Organic Chemistry

1
Organic Chemistry

• William H. Brown
• Christopher S. Foote
• Brent L. Iverson

2
Alcoholsand Thiols

• Chapter 10

3
Structure - Alcohols

• The functional group of an alcohol is an -OH
  group bonded to an sp3 hybridized carbon
• bond angles about the hydroxyl oxygen atom are
  approximately 109.5
• Oxygen is sp3 hybridized
• two sp3 hybrid orbitals form sigma bonds to
  carbon and hydrogen
• the remaining two sp3 hybrid orbitals each
  contain an unshared pair of electrons

4
Nomenclature-Alcohols

• IUPAC names
• the parent chain is the longest chain that
  contains the OH group
• number the parent chain to give the OH group the
  lowest possible number
• change the suffix -e to -ol
• Common names
• name the alkyl group bonded to oxygen followed by
  the word alcohol

5
Nomenclature-Alcohols

• Examples

6
Nomenclature-Alcohols

• Examples

7
Nomenclature-Alcohols

• Examples

8
Nomenclature-Alcohols

• Examples

9
Nomenclature of Alcohols

• Compounds containing more than one OH group are
  named diols, triols, etc.

10
Nomenclature of Alcohols

• Compounds containing more than one OH group are
  named diols, triols, etc.

11
Nomenclature of Alcohols

• Compounds containing more than one OH group are
  named diols, triols, etc.

12
Nomenclature of Alcohols

• Compounds containing more than one OH group are
  named diols, triols, etc.

13
Nomenclature of Alcohols

• Compounds containing more than one OH group are
  named diols, triols, etc.

14
Nomenclature of Alcohols

• Unsaturated alcohols
• show the double bond by changing the infix from
  -an- to -en-
• show the the OH group by the suffix -ol
• number the chain to give OH the lower number

15
Physical Properties

• Alcohols are polar compounds
• 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

16
Physical Properties

• Hydrogen bonding when the positive end of one
  dipole is an H bonded to F, O, or N (atoms of
  high electronegativity) and the other end is F,
  O, or N
• the strength of hydrogen bonding in water is
  approximately 21 kJ (5 kcal)/mol
• hydrogen bonds are considerably weaker than
  covalent bonds
• nonetheless, they can have a significant effect
  on physical properties

17
Hydrogen Bonding
18
Physical Properties

• Ethanol and dimethyl ether are constitutional
  isomers.
• Their boiling points are dramatically different
• ethanol forms intermolecular hydrogen bonds which
  increase attractive forces between its molecules
  resulting in a higher boiling point
• there is no comparable attractive force between
  molecules of dimethyl ether

Dimethyl ether
Ethanol
bp -24C
19
Physical Properties

• In relation to alkanes of comparable size and
  molecular weight, alcohols
• have higher boiling points
• are more soluble in water
• The presence of additional -OH groups in a
  molecule further increases solubility in water
  and boiling point

20
Physical Properties
21
Acidity of Alcohols

• In dilute aqueous solution, alcohols are weakly
  acidic

22
Acidity of Alcohols
23
Acidity of Alcohols

• Acidity depends primarily on the degree of
  stabilization and solvation of the alkoxide ion
• the negatively charged oxygens of methanol and
  ethanol are about as accessible as hydroxide ion
  for solvation these alcohol are about as acidic
  as water
• as the bulk of the alkyl group increases, the
  ability of water to solvate the alkoxide
  decreases, the acidity of the alcohol decreases,
  and the basicity of the alkoxide ion increases

24
Reaction with Metals

• Alcohols react with Li, Na, K, and other active
  metals to liberate hydrogen gas and form metal
  alkoxides
• Alcohols are also converted to metal alkoxides
  by reaction with bases stronger than the alkoxide
  ion
• one such base is sodium hydride

25
Reaction with HX

• 3 alcohols react very rapidly with HCl, HBr, and
  HI
• low-molecular-weight 1 and 2 alcohols are
  unreactive under these conditions
• 1 and 2 alcohols require concentrated HBr and
  HI to form alkyl bromides and iodides

26
Reaction with HX

• with HBr and HI, 2 alcohols generally give some
  rearranged product
• 1 alcohols with extensive ?-branching give large
  amounts of rearranged product

27
Reaction with HX

• Based on
• the relative ease of reaction of alcohols with HX
  (3 gt 2 gt 1) and
• the occurrence of rearrangements,
• Chemists propose that reaction of 2 and 3
  alcohols with HX
• occurs by an SN1 mechanism, and
• involves a carbocation intermediate

28
Reaction with HX - SN1

• Step 1 proton transfer to the OH group gives an
  oxonium ion
• Step 2 loss of H2O gives a carbocation
  intermediate

29
Reaction with HX - SN1

• Step 3 reaction of the carbocation intermediate
  (an electrophile) with halide ion (a nucleophile)
  gives the product

30
Reaction with HX - SN2

• 1 alcohols react with HX by an SN2 mechanism
• Step 1 rapid and reversible proton transfer
• Step 2 displacement of HOH by halide ion

31
Reaction with HX

• For 1 alcohols with extensive ?-branching
• SN1 is not possible because this pathway would
  require a 1 carbocation
• SN2 is not possible because of steric hindrance
  created by the ?-branching
• These alcohols react by a concerted loss of HOH
  and migration of an alkyl group

32

Reaction with HX

• Step 1 proton transfer gives an oxonium ion
• Step 2 concerted elimination of HOH and
  migration of a methyl group gives a 3 carbocation

33
Reaction with HX

• Step 3 reaction of the carbocation intermediate
  (an electrophile) with halide ion (a nucleophile)
  gives the product

34
Reaction with PBr3

• An alternative method for the synthesis of 1 and
  2 bromoalkanes is reaction of an alcohol with
  phosphorus tribromide
• this method gives less rearrangement than with HBr

35
Reaction with PBr3

• Step 1 formation of a protonated
  dibromophosphite converts H2O, a poor leaving
  group, to a good leaving group
• Step 2 displacement by bromide ion gives the
  alkyl bromide

36
Reaction with SOCl2

• Thionyl chloride is the most widely used reagent
  for the conversion of 1 and 2 alcohols to alkyl
  chlorides
• a base, most commonly pyridine or triethylamine,
  is added to catalyze the reaction and to
  neutralize the HCl

37
Reaction with SOCl2

• Reaction of an alcohol with SOCl2 in the presence
  of a 3 amine is stereoselective
• it occurs with inversion of configuration

38
Reaction with SOCl2

• Step 1 formation of an alkyl chlorosulfite
• Step 2 nucleophilic displacement of this leaving
  group by chloride ion gives the chloroalkane

39
Alkyl Sulfonates

• Sulfonyl chlorides are derived from sulfonic
  acids
• sulfonic acids, like sulfuric acid, are strong
  acids

O
O
O
O
O
O
40
Alkyl Sulfonates

• A commonly used sulfonyl chloride is
  p-toluenesulfonyl chloride (Ts-Cl)

41
Alkyl Sulfonates

• Another commonly used sulfonyl chloride is
  methanesulfonyl chloride (Ms-Cl)

42
Alkyl Sulfonates

• Sulfonate anions are very weak bases (the
  conjugate base of a strong acid) and are very
  good leaving groups for SN2 reactions
• Conversion of an alcohol to a sulfonate ester
  converts HOH, a very poor leaving group, into a
  sulfonic ester, a very good leaving group

43
Alkyl Sulfonates

• This two-step procedure converts (S)-2-octanol to
  (R)-2-octyl acetate
• Step 1 formation of a p-toluenesulfonate (Ts)
  ester
• Step 2 nucleophilic displacement of tosylate

44
Dehydration of ROH

• An alcohol can be converted to an alkene by
  acid-catalyzed dehydration (a type of
  ?-elimination)
• 1 alcohols must be heated at high temperature in
  the presence of an acid catalyst, such as H2SO4
  or H3PO4
• 2 alcohols undergo dehydration at somewhat lower
  temperatures
• 3 alcohols often require temperatures at or
  slightly above room temperature

45
Dehydration of ROH
180C
Cyclohexanol
Cyclohexene

46
Dehydration of ROH

• where isomeric alkenes are possible, the alkene
  having the greater number of substituents on the
  double bond (the more stable alkene) usually
  predominates (Zaitsev rule)

47
Dehydration of ROH

• Dehydration of 1 and 2 alcohols is often
  accompanied by rearrangement
• acid-catalyzed dehydration of 1-butanol gives a
  mixture of three alkenes

140 - 170C
48
Dehydration of ROH

• Based on evidence of
• ease of dehydration (3 gt 2 gt 1)
• prevalence of rearrangements
• Chemists propose a three-step mechanism for the
  dehydration of 2 and 3 alcohols
• because this mechanism involves formation of a
  carbocation intermediate in the rate-determining
  step, it is classified as E1

49
Dehydration of ROH

• Step 1 proton transfer to the -OH group gives an
  oxonium ion
• Step 2 loss of H2O gives a carbocation
  intermediate

50
Dehydration of ROH

• Step 3 proton transfer from a carbon adjacent to
  the positively charged carbon to water the sigma
  electrons of the C-H bond become the pi electrons
  of the carbon-carbon double bond

51
Dehydration of ROH

• 1 alcohols with little ?-branching give terminal
  alkenes and rearranged alkenes
• Step 1 proton transfer to OH gives an oxonium
  ion
• Step 2 loss of H from the ?-carbon and H2O from
  the ?-carbon gives the terminal alkene

52
Dehydration of ROH

• Step 3 shift of a hydride ion from ?-carbon and
  loss of H2O from the ?-carbon gives a carbocation
• Step 4 proton transfer to solvent gives the
  alkene

53
Dehydration of ROH

• Dehydration with rearrangement occurs by a
  carbocation rearrangement

54
Dehydration of ROH

• Acid-catalyzed alcohol dehydration and alkene
  hydration are competing processes
• Principle of microscopic reversibility the
  sequence of transition states and reactive
  intermediates in the mechanism of a reversible
  reaction must be the same, but in reverse order,
  for the reverse reaction as for the forward
  reaction

55
Pinacol Rearrangement

• The products of acid-catalyzed dehydration of a
  glycol are different from those of alcohols

56
Pinacol Rearrangement

• Step 1 proton transfer to OH gives an oxonium
  ion
• Step 2 loss of water gives a carbocation
  intermediate

57
Pinacol Rearrangement

• Step 3 a 1,2- shift of methyl gives a more
  stable carbocation
• Step 4 proton transfer to solvent completes the
  reaction

58
Oxidation 1 ROH

• Oxidation of a primary alcohol gives an aldehyde
  or a carboxylic acid, depending on the
  experimental conditions
• to an aldehyde is a two-electron oxidation
• to a carboxylic acid is a four-electron oxidation

59
Oxidation of ROH

• A common oxidizing agent for this purpose is
  chromic acid, prepared by dissolving chromium(VI)
  oxide or potassium dichromate in aqueous sulfuric
  acid

Chromic acid
Chromic acid
60
Oxidation 1 ROH

• Oxidation of 1-octanol gives octanoic acid
• the aldehyde intermediate is not isolated

61
Oxidation 2 ROH

• 2 alcohols are oxidized to ketones by chromic
  acid

62
Chromic Acid Oxidation of ROH

• Step 1 formation of a chromate ester
• Step 2 reaction of the chromate ester with a
  base, here shown as H2O

63
Chromic Acid Oxidation of RCHO

• chromic acid oxidizes a 1 alcohol first to an
  aldehyde and then to a carboxylic acid
• in the second step, it is not the aldehyde per se
  that is oxidized but rather the aldehyde hydrate

64
Oxidation 1 ROH to RCHO

• Pyridinium chlorochromate (PCC) a form of Cr(VI)
  prepared by dissolving CrO3 in aqueous HCl and
  adding pyridine to precipitate PCC as a solid
• PCC is selective for the oxidation of 1 alcohols
  to aldehydes it does not oxidize aldehydes
  further to carboxylic acids

65
Oxidation 1 ROH

• PCC oxidizes a 1 alcohol to an aldehyde
• PCC also oxidizes a 2 alcohol to a ketone

66
Oxidation of Alcohols by NAD

• biological systems do not use chromic acid or the
  oxides of other transition metals to oxidize 1
  alcohols to aldehydes or 2 alcohols to ketones
• what they use instead is a NAD
• the Ad part of NAD is composed of a unit of the
  sugar D-ribose (Chapter 25) and one of adenosine
  diphosphate (ADP, Chapter 28)

67
Oxidation of Alcohols by NAD

• when NAD functions as an oxidizing agent, it is
  reduced to NADH
• in the process, NAD gains one H and two
  electrons NAD is a two-electron oxidizing agent

68
Oxidation of Alcohols by NAD

• NAD is the oxidizing in a wide variety of
  enzyme-catalyzed reactions, two of which are

69
Oxidation of Alcohols by NAD

• mechanism of NAD oxidation of an alcohol
• hydride ion transfer to NAD is stereoselective
  some enzymes catalyze delivery of hydride ion to
  the top face of the pyridine ring, others to the
  bottom face

70
Oxidation of Glycols

• Glycols are cleaved by oxidation with periodic
  acid, HIO4

71
Oxidation of Glycols

• The mechanism of periodic acid oxidation of a
  glycol is divided into two steps
• Step 1 formation of a cyclic periodate
• Step 2 redistribution of electrons within the
  five-membered ring

72
Oxidation of Glycols

• this mechanism is consistent with the fact that
  HIO4 oxidations are restricted to glycols that
  can form a five-membered cyclic periodate
• glycols that cannot form a cyclic periodate are
  not oxidized by HIO4

73
Thiols Structure

• The functional group of a thiol is an SH
  (sulfhydryl) group bonded to an sp3 hybridized
  carbon
• The bond angle about sulfur in methanethiol is
  100.3, which indicates that there is
  considerably more p character to the bonding
  orbitals of divalent sulfur than there is to
  oxygen

74
Nomenclature

• IUPAC names
• the parent is the longest chain that contains the
  -SH group
• change the suffix -e to -thiol
• when -SH is a substituent, it is named as a
  sulfanyl group
• Common names
• name the alkyl group bonded to sulfur followed by
  the word mercaptan

75
Thiols Physical Properties

• Because of the low polarity of the S-H bond,
  thiols show little association by hydrogen
  bonding
• they have lower boiling points and are less
  soluble in water than alcohols of comparable MW
• the boiling points of ethanethiol and its
  constitutional isomer dimethyl sulfide are almost
  identical

Alcohol
Thiol
65
6
78
35
117
1-Butanol
1-Butanethiol
98
76
Thiols Physical Properties

• Low-molecular-weight thiols STENCH
• the scent of skunks is due primarily to these two
  thiols
• a blend of low-molecular weight thiols is added
  to natural gas as an odorant the two most common
  of these are

77
Thiols preparation

• The most common preparation of thiols depends on
  the very high nucleophilicity of hydrosulfide
  ion, HS-

78
Thiols acidity

• Thiols are stronger acids than alcohols
• when dissolved an aqueous NaOH, they are
  converted completely to alkylsulfide salts

79
Thiols oxidation

• The sulfur atom of a thiol can be oxidized to
  several higher oxidation states
• the most common reaction of thiols in biological
  systems in interconversion between thiols and
  disulfides, -S-S-

80

• End of Chapter 10
• Alcohols and Thiols