By Tiffany Saunders
Animation with Chime
SN2 reaction between Cl- and CH3-Cl
SN2 reaction of Br- and CH3-Cl
The SN2 reaction
SN2 stands for bimolecular nucleophilic substitution. This reaction results in the net replacement of one atom or group for another.
The carbon is said to be electrophilic which means electron loving - wanting to take in electrons. In turn, atoms bearing lone pairs are called nucleophilic which means nucleus loving - wanting to give electrons to the nucleus. The nucleophile attacks the haloalkane with simultaneous expulsion of the leaving group. Bond making occurs at the same time as bond breaking. Because the two events take place "in concert", we call this process a concerted reaction. There are two extreme alternatives for such concerted displacement. The nucleophile could approach the substrate from the same side as the leaving group, one group exchanging for the other, which is called frontside displacement. The reaction displayed above however, is called a backside displacement, in which the nucleophile approaches the carbon from the side opposite the leaving group. Frontside displacement should give rise to a molecule with the same configuration as that of the starting material. Backside displacement should furnish a product with the opposite configuration.
The backside displacement always results in a product with the opposite configuration or mirror image. This is called the inversion of the molecule's configuration. A transformation in which a single pure stereoisomer of starting material is converted into a single pure stereoisomer of product is described as stereospecific. As the nucleophile approaches the back lobe of the sp3 hybrid orbital used by carbon to bind the halogen atom, the molecule becomes planar at the transition state, by changing the hybridization at carbon to sp2. The negative charge is no longer only on the nucleophile, but also partially on the leaving group. As the reaction proceeds to products, the inversion is carried out, the carbon returns to the tetrahedral sp3 configuration, and the leaving group becomes a fully charged anion.
SN2 reaction of HO- and 2-Bromobutane
The occurance of the SN2 displacement depends on a variety of factors. These include the nature of the leaving groups, the reactivity of the nucleophile, and the structure of the alkyl group in the substrate.
Nature of the Leaving Group
As a general rule, nucleophilic substition will occur only when the group being displaced, X, is readily able to depart, taking with it the electron pair of the C-X bond. The relative ease with which it can be displaced can be correlated with its capacity to accomodate a negative charge. Remember that a certain amount of negative charge is transferred to the leaving group in the transition state of the reaction.
For the halogens, leaving group ability increases along the series from fluorine to iodine. Thus, iodine is a good leaving group while fluorine is poor.
Weak bases are best able to accomodate negative charge and are the best leaving group
Effect of Nucleophilicity ( Strength of Nucleophile)
Nucleophilicity depends on a variety of different factors: charge, basicity, solvent, polarizability, and the nature of substituents.
Charge: Because nucleophilic attack is characterized by the formation of a bond with an electrophilic carbon center, the more negative the attacking species the faster the reaction should be.
Basicity: The more basic species is seemingly the more reactive nucleophile. Therefore, in proceeding from the left to the right of the periodic table, nucleophilicity decreases.
Solvent: Generally a solvent weakens the strength of a nucleophile. Smaller anions are more heavily and more tightly solvated than are larger ones because their charge is more concentrated. Solvation results in a solvent-induced barrier that impedes nucleophilic attack.
Polarizability: Larger elements have larger, more diffuse, and more polarizable electron clouds. These allow for more effective orbital overlap in the SN2 transition state. The result is a lower transition state energy and faster nucleophilic substition.
SN2 reaction of TMA and MeBr
The E2 reaction
The E2 reaction is another mode of reactivity of haloalkanes with nucleophiles. In it the nucleophile again acts as a base and again effects elimination, also by a bimolecular mechanism. The rate of alkene formation becomes proportional to the concentrations of both the starting halide and the base. The kinetics of elimination are again second order and the process is called bimolecular elimination. Strong bases can attack haloalkanes before carbocation formation. The target is a hydrogen on a carbon atom next to that carrying the leaving group. The E2 mechanism consists of a single step. Three changes take place:
1. Deprotonation by the base
2. Departure of the leaving group
3. Rehybridization of the reacting carbon centers from sp3 to sp2 to furnish the two p orbitals of the emerging double bond.
All three take place simultaneously: The E2 reaction is a one-step, concerted process.
There are four pieces of information to support the one-step process with an anti stereochemistry transition state. First, the second-order law requires that the haloalkane and the base both be involved in the rate-determining step. Second, it is found that better leaving groups result in faster eliminations. Third, the E2 transition state also contains a partially broken C-H bond. It is known that deuterium forms somewhat stronger bonds to carbon than does ordinary hydrogen, an effect resulting in slightly increased activation energies for cleavage of C-D bonds relative to those of C-H linkages. If a C-H bond breaks in the rate-determining step of the E2 reaction, then replacing H by D should lead to a decrease in the observed reaction rate, a result called an isotope effect. Fourth, its stereochemistry. An anti transition state is preferred, in which the base abstacts a proton at the same time as the leaving group departs, anti with respect to each other. As seen below, the anti elimination dictates the eventual configuration around the double bond. With the formation of the double bond, the molecule flattens out. Alkenes are most generally made by E2 reactions.
E2 reaction of OH- and 2-bromobutane
Competition between Substitution and Elimination
- Weakly basic nucleophiles give substitution
- Strongly basic nucleophiles give more elimination, especially as steric bulk increases
- Sterically hindered basic nucleophiles favor elimination.
E2 reaction of t-butyl bromide and OH-
The Addition reaction to a Carbonyl Group
The carbon- oxygen double bond is very prone to addition reactions. Electrophiles attack at oxygen and nucleophiles at carbon. Polar reagents add to the dipolar carbonyl group according to Coulomb's law. The reaction below is called a nucleophilic addition- protonation. It begins with nucleophilic attack and occurs under neutral or basic conditions. As the nucleophile approaches the electrophilic carbon, the latter rehybridizes, and the electron pair of the pi bond moves over to the oxygen, thereby producing the characteristic "tetrahedral intermediate, an alkoxide ion. Subsequent protonation, usually from a protic solvent such as water or alcohol, yields the final product.
Addition reaction of formaldehyde and OH-
Acknowledgements
I would like to thank Dr. Arvi Rauk and David Block for dedicating so much time and effort into this project. Without them I would not have had the chance to benefit from such a wonderful learning experience that will serve me well in future endeavors.