1. 10-1 Organic Chemistry William H. Brown Christopher S. Foote Brent L. Iverson William H. Brown Christopher S. Foote Brent L. Iverson

2. 10-2 Alcohols and Thiols Chapter 10

3. 10-3 Structure - Alcohols  The functional group of an alcohol is an -OH group bonded to an sp 3 hybridized carbon bond angles about the hydroxyl oxygen atom are approximately 109.5°  Oxygen is sp 3 hybridized two sp 3 hybrid orbitals form sigma bonds to carbon and hydrogen the remaining two sp 3 hybrid orbitals each contain an unshared pair of electrons

4. 10-4 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 -e-olchange the suffix -e to -ol  Common names alcoholname the alkyl group bonded to oxygen followed by the word alcohol

5. 10-5 Nomenclature-Alcohols  Examples

6. 10-6 Nomenclature of Alcohols  Compounds containing more than one OH group are named diols, triols, etc. CH 3 CHCH 2 HOOH CH 2 CH 2 OHOH CH 2 CHCH 2 HOHOOH 1,2-Ethanediol (Ethylene glycol) 1,2-Propanediol (Propylene glycol) 1,2,3-Propanetriol (Glycerol, Glycerine)

7. 10-7 Nomenclature of Alcohols  Unsaturated alcohols -en-show the double bond by changing the infix from -an- to -en- -olshow the the OH group by the suffix -ol number the chain to give OH the lower number

8. 10-8 Physical Properties  Alcohols are polar compounds they interact with themselves and with other polar compounds by dipole-dipole interactions  Dipole-dipole interaction:  Dipole-dipole interaction: the attraction between the positive end of one dipole and the negative end of another

9. 10-9 Physical Properties  Hydrogen bonding  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

10. 10-10 Hydrogen Bonding

11. 10-11 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 bp -24°C Ethanol bp 78°C Dimethyl ether CH 3 CH 2 OHCH 3 OCH 3

12. 10-12 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

13. 10-13 Physical Properties

14. 10-14 Acidity of Alcohols  In dilute aqueous solution, alcohols are weakly acidic

15. 10-15 Acidity of Alcohols

16. 10-16  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

17. 10-17 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

18. 10-18 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

19. 10-19 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

20. 10-20 Reaction with HX  Based on the relative ease of reaction of alcohols with HX (3° > 2° > 1°) and the occurrence of rearrangements,  Chemists propose that reaction of 2° and 3° alcohols with HX occurs by an S N 1 mechanism, and involves a carbocation intermediate

21. 10-21 Reaction with HX - S N 1 Step 1: proton transfer to the OH group gives an oxonium ion Step 2: loss of H 2 O gives a carbocation intermediate

22. 10-22 Reaction with HX - S N 1 Step 3: reaction of the carbocation intermediate (an electrophile) with halide ion (a nucleophile) gives the product

23. 10-23 Reaction with HX - S N 2  1° alcohols react with HX by an S N 2 mechanism Step 1: rapid and reversible proton transfer Step 2: displacement of HOH by halide ion

24. 10-24 Reaction with HX  For 1° alcohols with extensive  -branching S N 1 is not possible because this pathway would require a 1° carbocation S N 2 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

25. 10-25 Step 1: proton transfer gives an oxonium ion Step 2: concerted elimination of HOH and migration of a methyl group gives a 3° carbocation Reaction with HX

26. 10-26 Step 3: reaction of the carbocation intermediate (an electrophile) with halide ion (a nucleophile) gives the product

27. 10-27 Reaction with PBr 3  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

28. 10-28 Reaction with PBr 3 Step 1: formation of a protonated dibromophosphite converts H 2 O, a poor leaving group, to a good leaving group Step 2: displacement by bromide ion gives the alkyl bromide

29. 10-29 Reaction with SOCl 2  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

30. 10-30 Reaction with SOCl 2  Reaction of an alcohol with SOCl 2 in the presence of a 3° amine is stereoselective it occurs with inversion of configuration

31. 10-31 Reaction with SOCl 2 Step 1: formation of an alkyl chlorosulfite Step 2: nucleophilic displacement of this leaving group by chloride ion gives the chloroalkane

32. 10-32 Alkyl Sulfonates  Sulfonyl chlorides are derived from sulfonic acids sulfonic acids, like sulfuric acid, are strong acids A sulfonyl chloride A sulfonate anion (a very weak base and stable anion; a very good leaving group A sulfonic acid (a very strong acid) R-S-OH R-S-O - R-S-Cl O O O O O O

33. 10-33 Alkyl Sulfonates  A commonly used sulfonyl chloride is p- toluenesulfonyl chloride (Ts-Cl)

34. 10-34 Alkyl Sulfonates  Another commonly used sulfonyl chloride is methanesulfonyl chloride (Ms-Cl)

35. 10-35 Alkyl Sulfonates  Sulfonate anions are very weak bases (the conjugate base of a strong acid) and are very good leaving groups for S N 2 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

36. 10-36 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

37. 10-37 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 H 2 SO 4 or H 3 PO 4 2° alcohols undergo dehydration at somewhat lower temperatures 3° alcohols often require temperatures at or slightly above room temperature

38. 10-38 Dehydration of ROH 180°C CH 3 CH 2 OH H 2 SO 4 CH 2 =CH 2 + H 2 O 140°C CyclohexanolCyclohexene OH + H 2 O H 2 SO 4 CH 3 COH CH 3 CH 3 H 2 SO 4 CH 3 C=CH 2 CH 3 + H 2 O 50°C 2-Methyl-2-propanol (tert-Butyl alcohol) 2-Methylpropene (Isobutylene)

39. 10-39 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)

40. 10-40 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 OH H 2 SO 4 140 - 170°C + 3,3-Dimethyl- 2-butanol 2,3-Dimethyl- 2-butene (80%) 2,3-Dimethyl- 1-butene (20%)

41. 10-41 Dehydration of ROH  Based on evidence of ease of dehydration (3° > 2° > 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

42. 10-42 Dehydration of ROH Step 1: proton transfer to the -OH group gives an oxonium ion Step 2: loss of H 2 O gives a carbocation intermediate

43. 10-43 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

44. 10-44 Dehydration of ROHDehydration 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 H 2 O from the  -carbon gives the terminal alkene

45. 10-45 Dehydration of ROH Step 3: shift of a hydride ion from  -carbon and loss of H 2 O from the  -carbon gives a carbocation Step 4: proton transfer to solvent gives the alkene

46. 10-46 Dehydration of ROH  Dehydration with rearrangement occurs by a carbocation rearrangement

47. 10-47 Dehydration of ROH  Acid-catalyzed alcohol dehydration and alkene hydration are competing processes  Principle of microscopic reversibility:  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

48. 10-48 Pinacol Rearrangement  The products of acid-catalyzed dehydration of a glycol are different from those of alcohols

49. 10-49 Pinacol Rearrangement Step 1: proton transfer to OH gives an oxonium ion Step 2: loss of water gives a carbocation intermediate

50. 10-50 Pinacol Rearrangement Step 3: a 1,2- shift of methyl gives a more stable carbocation Step 4: proton transfer to solvent completes the reaction

51. 10-51 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

52. 10-52 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 Potassium dichromate Chromic acid K 2 Cr 2 O 7 H 2 SO 4 H 2 Cr 2 O 7 H 2 O 2H 2 CrO 4 + Chromium(VI) oxide CrO 3 H 2 O H 2 CrO 4 H 2 SO 4

53. 10-53 Oxidation: 1° ROH  Oxidation of 1-octanol gives octanoic acid the aldehyde intermediate is not isolated

54. 10-54 Oxidation: 2° ROH  2° alcohols are oxidized to ketones by chromic acid

55. 10-55 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 H 2 O

56. 10-56 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

57. 10-57 Oxidation: 1° ROH to RCHO  Pyridinium chlorochromate (PCC):  Pyridinium chlorochromate (PCC): a form of Cr(VI) prepared by dissolving CrO 3 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

58. 10-58 Oxidation: 1° ROH PCC oxidizes a 1° alcohol to an aldehyde PCC also oxidizes a 2° alcohol to a ketone

59. 10-59 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)

60. 10-60 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

61. 10-61 Oxidation of Alcohols by NAD + NAD + is the oxidizing in a wide variety of enzyme- catalyzed reactions, two of which are

62. 10-62 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

63. 10-63 Oxidation of Glycols  Glycols are cleaved by oxidation with periodic acid, HIO 4

64. 10-64 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

65. 10-65 Oxidation of Glycols this mechanism is consistent with the fact that HIO 4 oxidations are restricted to glycols that can form a five-membered cyclic periodate glycols that cannot form a cyclic periodate are not oxidized by HIO 4

66. 10-66 Thiols: Structure SHsulfhydryl  The functional group of a thiol is an SH (sulfhydryl) group bonded to an sp 3 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

67. 10-67 Nomenclature  IUPAC names: the parent is the longest chain that contains the -SH group -e-thiolchange the suffix -e to -thiol when -SH is a substituent, it is named as a sulfanyl group  Common names: mercaptanname the alkyl group bonded to sulfur followed by the word mercaptan

68. 10-68 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 117 78 65 1-Butanol Ethanol Methanol 98 35 6 1-Butanethiol Ethanethiol Methanethiol bp (°C) Alcoholbp (°C)Thiol

69. 10-69 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

70. 10-70 Thiols: preparation  The most common preparation of thiols depends on the very high nucleophilicity of hydrosulfide ion, HS -

71. 10-71 Thiols: acidity  Thiols are stronger acids than alcohols when dissolved an aqueous NaOH, they are converted completely to alkylsulfide salts

72. 10-72 Thiols: oxidation  The sulfur atom of a thiol can be oxidized to several higher oxidation states -S-S-the most common reaction of thiols in biological systems in interconversion between thiols and disulfides, -S-S-

73. 10-73 Alcohols and Thiols End of Chapter 10