Editing Acid dissociation constant (section)

== Acidity in nonaqueous solutions ==
A solvent will be more likely to promote ionization of a dissolved acidic molecule in the following circumstances:<ref name=loudon>{{citation
| last = Loudon
| first = G. Marc
| title = Organic Chemistry
| edition = 4th
| year = 2005
| publisher = Oxford University Press
| location = New York
| isbn = 0-19-511999-1
| pages = 317–318
}}</ref>
# It is a [[protic solvent]], capable of forming hydrogen bonds.
# It has a high [[donor number]], making it a strong [[Lewis base]].
# It has a high [[dielectric constant]] (relative permittivity), making it a good solvent for ionic species.
p''K''<sub>a</sub> values of organic compounds are often obtained using the aprotic solvents [[dimethyl sulfoxide]] (DMSO)<ref name=loudon /> and [[acetonitrile]] (ACN).<ref>{{cite book
| title = Advanced Organic Chemistry
| last = March
| first = J.
| author2 = Smith, M.
| author-link = Jerry March
| year = 2007
| publisher = John Wiley & Sons
| location = New York
| isbn = 978-0-471-72091-1
| edition = 6th
}} Chapter 8: Acids and Bases</ref>

{| class="wikitable"
|+ Solvent properties at 25&nbsp;°C
|-
! Solvent !! Donor number<ref name=loudon /> !! Dielectric constant<ref name=loudon />
|-
| Acetonitrile || 14 || 37
|-
| Dimethylsulfoxide || 30 || 47
|-
| Water || 18 || 78
|}

DMSO is widely used as an alternative to water because it has a lower dielectric constant than water, and is less polar and so dissolves non-polar, [[hydrophobic]] substances more easily. It has a measurable p''K''<sub>a</sub> range of about 1 to 30. Acetonitrile is less basic than DMSO, and, so, in general, acids are weaker and bases are stronger in this solvent. Some p''K''<sub>a</sub> values at 25&nbsp;°C for acetonitrile (ACN)<ref>{{cite journal
| last = Kütt
| first = A.
| author2 = Movchun, V.
| author3 = Rodima, T
| author4 = Dansauer, T.
| author5 = Rusanov, E.B.
| author6 = Leito, I.
| author7 = Kaljurand, I.
| author8 = Koppel, J.
| author9 = Pihl, V.
| author10 = Koppel, I.
| author11 = Ovsjannikov, G.
| author12 = Toom, L.
| author13 = Mishima, M.
| author14 = Medebielle, M.
| author15 = Lork, E.
| author16 = Röschenthaler, G-V.
| author17 = Koppel, I.A.
| author18 = Kolomeitsev, A.A.
| year = 2008
| title = Pentakis(trifluoromethyl)phenyl, a Sterically Crowded and Electron-withdrawing Group: Synthesis and Acidity of Pentakis(trifluoromethyl)benzene, -toluene, -phenol, and -aniline
| journal = J. Org. Chem.
| volume = 73
| issue = 7
| pages = 2607–2620
| doi = 10.1021/jo702513w
| pmid = 18324831
}}</ref><ref name=Ivo_AN>{{cite journal
| last = Kütt
| first = A.
| author2 = Leito, I.
| author3 = Kaljurand, I.
| author4 = Sooväli, L.
| author5 = Vlasov, V.M.
| author6 = Yagupolskii, L.M.
| author7 = Koppel, I.A.
| year = 2006
| title = A Comprehensive Self-Consistent Spectrophotometric Acidity Scale of Neutral Brønsted Acids in Acetonitrile
| journal = J. Org. Chem.
| volume = 71
| issue = 7
| pages = 2829–2838
| doi = 10.1021/jo060031y
| pmid = 16555839
| s2cid = 8596886
}}</ref><ref>{{cite journal
| last = Kaljurand
| first = I.
| author2 = Kütt, A.
| author3 = Sooväli, L.
| author4 = Rodima, T.
| author5 = Mäemets, V.
| author6 = Leito, I
| author7 = Koppel, I.A.
| year = 2005
| title = Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unification of Different Basicity Scales
| journal = J. Org. Chem.
| volume = 70
| issue = 3
| pages = 1019–1028
| doi = 10.1021/jo048252w
| pmid = 15675863
}}</ref> and dimethyl sulfoxide (DMSO).<ref>{{cite web
| url = http://www.chem.wisc.edu/areas/reich/pkatable/
| title = Bordwell pKa Table (Acidity in DMSO)
| access-date = 2008-11-02
| archive-url = https://web.archive.org/web/20081009060809/http://www.chem.wisc.edu/areas/reich/pkatable/
| archive-date = 9 October 2008
| url-status = dead
}}</ref> are shown in the following tables. Values for water are included for comparison.

{| class="wikitable"
|+ p''K''<sub>a</sub> values of acids
|-
! HA {{Eqm}} A{{sup|−}} + H{{sup|+}} !! ACN !! DMSO !! Water
|-
| [[p-Toluenesulfonic acid|''p''-Toluenesulfonic acid]] || 8.5 || 0.9 || ''Strong''
|-
| [[2,4-Dinitrophenol]] || 16.66 || 5.1 || 3.9
|-
| [[Benzoic acid]] || 21.51 || 11.1 || 4.2
|-
| [[Acetic acid]] || 23.51 || 12.6 || 4.756
|-
| [[Phenol]] || 29.14 || 18.0 || 9.99
|-
<!--
|}

{| class="wikitable" align="center"
|+ p''K''<sub>a</sub> values of acids conjugate to bases
|-
-->
! BH{{sup|+}} {{Eqm}} B + H{{sup|+}} !! ACN !! DMSO !! Water
|-
| [[Pyrrolidine]] || 19.56 || 10.8 || 11.4
|-
| [[Triethylamine]] || 18.82 || 9.0 || 10.72
|-
| [[Proton sponge]]{{nbsp|11}} || 18.62 || 7.5 || 12.1
|-
| [[Pyridine]] || 12.53 || 3.4 || 5.2
|-
| [[Aniline]] || 10.62 || 3.6 || 4.6
|}

Ionization of acids is less in an acidic solvent than in water. For example, [[hydrogen chloride]] is a weak acid when dissolved in [[acetic acid]]. This is because acetic acid is a much weaker base than water.
: <chem>HCl + CH3CO2H <=> Cl- + CH3C(OH)2+</chem>
: <math chem>\text{acid} + \text{base } \ce{<=>} \text{ conjugate base} + \text{conjugate acid}</math>

Compare this reaction with what happens when acetic acid is dissolved in the more acidic solvent pure sulfuric acid:<ref>{{Housecroft3rd}} Chapter 8: Non-Aqueous Media</ref>
:<chem>H2SO4 + CH3CO2H <=> HSO4- + CH3C(OH)2+</chem>

[[File:Carboxylic acid dimers.svg|thumb|upright=0.65|alt=This image illustrates how two carboxylic acids, C O O H, can associate through mutual hydrogen bonds. The hydroxyl portion O H of each molecule forms a hydrogen bond to the carbonyl portion C O of the other.|Dimerization of a carboxylic acid.]]
The unlikely [[diol|geminal diol]] species {{chem2|CH3C(OH)2+}} is stable in these environments. For aqueous solutions the [[pH]] scale is the most convenient [[acidity function]].<ref>{{cite book
| title = Acidity Functions
| last = Rochester
| first = C.H.
| year = 1970
| publisher = Academic Press
| isbn = 0-12-590850-4
}}</ref> Other acidity functions have been proposed for non-aqueous media, the most notable being the [[Hammett acidity function]], ''H''<sub>0</sub>, for [[superacid]] media and its modified version ''H''<sub>−</sub> for [[superbase|superbasic]] media.<ref>{{cite book
| last = Olah
| first = G.A
| author2 = Prakash, S
| author3 = Sommer, J
| title = Superacids
| publisher = Wiley Interscience
| location = New York
| year = 1985
| isbn = 0-471-88469-3
}}</ref>

In aprotic solvents, [[oligomer]]s, such as the well-known acetic acid [[Dimer (chemistry)|dimer]], may be formed by hydrogen bonding. An acid may also form hydrogen bonds to its conjugate base. This process, known as [[homoassociation|homoconjugation]], has the effect of enhancing the acidity of acids, lowering their effective p''K''<sub>a</sub> values, by stabilizing the conjugate base. Homoconjugation enhances the proton-donating power of toluenesulfonic acid in acetonitrile solution by a factor of nearly 800.<ref>{{cite journal
| last = Coetzee
| first = J.F.
| author2 = Padmanabhan, G.R.
| title = Proton Acceptor Power and Homoconjugation of Mono- and Diamines
| journal = J. Am. Chem. Soc.
| year = 1965
| volume = 87
| issue = 22
| pages = 5005–5010
| doi = 10.1021/ja00950a006
}}</ref>

In aqueous solutions, homoconjugation does not occur, because water forms stronger hydrogen bonds to the conjugate base than does the acid.

=== Mixed solvents ===
[[File:Acetic acid pK dioxane water.png|thumb|alt=The p K A of acetic acid in the mixed solvent dioxane/water. p K A increases as the proportion of dioxane increases, primarily because the dielectric constant of the mixture decreases with increasing doxane content. A lower dielectric constant disfavors the dissociation of the uncharged acid into the charged ions, H + and C H 3 C O O minus, shifting the equilibrium to favor the uncharged protonated form C H 3 C O O H. Since the protonated form is the reactant not the product of the dissociation, this shift decreases the equilibrium constant K A, and increases P K A, its negative logarithm.|p''K''<sub>a</sub> of acetic acid in dioxane/water mixtures. Data at 25&nbsp;°C from Pine ''et al.''<ref>{{cite book
| title = Organic chemistry
| last = Pine
| first = S.H.
| author2 = Hendrickson, J.B.
| author3 = Cram, D.J.
| author4 = Hammond, G.S.
| year = 1980
| publisher = McGraw–Hill
| isbn = 0-07-050115-7
| page = 203
}}</ref>]]

When a compound has limited solubility in water it is common practice (in the pharmaceutical industry, for example) to determine p''K''<sub>a</sub> values in a solvent mixture such as water/[[dioxane]] or water/[[methanol]], in which the compound is more soluble.<ref>{{cite journal
| last = Box
| first = K.J.
| author2 = Völgyi, G.
| author3 = Ruiz, R.
| author4 = Comer, J.E.
| author5 = Takács-Novák, K.
| author6 = Bosch, E.
| author7 = Ràfols, C.
| author8 = Rosés, M.
| year = 2007
| title = Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical Compounds
| journal = Helv. Chim. Acta
| volume = 90
| issue = 8
| pages = 1538–1553
| doi = 10.1002/hlca.200790161
}}</ref> In the example shown at the right, the p''K''<sub>a</sub> value rises steeply with increasing percentage of dioxane as the dielectric constant of the mixture is decreasing.

A p''K''<sub>a</sub> value obtained in a mixed solvent cannot be used directly for aqueous solutions. The reason for this is that when the solvent is in its standard state its activity is ''defined'' as one. For example, the standard state of water:dioxane mixture with 9:1 [[mixing ratio]] is precisely that solvent mixture, with no added solutes. To obtain the p''K''<sub>a</sub> value for use with aqueous solutions it has to be extrapolated to zero co-solvent concentration from values obtained from various co-solvent mixtures.

These facts are obscured by the omission of the solvent from the expression that is normally used to define p''K''<sub>a</sub>, but p''K''<sub>a</sub> values obtained in a ''given'' mixed solvent can be compared to each other, giving relative acid strengths. The same is true of p''K''<sub>a</sub> values obtained in a particular non-aqueous solvent such a DMSO.

A universal, solvent-independent, scale for acid dissociation constants has not been developed, since there is no known way to compare the standard states of two different solvents.