1. Experiment 18:
THE GRIGNARD REACTION

2. Objectives:
To synthesize a 3o alcohol from an alkyl halide and a ketone using a Grignard reaction.
To purify product using a liquid extraction method.
To determine purity using GC analysis.
To characterize starting materials and products using IR, 1H-NMR, and 13C-NMR spectra.

3. Before coming to lab… Review the following techniques:
Extraction
Drying organic solvents with MgSO4
Preparing GC samples
You will be expected to perform these will little review, as you learned these techniques in the first semester lab.

4. CHEMICAL EQUATION

5. MAKING THE GRIGNARD REAGENT
Organic halides react with magnesium metal in diethyl ether or THF to yield an organomagnesium halide: RMgX
DIETHYL ETHER
R-X + Mg > R-Mg-X
or THF
Where R= 1o, 2o, or 3o alkyl, aryl or alkenyl
X= Cl, Br, I
The C-Mg bond is a highly polar covalent bond. The carbon atom is both nucleophilic and basic making it very reactive with a wide variety of E+.

6. MECHANISM
3….which reacts with water when aqueous HCl is added, undergoing hydrolysis to form the product alcohol.
1. The Lewis acid Mg2+ forms an acid-base complex with the basic oxygen atom of the ketone, making the carbonyl group a better acceptor.
2. Nucleophilic addition of butyl group to acetone produces a tetrahedral intermediate…

7. WHEN THE GRIGNARD REAGENT MEETS WATER…
Since the carbon atom of a Grignard reagent is so nucleophilic and basic, it reacts with proton donors (Brönsted acids) such as H2O, ROH, RCOOH, RNH2 to yield hydrocarbons.
This makes it extremely important to keep the reaction flask and solvent completely dry of water.

8. OVERVIEW
Heat alkyl halide, magnesium turnings, and ketone in diethyl ether under reflux to synthesize intermediate.
Hydrolyze intermediate with HCl to produce neutral product.
Purify product by extraction.
Prepare GC sample.
Analyze product using GC to identify and determine purity.

9. EXPERIMENTAL PROCEDURE (Synthesis of Grignard reagent…)
Place Mg turnings in 50mL flask and place a CaSO4 tube in the top IMMEDIATELY!
Clamp flask to ring stand and set up remainder of reflux with addition apparatus.
Start reaction with a small amount of n-butylbromide and ether by scratching Mg surface and stirring with glass rod.
Add remaining n-butylbromide and ether to sep funnel.
Add to reaction mixture dropwise.
CaSO4 drying tube in adapter
Keck clips

10. EXPERIMENTAL PROCEDURE (Synthesis of alcohol product…)
Add acetone/ether to sep funnel.
Add to reaction mixture dropwise.
Cool reaction flask in water bath.
Transfer cooled liquid to 125 mL Erlenmeyer flask.
Add an ice cube and NH4Cl.

11. EXPERIMENTAL PROCEDURE (Purification…)
Set up an extraction apparatus.
Transfer the liquid from the flask to the funnel.
Extract with 5%HCl, 10% NaHCO3, and Sat. NaCl.
Transfer organic layer to a 50 mL flask and dry over MgSO4.
Transfer dried organic liquid to a beaker.
Submit a GC sample.

12. GC Retention Times (min)
Table 18.1
Compound
GC Retention Times (min)
Area Percent
Adjusted
Standard
Sample
methanol
---
acetone
n-butyl bromide
2-methyl-2-hexanol
octane
Record retention times for ALL peaks in standard chromatogram!
Record retention times and area % for ALL peaks present in sample chromatogram!
Calculate AA% for REACTANTS AND PRODUCT only!

13. Product Analysis (IR Spectroscopy)

14. Table 18.2 IR spectra available on p. 157, 158 of the lab manual!
Functional
Group
Base Values
n-butyl
bromide
2-methyl-2-
hexanol
Frequency
(cm-1) OH
stretch
sp3 CH
C-O stretch
C-Br stretch
IR spectra available on p. 157, 158 of the lab manual!
In discussion, only refer to frequencies which indicate a CONVERSION to product!

15. Product Analysis (1H-NMR Spectroscopy)

16. Product Analysis (13C-NMR Spectroscopy)
NMR solvent C1
29d
NMR solvent

17. Table 18.3 n-butylbromide 2-methyl-2-hexanol
(reactant)
2-methyl-2-hexanol
(product)
Enter chemical shifts ONLY based on the spectra on page 157, 158.
In discussion, only refer to signals which indicate a CONVERSION to product!

18. SAFETY CONCERNS
Diethyl Ether is EXTREMELY flammable. Use extreme caution at all times!
Be sure to wear goggles at ALL times during this experiment!
GLOVES are available upon request!

19. WASTE MANAGEMENT
RECOVERED MAGNESIUM WASTE: Unreacted magnesium & water rinse.
LIQUID AQUEOUS WASTE:
Aqueous extracts and washes.
LIQUID ORGANIC WASTE:
Crude Alcohol product.
MgSO4 WASTE:
Magnesium sulfate.

20. CLEANING Rinse condenser and Claisen adapter with wash acetone only.
Clean all other glassware with soap, water, brush, and rinse with wash acetone.
Leave all ground glass jointware in lab hood for inspection. DO NOT place any in lab drawer.
DO NOT return any glassware to lab drawer dirty or wet.

21. LABORATORY NOTEBOOK (Pre-lab)
OBJECTIVE (Must clearly state…)
What compounds will be made and how
How the compounds will be purified
How the identity and purity of the product will be determined
CHEMICAL EQUATION
Include the balanced chemical equation from top of p.153.
TABLE OF PHYSICAL DATA (Complete the following table using a site listed on WWW Links ONLY. Wikipedia is unacceptable!)
REFERENCE TO PROCEDURE (Must include…)
full title including edition and authors
page numbers where actual procedure can be found
Compound
MW (g/mol)
bp(oC)
d (g/mL)
HAZARDS
n-butyl bromide
Acetone
Diethyl ether
Hydrochloric acid
Methanol
2-methyl-2-hexanol

22. LABORATORY NOTEBOOK (In-lab)
DATA/CALCULATIONS
Physical state and color of product
Theoretical yield calculation
GC vial slot #
Give one example of an adjusted area % calculation
EXPERIMENTAL PROCEDURE
In paragraph form, describe the procedure that you actually followed during the lab.
Paragraph must be written in PAST TENSE, PASSIVE VOICE.
Include any volumes or weights of chemicals used during the experiment.
Include any mistakes, accidents or observations if applicable.