99-1 Organic Chemistry William H. Brown & Christopher S. Foote

99-2 Alcohols and Thiols Chapter 9

99-3 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

99-4 Nomenclature-Alcohols  IUPAC names the longest chain that contains the -OH group is taken as the parent the parent chain is numbered to give the -OH group the lowest possible number -e-olthe suffix -e is changed to -ol  Common names alcoholthe alkyl group bonded to oxygen is named followed by the word alcohol

99-5 Nomenclature-Alcohols

99-6 Nomenclature of Alcohols Problem: Write the IUPAC name for each alcohol.

99-7 Nomenclature of Alcohols  Compounds containing more than one -OH group are named diols, triols, etc.

99-8 Nomenclature of Alcohols  Unsaturated alcohols -en-the double bond is shown by the infix -en- -olthe hydroxyl group is shown by the suffix -ol number the chain to give OH the lower number

99-9 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

99-10 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

99-11 Hydrogen Bonding

99-12 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, which result in a higher boiling point

99-13 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

99-14 Physical Properties

99-15 Acidity of Alcohols  In dilute aqueous solution, alcohols are weakly acidic

99-16 Acidity of Alcohols

99-17  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.

99-18 Reaction with Metals  Alcohols react with Li, Na, K, and other active metals to liberate hydrogen gas and form metal alkoxides

99-19 Reaction with NaH  Alcohols are also converted to metal salts by reaction with bases stronger than the alkoxide ion one such base is sodium hydride

99-20 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

99-21 Reaction with HX with HBr and HI, 2° alcohols generally give some rearrangement 1° alcohols with extensive  -branching give large amounts of rearranged product

99-22 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

99-23 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

99-24 Reaction with HX - S N 1 Step 3: reaction of the carbocation intermediate (a Lewis acid) with halide ion (a Lewis base) gives the product

99-25 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

99-26 Reaction with HX  For 1° alcohols with extensive  -branching S N 1 not possible because this pathway would require a 1° carbocation S N 2 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

99-27 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

99-28 Step 3: reaction of the carbocation intermediate (a Lewis acid) with halide ion (a Lewis base) gives the product

99-29 Reaction with PBr 3  An alternative method for the synthesis of 1° and 2° alkyl bromides is reaction of an alcohol with phosphorus tribromide this method gives less rearrangement than with HBr

99-30 Reaction with PBr 3 Step 1: formation of a protonated dibromophosphite, which converts H 2 O, a poor leaving group, to a good leaving group Step 2: displacement by bromide ion

99-31 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

99-32 Reaction with SOCl 2  Reaction of an alcohol with SOCl 2 in the presence of a 3° amine is stereoselective; proceeds with inversion of configuration

99-33 Reaction with SOCl 2 Step 1: nucleophilic displacement of chlorine Step 2: proton transfer to the 3° amine gives an alkyl chlorosulfite

99-34 Reaction with SOCl 2 Step 3: backside displacement by chloride ion and decomposition of the chlorosulfite ester gives the alkyl chloride

99-35 Alkyl Sulfonates  Sulfonyl chlorides are derived from sulfonic acids sulfonic acids are strong acids like sulfuric acid

99-36 Alkyl Sulfonates  A commonly used sulfonyl chloride is p- toluenesulfonyl chloride (Ts-Cl)

99-37 Alkyl Sulfonates  Another commonly used sulfonyl chloride is methanesulfonyl chloride (Ms-Cl)

99-38 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

99-39 Alkyl Sulfonates  This two-step procedure converts (S)-2-octanol to (R)-2-octyl acetate Step 1: formation of a p-toluenesulfonate (Ts) ester

99-40 Alkyl Sulfonates Step 2: nucleophilic displacement of tosylate

99-41 Dehydration of ROH  An alcohol can be converted to an alkene by elimination of H and OH from adjacent carbons (a  -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

99-42 Dehydration of ROH

99-43 where isomeric alkenes are possible, the alkene having the greater number of substituents on the double bond usually predominates (Zaitsev rule)

99-44 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

99-45 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

99-46 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

99-47 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

99-48 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

99-49 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

99-50 Dehydration of ROH  Dehydration with rearrangement occurs by a carbocation rearrangement

99-51 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 backward reaction as for the forward reaction

99-52 Pinacol Rearrangement  The products of acid-catalyzed dehydration of a glycol are different from those of alcohols

99-53 Pinacol Rearrangement Step 1: proton transfer to OH gives an oxonium ion Step 2: loss of water gives a carbocation intermediate

99-54 Pinacol Rearrangement Step 3: a 1,2- shift of methyl gives a more stable carbocation Step 4: proton transfer to solvent completes the reaction

99-55 Oxidation: 1° ROH  A primary alcohol can be oxidized to 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

99-56 Oxidation: 1° ROH  A common oxidizing agent for this purpose is chromic acid, prepared by dissolving chromium(VI) oxide or potassium dichromate in aqueous sulfuric acid

99-57 Oxidation: 1° ROH  Oxidation of 1-octanol gives octanoic acid the aldehyde intermediate is not isolated

99-58 Oxidation: 1° ROH  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 PCC is selective for the oxidation of 1° alcohols to aldehydes; it does not oxidize aldehydes further to carboxylic acids

99-59 Oxidation: 1° ROH  PCC oxidation of a 1° alcohol to an aldehyde

99-60 Oxidation: 2° ROH  2° alcohols are oxidized to ketones by both PCC and chromic acid

99-61 Oxidation: 1° & 2° ROH  The mechanism of chromic acid oxidation of an alcohol involves two steps Step 1: formation of an alkyl chromate ester

99-62 Oxidation: 1° & 2° ROH Step 2: proton transfer to solvent and decomposition of the alkyl chromate ester gives the product

99-63 Oxidation: 1° & 2° ROH  In chromic acid oxidation of a CHO group, it is the hydrated form that is oxidized

99-64 Oxidation of Glycols  Glycols are cleaved by oxidation with periodic acid, H 5 IO 6 (or, alternatively HIO 4 2H 2 O)

99-65 Oxidation of Glycols the glycol undergoes a two-election oxidation periodic acid undergoes a two-electron reduction

99-66 Oxidation of Glycols  The mechanism of periodic acid oxidation of a glycol is divided into two steps Step 1: formation of a cyclic periodic ester Step 2: redistribution of electrons within the five- membered ring

99-67 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

99-68 Nomenclature  IUPAC names: the parent is the longest chain that contains the -SH group -e-thiolchange the suffix -e to -thiol as a substituent, it is a sulfanyl group  Common names: mercaptanname the alkyl group bonded to sulfur followed by the word mercaptan

99-69 Thiols: Physical Properties  The difference in electronegativity between S (2.5) and H (2.1) is 0.4. Because of the low polarity of the S-H bond, thiols show little association by hydrogen bonding have lower boiling points and are less soluble in water than alcohols of comparable MW

99-70 Thiols: Physical Properties  Low-molecular-weight thiols = STENCH the scent of skunks is due primarily to these two thiols

99-71 Thiols: preparation  The most common preparation of thiols, RSH, depends on the very high nucleophilicity of hydrosulfide ion, HS -

99-72 Thiols: acidity  Thiols are stronger acids than alcohols

99-73 Thiols: acidity  When dissolved an aqueous NaOH, they are converted completely to alkylsulfide salts

99-74 Thiols: oxidation  Thiols are oxidized to disulfides by a variety of oxidizing agents, including O 2. they are so susceptible to this oxidation that they must be protected from air during storage -S-S-the most common reaction of thiols in biological systems in interconversion between thiols and disulfides, -S-S-

99-75 Prob 9.22 From each pair of compounds, select the one more soluble in water.

99-76 Prob 9.24 From each pair of compounds, select the one more soluble in water.

99-77 Prob 9.25 Calculate the percent of each isomer present at equilibrium. Assume a value of  G° (equatorial to axial) for cyclohexanol is 4.0 kJ (0.95 kcal/mol).

99-78 Prob 9.26 Complete each acid-base reaction. Use curved arrows to show the flow of electrons.

99-79 Prob 9.26 (cont’d) Complete each acid-base reaction. Use curved arrows to show the flow of electrons.

99-80 Prob 9.27 From each pair, select the stronger acid and write a structural formula for its conjugate base.

99-81 Prob 9.28 From each pair select the stronger base. Write a structural formula for its conjugate acid.

99-82 Prob 9.29 In each equilibrium, label the stronger acid and base, and the weaker acid and base. Estimate the position of equilibrium.

99-83 Prob 9.32 Complete each equation, but do not balance

99-84 Prob 9.32 (cont’d) Complete each equation, but do not balance

99-85 Prob 9.34 When A or B is treated with HBr, racemic 2,3- dibromobutane is formed. When C or D is treated with HBr, meso 2,3-dibromobutane is formed. Explain.

99-86 Prob 9.36 Show how to bring about each conversion.

99-87 Prob 9.36 (cont’d) Show how to bring about each conversion.

99-88 Prob 9.37 Propose a mechanism for the following pinacol rearrangement.

99-89 Prob 9.40 Propose a mechanism for this reaction.

99-90 Prob 9.43 Show how to bring about this conversion.

99-91 Prob 9.44 Propose a structural formula for the product of this reaction and a mechanism for its formation.

99-92 Prob 9.45 Propose a mechanism for the formation of the products of this solvolysis.

99-93 Prob 9.46 Show how to convert cyclohexene to each compound.

99-94 Alcohols and Thiols End of Chapter 9