Substituted benzaldehydes oxidation

Although the fate of Cr(IV) is uncertain, (cf. the alcohol oxidation), some characteristics of the intermediate chromium species have been obtained by Wiberg and Richardson from a study of competitions between benzaldehyde and each of several substituted benzaldehydes. The competition between the two aldehydes for Cr(VI) is measured simply by their separate reactivities that for the Cr(V) or Cr(IV) is obtained from estimation of residual aldehyde by a C-labelling technique. If Cr(V) is involved then p values for oxidation by Cr(VI) and Cr(V) are 0.77 and 0.45, respectively. An isotope effect of 4.1 for oxidation of benzaldehyde by Cr(V) was obtained likewise. 

Lucchi , who studied the oxidation of substituted benzaldehyde derivatives found that chlorine atoms in the meta and para position accelerate the reaction and alkyl groups retard the oxidation. A Hammett plot of Lucchi s data yields a good straight line with the slope p = 1.06. These data suggest that the reaction proceeds by way of the chromic ester of hydrated benzaldehyde as intermediate, viz. 

Raja and Perumal reported the synthesis of novel 2,6-diaryl-3-(arylthio)piperidin-4-ones via a four-component reaction consisting of arylthioacetones, 2-substituted aromatic aldehydes and methylamine or ammonium acetate <06CPB795>. Further elaboration of this four component reaction to a novel five component tandem Mannich-enamine-substitution sequence involving the reaction of ethyl 2-[(2-oxopropyl)sulfanyl]acetate, two equivalents of a substituted aromatic aldehyde, and two equivalents of ammonium acetate is shown below <06T4892>. When this five-component tandem reaction involves para-substituted benzaldehydes, the cis (193) and trans (194) diastereomers of thiazones are obtained. Alternatively, orf/zo-substituted benzaldehydes form only the trans (194) diastereomer along with an air-oxidized product 195. 

Methylbenzenes were oxidized, and substituted benzaldehydes were... 

Oxidation of substituted toluenes to substituted benzaldehydes or their acetals is a reaction that is of high technical interest. It is performed by direct as well as indirect anodic oxidation. A number of direct oxidations is shown in Table 14, Nr. 4 to 6. 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

The kinetics of the oxidation of a series of para- and meto-substituted benzaldehydes by quinolinium chlorochromate are first order in substrate, oxidant, and hydronium ion the results were subjected to a Taft analysis. Oxidation of 2-pyridinecarboxaldehyde to the acid by dichromate follows an unusual mixed fourth-order rate law it is first order in hydronium ion and Cr(VI), and second order in aldehyde. 

Quinolinium dichromate (QDC) oxidations of primary and secondary alcohols both proceed via a cyclic chromate ester. Acrylonitrile polymerization was observed in the oxidation of several para- and meffl-substituted benzaldehydes to the corresponding benzoic acids by quinolinium chlorochromate (QCC). QCC oxidations of diphenacyl sulfide and of aromatic anils have been studied. 

Substituted benzylic alcohols and aromatic aldehydes can be oxidized efficiently to substituted benzaldehydes and benzoic acids, respectively, with F-Teda BF4.101,102 The conversion proceeds via the acid fluoride which enables aldehydes to function as acylating agents in a one-pot procedure. 

The imidazolidine-4-one 29, obtained by heating the methanol solution of an a-aminoamide and a 4-substituted benzaldehyde, is a mixture of two diastereomers which can be separated by chromatography. They are oxidized by MCPBA, separately or as a mixture, into the two diastereomeric l-hydroxyimidazolidine-4-ones 30. Hydrolysis of 30 by ethanolic HC1 and hydroxylamine hydrochloride gives the optically pure TV-hydroxyamino acid amide 31 (Scheme 9).[12]... 

Ni(acac)2 reacts with a variety of monodentate donors giving mono and bis adducts Ni(acac)2B (n = 1,2 B = H20, primary and secondary amines, pyridine and substituted pyridines, pyridine iV-oxide, alcohols, dioxane, substituted benzaldehydes).1558,1563-1570 Details of the structures of some complexes are reported in Table 78. The chelate ring of the coordinated /3-diketones is nearly planar, and, in thl mononuclear complexes, the Ni—O bond distances (as well as the C—O and C—C bond distances within the chelate ring) are substantially similar. Two different dinuclear structures have been found in the two complexes Ni2(acac)4B [B = py (197),1540,1571,1530 Ph3AsO (198)1542,1572]. 

The oxidation of substituted benzaldehydes to substituted benzoic acids by pyridinium fluorochromate (PFC) has been studied, and it has been found that the reaction is first order with respect to pyridinium fluorochromate but is of complicated order with respect to the aldehyde. The following scenario was proposed to account for this behavior ... 

Reaction Steps 3a and 3b also can be used to rationalize the observed para-substituent effects presented in Table III the more electron-releasing, para-substituted benzaldehydes retard the rate of oxidative addition (18) for RhCl(PPh3)3. Therefore, p-methyl- and p-methoxybenzaldehyde are expected to be decarbonylated slower than the unsubstituted benzaldehyde, as is observed in Table III. (This argument requires that Reaction 3a be saturated to the right, which is expected, in neat aldehyde solvent with electron-releasing, para-substituted benzaldehydes.) The unexpected slower rate for p-chloro-benzaldehyde could be accounted for ifK for this aldehyde is small and saturation of equilibrium in Equation 3a is not achieved. Note that fcobs is a function of K and k (see Equation 4b) under this condition. It is also possible that the rate-determining step is different for this aldehyde. Present research includes a careful kinetic analysis using several aldehydes so that K and k can be determined independently. 

The aldehyde group deactivates the ring and is meta directing. There are few useful examples, since not only is electrophilic attack more difficult than for benzene, but also the aldehyde group is prone to oxidation during the attack. Substituted benzaldehydes are therefore usually synthesized by functional group transformations or by direct formylation. 

Geeta S, Rao BSM, Mohan H, Mittal JP. (2004) Radiation induced oxidation of substituted benzaldehydes A pulse radiolysis study. J Phys Or Chem 17 194-198. 

On the synthetic side, single diastereomers of P-keto phosphine oxides have been generated from intermolecular acylation of phosphine oxides using either chiral esters or chiral phosphine oxides. In most cases, reduction of the ketone products was not affected by the presence of extra chiral centres. Addition of metallated phosphine oxides to proline-derived ketoaminals provides a new route to optically active P-hydroxy phosphine oxides. The P-hydroxy phosphine oxide 97 has been prepared by the caesium fluoride mediated reaction of silyl-substituted phosphine oxide 98 and benzaldehyde." The synthesis of two (E)-(6-hydroxy-2-hexen-l-yl)diphenylphosphine oxides (99) has been reported. The Horner-Wittig reactions of these compounds with various carbonyl compounds... 

Various ferrocene-based organosilanols 165 have been synthesized in two steps fi om chiral 2-ferrocenyl oxazolines 163. Diastereoselective ortho-lithiation with sec-BuLi followed by electrophilic attack with chlorosilanes gave diastereomerically enriched 164, which were oxidized in air with [IrCl(C8Hi2)]2 as catalyst to give, after purification, stereochemically homogeneous samples of 165. Their application in asymmetric phenyl transfer reactions to substituted benzaldehydes afforded products with high ee (up to 91%) <050L1407>. 

The Cu-promoted enantioselective oxidative dearomatisation of aUcynylbenzaldehydes followed by a cycloisomerisation leads to azaphilones, fused 4//-pyrans (Scheme 1) <05JA9342>, while an alternative synthesis involves oxidation of a 1/7-benzopyrylium salt derived from a substituted benzaldehyde (Scheme 2) <05JOC4585>. Treatment of azaphilones with primary amines results in cleavage of the pyran ring and the formation of vinylogous y-pyridones. 

The oxidation of substituted benzaldehydes by xanthine oxidase is sterically hindered by bulky substituents at the ortho (o) position (Table 3.5) [167], Increasing the size of the halo-substituent dramatically decreases the oxidation of the o-substituted compound, whereas that of the p-halobenzaldehyde increases due to the increased inductive effect. The positional specificity was not due to electronic effects, because the oxidation rate was also decreased with electron-donating o-substituents. Although the substrates of aldehyde oxidase have not been so rigourously examined, the enzyme does appear to be subject to similar steric considerations, as o-chloro- and o-nitrobenzaldehyde are oxidized at much lower rates than benzaldehyde itself [33]. 

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