Nucleophilic Aliphatic Substitution Reactions

What Role Does Solvent Play in Nucleophilic Aliphatic Substitution Reactions?

Key Terms/Concepts/Techniques

·  Principles of acid-base chemistry

·  Substitution at sp3 carbon atoms

·  Kinetics

·  Volumetric measurements

Objectives

·  To test the reactivity of alkyl halides in different solvent systems

·  To propose mechanism(s) consistent with the kinetic results as determined by changes in the color of an acid-base indicator

General Procedure: (Adapted from “Process Oriented Guided Inquiry Learning” Workshop – Washington College, Professor Frank Creegan, June 2006)

You will work in groups, as usual. Half of the groups will carry out the reaction of tert-butyl bromide in acetone/water; and the reaction of tert-butyl chloride in n-propanol/water. The other groups will carry out the reaction of tert-butyl bromide in n-propanol/water and the reaction of tert-butyl chloride in acetone/water. Your TA will tell you which groups will do which.

The apparatus consists of

·  A set of nine 25 mL Erlenmeyer flasks with corks – stockroom

·  A set of nine 12 x 75 mm test tubes with red plastic stoppers – stockroom

·  Magnetic stirrer (on your bench top)

·  Burets (on the side shelf)

·  Eppendorf pipets – in hood

Reagents consist of

·  A set of solvents (in burets): water, acetone, n-propanol

·  0.01 molar aqueous NaOH (in buret)

·  0.1 molar aqueous HCL (in Erlenmeyer flask in hood)

·  0.1 molar 2-bromo-2-methylpropane (tert-butyl bromide) (in acetone) (in Erlenmeyer flask in hood)

·  0.1 molar 2-chloro-2-methylpropane (tert-butyl chloride) (in acetone) (in Erlenmeyer flask in hood)

·  Bromothymol blue indicator (in small plastic dropper bottle in hood)


Specific Procedure:

Use an Eppendorf pipet to transfer 2.00 mL of assigned 0.1 M alkyl halide into each of four labeled test tubes.

As with all pipets, please be sure to have the tip below the surface of the liquid you are drawing into the tip. If any air gets into the tip you will need to expel all the contents of the tip (air and liquid) back into the solution and try again.

(The Eppendorf pipets for delivering the organic halide are calibrated to dispense 1000 μL (1.00 mL), but you will need 2000 μL for the experiment.

·  Stopper the test tubes. Note the volume delivered by the Eppendorf pipet you use.

·  Use an Eppendorf pipet to transfer 2.00 mL of 0.1 M HCl into a labeled test tube. (The Eppendorf pipets for delivering the HCl are calibrated to dispense 1000 μL (1.00 mL), but you will need 2000 μL for the experiment.

·  When you are done using the Eppendorf pipet for each reagent, dispose of the tips in the beaker marked for that purpose.

·  Stopper the test tube.

·  Label five 25 mL Erlenmeyer flasks in the following manner: Flask #1 HCl; flasks #2-#5 with the name tert-butyl bromide and the numbers 2, 3, 4, 5.

·  Using burets to dispense the liquids (water, 0.01 M NaOH, acetone or n-propanol), place the contents shown in Table #1 below into the five Erlenmeyer flasks. The volumes delivered from the burets must be measured with a great deal of accuracy (± 0.01 mL).

Read the bottom of the meniscus

Make sure there are no air bubbles in the buret tip

·  It is important that your timekeeper knows how to use the stopwatch. Practice!!!

·  Make copies of Tables 1-3 in your laboratory notebook.

Material / Flask #1 / Flask #2 / Flask #3 / Flask #4 / Flask #5
Water / 3.0 mL / 3.0 mL / 4.0 mL / 5.0 mL / 6.0 mL
0.01 M NaOH / 2.0 mL / 2.0 mL / 2.0 mL / 2.0 mL / 2.0 mL
Acetone or n-Propanol / 3.0 mL / 3.0 mL / 2.0 mL / 1.0 mL / none
Indicator / 3 drops / 3 drops / 3 drops / 3 drops / 3 drops

Table #1. Non-alkyl Halide Reagents for Each Reaction

·  Place flask #1 and its contents on a magnetic stirrer and clamp the flask to the support bars.

·  Start the stirrer in flask #1 to create good mixing. QUICKLY pour the 2.00 mL sample of the 0.1 M HCl from the test tube into flask #1 and begin timing IN SECONDS. Record the time for the color of the indicator to change from blue to yellow (for Bromothymol blue).

·  Remove the magnetic stir bar from the flask with a stir-bar retriever and wipe off the stir bar with a paper towel before placing in the next flask.

·  Mount flask #5 as above and start the stirrer in flask #5 to create good mixing. QUICKLY pour 2.00 mL of the 0.1 M tert-butyl bromide from one of the test tubes into flask #5 and begin timing IN SECONDS. Record the time for the color of the mixture to change from blue to yellow. (for bromothymol blue) Record the time in Table #2.

·  Remove the magnetic stir bar from the flask with a stir-bar retriever and wipe off the stir bar with a paper towel before placing in the next flask.

Repeat the procedure for the remaining three flasks (in the order flask #4, flask #3, flask #2).

Flask / Contents / Solvent = Acetone-Water / Solvent =
n-Propanol-Water
Flask #1 / HCl
Flask #2 / tert-butyl bromide
Flask #3 / tert-butyl bromide
Flask #4 / tert-butyl bromide
Flask #5 / tert-butyl bromide

Table 2a. Reactivity of tert-Butyl Bromide in Seconds

Flask / Contents / Solvent = Acetone-Water / Solvent =
n-Propanol-Water
Flask #2 / tert-butyl chloride
Flask #3 / tert-butyl chloride
Flask #4 / tert-butyl chloride
Flask #5 / tert-butyl chloride

Table 2b. Reactivity of tert-Butyl Chloride in Seconds

Calculate the percent composition (by volume) of water in each flask immediately after the addition of the alkyl halide and place these values in Table #3. (Remember that 0.01 M NaOH is, for this exercise, pure water.) Complete Table #3 to show the concentration of NaOH in each flask immediately after the addition of HCl or RBr as well as the concentration of HCl (flask #1) and RBr (Flasks #2-#5). Ignore the 3 drops of indicator in these calculations.

Material / Flask #1 / Flask #2 / Flask #3 / Flask #4 / Flask #5
% water / 70 / 70 / 80 / 90 / 100
[NaOH] / 4.00 x 10-4 M / 4.00 x 10-4 M / 4.00 x 10-4 M / 4.00 x 10-4 M / 4.00 x 10-4 M
[HCl] / 2.00 x 10-2 M
[RBr] / 2.00 x 10-2 M / 2.00 x 10-2 M / 2.00 x 10-2 M / 2.00 x 10-2 M

Table 3. Reagent Composition in Each Reaction


In-lab Notes:

Obtain data for Table 2 from a group using the other solvent systems. Enter this data in Table 2.

Chemical Waste/Housekeeping

1. All reaction mixtures should be placed in the halogen waste container in the hood.

2. The 12 x 75 mm test tubes may be disposed of in the “broken glass” container.

3. Your work area needs to be cleaned with soap and water and rinsed. Use a paper towel or sponge!

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