Author Topic: Synthesis of MMDA-3a and MMDA-3b Benzaldehydes  (Read 3108 times)

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imp

  • Guest
Synthesis of MMDA-3a and MMDA-3b Benzaldehydes
« on: October 12, 2003, 10:12:00 PM »
Substituted methylenedioxymethoxyamphetamines have proven to exhibit a variety of pleasant pharmacological effects. However, a reasonably OTC path to their synthesis has been very difficult to draft. For instance, croweacin-aldehyde can be prepared from its allylbenzene essential oil, croweacin, through oxidation with dispersed sodium dichromate. However, not only is croweacin very cumbersome to obtain from natural sources, but the method is also very impractical. So, a completely synthetic approach is most desired, and with a few modifications a nice procedure has been developed.

The general reaction scheme for 2-methoxy-3,4-methylenedioxybenzaldehyde (Croweacin-aldehyde) goes like...

i.   Preparation of pyrogallol 1-monomethyl ether
ii.   Methylenation to 1-methoxy-2,3-methylenedioxybenzene
iii.   Gatterman Formylation to the benzaldehyde

Now, by switching steps ii and iii, the aldehyde moiety will be introduced para to the methoxyl group and we can form 4-methoxy-2,3-methylenedioxybenzaldehyde instead.


Preparation of Pyrogallol 1-monomethyl ether
--------------------------------------------
refs:   Org. Syn., Vol. 25, 90 (19  )
   Monatsh., 25, 811 (1904)
   *** Can anybody get: Ann., 340, 232 (1905)??? SWIMs library is missing 1902-1908!

Method 1: From o-vanillin via Dakin

The apparatus consists of a 1-l. three-necked flask fitted with a gas inlet tube extending about 3 cm. into the flask and connected to the flask through a bubbler, a thermometer extending to the bottom, a mechanical stirrer, and a reflux condenser connected at the upper end with an exit tube leading to the hood. The reaction is carried out in an atmosphere of illuminating gas (Nitrogen can also be used).
In the flask are placed 60.8 g. (0.4 mole) of 2-hydroxy-3-methoxybenzaldehyde and 200 ml. of 2N sodium hydroxide (0.4 mole). The mixture is stirred until almost all the solid has dissolved. The stirrer is replaced by a dropping funnel which contains 284 ml. (0.5 mole) of 6% hydrogen peroxide. With occasional shaking, the hydrogen peroxide is added in portions of 20-25 ml. About 1 hour is required for the addition; the temperature is kept between 40 and 50 C. After the addition of the first portion of hydrogen peroxide, the temperature rises to about 45 C and a dark solution results. The temperature is allowed to fall to 40 C before the next portion of the peroxide is added.
After all the hydrogen peroxide is added, the reaction mixture is allowed to cool to room temperature and is then saturated with sodium chloride, after which it is extracted four times with 100-ml. portions of ether. The combined extracts are dried over sodium sulfate. The ether is removed by distillation on a steam bath, and the residue is then distilled under reduced pressure. Pyrogallol monomethyl ether is colledcted at 136-138 C/22 mm. The yield is 38-44.5 g. (68-80%) of a colorless to light yellow oil which solidifies on standing.  

Method 2: Selective mono-methylation of pyrogallol

a) With Methyl Iodide

SWIM has obtained this article, but doesn't know German. Instead, SWIM will scan the pages for Rhodium and he can decide what to do with them - if it is fine by you Rhodium? It will probably be next week though.

b) With Dimethyl Sulphate

Need that ref.!! Ann., 340, 232 (1905). It is probably most similar to the methyl iodide synthesis, but the paper itself might offer improvements and good reading. A good read is always worth the trouble.

Method 3: Decarboxylation of 2,3-dihydroxy-4-methoxybenzoic acid

Have this article too, and will scan.

Method 4: Oxidation of 5-hydroxyvanillin and decarboxylation of 5-hydroxyvanillic acid

SWIM has no literature on this reaction, it was just an idea. It seems simple enough, oxidation of 5-hydroxyvanillin to the benzoic acid, then a simple decarboxylation to pyrogallol 1-methyl ether. Or if you're going for croweacin-aldehyde, start from myristicinaldehyde. For many people, such as SWIM, 5-hydroxyvanillin/myristicinaldehyde is very easy to make from vanillin and in large quantities, so this is worth considering.


Methylenation to 1-methoxy-2,3-methylenedioxybenzene
----------------------------------------------------

The papers describing many of these reactions detail various general methylenation procedures. SWIM felt all were very out-dated, and much better procedures have been developed since.

USPs:

Patent US3436403


Patent US4082774


Patent US4183861


Patent US5936103



From

Patent US4082774



A typical procedure:

A solution of 110 g of catechol, 120 ml of 50% aqueous sodium hydroxide and 200 ml of DMSO was heated to 98°C and stirred at that temperature for 30 minutes. This solution at 98°C. was added over a 30 minute period to a refluxing solution of 120 ml of methylene dichloride in 300 ml of DMSO. Thereafter, the reaction mixture was stirred at reflux for 1.5 hours. Steam was then passed into the mixture to achieve steam distillation of the product. The distillate (600 ml) was extracted with 100 ml of methylene dichloride, which extract was washed once with 50 ml of water. The methylene dichloride solution was then concentrated in vacuo at 40°C. to yield 119.4 g. of a colorless oil. Gas chromatographic analysis showed 97.5 percent methylenedioxybenzene. Yield 116.4g (95.4%).


Gatterman Formylation
---------------------
refs:   JOC, vol. 16, pp.1736 (1951)
   Synth. Comm., 12(6), 485-487 (1982)
   Synth. Comm., 23(16), 2323-2329 (1993)

If the ether is first methylenated and then the aldehyde group is introduced, it enters ortho to the methoxyl, to give croweacin aldehyde. The yields in the Gatterman reaction are not very good in this case, since the methylenedioxy group is easily cleaved by Friedel-Crafts type reactions. If, on the other hand, the aldehyde group is introduced before the hydroxy groups are methylenated, then the aldehyde enters para to the methoxyl group. 

Here is a procedure used for the preparation of the aldehydes...

A solution of 28 g. of pyrogallol 1-methyl ether in 17 ml. of dry benzene was added to a cold (0 C) solution of 27.8 g. of aluminum chloride in 20 ml. of benzene, and the temperature was kept at 0 C while anhydrous hydrogen cyanide (20 g.) was distilled into the flask. A steady stream of anhydrous hydrogen chloride was then passed in for eight hours. For the first 2-3 hours the temperature was kept at 0-5 C and for the remainder of the time at 15-20 C. The reaction mixture was allowed to stand overnight, the solvent was decanted, and the thick residue was poured onto ice. The benzene and hydrogen cyanide were removed by steam-distillation, and the residue was extracted with ether. Evaporation of the ether and recrystallization of the residue of the redisue from boiling water gave 39% yield of the desired aldehyde, m.p. 117-118 C. This was methylenated using methylene chloride in methanolic potassium hydroxide solution. The yield of 2,3-methylenedioxy-4-methoxybenzaldehyde, m.p. 81-82 C, was 20%. This material was insoluble in dilute aqueous alkali and gave no ferric chloride test.

When pyrogallol 1-methyl ether was methylenated using methylene chloride, a 62% yield of methylenedioxymethoxybenzene, m.p. 41 C, was obtained. When this was subjected to the Gatterman reaction, as described above, it gave a 20% yield of croweacin aldehyde, m.p. 104 C, which is in agreement with the value reported by Penfold.


The Gatterman can be performed using acetone cyanohydrin instead...

As a type procedure, the formylation of mesitylene will be described: a mixture of 6 g. mesitylene (0.05 mol.) and 4.2 g. of acetone cyanohydrin (0.05 mol.) in 20 ml. of 1,2-dichloroethane was cooled to 0 C. Then 13.3 g. of aluminum chloride (0.1 mol.) was slowly added in the stirred mixture which was then allowed to warm up to room temperature. After refluxing for 24 h., the mixture was hydrolysed and dried on magnesium sulfate. The solvent was evaporated and the crude product distilled to yield 3.5 g. (48%) of 2,4,6-trimethylbenzaldehyde, bp : 71 C at 0.9 mm. 

Finally, another very nice Gatterman formylation procedure is the one on Rhodium's using zinc cyanide/AlCl3...

[

https://www.thevespiary.org/rhodium/Rhodium/chemistry/formylation.gattermann.html

]

imp

  • Guest
Acetone Cyanohydrin
« Reply #1 on: October 12, 2003, 10:13:00 PM »
Here is the synthesis of acetone cyanohydrin:

From Org. Synth. Coll. Vol. II, pp. 7:

Synthesis of Acetone Cyanohydrin

In a 5-l. three-necked, round-bottomed flask fitted with an efficient stirrer, a separatory funnel,
and a thermometer in a well is placed a solution of 500 g. (9.7 moles) of powdered 95 per cent sodium cyanide in 1.2 l. of water and 900 cc. (713 g., 12.3 moles) of acetone. The flask is surrounded by an ice bath, and the solution is stirred vigorously. When the temperature falls to 15 C, 2.1 l. (8.5 moles) of 40 per cent sulfuric acid is added over a period of three hours, the temperature being kept between 10 and 20 C. After all the acid has been added the stirring is continued for fifteen minutes and then the flask is set aside for the salt to settle. Usually a layer of acetone cyanohydrin forms and is decanted and separated from the aqueous layer. The sodium bisulfate is removed by filtration and washed with three 50-cc. portions of acetone. The combined filtrate and acetone washings are added to the aqueous solution, which is then extracted three times with 250-cc. portions of ether. The extracts are combined with the cyanohydrin previously separated and dried with anhydrous sodium sulfate. The ether and acetone are removed by distillation from a water bath, and the residue is distilled under reduced pressure. The low-boiling portion is discarded, and acetone cyanohydrin is collected at 78-82 C/15 mm. The yield is 640-650 g. (77-78 per cent of the theoretical amount).



SWIM wanted to make a mention of that Gatterman reacton on mesitylene in the previous post. This formylation is really interesting, especially for TMA-6 and other 2,4,6-compounds, due to their inability to undergo the Sommelet reaction. Chloromethylation of such compounds will succeed, but the Sommelet will fail due to both ortho positions being occupied - forming the benzylamine instead (SWIM has a ref. for that of course). So, other than a Vilsmeyer, the Gatterman will work on 1,3,5-substituted benzenes. Hmmm, wonder what the product from 2,4,6-trimethylbenzaldehyde might taste like.

SWIM also has an interesting paper where acetone cyanohydrin is used for a Mitsunobu reaction. The acetone cyanohydrin is the acidic component and the source of cyanide ion.


Edit:
SWIM mentioned that you can't use the Sommelet on ortho di-substituted chloromethyl compounds. But theoretically, couldn't one chloromethylate, then form the benzylamine, and finally oxidize to form the aldehyde?? Seems a bit lengthy, but it is possible. SWIM will try to find some refs.

Rhodium

  • Guest
2,6-Dimethoxyphenol & 2,6-Dimethoxybenzoquinone
« Reply #2 on: December 17, 2003, 12:40:00 PM »
Related material:

Post 245205 (missing)

(Rhodium: "Re: Benzaldehyde Of Croweacin?", Chemistry Discourse)


Also, as requested in

Post 464340

(imp: "Synthesis of MMDA-3a and MMDA-3b Benzaldehydes", Novel Discourse)


Ueber 1,3-Pyrogalloldimethyläther und über 2,6-Dimethoxychinon
C. Graebe, H. Hess

Ann. 340, 232 (1905)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/26-dimethoxyquinone.pdf)


Rhodium

  • Guest
Croweacinaldehyde from Pyrogallol (55%)
« Reply #3 on: January 23, 2004, 04:18:00 PM »
Preparation of 2-Methoxy-3,4-Methylenedioxybenzaldehyde (Croweacinaldehyde) from Pyrogallol
Tadashi Shirasaka, Yuki Takuma, And Naoshi Imaki

Synthetic Communications 20(8), 1213-1221 (1990)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/croweacinaldehyde.pyrogallol.html)

Abstract
2-Methoxy-3,4-methylenedioxybenzaldehyde (croweacinaldehyde) of high purity was prepared in 55% overall yield from pyrogallol.




Rhodium

  • Guest
Croweacinaldehyde & Isomers
« Reply #4 on: January 26, 2004, 02:10:00 PM »
Synthesis of the Yeast Antioxidant Benzofuran and Analogues
Brian A. McKittrick and Robert Stevenson

J. Chem. Soc. Perkin Trans. I, 709-712 (1984)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/croweacinaldehyde.pdf)


Methylenation of 3-methoxypyrocatechol (3) by treatment with methylene dibromide and potassium carbonate in dimethyl sulphoxide afforded 1-methoxy-2,3-methylenedioxybenzene (4) in about 80% yield. Several reports concerning the Vilsmeier formylation of (4) exist. In the first. Brownell and Weston9 reported the isolation of 2-methoxy-3,4-methylenedioxybenzaldehyde (5) as the sole product, a conclusion supported by later findings10. In contrast, Wagner and co-workers3,11 found that the product was a mixture of the aldehyde (5) and 4-methoxy-2,3-methylenedioxybenzaldehyde (6). This was substantiated by later work of Shulgin12 and Dallacker13, although there was a wide variation in the ratios of the two aldehydes reported. In our hands, the crude product obtained from compound (4) by treatment with phosphorus oxychloride and dimethylformamide furnished the isomers (5) and (6) in a 2:1 ratio, as estimated from integration of the 1H NMR spectrum. The mixture was separated by chromatography on silica gel.


The readily available 3,4-dihydroxy-5-methoxybenzaldehyde (9)16 was converted into the methylenedioxy derivative (10) by an improved procedure and then into the phenol (11) by Baeyer-Villiger oxidation with performic acid. Gattermann formylation of (11) with zinc cyanide gratifyingly yielded the required aldehyde (12) in over 80% yield.



Experimental

Mp's were determined with a Gallenkamp apparatus and are uncorrected. The silica gel used for chromatography was J. T. Baker (40-140 mesh) and light petroleum refers to the fraction boiling in the range 54-105°C. Ether refers to diethyl ether.

1-Methoxy-2,3-methylenedioxybenzene (4)

Anhydrous potassium carbonate (20 g) followed by dibromomethane (10 ml) were added to a solution of 3-methoxypyrocatechol (3) (11.3 g) in dimethyl sulphoxide (250 ml). The mixture was heated at 85°C for 2 h under nitrogen, then cooled and poured into water (250 ml). Extraction with ether (5 x 100 ml) and evaporation of the washed and dried (MgSO4) extract yielded an oil, which was distilled (65-75°C bath temperature at 0.05 mmHg). On standing, the distillate gave compound (4) as light yellow crystals (9.67 g), mp 39-41°C (lit.19 mp 41°C).

2-Methoxy-3,4-methylenedioxybenzaldehyde (5)

Phosphorus oxychloride (9.0 ml) was added dropwise during 10 min at room temperature to a solution of compound (4) (5.44 g) in dimethylformamide (7 ml). The mixture was stirred at room temperature for 30 min, then at 50°C for 1 h and at 90°C for 2 h, cooled, and diluted with water (50 ml) to yield a yellow precipitate which was dissolved in ether, washed with water, and dried. Evaporation of this extract gave a solid (4.5 g) whose integrated 1H NMR spectrum indicated the presence of isomers (5) and (6) in a 2:1 ratio. Chromatography of this mixture on silica gel with light petroleum–dichloromethane (3:7) yielded first the aldehyde (5) as needles (2.48 g) from ethanol, mp 102-104°C (lit.3 mp 103-105°C).

Continued elution with the same eluant gave mixtures of isomers (5) and (6), followed by pure 4-methoxy-2,3-methylenedioxybenzaldehyde (6), obtained as a solid (1.3 g), mp 82-85°C (lit.3 85-86°C).

3-Methoxy-4,5-methylenedioxybenzaldehyde (10)

Anhydrous potassium carbonate (20 g) and dibromomethane (10 ml) were added to a solution of 3,4-dihydroxy-5-methoxy-benzaldehyde (9) (13.5 g) in dimethyl sulphoxide (250 ml) and the mixture was heated at 90°C for 2.5 h under nitrogen. Dilution of the cooled mixture with water was followed by chloroform extraction (600 ml). Evaporation of the washed and dried extract gave a residual solid which on distillation (110-115°C at 0.5 mmHg) gave the methoxymethylenedioxy aldehyde (10), mp 130-132°C (lit.16 mp 131-132°C).

3-Methoxy-4,5-methylenedioxyphenol (11)

Formic acid (90%; 40 ml) was added to hydrogen peroxide solution (30%; 100 ml) and stirred at 0-5°C for 1 h. A solution of the benzaldehyde (10) (4.8 g) in formic acid (90%; 100 ml) was then added with continued stirring at 5°C for 3.5 h, after which additional performic acid (from 5 ml hydrogen peroxide and 20 ml formic acid) was then introduced. After the mixture had been stirred for a further 75 min, the reaction was quenched by the addition of sodium sulphite (10 g) and ice (400 ml) and extracted with ether (600 ml). After being washed with water, the extract was stirred vigorously at room temperature for 30 min with dilute sodium hydroxide solution (pH 12). The dark red basic phase was then separated, acidified with 3% hydrochloric acid, and re-extracted with ether. Evaporation of the washed and dried extract yielded a semi-solid residue which on distillation (ca. 100°C at 0.1 mmHg) gave the phenol (11) as a light tan solid (2.02 g), mp 85-88°C (lit.3 mp 89-91°C).

6-Hydroxy-2-methoxy-3,4-methylenedioxybenzaldehyde (12)

Zinc cyanide (310 mg) was added to a solution of the phenol (11) (180 mg) in ether (35 ml) and hydrogen chloride bubbled through the stirred mixture for 1.5 h at 0°C. Stirring was continued for a further 1.5 h after which the ether was decanted. Water (40 ml) was added to the gummy residue, and the mixture heated on the steam-bath for 15 min, then cooled and filtered. Recrystallization of the solid (175 mg) from light petroleum gave the aldehyde (12) as cream flakes, mp 124-125°C.

References

[3]

J. Am. Chem. Soc. 81, 4983 (1959)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/methoxymethylenedioxybenzene.pdf)
[9] W. B. Brownell and A. W. Weston, J. Am. Chem. Soc., 73, 4971 (1951)

Post 484720

(Rhodium: "Croweacinaldehyde", Novel Discourse)

[10] F. Benington and R. D. Morin, J. Org. Chem., 27, 142 (1962)
[11] A. F. Wagner and F. A. Kuehl, Jr.,

Patent US3000902

(Chem. Abstr., 1972, 56, 1339c).
[12] A. T. Shulgin, Can J. Chem., 46, 75 (1968)

Post 489559

(Rhodium: "Synthesis of Myristicinaldehyde/Apiolealdehyde", Novel Discourse)

[13] F. Dallacker, Chem. Ber., 102, 2663 (1969)

Post 477701

(Rhodium: "Synthesis of all Apiole Positional Isomers", Novel Discourse)

[16] G. E. Schneiders and R. Stevenson,  J. Org. Chem., 46, 2969 (1981)

Post 477377

(Rhodium: "Myristicin-derived Cathinones (Precursor prep)", Novel Discourse)

[19] K. N. Campbell, P. F. Hopper, and B. K. Campbell, J. Org. Chem., 16, 1736 (1951)

Post 489659

(Rhodium: "Myristicin & Myristicinaldehyde", Novel Discourse)



Rhodium

  • Guest
Croweacinaldehyde
« Reply #5 on: January 26, 2004, 02:43:00 PM »
A New Synthesis of Croweacin Aldehyde
W. B. Brownell and A. W. Weston
J. Am. Chem. Soc. 73, 4971-4972 (1951)

In a study associated with a previous investigation1, a simplified synthesis of croweacin aldehyde, 2-methoxy-3,4-methylenedioxybenzaldehyde (IV), was desired. This aldehyde has been prepared2 from daphnetin (I) by methylenation, followed by treatment with sodium hydroxide and dimethyl sulfate and ozonization of the resulting cinnamic acid (II).

As an approach to the synthesis of IV, 1-methoxy-2,3-methylenedioxybenzene (III) was treated with phosphorus oxychloride and N-methylformanilide3. The aldehyde (IV) was obtained in a 46% yield. Since III is readily prepared from o-vanillin by the method of Baker and co-workers4, the present work offers a convenient synthesis of croweacin aldehyde (IV).

Experimental

Croweacin Aldehyde (IV)

To 13.5 g. (0.1 mole) of N-methylformanilide there was added 15.3 g (0.1 mole) of phosphorus oxychloride. The solution was allowed to stand for 30 minutes and then 6g (0.04 mole) of 1-methoxy-2,3-methylenedioxybenzene4a (III) was added. The reaction mixture was heated at 100°C for two hours, cooled to room temperature and poured into ice-water. The solid product was collected by filtration and crystallized from dilute alcohol. The weight of material melting at 103°C (lit.2 104°C) was 3.3g (46%).

The 2,4-dinitrophenylhydrazone was prepared in the conventional manner and crystallized from ethyl acetate; mp 254-255°C (lit.2 254°C).

A portion of the aldehyde was oxidized with potassium permanganate to give croweacic acid, 2-methoxy-3,4-methylenedioxybenzoic acid, melting at 155°C (lit.2 153°C).

[1] K. E. Hamlin and A. W. Weston, J. Am. Chem. Soc. 78, 2210 (1949).
[2] A. R. Penfold, G. R. Ramage and J. L. Simonsen, J. Chem. Soc., 756 (1938).
[3] L. N. Ferguson, Chem. Revs., 38, 231 (1946).
[4a] W. Baker, L. V. Montgomery and H. A. Smith, J. Chem. Soc., 1281 (1932);
[4b] W. Baker and R. I. Savage, J. Chem. Soc. 1607 (1938).


Rhodium

  • Guest
Synthesis of Myristicinaldehyde/Apiolealdehyde
« Reply #6 on: February 18, 2004, 08:36:00 AM »
Synthesis of Myristicinaldehyde and Apiolealdehyde
Alexander T. Shulgin

Can. J. Chem. 46, 75-77 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/myristicinaldehyde.shulgin.html)

Abstract
The conversion of isomyristicin to a Schiff base of myristicinaldehyde is described. The subsequent hydrolysis of this base to the free aldehyde establishes a convenient preparation of this material. Apiolealdehyde is similarly generated from isoapiole, suggesting that this procedure may have general application in the conversion of the natural aromatic ethers of essential oils to the correspondingly substituted benzaldehydes.

This article has been mentioned in the following posts:

Post 484717

(Rhodium: "Croweacinaldehyde  & Isomers", Novel Discourse)

Post 452949

(GC_MS: "myristicinaldehyde", Chemistry Discourse)

Post 355957

(GC_MS: "How dangerous is tetranitromethane?", Chemistry Discourse)



Rhodium

  • Guest
Myristicin & Myristicinaldehyde
« Reply #7 on: February 18, 2004, 06:30:00 PM »
The Preparation of Methylenedioxy-Methoxybenzaldehydes
Kenneth N. Campbell, Paul F. Hopper, Barbara K. Campbell

J. Org. Chem. 16, 1736-1741 (1951)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/methylenedioxymethoxybenzaldehydes.pdf)

This article has been referenced in the following posts:

Post 464340

(imp: "Synthesis of MMDA-3a and MMDA-3b Benzaldehydes", Novel Discourse)

Post 464339

(imp: "2-Alkoxy-4,5-methylenedioxybenzaldehyde Synthesis", Novel Discourse)

Post 484717

(Rhodium: "Croweacinaldehyde  & Isomers", Novel Discourse)

____ ___ __ _

The Synthesis of N-(3-Methoxybenzyl)-N-methyl-3-methoxy-4,5-methylenedioxyphenethylamine
Alexander R. Surrey

J. Am. Chem. Soc. 70, 2887-2890 (1948)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/myristicin.pdf)

Summary: Synthesis of Myristicin, isomerization to Isomyristicin and oxidation to Myristicinaldehyde.

The article has earlier briefly been mentioned in

Post 71408 (missing)

(Scooby_Doo: "Re: has startinout won the OTC safrole comp?", Novel Discourse)

____ ___ __ _

Myristicinaldehyde
C. E. Redemann, B. B. Wisegarrer, and R. N. Icke.
J. Org. Chem. 13, 886-890 (1948)

Fractional distillation of 700 g of Dodge and Olcott heavy nutmeg oil gale 436 g of myristicin, bp 152-155°C/18mmHg.
This was isomerized to isomyristicin by boiling under reflux for 24 hrs. with 1.4 L of 3 N ethanolic potassium hydroxide. From this mixture was isolated 352 g of isomyristicin, bp 162-163°C/15mmHg, which after recrystallization from methanol gave isomyristicin as white needle-crystals, mp 43-44°C, Power [J. Chem. Soc. 31, 2055 (1907)] gives 44°C.
The isomyristicin was oxidized in 96g batches according to Salway [J. Chem. Soc. 95, 1208 (1909)]. The aldehyde was obtained as a white crystalline powder, mp 131-132°C, in 41% yield. The aldehyde gave a 2,4-dinitrophenylhydrazone, dark brown-red needles, mp 232°C, identical with that described by Baker [J. Chem. Soc. 443 (1939)].


Rhodium

  • Guest
5-Hydroxypiperonal and Myristicinaldehyde
« Reply #8 on: May 02, 2004, 01:02:00 PM »
The Synthesis of Hydroxybenzaldehydes from Bromobenzaldehydes via Lithiated Schiff's Bases: Preparation of 5-Hydroxypiperonal and Related Compounds
Peyton Jacob, III and Alexander T. Shulgin

Synthetic Communications, 11(12), 969-977 (1981)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/5-hydroxy-piperonal.shulgin.html)

Introduction
Myristicinaldehyde (3-methoxy-4,5-methylenedioxybenzaldehyde) and 3,4,5-trimethoxybenzaldehyde are intermediates in the synthesis of numerous alkaloids and pharmacological agents. As a part of our studies on the synthesis and pharmacological action of ring-substituted phenethylamines, we had need of a general method for the preparation of the 3-alkoxy homologs of these two aldehydes. The published syntheses of myristicinaldehyde generally utilized myristicin (3-methoxy-4,5-methylenedioxyallylbenzene) as a starting material, which is readily available only from botanical sources; 3,4,5-trimethoxybenzaldehyde is usually prepared by the methylation and reduction of gallic acid. Consequently, the 3-alkyl homologs are not readily synthesized from these natural products and have not been reported in the literature [...]


Rhodium

  • Guest
Myristicin Derivatives
« Reply #9 on: May 26, 2004, 04:02:00 PM »
Preparation of Myristicinaldehyde
A. H. Salway, J. Chem. Soc. 95, 1204-1220 (1909)

Myristicin (5 parts) was heated for twenty-four hours on the water-bath with a solution of potassium hydroxide (4 parts) in 15 parts of alcohol, whereby a quantitative yield of isomyristicin was obtained (compare Semmler, Ber., 1891, 24, 3818; Thorns, Ber, 1903, 36, 3446).

The latter substance, in portions of 10 grams at a time, was then shaken into an emulsion with water at 60°C, and a solution of 20 grams of potassium permanganate in 500 mL of water gradually added with constant agitation, the temperature being kept at 60-65°C. After all the permanganate had been added, for which about an hour was necessary, the mixture was cooled, filtered, and the manganese precipitate well washed with cold water. The precipitate, which contained the myristicinaldehyde, was dried on a porous plate, and afterwards extracted in a Soxhlet apparatus with chloroform. The chloroform extracts from several such oxidations were united, the solvent removed, and the solid residue well washed with cold ether to remove unoxidised isomyristicin. The yield of myristicinaldehyde was 40-45% of the isomyristicin employed.

A quantity of myristicinic acid, varying from 15 to 20%, was always formed by the oxidation, and could be obtained by acidifying the filtrate from the manganese precipitate.
____ ___ __ _

Preparation of Homomyristicinic Acid
G. Y. Moltrasio and D. Giacopallo and M. J. Vernengo

Org. Prep. Proced. Int. 4(1), 13-18 (1972)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/myristicinaldehyde-homomyristicinic.acid.html)

Summary
Synthesis of 5-Methoxy-4,5-methylenedioxyphenylacetic acid (Homomyristicinic acid) from myristicin via isomyristicin, myristicinaldehyde and the corresponding benzyl alcohol, benzyl chloride and phenylacetonitrile.
____ ___ __ _

Petroselinic Acid and Nonsaponifiable Constituents of Parsley Seed Oil
O. S. Privett, J. D. Nadenicek, R. P. Weber, and F. J. Pusch

J. Am. Oil. Chem. Soc. 40, 28-30 (1963)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/parsley.seed.oil.pdf)

Abstract
Selective extraction of parsley seed oil (Petroselinum sativum) facilitates the isolation of myristicin (5-allyl-1-methoxy-2,3-methylenedioxybenzene) and is also useful for the preparation of petroselinic acid from the triglycerides of this oil.
____ ___ __ _

Über Myristicin und seine Derivate. II. Myristicinaldehyd
F. W. Semmler

Chem. Ber. 24, 3818-3823 (1891)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/myristicinaldehyde.semmler.pdf)
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Derivate des Methylendioxybenzols, 6. Mitt.
Über die Gewinnung und elektrophile Substitutionen des Myristicinsäuremethylesters and seiner Derivate

F. Dallacker, F. Gohlke and Maria Lipp

Monatsheft 91, 1089-1102 (1960)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/myristicin.dallacker.pdf)

Abstract
Aus dem Petersiliensamenöl isolierten wir Apiol, Myristicin und Safrol. Durch Ozonisierung wurden die entsprechenden Aldehyde dargestellt, die zur Säure weiteroxydiert und als Ester getrennt werden konnten. Ausserdem beschreiben wir die Bildung von Brom-, Nitro- and Aminoderivaten des Myristicinsäuremethylesters.