Author Topic: Anise oil as PMA precursor  (Read 4619 times)

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Rhodium

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Peracid Epoxidation of trans-Anethole
« Reply #20 on: June 03, 2004, 08:26:00 PM »
Peracid Epoxidation of p-Methoxy-trans-?-Methylstyrene (trans-Anethole)
Rebecca S. Centko and Ram S. Mohan
J. Chem. Educ. 78(1), 77-78 (2001)

Epoxidation of alkenes using peroxyacids is one of the most fundamental reactions in organic chemistry, yet there are very few examples of laboratory experiments that illustrate this important reaction (Ref 1). The inherent instability of many epoxides in acidic solutions makes the synthesis of acid-sensitive epoxides by this route difficult. Frequently, the carboxylic acid formed from the peracid during epoxidation reacts with acid-sensitive epoxides to give ?-hydroxyesters as the major product. Procedures have been developed for epoxidation of alkenes in the presence of buffers to minimize this problem (Ref 2).

Overview of the Experiment

The entire reaction, including the work up, takes only about an hour. Analysis of NMR and IR spectra of the product obtained in the absence of a buffer indicates that the ester, which has been assigned structure 3, is the major product.

The formation of 3 as the major product (Note 1) rather than 4, can be attributed to a significant contribution to the resonance hybrid by the highly stable p-methoxy-substituted benzylic cation resonance form 3a (Scheme II). This is consistent with the fact that in acid-catalyzed reactions, epoxides suffer attack at the carbon that can best stabilize positive charge (Scheme II).



Experimental Section

Procedure A (No Buffer)

A solution of trans-anethole (0.50 g, 3.4 mmol) in CH2Cl2 (10 mL) was stirred and cooled in an ice bath as a solution of MCPBA (0.92 g, 3.7 mmol) in CH2Cl2 (10 mL) was added dropwise. The resulting mixture was stirred in the ice bath for an additional 20 min. The mixture was washed with 10% Na2CO3 (5 x 15 mL) and saturated NaCl solution (15 mL). (Note 2) The organic layer was dried (Na2SO4) and the solvent was removed on a rotary evaporator (Note 2) to give 1.02 g (94%) of a viscous oil.

Procedure B (Buffered Epoxidation)

A biphasic mixture of a solution of trans-anethole (0.50 g, 3.4 mmol) in CH2Cl2 (10 mL) and 10% aqueous Na2CO3 solution (20 mL) was stirred well and cooled in an ice bath as a solution of MCPBA (1.4 g, 5.7 mmol, 1.7 equiv) in CH2Cl2 (20 mL) was added dropwise. After the addition was complete, the mixture was stirred for an additional 20 min in the ice bath. The organic layer was separated and washed with 10% aqueous Na2CO3 solution (5 x 25 mL) and saturated NaCl solution (15 mL). The organic layer was dried (Na2SO4) and the solvent was removed on a rotary evaporator to yield 0.52 g (95%) of a pleasant-smelling oil.


Notes

1. Based on the 1H NMR spectrum, there appears to be only one major product, which has been assigned structure 3 on mechanistic grounds. The ester carbonyl can also be clearly seen in the IR spectrum of 3.
2. The excess peracid is removed by washing with 10% aqueous Na2CO3. The absence of peracid can be tested using starch-iodide paper.
3. Solvent can also be removed using a water bath maintained at 50°C.

The IR spectrum of the unbuffered reaction product shows the presence of an OH group and also an ester carbonyl, suggesting the formation of a hydroxy ester. What is the theoretical yield of the product, assuming it is the epoxide? How does this compare to the observed yields? The observed yield of product in the absence of buffer is almost twice the theoretical yield. This gives the first hint that the expected product has not formed. Rather, the higher mass recovery must be due to formation of a product with a much larger formula weight. Buffered epoxidation gives product in a yield comparable to the theoretical yield of the expected epoxide.


Further Notes

* Commercial MCPBA, available from ACROS chemicals, is 70 % per acid by weight. We confirmed this by iodometric titration according to the procedure of Vogel (Textbook of Practical Organic Chemistry, 5th Ed.; Vogel, A. I.; Longman Scientific and Technical: New York, 1989, p 455)
* Because trans-anethole is very inexpensive, it was chosen rather than the much more expensive p-methoxystyrene.
* Peroxy acids (pKa ~8) are much weaker acids than carboxylic acids (pKa ~4). This allows for selective extraction of 3-chlorobenzoic acid. However, some of the MCPBA does react with Na2CO3, as is evident by the fact that the reaction does not go to completion when only 1 equiv. of MCPBA is used in presence of Na2CO3.
* The reaction mixture must be stirred very efficiently with a magnetic stir bar.
* If the organic layer is not extracted several times with Na2CO3, some of the 3-chlorobenzoic acid still remains in the organic layer.
* An alternative to the experiment described can be further purification of the ester by column chromatography (Rf 0.38, 40% ethyl acetate-60 % hexanes). The epoxide is not stable to silica gel.
* The ester and epoxide are not very volatile. Hence solvent can be easily removed using a water bath maintained at 50°C. The epoxide is very reactive and undergoes decomposition at higher temperatures.


Literature Cited

1. For examples of epoxidation see Bradley, L. M.; Springer, J. W.; Delate, G. M.; Goodman, A. J. Chem. Educ. 1997, 74, 1336. Garin, D. L.; Gamber, M.; Rowe, B. J. Chem. Educ. 1996, 73, 555.
2. Mohan, R. S.; Whalen, D. L. J. Org. Chem. 1993, 58, 2663-2669. Svensson, A.; Ulf, L. M.; Somfai, P. Synth. Commun. 1996, 26, 2875–2880.


Rhodium

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Neolignan Impurity in Anethole Peracid Oxidation
« Reply #21 on: July 06, 2004, 11:02:00 PM »
Interesting article, they are touching upon the same subject as in this yesteryear post of mine:

Post 409525

(Rhodium: "Why asarone cannot be oxidized with peracids", Methods Discourse)


A neolignan-type impurity arising from the peracid oxidation reaction of anethole in the surreptitious synthesis of 4-methoxyamphetamine (PMA)
Dieter Waumans, Bas Hermans, Noël Bruneel and Jan Tytgat

Forensic Science International 143(2-3), 133-139 (2004)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/forensic/anethole.peracid.neolignan.pdf)

Abstract
The neolignan-type substance 2,4-dimethyl-3,5-bis(4’-methoxyphenyl)tetrahydrofuran is presented as a new forensic marker compound for the peracid oxidation of anethole. It is hypothesized that the formation of a stable intermediary carbocation in the hydrolysis reaction of anethole epoxide is not only responsible for the presence of 1,2-diols (and its esters) and 4-methoxyphenyl-2-propanone (PMP2P) but can also be the cause for the creation of this neolignan impurity due to interaction with anethole itself. Moreover, the applicability of this new forensic marker is demonstrated by its retrieval in clandestinely manufactured 4-methoxyamphetamine (PMA) preparations.


2.3. Synthesis procedures

2.3.1. Preparation of performic and peracetic acid


Performic acid was prepared by adding 6.8 g freezer-cold 30% hydrogen peroxide to 24.0 g formic acid (98–100%). This mixture is stirred for ca. 1 h before using it in further syntheses. Due to the instability of performic acid, the solution has to be prepared fresh for every experiment. A stock solution of peracetic acid was prepared by combining 288.0 g of 30% hydrogen peroxide and 4.0 g concentrated sulfuric acid with 100.0 g glacial acetic acid. The reaction mixture was stored for 5 days in a dark and well-ventilated place, after which it was ready for use [13].

2.3.2. Peracid oxidation of anethole

2.3.2.1. Peracid oxidation of anethole dissolved in acetone

A 250 mL round-bottomed flask was equipped with a magnetic stirbar and a thermometer, and charged with a solution of 6.0 g anise oil in 30 mL acetone. Performic acid solution was added at such a rate that the reaction mixture temperature did not exceed 38 °C. After addition of the whole performic acid solution, the reaction was allowed to continue for ca 12 h. The reaction mixture was poured in its equal volume of cold distilled water (dH2O) and extracted with 2×50  of mL dichloromethane (DCM). The yellow organic phase was isolated and washed with 75 mL of dH2O, after which the organic phase was dried over Na2SO4. After evaporation of the solvent under reduced pressure, an aromatically scented yellow oil weighing 8.1 g remained.

Peracetic acid: substituting performic acid for 25.5 g peracetic acid solution yielded 5.8 g of a yellow oil after a similar work-up.

2.3.2.2. Peracid oxidation of anethole dissolved in dichloromethane

A 250 mL round-bottomed flask was equipped with a magnetic stirbar and a thermometer, and charged with a solution of 6.0 g anise oil in 25 mL of DCM. Performic acid solution was added to the vigorously stirred reaction mixture at such a rate that the reaction mixture temperature did not exceed 38 °C. The reaction was allowed to continue another 12 h after addition of the final performic acid solution. Subsequently, the reaction mixture was carried over to a separation funnel and the organic layer isolated. The aqueous phase was extracted with 50 mL of DCM and thereupon discarded. The combined organic phases were washed with 3×50 mL of dH2O, after which it was dried over Na2SO4. This yielded 5.8 g of a bordeaux red viscous oil

Peracetic acid: substituting performic acid for 25.5 g peracetic acid yielded 4.9 g of a yellow oil after a similar work-up.



3. Results and discussion

3.1. 2,4-dimethyl-3,5-bis(4’-methoxyphenyl) tetrahydrofuran in the performic and peracetic acid oxidation reaction of anethole


The presence of (1) in four reaction mixtures has been evaluated: performic and peracetic acid have been chosen as peracids, while acetone and DCM have been utilized as solvent. These are the most trivial choices when it comes down to simulating the peracid oxidation of a propenylbenzene in clandestine laboratories. Experiments conducted in the past revealed that anise oil had been used as PMA precursor, i.e. applied without prior purification of anethole by means of fractional distillation under reduced pressure. Hence, our choice for anise oil and not anethole. Moreover, it is known that anise oil has a very high anethole content [14]. As a rule, anise oil consists for 80–90% of anethole (cis and trans isomers, (3a) and (3b), respectively; predominantly present as trans) and there usually is a small percentage of methyl chavicol ((3c), the allyl isomer of anethole) as well (Fig. 1).





Fig. 1.
Structural formulas: (1) 2,4-dimethyl-3,5-bis(4’-methoxyphenyl) tetrahydrofuran; (2) magnosalicin; (3a) cis-anethole; (3b) trans-anethole; (3c) methyl chavicol.



4. Conclusion

It has been found that 2,4-dimethyl-3,5-bis(4’-methoxyphenyl) tetrahydrofuran, a chemical substance with a neolignan structure, is formed during the performic and peracetic acid mediated oxidation of anethole. Taking into consideration the manner this impurity is formed during the reaction, it can be argued that this compound is a selective marker for the peracid oxidation reaction of anethole. Its applicability is demonstrated by its presence in clandestinely manufactured preparations. It should be noted, however, that the presence of this impurity depends on a great deal on the underground chemist’s work-up abilities and/or mindset. Since the new impurity is a high-boiling substance, it is unlikely to retrieve it if intermediary purification of PMP2P has occurred.


abolt

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This yielded 5.8 g of a bordeaux red viscous...
« Reply #22 on: July 07, 2004, 10:16:00 AM »
This yielded 5.8 g of a bordeaux red viscous oil


I know I shouldn't be in here guys but I would like to add something that may, or may not, be of interest:

Performic oxidation of Anethole isolated from Illicum Verum.

61 grams anethole (isolated by double crystallisation)
21 grams Bicarb
45 mls 50% H2O2
85 mls 85% HCOOH
200 mls DCM

2 neck 1 litre FBF
500 ml dropping funnel
500 mm Leibig
Magnetic stirrer
50 mm stir bar

Performic was cooled in the freezer for 1 hour prior to addition and added, with vigorous stirring, in roughly 1/4 lots every 25 mins via drip. The performic acid was returned to the freezer until required. Cool water was added to a water bath surrounding the FBF, to keep a slight reflux going.

The performic addition was over in ~ 1 hour 45 mins. The exothermic reaction continued for roughly 3 hours after the performic addition.

After a total of 24 hours stir time the peracid was decanted and the DCM was washed twice with H2O and once with Brine.

The interesting thing is that reaction took on no color

No orange, No Bordeux Red......the upper acidic aqueous layer was cloudy white and the lower DCM/oil layer was clear with a slight beige tint.

The DCM was stripped and left a yellow oil that had an agreeable citrus type odor. One ml of this liquid was placed into a test tube of water and it sunk. The glycol was then heated to 80C. When heated, 100 ml MeOH, 135 ml 33% HCl & 195 ml H2O was added and this mixture was heated to reflux with good stirring for 3 hours 15 minutes, cooled, the lower oil portion was decanted and the aqueous layer extracted with 1 x 200 & 1 x 100 DCM.

The DCM extracts were pooled with the mother liquid, washed with 2 x 200 ml 5 % NaOH, 1 x 200 Brine and the DCM stripped.

Bisulfate tested positive for a yield of 62 grams raw PMP2P.

The distillation of the (assumed) PMP2P afforded 40 grams of clear/yellow oil using a shitty aspirator for vacuum.

Now, what I have noticed is that when Isosafrole and Anethole were distilled at atmospheric temperatures (with a hotplate temp that reached over 330 celcius) the contents of the Isosafrole distillation flask turned yellow/gold and the contents of the Anethole distillation flask turned Deep burgundy red.

I wonder if there is some correlation between this and the performic colorations?

.......I will get out of here now. :P  :)


Osmium

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> the contents of the Isosafrole ...
« Reply #23 on: July 07, 2004, 11:18:00 AM »
> the contents of the Isosafrole distillation flask turned yellow/gold
> and the contents of the Anethole distillation flask turned Deep
> burgundy red.

Even quite pure chemicals will discolour when heated to such temperatures, especially when oxygen is present.

> (2) magnosalicin

That's the compound I seem to remember is formed when you try anything like this with asarone, right?
There is another one I think, that is being produced when asarone is acidified. It consists of two condensed molecules of asarone but isn't symmetrical. Does anyone know its structure or name?


jsorex

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Why Asarone Cannot be Used in the Performic...
« Reply #24 on: July 07, 2004, 07:40:00 PM »
Why Asarone Cannot be Used
in the Performic Oxidation

https://www.thevespiary.org/rhodium/Rhodium/chemistry/asarone.performic.html




lugh

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Dimerization/Polymerization of Propenylbenzenes
« Reply #25 on: July 08, 2004, 03:25:00 AM »
According to abstracts of these articles by Balbiano et al; acid catalyzed dimerization/polymerization occurs with propenylbenzenes, not allylbenzenes  ::)  If that is the case, then probably the interior double bond comprises one side of the dimer; and the other side is probably a methoxy/methylenedioxy group, depending on which propenylbenzene is involved  ;)  Ber 36 1375-84 (1903) & 42 1502-6 (1909):



8)


methyl_ethyl

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Peracid Oxidation of Anethole: Impurities (PMA)
« Reply #26 on: July 14, 2004, 04:14:00 AM »
This is a poster presentation that describes the common impurtites that are formed during the peracid oxidation of anethole in the synthesis of PMA.



EVALUATION OF THE IMPURITIES FORMED DURING THE
PERACID OXIDATION OF ANETHOLE IN THE CLANDESTINE
SYNTHESIS OF P-METHOXYAMPHETAMINE (PMA)


Introduction:The profiling of synthesis impurities is of utmost importance
in forensic chemistry. This poster presents an overview of
impurities formed during the peracid oxidation of anethole
(the major component of anise oil) in the synthesis of PMA.


I hope this is not been posted before, a quick search yielded no results here or rhodi's site.

regards,

m_e