chap 7. acid and bases
TRANSCRIPT
Chap 7. Acid and BasesBrønsted Acid:Proton donor
Base:Proton acceptor
Solvent usually acts as an acid (to donate H+) or as base (to accept H+)
][][loglog
][]][[
−
+−
−+=−=
−=
AHApHKpK
HAHAK
aa
a
AH
HAa
AH
HA
AH
HAa
rrr
K
HArHrAr
aaa
K
+−
+−+−
⋅=
−
⋅=
⋅=
+−
][][][*
CH3COH
O
+ H3O+ + CH3 CO-O
H2Oacid base conj. acid conj. base
CH3COH
O
+ HSO4-+H2SO4
acidbase conj. acid conj. baseCH3COH
+OH
C6H5NH2 + NH3+-NH2
acid base conj. acidconj. baseC6H5NH-
For A-H A- + H+
solvated
The stronger the acid is, the weaker the conjugate base is.The stronger the base is, the weaker the conjugate acid is.
activity activity coefficient
Leveling effect:
M101.005][ M103.11][
0.5by differ the,5,4if3-3-
21
×=×=
==++ HH
pHpKpK aa measurable
000043.1 )10
10(099990][HA ofn sol' M 0.1for
3,1000043.1
)1010
(099900][HA ofn sol' M 0.1for
2,10
32
2
3
22
1
2
1
1
=
==
−===
==
−==
+
+
pH-x.
xM .H
pKKpH
-x.xM .H
pKK
a
a
if H-A1 A-++ H2O H3O+
if H-A2 A-++ H2O H3O+
no measurable difference
pKa(H2O) = 15.75pKa(H3O+) = -1.75
pH=2.507 pH=2.998
Lewis Acid:electron pair acceptor
Base:electron pair donorLewis acid + Lewis base adductBMe3 + NH3 Me3B:NH3
BF3 + OEt2 F3B:OEt2
Li + OMe
HLi:O
Me
H
+
Lewis acids: SO3, BF3, AlCl3, SnCl4, FeCl3, ZnCl2, H+, Ag+, Ca+2
Lewis bases: C6H5N, (C2H5)2O, NH3, OH-, CO32-, HCO2-, SH-, CH3CO2-
Brønsted base can be Lewis base, e.g. OH-
Brønsted acid may not be Lewis acid, e.g. AlCl3, or HCl
The ionization of an acid (base) depend on the basicity(acidity) of the medium in which it is ionizing.
→ 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
→ Relative strengths of acids stronger than the conjugate acidsof a solvent cannot be determined in that solvent.
→ Relative strengths of bases stronger than the conjugate basesof the solvent cannot be determined in that solvent
(acidity can be measured for acid stronger than H2O, and weaker than H3O+)
The acidity range varies dramatically. strong acid HI, HClO4…weak acid methane,
To measure very strong acid → use mix of H2O/H2SO4To measure very weak acid → NH3, DMSO…
For a base with known pKBH+, in a series of acid sol’n measure I → H0 for the series of acid sol’n
use H0 to measure the pKB2H+ of a weaker base from pKB2H+ to measure H0 for even more acidic sol’n from H0 of these sol’n to measure pKB3H+ even weaker base
][][,loglog
log]log[][
][loglog
][][][
BBHI
rrr
pHIpK
rrr
HBH
BK
BHrHrBr
aaa
K
BH
HBBH
BH
HBBH
BH
HB
BH
HBBH
+
++
+
+
=⋅
−+=
⋅++=
⋅=
⋅=
+
+
+
+
+
+
+
+
+
+
+
H0, if activity co. rB-, rBH+, rH+→ 1then H0→ pH
BH+ B + H+KBH+
Acidity Function, H0
Acid-Base Catalyzed Reactionsacid-catalyzed
base-catalyzed
Specific acid catalysis
General acid catalysis
Similar for general base (or specific base catalysis)To differentiate specific or general acid catalysis
use buffer to keep [H+] const, with changing bufferconstant rate → specific acid catalysischanging rate → general acid catalysis
R C
O
R + H+ R C
+OH
R
R C
+OH
R + Nu R C
OH
R+Nu
→ product
more reactive
Ph C
O
CH3 + B- Ph C
-OCH2
Ph C
-OCH2 + PhCH O
+ BH
PhCHCH2CH2PhO -O
→ product
more nucleophilic
S + HA SH+
SH+ P ....... fast
k1
k-1k2
+ A- ....... r.d.s
]][[][1 HASk
dtPdrate ==
]][[][1 i
iHASk
dtPd
==∑if more than one acid available in sol’n,
general
S + H+ SH+ ....... fast
SH+ P ....... r.d.s
k1
k-1k2]][[
][
1
1+
+
−
==HS
SHkkK
]][[]][[][][22
++++==== HSkHSKkSHk
dtPdrate SH
reaction proceed only through protonated species
depends only on the conc’nof H+, not the donor in sol’n
Brønsted Catalysis Law
For general acid catalysis, the acidity of each acid will affectthe rate.
ka = Ga(Ka)α
plot log ka v.s log Ka for a series of related acid gives a linear curve with slope of α
log kHA = αlog Ka + constant
( log kHB = βlog Kb + constant )
sensitivity of the rate constant to structural change
O CH
OEt
OEt
H+
slowH2O/Dioxane
OH
CH
OEt
OEt
OH
CH
OEt
OEt
fastCHO
OEt
Substituent Effect on acidity
the acid strengthening effect of ortho-substituent
the ortho group remove the planarity
resonance effect:decrease the acidity
inductive effect:acid strengthening
C
O-
O
X
C
O-
O-
C
O-
O
Addition to Carbonyl GroupHydration of aldehyde and ketone
General base catalysis and general acid catalysisbase-catalysis
acid-catalysis
for the equilibrium the catalytic efficiency depends on acid strengthening
e--withdrawing group favors hydrate
angle strain favors hydrate
HO OH O
∆θ = 49°/2 ∆θ = 60°/2
60° 60°
O
HO
H
O
H
O
H
Steric effcet
bulky group favors ketone
conjugate aromatic group favors ketone
increasing alky substitution
CH3C COCH3
O O
The hydration may be unfavorable, but the equilibrium is established fast
t1/2 ~ 1min in neutral condition<< 1 min in acidic or basic condition
hemiketal, hemiacetal, ketal, acetal
To drive equilibrium to ketal, dehydration or azeotrope are used
O
O
OO
O
O
in general less favorable than methanol for steric reason
R2C O + H2O* R2C OH
*OH
R2C O* + H2O
R2C OHOR'
Kd R2C O + R'OHFor
hemiketal→ can be catalyzed by acid or base
can only be catalyzed by acidso stable in base
R2C O + R'OH R2C OR'
OH
R2C OR' + H2O
R2C OR'
OH
+ R2C OR'
OH2
R2C OR'
OH2
R2C OR' + R'OH R2C OR'
HOR'
R2C(OR')2 + H+
H+
ketal
Enolization of Carbonyl Compounds
1. catalyzed by acid or base2. first order in ketone, zero order in X2
3. if chiral at α-carbon, the rate of bromination is the same as rate of racemization and rate H-exchange→ rate-determining step is the formation of enol or enolate
in acid-catalysis
in base-catalysis
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
Hydrolysis of Acetal by acid-catalysis
Mechanistic Evidences
1. C-O cleavage between carbonyl C and O is shown by isotope labeling experiment, stereochemistry of R group.
(no racemization or inversion)
2. Hammetρ value
3. ΔS┿ nearly zero or slightly positive
4. kinetic solvent isotope effect kD3O+/ kH3O+ ~ 2-3
5. the reaction is specific acid catalyzed→ a pre-equilibrium exist for protonation of ketal/acetal
X
CH
OEt
OEt X
CH
O
+ 2 EtOH
ρ = -3.35
R
C
R
OR'
OR'
R
C
R
HOR'
OR'
H+
fast
R
C
R
OR'slow
H2O
Possible Transition State
r.d.s. add’n of amine to carbonyl
r.d.s. acid-catalyzed dehydration
General Acid catalysis for some “reactive” acetal-ketal
the rate-determining step changes depending on pH
different ρ may be observed for at different pH
reactive due tostable carbonium (stabilized by alkoxyand aromaticity)
good leaving group
ring strain relived
stable carbonium
aryl stabilization and relief of steric strain
protonation partially rate-determining step
OC2H5
OC2H5
O O
NO2
O
OC2H5
(Ar)2C(OC2H5)2
PhCH[OC(CH3)3]2
addition dehydration
Acid-catalyzed Hydrolysis of Ester
AAc2 Mechanism
AAc1 Mechanism
at 9.8M H2SO4, ΔS┿ +17eV (support AAc1)ΔH┿ 28.4kcal
No carbonyl oxygen exchange (rule out AAC2)
AAl1 Mechanism
the hydrolysis mechanism depends on structure and condition
evidence for switching of mechanism kinetic parameters, exchange experiment
CH3 CO
ORH2SO4 CH3 C
OOH + ROH
CH3 CO
OEtH2SO4 CH3 C
OOH + EtOH
2.32.798.4-17.016.362.2-15.316.940.0ΔS┿
ΔH┿% H2SO4
Base-Catalyzed Hydrolysis of EsterBAl2 Mechanism
Ruled out for most ester by labeling experiment
but in highly strained case
BAc2 Mechanism
Substituent effect:Electron-withdrawing groups in R and R’favor hydrolysis
Evidences:kinetics, isotope labelingdependence of [OH-], activation parameters
Acyl-O cleavage, exchange with solvent…
O*H
CH3
O
H2Oneutral pH
*OH
O OH
H2Oacidic (pH<1)basic (pH>9)
OH
O OH
OH
CH3
O
H2Oneutral pH
H2Oacidic (pH<1)basic (pH>9)
OH
O OH
OH
O OH
(+)-β-butyrolactone(-)-hydroxy butyric acid
(+)-hydroxy butyric acid
R
O
OR'
k1
k-1R OR'
O
OH
1818
R
O
OH
18
+ R'O-
R OR'
OH
OH
18
R OR'
OH
O-
18
R
O
OH18 + R'O-
R
O
OR'
18+ H2O
OH-
k3
k-3
k4, H2Ok-4, OH-
k-4, OH-
k1
k-1
k3
k-3
18
Isotope labeling experiment for BAC2 mech.
If the recovered ester loses 18O, a tetrahedral intermediate is indicated.If no loss of 18O, the BAC2 mechanism can not be eliminated yet (k4<<k3, k-1)
If the 18O is labeled as R C-18OR, loss of 18O in the product should be observed.
O
BAl1 Mechanism
for eater from a strong acid (carboxylate ion stable) for R’ a tertiary or benzylic alky group (carbocation stable)or conc’n of base too low
with BAl1 mechanism, R’OH will be racemized
Nucleophilic Catalysis
COOH
COOR
OH- COOH
COO-
R = , , racemization occursCH3 O *CH *CHCH3
Mixed anhydride