[djay]

Hi everyone,

I need help for a lab. It is a reaction with a nitrile and i have to form the final molecule as shown in the picture.
I tried to do it indirectly using Ritter reaction but it was giving me relatively low yield (which I don't know why).
I had 3 classes of organic chemistry but we vaguely learned reactions with nitrogenated compounds

[discodermolide]

Hi everyone,

I need help for a lab. It is a reaction with a nitrile and i have to form the final molecule as shown in the picture.
I tried to do it indirectly using Ritter reaction but it was giving me relatively low yield (which I don't know why).
I had 3 classes of organic chemistry but we vaguely learned reactions with nitrogenated compounds

An idea: Try adding methyl Gringard to the nitrile and trapping the intermediate iminium ion with metnyl iodide or other methyl source. Then hydrogenate the imine.

[Dan]

How about:

1. MeMgBr; aqueous protic workup gives the methyl ketone
2. Reductive amination of the ketone with methylamine gives the target

IMO, hydrolysis of the imine in the workup of step 1 will be easier than trapping with MeI. The "trapped" methylated imine would still be susceptible to hydrolysis on workup anyway.

[discodermolide]

How about:

1. MeMgBr; aqueous protic workup gives the methyl ketone
2. Reductive amination of the ketone with methylamine gives the target

IMO, hydrolysis of the imine in the workup of step 1 will be easier than trapping with MeI. The "trapped" methylated imine would still be susceptible to hydrolysis on workup anyway.

Reductive amination is quite difficult to control and you get quantities of the tertiary amine in this case as well as other amination products, i.e. messy. Methylamine is a gas and this would make the experimental set-up more complicated. I would suggest methyl tosylate as a "methyl" source.

[Dan]

Reductive amination is quite difficult to control and you get quantities of the tertiary amine in this case as well as other amination products, i.e. messy.

Yes, that's a potential issue. A large excess of methylamine and a low conc. of the ketone might be OK though. You could even pre-generate the imine before applying the reducing agent.

Methylamine is a gas and this would make the experimental set-up more complicated.

It's commerically available as a aqueous and alcoholic solutions that are easy to handle. Also available as it's HCl salt which melts >200^oC.

Both approaches have their merits.

[djay]

thanks a lot guys. I'll try those.

but just to be sure, what are the conditions that I should use for the reactions (pH, temperature, concentrations...)
I had a lot of theory but learned very little about the conditions and what is the order of the steps that I should use. I don't want to have side-reactions with by-products.

I forgot to say I used ethanol as solvent but I think there is a better one.

[discodermolide]

thanks a lot guys. I'll try those.

but just to be sure, what are the conditions that I should use for the reactions (pH, temperature, concentrations...)
I had a lot of theory but learned very little about the conditions and what is the order of the steps that I should use. I don't want to have side-reactions with by-products.

I forgot to say I used ethanol as solvent but I think there is a better one.

Use THF

[djay]

I assume room temperature and pressure will give high yield.