalent, ether-soluble alcohol and the ionic water-soluble magnesium salt:

The great versatility of this reaction lies in the wide range of reactants that undergo the reaction.

23. 2 Phenylmagnesium Bromide (Phenyl Grignard Reagent)

All apparatus and reagents must be absolutely dry. The Grignard reagent is prepared in a dry l00mL round bottomed flask fitted with a long reflux condenser. A calcium chloride drying tube inserted in a cork that will fit either the flask or the top of the condenser is also made ready.The flask, condenser, and magnesium (2g =0. 082 mole of magnesium turnings) should be as dry as possible to begin with, and then should be dried in a 110℃ oven for at least 35 min. Alternatively, the magnesium is placed in the flask, the calcium chloride tube is attached directly, and the flask is heated gently but thoroughly with a cool luminous flame. Do not overheat the magnesium. It will become deactivated through oxidation or, if strongly overheated, can burn. The flask on cooling pulls dry air through the calcium chloride. Cool to room temperature before proceeding! Extinguish all flames! Ether vapor is denser than air and can travel along bench tops and into sinks. Use care.

Make an ice bath ready in case control of the reaction becomes necessary, although this is usually not the case. Remove the drying tube and fit it to the top of the condenser. Then pour into the flask though the condenser 15mL of absolute ether (absolutely dry, anhydrous) and 9mL (13. 5g = 0. 086mole) of bromobenzene are absolutely dry. (More ether is to be added as soon as the reaction starts, but at the outset the concentration of bromobenzene is kept high to promote easy starting. ) If there is no immediate sign of reaction, insert a dry stirring rod with a flattened end and crush a piece of magnesium firmly against the bottom of the flask under the

surface of the liquid, giving a twisting motion to the rod. When this is done properly the liquid becomes slightly cloudy, and ebullitioncommences at the surface of the compressed metal. Be careful not to punch a hole in the bottom of the flask. Attach the condenser at once, swirl the flask to provide fresh surfaces for contact, and, as soon as you are sure that the reaction has started, add 25mL more absolute ether through the top of the condenser before spontaneous boiling becomes too vigorous (replace the drying tube). Note the volume of ether in the flask. Cool in ice if necessary to slow the reaction but do not overcool the mixture; the reaction can be stopped by too much cooling. Any difficulty in initiating the reaction can be dealt with by trying the following expedients in succession.

( 1) Warm the flask with your hands or a beaker of warm water. Then see if boiling continues when the flask (condenser attached) is removed from the warmth. (2) Try further mashing of the metal with a stirring rod.

(3) Add a tiny crystal of iodine as a starter (in this case the ethereal solution of the final reaction product should be washed with sodium bisulfite solution to remove the yellow color).

(4) Add a few drops of a solution of phenylmagnesium bromide or of methyl-

magnesium iodide（which can be made on a test tube).

( 5) Start afresh, taking greater care with the dryness of apparatus and reagents, and sublime a crystal or two of iodine on the surface of the magnesium to generate Gattermann' s “activated magnesium'' before beginning the reaction again.

Once the reaction begins, spontaneous boiling in the diluted mixture may be slow or become slow. If so, mount the flask and condenser on the steam bath (one clamp supporting the condenser suffices) and reflux gently until the magnesium has disintegrated and the solution has acquired a cloudy or brownish appearance. The re action is complete when only a few small remnants of metal (or metal contaminants) remain. Check to see that the volume of ether-has not decreased. If it has, add more anhydrous ether. Since the solution. of Grignard reagent deteriorates on standing, the next step should be started at once.

23. 3 Triphenylmethanol

Mix 5g (0. 037mole) of methyl benzoate and 15 mL of absolute ether in a separatory funnel, cool the flask containing phenylmagnesium bromide solution briefly in an ice bath, remove the drying tube, and insert the stem of the separatory funnel into the top of the condenser. Run in the methyl benzoate solution slowly with only such cooling as is required to control the mildly exothermic reaction, which affords an intermediate addition compound that separates as a white solid. Replace the calcium chloride tube, swirl the flask until it is at .room temperature and the reaction has subsided .The reaction is then completed by either refluxing the mixture for one half hour, or stopping the flask with the calcium chloride tube and letting the mixture stand overnight (subsequent refluxing is then unnecessary).

Pour the reaction mixture into a 250 mL Erlenmeyer flask containing 50 mL of 10 % sulfuric acid and about 25 g of ice and use both ordinary ether and 10 % sulfuric acid to rinse the flask. Swirl well to promote hydrolysis of the addition compound;