Alkyl Halides and Elimination Reactions

•Dehydrohalogenation is an example of elimination.

• Negatively charged oxygen compounds like HO¯ and its alkyl derivatives, RO¯ (called alkoxides) are common bases used in elimination reactions.

• Example products of dehydrohalogenation. Notice the same starting material can produce different products

• A double bond consists of a bond and a bond.

Alkenes—Orbital view

• Alkenes are classified by the number of carbon atoms bonded to the carbons of the double bond.

•Free Rotation around sigma (single) bonds

•Pi bonds are not free to rotate

• Because of this lack of free-rotation, two stereoisomers of 2-butene are possible. cis-2-Butene and trans-2-butene are diastereomers, because they are stereoisomers that are not mirror images of each other.

Alkenes & Stereoisomers

Alkenes & Stereoisomers

• When two groups on each end of a carbon-carbon double bond are different from each other, two diastereomers are possible.

Cis and trans--stability

• Trans alkenes are more stable than cis alkenes because the groups bonded to the double bond carbons are further apart, reducing steric interactions.

* Go back to the chain orientation during elimination To see how these two are formed.

• The greater the percent s-character, the more readily an atom accepts electron density. Thus, sp2 carbons are more able to accept electron density and sp3 carbons are more able to donate electron density.

Number of substituents and stability

• There are two mechanisms of elimination—E2 and E1, just as there are two mechanisms of substitution, SN2 and SN1.

• E2 mechanism—bimolecular elimination

• E1 mechanism—unimolecular elimination

• The E2 and E1 mechanisms differ in the timing of bond cleavage and bond formation, (similar to the SN2 and SN1 mechanisms).

• E2 and SN2 reactions have some features in common, and so do E1 and SN1 reactions.

Mechanisms of Elimination

• E2 is the most common and it follows second-order kinetics with both the alkyl halide and the base in the rate equation

Mechanism of E2 Elimination

rate = k[(CH3)3CBr][¯OH]

• The reaction is concerted—all bonds are broken and formed in a single step.

Mechanism of E2 Elimination

Example energy diagram for an E2 reaction:

• The type of the base, the leaving group and the solvent affect the rate.

• Since the base appears in the rate equation, the rate of the E2 reaction increases as the strength of the base increases.

• Strong, negatively charged bases like¯OH and ¯OR favor E2 mechanisms.

Mechanisms of E2 Elimination

Mechanism of E2 Elimination

• The SN2 and E2 mechanisms differ in how the R group impacts reaction rate.

E2 vs SN2 reactions (elimination vs substitution)

Why ?...

• The increase in E2 reaction rate with increasing alkyl substitution can be seen when looking at stability of the transition state.

• Since the double bond is partially formed in the TS, increasing the stability of the double bond with alkyl substituents stabilizes the transition state (lowers Ea, and increasing the rate of the reaction).

E2 transition state stability vs rxn rate

Examples:

Overview of E2 mechanism

• When more than one product can form, the major product is the more stable product—the one with the more substituted double bond.

Zaitsev’s (Saytzeff) Rule

• A reaction is regioselective when it yields mostly one constitutional isomer when more than one product is possible.

Zaitsev’s (Saytzeff) Rule: “E2 Rxns are Regioselective”

• A reaction is stereoselective when it forms mostly or exclusively one stereoisomer when two or more are possible.

• The E2 reaction is stereoselective because one stereoisomer is formed preferentially.

Zaitsev’s (Saytzeff) Rule

The E1 reaction

• The dehydrohalogenation of (CH3)3CCI with H2O to form (CH3)2C=CH2 follows an E1 mechanism with first-order kinetics:

The E1 reaction,…remember your lab experiment?

rate = k[(CH3)3CCI]

• As with SN1, the E1 reaction is a two-step mechanism: the bond to the leaving group breaks first before the bond is formed. The slow step is unimolecular, involving only the alkyl halide.

• The E1 and E2 mechanisms both involve the same number of bonds broken and formed, the difference is timing.

E1 mechanism (similar to SN1)

Mechanism of E1 elimination

An example energy diagram for an E1 reaction:

• The rate of an E1 reaction increases as the number of R groups on the carbon with the leaving group increases (same with E2).

The E1 reaction

The strength of the base usually determines whether a reaction follows the E1 or E2 mechanism. Strong bases like ¯OH and ¯OR favor E2 reactions, whereas weaker bases like H2O and ROH favor E1 reactions.

• E1 reactions are also regioselective, favoring formation of the more substituted, more stable alkene.

E1 reactions: Zaitsev’s rule also applies for E1

Summary of the E1 mechanism.

• NOTE: SN1 and E1 reactions have exactly the same first step—formation of a carbocation. They differ in what happens to the carbocation.

SN1 vs E1 Reactions

• Because E1 reactions occur with a competing SN1 reaction.

• The transition state of an E2 reaction consists of four atoms from an alkyl halide all aligned in a plane.

• There are two ways for the C—H and C—X bonds to be coplanar.

Stereochemistry of the E2 Reaction

• E2 elimination occurs most often in the anti periplanar geometry which allows the molecule to react in the lower energy staggered conformation, letting the incoming base and leaving group to be further away from each other.

Stereochemistry of the E2 Reaction

Two possible geometries for the E2 reaction

• The stereochemical requirement of an anti periplanar geometry in an E2 reaction has big consequences for six-membered rings.

Stereochemistry of the E2 Reaction

• For E2 elimination, the C-Cl bond must be anti periplanar to the C—H bond on a carbon, which occurs only when the H and Cl atoms are both in the axial position.

• The requirement for trans diaxial geometry means that elimination must occur from the less stable conformer, B.

Stereochemistry of the E2 Reaction

The trans diaxial geometry for the E2 elimination in chlorocyclohexane

• What about the E2 dehydrohalogenation of cis- and trans-1-chloro-2-methylcyclohexane ?

Stereochemistry of the E2 Reaction

• This cis isomer exists as two conformations, A and B, each of which as one group axial and one group equatorial. E2 reaction must result from conformation B, which contains an axial Cl atom.

• Because conformation “B” has two different axial hydrogens, labeled Ha and Hb, so the E2 reaction occurs in two different directions giving two different alkenes.

* Zaitsev says the major product contains the more stable trisubstituted double bond.

Stereochemistry of the E2 Reaction

• The trans isomer of 1-chloro-2-methylcyclohexane exists as two conformers: C, having two equatorial substituents, and D, having two axial substituents.

Stereochemistry of the E2 Reaction

• E2 reaction must occur from D, since it contains an axial Cl atom.

• Because conformer D has only one axial H, the E2 reaction occurs only in one direction to give only a single product. Not predicted by the Zaitsev rule.

Stereochemistry of the E2 Reaction

• The strength of the base is the most important factor.

• Strong bases favor the E2 mechanism.

• Weak bases favor the E1 mechanism.

When is the Mechanism E1 or E2?

• Two consecutive elimination reactions produce two bonds of an alkyne.

E2 Reactions & the synthesis of Alkynes

• NOTE: Two elimination reactions are needed to remove two moles of HX from a dihalide substrate.

• Two different starting materials can be used—a vicinal dihalide or a geminal dihalide.

E2 Reactions & the synthesis of Alkynes

• Very strong bases (such as ¯NH2 or KOC(CH3)3 in DMSO) are needed to synthesize alkynes by dehydrohalogenation.

E2 Reactions & the synthesis of Alkynes

• Very strong bases are needed because the transition state for the second elimination reaction includes partial cleavage of the C—H bond which is sp2 hybridized (and sp2 hybridized C—H bonds are stronger than sp3 hybridized C—H bonds).

E2 Reactions & the synthesis of Alkynes

Examples of dehydrohalogenation of dihalides to produce alkynes

E2 Reactions & the synthesis of Alkynes

• Good nucleophiles that are weak bases favor substitution over elimination—(examples: I¯, Br¯, HS¯, ¯CN, and CH3COO¯)

Predicting the Mechanism— SN1, SN2, E1 or E2

• Bulky nonnucleophilic bases favor elimination over substitution—KOC(CH3)3, DBU, and DBN are too sterically hindered to attack tetravalent carbon, but are able to remove a small proton, favoring elimination over substitution.

Predicting the Mechanism— SN1, SN2, E1 or E2

Predicting the Mechanism— SN1, SN2, E1 or E2

Predicting the Mechanism— SN1, SN2, E1 or E2

Predicting the Mechanism— SN1, SN2, E1 or E2

Elimination Rxns