CH. 14 - Carboxylic Acids, Esters, Amines, and Amides: Physiological Chemistry

Properties and Nomenclature of Carboxylic Acids

• Definition of Carboxyl Group: A carboxylic acid contains a carboxyl group, which is a structural unit consisting of a hydroxyl group ($-OH$) attached to the carbon atom in a carbonyl group ($C=O$).

• IUPAC Naming Conventions:     * The IUPAC name is derived by replacing the final "-e" in the alkane name with the suffix "-oic acid."     * Examples of simple transformations:         * Methane ($CH_4$) becomes Methanoic acid ($H-COOH$).         * Ethane ($CH_3-CH_3$) becomes Ethanoic acid ($CH_3-COOH$).

• Numbering Substituents: In IUPAC nomenclature, substituents are numbered starting from the carboxyl carbon, which is assigned as carbon 1.     * Example: 3-Methylbutanoic acid.     * Example: 2,3-Dichlorobenzoic acid.

• Selected Carboxylic Acids (IUPAC vs. Common Names):     * Methanoic acid: Common name is Formic acid ($H-C-OH$ with a carbonyl group). Found in red ant stings, which cause skin irritation.     * Ethanoic acid: Common name is Acetic acid ($CH_3-C-OH$ with a carbonyl group). It provides the sour taste in vinegar.     * Propanoic acid: Common name is Propionic acid ($CH_3-CH_2-C-OH$ with a carbonyl group).     * Butanoic acid: Common name is Butyric acid ($CH_3-CH_2-CH_2-C-OH$ with a carbonyl group).

• Naming Methodology (Example: 2-methylpentanoic acid):     * Step 1: Identify the longest carbon chain. For a five-carbon chain, the corresponding alkane is pentane; replace the "-e" to get pentanoic acid.     * Step 2: Name and number substituents. With a methyl group on the second carbon (counting the carboxyl carbon as 1), the name is 2-methylpentanoic acid.

Physical Properties, Acidity, and Salts of Carboxylic Acids

• Polarity: Carboxylic acids are strongly polar molecules because they possess two polar functional groups: the hydroxyl group ($-OH$) and the carbonyl group ($C=O$).

• Solubility in Water:     * Carboxylic acids form hydrogen bonds with water molecules.     * Acids containing one to five carbon atoms are very soluble in water.     * As the number of carbon atoms increases, the solubility decreases because the nonpolar portion of the molecule becomes larger.     * Solubility data:         * Methanoic, Ethanoic, Propanoic, Butanoic, and Pentanoic acids are Soluble.         * Hexanoic acid and Benzoic acid are Slightly soluble.

• Acidity: Carboxylic acids are categorized as weak acids. They ionize in water to produce carboxylate ions and hydronium ions ($H_3O^+$). The negative charge in the carboxylate ion is stabilized by the presence of two oxygen atoms.

• Neutralization and Carboxylate Salts:     * Neutralization: Carboxylic acids react with strong bases (e.g., $NaOH$ or $KOH$) to produce a carboxylic acid salt and water.     * Naming Salts: The name of the salt is formed by replacing the "-ic acid" suffix with "-ate."     * Physical Properties of Salts: These are ionic compounds with strong attractive forces. They are typically solids at room temperature, have high melting points, and are usually soluble in water.

• Preservatives and Flavor Enhancers:     * Sodium propionate: A preservative added to cheeses, breads, and bakery items to prevent spoilage by microorganisms.     * Sodium benzoate: Inhibits the growth of mold and bacteria. It is commonly added to fruit juices, margarine, relishes, salads, and jams.     * Monosodium glutamate (MSG): Added to meats, fish, vegetables, and baked goods to enhance flavor.

Carboxylic Acids in Metabolism

• Glycolysis: In the metabolic breakdown of glucose, one glucose molecule is converted into two molecules of pyruvate. Pyruvate is the carboxylate salt of pyruvic acid.

• Anaerobic Conditions: During strenuous exercise when oxygen levels are low, pyruvic acid is reduced to lactic acid (or the lactate ion).

• The Citric Acid Cycle (Krebs Cycle):     * Di- and tricarboxylic acids are oxidized and decarboxylated (removal of $CO_2$) to produce cellular energy.     * At the cycle's start, citric acid is oxidized to a five-carbon alpha-ketoglutaric acid ($\alpha\text{-ketoglutaric acid}$).     * $\alpha\text{-Ketoglutaric acid}$ loses $CO_2$ to form a four-carbon succinic acid.     * A series of subsequent reactions converts succinic acid into oxaloacetic acid involving processes like hydration and oxidation.

Esters: Preparation, Nomenclature, and Applications

• History and Health: In the 1800s, chemists found salicin in willow tree bark provided pain relief. The body converts salicin to salicylic acid, which causes stomach irritation. Bayer developed acetylsalicylic acid (aspirin), an ester derivative that is less irritating but still effective for pain. Daily low-dose aspirin is used to reduce heart attack and stroke risk.

• Esterification: This is the synthesis of an ester through the reaction of a carboxylic acid and an alcohol in the presence of heat and an acid catalyst. Structurally, the hydrogen in the acid's $-OH$ group is replaced by an alkyl group from the alcohol.     * Example: Ethanoic acid + 1-propanol $→$ propyl ethanoate (smells like pears).

• Nomenclature of Esters:     * The name consists of two words.     * Word 1: The name of the alkyl group derived from the alcohol.     * Word 2: The name of the carboxylate from the acid (replace "-ic acid" with "-ate").     * Examples:         * Ethyl ethanoate (Common: Ethyl acetate).         * Methyl propanoate (Common: Methyl propionate).         * Ethyl benzoate.

• Flavor and Fragrance: Esters are responsible for the aromas and flavors of many fruits. Small esters are volatile (can be smelled) and water-soluble (can be tasted).     * Propyl ethanoate: Pears.     * Pentyl ethanoate: Bananas.     * Octyl ethanoate: Oranges.     * Ethyl butanoate: Pineapples.     * Pentyl butanoate: Apricots.

• Oil of Wintergreen: Methyl salicylate is an ester with a minty odor used in skin ointments. It acts as a counter-irritant, passing through the skin and producing heat to soothe sore muscles.

Hydrolysis of Esters

• Acid Hydrolysis: An ester reacts with water in the presence of an acid catalyst and heat to produce a carboxylic acid and an alcohol. Water provides the $-OH$ group to reform the carboxyl group.

• Base Hydrolysis (Saponification): An ester reacts with a strong base under heat. This reaction produces a carboxylic acid salt and an alcohol.

Amines: Classification and Properties

• Definition: Amines are derivatives of ammonia ($NH_3$) where one, two, or three hydrogen atoms are replaced by alkyl or aromatic groups.

• Classification:     * Primary ($1^∘$) amine: One carbon group bonded to the nitrogen atom.     * Secondary ($2^∘$) amine: Two carbon groups bonded to the nitrogen atom.     * Tertiary ($3^∘$) amine: Three carbon groups bonded to the nitrogen atom.

• Nomenclature of Simple Amines: Named as alkylamines by listing alkyl groups in alphabetical order followed by the suffix "-amine." Prefixes like "di-" or "tri-" denote duplicate groups.     * Examples: Ethylamine, Dimethylamine, Ethyldimethylamine.

• Aromatic Amines: The amine derivative of benzene is called aniline. If alkyl groups are attached to the nitrogen, the prefix "N-" is used (e.g., N-methylaniline). Aniline is used to produce dyes for fibers like cotton and silk.

• Solubility and Hydrogen Bonding:     * Amines with fewer than six carbons are soluble in water.     * Primary ($1^∘$) and secondary ($2^∘$) amines can form hydrogen bonds with water; $1^∘$ amines form more bonds than $2^∘$.     * Tertiary ($3^∘$) amines lack a hydrogen atom on the nitrogen and can only form hydrogen bonds with water via the lone pair on the nitrogen atom.     * Solubility decreases when nonpolar hydrocarbon chains exceed six carbons because the nonpolar effect diminishes the impact of hydrogen bonding.

• Basicity: Ammonia and amines ($1^∘$ and $2^∘$) act as Brønsted–Lowry bases. The lone electron pair on the nitrogen accepts a proton ($H^+$) from water, creating an ammonium ion ($NH_4^+$) and a hydroxide ion ($OH^-$).

Amine Salts and Alkaloids

• Neutralization and Amine Salts: Formed when an amine (acting as a base) reacts with an acid (e.g., citric acid). For example, the acids in lemon juice neutralize the "fishy" odor of amines in fish.

• Naming Amine Salts: Use the alkylammonium ion name followed by the name of the negative ion.

• Medical Importance of Amine Salts: Most amines are converted into ammonium salts for use as drugs because the salts are water-soluble, odorless, and solids at room temperature.     * Ephedrine: A bronchodilator used in the decongestant Sudafed.     * Diphenylhydramine: The active ingredient in Benadryl, used for relief from itching and rashes.

• Cocaine: Extracted as an ammonium salt (cocaine hydrochloride) using acidic $HCl$. It can be converted to its free base form ("crack cocaine") by treatment with a strong base.

• Alkaloids: Nitrogen-containing, physiologically active compounds produced by plants. Many are habit-forming.     * Nicotine: A stimulant that increases adrenaline, heart rate, and blood pressure by activating brain pleasure centers.     * Caffeine: Found in coffee, tea, and chocolate; a CNS stimulant that increases alertness but can cause insomnia.     * Morphine and Codeine: Alkaloids from the oriental poppy plant used as potent painkillers.

Amides: Preparation, Selection, and Hydrolysis

• Definition: Amides are carboxylic acid derivatives where a nitrogen group replaces the hydroxyl group.

• Preparation (Amidation): Amides are produced by reacting a carboxylic acid with ammonia, a primary amine, or a secondary amine under heat.

• Nomenclature of Amides:     * Drop the "-oic acid" (IUPAC) or "-ic acid" (common) from the acid name and add "-amide."     * Groups attached to the nitrogen use the prefix "N-" followed by the alkyl name.     * Example: N-methylbutanamide (formed from butanoic acid and methylamine).

• Amides in Health and Medicine:     * Urea: The end product of protein metabolism, removed from the blood by kidneys. Malfunction leads to uremia (toxic levels of urea).     * Barbiturates: Cyclic amides of barbituric acid. They act as sedatives (small dose) or sleep inducers (large dose). Examples: phenobarbital (Luminal) and pentobarbital (Nembutal).     * Acetaminophen (Tylenol): An aspirin substitute and amide that reduces fever and pain but has minimal anti-inflammatory effects.

• Hydrolysis of Amides:     * Acid Hydrolysis: Produces a carboxylic acid and an ammonium salt.     * Base Hydrolysis: Requires heat and produces the salt of the carboxylic acid and an amine (or ammonia). The amide bond breaks between the carboxyl carbon and the nitrogen.     * Example: Hydrolysis of N-methylpentanamide with $NaOH$ yields sodium pentanoate and methylamine.