Lecture Organic chemistry - Chapter 20: Carboxylic acid derivatives. The main contents of this chapter include all of the following: Inductive effects, resonance effects, acyl halides, reactions, anhydrides, esters, amides | Chapter 20: Carboxylic Acid Derivatives OH bad leaving group What is the relative reactivity of these carboxylic acid derivatives? Most reactive Least reactive L to the right, when acting as Nu, displaces L to the left = L No catalyst needed No catalyst needed Origins of Reactivity Trends Inductive effects Elements to the right in a row of Periodic Table are more electronegative (nuclear charge increase). Donating ability of L increases from right to left in the periodic table. 2. Resonance effects Acetyl chloride Acetamide Differences reflected in pKa values Basicity Protonation gets easier from L = X to O to N For the same reason, deprotonation gets more difficult A. Acyl Halides Names: Alkanoic acid → alkanoyl halide Cyclohexanecarbonyl fluoride Cycloalkanecarboxylic acid → cycloalkanecarbonyl halide Mechanism: Example: 1. Water: Hydrolysis gives RCOOH Reactions General Reaction Example: 60% 2. Alcohols: R’OH converts acyl chlorides into esters , -SO2 Works for NH3, RNH2, and RNHR’ | Chapter 20: Carboxylic Acid Derivatives OH bad leaving group What is the relative reactivity of these carboxylic acid derivatives? Most reactive Least reactive L to the right, when acting as Nu, displaces L to the left = L No catalyst needed No catalyst needed Origins of Reactivity Trends Inductive effects Elements to the right in a row of Periodic Table are more electronegative (nuclear charge increase). Donating ability of L increases from right to left in the periodic table. 2. Resonance effects Acetyl chloride Acetamide Differences reflected in pKa values Basicity Protonation gets easier from L = X to O to N For the same reason, deprotonation gets more difficult A. Acyl Halides Names: Alkanoic acid → alkanoyl halide Cyclohexanecarbonyl fluoride Cycloalkanecarboxylic acid → cycloalkanecarbonyl halide Mechanism: Example: 1. Water: Hydrolysis gives RCOOH Reactions General Reaction Example: 60% 2. Alcohols: R’OH converts acyl chlorides into esters , -SO2 Works for NH3, RNH2, and RNHR’ Reaction: 3. Amines turn acyl chlorides into amides Mechanism: One equiv used up as base R2CuLi 4. Organocuprates transform acyl chlorides into ketones Examples: 1. THF 2. H+, H2O Does not add to ketone carbonyl 5. Reduction of acyl chlorides results in aldehydes Use modified (less reactive form of) LiAlH4: Does not touch the aldehyde product Via addition-elimination B. Anhydrides Names: Add anhydride to the alkanoic acid name Acetic anhydride Pentanedioic anhydride = Leaving group + + Reactions: Similar to acyl halides, but anhydrides are less corrosive, cheaper Mechanism: Examples: Regioselective reaction? Cyclic anhydrides react by ring opening: Allows the regioselective functionalization of a dioic acid. For example, problem: Heating the dioic acid or SOCl2 produces the cyclic anhydride: Δ Now, treat with nucleophile to ring open: Friedel-Crafts Reactivity C. Esters Names: Alkyl alkanoate Methyl acetate Cyclic: Lactone β-Propiolactone Common name 1,1-Dimethylethyl butanoate Note .
