Organic Chemistry: Carboxylic Acid Derivatives, Enolates, and Amine Synthesis

Flashcards covering the vocabulary and mechanisms of carboxylic acid derivatives, enol/enolate chemistry, condensation reactions, and amine synthesis based on the lecture notes.

Acyl Chlorides to Amides

A reaction where acyl chlorides react with amines in the presence of a weak base like pyridine ($pyr$) to form amides and $HCl$.

Pyr (Pyridine)

A weak amine base used in acyl chloride reactions to react with the produced $HCl$.

Anhydride Reactivity

Functional groups that are less reactive than chlorides; they can be used for Ester and Amide synthesis via nucleophilic attack and deprotonation, leaving a $RCOO^-$ group.

Fischer Esterification

An acid-catalyzed reaction of a carboxylic acid to an ester via five steps: 1) protonate $C=O$, 2) Nu attack, 3) deprotonate $ORH^+$, 4) protonate $OH$, 5) loss of $H_2O$ to make $C=O$. It does not work with base because it deactivates by forming a carboxylate salt.

Base-promoted Ester Hydrolysis

A three-step mechanism involving nucleophilic attack of $OH^-$, elimination of $OR$, and deprotonation; described as base-promoted (not catalyzed) because the base is not regenerated.

Amides

The least reactive carboxylic acid derivative; they require forcing conditions such as strong acid or base to react.

Acid-Catalyzed Tautomerization Mechanism

A two-step process involving protonating the oxygen and then deprotonating the $\text{α}$ carbon.

Enols

Electron-rich species that act as nucleophiles (NU) and are more electron-rich than alkenes.

Enolate Formation

A mechanism where a base removes a proton ($H$) on the $\text{α}$ carbon to form a resonance-stabilized structure with partial negative charges on both the carbon and oxygen.

Ambident

A term describing enolates because they possess two reaction sites (the Oxygen and the Carbon), though the Carbon site is generally preferred.

Acid-catalyzed $\text{α}$ Halogenation

A reaction typically using acetic acid as a solvent and catalyst where a carbonyl is protonated, the $\text{α}$ carbon is deprotonated to form an enol, the enol reacts with $X_2$, and $X^-$ deprotonates the $OH$.

Base-promoted Halogenation

A two-step mechanism where a base deprotonates the $\text{α}$ carbon to form an enolate, which then reacts with $X_2$; the base is not regenerated in this process.

DIBAL (Diisobutylaluminum hydride)

A reducing agent that can convert an ester or a nitrile into an aldehyde.

Malonic Ester Synthesis

A three-part mechanism: 1) deprotonation to remove the $\text{α}$ proton, 2) nucleophilic enolate displacement of a halogen on an alkyl halide, 3) heating with aqueous acid to cause decarboxylation (loss of $CO_2$).

E1cB Mechanism

Elimination Unimolecular conjugate Base; a two-step process where an enolate is formed (resonance stabilized) and then $OH^-$ leaves to form a $\text{π}$ bond. It occurs even though $OH^-$ is a poor leaving group due to the stability of the conjugated double bond.

Claisen Reaction

A nucleophilic acyl substitution reaction of esters that results in a $\beta$-keto ester product; it requires ethoxide for deprotonation followed by acid workup.

Michael Reaction

A reaction involving deprotonation followed by nucleophilic attack on the $\beta$ carbon of a carbonyl compound, and finally protonation; acid workup is used to prevent the reaction from reversing.

Robinson Annulation

A reaction sequence that combines a Michael reaction with an intramolecular Aldol reaction and an E1cB dehydration to form a cyclic product.

Reductive Amination

A two-step process converting an aldehyde or ketone into a $1^{\text{ο}}$, $2^{\text{ο}}$, or $3^{\text{ο}}$ amine using $NaBH_3CN$ as the reducing agent.

Polyalkylation

An issue with direct nucleophilic substitution (alkylation via $S_N2$) of amines where the reaction doesn't stop, making it difficult to control the degree of alkylation.

Gabriel Synthesis

A specialized method mentioned for the synthesis of amines.