Eliminations

Elimination Reactions So far we have discussed only one reaction type: substitutions. We now introduce a new reaction type: eliminations. They are related to substitution reactions and often accompany them. Instead of substituting one functional group for another, a functional group is eliminated from the substrate/reactant. The E2 reaction is a bimolecular elimination reaction. Zaitsev’s Rule: in the elimination of HX from an alkyl halide, the more highly substituted alkene predominates. The more substituted double bond is more stable due to the electron donating ability of alkyl groups. Also, the more substituted alkenes have more sp2-­‐
sp2 C—C bonds, which are more stable as they have more s-­‐character. >
>
tri
tetra
~
di (geminal)
>
>
di-cis
di-trans
>
mono
unsubstituted
This is the same phenomenon (hyperconjugation) that stabilizes carbocations. In general, more electron density in a bond results in a stronger bond: a covalent bond is the sharing of two electrons; the more fully there are two electrons, the stronger the bond. The transition state of the E2 reaction is said to be late, as it represents the product alkene to a significant extent (thus explaining Zaitsev’s Rule). Mechanism: The E2 reaction is concerted: the leaving group leaves at the same time as the hydrogen is removed. The reaction obeys second-­‐order kinetics: Rate = k[alkyl halide][base] As with SN2, the rate is dependent on both the concentration of the base and the electrophile. The transition state involves the anti-­‐periplanar arrangement of the hydrogen with the leaving group: they must have a 180° dihedral angle: in the same plane, but opposite each other. The reason is the orbital overlap of the LG with the C—H bond to form the new π-­‐bond. Note the stereochemical consequences of the anti-­‐periplanar mechanism. SN2 versus E2: Primary alkyl halides will give predominantly SN2 products. More substituted alkyl halides will give more E2. O
EtO–
+
Br
EtOH
E2, 9%
SN2, 91%
Br
EtO–
O
+
EtOH
SN2, 40%
EtO–
Br
EtOH
E2, 60%
+
O
SN2, 13%
E2, 87%
Base versus nucleophile: Strong bases (e.g., HO–, NH2–, RO–) favor E2. Likewise, good nucleophiles that are weak bases (e.g., I–, RSH) will favor SN2. E1: A less common, less useful reaction is the E1 reaction. It often accompanies SN1 reactions and rarely occurs in high yield. This unimolecular elimination reaction involves formation of a carbocation as a first step followed by loss of the leaving group. Rate = k[alkyl halide] Geometry (anti-­‐periplanar) is not important, as the carbocation can overlap with any acidic (α to the carbocation) hydrogen. The E1 reaction obeys Zaitsev’s rule to give the more substituted double bond. SN1/SN2/E2/E1 summary/comparison: (1) Primary alkyl halides will prefer SN2 unless a strong hindered base is used in which case E2 will be favored. For example, t-­‐butoxide is a sterically hindered base. Due to its bulk, it is not very nucleophilic. (2) Secondary alkyl halides: SN2 with a weak base (e.g., RCO2–, CN–) or a very good nucleophile (e.g., RS–). E2 with a strong base. (3) With tertiary alkyl halides: E2 with a strong base; SN1 with a weak base. (4) Secondary and tertiary alcohols can undergo dehydration via an E1 mechanism.