The Baeyer-Villiger oxidation is a transformation in organic chemistry that inserts an oxygen atom between the carbonyl carbon of a ketone and an adjacent carbon atom:

The reaction is often performed using a peroxyacid such as mCPBA (meta-chloroperbenzoic acid). Other oxidants can be used under certain circumstances including hydrogen peroxide, peroxyacetic acid, peroxytrifluoroacetic acid, and other organic peroxy acids and peroxides.

Mechanism:

The mechanism involves the acid-promoted nucleophilic attack of the carbonyl carbon atom of the ketone starting material by the oxygen atom of the peroxy acid that is not bonded to carbon. This produces the tetrahedral intermediate known as the Criegee intermediate. A pair of electrons on the oxygen atom in the species formed is then used to form a carbon oxygen double bond, and one of the alkyl groups undergoes a 1,2 shift from the carbon atom of the carbonyl to the oxygen atom of the peroxy acid. The carboxylate analog of the peroxy acid is eliminated and the resulting ester product is formed.

Regio- and Stereochemistry:

The regiochemistry and stereochemistry of the reaction products are highly predictable. The group that migrates is the group that is best able to stabilize a developing positive charge in the transition state. Usually, but not always, the more highly substituted group will migrate. If one of the groups is particularly capable of stabilizing a positive charge, such as allyl or benzyl, it will usually migrate even if it is not the most highly substituted group. When the carbon atom that migrates is an asymmetric (i.e. chiral) center, the reaction usually proceeds with retention of configuration.

When aldehydes are subjected to the reaction conditions the hydrogen atom attached to the carbonyl carbon usually migrates and gives rise to the carboxylic acid. If the group attached to carbon is particularly well suited to stabilize a positive charge however, that group may undergo migration to produce the formic acid ester (i.e. formate).

References:

Baeyer, A.; Villiger, V. “Einwirkung des Caro’schen Reagens auf Ketone” (abstract). Ber. 1899, 32 (3): 3625–3633.

Burton, J.W.; Clark, J.S.; Derrer, S.; Stork, T.C.; Bendall, J.G.; Holmes, A.B. “Synthesis of Medium Ring Ethers. 5. The Synthesis of (+)-Laurencin” (Abstract). J. Am. Chem. Soc. 1997, 119 (32): 7483–7498.

M. A. Goodman, M. R. Detty. “Selenoxides as Catalysts for Epoxidation and Baeyer-Villiger Oxidation with Hydrogen Peroxide” Synlett, 2006, 1100-1104.

S. Murahashi, S. Ono, Y. Imada, Angew. “Asymmetric Baeyer-Villiger Reaction with Hydrogen Peroxide Catalyzed by a Novel Planar-Chiral Bisflavin” Chem. Int. Ed., 2002, 41, 2366-2368.

G. A. Olah, Q. Wang, N. J. Trivedi, G. K. S. Prakash. “Baeyer-Villiger Oxidation of Ketones to Esters with Sodium Percarbonate/Trifluoroacetic Acid”, Synthesis, 1991, 739-740.

Michael Renz, Bernard Meunier (1999). “100 Years of Baeyer-Villiger Oxidations”. European Journal of Organic Chemistry 1999 (4): 737–750.

Tags: chemistry, ester, ketone, name reaction, Name Reactions, organic chemistry, oxidation, science, synthesis

An example of the experimental procedure of the Dieckmann condensation is exemplified by the synthesis of 3-quinuclidone hydrochloride. This preparation involves two steps. In the first step, 1-((ethoxycarbonyl)methyl)-4-carbethoxypiperidine is treated with potassium ethoxide in refluxing toluene leading to the formation of the bridgehead bicyclic system via the Dieckmann condensation. In the second step, the intermediate is decarboxylated via treatment with concentrated hydrochloric acid.

Experimental:

3-Quinuclidone hydrochloride

1. Dieckmann Condensation:

Freshly cut potassium (40 g, 1.03 mol) is added to 165 mL of dry toluene under inert atmosphere. The mixture is heated at reflux until the potassium has melted. Absolute ethanol (63 mL, 49.3 g, 1.07 mol) is then added over 30 minutes to the rapidly stirred solution at reflux. Upon the disappearance of the potassium metal, the temperature of the reaction mixture is raised to 130 °C and 1-((ethoxycarbonyl)methyl)-4-carbethoxypiperidine (100 g, 0.411 mol) in 250 mL of dry toluene is added dropwise over 2 hours.

After heating at 130 °C for an additional 3 hours, the reaction mixture is cooled to 0 °C followed by slow addition of 250 mL 10M hydrochloric acid. The resulting mixture is then extracted with 10M hydrochloric acid (2X125 mL).

2. Decarboxylation:

The combined aqueous fractions are heated at reflux for 15 hours followed by the addition of 5 g of activated charcoal. The resulting mixture is then filtered and evaporated to dryness in vacuo. The crude product is then dissolved in 150 mL of water and saturated aqueous potassium carbonate is added very slowly to avoid foaming until the solution has become basic. The resulting solution is then treated with solid potassium carbonate until a slurry is obtained, followed by extraction with diethyl ether (4X200 mL). The combined organic fractions are then treated with calcined potassium carbonate. After 60 minutes the mixture is filtered and concentrated in vacuo. The resulting solid is then treated with 75 g of ice and 10M hydrochloric acid (65 mL, 75 g) followed by evaporation to dryness. The resulting material is then purified via recrystallization from hot water and boiling isopropanol.

Tags: chemistry, compound, Compounds, condensation, ester, ketone, organic chemistry, science, synthesis

The Friedel-Crafts acylation is an example of an electrophilic aromatic substitution reaction. The overall transformation involves the displacement of an aryl hydrogen atom with an acyl moiety derived from the corresponding acyl chloride. The product of the reaction is an alkyl aryl ketone.

The acyl chloride is first converted to the acylium ion intermediate by reacting it with a Lewis acid catalyst such as aluminum trichloride. The Lewis acid coordinates to the chloride and the activated chloride ion is then eliminated to produce the acylium ion. The acylium ion is now sufficiently electrophilic to undergo nucleophilic attack by the π-system of the aromatic ring. Deprotonation at the aryl carbon that now bears the acyl group restores aromaticity and a neutral charge to the aromatic ring.

The acyl aromatic compound produced by the Friedel-Crafts acylation can undergo a number of different transformations and functional group manipulations. The carbonyl moiety can be reduced to a methylene by means of either the Clemmensen Reduction or the Wolff-Kishner Reduction. This sequence of reactions is formally equivalent to the Friedel-Crafts alkylation but does not suffer from the same problems such as carbocation rearrangements and polyalkylation.

The Friedel-Crafts alkylation reaction is related to the acylation in that both reactions are electrophilic aromatic substitution reactions and both employ aluminum trichloride to activate an organohalide. The starting material for the alkylation is an alkylhalide and the reaction introduces an alkyl group to the aromatic ring. See the synthesis of 1,1-diphenylacetone for an example of the laboratory procedure for this reaction.

Tags: acylation, chemistry, ketone, name reaction, Name Reactions, organic chemistry, synthesis