Benzil derivatives

The synthesis of methylimidazole-thiophene compounds was reported by Santos et al. [46] and has been included for completeness, although no biological activity has been reported for these heterocycles. The formation of these imidizole-thiophenes (24a-d), occurs via the condensation of 2-formylthiophene (25) with benzil derivatives (26a-d) in the presence of ammonium acetate to yield the imidazole-thiophene compounds (27a-d). These compounds can then be N-methylated by treatment with iodomethane in... 

The first 1,3,2-diazastiboles and -bismoles were prepared from A, A -bisltrimethylsilyl)-1,4-diazabutadiene derivatives (derived from phenanthraquinone or benzil) and the appropriate MCI3 (M = Sb, Bi), as shown in Scheme 10.4 for the benzil derivative the crystalline compounds 47 and 48 are dimers. 

Tab. 22. Oxidative cyclization of benzil derivatives mediated by several oxidants.

Benzilic acid rearrangement is usually carried out by heating benzil derivatives and an alkali metal hydroxide in aqueous organic solvent. This reaction also proceeds efficiently in the solid state. For example, a mixture of finely powdered benzil (35a) (0.5 g, 2.38 mmol) and KOH (0.26 g, 4.76 mmol) was heated at 80 °C for 0.2 h, and the reaction mixture was mixed with 3N HCl (20 ml) to give benzilic acid (39a) as colorless needles (0.49 g, 90% yield) [13]. Since the product is collected simply by filtration, this method is very simple and economical. Similar treatment of benzil derivatives (35b-g) in the solid state also gave the corresponding benzilic acid (39b-g) in good yields (Table 15-8) [13],... 

In the seco-phthalide-isoquinoline series the benzil derivatives bicucullinidine (278, R =R =Me) and bicucullinine (278, R R -CHa) have been prepared by oxidation of the deoxybenzoin alkaloids adlumiceine and adlumidiceine (Kh.Kiryakov and Mard-irosyan, Dokl.Bolg.Akad.Nauk, 1981, 1717), the analogue... 

A synthesis of 2,3-diarylpyrroles was based on the use of a difunctional phosphine imine which is capable of both Wittig and aza-Wittig condensation. <94J0C4551> The reagent is prepared from benzotriazole, formaldehyde, sodium azide and triphenylphosphine which gives the precursor 13. Reaction with methylidene-triphenylphosphorane and butyllithium generated 14 which reacted with benzil derivatives to give the pyrroles. 

A few synthetic approaches were reported to obtain sets of new 1,2,4-triazine derivatives. A well-known synthetic protocol was used to prepare a series of the 1,2,4-triazine derivatives 14 bearing a piperazine amide moiety. The synthetic route included the condensation of S-methyl thiosemicarba-zide 15 and benzil derivatives 16 followed by nucleophilic substitution of the methylthio group with piperazine resulting in 1,2,4-triazines 17 and further functionalization of the piperazine moiety. In vitro antitumor activity against breast cancer cells of the 1,2,4-triazines 14 was evaluated using the XTT method, BrdU method, and flow cytometric analysis. A few of the compounds demonstrated antiproliferative effect comparable with an effective anticancer drug, cisplatin (14BMC6313). 

A series of benzil derivatives related to combretastatin A-4 have been synthesized by the oxidation of diarylalkynes promoted by Pdl2 in DMSO (Figure 8.5) [56]. Several benzils exhibited antiproliferative activity and inhibited cell growth of four... 

A natural benzil derivative, which appears to be biogenetically related to the stilbenes, has been isolated from the Leguminosae species, Zollernia paraensis which contains 2,4,2 -trihydroxy-4 -methoxybenzil (45). 

In view of these results it is not surprising that even more sterically hindered carbonyl derivatives of Rf are also not accessible (22), An attempted synthesis of (Rf)2C0 from RpLi and dimethyl carbonate gave the methyl ester of 2,4,6-tris(trifluoromethyl)benzoic acid instead (25% yield). Similarly, treatment of RpLi with oxalyl dichloride did not yield the desired benzil derivative. In this reaction a 45% yield of 2,4,6-tris(trifluoromethyl ) -2-oxoethanoic acid, RfC(0)C00H, was obtained (22), All these experiments clearly demonstrate that in organic Rf chemistry steric hindrance is an important factor guiding the reactivity of various substrates. 

Scheme 8.70 Synthesis of polyarylated oxazoles from benzylamine and benzil derivatives.

Usually prepared by the action of NaCN on benzaldehyde in dilute alcohol. It is oxidized by nitric acid to benzil, and reduced by sodium amalgam to hydrobenzoin PhCHOHCHOHPh by tin amalgam and hydrochloric acid to des-oxybenzoin, PhCH2COPh and by zinc amalgam to stilbene PhCH = CHPh. It gives an oxime, phenylhydrazone and ethanoyl derivative. The a-oxime is used under the name cupron for the estimation of copper and molybdenum. 

This rapid formation of the crystalline quinoxaline derivative can therefore be used to identify 1,2-diketones conversely, a nuclear-substituted o-phenyl-enediamine can be identified by the quinoxaline derivative which it forms with a known 1,2-diketone such as benzil. 

These products were originally named indil derivatives, since they are structurally analogous to the bettor known compound benzil (CeHsCOCOCeHs) and its derivatives. 

The reaction of l-amino-2-methylpyridinium tosylate and its 5-methyl derivative with benzil in the presence of NEt3 in boiling MeCN, and the treatment of the reaction mixture with 60% HCIO4 and 40% HBF4 gave 2,3-diphenylpyrido[l,2-fe]pyridazinium salt (58) (96JOC4423) and its 7-methyl derivative (01CPH77), respectively. 

Amino-5-hydrazinopyrazole dihydrochloride 300 is a good source for the synthesis of this type of heterocyclic compound [78JCS(P1)885] and it was prepared by reaction of malononitrile with two equivalents of hydrazine. Reaction of 300 with ethyl pyruvate afforded 301. Unstable hydra-zone 302 formed when 300 was boiled with diacetyl rapidly cyclized to 303. Reaction of 300 with benzil gave 304 directly, which gave an acetyl derivative and resisted reductive deamination. On the other hand, a polymer was isolated from the reaction of 300 with glyoxal (Scheme 65). 

Treatment of the derivatives of 7-azalumazines, 514, with alcoholic sodium hydroxide caused a benzilic acid type of rearrangement via 515, followed by decarboxylation and oxidation by air or potassium permanga-... 

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

These conclusions were supported by the results obtained in a study of the reactions of various types of acetylenes with TTN (94). Hydration of the C=C bond was found to occur to a very minor extent, if at all, with almost all of the compounds studied, and the nature of the products formed was dependent on the structure of the acetylene and the solvent employed. Oxidation of diarylacetylenes with two equivalents of TTN in either aqueous acidic glyme or methanol as solvent resulted in smooth high yield conversion into the corresponding benzils (Scheme 23). The mechanism of this oxidation in aqueous medium most probably involves oxythallation of the acetylene, ketonization of the initially formed adduct (XXXV) to give the monoalkylthallium(III) derivative (XXXVI), and conversion of this intermediate into a benzoin (XXXVII) by a Type 1 process. Oxidation of (XXXVII) to the benzil (XXXVIII) by the second equivalent of reagent would then proceed in exactly the same manner as described for the oxidation of chalcones, deoxybenzoins, and benzoins to benzils by TTN. The mechanism of oxidation in methanol solution is somewhat more complex and has not yet been fully elucidated. 

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