Alcohols, Phenols, Ethers, and Their Sulfur Analogs

Alcohols, Phenols, Ethers,

and Their Sulfur Analogs

McMurry, ‘Fundamentals of

Organic Chemistry’, 7th Ed.

Chapter 8

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Alcohols, Phenols, Ethers, and Their

Sulfur Analogs

Alcohols contain an OH group connected to a a saturated C

(sp3), R-OH

Phenols contain an OH group connected to a carbon in a

benzene ring, Ar-OH

Methanol, CH3OH, called methyl alcohol, is a common solvent,

a fuel additive, produced in large quantities

Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel,

beverage

Phenol, C6H5OH (“phenyl alcohol”) has diverse uses - it gives

its name to the general class of compounds

An ether has two organic groups (alkyl, aryl, or vinyl) bonded

to the same oxygen atom, R–O–R

Diethyl ether is used industrially as a solvent

Thiols (R–SH), thiophenols (Ar-SH) and sulfides (R–S–R) are

sulfur (for oxygen) analogs of alcohols and ethers

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Why this Chapter?

To begin to study oxygen-containing functional

groups

These groups lie at the heart of biological chemistry

To finish covering functional groups with C-O and C-

S single bonds

Focus on ethers and look at thiols and sulfides

before going on to C=O

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8.1 Naming Alcohols and Phenols, and

Ethers

Alcohols

General classifications of alcohols based on

substitution on C to which OH is attached

Methyl (C has 3 H’s), Primary (1°) (C has two H’s,

one R), secondary (2°) (C has one H, two R’s),

tertiary (3°) (C has no H, 3 R’s)

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IUPAC Rules for Naming Alcohols

Step 1. Select the longest carbon chain containing the

hydroxyl group, and derive the parent name by

replacing the -e ending of the corresponding alkane

with -ol

Step 2. Number the chain from the end nearer the

hydroxyl group

Step 3. Number substituents according to position on

chain, listing the substituents in alphabetical order

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Common names

Name substituents on aromatic ring by their

position from OH

Phenols

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Ethers

Simple ethers are named by identifying the two

organic substituents and adding the word ether

If other functional groups are present, the ether

part is considered an alkoxy substituent

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8.2 Properties of Alcohols and Phenols:

Hydrogen Bonding and Acidity

The structure around O of the alcohol or phenol is similar to that in

water, sp3 hybridized

Alcohols and phenols have much higher boiling points than similar

alkanes and alkyl halides

A positively polarized -OH hydrogen atom from one molecule is

attracted to a lone pair of electrons on a negatively polarized oxygen

atom of another molecule

This produces a force that holds the two molecules together

These intermolecular attractions are present in solution but not in the

gas phase, thus elevating the boiling point of the solution

Figure 8.1 Hydrogen bonding in alcohols and phenols.

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Properties of Alcohols and Phenols: Acidity and

Basicity

Weakly basic and weakly acidic

Protonated by strong acids to yield oxonium ions,

ROH2+

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Alcohols and phenols are weak acids: Can transfer

a proton to water to a very small extent

Produces H3O+ and an alkoxide ion (RO), or a

phenoxide ion (ArO)

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Acidity Measurements

The acidity constant, Ka, measures the extent to

which a Brønsted acid transfers a proton to water

[A] [H3O+]

Ka = ————— and pKa = log Ka

[HA]

Relative acidities are more conveniently presented

on a logarithmic scale, pKa, which is directly

proportional to the free energy of the equilibrium

Differences in pKa correspond to differences in free

energy

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pKa Values for Typical OH Compounds

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Generating Alkoxides from Alcohols

Alcohols react with alkali metals to yield alkoxides

Alkoxides are bases used as reagents in organic

chemistry

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Phenol Acidity

Phenols (pKa ~ 10) are much more acidic than

alcohols (pKa ~ 16) due to resonance stabilization

of the phenoxide ion

Phenols react with NaOH solutions (but alcohols do

not), forming salts that are soluble in dilute aqueous

solution

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Resonance stabilized phenoxide ion

Figure 8.2 A resonance-stabilized phenoxide ion is more stable than an alkoxide ion.

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8.3 Synthesis of Alcohols from Carbonyl

Compounds

General method for preparing alcohols

Note that organic reduction reactions add the

equivalent of H2 to a molecule

Reduction of Carbonyl Compounds

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Reduction of Aldehydes and Ketones

Aldehydes gives primary alcohols

Ketones gives secondary alcohols

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Reduction Reagent: Sodium Borohydride

NaBH4 is not sensitive to moisture and it does not

reduce other common functional groups

Lithium aluminum hydride (LiAlH4) is more powerful,

less specific, and very reactive with water

Both add the equivalent of “H-”, hydride

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Mechanism of Reduction

The reagent adds the equivalent of hydride to the

carbon of C=O and polarizes the group as well

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Reduction of Carboxylic Acids and Esters

Carboxylic acids and esters are reduced to give

primary alcohols

LiAlH4 is used because NaBH4 is not effective

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Grignard Reactions of Carbonyl Compounds

Alkyl, aryl, and vinylic halides react with

magnesium in ether or tetrahydrofuran to generate

Grignard reagents, RMgX

Grignard reagents react with carbonyl compounds

to yield alcohols (addtion of carbanion (R:- +MgX))

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Reactions of Grignard Reagents with Carbonyl

Compounds

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Reactions of Esters and Grignard Reagents

Yields tertiary alcohols in which two of the

substituents carbon come from the Grignard

reagent

Grignard reagents do not add to carboxylic acids –

they undergo an acid-base reaction, generating the

hydrocarbon of the Grignard reagent

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The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give bond

Tertiary alcohols are readily dehydrated with a strong acid

8.4 Reactions of Alcohols

Zaitsev’s rule

Dehydration of Alcohols

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Figure 8.3 Mechanism of the acid-catalyzed dehydration

of a tertiary alcohol to yield

an alkene.

E1 process

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Biological dehydration

E1cB mechanism

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Oxidation of Alcohols

Can be accomplished by inorganic reagents, such as

KMnO4, CrO3, and Na2Cr2O7 or by more selective,

expensive reagents

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The most common current choice for preparing an

aldehyde from a primary alcohol in laboratory is to

use periodinane

Too expensive for large-scale use in industry

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Oxidation of primary alcohols produce carboxylic

acids (in aqueous acid solution)

Oxidation of secondary alcohols produce ketones

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Mechanism: Oxidation of an 2°Alcohol with CrO3

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Mechanism: Oxidation of an 1°Alcohol to a

Carboxylic Acid

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Conversion into Ethers: The Williamson ether synthesis

Reaction of metal alkoxides and primary alkyl

halides and tosylates

Best method for the preparation of ethers

Alkoxides prepared by reaction of an alcohol with a

strong base such as sodium hydride, NaH

SN2

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Mechanism: SN2 reaction

E2 elimination with more hindered substrate

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In theory, unsymmetrical ethers can be synthesized

in two different ways; in practice, one path is usually

preferred.

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8.5 Reactions of Phenols

Alcohol-Like Reactions of Phenols

Electrophilic Aromatic Substitution Reactions of

Phenols

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Oxidation of Phenols: Quinones

Reaction of a phenol with strong oxidizing agents

yields a quinone

reduction

oxidation

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Quinones in Nature

Ubiquinones (coenzyme Q)mediate

electron-transfer processes

involved in energy production

through their redox reactions

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8.6 Reactions of Ethers

Ethers are generally unreactive

Strong acid will cleave an ether at elevated

temperature

HI, HBr produce an alkyl halide from less hindered

component by SN2 (tertiary ethers undergo SN1)

SN1

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8.7 Cyclic Ethers: Epoxides

Cyclic ethers behave like acyclic ethers, except if

ring is 3-membered

Tetrahydrofuran (THF) is used as solvent.

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Preparation of Epoxides Using a Peroxyacid - Epoxide: three-membered ring ethers

Treat an alkene with a peroxyacid

(mCPBA)

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Reactions of Epoxides: Ring-Opening

Water adds to epoxides with dilute acid at room

temperature: Product is a 1,2-diol (on adjacent C’s:

vicinal)

Anhydrous HF, HBr, HCl, or HI combines with an

epoxide: trans-halohydrins formation

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Bases and nucleophiles preferably add to less

hindered site if primary and secondary C’s

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8.8 Thiols and Sulfides

Thiols (RSH), are sulfur analogs of alcohols

Named with the suffix -thiol

-SH group is called “mercapto group” (“capturer of

mercury”)

Sulfides (RSR), are sulfur analogs of ethers

Named by rules used for ethers, with sulfide in place of

ether for simple compounds and alkylthio in place of alkoxy

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Formation and Reaction

Thiols: from alkyl halides by displacement with a

sulfur nucleophile such as –SH

Thiolates (RS) are formed by the reaction of a thiol

with a base

Thiolates react with primary or secondary alkyl

halide to give sulfides (RSR’)

SN2

SN2

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Oxidation of Thiols to Disulfides

Reaction of an alkyl thiol (RSH) with bromine or

iodine gives a disulfide (RSSR)

reduction

oxidation

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Epoxy Resins and Adhesives