Safrole from salicylic aldehyde

ApprenticeCook · DILLIGAF

I was just looking up a few references when i came across this reaction... one of those damn related pages links got me!

This is the general outline:
"An efficient solid-state oxidation of organic molecules is described using a stable, inexpensive, and easily handled reagent, the urea-hydrogen
peroxide adduct. The generality of the reaction has been demonstrated in oxidation of several molecules, namely hydroxylated aldehydes and
ketones (to hydroxylated phenols), sulfides (to sulfoxides and sulfones), nitriles (to amides), and nitrogen heterocycles (to N-oxides)."

This could be used on things like salicylic aldehyde to pyrocatechol, the document gives reference to this exact exampe, 85% in 1.5hrs at 55oC. This can then be converted to 3,4-methylenedioxybenzene via the normal routes onto safrole via information on rhodium mirrors.

DMSO could also be prepared by this method by using dimethylsulphide (synth?) if you have no access to its purchase. The paper gives information on larger sulphides, one being phenylmethylsulphide converted to phenylmethylsulphoxide 80% (10% went to sulfone) in 15min at 85oC.

ref:
ORGANIC LETTERS 1999 Vol. 1, No. 2 189-191
DOI: 10.1021/ol990522n

Thoughts:
If one could obtain obtain a reasonable source of salicyclic aldehyde or find an easy way to reduce salicylic acid, it would put safrole production back on track.
Look at rhod mirrors for conversion of 3,4-methylenedioxybenzene to safrole. There are a few.

MistaMiyagi · Dream Team

As derived from the 1913 Webster's dictionary:

Salicylal
A thin, fragrant, colorless oil, HO.C6H4.CHO, found in the flowers of meadow sweet (Spiræa), and also obtained by oxidation of saligenin, etc. It reddens on exposure. Called also salycylol, salicylic aldehyde, and formerly salicylous or spiroylous acid.

Saligenin
A phenol alcohol obtained by the decomposition of salicin, as a white crystalline substance; called also hydroxy-benzyl alcohol; ortho-hydroxybenzyl alcohol, saligenol, salicyl alcohol. HOCH2.C6H4.OH

Salicin
A glucoside found in the leaves of several species of willow (Salix) and poplar, and extracted as a bitter white crystalline substance. Called also salicyl alcohol glucoside, salicyl alcohol &--946;-D-glucopyranoside, saligenin &--946;-D-glucopyranoside, C13H18O7. It is used in biochemistry as a standard substrate for evaluating the potency of &--946;-glucosidase in enzymatic preparations. It is also an analgesic.

Below is derived from a medical monograph on salicin:

List of Salicin-containing plants

Salix alba
Salix tetresperma
Salix fragilis
Populus nigra
Populus alba
Populus tremula
Filipendula ulmaria

Extraction of Salicin
Depending on the source, the bark of the plant is peeled off and dried under strict aseptic conditions. The properly dried bark is then extracted with 80% ethanol and 20% water. The hydro-ethanolic extract is then subjected to evaporation under reduced pressure.

IndoleAmine · Dreamreader Deluxe

Buy it at your local pharmacy - its as unsuspicious as vanillin, and is a precursor for making acetylsalicylic acid (aspirin)...

(tell them you want to make some out of chemical interest, its a common school chem experiment AFAIK Wink

)

ApprenticeCook · DILLIGAF

So under what name is it sold? is it a common product?
I moved this to essential methods, its not really talking directly about phenethylamine synthesis, simply base precursors thereof...

-AC

IndoleAmine · Dreamreader Deluxe

Sold as "salicylic aldehyde", and no, not common. Had to ask and have them order it.

(but they dont even have clove oil in stock either..)

i_a

Dr. Weird · Tue Apr 12, 2005 5:37 am

If you could reduce salicylic acid, that would be easy to find since it is common in acne medications.

ApprenticeCook · DILLIGAF

as a 3% topical application....
If reduction of salicylic acid is possible to do this its easier to acidify asprin... more yield for less $$.

Anyone got ideas of reduction?
-AC

brain · Linguist Extraordinaire

ApprenticeCook · DILLIGAF

IndoleAmine · Dreamreader Deluxe

salicylaldehyde can be de-formylated to give pyrocatechol (1,3-dihydroxybenzene).

This can be transformed into 1,3-methylenedioxybenzene through methylenation with strong mineral base and dihaloalkane like DCM or dibromomethane (DBM).

And then you can do several things to make it become an aldehyde, for example:

- Do a "Duff formylation" with "urotropina/kwas trifluorooctanowy" on it... Wink

(=hexamine/trifluoroacetic acid)

- brominate with Br2 in THF to get mostly(?) 1-Br-3,4-methylenedioxybenzene, then do a "Bouveault Aldehyde Synthesis" (grignard addition of 3,4-methylendioxybenzyl-MgBr grignard reagent to "N,N-dimetyloformamid"/DMF)

both give you piperonal...

i_a

IndoleAmine · Dreamreader Deluxe

Pyrocatechol can be bought.

demorol · Wed Apr 13, 2005 12:56 am

IndoleAmine · Dreamreader Deluxe

Dr. Weird · Mon Apr 18, 2005 6:16 am

okay, I got a little lost in here, first off pyrocatechol is 1,2-Dihydroxybenzene and safrole is 3,4-methylenedioxyallylbenzene or 5-Allyl-1,3-benzodioxole so how do you get from 1,2 to 1,3 or did you mean 1,3-benxodioxole which is also 1,2-Methylenedioxybenzene tehn you just need the 5-allyl to get your safrole.
the 1,3-dihydroxybenzene is resorcinol but you only need 1,2 and by adding the 5-allyl you get 3,4-methylendioxyallylbenzene, right? so how do you end up with 3,4-Methylenedioxybenzaldehyde aka 1,3-benzodioxole-5-carbaldehyde ?

ApprenticeCook · DILLIGAF

check your naming, you got it wrong.
Safrole --> 3,4-methylenedioxyallylbenzene

So your not moving OH groups... the 1,2 stays 1,2.... but seeing as the allyl group takes numbering priority the 1 position is given to the allyl attachment and the ethers get 3,4... draw it out and count the numbers round to check it out.

-AC