Benzophenone hydrazones, oxidation

C. Diphenyldiazomethane. In a pressure bottle are placed 19.6 g. (0.1 mole) of benzophenone hydrazone, 22 g. (0.1 mole) of yellow oxide of mercury, and 100 ml. of petroleum ether (b.p. 30-60°). The bottle is closed, wrapped in a wet towel, and shaken mechanically at room temperature for 6 hours. The mixture is then filtered to remove mercury and any benzophenone azine (Note 5), and the filtrate is evaporated to dryness under reduced pressure at room temperature. The crystalline residue of diphenyldiazomethane melts when its temperature reaches that of the room (Note 6), but it is difficult to purify and this product is pure enough for all practical purposes. The material weighs 17.3-18.6 g. (89-96%). The product should be used immediately (Note 7). 

Diphenyldiazomethane has been prepared only by oxidation of benzophenone hydrazone.3 The procedure given above is that of Staudinger, Anthes, and Pfenninger, with minor changes. The method of preparation of benzophenone hydrazone given above is a modification of the procedure of Curtius and Rauter-berg.4... 

Most solid-phase syntheses of pyrazoles are based on the cyclocondensation of hydrazines with suitable 1,3-dielectrophiles. The reported examples include the reaction of hydrazines with support-bound a,(3-unsaturated ketones, 1,3-diketones, 3-keto esters, a-(cyano)carbonyl compounds, and a, 3-unsaturated nitriles (Table 15.19). Pyrazoles have also been prepared from polystyrene-bound 3-(hydrazino)esters, which are generated by the addition of ester enolates to hydrazones (Entry 7, Table 15.19 see also Section 10.3). Benzopyrazoles can be prepared from support-bound hydra-zones using the reaction sequence outlined in Figure 15.11. Oxidation of a polystyrene-bound benzophenone hydrazone yields an a-(acyloxy)azo compound. Upon treatment with a Lewis acid, this intermediate is converted into a 1,2-diazaallyl cation,... 

Curini, M. Rosati, O. Pisani, E. Preparation of diphenylmethyl esters by oxone oxidation of benzophenone hydrazone. Tetrahedron Lett. 1997, 38, 1239-1240. 

The oxidation is carried out by refluxing the benzhydryl waste in aqueous 30% nitric acid (see footnote 17, example 37). The benzophenone produced is easily converted to benzophenone hydrazone for recycle to the DDM process. See also Rivkin, S. M. J. Appl. Chem. (USSR), 1938, 11, 83 (Chem. Abstr., 1938, 32, 4566). The nitric acid oxidation process was adopted by Albright and Wilson, our benzophenone hydrazone supplier. 

The second project was to determine whether the anodic oxidation of benzophe-none hydrazone could be manipulated to produce diphenyldiazomethane (DDM) as the end product in high yield. Literature evidence95 indicated that the anodic oxidation of benzophenone hydrazone using either a platinum or graphite anode under various conditions with a variety of electrolytes gave a number of products that were... 

Chiba and co-workers gave no indication that the anodic oxidation of benzophenone hydrazone could be stopped at the DDM stage. Professor Martin and Dr. John Hulteen, Colorado State University, were, however, able to devise conditions, based... 

FIGURE 2. Electrochemical oxidation of Benzophenone Hydrazone to Diphenyldia-zomethane. 

Certain aromatic diazohydrocarbons are conveniently prepared by the oxidation of hydrazones. Thus benzophenone hydrazone (R = CjH5) reacts with mercuric oxide in petroleum ether at room temperature during 6 hours ro furnish diphenyidiazomethane in 89% to 96% yield. Hydrazones of substituted benzophenones have been similarly treated. Phenylbenzoyl-... 

A mixture of 39.2 g. (0.20 mole) of benzophenone hydrazone Org. Syntheses Coll. Vol. 2, 497 (1943)], 44 g. (0.20 mole) of yellow mercuric oxide, and 200 ml. of petroleum ether (b.p. 30-40°) is agitated with moderate external cooling for 9 hours. The deep red petroleum ether solution is filtered, and the solvent is removed from the filtrate under vacuum without heating the mixture. The resulting deep red crystals of diphenyldiazomethane, m.p. 29-30°, weigh between 33 and... 

Amino acid 4-toluenesulfonate or 2-naphthalenesulfonate salts are esterified in high yield with diazodiphenylmethane in DMF (50 °C, 10min).P " l Diazodiphenylmethane is prepared by oxidation of benzophenone hydrazone, e.g. with yellow mercury(II) oxide in the presence of base, and can be stored in the dark.P P l In situ oxidation of the benzophenone hydrazone is performed with peracetic acid/l2 (trace) in the presence of the N-protected amino acids or peptides.P P l This method is not compatible with sulfur-containing amino acid residues. Alternatively, Dpm esters of protected amino acids and peptides are obtained using benzhydryl chloride or diphenylmethanol by standard esterification procedures. 

The synthesis of tazobactam from 6-APA (Scheme 6.15) proceeded via the 2- -(chloromethyl)penam ester (81 a), which was first prepared by Gottstein and co-workers [47] during the synthesis of 2-/S-(chloromethyl)-2-a-methylpenam-3a-carboxylic acid 1,1-dioxide (29). 6-APA (8) was converted to 6a-bromopenicillanic acid (77) by treatment with sodium nitrite and hydrobromic acid. Oxidation with peracetic acid in the presence of benzophenone hydrazone gave benzhydryl 6a-bromopenicillanate-l-oxide (78) and reduction with zinc and acetic acid gave benzhydryl penicillanate-1-oxide (79). The unsymmetrical azetidinone disulphide (80) was obtained by heating with 2-mercaptobenzothiazole reaction with copper (II) chloride... 

Of aromatic ketone hydrazones, benzophenone hydrazone is oxidized with yellow mercuric oxide [387, 390] or red mercuric oxide [387], fluo-renone hydrazone is oxidized with mercuric oxide [5SS] or nickel peroxide [935], and di-a-thienyl ketone hydrazone and phenyl naphthyl ketone hydrazones are oxidized with silver oxide or manganese dioxide [370] (equations 459-461). 

The formation of diphenylmethyl esters when benzophenone hydrazone is oxidized in the presence of carboxylic acids most likely involves diphenyldiazomelhane as intermediate. 

Preparation of the reagent by oxidation of benzophenone hydrazone (Aldrich) with yellow mercuric oxide in petroleum ether requires 6 hrs. and gives a liquid product. An improved procedure is based upon the finding that the reaction is catalyzed by base, probably as follows ... 

A mixture of 13 g. of benzophenone hydrazone, 15 g. of anhydrous sodium sulfate, 200 ml. of ether, 5 ml. of ethanol saturated with potassium hydroxide, and 35 g. of yellow mercuric oxide is shaken for 75 min. in a pressure bottle wrapped with a wet towel. The solution is filtered and evaporated and the residue is taken up in petroleum ether evaporation gives a residue which solidifies to dark red crystals, m.p. 29-32° yield 89%. 

Ph3Bi(OOtBu)2 oxidizes a methyl group in diethyl ether to afford ethoxyacetic acid as the initial product [350], The peroxide also oxidizes toluene and ethylbenzene to benzaldehyde and acetophenone, respectively, via radical intermediates [343]. Thiophenol, benzophenone hydrazone, and hydrazobenzene are efficienfly oxidized by organobismufh(V) compounds [341a, c]. 2,6-Dialkylphenols are oxidatively dimerized by PhsBiCOs [300e]. 

Nickel peroxide oxidizes benzophenone hydrazone to diphenyldiazomethane in quantitative yield.9... 

Oxidation, arylmethyl group to a carboxylic acid, with CrOj, 30 with KMnOi, 39, 219, 265 benzophenone hydrazone to diphenyl-diazomethane, 134 fluorene to fluorenone, 163 indene to homophthalic acid, 173 8-hydroxyquinoline to quinolinic acid, 266... 

Diphenyldiazomethane 386 A mixture of benzophenone hydrazone (13 g, 0.066 mole), anhydrous sodium sulfate (15 g)> ether (200 ml), ethanol saturated with potassium hydroxide (5 ml or 10 ml if red mercuric oxide is used), and yellow (or red) mercuric oxide (35 g) is shaken in a pressure flask for 75 min. The solids are then filtered off and the solvents are removed in a vacuum at room temperature. The dark red oily product is dissolved in light petroleum (b.p. 30-60°) and this solution is filtered and the solvent is again removed in a vacuum at room temperature. The oil produced is frozen in Dry Ice and gradually allowed to warm to room temperature, whereupon dark red crystals, of m.p. 29-32°, are obtained in 89% yield [cf. also Organic Syntheses, 24, 53 (1944)]. 

Oxidation. Durst and co-workers find that this combination rapidly oxidizes catechols to ortho-quinones and hydroquinones to para-quinones at -25 to 0°. Based on NMR and IR, yields are quantitative. In addition, anthrone is converted into bianthrone (75% isolated yield) and benzophenone hydrazone is oxidized to diphenyldiazomethane. 

Stoichiometrically, one equivalent of HgO is necessary for the dehydrogenation of a hydrazone. Examples have been published in Organic Syntheses Smith and Howard (1955) described the procedure for diphenyldiazomethane, obtained from benzophenone hydrazone in petroleum ether in 89-96% yield. The necessity for the absence of moisture is emphasized, but no activation of the mercury(n) oxide seems to be required. Andrews et al. (1988) have reported on the dehydrogenation of acetone hydrazone to 2-diazopropane (70-90% yield) in ether in the presence of catalytic amounts of KOH in ethanol. There are also cases where two equivalents are used, e.g., the procedure for (benzoyl)(phenyl) diazomethane (2.62, yield 87-94%) published in Organic Syntheses by Nenitzescu and Solomonica (1943). Neither these nor other authors have explained, however, why two equivalents would be necessary. 

NCS is also regularly used for the direct oxidation of alcohols to ketones. The presence of Triethylamine serves to activate the reagent for rapid quantitative oxidation of catechols and hy-droquinones to o- and p-quinones, respectively, and for the oxidation of benzophenone hydrazone to diphenyldiazomethane. N-Chlorosuccininude—Dimethyl Sulfide is also used in the mild oxidation of alcohols, as well as in the conversion of allylic alcohols to allylic chlorides. 

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