Alkyl halides and alcohols

Transcript Alkyl halides and alcohols

Alkyl halides Nucleophilic substitution and elimination reactions © E.V. Blackburn, 2011

Alkyl halides - industrial sources HCl H C C H H 2 C=CHCl HgCl 2 vinyl chloride H H vinyl H © E.V. Blackburn, 2011

Alkyl halides - industrial sources HCl H C C H H 2 C=CHCl HgCl 2 vinyl chloride Cl 2 H 2 C=CH 2 H 2 C=CHCl 500 o CH 3 Cl + Hg 2 F 2 CH 3 F + Hg 2 Cl 2 CCl 4 + SbF 3 CCl 2 F 2 Freon-12 © E.V. Blackburn, 2011

Preparation from alcohols HX R-OH R-X or PX 3 or SOCl 2 SOCl 2 - thionyl chloride RCH 2 OH + SOCl 2 RCH 2 Cl + HCl +SO 2 © E.V. Blackburn, 2011

Halogenation of hydrocarbons X 2 /h  R-H RX CH 3 Br 2 h  CH 2 Br lachrymatory © E.V. Blackburn, 2011

Addition of HX to alkenes C C HX C C H X © E.V. Blackburn, 2011

Addition of halogens to alkenes and alkynes X 2 C C C C X X C C 2X 2 X X C C X X © E.V. Blackburn, 2011

Finkelstein reaction acetone R-X + NaI R-I + NaX soluble insoluble © E.V. Blackburn, 2011

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: R-X + Nu R-Nu + X the leaving group © E.V. Blackburn, 2011

Nucleophiles • reagents that seek electron deficient centres • negative ions or neutral molecules having at least one unshared pair of electrons H 3 C C C + CH 3 -Br H 3 C C C CH 3 + Br H 3 C O H + CH 3 -I H 3 C + O CH 3 H + I nucleophile leaving group © E.V. Blackburn, 2011

Leaving groups • a substituent that can leave as a weakly basic molecule or ion Nu CN Cl Ph 3 P: + L Nu L Br  NC  Br OH 2 +  Cl Br  PH 3 P  OH 2  Br Nu NC Cl + Ph 3 P + L: + Br + H 2 O + Br © E.V. Blackburn, 2011

Nucleophilic substitution CH 3 Br + CH 3 OH + Br A knowledge of how reaction rates depend on reactant concentrations provides invaluable information about reaction mechanisms. What is known about this reaction?

Nucleophilic substitution CH 3 Br + CH 3 OH + Br [CH 3 Br] I 0.001 M 0.002 M 0.002 M [OH ] I 1.0 M 1.0 M 2.0 M initial rate 3 x 10 -7 mol  L -1  s -1 6 x 10 -7 mol  L -1  s -1 1.2 x 10 -6 mol  L -1  s -1 rate a [CH 3 Br][OH ] rate = k[CH 3 Br][OH ] © E.V. Blackburn, 2011

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

and the order with respect to B is

Nucleophilic substitution CH 3 CH 3 -C-CH 3 + OH Br CH 3 CH 3 -C-CH 3 OH + Br [(CH 3 ) 3 CBr] I 0.001 M 0.002 M 0.002 M [OH ] I 1.0 M 1.0 M 2.0 M initial rate 4 x 10 -7 mol  L -1  s -1 8 x 10 -7 mol  L -1  s -1 8 x 10 -7 mol  L -1  s -1 rate a [(CH 3 ) 3 CBr][OH ] 0 rate = k[(CH 3 ) 3 CBr] © E.V. Blackburn, 2011

OH The S N 2 mechanism CH 3 Br + CH 3 OH + Br Br rate = k[CH 3 Br][OH ]  HO  Br HO + Br 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) © E.V. Blackburn, 2011

OH Stereochemistry of the S N 2 reaction Br C 6 H 13 H H 3 C Br (-)-2-bromooctane [ a ] = -34.6

o  HO C 6 H 13 H H 3 C OH (-)-2-octanol [ a ] = -9.9

o  Br HO + Br C 6 H 13 HO H CH 3 (+)-2-octanol [ a ] = +9.9

o © E.V. Blackburn, 2011

Stereochemistry of the S N 2 reaction C 6 H 13 C 6 H 13 NaOH H Br HO H S N 2 H 3 C (-)-2-bromooctane CH 3 (+)-2-octanol [ a ] = -34.6

o [ a ] = +9.9

o optical purity = 100% A

Walden

inversion.

P. Walden,

Uber die vermeintliche optische Activät der Chlorumarsäure und über optisch active Halogen bernsteinsäre

Ber.

, 26, 210 (1893) © E.V. Blackburn, 2011

The S N 1 mechanism CH 3 CH 3 -C-CH 3 + OH Br CH 3 CH -C-CH OH rate = k[(CH 3 ) 3 CBr] 3 3 + Br CH 3 H 3 C C CH 3 Br slow H 3 CH 3 C C + CH 3 + OH H 3 CH 3 C C + CH 3 fast + Br CH 3 H 3 C C OH CH 3 © E.V. Blackburn, 2011

Carbocations G.A. Olah,

J. Amer. Chem. Soc.,

94, 808 (1972) CH 3 CH 3 CH 3 CH 2 CH 3 CHCH 3 CH 3 CCH 3 + + + + 1 o 2 o 3 o sp 2 © E.V. Blackburn, 2011

Carbocation stability R R C R + 3 o > R C H + R 2 o > R C H + H 1 o > H C H + H Hyperconjugation stabilizes the positive charge.

H H H H H © E.V. Blackburn, 2011

Stereochemical consequences of a carbocation 1.

CH 3 H 3 C C CH 3 Br slow H 3 CH 3 C C + CH 3 + Br C 6 H 13 H H 3 C Br (-)-2-bromooctane [ a ] = -34.6

o OH H 2 O S N 1 ?

Stereochemical consequences of a carbocation 1.

CH 3 H 3 C C CH 3 Br slow C 6 H 13 H H 3 C Br (-)-2-bromooctane [ a ] = -34.6

o OH H 2 O S N 1 H 3 CH 3 C C + CH 3 + Br (+)-C 6 H 13 CHOHCH 3 reduced optical purity Why?

Stereochemical consequences of a carbocation C 6 H 13 H H 2 O HO C 6 H 13 H + CH 3 X CH 3 inversion predominates retention © E.V. Blackburn, 2011

Carbocation rearrangements (CH 3 ) 3 CCH 2 Br C 2 H 5 O S N 2 (CH 3 ) 3 CCH 2 OC 2 H 5 Williamson ether synthesis C 2 H 5 OH S N 1 (CH 3 ) 2 CCH 2 CH 3 OC 2 H 5 + (CH 3 ) 2 C=CHCH 3 a rearrangement and elimination © E.V. Blackburn, 2011

Carbocation rearrangements + CH 3 CH 2 CH 2 CH 2 + CH 3 CH 2 CHCH 3 1 o 2 o + H C C + H + R C C + R 1,2 hydride and alkyl shifts © E.V. Blackburn, 2011

Carbocation rearrangements (CH 3 ) 3 CCH 2 Br + (CH 3 ) 3 CCH 2 H 3 C CH 3 H + CH 3 H H 3 C CH 3 + CH 2 CH 3 C 2 H 5 OH CH 3 H 3 C CH 2 CH 3 + H OC 2 H 5 H 3 C CH 3 + CH 2 CH 3 -H + CH 3 H 3 C CH 2 CH 3 + H OC 2 H 5 H 3 C CH 3 CH 2 CH 3 OC 2 H 5 © E.V. Blackburn, 2011

OH Steric effects in the S N 2 reaction   Br HO Br HO + Br Look at the transition state to see how substituents might affect this reaction.

 HO  Br © E.V. Blackburn, 2011

Steric effects in the S N 2 reaction  HO  Br The order of reactivity of RX in these S N 2 reactions is CH 3 X > 1 o > 2 o > 3 o © E.V. Blackburn, 2011

Steric effects in the S N 2 reaction RBr + I RI + Br reactivity CH 3 Br 150 > CH 3 CH 2 Br 1 > (CH 3 ) 2 CHBr 0.01

> (CH 3 ) 3 CBr 0.001

Structural effects in S N 1 reactions 3 o > 2 o > 1 o > CH 3 X R-X  +  R X R + + X HCO 2 H RBr + H 2 O ROH + HBr (CH 3 ) 3 CBr > (CH 3 ) 2 CHBr > CH 3 CH 2 Br > CH 3 Br 100,000,000 45 1.7 1 © E.V. Blackburn, 2011

Nucleophilicity Rates of S N 2 reactions depend on concentration and nucleophilicity of the nucleophile.

A base is more nucleophilic than its conjugate acid: CH 3 Cl + H 2 O  CH 3 Cl + HO  CH 3 OH CH 3 OH 2 + slow fast The nucleophilicity of nucleophiles having the same nucleophilic atom parallels basicity: RO > HO >> RCO 2 > ROH >H 2 O © E.V. Blackburn, 2011

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 O H N H 3 C CH 3

N,N

-dimethylformamide DMF (H 3 C) 2 N O P N(CH 3 ) 2 N(CH 3 ) 2 hexamethylphosphoramide HMPA H 3 C O S CH 3 dimethyl sulfoxide DMSO These solvents dissolve ionic compounds.

Solvent polarity Cl H H H I Cl   I 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.

R-X Solvent polarity  +  R X R + + X 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) 131 I + CH 3 I  CH 3 131 I + I Relative rates: in water, 1; in methanol, 16; in ethanol, 44 b) (

-C 3 H 7 ) 3 N + CH 3 I  (

-C 3 H 7 ) 3 N + CH 3 I Relative rates: in

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 .

S N 1 v S N 2 S N 1 S N 2 kinetics: 1st order second order reactivity: 3 o > 2 o > 1 o > CH 3 X CH 3 X > 1 o > 2 o > 3 o rearrangements no rearrangements partial inversion inversion of configuration eliminations possible © E.V. Blackburn, 2011

Functional group transformations using S N 2 reactions R = Me, 1 o , or 2 o CN R-CN nitrile 'R C C R C C R' alkyne © E.V. Blackburn, 2011

ROH + HX - an S N reaction ROH + HX RX + H 2 O HX: HI > HBr > HCl ROH: 3 o > 2 o > 1 o < CH 3 OH HBr or CH 3 CHCH 3 OH NaBr/H 2 SO 4 CH 3 CHCH 3 Br © E.V. Blackburn, 2011

Experimental facts 1. The reaction is acid catalyzed 2. Rearrangements are possible CH 3 H H 3 C C C H OH CH 3 HCl CH 3 H H 3 C C C Cl H CH 3 3. Alcohol reactivity is 3 o > 2 o > 1 o < CH 3 OH © E.V. Blackburn, 2011

Reaction of primary alcohols with HX 1. ROH + HX 1 o + ROH 2 + X + 2. ROH 2 + X   + X R OH 2 RX + H 2 O S N 2 HX: HI > HBr > HCl © E.V. Blackburn, 2011

Alkyl halides and alcohols

Transcript Alkyl halides and alcohols

Directory