Alcohols Biological Activity Nomenclature Preparation Reactions Some Alcohols
Alcohols Biological Activity Nomenclature Preparation Reactions
Some Alcohols
Alcohols are Found in Many Natural Products
Paralytic Shellfish Poisoning
Ethanol: the Beverage
Methanol: Not a Beverage
Oxidation levels of oxygen- halogen- and nitrogencontaining molecules
Acidity of Alcohols • Due to the electronegativity of the O atoms, alcohols are slightly acidic (p. Ka 16 -18). • The anion dervived by the deprotonation of an alcohol is the alkoxide. • Alcohols also react with Na (or K) as water does to give the alkoxide (red-ox):
Withdrawing Groups Enhance Acidity alcohol CH 3 OH CH 3 CH 2 OH CF 3 CH 2 OH (CH 3)3 COH (CF 3)3 COH p. Ka 15. 54 16. 00 12. 43 18. 00 5. 4
Physical Properties b. p. o. C CH 3 CH 2 CH 3 CH 3 OCH 3 CH 2 OH m. D sol. in H 2 O -42 0. 08 i -25 1. 3 ss 78 1. 7 vs
Intermolecular H-Bonding
Alcohol Nomenclature
Nomenclature
Preparation of Alcohols • • Reduction of ketones and aldehydes Reduction of esters and carboxylic acids Hydration of Alkenes Nucleophilic addition – Grignard reaction – Acetylide addition • Substitution • Epoxide opening
Na. BH 4 Reduction
Some Examples
Two Alcohol Products Form in Lab
Li. Al. H 4 Reduction a Stronger Reducing Agent
Li. Al. H 4 is a much stronger reducing agent
Na. BH 4 is More Selective
Oxymercuration Hydration Markovnikov
Hydroboration Hydration Anti-Markovnikov
Base Catalyzed Ring-Opening of Epoxides
Acid Catalyzed Ring-Opening Aqueous and in Alcohol
Regiochemistry Ring Opens at More Hindered Site
Nucleophilic addition to Carbonyl Compounds Acetylides
Organometallic Chemistry Grignard Reaction
Grignard Reagents React With Ketones to form tertiary alcohols
Grignard Reagents React With Aldehydes to form secondary alcohols
Grignard Reagents React With Formaldehyde to form primary alcohols
Grignard Reagents react (twice) with Esters to form 3 o Alcohols
Grignard Reagents open Epoxides
Ring-Opening is Sterically Controlled
Grignard Summary
Grignard Summary
Grignard Reagents are exceptionally strong bases
Synthesis
Retrosynthetic Analysis
4 -Step Synthesis
Synthesize Using Only 1, 2, or 3 Carbon Reagents
Retrosynthesis
Reactions of Alcohols Oxidation R-X, Ether, and Ester Preparation Protection of Alcohols Synthesis The Logic of Mechanisms
Alcohols are Synthetically Versatile
Oxidation - Reduction
Oxidation of 2 o Alcohols with Cr(VI)
Mechanism
Oxidation of 1 o Alcohols
PCC oxidizes 1 o Alcohols to Aldehydes
Oxidation of 1 o Alcohols to Aldehydes: PCC
Oxidation Summary
Reduction Summary
Conversion of Alcohol into a Leaving Group • Form Tosylate (p-Ts. Cl, pyridine) • Use strong acid (H 3 O+) • Convert to Alkyl Halide (HX, SOCl 2, PBr 3)
Formation of p-Toluenesulfonate Esters
Best to use p-Ts. Cl with pyridine
Reactions of Tosylates: Reduction, Substitution, Elimination
Alcohols to Alkyl Halides
SN 1: Carbocations can Rearrange
Lucas Test
Qualitative test for Alcohol Characterization
Other Simple Qualitative Tests
1 o and 2 o Alcohols: best to use SOCl 2, PBr 3, or P/I 2
Thionyl chloride mechanism in Pyridine – SN 2, Inversion
Dehydration of Alcohols – E 1
Methide Shift is Faster than Loss of H+
Provide a sequence of steps
2 Approaches
Alternate Approach
Propose a Mechanism
Both approaches seem logical
Take the Blue Route
Problem Set: Road Map Problem
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