Preparation of alcohols by reduction of aldehydes and ketones Hydrogenation sodium borohydride (NaBH4) with aqueous or alcoholic solution; lithium

m aluminum hydride (LiAlH4) with anhydrous diethyl ether or THF Mechanism 15.1 (p. 653) Aldehyde forms primary alcohol Ketone forms secondary alcohol LiAlH4 also reduces carboxylic acids to primary alcohols

Preparation of alcohols from epoxides Grignard reagents react with ethylene oxide to yield primary alcohols plus whatever R was attached to MgBr

Preparation of diols Vicinal diols (syn dihydroxylation) Osmium tetraoxide (OsO4) reacts rapidly with alkenes to give cyclic osmate esters. They are fairly stable but are readily cleaved in the presence of an oxidizing agent (e.g. tertbutyl hydroperoxide). It is used only in catalytic amounts Enantioselective synthesis of chiral dials K2OsO2(OH)4 as the osmium source, K3Fe(CN)6 as the oxidant, and naturally occurring alkaloids like dihydroquinidine

Conversion of alcohols to ethers (mechanism 15.2, p. 660) Condensation reactions Heat in the presence of an acid catalyst (e.g. H2SO4) Converts primary alcohols to ethers, forming a larger molecule from the two starting materials, and then releasing a smaller one Diols react intramolecularly to form cyclic ethers when a 5 or 6-membered ring can result (ex. oxane)

Fischer Esterification Acid-catalyzed (H2SO4) condensation of an alcohol and a carboxylic acid yields an ester and water Reversible action that lies slightly in favor of the products

Esters and HCl are also formed by the reaction of alcohols with acyl chlorides (RC=OCl) in the presence of a weak base (e.g. pyridine) Acid anhydrides (RC=OOC=OR) react with pyridine, forming an ester and a carboxylic acid

Acid chloride mechanism 19.1 (p. 822) Acid anhydride mechanism 19.2 (p. 824-825)

Oxidation of Alcohols RCH2OH oxidize RC=OH oxidize RC=OOH (primary alcohol to aldehyde to carboxylic acid) Oxidizing agents for carboxylic acids: Na2Cr2O7 or K2Cr2O7 with H2SO4, H2O Oxidizing agents for aldehydes: PCC or PDC, each in CH2Cl2 RCOHHR oxidize RC=OR (secondary alcohol to ketone) (same oxidizing agents) KMnO4 and chromic acid (Na2Cr2O7, H3O+) oxidize secondary alcohols to ketones, and primary alcohols to carboxylic acids.

Biological Oxidation of Alcohols

Oxidative cleavage of vicinal diols Vicinal diol is broken into two carbonyl in the presence of periodic acid (HIO4) or sodium periodate (NaIO4) with THF and H2O

Thiols (RSH) Thiols (mercaptans) are sulfur analogues of alcohols. Thiols have a pKa ~ 10 and are stronger acids than alcohols. RS and HS are weakly basic and strong nucleophiles. Thiolates react with 1 and 2 alkyl halides to yield sulfides (SN2).

Oxidized form on right, reduced form on left