[alin823]

Hi,

I am trying to couple a hydroxyl group with an amine group.
I know Carbonyldiimidazole (CDI) can do that, but CDI is not easy to remove once the coupling reaction is done.

Do you guys recommend any other compounds to couple R-NH2 with R-OH?

Thanks

[rucik5]

Hi,
I assume the OH is not from carboxylic acid and so you don't want the amide. I dont know to couple them directly and I'm not sure how is it doable with CDI. I think one would rather take the amine to hydroxylamine and convert the OH to a good leaving group. There is a procedure: triphenylphosphine, carbon tetrachloride, and DBU in the presence of catalytic amounts of TBAI in acetonitrile to get the oxime (R1R2C=NOH and alcohol R3OH) to R1R2C=N-O-R3.
Other ways to place an N-O bond that I can think of at the moment:
-Mitsunobu with hydroxyphthalimide on the alcohol (OMs, OTs...)
-Mesylate, then DBU/Boc-N-OR, deprotect
-There is some Buchwald chemistry which allows N-O formation
-Copper-catalyzed N-arylation of hydroxylamines if you've got N-Ar
Not sure if this is of any use;) good luck, maybe I'm missing something simple.

[alin823]

Many thanks for your reply.
Actually, I am looking for a coupling agent to linker R-NH2 to R-OH. So it doesn't have
to form N-O bond.

Do you recommend any chemicals to use?

Thanks,

[Honclbrif]

Many thanks for your reply.
Actually, I am looking for a coupling agent to linker R-NH2 to R-OH. So it doesn't have
to form N-O bond.

Do you recommend any chemicals to use?

Thanks,

The way you worded your question, it sounded like you were trying to make a hydroxylamine.

So you're trying to do the reaction

R-NH₂ + R'-OH  R-NH-R'

In that case you need to activate the alcohol by forming something like a tosylate or converting it to a bromide or iodide, then use the amine as a nucleophile to displace the activated leaving group

[Dan]

Alkylating primary amines by S_N2 can be problematic since the secondary amine product can also react with the alkylbromide/iodide/tosylate etc. to give tertiary amines and then even quaternary ammonium salts. It can be done, but sometimes it's messy.

The classic alternative is condensation of an amine and an aldehyde (or ketone) followed by reduction of the formed imine (reductive amination).

RCH₂OH --[Ox]--> RCHO

R'NH₂ + RCHO ---(-H₂O)---> R'N=CHR --[H]--> R'NHCH₂R

[Honclbrif]

Dan's right. Don't know what I was thinking.

[alin823]

Many thanks to you guys.
I really appreciate these responses.
I think it's good to try conversion of hydroxyl group first, then react with the primary amine.

Actually, I am finding a way to couple (3-Aminopropyl)triethoxysilane  with Methoxy Polyethylene glycol.

I prefer using a heterobifunctional linker agent to couple the primary amine with the OH group. Will it be more convenient than converting the OH group into other functional groups?

Thanks

[Åke]

Do you guys recommend any other compounds to couple R-NH2 with R-OH?

Thanks

There is a relatively unknown way to make amines from alcohols directly, without first transforming -OH into a leaving group (e.g. halide or mesylate, tosylate, triflate) check the literature for Fukuyama amine synthesis, especially when conducted under Mitsunobu conditions. This method, like Gabriel amine synthesis, is of relatively poor atom economy.