ALCOHOL

<SKO3013>
<BASIC ORGANIC CHEMISTRY)
DR YUHANIS MHD BAKRI
DEPARTMENT OF CHEMISTRY
FACULTY OF SCIENCE AND MATHEMATICS
UNIVERSITI PENDIDIKAN SULTAN IDRIS Also adapted from: Organic
Chemistry, 9th Edition, Global
Edition. L. G. Wade, Jr.
 Alcohols Classifications

C H3 OH
C H3 CH C H 2OH C H3 CH C H 2C H 3
* *
Primary alcohol Secondary alcohol
• Alcohols are organic compounds
containing hydroxyl groups. C H3
C* OH OH
• They are some of the most useful C H3

compounds in nature, industry, C H3

and around the house.

 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
 Alkenols (Enols)

• The 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
C H2 C HC H 2C HC H 3
5 4 3 2 1
Old: 4-penten-2-ol
New: pent-4-ene-2-ol
Naming Priority
 Hydroxy Substituent

• When —OH is part of a higher priority class of

compound, it is named as hydroxy.
carboxylic acid
OH
C H 2C H 2C H 2C OOH
4 3 2 1

4-hydroxybutanoic acid
also known as γ-hydroxybutyric acid (GHB)
 Common Names

• Alcohol can be named as alkyl alcohol.

• Useful only for small alkyl groups

C H3 OH
C H3 CH C H 2OH C H3 CH C H 2C H 3

isobutyl alcohol sec-butyl alcohol

IUPAC: 2-methylpropan-1-ol IUPAC: butan-2-ol
 Naming Diols

• Two numbers are needed to locate the two

—OH groups.
• Use -diol as the suffix instead of -ol.

1 2 3 4 5 6

hexane-1,6-diol
 Phenol Nomenclature
• The —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 4-methylphenol
(meta-chlorophenol) (para-cresol)
 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.

 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.
Solubility in Water

Small alcohols are miscible in water,

but solubility decreases as the size of
the alkyl group increases.
 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.
 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.
 Synthesis of Alcohols (Review)

• Alcohols can be synthesized by nucleophilic

substitution (usually SN2) of alkyl halide.
• Addition of water to double bonds also
produces alcohols:
– Water in acid solution (suffers from
rearrangements)
– Oxymercuration–demercuration
– Hydroboration–oxidation
 Grignard Reagents

• Formula R—Mg—X (reacts like R:– +MgX)

• Ethers are used as solvents to stabilize the complex.
• Iodides are the most reactive. Fluorides generally do not react.
• May be formed from primary, secondary, or tertiary alkyl
halides
 Organolithium Reagents

• Reacts the same way as a Grignard

• Can be produced from alkyl, vinyl, or aryl halides,
just like Grignard reagents
• Ether is not necessary; a wide variety of solvents
can be used.
 Addition to
Carbonyl Compounds

• The carbonyl carbon is partial positive

(electrophilic).
• Nucleophiles will attack the carbonyl, forming
an alkoxide.
Mechanism of Addition of the
Organometallic to the Carbonyl
 Formation of Primary Alcohols Using
Organometallics

• Reaction of a Grignard with formaldehyde will produce

a primary alcohol after protonation.
 Synthesis of 2° Alcohols

• Addition of a Grignard reagent to an aldehyde

followed by protonation will produce a secondary
alcohol.
 Synthesis of 3° Alcohols

• Tertiary alcohols can be easily obtained by

addition of a Grignard to a ketone followed by
protonation with dilute acid.
 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:
 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.
 Reduction of Carbonyl

• Hydride reagents add a hydride ion (H–), reducing

the carbonyl group to an alkoxide ion with no
additional carbon atoms.
• Protonation gives the alcohol.
• Reduction of aldehyde yields 1° alcohol.
• Reduction of ketone yields 2° alcohol.
 Hydride Reagents

• Called complex hydrides because they do not have

a simple hydride structure such as Na+H– or Li+H–
• The bonding to the metal makes the hydrides more
nucleophilic and less basic.
 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 aldehydes or ketones, not with
esters or carboxylic acids.
• Can reduce a ketone or an aldehyde in the
presence of an acid or an ester
 Mechanism of
Hydride Reduction

• Reaction 1: The hydride attacks the carbonyl of the aldehyde

or the ketone, forming an alkoxide ion.
• Reaction 2: Protonation of the intermediate forms the alcohol.
 Examples of
NaBH4 Reduction
 Lithium Aluminum Hydride

• Stronger reducing agent than sodium

borohydride
• Dangerous to work with
• Reduces ketones and aldehydes into the
corresponding alcohol
• Converts esters and carboxylic acids to 1°
alcohols
 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.
 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.
Comparison
 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.
 Selective Reductions

• Hydride reagents are more selective, so they

are used more frequently for carbonyl
reductions.
 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.
 Nomenclature

CH3—SH CH3CH2CH2CH2—SH HS—CH2CH2—OH

methanethiol butane-1-thiol 2-mercaptoethanol

methyl mercaptan n-butyl mercaptan

• Common names are formed like those of

alcohols, using the name of the alkyl group
with the word mercaptan.
 Acidity of Thiols

• Thiols are more acidic than alcohols.

 Synthesis of Thiols

• Thiols are commonly made by an SN2 reaction, so

primary alkyl halides work better.
• To prevent a second alkylation, use a large excess of
sodium hydrosulfide with the alkyl halide.
 Thiol Oxidation

Thiols can be oxidized to form disulfides. The disulfide bond can

be reduced back to the thiols with a reducing agent.
 Types of Alcohol Reactions

• Dehydration to alkene
• Oxidation to aldehyde, ketone
• Substitution to form alkyl halide
• Reduction to alkane
• Esterification
• Tosylation
• Williamson synthesis of ether
Summary Table
 Oxidation States

• Inorganic chemistry:
– Oxidation is a loss of electrons.
– Reduction is a gain of electrons.
• Organic chemistry
– Oxidation: Gain of O, O2, or X2; loss of H2
– Reduction: Gain of H2 (or H–); loss of O or O2; and loss of
X2
– Neither: The gain or loss of H+, H2O, –OH, HX, etc. is
neither an oxidation nor a reduction.
Oxidation States of Carbons
 Oxidation of 2° Alcohols
• A 2° alcohol becomes a
ketone.
• Traditional oxidizing
agents are chromium-
based reagents such as
Na2Cr2O7 in H2SO4.
• Active reagent probably is
H2CrO4 or HCrO4–.
• Color change is orange to
greenish-blue.
• Chromium is highly toxic
and difficult to dispose of
properly.
 Formation of the Acid
Chromate Ion

• CrO3 will also produce chromic acid in the

presence of H2SO4 and H2O.
Oxidation Mechanism
Oxidation of 1° Alcohols to Carboxylic Acids

• Chromic acid reagent oxidizes primary alcohols to

carboxylic acids.
• The oxidizing agent is too strong to stop at the
aldehyde.
 Pyridinium Chlorochromate (PCC)

• PCC is a complex of
chromium trioxide,
pyridine, and HCl.
• It oxidizes primary
alcohols to aldehydes.
• It oxidizes secondary
alcohols to ketones.
Pyridinium Chlorochromate (PCC)
 3° Alcohols Cannot Be Oxidized

• Carbon does not have hydrogen, so oxidation is

difficult and involves the breakage of a C—C
bond.
• Chromic acid test is for primary and secondary
alcohols because tertiary alcohols do not react.
 Sodium Hypochlorite (NaOCl)

• Sodium hypochlorite (household bleach) can oxidize

alcohols without heavy metals or generating hazardous
waste.
• This is a much better option for acid-sensitive
compounds.
 Solved Problem 1
Suggest the most appropriate method for each of the following laboratory syntheses:
(a) cyclopentanol ––––––> cyclopentanone

Solution
Many reagents are available to oxidize a simple secondary alcohol to a ketone. For a
laboratory synthesis, however, dehydrogenation is not practical, and cost is not as large a
factor as it would be in industry. Most labs would have chromium trioxide or sodium
dichromate available, and the chromic acid oxidation would be simple. PCC and the Swern
oxidation would also work, although these reagents are more complicated to prepare and
use.
 Solved Problem 1 (Continued)
Suggest the most appropriate method for each of the following laboratory syntheses:
(b) 2-octen-l-ol ––––––> 2-octenal (structure below)

Solution
This synthesis requires more finesse. The aldehyde is easily over-oxidized to a carboxylic
acid, and the double bond reacts with oxidants such as KMnO4. Our choices are limited to
PCC or the Swern oxidation.
 Alcohol As a Nucleophile

• Alcohols (ROH) are weak nucleophiles.

• Alkoxides (RO–) are strong nucleophiles.
• New O—C bond forms; O—H bond breaks.
 Alcohol As an Electrophile

• Alcohols are weak electrophiles because the OH– is not

a good leaving group.
• Protonation of the hydroxyl group converts it into a
good leaving group (H2O).
 Reduction of Alcohols
• Dehydrate with concentrated H2SO4, then add H2.

• Make a tosylate, then reduce it with LiAlH4.

 Reaction of Alcohols with Acids

• The hydroxyl group is protonated by an acid to convert

it into a good leaving group (H2O).
• Once the alcohol is protonated, a substitution or
elimination reaction can take place.
 Reaction of Alcohols 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.
 SN1 Mechanism
Step 1: Protonation

Step 2: Formation of the carbocation

Step 3: Bromide attacks the carbocation.

SN2 Mechanism
 Reaction with HCl
• Chloride is a weaker nucleophile than bromide because
it is small and less polarizable.
• Addition of ZnCl2, which bonds strongly with
oxygen of the OH, promotes the reaction.
• Lucas test: ZnCl2 in concentrated HCl
– 1° alcohols react slowly or not at all.
– 2° alcohols react in 1–5 minutes.
– 3° alcohols react in less than 1 minute.
 SN2 Reaction with the
Lucas Reagent

• Primary alcohols react with the Lucas reagent (HCl and

ZnCl2) by the SN2 mechanism.
• Reaction is very slow. The reaction can take from several
minutes to several days.
 SN1 Reaction with the
Lucas Reagent

Secondary and tertiary alcohols react with the Lucas reagent

(HCl and ZnCl2) by the SN1 mechanism.
 Limitations of HX Reactions

• Poor yields of alkyl chlorides from primary and

secondary alcohols
• Elimination competes with substitution.
• Carbocation intermediate may undergo a
rearrangement.
• Limited ability to make alkyl halides
 Solved Problem 2
When 3-methyl-2-butanol is treated with concentrated HBr, the major product is 2-bromo-
2-methylbutane. Propose a mechanism for the formation of this product.

Solution
The alcohol is protonated by the strong acid. This protonated secondary alcohol loses
water to form a secondary carbocation.
 Solved Problem 2 (Continued)
Solution (Continued)
A hydride shift transforms the secondary carbocation into a more stable tertiary cation.
Attack by bromide leads to the observed product.
 Reactions with
Phosphorus Halides

• Good yields with 1° and 2° alcohols

• PCl3 for alkyl chlorides (but SOCl2 better)
• PBr3 for alkyl bromides
• P and I2 for alkyl iodides (PI3 not stable)
Examples
 Mechanism with PBr3

• Oxygen attacks the phosphorus, displacing one of the

halides.
• Br– attacks back-side (SN2).
 Dehydration Reactions

• Concentrated H2SO4 produces alkene.

• Carbocation intermediate for 2° and 3° alcohols
• Zaitsev product
• Bimolecular dehydration produces ether.
• Low temp, 140 °C and below, favors ether formation.
• High temp, 180 °C and above, favors alkene formation.
 Dehydration of Alcohols

• Alcohol dehydration generally takes place through the

E1 mechanism.
• Rearrangements are possible.
• The rate of the reaction follows the same rate as the ease of
formation of carbocations: 3° > 2° > 1°.
• Primary alcohols rearrange, so this is not a good reaction for
converting 1° alcohols into alkenes.
 Mechanism of Dehydration: E1
Step 1: Protonation

Step 2: Formation of the carbocation

Step 3: Loss of a proton forms the alkene.

 Periodic Acid Cleavage
of Glycols

• Glycols can be oxidatively cleaved by periodic acid

(HIO4) to form the corresponding ketones and
aldehydes.
• Useful for determining the structure of sugars.
 Fischer Esterification

• Reaction of an alcohol and a carboxylic acid produces

an ester.
• Sulfuric acid is a catalyst.
• The reaction is an equilibrium between starting materials and
products, and for this reason the Fischer esterification is seldom
used to prepare esters.
 Reaction of Alcohols with
Acyl Chlorides

• The esterification reaction achieves better results by reacting the

alcohol with an acyl chloride.
• The reaction is exothermic and produces the corresponding ester
in high yields with only HCl as a by-product. Pyridine neutralizes
the HCl.
 Alkoxide Ions: Williamson
Ether Synthesis

• Ethers can be synthesized by the reaction of alkoxide ions with primary alkyl
halides in what is known as the Williamson ether synthesis.
• This is an SN2 displacement reaction and, as such, works better with primary
alkyl halides to facilitate back-side attack.
• If a secondary or tertiary alkyl halide is used, the alkoxide will act as a base
and an elimination will take place.