Brønsted Acid Proton donor Base Proton acceptor O CH 3 COH + H H 3 O + + CH 3 CO -

Transcription

1 hap 7. Acid and Bases Brønsted Acid Proton donor Base Proton acceptor acid base conj. acid conj. base 3 2 S S 4 base acid conj. acid conj. base 6 5 N 2 N N - N 3 acid base conj. base conj. acid For A- A - solvated Solvent usually acts as an acid (to donate ) or as base (to accept ) K K a pk * a [ A ][ ] = [ A ] a = log K activity a a r A = = aa r r A = Ka r A a [ A ] = p log [ A ] activity coefficient A [ A r A ] r [ [ A ] ] The stronger the acid is, the weaker the conjugate base is. The stronger the base is, the weaker the conjugate acid is.

2 Lewis Acid electron pair acceptor Base electron pair donor Lewis acid Lewis base adduct BMe 3 N 3 Me 3 B:N 3 BF 3 Et 2 F 3 B:Et 2 Li Me Me Li: Lewis acids: S 3, BF 3, All 3, Snl 4, Fel 3, Znl 2,, Ag, a 2 Lewis bases: 6 5 N, ( 2 5 ) 2, N 3, -, 3 2-, 2-, S -, 3 2- Brønsted base can be Lewis base, e.g. - Brønsted acid may not be Lewis acid, e.g. All 3, or l Leveling effect The ionization of an acid (base) depend on the basicity(acidity) of the medium in which it is ionizing. pka( 2 ) = pka( 3 ) = if -A 1 A K = 10, pka = x 2 for 0.1M sol'n of A1 [ ] = M ( = 10 ) 01. -x p = if -A 2 A K = 10, pka = x 3 for 0.1M sol'n of A2 [ ] = M ( = 10 ) 01. -x p = no measurable difference if pk a = 4, pk 5, the differ by a = p measurable [ ] = M [ ] = M p=2.507 p=2.998

3 1. No acid stronger than the conjugate acid of a solvent can exist in appreciable concentration in that solvent. 2. No base stronger than the conjugate base of a solvent can exist in appreciable concentration in that solvent elative strengths of acids stronger than the conjugate acids of a solvent cannot be determined in that solvent. elative strengths of bases stronger than the conjugate bases of the solvent cannot be determined in that solvent (acidity can be measured for acid stronger than 2, and weaker than 3 ) The acidity range varies dramatically. strong acid weak acid I, l 4 methane, To measure very strong acid use mix of 2 / 2 S 4 To measure very weak acid N 3, DMS Acidity Function, 0 B K B B K log K pk B B B ab a rb [ B] r [ ] = = a r [ B ] B B [ B] rb r = log log[ ] log [ B ] r B rb r [ B ] = log I p log, I = r [ B] 0, For a base with known pk B, in a series of acid sol n measure I 0 for the series of acid sol n B use 0 to measure the pk B2 of a weaker base from pk B2 to measure 0 for even more acidic sol n from 0 of these sol n to measure pk B3 even weaker base if activity co. r B -, r B, r 1 then 0 p

4 acid-catalyzed base-catalyzed Ph Ph Acid-Base atalyzed eactions Nu Nu - Specific acid catalysis General acid catalysis 3 B - Ph 2 Ph k 1 S S... fast k -1 S k 2 P... r.d.s k 1 product more reactive Similar for general base (or specific base catalysis) To differentiate specific or general acid catalysis use buffer to keep [ ] const, with changing buffer constant rate specific acid catalysis changing rate general acid catalysis - 2 B - Ph 2 2 Ph S A S A -... r.d.s k -1 S k 2 P... fast d[ P] rate = = k1[ S][ A] dt if more than one acid available in sol n, d[ P] = = k1[ S][ Ai ] dt general i K = k k more nucleophilic 1 1 product [ S ] = [ S][ ] d[ P] rate = = k2[ S ] = k2k[ S][ ] = k [ S][ ] S dt reaction proceed only depends only on the conc n through protonated species of, not the donor in sol n

5 Brønsted atalysis Law For general acid catalysis, the acidity of each acid will affect the rate. k a = G a (K a ) plot log k a v.s log K a for a series of related acid gives a linear curve with slope of log k A = log K a constant ( log k B = log K b constant ) sensitivity of the rate constant to structural change Et Et slow 2 /Dioxane Et Et Et Et fast Et

6 Substituent Effect on acidity the acid strengthening effect of ortho-substituent X the ortho group resonance effect inductive effect -

7 Addition to arbonyl Group ydration of aldehyde and ketone General base catalysis and general acid catalysis base-catalysis acid-catalysis for the equilibrium the catalytic efficiency depends on acid strengthening 60 θ = 49 /2 θ = 60 /2 angle strain favors hydrate e - -withdrawing group favors hydrate 3 3 bulky group favors ketone Steric effcet increasing alky substitution conjugate aromatic group favors ketone

8 The hydration may be unfavorable, but the equilibrium is established fast * 2 2 * 2 t 1/2 ~ 1min in neutral condition << 1 min in acidic or basic condition hemiketal, hemiacetal, ketal, acetal 2 ' 2 ' 2 2 For 2 ' ' 2 ' 2 2 ' 2 ' 2 ' 2 ' ' 2 ' 2 K d 2 ' * 2 hemiketal can be catalyzed by acid or base can only be catalyzed by acid so stable in base 2 (') 2 ketal in general less favorable than methanol for steric reason To drive equilibrium to ketal, dehydration or azeotrope are used

9 Enolization of arbonyl ompounds 1. catalyzed by acid or base 2. first order in ketone, zero order in X 2 3. if chiral at -carbon, the rate of bromination is the same as rate of racemization and rate -exchange rate-determining step is the formation of enol or enolate in acid-catalysis in base-catalysis

10 For unsymmetrically substituted ketone, the enolization / halogenation depends on condition in acid-catalysis, more substituted enol is formed in base-catalysis, less substituted enolate is formed the preference is based on both kinetic and thermodynamic reasons Kinetic reason Thermodynamic reason favored

11 ydrolysis of Acetal by acid-catalysis Possible Transition State Mechanistic Evidences 1. - cleavage between carbonyl and is shown by isotope labeling experiment, stereochemistry of group. (no racemization or inversion) 2. ammet value Et 2 Et X Et X ρ = S nearly zero or slightly positive 4. kinetic solvent isotope effect k D3 / k 3 ~ the reaction is specific acid catalyzed a pre-equilibrium exist for protonation of ketal/acetal ' ' fast ' ' slow ' 2

12 General Acid catalysis for some reactive acetal-ketal reactive due to stable carbonium (stabilized by alkoxy and aromaticity) protonation partially ratedetermining step 2 5 N 2 good leaving group ring strain relived (Ar) 2 ( 2 5 ) 2 stable carbonium Ph[( 3 ) 3 ] 2 aryl stabilization and relief of steric strai addition dehydration the rate-determining step changes depending on p r.d.s. add n of amine to carbonyl r.d.s. acid-catalyzed dehydration different may be observed for at different p

13 A Ac 2 Mechanism Acid-catalyzed ydrolysis of Ester A Ac 1 Mechanism at 9.8M 2 S 4, S 17eV (support A Ac 1) 28.4kcal No carbonyl oxygen exchange (rule out A A 2)

14 A Al 1 Mechanism the hydrolysis mechanism depends on structure and condition 3 2 S evidence for switching of mechanism kinetic parameters, exchange experiment Et 2 S 4 3 Et % 2 S S

15 B Al 2 Mechanism Base-atalyzed ydrolysis of Ester uled out for most ester by labeling experiment but in highly strained case * 3 2 neutral p 2 acidic (p<1) basic (p>9) * 3 ()-β-butyrolactone 2 neutral p 2 acidic (p<1) basic (p>9) ()-hydroxy butyric acid (-)-hydroxy butyric acid B Ac 2 Mechanism Evidences kinetics, isotope labeling dependence of [ - ], activation parameters Acyl- cleavage, exchange with solvent Substituent effect Electron-withdrawing groups in and

16 Isotope labeling experiment for B A 2 mech. 18 ' 18 k 1 ' k -1 k 3 k '- k 4, 2 18 ' k -4, k-4, - ' k 1 k ' k3 k -3 '- 18 If the recovered ester loses 18, a tetrahedral intermediate is indicated. If no loss of 18, the B A 2 mechanism can not be eliminated yet (k 4 <<k 3, k -1 ) If the 18 is labeled as - 18, loss of 18 in the product should be observed

17 B Al 1 Mechanism for eater from a strong acid (carboxylate ion stable) for a tertiary or benzylic alky group (carbocation stable) or conc n of base too low with B Al 1 mechanism, will be racemized - - = 3 *, 3 *, racemization occurs Nucleophilic atalysis Mixed anhydride