Organic Chemistry Midterm 1

NaOH / KOH (with haloalkanes)

Strong base, strong nucleophile • SN2 favored for methyl/1° substrates • E2 competes for 2° and dominates for 3° • SN2: backside attack, inversion • E2: anti-periplanar β-H, alkene

NaOCH3 / NaOEt

Strong base, good nucleophile • Small/unhindered • SN2 for 1°; E2 often for 2°/3° • E2 usually favors Zaitsev alkene

KOtBu / NaOtBu

Strong bulky base • E2 favored • Often Hofmann (less substituted) alkene • Concerted β-H removal

H2O / ROH (with haloalkanes)

Weak nucleophile, weak base • SN1/E1 favored with 3° and suitable 2° • Carbocation intermediate; rearrangements possible • Heat increases elimination

NaI / NaBr (in acetone)

Good nucleophile, weak base • SN2 favored for 1° substrates • Backside attack, inversion • Substitution product

NaBH4

Reducing agent • Aldehyde → 1° alcohol; ketone → 2° alcohol • Hydride attack → tetrahedral alkoxide → proton transfer • No carbocation

LiAlH4 (LAH)

Strong reducing agent • Aldehyde → 1° alcohol; ketone → 2° alcohol • Hydride attack → tetrahedral alkoxide → proton transfer • Requires protonating workup

RMgBr (Grignard)

Strong carbon nucleophile • Attacks aldehydes and ketones • Nu attack → tetrahedral alkoxide → proton transfer • Formaldehyde → 1°; other aldehyde → 2°; ketone → 3° alcohol

RLi (organolithium)

Strong carbon nucleophile and base • Adds carbon group to aldehyde or ketone • Nu attack → tetrahedral alkoxide → proton transfer • Alcohol after workup

PCC

Mild oxidizing agent • 1° alcohol → aldehyde • 2° alcohol → ketone • 3° alcohol → no reaction under these conditions

CrO3 / H2SO4

Strong oxidizing agent • 1° alcohol → carboxylic acid • 2° alcohol → ketone • 3° alcohol → no reaction under these conditions

KMnO4

Strong oxidizing agent • 1° alcohol → carboxylic acid • 2° alcohol → ketone • 3° alcohol → no reaction under usual conditions

HBr / HI (with alcohols)

Alcohol → alkyl halide • Proton transfer → oxonium (ROH2+) • 1° usually SN2; 2°/3° SN1 in lecture framework • SN1 may rearrange

HCl (with alcohols)

Alcohol → alkyl chloride • Protonation → oxonium • SN1 often for 3° alcohols • Outcome depends on substrate and conditions

PBr3

1°/2° alcohol → alkyl bromide • Activates OH as leaving group • SN2; backside attack and inversion • No carbocation

SOCl2 + pyridine

1°/2° alcohol → alkyl chloride • Activates OH as leaving group • SN2 kinetics and inversion in lecture • No carbocation

TsCl + pyridine

Alcohol → alkyl tosylate (ROTs) • Turns poor OH leaving group into excellent OTs • C–O bond stays intact; retention at carbon • OTs can leave in later substitution/elimination

H2SO4 + heat (with alcohol)

Acid-catalyzed dehydration → alkene • Proton transfer → oxonium • 1° E2; 2°/3° E1 in lecture framework • E1: carbocation, possible rearrangement

H3PO4 + heat (with alcohol)

Acid-catalyzed dehydration → alkene • Proton transfer → oxonium • 1° E2; 2°/3° E1 in lecture framework • E1: carbocation, possible rearrangement

KH / BuLi / LDA (with alcohol)

Strong bases • Deprotonate OH → alkoxide (RO−) • Acid–base reaction • Alkoxide is strong nucleophile

Alkoxide (RO−) + R–X

Williamson ether synthesis • SN2; alkoxide attacks carbon bearing leaving group • Ether (R–O–R′) product • Best with methyl/1° R–X

Halohydrin + strong base

Intramolecular Williamson ether synthesis • Strong base forms alkoxide intermediate • Intramolecular SN2 ring closure • Three-membered epoxide forms

Epoxide + strong Nu−

Basic nucleophilic ring opening • SN2 at LESS substituted carbon • Backside attack → alkoxide → proton transfer • Ring-opened alcohol

Epoxide + H3O+

Acid-catalyzed ring opening • Protonation → oxonium • Water attacks MORE substituted carbon • Proton transfer → diol

Epoxide + HX

Acid-catalyzed ring opening • Protonation → oxonium • Halide attacks MORE substituted carbon • Halohydrin product

Epoxide + ROH / H+

Acid-catalyzed ring opening • Protonation → oxonium • Alcohol attacks MORE substituted carbon • Proton transfer → alkoxy alcohol

Epoxide + RMgBr, then H3O+

Strong carbon nucleophile • SN2 ring opening at LESS substituted carbon • Alkoxide intermediate → proton transfer • New C–C bond and alcohol