Benzaldehydes kinetics

To illustrate the development of a kinetic expression from a postulated reaction mechanism, let us consider the base-catalyzed reaction of benzaldehyde and acetophenone. 

Chapters 1 and 2. Most C—H bonds are very weakly acidic and have no tendency to ionize spontaneously to form carbanions. Reactions that involve carbanion intermediates are therefore usually carried out in the presence of a base which can generate the reactive carbanion intermediate. Base-catalyzed condensation reactions of carbonyl compounds provide many examples of this type of reaction. The reaction between acetophenone and benzaldehyde, which was considered in Section 4.2, for example, requires a basic catalyst to proceed, and the kinetics of the reaction show that the rate is proportional to the catalyst concentration. This is because the neutral acetophenone molecule is not nucleophihc and does not react with benzaldehyde. The much more nucleophilic enolate (carbanion) formed by deprotonation is the reactive nucleophile. 

The dehydration reactions have somewhat higher activation energies than the addition step and are not usually observed under strictly controlled kinetic conditions. Detailed kinetic studies have provided rate and equilibrium constants for the individual steps in some cases. The results for the acetone-benzaldehyde system in the presence of hydroxide ion are given below. Note that is sufficiently large to drive the first equilibrium forward. 

Consider the kinetic isotope effect that would be observed in the reaction of semicarbazide with benzaldehyde ... 

For the kinetically controlled formation of 1,3-disubstituted tetrahydro-P-carbolines, placing both substituents in equatorial positions to reduce 1,3-diaxial interactions resulted in the cw-selectivity usually observed in these reactions." Condensation reactions carried out at or below room temperature in the presence of an acid catalyst gave the kinetic product distribution with the cw-diastereomer being the major product observed, as illustrated by the condensation of L-tryptophan methyl ester 41 with benzaldehyde. At higher reaction temperatures, the condensation reaction was reversible and a thermodynamic product distribution was observed. Cis and trans diastereomers were often obtained in nearly equal amounts suggesting that they have similar energies."... 

No comparable study of the hydration of the C=N bond has been made although its properties lie between those of the C=C and C=0 bonds. The hydration of SchifiFbases, such as benzylideneaniline (1), to cations of Dimroth bases, such as 2, is well-known, but attempts to follow this reaction kinetically have been frustrated by the ready breakdown of the neutral species, e.g. 2, to benzaldehyde and aniline. About ten years ago, workers in this Department were surprised to find the C=N bond in many pteridines is capable of hydration, analogous to the reaction 1 f 2. The surprise stemmed principally... 

Kinetic isotope effect. The oxidation of benzaldehyde by permanganate ions is believed to occur by hydride abstraction. What value of k /kD do you predict for C6H5CHO/ C6H5CDO For C6H5CHO/C6D5CHO ... 

Sodium dodecyl sulfate and hydrogen dodecyl sulfate have been used as catalysts in the denitrosation iV-nitroso-iV-methyl-p-toluenesulfonamide [138]. The kinetics of condensation of benzidine and p-anisidine with p-dimethylamino-benzaldehyde was studied by spectrophotometry in the presence of micelles of sodium dodecyl sulfate, with the result that the surfactant increases the rate of reaction [188]. The kinetics of reversible complexation of Ni(II) and Fe(III) with oxalatopentaaminecobalt(III) has been investigated in aqueous micellar medium of sodium dodecyl sulfate. The reaction occurs exclusively on the micellar surface [189]. Vitamin E reacts rapidly with the peroxidized linoleic acid present in linoleic acid in micellar sodium dodecyl sulfate solutions, whereas no significant reaction occurs in ethanol solution [190]. 

Evans Jr. and coworkers reported a similar olefination reaction employing spirooxyphosphoranes of type 66. Upon treatment with a strong base (LiHMDS) and subsequent addition of benzaldehyde, the reaction proceeded to form anionic P(VI) intermediates (67,6 -106 to -116 ppm) that decomposed at room temperature to form the corresponding olefins and spiropentaoxyphosphoranes [ 105]. The stereoselectivity (E Z ratio) of the double bond-forming reaction depended upon the conditions evidence indicated the possibility of kinetic or thermodynamic control (Scheme 21). 

A model developed by Leksawasdi et al. [11,12] for the enzymatic production of PAC (P) from benzaldehyde (B) and pyruvate (A) in an aqueous phase system is based on equations given in Figure 2. The model also includes the production of by-products acetaldehyde (Q) and acetoin (R). The rate of deactivation of PDC (E) was shown to exhibit a first order dependency on benzaldehyde concentration and exposure time as well as an initial time lag [8]. Following detailed kinetic studies, the model including the equation for enzyme deactivation was shown to provide acceptable fitting of the kinetic data for the ranges 50-150 mM benzaldehyde, 60-180 mM pyruvate and 1.1-3.4 U mf PDC carboligase activity [10]. 

Simulation profile of fed batch PAC biotransformation kinetics at 6°C with initial PDC activity of 4.0 U carboligase ml, 90 mM benzaldehyde and 108 mM sodium pyruvate. Feeding was performed hourly as illustrated in Fig. 3 and the initial reaction volume of 30 ml (which would be used experimentally) increased to 45 ml at the end of reaction. 

The chromic acid oxidation of benzaldehyde to benzoic acid in aqueous solution was examined by Graham and Westheimer, and in acetic acid solution by Wiberg and Mill . With water as solvent the kinetics are... 

Typical non-enolising aldehydes are formaldehyde and benzaldehyde, which are oxidised by Co(III) Ce(IV) perchlorate and sulphate , and Mn(III) . The main kinetic features and the primary kinetic isotope effects are the same as for the analogous cyclohexanol oxidations (section 4.3.5) and it is highly probable that the same general mechanism operates. kif olko20 for Co(III) oxidation of formaldehyde is 1.81 (ref. 141), a value in agreement with the observed acid-retardation, i.e. not in accordance with abstraction of a hydroxylic hydrogen atom from H2C(OH)2-The V(V) perchlorate oxidations of formaldehyde and chloral hydrate display an unusual rate expression, viz. 

Laine and co-workers have studied the mechanism involved in rhodium-catalysed benzaldehyde hydrogenation, using [Rh6(CO)i6] as catalyst precursor. Following kinetic arguments, the authors proposed cluster catalysis with a limiting step corresponding to the break of metal-metal bond and/or isomerisation of the cluster formation [22]. 

The first element of stereocontrol in aldol addition reactions of ketone enolates is the enolate structure. Most enolates can exist as two stereoisomers. In Section 1.1.2, we discussed the factors that influence enolate composition. The enolate formed from 2,2-dimethyl-3-pentanone under kinetically controlled conditions is the Z-isomer.5 When it reacts with benzaldehyde only the syn aldol is formed.4 The product stereochemistry is correctly predicted if the TS has a conformation with the phenyl substituent in an equatorial position. 

The Claisen-Schmidt condensation of 2 -hydroxyacetophenone and different chlorinated benzaldehydes over MgO has been investigated through kinetic and FTIR spectroscopic studies. The results indicate that the position of the chlorine atom on the aromatic ring of the benzaldehyde substantially affects the rate of this reaction. In particular, the rate increases in the following order p-chlorobenzaldehyde < m-chlorobenzaldehyde < o-chlorobenzaldehyde. The difference between the meta and para-substituted benzaldehyde can be attributed to electronic effects due to the difference in the Hammett constants for these two positions. Steric effects were found to be responsible for the higher rate observed with the o-chlorobenzaldehyde. 

It was in 1924 when Christiansen [3] put forward the conception of the chain mechanism of oxidation and explained the action of antioxidants via chain termination by the antioxidant [3]. Three years later, Backstrom and coworkers [4—6] experimentally proved the chain mechanism of benzaldehyde oxidation (see Chapter 1) and the mechanism of antioxidant (hydroquinone) action via chain termination. The systematic study of the oxidation kinetics of esters of nonsaturated acids was performed by Bolland and ten Have [7,8], They observed in the kinetic experiments that substrates are oxidized by the chain mechanism with chain propagation via the cycle of reactions (see Chapter 2). 

General Methods. Methanol used in kinetic runs was distilled from sodium methoxide or calcium hydride in a nitrogen atmosphere before use. Freshly distilled cyclohexanol was added to the methanol in the ratio 6.0 ml cyclohexanol/200 ml MeOH and was used as an internal standard for gas chromatographic (GC) analysis. Benzaldehyde was distilled under vacuum and stored under nitrogen at 5°. Other aldehydes (purchased from Aldrich) were also distilled before use. The corresponding alcohols (purchased from Aldrich) were distilled and used to prepare GC standards. All metal carbonyl cluster complexes were purchased from Strem Chemical Company and used as received. Tetrahydrofuran (THF) was distilled from sodium benzophenone under nitrogen before use. 

Figure 3 shows the results of varying the CO pressure. The maximum activity appears to lie near 600 psi for benzaldehyde reduction. Figure 3 is an attempt to elucidate an apparent reaction order with respect to the arithmetically averaged CO pressure. At pressures less than 400 psi, the order is nearly first order. The situation at higher pressures is not clear however, it is reasonable to speculate that the dominant aspects of the kinetics shift at these pressures. The data suggest the shift is to zero-order dependance. 

Because of the complexity of the rhodium-catalyzed reduction of benzaldehyde to benzyl alcohol with CO and H20, it is not possible to fully elucidate the mechanism of catalytic reduction given the extent of the kinetic studies performed to date. However, the results do allow us to draw several important conclusions about the reaction mechanism for benzaldehyde hydrogenation and several related reactions. 

The pyridine-catalysed lead tetraacetate oxidation of benzyl alcohols shows a first-order dependence in Pb(OAc)4, pyridine and benzyl alcohol concentration. An even larger primary hydrogen kinetic isotope effect of 5.26 and a Hammett p value of —1.7 led Baneijee and Shanker187 to propose that benzaldehyde is formed by the two concurrent pathways shown in Schemes 40 and 41. Scheme 40 describes the hydride transfer mechanism consistent with the negative p value. In the slow step of the reaction, labilization of the Pb—O bond resulting from the coordination of pyridine occurs as the Ca—H bond is broken. The loss of Pb(OAc)2 completes the reaction with transfer of +OAc to an anion. 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

The oxidation of benzaldehyde with dioxygen in the presence of Co(II) and bromide ion also shows non-linear kinetic phenomena. The net reaction of the oxidation process is given as follows ... 

Kinetic and mechanistic studies by Casey et al. provided further insight into the mechanistic details of the hydrogenation of ketones and aldehydes, using a more soluble analogue of Shvd s catalyst (with p-tolyl groups instead of two of the Ph groups) [72]. The kinetics of hydrogenation of benzaldehyde by the Ru complex shown in Eq. (43) were first order in aldehyde and first order in the Ru complex the... 

An important feature of saturated oxazolo[3,4- ]pyridines is their easy epimerization at the aminal C-l stereocenter. A quite explicit example has been reported by Moloney et al. and is depicted in Scheme 46. The reaction between lactam 157 and benzaldehyde produces a mixture of hexahydro-oxazolo[3,4- ]pyridines, the kinetic product 158 being the major one. Equilibration of the mixture with boric acid allows the ratio of diasteroisomers to be reversed since /rarcr-oxazolidine 159 is now the major product <1998TL1025> the equilibration of epimeric oxazolidines via ring-chain tautomerism has been investigated in detail and explains the epimerization observed for some hexahydro-oxazolo[3,4-4]pyridines <1993JOC1967>. 

Panoutsopoulos GI, Beedham C. Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes. Acta Biochim Pol 2004 51(3) 649-663. 

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