vulture
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Boc protection of amines - Mono or Di?
I have a primary amine connected through an alkoxychain to a fenyl group (so I assume it should behave as a primary amine). I protected this using
Boc2O, CH3CN and DMAP.
Both NMR and MS (twice loss of isobutene and CO2) seem to indicate it has been diprotected, but I was operating under the assumption that NHBoc was
the norm.
It doesn't pose any problems to the intended use, but I fear this might cause problems with some reviewers. Has anybody seen this before?
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Sedit
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Im looking into N-protected amino acids so perhaps this reference I just found a few minutes ago would help. I would like to go BOC but an unable so
more then likely Ts or Ac protection will be used.
Attachment: amino acid protection..PDF (1.5MB)
This file has been downloaded 1470 times
I don't know if what you seek is in there since iv not fully covered the text yet but I hope it helps.
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Nicodem
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Quote: Originally posted by vulture  | I have a primary amine connected through an alkoxychain to a fenyl group (so I assume it should behave as a primary amine). I protected this using
Boc2O, CH3CN and DMAP.
Both NMR and MS (twice loss of isobutene and CO2) seem to indicate it has been diprotected, but I was operating under the assumption that NHBoc was
the norm.
It doesn't pose any problems to the intended use, but I fear this might cause problems with some reviewers. Has anybody seen this before?
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Bis-Boc protection of amines is uncommonly done so easily, but if you used too much DMAP, it is not inconceivable at all. At least not to such a
degree that reviewers would insist on evidence other than a proper compound characterization. The way to deal with such cases is to do a very thorough
characterization, also including HRMS and EA in the experimental (so that you eliminate doubts about the structural assignation) and including an
explanation supported with solid references in the discussion part. This way no reviewer can object, as you showed that you were aware of the unusual
experimental results, but that you did a proper scientific analysis and a literature search. In your case I would include a reference showing that
N-Boc amines can be further bis-Boc protected with Boc2O in MeCN with DMAP catalysis. A 10 sec googling gives this with the seventh example being relevant and pointing to DOI: 10.1021/ol0361599.
In the view of the recent discussion in Forum matters, I'm now forced to define the above acronyms:
Boc = tert-butoxycarbonyl, tert-butyl carbamate
DMAP = 4-dimethylaminopyridine
Me = methyl
HRMS = high resolution mass spectroscopy
EA = elemental analysis
DOI = digital object identifier
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chemrox
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Do we really have to spell out abbreviations that are found in chemistry glossaries? (I know I was a whiner in the past but have since reformed and
shut my damned mouth about common shortcuts.)
why do the EA on this one? Isn't that going a step beyond thorough?
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smuv
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EA is pretty standard when publishing a compound that is new to literature; high-res mass spec can substitute, but it is really best to report high
res MS AND EA; this way there is absolute certainty about the molecular formula.
[Edited on 12-15-2010 by smuv]
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chemrox
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yes of course you're right .. sigh..
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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smuv
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no biggie, it is very journal dependent. For JACS you are more likely to get away without EA than JOC for example.
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Fleaker
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I've had the same thing happen--it is certainly too much DMAP.
Neither flask nor beaker.
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