Chapter 8: Noncovalent Intermolecular Interactions, Nomenclature, and Solubility of Alkyl Halides, Alcohols, Thiols, Ethers, and Sulfides

Noncovalent Intermolecular Interactions and Functional Groups

Definitions and Classification of Alkyl Halides, Alcohols, Thiols, Ethers, and Sulfides

This section introduces the main functional groups relevant to organic chemistry and their classification based on structure and bonding.

• Alkyl halide: A compound where a halogen (F, Cl, Br, I) is bonded to the carbon of an alkyl group.

• Alcohol: Contains a hydroxyl group (–OH) bonded to an alkyl carbon.

• Thiols: Contain a mercapto or sulfhydryl group (–SH) bonded to an alkyl carbon.

• Ethers: Compounds with an oxygen atom bonded to two carbon groups.

• Sulfides (thioethers): Sulfur analogs of ethers, with sulfur bonded to two carbon groups.

Special Cases:

• Phenol: OH group bonded to an aryl (aromatic) carbon.

• Enol: OH group bonded to an sp2-hybridized carbon of a double bond.

Classification by Substitution

• Alkyl halides and alcohols are classified by the number of alkyl groups attached to the α-carbon (the carbon bonded to the halogen or oxygen):

  • Primary (1°): One alkyl group attached

  • Secondary (2°): Two alkyl groups attached

  • Tertiary (3°): Three alkyl groups attached

Nomenclature of Alkyl Halides, Alcohols, Thiols, Ethers, and Sulfides

Steps for IUPAC Nomenclature

1. Identify the principal group (e.g., –OH, –SH).

2. Identify the principal chain (longest chain containing the principal group, double/triple bonds, or greatest number of substituents).

3. Number the chain to give the principal group the lowest possible number.

4. Assemble the name: cite the principal group by its suffix and number, then list substituents in alphabetical order.

Common and IUPAC Names

• Alkyl Halides: Common names use the alkyl group name followed by the halide (e.g., ethyl chloride). IUPAC names treat halogens as substituents (e.g., 2-chloropropane).

• Alcohols: Common names specify the alkyl group + "alcohol" (e.g., methyl alcohol). IUPAC names use the suffix "-ol" (e.g., ethanol).

• Glycols: Compounds with two or more –OH groups on different carbons (e.g., ethylene glycol, glycerol).

• Thiols: Named as mercaptans in the common system (e.g., ethyl mercaptan); IUPAC uses "thiol" as a suffix (e.g., ethanethiol).

• Ethers and Sulfides: Common names cite the two groups attached to O or S, followed by "ether" or "sulfide" (e.g., diethyl ether, ethyl methyl sulfide). Substitutive names use "alkoxy" (RO–) or "alkylthio" (RS–) as substituents (e.g., 2-methoxypropane).

Heterocyclic Nomenclature

• Cyclic ethers and sulfides with at least one atom other than carbon are called heterocyclic compounds (e.g., furan, tetrahydrofuran, thiophene, 1,4-dioxane, oxirane).

• Epoxides: Cyclic ethers with a three-membered ring; parent compound is oxirane.

Structures and Properties

Bond Angles and Bond Lengths

• Bond angles at α-carbons are nearly tetrahedral (sp3 hybridized).

• Bond angles at O or S are affected by lone pairs, typically less than 109.5° (e.g., 104.5° in water).

• Bond lengths vary by group; for example, C–O and C–S bonds are longer than C–H bonds.

	Group 4A	Group 5A	Group 6A	Group 7A
H3C–X	CH3–CH3 153.6 pm	CH3–NH2 147.4 pm	CH3–OH 142.6 pm CH3–SH 181.2 pm	CH3–F 139.1 pm CH3–Cl 178.1 pm CH3–Br 193.9 pm CH3–I 212.9 pm

Noncovalent Intermolecular Interactions

Types of Noncovalent Interactions

• Van der Waals (dispersion) forces: Weak attractions due to temporary dipoles.

• Dipole–dipole attractions: Between molecules with permanent dipoles.

• Hydrogen bonding: Strong dipole–dipole interaction involving H bonded to N, O, or F.

• Charge–dipole attractions: Between ions and polar molecules.

• Steric effects: Repulsions due to spatial crowding.

Key Points on Intermolecular Associations

• Hydrogen bonding increases boiling points significantly.

• Permanent dipoles also raise boiling points compared to nonpolar molecules of similar size.

• Van der Waals forces depend on surface area, shape, and polarizability.

Physical Properties and Trends

Boiling Points and Densities

• Alkyl halides have significant dipole moments but often lower boiling points than alkanes of similar mass due to smaller surface area and weaker van der Waals forces.

• Alcohols have much higher boiling points due to hydrogen bonding.

Hydrogen Bonding

• Requires a hydrogen bond donor (H attached to N, O, or F) and an acceptor (lone pair on N, O, or F).

• Hydrogen-bonded networks are common in water and alcohols, leading to unique physical properties.

Solutions and Solubility

Introduction to Solutions

• Solute is added to solvent.

• If a single clear liquid phase forms, the solute is soluble in the solvent.

• Free energy of solution: $\Delta G_{\text{solution}} = G(\text{solution}) - [G(\text{pure solute}) + G(\text{pure solvent})]$

• Solution formation is favorable if $\Delta G_{\text{solution}} < 0$.

Solution Energetics

• Mixing enthalpy: $\Delta H_{\text{mixing}} = 0 \implies \Delta G_{\text{mixing}} = -T\Delta S_{\text{mixing}}$

• Noncovalent interactions contribute to $\Delta G_{\text{inter}}$.

• Total free energy change: $\Delta G_{\text{solution}} = \Delta G_{\text{inter}} + \Delta G_{\text{mixing}}$

Classification of Solvents

• Protic: Can donate H-bonds (e.g., water, alcohols).

• Aprotic: Cannot donate H-bonds.

• Polar: High dielectric constant ($\varepsilon > 15$).

• Apolar: Low dielectric constant.

• Donor: Lewis base (can donate electron pairs).

• Nondonor: Cannot donate electron pairs.

Solvent	Structure	Boiling Point (°C)	Dielectric Constant	Dipole Moment	Class: Protic	Class: Polar
Hexane	CH3(CH2)4CH3	69	1.9	0.0	No	No
1,4-Dioxane		101.3	2.2	0.4	No	No
Diethyl ether	CH3CH2OCH2CH3	34.6	4.3	1.2	No	No
Acetone	CH3COCH3	56.2	20.7	2.7	No	Yes
Water	H2O	100	78.5	1.9	Yes	Yes

Solubility of Covalent Compounds

• "Like dissolves like": Polar solutes dissolve in polar solvents; nonpolar in nonpolar.

• Miscible liquids form a solution in any proportion (e.g., methanol and water).

• Alcohols can both donate and accept hydrogen bonds, enhancing water solubility.

Solubility in Water and Chain Length of Alcohols

• Short-chain alcohols (e.g., methanol, ethanol) are miscible with water.

• As the hydrocarbon chain length increases, water solubility decreases.

• Rule of thumb: One –OH group per five carbons usually confers significant water solubility.

Xenobiotic Metabolism

• Xenobiotic: A substance not normally found in living organisms.

• Low water-solubility xenobiotics are metabolized to more water-soluble forms for excretion.

Solubility of Hydrocarbons in Water

• Hydrocarbons have very low, but measurable, water solubility (e.g., pentane: $5 \times 10^{-4}$ M).

• Hydrophobic bonding: Hydrocarbon groups associate in water, releasing low-entropy water and increasing overall entropy.

Steps in Dissolving a Solid Covalent Compound

1. Solid must melt (become a liquid).

2. Liquid must dissolve in the solvent.

Overall free energy change: $\Delta G^*_f (\text{solid}) = \Delta G^*_m,298 + \Delta G^*_f (\text{liquid})$

Symmetry, Melting Points, and Solubility

• Symmetrical compounds have higher melting points and are less soluble.

• Higher melting point solids have greater $\Delta G^*_{m,298}$ and lower solubility.

Solubility of Ionic Compounds

• Measured by the dielectric constant ($\varepsilon$) of the solvent.

• Stabilization of ions involves charge–dipole, hydrogen bonding, and donor interactions.

Case Study: NaCl in Water

• NaCl dissolves due to charge–dipole interactions, hydrogen bonding, and donor interactions with water molecules.

Acid–Base Reactions and Solubility

• Acid–base reactions can convert poorly soluble compounds into highly soluble salts (e.g., benzoic acid to sodium benzoate).

Applications: Enantiomeric Resolution and Drug Solubility

Enantiomeric Resolution

• Noncovalent interactions, solubility, and solvation are crucial for separating enantiomers.

• Selective crystallization uses a seed crystal of the desired enantiomer to form diastereomeric crystals, enhancing purity.

Cell Membrane and Drug Solubility

• Drug solubility is essential for biological activity; drugs must be water-soluble and able to cross cell membranes.

• Cell membranes are composed of phospholipids, which have amphipathic properties (hydrophilic head, hydrophobic tail).

• Phospholipid bilayers form barriers that drugs must traverse to reach their targets.

Component	Property
Polar head group	Hydrophilic, interacts with water
Nonpolar tail	Hydrophobic, not solvated by water
Amphipathic molecule	Contains both hydrophilic and hydrophobic regions

Summary: Understanding noncovalent interactions, nomenclature, and solubility principles is essential for predicting the behavior of organic molecules in biological and chemical systems.