Author Topic: Substituted Vanillins are Resistant to Oxidation  (Read 2534 times)

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Rhodium

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Substituted Vanillins are Resistant to Oxidation
« on: December 01, 2003, 03:35:00 PM »
I was researching literature methods for the preparation of bromine-substituted vanillins, when I found a few articles discussing not only my topic of interest, but also the fact that some benzaldehydes seems to be unusually insensitive to oxidation - many benzaldehydes tend to oxidize in air to the corresponding acid. This seems to be no problem with benzaldehydes like vanillin, 5-bromovanillin, syringaldehyde and a few other related derivatives.

New Monobromo Derivatives Of Vanillin
By L. Chas. Raiford And W. C. Stoesser
JACS 49, 1077-80 (1927)

Hitherto, the only known bromine derivative of vanillin is that melting at 164°C1 and having the halogen in Position 5 (CHO = 1). In the work reported here two other derivatives have been obtained, melting at 154-155°C and 178°C, respectively. The first of these was prepared from an aminovanillin2, mp 127°C, by the Sandmeyer reaction. The structure of the amine has been [determined to be] 2-bromovanillin.

When an acetic acid solution of vanillin is treated with bromine at room temperature, the 5-bromo compound1 appears to be the only product4, regardless of the amount of bromine employed. If acetylvanillin is used, and the bromination is carried out with one molecular proportion of bromine; under the conditions just stated, three products are formed: 5-bromovanillin, a second monobromo derivative, mp 178°C, which was shown by mixed-melting-point determinations to be different from the other two, and in which bromine must occupy Position 6, along with a dibromo derivative; mp 218°C5. Bromination of the acetylated compound in the presence of sodium acetate6 gives the 6 derivative only; however, this product is very readily converted into the dibromo compound specified above, while the 5 derivative undergoes further bromination with difficulty5. Nevertheless, both give the same dibromo product from which it follows that the latter is 5,6-dibromovanillin. It seems probable, therefore, that the presence of the three products in the mixture obtained by brominating acetylvanillin in the absence of sodium acetate may be explained as follows. The liberation of hydrogen bromide in the formation of 6-bromovanillin, which is easily obtained from the acetyl derivative, hydrolyzes some of the acetyl compound to free vanillin. The latter gives only the 5 derivative under the conditions of this experiment while, as stated above, the 6 derivative readily gives the dibromo compound.

2-Bromovanillin

[2-Aminovanillin] was dissolved in an excess of dil. hydrobromic acid and diazotized with the calculated quantity of sodium nitrite. The resulting liquid was added gradually with stirring to cuprous bromide solution, and the mixture heated on a water-bath until no more nitrogen was evolved. After 24 hours, half a volume of conc. hydrochloric acid was added and the solid filtered off; yield, 83%. Boiling its dilute alcoholic solution with animal charcoal, filtering and cooling the filtrate gave nearly colorless needles; mp 154-155°C.

6-Bromovanillin

A mixture of 7.5 g. each of acetylvanillin and dried sodium acetate, 0.1 g. of iodine and slightly more than one molecular proportion of bromine in 35 mL of acetic acid was warmed to 45°C, then allowed to cool and stand overnight. When the mixture was poured into water, an oil separated. Shaking caused it to solidify; yield 87.6%. Hydrolysis with potassium hydroxide gave a 92.6% yield of the bromovanillin. Repeated crystallization from alcohol gave colorless needles; mp 178°C.

6-Bromovanillin oxime, Colorless needles from EtOH/H2O, mp 158-159°C

[1] Tiemann and Haarmann [Ber., 7, 615 (1874)], who first prepared it, recorded 160-161°C.
[2] Sumuleanu [Ann. Sci. Univ. Jussy, 2,131 (1902-1903)] found 128-129°C.
[3] Pschorr and Sumuleanu, Ber., 32, 3408 (1899).
[4] Report by Raiford and Hilman soon to be published from this Laboratory.
[5] The preparation by other methods and the properties of this compound are described in a succeeding paper by Raiford and Hilman.
[6] This interacts with the hydrogen bromide which is formed during the substitution, and thus prevents hydrolysis of the acetyl derivative. This difference in directive influence between the hydroxyl and the acetoxyl radicals will be further studied in this Laboratory.




Effect Of Substituents In Certain Condensations Of Benzaldehyde
By L. Chas. Raiford And William F. Talbot
JACS 54, 1092 (1932)

Previous work in this Laboratory1 has shown that the interaction of bromine and chlorine derivatives of vanillin with amino compounds is not noticeably hindered unless both positions ortho to the aldehyde group are substituted; even then the hindrance is much less than might be expected.

Subsequent work has shown that certain substituents prevent this condensation from taking place. Thus, o- and p-nitrobenzaldehyde4, salicylaldehyde5, 5-bromo- and 5,6-dibromovanillin6 failed to give the expected benzoins when treated with potassium cyanide in the usual way. One purpose of the present work was to test the effect of substituents indicated in the last two examples by further study of vanillin derivatives.

Irvine5 found that salicylaldehyde methyl ether undergoes the benzoin condensation if none of the free salicylaldehyde is present, which suggests that the hydroxide radical may prevent the reaction. This radical as a phenyl substituent causes acidic properties, and since Lachman7 found that acids prevent the condensation, it was interesting to study the behavior of the alkali salts of such compounds. When the potassium salts of 5-bromovanillin and p-hydroxybenzaldehyde, respectively, were subjected to the action of potassium cyanide in the usual way, the starting materials were recovered almost quantitatively, and no benzoin was detected, Vanillin, likewise, does not give a benzoin, but the methyl ether, veratraldehyde does.

When the 2-bromo- and 6-bromo-derivatives of 3,4-dimethoxybenzaldehyde were boiled with the cyanide solution, starting material alone was recovered although special search was made for the acid and the benzoin. In the case of the 6-derivative, which was most readily obtained in quantity, attempts to bring about the condensation by variation of the kind and amount of solvent used were unsuccessful. Nothing but starting material could be isolated from the reaction mixtures.

These failures, as well as observations made by others, tend to support the view of Staudinger10 according to which only aldehydes that are easily oxidized to the related acids may be expected to undergo the benzoin condensation11.

5-Bromo-3,4-dimethoxybenzaldehyde

This was made by a variation of Dakin's20 method. Fifty grams of 5-bromovanillin was dissolved in 300 mL of methyl alcohol and 13g of potassium hydroxide dissolved in the smallest possible quantity of water was added. While the mixture was kept warm on a water-bath, 80 cc. of dimethyl sulfate was added as rapidly as the vigor of the reaction would permit, and the mixture was then evaporated almost to dryness. About 200 mL of water was next added, the mixture extracted with ether, the extract dried over anhydrous sodium sulfate and the ether distilled off. The residue distilled at 157-162°C/5 mmHg, yield 95%. The product melted at 59.5°C, which is also the melting point of the first portion to solidify from the melted material21. The purity of the product here under consideration was checked by a Carius determination of halogen.

2-Bromo-3,4-dimethoxybenzaldehyde

This was obtained in 74% yield by alkylation of 2-bromovanillin24 as described above under the 5-bromo compound. After two crystallizations from dilute methyl alcohol it was obtained in colorless needles that melted at 85-85.5°C.

[1] Raiford and others, JACS, 49, 1077, 1571 (1927); 50, 2556 (1928); 52, 4576 (1930).
[4] Homolka, Ber., 17, 1902 (1884).
[5] Irvine, J. Chem. Soc , 79, 670 (1901).
[6] Raiford and Hilman, JACS, 49, 1571 (1927). Lachman, JACS 46, 708 (1924).
[10] Staudinger. Ber. 46, 3535 (1913).
[11] ortho- and para-hydroxybenzaldehyde [Dakin, Am. Chem. J., 42, 478 (1909)], vanillin [Tiemann, Ber., 9, 415 (1876)] and 5-bromo-vanillin [Brady and Dunn, J. Chem. Soc., 107, 1859 (1915)] cannot be oxidized to the respective acids by the usual means, and neither of them undergoes the benzoin condensation.
[20] Dakin, Am. Chem. J., 42, 494 (1909).
[21] Dakin reported 65-66°C. He recorded no analysis for his product, but assumed that its purity was confirmed by the fact that it could be oxidized into the corresponding acid, the melting point of which he did not check, and that the methyl ester of this acid melted at 69-70°C, although Zincke and Francke [Ann., 293, 185 (1896)] found 71-72°C for the ester.
[24] Raiford and Stoesser, JACS, 49, 1077 (1927).

Summary and Conclusions

[1] Several substituted benzaldehydes have been subjected to the action of potassium cyanide as required in the benzoin condensation. In cases where a bromine atom occupied the ortho position with respect to the aldehyde group, the required benzoin was not obtained.
[2] Some confirmation has been found for the theory that the hydroxyl group as a substituent in benzaldehyde prevents the benzoin condensation.




Preparation of Substituted Vanillic Acids
Raiford & Potter
J. Am. Chem. Soc. 55, 1682-85 (1933)

Benzaldehyde1 and anisaldehyde2 are easily oxidized by air to the corresponding acids. p-Hydroxybenzaldehyde3 and protocatechuic aldehyde4 are more resistant and are not oxidized readily by potassium permanganate solution but require fusion with caustic potash to give the acids. Tiemann5 found that treatment of vanillin solutions with oxidizing agents caused hardly any change, or else complete decomposition, depending on conditions. Vogel6 prepared 5-nitrovanillic acid, and Brady and Dunn7 obtained the 5-bromo compound by hydrolysis with alkali of the corresponding nitriles which, in turn, had been obtained from the respective oximes. Bromovanillin could not be oxidized by acetic acid solution of chromic acid or by alkaline permanganate. The recent syntheses in this Laboratory of all chlorine and bromine substitution products of vanillin required by theory provided material from which the corresponding acids might be prepared. Since the latter cannot be obtained by oxidation of the aldehydes in the usual ways the methods of Vogel and of Brady and Dunn were tested further8.

[1] Wöhler and Liebig, Ann., 3, 250 (1832)
[2] Cahows, Ann. 66, 308 (1845)
[3] Bucking, Ber. 9, 529 (1876)
[4] Fittig and Remsen, Ann., 159, 150 (1871)
[5] Tiemann, Ber. 9, 415 (1876)
[6] Vogel, Monatsh. 20, 389 (1899)
[7] Brady and Dunn, J. Chem. Soc. 107, 1860 (1915)
[8] Raiford and others, J. Am. Chem. Soc. 62, 4576 (1930)

sYnThOmAtIc

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Awesome!!
« Reply #1 on: December 18, 2003, 09:43:00 AM »
While you are on this topic do you have the full article by Lange below that both you and the book of exstacy refer to for demethylations.. I am interested in the HCL demethylation cited in TBOE of 50% yield protocatechuic aldehyde from vanillin using HCL..... 

Lange, J. Org. Chem., Vol 27, 2037-2039 (1962)


 Can the 5-bromo-3,4,diMeO benzaldehyde be reacted like 5-bromovanillin to get 3,4,5 TMB? That is either react it with the cu powder method or methoxide then reflux with DMS?

Also does anybody have the Ozone reference for making benzaldehydes in high 90's yield? Alright I found what I was looking for that I saw a long time ago 3bases long ass, badass post, but I was right none for vanillin in english

 I'm interested in evaluating it's use in making 2,5 DMB from anethole instead of bichromate.. and also in the production of vanillin from eugenol...

There also contained the Uv/air oxidation that didn't work or at least I couldn't get to work!!

Is it really just as eaasy as passing ozone through the solution for a few hours and distill? does it have to be -60c. So a stream of ozone through isoeugenol would do the same?

Any input or pointers would very helpful here...

Edit: Nevermind I finally dug up an article and it seems that a PTC was also used and a yield of 10% was obtained.. I think I could find better uses for vanillin than to waste it like that.....

But any help on the release of some articles giving procedures for making vanillin from eugenol and isoeugenol would be nice seeing as das un deutch.

Rhodium

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Vanillin to Protocatechualdehyde (AlCl3/Py)
« Reply #2 on: December 18, 2003, 05:16:00 PM »
Vanillin to Protocatechualdehyde
Robert Lange
J. Org. Chem. 27, 2037-2039 (1962)



Anhydrous aluminum chloride (9.7 g, 0.0724 mole) was suspended in a solution of 10 g (0.0658 mole) of vanillin in 100 ml of methylene chloride in an apparatus protected from atmospheric moisture. While stirring briskly and cooling to maintain the temperature at 30-35°C, 22.9 g (0.290 mole) of pyridine was added slowly. The reaction was vigorous; the resulting clear, light orange solution of the reaction complex was heated to reflux (45°C) and maintained at that temperature while stirring for 24 hours. The solution, which had darkened only slightly during the reflux period, was cooled to 25°C and the product was hydrolyzed, while stirring and maintaining the temperature at 25-30°C by the addition of dilute (15-20%) hydrochloric acid intil the mixture was definitely acidic to congo red indicator. Of the two phases present at this time, the lower methylene chloride layer contained most of the small amount of unchanged vanillin and essentially no protocatechualdehyde; the latter was dissolved in the aqueous phase. Evaporation of the methylene chloride yielded 0.8 g of vanillin. Extraction of the aqueous phase with ether, followed by evaporation of the ether left 7.9g (87%) of pale yellow crystals of protocatechualdehyde melting at 153-154°C.

An equimolar amount of triethylamine can be used instead of the pyridine, with a reduction in yield to 61.5%.