Experiment 18:

THE GRIGNARD REACTION

OH

CH3CH2CH2CH2BrMg

etherCH3CH2CH2CH2MgBr

C

CH3

CH3CH2CH2CH2

CH3

OMgBr C

CH3

CH3CH2CH2CH2

CH3

CH3C

O

CH3

H3O+

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.

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.

CHEMICAL EQUATION

OH

CH3CH2CH2CH2BrMg

etherCH3CH2CH2CH2MgBr

C

CH3

CH3CH2CH2CH2

CH3

OMgBr C

CH3

CH3CH2CH2CH2

CH3

CH3C

O

CH3

H3O+

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+.

CMgX+

-

MECHANISM

2. Nucleophilic addition of butyl group to acetone produces a tetrahedral intermediate…

3….which reacts with water when aqueous HCl is added, undergoing hydrolysis to form the product alcohol.

+ Mgether

Grignard reagent(butyl magnesium bromide)

CH3CH2CH2CH2Br CH3CH2CH2C

MgBr

CH3C CH3

O

CH3CH2CH2CH2

CH3C

O

CH3

CH2CH2CH2CH3

OH H

CH3C

O

CH3

CH2CH2CH2CH3

H

+

HOMgBr

n-BUTYL BROMIDE

2-METHYL-2-HEXANOL

H

H

CH3CH2CH2C MgBr

H

H

C

H3C CH3

OMgBr

MgBr

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.

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.

MgBr+

O

H

H

+ HOMgBr

butyl magnesium bromide butane

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.

EXPERIMENTAL PROCEDURE(Synthesis of Grignard reagent…)

iron ring

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.

Keck clips

CaSO4 drying tube in adapter

EXPERIMENTAL PROCEDURE

(Synthesis of alcohol product…)

iron ring

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.

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.

Table 18.1

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!

Compound GC Retention Times (min) Area

PercentAdjusted

Area Percent

StandardSample

methanol ---acetone

n-butyl bromide2-methyl-2-

hexanoloctane ---

Product Analysis(IR Spectroscopy)

Table 18.2

FunctionalGroup

Base Values

n-butylbromide

2-methyl-2-

hexanol

Frequency(cm-1)

Frequency(cm-1)

Frequency(cm-1)

OH stretch 2500-3300

sp3 CHstretch 2850-3000

C-O stretch

1000-1200

C-Br stretch

500-700

• IR spectra available on p. 157, 158 of the lab manual!• In discussion, only refer to frequencies which indicate a CONVERSION to product!

Product Analysis(1H-NMR Spectroscopy)

Br CH2 CH2 CH2 CH3

1 2 3 4

H3CC

CH3

CH2 CH2 CH2 CH3

OH1

2

1

3 4 5 6

Product Analysis(13C-NMR Spectroscopy)

NMR solvent

NMR solvent

C1

29

H3CC

CH3

CH2 CH2 CH2 CH3

OH1

2

1

3 4 5 6

Br CH2 CH2 CH2 CH3

1 2 3 4

Table 18.3

Br CH2 CH2 CH2 CH3

1 2 3 4

H3CC

CH3

CH2 CH2 CH2 CH3

OH1

2

1

3 4 5 6

n-butylbromide(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!

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!

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.

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.

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 bromideAcetone

Diethyl etherHydrochloric acid

Methanol2-methyl-2-

hexanol

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.