1. Experiment 15: SUBSTITUENT EFFECTS ON THE RATE OF ELECTROPHILIC AROMATIC SUBSTITUTION

2. 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.

3. Before coming to lab…  Review these techniques: TLC Analysis Acid-base Extraction

4. 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. Br 2 red

5. MECHANISM An electron pair from the aromatic ring attacks Br 2, 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.

6. 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.

7. 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 < CH 3 < NHCOCH 3 < OCH 3 < OH < NH 2  Deactivating groups are electron withdrawing groups and their activities relative to hydrogen are: NO 2 < COR < CHO < I < Br < Cl < F < H

8. SUBSTITUENT EFFECTS

9. 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.

10. SYNTHESIS  Place small amount of monosusbtituted aromatic compound in small test tube.  Place test tubes in water bath.  Add Bromine solution to each.  Record the 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.

11. Table 15.1 Aromatic Compound Structure (fill in appropriate substituent) Reaction Order ethyl benzene  Rank in order 1-6.  Record reaction time in lab notebook. anisole acetanilide phenol benzaldehyde nitrobenzene

12. PURIFICATION/ISOLATION  Once colorless, 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.

13. 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 R f value of all spots and identify product in sample solution.

14. Tables 15.2 and 15.3 R f Values IdentificationStandardSample o- bromoacetanili de  Rf values are UNITLESS  Rf values are 2 decimal places ONLY! m- bromoacetanili de NOT AVAILABLE (n/a) p- bromoacetanili de Product Name  Write in name of product formed from bromination of acetanilide. Product Structure  Draw structure of major product formed.

15. 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.

16. 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!

17. WASTE MANAGEMENT  Place aqueous waste from extraction in bottle labeled “Aqueous Waste (EAS)”  Place all other waste from experiment in bottle labeled “Organic Waste (EAS)”  Place used TLC plates and filter papers in yellow trash can.  Place used TLC spotters broken glass box.

18. 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.