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    TMA-2 from Calamus oil: Oxidation of asarone via Wacker Oxidation 
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This is a repeat of what I wrote under "TMA-2 from Calamus Oil", an idea
that no one responded to.

Asarone can probably be used in the Wacker oxidation just as isosafrole
can. The expected yield of the P2P is about 66%, with the P1P derivitive
being the only contaminant in abut 18% yield -- with their being no
internal alkene anywhere! How do I know this? Well, in the article by Jiro
Tsuji, et. al., entitled "A Palladium Catalyzed Conversion Of Halohydrins
To Ketones" pulished in Tetrahedron Letters, vol. 23, no. 30, pp 3085-3088,
1982 is a new synthesis of various 1-ketones using palladium acetate and
another exotic catalyst to effect what I guess is the rearrangement of a
1,2-halohydrin to form the ketone product. On the last page of the article
is an interesting diagram with information which illustrates several
reactions schemes. The first is the quantitative formation of the
1,2-halohydrin from isosafrole -- yes, they fucking used ISOSAFROLE as
their example -- which is then rearranged to the 1-ketone in 75% yield. The
second illustration is the one of particular interest, because it uses the
standard Wacker oxidation to try and achieve the same goal falling short of
expectation yielding 18% of MD-P1P and 66% of MD-P2P. (Awe! How absolutely
fucking terrible for the researchers -- but not for us bees!) The third and
last reaction is an oxidation of isosafrole using m-chloro perbenzoic acid
to form the intermediate epoxide, which is then rearranged to the final
MD-P2P via some boron triflouride reagent I'm not familiar with to yield
MD-P2P in 69% yield. Well, it seems to me that if isosafrole can be
oxidized to MD-P2P efficiently using the Wacker reaction, I see no reason
why asarone cannot be made to do the same to produce its respective P2P.
This may indeed be the boon for those wiching to synthesize TMA-2. After
making the P2P, aminating it via sodium cyanoborohydride/ammonium acetate
should be a snap! And remember, TMA-2 is about 3 times more potent than
MDA, yielding in a sense, more product for less precursor! Furthermore, I
don't believe that Calamus Oil has at this point the same scrutiny that
Sassafras oil does. Those of you bees reading this, start to stock up and
lets get some dreams posted!

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I happened to have two significant references to the above post:

1. "One-Pot Two-Steps Synthesis Of 1,2-Diol" - Syn. Comm., 19, 1939 (1989).

The authors used propenyl benzene as one of their examples:

To a stirred dispersion of propenylbenzene (3.0.10-3 mole) in distilled
water (20 ml) the powdered m-chloroperbenzoic acid (3.3.10-3 mole) was
added in small portions over a period of 5-10 min. At 0degC the mixture was
stirred at 20degC for 1hr.

If so desired, epoxide could be rearranged with the BF3 reagent as
indicated in the first post, or, the reaction above could be continued by
adding 10% H2SO4 (0.5 ml) and allowing the mixture to stand (stir?) for 4
hr. at 100degC. Solid NaOH is then added until the solution becomes limpid.
The aqueous solution is saturated with NaCl and then extracted three times
with ethylacetate. The extracts are dried and the solvent removed under
reduced pressure. The crude diol is crystallized by ethylacetate or by 1:1
mixture of ethyl ether - n-pentane.

The diol can then be dehydrated by any number of methods, the typical one
being reflux for 2-3 hrs with 15-20% H2SO4.

A few other references to effect the same transformation are more obscure
but included here anyway:

J Pharm Soc Jpn.  74, 975 (1954)
J Assoc Off Anal Chem. 61, 951 (1978)

An example of the reaction delineated in the two above references is provided
in the experimental details of J.O.C 1984, 49, 1830-1832 "Electrochemical
Proceedure for a Practical Preparation of Piperonal From Isosafrole" in
which they prepare the 1,2-diol and the 1,2-halohydrin through an electro-
chemical process. Anyway, here's there method of dehydrating the diol:

A solution of the 1,2-diol (from isosafrole; 100mg, 0.5mmol) and p-TsOH
(200mg) dissolved in a distilled benzene (20ml) was refluxed for 20 min.
The usual workup gave MD-P2P (75mg, 84%).

The same article presents two other references to effect the same reaction:

The first is the Tetrahedron Letters article mentioned in the initial post.

The second is Tetrahedron Letters, vol. 24, no. 28, pp 2857-2860, 1983.
"Electrogenerated Acid As A Powerful Catalyst For The Transformation Of Epoxides
To Ketones And Acetonides". Isosafrole-epoxide forms MD-P2P in 82% yield.

The 1,2-halohydrins of isosafrole mentioned in the first post are formed
quantitatively from N-bromosuccinimide, dimethylsulfoxide, water and
isosafrole. The references are JACS, 90, 5948, (1968) and... Shit! I'm
here staring at the Organic Syntheses article and there is no information
on it that indicates where it can be found! I know that it isn't in the
first three collective volumes. The article, however, is titled
"Bromohydrins From Alkenes And N-Bromosuccinimide In Dimethylsulfoxide:
erythro-2-Bromo-1,2-Diphenylethanol" and uses propenylbenzene as one of its
examples. The final yield of bromohydrin was 92-95% Following is the
experimental details:

A 500ml, round-bottom flask equipped with a magnetic stirring bar and a
thermometer is charged with 18g (100mmol) of (E)-stilbene (Note 1), 5ml
(28mmol) of water, and 300ml (4.23 mole) of dimethylsulfoxide (DMSO) (Note 2). 
The resulting suspension is stirred for five minutes at room temperature 
(20-25degC)(Note 3). Stirring is continued as 35.6 g (200mmol) of N-Bromo-
succinimide (NBS) (Note 4) is added in small portions over calculated 10 min. 
A yellow color appears when the first portion of NBS is added, and by the 
time the addition is complete, the solution is bright orange. During the 
addition the temperature of the mixture rises to 50-55°C, and all of 
(E)-stilbene dissolves. The contents of the flask are stirred for antoher 
fifteen minutes and poured into 1L of ice water; the product separates 
immediately as a white solid (Note 5). The aqueous slurry is transferred to 
a separatory funnel with the aid of 50ml portions of water and diethyl ether, 
and extracted with four 200ml portions of ether. The combined ethereal 
extracts are washed with 250ml of water and 250ml of sodium chloride solution, 
dried over anhydrous magnesium sulfate, and evaporated with a rotary evaporator 
at a water bath temperature of calculated 30°C. The pale yellow, crystalline 
residue is dissolved, to the extent possible, in 600ml of hot hexane, and the 
resulting suspension is filtered while hot, removing a small amount of insoluble 
impurity. Cooling the filtrate provides colorless fibers of analytically pure
erythro-2-bromo-1,2-diphenylethanol, m.p. 83-84°C (Note 6); a second crop
of crystals is obtained by concetrating the mother liquor to 200ml (Note 7). 
The combined yield is 22-24.9g (80-90% of theoretical)

Keep in mind that to get the 1,2-bromohydrin of isosafrole, one has to use
isosafrole in place of (E)-stilbene in the above experiment.

NOTES:

1. Not applicable. Information is about where one can purchase (E)-stilbene.

2. Reagent Grade dimethylsulfoxide was used without purification. The
amount of dimethylsulfoxide can be varied. A large excess is employed in
this case to facilitate dissolution of the stilbene. This may or may not be
applicable to isosafrole. Reagent grade DMSO may also not be required in
this reaction. Technical grade can easily be obtained in pint amounts at
feed stores that cater to those who raise horses and cattle. It is used
medicinally as a topical agent for introducing drugs more easily through
skin absorption. Cost is about $10.00 or less. It is there available on the
shelf as DMSO.

Note 3. The suspension may be warmed to dissolve the alkene more rapidly.
        If the suspension is warmed, it MUST be cooled below 30øC before
        proceeding further to prevent a vigorous reaction when the NBS is
        added. The submitters recommend that the warm suspension be cooled
        under an atmosphere of nitrogen.

Note 4. Recommendations are given on purifying the NBS. Recrystallize from
        10 times its weight in water. Probably not necessary though.
        Solutions of NBS in DMSO cannot be stored, since the solvent is
        oxidized by the brominating reagent.

Note 5. The product does not appear to deteriorate if allowed to stand at
        this point.

Note 6. The submitters recrystallized the product from 600ml of petroleum ether.

Note 7. The submitters found that the residue (2.8g) obtained upon
        evaporation of the mother liquor was largely the end product
        contaminated with a small amount of succinimide.

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