8.13 Substitution and Elimination as Competing Reactions 2

Two Reaction Types b-elimination C X : – + + H Y H C Y : – + H X C X : Alkyl halides can react with Lewis bases in two different ways; nucleophilic substitution or elimination. b-elimination C X : – + + H Y H C Y : – + H X C X : – + Y nucleophilic substitution 2

Two Reaction Types b-elimination C X : – + + H Y H C Y : – + H X C X : How can we tell which reaction pathway is followed for a particular alkyl halide? b-elimination C X : – + + H Y H C Y : – + H X C X : – + Y nucleophilic substitution 2

Elimination versus Substitution 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. 2

Example CH3CHCH3 Br NaOCH2CH3 ethanol, 55°C CH3CHCH3 OCH2CH3 + (13%) (87%) 4

Figure 8.11 E2 CH3CH2 O •• • • – Br 5

Figure 8.11 SN2 CH3CH2 O •• • • – Br 5

When is substitution favored? 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

Uncrowded Alkyl Halides Decreased crowding at carbon that bears the leaving group increases substitution relative to elimination. primary alkyl halide CH3CH2CH2Br NaOCH2CH3 ethanol, 55°C CH3CH2CH2OCH2CH3 + CH3CH=CH2 (91%) (9%) 8

primary alkyl halide + bulky base But a crowded alkoxide base can favor elimination even with a primary alkyl halide. primary alkyl halide + bulky base CH3(CH2)15CH2CH2Br KOC(CH3)3 tert-butyl alcohol, 40°C CH3(CH2)15CH2CH2OC(CH3)3 + CH3(CH2)15CH=CH2 (13%) (87%) 9

When is substitution favored? 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 2

Weakly Basic Nucleophile Weakly basic nucleophile increases substitution relative to elimination secondary alkyl halide + weakly basic nucleophile CH3CH(CH2)5CH3 Cl KCN pKa (HCN) = 9.1 DMSO CH3CH(CH2)5CH3 CN (70%) 10

Weakly Basic Nucleophile Weakly basic nucleophile increases substitution relative to elimination secondary alkyl halide + weakly basic nucleophile I NaN3 pKa (HN3) = 4.6 N3 (75%) 10

Tertiary Alkyl Halides 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. 2

2M sodium ethoxide in ethanol, 25°C 1% 99% (CH3)2CCH2CH3 Br Example CH3CCH2CH3 OCH2CH3 CH3 CH2=CCH2CH3 CH3 CH3C=CHCH3 CH3 + + ethanol, 25°C 64% 36% 2M sodium ethoxide in ethanol, 25°C 1% 99% 12