Alkyl Halides and Nucleophilic Substitution Copyright The Mc

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Interesting Alkyl Halides 4

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Reactions of Alkyl Halides 7

General Features of a Substitution Reaction Three components are necessary in any substitution reaction. 8

When a neutral nucleophile is used, the substitution product bears a positive charge. 9

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Nucleophiles Basicity is a thermodynamic property Nucleophilicity is a kinetic property 12

• Steric hindrance decreases nucleophilicity but not basicity. 13

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But what is the order of bond making and bond breaking? In theory, there are two possibilities. [1] Bond making and bond breaking occur at the same time. This is an example of an SN 2 (substitution nucleophilic bimolecular) mechanism. 15

[2] Bond breaking occurs before bond making. This is an example of an SN 1 (substitution nucleophilic unimolecular) mechanism. 16

SN 2 Reaction CH 3 Br + OH– Rate = k[CH 3 Br][OH-] CH 3 OH + Br– a second-order reaction

All SN 2 reactions proceed with backside attack of the nucleophile, resulting in inversion of configuration at a stereogenic center. 18

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The SN 2 reaction is a key step in the laboratory synthesis of many important drugs. 22

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• The rate of an SN 1 reaction is affected by the type of alkyl halide involved. • This trend is exactly opposite to that observed in SN 2 reactions. 27

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The Hammond Postulate 30

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• The strong nucleophile favors an SN 2 mechanism. • The weak nucleophile favors an SN 1 mechanism. 33

• A better leaving group increases the rate of both SN 1 and SN 2 reactions. 34

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In addition to substitution, an alkyl halide can undergo an elimination reaction The E 2 Reaction

The Regioselectivity of the E 2 Reaction The major product of an E 2 reaction is the most stable alkene The greater the number of substituents, the more stable is the alkene (The Zaitsev Rule)

Potential Energies of Pentene Isomers

Consider the regioselectivity of the E 2 reaction The alkene with the bulkiest groups on opposite sides of the double bond will be formed in greater yield, because it is the more stable alkene

The E 1 Reaction

Elimination from Cyclic Compounds In an E 2 reaction, groups to be eliminated must be trans to one another (anti-coplanar)

Competition Between Substitution and Elimination Alkyl halides can undergo SN 2, SN 1, E 2 and E 1 1) decide whether the reaction conditions favor SN 2/E 2 or SN 1/E 1 • SN 2/E 2 reactions are favored by a high concentration of nucleophile/strong base • SN 1/E 1 reactions are favored by a poor nucleophile/weak base 2) decide how much of the product will be the substitution product and how much of the product will be the elimination product

Apakah mekanisme reaksi yang berkaitan dengan reaksi berikut, substitusi SN 1 atau SN 2? Jelaskan alasan Saudara 1. (CH 3)3 CBr + CH 3 OH (CH 3)3 COCH 3 + HBr 2. CH 3 CH 2 I + Na. CN CH 3 CH 2 CN + Na. I