PHOrgChem (Lecture) | Module 9 (PART 2: AMIDE, ACID ANHYDRIDE, ACID HALIDE, and THIOESTER)

Amide

Derived from carboxylic acids but instead of a hydroxyl group (-OH), the carbonyl is attached to an amine group (-NH₂ or -NR₂) (primary, secondary, or tertiary)

R-CO-NH2

GENERAL FORMULA for simple amides

R-CO-NR2

GENERAL FORMULA for more complex amides

Amide

Polar molecules, but generally less polar than carboxylic acids.

Carboxylic Acid

Amides are polar molecules, but generally less polar than?

Amide

Found in nature especially in proteins

• amino acids are linked together by ____ bonds called peptide bonds (amides linking amino acids).

Proteins

Amides are found in nature especially in?

Peptide Bonds

Amide—amino acids are linked together by amide bonds called?

Amide

Relatively stable, with high melting points and high boiling points due to strong hydrogen bonding and dipole-dipole interactions

Strong Hydrogen Bonding, and Dipole-Dipole Interactions

Amides are relatively stable, with high melting points and high boiling points due to?

Relatively Stable

PHYSICAL PROPERTIES: Amides are __________, with high melting points and high boiling points due to strong hydrogen bonding and dipole-dipole interactions

Size

PHYSICAL PROPERTIES: Amides are solids or liquids at room temperature depending on?

Small Amides

PHYSICAL PROPERTIES: Amides are soluble in water, especially? (due to hydrogen bonding)

Alcohol, and Ether

PHYSICAL PROPERTIES: Amides have good solubility in organic solvents like?

carboxylic acid, and amines

CHEMICAL PROPERTIES: Relatively stable, but can undergo hydrolysis in the presence of strong acid or bases, breaking down into?

Ammonium Salts

CHEMICAL PROPERTIES: Amides react with strong acids to form?

Nucleophilic Substitution Reaction

CHEMICAL PROPERTIES: Amides undergo this reaction where the nitrogen is replaced by another group (such as in the formation of esters).

High Boiling Point

PHYSICAL PROPERTIES: Boiling Point of Amides

Amine

CHEMICAL PROPERTIES: Reduction—Amides can be reduced to _____ using reducing agents like LiAlH₄

Degradation

CHEMICAL PROPERTIES: tough compounds but undergo __________ under high heat into simpler chemicals often forming amine and carbonyl compounds

amine, and carbonyl compounds

CHEMICAL PROPERTIES: tough compounds but undergo degradation under high heat into simpler chemicals often forming?

Lidocaine

DRUGS: Local anesthetic

Cream, gels, or injectables

DRUGS: Formulations of Lidocaine

more stable, and less prone to hydrolysis

DRUGS: - amide groups in Lidocaine are ________, and ____________ or being broken down by water.

Lidocaine

DRUGS: Does not degrade easily in the body or in storage due to water exposure. More stable overtime compared to drugs with esters

Shelf Life, and Consistent Potency

DRUGS: This stability of amides allows Lidocaine to have longer _______, and __________________

Liver

DRUGS: Lidocaine is still metabolized in the ____ by enzymes. They break down amide bonds to convert lidocaine into inactive metabolites

Inactive Metabolites

DRUGS: Lidocaine is still metabolized in the liver by enzymes. They break down amide bonds to convert lidocaine into?

Ester Based Anesthetics

DRUGS: This process of metabolizing the drug in liver by enzymes is slower than ____________ hydrolysis, meaning that lidocaine can have longer duration of action

Lidocaine

DRUGS: Often preferred for long acting local anesthetic because the drug maintains potency and effectiveness

Captopril

DRUGS: Treats high blood pressure and heart failure

Captopril

DRUGS: More resistant to hydrolysis, meaning it is less likely to break down prematurely in body or storage. It has better stability overtime

Captopril

DRUGS: it is still metabolized in the liver by enzymes but slower than with ester based drugs. This drug can remain active longer in body and have prolonged therapeutic effect

Acid Anhydride

Organic compound formed by removing a molecule of water from two carboxylic acids or an acid and one of its derivative (think of it as 2 carboxyl group connected an oxygen atom)

Acid Anhydride

Reactive and typically used in chemical reaction for the synthesis of other compounds like esters, and amides (e.g., esterification, acylation).

Esters, and Amides

Reactive and typically used in chemical reaction for the synthesis of other compounds like?

Reactive

Acid Anhydrides are _____ and typically used in chemical reaction for the synthesis of other compounds like esters and amides (e.g., esterification, acylation).

Synthesis

Acid Anhydrides are reactive and typically used in chemical reaction for the ______ of other compounds like esters and amides (e.g., esterification, acylation).

Acid Anhydride

Polar molecules with high reactivity due to the presence of the carbonyl group (C=O) which makes them sensitive to moisture

Acid Anhydride

Can be synthesized from carboxylic acids or their salts

carboxylic acids, or their salts

Acid Anhydride can be synthesized from?

Less

Acid Anhydrides are ____ soluble in water but reacts vigorously and quickly with it to form original carboxylic acids.

Original Carboxylic Acid

Acid Anhydrides are less soluble in water but reacts vigorously and quickly with it to form?

Colorless to Pale or Light Yellow Liquid or Solid

PHYSICAL PROPERTIES: Appearance of Acid Anhydride

alcohol, ether, and chloroform

PHYSICAL PROPERTIES: Acid Anhydrides are Moderately Soluble in Organic Solvents like?

Moderately

PHYSICAL PROPERTIES: Acid Anhydrides are _______ soluble in organic solvents (like alcohol, ether, and chloroform)

Do not mix well, or less soluble

PHYSICAL PROPERTIES: Acid Anhydrides are this when mixed with water

Sharp, Irritating

PHYSICAL PROPERTIES: Odor of Acid Anhydride

Carboxylic Acid

PHYSICAL PROPERTIES: Acid Anhydrides have sharp, irritating odor due to the release of __________ when they react with water

water, alcohols, and amines

CHEMICAL PROPERTIES: Acid Anhydrides are highly reactive particularly with?

Moisture

CHEMICAL PROPERTIES: Acid Anhydrides react violently when exposed to?

Carboxylic Acid

CHEMICAL PROPERTIES: Acid Anhydride reacts vigorously with water to form?

Ester

CHEMICAL PROPERTIES: Acid Anhydride react with alcohols to form?

Amide

CHEMICAL PROPERTIES: Acid Anhydride react with amine to form?

Nucleophilic Acyl Substitution

CHEMICAL PROPERTIES: Acid Anhydride reacts with other nucleophiles ● used in making more complex molecules because of nucleophilic acyl substitution ● makes them versatile in both synthetic chemistry and industrial processes

Alcohol

CHEMICAL PROPERTIES: Acid Anhydride can be reduced to corresponding _______ under certain conditions.

High Boiling Point

PHYSICAL PROPERTIES: Boiling Point of Acid Anhydride

Ciclopirox

DRUGS: Antifungal

Ciclopirox

DRUGS: Acid anhydride is reactive making this drug prone to hydrolysis or other chemical reaction— especially in moist or aqueous environments

Ciclopirox

DRUGS: when exposed to moisture, it can break down into two acids which can reduced effectiveness

Shorter Shelf Life

DRUGS: Acid Anhydride in Ciclopirox is Prone to Hydrolysis = ?

Ciclopirox

DRUGS: acid anhydride group may be broken down by enzymes or undergo hydrolysis which affects how the drug is absorbed or how long it remains effective. Break down might be less active than original which can influence duration of drug action

Acetyl Salicylic Acid

DRUGS: Aspirin are also called as?

Acetic Acid, and Salicylic Acid

DRUGS: Acetyl Salicylic Acid (Acid Anhydride) are prone to hydrolysis. when exposed to moisture/humid/water/moist environment or air, it can break down into?

Salicylic Acid

DRUGS: Reduces aspirin effectiveness as it loses acetyl group turning to inactive form?

Inactive Form

DRUGS: Reduces aspirin effectiveness as it loses acetyl group turning to?

Acetyl Group

ACETYL SALICYLIC ACID: metabolized by enzymes and breaks down into _____________, however this process occurs after it is absorbed and done its job in the body so it does not affect the primary function of the drug in the body

Acyl Halide

Acid Halide are also known as?

Acyl Halide

Polar molecules due to the presence of the carbonyl group and halogen

Sharp, Irritating

PHYSICAL PROPERTIES: Odor of Acid Halide

ether, chloroform, and benzene

PHYSICAL PROPERTIES: Acid Halides are soluble in organic solvents like?

Acid Halide

PHYSICAL PROPERTIES: react violently with water, breaking down into carboxylic acid and releasing toxic fuels.

Toxic Fuels

PHYSICAL PROPERTIES: Acid halide react violently with water, breaking down into carboxylic acid and releasing?

High Boiling Point

PHYSICAL PROPERTIES: Boiling Point of Acid Halide

Colorless to Pale Yellow Liquid or Solid

PHYSICAL PROPERTIES: Appearance of Acid Halide

Hydrogen Chloride

PHYSICAL PROPERTIES: Acid Halide’s odor is sharp and irritating due to the release of this gas when reacting with water.

Poorly Soluble

PHYSICAL PROPERTIES: Solubility of Acid Halide to Water

Highly Reactive

CHEMICAL PROPERTIES: due to the presence of the carbonyl group (C=O) and halogen (X).

Carboxylic Acid

CHEMICAL PROPERTIES: Acid Halide is reactive with water—Breaks down into ________ and releasing toxic fuels

Hydrogen Halide

CHEMICAL PROPERTIES: Acid Halide is reactive with water—Forms carboxylic acids and release?

Ester

CHEMICAL PROPERTIES: Acid Halide react with alcohol forming?

Amide

CHEMICAL PROPERTIES: Acid Halide react with amine forming?

Nucleophilic Acyl Substitution

CHEMICAL PROPERTIES: Acid Halide react with nucleophiles (e.g., amines, alcohols)

aldehydes, or alcohols

CHEMICAL PROPERTIES: Acid Halides can be reduced to _______, or _________ under specific conditions.

Benzoyl chloride

DRUGS: BENZENE CARBOXYLIC ACID CHLORIDE

benzoic acid, and hydrochloric acid

DRUGS: Benzoyl chloride quickly undergoes hydrolysis, breaking down into?

Benzoyl chloride

DRUGS: This is not directly used as drug. Important intermediate in production of other compounds (Acid Halide)

Benzoyl peroxide

DRUGS: for acne treatment

acetic acid, and hydrochloric acid

DRUGS: Acetyl chloride reacts rapidly to form?

Acetyl chloride

DRUGS: This is not directly used as drug. Used in synthesis of drugs and other chemicals (Acid Halide)

Thioester

similar to esters, but with a sulfur atom (S) replacing the oxygen atom in the ester linkage

Carboxylic acid, and Thiol

Thioesters are formed by reaction (Hydrolysis) of a _______, and _____

Thioester

More reactive and Less stable than oxygen esters due to the sulfur atom being less electronegative than oxygen.

More Reactive, and Less Stable

PHYSICAL PROPERTIES: Thioesters are _________, and _______ than oxygen esters due to the sulfur atom being less electronegative than oxygen.

Thioester

Often found in biological systems, like acetyl-CoA which is crucial for energy production.

Acetyl-CoA

Thioesters are often found in biological systems, like __________ which is crucial for energy production.

Garlic-Like, Musty (Mustard)

PHYSICAL PROPERTIES: Odor of Thioester

Colorless to Pale Yellow Liquid or Solid

PHYSICAL PROPERTIES: Appearance of Thioester

Moderately High Boiling Point

PHYSICAL PROPERTIES: Boiling Point of Thioester

Thioester

PHYSICAL PROPERTIES: They have moderately high boiling point, but lower than esters of similar molecular weight due to weaker intermolecular forces