Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 328

Brief Organic Chemistry

Summer 2004

Lecture Notes: 16 June

© R. Paselk 2004
 
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Nucleophilic Substitution Reactions, cont.

SN2 reaction (Substitution Nucleophilic 2nd order). Recall our example from last time:

I->Br->Cl->>F->CH3CO2->HO->CH3O->H2N-

We've looked at the SN2 reaction in some detail, noting that it did not occur significantly for highly substituted carbons due to steric hindrance. However we frequently do get substitution at these centers. What's happening in these cases?

The SN1 Reaction (Substitution Nucleophilic 1st order). Generally the SN1 reaction is restricted to tertiary reactants (and for secondary reactants in protic solvents with poor nucleophiles) and only occurs under acidic or neutral conditions. Looking at the preparation of alkyl halides we can start with an alcohol in a hydroxylic (protic) solvent such as water or alcohol. Tertiary alcohols go rapidly under these conditions, whereas secondary and primary alcohols go much slower, and the methyl halides are non-reactive:

R-OH + HX Æ R-X + H2O

Reactivity:

most reactive R3COH > R2CHOH > RCH2OH least reactive

Also find that these reactions are first order - only the alcohol concentration affects the rate, and they lead to racemic mixtures of products when conducted with chiral reactants. This leads to the following mechanism in acid:

This is now a three step mechanism: 1) protonation, 2) loss of neutral water to form a carbocation intermediate (slow step), 3) attack by the halide on the carbocation to form the alkyl halide. (In neutral solution the mechanism would become two step, the protonation step missing.)

So does this mechanism fit our observations regarding this reaction?

Looking at SN1 reactions more generally, the leaving group will also affect the reactivity (rate of reaction). Thus acid will catalyze the synthesis of alkyl halides from alcohols since water will be a better leaving group than hydroxide. The reactivity resulting from some common leaving groups is shown below:

most reactive I- > Br- > H2O = Cl- >> F- > CH3CO2- least reactive

Protic solvents favor SN1 reactions by stabilizing the carbocation intermendiate so it can more readily form.

 

Elimination Reactions

Reactions of alkyl halides with nucleophiles can lead to substitutions , as we have seen, or to β-eliminations, which lead to alkene formation (dehydrohalogenation). We will again look at two type of reactions: second order and first order.

The E2 Reaction: The E2 reaction (Elimination 2nd order) is favored when secondary or tertiary alkyl halides are reacted with strong bases such as hydroxide or alkoxides {RO-}:

The E2 reaction involves a bimolecular transition state in a single step reaction. The mechanism is as follows:

Note the geometry of the transition state {anti periplanar geometry}:

Note that the anti periplanar mechanism predicts the steric results of experiment: meso -1,2-Dibromo-1,2-diphenylethane treated in strong base gives (E )-1-Bromo-1,2-diphenylethylene {remember rules: highest priority by Z, then E = opposite sides}.

The E1 Reaction: Similar to the SN1 reaction - both are preferred when alcohols are treated to give neutral water as a leaving group. As with the SN1 reaction there is a unimolecular, carbocation, intermediate resulting in first order kinetics.

Let's look at an example reaction, the dehydration of 2-Methyl-2-butanol:
Notice that we get two products, the major one being predicted by Zaitzev's Rule.
 
So how does this reaction occur? The mechanism involves a carbocation intermediate. The formation of this intermediate is enhanced in acidic solution by protonation:
 

Summary of Reactivities for Substitution and Elimination

How do we determine whether a reaction will go via an elimination or a substitution and whether it will be first or second order? Unfortunately there is a lot of overlap between these reactions, but we can make some generalizations:

Primary (1°) carbons normally react by an SN2 pathway. With good nucleophiles such as Br-, I-, CN-, RS-, or NH3 get only SN2 reactions. However, with strong base (hydroxide or alkoxide) get some competition by E2 reaction, though SN2 still predominates.

Secondary (2°) carbons go by either SN2 or E2:

Tertiary (3°) carbons go by SN1, E1, or E2:

 

Alcohols, Ethers, and Thiols

Alcohols are characterized by having an -OH group bonded to a saturated, sp3 hybridized carbon and ethers have two carbons linked through an oxygen (C-O-C). All of these molecules are widely represented in nature and are important in industry and as pharmaceuticals.

Thiols and sulfides are the sulfur analogs of alcohols and ethers respectively. Since sulfur resides just below oxygen on the Periodic table we might expect it to have similar properties. Recall though, that it is larger and less electronegative than oxygen, so bonds from carbon to sulfur will be less polarized.

Alcohol Nomenclature: As we've seen already, alcohols can be classified as primary (1°), secondary (2°), or tertiary (3°):

Alcohols are given IUPAC names based on the alcohol being derivatives of the parent alkane. Note that alcohols have the highest priority of the groups we've seen thus far, so if an -OH is present it's an alcohol. As previously we can mane in a stepwise process:

You should also know the common names for a few alcohols, tert -Butyl alcohol and:


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Last modified 16 June 2004