Organic Chemistry, 7th Edition L. G. Wade, Jr.

Chapter 10
Structure and Synthesis of Alcohols

Copyright 2010 Pearson Education, Inc.

Structure of Water and Methanol

Oxygen is sp3 hybridized and tetrahedral. The HOH angle in water is 104.5. The COH angle in methyl alcohol is 108.9.
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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.
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Examples of Classifications
CH3 CH3 CH CH2OH *
CH3 OH CH CH2CH3

Primary alcohol

Secondary alcohol

CH3 CH3

* OH C
CH3

Tertiary alcohol

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.

Examples of Nomenclature
CH3 CH3
3

OH CH3
1

CH CH2OH
2 1

CH CH2CH3
2 3 4

2-methyl-1-propanol 2-methylpropan-1-ol

2-butanol butan-2-ol

2 CH3

CH3 1 C OH

CH3

2-methyl-2-propanol 2-methylpropan-2-ol

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
OH

CH2
5

CHCH2CHCH3
4 3 2 1

4-penten-2-ol pent-4-ene-2-ol

Naming Priority
Highest ranking 1. Acids 2. Esters 3. Aldehydes 4. Ketones 5. Alcohols 6. Amines 7. Alkenes 8. Alkynes 9. Alkanes 10. Ethers 11. Halides
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Lowest ranking

Hydroxy Substituent
When OH is part of a higher priority class of compound, it is named as hydroxy.
carboxylic acid

OH CH2CH2CH2COOH
4 3 2 1

4-hydroxybutanoic acid also known as g-hydroxybutyric acid (GHB)

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Common Names
Alcohol can be named as alkyl alcohol. Useful only for small alkyl groups.
CH3 CH3 CH CH2OH
CH3 OH CH CH2CH3

isobutyl alcohol

sec-butyl alcohol

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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
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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

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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.
OH

OH H3C

Cl

3-chlorophenol (meta-chlorophenol)

4-methylphenol (para-cresol)
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Solved Problem 1
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.

The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol.

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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.

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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.
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Solubility in Water

Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases.
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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
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Ethanol
Fermentation of sugar and starches in grains 1215% 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
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Acidity of Alcohols
pKa range: 15.518.0 (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!
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Table of Ka Values

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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.
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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.
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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.
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Synthesis of Alcohols (Review)

Alcohols can be synthesized by nucleophilic substitution of alkyl halide. Hydration of alkenes also produce alcohols:
Water in acid solution (suffers from rearragements) Oxymercurationdemercuration Hydroborationoxidation
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Synthesis of Vicinal Diols

Vicinal diols can be synthesized by two different methods: Syn hydroxylation of alkenes
Osmium tetroxide, hydrogen peroxide Cold, dilute, basic potassium permanganate

Anti hydroxylation of alkenes

Peroxyacids followed by hydrolysis
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Organometallic Reagents
Carbon is negatively charged so it is bonded to a metal (usually Mg or Li). It will attack a partially positive carbon.
CX CO

Good for forming carboncarbon bonds.

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Grignard Reagents

Formula RMgX (reacts like R:- +MgX). Ethers are used as solvents to stabilize the complex. Iodides are most reactive. May be formed from any halide.
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Reactions with Grignards

Br + Mg ether MgBr

Cl CH3CHCH2CH3 + Mg ether

MgCl CH3CHCH2CH3

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Organolithium Reagents
Formula RLi (reacts like R:- +Li) Can be produced from alkyl, vinyl, or aryl halides, just like Grignard reagents. Ether not necessary, wide variety of solvents can be used.

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Reaction with Carbonyl

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Formation of Primary Alcohols Using Grignard Reagents

Reaction of a Grignard with formaldehyde will produce a primary alcohol after protonation.

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Synthesis of 2 Alcohols

Addition of a Grignard reagent to an aldehyde followed by protonation will produce a secondary alcohol.
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Synthesis of 3 Alcohols

Tertiary alcohols can be easily obtained by addition of a Grignard to a ketone followed by protonation with dilute acid.

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Solved Problem 2
Show how you would synthesize the following alcohol from compounds containing no more than five carbon atoms.

Solution
This is a tertiary alcohol; any one of the three alkyl groups might be added in the form of a Grignard reagent. We can propose three combinations of Grignard reagents with ketones:

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Solved Problem 2 (Continued)

Solution (Continued)

Any of these three syntheses would probably work, but only the third begins with fragments containing no more than five carbon atoms. The other two syntheses would require further steps to generate the ketones from compounds containing no more than five carbon atoms.

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Grignard Reactions with Acid Chlorides and Esters

Use two moles of Grignard reagent. The product is a tertiary alcohol with two identical alkyl groups. Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent.
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Reaction of Grignards with Carboxylic Acid Derivatives

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Mechanism
Step 1: Grignard attacks the carbonyl forming the tetrahedral intermediate.

H3C R MgBr C O Cl

CH3 R C O

MgBr

Cl

Step 2: The tetrahedral intermediate will reform the carbonyl and form a ketone intermediate.

CH3 R C O Cl MgBr

CH3 R C + O
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MgBrCl

Mechanism continued
Step 3: A second molecule of Grignard attacks the carbonyl of the ketone. CH3 CH3 R MgBr + R C R C O O R MgBr

Step 4: Protonation of the alkoxide to form the alcohol as the product.

CH3
R C O R MgBr

HOH

CH3
R C OH R
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Addition to Ethylene Oxide

Grignard and lithium reagents will attack epoxides (also called oxiranes) and open them to form alcohols. This reaction is favored because the ring strain present in the epoxide is relieved by the opening. The reaction is commonly used to extend the length of the carbon chain by two carbons.
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Limitations of Grignard
Grignards are good nucleophiles but in the presence of acidic protons it will acts as a strong base. No water or other acidic protons like OH, NH, SH, or terminal alkynes. No other electrophilic multiple bonds, like CN, CN, SO, or NO.
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Reduction of Carbonyl
Reduction of aldehyde yields 1 alcohol. Reduction of ketone yields 2 alcohol. Reagents:
Sodium borohydride, NaBH4 Lithium aluminum hydride, LiAlH4 Raney nickel

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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.
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Mechanism of Hydride Reduction

The hydride attacks the carbonyl of the aldehyde or the ketone. A tetrahedral intermediate forms. Protonation of the intermediate forms the alcohols.
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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 1 alcohols.
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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.
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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.
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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.
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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 an SN2 reaction so primary alkyl halides work better.
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Synthesis of Thiols

The thiolate will attack the carbon displacing the halide. This is an SN2 reaction so methyl halides will react faster than primary alkyl halides. To prevent dialylation use a large excess of sodium hydrosulfide with the alkyl halide.
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Thiol Oxidation

Thiols can be oxidized to form disulfides. The disulfide bond can be reduced back to the thiols with a reducing agent.
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