Starting with benzene, describe the synthesis of 2-phenylethan-1-amine providing all the reagents and conditions.

I am not really great at organic chemistry and my knowledge is pretty limited.

I am currently thinking of forming toluene by Grignard reagent and then reacting with $\ce{Cl2}$ to form benzyl chloride. Then react with sodium cyanide to form benzyl cyanide and then react it with $\ce{HCl}$ and $\ce{H2O}$ to form an amide. Then reduce it with $\ce{LiAlH4}$ to form the compound.

I am not sure if that is correct as it seems a bit complicated for the synthesis of a seemingly simple compound. Also I am not sure on the exact conditions for the chlorination step.

I was also thinking of acylation with ehtanoyl chloride followed by Wolff-Kishner reduction to form ethyl benzene. However I am not sure on how to from the $\ce{NH2}$ group.

  • 1
    $\begingroup$ @Loong sorry about the confusion. I mean 2-phenylethan-1-amine. $\endgroup$ – Nanoputian Jan 23 '16 at 12:13

Several thoughts:

  • I can't see how you form toluene with a Grignard - it's certainly possible though
  • Radical chlorination of toluene with $\ce{Cl2}$ isn't the cleanest reaction.
  • To reduce the nitrile to the amine, you don't need to go through the amide.

Also, from ethylbenzene, it's very hard to introduce that amine group cleanly. You effectively just have a compound with C-H groups and you have to somehow introduce some kind of functional group into the non-benzylic position. Try to think backwards instead of forward!

The amine you want can be obtained by direct reduction of a nitrile either by simple $\ce{LiAlH4}$ reduction or hydrogenation:


That arrow essentially means "can be made from".

Of course, that's easy to make using a nucleophilic substitution reaction with $\ce{CN-}$ and benzyl chloride (for example):


To get from benzene to benzyl chloride, you could use a Blanc chloromethylation. So your forward synthesis would be:

Forward 1

and you might want to use catalytic $\ce{KI}$ in the nucleophilic substitution step. Of course, for such a simple compound, there are tons of ways to synthesise it. The amine could be made from reduction of an azide, or by a reductive amination, and so on. I strongly doubt my proposed route is the most efficient. Still, I think it should work.

Theoretically, you could use a Friedel-Crafts alkylation and a radical bromination to get to benzyl bromide instead:

enter image description here

I don't like the alkylation step though.

  • $\begingroup$ Good answer, but there's just one thing that I don't get at all....why orthocresol? $\endgroup$ – najayaz Jan 23 '16 at 12:36
  • $\begingroup$ Great answer! Thanks for working through all the steps. I am sure this will be beneficial for other questions also. However is there are another way of synthesising benzyl chloride, as we haven't been taught blanc chloromethylation. $\endgroup$ – Nanoputian Jan 23 '16 at 12:42
  • $\begingroup$ @orthocresol Also quick question, what program did you use to draw the diagrams? Is it free to use? $\endgroup$ – Nanoputian Jan 23 '16 at 13:00
  • $\begingroup$ @Nanoputian You can use Friedel-Crafts alkylation and radical chlorination with N-chlorosuccinimide. Alternatively you can replace the FC alkylation with a Gattermann reaction and reduce with Clemmensen or Wolff-Kishner - just Google all those names, Wikipedia has articles on them. For the diagrams, I use ChemDraw because I have an institutional license. If you don't have one then it costs a huge amount of money. I believe there are free alternatives though, so you can probably find them with a search. $\endgroup$ – orthocresol Jan 23 '16 at 14:14
  • 3
    $\begingroup$ @G-man Personally, I'm not sure either. I've actually used meta- and para- on other websites as well. The cresol part, however, has an origin - it's from a long time ago when I was talking with someone about whether methylphenol or hydroxytoluene was the correct IUPAC name. $\endgroup$ – orthocresol Jan 23 '16 at 14:17

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