Alcohols

Properties

polar, hydrogen bonding, pK_a gets lower with induction & resonance

Nucleophilic Substiution of Alkohalids

Sn rections; get OH in replace of halogen/LG

Sn2 reactions

on primary and secondary carbons; strong nucleophile; backside attack/reverse stereochemistry; strong leaving group

Sn1

weak nucleophile; secondary and tertiary to stabilize carbocation intermediate; racemic mixture/mix of stereochemsitry; strong leaving group; can be HOH (alcohols) or HOR (ethers)ik

Markovnikoc Hydration of Alkenes

H₂SO₄, H₂O or 1) Hg(OAc)₂, H₂O 2) NaBH₄; carbon cation intermediate is stabilized by hyperconjugation

anit-markovnikov hydration of alkenes

1) BH₃, THF 2) H₂O₂, NaOH; racemic mixture; no carbocation intermediate

Addition to Carbonyls with Alkyne Nucleophile

1) R-CC^-Na⁺ 2) H₃O⁺; makes triple C-C bond

Addition to Carbonyls with Grignard Addition

1) R’-MgBr 2) H₃O⁺; can add single C-C bond

Addition to Carbonyl with Hydride Addition

1) LiAlH₄ or NaBH₄ 2) H₃O⁺; adds H onto ketone/aldehyde

Oxidation of Alcohols

easily oxidized using transition metals (Cr, Mn); common oxidizing reagents (KMnO₄, H₂CrO₇, NaOCl); nonmetal oxidants (I, S); need H on carbon from C=O to work; no tertiary alcohol can be oxidized

Chromium oxidation (Jones)

Na₂Cr₂O₇ or CrO₃ + H₂SO₄ → H₂CrO₄ (very unstable) that can oxidize alcohol; need H on carbon

Primary Alcohols Jones Oxidation

carboxylic acid; reacts to aldehyde but then in equilibrium with hydrate & gets oxidized again bc has H to carboxylic acid

Secondary Alcohol Jones Oxidation

ketone

Tertiary Alcohol Jones Oxidation

no rxn bc no H

Basic oxidiations

PCC & Swern Oxidation

PCC Reaction

uses PCC as reagent to get aldehyde w/ primary, ketone w/ secondary

Swern Oxidation

uses Swern reagents (COCl)₂, EtN, DMSO to get aldehyde for primary, ketone for secondary; avoids using transition metals

Alcohols as Nucleophiles

NaH or NaNH₂ (bases) remove H from weak nucleophile to get strong nucleophile

Alcohols as Electrophils

make carbocation or with leaving group on it

Acid Activation

alcohol + H⁺ → carbocation; acidic conditions, rearrangment, make positive on O

Tosylation

alcohol + 1)TsCl, pyridine 2) NaBr → Br on carbon; makes leaving group; basic conditions; intermediate of OTs

Conversion of Alcohols into Halides

indirect route via Ts, reactions with HX, Phosphorous Halides, thionyl chloride

Indirect Route via Ts

alcohol + 1)TsCl, pyridine 2) NaX → replaced with X; aka tosylation; basic conditions

Reactions with HX

alcohol + HX → carbon-X; makes OH a leaving group as H₂O so carbocation that X can attack; use with tertiary carbons; acidic conditions

Phosphorous Halides

alcohol + PX₃ → carbon-X; inversion of stereochemistry; Br → PBr₃, Cl → PCl₃, I → P + I₂ for PI₃; O attacks P & makes good leaving group for X to come in

Thionyl Chloride

alcohol + SOCl₂ → carbon-Cl; same stereochemistry bc Cl on same plane as O; concerted; O attacks S, Cl takes H & O=S so Cl can attack carbon in C-O

Acid-H

acidic H

NaH

basic H

LiAlH₄

nucleophilic H

Reduction to Alkanes

alcohol + 1)TsCl, pyridine 2) LiAlH₄ → C-H; make OTs intermediate; basic conditions

Elimination of Alcohols to Alkenes

alcohol + POCl₃, pyridine → alkene (double bond); elimination 2; O attacks P for leaving group stability & pyridine attacks H to form double bond

Synthesize 1,2-diol

alkene + OsO₄, H₂O₂ → 2 OH; syn addition

Pinacol Rearrangement

1,2-diols + H₂SO₄ → C=O; use acid for leaving groups; rearrangement; resonance; acidic conditions

Periodic Cleavage

HIO₄ + 1,2-diols → two ketones; forms intermediate like ozonolysis

Williamson ether Synthesis

alkyl w/ leaving group + NaOR → carbon-OR; Sn2 w/ R instead of H