[James Newby]

In my lab project i had to synthesise a starting material to test a cascade reaction.  I'd made the nitrile shown below and planned to convert it to the aldehyde using DIBAL-H at -78 with a HCl workup also at -78.  Despite many successful DIBAL attempts in the past this one didn't work.  I looked in the literature for examples similar to my reaction and there were none available:

R2N-C(CN)H-CH2-CH2-CH2- Cl  where R is an allyl group

DIIBAL was in hexanes and the bottle had been used the day before to perform a successful reduction.

Sorry i don't know how to insert a picture from chemdraw!

I believe the Nitrogen atom 3 positions from the nitrile plays a role but cannot work out what it is.  Does anyone have experience doing this??  I would have thought this would be a common synthetic route to making amino aldehydes

[macman104]

You can save your chemdraw file as an image (I usually save as PNG), and then when you post click the "additional" link and upload the image file.

[James Newby]

In my lab project i had to synthesise a starting material to test a cascade reaction.  I'd made the nitrile shown below and planned to convert it to the aldehyde using DIBAL-H at -78 with a HCl workup also at -78.  Despite many successful DIBAL attempts in the past this one didn't work.  I looked in the literature for examples similar to my reaction and there were none available:

In my lab project i had to synthesise a starting material to test a cascade reaction.  I'd made the nitrile shown below and planned to convert it to the aldehyde using DIBAL-H at -78 with a HCl workup also at -78.  Despite many successful DIBAL attempts in the past this one didn't work.  I looked in the literature for examples similar to my reaction and there were none available:

You can save your chemdraw file as an image (I usually save as PNG), and then when you post click the "additional" link and upload the image file.

Big thankyou to macman

DIIBAL was in hexanes and the bottle had been used the day before to perform a successful reduction.

I believe the Nitrogen atom 3 positions from the nitrile plays a role but cannot work out what it is.  Does anyone have experience doing this??  I would have thought this would be a common synthetic route to making amino aldehydes

[James Newby]

*Ignore me, I am impatient*, has anyone got any ideas, no matter how crazy?  Ill consider anything!

[nj_bartel]

Was it just a straight up NR?  Or is there any possibility you S_N2'd the chloride or E2'd there?

[James Newby]

NR? nucleophilic reduction?  The H on the DIBAL doesnt undergo SN substitution with carbon-chlorine bonds.  I think a reactive intermediate has cyclised in my reaction, several 5 membered rings can be made.

Im curious about the amino nitrile -> amino aldehyde and why this hasnt been published, this is my real question i think.

[nj_bartel]

*no reaction*

I'm just shooting in the dark - the chemistry is above my level, just hoping to trigger something in your head 

Would your amine undergoing a menshutkin reaction have any effect on the dibal reduction?

[James Newby]

Thanks i'll ask my professor.  Any help is useful! Do you know if menshutkin is formed in acidic or basic conditions?  I havent been taught this but i will read the papers on monday

[nj_bartel]

I don't know for sure, but basic or nearly neutral would be the only conditions that make sense to me - otherwise you'd end up protonating the amine and killing it as a nucleophile.

[snarfsnarfsnarf]

DIBAL converts the CN to an aldehyde

R-C=N+ R₂AlH --> R-CH=N-AlR₂ --H⁺, H20--> RCHO

I can't find the mechanism at the moment and I have 2 finals tomorrow but I'll let you know if I find it.

[Markov]

Could you isolate anything (starting material, corresponding alcohol, polymerized material (gunk)? Or did your stuff disappear in a water phase or elsewhere?

A few reflections on your story:

-DIBAL reduction of nitrile to aldehyde is usually a very good reaction

-The workup and isolation may mess things up, particularly if you don't use enough HCl (should use a pretty huge excess), or do it too cold (water solidifies if charged into a too cold soup). (Why? If there is some DIBAL alive in the presence of the aldehyde, you'd expect some to see some alcohol there) 

-The amine in your starting material may disturb the synthesis. Also -Amino aldehydes can be unstable in themselves (e.g. condensation/ dimerization/polymerization).

-Maybe find a 'model substrate', i.e a similar nitrile, which does not have the amine component from the start? And try the reaction with that first. If that works, you may rule out errors in experimental technique and interference from bad reagents and or moisture in the system.

-I would expect that primary alkyl chloride is inert and is not part of the problem. 

-Old old bottles of DIBAL are usually fine. Personally, I recommend storage at RT, as cooling may cause precipitation.

[James Newby]

Thanks for the replies.  The reaction works with almost 100% yields with a nitrile containing both a chloride and alkene tether.  Adding in the nitrogen atom on the alkene tether seems to affect the reactivity of the nitrile.  The amino aldehydes being unstable is interesting.  The project is finished and written up now, its going to be repeated next year by a phd student and hopefully they will have more success than i have!