[eskil]

Hi guys,

New to the forum. I know the uses of Fmoc chloride but I just saw 2,7-Di-tert-butyl-9-fluorenylmethyl chloroformate in a catalogue but I don't see what the use of those extra tert-butyl groups would be. Does anyone know?

Also, what's the use of 9-Fluorenylmethyl carbamate, its  basically Fmoc chloride with -NH2 in place of -Cl?

Best,
eskil

[mamid]

Those t-Bu groups provide better solubility in many common organic solvents. Check the references in Green & Wuts for details.
As for the carbamate, I have no idea at the moment.

[discodermolide]

A carbamate is normally used as a protecting group for amines, usually primary.

[eskil]

A carbamate is normally used as a protecting group for amines, usually primary.

Yeah, Fmoc chloride for example, but 9-Fluorenylmethyl carbamate? Looks like a very expensive way to protect ammonia... Or is the carbamate itself used to attach Fmoc on amines 

Those t-Bu groups provide better solubility in many common organic solvents. Check the references in Green & Wuts for details.
As for the carbamate, I have no idea at the moment.

Thanks mamid, never thought of that...

[kriggy]

The FMOC group is introduces by reacting FMOC-Cl with the amino compound, it is then removed by use of piperidine. I think the FMOC carbamate can have some uses in synthesis too. Im not realy sure about the reactivity of the carbamates or FMOC carbamate but I suppose it could be N-alkylated under some conditions? I suppose the carbamate can be deprotonated by base like LDA or tButOK and then racted with some alkylhalide (at least the protective group part of organic-chemistry.org says so)

[eskil]

Thanks, still doesn't answer the question why someone would pour ammonia over Fmoc-Cl and  put it on the market.

[discodermolide]

I would assume it undergoes an amine exchange liberating ammonia and putting the carbamate on the new amine.
It may well be a bit more stable than the chloroformate. Also it won't produce HCl, which means you don't have to use a base. This is an advantage in amino acid protection where the presence of a base may cause racemisation.

[eskil]

Thanks, I had the impression that Fmoc-OSu would do what you mention but better. I don't see how amine exchange could happen easily.

[kriggy]

I would assume it undergoes an amine exchange liberating ammonia and putting the carbamate on the new amine.
It may well be a bit more stable than the chloroformate. Also it won't produce HCl, which means you don't have to use a base. This is an advantage in amino acid protection where the presence of a base may cause racemisation.

Oh that brings a questions I wanted to ask few weeks ago, is the hydrogen that acidic that it can be deprotonated and the amino acid can form racemate? It happened to my girlfriend in a lab and I found it very unlikely that it can happen.. Could pyperidine be the cause of the racemization?

[discodermolide]

Basically (pun) yes. Racemisation of amino acids is a textbook series for itself. A lot depends on the amino acid and the base, solvent, temperature, wind direction, time of day, mood of chemist, and so on.
Piperidine is actually quite a strong base.

[discodermolide]

Thanks, I had the impression that Fmoc-OSu would do what you mention but better. I don't see how amine exchange could happen easily.

Why not? Ammonia is a good leaving group.

[eskil]

Thanks, I had the impression that Fmoc-OSu would do what you mention but better. I don't see how amine exchange could happen easily.

Why not? Ammonia is a good leaving group.

Not good enough to happen before deprotonation of the benzylic hydrogen and release of CO₂ I would assume.

[discodermolide]

I doubt that mode of reaction can happen. Do you have literature precedents?

[eskil]

I doubt that mode of reaction can happen. Do you have literature precedents?

For what, standard deprotection of Fmoc? Sure: https://en.wikipedia.org/wiki/Fluorenylmethyloxycarbonyl_chloride

[discodermolide]

No, for the removal (deprotection) by the amino group of amino acids.