Sciencemadness Discussion Board
Not logged in [Login - Register]
Go To Bottom

Printable Version  
Author: Subject: Synthesis of Indole-3-butyric acid (rooting hormone) - how difficult is this?
RogueRose
International Hazard
*****




Posts: 943
Registered: 16-6-2014
Member Is Online

Mood: No Mood

[*] posted on 16-6-2017 at 23:36
Synthesis of Indole-3-butyric acid (rooting hormone) - how difficult is this?


I've recently seen some other compounds that have a similar structure as this and was wondering if there was a way to synthesize this with a moderate lab.

Here is theWiki page link

What the compound looks like.





View user's profile View All Posts By User
Melgar
International Hazard
*****




Posts: 1831
Registered: 23-2-2010
Location: NYC
Member Is Online

Mood: Aromatic

[*] posted on 17-6-2017 at 04:29


Starting with indole, it should be easy enough, since the 3-position is most active. Cleave THF with HBr, to 4-bromobutanol, then use it for FC alkylation and oxidize? Just a guess, no idea if it'd work. The acetic acid version could be produced from tryptophan though, which is probably easier to get than indole.



The first step in the process of learning something is admitting that you don't know it already.
View user's profile View All Posts By User
Jon snow
Harmless
*




Posts: 8
Registered: 6-1-2016
Member Is Offline

Mood: No Mood

[*] posted on 17-6-2017 at 04:33


Maybe it could be possible to do a fisher indole synthesis using phenylhydrazine and 6-oxohexanoic acid but i don't know where you could find this second reagent
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1061
Registered: 3-11-2013
Member Is Online

Mood: No Mood

[*] posted on 17-6-2017 at 05:12


Can you use gramine as a precursor? Indole chemistry is a bit odd because of the various "quinoid" intermediates that allow unexpected rearrangements and alkylations. Gramine as such transfers an "indole-3-methyl" synthon to carbanions like nitropropane.

https://en.m.wikipedia.org/wiki/Gramine

I'm thinking graminium and ethyl pyruvate/NaOEt to get to alpha-oxo-indole-3-butyrate and then reduce the carbonyl with hydrazine.

[Edited on 17-6-2017 by clearly_not_atara]
View user's profile View All Posts By User
CuReUS
International Hazard
*****




Posts: 822
Registered: 9-9-2014
Member Is Offline

Mood: No Mood

[*] posted on 17-6-2017 at 06:46


I see 3 ways to make it :-
1.reacting acrylic acid with indole to get indole-3-propionic acid and then doing the arndt-eistert reaction -http://www.organic-chemistry.org/abstracts/literature/443.sh...
2. using bacteria - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656143/
3. from indole - " Nametkin et al. Doklady Akademii Nauk SSSR, 1941 , vol. 32, p. 333 "
View user's profile View All Posts By User
zed
International Hazard
*****




Posts: 1618
Registered: 6-9-2008
Location: Great State of Jefferson, City of Portland
Member Is Offline

Mood: Semi-repentant Sith Lord

[*] posted on 24-6-2017 at 16:35




Indole can be alkylated by Alcohols under some conditions. Like with Ethylene Glycol, base, heat and pressure, to produce tryptophol. Can also be alkylated by Glycolic Acid and base to produce Indole acetic acid. Not immune to alkylation via Acrylic Esters and base, or via reflux with acetic anhydride.

Could produce the iso-butyric acid via methyl-methacrylate.

Some folks use this approach. https://commons.wikimedia.org/wiki/File:Synthesis_of_indole-...

Then of course, is the popular e-bay synthesis. Where you send off nine bucks to a stranger, and you magically find 10 grams of Indole-3-Butyric Acid in your mailbox a few days later (Free Shipping).
http://www.ebay.com/itm/IBA-K-Indole-Butyric-Acid-Water-Solu...

I like that one!



[Edited on 25-6-2017 by zed]

[Edited on 25-6-2017 by zed]

[Edited on 25-6-2017 by zed]
View user's profile View All Posts By User
CuReUS
International Hazard
*****




Posts: 822
Registered: 9-9-2014
Member Is Offline

Mood: No Mood

[*] posted on 25-6-2017 at 10:30


Quote: Originally posted by zed  

Indole not immune to alkylation via Acrylic Esters and base

Quote: Originally posted by CuReUS  
1.reacting acrylic acid with indole to get indole-3-propionic acid...

https://www.google.com/patents/US3062832

[Edited on 25-6-2017 by CuReUS]
View user's profile View All Posts By User
zed
International Hazard
*****




Posts: 1618
Registered: 6-9-2008
Location: Great State of Jefferson, City of Portland
Member Is Offline

Mood: Semi-repentant Sith Lord

[*] posted on 26-6-2017 at 14:29


Perhaps I was imprecise. Seems to me, this action can also be accomplished by refluxing indole with an acrylic ester, in acetic anhydride. I've got a paper somewhere.

Making it possible to produce our desired products, utilizing acrylic esters, rather than free acids.

There has been recent work alkylating indoles with alcohols, utilizing Pt or Iridium catalysts.

One potential alkylating agent, which could produce our desired product, might be difficult to obtain.

Gamma-Hydroxy Butyric Acid.......GHB!

https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid

PS. The Lactone used to alkylate Indole, to produce the Indole 3-Butyric Acid, that you initially inquired about (earlier post).......Appears to be Gamma- Butyrolactone. A precursor to GHB. It also, might be hard to come by.

Buying your simple Auxin on ebay might be the easiest thing. The precursors are harder to buy, than the finished product.
Even Indole itself, used to be considered a suspicious purchase.



[Edited on 26-6-2017 by zed]

[Edited on 26-6-2017 by zed]

[Edited on 27-6-2017 by zed]

[Edited on 27-6-2017 by zed]
View user's profile View All Posts By User
boilingstone2
Harmless
*




Posts: 6
Registered: 6-7-2017
Member Is Offline

Mood: No Mood

[*] posted on 14-7-2017 at 17:15



Quote:

Maybe it could be possible to do a fisher indole synthesis using phenylhydrazine and 6-oxohexanoic acid but i don't know where you could find this second reagent


One possible route to 6-oxohexanoic acid could be to:

1. Start by performing a Baeyer-Villiger oxidation on cyclohexanone to yield the caprolactone

2. Hydrolyze the caprolactone with dilute acid to yield 6-hydroxyhexanoic acid

3. Oxidize the 6-hydroxyhexanoic to 6-oxohexanoic acid

Does this sound feasible? Shouldn't the hydrolysis of lactones proceed like the hydrolysis of most esters?

The cyclohexanone will be much easier to get your hands on, and you could even try synthesizing it yourself if you felt so inclined. Same goes for phenylhydrazine, there are a few videos on the synthesis of phenylhydrazine on youtube I believe.
View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 1827
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 14-7-2017 at 18:34


your route to 6-oxohexanoic acid sounds plausible. Step 2 may require base rather than acid, not sure of the equilibrium in acid. But overall it looks reasonable. Or try to find 1,6-dihydroxyhexane and partially oxidize it. Or monoprotect and then oxidize.
View user's profile View All Posts By User
Waffles SS
Fighter
*****




Posts: 817
Registered: 7-12-2009
Location: My Lab
Member Is Offline

Mood: No Mood

[*] posted on 15-7-2017 at 18:58



Reaxys search of IBA
Attachment: IBA.pdf (176kB)
This file has been downloaded 113 times
View user's profile View All Posts By User
Jon snow
Harmless
*




Posts: 8
Registered: 6-1-2016
Member Is Offline

Mood: No Mood

[*] posted on 16-7-2017 at 06:36


Boilingstone2 I find the idea of the Baeyer-Villigen reaction great since cyclohexanone is quite easy to find and if it's non available it's easy produced via cyclohexanol but as Dr.Bob pointed out a base hydrolysis sounds better to me as the equilibrium for the acid hydrolysis of a lactone usually isn't great.
Also now that I'm thinking a little bit more about the Fisher indole synthesis I presume that it might be better to use the acetal of the aldehyde but this should be easily obtainable using Trimethyl orthoformate or a similar reagent
View user's profile View All Posts By User
boilingstone2
Harmless
*




Posts: 6
Registered: 6-7-2017
Member Is Offline

Mood: No Mood

[*] posted on 16-7-2017 at 14:01


Jon Snow:
Great! Looking further into the hydrolysis of lactones, I learned it is more difficult than the hydrolysis of something like ethyl acetate (I'm being careful not to say "a normal ester") because there is only 1 mol of product generated rather than 2 mol, which makes the change in entropy much less, therefore making the reaction not as energetically favored.

Still though! Simply substituting the acid hydrolysis step for a base hydrolysis would hardly make this method any less feasible.

I can try and dig up some documentation I found regarding the baeyer-villiger oxidation. While I've never attempted it, the reagents involved (if one tries to scrape by using peracetic acid) sound within the reach of amateur chemists.

Any clue as to why an acetal would work better for the Fischer indole synthesis? Just looking on wikipedia, the mechanism seems to start with a the formation of a hydrazone, which I don't immediately see happening using an acetal.
View user's profile View All Posts By User
NEMO-Chemistry
International Hazard
*****




Posts: 1560
Registered: 29-5-2016
Location: UK
Member Is Offline

Mood: No Mood

[*] posted on 28-10-2017 at 07:52


I am also interested in this synth, some of what I have found is confusing. However org synth has procedure for similar compound (IAA) that is here

http://www.orgsyn.org/demo.aspx?prep=CV5P0654

I have seen part of a paper that showed going from IAA to IBA, but the pdf was corrupt when I downloaded. So at the moment I have no idea if the pathway mentioned was biological or doable in a lab. As a side note IAA while not as effective as IBA, it is still pretty good on its own.

For my application I need different Auxins in a gel type material sold for planting cuttings, has anyone got a patent for the actual Gel? or knows how to make the clear Gel? I dont think Agar or similar will do.

EDIT
Rose as another side note
I have always used willow water for rooting, it wasnt until recently I discovered that the main ingredient for rooting in willow water, is infact ASPIRIN!! Kind of makes sense once you know though.

[Edited on 28-10-2017 by NEMO-Chemistry]

Not sure how much help this is, it came from wiki commons



[Edited on 28-10-2017 by NEMO-Chemistry]

Synthesis_of_indole-3-butyric_acid.png - 38kB
View user's profile View All Posts By User
Quaff
Banned
*




Posts: 24
Registered: 31-10-2017
Member Is Offline

Mood: No Mood

[*] posted on 1-11-2017 at 14:29


1) ethyl succinate + PCl3 ------> ethyl succinyl chloride
2) indole + ethyl succinyl chloride ------> ethyl indole-3-butyrate
3) de-esterify
View user's profile View All Posts By User

  Go To Top