Chapter 11 Reaction with Alcohols

Ch 11 deals with reactions involving alcohol or alcohol derivatives as the starting material. Keep in mind the different reactions you have
learned in O.Chem 1 on how to form alcohols (see Ch 10 chart).
Oxidation of Alcohols (Add more C-O bonds)
Reaction
Oxidation of
Alcohols with
a chromium
(VI)reagent

Example (Mechanism)
An Alcohol can react with various chromium VI oxidation reagents, such as CrO3,
Na2Cr2O7, H2CrO4, which will oxidize the alcohol to form a carbonyl group. A
secondary alcohol will first react with the chromic acid to form a chromate ester

Water will then attack the chromate ester, displacing the chromium and forming a
ketone, with Cr(IV) as a byproduct

However, when a primary alcohol reacts with chromium, chromium will continue to
oxidize the aldehyde into a carboxylic acid (similar to KMnO4 in extreme conditions)

Remember, for Cr(VI) reagents,

Secondary alcohol + Cr(VI) ketone
Primary alcohol + Cr(VI) carboxylic acid

Reactants, Reagent,
Products
o
Reactant- Alcohol (only 1
o
and 2 !)
Reagent A Chromium (VI)
reagent (Na2Cr2O7, or
CrO3 in H2SO4, or H2CrO4)
Product An Carbonyl
nd
group (if 2 , will form a
st
ketone, if 1 , will further
oxidize to a carboxylic
acid)

Important things to
note
-Dont need to know
the mechanism, just
know what reacts and
what is formed!!
- A Chromium reagent
is needed
-Usually reacts in an
Acidic environment
(H2SO4)
o
-2 alcohol ketone,
o
1 alcohol carboxylic
acid
-No specific
stereochemistry
-Will also reduce
alcohols that are on
Benzylic or allyic
positions!
-Note that this will not
work on Tertiary
Alcohols since there are
no hydrogen available

Oxidation of
alcohols with
a pyridinium
Chromate
compound
(PDC or PCC)

If a primary alcohol is reacted with Cr(VI) in non-acidic conditions, it will only oxidize
once, to form an aldehyde instead of a carboxylic acid. A good reagent for this is
pyridinium chlorochromate (PCC) or pyridinium dichromate (PDC). These are Cr(VI)
reagents that are buffered with a pyridine base.

Reactant 1 or 2
o
alcohol, (can react with 2 ,
but not as effective)
Reagent Either
Pyridinium dichromate
(PDC) or Pyridinium
chlorochromate (PCC),
which is CrO3, pyridine and
HCl
o
Product 2 ketone
o
1 aldehyde

-Dont need to know

the mechanism, just
know what reacts and
what is formed!!
-Will also reduce
alcohols that are on
Benzylic or allyic
positions!
-PDC and PCC are
soluble in nonpolar
solvents (like CH2Cl2),
-Remember,
o
2 ketone
o
1 aldehyde
-You can just write PDC
or PCC whenever you
need to specify the
reagents

Reactant- Alcohol (can be

nd
st
either 2 or 1 )
Reagent Dimethyl
Sulfoxide(DMSO), oxalyl
chloride, and a hindered
base (like triethylamine).
For reactions, just write
DMSO
Product An Carbonyl
nd
group (if 2 , will form a
st
ketone, if 1 , will remain
an aldehyde)

-Dont bother to
memorize the
mechanism, just
recognize the reaction,
reagents & product
-Remember,
o
2 ketone
o
1 aldehyde
-FYI, it is a smelly
reaction
-Essentially similar to
PDC and PCC in terms
of what product is
formed

PCC and PDC can also react with secondary alcohols to form ketones, similar to Cr(VI)

Swern
Oxidation

-For PDC and PCC, 2 ketone, 1 aldehyde

Similar to PDC or PCC, a primary alcohol can be oxidized by dimethyl sulfoxide
(DMSO), to form an aldehyde. You do NOT need to know the mechanism, and I
recommend you do NOT memorize it (Just write DMSO and youll be fine ). You can
also react this with a secondary alcohol to form a ketone

Other
miscellaneous
oxidizing
reagents

Here, Ive listed several other oxidizing reagents that the book and Dr. Biewer go
through. They arent as important as the ones listed above, but be able to recognize it
if he does ask about it (Especially MnO2)
Sodium hypochlorite (NaOCl), potassium permanganate (KMnO4), and nitric acid
o
(HNO3) are all strong oxidizing agent similar to Cr(VI), if reacted with a 2 alcohol,
o
will form a ketone. if 1 , will form a carboxylic acid

A special reagent to note is Manganese oxide (MnO2). MnO2 can only react with
benzylic (alcohol adjacent to benzene ring), or allylic (alcohol adjacent to double
bond) alcohols, forming aldehydes from primary alcohols Keep in mind other
oxidizing reagents such as Cr(VI) and PCC/PDC work on benzylic/allylic positions,
but MnO2 is a weaker oxidizing reagent to where it only works on allylic or benzylic
positions! It does not completely oxidize primary alcohols to carboxylic acids!

Reactant- Alcohol (can be

nd
st
either 2 or 1 )
Reagent NaOCl, KMnO4,
HNO3, or MnO2
Product
o
2 alcohol ketone,
o
1 alcohol carboxylic
acid
For MnO2, forms benzylic
or allylic
aldehydes/ketones

-Dont need to know

the mechanism, just
know what reacts and
what is formed!!
-Not as important as
previous oxidizing
agents, but be able to
recognize it.
-Pay special attention
to MnO2, because it
was asked before on a
previous quiz and exam
(my first quiz and exam)

Nucleophilic/Electrophilic reactions of alcohols

Reaction
Williamson
ether
synthesis

Example (Mechanism)
To make an alcohol nucleophilic, a hydrogen is extracted from oxygen, commonly
+
using Na . The alkoxide ion can then react as a nucleophile, attacking any
electrophile. If reacted with an alkyl halide, an ether is formed. Keep in mind pKa
values! Alcohols are also weak bases and can extract hydrogens from more acidic
compounds

Reactants, Reagent,
Products
Reactant- Alcohol (can be
o
o
o
either 1 , 2 , or 3 )
Reagent A strong base
+
(Na ), and then any
electrophile (alkyl halide)
Product If reacted with
an alkyl halide, an ether is
formed

Important things to note

- Know the entire
mechanism and
reagents used!
-Keep in mind pKa
values! A hydrogen cant
be extracted from a
stronger acid!
-Will also compete with
E2 reactions!

Esterfication
of Carboxylic
acids (Fischer
esterfication)

-An alcohol can react with a carboxylic acid (has to be protonated first, usually
occurs in an acidic solution), forming a tetrahedral intermediate

-One of the alcohols will be protonated, leaving as water, forming an ester with the
alcohol attached to the carbonyl carbon. Notice that all of these steps are in
equilibrium, which means that it is reversible

Reactant- An Alcohol
Reagent Carboxylic acid
or acid chloride (Needs to
protonate the oxygen first
for carboxylic acid
though)
Product Ester, with the
alcohol attached to the
carbonyl carbon.

- Know the mechanism!

It is important for future
reactions when you get
to carboxylic acid
reactions!
-For a carboxylic acid,
the oxygen needs to be
protonated first (acidic
solution). The acid
chloride does not need
to be placed in an acidic
solution
-Remember that this is
in equilibrium, and can
go the opposite
direction as well!

Reactant- An Alcohol
Reagent A tosylate
compound, (can be TsOH,
TsCl, etc.), then any
nucleophile
Product A tosylate
ester, than whatever
nucleophile substituting

-Know the mechanism

and stereochemistry!
-Remember that
attaching the tosylate
group to the alcohol
doesnt change the
stereochemistry, but
reacting it with a

The reaction can be summed up as the following. Know the mechanism!

-An alcohol can also react with an acid chloride similarly, forming a tetrahedral
intermediate, kicking out chloride and forming an ester. Since chloride is a good
leaving group (weak base), the acid chloride does not need to be protonated unlike
carboxlic acids. They dont need to be placed in an acidic solution.

Formation
and reaction
of tosylate
esters

An alcohol can react with a tosylate group (TsOH, TsCl), forming a tosylate ester.
Note that this reaction does not change the stereochemistry of the alcohol

Remember from O.Chem 1 that alcohols are horrible electrophiles. However,

tosylate esters are good electrophiles since the tosylate group is stabilized by
resonance, so a good nucleophile can react with the tosylate ester in an SN2
reaction (remember inversion of configuration!).

for the original alcohol,

with the stereochemistry
switched

nucleophile results in an
inversion of
sterochemistry (switch
wedge to dash, and vise
versa)
-Can react the alcohol
with either TsOH or TsCl

Reactants, Reagent,
Products
Reactant- An alcohol
Reagent HBr
Product Alkyl bromide
(Same stereochemistry
and regiochemistry apply
for the SN1 or SN2
reactions)

Important things to note

Reactions of Alcohols with Hydrohalic Acids

Reaction

Example (Mechanism)

Reaction with
Hydrobromic
Acid

Tertiary and secondary alcohols can undergo a SN1 reaction with HBr, with the HBr
first protonating the alcohol, forming a good leaving group, forming a carbocation
(look for rearrangements!). The bromine will then attack the carbocation, forming
o
o
o
an alkyl bromide. Remember the rules for SN1 reactions! (3 and 2 , rarely 1 )

Primary alcohols mainly undergo SN2 reactions, with the HBr first protonating the
alcohol, forming a good electrophile, bromine then attacking the alcohol to form the
alkyl bromide (Remember the rules for SN2 reactions!)

Reaction of
alcohol with
HCl and ZnCl2
(Lucas
reagent)

An alkyl chloride can be formed with the addition of HCl to an alcohol, but usually
requires a lewis acid (ZnCl2) since it is a weaker nucleophile. Together ZnCl2 and HCl
make up a reagent called Lucas Reagent. ZnCl2 will first attach to the alcohol, then
leaving to form a carbocation.

Reactant- An Alcohol
o
o
o
(usually 3 or 2 , rarely 1
(Remember SN1 trends!)
Reagent Lucas reagent
(consists of HCl and ZnCl2)
Product Alkyl Chloride
(Rearrangements are
possible to form a more
stable carbocation)

-Know the mechanism,

and the mechanism it
will go through from the
o
o
type of alcohol (1 , 2 ,
o
3 .)
-Tertiary and secondary
alcohols mainly undergo
SN1, primary usually only
goes through SN2

-Not as important as HBr

reactions, but know the
general mechanism and
the reagents used.
-Very similar to a SN1
reaction, so dont forget
the rules for SN1
reactions!
-ZnCl2 is required as a
Lewis base to promote

Since a carbocation is formed, be sure to look for any rearrangements! Afterwards,

the chloride ion will attack the carbocation, forming the alkyl chloride. This is similar
to a SN1 reaction

the reaction of the

alcohol and HCl
-There is no specific
stereochemistry!

The overall reaction is summed up below

Reaction of
alcohols with
Phosphorus
halides (PI3,
PBr3, or PCl3)

Reaction of
alcohols with
Thionyl
Chloride
(SOCl2)

Alcohols (1 , 2 , rarely 3 ), can react with phosphorus halides (Cl, Br, I, no F!) in a
SN2 mechanism to form alkyl halides without rearrangements. Different reagents
are used depending on which halide you are trying to add, but the mechanism is the
same.
-The alcohol will displace a halogen from the phosphorus halide, which will in turn
attack the very electrophilic carbon, with the alcohol-phosphorus compound leaving
(very good leaving group). Dont forget to switch the stereochemistry!

Common phosphorus halides include

-Chlorines - PCl3, PCl5, Bromines - PBr3, Iodines PI3, P/I2
Hint: Pretty much whenever you see phosphorus with a halide, think SN2!
An alcohol can react with thionyl chloride (SOCl2), to form an alkyl chloride (often
the best reagent to use). The alcohol will first attack SOCl2, kicking out a chloride.

Reactant An alcohol (1
o
o
or 2 , rarely 3
Reagent Phosphorus
halide, see the list written
to the left
Product An alkyl Halide
(SN2 reaction, so note
inverse configuration)

Reactant- An Alcohol (1 ,
o
o
2 , or 3 )
Reagent Thionyl
Chloride (SOCl2)
Product Alkyl Chloride
(Same stereochemistry)

-Know the reaction and

the mechanism!
-Similar to a SN2
reaction!
-Good reagents for
adding Bromine and
iodine to alcohols, but
SOCl2 is usually better
than phosphorus
chloride in adding Cl.
-Whenever you think
phosphorus, think SN2!

- Do not need to know

the mechanism, but
know the reagent and
what is formed!
-Usually the best reagent
to use when trying to
convert an alcohol to an
alkyl chloride

In turn, the chlorosulfite ester ionizes, kicking out the R group originally attached to
the alcohol. The R group (ethyl in this example), will extract the remaining chloride
to form the alkyl chloride. You do NOT need to memorize the mechanism, but
know at least two things:
1)Essentially, this is similar to a SN1 reaction with no rearrangement
2)Stereochemistry of the original alcohol does NOT change (dash stays dash, etc.)

-Dont forget to keep the

same stereochemistry!

Below is a chart from the book (pg 483) of the best reagents to use to convert alcohols to alkyl halides. This is useful whenever you need to do synthesis
problems, so keep them in mind

Reactions with Diols

Reaction
The Pinacol
Rearrangement

Example (Mechanism)
If a pinacol (vicinal diol) is placed in an acidic solution, it can undergo what is
called the pinacol rearrangement. One of the alcohols will be protonated and
leave, forming a carbocation

Reactants, Reagent,
Products
Reactant- A pinacol
(Vicinal Diol)
Reagent An Acidic
environment (H2SO4, or
+
any H source)
Product Pinacolone
(keto form of the
carbonyl)

Important things to note

-Know the mechanism,
reagents and what is
formed!
-The diol has to be able
to undergo a methyl shift
for this mechanism to
work. Otherwise, it will
not go through this
reaction!
-The reason for the
methyl shift is because of

The carbocation will undergo a methyl shift, with the carbocation being on the
secondary alcohol. This allows for resonance with the oxygen, which is why this
shift takes place! Note that this reaction only takes place if there is a methyl to
shift with!

the stability of the

oxonium ion due to
resonance
-There is no specific
stereochemistry!

The hydrogen attached to the oxygen will then leave, forming the ketone product.

Periodic Acid
cleavage of
Glycols

A glycol (1,2 diol) can react with periodic acid (HIO4), cleaving the alcohols and
forming ketones and aldehydes. The aldehydes will not oxidize to carboxylic
acids; they will remain aldehydes

It is similar to the cleavage reactions with ozone, but reacts with diols, not the
alkene form. Easy way to think about this reaction is to break the bond connecting
the alcohols, and replace the alcohols with a double bond O. Any tertiary alcohol
will form a ketone; any secondary alcohol will form an aldehyde.

Reactant- A glycol (1,2

Diol, can be formed by
Alkene + OsO4 or KMnO4)
Reagent Periodic acid
(HIO4)
Product ketones and
aldehydes

-Dont need to know the

mechanism, but what is
reacted and formed
- Similar to the Ozone
reaction with a alkene
(will actually get you
same products)
-There is no specific
stereochemistry!