Acids and Bases

Using Molecular Structure to Predict Equilibrium

Atom effects, resonance delocalization, inductive effect, and orbital bearing the charge (ARIO) can also be used to predict acid-base reactions based on the ARIO effects of acid and conjugate acid.

The structure of a molecule correlates to acidity and is used to predict the outcome of acid-base reactions. Atom effects (electronegativity and the size of the atom bearing a charge), resonance delocalization effects, inductive effects, and the hybridization of the orbital bearing a charge all play a role in the acidity level of a molecule. One way to remember these effects is the acronym ARIO:

Atom effects (electronegativity and/or size of atom bearing charge)
Resonance delocalization
Inductive effect
Orbital bearing the charge (hybridization)

Atom Effects

The effect of the atom connected to the hydrogen can affect the acidity of that hydrogen. The periodic trends are used to determine the acidity.
Electronegativity is the tendency of an atom to attract electrons toward itself when forming bonds. Atoms with increased electronegativity are more stable after the addition of a negative charge. One example of the effect of electronegativity on acidity is demonstrated by the comparison of a hydrogen connected to an oxygen atom versus a hydrogen connected to a carbon atom. Oxygen is the more electronegative atom, and so it is more stable with a negative charge than a carbon with a negative charge. This stability results in a lower pKa value for oxygen than carbon, which indicates that oxygen is a stronger acid. In general, molecules with a hydrogen bonded to oxygen, such as methanol, are more acidic than molecules with a hydrogen bonded to carbon, such as ethane.
H3CCH3H3COHEthaneMethanolpKa=50pKa=15.5\begin{gathered}{\rm {H}_3C}{-}{\rm{CH}}_3&{\rm {H}_3 {C}}{-}\rm{OH}\\{\text{Ethane}}&{\text{Methanol}}\\{\rm {p}}K_{\rm a}=50&{\rm {p}}K_{\rm a}=15.5\end{gathered}
Electronegativity increases from left to right across a period (row) on the periodic table and from bottom to top within a group (column) on the periodic table. Because electronegativity is a periodic trend, the atomic effect of electronegativity can be applied using a periodic trend. Moving from left to right across the periodic table within a period increases the acidity. Likewise, moving from bottom to top within a group increases the acidity.

Periodic Trends for Electronegativity

The electronegativity of atoms increases when moving up a group (column) within the periodic table. This is because of the decreasing atomic radius and the closeness of the valence electrons to the nucleus. The electronegativity of atoms increases from left to right across a period (row) within the periodic table. This is because the valence shell is more than half full on the right side of the periodic table, making it easier to pull an electron rather than donate an electron.
The more stable and weaker a conjugate base, the stronger the acid that generated that conjugate base. Fluorine is the most electronegative atom. When HF dissociates, it forms fluoride, F, which is very stable because fluoride is more electronegative than oxygen, nitrogen, and carbon.
Electronegativity (highest first)F>O>N>CAcidity (strongest first)HF>H2O>NH3>CH4\begin{gathered}{\text{Electronegativity (highest first)}}&\rm{F}>{O}>{N}>{C}\\{\text{Acidity (strongest first)}}&\rm{HF}>{\rm{H}_2{O}>{NH_3}>{CH_4}}\end{gathered}
The size of anions affects their stability in a similar fashion to resonance delocalization. Anions that are larger have more room to spread out a negative charge and are therefore more stable. This is what makes hydrogen iodide (pKa=10)({\rm {p}}K_{\rm {a}}=-10) a stronger acid than hydrogen fluoride (pKa=3.2)({\rm {p}}K_{\rm {a}}=3.2).
HFHIHydrogen fluorideHydrogen iodidepKa=3.2pKa=10\begin{gathered}\rm {H{-}F}&{\rm H{-} I}\\\text{Hydrogen fluoride}&\text{Hydrogen iodide}\\{\rm {p}}K_{\rm a}=3.2&{\rm {p}}K_{\rm a}=-10\end{gathered}
Size increases down a group (column) in the periodic table; therefore, the strength of an acid increases down a column in the periodic table.

Periodic Trends for Atomic Radius

The atomic radius of atoms increases when moving down a group (column) within the periodic table. This is because of the increasing number of energy levels causing valence electrons to be farther away from the nucleus and thus have a larger atomic radius. The atomic radius of atoms increases from right to left across a period (row) within the periodic table. This is because of a larger attraction of valence electrons from the nucleus as protons are added going right to left across the period.
In group 17, the halogens, the size increases down the chart; so iodine is the largest atom and, thus, HI is the strongest HX acid. Fluorine is the smallest atom, and HF is the weakest HX acid. Larger atoms are more polarizable and have a much larger volume. Thus, larger atoms are able to disperse the negative charge that results from the dissociation of HX better than smaller atoms.
Largest atomic radiiI>Br>Cl>FSmallest atomic radiiStrongest acidHI>HBr>HCl>HFWeakest acid\begin{gathered}{\text{Largest atomic radii}}&{\rm{I}>{Br}>{Cl}>{F}}&{\text{Smallest atomic radii}}\\\\\text{Strongest acid}&{\rm{HI}>{HBr}>{HCl}>{HF}}&\text{Weakest acid}\end{gathered}
The strongest acids have the most stable conjugate base. HI is a very strong acid. When HI dissociates, iodide is a very stable and weak conjugate base. Because it is so large, it is able to spread the negative charge over a very large volume and form a stable, weak conjugate base.

It may seem counterintuitive that HI is a stronger acid than HF, because fluorine is more electronegative than iodine. But iodine is larger than fluorine. Therefore, there are two competing trends with the halogens—size and electronegativity. Size is a more important trend than electronegativity for the halogens, and HI is the stronger acid.

Resonance Delocalization

If a conjugate base has resonance structures, it will be a more stable (weaker) conjugate base and, therefore, formed from a stronger acid.
Delocalization of a negative charge is possible on molecules that have resonance structures. A resonance structure is one of two or more Lewis structures with multiple equivalent representations. This delocalization of the negative charge is a stabilizing factor, and the more atoms the charge is spread over, the more stable the anion. Anion stability equates to base stability, which means a stable base is a weak base. Therefore, if a base has resonance structures, it will be a stable, weak base and is generated from a strong acid. For example, the carboxylate anion is stabilized by resonance, while the ethoxide anion is not. Resonance is the method that organic chemists use to deal with organic molecules that have two or more Lewis structures with multiple equivalent representations.

Effect of Resonance Stabilization on Acidity

Resonance structures make the conjugate base of an acid more stable and weaker, making the acid stronger. The conjugate base of carboxylic acids has resonance structures, so it is more acidic than ethanol.
When a conjugate base is more stable, it is weaker. These conjugate bases come from acids that dissociate,and the equilibrium shifts toward the products (conjugate base). Resonance structures in a conjugate base make the molecule a weaker and more stable conjugate base, which means it was formed from a stronger acid. Resonance will spread out or delocalize the negative charge over multiple atoms. This is similar to how a large iodide spreads out the negative charge over its larger volume. Without resonance, a charge is "locked in"—localized on one atom—which makes that structure a less stable and stronger conjugate base. Phenol has resonance structures, but cyclohexanol has none. Therefore, phenol is a stronger acid because its conjugate base is stabilized by the resonance structures it forms. Resonance structures help stabilize a conjugate base and, thus, decrease the basicity of the conjugate base, which means that the conjugate base was generated from a stronger acid.

Phenol versus Cyclohexanol

Resonance structures make an acid stronger, which lowers its pKa. Phenol has resonance, so it is a stronger acid than cyclohexanol, which does not have resonance.

Inductive Effect

The inductive effect comes from the presence and location of electronegative atoms. The inductive effect stabilizes (weakens) a conjugate base; therefore, the conjugate base was formed from a strong acid.

An electronegativity difference between atoms creates a bond polarity, which leads to the inductive effect. The inductive effect relies on the intrinsic tendency of the molecule to withdraw or release electrons because of its electronegativity. As the distance between the electronegative atom and the acidic hydrogen atom increases, the inductive effect weakens. Electronegativity increases from left to right across a row (period) on the periodic table and from bottom to top within a group (column) on the periodic table. Fluorine, chlorine, nitrogen, and oxygen are some atoms that often create an inductive effect within a molecule.

The inductive effect weakens conjugate bases. Unlike the resonance effect, double bonds are not necessary, but the polarity of the bond is essential. The inductive effect is a permanent displacement of a shared electron pair of a covalent bond towards the more electronegative atoms or groups. As the inductive effect withdraws the negative charge from an atom, the charge is split over a larger volume and stabilizes. The inductive effect is similar to the polarizability of the electron cloud of larger atoms.

The inductive effect also stabilizes the anion, but to a lesser extent than resonance delocalization. The difference in electronegativities between two atoms causes the flow of electrons from the less electronegative atom toward the more electronegative atom. In a simple molecule such as water (H2O), this effect yields a bond dipole with a slightly positive end and a slightly negative end. In larger, more complex molecules, there might be many such bond dipoles. For example, there is a large difference in acidity between acetic acid and trichloroacetic acid. This difference is because carbon is more electronegative than hydrogen. In a carbon-hydrogen bond, the more electronegative carbon pulls the electron pair towards it and away from the hydrogen. Therefore, the carbon is on the negative end of carbon-hydrogen dipole with the hydrogen being on the positive end of the dipole. When the hydrogens are replaced with chlorines, the bond dipoles are reversed. This now puts carbon on the positive end of the carbon-hydrogen dipole, and the inductive effect works beneficially to stabilize the negative charge on the carboxylate anion.

ARIO: Impact of the Inductive Effect on Acidity

Compounds with electronegative atoms near an acidic hydrogen will be more acidic because of the inductive effect. Chlorine atoms make trichloroacetic acid more acidic than acetic acid. Trifluoroacetic acid is even more acidic.
Acetic acid (CH3COOH) is acidic because of both the atom and resonance effect. The acidic proton of acetic acid is connected to an electronegative oxygen atom, and the oxygen atom attached to the acidic proton is adjacent to a carbon-oxygen double bond. Because of this, acetic acid has a pKa of 4.76. Both acetic acid and trifluoroacetic acid (CF3COOH) are acidic because of both the atom and the resonance effect. However, trifluoroacetic acid also has a very strong inductive effect because of the presence of the three fluorine atoms and is, therefore, more acidic than acetic acid. Additionally, acetic acid contains a methyl group, which is an electron donating group (as opposed to halogens which are electron withdrawing groups). Electron donating groups create a reverse inductive effect and make an acid a weaker acid. Trifluoroacetic acid has a pKa of 0.23.

ARIO Effect on pKa of Various Compounds

Compound pKa Atom Effect Resonance Effect Inductive Effect Summary
Ethanol (CH3CH2OH) 15.5 Bonded to oxygen Absent Absent Only atom effect, so higher pKa
Acetic acid (CH3COOH) 4.76 Bonded to oxygen Present Decreasing acidity Resonance effect and a reverse inductive effect because of an electron donating group (alkyl group, CH3)
Formic acid (HCOOH) 3.75 Bonded to oxygen Present Absent Resonance effect, so low pKa
Trichloroacetic acid (CCl3COOH) 0.66 Bonded to oxygen Present Increasing acidity Resonance and inductive effect, very low pKa
Trifluoroacetic acid (CF3COOH) 0.23 Bonded to oxygen Present Increasing acidity Resonance and strongest inductive effect, lowest pKa

Ethanol has a higher pKa (less acidic) than formic acid, acetic acid, trichloroacetic acid, and trifluoroacetic acid because ethanol only exhibits an atom effect while the other compounds also have a resonance effect. Formic acid is more acidic than acetic acid because acetic acid has a donating group, which adds electron density. Trichloroacetic acid and trifluoroacetic acid are very acidic because of the inductive effect. Fluorine has a slightly larger inductive effect because it is more electronegative.

Orbital Bearing the Charge (Hybridization)

The hybridization of the atom connected to the hydrogen also helps explain qualitatively the strength of an acid. The more s character in the acid, the stronger the acid. An sp-hybridized orbital (alkyne) is more acidic than an sp2-hybridized orbital (alkene), which is more acidic than an sp3-hybridized orbital (alkane).

Orbital hybridization also plays a role in the acidity of a molecular structure. Acidity is linked to stability, and an increase in stability of an anion leads to an increase in acidity. An orbital is a region in which an electron has a high probability of being located. Orbitals are described by the quantum numbers s, p, d, and f, which differ from one another by their shapes. A hybrid orbital is an electron orbital that forms when two atomic orbitals combine to form a covalent bond.

Hybrid orbitals consist of a combination of one s orbital and either one, two, or three p orbitals. As s orbitals are closer to the nucleus, these electrons are lower in energy than those in the p orbitals. Therefore, hybrid orbitals that have a high s-to-p ratio (sp) form more stable anions than those that have a low s-to-p ratio (sp3). An sp hybrid orbital is one that forms from combining one s and one p orbital. An sp3 hybrid orbital is one that forms from combining one s and three p orbitals.

The more s character in the acid, the more closely the electrons are held to the nucleus, making the conjugate base more stable. The more s character of the bond to the hydrogen, the more acidic the hydrogen. The greater the s character of the hybrid orbital, the greater the electronegativity and, thus, the stronger the acid.

Therefore, sp-hybridized alkynes (triple bonds) are stronger acids than sp2-hybridized alkenes (double bonds), which are stronger acids than sp3-hybridized alkanes (single bonds). This is because of the conjugate base being stabilized. The triple-bonded sp orbital stabilizes the negative charge better than a double-bond sp2-hybridized orbital, which handles it better than a single-bond sp3-hybridized orbital.
Stronger acidssp-hybridized>sp2-hybridized>sp3-hybridizedWeaker acids\begin{aligned}{\text{Stronger acids}}\hspace{10pt}sp\text{-hybridized}\;>\;sp^2\text{-hybridized}\;>sp^3\text{-hybridized}\hspace{10pt}\text{Weaker acids}\end{aligned}
H3CCH3H2C=CH2HCCHEthaneEtheneEthynesp3sp2sppKa=50pKa=44pKa=25\begin{gathered}{\rm {H}_3{C}{-}{CH}}_3&{\rm {H}_2{C}{=}{CH}}_2&{\rm{HC}{\equiv}{CH}}\\\text{Ethane}&\text{Ethene}&\text{Ethyne}\\sp^3&sp^2&sp\\{\rm {p}}K_{\rm a}=50&{\rm {p}}K_{\rm_{a}}=44&{\rm {p}}K_{\rm {a}}=25\\\end{gathered}