zephler1
Harmless
Posts: 41
Registered: 16-11-2013
Member Is Offline
Mood: No Mood
|
|
Why does NaCNBH3+GAA+formaldehyde not do pictet Spengler?
The mechanism shows that tryptamine would do the pictet Spengler ring closure due to a proton being present, however, Rhodiums page has a bunch of
procedures that say the authors used GAA, NaCNBH3 & formaldehyde with tryptamine to afford the dimethylated species. Yes NaCNBH3 is mild enough
to leave the formaldehyde alone, but umm win out the competing reaction of ring closure? BTW, the above reaction was reported to yield material with
a MP of 47-50c
|
|
|
Tsjerk
International Hazard
Posts: 3032
Registered: 20-4-2005
Location: Netherlands
Member Is Offline
Mood: Mood
|
|
pictet Spengler ring closure is acid catalyzed, the acetic acid reacts with the cyanoborohydride to di-acetate-cyanoborohydride. There is no free acid
present.
You can also use NaBH(CN)3, instead of reacting NaBH3CN with acetic acid.
|
|
|
Methyl.Magic
Hazard to Others
Posts: 139
Registered: 14-5-2007
Member Is Offline
Mood: No Mood
|
|
you can di-alkylate using MeI (or other alkylating agent) and CsCO3. works well
|
|
|
zephler1
Harmless
Posts: 41
Registered: 16-11-2013
Member Is Offline
Mood: No Mood
|
|
thanks for the info. I also wonder why N-alkylation of the indole N would not occur? Sterics with an itty bitty methyl wouldn't be much of an issue
I think?
|
|
|
Dr.Bob
International Hazard
Posts: 2736
Registered: 26-1-2011
Location: USA - NC
Member Is Offline
Mood: No Mood
|
|
Because indole N's are not very nucleophilic or very basic, due to resonance effects with the ring. They are more like like deactivated anilines,
rather than like a alkyl amine. But it is possible to react them, usually requires either long times, higher temps, stronger bases or more reactive
reagents.
But you can do a reductive amination on an aminoindole at the ring -NH2 without reacting at the indole NH in most cases. But if you deprotonate it
first with NaH, then it will react with most alkylating reagents. But most indole will not react quickly with only K2CO3, I did one alkylation with
it that took 2 weeks to go to completion.
|
|
|
Nicodem
|
Thread Moved
3-5-2014 at 09:30 |
thebean
Hazard to Others
Posts: 116
Registered: 26-9-2013
Location: Minnesota
Member Is Offline
Mood: Deprotonated
|
|
This is a little off topic but is GAA glacial acetic acid?
"You need a little bit of insanity to do great things."
-Henry Rollins
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
