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									                Montgomery College Takoma Park/Silver Spring Campus

                               CH 203 Organic Chemistry I

                  NUCLEOPHILIC SUBSTITUTION REACTIONS

Introduction and Background
       Nucleophilic substitution is a class of reactions that gets much attention in
sophomore organic chemistry and most text books (if not all) contain at least one chapter
dedicated to the topic. Simply stated, a substitution reaction is where one part of a
molecule is replaced by another group (Figure 1). This class of reaction is introduced in

                             Figure 1 Substitution Reaction


basic chemistry classes and usually involves inorganic salts where A is a cation and B
and C are counter anions. The organic counterpart to this reaction is the nucleophilic
substitution reaction (Figure 2) and involves one neutral component (the electrophile)
                      Figure 2 Nucleophilic Substitution Reaction




and a second component that can either be neutral or negatively charged (the
nucleophile).    There are three main criteria that must be met for this reaction to take
place; 1) X must be bonded to an sp3 carbon, 2) the X in R-X must be a good leaving
group (i.e. Cl, Br, I, etc.), and 3) Y must have a pair of electrons that can be used to make
the new R-Y bond (i.e. a negatively charged atom or a neutral heteroatom with a lone pair
of electrons). There are several other factors, however, which determine the efficiency of
the reaction. Issues such as steric hindrance on either the nucleophile or the electrophile
and how willing the nucleophile is to share its electrons (nucleophilicity) will dictate how
well the reaction will proceed.
       In addition to affecting the feasibility of the reaction, the electrophile also
determines the reaction mechanism. Recall from lecture that there are two possible
mechanisms by which substitution reactions can occur (SN1, or SN2, Figure 3). In the
SN1 process, the leaving group leaves first resulting in the formation of a carbocation
intermediate. Subsequently, the cation is attacked by the nucleophile. For this process,
not only must the leaving group be very good (i.e. able to support a negative charge very
well) but the carbocation intermediate must be stabilized by the R group. The SN2
process does not produce an intermediate and happens in a concerted process whereby
                           Figure 3 SN1 and SN2 Mechanisms




the nucleophile is forming the new bond simultaneously with the leaving group bond
breaking (see the transition state). In this process, it becomes the steric hindrance that is
important. If the R group and/or the nucleophile are very bulky, the process will slow
down significantly or possibly not happen. In summary the relative rates for the two
types of mechanisms are:
               SN2 process:     CH3 > 1 > 2 >>> 3
               SN1process:       3 > 2 > 1 >>> CH3
       As can be seen, the relative rates of these follow opposite trends. It is typically
understood that a methyl halide will not undergo a reaction under SN1 conditions and 3
alkyl halides will not undergo a reaction under SN2 conditions.            In addition, the
nucleophilic substitution reaction will never take place on an sp2 carbon under standard
conditions (either SN1 or SN2 conditions).
       The predictability of the reaction mechanism at the extremes (3, 1, or methyl) is
very straightforward for either SN1 or SN2. However there is the matter of the 2 alkyl
halides to think about. In this case it is usually the leaving group that dictates which
mechanism the reaction will follow.
       In today’s lab, several alkyl halides will be investigated experimenatally to
determine whether they prefer the SN1 or SN2 reaction process. In order to do this, one
must be able to alter the conditions to favor either the SN1 or SN2 process.
       The SN2 conditions will be to treat an alkylhalide with sodium iodide in acetone
(Figure 4). Under these conditions, the iodide ion is the nucleophile. Sodium iodide is
                                 Figure 4 SN2 Conditions




soluble in acetone whereas the byproduct NaX, where X = chlorine or bromine, is not
soluble in acetone. Therefore, if the the substitution takes place, a precipitate will be
observed.
       The SN1 conditions involve the use of a solution of silver nitrate (AgNO3) in
ethanol (Figure 5). Under these conditions, the silver will coordinate with the halogen to
                                 Figure 5 SN1 Conditions




aid in its “leaving” and the ethanol will act as a weak nucleophile. Remember that in
order for the ethanol to attack, the halide must leave first (see Figure 3, SN1). Silver
nitrate is soluble in ethanol whereas the silver halide salt (AgX) is not. So, if the reagent
is able to undergo the SN1 reaction (forming a stable carbocation intermediate), then the
precipitate of AgX will be observed. However, if no precipitate is observed, then step 2
cannot take place.
       Using the conditions described above, you can now evaluate several alkyl halides,
qualitatively, to determine their capacity for undergoing the substitution under either SN1
or SN2 reaction or both. In addition, if no precipitate is observed initially while the
solution is at room temperature, the reaction will be heated slightly to see if the increased
energy will allow the reaction to proceed. Depending on the substrate, the reaction rate
under the experimental conditions may vary and doing this experiment will give some
insight into the rate at which the reactions occur. (Remember to think about the structure
of the alkyl halide and what result you expect while performing each experiment).
                  NUCLEOPHILIC SUBSTITUTION REACTIONS

Experimental Procedure:

SN2 Conditions
1. Using a hot plate, heat a beaker of water to approximately 45 – 50C.

2. Obtain 8 small test tubes and label them according to the alkyl halide that will be
   tested.

3. To each of the test tubes, add 1 mL of the solution of 18% sodium iodide in acetone.

4. Add 5-8 drops of the alkyl halide to each test tube.
   a. Shake immediately and determine if a precipitate persists (record results in the data
      sheet).
   b. After 5 minutes (shaking periodically), (if more and more precipitate forms over
      time, indicate in the data table that the reaction is slow). If after 5 minutes no
      precipitate is observed, move on to step 5.
         i. If precipitate has formed, then consider the study of that alkyl halide complete.

5. For the alkyl halide(s) with no precipitate, place the test tube in the previously heated
   beaker of water and heat for an additional 5 minutes (shaking periodically).

6. Record the results in the data table and remember to indicate if the reaction seemed to
   be slow or fast after heating.

SN1 Conditions
1. Clean the 8 test tubes (or use a different set of 8) and label with the alkyl halide that
   will be tested (same as step 1 for the SN2 conditions).

2. To each of the test tubes, add 1 mL of the 1% silver nitrate in ethanol solution.

3. Add about 5-8 drops of the alkyl halide to each test tube.
   a. Shake immediately and determine if a precipitate persists (record results in the data
      sheet).
   b. After 5 minutes (shaking periodically), (if more and more precipitate forms over
      time, indicate in the data table that the reaction is slow). If after 5 minutes no
      precipitate is observed, move on to step 5.
         i. If precipitate has formed, then consider the study of that alkyl halide complete.

4. For the alkyl halide(s) with no precipitate, place the test tube in the previously heated
   beaker of water and heat for an additional 5 minutes (shaking periodically).

5. Record the results in the data table and remember to indicate if the reaction seemed to
   be slow or fast after heating.
                                                                 DATA TABLE


Substrate           1                2                3                 4                 5                  6                    7            8



                                                                   1-bromo-2-        2-chloro-2-
 Name        1-chlorobutane   1-bromobutane     2-bromobutane                                         3-bromopropene     1-bromopropene   Bromobenzene
                                                                  methylpropane     methylpropane




  RT*




 50C*




         *If the precipitate does not persist immediately, record the approximate time at the given temperature it took for the
          precipitate to form.
Post Lab questions

1. Compare substrates 1 and 2 (Br vs Cl as leaving group) for both SN1 and SN2.




2. Compare substrates 2, 3, and 4 (1 vs 2 vs 3) for both SN1 and SN2.




3. Compare substrates 4 and 5 (Br vs Cl as leaving group) for both SN1 and SN2.




4. Compare substrates 2 and 6 (1 vs allylic) for both SN1 and SN2.




5. Comment on the reactivity of substrates 7 and 8 for both SN1 and SN2.
    Pre Lab Questions

    1. Fill in the table below. In the expected results, indicate if you think the reaction will
       require heat (i.e. the reaction will go, but will happen at a slower rate).
                                                                               Expected Results
                              Structure               1, 2, 3, or sp2
                                                                           (SN1, SN2, both, or neither)


1-chlorobutane




1-bromobutane




2-bromobutane




 1-bromo-2-
methylpropane



 2-chloro-2-
methylpropane




1-bromopropene




3-bromopropene




bromobenzene

								
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