[shch0730]

I preferably want a practical way to do this not a way that would work on paper.

I tried to get a NH2 group on benzene first:

~Benzene + HNO3/H2SO4 ---> Benzene-NO2

~convert that to an amine by hydrogenation H2/Pd

But then I couldnt use a Friedel Craft Acylation to add an aldehyde to the ring because the aryl amine will react with the acyl chloride and make the reaction extremely slow:

Benzene-NH2 + CHOCl ---> Benzene-NHCHO

but on the other hand, that could be the protecting group to the amine. Is there any other way to add a carboxylic acid onto the benzene ring after that step?

any thought is highly appreciated. Thank you.

[sjb]

I preferably want a practical way to do this not a way that would work on paper.

I tried to get a NH2 group on benzene first:

~Benzene + HNO3/H2SO4 ---> Benzene-NO2

~convert that to an amine by hydrogenation H2/Pd

But then I couldnt use a Friedel Craft Acylation to add an aldehyde to the ring because the aryl amine will react with the acyl chloride and make the reaction extremely slow:

Benzene-NH2 + CHOCl ---> Benzene-NHCHO

but on the other hand, that could be the protecting group to the amine. Is there any other way to add a carboxylic acid onto the benzene ring after that step?

any thought is highly appreciated. Thank you.

Why not try the other way around, putting an acid functionality on first?

[nox]

Benzene + I2/HNO3 or Benzene + ICl (source of I+) ---> Iodobenzene

Iodobenzene + HNO3/H2SO4 ---> p-iodonitrobenzene (+ some ortho isomer)

p-iodonitrobenzene + BuLi/-78 deg (Li-halogen exchange) then quench with CO2 ---> p-nitrobenzoic acid

p-nitrobenzoic acid + H2/Pd/C or SnCl2 or H2/Pt/C(vanadium doped) ---> p-aminobenzoic acid

[Doc Oc]

I preferably want a practical way to do this not a way that would work on paper.

I tried to get a NH2 group on benzene first:

~Benzene + HNO3/H2SO4 ---> Benzene-NO2

~convert that to an amine by hydrogenation H2/Pd

But then I couldnt use a Friedel Craft Acylation to add an aldehyde to the ring because the aryl amine will react with the acyl chloride and make the reaction extremely slow:

Benzene-NH2 + CHOCl ---> Benzene-NHCHO

but on the other hand, that could be the protecting group to the amine. Is there any other way to add a carboxylic acid onto the benzene ring after that step?

any thought is highly appreciated. Thank you.

Why not try the other way around, putting an acid functionality on first?

The acid would be meta-directing.

Nox's route is the one I would've suggested, although we didn't learn teach Li/halide exchange when I was a TA so we taught Grignard (same overall reaction though so either is fine).

[sjb]

Why not try the other way around, putting an acid functionality on first?

The acid would be meta-directing.

Nox's route is the one I would've suggested, although we didn't learn teach Li/halide exchange when I was a TA so we taught Grignard (same overall reaction though so either is fine).

But of course. I didn't necessarily mean install a CO₂H directly, there are other functionalities that you can convert into the acid that are o/p directing

[orgstudy]

well you can add amine then protect it by  making C6H5-NH-COCH3
then adding NO2 at para ... make it NH2 ... Use denzene diazonium rxn to get Br there . then add Mg in presence of ether
you get --- BrMg-C6H4-NH-COCH3 ---

... then use CO2 and to remoe protecting group ... use just H+/H2O

this is a long method but it ensure least ammount of isomers!!!!

[jake.n]

You could also do it in the following order without the use of a grignard:

FC alkylation -> alkylbenzene
nitration -> p-nitrobenzene
benzyllic oxidation -> p-nitrobenzoic acid
nitro reduction -> p-aminobenzoic acid

However the halogenation route would probably be easier to control than the alkylation.  With the right reaction time/temp and a bulky alkyl group you could probably make this work, though.

[orgstudy]

can you tell some regents which can reduce only nitro but not benzoic acid?

[jake.n]

Catalytic hydrogenation, as Nox pointed out above.

[orgstudy]

but catalitic hydrogenation will also reduce the benzene ring

[movies]

but catalitic hydrogenation will also reduce the benzene ring

Only at very high pressure & temperature.  Generally, a nitroaromatic can be reduced to an aniline in a few hours under 1 atm of H₂ with Pd/C.

There are actually a lot of other alternative reductants that can be used for this as the aromatic nitro group is on of the easiest groups to reduce.  This can be handy if you have an alkene somewhere else in the molecule.


On another note, in the original post a F–C acylation with CHOCl was proposed.  This is not a feasible reaction since CHOCl is not a stable molecule (I believe it rapidly decomposes to HCl and CO).

[nox]

Hydrogenation with vanadium doped Pt/C will selectively reduce nitro groups in the presence of alkenes.

[orgstudy]

and i remember now .. also Sn/HCl