The Grignard Synthesis Miniscale Synthesis of Triphenylmethanol from Ethyl Benzoate

1. The Grignard SynthesisMiniscale Synthesis of Triphenylmethanol from Ethyl Benzoate Organic Chemistry Lab II, Spring 2010 Dr. Milkevitch March 29 & 31, 2010

2. Today’s Experiment • Take a look at some very important chemistry • Prepare a Grignard Reagent • Group of very important synthetic reagents • React it with an ester • Make an alcohol • Purpose: • Learn about organometallic reagents • Prepare one: phenylmagnesium bromide • Accomplish a reaction in low water conditions • Use the Grignard reagent to make an alcohol

3. Background • Organometallic Reagents • Extremely useful group of organic compounds • Allow for some interesting chemistry to take place • Their use: • Make carbon-carbon bonds • Grignard Reagents • Developed by Victor Grignard in the turn of the 20th century • Discovered: • Organic halides and magnesium form organomagnesium reagents • Called organometallic compounds

4. Organometallic Compounds • Contain metal-carbon bonds • Many examples in chemistry • In Organic Chemistry: • 2 main “classes” of organometallic compounds • Organomagnesium reagents (“Grignards”) • Organolithium reagents • Usefulness of these compounds • The carbon atoms is nuclophilic • Widely used to make new carbon-carbon bonds • Used to attach carbonyl groups of aldehydes, ketones, and esters

5. Formation of the Reagent • Formed by reaction of an alkyl halide with magnesium metal • Reaction commonly done in ether solvents • Under very low water conditions

6. Result: Grignard Reagent • Carbon-magnesium bonds are polar • Carbon atom has a partial negative charge • Makes the carbon nucleophilic • Its going to “look” for a positive charge • Capable of attacking electrophilic carbons • Such as carbons in carbonyl groups

7. Function of the Ether Solvent • Grignard reagents • Commonly formed in ether solvents • They stabilize the Grignard reagent • Protect it from oxidation • Must use anhydrous solvents • Grignards are very sensitive reagents • Grignards are strong bases • Will react with any reagent with an acidic proton • Water • Alcohols • Carboxylic acids • Destroys the reagent

8. Closeup: Grignards

9. Reaction of Grignards: Today’s Experiment Part 1: Formation of the Grignard Reagent

10. Part 2: First Reaction with Ethyl Benzoate ether

11. Reaction of Grignards: Part 2 (not isolable)

12. Reaction with 2nd Equivalent of Grignard Reagent

13. Procedure I • All glassware must be dry • Dried in the 120 deg C oven overnight • Already done! • RB flask, stir bar, condenser, drying tube 125 ml erlenmeyer flask, Claisen adaptor, grad cylinder, several small erlenmeyer flasks • Remove from oven, allow to cool, assemble according to diagram on next slide • CAUTION: It will be hot!!!!!!!!

14. Reaction Setup

15. Procedure II • Allow glassware to cool before assembling • Weigh out 960 mg of Mg turnings • Place in RB flask with stir bar • Assemble apparatus • In the addition funnel • Place 4.2 ml of dry bromobenzene • 20 ml of anhydrous ethyl ether • Swirl to mix • Have a ice bath standing by to cool reaction if necessary • Add about 1 ml of bromobenzene/ ether to the RB flask • Open stopcock, let ~ 1 ml of bromobenzene /ether to go into the flask • Turn on cooling water in the condenser • Look for cloudiness/ bubbles on the metal surface • Indicates the reaction has begun! • If after about 5 min you don’t see anything • Add a small crystal of iodine • Wait another 5 min, if again no reaction occurs…..

16. Procedure III • Ask for assistance • I will come over and work some type of magic in the attempt to get your reaction started • I won’t tell you what I’m doing, because I’m not sure what I will do to get your reaction going • I’ll giggle it around and look at it a lot, and say “hmmmm” a great deal • And your reaction will probably, eventually start • We hope! • In all likelihood, it will eventually begin • Once the reaction has started, turn on the stirrer • Add the remainder of the bromobenzene/ ether solution dropwise to maintain a steady reflux • Addition should take ~ 45 min • When addition is done, add 3 ml of ether to the addition funnel • To rinse down any residual bromobenzene • Add this rinse to the RB flask • Fit the flask with a heating mantle • Reflux the mixture gently for 15 min • When the 15 min is over, most of the Mg should be gone • But its not likely • Proceed with the experiment

17. Procedure IV • Add 1.41 ml of ethyl benzoate to 10 ml of anhydrous ether • Place this in the addition funnel • Add the ethyl benzoate solution to the Grignard reagent at rate that will maintain a steady reflux • After all the ethyl benzoate has been added • Reflux the solution (with stirring) for 30 min • When complete, remove from heat and allow to cool • Parafilm flask and set it aside until the next lab period • DO NOT USE A GLASS STOPPER • Place flask inside a beaker • Place in the hood until next week