[Ion.liq]

Hi everyone

I need your help. I need to synthesize tertiary amine from secondary alcohol and amine. I thought about conversion -OH group to mesyl group, and the next step amination reaction with e.g. pyrrolidine. But what should I use to take mesyl group? NaOH in toluene?

[OrganicDan96]

MsCl with tryethylamine is good and you could try DMAP if you are having trouble.

[Ion.liq]

But I have cyclohexyl mesylate. I have a problem with conversion this compounds to amine. What should I use to transform this mesylate compounds to amine like the last compound in previous post?

[wildfyr]

What is your problem exactly? Have you just tried plain old: 1 equivalent cyclohexylmesylate + 2 equivalents pyrrolidone+heat?

[clarkstill]

One doesn't normally make amines in this way due to issues with over-alkylation leading to ammonium salts. If you're going to use this route I would suggest using pyrrolidine in vast excess.

 Have you considered reductive amination with cyclohexanone? It would cut out a step and probably work better...

[wildfyr]

Good point, that mesylate will be very reactive. Thanks for teaching me something.

[rolnor]

I dont think there is risc of ammoniumsalt formation, it would be very difficult because of steric hindering?

[rolnor]

The amine you want to make is also commersially available although a bit expensive, Chemtronica here in Sweden has it.

[clarkstill]

I'm guessing this is a fairly poor substrate for SN2 since the mesylate is secondary and the nucleophile is a little bulky too. As rolnor says, this probably means forming ammonium ions is unlikely, but it might mean E2 reactions start to compete.

If you have some NaCNBH3 or NaBH(OAc)3 lying around I'd try the reductive amination route

[kriggy]

I suppose you could heat it in neat pyrrolidine to be sure there is no over-alkylation. Reductive amination is good idea to try as well. The best is IMO, to look into chemical literature because Im sure someone else did that already. And because Im a nice guy that has cofee break atm, I did some search for you. Reductive amination seems like a way to go

reductive amination
Synthetic Communications, 2009, vol. 39, # 16, p. 2907 - 2916

cyclohexyl amine + dibromo butane under microwave conditions
 Journal of Organic Chemistry, 2006, vol. 71, # 1, p. 135 - 141

[Doc Oc]

Exhaustive alkylation is a concept that is overstated in lecture courses. I've done lots of amine alkylations and almost never run into problems with overalkylation. In fact, I've had more recent trouble with reductive amination of an aldehyde going more than once as opposed to amine overalkylation.

The problem with this particular synthesis is that mesyl groups are extremely hot and are much more likely to eliminate to the alkene. I would try a tosyl group instead or convert it to a halide, bromo or iodo ideally.

[wildfyr]

Mesyl could eliminate in the presence of pyrrolidone? Usually amines are pretty darn good about acting as nucleophiles instead of bases as long as you aren't really cooking the reaction.

Cyclic alkyl amines are usually better nucleophiles than their secondary structure would have you guess at a glance.

[Enthalpy]

Industrially, heat and a nickel catalyst suffice to transform ethanolamine into diaminoethane. The reactants and product here look nicely stable.
So, how much do you dislike heat and gases in a lab? Or would something else go wrong?

[kriggy]

I dont think he has acces to industrial nickel catalyst