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 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)