Nucleophilic substitution and elimination reactions Alkyl halides Nucleophilic substitution and elimination reactions

Alkyl halides - industrial sources

Alkyl halides - industrial sources

Preparation from alcohols SOCl2 - thionyl chloride

Halogenation of hydrocarbons

Addition of HX to alkenes

Addition of halogens to alkenes and alkynes

Finkelstein reaction

Nucleophilic substitution reactions The halide ion is the conjugate base of a strong acid. It is therefore a very weak base and little disposed to share its electrons. When bonded to a carbon, the halogen is easily displaced as a halide ion by stronger nucleophiles - it is a good leaving group. The typical reaction of alkyl halides is a nucleophilic substitution:

Nucleophiles reagents that seek electron deficient centres negative ions or neutral molecules having at least one unshared pair of electrons

Leaving groups a substituent that can leave as a weakly basic molecule or ion

Nucleophilic substitution A knowledge of how reaction rates depend on reactant concentrations provides invaluable information about reaction mechanisms. What is known about this reaction?

Nucleophilic substitution [CH3Br]I [OH-]I initial rate 0.001 M 1.0 M 3 x 10-7 molL-1s-1 0.002 M 1.0 M 6 x 10-7 molL-1s-1 0.002 M 2.0 M 1.2 x 10-6 molL-1s-1 rate a [CH3Br] [OH-] rate = k[CH3Br][OH-]

Order - a summary The order of a reaction is equal to the sum of the exponents in the rate equation. Thus for the rate equation rate = k[A]m[B]n, the overall order is m + n. The order with respect to A is m and the order with respect to B is n.

Nucleophilic substitution [(CH3)3CBr]I [OH-]I initial rate 0.001 M 1.0 M 4 x 10-7 molL-1s-1 0.002 M 1.0 M 8 x 10-7 molL-1s-1 0.002 M 2.0 M 8 x 10-7 molL-1s-1 rate a [(CH3)3CBr] [OH-]0 rate = k[(CH3)3CBr]

The SN2 mechanism rate = k[CH3Br][OH-] References of interest: E.D. Hughes, C.K. Ingold, and C.S. Patel, J. Chem. Soc., 526 (1933) J.L. Gleave, E.D. Hughes and C.K. Ingold, J. Chem. Soc., 236 (1935)

Stereochemistry of the SN2 reaction

Stereochemistry of the SN2 reaction A Walden inversion. P. Walden, Uber die vermeintliche optische Activät der Chlorumarsäure und über optisch active Halogen-bernsteinsäre, Ber., 26, 210 (1893)

The SN1 mechanism

Carbocations G.A. Olah, J. Amer. Chem. Soc., 94, 808 (1972)

Carbocation stability Hyperconjugation stabilizes the positive charge.

Stereochemical consequences of a carbocation

Stereochemical consequences of a carbocation Why?

Stereochemical consequences of a carbocation retention inversion predominates

Carbocation rearrangements Williamson ether synthesis a rearrangement and elimination

Carbocation rearrangements 1,2 hydride and alkyl shifts

Carbocation rearrangements

Steric effects in the SN2 reaction Look at the transition state to see how substituents might affect this reaction.

Steric effects in the SN2 reaction The order of reactivity of RX in these SN2 reactions is CH3X > 1o > 2o > 3o

Steric effects in the SN2 reaction

Structural effects in SN1 reactions 3o > 2o > 1o > CH3X

RO- > HO- >> RCO2- > ROH >H2O Nucleophilicity Rates of SN2 reactions depend on concentration and nucleophilicity of the nucleophile. A base is more nucleophilic than its conjugate acid: CH3Cl + H2O  CH3OH2+ slow CH3Cl + HO-  CH3OH fast The nucleophilicity of nucleophiles having the same nucleophilic atom parallels basicity: RO- > HO- >> RCO2- > ROH >H2O

I- > Br- > Cl- > F- Nucleophilicity When the nucleophilic atoms are different, their relative strengths do not always parallel their basicity. In protic solvents, the larger the nucleophilic atom, the better: I- > Br- > Cl- > F- In protic solvents, the smaller the anion, the greater its solvation due to hydrogen bonding. This shell of solvent molecules reduces its ability to attack.

Nucleophilicity Aprotic solvents tend to solvate cations rather than anions. Thus the unsolvated anion has a greater nucleophilicity in an aprotic solvent.

Polar aprotic solvents These solvents dissolve ionic compounds.

Solvent polarity more polar transition state less solvated than reagents A protic solvent will decrease the rate of this reaction and the reaction is 1,200,000 faster in DMF than in methanol.

Solvent polarity less polar more polar greater stabilization by polar solvent The transition state is more polarized. Therefore the rate of this reaction increases with increase in solvent polarity. A protic solvent is particularly effective as it stabilizes the transition state by forming hydrogen bonds with the leaving group.

Solvent polarity Explain the solvent effects for each of the following second order reactions: a) 131I- + CH3I  CH3131I + I- Relative rates: in water, 1; in methanol, 16; in ethanol, 44 b) (n-C3H7)3N + CH3I  (n-C3H7)3N+CH3 I- Relative rates: in n-hexane, 1; in chloroform, 13 000

I- > Br- > Cl- > H2O > F- > OH- Leaving group ability Weak bases are good leaving groups. They are better able to accommodate a negative charge and therefore stabilize the transition state. Thus I- is a better leaving group than Br-. I- > Br- > Cl- > H2O > F- > OH-

SN1 v SN2 SN1 SN2 kinetics: 1st order second order reactivity: 3o > 2o > 1o > CH3X CH3X > 1o > 2o > 3o rearrangements no rearrangements partial inversion inversion of configuration eliminations possible

Problems Try problems 6.6 – 6.11 and 6.14 – 6.16 in chapter 6 of Solomons and Fryhle.

Functional group transformations using SN2 reactions R = Me, 1o, or 2o

Problems Try problems 6.12 and 6.17 in chapter 6 of Solomons and Fryhle.

ROH + HX - an SN reaction

Experimental facts 1. The reaction is acid catalyzed 2. Rearrangements are possible 3. Alcohol reactivity is 3o > 2o > 1o < CH3OH

The mechanism

Reaction of primary alcohols with HX SN2