The Hive > Methods Discourse
Benzaldehyde + MEK acid catalyzed aldol
psychokitty:
Maybe this might work to effect a more OTC Baeyer-Villiger transformation.
Facile Oxidation of Aldehydes to Acids and Esters with Oxone
Benjamin R. Travis, Meenakshi Sivakumar, G. Olatunji Hollist, and Babak Borhan*
ORGANIC LETTERS 2003 Vol. 5, No. 7 1031-1034
Abstract:
A highly efficient, mild, and simple protocol is presented for the oxidation of aldehydes to carboxylic acids utilizing Oxone as the sole oxidant. Direct conversion of aldehydes in alcoholic solvents to their corresponding ester products is also reported. These reactions may prove to be valuable alternatives to traditional metal-mediated oxidations.
Description of the art:
As a fortuitous extension of the solvent study, the oxidation of aldehydes with Oxone in alcoholic solvents cleanly provided high conversion to esters. Thus, the oxidation of benzaldehyde in methanol did not yield the expected carboxylic acid, but instead the methyl ester was obtained. The present strategy complements other known methods that directly convert aldehydes to esters such as oxidation in the presence of alcohol with Br2 or I2, NBS/AIBN, PDC, HCN/MnO2, or performed electrochemically.21-25 Additionally, we found that other alcohols such as ethanol, n-propanol, and 2-propanol also provide their corresponding esters in excellent yields, although oxidation in tert-butyl alcohol furnished the carboxylic acid as the sole product (Table 3, entries 1-9). It is important to note that the esters are not obtained as the result of the oxidation of aldehydes to carboxylic acids followed by Fischer-type esterification of the acids in alcoholic solvents. Incubation of benzoic acid in methanol with Oxone for a prolonged period did not result in the isolation of methyl benzoate, but in fact the starting acid was re-isolated quantitatively.
The direct oxidation of a variety of aryl and alkyl aldehydes to their corresponding methyl esters is also illustrated in Table 3 (entries 10-19). Oxidation of aryl aldehydes with electron-withdrawing substituents showed slow conversion to the esters (Table 3, entries 10 and 11) initially providing dimethyl acetals in addition to the ester products. This was overcome by heating the reactions to reflux overnight, which provided clean conversion to the desired methyl esters 1b and 2b. Oxidation of 6 and 9 (electroneutral aromatics aldehydes) and 19-23 (aliphatic aldehydes) proceeded smoothly at rt to furnish the desired methyl esters in excellent yields. In the case of electronrich aromatic substrates, as with the oxidations to carboxylic acids in DMF, the Dakin products were observed. thus, 4-hydroxybenzaldehyde, 12, and p-anisaldehyde, 13, provided primarily phenols 16 and 17 in 77% yield for both (Scheme 3), along with small amounts of the corresponding sters (Table 3, entries 14 and 15). Additionally, oxidation of 27 provided 75% yield of the ç-ketomethyl ester product 30 (methyl ester of 29).
Noteworthy, is the fact that isopropyl esters are made with ease in high yields. However, as mentioned above, tert-butyl esters cannot be accessed, most probably due to the sterics of the bulky alcohol. Although at this time conversion of aldehydes to esters proceed best if the reaction is performed in the alcoholic solvent (in order to circumvent the formation of carboxylic acids), studies are underway with mixed solvents and show promising indications that the oxidation to carboxylic acids could be retarded in favor of esterification. Thus, it could be possible to lessen the amounts of alcohol used in the oxidation.
Although any mechanistic discussion is speculative at this point, we believe that the oxidation proceeds via a Baeyer-Villiger process. As depicted in Scheme 4, the proposed intermediates in the oxidation of aldehydes to carboxylic acids and esters are mixed peroxyacetals A and B. Rearrangement of intermediates A and B would yield the products by expelling bisulfate. Corroboration for the proposed mechanism is based on the well-understood oxidation of aldehydes to carboxylic acids with peroxyacids.26 Also, recently it has been demonstrated that acetals are oxidized to their corresponding esters with Oxone,10 and thus, intermediate B could be derived from either the hemiacetal or acetal (Scheme 4). It should be pointed out that Oxone is slightly acidic and, therefore, could catalyze the formation of the presumed peroxyacetals. Presently, mechanistic studies including use of 18O-labeled aldehydes and NMR experiments to observe transient intermediates are underway.
In conclusion, we have demonstrated a simple and effective one-pot protocol to oxidize aldehydes directly to acids or esters. These reactions are facile, high-yielding, and easy to work up (most do not require chromatography) and should provide a mild oxidative alternative for organic chemists. The mechanism of these transformations is being investigated and will be reported in due course.
Experimental:
(A bit too simple.)
Aldehyde (1 equiv), Oxone (1 equiv), ROH (0.2 M), 18 h, rt.
bio:
Some nice articles you found psychokitty.
Assuming you have a basic understanding of the procedure of this thread (Rhodium posted some dwgs somewhere) I wanted to ask you if you have any input on the following:
In the patent twodogs cited where he got the idea of using perborate it states ......(paraphrased)near quantitative yields of the B/V product can be achieved in the oxidation by appropriate recycling..........
That's it no experimental, examples, discussion, nothing.
Will be making a few more runs with the MePhBuO soon and will try some recycling ideas at small test scale. Ah.... so many reactions so little time...
Now I suppose that the simplest and easiest way to do this would be to simply filter, add more perborate and run it again. Maybe removing some water (dessicant) would be helpful. Hopefully the selectivity is such that the ketone enol ester would not be damaged. Another place would be after the isolation before the hydrolysis or even after the hydrolysis itself.
Any thoughts on this?????? I have various improvements on the overall procedure but nobody seems to be interested enough in this method (except one bee I know of) to
actually do it. So I don't waste my time but I do thank you and the Hive for all the great stuff, especially Rhodium for finding several of the key references for this and similar reactions.
psychokitty:
In the patent twodogs cited where he got the idea of using perborate it states ......(paraphrased)near quantitative yields of the B/V product can be achieved in the oxidation by appropriate recycling..........
That's it no experimental, examples, discussion, nothing.
Will be making a few more runs with the MePhBuO soon and will try some recycling ideas at small test scale. Ah.... so many reactions so little time...
--- End quote ---
Actually, the segment in the patent to which you refer goes like this:
The present invention provides a safe and economical process for oxidizing aldehydes and ketones using an alkali metal perborate, such as sodium perborate, as the oxidant. Alkali metal perborates are safe and economical to use, and the sodium borate by-product thus formed is safely handled and is a valuable product that can be sold in its own right. In addition, the oxidation is carried out under easily maintained reaction conditions and provides selectivities approaching 100% so that all of the starting aldehydes or ketones can be converted to final product by appropriate recycling. It can be seen that the use of the alkali metal perborate provides a substantial advance in the oxidation of aldehydes and ketones.
--- End quote ---
All the authors are trying to say is that because the use of sodium perborate is so exceptionally selective, there won't be any byproducts to the reaction, and whatever starting materials are left over--in this case, the intermediate aldol condensation product of benzaldhyde and MEK--can be reused in another sodium perborate Baeyer-Villiger reaction.
Anyway, that's my interpretation. I could be wrong.
Here's the a text copy of the patent in question, for all those who would like to read it:
( 1 of 1 )
United States Patent 4,988,825
Bove January 29, 1991
Oxidation of aldehydes and ketones using alkali metal perborates
Abstract
Aldehydes and ketones, other than acetone, are oxidized with an alkali metal perborate in the presence of an acid.
Inventors: Bove; John L. (Ridgewood, NJ)
Assignee: Cooper Union Research Foundation, Inc. (New York, NY)
Appl. No.: 910615
Filed: September 23, 1986
Current U.S. Class: 549/272; 549/273; 549/295; 560/231; 562/528
Intern'l Class: C07D 313/18; C07D 313/04
Field of Search: 549/272,273,295 562/528 560/231
References Cited [Referenced By]
U.S. Patent Documents
3122586 Feb., 1964 Berndt et al.
3154586 Oct., 1964 Bander et al.
3483222 Dec., 1969 Sennewald et al.
3716563 Feb., 1973 Brunie et al. 549/524.
3833613 Sep., 1974 Field 549/272.
4160769 Jul., 1979 Higley.
4213906 Jul., 1980 Mares et al. 549/272.
4286068 Aug., 1981 Mares et al. 549/272.
4338260 Jul., 1982 Schirmann 260/502.
Foreign Patent Documents
1096967 Dec., 1967 GB 549/272.
Other References
Y. Ogata et al., Bulletin of the Chemical Society of Japan, vol. 52(2), (1979), pp. 635-636.
A. Baeyer et al., Ber., 1899, 32, 3625-3633.
A. Baeyer et al., Ber., 1900, 33, 858-864.
Ogata et al., Chem. Abst. 90:167685, (1979).
McKillop et al., Tetrahedron Letters, 24, No. 14, (1983), 1505-1508.
McKillop et al., Tetrahedron, 43, pp. 1753-1758 (1987).
A. Rashid et al., J. Chem. Soc. (C) (1967), pp. 1323-1325.
Description
The present invention is directed to the oxidation of aldehydes and ketones to the corresponding acids and esters, respectively using an alkali metal perborate as the oxidant.
The oxidation of ketones, including cyclic ketones, to esters through the use of peracids is known as the Baeyer-Villager Reaction (A. Von Baeyer and V. Villager, Ber., 1899, 32, 3265; 1900, 33, 858) While widely applied, particularly for the oxidation of cyclohexanone to epsilon-caprolactone, nevertheless the use of a peracid presents problems of safety and disposal and/or recycling of organic compounds.
The present invention provides a safe and economical process for oxidizing aldehydes and ketones using an alkali metal perborate, such as sodium perborate, as the oxidant. Alkali metal perborates are safe and economical to use, and the sodium borate by-product thus formed is safely handled and is a valuable product that can be sold in its own right. In addition, the oxidation is carried out under easily maintained reaction conditions and provides selectivities approaching 100% so that all of the starting aldehydes or ketones can be converted to final product by appropriate recycling. It can be seen that the use of the alkali metal perborate provides a substantial advance in the oxidation of aldehydes and ketones.
In particular, the present invention provides a method of preparing acids or esters, which comprises oxidizing an aldehyde (other than acetone) or a ketone with an alkali metal perborate in the presence of an acid.
With the exception of acetone, the present invention is applicable to the oxidation of aldehydes and ketones to form the corresponding esters and/or acids. Aromatic and aliphatic aldehydes and ketones may be used, such as benzaldehyde and methylethyl ketone and the like, as well as cyclic ketones, such as cyclohexanone and the like. Aliphatic and cycloaliphatic aldehydes and ketones containing olefinic unsaturation may likewise be employed to form the corresponding unsaturated ester and/or acid. When ketones are oxidized according to the present invention, the product obtained will be the corresponding ester, but in some cases a mixture of the ester and acid will be produced.
In a preferred embodiment, the present invention may be used for the preparation of esters and/or acids of the formula (I) ##STR1## which comprises reacting an aldehyde or ketone of the formula (II) ##STR2## wherein R.sup.1 is alkyl or aryl, R.sup.2 is hydrogen, alkyl or aryl, or R.sup.1 and R.sup.2 are both hydrogen, or R.sup.1 and R.sup.2 together represent alkylene, provided that R.sup.1 and R.sup.2 may not both be methyl. When R.sup.1 and R.sup.2 is alkyl, R.sup.1 and R.sup.2 may be straight or branched chain alkyl, suitably straight or branched chain alkyl of from 1 to about 15 carbon atoms, such as from 1 to about 10 carbon atoms. When R.sup.1 or R.sup.2 is aryl, R.sup.1 and R.sup.2 may be aryl of from 1 to about 4 rings, including fused rings, and may suitably contain from about 6 to about 30 carbon atoms. Suitably, R.sup.1 or R.sup.2 maybe phenyl, naphthyl, biphenyl and the like. When R.sup.1 and R.sup.2 together represent alkylene, the alkylene may suitably be straight or branched chain alkylene of from about 1 to about 15 carbon atoms in the carbon-to-carbon chain, such as from 1 to about 10 carbon atoms in the carbon-to-carbon chain. Usually when R.sup.1 and R.sup.2 together represent alkylene, there will be from about 1 to about 30 carbon atoms in total, preferably from about 3 to about 15 carbon atoms in total.
In the above formulas (I) and (II), alkyl and alkylene may be unsubstituted or substituted by aryl, halogen, nitro or the like, while the aryl may be substituted by alkyl, preferably lower alkyl, i.e. from about 1 to about 6 carbon atoms, halogen, nitro or the like.
Preferably, R.sup.1 may represent alkyl of from about 1 to about 10 carbon atoms, phenyl, or alkylene of from about 3 to about 15 carbon atoms with from about 3 to about 9 carbon atoms in the carbon-to-carbon chain, said alkyl, phenyl or alkylene being unsubstituted or substituted by halogen, cyano or nitro or, in the case of phenyl, lower alkyl. Further, R.sup.2, or both R.sup.1 and R.sup.2 may represent hydrogen.
While sodium perborate tetrahydrate will normally be used, both in terms of economy and convenience, other alkali metal perborates may be employed of the formula (III)
MBO.sub.3.nH.sub.2 O (III)
wherein M is an alkali metal, preferably sodium or potassium, and n is 1 to 4, usually 4. Suitably, the oxidation is carried out with the perborate (III) in the presence of an acid that hydrolyzes in water to form hydronium ions, such as mineral acids, sulfonic acids, organic acids, and the like, but a Lowry-Bronsted acid or Lewis acid may also be used, such as BF.sub.3. Glacial acetic acid is safe and economical and hence is presently preferred. Other useful organic acids include trifluoroacetic acid and formic acid.
When an organic acid is employed, it may also serve as a solvent. If a solvent or co-solvent is required, any suitable inert solvent may be employed, such as acetone, halogenated hydrocarbons, such as methylene chloride, chloroform and the like, aliphatic and aromatic esters, benzene and the like. It is noted that acetone, while a ketone, is nevertheless not oxidized by the perborate (III) and hence may be used as a solvent, if desired.
Usually, the oxidation will be initiated at a temperature of from about 30.degree. to about 70.degree. C., usually from about 40 to about 60.degree. C. While lower temperatures can be used, reaction rates will necessarily be slower. Temperatures higher than about 70.degree. C. may be used, if required or desired, depending upon the desired reaction rate. However, the reaction is exothermic and hence external cooling may be needed to control the reaction temperature, even at the lower temperatures employed.
The present invention is illustrated in terms of its preferred embodiments in the following Examples. In this specification and the appended claims, all parts and percentages are by weight, unless otherwise stated.
EXAMPLE 1
Preparation Of Epsilon-Caprolactone
To a 200 ml roundbottom flask was added 4.9 grams (0.05 mole) of cyclohexanone, 50ml of glacial acetic acid, and 11.4 grams (0.075 mole) of sodium perborate tetrahydrate. The mixture was heated to 50.degree. C. using a water bath. The reaction temperature was maintained in the range of 50-55.degree. C., while stirring the mixture with a magnetic stirrer for four hours, after which the reaction mixture was cooled to room temperature, and the solid sodium borate was separated from the mixture using section filtration. The acetic acid was stripped from the remaining liquid residue using a rotary evaporator, and the remaining epsilon-caprolactone was purified by vacuum distillation. Yield: 91% theoretical.
EXAMPLE 2
Preparation of Benzoic Acid
The procedure of Example 1 was followed using 5.3 grams (0.05 mole) of benzaldehyde as the starting material. Crude benzoic acid formed was purified by recrystallization. Yield: about 50% theoretical.
EXAMPLES 3-6
Following the procedure of Example 1, the ketones set forth below were oxidized with sodium perborate at a temperature of about 55.degree. C. to provide the esters and acid set forth in Table 1 below.
TABLE 1
______________________________________
Example
Starting Material
End Product Yield
______________________________________
##STR3##
##STR4## 75%
4
##STR5##
##STR6## 74%
5
##STR7##
##STR8## 68%
6
##STR9##
##STR10## 24%
HOOC(CH.sub.2).sub.5COOH
38%
The most current patent detailing this reaction process, which has links to the relevant patent history of the prior art, is as follows:
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=/netahtml/search-bool.html&r=2&f=G&l=50&co1=AND&d=ptxt&s1=%27sodium+perborate%27&s2=Baeyer-Villiger&OS=%22sodium+perborate%22+AND+Baeyer-Villiger&RS=%22sodium+perborate%22+AND+Baeyer-Villiger
psychokitty:
Information in this post relevant to this thread taken from the PDF documents found in Post 531053 (psychokitty: "Propenylbenzenes anyone?", Chemistry Discourse):
SOME ALPHA-ALKYLCINNAMIC ACIDS AND THEIR DERIVATIVES
BY MARSTON TAYLOR BOGERT AND DAVID DAVIDSON
J.A.C.S. v. 54 pp.334-338 (1939)
The phenomenal success of a-amylcinnamic aldehyde and other a-alkylcinnamic aldehydes as perfume bases, led us to prepare several of the corresponding methyl ketones (methyl- (a-alkyl-)-styryl ketones) (111). These were synthesized by condensing benzaldehyde with alkyl acetones (11) by means of hydrogen chloride. . . .
. . . Ethyl, n-propyl, n-butyl and n-amyl derivatives are reported in this paper. The attempt to prepare the isopropyl derivatives by starting with isopropyl acetone, (CH3)2CHCH2COCH3, gave an anomalous result, since it was not found possible to prepare a solid oxime from the supposed methyl (a-isopropyl-)-styryl ketone, nor to oxidize it to a-isopropylcinnamic acid. . . .
Experimental:
One-half mole of benzaldehyde was mixed with one mole of the alkyl acetone and one-fourth mole of hydrogen chloride gas passed into the cooled mixture. The mixture, which soon became red, was then shaken for sixteen to twenty hours. At the end of this time the water formed in the reaction had separated as aqueous hydrochloric acid and was removed. Without further treatment, the oil was distilled under diminished pressure (about 20 mm.). Somewhat more than half of the alkyl acetone was recovered and a small residue, probably consisting of dibenzal-alkyl acetone (styryl-( a-alkyl-)- styryl ketone), remained in the flask. The principal fraction, consisting of crude methyl (a-alkyl-)-styryl ketone, was obtained in a yield of about 90% based on the alkyl acetone consumed, or about 75% based on the benzaldehyde employed. The crude alkyl acetone fraction was treated with one-half mole of benzaldehyde and sufficient alkyl acetone to replace that consumed in the first reaction. Hydrogen chloride was then added and the reaction carried out as before. The process was repeated three times but could probably be carried on indefinitely. By using two moles of alkyl acetone to one of benzaldehyde and reworking the recovered alkyl acetone in this way, the amount of dibenzal derivative formed was greatly reduced, with consequent improvement in the yield of the desired product. The crude methyl (a-alkyl-)-styryl ketone may be used directly for the preparation of the a-alkylcinnamic acids. To purify it, the crude product was washed with saturated sodium bisulfite, followed by water and then treated with alcoholic potassium hydroxide, thrown into water, acidified with acetic acid, extracted with benzene, dried over sodium sulfate and distilled. A middle fraction was taken for analysis. The methyl (a-alkyl-)-styryl ketones are liquids having a greenish-yellow tinge, with a floral odor which resembles, but is much weaker than, that of the a-alkylcinnamic aldehydes.
Physiologically Active Phenethylamines. I. Hydroxy- and Methoxy-alpha-methyl-beta-Phenethylamines (beta-Phenylisopropylamines)
E. H. WOODRUFF AND THEODORE W. CONGER
J.A.C.S. Feb 1938 v. 60 pp. 465-467
. . . An excellent preparation for a-alkylcinnamic acids is that recently carried out by Bogert and Davidson" who oxidized with hypohalite methyl (a-alkyl styryl) ketones prepared by condensing benzaldehyde with a methyl alkyl ketone in the presence of dry hydrogen chloride gas. With modification this was found to give excellent yields of the methoxy-a-methylcinnamic acids The other steps in the synthesis follow essentially experimental procedures already appearing in the literature. . . .
. . . When condensing the methoxy aldehydes with methyl ethyl ketone it was necessary to cool the aldehyde-ketone mixture in an ice salt bath during the addition of the hydrogen chloride gas and to allow the reaction to proceed in an electric refrigerator at 0-5 °C or in the freezing chamber at -10 to -5 °C for twenty-four to forty-eight hours, instead of at room temperature. It was found further that a practical grade of methyl ethyl ketone could be used. In this case instead of recovering the unused ketone the reaction mixture was taken up in ether, neutralized with solid sodium carbonate and washed thoroughly with water before drying with anhydrous magnesium sulfate and distilling.
These changes were found to be of particular value in the case of the m-methoxy compound.
psychokitty:
100 Years of Baeyer-Villiger Oxidations
Michael Renz, Bernard Meunier
European Journal of Organic Chemistry Volume 1999, Issue 4 , Pages 737 - 750
Abstract:
In the present review, we report the discovery of the formation of esters and lactones by oxidation of ketones with a peroxide derivative, namely the Baeyer-Villiger reaction. This reaction was first reported by Adolf von Baeyer and Victor Villiger a century ago in 1899, just one year after the oxidant they used (KHSO5) has been described. Furthermore, Baeyer and Villiger established the composition of this new inorganic peroxide and showed that its instability was the reason of a controversy between several European chemists between 1878 and 1893. For the first 50 years the mechanism of the Baeyer-Villiger reaction was a matter of debate. A side product, 1,2,4,5-tetraoxocyclohexane, was ruled out as an intermediate in the ester formation by Dilthey. Criegee postulated a nucleophilic attack of the oxidant on the carbonyl group. This mechanism was confirmed by von E. Doering by a labeling experiment with [18O]benzophenone. The rearrangement step occurs with retention of the stereochemistry at the migrating center. The competitive migration and the rate-determining step are also discussed in this review.
Chemistry: How green was my ester
GIORGIO STRUKUL
Nature 412, 388 - 389 (26 July 2001); DOI:doi:10.1038/35086670
Introduction:
Hydrogen peroxide is an ideal oxidant. It cannot yet be used widely, because viable catalysts aren't available for many industrially important processes. But there are encouraging indications of progress.
Chemistry has turned green. The increased awareness of environmental problems has generated an overly simplistic division, however, especially in the media, between ‘bad’ chemistry — which first pollutes and then (sometimes) cleans up — and ‘good’, green chemistry. Chemists themselves are partly responsible for setting up this misleading contrast. But they are nonetheless among the leaders in trying to find less wasteful or damaging ways to handle the planet’s resources.
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