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                     Piperonal from isosafrole - by Station
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Davies and Hodgson, The Preparation of Aldehydes by the Ruptive Oxidation
of the Ethylene Linkage.  J.S.C.I., June 1943, 91-93.

        The preparation of aromatic aldehydes by the oxidation of compounds with
side-chains containing ethylenic linkages via potassium permanganate and
potassium dichromate was investigated, including the oxidation of isosafrole to
piperonal and of isoeugenol to vanillin.

        Since the initial materials are not completely miscible with water, the
effect of introducing a dispersing agent was studied; for this purpose
sulphanilic acid (which had the additional advantage of protecting the aldehyde
when formed from further oxidation) and also Dispersol were used. The oxidation
of isosafrole to piperonal by potassium permanganate under tested reaction
conditions was far too vigorous, and the main product was piperonylic acid,
whereas sodium dichromate and sulphuric acid afforded a 70% yield of piperonal,
which was increased to 80% and 86.5% by the use of Dispersol and sulphanilic
acid respectively as dispersing agents.  The higher yield promoted by the
sulphanilic acid was ascribed to ephemeral formation of a Schiff's base with the
aldehyde when formed.  With isoeugenol, in which the benzene structure is not
immobilized by the clamping arrangement of the methylenedioxy-group, the chromic
acid oxidation gives a yield of 67% of vanillin as compared with the 86.5% of
piperonal obtained from isosafrole.

Experimental:  The preparation of aldehydes

        (a) Without dispersing agent.
A mixture of isosafrole (32.4 g., 0.2 g.- mol.), 50% aqueous sulphuric acid (160
g.) and water (1 L) at 30-40C was vigorously stirred during the gradual addition
over 30 minutes of a solution of sodium dichromate (44 g., 0.13 g.-mol + 10%
excess) in water (200 c.c.). Reduction of the dichromate to green chromium salt
appeared to be almost immediate; the mixture was twice extracted with benzene
(600 c.c.), and the combined extracts were washed with 5% aqueous sodium
hydroxide (200 c.c.) followed by water (500 c.c.).  The extract was then dried
over anhydrous calcium chloride, and the benzene removed, when the light brown
residual oil crystallised on keeping (26 g.).  The crude product was refluxed
with ethyl alcohol (200 c.c.) and animal charcoal (10 g.), the crude solution
filtered hot,, and the bulk reduced to 100 c.c., when the piperonal was obtained
in white crystals, m.p. 36-37C (yield 21 g. of pure product, i.e., 70%).

        (b) With sulphanilic acid as dispersing agent.
Details were as in (a), except that the isosafrole was added to a solution of
sulphanilic acid (12 g.) and sulphuric acid (80 g., d 1.84) in water (1 L).
Yield of pure product, 26 g. (86.5%). (c) Details were as in (a) except that
Dispersol (5 g.) was present in the oxidation medium.  Yield of pure product,
24 g. (80%).

Experimental--Variations in temperature and in amount of oxidizing agent used:

Variation                                                       Yield %
(1) Standard experiment above                                   86.5%
(2) Expt. (1) 50% excess of sodium dichromate                   82.0%
(3) Expt. (1) with theoretical sodium dichromate                69.0%
(4) Expt. (1) at 20C                                            78.5%
(5) Expt. (1) at 80C                                            73.0%

Experimental--Oxidation of isoeugenol to vanillin

        The best results were obtained by using the optimum conditions of the
previous oxidation, viz., sodium dichromate (10% excess) with sulphanilic acid
as dispersing agent.  Yield, 67%.  With alkaline potassium permanganate, only a
21% yield of vanillin was obtained.

Experimental--The isomerization of safrole to isosafrole

        Metallic sodium (30 g.) was caused to react with ethyl alcohol (400 ml,
dried over quicklime), and the mixture charged into a stainless steel autoclave
(1 litre capacity) together with safrole (300 g.) and the temperature raised to
180C during 2 hours, when the pressure was 300 lb. per sq. in.  The temperature
was maintained at 180-185C for 6 hours; the contents of the autoclave were then
poured into a solution of sodium chloride (200 g.) in water (1 L), and the oil
was removed, washed with 20% sodium chloride (200 g.), and dried over anhydrous
sodium sulphate.  Two such preparations were combined and fractionated through a
2-ft. column packed with 1/4-in. Lessing rings; the results for the various
fractions are given below.

        Weight          B.P./6 mm.              Refr. index     Sp. gr.
        g.                                      at 15C          at 15C

1       80              Up to 100C              1.4872          1.035
2       130             100-110C                1.5633          1.105
3       352             110-115C                1.5786          1.132
4       30              115-130C                1.5791          1.138

Fraction 3 was employed for isosafrole in the oxidations above (literature
gives d13 1.122; n20 1.5872).

This manuscript is being offered for its informational and educational value
only, and it is intended and expected that the information will be used solely
by legitimate researchers and forensic chemists investigating these compounds.
No synthesis of these substances, the manufacture of which is illegal without
governmental license, should be undertaken without approval from the appropriate
governmental authorities. The authors do not want to assist, counsel, urge,
otherwise encourage or cause a criminal act, particularly in view of the fact
that possession of the listed precursor chemicals safrole, isosafrole and
piperonal is subject to mandatory sentences and manufacture of methylenedioxy-
amphetamine and methylenedioxymethamphetamine is punishable by sentences up to
life in prison.

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