Nucleophilic Substitution Reactions

Introduction:

    Substitution reactions are an important class of reactions because of their synthetic utility and importance in understanding the mechanism of a variety of organic reactions.  Substitution reactions allow the introduction of a variety of functional groups into organic molecules:



    Chemists have studied the mechanism of substitution reactions in great detail.  The results of these studies have indicated that substitution reactions can be broadly divided into two mechanistic types, called SN2 and SN1.   SN2 (Substitution,Nucleophilic, 2nd order) reactions proceed via a one step mechanism in which the incoming nucleophile attacks the electrophilic carbon center from the side opposite the leaving group.   This reaction mechanism implies that  the stereochemistry of a chiral center will be inverted.   Since the reaction occurs in one step without the formation of an intermediate, and both the nucleophile and the electrophile are involved in the formation of the transition state, the reaction is second order overall:  rate =[RX][:Nu]

    SN1 reactions (Substitution,Nucleophilic, 1st order) proceed via two steps:  (1) slow dissociation of the C-X bond to form an intermediate carbocation and (2) a fast second step in which the C-Nu bond is formed.  Since only RX is involved in the slow step, the reaction is first order overall:  rate =k[RX].  Since the

intermediate carbocation is trigonal planar, the nucleophile can attack with equal probability from above or below.  This will result in racemization of a chiral center, since equal amounts of each enantiomer will result.

 

You may want to review the chapter on kinetics from your general chemistry text.  In addition, there is a very good web site that goes into a great deal of detail about the factors that we will be studying today:  http://www.usm.maine.edu/~newton/Chy251_253/Topics.html

Purpose:

The purpose of this lab is investigate how different factors effect the rate of SN1 and SN2 reactions.  Specifically, we will be looking at the following two reactions:

R—X  +  CH3CH2OH 
AgNO3

R—OCH2CH3  +  AgX(ppt)  +  H+  + NO3-

R—X  +  NaI


R—I   + NaX
Kinetic studies have shown that the reaction of an alkyl halide with ethanol in the presence of silver nitrate proceeds through an SN1 mechanism.  The silver coordinates with the leaving group and helps form a carbocation.  The ethanol solvent will act as the nucleophile, forming the ethyl ether.  Similar studies have shown that the reaction of an alkyl halide with sodium iodide proceeds through an SN2 mechanism.  Given this, you will be investigating how the structure of the alkyl halide (substrate - the species being attacked), the structure of the nucleophile (the species attacking), the type of leaving group, and even the solvent affect the rates of these two reactions.


Procedure
:


Before you come into lab, make sure you have filled in your table of reagents and products.  In addition, you will need to draw three dimensional representations of each of the alkyl halides and classify them as primary, secondary, or tertiary.

It is EXTREMELY important that all of your test tubes are clean and DRY (if they need to be washed, give them a final rinse with small amount of acetone and blow dry with air).  Finally, it is important that you know exactly what you are going to be doing so you can work more efficiently.

Substrate Structure:
  1. Add 2 mL of 15% sodium iodide (in acetone) into each of three clean, dry test tubes.  Add 2 drops of 1-bromobutane to the first test tube;  add 2 drops of 2-bromobutane to the second test tube; and add 2 drops of 2-bromo-2-methylpropane to the third test tube.  Stopper the test tubes with cork stoppers and shake to ensure good mixing.  Observe closely for 15-20 minutes for the appearance of cloudiness or precipitation.  Continue observing at intervals throughout the lab period.  Record your observations.
  2. Add 2 mL of 0.1 M silver nitrate (in absolute ethanol) into each of  three clean, dry test tubes.  Add 1 drop of 1-bromobutane to the first test tube;  add 1 drop of 2-bromobutane to the second test tube; and add 1 drop of 2-bromo-2-methylpropane to the third test tube.  Stopper the test tubes with cork stoppers and shake to ensure good mixing.  Observe closely for 15-20 minutes for the appearance of cloudiness or precipitation.  Continue observing at intervals throughout the lab period.  Record your observations.
Steric Effects:
  1. Add 1 mL of 15% sodium iodide (in acetone) into each of two clean, dry test tubes.  Add 2 drops of 1-bromobutane to the first test tube, and add 2 drops of 1-bromo-2,2-dimethylpropane to the second test tube.  Stopper the test tubes with cork stoppers and shake to ensure good mixing.  Record your observations.
Effect of Leaving Group:
  1. Add 1 mL of 15% sodium iodide (in acetone) into each of two clean, dry test tubes.  Add 2 drops of 1-bromobutane to the first test tube, and add 2 drops of 1-chlorobutane to the second test tube.  Stopper the test tubes with cork stoppers and shake to ensure good mixing.  Record your observations.
  2. Add 2 mL of 0.1 M silver nitrate (in absolute ethanol) solution into each of two clean, dry test tubes.  Add 1 drops of 2-bromo-2-methylpropane to the first test tube, and add 1 drop of 2-chloro-2-methylpropane to the second test tube.  Stopper the test tubes with cork stoppers and shake to ensure good mixing.  Record your observations.  
Rate Laws:
  1. Add 1.0 mL of 15% sodium iodide (in acetone) into each of two clean, dry test tubes.  At the same time, add 0.1 mL of 1.0 M 1-bromobutane to the first test tube, and add 0.1 mL of 2.0 M 1-bromobutane to the other.  Record your observations.
  2. Add 1.0 mL of 1.0 M 1-bromobutane into each of two clean, dry test tubes.  At the same time, add 0.1 mL of 7.5 % sodium iodide (in acetone) to the first test tube, and add 0.1 mL of 15% sodium iodide (in acetone) to the other.  Record your observations.
  3. Add 0.5 mL of 0.1 M 2-chloro-2-methylpropane (in ethanol) into a clean, dry test tube.  Into a second clean, dry test tube, add 0.5 mL of 0.2 M 2-chloro-2-methylpropane (in ethanol).  At the same time, add 1.0 mL of 0.1 M silver nitrate (in ethanol) to each of the two test tubes.  Record your observations.
  4. Add 1.0 mL of 0.1 M silver nitrate solution (in ethanol) into a clean, dry test tube.  Into a second clean, dry test tube, add 0.5 mL of 0.1 M silver nitrate solution (in ethanol) and 0.5 mL of ethanol.  At the same time, add 1.0 mL of 0.1 M 2-chloro-2-methylpropane to each of the two test tubes.  Record your observations.

Conclusions
:

 

 (Dreated by C. Snelling)
Updated 12/01/08 by J. Neilan)