CHAPTER 6 Properties and Reactions of Haloalkanes:

             Bimolecular Nucleophilic Substitution


6-1      Physical Properties of Haloalkanes

The strength of the bond between carbon and the halogens decreases going down the periodic table. The C-F bond is difficult to break because it is so strong.

The boiling points of haloalkanes increases going down the periodic table, but not in a linear fashion.

6-2      Nucleophilic Substitution

Replacement of the halogen in a haloalkane can be accomplished by reaction with a nucleophile. There are a number of nucleophiles that will replace a halogen with a different functional group. For example, -OH, -OR, -I, -CN, -SR, NH3, and PR3 can be used as nucleophiles.

6-3      Reaction Mechanisms Involving Polar Functional Groups: Using “Electron-Pushing” Arrows

Curved arrows are used in organic chemistry to track bond changes. The arrows always show the movement of electrons and are never used to move atoms. Moving electrons away from a negatively charged atom changes it to neutral---moving electrons toward a neutral atom changes it to negatively charged.

6-4      A Closer Look at the Nucleophilic Substitution Mechanism: Kinetics

There are three distinct ways in which a substitution reaction can occur: 1) make new bond then break old; 2) break old bond then make new bond; 3) make and break at the same time. Reactions at sp3-hybrized carbon atoms can not occur by the first pathway as it would lead to an intermediate with five bonds to carbon. The second pathway would not involve the nucleophile in the rate determining step and so the reaction rate will not vary with the concentration of the nucleophile. Experimentally, it is found that the rate of the reaction of methyl bromide with hydroxide ion varies with the concentration of both species. Therefore, the third pathway is involved in this reaction.

6-5      Frontside or Backside Attach? Stereochemistry of the SN2 Reaction

SN2 reactions proceed through a transition state where the carbon undergoing substitution is sp2 hybridized. This arrangement provides for maximal bonding to the substituents not undergoing reaction while maintaining some bonding to the nucleophile and to the leaving group. This arrangement also provides for maximum distance between the nucleophile and the leaving group which are typically (but not always) partially negatively charged.

6-6      Consequences of Inversion in SN2 Reactions

SN2 reactions invert the stereochemistry at the carbon undergoing substitution. This inversion will change an R stereocenter into an S,  and an S into an R (so long as the priority of the nucleophile and leaving group are the same)>

6-7      Structure and SN2 Reactivity: The Leaving Group

The leaving group is determined primarily by the source of the starting material. Typically, Cl, Br, and sulfonate esters are used.

6-8      Structure and SN2 Reactivity: The Nucleophile

The nature of the nucleophile is dictated by the desired product. All other factors being equal, a negatively charge nucleophile will react faster than a neutral one (e.g. -OH faster than OH2). Nucleophilicity also increases proceeding to the left in the periodic table.

6-9      Structure and SN2 Reactivity: The Substrate

Steric hinderance in the transition state increases as the degree of substitution increases. These steric interactions increase the energy of the transition state and thus raise the activation energy until, with tertiary substrates, elimination becomes very much faster and dominates the reaction.

Solvent plays a role in the rate of SN2 reactions. Polar protic solvents such as H2O decrease the rate of reacation by solvation of the nucleophile. Some of this solvation must be removed for the nucleophile to undergo reaction. Aprotic polar solvents such as DMF are used to increase the rate relative to polar protic solvents.