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

Printable Version  
Author: Subject: Methyl ester and o-methylation of sinapic acid
DrDevice
Hazard to Self
**




Posts: 65
Registered: 19-3-2012
Member Is Offline

Mood: Incompatible with carbon based lifeforms

[*] posted on 26-5-2021 at 04:32
Methyl ester and o-methylation of sinapic acid


Sinapic acid (or sinapinic acid) is a hydroxycinnamic acid prevalent in mustard plant byproduct. It can be esterified as per carboxylic acids, and o-methylated as per phenols. Of interest is the ease of o-methylation using DMC and a phase transfer catalyst.


hydroxy cinnamates.png - 21kB

Esterification of sinapic acid


6.9g sinapic acid @224.21 = 30.8mmol, is suspended in 30ml MeOH.

Prepare methanolic HCL by adding 1.2 equiv (2.9g) of acetyl chloride dropwise to 40ml ice-cold MeOH.

The methanolic HCL is added slowly to the sinapic acid suspension, then stirred for 11 hours at 40 - 45C (It may take much less time than this; I just let it run overnight). The ester is obvious in the reaction mix as crystalline material.

TLC at 11 hrs (1:1 EtOAc:hexane) showed no trace of the source acid.

100 ml water is added to the reaction mixture and chilled in the fridge for a few hours. The raw methyl ester is filtered off, then dissolved in EtOAc. The solution is washed with 30ml 5% sodium bicarbonate solution, organic fraction washed with brine, then dried with MgSO4, and solvent evaporated.

The ester is re-crystalized from 1:1 EtOH:water, for a total yield of 5.7g, or 78%. MP ~ 86C (I can't find a literature MP value)

O-methylation of methyl sinapate using DMC and PTC

If you have access to a modest pressure vessel, dimethyl carbonate and tetrabutylammonium bromide, o-methylation can be done avoiding the use of (eg) dimethyl sulfate or methyl iodide.

5.65g methyl sinapate (23.4mmol), 40ml DMC, 0.1 equiv of TBAB (0.76g), and 1.5 equiv K2CO3 are combined in a 100ml glass flask capable of sustaining 140C at elevated pressure. (I don't know just how much pressure is involved here, but I've had no failures to date. I do however use a "blast shield" around my oil bath in case of catastrophic failure. I use a flask manufactured by "Ace" glass)

A stir bar is added and the flask flushed with nitrogen prior to screwing down the lid. The flask is immersed in an oil bath at 140C and contents magnetically stirred.

After 8 hrs, the flask is removed from the oil bath and allowed to cool to RT. The lid is cautiously unscrewed and CO2 comes out of solution.

TLC (1:3 EtOAc:hexane) shows a spot at Rf = 0.52, compared to 0.24 for the source methyl sinapate. No trace of the methyl sinapate is seen in the reaction product.

The solids are filtered and washed thoroughly with acetone, and the filtrates combined and evaporated. The yellow material is re-crystalized twice from 1:1 EtOH:water to yield a fluffy slightly crystaline white solid, methyl 3,4,5-trimethoxycinnamate, MP 93 - 94C, lit. 99 - 100C). Yield exactly 5.00g, 19.8mmol, 85%, so quite a good result!

So I guess there are still some impurities in there - or maybe cis- / trans- isomers?? Nothing shows up on the TLC though with the eluents I have tried.

I've tried the process with other hydroxycinnamic acids: o-coumaric acid works fine, but ferulic acid is offering some "random" results I haven't got to the bottom of yet.

Next stop - amidation. I'm getting some encouraging results with @kmno4's"put it in a bottle with ammonia solution and leave it for several weeks" approach. Also playing with reduction of the double bond with NiCl2/Zn.



[Edited on 26-5-2021 by DrDevice]
View user's profile View All Posts By User
njl
International Hazard
*****




Posts: 584
Registered: 26-11-2019
Location: under the sycamore tree
Member Is Offline

Mood: ambivalent

[*] posted on 26-5-2021 at 11:33


Really refreshing stuff! Would love to hear more about the other acids you tried, and the experiments you have planned.



Reflux condenser?? I barely know her!
View user's profile View All Posts By User
karlosĀ³
International Hazard
*****




Posts: 1377
Registered: 10-1-2011
Location: yes!
Member Is Offline

Mood: aminoketonologisch 8)

[*] posted on 26-5-2021 at 11:48


Sounds cool.
Have you bought or isolated those acids, or synthesised them yourself?
View user's profile View All Posts By User
DrDevice
Hazard to Self
**




Posts: 65
Registered: 19-3-2012
Member Is Offline

Mood: Incompatible with carbon based lifeforms

[*] posted on 28-5-2021 at 19:00


I bought the sinapic acid. I did try to do an extraction of sinapoyl choline from mustard cake, the remnants of mustard seed after oil extraction, but with a singular lack of success.

I'll write up the ferulic acid experiment separately - mostly based around o-methylation of ethyl ferulate. I am getting two distinct products, one of which is a very low melting point solid, which doesn't line up with any known melting point I can find of any ferulic acid derivative.

The amide is interesting and results are encouraging. Not ready to "publish" my results yet, but I'm fairly confident I have synthesized "3,4,5-trimethoxycinnamide" - melting point is consistent. Interestingly, this is also known as "cintriamide", and seems to have some history as an anti-psychotic drug. Can't find much in the literature about its therapeutic use, however.

I'm also planning on some work in reducing the double bond using Ni/ZnCl2. Watch this space.
View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2349
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 30-5-2021 at 06:58


If you have the pressure tube, then you could put the ester and some source of ammonia (ideally a solution in isopropanol) in it, then heat it to 120 or more for a gew hours, that will often displace a methyl ester.
View user's profile View All Posts By User

  Go To Top