Essential Organic Chemistry: Reactions & Functional Groups
Carboxylic Acids: Properties & Reactions
- Oxidation: Primary alcohols or aldehydes
- Hydrolysis of Esters: Acidic or basic mechanisms
- Hell-Volhard-Zelinsky (HVZ) Reaction: α-halogenation via PBr3 and Br2
Key Characteristics of Carboxylic Acids
- Polar and acidic nature
- Form strong hydrogen bonds
- Undergo nucleophilic substitution reactions
Acid Derivatives: Synthesis & Reactivity
Includes acid chlorides, esters, amides, and anhydrides.
Synthesis Methods
- From acids using SOCl2 (for acid chlorides)
- From acids using acetic anhydride (for anhydrides)
- Fischer esterification (for esters)
Named Reactions
- Claisen Condensation: Ester + ester → β-keto ester (via enolate)
- Reformatsky Reaction: α-haloester + carbonyl + Zn → β-hydroxy ester
- Perkin Reaction: Aldehyde + acid anhydride → α,β-unsaturated acid
Reactivity Order Toward Nucleophilic Acyl Substitution
Acid chloride > Anhydride > Ester > Amide
All acid derivatives undergo nucleophilic acyl substitution.
Active Methylene Compounds: Ethyl Acetoacetate
Ethyl acetoacetate is a prime example of an active methylene compound.
Properties & Reactions
- Prepared via Claisen condensation
- Enolate formed via α-H abstraction
- Undergoes alkylation, condensation, hydrolysis, and decarboxylation
- Exhibits keto-enol tautomerism
- Highly useful in organic synthesis
Amines (Primary, Secondary, Tertiary): Synthesis, Reactions & Tests
Synthesis Methods
- Alkyl halides + NH3
- Gabriel Synthesis: Specifically for primary (1°) amines
- Hoffmann Bromamide Degradation: From amides, yielding primary (1°) amines
Elimination Reactions
- Hoffmann Elimination: Favors less substituted alkene products
- Saytzeff Elimination: Favors more substituted alkene products
Qualitative Tests for Amines
- Carbylamine Test: R-NH2 + CHCl3 + KOH → isocyanide (strong, unpleasant odor), specific for primary (1°) amines
- Hinsberg Test: Differentiates primary (1°), secondary (2°), and tertiary (3°) amines based on solubility
Basicity & Reactivity
- Amines are basic in nature (order in gas phase: 1° > 2° > 3°)
- Solubility and reactivity are influenced by hydrogen bonding and molecular structure
Electrophilic Substitution in Aniline
Aniline features a strongly activating -NH2 group, making the aromatic ring highly reactive toward electrophiles.
- Common reactions include nitration, bromination, and sulfonation, yielding ortho/para products.
- Protection of the -NH2 group (e.g., via acetylation) is often necessary to prevent excess substitution.
Amine Reactions with Nitrous Acid (HNO2)
- Primary (1°) Amines: RNH2 → ROH + N2↑ (alcohol formation with nitrogen gas evolution)
- Secondary (2°) Amines: R2NH → nitrosoamine (formation of N-nitroso compounds)
- Tertiary (3°) Amines: Generally no reaction under these conditions
This reaction is useful for testing amine types and for diazonium salt formation.
Diazonium Salts: Formation & Reactions
Formation
From aromatic primary (1°) amines + NaNO2 + HCl at 0–5°C.
Key Reactions
- Sandmeyer Reactions: ArN2+ → ArOH, ArH, ArX (e.g., ArCl, ArBr, ArCN)
- Azo Dye Formation: ArN2+ + Ar’H → azo dye (coupling reactions)
Diazonium salts are unstable at high temperatures and serve as key intermediates in dye chemistry.
Heterocyclic Compounds: Properties & Reactivity
Examples include Furan, Pyrrole, Thiophene, and Pyridine, synthesized via cyclization or from precursors.
Electrophilic Aromatic Substitution (EAS)
- Occurs at the α-position in 5-membered rings (Furan, Pyrrole, Thiophene).
Nucleophilic Aromatic Substitution (NAS)
- Occurs in 6-membered rings (e.g., Pyridine) at the ortho/para positions.
Basicity & Aromaticity
- Pyridine: Basic, as the lone pair on nitrogen is not part of the aromatic ring.
- Pyrrole: Less basic, as its nitrogen lone pair is involved in the aromatic sextet.
- Thiophene, Furan: Aromatic and readily undergo EAS.
Detailed Explanations & Reaction Mechanisms
Hell-Volhard-Zelinsky (HVZ) Reaction
Reaction Summary
Carboxylic acid + Br2 + PBr3 → α-bromo acid
Mechanism
- PBr3 converts the carboxyl group (-COOH) into an acid bromide (R-COBr).
- The acid bromide undergoes halogenation at the α-position with Br2 in the presence of PBr3.
- The intermediate is a brominated α-carboxylic acid.
This reaction is crucial for introducing a bromine atom at the α-position (next to the carboxyl group) of carboxylic acids.
Reactivity of Acid Derivatives Toward Nucleophiles
Reactivity Order
Acid chlorides > Anhydrides > Esters > Amides
- Acid chlorides are the most reactive due to the electron-withdrawing chlorine group and its ability to stabilize the leaving group.
- Anhydrides are also reactive but slightly less so than acid chlorides.
- Esters have an -OR group, which is less electron-withdrawing than chlorine or an acyl group.
- Amides are the least reactive due to the electron-donating effect of the nitrogen, which stabilizes the carbonyl group.
Claisen Condensation Mechanism
Reaction Summary
Ester + Ester (in presence of base) → β-keto ester
Mechanism
- A strong base (e.g., NaOEt) deprotonates the α-carbon of one ester molecule, forming a resonance-stabilized enolate ion.
- The enolate attacks the carbonyl carbon of another ester molecule.
- This results in a β-keto ester after the expulsion of the alkoxide ion (the leaving group).
This reaction is vital for forming carbon-carbon bonds and synthesizing β-keto esters.
Reformatsky vs. Perkin Reactions
Reformatsky Reaction
- Reactants: α-halo ester + aldehyde/ketone
- Product: β-hydroxy ester
- Mechanism: A zinc catalyst facilitates the formation of an enolate from the α-halo ester, which then attacks the carbonyl group of the aldehyde or ketone.
Perkin Reaction
- Reactants: Aromatic aldehyde + acid anhydride
- Product: α,β-unsaturated carboxylic acid
- Mechanism: A base abstracts a proton from the acid anhydride, forming an enolate. This enolate then attacks the carbonyl carbon of the aromatic aldehyde.
Keto-Enol Tautomerism in Ethyl Acetoacetate
Concept
Keto-enol tautomerism describes the equilibrium between the keto form (typically more stable) and the enol form (less stable but often more reactive) of a compound.
In ethyl acetoacetate, the keto form is a β-diketone. The enol form features an -OH group at the β-position. The enolate, derived from the keto form, plays a critical role in various reactions such as alkylation and condensation.
Carboxylic Acid Synthesis from Alcohols & Aldehydes
From Primary Alcohols
Primary alcohol → Aldehyde → Carboxylic acid (via oxidation with reagents like K2Cr2O7 or KMnO4).
From Aldehydes
Aldehyde → Carboxylic acid (via oxidation with reagents like KMnO4, Ag2O, or CrO3).
Gabriel vs. Hoffmann Bromamide Synthesis
Gabriel Synthesis (for Primary Amines)
- Phthalimide reacts with an alkyl halide in the presence of a base to form N-alkylphthalimide.
- The N-alkylphthalimide is then hydrolyzed (typically with alkaline hydrolysis), releasing the primary amine.
Hoffmann Bromamide Degradation (for Primary Amines)
Amide + Br2/NaOH → Primary (1°) amine (this reaction results in the loss of one carbon atom).
Carbylamine & Hinsberg Tests for Amines
Carbylamine Test (for Primary Amines)
Primary (1°) amine + CHCl3 + KOH → Isocyanide (carbylamine), characterized by a strong, unpleasant odor.
Hinsberg Test (for Distinguishing Amines)
- Primary (1°) Amine: Forms a sulfonamide that is soluble in aqueous NaOH.
- Secondary (2°) Amine: Forms a sulfonamide that is insoluble in aqueous NaOH.
- Tertiary (3°) Amine: Does not react with Hinsberg reagent.
Electrophilic Substitution in Aniline
Aniline (C6H5NH2) is a highly activating group in electrophilic aromatic substitution reactions. The lone pair on the nitrogen atom donates electron density to the aromatic ring, significantly increasing its reactivity toward electrophiles.
Substituents typically direct to the ortho and para positions relative to the -NH2 group.
Common reactions include nitration, bromination, and sulfonation.
Diazonium Salt Reactions: Phenol, Benzene, Azo Dyes
Diazonium salts (ArN2+Cl-) are versatile intermediates that react with various compounds:
- To Phenol: Reacts with water to form hydroxybenzene (ArOH).
- To Benzene: Coupling reactions with activated aromatic compounds (like phenols or anilines) lead to the formation of azo dyes.
- Azo Dyes: Formed when the diazonium group couples, typically at the para position, with compounds such as phenols or aniline.
Comparing Basicity: Ammonia, Methylamine, Aniline
- Ammonia (NH3): The lone pair on nitrogen is readily available, making it a relatively basic compound.
- Methylamine (CH3NH2): The methyl group is electron-donating, which increases the electron density on the nitrogen, making methylamine more basic than ammonia.
- Aniline (C6H5NH2): The lone pair on nitrogen is delocalized into the aromatic ring via resonance, reducing its availability for protonation. This makes aniline significantly less basic than methylamine and even ammonia.
Order of Basicity
Methylamine > Ammonia > Aniline
Aromatic Character: Furan, Pyrrole, Thiophene
- Furan (C4H4O): Oxygen donates one of its lone pairs to the ring, contributing to aromaticity, but its aromatic character is generally weaker compared to pyrrole.
- Pyrrole (C4H5N): Nitrogen donates its lone pair, which strongly contributes to the aromatic sextet, resulting in significant aromaticity and higher reactivity.
- Thiophene (C4H4S): Sulfur also has a lone pair that contributes to aromaticity, making its aromatic character comparable to pyrrole.
Pyrrole vs. Furan: Electrophilic Reactivity
Pyrrole is more reactive than furan toward electrophiles because:
- Pyrrole’s nitrogen atom has a more delocalized lone pair, which interacts strongly with the ring’s π-electrons. This increases the electron density within the ring, making it more susceptible to electrophilic attack.
- In contrast, furan’s oxygen lone pair is less involved in the aromatic system, resulting in lower electron density and thus less reactivity toward electrophiles.
Pyridine: Electrophilic & Nucleophilic Substitution
Electrophilic Substitution (E+)
Pyridine is less reactive toward electrophiles compared to benzene. The electronegative nitrogen atom withdraws electron density from the ring, deactivating it and making it electron-poor, particularly at the 3-position.
Nucleophilic Substitution (Nu-)
Pyridine readily undergoes nucleophilic substitution, especially at the 2 and 4 positions. The electron-withdrawing nitrogen atom makes these positions more susceptible to nucleophilic attack.
Electrophilic Substitution in Thiophene
Thiophene is an aromatic heterocyclic compound where the sulfur atom donates electron density to the ring, activating it toward electrophilic substitution.
Mechanism Steps
- An electrophile (E+) attacks the α-position (2- or 5-position) of the thiophene ring.
- This attack forms a resonance-stabilized arenium ion intermediate.
- Loss of a proton (H+) from the arenium ion restores aromaticity, yielding the substituted thiophene product.