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

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

Guidelines for Determining Basicity and Nucleophilicity 1.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 H 2 O

RankNucleophileRelative rate good HO –, RO – 10 4 fairRCO 2 – 10 3 weakH 2 O, ROH1 When the attacking atom is the same (oxygen in this case), nucleophilicity increases with increasing basicity. Table 8.4 Nucleophilicity

Guidelines for Determining Basicity and Nucleophilicity 2.If the comparison is made in the same period; both nucleophilicity and basicity increase going to the left. NH 2 - > OH - >F - More Basic and Nucleophilic

Guidelines for Determining Basicity and Nucleophilicity 3.If the comparison is made going down a group; basicity increases going up while nucleophilicity increases going down. F - Cl - Br - I - Increasing Basicity Increasing Nucleophilicity

Basicity Trend Down a Group Acid Conjugate Base HF; weak acid F - ; strong conj. base HCl; strong acid Cl - ; weak conj. base HBr; strong acid Br - ; weak conj. base HI; strong acid I - ; weak conj. base

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

RankNucleophileRelative rate strongI - >10 5 good Br fairCl -, F A tight solvent shell around an ion makes it less reactive. Larger ions are less solvated than smaller ones and are more nucleophilic. Table 8.4 Nucleophilicity

Guidelines for Determining Basicity and Nucleophilicity 4.Steric hinderance decreases nucleophile strength and increases base strength.

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

Substitution vs. Elimination Effect of Alkyl Halide 1° RX Formation of carbocation will not happen; rules out E1 or S N 1 Since primary alky halides are not sterically hindered; substitution likelySince primary alky halides are not sterically hindered; substitution likely Bulky Base favors elimination over substitutionBulky Base favors elimination over substitution

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.

Substitution vs. Elimination Effect of Alkyl Halide 3° RX S N 2 is unlikely due to steric hinderanceS N 2 is unlikely due to steric hinderance Weak Nucleophile/ Polar Protic Solvent -> E1/S N 1Weak Nucleophile/ Polar Protic Solvent -> E1/S N 1 –Steric hinderance of 3° RX make substitution unlikely except in solvolysis reactions Strong Base/ Bulky Base -> E2Strong Base/ Bulky Base -> E2

(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

Substitution vs. Elimination Effect of Alkyl Halide 2° RX All mechanisms are possible Strong Nucleophile but Weak Base -> S N 2Strong Nucleophile but Weak Base -> S N 2 Weak Nucleophile/Weak Base -> S N 1/E1Weak Nucleophile/Weak Base -> S N 1/E1 Strong Base/ Bulky Base -> E2Strong Base/ Bulky Base -> E2

Elimination vs. Substitution Nucleophilicity vs. Basicity Strong Nucleophiles SN2SN2SN2SN2 Strong Bases E2 Weak Nucleophiles/ Weak Base E1 or S N 1 Sterically Hindered Base or Nucleophile Elimination over Substitution

Substitution vs. Elimination Protic Polar -> E1, S N 1Protic Polar -> E1, S N 1 Aprotic Polar -> E2 / S N 2Aprotic Polar -> E2 / S N 2 High Concentration -> S N 2/ E2High Concentration -> S N 2/ E2 Low Concentration -> S N 1/E1Low Concentration -> S N 1/E1 Solvent Effect Effect of Nucleophile/Base Concentration