Experiment 15:

SUBSTITUENT EFFECTS ON THE RATE OF

ELECTROPHILIC AROMATIC SUBSTITUTION

Objectives:

To explore how different substituent groups on an aromatic ring affect the rate and orientation of electrophilic aromatic substitution using a qualitative bromine test.

To determine directing ability of acetamide group using TLC analysis.

Before coming to lab…

Review these techniques:

TLC Analysis

Acid-base Extraction

CHEMICAL EQUATION• The progress of the bromination of an

aromatic ring can be followed easily by a color change.

• The more reactive the aromatic ring is, the faster the color will disappear.

G G

+ HBr+

Br

colorless colorless colorless

Br2

red

MECHANISM

CH2CH2CH3

Br Br

CH2CH2CH3

H

H

H

BrH

Br

CH2CH2CH3

H

Br

HBr+ +

An electron pair from the aromatic ring attacks Br2, forming a new C-Br bond…

…and leaving a nonaromatic, carbocation intermediate.

The carbocation intermediate loses H+, and the neutral substitution product forms as two electrons from the C-H bond move to regenerate the aromatic ring. HBr forms as a byproduct.

REACTIVITY OF AROMATIC RINGS

The substituent ALREADY ON the aromatic ring determines the position and rate of substitution of the second (INCOMING) electrophile.

We use the reactivity of BENZENE (no substituent) as a reference point.

REACTIVITY OF AROMATIC RINGS

If we use the reactivity of benzene (substituent = H) as a reference point, activating substituents are all electron donating groups, and their relative activation strengths are:

H < Phenyl < CH3 < NHCOCH3 < OCH3 < OH < NH2

Deactivating groups are electron withdrawing groups and their activities relative to hydrogen are:

NO2 < COR < CHO < I < Br < Cl < F < H

SUBSTITUENT EFFECTS

GENERALIZATIONS

Substituents in which the atom bonded to the ring has an unshared pair of electrons, with the exception of alkyl and phenyl groups, are ortho-para directing. All other substituents are meta directing.

All ortho/para directors are activators, with the exception of halogens. Halogens are ortho-para deactivators.

All meta directors are deactivators.

Alkyl and Phenyl groups are also ortho-para directing.

OVERVIEW React bromine solution with six

monosubstituted aromatic compounds.

Follow rate of reaction based on color change.

Neutralize and extract acetanilide product to purify compound for further analysis.

To analyze the bromoacetanilide product to identify product substitution.

SYNTHESIS

Place small amount of monosubstituted aromatic compound in small test tube.

Place test tubes in water bath. Add Bromine solution to each. Record the approximate amount

of time it takes for the solution to lose color.

Place in hot water bath if necessary to complete reaction.

After 1 hour, estimate the reaction order based on the relative amount of color lost.

Table 15.1

Compound

ethyl benzene

anisole acetanilide

phenol benzaldehyde

nitrobenzene

Structure

***Aromatic ring is given for each compound…remember to complete structure with appropriate substituent!***

OPA, OPD, or MD

***Identify each substituent as an ortho/para activator (OPA), ortho/para deactivator (OPD), or a meta deactivator (MD).***

Reaction Order

***Simply record the order that the reactions occurred. Actual reaction times are not required. 1=fastest 6=slowest! ***

PURIFICATION/ISOLATION

Once pale yellow, remove acetanilide tube.

Add deionized water to tube.

Add 5 drops of NaOH. Test pH using glass rod.

Repeat until the solution is basic.

Add ethyl acetate. Place small cork in top of test tube, and shake to mix.

Allow layers to separate.

I’m

ACETANILIDE!

ANALYSIS

• Prepare TLC plate and chamber.

• Apply provided standards to TLC plate.

• Apply TOP layer from test tube to TLC plate ( sample solution).

• Develop plate and visualize spots using UV lamp.

• Calculate Rf value of all spots and identify product in sample solution.

A B CU D

A B CU

filter paper

D

Tables 15.2 and 15.3

Rf Values

Identification Standard Sample

o-bromoacetani

lide

***Rf values are 2 decimal places, never more, never less. And unitless.***

m-bromoacetani

lide

p-bromoacetani

lideMAJOR

Product Name

***Write in name of product formed from bromination of acetanilide.***

MAJORProduct Structure

***Draw structure of major product formed.***

HINTS…

Be sure that your test tubes do NOT contain any acetone. It reacts very quickly with bromine and can give inaccurate test results.

If after the one hour period of heating in the water bath the solutions have not completely lost their color, estimate by the relative amount of color lost.

SAFETY CONCERNS

CAUTION: In this experiment you are using bromine, which is poisonous and can cause severe burns!

All aromatic solutions are prepared in glacial acetic acid which can cause severe burns!

WASTE MANAGEMENT

Place ALL liquid waste in container labeled “LIQUID ORGANIC WASTE”.

Place used TLC plates and filter papers in yellow trash can.

Place used TLC spotters broken glass box (NOT TRASHCAN!!!!!!!!!!!).

CLEANING UP…

TEST TUBES: clean all test tubes with soap/water/brush and rinse with wash acetone. Leave inverted in test tube rack to dry.

TLC CHAMBER: remove filter paper and leave in drawer with cap off.

BEAKER: if only used for water, simply dry out with a paper towel.

GRADUATED CYLINDER: rinse any excess bromine solution into wash acetone container. Clean with soap/water/brush and rinse with wash acetone.

LABORATORY NOTEBOOK(Pre-lab)

• OBJECTIVE (Must clearly state…)• What you will be doing• How you are going to do it• How you will determine if it worked

• CHEMICAL EQUATION • Include the chemical equation from the top of page 131 of the lab manual.

• 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) HAZARDSEthylbenzene

Anisole

Acetanilide

Phenol

Benzaldehyde

Nitrobenzene

Acetic acid

Ethyl acetate

Hexane

bromine

LABORATORY NOTEBOOK(In-lab)

• DATA/CALCULATIONS• Reaction rates of aromatic compounds with bromine solution.• Sketch TLC diagram, including all cm measurements• TLC developing solvent system• Show at least one TLC Rf 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.

For next lab…

Pre-lab notebook entry for Experiment 17 will be due at the beginning of lab!

Final lab report for Experiment 15, along with completed lab notebook pages, will be due at the beginning of lab!