[Fry]

Is it possible to react R-NH2 with isopropyl alcohol to create a di-isopropylamine derivative? The acid catalyzed Sn1 mechanism works on paper but how feasible is this in the lab? I guess it comes down to whether or not the amine would protonate before the iso and im thinking yes..

I had acetone in mind at first but I figured yields would be quite low due to acetones tendency to polymerize.

Thanks,
Peace.

[kiwi]

no i doubt you'll get anywhere with that approach. try reductive amination with acetone and either NaBH3CN or NaBH(OAc)3

[Dan]

If you're after the tertiary amine (R-NⁱPr₂) you could always activate the hydroxyl (triflate, tosylate, mesylate etc.) and try an Sn2 with the amine.

The reductive amination approach would give R-NHⁱPr.

[kremar]

if your Sn* reaction yields the tertiary amine, it will be a better nucleophile than your secondary amine, and it will keep on reacting.
you should add the activated alcohol (one of Dan's proposed derivates) to an excess of the amine to ensure that doesnt happen.

to give a lenghty but working solution: like Dan stated, reductive amination of acetone with R-NH2 will yield R-NH-iPr. but further reaction of this secondary amine with acetone will yield the enamine, which can be reduced to the tertiary amine with diborane in THF followed by reflux in methanol or ethanol. temperature should be kept low in the first step to avoid beta-elimination of the borane adition intermediary.