[Messi]

Hi guys,

I have a few reactions I am thinking of, and am wondering if they woudl theoretically work... They are fairly basic reactions... so I think they would, but a simply "yes" or "no" would be greatly appreciated! For reaction #1 shown below would it work? For reaction #2, how can I form the corresponding amine?

The picture is shown below (took a picture of my drawing)

Thanks!

[orgopete]

1) Would work, a little sloppy, but I'm sure the product could be found among the dialkylated amine.

2) What is the "?"?

[camptzak]

when you say the product could be found among the dialkylated amine, what does that mean? the product is a secondary amine.

[discodermolide]

I think he means that the product amine, in the first reaction, can also react with the tosylate, probably better that the original amine.

[Dan]

For #1, remember that Ts = ArSO₂

Reaction of TsCl with an alcohol ROH gives a sulfonate (ArSO₃R), not a sulfone (ArSO₂R):

ROH + TsCl  ROTs + HCl

[Messi]

Thanks for the response guys.

Dan, thanks for this, I simply forgot to include the "O" when I drew my ROTs.

Orgopete, thanks for your reply as well. Yes, the dialkylated amine would be seen as a major product. Any ideas how I could simply get the mono-substituted amine (what reaction)? Also, I guess when I do my reaction, I'll have to a run a column to isolate my mono-substituted product.

The question mark in the second reaction was me not being sure what reagents to use to form my desired product. Could you guys give me a hand in that regard?

Thanks!

On a side note, does the reaction below work? I am following orgopete's advice and looking at other ways of creating my amine.

[discodermolide]

Try looking at a reductive amination.

[Messi]

I am confused. I just want to make my amine so I can continue my reactions and form something else after that!

When you say reductive amination, I understand that, but I don't think I have any chemicals that will allow me to make my wanted amine with that reaction mechanism.

1) Would work, a little sloppy, but I'm sure the product could be found among the dialkylated amine.

What eluent system should I use to isolate my monoalkylated amine?

2) What is the "?"?

I don't know what the "?" should be. Could you give me a hand?

[Dan]

I am confused. I just want to make my amine so I can continue my reactions and form something else after that!

The main point that you need to understand is that alkylation of amines by S_N2 reactions with alkyl halides or (alkyl sulfonates) is not a good general method because it can be difficult to control the product distribution - you often get alkylation. Think about mixing MeI and ammonia - you will get a mixture of methylamine, dimethylamine, trimethylamine and tetramethylammonium iodide.

This is a classic problem discuessed in any organic textbooks, and there are several well established workarounds including: Azide displacement, Delepine reaction, Gabriel synthesis, reductive amination, reduction of an amide, Curtius rearrangement and Hoffman rearrangement. Look these up for some inspiration for your problem.

When you say reductive amination, I understand that, but I don't think I have any chemicals that will allow me to make my wanted amine with that reaction mechanism.

Design the route, then buy in what you need. The materials required for the purification of a messy S_N2 reaction may cost more than just buying the reagents for a well planned synthesis.

What eluent system should I use to isolate my monoalkylated amine?

That can only be determined experimentally.

[Messi]

Dan, great stuff! Thanks for this! Super clear now!

On a side note, anyone know what reagents I need to use below to form my amine with a halide group on it?

*Look @ picture below* What could I use as the question mark?

[Dan]

Hint: Start from proline

[Messi]

Thanks for the hint Dan! I got it, minus one step... not sure how to do it.

I wrote my reaction mechanism below. I am not sure how I can reduce the carbonyl without affecting the chloride?

[discodermolide]

Firstly you will have to protect the nitrogen before doing anything else.
Secondly there are ways of reducing an acid/ester to the corresponding alcohol. From there you can obtain the halide.

[Messi]

Thanks  discodermolide.

How does my refined reaction mechanism below look?

[Dan]

How do you propose to tosylate the alcohol without tosylating the amine?