All right let's look at benzene side chain reactions. So most reactions on a benzene
substituent are going to be identical to their respective reactions elsewhere that we've studied
with a rather it's alkene reactions or whatnot but the proximity of the aromatic system does
change reactivity in some cases and so we want to look at a few of those some are the same some are
going to be a little bit different here's some common ways that we can exploit the substituents
on a benzene for reactivity. All right so I've got this rather nasty looking benzene derivative here
to show the difference in these what are called decarbon- decarbonylation reactions means removal
of the carbonyl from not just benzene but any compound and we have here if we were to take off
these groups all three of these reactions would do the same thing so the first reaction here's
the Wolff-Kishner and it's going to remove that carbonyl to form that primary alkyl-substituted
benzene. Catalytic reductions one of our come one of our reactions that does change when the
carbonyl is right next to benzene instead of forming an alcohol and needing Raney nickel to
do this reduction it forms just the alkyl group removes the carbonyl also we have the Mozingo
reaction where we make a thioacetal in step one and then in step two the thioacetal is reduced
and removed entirely and replaced with hydrogen so a substitution type reaction there for that
thioacetal. We get the same thing these primary alkyl substituted benzenes it's good to have a
way to get to those because as we've talked about before the Friedel-Crafts alkylation
would cause a rearrangement
in this particular one to an isopropyl benzene okay so it would rearrange in the process of
reaction so Wolff-Kishner all three of these are going to avoid that occurring so the way we
would get there is we would form this substituted benzene, the acyl substituted benzene, by doing the
Friedel-Crafts acylation instead. Aqueous workup to remove the Lewis acid and we get our carbonyl
substituted benzene there our ketobenzene. Now from there we do the Wolff-Kishner one
of these three reactions to remove the carbonyl. Well suppose these other groups are in place and
they're there because they pose a particular difficulty for the other two ways silyl ether
so this is the protection so TMS here stands for trimethylsilyl they are unstable to acid
and so in acidic conditions with the Mozingo could potentially cause that TMS group to be
removed and catalytic hydrogenation with either palladium on carbon or Raney nickel would cause
a problem where this alkene group would be reduced but with our Wolff-Kishner there both of those
functional groups are rock stable to base and so we maintain those two groups throughout the
reaction so this little chemoselectivity practice here with three different ways of accomplishing
the same thing but in the presence of other functional groups you can have complications okay
so making sure that we note that here as why we have different options for this process all
right moving on another way we can make these carbon-carbon bonds to benzene is with coupling
reactions so we can make our bromo and chloro benzenes from halogenation of benzene with iron (III)
bromide catalyst or iron (III) chloride for that matter and we can react benzene, benzyl halides
here, with- or halo benzenes- with our alkyl borane so with the Suzuki we can make an alkyl borane
that is either primary alkyl we can use a alkenyl borane so that would look something
like this trans alkenyl's are our option there and we can also do leave that there alkenyl and
we can also do an aryl borane so the aryl borane is made from bromobenzene treating
it with lithium first to make the aryl lithium and then reaction with a
trialkoxy borane would form this reagent which can be used to couple to an alkyl or an alkenyl halide
okay so these halides that can be coupled to the coupling
partner aryl is one possibility but any sp2
whether it's cis or trans can be coupled to Suzuki reagents okay so again review
our alkyl our organometallic reactions video for the full treatment of those but for these
reactions that we just drew again we can make the aryl borane from the second reaction but
we can also make a primary alkyl substituted benzene for carbons there from the alkyl
borane okay so same thing no rearrangement we do it with a coupling reaction instead
all right well Gilman's also a possibility for coupling Gilman reagents can couple to
aryl bromides they can couple to primary alkyl they can couple to alkenyl bromides
and chlorides okay so again or iodines for that matter so they can couple to all three
of those we get the same product here with our Gilman coupling as we did with Suzuki
1-2-3-4 carbons in that group and we could do primary alkyl with our Gilman reagent like we see
here we can do alkenyl or we can make an aryl Gilman reagent like we see the recipe for below
with an excess of that bromide or two equivalents of that bromide our aryl bromide there
we'd be able to get our Gilman reagent to use with its coupling partner okay another way to
do that. All right so let's look at halogenation so typically we have best results with
tertiary halides we've said before but when benzene is involved it increases the reactivity
of this benzyl position so the carbon right next to a benzene is a benzyl position and that benzyl
position is highly susceptible to bromination in fact we're going to see nearly quantitative
hundred percent yield of this benzyl brominated reaction product okay so we don't need NBS and
peroxide and heat but we can use NBS, peroxide, and heat to make the exact same compound we
can think of this as allylic benzylic is like allylic in that it's next door to an sp2 system
so we just substitute a hydrogen for a bromine radical bromination benzylic bromination here
like allylic from our radical studies. Well once we've got a halide in that position SN2 and E2
works the same as before this is just review with a secondary halide like we have here could be a
tertiary could be a primary so we have different rules for what art that guides us through SN2/ E2
like we studied before, but with a secondary halide with a good nucleophile in a weak base we're gonna
see SN2 as the major product and so here's a good way to make an ester use a carboxylate as
a nucleophile it's a good nucleophile weak base pKa less than 15 on those weak bases
good nucleophiles we have a list that we learn back to a substitution-elimination so we get
our substitution there. Well if we have a good nucleophile or poor nucleophile in a strong
base with a secondary halide we are going to have elimination to the Zaitsev product be our number one
reaction path in that situation. To make that yield a little better benzene tends to favor elimination
anyway but we could make that into a methoxide to ensure that at least we're bulky enough to really
suppress SN2 there, t-butoxide as well. All right, suppose we have reductions here with catalytic
hydrogenation. Alkenes, carbonyls, and nitro groups are all going to be reduced with palladium on
carbon reduction hydrogen atmosphere so this is a little bit different benzaldehyde would reduce
straight to toluene okay if it was just a normal ketone we would require hydrogen and Raney nickel
ketone or aldehyde for that matter and it would make an alcohol product and instead here with
benzene's it's super reactive goes all the way to an alkyl group alright palladium on carbon
does the same as we're used to with alkenes attached directly to the benzene anything
off the benzene follows that's more than one carbon away not on that benzylic position would
reduces we're used to seeing it from before. Nitro groups are also reduced to anilines
okay so nomenclature here's benzaldehyde here styrene here's nitrobenzene and then we are
reduced to toluene, ethylbenzene, and aniline as our products here okay looking at nitriles we need
Raney nickel still they're less reactive than our typical groups so we still stick with Raney nickel
here what do we get? We get a primary amine from that nitrile you get a CH2 from the carbon side
get an NH2 from the nitrogen side. Benzene itself can be reduced so this isn't a side chain reaction
we'll throw this in here but only under extreme conditions so we've got high temperature and 25
atmospheres typically a lot of these hydrogenations are done at elevated atmospheres of hydrogen this
is just one recipe that gets it done nickel, zero catalyst there, low valent nickel shiny stuff
powder form probably gets this done to reduce to a cyclohexane okay but extreme conditions lots
of ways to do some of these reductions we're just giving you one way for our purposes here
okay what if we're doing oxidation so here's a here's a complicated looking thing here so I
did this to just illustrate what happens if it's a methyl, if it's a primary, if it's a secondary,
or if it's excuse me a methyl group you know if we're ignoring we'll go ahead and call this
a primary since one other carbon, ehh it's a methyl, it's still a methyl here though it approximates
a secondary position here it approximates a tertiary here it approximates a quaternary
position attached to benzene so there are no hydrogens on this last one the quaternary alright
anything with a hydrogen allows the oxidation to proceed all the way to a carboxylic acid
and it clips off any additional hydrogen's that may be present okay so this extra hydrogen here
here and here they're all clipped off replaced by a carboxylic acid where the carbon that's
directly attached in that benzylic position is located there are no hydrogens then there's
no oxidation that will occur but chromic acid is very reactive and non-selective with alkyl
groups on benzene so you got to be careful when we use it. If we want a milder reagent that's not
going to affect we can even draw in a methyl down here it's not going to affect our other
groups well we can use bleach, we can use a sodium hypochlorite that is, we can use
PCC we can use Swern oxidation to do a mild oxidation like we would normally expect for
a benzene compound ok so general overview more reactions out there but this is a good overview
of things we can do to the benzylic position things that stay the same things that change.