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Superacid derivativesin your pocket?Ivo Leito
University of TartuEstonia
University of Shanghai for Science and Technology, March 2011
C
FFF
F
F F
FF F F
FF
OHNO2
NO2
O2N
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Overview
• Acidity, basicity, acids, bases• In solutions• In the gas phase• Measurement of acid strength
• Superacids• Measurement of their strength• Design of superacids
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“Acid is a sour substance”• Acids have been in use since long time
• Food preservation• Making paints and dyes• …
• Obtaining:• Sour fruits (citric acid)• Fermentation (acetic acid)• Heating minerals (sulfuric acid, …)
H O
O
H
HH
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“Alkali is caustic substance”• Alkalies (inorganic bases) have also been
in use for a long time• Washing (NaOH, one of the starting materials of
soap)• Constrauction (Lime - CaO, Ca(OH)2 – lime
mortar)
• Obtained:• Ashes• Limestone
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Ancient landmarks
Preparation of H2SO4 and HCl Jābir ibn Hayyān, 8. saj
Soap-making, Babylon, 2800 BC
Lime processing, Since antiquity
Vineager, Since antiquity
In 18. Century all common acids andalkalies were known and in use Images: Wikipedia
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The essence of acidity?
But the origin of acidity was stilllargely unclear
18. century: The role of acids islarge
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The Origin of Acidity?Antoine Lavoisier, 1776: acids are compounds that
contain oxygen (oxygen: producer of acid)
Humphrey Davy, 1810: HCl, HBr,H2S etc do not contain oxygen
Justus von Liebig, 1838: acids are compounds, inwhich H atom can be substituted by a metal atom
Images: Wikipedia
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Modern Understanding• Acids dissociate in solution
giving H+ ion
• Different acids dissociate to a differentextent
• Acidity of a solution:pH = -log[H+]
• Acid: proton donor,conjugate acids and bases
Svante Arrhenius (1859-1927)Nobel prize 1903
Wilhelm Ostwald (1853-1932)Nobel prize 1909
Søren Sørensen (1868-1939)
Johannes Nicolaus Brønsted (1879-1947)Images: Wikipedia
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Acidity of molecules and acidity of media
• Brønsted acidity of a molecule refers to itsability to donate proton to othermolecules• Usually defined in terms of equilibrium constants
(Ka, pKa) or deprotonation energies (GA or ΔGacid)
• Brønsted acidity of a medium refers to theability to donate proton to molecules inthe medium• In aqueous solution: pH• Strongly acidic solutions: H0
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• Acidity (acid strength) of molecules insolution is usually defined in theframework of the Brønsted theory via thepKa values
HA + S A- + SH+
Acidity of molecules in solution
Ka
HA)()SH()A(loglogp aa a
aaKK+− ⋅
−=−=
Acid Base Conjugate baseof acid HA
Conjugate acidof base S
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+ S + SH+
pKaH2O = 10
+ S + SH+
pKaH2O = ~ 0
Acidity and molecular structure
ONO2
NO2
O2N
-OHNO2
NO2
O2N
OH O
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Acid-base reaction in a non-aqueoussolvent
K1 K2 K3
(AH)S + (:B)S (AH⋅⋅⋅:B)S (A¯:⋅⋅⋅HB+)S or (A¯: HB+)S
HB complex HB complex contact ion pair
K3 K4
(A¯: // HB+)S (A¯:)S + (HB+)S
solvent-separated ion pair free ions
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• Acidity of molecules in the gas phase isexpressed via deprotnation Gibbs' freeenergy
HA A- + H+
• ΔGºacid is called gas-phase acidity of HA• "º" is often omitted
Acidity of molecules in the gas phase
Ka
a0acid lnGA KRTG −=Δ=
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Example of acidity differences in differentmedia
• In water HBr is 1013 times stronger than 2,4-DNP
• In the gas phase HBr is 107 times weaker than2,4-DNP
16.7
5.5
pKa(MeCN)
226.2308.63.962,4-Dinitro-phenol
233.4318.3ca -9HBr
pKa (GP)
ΔGa (GP)kcal/mol
pKa(water)
Acid
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HAS
S
S
S
S
S
SSHA
desolva-tion
ΔG°ds(HA) > 0
A-H+
Dissociation in the gas phase – Gas-phase acidiyΔG°a(HA) >>> 0
Solution
Gas phase
+
SH+
SH+S
S S
S
S
S
S
SDissociationin solution
ΔG°a(HA,s) A-S
S S
S
S
S
S
+
−ΔG°a(SH+) << 0
ΔG°s(SH+) << 0
ΔG°s(A-) << 0
S
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Acidity of solutions: pH
• Simplified:pH = -log[H+]
• Expresses the abilityof te medium todonate proton
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Unified acidty scale
–800 –900 –1000 –1200–1100 –1300 –1400 –1500
140 160 180 200 220 240 260
H2SO4 143.1 H2O
HF
MeCN
DMSO
Et2O
CH2Cl2
C6H6
SO2
12.6 34
39
86*
86*
120*
HSO3F 7
μabs(H+) in kJ mol–1
pHabs
superacidic medium acidic medium
1 bar 10–20 bar gaseous HCl (for comparison)
140 160 180 200 220 240 260*approximate value, calculated autoprotolysis
Himmel, Goll, Leito, Krossing Chem. Eur. J. 2011, 17, 5808
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What is a superacid?• Superacidic medium:
A Brønsted superacid is a medium, in which the chemical potential of the proton
is higher than in pure sulfuric acid
Himmel, Goll, Leito, Krossing Chem. Eur. J. 2011, 17, 5808
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What is a superacid?• Superacidic molecule:
Superacidic molecule in a given medium isone that is more acidic than H2SO4 in that
medium
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Why do we need to measure acidity?
• Acidity is a core parameter of an acidicmolecule
• Rationalization and prediction of mechanisms of chemical and industrialprocesses
• Design of novel acids and bases• Development of theoretical calculation
methods
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How to measure solution acidities of highly acidic molecules?
• H0 scale• The classical approach• Different H0 refer to different media• H0 is rather a characteristic of a medium than of a
molecule
• X-H vibrational frequencies• Indirect: characterizes
hydrogen bond rather than acidity
• Equilibrium measurement (pKa) in a lowbasicity solvent• Obvious, but almost unused appraoch!
Stoyanov, et al JACS, 2006, 128, 8500
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Solvent• As low basicity as possible• As high ε as possible• As high pKauto as possible• Easy to purify, reasonably inert, electrochemically
stable, transparent in UV, readily available, widelyused
• There is no ideal solvent• Wth increasing ε as a rule basicity also increases
• Water cannot be used
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Non-aqueous pKa values: not trivial
• Processes are often more complex thansimple ionic dissociation• Ion-pairing, homoconjugation, …
• Measurement of a(SH+) is not trivial• Traces of moisture can significantly affect
results
• Working in an inert gas atmosphere (glovebox) isnecessary
K. Kaupmees et al, J. Phys. Chem. A2010, 114, 11788
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Approach: Relative measurement
• Measurement of pKa differences• ΔpKa values
• No need to measure a(SH+) in solution• Many of the error sources cancel out,
either partially or fully• Traces of moisture• Impurities in compounds• Baseline shifts and drifts
• Technique: UV-Vis spectrometry
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0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
190 240 290 340 390wavelength (nm)
Abs
orba
nce
(AU
)
anion
neutral0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
190 240 290 340 390wavelength (nm)
Abs
orba
nce
(AU
)
neutral
anion
UV-Vis ΔpKa measurementCompound 1 Compound 2
Mixture
87.0]A[]HA[]HA[]A[loglog
)HA(p)HA(pp
-21
2-1
1a2aa
=⋅
⋅=−=
−=Δ
K
KKK
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
190 240 290 340 390
wavelength (nm)
Abs
orba
nce
(AU
)
anion
neutral
CN
CN
NC
CF2SO2
SO2CF3
SO2CF3
OH
CN
CN
NC
CF2SO2
SO2CF3
SO2CF3
OH
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1,2-Dichloroethane• Advantages of 1,2-DCE:
• Very low basicity (B' = 40), low anion-solvating ability→ strong superacids are measurable
• pKauto unmeasurably high• Reasonably inert and stable, readily available, widely
used, dissolves also many ionic compounds well• Transparent in UV down to 230 nm
• Limitations:• ~Low polarity (ε = 10)
• Ion-pair acidities
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1,2-DCE acidityscale
A. Kütt et al J. Org. Chem.2011, 76, 391
• The most acidicequilibrium acidityscale in a constant-compositionmedium
• Relative acidities
• Acidity increasesdownwards
No Acid pK a(DCE) Directly measured ΔpK ip values in DCE a pK
1 Picric acid 0.0
2 HCl -0.4
3 2,3,4,6-(CF3)5-C6H-CH(CN)2 -0.7
4 4-NO2-C6H4SO2NHTos c -1.5
5 HNO3 -1.7
6 4-NO2-C6H4SO2NHSO2C6H4-4-Cl -2.4
7 H2SO4 -2.5
8 C6(CF3)5CH(CN)2 -2.6
9 (4-NO2-C6H4-SO2)2NH -3.7
10 3-NO2-4-Cl-C6H3SO2NHSO2C6H4-4-NO2 -4.1
11 (3-NO2-4-Cl-C6H3SO2)2NH -4.5
12 HBr -4.9
13 4-NO2-C6H4SO2CH(CN)2 -5.1
14 2,4,6-(SO2F)3-Phenol -5.9
15 2,4,6-Tf3-Phenol d -6.4
16 CH(CN)3 -6.5
17 4-Cl-C6H4SO(=NTf)NHTos -6.8
18 NH2-TCNP e -6.8
19 2,3,5-tricyanocyclopentadiene -7.0
20 Pentacyanophenol -7.6
21 4-Cl-C6H4SO(=NTf)NHSO2C6H4-4-Cl -7.6
22 HI -7.7
23 4-NO2-C6H4SO2NHTf -7.8
24 Me-TCNP -8.6
25 3,4-(MeO)2-C6H3-TCNP -8.7
26 4-MeO-C6H4-TCNP -8.7
27 C(CN)2=C(CN)OH -8.8
28 4-Cl-C6H4SO(=NTf)NHSO2C6H4-NO2 -8.9
29 2,4-(NO2)2-C6H3SO2OH -8.9
30 C6F5CH(Tf)2 -9.0
31 HB(CN)(CF3)3 -9.3
32 Ph-TCNP -9.4
33 HBF4 -10.3
34 FSO2OH -10.5
0.20 0.24
0.51
0.42 0.65
1.14 1.12 0.33
0.94
0.64
0.80 1.03
1.33
0.19 0.62
0.39 0.93 1.35
0.36 0.80
0.47 1.48
1.02 1.02 1.05
1.26 0.24
0.12
1.13 1.01
0.08
1.78 2.08
0.28 1.00
0.74 0.77 1.09
1.48 0.73 0.71
0.36
0.05
0.88
0 01
1.06 1.23
0.26 1.34
1.57 1.56 1.62
0.83
0.47 0.44 1.33 0.13
0.52 0.60
0.59 0.67
0.74
1.61 0.59 0.22
0.06
0.28 0.46 0.24
0.12 0.12
0.09
-0.02 0.13 1.42
0.96 1.04
1.13
1.01
1.64
1.10 0.98
0.93
0.90 0.81
1.00 1.56
1.77
0.67 0.84
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1,2-DCE acidityscale
• Aqueous pKa (H0)values down to-10 .. -15
29 2,4-(NO2)2-C6H3SO2OH -8.9
30 C6F5CH(Tf)2 -9.0
31 HB(CN)(CF3)3 -9.3
32 Ph-TCNP -9.4
33 HBF4 -10.3
34 FSO2OH -10.5
35 3-CF3-C6H4-TCNP -10.5
36 H-TCNP -10.7
37 [C6H5SO(=NTf)]2NH -11.1
38 [(C2F5)2PO]2NH -11.3
39 2,4,6-(NO2)3-C6H2SO2OH -11.3
40 [C(CN)2=C(CN)]2CH2 -11.4
41 TfOH -11.4
42 C6H5SO(=NTf)NHTf -11.5
43 TfCH(CN)2 -11.6
44 Br-TCNP -11.8
45 [C(CN)2=C(CN)]2NH -11.8
46 3,5-(CF3)5-C6H3-TCNP -11.8
47 Tf2NH -11.9
48 4-Cl-C6H4SO(=NTf)NHTf -12.1
49 Cl-TCNP -12.1
50 (C3F7SO2)2NH -12.2
51 (C4F9SO2)2NH -12.2
52 CN-CH2-TCNP -12.3
53 (C2F5SO2)2NH -12.3
54 CF3-TCNP -12.7
55 HClO4 -13.0
56 CF2(CF2SO2)2NH -13.1
57 4-NO2-C6H4SO(=NTf)NHTf -13.1
58 HB(CN)4 -13.3
59 (FSO2)3CH -13.6
60 Tf2CH(CN) -14.9
61 2,3,4,5-tetracyanocyclopentadiene -15.1
62 CN-TCNP -15.3
63 Tf3CH f -16.4
64 CF3SO(=NTf)NHTf f -18
0.23 0.21 0.40
1.73
2.16
0.22 1.46
1.76 1.92
0.44 0.19
0.89 0.86
0.36
0.19
0.12
1.06
1.29
1.05
0.01
0.31
0.21
0.73 0.75 0.06
0.40
0.45
0.10
0.36 0.46
0.96
0.07 0.11
0.80
0.56
0.80
0.40
0.19 0.10
0.02
0.77
0.15
0.13 0.10
1.04
0.27
0.21
1.04
0.69
0.72
0.93
0.30
0.44
0.42
1.06
0.40
0.47
0.29
0.43
0.19
0.20 0.25
0.32
0.10
0.09 0.07 0.04
0.63 0.67
0.44 0.21
0.49 0.47
0.47
0.84 0.73 0.78
0.58 0.60
0.01
0.22
0.46
0.21
1.06 1.23
0.26 1.34
1.57 1.56 1.62
0.83
0.47 0.44 1.33 0.13
0.52 0.60
0.59 0.67 0.06
0.29
0.84 0.89 0.91
0.93 0.28
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Important aspects for superacids• Brønsted acidity
• As strong as possible• "Clean" protonation desirable• Lewis acidity is usually not desirable
• Stability under superacidic conditions• Weak coordinating properties of the
anions
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Superacid derivatives in your pocket!
Li-ion battery containsultrapure lithium salt(LiBF4, LiClO4, etc)and ultrapure solvent.
Purity must be analysed!
These are salts ofsuperacids!
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POO
O
H SO
OOHF3C
Design of superacidic molecules• "Acid-based" approach:
• Pick a parent acid• Introduce substituents
• electronegative, strong electronacceptors, highly polarizable
ΔGacid = 303 kcal/mol(DFT B3LYP/6-311+G**)
ΔGacid = 299.5 kcal/mol(DFT B3LYP/6-311+G**)
Leito et al J. Mol. Stru.Theochem, 2007, 815, 43
P
CN
CN
CNCN
NC
NC
H
Koppel, Yagupolskii et alto be submitted
SN
NOHF3C
S
S
CF3
CF3
OO
OO
ΔGacid = 260 kcal/mol(DFT B3LYP/6-311+G**)
ΔGacid = 256 kcal/mol(DFT B3LYP/6-311+G**)
ΔΔGacid =47 kcal/mol
ΔΔGacid =40 kcal/mol
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S OHN
NF3C
S
S
OOCF3
CF3OO
:
:
:
:
:
:
. .
. .
. .
. .S ON
NF3C
S
S
OOCF3
CF3OO
H
:
:
:
:
:
. .
. .
. .
. .
. .
. .P
CN
CN
CNCN
NC
NC
H
::
:
: :
:P
CN
CNCN
NC
NCN H
::
:
: :
. .
Basicity Centers on Substituents
It is not only about the acceptorpower but also about basicity!
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Design: Anion-based approach• Design an anion, which
• Has delocalized charge• Is as stable as possible• Has as few as possible protonation sites and
those are of low basicity
Not looking at any particular aciditycenter
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Superacids: breaking the “limits of growth”• We have designed superacidic molecules that are
more acidic than H2SO4 by up to 100 orders of magnitude (!)
C
FFF
F
F F
FF F F
FF
H+
-
C
F3CCF3F3C
CF3
F3C CF3
F3CF3C CF3CF3
CF3
CF3
H+
- B CN
CNNC
NC
NC CN
H+-
- Leito et al, J Mol Stru Theochem.2007, 815, 41
- Kütt et al Chem Phys Chem,2009, 10, 499
- Kütt et al, J. Org. Chem. 2008, 73, 2607
- Kütt et al, J. Org. Chem. 2006, 71, 2829
- Kütt et al, J. Org. Chem. 2011, 76, 391
- Lipping et al, J. Phys. Chem. A, 2009, 113,12972
CH(CN)2F3C
F3C CF3
F3C CF3
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ΔGacid all values in kcal/mol
302
286.5
260
300 299.5
CF3SO2
NHCF3SO2
266.5
CF3SO2OH
267.2
H
NC
NC
CNCN
CN
276.6HPF6
C
HHH
H
H H
HH H H
HH
H+
-
280
H2SO4
288HBF4
SN
NOHF3C
SO2CF3
SO2CF3
260
284.0
Superacidity in thegas phase
C2F5SO2
NHC2F5SO2
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250
200
225
C
FFF
F
F F
FF F F
FF
H+
-
C
F3CCF3F3C
CF3
F3C CF3
F3CF3C CF3CF3
CF3
CF3
H+
-
C
ClClCl
Cl
Cl Cl
HH H H
HH
H+
-243
213
< 175
240HB(CF3)4
225CCN
CNCN
CN
CNNC
NC NC
NCNC CN
CN
H+
-
255.5 HSbF6
250.8 HAuF6250 B CN
CNNC
NC
NC CN
H+-
- Kütt et al Chem Phys Chem,2008
- Kütt et al, JOC, 2008, 73, 2607
- Leito et al, J Mol Stru Theochem.2007, 815, 41
- Leito et al, JPC A, 2009, 113, 8421
- Koppel et al, JACS, 2000,122, 5114
P
CN
CN
CNCN
NC
NC
H+-
256
Acidity in thegas phase
C
ClClCl
Cl
Cl Cl
ClCl Cl Cl
ClCl
H+
GA = 241 ± 29 kcal/mol
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ThanksThankstoto all all thesethese
peoplepeople!!
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Collaboration
• Y.L. Yagupolskii(IOC, Ukrainian Academy of Sciences, Kiev)
• I. Krossing, D. Himmel(Freiburg University)
• A.A. Kolomeitsev, G.-V. Röschenthaler(IIPC, University of Bremen)
• M. Rueping (Aachen University)
• V.M. Vlasov (IOC, Russian Academy o Sciences, Novosibirsk)
• M. Mishima (IMCE, Kyushu University)
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39Overview: http://tera.chem.ut.ee/~ivo/HA_UT/
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Thank you!