ttso
Harmless
Posts: 2
Registered: 16-2-2011
Member Is Offline
Mood: No Mood
|
|
Primary amine to primary alcohol
Hello everyone. I have a question about "Primary amine to primary alcohol"
I've tried that the primary amine add NaNO2 and Ac2O in AcOH for 17h , then used NaOMe to give primary alcohol .
Indeed,it can work,but the yields and convertion are low.
I also read some literature that used KOH and diethylene glycol/ 210 oC. I think the temp is too harsh for my substrate . ( six-ring azasugar,
functional group contaning Cbz and OBn and a allyl chain)
Can anyone else help me to figure out this problem or give me some suggestion in transformation?
Thanks a lot.
[Edited on 17-2-2011 by ttso]
|
|
|
Magic Muzzlet
Hazard to Others
Posts: 146
Registered: 22-7-2010
Member Is Offline
Mood: No Mood
|
|
Well.... What is the substrate?
|
|
|
DJF90
International Hazard
Posts: 2266
Registered: 15-12-2007
Location: At the bench
Member Is Offline
Mood: No Mood
|
|
Amines can be converted to leaving groups using pyrylium salts: http://curlyarrow.blogspot.com/2009/09/how-to-turn-amine-int...
I suppose the nitrogen can then be displaced by hydroxide, although you may also experience elimination (depending on the substrate)
|
|
|
Melgar
Anti-Spam Agent
Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline
Mood: Estrified
|
|
Strong oxidizers like sodium hypochlorite can remove the amino group on amino acids, which then undergoes a rearrangement that creates an aldehyde.
In any case, the -NH2 can be oxidized to -NO2 by something like potassium permanganate, which may be easier to replace with a hydroxyl group since it
makes a better leaving group.
|
|
|
DJF90
International Hazard
Posts: 2266
Registered: 15-12-2007
Location: At the bench
Member Is Offline
Mood: No Mood
|
|
Primary amines are seldom converted to nitro compounds in good yield, especially with something like permanganate. I also doubt very much that the
nitro group would be a better leaving group, or even a leaving group at all. You might try diazotisation in aqueous conditions, but I wouldnt expect
too much from it; just an idea.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
Due to some (work related) coincidence I just stumbled into Katritzky et al. article on the same topic as the one referred in that blog and thought to
reply here (the article is attached). That is a very interesting reaction described in that blog. C-Alkylation of 2-nitropropane is highly unusual. I
have only seen it done with p-nitrobenzyl halides or other very electron poor ArylCH2X (but that is a classical example of SRN1 mechanism),* while
normal alkylating reagents always start with O-alkylation followed by the decomposition of the resulting O-alkyl nitronate to aldehydes or ketones
(e.g., JACS, 77, 1114 or JACS, 71, 1767).
I don't think the author of the blog even realizes the exceptionality of his 2-nitropropane alkylation (despite some replies pointing it out). If it
turns out that it is the 2,4,6-triphenylpyridinium leaving group that somehow causes the reaction to go via SRN1 mechanism (accepting an electron from
the nitronate?), it would make for an interesting discovery that would allow the C-benzylation of nitroalkanes with any benzyl group, not just limited
to the nitro substituted ones. Seems like a perfect research project for amateur chemists (and highly publishable also!).
* For such examples see:
http://euch6f.chem.emory.edu/nucleophilic.html
DOI: 10.1021/ja01178a066
DOI: 10.1021/jo01168a002
DOI:10.1016/S0040-4039(99)00790-X
DOI:10.1016/S0040-4020(63)80038-1
PS: Otherwise the general umpolung methodology for primary amines is the N-ditosylation which gives the electrophilic N,N-ditosylamines that are able
to undergo SN2 substitutions with ease provided they are of -CH<sub>2</sub>NTs<sub>2</sub> type. In this case one would
alkylate potassium acetate in DMF to obtain the alkyl acetate and hydrolyse that to the alcohol. But regarding the question of the original poster, I
have no idea without first seeing the structure of the substrate, but I do know "KOH and diethylene glycol/ 210 oC" is no method for such conversions
(seems like someone confused the hydrolysis of amides with amines->alcohol transformation).
Attachment: Preparation of azides, phthalimides, and sulphonamides from primary amines.pdf (121kB)
This file has been downloaded 1815 times
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
smaerd
International Hazard
Posts: 1262
Registered: 23-1-2010
Member Is Offline
Mood: hmm...
|
|
@Nicodem - can you find a reference for the n,n-ditosylation of primary amines? I'm very curious about this and am having a hard time finding
anything.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
Quote: Originally posted by smaerd  | | @Nicodem - can you find a reference for the n,n-ditosylation of primary amines? I'm very curious about this and am having a hard time finding
anything. |
I can hardly belive you can't find much. There is plenty of literature examples on the synthesis of primary alkylamine N,N-disulfonimides. Admittedly,
this is classically done via a two step synthesis, first making the sulfonamide, deprotonating it (e.g., with NaH) and sulfonating it again to get to
the imide. Though, there is a limited number of examples where the N,N-disulfonation occurs directly with the arenesulfonyl chloride and
triethylamine. An arenesulfonyl chloride with NaH/DMF or Cs2CO3/MeCN can also give N,N-disulfonimides directly.
A cursory literature search gives this variety of methods:
DOI: 10.1021/je60075a025
DOI: 10.1002/adsc.201100285
DOI: 10.1016/j.tetlet.2008.08.054
DOI: 10.1002/hlca.19800630806
DOI: 10.1021/ja061606b
DOI: 10.1073pnas.0904264106
and many others...
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
smaerd
International Hazard
Posts: 1262
Registered: 23-1-2010
Member Is Offline
Mood: hmm...
|
|
Really appreciate the DOI's. I did find one example using THF and NaH but that was about where it stopped, think my nomenclature is lacking. This
seemed to be the most useful DOI: 10.1002/hlca.19800630806 .
Learning new synthetic techniques day by day,
Thanks for taking the time and replying as always.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
| Quote: Originally posted by Nicodem | That is a very interesting reaction described in that blog. C-Alkylation of 2-nitropropane is highly unusual. I have only seen it done with
p-nitrobenzyl halides or other very electron poor ArylCH2X (but that is a classical example of SRN1 mechanism),* while normal alkylating reagents
always start with O-alkylation followed by the decomposition of the resulting O-alkyl nitronate to aldehydes or ketones (e.g., JACS, 77, 1114 or JACS,
71, 1767).
I don't think the author of the blog even realizes the exceptionality of his 2-nitropropane alkylation (despite some replies pointing it out). If it
turns out that it is the 2,4,6-triphenylpyridinium leaving group that somehow causes the reaction to go via SRN1 mechanism (accepting an electron from
the nitronate?), it would make for an interesting discovery that would allow the C-benzylation of nitroalkanes with any benzyl group, not just limited
to the nitro substituted ones. Seems like a perfect research project for amateur chemists (and highly publishable also!). |
Well, it turns out that, in his blog, Curly Arrow cited the not most relevant of the Katritzky et al. papers on the topic of alkylations with
pyridinium salts. I just stumbled to the paper where this type of alkylations of nitronates (derived from nitromethane, nitroethane or 2-nitropropane)
with 1-benzyl and 1-alkyl-2,4,6-triphenylpyridiniums is studied:
Carbon-alkylation of simple nitronate anions by N-substituted pyridiniums
Alan R. Katritzky, George De Ville, Ranjan C. Patel
Tetrahedron 1981, 37, Supplement 1, 25–30. DOI: 10.1016/0040-4020(81)85037-5
Attachment: 0025-0030.pdf (383kB)
This file has been downloaded 1287 times
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
smaerd
International Hazard
Posts: 1262
Registered: 23-1-2010
Member Is Offline
Mood: hmm...
|
|
I did read this entry on the their blog. Really interesting. Thanks for uploading the according article.
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
