Benzils addition reactions

The addition of benzophenone, for example, affords low yields of the four isomeric oxetanes (66, R = Ph), (67, R = Ph), (68) and (69). These addition reactions take place in competition with the conversion of the alkene into (70) and (71). The conversion to these alkenes presumably is the result of energy transfer from the excited ketone. The addition of methyl phenylglyoxalate to the alkene (65) affords a single adduct (72) in 70% yield while the addition of benzil to the same alkene yields the two adducts (66, R = PhCO, 31%) and (67, R = PhCO, 6%) ... 

Phenylbenzoyldiazomethane may be prepared by the oxidation of benzil-monohydrazone with mercuric oxide in the presence of dry etber as a solvent Tbe addition of a little alcoholic potassium hydroxide serves to catalyse the reaction ... 

The reaction of diketosulfides with 1,2-dicarbonyl compounds other than glyoxal is often not efficient for the direct preparation of thiophenes. For example, the reaction of diketothiophene 24 and benzil or biacetyl reportedly gave only glycols as products. The elimination of water from the P-hydroxy ketones was not as efficient as in the case of the glyoxal series. Fortunately, the mixture of diastereomers of compounds 25 and 26 could be converted to their corresponding thiophenes by an additional dehydration step with thionyl chloride and pyridine. 

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. 

B. l,3>2>Dioxaphospholens.—The kinetics of the addition of trialkyl phosphites to benzil have been investigated spectrophotometrically. The second-order reaction of trimethyl phosphite in dioxan has activation parameters of A// = 8.4 kcal mol and AS = — 47.5 e.u. In benzene the rate constant increases linearly with low concentrations of added organic acid and decreases linearly with low concentrations of added base. The Diels-Alder mechanism is considered unlikely on the basis of these data, and the slow step is considered to be nucleophilic addition of the phosphite to the carbon of the carbonyl group (see Scheme). 

Reaction of perthiophosphonic anhydrides (64) with amines leads first to (105) and then, by further attack, to (106). With ammonia itself the second addition proceeds at the same phosphorus atom as the initial attack, giving (107) and (108). The anhydride (64) is also reported to react with 1,3-dioIs to give cyclic phosphonyl disulphides (109). Thermal decomposition of phenylphosphinic anhydride (110) may lead to the formation of PhP since in the presence of benzil the formation of the phosphorane (111) was observed. ... 

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. 

We have already discussed a large group of reactions in which carbanions add to the C=0 group (cf. pp. 221-234), including examples of intramolecular carbanion addition, e.g. an aldol reaction (p. 226), Dieckmann reaction (p. 230), and the benzilic acid rearrangement (p. 232), and also to the C=C—C=O system, the Michael reaction... 

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. 

Symmetrical and unsymmetrical benzoins have been rapidly oxidized to benzils in high yields using solid reagent systems, copper(II) sulfate-alumina [105] or Oxone-wet alumina [105, 106] under the influence of microwaves (Scheme 6.32). Conventionally, the oxidative transformation of a-hydroxy ketones to 1,2-diketones is accomplished by reagents such as nitric acid, Fehling s solution, thallium(III) nitrate (TTN), ytterbium(III) nitrate, ammonium chlorochromate-alumina and dayfen. In addition to the extended reaction time, most of these processes suffer from drawbacks such as the use of corrosive acids and toxic metals that generate undesirable waste products. 

Other reactions involving the addition of carbanions are reactions like Perkin s reaction, Claisen condensation, benzilic acid rearrangement and Michael addition. 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Reduction of 2-amino-3-nitrodibenzothiophene in the presence of acetic acid yields the imidazole (109) and by conducting this reaction in the absence of acetic acid 2,3-diaminodibenzothiophene should be readily accessible. A similar reduction of 3-amino-4-nitrodibenzothio-phene yields 3,4-diaminodibenzothiophene (60%). In addition to the typical reactions described above for the 1,2-diamino compound, 3,4-diaminodibenzothiophene condenses with benzil to give the quinoxaline... 

Reaction of carboxylate ion with nitrophenyl sulfites gives the carboxylate />-nitrophenyl esters. If the y>-nitrophenyl sulfite is unsymmetncal (02NC6H40S(0)0R, where R is ethyl or phenyl), carboxylate attacks the/>-nitrophenyl side (69). Some amino acids react with methyl and benzyl sulfites in the presence of y>-toluenesulfonic acid to give methyl and benzyl esters of the amino acids as />-toluenesulfonate salts (70). With alcohols, the conversion of benzil to a monoacetal upon addition of sulfuric acid to the benzil in methanol and dimethyl sulfite proceeds in high yield (71). 

When diphenylacetylene dissolved in cold chloroform reacts with iodine monofluoride suspended in trichlorofluoromethane, the iodine atoms in the primary addition product are easily replaced by fluorine to give l,1,2,2-tetrafluoro-1,2-diphenylethane (60%) along with benzil (10%). Since the C —Br bond is stronger than the C —I bond, the reaction of bromine monofluoride with diphenylacetylene gives 1,1-dibromo-2,2-difluoro-1,2-diphenylethane (65%) and benzil (15%). 

In reactions with benzophenone and aromatic vicinal polyketones, such as benzil, 1,3-diphenyl-propanc-l,2,3-trionc. and indane-l,2.3-trione monohydrate (ninhydrin). all the carbonyl oxygen atoms are replaced by fluorines to give the a,w-diphenylperfluoroalkanes 2 or 1,1.2,2,3,3-hexafluoroindane (3) in moderate yield. The yields increase upon the addition of hydrogen fluoride.41... 

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