2-Alkoxy-4,5-methylenedioxybenzaldehyde made easy?

[GC_MS]

I recently found an article which might be of interest to fellow bees, because it might open a new route to 2-alkoxy-4,5-methylenedioxybenzaldehydes. MMDA-2 and its Tweetio analogue EMDA-2 (both described in

PiHKAL #133

(http://www.erowid.org/library/books_online/pihkal/pihkal133.shtml)) are the end products I had in mind.
I'd be interested in pursuing its synthesis following the method(s) I have in mind. However, Fatum is not my partner in crime these days and a lack of time necessitates me to abandon or dramatically postpone the project. I decided to communicate my findings with the Fellow Bees, in the hope there would be others interested in the project. Maybe they can add their theoretical comments, or in the most ideal circumstances, try the synthesis in their own lab.

PART I. Synthesis of 2-methoxy-4,5-methylenedioxycinnamic acid

Reference: CK Sehgal, PL Kachroo, RL Sharma, SC Taneja, KL Dhar, CK Atal. Synthesis of cis and trans 2-methoxy-4,5-methylenedioxycinnamoylpiperidide and revised structure of a new alkaloid from Piper peepuloides. Phytochemistry 18 (1979) 1865-1867. DOI:

10.1016/0031-9422(79)83072-1

Synthesis of 4,5-methylenedioxycoumarin (ayapin)

Esculetin (1 g) was dissolved in 90 mL dry acetone and 10 mL DMF. To this solution were added 25 g potassium carbonate and 10 mL CH₂I₂. The mixture was refluxed on a water bath for 40 hours. The product crystallized from EtOAc-petroleum ether (500 mg), mp 230°C (lit mp 232°) [2]. It analyzed for C₁₀H₆O₄.

Synthesis of 2-methoxy-4,5-methylenedioxy-trans-cinnamic acid

A solution of ayapin (300 mg) in aqueous NaOH (60%) was warmed on a water bath until the coumarin was completely dissolved. To this was added DMS (3 mL) slowly with continuous stirring. The mixture was warmed at 50°C and stirred for 6 hours. The reaction mixture was then cooled to 0°C and acidified with diluted HCl. The precipitate was collected, dried and crystallization from acetone gave the cinnamic acid (200 mg), mp 244°C. It analyzed for C₁₁H₁₀O₅

Synthesis of 2-methoxy-4,5-methylenedioxy-cis-cinnamic acid

6,7-Methylenedioxycoumarin (450 mg) was dissolved in 20 mL dry THF. 500 mg of NaH (60%) dispersed in oil were added slowly to the stirred solution, the temperature being maintained at 25°C. MeI (3 mL) was then added and stirring continued for a further 4 hours. The mixture was cooled and 40 mL 0.5 N HCl was added. It was then extracted with EtOAc and the organic layer was washed and dried. After removal of the solvent, 300 mg of a mixture of cis- and trans-(4:1) 2-methoxy-4,5-methylenedioxycinnamic acid was obtained.

Notes on Part I.

1. The author methylated the phenyl bound hydroxyl group that came available after hydrolysis of the coumarin to its corresponding cinnamic acid. I suppose that DMS and MeI can be substituted for diethyl sulfate and EtI, respectively. This should result in 2-ethoxy-4,5-methylenedioxycinnamic acid.

2. Esculetin... Hey, thank you GC_MS! Let's grab the chem supplier's catalogue and... only $100 for a 5 g quantity? Sounds OK, no? I guess not. That is why I included a limited literature search on the synthesis of esculetin.
Esculetin, aesculetin, 6,7-dihydroxycoumarin: it's all the same for CAS 305-01-1, or:



Description of its synthesis using 1,2,4-triacetoxybenzene and hydrosuccinic acid:

- Amiard et al. Bull Soc Chim Fr (1947) 512
- Ishifuku et al. Yakugaku Zasshi 73 (1953) 332; CA.1954 2695
- HB Singh et al. Indian J Chem A 20(10) (1981) 1026
- YA Jackson. Heterocycles 41(9) (1995) 1979

Description of its synthesis using 3,4-dihydroxycinnamic acid (caffeic acid):

- F Borges et al. Helv Chim Acta 75(4) (1992) 1061 [45 days reaction time!]
- M Sato et al. Chem Pharm Bull 33(3) (1985) 1289

A final addition: 1,2,4-triacetoxybenzene is easily obtained via the Thiele-Winter acetoxylation of 1,4-benzoquinone (80%+ and even 95% with triflic acid catalyst). About the synthesis of 3,4-dihydroxycinnamic acid: I'd prepare it via the Perkin reaction of 3,4-dihydroxybenzaldehyde (demethylation of vanillin), or via a similar process (e.g. HOAc and NaBH₄ instead of AcO₂). I found one reference to an article describing the synthesis of caffeic acid, but I don't have access to it right now: J prakt Chem 145 (1936) 265.

PART II. Synthesis of 2-alkoxy-4,5-methylenedioxybenzaldehyde

Cinnamic acids can be oxidized to their corresponding benzaldehydes using KMnO₄/alumina. The procedure can be found on

Rh's site

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/benzaldehydes.kmno4.html), or you can take a look at the original article: S Lai et al. Synthesis (2001) 1644, DOI:

10.1055/s-2001-16760

.
Drawbacks: the article didn't test the cinnamic acids I discussed here, so there still is a chance that it won't work (for a reason I don't see). Also, the article works on a small scale. The article does work as described for some propenylbenzenes, but I only tested them on microscale as well.

Voila, that's it. Input - theoretical and practical - always welcome.

[GC_MS]

Although aesculetin can be prepared synthetically, there seems to be an interesting natural source. I actually dare to say very interesting, because its natural source is very common.
Aesculetin can be prepared by hydrolysis of aesculin (or esculin), which is a natural glucoside of the latter:



So basically, if you would be able to gather some m³ of aesculin, you might have a reliable source for MMDA-2   .

The following is a resume of FSH Head et al. Natural glucosides. Part II. The constitution of Æsculin. J Chem Soc (1930) 2434-2437.

- The glucoside aesculin was first isolated in the pure state from the bark of Æsculus hippocastanum by Minor (Arch Pharm 38 (1831) 130.
- Rochleder and Schwartz (Ann 87 (1853) 186; 88 (1853) 356) demonstrate that aesculin is a monoglucoside of aesculetin and that it was hydrolyzed by emulsin as well as by mineral acids.
- Synthesis of aesculetin by Gattermann and Koebner (Ber Deutsch chem Ges 32 (1899) 287).
- Conversion of aesculetin into into 2,4,5-trimethoxycinnamic acid by Tiemann and Will (Ber Deutsch chem Ges 15 (1882) 2072); oxidation of this cinnamic acid to asaraldehyde and asaronic acid by Moore (J 99 (1911) 1047).
- Glucose is the sugar derived from aesculin (Schunck and Marchlewski. Ann 278 (1893) 349; ter Meulen. Rec Trav Chim 24 (1905) 446).

And for the plant n00bs amongst us, Æsculus hippocastanum is horse chestnut. A very good start to find out everything you need to know about horse chestnut and aesculin:

http://www.herbmed.org/viewherb.asp?varHerb_ID=14

Also, did you notice the reference to Tiemann's article? I'll fetch it ASAP, because the possibility of obtaining asaraldehyde from horse chestnut bark needs further exploration...  

[GC_MS]

L Gattermann, M Koebner. Synthese des Daphnetins und Aesculetins. Ber Deutsch chem Ges 32 (1899) 287-288.

Synthesis of aesculetin

[...]2 g 2,4,5-trihydroxybenzaldehyde, 3 g anhydrous NaOAc and 10 g acetic anhydride are heated for 4-5 hours at 170-180°C. Dilution and mixing with cold water causes precipitation; the precipitate is isolated and recrystallized from hot water. When the solution cools down, colourless needle-shaped crystals (133-134°C) are formed. This substance is, according to the mp, diacetylaesculetin.
Saponification of this product is easy and yields aesculetin. [...]

Additional notes

It seems that our good friend Ludwig Gattermann first acetylates the 2,4,5-trihydroxybenzaldehyde to obtain 2,4,5-triacetoxybenzaldehyde, which is converted to 6,7-diacetoxycoumarin due to the loss of water (interaction between the -CHO and acetoxy group at position 2). I don't think it is possible to subject 1,2,4-triacetoxybenzene to a formylation reaction without ending up with 99% undesired crap (correct me if I'm wrong), so I think that you'll have to synthesize the 2,4,5-trihydroxybenzaldehyde (which, I think - but correct me if necessary - is only achievable in decent yield via the Gattermann formylation reaction).
Also, for the fans of chemistry history, Gattermann proves the constitution of asarone in a new, seperate article on the next page (i.e. 289)   .

[Vitus_Verdegast]

Quite a nice piece of chemistry you present here.  

Here is some additional information on the aesculin content of Aesculus hippocastanum L. bark:

HPLC Analysis of Esculin and Fraxin in
Horse-Chestnut Bark (Aesculus hippocastanum L.)

Croatica Chemica Acta 72 (4) 827-834 (1999)

Full-text PDF:

http://public.srce.hr/ccacaa/CCA-PDF/cca1999/v72-n4/CCA_72_1999_827-834_STANIC.pdf

Abstract:
Selective and sensitive HPLC method was used for simultaneous determination of esculin and fraxin in a methanolic extract of horse-chestnut bark (A. hippocastanum L.). The samples were separated on a LiChrospher RP 18 column (150 x 4 mm i.d.) with the mobile phase consisting of acetic acid, 1%, and methanol (84:16 v/v) at a flow rate of 1.0 mL/min and quantified by measuring the UV absorbance at 340 nm. The assay of esculin and fraxin is linear over the range 0.02–2 mg/mL. It was shown that the bark gathered from older branch sections (5 cm in diameter) during the four seasons contained the greatest amount of esculin (3.6–6%) and fraxin (1.5–2.6%). Nevertheless, the bark of horse-chestnut tree (40 cm in diameter) was found to be the richest source of esculin (7.9%) as well as of fraxin (3.1%). In contrast, the bark of young shoots contained the lowest amount of esculin (0.4–0.8%) and fraxin (0.2–0.3%).

Key words: Horse-chestnut bark, esculin, fraxin, seasonal variation, reversed-phase high- performance liquid chromatography, UV detection

It is obvious that the highest content of esculin and fraxin was found in the oldest bark samples (branch diameter of 5 cm) during the whole growing period. The values differed from 3.61% in autumn to 5.96% in summer for
esculin and from 1.53% to 2.62% for fraxin. In the same period, the coumarin content in the youngest bark (branch diameter of 1 cm) varied in a range from 1.06% to 3.01% for esculin and from 0.45% to 1.04% for fraxin.
As regards the quantities of esculin and fraxin throughout the seasons, it was found that all summer samples were the richest plant material (Figure 4). In contrast, the samples from autumn or spring contained the lowest amount of these substances. It is also evident that the ratio of fraxin and esculin varied from about 1:2 to 1:3 in all samples analyzed.

Also, no severe damage to the trees is done, as the article states that the external bark layer (the cork) contains much more aesculin than the internal one.  


One could perhaps extract the dried, ground bark with alcohol, evaporate this to dryness, wash residue with petroleum ether, add acidified water, remove the coloring with a little chloroform, and extract the glucoside fraction with ether.
This is how the glucoside hydrangin is extracted from the shrub Hydrangea arborescens L., as described in the American Journal of Pharmacy, Vol. 59 (1887):

http://www.ibiblio.org/herbmed/eclectic/journals/ajp1887/03-hydrangea.html

Additional note on fraxin :

Fraxin  (= 7-hydroxy-6-methoxycoumarin-8-glucoside) is a colorless, crystalline substance found in Fraxinus sp. (Ash Tree) and together with aesculin in the Horse Chestnut Tree. It shows a delicate fluorescence in alkaline solutions. A synonym for fraxin is paviin.

The aglycon of fraxin is fraxetin, or 6-methoxy-7,8-dihydroxycoumarin (the glucose part being split off).
 We need to find a good procedure to separate fraxin/fraxetin from aesculin/aesculetin.
Do not throw the fraxin fraction away, 'cause after applying GC_MS's above procedure on it, 2,5-dimethoxy-3,4-methylenedioxybenzaldehyde is obtained, precursor for DMMDA.  

[Vitus_Verdegast]

More data on the extraction of aesculin and the synthesis of aesculetin:

http://www.swsbm.com/SayreMM/Sayre%27s_Materia_Medica-3.pdf

A Manual of Organic Materia Medica and Pharmacognosy by Lucius E. Sayre, B.S., Ph. M (4th edition, 1917)

331. ÆSCULUS HIPPOCASTANUM Linné.—HORSE-CHESTNUT. (Bark and Fruit.)
Habitat: Asia; cultivated as an ornamental tree in Europe and North America.
The bark contains a bitter glucosid, esculin, isomeric with quinovin in cinchona bark, for which it is used as a substitute in Europe.
[...]
Preparation of Esculin.
—Precipitate a decoction of the bark with lead acetate, treat the filtrate with H₂S, evaporate and recrystallize.

Yuck!  This is just posted as an historical example and it is not recommended to perform it the crazy old chemist's way.

Patent WO02053552

Provided are esculetin compounds, intermediates thereof, a process for preparation of the esculetin compounds, and antimould and herbicide compositions for agricultural and horticultural use, containing the compounds or the intermediates. The process for preparation of the esculetin compounds is an industrially practicable one which enables the preparation of esculetin compounds of the general formula (2) at a low cost in high yield and is characterized by cyclizing a trihydroxy- benzaldehyde of the general formula (1) with acetic anhydride or the like in an aprotic polar solvent in the presence of a weak base. (1) (2)



This old USSR patent looks interesting, but we'll need the assistance of a friendly Hyperlab bee to translate it for us (it's only 2 pages   ) :

Patent SU595320

METHOD OF EXTRACTING ESCULETIN FROM VEGETABLE RAW MATERIAL

I forgot to add for fraxin that the coumarin can also be fully methylated to yield the very interesting 2,3,4,5-tetramethoxybenzaldehyde ;

I must say this definately calls for some champagne, all these psychedelic possibilities just coming from the bark of one very common tree.
Move over Sassafras albidum Nees! Make room for the Horse-Chestnut Tree!    

[GC_MS]

I'm just goint through Naturally occurring plant coumarins in "Fortschritte der Chemie organischer Naturstoffe", and it is astonishing how many plant there are in my back garden that contain interesting coumarins. If they contain much of the coumarin, that is (and which is not mentioned in the book... a shame).

[Antoncho]

Beelow follows the translation of the essential details from

Patent SU595320

, as requested by Vitus_Verdegast above as well as in Post 460563 (not existing).




…The invention is concerned with improved isolation of esculetin from the plant matter.

According to the priorly known method, the plant material is xtracted w/aqueous alcohol (50+-5 C), the extract is conc’d till 1/36-1/38 of original volume, then treated with n-butanol/chloroform (2:3), the organic phase is evaporated, the residue is dissolved in aq. Ethanol, the soln. is treated w/CCl4 and crystallized.

However, thus obtained preparation contains admixtures of various other coumarins: fraxin, scopoletin and umbelliferon (sp?) and can’t bee used as a standard for determination of esculetin in the products of pharmaceutical and flavoring industry.

According to the present invention, the crude plant matter is xtracted w/aqueous alcohol, the extract is conc’d till 1/36-1/38 of original volume, and then additionally dissolved in water at 40-60 C, chromatographed thru a poliamide sorbent, eluted w/water, chromatographed and then again eluted w/aq. Alcohol. 20-25% EtOH is preferentially used.

Example 1.

1kg of dry macerated cichorium grass (Cichorium intybus L.) is loaded into a percolator and xtracted w/stirring 3x1200 mls 50% EtOH, each xtraction taking 45 mins. The extracts are pooled, evaporated till volume of 1 liter and treated with 6x2000mls n-butanol:CHCl3 (2:3), the organic phase is separated, vac distilled and the remaining resin is dissolved at 40-60 Ñ in 250mls water and placed into a chromatography column filled w/a polyamide sorbent (d=5cm, h=50cm). Demineralised water is used as an eluent, collecting 250mls fractions. The separation of oxycoumarins’ mixture is observed in a filtered UV light (lambda=360 nanometers). The fractions from 1 to 15 contain esculin, cichoriin, scopoletin, umbelliferon. The fractions 16-26, containing mainly esculetin (along with some esculin), are conc’d in vacuo until dry, dissolved in 100-150mls 20% aq ethanol and again pulled thru a column (d=5cm, h=30cm) using 20-25% EtOH, collecting 200ml fractions. Fractions 4-15, containing chromatographically pure esculetin, are evap’d in vacuo and crystallized from 30-35% EtOH.

The yield is 1 g (75-80% of total content).






This route definitely takes some patience


Antoncho

[GC_MS]

Thanks to our Russian connection for the translation!

However, thus obtained preparation contains admixtures of various other coumarins: fraxin, scopoletin and umbelliferon (sp?) and can’t bee used as a standard for determination of esculetin in the products of pharmaceutical and flavoring industry.









If I was trying to obtain 2,4,5-trimethoxycinnamic acid, I might want to methylate just about every available phenyl OH and seperate them only afterwards via distillation.

Umbelliferron -> 2,4-dimethoxycinnamic acid/benzaldehyde
Scopoletin -> 2,4,5-trimethoxycinnamic acid/benzaldehyde
Fraxin -> 2,3,4,5-tetramethoxycinnamic acid/benzaldehyde
Esculin -> 2,4,5-trimethoxycinnamic acid/benzaldehyde

[Vitus_Verdegast]

Artemisia annua L.

Patent US6337095

Abstract

The invention relates to a process for the isolation of compound scopoletin which is used as nitric oxide synthesis inhibitor from Artemisia annua and other plant families, said process comprising extraction of dried powdered material of different plant parts with an aqueous acetonitrile solvent in the ratio of 1:5 for 6 to 8 hrs., concentration of the extracted solvent upto 30% of its original extract under vacuum, partitioning the concentrated extract with halogenated solvent to transfer scopoletin in the non-polar halogenated solvent, drying halogenated solvent over anhydrous sodium sulphate and evaporating the solvent, crystallizing the residues in methanol and filtering the crystals, concentrating the filtrate and chromatographed on silica gel, eluting scopoletin in chloroform/methanol mixture; and crystallization of the fractions containing the scopoletin to get the pure scopoletin compound.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a process for the isolation of compound scopoletin which is used as nitric oxide synthesis inhibitor from Artemisia annua and other plant families, said process comprising:

a) extraction of dried powdered material of different plant parts with an aqueous acetonitrile solvent in the ratio of 1:5 for 6 to 8 hrs.,

b) concentration of the extracted solvent up to 30% of its original extract under vacuum,

c) partitioning the concentrated extract with halogenated solvent to transfer scopoletin in the non-polar halogenated solvent,

d) drying halogenated solvent over anhydrous sodium sulphate and evaporating the solvent,

e) crystallizing the residues in methanol and filtering the crystals,

f) concentrating the filtrate and chromatographed on silica gel,

g) eluting scopoletin in chloroform methanol mixture; and crystallization of the fractions containing the scopoletin to get the pure scopoletin compound.

In one embodiment of the invention, Artemisia annua plant was selected for the isolation of scopoletin. Artemisia annua ariel parts from Spain have reported 0.02% scopoletin and England (cult) 0.034%. China has also reported the presence of scopoletin from the whole plant (Brown, G. D.: Two new compounds from Artemisia annua: J.Nat. Prod. 58, 300 (1992); Marco, J. A.; Sawz, J. F.; Bea, J. F.; Barber, O.: Phenolic constituents from Artemisia annua: Pharmazie 45, 382-383 (1990); Liu, H. M.; Li, G. L., Wu, H. Z.: Studies on the constituents of Quinghao:Yao Hsuch Hsuch Pao, 37, 129-143 (1979)).

In India CIMAP, Lucknow, has developed a new variety of Artemisia annua "Jeevan raksha" producing high content of artemisinin and biomass (stems & leaves). Artemisinin and its derivative are reported as potent against chloroquine resistant multi drug resistant and severe complicated malaria.(!) Artemisia annua plant is the only source of artemisinin.

Screening of all the three major parts of the A. annua plant of the new variety for scopoletin was carried out by HPLC. The content of scopoletin obtained in different plant parts are as follows; leaves 0.2%, Stems 0.3% and roots 0.004%. The yield of the scopoletin is very high as compared to other reported plants. The stem part of the plant Artemisia annua is a waste material as no artemisinin is present in the stems. The biomass of the stem portion of the plant is five times more than of the leaves. Therefore, we have selected the stem part of the plant Artemisia annua for the isolation of scopoletin. Also the stem portion of the stems was found to contain less colouring and fatty material which eases the isolation and purification of scopoletin.

In the prior art, it has been observed that non polar solvents for extraction of the plant materials were employed, resulting in less recovery of coumarins. Still, polar solvents (methanol and ethanol) used for the extraction of coumarins resulted in a higher amount of total extract having more colouring and fatty material. The separation of fatty and colouring matter is a difficult task. In the present invention, we have selected aqueous acetonitrile solvent for the extraction which yielded a higher amount of scopoletin with less amount of colouring and fatty material. Also, the separation of water from acetonitrile for recovery of the pure solvent for reuse is much easier.

In the prior art the scopoletin was purified from the crude extract through acid base treatment or by sublimation method which reduces the amount of scopoletin due to rearrangements and thermal decomposition. In the present invention of the improved process, selective transfer of the coumarins from the aqueous extract into the non polar phase was carried out by partitioning the aqueous phase with chlorinated solvent (Carbon tetrachloride, dichloromethane, chloroform). By employing this step, most of the colouring and fatty material is left in the polar phase thereby enriching the scopoletin in the non polar phase which is easily crystallisable (50-60%) in the crude extract itself The scopoletin left in the mother liquor after crystallization is subjected to column chromatography over silica gel in ratio of only 1:10 for complete isolation of the pure scopoletin. The partition of scopoletin from aqueous extract to non polar solvent reduces the bulkiness of the crude extract by 60-70% which in terms requires less amount of silica gel and solvent in the process.


The process consists of the following operations:

1. Shade drying and grinding of the stems of Artemisia annua.

2. Extracting the powdered Artemisia annua stems with aqueous acetonitrile solvent by cold percolation.

3. Concentrating the total extract under vacuum.

4. Partitioning of the aqueous acetonitrile phase with halogenated solvent.

5. Removal of moisture from the total halogenated extract.

6. Distillation of the halogenated solvent for obtaining the residual extract.

7. Crystallisation of the scopoletin from the residual extract.

8. Filtration and concentration of mother liquor.

9. Column Chromatography of mother liquor over silica gel for recovery of pure scopoletin.

The present invention is to provide a process for the extraction and isolation of scopoletin from the plant Artemisia annua to overcome the drawbacks of the hitherto known process. The invention more particularly provides a process which gives a cheaper and higher yield of nitric oxide synthesis inhibitor compound scopoletin from the natural source.

Accordingly, the present invention provides a process for the extraction and isolation of scopoletin from Artemisia annua which comprises extraction of a plant part, preferably dried stem powder of Artemisia annua with aqueous acetonitrile solvent in the ratio of 1:5, concentration of the extract under a vacuum, partitioning of the concentrated extract with a non polar halogenated solvent, distillation of the halogenated solvent, crystallization of the residue in methanol, filtration of scopoletin, concentration of the mother liquor and performing chromatography over silica gel for obtaining pure scopoletin.

In an embodiment, of the invention the solvent used for the extraction is selected in different ratios of acetonitrile:water from 1:9 to 9:1.

In another embodiment, of the invention the halogenated solvent used for partitioning is to be selected from dichloromethane, carbon tetrachloride, chloroform etc. In another embodiment of the invention the plant part for extraction of scopoletin is selected from stems, leaves, roots etc.

In another embodiment, of the invention the separation of scopoletin over silica gel whereas the ratio of crude extract to silica gel is selected from 1:5 to 1:20 preferably either from 1:5, 1:10 or 1:20.

The details of the invention provided in the following examples are given by way of illustration only should not be construed to limit the scope of the present invention

Yet another embodiment of the invention, extraction and isolation of scopoletin is from plant families such as Umbelliferae, Rutaceae, Compositae, Leguminosae, Moraceae, Caryophyllacae, etc.

Still another embodiment of the invention, the scopoletin is crystallized in the solvent which is selected from chloroform, acetone, methanol and mixtures thereof.

One another embodiment of the invention, scopoletin isolated from different parts of Artemisia annua is in the range of 0.25-0.30% in stem, 0.16-0.20% in leaves, and 0.003-0.004% in roots.

Also another note on aesculin/fraxin from the Horse Chestnut tree:

Pure aescul(et)in from a chemical supply company may be rather expensive, but a standardized Cortex hippocastani (chestnut bark) extract, containing 55% aesculin, is readily available.

[GC_MS]

Pure aescul(et)in from a chemical supply company may be rather expensive, but a standardized Cortex hippocastani (chestnut bark) extract, containing 55% aesculin, is readily available.

The only reason why it is that expensive is because it is used in some well-known "expensive research branches", such as bacteriology. It would cost only pennies if it was "just a spice".  

[GC_MS]

Last night, I went to the woods to collect some chestnut bark. As the wood only consists of horse chestnuts, there is not chance of mistaking another tree for the chestnuts. I collected ca 1 kg of bark in no time. The older trees have an easily peelable bark. I think I had to use my knife at only one occasion. Also very important: the bark can be removed without really wounding the tree. Anyway, I tried to keep the trees as intact as possible and never took more then 100 g bark per tree. The bark is currently drying, and I hope to start some extractions within a week.

Also, prepare for new roommates. Mine is called Shiitake the Spider.  

[Rhodium]

Quoted from

Post 460298

(ClearLight: "translation coming", Methods Discourse)

oxidation of this cinnamic acid to asaraldehyde and asaronic acid by Moore (J 99 (1911) 1047).

For the record, I checked out J. Chem. Soc 99, 1047 (1911) at the library, and unfortunately found it to be useless, as they mention neither their yields nor what oxidant they used for the transformation.