8.13 Substitution and Elimination as Competing Reactions

Alkyl halides can react with Lewis bases in two different ways; nucleophilic substitution or elimination. C C H X + Y :– C C Y H X :–+ C C +HY X :–+  -elimination nucleophilic substitution Two Reaction Types

How can we tell which reaction pathway is followed for a particular alkyl halide? C C H X + Y :– C C Y H X :–+ C C +HY X :–+  -elimination nucleophilic substitution Two Reaction Types

A systematic approach is to choose as a reference point the reaction followed by a typical alkyl halide (secondary) with a typical Lewis base (an alkoxide ion). The major reaction of a secondary alkyl halide with an alkoxide ion is elimination by the E2 mechanism. Elimination versus Substitution

CH 3 CHCH 3 Br NaOCH 2 CH 3 ethanol, 55°C CH 3 CHCH 3 OCH 2 CH 3 CH 3 CH=CH 2 + (87%) (13%) Example

Br E2 Figure 8.11 CH 3 CH 2 O –

Br SN2SN2SN2SN2 Figure 8.11 CH 3 CH 2 O –

Given that the major reaction of a secondary alkyl halide with an alkoxide ion is elimination by the E2 mechanism, we can expect the proportion of substitution to increase with: 1)decreased crowding at the carbon that bears the leaving group When is substitution favored?

Decreased crowding at carbon that bears the leaving group increases substitution relative to elimination. primary alkyl halide CH 3 CH 2 CH 2 Br NaOCH 2 CH 3 ethanol, 55°C CH 3 CH=CH 2 + CH 3 CH 2 CH 2 OCH 2 CH 3 (9%) (91%) Uncrowded Alkyl Halides

primary alkyl halide + bulky base CH 3 (CH 2 ) 15 CH 2 CH 2 Br KOC(CH 3 ) 3 tert-butyl alcohol, 40°C + CH 3 (CH 2 ) 15 CH 2 CH 2 OC(CH 3 ) 3 CH 3 (CH 2 ) 15 CH=CH 2 (87%)(13%) But a crowded alkoxide base can favor elimination even with a primary alkyl halide.

Given that the major reaction of a secondary alkyl halide with an alkoxide ion is elimination by the E2 mechanism, we can expect the proportion of substitution to increase with: 1)decreased crowding at the carbon that bears the leaving group 2) decreased basicity of the nucleophile When is substitution favored?

Weakly basic nucleophile increases substitution relative to elimination KCN CH 3 CH(CH 2 ) 5 CH 3 Cl pK a (HCN) = 9.1 (70%) DMSO CH 3 CH(CH 2 ) 5 CH 3 CN secondary alkyl halide + weakly basic nucleophile Weakly Basic Nucleophile

Weakly basic nucleophile increases substitution relative to elimination NaN 3 pK a (HN 3 ) = 4.6 (75%) secondary alkyl halide + weakly basic nucleophile Weakly Basic Nucleophile I N3N3N3N3

Tertiary alkyl halides are so sterically hindered that elimination is the major reaction with all anionic nucleophiles. Only in solvolysis reactions does substitution predominate over elimination with tertiary alkyl halides. Tertiary Alkyl Halides

(CH 3 ) 2 CCH 2 CH 3 Br + CH 3 CCH 2 CH 3 OCH 2 CH 3 CH 3 CH 2 =CCH 2 CH 3 CH 3 CH 3 C=CHCH 3 CH 3 + ethanol, 25°C 64% 36% 2M sodium ethoxide in ethanol, 25°C 1% 99% Example