Difficulty: Intermediate | Prerequisites: Functional groups (Ch. 8.1-8.2), intermolecular forces (Ch. 8.4-8.5)
This section covers why some compounds dissolve in some solvents and not others. It brings together everything from the intermolecular-forces section and applies it to real mixtures. The central idea is "like dissolves like": the intermolecular forces in the solute must be compatible with those in the solvent. You will also meet specialised cation-binding molecules (crown ethers, cryptands) that have important applications in chemistry and biology.
Whether a compound dissolves in a given solvent depends on the compatibility of their intermolecular forces: "like dissolves like." Entropy of mixing always favours dissolution, but if the solute-solvent interactions are much weaker than the solute-solute or solvent-solvent interactions, the compound stays insoluble. Ionic compounds need solvents that can solvate both cations and anions through charge-dipole interactions, donor interactions and hydrogen bonding.
Solute
The substance added to (dissolved in) a large amount of liquid.
Solvent
The liquid that does the dissolving.
Solution
A single, clear, homogeneous liquid formed when a solute dissolves in a solvent.
Soluble
Describes a solute that can be dissolved in a given solvent.
Insoluble
Describes substances that do not mix or react with each other to form a solution.
Entropy of mixing
A quantitative description of the probability of solution formation that is completely independent of intermolecular interactions. In simple terms, mixing increases disorder, and this entropy gain always favours dissolution.
Protic solvent
A solvent whose molecules can act as hydrogen-bond donors (e.g. water, ethanol, methanol).
Aprotic solvent
A solvent that cannot donate hydrogen bonds (e.g. acetone, DMSO, DMF).
Polar solvent
A solvent with a high dielectric constant (e.g. water, DMSO).
Apolar solvent
A solvent with a low dielectric constant (e.g. hexane, benzene).
Donor solvent
A solvent whose molecules contain oxygen or nitrogen that can donate nonbonding electron pairs (act as Lewis bases).
Nondonor solvent
A solvent that cannot act as a Lewis base.
Dielectric constant
A property of the solvent that scales the electrostatic interaction energy between two charges. A high dielectric constant weakens ion-ion attractions and favours ion separation.
Solvation
The favourable interaction of a dissolved molecule or ion with solvent molecules.
Solvation shell
The layer of solvent molecules surrounding a dissolved ion.
Ion pair
A pair of ions closely associated with each other (cation next to anion) in solution.
Dissociated ions
Ions that move independently in solution, each surrounded by its own solvation shell.
Hydrophobic bonding
The tendency of hydrocarbon groups to associate with each other in aqueous solution, driven by the entropic cost of organising water molecules around nonpolar surfaces.
Xenobiotic
Any substance that is not a normal constituent of a living organism, such as a drug or environmental pollutant.
Ionophore
A molecule that forms strong complexes with ions, effectively carrying them across barriers.
Crown ether
A heterocyclic ether containing regularly spaced oxygen atoms in a ring. The ring size determines which cation it binds. The bracket number is the total atom count in the ring; the hyphenated number is the count of oxygens (e.g. [18]-crown-6 has 18 ring atoms, 6 of which are oxygens).
Cryptand
A nitrogen-containing analogue of a crown ether, forming a three-dimensional cage that can encapsulate a cation.
Ionophore antibiotic
A biologically important ionophore that interferes with the growth or survival of microorganisms by disrupting their ion transport.
A good solvent usually shares some of the molecular characteristics of the compound being dissolved. When the intermolecular forces between solute and solvent are similar to those within the pure liquids, the free-energy cost of mixing is modest, and the positive entropy of mixing drives the formation of a solution.
Dipole-induced-dipole interactions also contribute: a polar molecule can create temporary dipoles in a neighbouring nonpolar molecule.
Compounds that are both hydrogen-bond donors and acceptors have the best water solubility.
Compounds that are only hydrogen-bond acceptors dissolve in water less well, but better than compounds with no hydrogen-bonding capability at all.
Hydrocarbon portions of a molecule reduce aqueous solubility.
A useful rule of thumb: a compound with one -OH group for every five carbon atoms usually has significant water solubility.
Solvents are classified along three axes:
Protic vs. aprotic: Can the solvent donate hydrogen bonds? Water and ethanol are protic; acetone and DMSO are aprotic.
Polar vs. apolar: Does the solvent have a high dielectric constant? Water (dielectric constant 78) is highly polar; hexane (1.9) is apolar.
Donor vs. nondonor: Can the solvent donate lone pairs (act as a Lewis base)? THF and DMF are donors; dichloromethane is a nondonor.
Dipolar solvents consist of molecules with significant dipole moments. The dielectric constant quantifies the solvent's ability to weaken the electrostatic interaction between charges.
Hydrocarbons are poorly soluble in water. When a nonpolar molecule such as pentane is placed in water, the water molecules at the water-pentane interface become more ordered, losing motional freedom. This lowers the entropy of the system, making dissolution unfavourable.
Hydrophobic bonding is the tendency of hydrocarbon groups to cluster together in aqueous solution, which releases the ordered water molecules back into the bulk and restores entropy. This is the driving force behind micelle formation, protein folding (burying nonpolar residues inside) and membrane assembly.
Most ionic inorganic compounds are solids with strong lattice energies. For a solvent to dissolve an ionic compound, the solvation energy must be large enough to compensate for breaking apart the crystal lattice.
Ion solvation occurs through three mechanisms:
Charge-dipole interactions: The solvent's dipole moment vectors orient so the negative end points towards the cation, stabilising it.
Hydrogen-bonding interactions: If the solvent is protic, it can hydrogen-bond to anions, solvating negative charges.
Donor interactions: A donor solvent acts as a Lewis base, donating lone pairs to cations.
Ionic compounds are relatively soluble in solvents where ions are well separated and well solvated.
Crown ethers are heterocyclic ethers with regularly spaced oxygen atoms around a ring. The oxygen lone pairs point inward and coordinate metal cations. The size of the ring determines which cation is the best fit (e.g. [18]-crown-6 binds K+ particularly well).
In the naming convention, the bracketed number is the total atom count in the ring, and the hyphenated number after "crown" is the number of oxygens. Dibenzo variants incorporate aromatic rings into the crown.
Cryptands are the three-dimensional, nitrogen-containing analogues of crown ethers. They wrap around a cation more completely, forming even stronger complexes.
Ionophore antibiotics are biologically important ionophores that transport ions across cell membranes, disrupting the ion gradients that microorganisms need to survive.
Dielectric constant equation: E = k(q1 * q2) / (epsilon * r), where E is the interaction energy between two ion charges q1 and q2 separated by distance r, and epsilon is the dielectric constant of the solvent. A high epsilon weakens the attraction between ions, favouring dissolution.
Entropy of solution: T * delta S (solution) = T * delta S (intermolecular) + T * delta S (mixing). The mixing term is always positive (favours dissolution). The intermolecular term can be negative if dissolving the solute forces the solvent into a more ordered arrangement.
Free energy of dissolving a solid: delta G (solid) = delta G (melting at 298 K) + delta G (liquid dissolution). Melting the solid is part of the overall solution process.
Students often assume that all polar compounds dissolve in water. Polarity helps, but a large hydrocarbon portion can overwhelm the effect. The one -OH per five carbons rule is a better guide.
Students confuse "protic" with "polar." A solvent can be polar without being protic (e.g. DMSO has a high dielectric constant but no O-H or N-H bond to donate). The two classifications are independent.
Students sometimes think hydrophobic bonding is an attractive force between nonpolar molecules. It is better understood as an entropy-driven clustering: the hydrocarbon groups come together because this releases the ordered water molecules around them, increasing the system's entropy.
Students forget that dissolving a solid involves two steps: melting the solid (breaking the crystal lattice) and then mixing the liquid solute with the solvent. Both contribute to the overall free energy.
"Like dissolves like" is the most commonly tested principle from this section. Be prepared to predict whether a given solute will dissolve in a given solvent by comparing their intermolecular forces.
Solvent classification questions (protic vs. aprotic, polar vs. apolar, donor vs. nondonor) appear frequently. Know which common solvents fall into which categories.
Crown ether selectivity (matching ring size to cation size) is a favourite exam topic. Know that [18]-crown-6 is a good fit for K+.
Expect questions asking you to explain why a particular ionic compound is soluble in one solvent but not another, in terms of charge-dipole interactions, hydrogen bonding and donor interactions.
Hydrophobic bonding and its entropic origin may appear as a short-answer or conceptual question.
True or false: A protic solvent must also be polar. (False. Protic means the solvent can donate hydrogen bonds. A solvent can be protic with a modest dielectric constant.)
Fill in the blank: The tendency of hydrocarbon groups to cluster together in water is called ______ bonding. (Hydrophobic.)
True or false: Entropy of mixing always opposes the formation of a solution. (False. Entropy of mixing always favours dissolution.)
Fill in the blank: In [18]-crown-6, the ring contains ______ total atoms, of which ______ are oxygens. (18; 6.)
True or false: A donor solvent acts as a Lewis acid. (False. A donor solvent acts as a Lewis base, donating lone pairs to cations.)
Q: Explain why ethanol is miscible with water but hexane is not.
A: Ethanol has an -OH group that can form hydrogen bonds with water (it is both a donor and an acceptor), so the solute-solvent interactions are comparable to the solvent-solvent interactions in pure water. Hexane is nonpolar, with only van der Waals forces. Dissolving hexane in water would break strong water-water hydrogen bonds and replace them with weak hexane-water van der Waals interactions, which is energetically unfavourable. The entropy of mixing alone cannot overcome this.
Q: Classify DMSO (dimethyl sulfoxide) as protic or aprotic, polar or apolar, and donor or nondonor.
A: Aprotic (no O-H or N-H bond), polar (high dielectric constant, roughly 47), and donor (the sulfoxide oxygen has lone pairs that can coordinate to cations).
Q: Why does [18]-crown-6 selectively bind potassium ions?
A: The cavity size of [18]-crown-6 is a near-perfect match for the ionic radius of K+. The six inward-pointing oxygen lone pairs coordinate the cation, stabilising it. Smaller cations (Na+) rattle around in the cavity; larger ones (Cs+) do not fit.
Q: A student dissolves a small amount of 1-octanol in water and observes low solubility. They then try 1-butanol and find it dissolves readily. Explain the difference.
A: 1-Butanol has one -OH group and four carbons, close to the one -OH per five carbons guideline. Its -OH can hydrogen-bond with water strongly enough to offset the hydrophobic effect of the short hydrocarbon tail. 1-Octanol has the same single -OH but eight carbons, so the nonpolar portion overwhelms the hydrogen-bonding capability, and the compound is largely insoluble.
Q: What are the three mechanisms by which a solvent solvates ions from an ionic crystal?
A: Charge-dipole interactions (the solvent's dipole aligns with the ion's charge), hydrogen-bonding interactions (a protic solvent hydrogen-bonds to anions), and donor interactions (a donor solvent donates lone pairs to cations as a Lewis base).
Solubility principles reappear throughout organic chemistry whenever you choose a solvent for a reaction (SN1 vs. SN2 reactions, for example, are strongly influenced by solvent polarity and protic vs. aprotic character).
Hydrophobic bonding is a foundational concept in biochemistry. It drives protein folding, membrane formation and the binding of drugs to receptors.
Crown ethers and cryptands come back in organometallic chemistry and catalysis, where they are used to solubilise metal salts in nonpolar solvents and to activate nucleophilic anions.
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