[Urbanium]

Could someone take a quick look at one experimental procedure from the following paper's additional material:

http://pubs.acs.org/doi/suppl/10.1021/ol403350e

the procedure is about protection of cysteine woth Boc, a short section in the middle of page 35. Why do these authors use big amounts of NaHCO₃ in this procedure? Do they think it's better to have higher pH to have both SH and COOH groups deprotonated so protection of amine would be more efficient?

I'm paticularly skeptical about using the mixture of THF and H₂O and later neturalizing with conc. HCl? Shouldn't that bring the issue of Boc deprotection?

Above which pH values is Boc relatively stable, is there some rule of thumb?

[TheUnassuming]

When I've seen/done Boc protections with water as a solvent it usually has an excess of sodium bicarb or similar around, though ostensibly it isn't really necessary.   Probably isn't necessary for them to be running it under argon either . 
I wouldn't worry about the solvent choice, its a relatively common mix for various reaction sets. 
Neutralizing with conc. HCl has to be carefully monitored.  They do say they bring it down to 2.9 which is perfectly fine, especially for their conditions at the time (chilled with an organic layer on top). 
I'd say around pH=1 you will start to get deprotection at rt.  I do most of my boc deprotections with TFA/DCM/H2O mixes, and that usually takes a few hours depending on substrate. 

[Urbanium]

Why is in some cases better to use HCO₃^- as a base instead of DMAP? So far I always used DMAP.


When browsing through the literature, I found that some people add sodium deuteroxide to D₂O solutions when taking spectra of aminoacids and related compounds. Why? Is that some kind of shift reagent, or it racemizes the compound or what?


My reaction outcome doesn't look so good, here's the spectrum (n.b. one set of peaks most probably belongs to traces of ethyl acetate, I guess the product is stable enough to be left on hi-vac pump overnight at room temperature)?

I'm not quite sure why do I have a bunch of these smaller peaks in the spectrum...?

[Dan]

It might not be that bad, you have a hell of a lot of solvent in there (EtOAc and THF) but most of the other peaks look like they correspond to the reported spectrum. I'd dry it properly then reassess it and purify by chromatography if necessary.

Did you leave it for 30 h as stated in the prep? Have you analysed the crude by TLC? I ask because there's only 6 h between your posts.

[Urbanium]

Actually I left it to stir for approx. 40 hours, I wrote the first post after I recorded the spectra. Are there really traces of THF? I thought it's only EtOAc.

I left the flask on hi-vac a couple of hours ago, but the sample looks like a very viscous liquid which is bubbling occasionally and EtOAc is evaporating quite slowly.


Could anyone give me a clue about NaOD (the question above), what is its role when recording the spectra of aminoacids/oligopeptides?

[discodermolide]

NaOD will deuterate any exchangeable protons, NH, OH, etc. This will remove the corresponding signals from these functional groups.
It will also hinder the formation of rotamers which are formed because of the nature of the Boc protected amines. This will also simplify the spectra. Watch it though if you have chiral material as it may start to racemise under the basic conditions, so don't add too much.

[Babcock_Hall]

If they used argon, perhaps they were trying to keep their sulfhydryl group from oxidizing.

[Dan]

I left the flask on hi-vac a couple of hours ago, but the sample looks like a very viscous liquid which is bubbling occasionally and EtOAc is evaporating quite slowly.

Throw in a (pre-weighed) stirrer bar, it gives the solvent something to nucleate on, which speeds up drying.

[Urbanium]

NaOD will deuterate any exchangeable protons, NH, OH, etc. This will remove the corresponding signals from these functional groups.
It will also hinder the formation of rotamers which are formed because of the nature of the Boc protected amines. This will also simplify the spectra. Watch it though if you have chiral material as it may start to racemise under the basic conditions, so don't add too much.

What is the point of that? Isn't it better to have these signals visible and have control of everything than to suppress them? Is that done when working with oligopeptides, to simplify or for something else?

The spectrum of cysteine I have above already lacks these protons (there is nothing further downfield), and it is recorded in pure D₂O. Is there any way I could make them visible (apart from using DMSO as a solvent, tried but it doesn't quite work for me).


btw thanks for answers everyone!

[TheUnassuming]

Why is in some cases better to use HCO₃^- as a base instead of DMAP? So far I always used DMAP.

I would use bicarb simply because it is cheaper than DMAP and less toxic.  DMAP is also a rather poor base when it comes down to it and typically functions more as an addition/elimination catalyst. 

Actually I left it to stir for approx. 40 hours, I wrote the first post after I recorded the spectra. Are there really traces of THF? I thought it's only EtOAc.

I left the flask on hi-vac a couple of hours ago, but the sample looks like a very viscous liquid which is bubbling occasionally and EtOAc is evaporating quite slowly.

I'll second the stir bar suggestion.  With oils, even with the stir bar trick, it will typically take longer on high vac than you expect to get rid of the solvent to an acceptable level on NMR. 

What is the point of that? Isn't it better to have these signals visible and have control of everything than to suppress them? Is that done when working with oligopeptides, to simplify or for something else?

The spectrum of cysteine I have above already lacks these protons (there is nothing further downfield), and it is recorded in pure D₂O. Is there any way I could make them visible (apart from using DMSO as a solvent, tried but it doesn't quite work for me).

As far as exchange, NaOD will just guarantee you don't have blips from NH or OH.  Rotamers for me have just made the spectra more complicated without really providing any additional important information.  Since this is a known compound though I wouldn't worry too much about getting perfectly pretty spectra.  Just make sure its the right one and an acceptable purity for your next step.   

[Urbanium]

Thanks, I see now what's the point of MeOD. And I actually had these rotamer signals.