ChemistryForever
Hazard to Self
Posts: 64
Registered: 6-12-2018
Member Is Offline
|
|
Indole
How can I synthesize indole ? I mean with no substituents on the rings.
|
|
|
DoctorOfPhilosophy
Hazard to Others
Posts: 130
Registered: 12-6-2012
Location: Ontario, Canada
Member Is Offline
Mood: enthralled
|
|
Can you be more specific about what starting materials and equipment you have access to? For example you could use a microwave oven: https://www.sciencedirect.com/science/article/pii/S004040390...
|
|
|
Assured Fish
Hazard to Others
Posts: 319
Registered: 31-8-2015
Location: Noo Z Land
Member Is Offline
Mood: Misanthropic
|
|
The classic fischer indole synthesis is the go to really. https://en.wikipedia.org/wiki/Fischer_indole_synthesis
The reference that Doc gave is just a microwave assisted version of it as opposed to simply refluxing the acid, aldehyde, phenylhydrazine mixture
which is suspect just speed up the reaction times and also decarboxylates the product.
In that paper they used pyruvic acid as the aldehyde which led to indole-2-carboxylic acid, this could be decarboxylated in a second step if you do
not have access to a proper laboratory microwave.
The reaction is supposed to be quite robust and can be carried out with many different substituents of both the phenyl hydrazine ring and the
aldehyde.
If you do not want to have to decarboxylate anything then acetaldehyde would get you straight to the indole however care would be needed when adding
the aldehyde to the phenyl hydrazine solution as the addition is exothermic and acetaldehyde is quite volatile.
Sufficiently advanced science is indistinguishable from madness.
|
|
|
pomegranate
Harmless
Posts: 13
Registered: 13-12-2018
Member Is Offline
|
|
my new thread posts aren’t working, after i post them and they show up. i go to edit but the post isn’t found.
so i need to see if this post here works.
|
|
|
pomegranate
Harmless
Posts: 13
Registered: 13-12-2018
Member Is Offline
|
|
this might work, what do you all think
let me edit this, it looks like i’m jacking your thread in the first couple sentences. this relates to your thread, i just happen to be trying to
look around this same direction and skimmed off all the irrelevant data from a post i am trying to make a thread about,. the pertinent information to
your thread is here as follows;
i’m looking at a benzofuran from 2-iodianisole cyclization that uses terminal acetylides. if it can be done with plain acetylene, than an
unsubstituted dihydro-benzofuran
or in this case, maybe an indile could be made. the literature sources two prior attempts that use things like SMe (TMe) or NH2 inbplace if the
anisole OMe, or OH.
two papers may apply, but there is an iodine that ends up on the 3-position if the dihydro-benzofuran or indole, but (i am unsure, because i am only
learning) that it could be reduced off, and possibly retain the double bond in the furan or in this case indole,
some sources include::
• https://pubs.acs.org/doi/10.1021/jo051299c
(https://www.google.com/amp/s/www.researchgate.net/publicatio...)
*https://www.google.com/amp/s/www.researchgate.net/publication/7445031_Synthesis_of_23-Disubstituted_Benzo_b_furans_by_the_Palladium-Catalyzed_Couplin
g_of_o-_Iodoanisoles_and_Terminal_Alkynes_Followed_by_Electrophilic_Cyclization/amp*
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594699/pdf/nih...
*https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594699/pdf/nihms-445477.pdf*
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594699/)
• http://www.orgsyn.org/content/pdfs/procedures/v91p0283.pdf
http://gen.lib.rus.ec
but while novel or maybe usefull for hard to substitute indoles, maybe the fischer synthesis or the other things these guys know are better of course.
they could vet this perhaps
[Edited on 15-12-2018 by pomegranate]
[Edited on 15-12-2018 by pomegranate]
[Edited on 15-12-2018 by pomegranate]
[Edited on 15-12-2018 by pomegranate]
[Edited on 15-12-2018 by pomegranate]
[Edited on 15-12-2018 by pomegranate]
|
|
|
Texium
|
Thread Moved
15-12-2018 at 20:22 |
Jackson
Hazard to Others
Posts: 189
Registered: 22-5-2018
Location: U S of A
Member Is Offline
Mood:  Happy about new glassware
|
|
React phenylhydrazine with acetaldehyde under hcl or h2so4 in a microwave.
|
|
|
Assured Fish
Hazard to Others
Posts: 319
Registered: 31-8-2015
Location: Noo Z Land
Member Is Offline
Mood: Misanthropic
|
|
NO.
Acetaldehyde is very very volatile and flamable, a well cooled reflux condensor is mandatory, you will also need a solvent and water wont cut it,
ethanol (often anhydrous) is usually used.
Also you should not be doing chemistry in a kitchen microwave, they are not the same as laboratory microwaves, you can get away with a few things here
and there but your taking alot of risks.
Not to mention the fact that forming the schiff base is exothermic, i strongly advise against using a microwave for this kinda thing.
Jackson your explanation shows that you have sweet fuck all knowledge on this particular reaction, please shut up and go read about it.
Sufficiently advanced science is indistinguishable from madness.
|
|
|
Tsjerk
International Hazard
Posts: 3022
Registered: 20-4-2005
Location: Netherlands
Member Is Offline
Mood: Mood
|
|
Fischer indole synthesis is nice and famous synth to run. Microwave is not necessary as it will run anyway with some heating. Find a reference as
follow it. It will be doable.
|
|
|
ChemistryForever
Hazard to Self
Posts: 64
Registered: 6-12-2018
Member Is Offline
|
|
I know about Fischer indole synthesis, but for unsubstituted indole it would use acetaldehyde, not a ketone. So this is why i was asking, does this
work with aldehydes?
|
|
|
Nakhimov
Harmless
Posts: 16
Registered: 8-12-2018
Member Is Offline
|
|
A few possible synthetic routes:
1. o-toluidene and chloroform via formation of an diazonium species [Fluorescent probe for detecting silver ion, its preparation method and
application, Quing, et al.]
2. Dehydration of 2-aminobenzeneethanol [Iridium Catalysts for Acceptorless Dehydrogenation of Alcohols to Carboxylic Acids: Scope and Mechanism,
Cherepakhin, Valeriy and Williams, Travis J. and Iridium(III)- benzoxazolyl and benzothiazolyl phosphine ligands catalyzed versatile alkylation
reactions with alcohols and the synthesis of quinolines and indole, Huang et al.]
3. aniline and oxirane via zinc chloride/silver catalytic route [Process for the preparation of indoles, Xiaoqiang et al.]
4. 2-phenylamino-ethanol and a silver catalyst [also by the Xiaoqiang method above]
Realistically, given the nuisance of using silver catalysts in a home lab setting, have you considered using a ketone with a reasonably good leaving
group? You could possibly do a second step to kick off the unwanted substituent. It would reduce yields but should be pretty feasible.
|
|
|
AvBaeyer
National Hazard
Posts: 644
Registered: 25-2-2014
Location: CA
Member Is Offline
Mood: No Mood
|
|
Acetaldehyde is very problematical in the Fischer indole synthesis as are most aliphatic aldehydes. See Robinson's tome on the Fischer Indole
Synthesis (a very big book). Despite having to add a second reaction step, Assured Fish's suggestion using pyruvic acid and phenylhydrazine followed
by decarboxylation may be the most facile synthesis. I base this on the knowledge that both phenylhydrazine and pyruvic acid can be synthesized from
easily available starting materials available to the hobbyist. Perhaps the best method currently would be reaction of o-nitrotoluene with
dimethylformamide dimethyl acetal followed by reduction to get indole directly. This process is fully documented in "Organic Syntheses" and is a
widely used method for synthesis of indoles. Either of the mentioned methods would work well and the choice would depend on availability of reagents.
At some risk, I suggest that the OP learn to do some basic literature searching to find leads for the information being asked for. The question is so
basic that even wikipedia would be useful.
AvB
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
