[dubz]

hi guys! it's me again..i haven't read about synthesis pathways but there's a problem here on a prob set that tells me to do a synthesis pathway starting from benzene to produce 3-chloro-5-methylaniline..how do you this this stuff?  thanks..

[kriggy]

Try to think from the other side. How can you do aniline from benzene, how clorbenzen how toluene?

[dubz]

well, i initially thought of that but i'm not sure if i read anything about this one..but i dont know what kind of reagents to use..sorry i'm still a student =(

[kamiyu]

I am not pretty sure about the following route:

1. nitration, HNO3/H2SO4==> get nitrobenzene

2. chlorination, AlCl3/Cl2 ==> get meta chloro

3. bromination, FeBr3/Br2 ==> get meta bromo

4. lithiation/electrophile external quench, n-BuLi/CH3I ==> replace Br by CH3 (But this is arguable because n-Butyllithium usually not applied to nitro-sub. aromatics)

You may change this step to Grignard.

5. Reduction of NO2, tons of methods available such as H2/Pd, hydrazine hydrate with Pd/C....

[orgopete]

When the substitution pattern is 1,3,5 and a methyl group is present, this suggests a different substitution strategy must be used. Although it can seem plausible that one could introduce a methyl group by a Friedel-Crafts reaction on nitrobenzene, this reaction fails. A FC reaction fails with deactivating groups on a benzene ring. A solution is to introduce an activating group that must be removed in the end. I think this problem requires this strategy. Most textbooks include some examples.

[zsinger]

I am not pretty sure about the following route:

1. nitration, HNO3/H2SO4==> get nitrobenzene

2. chlorination, AlCl3/Cl2 ==> get meta chloro

3. bromination, FeBr3/Br2 ==> get meta bromo

4. lithiation/electrophile external quench, n-BuLi/CH3I ==> replace Br by CH3 (But this is arguable because n-Butyllithium usually not applied to nitro-sub. aromatics)

You may change this step to Grignard.

5. Reduction of NO2, tons of methods available such as H2/Pd, hydrazine hydrate with Pd/C....

Why not use Methyl lithium for step 4.  Otherwise, Orgopete is correct as usual.  This would be a series of adding, subtracting, adding, etc……….not a fun synthesis!
        -Zack

[kamiyu]

Could you please tell me the reason for methyllithium??

Are you intended to do nucleophilic aromatic addition reaction?

[orgopete]

Well in that case, Gatterman-Koch, chlorination, nitration, reduction of aldehyde to methyl and reduction of nitro to aniline.

[zsinger]

Could you please tell me the reason for methyllithium??

Are you intended to do nucleophilic aromatic addition reaction?

Yes, but I may be wrong….never tried it.  These EAS and NAS reactions are finicky at best, unless you have superior lab technique.  And I do mean superior.  I consider myself an intermediate chemist (3 practical lab experience years), and I am crapola when it comes to the ring reactions……thats why I stay away from them unless I get them in a starting material with a workable functional group already attached.  Hope this helps/ is not too preachy.
            -Zack

[kamiyu]

Well in that case, Gatterman-Koch, chlorination, nitration, reduction of aldehyde to methyl and reduction of nitro to aniline.

I wonder if you have a formyl group on the benzene ring. Will nitration work?

I mean the electron density of the ring is already weakened.

Thus, the nitration may require very harsh condition such as using white fuming nitric acid (ordinary nitric acid further dehydrated by conc. H2SO4)

[orgopete]

I wonder if you have a formyl group on the benzene ring. Will nitration work?

I mean the electron density of the ring is already weakened.

Thus, the nitration may require very harsh condition such as using white fuming nitric acid (ordinary nitric acid further dehydrated by conc. H2SO4)

http://en.wikipedia.org/wiki/3-Nitrobenzaldehyde