Chemistry 331 - Winter 1996
Elements of Organic Chemistry I

Professor Carl C. Wamser

Chapter 8 - Alcohols

• functional groups:
• alcohol: C-O-H
• ether: C-O-C
• phenol: Ar-O-H
  (Ar = aryl group)

• based on the carbon the OH group is attached to:
  1° , 2° , 3°
• methyl alcohol
  CH₃OH
• ethyl alcohol
  CH₃CH₂OH (1°)
• isopropyl alcohol
  (CH₃)₂CHOH (2°)
• t-butyl alcohol
  (CH₃)₃COH (3°)

• OH group takes priority (even over -ene or -yne)
  - it must be in the parent chain
  - the direction of numbering gives it the lowest possible number
• -ol suffix with number designation
• name other substituents and multiple bonds as usual

• common names for alcohols:
  alkyl alcohol
  
• cyclohexyl alcohol or cyclohexanol
  
• trans-4-methylcyclohexanol

• (R)-3-methyl-5-hexen-3-ol

• OH group assumed number 1
  
• 4-chloro-3-methylphenol

• alkyl alkyl ether (common)
  
  benzyl methyl ether
• alkoxy substituent (IUPAC)
  
  (S)-2-ethoxypentane

• sp3 O with two covalent bonds and two lone pairs
• O lone pairs attract polar H bonds
• covalent O-H bond strength ~ 100 kcal/mole
• O...H (H-bond) strength ~ 5 kcal/mole

• alcohols have higher boiling points than alkanes (nonpolar)
  or alkyl halides (polar, but no H-bonds)
• ethers are polar but have no H-bonds
  (pentane and diethyl ether both boil at about 35°)
• H-bonds hold together the strands of DNA ("velcro" effect)

• remember analogy with water
• reactions as bases:
  H2O + H+ <==> H3O+
  ROH + H+ <==> ROH2+ (an oxonium ion)
• reactions as acids:
  H2O + B- <==> B-H + OH-
  ROH + B- <==> B-H + RO- (an alkoxide ion)

• alcohols about as acidic as water
  MeOH more acidic, EtOH less acidic
  3° alcohols much weaker acids
• pKa values: 3° > 2° > 1° > MeOH
  18 , 17, 16, 15.5 (compare H2O: pKa = 15.7)
• tBuOH + NaOH ---> unfavorable

• deprotonation of alcohols gives alkoxide anions
  CH3OH + NaNH2 ---> NH3 + CH3O- Na+ (sodium methoxide)
• most commonly made by direct reaction with active metals
  CH3OH + Na ---> 1/2 H2 + CH3O- Na+
  (CH3)3COH + K ---> 1/2 H2 + (CH3)3CO-K+

• phenoxide anions are stabilized by resonance with the aromatic ring
• pKa of phenol is 10
  (deprotonated by NaOH at pH 10)
• electron withdrawing groups further stabilize the phenoxide anion
  (especially ortho or para)
• pKa of p-nitrophenol is 7

• alcohols are just the first of the many possible oxygen functional groups
• oxidation leads to increasing number of bonds to oxygen
  alkane --> alcohol --> carbonyl --> carboxyl --> CO2
• reduction leads to decreasing number of bonds to oxygen
  CO2 --> carboxyl --> carbonyl --> alcohol --> alkane

• hydration of alkenes
  follows Markovnikov's Rule
  1-hexene --(H+, H2O)--> 2-hexanol
• reduction of carbonyl and carboxyl compounds
  reducing agents:
  sodium borohydride (NaBH4)
  lithium aluminum hydride (LiAlH4)

• reductions to prepare alcohols:
• aldehydes or ketones plus NaBH4
• carboxylic acids or esters plus LiAlH4
• oxidations of alcohols:
• 1° alcohol to aldehyde with PCC
• 2° alcohol to ketone with CrO3
• 1° alcohol to carboxylic acid with CrO3

• Williamson ether synthesis
• an SN2 reaction with an alkoxide as nucleophile
• the alkyl halide should be methyl or 1°

• acid/base reactions
• oxidation reactions
• elimination (dehydration)
• substitution (C-O bond cleavage)

• substitution (and elimination)
  OH is a poor leaving group
  but initial protonation creates a good leaving group (H2O)
• dehydration (E1 mechanism)
• halide substitution (SN1)
  tBuOH + HBr --> tBuOH2+ --> tBu+ --> tBuBr

• ethers are generally unreactive
  (make good solvents)
• react with strong acid
  (protonated form can undergo SN1 or SN2 substitution)

• the phenol C-O bond is rarely cleaved
  (SN1, SN2, E1, and E2 don't work for aryl groups)
• phenoxide anions are good nucleophiles
• electrophiles add readily to the benzene ring
  OH is activating and an o,p-director

• phenols are readily oxidized to quinones
• reduction of quinones gives a hydroquinone
  a common reversible redox pair

• cyclic 3-membered ring ethers
• named as 1,2-epoxyalkane
• prepared from alkenes
• unlike other ethers, these react easily to undergo ring opening

• acid-catalyzed hydration
• base-catalyzed hydration
• product is trans diol
  (backside attack as in the reaction of bromonium ions)

• thiols: C-S-H group
  (analogous to alcohols)
• sulfides: C-S-C group
  (analogous to ethers)
• disulfides: C-S-S-C group
  (analogous to peroxides)
• similar to oxygen analogs except:
  better nucleophiles
  easier to oxidize

• name alcohols, phenols, ethers, epoxides, thiols, sulfides, and disulfides
• predict relative favorability of acid-base reactions from pKa values
• develop appropriate synthetic reactions for alcohols, phenols, ethers, epoxides, thiols, sulfides, and disulfides
• predict products from the reactions of alcohols, phenols, ethers, epoxides, thiols, sulfides, and disulfides