Chapter 5 Alcohols Thiols Ethers

Structure of Water and Methanol Oxygen is sp3 hybridized and tetrahedral. The H—O—H angle in water is 104.5°. The C—O—H angle in methyl alcohol is 108.9°. Chapter 10 2 2

Classification of Alcohols Primary: carbon with —OH is bonded to one other carbon. Secondary: carbon with —OH is bonded to two other carbons. Tertiary: carbon with —OH is bonded to three other carbons. Aromatic (phenol): —OH is bonded to a benzene ring. Chapter 10 3 3

Examples of Classifications H 3 2 O * C H 3 O 2 * C H 3 O * Chapter 10 4 4

Examples of Classifications H 3 2 O * C H 3 O 2 * Primary alcohol C H 3 O * Chapter 10 5 5

Examples of Classifications H 3 2 O * C H 3 O 2 * Primary alcohol Secondary alcohol C H 3 O * Chapter 10 6 6

Examples of Classifications H 3 2 O * C H 3 O 2 * Primary alcohol Secondary alcohol C H 3 O * Tertiary alcohol Chapter 10 7 7

IUPAC Nomenclature Find the longest carbon chain containing the carbon with the —OH group. Drop the -e from the alkane name, add -ol. Number the chain giving the —OH group the lowest number possible. Number and name all substituents and write them in alphabetical order. Chapter 10 8 8

Examples of Nomenclature H 3 2 O C H 3 O 2 3 2 1 1 2 3 4 2-methyl-1-propanol 2-methylpropan-1-ol 2-butanol butan-2-ol C H 3 O 2 1 2-methyl-2-propanol 2-methylpropan-2-ol Chapter 10 9 9

Alkenols (Enols) Hydroxyl group takes precedence. Assign the carbon with the —OH the lowest number. End the name in –ol, but also specify that there is a double bond by using the ending –ene before -ol C H 2 3 O 5 4 3 2 1 4-penten-2-ol pent-4-ene-2-ol Chapter 10 10 10

Naming Priority Highest ranking Acids Esters Aldehydes Ketones Alcohols Amines Alkenes Alkynes Alkanes Ethers Halides Lowest ranking Chapter 10 11 11

Hydroxy Substituent When —OH is part of a higher priority class of compound, it is named as hydroxy. carboxylic acid C H 2 O 4 3 2 1 4-hydroxybutanoic acid also known as g-hydroxybutyric acid (GHB) Chapter 10 12 12

Common Names Alcohol can be named as alkyl alcohol. Useful only for small alkyl groups. C H 3 2 O C H 3 O 2 isobutyl alcohol sec-butyl alcohol Chapter 10 13 13

Naming Diols Two numbers are needed to locate the two —OH groups. Use -diol as suffix instead of -ol. 1 2 3 4 5 6 hexane-1,6- diol Chapter 10 14 14

Glycols 1, 2-diols (vicinal diols) are called glycols. Common names for glycols use the name of the alkene from which they were made. ethane-1,2- diol ethylene glycol propane-1,2- diol propylene glycol Chapter 10 15 15

Phenol Nomenclature —OH group is assumed to be on carbon 1. For common names of disubstituted phenols, use ortho- for 1,2; meta- for 1,3; and para- for 1,4. Methyl phenols are cresols. 3-chlorophenol (meta-chlorophenol) 4-methylphenol (para-cresol) Chapter 10 16 16

Solved Problem 1 Solution Give the systematic (IUPAC) name for the following alcohol. Solution The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl group. The longest chain containing the carbon bonded to the —OH group is the one outlined by the green box, containing five carbon atoms. This chain is numbered from right to left in order to give the hydroxyl-bearing carbon atom the lowest possible number. Copyright © 2006 Pearson Prentice Hall, Inc. The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol. Chapter 10 17 17

Physical Properties Alcohols have high boiling points due to hydrogen bonding between molecules. Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases. Chapter 10 18 18

Boiling Points of alcohols Alcohols have higher boiling points than ethers and alkanes because alcohols can form hydrogen bonds. The stronger interaction between alcohol molecules will require more energy to break them resulting in a higher boiling point. Chapter 10 19 19

Solubility in Water Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases. Chapter 10 20 20

Methanol “Wood alcohol” Industrial production from synthesis gas Common industrial solvent Toxic Dose: 100 mL methanol Used as fuel at Indianapolis 500 Fire can be extinguished with water High octane rating Low emissions Lower energy content Invisible flame Chapter 10 21 21

Ethanol Fermentation of sugar and starches in grains 12–15% alcohol, then yeast cells die Distillation produces “hard” liquors Azeotrope: 95% ethanol, constant boiling Denatured alcohol used as solvent Gasahol: 10% ethanol in gasoline Toxic dose: 200 mL Chapter 10 22 22

Acidity of Alcohols pKa range: 15.5–18.0 (water: 15.7) Acidity decreases as the number of carbons increase. Halogens and other electron withdrawing groups increase the acidity. Phenol is 100 million times more acidic than cyclohexanol! Chapter 10 23 23

Table of Ka Values Chapter 10 24 24

Formation of Alkoxide Ions Ethanol reacts with sodium metal to form sodium ethoxide (NaOCH2CH3), a strong base commonly used for elimination reactions. More hindered alcohols like 2-propanol or tert-butanol react faster with potassium than with sodium. Chapter 10 25 25

Formation of Phenoxide Ion The aromatic alcohol phenol is more acidic than aliphatic alcohols due to the ability of aromatic rings to delocalize the negative charge of the oxygen within the carbons of the ring. Chapter 10 26 26

Charge Delocalization on the Phenoxide Ion The negative charge of the oxygen can be delocalized over four atoms of the phenoxide ion. There are three other resonance structures that can localize the charge in three different carbons of the ring. The true structure is a hybrid between the four resonance forms. Chapter 10 27 27

Synthesis of Alcohols (Review) Alcohols can be synthesized by nucleophilic substitution of alkyl halide. Hydration of alkenes also produce alcohols: Chapter 10 28 28

Synthesis of Vicinal Diols Vicinal diols can be synthesized by two different methods: Syn hydroxylation of alkenes Cold, dilute, basic potassium permanganate Chapter 10 29 29

Reduction of Carbonyl Reduction of aldehyde yields 1º alcohol. Reduction of ketone yields 2º alcohol. Reagents: Sodium borohydride, NaBH4 Lithium aluminum hydride, LiAlH4 Raney nickel Chapter 10 30 30

Sodium Borohydride NaBH4 is a source of hydrides (H-) Hydride attacks the carbonyl carbon, forming an alkoxide ion. Then the alkoxide ion is protonated by dilute acid. Only reacts with carbonyl of aldehyde or ketone, not with carbonyls of esters or carboxylic acids. Chapter 10 31 31

Lithium Aluminum Hydride LiAlH4 is source of hydrides (H-) Stronger reducing agent than sodium borohydride, but dangerous to work with. Reduces ketones and aldehydes into the corresponding alcohol. Converts esters and carboxylic acids to 1º alcohols. Chapter 10 32 32

Reduction with LiAlH4 The LiAlH4 (or LAH) will add two hydrides to the ester to form the primary alkyl halide. The mechanism is similar to the attack of Grignards on esters. Chapter 10 33 33

Reducing Agents NaBH4 can reduce aldehydes and ketones but not esters and carboxylic acids. LiAlH4 is a stronger reducing agent and will reduce all carbonyls. Chapter 10 34 34

Catalytic Hydrogenation Raney nickel is a hydrogen rich nickel powder that is more reactive than Pd or Pt catalysts. This reaction is not commonly used because it will also reduce double and triple bonds that may be present in the molecule. Hydride reagents are more selective so they are used more frequently for carbonyl reductions. Chapter 10 35 35

Thiols (Mercaptans) Sulfur analogues of alcohols are called thiols. The —SH group is called a mercapto group. Named by adding the suffix -thiol to the alkane name. They are commonly made by a substitution. Primary alkyl halides work better. Chapter 10 36 36

Synthesis of Thiols The thiolate will attack the carbon displacing the halide. This is a substitution reaction methyl halides will react faster than primary alkyl halides. To prevent dialylation use a large excess of sodium hydrosulfide with the alkyl halide. Chapter 10 37 37

Alcohol Reactions Dehydration to alkene Oxidation to aldehyde, ketone Substitution to form alkyl halide Reduction to alkane Esterification Williamson synthesis of ether Chapter 11 38

Summary Table Chapter 11 39

Oxidation States Easy for inorganic salts (reduced, organic oxidized) CrO42- reduced to Cr2O3 KMnO4 reduced to MnO2 Oxidation: loss of H2, gain of O, O2, or X2 Reduction: gain of H2 or H-, loss of O, O2, or X2 Neither: gain or loss of H+, H2O, HX Chapter 11 40

Oxidation States Easy for inorganic salts (reduced, organic oxidized) CrO42- reduced to Cr2O3 KMnO4 reduced to MnO2 Oxidation: loss of H2, gain of O, O2, or X2 Reduction: gain of H2 or H-, loss of O, O2, or X2 Neither: gain or loss of H+, H2O, HX Chapter 11

1º, 2º, 3º Carbons Chapter 11

Oxidation of 2° Alcohols 2° alcohol becomes a ketone Reagent is Na2Cr2O7/H2SO4 = H2CrO4 Active reagent probably H2CrO4 Color change: orange to greenish-blue => Chapter 11

Oxidation of 1° Alcohols 1° alcohol to aldehyde to carboxylic acid Difficult to stop at aldehyde Use pyridinium chlorochromate (PCC) to limit the oxidation. PCC can also be used to oxidize 2° alcohols to ketones. Chapter 11

3° Alcohols Don’t Oxidize Cannot lose 2 H’s Basis for chromic acid test Chapter 11

Alcohol as a Nucleophile ROH is weak nucleophile RO- is strong nucleophile New O-C bond forms, O-H bond breaks. Chapter 11

Alcohol as an Electrophile OH- is not a good leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H+. Convert to tosylate (good leaving group) to react with strong nucleophile (base).  + C-Nuc bond forms, C-O bond breaks Chapter 11

Reduction of Alcohols Dehydrate with conc. H2SO4, then add H2 Chapter 11

Reaction with HBr -OH of alcohol is protonated -OH2+ is good leaving group 3° and 2° alcohols react with Br- via SN1 1° alcohols react via SN2 Chapter 11

Reaction with HCl Chloride is a weaker nucleophile than bromide. Add ZnCl2, which bonds strongly with -OH, to promote the reaction. The chloride product is insoluble. Lucas test: ZnCl2 in conc. HCl 1° alcohols react slowly or not at all. 2 alcohols react in 1-5 minutes. 3 alcohols react in less than 1 minute. Chapter 11

Limitations of HX Reactions Poor yields of 1° and 2° chlorides May get alkene instead of alkyl halide Chapter 11

Reactions with Phosphorus Halides Good yields with 1° and 2° alcohols PCl3 for alkyl chloride (but SOCl2 better) PBr3 for alkyl bromide Chapter 11

Dehydration Reactions Conc. H2SO4 (or H3PO4) produces alkene Carbocation intermediate Zaitsev product Bimolecular dehydration produces ether Low temp, 140°C and below, favors ether High temp, 180°C and above, favors alkene Chapter 11

Ethers Ethers contain an sp3 hybridized oxygen atom Hydrogen Oxide Aka Water Alcohol Ether Ethers contain an sp3 hybridized oxygen atom Ethers do not hydrogen bond between each other, but will hydrogen bond with water and alcohols. Ethers are polar and water soluble

Ether Nomenclature Common System Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether. Examples

Ether Nomenclature Common System Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether. Examples Dimethyl ether

Ether Nomenclature Common System Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether. Examples Dimethyl ether Ethylmethyl ether

Ether Nomenclature Common System Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether. Examples Dimethyl ether Ethylmethyl ether Isopropylmethyl ether

Ether Nomenclature Common System Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether. Examples Dimethyl ether Ethylmethyl ether Isopropylmethyl ether Sec-butylcyclopropyl ether

Ether Nomenclature IUPAC System Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy. Examples Methoxymethane

Ether Nomenclature IUPAC System Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy. Examples Methoxymethane Methoxyethane

Ether Nomenclature IUPAC System Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy. Examples Methoxymethane Methoxyethane 2-Methoxypropane

Ether Nomenclature IUPAC System Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy. Examples Methoxymethane Methoxyethane 2-Methoxypropane 2-Cyclopropoxybutane

Ether Formation Primary alcohols can dehydrate to ethers This reaction occurs at lower temperature than the competing dehydration to an alkene This method generally does not work with secondary or tertiary alcohols because elimination competes strongly The mechanism is an SN2 reaction:

Williamson Ether Synthesis Good for unsymmetrical ethers

Dehydration Mechanisms Chapter 11

Esterification Fischer: alcohol + carboxylic acid Nitrate esters Phosphate esters Chapter 11

Fischer Esterification Acid + Alcohol yields Ester + Water Sulfuric acid is a catalyst. Each step is reversible. Chapter 11

Sulfate Esters Alcohol + Sulfuric Acid => Chapter 11

Nitrate Esters Chapter 11

Phosphate Esters => Chapter 11

Phosphate Esters in DNA => Chapter 11

End of Chapter 5 Chapter 11