Benzil reaction conditions

Due to excellent yields, mild reaction conditions, and a fast reaction rate, the azolide method is well suited to the synthesis of isotopically labeled esters, even ones with very short half-lives, just as it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. An example is provided by the synthesis of [nC]-quinuclidinyl benzilate prepared from benzilic acid, CDI, and nC-labeled quinuclidinol.[147]... 

The development of the Grignard-type addition to carbonyl compounds mediated by transition metals would be of interest as the compatibility with a variety of functionality would be expected under the reaction conditions employed. One example has been reported on the addition of allyl halides to aldehydes in the presence of cobalt or nickel metal however, yields were low (up to 22%). Benzylic nickel halides prepared in situ by the oxidative addition of benzyl halides to metallic nickel were found to add to benzil and give the corresponding 3-hydroxyketones in high yields(46). The reaction appears to be quite general and will tolerate a wide range of functionality. 

Benzoins are useful intermediates for the synthesis of other compounds because they can be oxidized to 1,2-diones and reduced in stages to various products, depending upon the reaction conditions. The 1,2-diketone known as benzil, which is obtained by nitric acid oxidation of benzoin, undergoes a base-... 

Sterically demanding benzilic acid was used to optimize the reaction conditions in respect to reagent excess and reaction time. Complete conversion (98%) of benzilic acid to the corresponding methyl ester was obtained with two equivalents of the methyl triazene resin 10 after 6 h 96% conversion was obtained when using the n-butyl triazene resin 10. The reaction between p-nitrophenylacetic acid (1 equiv., 2 mg/ml) and the polymer-supported triazene (2 equiv.) in DCM was monitored by HPLC. A 53% conversion from the acid to the ester product was observed after 5 min data analysis indicated a second-order reaction as observed in homogeneous solution. 

The sensitivity, or otherwise, of the ct-dicarbonyl substrate determines the reaction conditions. However, variations in conditions are not especially large. Although 1 equiv. of base may be used, more usually an excess is employed — sometimes 10 equiv. or more to accelerate the reaction. Studies on the reaction of hydroxides with benzil indicate that the rate depends to some extent on the cation, and it can be advantageous to use Ba(OH)2 rather than the more usual NaOH or KOH. With hydroxide ion, favored solvents are water and aqueous ethanol. Heterogeneous conditions, for example potassium hydroxide and diethyl ether or sodamide and toluene, have also been employed. The reactions are conducted at room temperature (sometimes requiring up to 4 d) or under reflux (10 min-24 h). With methoxide or -butoxide the corresponding anhydrous alcohol or benzene are employed as solvents. ... 

Oxalyl chloride affords diketones (benzene gives benzil) but under the reaction conditions oxalyl chloride decomposes partly to phosgene, so that the acid chloride or monoketone may also be formed.606 The method thus has value also for preparation of carboxylic acids as examples, carboxylation of mesitylene in 65-70% yield by oxalyl chloride is recorded in Organic Syntheses,601 and l,l-di-(p-tolyl)ethylene gives 3,3-di-(/ -tolyl)acrylic acid in 80% yield.608... 

Condensation of urea with carbonyl compounds A rapid and efficient MW-assisted synthesis of hydantoins and thiohydantoins was described by Muccioli et al. [117]. The most straightforward conditions for synthesis of phenytoin are the base-catalyzed condensation using benzil and urea, known as the Biltz synthesis (Eq. 33). MW activation of the Biltz synthesis of phenytoin improved both yield and reaction time. The first step consists in MW activation of the reaction of benzil with (thio)urea the second includes the conversion of the resulting 2-(thio)hydantoin to hydantoin using hydrogen peroxide. When reactions were performed at the same temperature under both reaction conditions, yields were by far better under the action of MW and emphasized the evident specific MW effects. These are perfectly expected when one considers the polar TS involved in the first step (nucleophilic addition of neutral NH2 group on carbonyl moiety). 

Reaction conditions were optimized by anploying 4-chlorobenzaldehyde as the test compound. A higher yield (94%) was obtained when equimolar amounts of benzil (1 mmol) and aldehyde (1 nunol) along with ammonium acetate (5 mmol) were allowed to react in the presence of 0.01 g of the catalyst at llO C. The protocol was then extended to different aromatic aldehydes bearing ortho-, meta-, and para-substitutions under solvent-free conditions the corresponding results are giveu in... 

Reaction Conditions. Heat the mixture with stirring in a sand bath at 150-160 °C for 5-10 min. The benzil should dissolve during this time. 

In 1910, Hinsberg described the reaction between benzil and diethylthiodiacetate, resulting in the preparation of the thiophene ring system. The reaction was run under Claisen condensation conditions, and after hydrolysis with aqueous acid at reflux, the free dicarboxylic acid 1 was produced. 

The synthesis of imidazoles is another reaction where the assistance of microwaves has been intensely investigated. Apart from the first synthesis described since 1995 [40-42], recently a combinatorial synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles has been described on inorganic solid support imder solvent-free conditions [43]. Different aldehydes and 1,2 dicarbonyl compounds 42 (mainly benzil and analogues) were reacted in the presence of ammonium acetate to give the trisubstituted ring 43. When a primary amine was added to the mixture, the tetrasubstituted imidazoles were obtained (Scheme 13). The reaction was done by adsorption of the reagent on a solid support, such as silica gel, alumina, montmorillonite KIO, bentonite or alumina followed by microwave irradiation for 20 min in an open vial (multimode reactor). The authors observed that when a non-acid support was used, addition of acetic acid was necessary to obtain good yields of the products. 

Ketones are oxidatively cleaved by Cr(VI) or Mn(VII) reagents. The reaction is sometimes of utility in the synthesis of difunctional molecules by ring cleavage. The mechanism for both reagents is believed to involve an enol intermediate.206 A study involving both kinetic data and quantitative product studies has permitted a fairly complete description of the Cr(VI) oxidation of benzyl phenyl ketone.207 The products include both oxidative-cleavage products and benzil, 7, which results from oxidation a to the carbonyl. In addition, the dimeric product 8, which is suggestive of radical intermediates, is formed under some conditions. 

The well documented oxidation of 1,10-phenanthroline (4) to 2,2 -bipyridyl-3,3 -dicarboxylic acid (53) by alkaline permanganate has been repeated. It is now found that 4,5-diazafluoren-9-one (54) is consistently a coproduct of the reaction in 20% yield.253 This provides a convenient route to this hitherto difficultly accessible compound. The formation of 4,5-diazafluoren-9-one almost certainly occurs by way of the intermediate, but not isolated, l,10-phenanthroline-5,6-dione, which is known to undergo a benzilic acid type rearrangement in the presence of hydroxide ions to give the diazafluorenone. This rearrangement of l,10-phenanthroline-5,6-dione has recently been studied further.115 Under some conditions 5,6-dihydro-5,6-dihydroxy- 1,10-phenanthroline can be isolated with the diazafluorenone. 

In 2003, Balalaie and co-workers published a new paper in the area of imidazole synthesis39. In the above examples reported by Westman, ammonium acetate and primary amines act as the nitrogen source for the imidazole ring. In the Baladie novel one-pot three-component method, ammonium acetate was replaced by benzonitrile derivatives. Thus, benzil, primary amines and benzonitrile derivatives underwent a condensation reaction on acidic silica gel as the solid support, Scheme 5.23. The reaction mixtures were irradiated for 8 min in a domestic oven under solvent-free conditions to give the products in 58-92% yield. 

The photosensitized dimerization of isoprene in the presence of benzil has been investigated. Mixtures of substituted cyclobutanes, cyclohexenes, and cyclooctadienes were formed and identified (53). The reaction is believed to proceed by formation of a reactive triplet intermediate. The energy for this triplet state presumably is obtained by interaction with the photoexcited benzil species. Under other conditions, photolysis results in the formation of a methylcydobutene (54,55). 

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