The “free-base” form of cocaine (C₁₇H₂₁NO₄) and its protonated hydrochloride form (C₁₇H₂₂ClO₄) are shown below; the free-base form can be converted to the hydrochloride form with one equivalent of HCl. For clarity, not all the carbon and hydrogen atoms are shown; each vertex represents a carbon atom with the appropriate number of hydrogen atoms so that each carbon makes four bonds to other atoms.
a. Which form of cocaine, the free base or the hydrochloride, is relatively water-soluble?

Verified step by step guidance

1. Identify the structural differences between the free-base form of cocaine (C₁₇H₂₁NO₄) and its hydrochloride form (C₁₇H₂₂ClO₄). The hydrochloride form includes an additional HCl group compared to the free-base form.
2. Understand the impact of the HCl group on solubility. The addition of HCl to the cocaine molecule results in the formation of a salt, which typically enhances solubility in water due to the ionic character of the salt.
3. Recognize that the free-base form of cocaine is more nonpolar compared to its hydrochloride form. Nonpolar substances tend to be less soluble in water, which is a polar solvent.
4. Consider the role of hydrogen bonding and ion-dipole interactions. The hydrochloride form can participate in more extensive hydrogen bonding and ion-dipole interactions with water molecules due to its ionic nature, further increasing its solubility.
5. Conclude that the hydrochloride form of cocaine is relatively more water-soluble than the free-base form due to its ionic character and ability to form favorable interactions with water.

Key Concepts

Solubility and Polarity

Solubility refers to the ability of a substance to dissolve in a solvent, which is often influenced by the polarity of the molecules involved. Polar substances tend to dissolve well in polar solvents (like water), while nonpolar substances are more soluble in nonpolar solvents. The presence of functional groups, such as amines or carboxylic acids, can enhance a compound's polarity and, consequently, its solubility in water.

Acid-Base Chemistry

Acid-base chemistry involves the transfer of protons (H+) between substances. In this context, the free-base form of cocaine is a neutral base, while the hydrochloride form is a salt formed by the protonation of the base with hydrochloric acid. This protonation increases the compound's polarity, which typically enhances its solubility in water due to the ionic nature of the hydrochloride form.

Ionic vs. Molecular Compounds

Ionic compounds, such as hydrochloride salts, are formed from the electrostatic attraction between positively and negatively charged ions. These compounds generally have higher solubility in water compared to molecular compounds, which are held together by covalent bonds. The ionic nature of the hydrochloride form of cocaine allows it to interact more favorably with water molecules, leading to increased solubility compared to its free-base counterpart.