Substitution and Elimination as Competing Reactions

1. -elimination – + + : H Y X C C H – + : Y C C H X – + : X C C Y nucleophilic substitution Substitution and Eliminationas Competing Reactions Alkyl halides can react with Lewis bases by nucleophilic substitution and/or elimination.

2. Nucleophilicity vs. Basicity • All Nucleophiles act like Bases and vice-versa. • Base; Ability to accept proton • measured by thermodynamics • Nucleophilicity; ability to cause substitution reaction (depends on reaction conditions) • measured by kinetics

3. Guidelines for Determining Basicity and Nucleophilicity • When the same nucleophilic atom is compared; the anion is both more basic and nucleophilic with respect to the neutral molecule. OH- More Basic & Nucleophilic Than H2O

4. Table 8.4 Nucleophilicity • Rank Nucleophile Relative rate • good HO–, RO– 104 • fair RCO2– 103 • weak H2O, ROH 1 When the attacking atom is the same (oxygenin this case), nucleophilicity increases with increasing basicity.

5. Guidelines for Determining Basicity and Nucleophilicity • If the comparison is made in the same period; both nucleophilicity and basicity increase going to the left. NH2- > OH- >F- More Basic and Nucleophilic

6. Guidelines for Determining Basicity and Nucleophilicity • If the comparison is made going down a group; basicity increases going up while nucleophilicity increases going down. F-Cl- Br- I- Increasing Nucleophilicity Increasing Basicity

7. Basicity Trend Down a Group

8. Nucleophilicity Trend Down a Group • Solvation • small negative ions are highly solvated in protic solvents • large negative ions are less solvated • As solvation increases; nucleophile • strength decreases

9. Table 8.4 Nucleophilicity • Rank Nucleophile Relative rate • strong I- >105 • good Br- 104 • fair Cl-, F- 103 A tight solvent shell around an ion makes itless reactive. Larger ions are less solvated thansmaller ones and are more nucleophilic.

10. Guidelines for Determining Basicity and Nucleophilicity • Steric hinderance decreases nucleophile strength and increases base strength.

11. -elimination – + + : H Y X C C H – + : Y C C H X – + : X C C Y nucleophilic substitution Substitution and Eliminationas Competing Reactions Alkyl halides can react with Lewis bases by nucleophilic substitution and/or elimination.

12. Substitution vs. Elimination Effect of Alkyl Halide1° RX • Formation of carbocation will not happen; rules out E1 or SN1 • Since primary alky halides are not sterically hindered; substitution likely • Bulky Base favors elimination over substitution

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

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

15. Substitution vs. Elimination Effect of Alkyl Halide3° RX • SN2 is unlikely due to steric hinderance • Weak Nucleophile/ Polar Protic Solvent -> E1/SN1 • Steric hinderance of 3° RX make substitution unlikely except in solvolysis reactions • Strong Base/ Bulky Base -> E2

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

17. Substitution vs. Elimination Effect of Alkyl Halide2° RX • All mechanisms are possible • Strong Nucleophile but Weak Base -> SN2 • Weak Nucleophile/Weak Base -> SN1/E1 • Strong Base/ Bulky Base -> E2

18. Elimination vs. SubstitutionNucleophilicity vs. Basicity

19. Substitution vs. Elimination • Protic Polar -> E1, SN1 • Aprotic Polar -> E2 / SN2 • High Concentration -> SN2/ E2 • Low Concentration -> SN1/E1 Solvent Effect Effect of Nucleophile/Base Concentration