Comprehensive Notes – Carboxylic Acids & Their Derivatives

Physical & Chemical Properties of Carboxylic Acids

  • Molecular fragment: extR–COOHext{R–COOH} (R = alkyl or aryl)
  • Bonding / polarity
    • Highly polar extC=Oext{C=O} and extO–Hext{O–H} bonds ⇒ strong dipole–dipole interactions.
    • Inter-molecular H-bonding:
    • Acid–acid: dimer formation (H–O⋅⋅⋅O=C↔C=O⋅⋅⋅H–O)\big(\text{H–O···O=C} \leftrightarrow \text{C=O···H–O}\big).
    • Acid–water: explains limited solubility of short chains.
  • Hydrophobic vs. hydrophilic portions
    • Alkyl chain (hydrophobic) resists water; polar head (hydrophilic) interacts.
  • Boiling-point trend (≈ strength of H-bonding)
    \text{Carboxylic acids} > \text{Alcohols} > \text{Aldehydes ≈ Ketones} > \text{Alkanes}
  • Boiling point rises with molar mass.
  • Solubility in H2O\text{H}_2\text{O}
    • C<em>1!→!C</em>3\text{C}<em>1!\rightarrow!\text{C}</em>3 completely miscible.
    • Solubility falls as chain length ↑.
  • Salts
    • Alkali-metal salts (Na, K, NH₄⁺) → water-soluble soaps.
    • Heavy-metal (Ag⁺, Hg²⁺, Pb²⁺, Fe³⁺, Cd²⁺) salts → water-insoluble precipitates.

Nomenclature

  • IUPAC: longest chain containing –COOH–COOH → drop “-e”, add “-oic acid”.
    • HCOOH\text{HCOOH}: methanoic (formic) acid.
    • CH<em>3CH</em>2CH2COOH\text{CH}<em>3\text{CH}</em>2\text{CH}_2\text{COOH}: butanoic (butyric) acid.
  • Common names retain Greek/Latin prefixes + “-ic”.
    • CH3COOH\text{CH}_3\text{COOH}: acetic acid.
    • CH<em>3(CH</em>2)4COOH\text{CH}<em>3(\text{CH}</em>2)_4\text{COOH}: caproic acid.
  • Polyfunctional / substituted acids
    • Number chain w/ C-1 = carbonyl C.
    • Prefix locants for halides, nitro, alkyl, etc.
    • Example: BrCH<em>2CH</em>2CH2COOH\text{BrCH}<em>2\text{CH}</em>2\text{CH}_2\text{COOH} → 4-bromobutanoic acid.
  • Aromatic acids: benzoic acid core. Substituent positions ortho-(2), meta-(3), para-(4).

Acidity Fundamentals

  • Typical pKa\text{p}K_a:
    • Carboxylic acid ≈4.8\approx 4.8.
    • Phenol ≈10\approx 10.
    • Alcohol ≈16\approx 16.
  • Deprotonation:
    RCOOH+OH−  ⟶  RCOO−+H2O\text{RCOOH} + \text{OH}^- \;\longrightarrow\; \text{RCOO}^- + \text{H}_2\text{O}
  • Carboxylate stabilization: two equivalent resonance forms.
    \large \text{R–C(=O)–O}^- \;\rightleftarrows\; \text{R–C(-O^-) = O}
  • Aromatic acids > aliphatic acids ((\pi)-electron withdrawal by ring).
Inductive & Resonance Effects of Substituents
  • Electron-withdrawing groups (EWG; –NO<em>2,–X,–CN,–CHO,–COR,–COOR,–SO</em>3H–\text{NO}<em>2, –\text{X}, –\text{CN}, –\text{CHO}, –\text{COR}, –\text{COOR}, –\text{SO}</em>3\text{H})
    → stabilize anion, lower pKa\text{p}K_a, ↑ acidity.
  • Electron-donating groups (EDG; –R,–OH,–OR,–NH<em>2–\text{R}, –\text{OH}, –\text{OR}, –\text{NH}<em>2) → destabilize anion, raise pK</em>a\text{p}K</em>a, ↓ acidity.
  • Distance effect: ClCH<em>2COOH\text{ClCH}<em>2\text{COOH} more acidic than ClCH</em>2CH<em>2CH</em>2COOH\text{ClCH}</em>2CH<em>2CH</em>2COOH, because inductive pull diminishes with each CH2\text{CH}_2.
  • Multiplicity: Cl<em>3C–COOH\text{Cl}<em>3\text{C–COOH} > Cl</em>2CH–COOH\text{Cl}</em>2\text{CH–COOH} > ClCH2COOH\text{ClCH}_2\text{COOH}.

Laboratory Synthesis of Carboxylic Acids

  1. Oxidation of terminal alkenes (hot KMnO<em>4/OH−\text{KMnO}<em>4/\text{OH}^- → acid; if double bond terminal, side gives CO</em>2\text{CO}</em>2):
    RCH=CH<em>2→ΔKMnO</em>4RCOOH+CO2\text{RCH=CH}<em>2 \xrightarrow[\Delta]{\text{KMnO}</em>4} \text{RCOOH} + \text{CO}_2
  2. Oxidation of 1° alcohols / aldehydes:
    R–CH<em>2OH→KMnO</em>4(aq)/H+RCOOH\text{R–CH}<em>2\text{OH} \xrightarrow{\text{KMnO}</em>4\text{(aq)} / \text{H}^+} \text{RCOOH}
    R–CHO→H<em>2CrO</em>4RCOOH\text{R–CHO} \xrightarrow{\text{H}<em>2\text{CrO}</em>4} \text{RCOOH}
  3. Oxidation of alkyl-benzenes (regardless of chain length):
    Ar–CH<em>3→ΔKMnO</em>4,  OH−Ar–COOH\text{Ar–CH}<em>3 \xrightarrow[\Delta]{\text{KMnO}</em>4,\;\text{OH}^-} \text{Ar–COOH} (p-nitrotoluene, o-bromotoluene → respective benzoic acids)
  4. Hydrolysis of nitriles (adds one C):
    R–C≡N→H<em>2OH+  or  OH−R–COOH+NH</em>3\text{R–C≡N} \xrightarrow[\text{H}<em>2\text{O}]{\text{H}^+ \;\text{or}\; \text{OH}^-} \text{R–COOH} + \text{NH}</em>3
  5. Carbonation of Grignard reagents (adds one C):
    R–MgX+CO<em>2→Et</em>2OR–COO−MgX→H3O+R–COOH\text{R–MgX} + \text{CO}<em>2 \xrightarrow{\text{Et}</em>2\text{O}} \text{R–COO}^{-}\text{MgX} \xrightarrow{\text{H}_3\text{O}^+} \text{R–COOH}

α-Substitution (Hell-Volhard-Zelinsky)

  • Reagents: X<em>2/P\text{X}<em>2/P (usually Cl</em>2\text{Cl}</em>2 or Br2\text{Br}_2).
  • Step: halogen replaces α-H → XCH2COOH\text{XCH}_2\text{COOH} + HX\text{HX}.
  • Reactivity order: Br<em>2\text{Br}<em>2 larger → often mono-substitution only; Cl</em>2\text{Cl}</em>2 may continue.
  • Example: CH<em>3CH</em>2CH<em>2COOH→Cl</em>2/PClCH<em>2CH</em>2CH2COOH\text{CH}<em>3\text{CH}</em>2\text{CH}<em>2\text{COOH} \xrightarrow{\text{Cl}</em>2/P} \text{ClCH}<em>2\text{CH}</em>2\text{CH}_2\text{COOH}.
Electrophilic Substitution on Aromatic Acids
  • –COOH–\text{COOH} is a meta-directing, deactivating group (–I/–R).
    • Nitration: HNO<em>3/H</em>2SO4\text{HNO}<em>3/\text{H}</em>2\text{SO}_4 → m-nitrobenzoic acid.
    • Bromination: Br<em>2/FeBr</em>3\text{Br}<em>2/\text{FeBr}</em>3 → m-bromobenzoic acid.

Conversion to Functional Derivatives

General Leaving-Group Reactivity

\text{Acid chloride} > \text{Acid anhydride} > \text{Ester} \approx \text{Carboxylic acid} > \text{Amide}
Reason = quality of leaving group: Cl−\text{Cl}^- best; NH2−\text{NH}_2^- worst.

Acid Chlorides (RCOCl)
  • Preparation:
    RCOOH+SOCl<em>2  (or)  PCl</em>5  (or)  PCl<em>3\text{RCOOH} + \text{SOCl}<em>2 \;(or)\; \text{PCl}</em>5 \;(or)\; \text{PCl}<em>3 → RCOCl+SO</em>2+HCl\text{RCOCl} + \text{SO}</em>2 + \text{HCl}.
  • Physical: B.p ~ aldehydes, pungent, moisture sensitive.
  • Nucleophilic Acyl Substitution (NAS) mechanism (two-step: Nu attack ➜ tetrahedral intermediate ➜ LG departure).
    1. Hydrolysis: RCOCl+H2O→RCOOH+HCl\text{RCOCl} + \text{H}_2\text{O} → \text{RCOOH} + \text{HCl}.
    2. Aminolysis: RCOCl+2 NH<em>3→RCONH</em>2+NH4Cl\text{RCOCl} + 2\,\text{NH}<em>3 → \text{RCONH}</em>2 + \text{NH}_4\text{Cl}.
    3. Alcoholysis: RCOCl+ROH→RCOOR+HCl\text{RCOCl} + \text{ROH} → \text{RCOOR} + \text{HCl} (Fischer ester).
    4. Friedel–Crafts acylation: ArH+RCOCl  /AlCl3→Ar–COR+HCl\text{ArH} + \text{RCOCl}\; / \text{AlCl}_3 → \text{Ar–COR} + \text{HCl}.
    5. Gilman reagent: RCOCl+R’2CuLi→R–COR’\text{RCOCl} + \text{R'}_2\text{CuLi} → \text{R–COR'} (ketone).
    6. Reduction:
    • Strong LiAlH4\text{LiAlH}_4 → 1° alcohol.
    • Mild \text{LiAlH[OC(CH3)3]_3} → aldehyde.
Acid Anhydrides (RCO)2O(RCO)_2O
  • Preparation (dehydration of two acids):
    2 CH<em>3COOH→Δ(CH</em>3CO)<em>2O+H</em>2O2\,\text{CH}<em>3\text{COOH} \xrightarrow{\Delta} (\text{CH}</em>3\text{CO})<em>2\text{O} + \text{H}</em>2\text{O}.
    Dicarboxylic → cyclic anhydrides (succinic, phthalic).
  • Reactivity parallels acid chlorides but slower; products always liberate a carboxylic acid copy.
    1. Hydrolysis: (RCO)<em>2O+H</em>2O→2 RCOOH(RCO)<em>2\text{O} + \text{H}</em>2\text{O} → 2\,\text{RCOOH}.
    2. Aminolysis: (RCO)<em>2O+2 NH</em>3→RCONH<em>2+RCOONH</em>4(RCO)<em>2\text{O} + 2\,\text{NH}</em>3 → \text{RCONH}<em>2 + \text{RCOONH}</em>4.
    3. Alcoholysis: (RCO)2O+ROH→RCOOR+RCOOH(RCO)_2\text{O} + \text{ROH} → \text{RCOOR} + \text{RCOOH}.
    4. Acylation of aromatics (requires Lewis acid).
  • Used as acylating & dehydrating agents (acetylation in aspirin synthesis).
Amides (RCONH₂)
  • Synthesis: acid chloride or anhydride + NH3\text{NH}_3; or dehydration of ammonium salt.
  • Physical: very high B.p (H-bonding), solids.
  • Reactions:
    1. Hydrolysis:
    • Acidic: RCONH<em>2+H</em>2O+H+→RCOOH+NH4+\text{RCONH}<em>2 + \text{H}</em>2\text{O} + \text{H}^+ → \text{RCOOH} + \text{NH}_4^+.
    • Basic: RCONH<em>2+OH−→RCOO−+NH</em>3\text{RCONH}<em>2 + \text{OH}^- → \text{RCOO}^- + \text{NH}</em>3.
    1. Hofmann degradation: RCONH<em>2→Br</em>2/OH−R–NH<em>2+CO</em>2\text{RCONH}<em>2 \xrightarrow{\text{Br}</em>2/\text{OH}^-} \text{R–NH}<em>2 + \text{CO}</em>2 (loss of carbon).
Esters (RCOOR′)
  • Acid-catalyzed esterification (Fischer):
    RCOOH+R’OH⇌H2OH+RCOOR’\text{RCOOH} + \text{R'OH} \xrightleftharpoons[\text{H}_2\text{O}]{\text{H}^+} \text{RCOOR'}. Equilibrium – remove water for yield.
  • Hydrolysis:
    • Acidic (reverse Fischer).
    • Basic (saponification) RCOOR’+OH−→RCOO−+R’OH\text{RCOOR'} + \text{OH}^- → \text{RCOO}^- + \text{R'OH}.

Reduction of Carboxylic Acids

  • LiAlH<em>4\text{LiAlH}<em>4 (ether, then H</em>2O\text{H}</em>2\text{O}) → 1° alcohol:
    RCOOH→LiAlH<em>4RCH</em>2OH\text{RCOOH} \xrightarrow{\text{LiAlH}<em>4} \text{RCH}</em>2\text{OH}.

Structural / Spectroscopic Tidbits

  • C–O\text{C–O} single ≈ 1.36 A˚1.36\,\text{Å}, C=O\text{C=O} double ≈ 1.21 A˚1.21\,\text{Å}; resonance equalizes to ≈1.24 A˚\approx 1.24\,\text{Å}.
  • Planar sp2sp^2 carbon; overlap of p-orbitals.
  • Aromaticity concept: alternating single & double bonds, p-overlap.

Practical / Real-World Connections

  • Soap production relies on alkali-metal carboxylates (hydrophilic head + hydrophobic tail).
  • Aspirin, acetic anhydride, acetyl chloride central to pharmaceutical acetylations.
  • Benzoic acid acts as food preservative (inhibits fungal growth).
  • Understanding acidity guides drug design (ionization state ↔ absorption).

Ethical / Safety Notes

  • Acid chlorides release HCl\text{HCl} on hydrolysis → corrosive fumes; handle under fume hood.
  • LiAlH4\text{LiAlH}_4 reacts violently with water; strict anhydrous technique required.
  • KMnO4\text{KMnO}_4, Cr(VI)\text{Cr(VI)} oxidants are strong environmental hazards; proper waste disposal mandatory.

Summary Equations & Constants

  • General NAS mechanism:
    \require{mhchem} \ce{R-C(=O)-Z + Nu^- ->[1] R-C(=O)(Nu)Z^- ->[2] R-C(=O)-Nu + Z^-}
  • pKa hierarchy: \text{Carboxylic} (\approx4-5) < \text{Phenol}(\approx10) < \text{Alcohol}(\approx16).
  • Reactivity order of derivatives:
    \text{RCOCl} > (\text{RCO})2\text{O} > \text{RCOOR'} \approx \text{RCOOH} > \text{RCONH}2.