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

6-3

Curved arrows depict the movement of electrons.

The oxygen lone pair of electrons ends up being shared between the oxygen and the hydrogen.

The bonding pair electrons in the HCl molecule ends up as a lone pair on the chloride ion.

Mechanisms in organic chemistry are described by curved “electron pushing” arrows.

Notice that in the 1st and 3rd examples, the destination of the moving electrons is a carbon atom with a filled outer shell.

In these nucleophilic substitution and addition reactions, room must be made in the outer shell of the carbon atom to put the incoming electrons.

A Closer Look at the Nucleophilic Substitution Mechanism: Kinetics

6-4

Consider the reaction between chloromethane and sodium hydroxide:

This experimental data showing the reactants, products, and reaction conditions, gives no information on how the chemical reaction occurred or how fast it occurred.

By measuring the rate product formation beginning with several different sets of reactant concentrations, a rate equation or rate law can be determined.

A Closer Look at the Nucleophilic Substitution Mechanism: Kinetics

6-4

The reaction of chloromethane with sodium hydroxide is bimolecular.

The rate of a reaction can be measured by observing the appearance of one of the products, or by the disappearance of one of the reactants.

In the case of reaction between chloromethane and hydroxide ion:

doubling the hydroxide concentration (keeping the chloromethane concentration fixed) doubles the reaction rate.

doubling the chloromethane concentration (keeping the hydroxide concentration fixed) also doubles the reaction.

These observations are consistent with a second-order process whose rate law is:

Rate = k[CH3Cl][HO-] mol L-1 s-1.

All of the nucleophilic substitution reactions show earlier follow this rate law (with different values of k).

The mechanism consistent with a second order rate law involves the interaction of both reactants in a single step (a collision).

Two molecules interacting in a single step is call a bimolecular process.

Bimolecular nucleophilic substitution reactions are abbreviated SN2.

Bimolecular nucleophilic substitution is a concerted, on-step process.

A SN2 substitution is a one step process.

The bond formation between the nucleophile and the carbon atom occurs at the same time that the bond between the carbon atom and the electrophile is breaking.

This is an example of a concerted reaction.

There are two distinct stereochemical alternatives for an SN2 concerted reaction: frontside displacement and backside displacement:

In SN2 nucleophilic substitution reactions, the transition state of the reaction is simply the geometric arrangement of reactants and products as they pass through the point of highest energy in the single-step process.

Frontside or Backside Attack? Stereochemistry of the SN2 Reaction

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The SN2 reaction is stereospecific.

When (S)-2-bromobutane reacts with iodide ion, there are two possible theoretical products:

Frontside displacement: the stereochemistry at C2 is retained. The product is (S)-2-iodobutane.

Backside displacement: the stereochemistry at C2 is inverted. The product is (R)-2-iodobutane.

Only (R)-2-iodobutane is observed as a product. All SN2 proceed with inversion of configuration.

A process in which each stereoisomer of the starting material is transformed into a specific stereoisomer of product is called stereospecific.

The same reaction shown with Spartan molecular models and with electrostatic potential maps is:

Halfway through the course of an SN2 reaction, the sp3 hybridization of the carbon atom has changed to the planar sp2 hybridization (transition state).

As the reaction proceeds to completion the carbon atom returns to the tetrahedral sp3 hybridization.

The transition state of the SN2 reaction can be described in an orbital picture.

Consequences of Inversion in SN2 Reactions6-6

We can synthesize a specific enantiomer by using SN2 reactions.

When (R)-2-Bromooctane is reacted with HS-, only (S)-2-octanethiol is obtained:

If we had started with the S enantiomer of 2-bromooctane, only the R enantiomer of 2-octanethiol would have been produced.

In order to retain the R configuration of the starting 2-bromooctane, a sequence of two SN2 reactions is used:

The double inversion sequence of two SN2 processes results in a net retention of configuration.

When a substrate contains more than one stereocenter, inversion takes place only at the stereocenter being attacked by the nucleophile.

Note that in the first case a meso product is formed.