Autocatalysis

Autocatalysis. The kinetic curves developed by chemists in the U.S.S.R. (Section II,A,l,e) showing the dependence of the rate of gas evolution on time during the Chichibabin reaction revealed an interesting characteristic. It was observed that gas evolution began at a slow rate, followed by a sharp increase. This behavior was interpreted as evidence for the gradual accumulation of some compound in the reaction mixture during the induction period, which later catalyzed the amination process. The compound responsible was assumed to be simply the sodium salt of the aminoheterocyclic product. Indeed, introduction of such a sodium salt prior to the start of amination resulted in a rapid reaction with no observable induction period. The catalysis was theorized to result from a six-membered transition complex (17), which provides the required orientation of proton and hydride ion acceptors for hydrogen elimination. Proton abstraction should take place first, which then positions the transition complex structurally close to the dianionic (T-adduct (II). 

In protic solvents, the cr-adducts of some electron-deficient heterocycles form very rapidly, even at low temperatures. 

Characterization. Spectroscopic techniques have made it possible to identify ff-adducts in liquid ammonia. They have been detected and assigned structures by H- and C-NMR spectroscopy. The addition of the amide nucleophile to the sp carbon in the aromatic heterocycle changes its hybridization to sp, which causes an upheld shift of the carbon and hydrogen atoms. 

The first direct evidence for the existence of anionic cr-adducts was presented by Zoltewicz and Helmick (72JA682). They identified anionic (T-adducts 18, 19, and 20 by the addition of pyrazine, pyrimidine, and pyr-idazine, respectively, to excess sodium or potassium amide in liquid ammonia. Identification was made possible by H-NMR spectroscopy. 

Shortly after the publication of the tr-adducts from diazines, Zoltewicz and co-workers reported the identification of anionic a-adducts from treating quinoline and isoquinoline with excess potassium amide in liquid ammonia. H-NMR studies showed that 1-amino-1,2-dihydroisoquinolinide (21) was formed with isoquinoline. In the case of quinoline, kinetic and thermodynamic products were observed. At — 45°C, r-adduct formation between quinoline and sodium or potassium amide in liquid ammonia, gave a mixture of 2-amino-l,2-dihydroquinolinide (22) and 4-amino-l,4-dihydroquinolinide (23), with the former compound being predominant. Warming the mixture resulted in irreversible conversion of 22 into the more stable 23. 

Autocatalysis is the term applied to initiation resulting from hydroperoxide build-up during a reaction. The rate of initiation and the rate of oxidation increase as the hydroperoxide concentration builds up, thus producing the characteristic autocatalytic rate curve. If reactions producing radicals are both first and second order in hydroperoxide, then the rate of initiation (J i) may be written 

Substituting this expression in the usual rate expression 

Generally, the bimolecular term predominates, except at very low [ROOH], in which case 

This expression qualitatively fits a number of systems [60]. Van Sickle et al. [18] have made a careful study of the oxidation of cyclopentene and its autocatalysis at 50°C. This reaction yields about 75% 3-cyclo-pentenylhydroperoxide and 25% of the dimer hydroperoxide III 

They found that the rate of oxidation is linear with respect to [ROOH] up to 10% conversion (1 M ROOH), but at higher conversions the rate 

A reaction is called autocatalytic, when a reaction product acts as a catalyst on the reaction course [3]. 

Autocatalytic reaction is a chemical reaction in which a product also functions as a catalyst. In such a reaction, the observed rate of the reaction is often found to increase with time from its initial value [4]. 

In fact, in most mechanisms, the reaction rate is proportional to the concentration of a reaction product. Thus, the term of self-accelerating reaction would be more appropriate. But for sake of simplicity, we maintain the term autocatalytic. Our use of the word autocatalysis does not imply any molecular mechanism. 

Reaction kinetics involving such catalysts can be demonstrated by the following mechanism  

L is a mobile ligand which can leave the metal site (M) open briefly for reaction with A in the initial step of the catalytic cycle. The transformation of the M A complex into products completes the cycle. The equilibrium in step (1) lies far to the left in most cases, because the ligands protect the metal centers from agglomeration. Thus, the concentration of M is very small, and the total concentration of catalyst is cMr = cm a + cm l- The rate law which arises from this mechanism is 

This rate expression has a common feature of catalysis-that of rate saturation. The (nonseparable) rate is proportional to the amount of catalyst. If reaction step (2) is slow ( 2 is small and the first term in the denominator of 8.2-12 is dominant), the rate 

In this limit, the reaction is first order with respect to A, and most of the catalyst is in the form of M L. Notice the inhibition by the ligand. If reaction step (3) is slow (13 small), the rate simplifies to 

Processes are called autocatalytic if the products of a reaction accelerate their own formation. Autocatalytic reactions get faster as the reaction proceeds, sometimes dramatically, sometimes slowly and steadily. Exponential growth is a very basic non-chemical example. Of course the acceleration cannot be permanent the reaction will slow down and eventually come to an end once the starting materials have been used up. Only economists believe in sustainable growth. 

An extreme example of an autocatalytic reaction is an explosion. In this case, it is not directly a chemical product that accelerates the reaction, it is the heat generated by the reaction. The more heat produced, the faster the reaction the faster the reaction, the more heat, etc. 

There are many mechanisms that display autocatalytic behaviour. A minimal and very basic autocatalytic reaction scheme is presented below  

Starting with component A there is a relatively slow first order reaction to form the product B. The second reaction is of the order two, it opens another path for the formation of component B. As it is a second order reaction, the higher the concentration of B, the faster is the decomposition of A to form more B. The system of differential equations for this reaction scheme is given below (3.83)  

The organisation of the Matlab ODE solvers requires some explanation. For this example, the core is a function, ode autocat.m, that returns the derivatives of the concentrations at any particular time or better, for any set of concentration of the reacting species. Essentially it is the Matlab code for equation (3.83). 

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Figure C3.6.14 Space-time (y,t) plot of the minima (black) in the cubic autocatalysis front ( )(y,t) in equation C3.6.16 showing the nature of the spatio-temporal chaos.

Much of the early work was inconclusive confusion sprang from the production by the reaction of water, which generally reduced the rate, and in some cases by production of nitrous acid which led to autocatalysis in the reactions of activated compounds. The most extensive kinetic studies have used nitromethane,acetic acid, sulpholan,i and carbon tetrachloride as solvents. 

The kinetics of the reactions were complicated, but three broad categories were distinguished in some cases the rate of reaction followed an exponential course corresponding to a first-order form in others the rate of reaction seemed to be constant until it terminated abruptly when the aromatic had been consumed yet others were susceptible to autocatalysis of varying intensities. It was realised that the second category of reactions, which apparently accorded to a zeroth-order rate, arose from the superimposition of the two limiting kinetic forms, for all degrees of transition between these forms could be observed. 

The observation of two limiting kinetic forms was considered to be symptomatic of the occurrence of two reactions, designated non-catalytic and catalytic respectively. The non-catalytic reaction was favoured at higher temperatures and with lower concentrations of dinitrogen pentoxide, whereas the use of lower temperatures or higher concentrations of dinitrogen pentoxide, or the introduction of nitric acid or sulphuric acid, brought about autocatalysis. 

At relatively low temperatures, the effect of added nitric acid was to catalyse the reaction strongly, and to modify it to the autocatalytic form. At higher temperatures the effect of this additive was much weaker, as was the induced autocatalysis. Under these circumstances the catalysis was second-order in the concentration of nitric acid, and the presence of 0-25 mol l i of it brought about a sixfold change in the rate. 

Reducing the temperature or increasing the concentration of reactants, particularly of dinitrogen pentoxide, advanced the onset and increased the intensity of the autocatalysis. Added nitric acid and, to a greater extent sulphuric acid, made the effect more prominent. 

In contrast to its effect upon the general mechanism of nitration by the nitronium ion, nitrous acid catalyses the nitration of phenol, aniline, and related compounds. Some of these compounds are oxidised under the conditions of reaction and the consequent formation of more nitrous acids leads to autocatalysis. 

The kinetics of nitration of anisole in solutions of nitric acid in acetic acid were complicated, for both autocatalysis and autoretardation could be observed under suitable conditions. However, it was concluded from these results that two mechanisms of nitration were operating, namely the general mechanism involving the nitronium ion and the reaction catalysed by nitrous acid. It was not possible to isolate these mechanisms completely, although by varying the conditions either could be made dominant. 

Chloroanisole and p-nitrophenol, the nitrations of which are susceptible to positive catalysis by nitrous acid, but from which the products are not prone to the oxidation which leads to autocatalysis, were the subjects of a more detailed investigation. With high concentrations of nitric acid and low concentrations of nitrous acid in acetic acid, jp-chloroanisole underwent nitration according to a zeroth-order rate law. The rate was repressed by the addition of a small concentration of nitrous acid according to the usual law rate = AQ(n-a[HN02]atoioh) -The nitration of p-nitrophenol under comparable conditions did not accord to a simple kinetic law, but nitrous acid was shown to anticatalyse the reaction. 

Many reactions catalyzed by the addition of simple metal ions involve chelation of the metal. The familiar autocatalysis of the oxidation of oxalate by permanganate results from the chelation of the oxalate and Mn (III) from the permanganate. Oxidation of ascorbic acid [50-81-7] C HgO, is catalyzed by copper (12). The stabilization of preparations containing ascorbic acid by the addition of a chelant appears to be negative catalysis of the oxidation but results from the sequestration of the copper. Many such inhibitions are the result of sequestration. Catalysis by chelation of metal ions with a reactant is usually accomphshed by polarization of the molecule, faciUtation of electron transfer by the metal, or orientation of reactants. 

An instance of autocatalysis is the hydrolysis of methyl acetate, which is catalyzed by product acetic acid, A C. The rate equation may be... 

The reaction is sensitive to the presence of metallic silver at the start, indicating autocatalysis, and to the presence of silver carbonate, which was accidentally present in some investigations. 

There are many reactions in which the products formed often act as catalysts for the reaction. The reaction rate accelerates as the reaction continues, and this process is referred to as autocatalysis. The reaction rate is proportional to a product concentration raised to a positive exponent for an autocatalytic reaction. Examples of this type of reaction are the hydrolysis of several esters. This is because the acids formed by the reaction give rise to hydrogen ions that act as catalysts for subsequent reactions. The fermentation reaction that involves the action of a micro-organism on an organic feedstock is a significant autocatalytic reaction. 

The dependence of reaction rates on pH and on the relative and absolute concentrations of reacting species, coupled with the possibility of autocatalysis and induction periods, has led to the discovery of some spectacular kinetic effects such as H. Landolt s chemical clock (1885) an acidified solution of Na2S03 is reacted with an excess of iodic acid solution in the presence of starch indicator — the induction period before the appearance of the deep-blue starch-iodine colour can be increased systematically from seconds to minutes by appropriate dilution of the solutions before mixing. With an excess of sulfite, free iodine may appear and then disappear as a single pulse due to the following sequence of reactions ... 

Autocatalysis may arise when the nucleophilic atom of the reagent is bound to a hydrogen atom which is eventually eliminated during the reaction. This occurs with neutral reagents such as primary or secondary amines, thiols, and alcohols. If the displaced group (usually an anion) is a sufficiently weak base, the proton is effectively transferred to any basic reactant. Hence, the best known examples of autocatalysis involve chloro-A-heteroaromatic compounds as the substrates. 

In many instances the degree of solubility of the acidic reaction products determines whether autocatalysis occurs. Thus, the reaction of 5-chloroacridine with piperidine is autocatalytic in ethanol but not in toluene where most of the piperidine hydrochloride formed precipitates. ... 

Goi. As noted previously, an a-chlorine atom renders a ring-nitrogen atom very weakly basic. Cyanuric chloride (5) is a very weak base both because s-triazines are of low basicity and because each of the ring-nitrogen atoms is alpha to two chlorine atoms. Hence, this compound should be insensitive to acid catalysis or acid autocatalysis and this has been observed for the displacement of the first chlorine atom with alcohols in alcohol-acetone solution and with water (see, however. Section II,D,2,6). 

The reactivities of compounds of type 6 with aniline in acetone correlate quite well with substituent effects, and autocatalysis is unimportant here. In the less polar tetrahydrofuran, where the hydrochloride is only partly soluble, the reaction shows autocatalysis when aniline and -chloro aniline are reactants but not when the more basic -toluidine is involved. In these cases the solubility of the acidic product may also influence the differential behavior observed. 

Finally, with compounds of type 7, which have one chlorine atom and two ZR substituents, the reactions are, as expected, more frequently acid catalyzed than with compounds of type 6 e.g., the reaction with aniline in acetone is distinctly acid catalyzed. Again, reactions stiU occur, e.g., with benzylamine in tetrahydrofuran, in which autocatalysis is absent, possibly because of a combination of the marked basicity of the reagent and the low solubility of the acidic product. 

The azinones and their reaction characteristics are discussed in some detail in Section II, E. Because of their dual electrophilic-nucleophilic nature, the azinones may be bifunctional catalysts in their own formation (cf. discussion of autocatalysis below) or act as catalysts for the desired reaction from which they arise as byproducts. The uniquely effective catalysis of nucleophilic substitution of azines has been noted for 2-pyridone. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

A bifunctional autocatalytic effect of azinones in general is possible in certain nucleophilic reactions such as amination. Zollinger has found that 2-pyridone is the best catalyst for anilino-dechlorination of various chloroazines. It seems likely that examples of autocatalysis will be found when the substrate contains an azinone moiety. The azinone hy-products of displacement reactions may also function in this way as catalysts for the main reaction. 

GouldConsistent biniolecular rate constants at various concentrations and times were found except in cases of autocatalysis. For the rate equations used and details on the limits of error, the reader is referred to the original publications. 

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

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