Grignard Reagent Reactions

1
Grignard Reagent / Reactions
Preparation of a Grignard Reagent
(Phenylmagnesiumbromide) and reaction with Carbon
Dioxide to form Benzoic Acid through an
Electrophilic Addition reaction

• References
• Pavia - p. 303 309 313 314
• Schornick
• http//classweb.gmu.edu/jschorni/chem318

2
Grignard Reagent / Reactions

• Synthesis of Benzoic Acid Electrophilic
  Addition reaction between a freshly prepared
  Grignard Reagent (Organomagnesium Halide) acting
  as the Nucleophilie (Lewis Base) and the Carbonyl
  group of Carbon Dioxide acting as the positively
  charged Electrophile
• The Grignard Reagent must be prepared and reacted
  with the solid Carbon Dioxide before the end of
  the day
• Sonication of mixture of Magnesium, Bromobenzene
  Ether
• Reaction between Grignard Reagent and Carbon
  Dioxide
• Hydrolysis of Acid Salt
• Product Separation Liquid/Liquid Extraction
• Precipitation
• Vacuum Filtration
• Product Purification Recrystallization
• Product Verification Melting Point

3
Grignard Reagent / Reactions

• Laboratory Report
• Synthesis Experiment
• Mass, Moles, Molar Ratio, Limiting Reagent,
  Theoretical Yield
• Procedures
• Title Concise Simple Distillation, Dry Sample,
  IR Spectrum, etc.
• Materials Equipment (2 Columns in list (bullet)
  form)
• Note include all reagents principal
  equipment used
• Description
• Descriptions must be detailed, but concise
• Use list (bullet) form
• Use your own words (dont copy book)

4
Grignard Reagent / Reactions

• Laboratory Report (Cont)
• Results Neat, logically designed template to
  present results
• Summary
• Paragraph summarizing experimental observations,
  computed results, and principal absorptions from
  IR NMR
• Analysis Conclusions
• Limiting reagent
• Discuss the reaction in context with the results
  you obtained what evidence do you have to
  indicate you got the intended product?
• Yield How could the experimental process be
  improved?

5
Grignard Reagent / Reactions

• Background
• Grignard Reagents, aka, Organomagnesium Halides
• Prepared by Reaction of an Organic Halide and
  Magnesium metal turnings, usually in an Ether
  solvent
• Relative Reactivity of Halides is important
• RI gt RBr gt RCl gt RF
• Very few Organomagnesium Fluorides are produced.
• Aryl Grignards are more easily prepared from Aryl
  Bromides and Aryl Iodides than Aryl Chlorides
• Grignard Reagents are seldom isolated, but they
  can be stabilized briefly in Ether solution and
  then used in the preparation of other compounds
• The preparation of a Grignard Reagent usually
  produces a high yield (85 95)

6
Grignard Reagent / Reactions

• Reactions

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7
Grignard Reagent / Reactions

• Reactions (Cont)
• The Alkyl portion of the Grignard reagent behaves
  as if it had the characteristics of a Carbanion
  the carbon atom bears a formal negative charge
• The Magnesium portion bears the positive charge.
• Grignard Reagent, thus, acts as a Strong Base and
  is a strong Nucleophile that acts as a Lewis Base
  donating an Electron pair to the positively
  charged Electrophile
• Especially useful in Nucleophilic Addition
  reactions of the Carbonyl group, which has
  electrophilic character where the positive charge
  of the carbonyl carbon atom is attractive to the
  Grignard Nucleophile

8
Grignard Reagent / Reactions

• Reactions (Cont)

Grignard CO2 to produce Benzoic Acid
Grignard Ketone to Produce Tertiary Alcohol
9
Grignard Reagent / Reactions

• Reactions (Cont)

Grignard Aldehyde to Produce Secondary Alcohol
Grignard Formaldehyde to Produce Primary Alcohol
10
Grignard Reagent / Reactions

• Grignard with Benzophenone to form
  Triphenylmethanol

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11
Grignard Reagent / Reactions

• Grignard with Dry Ice (Solid CO2 ) to form
  Benzoic Acid Salt, which is then hydrolyzed with
  HCL to form Benzoic Acid
• Todays Experiment

12
Grignard Reagent / Reactions

• Preparation of Benzoic Acid
• Experimental Precautions
• The Grignard reaction is very reactive. It must
  be used in a reaction as soon as it is created.
• Moisture must be avoided. Water acts as an Acid
  in this reaction thus the acid proton competes
  for the Magnesium in an acid base reaction.
• Therefore, moisture could result in the
  formation of a Hydrocarbon R-H
• RMgX HOH ? R-H HO-
  Mg2 X-
• Stronger Stronger Weaker Weaker
  Base Acid Acid Base
• Anhydrous Ether is used to stabilize the Grignard

13
Grignard Reagent / Reactions

• Use as little heat as possible to avoid formation
  of Biphenyl

Note The Biphenyl produced from excessive heat
is not the same as the Hydrocarbon formed in an
acid - base reaction above.

• The Organic Ether layer contains Benzoic Acid,
  Biphenyl and Inorganic Salts.

• The Benzoic Acid is separated from the Biphenyl
  by converting it to an aqueous soluble form by
  washing with NaOH

14
Grignard Benzoic Acid Procedure

• Procedure (Ultrasonic Bath Version)
• NOTE Water/Moisture must be avoided - all
  glassware must be dry
• Weigh about 0.5g of Magnesium (Mg) to the nearest
  0.001g and place the Magnesium in a large
  oven-dried Centrifuge Tube.
• Obtain a vial of Bromobenzene (approximately 2.1
  mL) and weigh it to the nearest 0.001g.
• Transfer the Bromobenzene to the Centrifuge tube
  containg the Magnesium filings.
• Reweigh the empty vile to obtain the net mass of
  Bromobenzene.

15
Grignard Benzoic Acid Procedure

• Procedure (Ultrasonic Bath Version) (Cont)
• Add about 10 mL of Anhydrous Ether to the
  centrifuge tube containing the Bromobenzene and
  Magnesium.
• Add a very small piece of Iodine to the
  mixture.
• Tighten the screw cap and gently swirl the
  mixture.
• Loosen the screw cap and place the Centrifuge
  tube in the Sonication Bath to stimulate the
  reaction. The solution will begin to turn
  brownish/gray as the reaction proceeds
• After about 5 minutes in the Sonication bath,
  remove the Centrifuge tube, tighten the cap, and
  gently swirl the mixture to insure maximum
  exposure of the Magnesium filings to the
  Bromobenzene.

16
Grignard Benzoic Acid Procedure

• Procedure (Ultrasonic Bath Version) (Cont)
• Loosen the cap and replace the Centrifuge tube in
  the Sonication bath for about 50 minutes or so.
• Remaining in the Hood, remove the Centrifuge tube
  containing the Grignard reaction mixture from the
  Sonication Bath and pour the solution over
  approximately 10 g of Dry Ice (solid CO2) in a
  labeled 150 mL beaker. Leave the unreacted
  Magnesium particles in the Centrifuge tube.
• Rinse the Centrifuge tube with a few mL of Ether
  and add the Ether to the beaker containing the
  product.
• Place the labeled uncovered beaker in the hood
  until next lab.
• During the next lab you will hydrolyze, isolate
  and purify the product - Benzoic Acid

17
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure
• Slowly add about 8 mL of 6 M HCl to the beaker
  containing the product from last week
• Use the small spatula to stir and scrape the
  mixture until the solids are mostly in suspension
  in the HCL
• The mixture may show some reaction activity, such
  as frothing and increased temperature, which
  might include the reaction between any remaining
  Magnesium and the HCl to evolve Hydrogen
• If necessary, use a medicine dropper and small
  amounts of addition HCL to wash the sides of the
  beaker

18
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• When the reaction is complete and the solids
  particles are suspended in a relatively clear
  liquid, add 15 mL of Anhydrous Ether to the
  beaker and stir until the solids go into solution
• There should be two distinct layers in the beaker
• Transfer liquid mixture to a separatory funnel
• Rinse the sides of the beaker with additional
  Ether and transfer to the Separatory Funnel
• Repeat the Ether rinse as necessary

19
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Note The Benzoic Acid (and any by-product
  Biphenyl) is soluble in the Ether
• The inorganic compounds (MgX2) are
  soluble in the aqueous phase
• Separate organic phase from aqueous phase
• Stopper the separatory funnel and secure the
  stopper with your finger
• Shake the mixture gently, invert funnel, and open
  stopcock slowly to vent any gas
• Allow the layers to separate

20
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Discard the aqueous (lower) phase into a separate
  waste beaker and put aside
• Liquid / Liquid Extraction with Distilled Water
• Add 5 mL distilled water to the organic solution
• Shake the mixture gently, invert funnel, and
  open stopcock slowly to vent any gas
• Allow the layers to separate
• Discard aqueous phase
• Repeat steps a-d with an additional 5 mL
  distilled water
• Dispose of the organic phase at the end of the
  experiment

21
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Liquid / Liquid Extraction with Sodium Hydroxide
• To the organic layer, which contains the Benzoic
  Acid and by-product Biphenyl, add 5 mL 5 NaOH.
• Shake the mixture gently, invert funnel, and open
  stopcock slowly to vent any gas
• Allow the layers to separate
• Drain aqueous (bottom) layer into clean 100 ml
  beaker
• Repeat steps a-d with another 5 ml 5 Sodium
  Hydroxide
• Repeat steps a-d a 3rd time with 5 Sodium
  Hydroxide

22
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Note The Sodium Hydroxide converts the Benzoic
  Acid to the water-soluble Sodium Benzoate salt
• The Sodium Benzoate is thus transferred to
  the aqueous phase
• Discard the organic Ether layer into the waste
  jar in hood.
• Gently heat the combined aqueous extracts (about
  15 mL) containing the Benzoic Acid salt on a hot
  plate (set setting at 4-5) for about 10 minutes
  to remove any residual Ether, which is slightly
  soluble in water. Small bubbles will boil off.
• Note Dont overheat heat just enough to boil
  off Ether

23
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Cool the solution to room temperature
• Add 10.0 mL 6 M HCl and stir (a precipitate forms
  in the beaker.)
• Cool mixture in ice bath.
• Vacuum filter the product using a Buchner Funnel.
• Wash crystals on the filter 2 times with 5 mL
  cold water

24
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Recrystallize product from hot (near boiling)
  water.
• Transfer solid from Buckner Funnel to 100-150 mL
  beaker using cold Distilled Water to insure
  complete transfer
• Add an additional 15 mL of distilled water to
  mixture
• Heat solution to just below boiling point,
  swirling the mixture occasionally until all
  solids go into solution
• Check with instructor if you feel additional
  Distilled Water is needed to effect total solution

25
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Recrystallize Product (Cont)
• Allow solution to cool slowly to room temperature
  effecting recrystallization of the purified
  product leaving any dissolved impurities in
  solution.
• If the cooled solution does not appear to have
  sufficient water to suspend the purified crystals
  as a slurry, add 10 ml of Distilled Water,
  redissolve the mixture, and cool again slowly to
  room temperature.
• After mixture has reached room temperature, place
  the beaker in an ice/water bath for about a minute

26
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Cont)
• Clean and dry the Buckner Funnel, add a new
  filter, and weigh it to the nearest 0.001g
• Assemble the Buckner Funnel and vacuum filter the
  product
• Wash crystals on the filter with 5 mL cold
  Distilled Water
• Dry the product in the pre-weighed upper part of
  the Buckner Funnel for 1 Week

27
Grignard Benzoic Acid Procedure

• Week Two - Hydrolysis Purification of Benzoic
  Acid
• Procedure (Hydrolysis) (Cont)
• Weigh the dried product and Buckner Funnel to the
  nearest 0.001g
• Compute the mass of product (Benzoic Acid) by
  difference
• Determine the yield
• Determine the melting point of the product
• (MP of Benzoic Acid 122.4oC)
• NOTE If little or no yield was obtained, see
  next slide

28
Grignard Benzoic Acid Procedure

• The Experiment was a Bust!!
• Occasionally students get little or no yield for
  the Grignard / Benzoic Acid experiment
• The principal reason for this is the failure of
  the original reaction between Bromobenzene and
  Magnesium to form the Grignard Reagent
• There are two main indications of a failed
  reaction
• No precipitate forms upon the addition of the 6 M
  HCL to the aqueous NaOH washings
• The precipitate largely disappears after the
  first vacuum filtration

29
Grignard Benzoic Acid Procedure

• The Experiment Was a Bust
• In order to give the students full exposure to
  the complete procedure, the following steps
  should be performed
• Weigh out to the nearest 0.001 g approximately 3
  grams of Benzoic Acid supplied by the instructor
• Dissolve the Benzoic Acid in 15 mL Anhydrous
  Ethyl Ether.
• Wash the Ether phase 3 times with 5 mL 5 NaOH as
  before combining the 3 aqueous washings in a
  beaker
• Discard the Ether

30
Grignard Benzoic Acid Procedure

• The Experiment Was a Bust
• Gently heat the NaOH solution, approximately 15
  mL, to drive off any residual Ether
• Cool the solution to room temperature
• Add 10 mL HCL, as before, and place in water-ice
  bath.
• A precipitate should form
• Separate the precipitate by vacuum filtration
• Wash product on filter with 5 mL cold water
• Recrystallize the product from hot distilled
  water
• Vacuum Filtration
• Dry the Product
• Determine the Melting Point

31
Grignard Benzoic Acid Procedure

• Note Lab procedure sequence vs. Lab report
  procedure sequence
• The writing of the laboratory report does not
  always follow the exact physical sequence of
  procedures used in the lab.
• The measurement of the Mass of a reagent may be
  immediately followed by an apparatus set-up or
  transfer of the sample to a piece of apparatus.
• This same process could be repeated with the
  second or a third reagent used in the experiment.
  
• In your report, however, all determinations of
  Mass are followed immediately by all calculations
  that can be based on the Mass values, i.e. moles,
  molar ratios, limiting reagent, theoretical
  yield, etc.

32
Grignard Benzoic Acid Procedure

• In the Grignard experiment the following
  calculations are carried out before any procedure
  dealing with the mixing of the reagents and
  subsequent processing of the reaction mixture.
• Mass of first reagent
• Mass of second reagent
• Moles of both reagents (1 procedure)
• Set up Balanced Stoichiometric Equation
• Determine Molar Ratio
• Determine Limiting Reagent
• Compute Theoretical Yield

33
Grignard Benzoic Acid Procedure

• Use the following table form (handout) as a
  substitute for the table in the Lab Manual Data
  Report.

BalancedEquation Mol Wgt Grams Moles
34
Grignard Benzoic Acid Procedure
Hydrolysis of Benzoic Acid Salt
8 mL 6 M HCL20 mL Anhydrous EtherSeparatory
Funnel (Shake Gently)
Ether Layer
Aqueous Layer
Benzoic Acid Biphenyl
Inorganic Salts (Discard)
Add 5 mL 5 NaOH
Aqueous Layer
(Repeat 3 Times)
Biphenyl (Discard)
Soluble Benzoic Acid Salt(Trace of Ether)
Heat on Hot Plate in Hood to Drive off Ether Cool
to Room TemperatureAdd 10 mL 6 M HCl