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Part 6.
The Chemistry of Carboxylic Acids and their Derivatives
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Brown's Chemistry Advanced Level Pre-University Chemistry Revision Study
Notes for UK KS5 A/AS GCE IB advanced level organic chemistry students US
K12 grade 11 grade 12 organic chemistry reaction of acid/acyl chlorides with
water, alcohols, phenols, ammonia, ammines, nucleophilic addition mechanisms
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Part 6.7A
An introduction to the reactivity of carboxylic acid derivatives towards
nucleophiles and the preparation and reactions of acid chlorides (acyl chlorides)
Sub-index for this page
6.7A.0a
Introduction to the reactivity of carboxylic acid
derivatives towards nucleophiles
6.7A.0b
Preparation and
physical properties of acid chlorides
6.7A.1
Introduction to the specific reactivity of acyl chlorides
6.7A.2
Hydrolysis reaction of
acid/acyl chlorides and mechanism
6.7A.3
Reaction of
acid/acyl chlorides with alcohols/phenols (acylation) - esterification and mechanism
6.7A.4
Reaction of
acid/acyl chlorides with
ammonia (acylation) - primary amide formation & mechanism
6.7A.5
Reaction of
acid/acyl chlorides with
amines (acylation) - secondary/tertiary amide formation, mechanism
6.7A.6.
The reduction of acid/acyl chlorides
with LiAlH4 - conversion
to primary alcohol
6.7A.7 The reaction
of acyl/acid chlorides with aromatic hydrocarbons - ketone formation
6.7A.0a An introduction to the reactivity of carboxylic
acids and their derivatives
A theoretical mechanism
by which L, in a carboxylic acid derivative, is substituted by an incoming
nucleophile
One approach to the understanding the
comparative reactivity of carboxylic acid derivatives is to consider the
theoretical attack of a
negative or neutral nucleophile (-:Nuc
or :Nuc)
which ultimately displaces, what is referred to, as the
leaving group (:L-
or :L), shown in the mechanism diagrams
above.
The diagrams are a recognised
mechanistic pathway for the derivatives of carboxylic acids.
In the mechanisms to follow look
for the electron pair donation from the nucleophile:
e.g.
:OH2,
:NH3,
lone pairs on the oxygen atom of alcohols or phenols
RÖH
A reminder that
nucleophiles are electron pair donors (also classed as Lewis
bases).
In the actual mechanism, L
usually combines with a H atom in the elimination step, and this
will be shown in all the nucleophilic-addition mechanism shown from
now on.
e.g. for the following
leaving groups: Cl is eliminated as HCl, RCOO is eliminated as
RCOOH, O-R' is eliminated as R'OH and NH2 is
eliminated as NH3.
Note that both steps are
reversible.
This means a 'poor' leaving group
may not allow the reaction to proceed forwards to a significant
extent, or a very slow reaction leading to an equilibrium situation
e.g. the slow uncatalysed hydrolysis of an ester with pure water.
The carbonyl bond is polar,
δ+C=Oδ-,
due to the difference in electronegativity of carbon (2.5) and oxygen
(3.5).
The nucleophile (electron
pair donor) attacks the δ+C atom , forming a
sigma bond with it, and displaces the leaving group L - examples of
the theoretical leaving groups are also shown in the diagram.
The blue arrows show the electron
shifts that must happen to effect this change.
Always look for the lone pair on
the nucleophile e.g. on the oxygen atom of water and
alcohols/phenols or the nitrogen atom of ammonia and amines and
mention this in your description of the mechanism.
The ease of this reaction
depends on several factors.
(i) The strength of the single
C-L bond
Bond enthalpies = kJ/mol: C-O
= 360 > C-Cl = 338 > C-N = 305;
On the basis of bond
enthalpies, amides should be the most reactive, but this is not
the case - so we must now consider other factors.
However acid chlorides
(weaker C-Cl bond) are more reactive than acid anhydrides and
esters (stronger C-O bonds).
(ii) The electron-donating or
electron-withdrawing power of the L group towards the carbonyl
carbon atom
The chlorine atom, has the
more powerful electron-withdrawing group effect as well as a
very stable leaving group (chloride ion, a weak base), see (iii)
below.
The effect of C-O polarity is
reduced in esters because the leaving group L, has a C-O-C
linkage, and amides have a C-N-H linkage, both of which reduce
the effective delta plus of the carbon atom of the carbonyl
group.
This again favours increasing
the reactivity of acid chlorides (just the polar C-Cl bond).
(iii) The stability of the
leaving group :L-
The leaving group is poor if
it is a strong base i.e. a strong electron pair donor
The amide ion, NH2-,
is a very strong base and a weak leaving group, it would prefer
to rejoin the carbonyl carbon atom, this greatly reduces its
reactivity towards nucleophiles.
Note that in the case of
aldehydes and ketones, the H- or R-
potential leaving groups are very strong bases and not
displaced.
(iv) The polarity of the C-L
bond
In the case of acid/acyl chlorides,
the highly polarised situation of the
carbon - oxygen and carbon - chlorine bonds (electronegativities C 2.5, Cl
3.0 and O 3.5) i.e.
δ–Cl–Cδ2+=Oδ–
makes the bond highly susceptible to nucleophilic attack.
BUT, note there is no 2nd
atom attached to the chlorine to reduce its polarising effect,
e.g. as in the case of
O=C-O-H (acid), O=C-O-C (ester), O=C-N-H (amide)
The combination of the these factors
'usually' results in the reactivity order:
acid chloride >
acid anhydride > ester > amide
and this is why acid chlorides
are so reactive and very useful in organic synthesis reactions.
To illustrate this trend
consider the following:
Acid chlorides and acid
anhydrides readily react with alcohols and ammonia to yield esters
and amides respectively. They are also readily hydrolysed by water.
Esters react with ammonia and
ammines to yield amides, but are slow to hydrolyse in water without
an acid or alkali catalyst.
But the simple reversal of any of
these reactions on an amide is very difficult.
Carboxylic acid derivatives not
behave in the same way as aldehydes and ketones
Despite the its polarity, the
reactivity of the carbonyl C=O group is considerably modified by the
presence of the L group and these carboxylic acid derivatives do not as
readily undergo the addition - elimination reactions like aldehydes and
ketones e.g. they do not react with 2,4-dinitrophenylhydrazine.
Attack of a neutral nucleophile on
the δ+C atom of the carbonyl group in a carboxylic
derivative
You can construct a similar mechanistic
pathway for a neutral nucleophile like water as it hydrolyses and acid
chloride. though this requires you clearly show the elimination of the
hydrogen chloride molecule (more
on this in 6.7A.1)
TOP OF PAGE
and sub-index
6.7A.0b The preparation of acyl/acid chlorides
or RCOCl in very
abbreviated formulae
There are three basic ways of
synthesising acid chlorides in the laboratory,
all starting with the
corresponding carboxylic acid. In each case
R = alkyl or aryl.
In each case the -OH hydroxy group
of the carboxylic acid is
replaced by the -Cl chloride group.
The name is derived from the parent
acid with oyl replacing oic and suffixed with chloride i.e. ethanoyl
chloride is derived from ethanoic acid.
The lower aliphatic members of the
acid/acyl series are colourless liquids that fume in moist air - don't leave
open when not in use. They are highly corrosive hazardous
chemicals.
(a) Reaction with
phosphorus(V) chloride (phosphorus pentachloride)
RCOOH + PCl5
===> RCOCl + POCl3 + HCl
+ PCl5 ===>
+ POCl3 + HCl
From ethanoic acid, a preparation of
ethanoyl chloride, boiling point 51oC.
The acid chloride can be
separated from the POCl3 by distillation.
The ease of hydrolysis can be seen as
the volatile liquid will fume in air from hydrolysis if in contact with
water vapour in the air. More visible 'white clouds' are seen if
ethanoyl chloride vapour meets fumes from conc. ammonia solution due to
the formation of ammonium chloride.
Three reactions can be going on
...
CH3COCl +
H2O ===> CH3COOH + HCl
CH3COCl +
NH3 ===> CH3CONH2
+ HCl
NH3 + HCl
===> NH4Cl
Similarly to give butanoyl chloride
bpt. 80oC
+ PCl5 ===>
+ POCl3 + HCl
(b) Reaction with
phosphorus(III) chloride
(phosphorus trichloride)
RCOOH + PCl3
===> RCOCl + H3PO3
+ PCl3 ===>
+ H3PO3
+ PCl3 ===>
+ H3PO3
From pentanoic acid, preparation of
pentanoyl chloride, boiling point 128oC
The acid chloride would have to be
separated from the H3PO3 by distillation.
(c) Reaction with
thionyl chloride
RCOOH + SOCl2
===> RCOCl + SO2 + HCl
+ SOCl2 ===>
+ SO2 + HCl
From benzoic acid, preparation of
benzoyl chloride, boiling point 197oC
This last method has the advantage of
producing gaseous waste products and just leaving the acid chloride
behind for further purification.
Notes:
Ethanoyl chloride and pentanoyl chloride
are aliphatic acyl chlorides and benzoyl chloride is an aromatic
acyl chloride.
There is no methanoyl chloride, HCOCl is
too unstable a molecule, which is why R is only alkyl or aryl.
Uses of acid/acyl chlorides in
organic synthesis
In chemistry, acylation (or
alkanoylation) is the process of adding an acyl group (R-C=O)
to a compound.
The compound providing the acyl group
is called the acylating agent
e.g. acid/acyl chlorides
RCOCl or acid/acyl
anhydrides (R-C=O)2O,
where R = alkyl or aryl.
Physical properties
Acid/acyl chlorides are usually
colourless liquids at room temperature.
Some boiling points are quoted under
the preparations given above.
They dissolve in 'dry' organic
solvents, insoluble in water, but they do react with it - see
hydrolysis
reaction.
Lower members like ethanoyl chloride
are quite volatile at room temperature so take care ....
... the fumes are acrid and
dangerous, especially in the eyes, because the acid chloride vapour
fumes in contact with water - they hydrolyse to acidic hydrogen
chloride, which becomes hydrochloric acid in your body fluids!
TOP OF PAGE
and sub-index
6.7A.1 Introduction to the reaction mode and reactivity of
acid chlorides (acyl chlorides)
The high reactivity of acyl chlorides is
towards nucleophilic attack is partly due to the relatively weak C-Cl bond,
BUT, the highly polarised situation of the
carbon - oxygen and carbon - chlorine bonds (electronegativities C 2.5, Cl
3.0 and O 3.5) i.e.
δ–Cl–Cδ2+=Oδ–
makes the bond highly susceptible to nucleophilic attack
Note there is no 2nd atom
attached to the chlorine to reduce its polarising effect,
e.g. as in the case of
O=C-O-H (acid), O=C-O-C (ester), O=C-N-H (amide)
The ensuing mechanism is
called a nucleophilic addition elimination (because of the two
principal stages of the mechanism i.e. an addition followed by an
elimination), but overall it amounts to a nucleophilic substitution
mechanism.
The initial point of attack is the δ+
carbon atom with the addition of a nucleophiles (Nuc: in
diagram) like water, alcohols, ammonia and
amines (mechanism diagram 78a above).
These are all neutral
nucleophiles all of which are lone pair donors from the oxygen (:OR2)
or nitrogen (:NR3) atom where R = H, alkyl or aryl.
The oxygen atom of the carbonyl
group becomes negative (-) as the pi bond pair shift on to it.
Simultaneously, the oxygen or nitrogen
atom of the nucleophile
must carry a balancing positive charge (+) when they form the C-O or
C-N bond with the δ+ carbon atom to complete the addition step 1 of
the mechanism.
Note
(i) Acyl chlorides are more
reactive towards nucleophiles than carboxylic acids because the
hydrogen on the hydroxy group weakens the effect of the oxygen atom
in making the carbon atom less δ+ AND the C-OH bond is stronger
than the C-Cl bond.
(ii) The δ+ of the carbon
atom is subjected to an electron shift away from it by two, more
electronegative atoms (electronegativities: C = 2.5, Cl = 3.0 and O
= 3.5), which increases its δ+ and susceptibility to nucleophilic attack.
(iii) The C-Cl bond is weaker
than C-C, C-O or C-H bonds, so Cl is relatively mobile leaving
group.
(iv) Points (ii) and (iii) added
together, explain why acid chlorides undergo addition elimination
reactions in which the Cl atom leaves and is replaced by the
nucleophile - and more so than carboxylic acids.
After the addition of the
nucleophile, there are several electron and atom shifts before a small
molecule is eliminated, in this case hydrogen chloride - full and
simplified mechanisms are described in the following sections.
TOP OF PAGE
and sub-index
6.7A.2
The reaction of
acid chlorides (acyl chlorides) with water - hydrolysis
The hydrolysis of acyl chloride with water is a
nucleophilic addition–elimination
Examples of
nucleophilic addition of water to acid/acyl chlorides,
subsequent elimination on hydrolysis to give the carboxylic acid and
hydrochloric acid (hydrogen chloride
(i)
+ H2O ===>
+ HCl
ethanoyl chloride +
water ===> ethanoic acid + hydrogen chloride (fuming in damp
air)
With excess water, you will form
an aqueous solution mixture of the carboxylic acid and
hydrochloric acid e.g.
CH3COCl(l)
+ 2H2O(l) ===> CH3COOH(aq)
+ H3O+(aq) + Cl-(aq)
(ii)
+ H2O ===>
+ HCl
pentanoyl chloride +
water ===> pentanoic acid + hydrogen chloride
(fuming in damp air)
or
CH3(CH2)3COCl(l) +
2H2O(l) ===> CH3(CH2)3COOH(aq)
+ H3O+(aq) + Cl-(aq)
(iii)
+
H2O ===>
+ HCl
benzoyl
chloride + water ===> /benzoic acid + hydrogen
chloride (fuming in damp air)
or
C6H5COCl(l) + 2H2O(l)
===> C6H5COOH(aq) +
H3O+(aq) + Cl-(aq)
The mechanism
for the hydrolysis of acid/acyl chlorides
e.g.
R–COCl + H2O
==> R–COOH + HCl (in damp air)
R–COCl + 2H2O ==> R–COOH + H3O+ +
Cl–
(with excess water)
The reaction is effectively overall a
nucleophilic substitution of -Cl by -OH (via H2O), but
the reaction has a nucleophilic
addition - elimination mechanism.
The organic
hydrolysis product is a carboxylic acid.
mechanism 14 –
nucleophilic addition–elimination reaction for the hydrolysis of an
acid/acyl
chloride
[mechanism
diagram 14 above] The mechanism involves several rearrangements
and assumes excess water.
Step
(1) The
>Cδ+=Oδ–
carbonyl is highly polarised and the positive carbon is attacked by
the nucleophilic water molecule, acting as an electron pair
donor.
The water adds to form a highly unstable ionic intermediate
via a C–O bond from the lone pair donation and simultaneously the
π
electron pair of the C=O
double bond moves onto the oxygen atom to give it a full negative
charge.
The water is the nucleophile - the electron pair
donor to a partially positive carbon atom.
Step
(2) The C–Cl bond pair
moves onto the chlorine atom which leaves as a chloride ion and
simultaneously one of the lone pairs of electrons from the negative
oxygen atom shifts back to complete (reform) the C=O carbonyl bond.
Step
(3)
A water molecule abstracts a proton
to form the oxonium ion and the carboxylic acid product.
If only
limited water is available, e.g. like when the acid chloride liquid
fumes in air, step (3) could be written as a chloride ion
removing the proton to form hydrogen chloride i.e.
RCOOH2+
+ Cl– ===> RCOOH + HCl
In the above mechanism diagram 78b, I've
kept the initial step the same - the nucleophile water attacking the δ+
carbon atom of the carbonyl group.
However, I've 'conflated' steps 2 and 3
from the general mechanism shown in mechanism diagram 14 into a single step
to summarise the 2nd phase of the mechanism.
In this simplified version of the
mechanism, the equivalent of H+ and Cl- leave as HCl
gas - the elimination part of the mechanism to yield ethanoic acid.
The HCl product would react with excess
water to yield H3O+ and Cl-.
TOP OF PAGE
and sub-index
6.7A.3
The reaction of
acid chlorides (acyl chlorides) with alcohols and phenols - esterification
(a) The reaction
acyl/acid chlorides with alcohols/phenols
Acid/acyl chlorides form
esters with alcohols and phenols, an example of an a acylation
reaction - a reaction where an R-C=O group is inserted into
another molecules
Acyl chloride
esterification by
nucleophilic addition–elimination reaction between an acid chloride and
an alcohol.
Because acid chlorides react
with water, the reaction is usually carried in anhydrous
conditions - all reagents and glassware should be dry.
The organic synthesis of esters from the reaction of acid/acyl chloride
with alcohols Unlike
the acid catalysed reversible esterification reaction between a
carboxylic acid and an alcohol with ~2/3rds yield, this is a
non-reversible esterification reaction giving very high yields. The acyl chloride
and alcohol usually readily react at room temperature, especially if
both are aliphatic.
Examples of
nucleophilic addition of an alcohol to acid/acyl chlorides,
followed by elimination to give the ester and
hydrogen chloride.
(i) ethanoyl chloride
+ ethanol ===> ethyl ethanoate + hydrogen chloride
+ CH3-CH2-OH ===>
+ HCl
With ethanoyl chloride, the reaction
is called ethanoylation - a particular
case of acylation, adding an CH3-C=O group to a molecule.
(ii) ethanoyl chloride + phenol
===> phenyl ethanoate + hydrogen chloride
+  ===>
+ HCl
(iii) pentanoyl chloride +
propan-1-ol ===> propyl pentanoate + hydrogen chloride
+
 ===>
+ HCl
The mechanism
for the formation of an ester from an alcohol and an acid/acyl chloride
e.g.
R–COCl + R'OH
===> R–COOR' + HCl
[see mechanism
15 below]
effectively overall a
nucleophilic substitution of -Cl by -OR (via ROH)
mechanism 15 –
nucleophilic addition–elimination reaction for the esterification of an
acyl chloride
[mechanism
15 above] The mechanism involves several rearrangements
and is essentially the same mechanism as for water, i.e. one of the H's
is replaced by R'.
Step
(1) The
>Cδ+=Oδ–
carbonyl is highly polarised and the positive carbon is attacked by
the nucleophilic alcohol molecule, acting as an electron pair
donor.
The alcohol adds to form a highly unstable ionic intermediate
via a C–O bond from the lone pair donation and simultaneously the
π
electron pair of the C=O
double bond moves onto the oxygen atom to give it a full negative
charge.
The alcohol is the nucleophile - the electron pair
donor to a partially positive carbon atom.
Step
(2) The C–Cl bond pair
moves onto the chlorine atom and leaves as a chloride ion and
simultaneously one of the lone pairs of electrons from the negative
oxygen atom shifts to complete (reform) the C=O carbonyl bond.
Step
(3) The previously formed
chloride ion abstracts a proton to form the oxonium ion and the
ester product.
The reaction is
effectively, overall, the substitution of the –Cl chlorine atom with
an –OR group where R' =alkyl or aryl.
In the above mechanism diagram 78c, I've
kept the initial step the same - the nucleophile ethanol attacking the δ+
carbon atom of the carbonyl group.
However, I've 'conflated' steps 2 and 3
from the general mechanism shown in mechanism diagram 15 into a single step
to summarise the 2nd phase of the mechanism to yield ethyl ethanoate.
In this simplified version of the
mechanism, the equivalent of H+ and Cl- leave as HCl
gas - the elimination part of the mechanism.
(b) The reaction of
aromatic acid chlorides with phenols
The acyl chloride
and alcohol usually readily react at room temperature, especially if
both are aliphatic.
Another example of an a acylation
reaction - a reaction where an R-C=O group is inserted into another
molecules
However, phenols may require the presence of aqueous
sodium hydroxide to facilitate the reaction, especially if the acyl
chloride itself is itself a less reactive (than aliphatic) aromatic
e.g. C6H5COCl.
The alkali generates a negative
phenoxide ion (e.g. C6H5O–
from phenol C6H5OH), which is a more powerful
nucleophile than the original neutral phenol molecule.
benzoyl chloride + phenol
===> phenyl benzoate + hydrochloric acid
+
===>
+ H+ + Cl-
Notes:
Phenols are distinguished
from alcohols by having the OH hydroxy group directly to the benzene ring.
You can use aqueous conditions
because benzoyl chloride is more stable in water than the aliphatic
acid chlorides like ethanoyl chloride.
If you shake benzoyl
chloride with phenol dissolved in sodium hydroxide, you get an immediate
white precipitate of the ester phenyl benzoate.
The reaction is particularly fast because
the sodium hydroxide reacts with phenol (a very weak acid) to form the negative phenate ion - a much more powerful nucleophile than a neutral
alcohol OR water molecules. The structure of sodium phenoxide is shown on
the left.
TOP OF PAGE
and sub-index
6.7A.4
The reaction of
acid chlorides (acyl chlorides) with
ammonia
Ammonia forms amides with
acid/acyl chlorides
The organic synthesis of amides from acid/acyl chlorides and
ammonia, and again, another example of an a acylation reaction -
a reaction where an R-C=O group is inserted into another
molecules Because acid chlorides
react with water, the reaction is usually carried in anhydrous
conditions - all reagents and glassware should be dry.
Examples of
nucleophilic addition of ammonia to acid/acyl chlorides, subsequent elimination gives the
primary amide and hydrogen
chloride/hydrochloric acid
(i) ethanoyl chloride
+ ammonia ==> ethanamide + hydrogen chloride
+ NH3 ===>
+ HCl
This equation illustrates the
formation of the primary aliphatic amide, ethanamide
(i) pentanoyl chloride
+ ammonia ==> pentanamide + hydrogen chloride
+ NH3 ===>
+ HCl
This equation illustrates the
formation of the primary aliphatic amide, pentanamide
(iii) benzoyl chloride + ammonia
===> benzamide + hydrogen chloride
+ NH3 ===>
+ HCl
This equation illustrates the
formation of the primary aromatic amide, benzamide
Amines form N-substituted
amides with acid/acyl chlorides
(iv) benzoyl chloride
+ phenylamine ===> N-phenylbenzamide +
hydrogen chloride
+
===>
+ HCl
This equation illustrates the
formation of the secondary aromatic amide, benzamide
(v) need aliphatic example
Table illustrating and
explaining the differences between primary, secondary and tertiary amines and
amides
The mechanism
for the formation of a primary amide from an acid/acyl chloride and ammonia
e.g.
R–COCl + 2NH3 ==> R–CONH2 + NH4+
+ Cl–
[see mechanism
16 below]
The reaction is effectively overall a
nucleophilic substitution of -Cl by -NH2 (via NH3)
R = alkyl or aryl
mechanism 16 –
nucleophilic addition–elimination reaction for an acyl chloride forming
an amide from ammonia
[mechanism
16 above] The mechanism involves several rearrangements
and assumes excess ammonia.
Step
(1) The
>Cδ+=Oδ–
carbonyl bond is highly polarised and the positive carbon is attacked
by the nucleophilic ammonia molecule, acting as an electron
pair donor.
The ammonia adds to form a highly unstable ionic
intermediate via a C–N bond from the lone pair donation and simultaneously the
π electron pair of the C=O
double bond moves onto the oxygen atom to give it a full negative
charge.
The ammonia is the nucleophile - the electron pair
donor to a partially positive carbon atom.
Step
(2) The C–Cl bond pair
moves onto the chlorine atom and leaves as a chloride ion and
simultaneously one of the lone pairs of electrons from the negative
oxygen atom shifts to complete (reform) the C=O carbonyl bond.
Step
(3) Another ammonia
molecule abstracts a proton to form the ammonium ion and the primary
amide product.
In the above mechanism diagram 78d, I've
kept the initial step the same - the nucleophile ammonia attacking the δ+
carbon atom of the carbonyl group.
The product is a primary amide called
ethanamide.
However, I've 'conflated' steps 2 and 3
from the general mechanism shown in mechanism diagram 16 into a single step
to summarise the 2nd phase of the mechanism.
In this simplified version of the
mechanism, the equivalent of H+ and Cl- leave as HCl
gas - the elimination part of the mechanism.
In reality, the HCl will combine
with excess ammonia to give ammonium chloride, NH4Cl.
TOP OF PAGE
and sub-index
6.7A.5
The reaction of
acid chlorides (acyl chlorides) with
a primary
amine
The organic synthesis of
secondary amides from acid/acyl chlorides reacting with a
primary amine, AND the
formation of tertiary amides by acid chlorides reacting with
secondary amines.
Another example of an a acylation reaction - a reaction
where an R-C=O group is inserted into another molecules
Table illustrating and
explaining the differences between primary, secondary and tertiary amines and
amides
Because acid chlorides react
with water, the reaction is usually carried in anhydrous
conditions - all reagents and glassware should be dry.
Examples of
nucleophilic addition of ammonia to acid/acyl chlorides, subsequent elimination gives the amide and hydrogen
chloride/hydrochloric acid
(i) ethanoyl chloride +
methylamine ===> N-methylethanamide + hydrogen chloride
+
===>
+ HCl
This illustrates the
formation of a secondary amide, N-methylethanamide
(ii) ethanoyl chloride +
phenylamine ===> N-phenylethanamide + hydrogen chloride
+
===>
+ HCl
These illustrates the
formation of a secondary amide, N-phenylethanamide
(iii) ethanoyl chloride +
dimethylamine ===> N,N-dimethylethanamide + hydrogen chloride
+
===>
+ HCl
+
===>
+ HCl
This illustrate the
formation of a tertiary amide, N,N-dimethylethanamide
In each case the
hydrogen chloride will react with excess amine to give a salt
Table illustrating and
explaining the differences between primary, secondary and tertiary amines and
amides
The mechanism
for the formation of a secondary amide from an acid/acyl chloride and
a primary amine
e.g.
R–COCl + 2R'NH2 ==> R–CONHR' +
RNH3+
+ Cl–
[see mechanism
17 below]
The reaction is effectively overall a
nucleophilic substitution of -Cl by -NHR' (via R'NH2) or
-NR'2 (via R'2NH).
R and R' = alkyl or aryl
mechanism 17 –
nucleophilic addition–elimination reaction for an acyl chloride forming
a secondary amide (N–substituted amide) from a primary amine
[mechanism
17 above] The mechanism involves several rearrangements
and assumes excess of the primary amine and is in principal no different
than the reaction with ammonia.
Step
(1) The
>Cδ+=Oδ–
carbonyl is highly polarised and the positive carbon is attacked by
the nucleophilic primary amine molecule, acting as an
electron pair donor.
The alcohol adds to form a highly unstable
ionic intermediate via a C–N bond from the lone pair donation and simultaneously the
π
electron pair of the C=O
double bond moves onto the oxygen atom to give it a full negative
charge.
Step
(2) The C–Cl bond pair
moves onto the chlorine atom and leaves as a chloride ion and
simultaneously one of the lone pairs of electrons from the negative
oxygen shifts to complete (reform) the C=O carbonyl bond.
Step
(3) Another primary
molecule abstracts a proton to form an alkylammonium ion and the
free secondary amide.
FURTHER COMMENTS
The reaction is
effectively, overall, the substitution of the –Cl chlorine atom with
an amine/amino (–NH2) group or a substituted amide (–NHR)
group.
In the above mechanism diagram 78e, I've
kept the initial step the same - the nucleophile ethylamine attacking the δ+
carbon atom of the carbonyl group.
The product is a secondary amide
called N-ethylethanamide.
However, I've 'conflated' steps 2 and 3
from the general mechanism shown in mechanism diagram 17 into a single step
to summarise the 2nd phase of the mechanism.
In this simplified version of the
mechanism, the equivalent of H+ and Cl- leave as HCl
gas - the elimination part of the mechanism.
The HCl product would actually react
with excess amine to yield CH3CH2NH3+Cl-
in this case.
TOP OF PAGE
and sub-index
Table
illustrating and explaining difference between primary, secondary
and tertiary amines and amides
| Functional group |
PRIMARY |
SECONDARY |
TERTIARY |
Comments |
| AMINES |
 |
 |
 |
There are
prim/sec/tert aliphatic (alkyl) or aromatic (aryl) amines. |
| Aliphatic amine examples |
ethylamine |
ethylmethylamine |
triethylamine |
Aliphatic amine examples.
The N of the amine group NOT directly attached to a
benzene ring |
| Aromatic amine examples |
phenylamine |
diphenylamine |
N,N-diethylphenylamine |
Aromatic amine examples
The N of the amine group directly attached to a
benzene ring. |
| Acyl or acid AMIDES |
 |
 |
 |
The amide group
comprises an amine group attached to the C of a C=O carbonyl group,
which gives it its own unique chemistry i.e. its neither an amine,
aldehyde or ketone! |
| Examples of amides |
ethanamide |
N-methylbenzamide |
N,N-dimethylethanamide |
Examples of amides
both aliphatic and aromatic |
6.7.6
The
reduction of acid/acyl chlorides - conversion to primary alcohol
Acyl/acid chlorides, like carboxylic
acids esters, are reduced by the powerful reducing agent lithium
tetrahydridoaluminate(III), LiAlH4, giving the corresponding
primary alcohol.
LiAlH4 reacts with water and
ethanol, therefore the reaction must be carried out in a dry
inert solvent e.g. ethoxyethane ('ether') and NOT water or ethanol.
The general equation is:
RCOCl + 4[H] ===>
RCH2OH + HCl
The LiAlH4 effectively
generates the equivalent of a hydride ion (:H-)
which is a powerful nucleophile - lone pair of electrons donor.
Examples
(i) pentanoyl chloride + hydrogen ===>
pentan-1-ol
+ 4H ===>
+ HCl
(ii) benzoyl chloride + hydrogen ===>
phenylmethanol ('benzyl alcohol')
+ 4[H] ===>
+ HCl
TOP OF PAGE
and sub-index
6.7.7 The reaction of acyl/acid chlorides with
aromatic hydrocarbons - ketone formation
Acid chlorides will react with aromatic hydrocarbons like
benzene and methylbenzene to form ketones.
This is an example of a Friedel-Crafts acylation reaction
The reaction must be carried out in dry conditions using an
aluminium chloride catalyst.
You reflux the mixture of the acid chloride, aromatic
hydrocarbon and aluminium chloride in a fume cupboard.
Fumes of hydrogen chloride are given off.
Examples
(i) benzene + ethanoyl chloride == AlCl3
==> 1-phenylethanone + hydrogen chloride
+
===>
+ HCl
The IUPAC preferred name is 1-Phenylethan-1-one.
The product is also called 'acetophenone' 'methyl
phenyl ketone' or just 'MEK' in the chemical industry!
You might describe the product is half an aliphatic and
half an aromatic ketone.
(ii) benzene + benzoyl chloride == AlCl3
==> 1-phenylmethanone + hydrogen chloride
+
===>
+ HCl
The product is also called 'diphenyl ketone'.
You can describe this product as a completely aromatic
ketone.
Mechanism of acylation to give aromatic
ketones
[Friedel-Crafts reaction]
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