P-Nitrobenzaldehyde

The AFO reaction has seen very few variations since it was first reported in 1934. However, the most significant modification was reported in 1958 by Ozawa and further elaborated by Smith and others. Prior to this modification the intermediate chalcones were purified and then subjected to hydrogen peroxide in a basic medium. With the modification, the chalcone was generated in situ, from an aldehyde and a hydroxyacetophenone, and then allowed to react with aqueous hydrogen peroxide in the presence of sodium hydroxide to deliver the flavonol. Smith and coworkers conducted a limited study to examine the scope and limitations of this modification.Flavonols were delivered in 51-67% however, no flavonols were isolated with highly reactive aldehydes such as p-nitrobenzaldehyde and when 2-hydroxy-4-methoxyacetophenone was used. 

Problem 19,6 p-Nitrobenzaldehyde is more reactive toward nucleophilic additions than />methoxy-benzaldehyde. Explain. 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

B) p-Nitrobenzaldehyde.—A mixture of 45 g. (0.18 mole) of crude />-nitrobenzaldiacetate, 100 cc. of water, 100 cc. of alcohol, and 10 cc. of concentrated sulfuric acid is refluxed for thirty minutes, filtered through a fluted filter, and the filtrate chilled in an ice bath. The crystals are separated by suction filtration, washed with cold water, and dried in a vacuum desiccator. The first crop weighs 22-24 g- (82-89 Per cent of the theoretical amount), m. p. 106-106.5°. A second crop amounting to 2-3 g. is obtained by diluting the filtrate with about 300 cc. of water. The total yield is 24-25.5 g. (89-94 per cent of the theoretical amount) (Note 6). 

Reflux a mixture of 22 5 g. of crude p-nitrobenzal diacetate, 50 ml. of alcohol, 50 ml. of water and 5 ml. of concentrated sulphuric acid for 30 minutes, filter through a fluted paper, and cool the filtrate in ice. Collect the crystals by suction filtration, wash with cold water, and dry in a vacuum desiccator. The yield of p-nitrobenzaldehyde, m.p. 106 is 12 g. (3). 

Lewis-Acid Catalyzed. Recently, various Lewis acids have been examined as catalyst for the aldol reaction. In the presence of complexes of zinc with aminoesters or aminoalcohols, the dehydration can be avoided and the aldol addition becomes essentially quantitative (Eq. 8.97).245 A microporous coordination polymer obtained by treating anthracene- is (resorcinol) with La(0/Pr)3 possesses catalytic activity for ketone enolization and aldol reactions in pure water at neutral pH.246 The La network is stable against hydrolysis and maintains microporosity and reversible substrate binding that mimicked an enzyme. Zn complexes of proline, lysine, and arginine were found to be efficient catalysts for the aldol addition of p-nitrobenzaldehyde and acetone in an aqueous medium to give quantitative yields and the enantiomeric excesses were up to 56% with 5 mol% of the catalysts at room temperature.247... 

Diastereoselective reductive coupling of MVK and p-nitrobenzaldehyde performed under an atmosphere of elemental deuterium provides an aldol adduct incorporating a single deuterium atom at the former enone f>-pos-ition [69]. Deuterium incorporation at the a-carbon is not observed, excluding Morita-Baylis-Hillman pathways en route to product. Incorporation of a single deuterium atom suggests irreversible enone hydrometallation (Scheme 5). 

The aprotic diazotisation of tetrachloroanthranilic acid in the presence of benzaldehyde or />-methoxybenzaldehyde results in the formation of the 1,3-benzodioxan derivatives (131, R = Ph) and (131, R = >-C gH 4-OMe) respectively 155). The absence of products analogous to (129) in these reactions suggests that the formation of the compounds (131) do involve tetrachlorobenzyne. Some indication of the mechanism of these reactions was given by the fact that no analogous adduct has been isolated in attempted reactions of tetrachlorobenzyne with p-nitrobenzaldehyde. However, in the presence of acetone we obtained a low yield of the compound (132). 

The number of hydrazine groups per protein molecule can be determined by reacting a small portion of the hydrazine-modified protein with p-nitrobenzaldehyde, which forms a chromogenic product upon formation of the hydrazone derivative (Figure 1.111). 

Prepare a 0.5 mM p-nitrobenzaldehyde buffer by initially dissolving the compound at a higher concentration in organic solvent (e.g., methanol, DMF, or DMSO) and then adding the appropriate aliquot to 100 mM acetate, pH 5.0 to result in the final concentration. 

Add an aliquot of the hydrazine-modified protein solution to the p-nitrobenzaldehyde solution and incubate at 37°C for 1 hour or at room temperature for 2 hours. To assure accuracy, determine the linear response range of the test by adding a series of different concentrations of the hydrazine-modified protein solution to the p-nitrobenzaldehyde buffer. This is done by preparing a set of serial dilutions of the protein solution and... 

Treatment of an ethyl acetate solution of the 5-aminoimidazole (96 R1 = Me, R2 = S02Me) with p-nitrobenzaldehyde in the presence of trifluo-roacetic acid gave a crystalline product, which was assigned the tricyclic structure (176) on the basis of spectral data [82IJC(B) 1087]. 

Partially methylated derivatives of D-glucosone have been prepared by decomposition of the corresponding partially methylated phenylosazones with p-nitrobenzaldehyde osones have been obtained from 5-0-methyl-D-glucose phenylosazone and from 3,4,5-tri-O-methyl-D-glucose phenylosazone in this way.22 Although 6-0-methyl-D-glucose phenylosazone is not altered by heating with benzaldehyde or piperonal in aqueous ethanolic... 

It has recently been reported21 that a mixed osazone of 3,4-di-O-methyl-D-glucose can be converted, by treatment with p-nitrobenzaldehyde, into an osone which reacts with phenylhydrazine to give 3,4-di-O-methyl-D-glucose phenylosazone. Von Lebedev29 claimed to have obtained D-glu-cosone 6-phosphate, isolated as an amorphous lead salt, by the action of hydrochloric acid on the phenylosazone prepared from D-fructose 6-phosphate. 

Belikov et al (50) described three reactions to identify hydralazine. Sodium nitroprusside reacts with an alkaline aqueous solution of hydralazine to yield a red color when the mixture contains mineral acids, a green precipitate is formed, but with acetic acid, a red precipitate is formed. Cinnamaldehyde reacts with a hydrochloric acid solution of hydralazine to give a yellow precipitate, m.p. 197-200 C. p-Nitrobenzaldehyde reacts with an... 

A frequently reported spectrophotometric technique for the determination of hydralazine is based on reactions with aromatic aldehydes to form hydrazones with absorption in the visible region. Luk yanchikova et al (5 +) used p-nitrobenzaldehyde Wesley-Hadzija and Abaffy (55) and Ruggieri (56) used p-dimethylaminobenzaldehyde Luk yanchi-kova (57,58) used cinnamaldehyde Schulert (33) used p-hydroxybenzaldehyde and Zak et al (59) used p-methoxy-benzaldehyde, after testing cinnamaldehyde, salicylaldehyde, 3, +,5-trimethoxybenzaldehyde, and 1-naphthaldehyde. 

In the case of methyl vinyl ketone (MVK), similar reactivity is observed. Exposure of MVK (150 mol%) and p-nitrobenzaldehyde to basic hydrogenation conditions provides the corresponding aldol product in good yield, though poor dia-stereoselectivity is observed [24a]. Remarkably, upon use of tris(2-furyl)phos-phine as ligand and Li2C03 as basic additive, the same aldol product is formed with high levels of syn-selectivity [24 e]. Addition of MVK to activated ketones such as l-(3-bromophenyl)propane-l,2-dione is accomplished under similar con-... 

FIGURE 2. Peak shapes of the [M — NO]+ ions of (a) p-nitro-aniline (kinetic energy release 1240 meV) and (b) p-nitrobenzaldehyd (kinetic energy release 70 meV) Adapted from Reference 11... 

Anodic oxidation of formazane 18 [17], 1-arylmethylenesemicarbazide 19 [55], p-nitrobenzaldehyde phenylhydrazone 20 [56], and 2-benzoylpyridine phenylhydrazone 21 [57] afforded the corresponding heterocycles in a very good yield (Scheme 14). The homogeneous oxidation of compounds 18-20 was carried out by indirect electrolysis by the mediators generated in situ [58]. 

---