Grignard Reagent / Reactions
References: Slayden – p. 99 - 102 Pavia – p. 303 – 309; 313 – 314 Schornick
http://classweb.gmu.edu/~jschorni/chem318
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Preparation of a Grignard Reagent (Phenylmagnesiumbromide) and reaction with Carbon Dioxide to form Benzoic Acid through an Electrophilic Addition reaction
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 (Ether acts as solvent and Grignard stabilizer) 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
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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 (don’t copy book)
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Grignard Reagent / Reactions Laboratory Report: (Con’t)
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?
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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 > RBr > RCl > 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%)
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Grignard Reagent / Reactions Reactions:
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Grignard Reagent / Reactions Reactions (Con’t):
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 a 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
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Grignard & Ketone to Produce Tertiary Alcohol
Grignard & CO2 to produce Benzoic Acid
Grignard Reagent / Reactions Reactions (Con’t):
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Grignard & Aldehyde to Produce Secondary Alcohol
Grignard & Formaldehyde to Produce Primary Alcohol
Grignard Reagent / Reactions Reactions (Con’t)
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Grignard Reagent / Reactions Grignard with Benzophenone to form
Triphenylmethanol
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Grignard Reagent / Reactions
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Grignard with Dry Ice (Solid CO2 ) to form Benzoic Acid Salt, which is then hydrolyzed with HCL to form Benzoic Acid
Today’s Experiment
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
R:MgX + H:OH R-H + HO- + Mg+2 + X-
Stronger Stronger Weaker Weaker Base Acid Acid Base
Anhydrous Ether is used to stabilize the Grignard
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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
Note: The Biphenyl produced from excessive heat is not the same as the Hydrocarbon formed in an acid - base reaction above.
Grignard Reagent / Reactions Use as little heat as possible to avoid formation of Biphenyl
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Grignard Benzoic Acid Procedure Procedure (Ultrasonic Bath Version)
NOTE: Water/Moisture must be avoided:
“All glassware must be “dry”
Weigh a little more than 0.5g of Magnesium (Mg) (MW – 24.31) to the nearest 0.001 g and place the Magnesium in a large oven-dried Test Tube or Centrifuge Tube
Obtain a vial of Bromobenzene (MW – 157.01) and weigh it to the nearest 0.001g
Transfer the Bromobenzene to the test tube containing the Magnesium filings
Reweigh the empty vile to obtain the net mass of Bromobenzene
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Grignard Benzoic Acid Procedure Procedure (Ultrasonic Bath Version) (Con’t)
Add about 10 mL of Anhydrous Ether to the test tube containing the Bromobenzene and Magnesium
Add a very small piece of “Iodine” to the mixture
Add a cotton ball to the top of the test or loosely screw a cap on the Centrifuge tube (if used)
Place the 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 tube and gently swirl the mixture to insure maximum exposure of the Magnesium filings to the Bromobenzene
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Grignard Benzoic Acid Procedure Procedure (Ultrasonic Bath Version) (Con’t)
Replace the tube in the Sonication bath for about 40 minutes or so
Remaining in the Hood, remove the tube containing the Grignard reaction mixture from the Sonication Bath
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 tube with a few mL of Ether and add the Ether to the beaker containing the product
Store labeled beaker containing your product in the hood until next lab session
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Grignard Benzoic Acid Procedure Week 2 - Hydrolysis & Purification of Benzoic Acid
Slowly add about 10 mL of 6 M HCl to the beaker containing the product
Stir and scrape contents of the beaker with the spatula until the solids and liquid form a uniform mixture
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
add 10 mL Methyl –t-Butyl Ether to the beaker Continue to stir and scrape the mixture with a spatula
If solids still persist in the solution, use a medicine dropper and add small additional amounts of Methyl-t-Butyl Ether and stir
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Grignard Benzoic Acid Procedure Week 2 - Hydrolysis & Purification of Benzoic Acid
If some solids are still insoluble in either the ether layer or the aqueous layer, add small amounts of the 6 M HCl and stir.
Keep track of the volume of HCL added
There should be two distinct clear layers in the beaker
Note: The Benzoic Acid (and any by-product Biphenyl) is soluble in the Ether
The inorganic compounds (MgX2) are soluble in the aqueous phase
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic Acid
Liquid/Liquid Extraction:
Transfer the mixture to a 125 mL Separatory funnel
Rinse sides of beaker with additional ether and add to Separatory funnel
Insert stopper and secure it with your finger
Shake the mixture gently, invert funnel, point stem up and away from your face and slowly open stopcock to vent any gas
Allow the layers to separate (remove stopper)
Discard the aqueous (lower) phase into a separate waste beaker and put aside
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic
Acid
Liquid / Liquid Extraction with Distilled Water (Con’t)
● Add 5 mL distilled water to the organic solution
● Shake the mixture gently, invert the funnel, and slowly open stopcock to vent any gas
● Allow the layers to separate (remove stopper)
● Discard aqueous phase
● Repeat the liquid/liquid extraction with an additional 5 mL of distilled water
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic Acid
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 pointing away from your face, and slowly open stopcock to vent any gas
Allow the layers to separate (remove stopper) Drain aqueous (bottom) layer into clean, dry
100 ml beaker Repeat liquid/liquid extraction with another 5
ml 5% Sodium Hydroxide, draining bottom layer into your beaker
Repeat liquid/liquid extraction a 3rd time with5% Sodium Hydroxide
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic
Acid
Liquid / Liquid Extraction with Sodium Hydroxide (con’t)
Note: The Sodium Hydroxide converts the Benzoic Acid to the water-soluble Sodium
Benzoate salt
The Sodium Benzoate is thus transferredto the aqueous phase
Discard the organic Ether layer into the waste jar in the hood
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic
Acid
Remove Excess Ether
Gently heat the combined aqueous extracts (about 15 mL) containing the Benzoic Acid salt on a hot plate (set setting at 3-4) until formation of small bubbles (Ether) ceases. This removes any residual Ether, which is slightly soluble in water
Note: Don’t overheat; heat just enough to boil off Ether
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic Acid
Cool the solution to room temperature
Add 10.0 mL 6 M HCl and stir (a precipitate forms in the beaker)
Note: If little or no precipitate forms add an additional 3 ml HCL. If no precipitate forms inform instructor
Cool mixture in water/ice bath
Vacuum Filtration
Vacuum filter the product using a Buchner Funnel
Wash crystals on the filter 2 times with 5 mL cold distilled water
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic Acid
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
Note: The Benzoic Acid solution gives off a strong pungent vapor; avoid proximity to nose
Check with instructor if you feel additional Distilled Water is needed to effect total solution
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic
Acid
Recrystallize Product (Con’t)
Allow solution to cool slowly to room temperature effecting recrystallization of the purified product (Soluble impurities remain 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
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Grignard Benzoic Acid Procedure Week Two - Hydrolysis & Purification of Benzoic
Acid
2nd Vacuum Filtration
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 a pre-weighed weighing tray in the class drawer until next week
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Grignard Benzoic Acid ProcedureWeek Two - Hydrolysis & Purification of Benzoic Acid
Weigh the dried product & weighing tray 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
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Grignard Benzoic Acid ProcedureThe 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
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Grignard Benzoic Acid ProcedureThe 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
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Grignard Benzoic Acid ProcedureThe Experiment Was a Bust
Gently heat the NaOH solution, approximately 15 mL, to drive off any residual EtherCool the solution to room temperatureAdd 10 mL HCL, as before, and place in water-ice bathA precipitate should formSeparate the precipitate by vacuum filtrationWash product on filter with 5 mL cold waterRecrystallize the product from hot distilled waterVacuum FiltrationDry the ProductDetermine the Melting Point
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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.
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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 (HCL – Vol & Density)
Moles of both reagents (1 procedure)
Set up Balanced Stoichiometric Equation
Determine Molar Ratio
Determine Limiting Reagent
Compute Theoretical Yield
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BalancedEquation
Mol Wgt
Grams
Moles
CO2Mg Ether HCl MixedSalts
Grignard Benzoic Acid Procedure Use the following table form (handout) as a
substitute for the table in the Lab Manual Data Report.
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Hydrolysis ofBenzoic Acid Salt
Ether Layer Aqueous Layer
Benzoic Acid Biphenyl
Inorganic Salts (Discard)
Add 5 mL 5% NaOH
Biphenyl (Discard) Soluble Benzoic Acid Salt(Trace of Ether)
(Repeat 3 Times)
Heat on Hot Plate in Hood to Drive off Ether
Cool to Room TemperatureAdd 10 mL 6 M HCl
8 mL 6 M HCL20 mL Anhydrous Ether
Separatory Funnel (Shake Gently)
Aqueous Layer
Grignard Benzoic Acid Procedure
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