Functional Groups in Organic Compounds

Why This Matters

Functional groups are the reactive heart of organic chemistry—they determine how molecules behave, what reactions they undergo, and what physical properties they exhibit. When you're working through synthesis problems, predicting products, or explaining why one compound is more acidic than another, you're really analyzing functional groups. The exam will test your ability to recognize these groups, predict their reactivity patterns, and understand how electronegativity, hydrogen bonding, resonance, and polarity influence their behavior.

Don't just memorize structures and names. For each functional group, know what makes it reactive (is it a nucleophile? electrophile? acid? base?), how it affects physical properties (boiling point, solubility), and what transformations it undergoes. When you can connect a carbonyl's electrophilicity to its reaction with nucleophiles, or explain why carboxylic acids are more acidic than alcohols using resonance stabilization, you're thinking like an organic chemist—and that's exactly what earns full credit on synthesis and mechanism questions.

---

Hydrocarbons: The Carbon Backbone

These groups form the foundation of organic molecules. Their reactivity depends on bond saturation—the more unsaturated (more π bonds), the more reactive the compound becomes toward addition reactions.

Alkyl Groups

• Saturated hydrocarbon substituents derived from alkanes by removing one hydrogen; represented as $\text{R}-$ in structural formulas
• Classification as primary, secondary, or tertiary depends on how many carbons attach to the carbon bearing the substituent—this affects stability of carbocations and radicals
• Electron-donating through induction—alkyl groups stabilize adjacent positive charges, which is why tertiary carbocations are more stable than primary

Alkenes ($\text{C}=\text{C}$)

• Carbon-carbon double bond creates a region of high electron density above and below the molecular plane—this π bond is the site of reactivity
• Unsaturated hydrocarbons undergo addition reactions (hydrogenation, halogenation, hydration) rather than substitution
• Markovnikov's rule applies—in electrophilic addition, the hydrogen adds to the carbon with more hydrogens, forming the more stable carbocation intermediate

Alkynes ($\text{C}\equiv\text{C}$)

• Carbon-carbon triple bond consists of one σ bond and two π bonds, making alkynes even more unsaturated than alkenes
• Terminal alkynes are weakly acidic—the $\text{sp}$ hybridized carbon holds electrons more tightly, stabilizing the conjugate base ($\text{pK}_\text{a} \approx 25$)
• Undergo addition reactions twice—can add two equivalents of reagent, converting to alkenes then alkanes

---

Oxygen-Containing Groups: Polarity and Hydrogen Bonding

Oxygen's electronegativity creates polar bonds and enables hydrogen bonding. The degree of hydrogen bonding—and whether the group can donate or only accept H-bonds—determines boiling points and solubility.

Alcohols ($-\text{OH}$)

• Hydroxyl group attached to saturated carbon enables both hydrogen bond donation and acceptance, leading to high boiling points relative to molecular weight
• Classification as 1°, 2°, or 3° determines oxidation products: primary alcohols → aldehydes → carboxylic acids; secondary → ketones; tertiary cannot be oxidized
• Weakly acidic ($\text{pK}_\text{a} \approx 16$)—can be deprotonated by strong bases to form alkoxide nucleophiles

Ethers ($-\text{O}-$)

• Oxygen bonded to two carbon groups can accept hydrogen bonds but cannot donate them—results in lower boiling points than alcohols of similar mass
• Relatively unreactive due to lack of acidic hydrogens and poor leaving group ability—makes them excellent inert solvents
• Lewis bases through oxygen lone pairs—can coordinate with Lewis acids and stabilize cations in solution

Aldehydes ($-\text{CHO}$)

• Carbonyl group at terminal position with at least one hydrogen attached to the carbonyl carbon—this hydrogen makes aldehydes oxidizable to carboxylic acids
• Electrophilic carbonyl carbon is attacked by nucleophiles in addition reactions (Grignard reagents, hydride reductions, aldol reactions)
• Can be detected by Tollens' or Fehling's test—oxidation produces a visible change, distinguishing aldehydes from ketones

Ketones ($\text{C}=\text{O}$ flanked by carbons)

• Internal carbonyl group bonded to two carbon atoms—no oxidizable hydrogen means ketones resist oxidation under normal conditions
• Electrophilic but less reactive than aldehydes due to electron donation from two alkyl groups and increased steric hindrance
• Undergo nucleophilic addition and are key intermediates in aldol condensations and enolate chemistry

---

Carboxylic Acid Derivatives: The Reactivity Ladder

These groups all contain a carbonyl bonded to an electronegative atom. Reactivity in nucleophilic acyl substitution depends on leaving group ability—better leaving group means more reactive derivative.

Carboxylic Acids ($-\text{COOH}$)

• Carboxyl group combines carbonyl and hydroxyl—the resulting conjugate base is resonance-stabilized across two equivalent oxygens, making these the most acidic common organic functional group ($\text{pK}_\text{a} \approx 4-5$)
• Dimerization through hydrogen bonding creates cyclic dimers, leading to unusually high boiling points
• Parent compound for all acyl derivatives—can be converted to acid chlorides, esters, and amides through appropriate reactions

Esters ($-\text{COO}-$)

• Formed from carboxylic acid + alcohol via Fischer esterification (acid-catalyzed) or reaction of acid chloride with alcohol
• Moderate reactivity in nucleophilic acyl substitution—alkoxide is a decent leaving group; hydrolysis regenerates acid and alcohol
• Pleasant odors make them important in fragrances and flavors—lower boiling points than acids due to inability to form hydrogen-bonded dimers

Amides ($-\text{CONH}_2$)

• Least reactive carboxylic acid derivative because nitrogen's lone pair delocalizes into the carbonyl, reducing electrophilicity and making $\text{NH}_2^-$ a terrible leaving group
• Strong hydrogen bonding from both $\text{N}-\text{H}$ donors and $\text{C}=\text{O}$ acceptors gives amides the highest boiling points among derivatives
• Peptide bonds are amides—understanding amide stability and reactivity is essential for biochemistry connections

---

Nitrogen-Containing Groups: Bases and Beyond

Nitrogen's lone pair makes these groups basic and nucleophilic. Basicity depends on lone pair availability—resonance delocalization or electron-withdrawing groups reduce basicity.

Amines ($-\text{NH}_2$, $-\text{NHR}$, $-\text{NR}_2$)

• Derivatives of ammonia with alkyl/aryl groups replacing hydrogens—classified as primary (1°), secondary (2°), or tertiary (3°) based on substitution
• Basic and nucleophilic due to nitrogen's lone pair ($\text{pK}_\text{b} \approx 4$, or $\text{pK}_\text{a}$ of conjugate acid $\approx 10$)—react with acids and electrophiles
• Hydrogen bonding capability (1° and 2° amines) leads to higher boiling points than comparable hydrocarbons but lower than alcohols

Nitriles ($-\text{C}\equiv\text{N}$)

• Triple bond between carbon and nitrogen makes the carbon electrophilic—nitriles can be hydrolyzed to carboxylic acids or reduced to amines
• Polar but aprotic—useful as solvents; higher boiling points than hydrocarbons due to dipole-dipole interactions
• Linear geometry at the nitrile carbon due to $\text{sp}$ hybridization

Nitro Groups ($-\text{NO}_2$)

• Powerful electron-withdrawing group through both resonance and induction—dramatically increases acidity of adjacent hydrogens and deactivates aromatic rings
• Resonance structures show positive charge on nitrogen and negative charge distributed over oxygens
• Can be reduced to amines—important synthetic transformation for introducing $\text{NH}_2$ groups onto aromatic rings

---

Halides and Sulfur Groups: Substitution and Oxidation

These groups introduce unique reactivity patterns. Halides are excellent leaving groups for substitution reactions; thiols undergo oxidation chemistry that alcohols cannot.

Alkyl Halides ($-\text{F}$, $-\text{Cl}$, $-\text{Br}$, $-\text{I}$)

• Carbon-halogen bonds are polar with electrophilic carbon—reactivity in $\text{S}_\text{N}1$, $\text{S}_\text{N}2$, $\text{E}1$, and $\text{E}2$ depends on halide, substrate class, nucleophile, and solvent
• Leaving group ability increases down the periodic table ($\text{I}^- > \text{Br}^- > \text{Cl}^- > \text{F}^-$) due to decreasing bond strength and increasing anion stability
• Primary halides favor $\text{S}_\text{N}2$; tertiary favor $\text{S}_\text{N}1$/$\text{E}1$—this substrate classification is heavily tested in mechanism problems

Thiols ($-\text{SH}$)

• Sulfur analog of alcohols but more acidic ($\text{pK}_\text{a} \approx 10$) because sulfur better stabilizes negative charge due to larger atomic size
• Form disulfide bonds ($\text{R}-\text{S}-\text{S}-\text{R}$) through oxidation—critical for protein tertiary structure (cysteine residues)
• Distinctive odor—responsible for the smell of garlic, onions, and skunk spray

---

Quick Reference Table

---

Self-Check Questions

1. Rank the following in order of decreasing acidity and explain using resonance: carboxylic acid, alcohol, thiol, terminal alkyne.

2. Why are amides far less reactive than esters toward nucleophilic acyl substitution, even though both are carboxylic acid derivatives?

3. Compare the boiling points of an alcohol, ether, and alkane of similar molecular weight. What intermolecular forces explain the differences?

4. A primary alkyl bromide and a tertiary alkyl bromide are both treated with sodium hydroxide. Predict the major mechanism ($\text{S}_\text{N}1$, $\text{S}_\text{N}2$, $\text{E}1$, or $\text{E}2$) for each and explain your reasoning.

5. Which functional groups would you expect to find in a molecule that can both donate and accept hydrogen bonds, act as a weak acid, and be oxidized to a carbonyl compound? Justify your answer.