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Carboxylic acid derivatives (acid chloride, anhydride, ester, amide) undergo nucleophilic acyl substitution: Nu attacks C=O → tetrahedral intermediate → leaving group departs. Reactivity follows the leaving group ability: RCOCl (Cl-, excellent LG) > (RCO)2O (RCOO-, decent) > RCOOR' (-OR', moderate) > RCONH2 (-NH2, poor LG + strong +M donation). Key principle: you can always convert a more reactive derivative to a less reactive one (downhill): RCOCl + R'OH → RCOOR'; RCOCl + R'NH2 → RCONHR'. Going uphill requires special reagents: RCOOH + SOCl2 → RCOCl. Interconversion chart: Acid → (SOCl2) → Acid chloride → (R'OH) → Ester → (NaOH) → Carboxylate salt. Acid → (R'NH2 via acid chloride) → Amide → (Br2/NaOH, Hofmann) → Amine. The decreasing reactivity explains biological preference for amide bonds (peptides) — they are kinetically stable despite being thermodynamically vulnerable to hydrolysis.