Transcript Stereoselective Reduction of Ketones with Sodium Borohydride

The Grignard Synthesis
Miniscale Synthesis of Triphenylmethanol from Ethyl Benzoate
MgBr
Organic Chemistry Lab II, Spring 2010
Dr. Milkevitch
March 29 & 31, 2010
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
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
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
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
Br
MgBr
C H3C H2O C H2C H3
+ Mg(s)
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
Br

Mg

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
Closeup: Grignards
Br
O

Mg

O
Reaction of Grignards: Today’s Experiment
Part 1: Formation of the Grignard Reagent
Br
MgBr
C H3C H2O C H2C H3
+ Mg(s)
Part 2: First Reaction with Ethyl Benzoate

MgBr
O
C
O C H2C H3

ether
O MgBr
C
O C H2C H3
Reaction of Grignards: Part 2
OMgBr
O
C
C
OCH2CH3
Benzophenone
(not isolable)
Reaction with 2nd Equivalent of
Grignard Reagent
O
MgBr
C
Benzophenone
ether
O MgBr
OH
+ H 2O
triphenylmethoxymagnesium bromide
triphenylmethanol
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!!!!!!!!
Reaction Setup
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…..
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
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