Chem 334 - Fall 1999
Organic Chemistry I
Dr. Carl C. Wamser

Chapter 9 - Alcohols and Thiols

Functional groups

alcohol: R-O-H (hydroxyl group)
thiol: R-S-H (sulfhydryl group)

Alcohol Classification

• 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°)

Alcohol Nomenclature

• OH group takes priority over -ene
  - it must be in the parent chain
  - the direction of numbering gives it the lower possible number
• -ol suffix with number designation
• name other substituents and multiple bonds as usual
• more than one alcohol named as a -diol, -triol, etc.

Alcohol Examples

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

Alcohol Example

(R)-3-methyl-5-hexen-3-ol

Thiol Nomenclature

• the parent is the longest chain that contains the -SH group
• the IUPAC suffix is -thiol
• Common names: name the alkyl group bonded to sulfur followed by the word mercaptan
  example: 2-butanethiol or sec-butyl mercaptan

Structure of Alcohols

• sp3 O with two covalent bonds and two lone pairs
• The bond angle about oxygen is about 105°,
  explained as greater repulsions of the lone pairs
  towards the bonding pairs

Structure of Thiols

• The bond angle about sulfur in methanethiol is 100.3°,
  explained as greater p character in the bonding orbitals

Properties of Alcohols

• Alcohols are polar compounds due to the polar C-O and O-H bonds
• They interact with themselves and with other polar compounds by dipole-dipole interactions
• Dipole-dipole interaction:
  the attraction between the positive end of one dipole and the negative end of another

Hydrogen Bonding

• attraction between the positive end of one dipole (an H bonded to F, O, or N - atoms of high electronegativity) and the negative end of a dipole, usually a lone pair on F, O, or N
• in alcohols, O lone pairs interact with polar H bonds
• covalent O-H bond strength ~ 100 kcal/mole
• O...H (H-bond) strength ~ 5 kcal/mole

Effects of H-Bonding

• 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°, but 1-butanol has a bp of 117°)
• H-bonds hold together the strands of DNA ("Velcro" effect)
• H-bonding increases water solubility

Properties of Thiols

• The S-H bond is only slightly polar
• Thiols show little association by hydrogen bonding
• Thiols have lower boiling points and are less soluble in water than alcohols

Acid-Base Reactions

• 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)

Acidity of Alcohols

• 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

Alkoxide Anions

• 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+
• stability of alkoxides depends on solvation
  bulky alkoxides are less solvated and less stable (stronger bases)

Oxygen Functional Groups

• 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

Reactions of Alcohols

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

Substitution Reactions with HX

• substitution by halogens using HX
  OH is a poor leaving group
  but initial protonation creates a good leaving group (H2O)
• halide substitution (SN1 mechanism)
  tBuOH + HBr --> tBuOH2+ --> tBu+ --> tBuBr
  favored by relatively stable carbocation (3°)
• halide substitution (SN2 mechanism)
  MeOH + HBr --> MeOH2+ Br- --> MeBr + H2O
  concerted displacement of H2O by Br- (unstable carbocation)
• rearrangements are possible, even with 1° alcohols

Halogen Substitution with Other Reagents

• PBr3 + alcohol gives alkyl bromide, with less rearrangement than with HBr
• SOCl2 + alcohol gives alkyl halide, also with less rearrangement

Alkyl Sulfonates

• alcohol + RSO2Cl gives a sulfonate ester
• sulfonate esters are excellent leaving groups

Dehydration (Elimination) Reactions

• acid-catalyzed dehydration: 3° > 2° >1°
  favored by relatively stable carbocation,
  absence of nucleophile, high temperature
• same first step as for substitution:
  initial protonation creates a good leaving group (H2O)
• E1: carbocation loses H+ to form an alkene
  tBuOH + H2SO4 --> tBuOH2+ --> tBu+ --> (CH3)2C=CH2 + H+
• E2: less-substituted alcohols (unstable carbocations) show
  concerted loss of H2O and H+
• rearrangements are commonly observed during dehydration

The Zaitsev Rule

• predicts regiochemistry of alkene formation
• the major product in an elimination reaction is the more substituted alkene
  (generally more stable)
• dehydration of an alcohol forms the more stable (more substituted) alkene

Pinacol Rearrangement

• acid-catalyzed dehydration of a glycol (1,2-diol),
  with rearrangement

Alcohol Oxidation Reactions

• chromium (VI) oxidants:
  CrO3, H2CrO4, K2Cr2O7
• oxidation involves intermediate chromate ester
• 1° alcohol to carboxylic acid with any Cr(VI) reagent, e.g., CrO3
• 1° alcohol to aldehyde with PCC (avoids further oxidation)
• 2° alcohol to ketone with any Cr(VI) reagent

Glycol Oxidation Reactions

• periodic acid, H5IO6 (or HIO4·2H2O)
• C-C bond is cleaved and alcohols are oxidized
• intermediate is a cyclic periodic ester
• common degradation reaction for sugars

Thiol Reactions

• The most common preparation of thiols, RSH, depends on the very high nucleophilicity of hydrosulfide ion, HS-
• Thiols are stronger acids than alcohols
• When dissolved an aqueous NaOH, they are converted completely to alkylsulfide salts
• Thiols are oxidized to disulfides by a variety of oxidizing agents, including O2. They are so susceptible to this oxidation that they must be protected from air during storage
• The most common reaction of thiols in biological systems in interconversion between thiols and disulfides, -S-S-