Chapter 12

Alcohols, Phenols, Thiols, and Ethers

Denniston Topping Caret

5th Edition

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

12.1 Alcohols: Structure and Physical Properties

• An organic compound containing a hydroxyl group attached to an alkyl group

• Alcohols have the general formula R-OH

Physical Properties

• R-O-H has a structure similar to that of water• Hydroxyl group is very polar• Hydrogen bonds can form readily

12.1

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Alcohol Boiling Points

• Alcohols have abnormally high boiling points relative to their molecular weights due to their ability to hydrogen bond

CH3CH2OH

CH3CH2O

H

CH3CH2OH

Hydrogen bonds

12.1

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Hydrogen bonds in Ethane

Trends in Alcohol Boiling Points

CH3CH2OH

CH3O CH3

CH3CH2CH3 bp -42 oC

bp -23 oC

bp +78.5 oC

12.1

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Solubility

• Low molecular weight alcohols (up to 5-6 carbons) are soluble in water– Very polar – Hydrogen bond with the water molecule

• CH3CH2OH very soluble

• CH3OCH3 barely soluble

• CH3CH2CH2CH2OH, 7 g per 100 mL

– HOCH2CH2CH2CH2OH is very soluble

(two OH groups)

12.1

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High Molecular Weight Alcohol Solubility

• As molecular weight increases, alcohols become insoluble in water– Still polar – Ratio of hydroxyl groups to carbons in the

chain determines solubility• Diols and triols are more soluble than those with

only a single hydroxyl group

12.1

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12.2 Alcohols: Nomenclature• IUPAC: based on the longest chain

containing the OH carbon• The -e of the alkane name is replaced with -ol

• The chain is numbered from the end giving

the -OH carbon the lower number• The name is prefixed with the number

indicating the position of the OH group• For cyclic alcohols, the OH is at C-1

Naming Alcohols

CH3CHCHCH3OH

CH3

3-methyl-2-butanol

12.2

Alc

ohol

s:

Nom

encl

atur

e

1. Name the parent compound – 4 carbons = butane2. Replace the –e with –ol = butanol3. Number the parent chain to minimize number of carbon

with the –OH group = number from right to left4. Identify, name, and number all substituents = methyl on C-3

Naming Alcohols

OH

CH3 3-methylcyclohexanol

OH must be at C-1

12.2

Alc

ohol

s:

Nom

encl

atur

e

1. Name the parent compound – 6 carbon ring = cyclohexane2. Replace the –e with –ol = cyclohexanol3. Number the ring to minimize number of carbon with the

–OH group = number counterclockwise4. Identify, name, and number all substituents = methyl on C-3

Common Names of Alcohols12

.2 A

lcoh

ols:

N

omen

clat

ure

The common names for alcohols consist of the alkyl group name, a space, and the word alcohol

CH3 C CH3

CH3

OHCH3CH CH3

OHt-butyl alcohol isopropyl alcohol

12.3 Medically Important Alcohols

• Methanol– Colorless and odorless liquid– Used as a solvent– Toxic, can cause blindness and death if ingested– Can be used as a fuel

12.3

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ly I

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lcoh

ols

• An odorless and colorless liquid• Widely used as a solvent • The alcohol in alcoholic beverages

– Derived from fermentation of carbohydrates

– Beverage produced varies with the starting material and the fermentation process

Ethanol

12.3

Med

ical

ly I

mpo

rtan

t A

lcoh

ols

• Colorless, but has a slight odor• Commonly called rubbing alcohol• Toxic when ingested• Used as a:

– Disinfectant – Astringent– Industrial solvent

2-Propanol

12.3

Med

ical

ly I

mpo

rtan

t A

lcoh

ols

• Used as automobile antifreeze• Has a sweet taste, but is extremely

poisonous• Added to water

– Lowers the freezing point– Raises the boiling point

1,2-Ethanediol

OH CH2CH2OHethylene glycol(antifreeze)

12.3

Med

ical

ly I

mpo

rtan

t A

lcoh

ols

• Very viscous, thick• Has a sweet taste• Non-toxic• Highly water soluble• Used in:

• Cosmetics• Pharmaceuticals• Lubricants

• Obtained as a by-product of fat hydrolysis

1,2,3-Propanetriol

OH CH2CH CH2OHOH

glycerol(in fats,a moisturizer)

12.4 Classification of Alcohols

• Alcohols, depending on the number of alkyl groups attached to the carbinol carbon, are classified as:– Primary– Secondary – Tertiary

• Carbinol carbon is the carbon bearing the hydroxyl group

Structures of Different Alcohol Categories

12.4

Cla

ssif

icat

ion

of

Alc

ohol

s

Classify the Alcohols

a. Carbinol carbon has 2 other alkyls attachedb. Carbinol carbon has 3 other alkyls attachedc. Carbinol carbon has 1 other alkyl attachedd. Carbinol carbon has 2 other alkyls attached12

.4 C

lass

ific

atio

n of

A

lcoh

ols

12.5 Reactions Involving AlcoholsPreparation of Alcohols• Hydration

– Addition of water to the carbon-carbon double bond of an alkene produces an alcohol

– A type of addition reaction called hydration– Requires a trace of acid as a catalyst

• Hydrogenation– Addition of water to the carbon-oxygen double bond

of an aldehyde or ketone produces an alcohol– A type of addition reaction– Also considered a reduction reaction– Requires Pt, Pd, or Ni as a catalyst

Preparation of Alcohols12

.5 R

eact

ions

Inv

olvi

ng

Alc

ohol

s

Dehydration of Alcohols• Alcohols dehydrate with heat in the presence of strong

acid to produce alkenes• Dehydration is a type of elimination reaction

– A molecule loses atoms or ions from its structure– Here –OH and –H are removed / eliminate from adjacent carbon

atoms to produce an alkene and water– A reversal of the hydration reaction that forms alcohols

12.5

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Zaitsev’s Rule• Some alcohol dehydration reactions produce a

mixture of products• Zaitsev’s rule states that in an elimination reaction

the alkene with the greatest number of alkyl groups on the double bonded carbon is the major product of the reaction

12.5

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A

lcoh

ols

CH3

OH

CH3

major product:more substitutedalkene

warmH2SO4 orH3PO4

Predict the Product of Dehydration• What are the major and minor products when 3-

methyl-2-butanol is dehydrated?• Zaitsev’s rule states that in an elimination reaction the

alkene with the greatest number of alkyl groups on the double bonded carbon is the major product of the reaction

12.5

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lcoh

ols

Oxidation Reaction of Primary Alcohols

• Primary alcohols usually oxidize to carboxylic acids

• With some care (using CrO3 as the reagent) an aldehyde may be obtained

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Oxidation Reaction of Secondary Alcohols

• Secondary alcohols oxidize to ketones – This reaction is also an elimination of 2H

• The usual oxidizing agent is a Cr(VI) species• Tertiary alcohols do not oxidize as there is no H

on the carbonyl carbon to remove

12.5

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12.6 Oxidation and Reduction in Living Systems

• Oxidation– loss of electrons

• Reduction– gain of electrons

• These changes are easily detected in inorganic systems with formation of charged ions

• In organic systems it is often difficult to determine whether oxidation or reduction has taken place as there might be no change in charge

• In organic systems changes may be tracked:– Oxidation

• gain of oxygen• loss of hydrogen

– Reduction• loss of oxygen• gain of hydrogen

Organic Oxidation and Reduction12

.6 O

xida

tion

and

R

educ

tion

in L

ivin

g S

yste

ms

More oxidized form

More reduced formAlkane Alcohol Aldehyde Acid

Biological Oxidation-Reduction

• Oxidoreductases catalyze biological redox reactions

• Coenzymes (organic molecules) are required to donate or accept hydrogen

• NAD+ is a common coenzyme

O CCOO

-

HCH2COO

-

H OCCOO

-

CH2COO

-

+ NAD+

Malatedehydrogenase

+ NADH + H+

12.6

Oxi

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nd

Red

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Liv

ing

Sys

tem

s

12.7 Phenol

• Phenols are compounds in which the hydroxyl group is attached to a benzene ring– Polar compounds due to the hydroxyl group

– Simpler phenols are somewhat water soluble

– Components of flavorings and fragrances

• Phenols have the formula Ar-OH– Ar must be an aromatic ring (e.g., Benzene)

Phenol Derivatives

• Widely used in healthcare as: – Germicides

– Antiseptics

– Disinfectants

12.7

Phe

nols

Phenol Reactivity

• Phenols are acidic, but not as acidic as carboxylic acids

• They react with NaOH to give salt and water

OH+NaOH

ONa

+H2O

12.7

Phe

nols

12.8 Ethers• Ethers have the formula R-O-R

– R can be aliphatic or aromatic

• Ethers are slightly polar due to the polar C=O bond

• Do not hydrogen bond to one another as there are no –OH groups

Ether Physical Properties

• Ethers have much lower boiling points than alcohols due to the lack of hydrogen bonding

12.8

Eth

ers

Common Names of Ethers

• Common names for ethers consist of the names of the two groups attached to the O listed in alphabetical order (or size) and followed by ‘ether’

• Each of the three parts is a separate word• Name:

CH3 CH O

CH3

CH3

CH3CH2O

Isopropyl methyl ether Ethyl phenyl ether

12.8

Eth

ers

IUPAC Nomenclature of Ethers

• The IUPAC names for ethers are based on the alkane name of the longest chain attached to the oxygen

• The shorter chain is named as an alkoxy substituent– Alkane with the -ane replaced by -oxy

– e.g., CH3CH2O = ethoxy

CH3CH2CH2CH2CH2-O-CH3

1-methoxypentane

12.8

Eth

ers

Reactivity of Ethers• Chemically, ethers are moderately inert

– Do not normally react with reducing agents or bases

– Extremely volatile

– Highly flammable = easily oxidized in air

• Symmetrical ethers may be prepared by dehydrating two alcohol molecules– Requires heat and acid catalyst

CH3 CH2O CH2 CH3

CH3 CH2OH CH3CH2OH

H+ (H3PO4) warm

12.8

Eth

ers

Medical Uses of Ethers• Ethers are often used as anesthetics• Accumulate in the lipid material of nerve cells interfering with nerve impulse transmission• Today halogenated ethers are used routinely as general anesthetics

– Less flammable– Safer to store and to work with

CH3 CH2O CH2 CH3

Diethyl ether - First successful

general anesthetic

CH3O C C HF

F

Cl

Cl

Penthrane

12.8

Eth

ers

12.9 Thiols• Thiols have the formula R-SH• Similar in structure to alcohols with S replacing O• Disulfides have the formula R-S-S-R

– R may be aliphatic or aromatic

• Name is based on longest alkane chain with the suffix –thiol position indicated by number

CH2 CH2CH3 CHSH

CH3

3-methy-1-butanethiol

Thiols and Scent• Thiols, as many other sulfur-containing

compounds can have nauseating aromas– Defensive spray of North American striped skunk

– Onions and garlic

• Compare with pleasant scents below

12.9

Thi

ols

Naming Thiols

• Write the IUPAC name for the thiols shown

12.9

Thi

ols

Disulfide Formation

• The thiol-disulfide redox pair controls a critical factor in protein structure called a disulfide bridge– Two cysteine molecules

(amino acids) can undergo oxidation to form cystine

– Forms a new bond called a disulfide bond

12.9

Thi

ols

Disulfide Formation and Insulin Structure

12.9

Thi

ols

Reaction Schematic

Alcohol

Aldehyde

NO REACTION

Ketone

DehydrationIf primary

If tertiary

If secondary

+ H+ and heat

AlkeneHydration Carbonyl

Reduction

Oxidation

Summary of Reactions1. Preparation of Alcohols

a. Hydration of Alkenes

b. Reduction of Aldehyde or Ketone

2. Reactions of Alcoholsa. Dehydration

b. Oxidationi. Primary alcohol to aldehyde

ii. Secondary alcohol to ketone

iii. Tertiary alcohol does not react

3. Dehydration Synthesis of an Ether

Summary of Reactions