Sciencemadness Discussion Board - Total Synthesis of Carpanone from Catechol

Total Synthesis of Carpanone from Catechol

benzylchloride1 - 9-11-2009 at 22:38

I am currently working on the total synthesis of carpanone starting from catechol. Carpanone is a molecule that is composed of 6 rings with 5 stereocenters. The proposed synthesis starts from catechol which is methyleneated with dichloromethane in dimethyl sulfoxide to form 1,2-methylenedioxybenzene. The 1,2-methylenedioxybenzene is then nitrated in acetic acid with nitric acid and acetic anhydride to form 4-nitro-1,2-methylenedioxybenzene which is then reduced to form 4-amino-1,2-methylenedioxybenzene.
The resulting aniline will then be diazotized and hydrolyzed to form 4-hydroxy-1,2-methylenedioxybenzene, or sesamol. This will then be subjected to a Williamson ether synthesis with allyl bromide, The resulting allyl ether will then be treated with potassium hydroxide in dimethylsulfoxide to form 2-(trans-1-propenyl)-4,5-methylenedioxyphenol. This will then be subjected to a copper catalyzed phenolic cross coupling reaction which completes the total synthesis. This will be an interesting synthesis of a complex natural product which can readily be conducted in an amateur setting.
References: Fieser, Williamson; Organic Experiments, 3rd edition. The catechol methylenation can be found on the internet easily, Rhodium.

Experimental:
Step 1. Formation of 1,2-methylenedioxybenzene
27.5g of catechol, 50 ml dimethylsulfoxide, and 30 ml of 50% sodium hydroxide was placed in a 500ml flask. The catechol dissolved to form a very dark colored, viscous solution. This solution was heated at 98 Celsius for 30 minutes. Meanwhile, a solution of 30ml dichloromethane in 75 ml of dimethylsulfoxide was prepared in a 1000ml flask equipped with an mechanical stirrer and reflux condenser. The solution of bis sodiium catechol phenoxide was added rapidly to the DCM-DMSO solution. The solution was not added in portions because the solution would freeze slightly below 98C, clogging the addition funnel. About 25% of the solution was lost in this manner. The solution was then refluxed for 2 hours and steam distilled to recover the product. The steam distillate was extracted with 2-25ml portions of dichloromethane and the extracts were dried over magnesium sulfate, filtered and the solvent removed with a rotary evaporator leaving an water white oil with a characteristic odor. 14.5g of 1,2-methylenedioxybenzene was obtained, for a percentage yield of 47%. An infrared specrum indicated that no catechol was present due to the absence of hydroxyl absorbtions around 3500cm^-1.2 strong absorbtion bands centered around 1230 and 1045 cm6-1 indicate the presence of an ether. An absorbance around 1380cm^-1 indicates alkyl carbon due to the methylenedioxy group. This indicates that the first step in the synthesis was attempted.

Step 2. Nitration of 1,2-methylenedioxybenzene
After an unsucceful nitration of 1,2-methylenedioxybenzene using a acetic, sulfuric, nitric acid mix similar to the method used to nitrate acetanilide, another method was tried.
2.0g methylenedioxybenzene was dissolved in 10 ml glacial acetic acid in a 100 ml flask, a stirr bar was added and the mixture was chilled in an ice bath. 3.0ml of 70% nitric acid was added in small portions, truning the solution yellow. 3.0ml of acetic anhydride prepared from sodium acetate and disulfur dichloride was added. Immediately, a yellow precipitate of the nitro compound formed. The mixture was stirred for a hour in the ice bath. 50 ml of cold water was added with swirling, and the mixture was filtered. The yello colored nitro compound was then washed with 100ml of cold water and allowed to dry over night. I still need to recrystallize the product.
This file contains a sketic of the proposed synthetic route
[ Attachment: Carpanone Synthesis.skc (10kB)
This file has been downloaded 1229 times

[Edited on 10-11-2009 by benzylchloride1]

Nicodem - 10-11-2009 at 01:27

What is the reference for that synthetic route you depicted in the attachment? BTW, please use pictures instead.
As it is shown, it does not make much sense. Phenolic couplings requires phenols while you show an oxidation of a phenyl vinyl ether instead. All the total syntheses of carpanone that I could find use 6-propenyl-sesamol for the phenolic coupling/Diels-Alder tandem reaction. The 6-propenyl-sesamol is prepared by the base catalysed double bond isomerisation of 6-allyl-sesamol which itself is prepared via the Claisen rearrangement of O-allyl-sesamol.
Are you sure you did not misinterpreted your source?

benzylchloride1 - 10-11-2009 at 07:01

The reference for the synthesis of carpanone is Organic experiments by Fieser, Williamson, this book has a procedure for the complete synthesis of the desired product for students. My mistake, I forgot to draw the Clasien rearrangement leading to the ally phenol derivative, I will change the ISIS draw image when I have a chance.

mr.crow - 10-11-2009 at 07:43

There are also many patents concerning benzodioxole methyleneation that may avoid the problems in the first step.

I haven't heard of the Claisen rearrangement being done in DMSO before. Ethanol is also a good solvent, I am not sure is base has any effect in this case.

Nicodem - 10-11-2009 at 08:00

As long it is just a mistake, it does not really matter. I just found it impossible and was wandering what is all that about.

Why is the addition order reversed in the methylenation of catechole? Is there a particular reason? It only appears to have caused you troubles.

Nitration of 1,3-benzodioxole should work without acetanhydride. I do not understand why you could not get it nitrated with HNO3/H2SO4 in acetic acid, because several literature examples use such conditions. Check J. Het. Chem., 28, 625-634 (10.1002/jhet.5570280316) for a detailed study (yield was quantitative). At page 8 of patent US4554280 you have an example yielding 90% using just 65% HNO3 in acetic acid left stirring overnight.

What are you going to use for the reduction of the nitro compound? I would recommend you to use something simple, like hydrogenation over Pd-C which can be done at 1atm, or reduction with sodium dithionite. Most metal-acid reduction systems are difficult to work up and some give lots of azo dyes with electron rich nitroaromatics instead of cleanly reducing them to the amino product.

Quote:

I haven't heard of the Claisen rearrangement being done in DMSO before. Ethanol is also a good solvent, I am not sure is base has any effect in this case.

I think Benzylchloride1 made a mistake with that as well. The whole step of Claisen rearrangement and the subsequent step of double bond isomerisation is missing. DMSO is probably used for the isomerisation, and not for the Claisen. The Claisen rearrangement is most commonly done solventless as long as good care is taken in controlling the internal temperature (by keeping it bellow 250°C). Otherwise, clumsy chemists use reflux in N,N-dimethylaniline (an effective and easy to wash off solvent). Ethanol can not be used, unless in a closed vessel, for the obvious reason of its low boiling point.

[Edited on 10/11/2009 by Nicodem]

DJF90 - 10-11-2009 at 10:31

1,2-dichlorobenzene is supposedly an effective solvent for aromatic claisen rearrangements. Not sure about ease of work up though. DMSO is high boiling so that might relate to the use of it as a solvent in this step, and it likely stabilises the transition state also. Ethanol cannot be used for a claisen rearrangement, it boils at a temperature far too low of whats needed.

The methylenation step would likely be higher yeilding using diiodomethane, obtainable via a finkelstein reaction on dichloromethane among other methods. The use of alkali carbonate or hydride as base for forming the di-phenoxide would be advantageous also, preventing loss of diiodomethane to Sn2 with hydroxide. DMSO should be fine as a solvent for the reaction, although you might consider using an alternative with lower boiling point to aid ease of removal.

Using carbonate or hydride as the base, the reaction should be one pot. Why you added the phenoxide solution to the DMSO-DCM is beyond me, reverse addition would have been far more applicable/advantageous.

mr.crow - 10-11-2009 at 11:34

Ethanol/water speeds up the Claisen reaction so it works at reflux temperatures. DMSO should work either way since its also polar.

You need a really strong polar aprotic solvent for the methyleneation because of the lower reactivity. DMSO and n-methyl pyrrolidone seem to be the best, and sometimes a catalyst like CuO is used (according to various patents)

I think adding the phenoxide to the CH2Cl2 is done so there is always an excess of CH2Cl2 to prevent byproducts from forming (two catechols being coupled together). There are of course different ways of doing it.

DJF90 - 10-11-2009 at 17:21

Ethanol/water speeds up the claisen rearrangement? How so? I dont think I've ever seen a claisen run below 100C, of which your ethanol/water mix will certainly boil below... and if such a reaction would work, I would suspect it would likely take a week or longer!

Quote:

You need a really strong polar aprotic solvent for the methyleneation because of the lower reactivity.

Lower reactivity of what? The di-phenoxide or the dihalomethane (or di-chloro vs. di-iodo?)? Try and specify. Any solvent that promotes Sn2 reaction should be applicable - chloride is a crappy leaving group hence the suggestion to use the di-iodomethane instead.

As to your suggestion of adding the di-phenoxide to the DCM is done so excess DCM is present to prevent the formation of bis-methylene bridged catechols, there are two counter-arguments to this.

The first is that the solution of DCM-DMSO should be added rapidly - the Sn2 reaction (with DCM in particular, cf di-iodomethane) should be slower than the rate of mixing, allowing DCM to be present in excess before the reaction "starts".

The second is that, once one halide has been displaced, the halomethylene group is bound to the now mono-phenoxide, and thus intramolecular cyclisation (5-exo-trig) is far more entropically (and kinetically) favourable than the approach of another dihalomethane molecule to your phenoxide and subsequent attack, unless of course you use the dihalomethane as your reaction solvent.

mr.crow - 10-11-2009 at 19:24

Here is a google book talking about the solvent effects

http://books.google.ca/books?id=55IGjy3CiAUC&lpg=PT16&am...

Wonder why they list ethanol/water if its at 170 degrees, doesn't make sense. The reaction is exothermic so you wouldn't want to speed it up 100 times anyways.

Now for methyleneation the dichloride is very unreactive but more desirable then using di-iodo

Here is a paper, I can't remember where I found it. http://rapidshare.com/files/305281382/methylation_of_catecho... (will be deleted after 10 downloads or 90 days

)

The Methylenation of Catechols, J. Chem. SOC. (C), 1969

He talks about the formation of byproducts, and adds the catechol and NaOH to the solvent mixture.

[Edited on 11-11-2009 by mr.crow]

Sedit - 10-11-2009 at 19:33

To prevent loss after 10 downloads I saved it to my site and linked it.

File secured....
http://www.thevespiary.org/sedit/Chemistry%20-%20Organic/met...

Nicodem - 11-11-2009 at 00:53

Quote: Originally posted by mr.crow

Here is a google book talking about the solvent effects

http://books.google.ca/books?id=55IGjy3CiAUC&lpg=PT16&am...

Wonder why they list ethanol/water if its at 170 degrees, doesn't make sense. The reaction is exothermic so you wouldn't want to speed it up 100 times anyways.

Always check the original source when uncertain. In that review, there is no claim of the reaction rate being measured at reflux temperature. Moreover, in the table the temperature of 170°C is explicitly mentioned, which means the kinetic measurement with ethanol/water solvent was done in a closed vessel (see J. Org. Chem., 36, 2196-2199). The authors of the paper did not find any clear correlation of the reaction rate with the solvent polarity. Instead they found out the best solvents are those that are more acidic and/or more protic. This is not even surprising given that acid catalysed aromatic Claissen rearrangement (for example catalysed with BCl3) occurs at -40 to 0°C (which is a 10 magnitudes reaction rate increase; see Helvetica chimica acta, 56, 14-75). Anyway, all this is pointless as the most practical way of doing a thermal aromatic Claisen rearrangement is by doing it solventless. The reaction is over in few minutes at 200-220°C and all there is to do is take care the exotherm does not increase the temperature too high (thus oil bath and slow heating!).

Quote:

Here is a paper, I can't remember where I found it. http://rapidshare.com/files/305281382/methylation_of_catecho... (will be deleted after 10 downloads or 90 days

)

The Methylenation of Catechols, J. Chem. SOC. (C), 1969

The papers you downloaded from this forum need not to be uploaded again. You can just post the link to the thread where you found them. For example: Methylenation of catechol derivetives (Base cataylized)

mr.crow - 11-11-2009 at 07:06

Thanks Nicodem, Im a total noob when it comes to sources

That is indeed where I found the paper from, but forgot.

According to the book the claisen reaction does in fact work with ethanol at reflux temperature, but only for catechol mono-allyl ether and a base catalyst. This is clearly not the case for benzylchloride1's compound though.

benzylchloride1 - 12-11-2009 at 21:31

I am sorry for not getting to this sooner. Here is the corrected ISIS draw flow chart of the synthesis. I accidently forgot the whole part with the Clasien rearrangement; my mistake. The procedure uses potassium tert-butoxide in dimethyl sulfoxide for the rearrangement reaction. I am going to try sodium isoprpoxide which can be madeby drying 2-propanol with sodium hydroxide and distilling. It is not very pure, but it is a much stronger base then just sodium hydroxide and small quantites dissolve in water with a hissing sound and the solid has a slight odor of isopropanol, even though it is bone dry in appearance. I will post the infrared spectrum I ran of the 1,2-methylenedioxybenzene as soon as I have a chance. I am debating what to do as far as the reduction of the nitro compound. I could use the procedure in Organic Syntheses Collective volume II where nitro compounds are reduced with iron in an alcoholic solution, after the reduction, the solution is filtered from the iron and concentrated, leaving the amine or use hydrazine dissolved in 2-propanol as the reducing agent. When I tried to nitrate 1,2-methylenedioxybenzene in a acetic acid, sulfuric acid mixture in the cold, a purple mixture resulted after adding ice cold sulfuric acid to the solution of the methylenedioxybenzene in acetic acid. This indicated to me that the formaldehyde ketal was hydrolyzed, producing catechol, which subsequently formed a carbo ation in the highly acid solution giving rise to the intense dark purple color. After adding the nitric acid and working up the mixture, no solid was obtained, every thing had dissolved in the water used for the work up, forming a dark brown solution. The nitration with acetic acid, nitric acid and an acetic anhydride works wonders. Actic anhydride is very easy to make and using it in this synthesis should raise no objections. I am also going to investigate some methods of catechol methyleneationthat use phase transfer catalysts, as I need around 50 more grams of the 1,2-methylenedioxybenzene. I will probably only obtain a gram or less of product if every thing works well.

[Edited on 13-11-2009 by benzylchloride1]

Attachment: Carpanone Synthesis.skc (11kB)
This file has been downloaded 862 times

[Edited on 13-11-2009 by benzylchloride1]

Nicodem - 14-11-2009 at 07:59

There's not much I can comment on your ambitious plans except good luck and a couple of trivial remarks:

Personally I think you will be sorry for choosing Fe + HCl as a reduction system. Sounds like lots of dirty work.

Using Na2CO3 as a base in the O-allylation of sesamol also sounds like a very bad idea if you value your starting material. Use dried and finely ground K2CO3 in acetonitrile or acetone. Alternatively use KOH in ethanol. Is there a reason why you don't want to follow a literature example here? I would be wandering the same about the nitro reduction, but I guess in that case you are limited by reagent choice. But surely you don't have troubles obtaining K2CO3?

Quote: Originally posted by benzylchloride1

The procedure uses potassium tert-butoxide in dimethyl sulfoxide for the rearrangement reaction. I am going to try sodium isoprpoxide which can be madeby drying 2-propanol with sodium hydroxide and distilling. It is not very pure, but it is a much stronger base then just sodium hydroxide ...

I think you got it wrong. NaOH in DMSO is a considerably stronger base NaOiPr in DMSO (just compare the pKa's of H2O and iPrOH in DMSO: 31.2 vs. 29.3; and t-butoxide is approximately equally basic as isopropoxide: pKa 29.4). I think your misconception of basicity comes from your comparison with water as solvent which is something completely different. Water molecules solvate anions while DMSO does not (always keep this in mind with aprotic solvents!). Therefore the more hydrophilic the anion, the more basic it is in DMSO compared to H2O as solvent. For example in water hydroxide is a weaker base than ethoxide, but in ethanol as solvent it is the opposite (hydroxide is as stronger base there than ethoxide is!).

Of course, with less polar solvents one must not ignore the effect of the counterion which is something that you can often ignore with water as solvent. For example, in water, LiOH, NaOH, KOH, RbOH and CsOH are all practically equally potent bases (the acidity of cations in water can be neglected due to a very efficient solvation), but in other solvents this is not true any more. There the basicity increases from LiOH to CsOH. So if you compare NaOH vs. tBuOK in DMSO, then they might be similarly strong bases, but if you compare KOH with tBuOK in DMSO, then KOH is stronger.

In this particular case tBuOK is only used out of convenience, simply because it is ubiquitous in organic labs, it dissolves in DMSO without problems (unlike KOH which takes ages), and moreover it allows the experimenter not to be bothered with a theory he does not fully understand.

My advice is therefore not to bother with isopropoxides and such. Just use KOH, which is the most commonly used base for base catalysed double isomerizations anyway.

Quote:

Here is the corrected ISIS draw flow chart of the synthesis.

For being internet user friendly, I seriously think most people better appreciate a normal GIF attachment of a scheme so that it does not require external software like ChemSketch. Like this:

[Edited on 15/11/2009 by Nicodem]

benzylchloride1 - 15-11-2009 at 22:58

Nicodem, thanks for your help on this synthesis. I am considering using a catalyzed hydrazine reduction of the nitro compound, since the reduction with iron would probably lead to a mess. I am planning on using potassium hydroxide as the base for the ether synthesis and the isomerization of the double bond since I have plently of it. I ran a half scale methylenation of catechol, adding a solution of catechol in DMSO, along with a suspension of sodium hydroxide to a refluxing solution of dichloromethane in DMSO, after steam distillation, extract with DCM, drying and removal of the solvent, around 40g of 1,2-methylenedioxybenzene was left. I started from 55g of catechol, so the yield was 70%. I nitrated 20 g of the 1,2-methylenedioxybenzene with 75 ml glacial acetic acid, 10 ml 70% nitric acid and 2.0 ml acetic anhydride catalyst. The product precipitated as a tannish crystalline material. The product was then recrystallized from methanol. It is currently drying a room temperature. The product from a 2 g scale nitration by the same method melted at 147 degrees Celsius, which is the same as the literature melting point. I will be running test reduction of the nitro compound this week. I am afraid that the hydrolysis of the diazonium salt to the phenol will give a very low yield of the desired product, sesamol, 4-hydroxy-1,2-methylenedioxybenzene. I have converted aniline to phenol by this method, with 40% yields. Is there any way of increasing the yields of this reaction?

[Edited on 16-11-2009 by benzylchloride1]

Arrhenius - 15-11-2009 at 23:17

I was going to suggest SnCl2*2H2O mediated reduction of the nitro group, because it's quick and easy. But it requires >3eq to fully reduce the nitro group. Yields are typically 80-100%. If you have the means, catalytic hydrogenation is probably the best option.

Well, now that I've looked up the price, the tin(II) chloride method looks a quite reasonable. If you use ~4eq tin, and 1eq HCl, the reaction should go in about 15-30 minutes at room temp. If you want, I'll look in my notebooks for a procedure.

[Edited on 16-11-2009 by Arrhenius]

sonogashira - 16-11-2009 at 02:52

Quote: Originally posted by benzylchloride1

I am afraid that the hydrolysis of the diazonium salt to the phenol will give a very low yield of the desired product, sesamol, 4-hydroxy-1,2-methylenedioxybenzene. I have converted aniline to phenol by this method, with 40% yields. Is there any way of increasing the yields of this reaction?

[Edited on 16-11-2009 by benzylchloride1]

Maybe you can try (instead of nitration) bromination and Cu(I) catalysed addition of OH?

benzylchloride1 - 17-11-2009 at 07:46

The nitrated product weighed 20 grams, for a percentage yield of 75%, based on 1,2-methylenedioxybenzene. Infrared spectra of 1,2-methylenedioxybenzene, and 4-nitro-1,2-methylenedioxybenzene taken with my new spectrophotometer are attached in PDF format. You will have to select a program that can open PDF files on your computer in order to open these files.

Attachment: IR of 1,2-methylenedioxybenzene (1.2MB)
This file has been downloaded 709 times

Attachment: IR of 4-nitro-1,2-methylenedioxybenzene (1.1MB)
This file has been downloaded 686 times

[Edited on 17-11-2009 by benzylchloride1]

Nicodem - 17-11-2009 at 12:50

Somehow you managed to lose the .pdf extensions in the attachments, so those trying to open them should either specify Adobe Reader as the program to open them or to save them renaming them by adding the .pdf.

The IR look fine. 1,3-Benzodioxole corresponds to the spectra at SDBS. So does the spectra of the nitro derivative.

Congratulations, two out of many steps are done.

benzylchloride1 - 10-12-2009 at 09:56

A synthesis progress report:
The reduction of 4-nitro-1,2-methylenedioxybenzene in 2-propanol with iron filings and hydrochloric acid was successful. Around a 60% yield of the (3,4-methylenedioxy)aniline was obtained after redistillation of the crude product. The product was slightly yellow in color and would crystallize after standing in a cold room for several hours. The infrared spectrum of the product matched the reference spectrum on the Aldrich website. The diazotization and hydrolysis of the diazonium salt with a large excess of copper (II) nitrate was unsuccessful; upon steam distillation of the reaction mixture, a yellow crystalline material was obtained that did not melt below 100 C; and the IR spectrum did not match the Aldrich reference spectrum for sesamol. I am working on the bromination of 1,2-methylenedioxybenzene with sodium bromide, ammonium persulfate in methanol, catalyzed by a small quantity of sulfuric acid. Does any one have a procedure for the copper (I) catalyzed hydrolysis of aryl bromides? I have also completed the synthesis of the allyl bromide required for the Williamson ether synthesis. I synthesized allyl alcohol via the method in Vogels Textbook by the dehydration of glycerin with formic acid; the method works extremely well, but much of the alcohol is lost in purification. Allyl alcohol is one of the most unpleasant chemicals I have ever worked with! I synthesized the allyl bromide by distilling a mixture of allyl alcohol, constant boiling hydrobromic acid and sulfuric acid. The procedure can be found in Vogel and gives around an 80% yield of the allyl bromide.

Sedit - 10-12-2009 at 17:06

Benzylchloride do you have a reference by any chance on the use of Cu(NO3)2 for the formation of diazonium salt?

[Edit]

Im assuming you are speaking of this correct? The use of the Cu(II) to form the phenol FROM the diazonium ion.

[Edited on 11-12-2009 by Sedit]

Arrhenius - 10-12-2009 at 21:17

For direct hydroxylation of aryl halides see:

Tetrahedron (2006) 62(19) 4728-4732 (microwave conditions)
Angewandte Chemie International Edition (2009) 48(46), 8729-8732 (Cu(I) cat., phen (ligand), KOH)

Angewandte Chemie International Edition (2009) 48(46), 8725-8728.

This last one is probably your best bet, as they show numberous beta-diketone ligands that work. They also show proline as a ligand (70% yield), but with CsOH as the hydroxide source. Other examples shown use KOH.

Here's the supporting info on that paper: http://www3.interscience.wiley.com/cgi-bin/fulltext/12264930...

Vogelzang - 11-12-2009 at 14:35

Quote: Originally posted by benzylchloride1

The nitrated product weighed 20 grams, for a percentage yield of 75%, based on 1,2-methylenedioxybenzene. Infrared spectra of 1,2-methylenedioxybenzene, and 4-nitro-1,2-methylenedioxybenzene taken with my new spectrophotometer are attached in PDF format. You will have to select a program that can open PDF files on your computer in order to open these files.

[Edited on 17-11-2009 by benzylchloride1]

The resolution looks pretty good. Even the weak bands show up. What kind of spectrophotometer did you use?

benzylchloride1 - 13-12-2009 at 21:23

Here is the reference for the hydrolysis of aryl diazonium salts to phenols using copper (II) nitrate. I currently own a Perkin Elmer 1310 infrared spectrophotometer; I purchased it off of Ebay recently, the diffraction gratings needed to be realigned. This instrument has a pyroelectric detector which seldom fails. No replacement thermocouples are available for my Perkin Elmer 467 IR, so I opted to buy a more modern instrument.

Attachment: Hydrolysis of diazonium salts to phenols.pdf (825kB)
This file has been downloaded 1097 times

[Edited on 14-12-2009 by benzylchloride1]

Nicodem - 15-12-2009 at 01:05

Too bad the diazonium hydrolysis did not work out. Don't get too frustrated - organic synthesis is all about coping with frustration anyway. You set yourself a difficult goal and the stage to which you ended up is already a great success.

I did a literature search and this is what I got.

5-amino-1,3-benzodioxole => sesamol

Only one reference in some old and near to impossible to get journal: Malagnini, Armanni, Rendiconti della Soc. chim. di Roma, 5 (1907) 135. Beilstein gives no details except for "Diazotization" wile I could not locate a CA abstract. If trusting this source it at least appears possible, but not even the yield is known.

I think your best bet is to use the usual synthesis of sesamol from piperonal. Piperonal can be made by formylation of 1,3-benzodioxole (I would guess the most amateur friendly method would be using the Duff formylation). Piperonal is then subjected to the Baeyer-Villiger oxidation:
WO2009035652 (with performic acid)
WO2007016431 (with peracetic acid)
Synthetic Communications, 38 (2008) 784-788 or J. Org. Chem., 72 (2007) 10283-10286. (using MCPBA)
There are also many other examples. See also the review in Organic reactions, vol 43 where other references for piperonal BV oxidation can be found.

sesamol => O-allyl-sesamol

With allyl cloride and KOH/ethanol:
Beroza, Journal of Agricultural and Food Chemistry, 4 (1956) 49-52. DOI: 10.1021/jf60059a002

With allyl bromide and K2CO3/acetone:
Devakumar, Saxena, Mukerjee, Agricultural and Biological Chemistry, 49 (1985) 725-730.
Fujimura, Fu, Grubbs, Journal of Organic Chemistry, 59 (1994) 4029-4031. DOI: 10.1021/jo00094a002
Maiti et al. Tetrahedron Letters, 42 (2001) 2389-2392. DOI: 10.1016/S0040-4039(01)00153-8
Kimpe et al. Tetrahedron Letters, 44 (2003) 4199-4202. DOI: 10.1016/S0040-4039(03)00902-X
Petit, Bourgeois, Journal of Chemical Research, Synopses, 3 (2004) 194-195.
Jimenez-Gonzalez et al. Chemistry--A European Journal, 12 (2006) 8762-8769. DOI: 10.1002/chem.200600332

Vogelzang - 16-12-2009 at 18:37

Here's the schematics from the 1310, 1320, 1330 instruction manual. You can see that it has a lot of digital electronics in it.

Attachment: PE1310-Fig7-1-6.pdf (952kB)
This file has been downloaded 562 times

benzylchloride1 - 24-1-2010 at 22:30

I have been experimenting with the bromination of 1,2-methylenedioxybenzene in methanol using using sodium bromide, ammonium persulfate and a small quantity of sulfuric acid, initial yields look to be good. I am planning on doing something quite interesting reguarding the synthesis os sesamol. I plan to convert the bromo compound into a Grignard reagent and react it with a borate ester and hydrolyze to form the aryl boronic acid. The boronic acid can then be oxidized with hydrogen peroxide to form sesamol. I am planning on prparing isopropyl borate since methyl borate boiling point is to close to that of methanol to make separation feasible. Vogel describes a preparation of butyl borate, but I do not have any 1-butanol. Propy borate is a possibility since 1-propanol can be distilled from some chimney creosote remover sprays that contain it along with manganese (II) nitrate.

Vogelzang - 27-1-2010 at 14:28

You might be interested in this article.

Attachment: Labdev1970-p217-218.pdf (197kB)
This file has been downloaded 692 times

Arrhenius - 28-1-2010 at 21:19

Forming the aryl boronic acid in high yield may prove trickier than in sounds. Your triisopropyl borate (most preferable) must be dry and free of alcohols (preferably distilled from Naº). Also, the order of addition and temperature are important, or you'll get diphenylborinic acid, etc. Aryl boronic acids are often nice crystalline solids, but they can be a pain to purify or characterize due to an equilibrium with the 'anhydride' dimer/trimer. Other than that, it sounds like a good idea

Though I believe there are reliable copper(I) catalyzed reactions to go from the aryl halide to the phenol.

benzylchloride1 - 1-1-2012 at 20:42

I have been gradually working on the carpanone synthesis, but grad school has slowed down my progress. I had to rethink my initial strategy to produce sesamol. I ended up running a Blanc chloromethylation reaction on the 1,3-benzodioxole, and then running a Sommlet reaction to produce the piperonal. I then ran a Dakin oxidation on the piperonal and subsequently hydrolyzed the resulting formate ester to make the sesamol. I then made allyl bromide via the procedure in Organic Syntheses using glycerol.I then ran a Williamson ether synthesis and then a Claisen Rearrangement to produce 2-allylsesamol. I attempted to isomerize the 2-allylsesamol using potassium hydroxide in DMSO, but all I recovered was a small amount of the starting material, I then resorted to using potassium tert-butoxide as in the literature procedure to produce a putative propenyl sesamol which I am working on trying to confirm as the desired product. The UV-vis spectrum demonstrates a large bathochromic shift when compared to the starting 2-allyl sesamol. The infrared spectra are fairly similar. I am working on getting my NMR to work, hopefully it will be fully working by summer. I am also working on a structural degradation of the suspected 2-propenylsesamol to produce the corresponding benzaldehyde which I will make a 2,4-dinitrophenylhydrazone derivative of for identification. I have not been able to find melting point data for the 2,4-DNP hydrazone of this aldehyde in any of my books or using Scifinder. I have also ran a test oxidative coupling on the suspected 2-propenylsesamol, but I still need to purify the product. I will make further updates as I have time to upload my infrared and UV-visible spectra. Hopefully, I will soon have my NMR operational and I will post NMR spectra as well. I have attached a drawing of the aldehyde that I need derivative information on.

[Edited on 2-1-2012 by benzylchloride1]

Attachment: 2-hydroxyl-4,5-methylenedioxybenzaldehyde.pdf (10kB)
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kavu - 2-1-2012 at 03:54

What about Friedel-Crafts acylation of 1,3-benzodioxole with acetyl chloride. Dakin reaction of the ketone should produce the desired phenol. This method would eliminate the use of the easily oxidised aldehyde. I'll have to take a further look on reaxys once I get back to the uni.

[Edited on 2-1-2012 by kavu]