hemist C ry 3B Lecture 21 T uesday April 14t h , 2009
Carboxylic acids that have a ketone or another
carboxylic acid in the beta position can undergo
decarboxylation with heat. This reaction will not
go unless you heat it up. 2 reagents were
i nt roduced to reduce carbonyls: NaBH4, and
L iAl H4. They both look the same but 2 were
i nt roduced for a reason. LiAlH4 does some things
t hat NaBH4 wont do. If you take a carboxy group
and add LiAlH4 followed by an acidic work up,
t hen you will reduce the carboxy group all the
way down to a primary alcohol. If you t ry to do
t his with NaBH4 and an alcohol, you will just
end up with the carboxylate.
There is a tentative mechanism for L iAlH4 which
is not very well understood but rational. The very
f irst thing that happens when you add LiAlH4 to
a carboxylic acid is that it deprotonates it. I t
r eleases Hydrogen gas and you basically end up
w ith Aluminum t r i hydride. Lewis base lewis
acid. we have a carbonyl and we can add a
n ucleophile: the aluminum still has hydrogens
w hich are delta - . We get an aldehyde out. Al-O
bonds are very strong but B-O bonds are not
nearly as strong. So when Boron gets to that
point, nothing else happens. We get an aldehyde
i nstead of an alcohol; if we form an aldehyde in
t he presence of LiAlH4 or another hydride
source, i t will not hang around. The aldehyde will
be reduced further by more LiAlH4.
Deuterium will stick to the carbons. L iAlH4
r educes carboxylic acids to a primary alcohol
a fter i t is worked up with acid and the two
hydrogens or deuteriums come from the LiAlH4.
We have a keto acid with LiAlH4 which also
r educes the keto group to a secondary alcohol. If
we reacted this with NaBH4 however, in
methanol, and H3O+, we will end up with the
carboxylic acid untouched. They both reduce
ketones but LiAlH4 also reduces carboxy groups.
Carboxylic acid derivatives: Nomenclature of
carboxylic acid derivatives: X refers to halogens
so these are the acid halides. This molecule is
acetyl chloride. The acetyl group is circled. In
I UPAC, it is based on carboxylic acid chemistry
so we have 2 carbons to make it ethanoic acid but
i t is an ethanoic acid derivative. We are going to
d rop the ic acid suffix and we will add a yl
followed by the name of the halogen. 4 carbons
r efers to butanoyl bromide. Benzoic acid will
become benzoil acid. Acid halides are good
r eagents for adding this type of group (acetyl
g roup) into a variety of situations. Then there
a re the acid anhydrides. The name comes from
t he fact that if you take two carboxylic acids and
heat them up with the r ight catalysts, you can
b ring them together and lose water and make a
bond between the two. The most common
anhydride is acetic anhydride. The I UPAC name
for i t is ethanoic anhydride. Benzoic anhydride.
B ut what if we have an unsymmetrical
anhydride? We have to figure out the parent
names of the carboxylic acid: benzoic acid and
butanoic acid. This molecule is then benzoic
butanoic anhydride. We lost a water!
Esters: R cannot be an H otherwise it would be a
carboxylic acid. The most common ester is ethyl
acetate. The acetate function is the conjugate
base of acetic acid. The I UPAC name is ethyl
ethanoate; i t is not ethanoic acid because i ts not
an acid anymore. Take ethanoic acid and take the
ic acid and replace i t with an ate. I t is the
conjugate base of ethanoic acid. This next
molecule is methyl benzoate. The other molecule
is butyl butanoate. For esters, besides being
acyclic you can also have a cyclic ester. These are
commonly called lactones as a class of molecules.
Amides. The conjugate bases of amines are
amides. A common name for this amide is
acetamide. The I UPAC name is ethanamide.
Benzamide is shown too. That is the name when
you have only hydrogens. But sometimes there is
something attached to Ni t rogen that is not a
hydrogen. I ts very common to have amides with
t hings attached to them besides only hydrogens.
We have a benzamide derivative and it is called
N -Methylbenzamide. We also have N-ethyl-Nmethylbutanamide. If two of the same thing is
a ttached to the N, then you get a molecule like
N ,N-dipropyl hexanamide. We can also have
cyclic amides: they are mostly known as lactams.
T hese are imides or the nit rogen analog of
anhydrides. This is Phthalimide, and one we are
a lready familiar with is NBS or NBromosuccinimide. This next molecule is also
considered a carboxylic acid derivative and it is
t he nit r ile function even though i t is a cyano
g roup.
Synthesis esters: of you can take a carboxylic acid
p lus an alcohol and you will get an ester plus
water. K equilibrium for this reaction is about 1.
Youre replacing an OH with an OEt, and you are
r eplacing the ethyl with an H; it is almost
t hermoneutral. Lets do a mechanism for this; but
we should keep in mind that if we want to make
an ester if Keq is 1, we could remove water or
have excess ethanol/acetic acid. We would use
excess alcohol. I t is just LeChatliers principle. If
your alcohol is not super expensive and very
soluble in water, then you want to use an excess
of alcohol; we usually use the alcohol as our
solvent in these types of reactions. Lets go over
t he mechanism now: we have an acid like HCl. If
you look at what is going on, we are exchanging
t he OH group for an OEt group so the OEt has to
add to the carbonyl. We cant really do an SN2
r eaction because i t is an sp2 hybridized carbon.
T he other possibility is protonating the hydroxyl
g roup to lose water and generate a carbocation
and then bring ethanol in? We protonated the
hydroxyl group because i t looked like an alcohol
but we cant do an sn2. But then cant we have
t he alcohol fall off? That will create the Acylium
ion. But that is not what happens. Where does
t he proton go? We have 2 oxygens. We must
r esort back to resonance structures. How did we
k now to protonate the Oxygen that we
p rotonated? The oxygen retains a minus charge
w ith the resonance structures. When we add acid
t o carboxylic acids or their derivatives i t will
p rotonate the carbonyl. We have a symmetrical
i ntermediate where we have 2 OH groups that
we cant tell the difference between anymore. The
goal of the reaction is to lose water. We simply
need to protonate one of the hydroxyl groups, lose
water, and then we need something to pull off the
hydrogen on the other hydroxyl group like
Chloride. That is acid catalyzed esterification of
a carboxylic acid. This has 2 steps: addition and
elimination. Base catalyzed formation doesnt
work but why? The very fi rst thing that happens
is an acid base reaction between the ethoxide and
t he carboxylic acid with K equilibrium of 10^12 =
10^16-4. You cant do anything more with this. If
you want to have ethoxide add to this species, you
a re having a negatively charged nucleophile
coming to a negatively charged electrophile.
Carboxylates are not electrophiles so this
wouldnt work.
How about the reverse reaction? I t is called an
ester hydrolysis. I t is the exact reverse
mechanism as the mechanism shown previously.
You will protonate the carbonyl first. Then you
w ill add water. Can we do base catalyzed ester
hydrolysis? Yes. We can hydrolyze esters under
acidic conditions. The base is stoichiometrically
consumed in this reaction. The base will attack
t he carbonyl. We have another K eq of 10^12 and
i t is an i r reversible reaction and i t is an acid base
r eaction. Base is consumed in this hydrolysis. We
need one equivalent of hydroxide to one
equivalent of ester.
If I want to hydrolyze an ester, I just add aqeous
acid and you get benzoic acid. if I want to
hydrolyze i t under basic conditions I have to add
hydroxide as step 1, step 2 will be H3O+, and if
you want this then you have to protonate the
carboxylate when i t was all done. If we left out
s tep 2, then the carboxylate is the final product.
we have a methyl ester and put i t in ethanol so it
is our solvent. We are putting in an acid catalyst
as well so what we are going to get is the ethyl
ester. The mechanism is identical to that of
esters from carboxylic acids. If we had just oen
equivalent of alcohol and one equivalent of ester
t hen K equilibrium would be one. If we want to
d rive this reaction to the r ight we need an excess
of ester or alcohol. We can also catalyze this
r eaction under basic conditions because there are
no protons to pull off. There are no carboxy
p rotons that are formed. This is known as
t ransesterification. Were changing one ester into
another ester.
Now we have an ester with an alcohol built in.
A dding in an acid catalyst to get an
i ntramolecular cycliczation to generate a lactone.
T his is no different from making a hemiacetal or
hemiketal. Making lactones is the same as
m aking esters because they are just cyclic esters.
We have this lactone known as crystal violet
l actone. When you add a source of protons, the
cyclic pentane opens up to a carbocation. There is
no water present here so I dont have anything
adding to the carbonyl but I need an acid
catalyst.