Author Topic: Piperonal + CH2N2 -> MDP2P + Safrole Epoxide  (Read 3914 times)

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Rhodium

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Piperonal + CH2N2 -> MDP2P + Safrole Epoxide
« on: May 27, 2004, 03:07:00 AM »
Alkylation of aldehydes with diazomethane generally yields the corresponding methyl ketone. Thus the reaction of diazomethane piperonal is expected to give 3,4-methylenedioxyacetophenone:



This, however, is not the case when piperonal is reacted with diazomethane in methanolic solution. Only a trace of the expected acetophenone is formed, while a mixture of 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and safrole epoxide is formed in good yield. Also, as it is known that lithium iodide and other salts isomerizes safrole epoxide to MDP2P (but not sulfuric acid, which yields the aldehyde), the resulting crude mixture can very likely be processed as is, to give MDP2P exclusively as the end product.


References:

Über die Einwirkung von Diazo-methan auf Piperonal. I.
Erich Mosettig

Chem. Ber. 61, 1391-1395 (1928)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/piperonal.diazomethane-1.pdf)
____ ___ __ _

Über die Einwirkung von Diazo-methan auf Piperonal. II.
Erich Mosettig

Chem. Ber. 62, 1271-1278 (1929)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/piperonal.diazomethane-2.pdf)
____ ___ __ _

Über die Einwirkung von Diazo-methan auf Piperonal. III.
Erich Mosettig & Karl Czadek

Monatsh. 57, 291-304 (1931)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/piperonal.diazomethane-3.pdf)

I'd be very delighted if anyone fluent in german could review the above documents and present an english summary of their complete findings, as well as a detailed experimental procedure.


Aurelius

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Plain Benzaldehyde?
« Reply #1 on: May 27, 2004, 04:30:00 AM »
what about other examples?  Substituted, Not, and all the myriads of analogues?  (I know you're waiting on the german.)

Nice detour around nitroethane.


Rhodium

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piperonal is an anomaly
« Reply #2 on: May 27, 2004, 05:51:00 AM »
Some nitro-benzaldehydes may give rise to styrene epoxides, but most other benzaldehydes yields acetophenones with diazomethane.

Mosettig was greatly surprised about the above result - piperonal is an anomaly. 6-nitropiperonal gives 6-nitro-3,4-methylenedioxyacetophenone according to his third article above.


Lego

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Translation of Chem. Ber., 1928, 61, 1391-1395
« Reply #3 on: May 31, 2004, 12:49:00 AM »
Über die Einwirkung von Diazo-methan auf Piperonal
Erich Mosettig

Chem. Ber., 1928, 61, 1391-1395

(https://www.thevespiary.org/rhodium/Rhodium/pdf/piperonal.diazomethane-1.pdf)

[...]

As the experiments show (see below) the addition of methanol and the way the aldehyde is added to reaction are very important. By varying both parameters the relative and absolute amounts of the reaction products can be influenced, e.g. if piperonal is dissolved in ether and mixed with diazomethan in ether acetopiperon is obtained as a main product and the non-ketone product is a trace product.

[...]

Description of the experiments

10 g Piperonal were melted in a 500 ml Erlenmeyer flask, the flask was put in a ice-salt-mixture and on the piperonal which solidified to a disc a cooled solution of 350 ml diazomethan in ether9 and 60 ml methanol was poured over a period of 10 min. After standing for 2 days at room temperature the solution completely lost its colour. 10 more grams of piperonal were treated in the same way and solutions were combined. After removal of the solvent 23 g of a weakly coloured oil with an intense and pleasent smell were isolated. It distilled with a decomposition at 140-145 °C at 9-10 mm pressure. The distillation residue is viscous, light yellow oil which decomposes on further distillation and was not investigated any further. The distillate were 20 g of a completely colourless oil with low viscosity. It was dissolved in 300 ml ether and shaken mechanically for 3 h in 150 ml of a saturated sodium bisulfite solution in a seperating funnel.
The precipitated bisulfite product was collected by filtration, washed with ether, the keton was liberated with concentrated sodium carbonate solution and extracted with ether. After drying with sodiums sulfate and evaporation of the solvent 4.4 g oil were obtained which was colourless and almost odourless after vacuum distillation (boiling point: 140-145 °C). The semicarbazone was prepared in the same manner, recrystallized twice from methanol and had a melting of 163-165 °C. The melting point of piperonylacetone (MD-P2P) which was prepared according to Höring10 by isomerisation of isosafroloxide had a melting point of 163-164 °C. The mixed melting point of both semicarbazones was 163-164 °C.

After isolating the ketone from the ether solution the ether was washed several times with water and very diluted KOH solution, dried and after evaporated gave 12 g oil. In order to further purify it was digested about ten times with each 30 ml cold petroleum ether (boiling point: 20-30 °C). 2.2 g of a colourless, but very viscous oil could not be dissolved. Only a few amount of acetopiperon could be detected as the semicarbazone. The pooled petroleum ether gave 9.5 g of a colourless oil (boiling point: 145-147 °C) which was treated with seed crystals of acetopiperon and immediately formed a crystalline precipitate, which was filtrated and recrystallized from water. Yield: 0.7 g, melting point: 87-88.5 °C.

[...]

In order to understand the the influence of methanol in the reaction of piperonal and diazomethane two experiments without methanol were performed:

Experiment I: To a solution of 5 g piperonal in ether a solution of diazomethane in ether was added while the whole mixture was cooled. The nitrogen development ceased within a short time and after two weeks the solution was discoloured. The overall yield is bad. The main product was acetopiperon (2.5 g). The non-ketone product was only present in traces and could not be isolated.

Experiment II: On 10 g solid piperonal a solution of diazomethane in ether (prepared of 20 ml nitrosomethylurea) was poured at -15 °C. The devolopment of nitrogen is vigorous at the beginning but ceases after a short time. After two weeks the solution is discoloured. The yield is not good, too (2 g piperonylacetone, 1.5 g acetopiperon und about 2 g of non-keton product). The yield of acetonpiperon might be increased if the vacuum distillation is avoided while isolating the last two products.

9 The diazomethane solution was prepared in the usual manner from 20 ml nitrosomethylurea and 25% KOH in methanol.
10 P. Höring, B. 38, 3481 (1905)




Acetopiperon = 3,4-Methylendioxyacetophenone


The rest of the articles will bee translated after some hours of sleep......


GC_MS

  • Guest
Reaction mechanism
« Reply #4 on: June 25, 2004, 01:50:00 PM »
I was wondering if the following could be a valid reaction mechanism...

Diazomethane will add to the carbonyl group of an aldehyde or a ketone. The formed intermediary will eliminate N2 and undergo a rearrangement, yielding the corresponding ketone and/or epoxide.

In a first instance, diazomethane reacts with piperonal forming the corresponding acetophenone. Nothing special, since benzaldehydes are known to undergo this reaction fairly well.
In a second instance, the previously formed acetophenone will react with diazomethane as well, yielding the corresponding ?-ketone and the epoxide. Theoretically, the acetophenone should yield a mixture of P2P and the benzophenone.

So I think that this might be what really happens... the formed acetophenone reacts further with diazomethane yielding MDP2P and some epoxide. Comments? Thoughts?


GC_MS

  • Guest
visualization
« Reply #5 on: June 28, 2004, 09:56:00 AM »


Maybe visualization helps a bit...

In a first step, diazomethane reacts with piperonal yielding the expected 3.4-methylenedioxyacetophenone. The latter can react further with more diazomethane giving (theoretically) a mixture of MDP1P and MDP2P. Aryl migration is prefered, so MDP2P forms the major product (and MDP1P the minor).

Why it works this way for piperonal and not for the other benzaldehydes is something I don't understand. However, I thought they used ether as a solvent if diazomethane is used in the reaction. Diazomethane is used as a methylating agent for alcohols (I vaguely remember a post about this from our Russian partners).

ROH + CH2=N=N ---> ROCH3 + N2

But the reaction needs a catalyst. Also, you can use some more information using google for diazomethane and homologation.


Rhodium

  • Guest
Benzyl Alkyl ketones by the inverse route
« Reply #6 on: September 11, 2004, 06:51:00 AM »
It seems like benzyl alkyl ketones are available by the addition of Ph-CH=N2 (prepared from benzaldehyde tosylhydrazone) to aliphatic aldehydes as well:

A Simple Method for the Synthesis of Substituted Benzylic Ketones:
Homologation of Aldehydes via the in Situ Generation of Aryldiazomethanes from Aromatic Aldehydes

Steven R. Angle and Martin L. Neitzel, J. Org. Chem. 65, 6458-6461 (2000)
DOI:

10.1021/jo000446y



Abstract
A general method for the homologation of aldehydes to benzylic ketones has been developed. Aryldiazomethanes were generated in situ in the presence of an aldehyde by simply heating the tosylhydrazones of aromatic aldehydes in the presence of a stoichiometric amount of base in polar protic solvents. The resulting polar protic solvent promoted homologation afforded benzylic ketones in moderate to excellent yields with a variety of aldehydes. Isolation of the tosylhydrazones was not necessary; they could be prepared in ethanol and carried through the sequence without isolation. This methodology allows easy access to a wide variety of substituted aryldiazomethanes that would be difficult, or even impossible, to prepare via conventional methods and circumvents the toxicity and stability problems associated with the isolation and/or handling solutions of aryldiazomethanes.



Lithium bromide catalyzed homologation of aldehydes with aryldiazomethanes
C.A. Loeschorn, M. Nakajima, P.J. McCloskey, J.P. Anselme, J. Org. Chem. 48, 4407-4410 (1983)

Homologation of Aldehydes with Aryldiazomethanes. General Procedure.

To a stirred mixture of the aldehyde (0.015 mol) and a tenfold equivalent of lithium bromide (11.5g, 0.15 mole) in 100 mL of anhydrous ether cooled in an ice-salt bath (-5°C to 0°C) was added through an addition funnel a dilute solution of approximately 0.015 mol of phenyldiazomethane  in 125 mL of anhydrous ether. The reaction flask was protected from light with aluminum foil. The length of time for completion of the  reaction varied from immediate reaction to a couple of days depending upon the aldehyde employed. The completion of the reaction was  heralded by the disappearance of the deep wine-red color of the phenyldiazomethane. Water was added and the ethereal layer was separated and dried over magnesium sulfate for 1-2 h. The ether was removed in vacuo, leaving the crude product. Purification varied depending upon the product to be isolated. The yields given were estimated from the NMR, and the weights are those of the crude products.

1-Phenyl-2-butanone (5.2 g, 81%), clear liquid (distillation);
IR (neat): 1701 cm-1; the structure was confirmed by the addition of an authentic sample (Aldrich) to the NMR sample;
NMR (CDCl3) ? 7.19 (s, 5 H), 3.60 (s, 2 H), 2.40 (q, 2 H), 1.00 (t, 3 H).