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hey it's professor Dave let's talk about carboxylic acids and derivatives
so we've looked at a lot of chemistry involving carboxylic acids but now let's
do a little bit of a comprehensive survey of carboxylic acids and their
derivatives so obviously you want to remember what a carboxylic acid is that
is this here so that's abbreviated COOH or a "COOH" group and so we know that we
have a carbonyl next to an OH that is a carboxylic acid and as we
replace OH with other groups we can start to get what we call derivatives of
carboxylic acids so if we take away the OH and we place a chlorine atom that's
going to be called an acid chloride so that has some interesting utility then
we can have something called an acid anhydride this is pretty interesting
we've got a carbonyl an oxygen and then another carbonyl and we have alkyl on
both sides, R prime merely indicates that these need not be
identical alkyl groups they could be identical they could be different alkyl
groups so that's an acid anhydride and then of course we can get an ester which
is carbonyl and then OR so it's different from a carboxylic acid because
instead of a proton we've got more alkyl on the other side of that oxygen so this
is no longer an acid there's no acidic proton there then in addition we can
have an amide and so sorry this is not amine this is amide so we can have an
amide where we have a carbonyl and then nitrogen so instead of an oxygen there
we've got carbonyl nitrogen and this can be a primary secondary or tertiary and
that if we have NH2 so we just have two hydrogens that's going to be primary if
one of those hydrogens is replaced with some alkyl group that's going to be a
secondary and then if we've got no hydrogens but instead two more alkyl
which can be the same or different right we've got R prime R double prime
then that can be a tertiary amide so those are some of the derivatives we're
gonna be talking about carboxylic acids themselves are very common there's a lot
of naturally occurring carboxylic acids so for example acetic acid is what gives
vinegar its sour taste carboxylic acids with short chains are found in dairy
products so for example the buttery taste of butter comes from butyric acid
and goat cheese derives its strong taste from a high level of caproic acid
long-chain fatty acids like palmitic acids are components of phospholipids
which are the constituents of biological bilayer membranes and so because these
establish the borders of what is inside a cell and what is outside without these
long-chain saturated carboxylic acids life could not exist so now let's go
over a few properties of carboxylic acids so here we've got acetic acid and
as we can imagine a carboxylic acid is an acid as the name suggests but they're
pretty weakly acidic so acetic acid is got a pKa of around 4.8 so this will
largely dissociate in water but it's it's still not especially acidic however
we can enhance the acidity by adding electron withdrawing groups on on really
any position but especially alpha to the carbonyl so here's trifluoroacetic acid
so we've got three fluorines there and this has got a pKa of 0.25 so that's
already several orders of magnitude more acidic than acetic acid so and of course
we understand why right what if this we know that the acidity of a molecule is
proportional to the stability of its conjugate base and so if we lose that
proton we've got that negative charge and anything that's gonna stabilize that
negative charge will stabilize the conjugate base and therefore increase
the acidity of a molecule so we've got fluorines that are withdrawing electron
density away that are stabilizing that anion and so that's why these increase
the acidity of the molecule and so we can see we don't always see this we can
see longer chain carboxylic acids and we can see halogens or other withdrawing
groups in different positions and I do have a practice problem that compares
the acidity of various various carboxylic acids so that may be of use
to you but now that we've talked about some of the
basic properties of carboxylic acids let's go ahead and check out some
applications so let's look at some things that we can do with carboxylic
acids so obviously there's the potential for chemistry at the carbonyl carbon but
oftentimes we need to activate that first so one thing we can do is react
carboxylic acid with thionyl chloride and so what's going to happen is first
we're going to evolve HCl and we're going to get to this intermediate here
and then we're gonna evolve SO2 and we're gonna get to the acid chloride so
an acid chloride is a more activated compound these are great from acid
chlorides we can do a lot of different things so with an acid chloride one
thing we can do this is this is a lot more susceptible to nucleophilic attack
so we can have an alcohol attack so let's have that go ahead and attack here
and that is going to take us from this sp2 center to an sp3 hybridized
intermediate so now we're in sp3 and so we've got this zwitterionic intermediate
here we've got O minus and O plus and some base is going to go ahead and grab this
proton now this could be some amine that's acting as a proton sponge is most
likely the case or something in solvent but so a base is going to grab that and
we get to this situation here and then this is gonna go ahead and reform the
carbonyl but now we'll kick off chlorine and so what we've done is we've
generated an ester so we've seen how we can go from a carboxylic acid to an acid
chloride to an ester so this is a useful technique for synthesizing esters now we
do have to be aware that esters are susceptible to hydrolysis especially in
basic conditions so we have to be careful this can definitely hydrolyze
and go right back to the carboxylic acid which is a technique that we could do
deliberately as well and so that's a little bit of chemistry involving
carboxylic acids - acid chloride - ester we can also do chemistry with an
hydrides and so we may have an anhydride now this could be a
symmetrical anhydride if this was R just a regular R implying that the
alkyl groups were identical that would be a symmetrical anhydride we can also
have an asymmetrical anhydride so that's with R prime where we have different
groups here now that means that a nucleophile is going to be able to
attack either carbons so we could attack here but we also could attack here so
either way we're gonna pop that pi bond up onto an oxygen and when it comes back
down we're gonna kick off the rest of the molecule right that's a very stable
leaving group because of the resonance up the rest of the molecule there so
that's that's that's why this is much more receptive to nucleophilic attack
than a carboxylic acid right that's not going to be that good of a
leaving group of course but this whole portion of molecule is because of that
resonance stabilization so with an anhydride a nucleophile can attack one
of these carbons so we pop that pi bond up comes back down kicks that off or it
can do that here pop this up and when it comes back down kick all this off so we
have two possibilities here we can have the nucleophile on this carbon over here
with this carboxylate or we can have the opposite situation right if the
nucleophile attacked here instead then we would get this product and this
carboxylate so anhydride chemistry is very common we can do we can actually
use very clever approaches where electronics something about the
electronics of the substrate will direct the nucleophile to one carbonyl over the
other so we have different ways of utilizing this in synthetic chemistry to
get a desired product one over the other and then we also want to be aware of how
we can possibly get amides and so one example is this Schotten-Baumann
amidation and so this is actually a very old reaction it was discovered by these
guys that we could take an acid chloride and then if we add an amine in some
organic solvent and then we're running this in aqueous sodium hydroxide we will
go from here all the way to the amat and so this is some old chemistry in pretty
important chemistry as amides are very important molecule so that's called the
Schotten-Baumann amidation.
so let's look at one more thing let's say that we want to synthesize some
ketones from some carboxylic acid derivatives so say we want to go from an
ester or an acid chloride to a ketone now we may not be immediately sure of
how to do this remember that we we we've talked a lot about grignard reactions
but we know that starting with an ester if we use some grignard reagent we're
not going to be able to stop at the ketone right we know that one equivalent
is gonna add it's gonna kick off the alkoxy group but then another equivalent
is gonna is gonna go ahead and attack and we'll get we'll get two equivalents
of that alkyl group on there so that's not really gonna work but we have some
other ways to do this we have some other ways to get ketones and so one way
involves using something called a Weinreb amide so this is a Weinreb amide
notice that it is an amide and we do have this methoxy group right here we
have N attached to OCH3 and so what we can do is we can actually use a
grignard reagent with this and so the grignard da the grignard reagent is
going to attack at the carbonyl carbon as we would expect and then look at this
add up to that we get as an intermediate this is actually quite stable because we
have this chelation going on we have MgCl interacting with both of these
oxygen atoms and so now what's going to happen is once we hydrolyze this we're
gonna get to this situation here and when we protonate this so this this
nitrogen can actually protonate and that is going to cause an unstable situation
where this is actually going to snap shut so this proton can go and we're
gonna snap that shut and we can kick off the rest of this group here and so
that's gonna give us our ketone so we got that alkyl group on there from that
from the grignard reagent and then this was stable because of this chelation but
then once that nitrogen was sufficiently protonated this all just snaps shut not
and that one away so that's what got us our our ketone so there's one way that
we're gonna get a ketone from an amide and here's another way actually we can
do this another way too let's say that we've got an amide here we can react
this with thionyl chloride so let's just let's put this here and this will go and
attack sulfur and so that's going to get us to this situation so notice that
oxygen attacked sulfur and then that kicked off a chlorine and that chlorine
grabbed one of those extra hydrogens so we've got HCl evolving as a by-product
and now this is an interesting situation what if we do this so let's have this
lone pair attack here that is going to sever this carbon oxygen bond which is
going to go and which is going to go right there and then let's have this
chloride grab that proton so and then I suppose that would probably go right
there so this is an interesting shuffling of electron so that's going to
get us to a nitrile right because this nitrogen put the lone pair they're
forming that third bond we've now got a triple bond between the carbon and
nitrogen we've lost that carbon oxygen bond that went over here and attacked
sulfur so we're evolving SO2 and we're also evolving HCl so we've got these
byproducts but we get a nitrile so recall that a nitrile is CN any CN
triple bond so this is a nitrile functional group and now we can do
grignard again so a grignard reagent actually can attack the carbon on a
nitrile just like it would attack a carbonyl it actually behaves very
similarly and so that's gonna pop this up there and we've got N- interacting
with the MgCl in the intermediate so that behaved very similarly to other
examples of grignards that we would have seen and then hydrolysis is going to
take this all the way to the ketone and so there is another way that we have to
synthesize ketones from an 'its so hopefully now we've gone through a lot
of different derivatives of carboxylic acids and some of their synthetic applications.