Mechanistic Evidence

The mechanism for polymerization of propylene with heterogeneous catalysts is very similar to that of ethylene. Studies with a homogeneous catalyst of a lanthanide element provided early mechanistic evidence. The complex used in these studies was 6.15. In 6.15 lutetium is in a 3+ oxidation state and has the electronic configuration of 4fu. In other words Lu3+ has a full/shell and 6.15 is a diamagnetic complex. 

Apart from providing direct spectroscopic evidence for the various catalytic steps, experiments with 6.15 and other lanthanide cyclopentadiene complexes also established that paramagnetic metal ions do not have any special effect on the oligomerization reaction. The mechanism proposed on the basis of these studies is as shown in Fig. 6.5. 

The conversions of 6.16 to 6.17 and 6.19 to 6.20 are the chain-propagation steps. The conversions of both 6.17 and 6.20 to 6.18 by /3-hydride elimination are the chain-termination steps. The last two reactions are also the ones where the product polypropylene is formed. Conversion of 6.16 to 6.18 without the intermediacy of 6.17 also involves /8-hydride elimination, and the product formed is isobutylene. 

The discovery of homogeneous metallocene catalysts in the 1980s was a very important milestone in polymer technology. With these catalysts the plastic industry is poised to move into an era of an entirely new range of polymeric materials with several specific advantages. From the initial discovery in the 1980s, close to five billion dollars is estimated to have been invested by several large chemical companies in research and development. In a relatively short time, this has resulted in approximately fifteen hundred patent applications Close to 0.5 million tons of metallocene-catalyzed polypropylene is expected to be manufactured by the year 2003. 

Sandwich or metallocene complexes have been known for almost 50 years. However, only in the 1970s was it discovered that when trimethyl aluminum was used as a co-catalyst, small amounts of water greatly increased the polymerization activity of a metallocene catalyst. As we shall see in the following sections, this apparently simple observation has an interesting mechanistic explanation. We first discuss the general structures of the metallocene catalysts and the co-catalysts. 

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Further mechanistic evidence comes from trapping experiments. When bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction (Section 14.5) occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene. Ben-zyne is too reactive to be isolated as a pure compound but, in the presence of water, addition occurs to give the phenol, in the presence of a diene, Diels-Alder cycloaddition takes place. 

The gas-phase photolysis of 2-furaldehyde in the it -n and ir <-it transitions76 proceeds with fragmentation to CO, furan and C3-hydrocarbons, but a certain amount of resinification is also noted (about 5% quantum yield with excitation of the it - n transition). The latter observation prompted a study of the vacuum liquid-phase photolysis by sunlight or by light from a medium-pressure mercury arc at room temperature24 7S. The resin obtained was submitted to fractionation and structural analysis. On the basis of the results obtained and other mechanistic evidence, the following sequence of events was postulated for the photopolymerization ... 

Further mechanistic evidence was provided by Benkeser and Krysiak658, who determined the effects of added salts and water on the rates of cleavage of xylyltrimethylsilanes by p-toluenesulphonic acid in acetic acid at 25 °C, the progress of the reaction being followed by dilatometry the first-order rate coefficients are given in Table 227. Clearly the addition of water retards the reaction, as... 

Scheme 15 Cross-coupling experiments to obtain mechanistical evidence (a) complex 67 (5 mol%), PhMgBr, THF [9]...

Several pieces of mechanistic evidence implicate allylic radicals or cations as intermediates in these oxidations. Thus 14C in cyclohexene is distributed in the product cyclohexenone indicating that a symmetrical allylic intermediate is involved at some stage.159... 

Landrum J. T. and Bone R. A., Eds. (2004). Mechanistic evidence for eye diseases and carotenoids. In Carotenoids in Health and Disease. New York Marcel Dekker. 

There is mechanistic evidence to show that this formal (3 + 3) cycloaddition starts with attack of betaine-C at CI<2 of the three-ring (429) and leads to 2-pyrone formation either by a concerted process (429 — 428) or stepwise via cyclobutenone and 0-acyl vinylketene intermediates (430/431) depending on the leaving group ... 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

Another piece of mechanistic evidence was reported by Snapper et al. [14], who describe a ruthenium catalyst caught in action . During studies on ring opening metathesis, these authors were able to isolate and characterize carbene 5 in which a tethered alkene group has replaced one of the phosphines originally present in Id. Control experiments have shown that compound 5 by itself is catalytically active, thus making sure that it is a true intermediate of a dissociative pathway rather than a dead-end product of a metathetic process. 

Strong mechanistic evidence from rodent models of autoimmune disease of viral or other infectious agents affecting autoimmunity or progression to overt disease, but harder to demonstrate in humans. Enterovirus (Coxsackie virus) focus of epidemiologic studies in type 1 diabetes, Epstein-Barr virus focus of epidemiologic studies in multiple sclerosis and systemic lupus erythematosus. 

Hutzler, J.M., Wienkers, L.C., Wahlstrom, J.L., Carlson, T.J. and Tracy, T.S. (2003) Activation of cytochrome P450 2C9-mediated metabolism mechanistic evidence in support of kinetic observations. Archives of Biochemistry and Biophysics, 410 (1), 16-24. 

The mechanistic evidence from relative kinetic data can be greatly enhanced when correlations with other independent quantities are constructed, and thus links between the catalytic processes and other phenomena are found. Boudart (7) was first to point out the possibilities of such correlations. When a relationship of a catalytic reaction to a noncatalytic chemical transformation is established in this way, the catalytic mechanism can be elucidated on the basis of analogy. Moreover, if the relationships are linear, the interpretation of their slopes yields additional information. 

For non-threshold effects (e.g., sensitization, mutagenicity, genotoxicity, genotoxic carcinogenicity), the dose-response curve, in the absence of mechanistic evidence to the contrary, is assumed to be linear. 

Since the first report in 1973, there has been significant growth in the use of rhodium catalysis to cleave strained ethers and amines, particularly in the preparation of enan-tiomericaUy enriched decalins, cyclohexenes, amino alcohols, and diamino compounds. This chapter describes the major advances in synthetic capabihties and outlines the mechanistic evidence pointing to a working model for the reaction pathway in these processes. 

Controlled double-potential techniques have also allowed measurement of relative emission intensity as a function of the time in which each of the potential steps is allowed to proceed. Comparisons of the emission intensities obtained with those predicted by mathematical models68,69 have been used as mechanistic evidence,85,67 see Sect. IV-B. 

Little mechanistic work has been reported on the direct reaction of F-vinyl halides with Zn°. Jairaj and Burton have studied the mechanistic details of the reaction between Z-l-iodopentafluoropropene with Zn° and have presented mechanistic evidence consistent with the formation of a vinyl carbanion that is captured in situ by zinc halide to form the vinylzinc reagent45. Their mechanism is presented in Scheme 1. 

Willson, R. L. Free radicals and tissue damage Mechanistic evidence from radiation studies. In Biochemical Mechanisms of Liver Injury (Slater, T. F., ed.), London-New York-San Francisco, Academic Press, 1978, pp. 123-224... 

Mechanistic evidences show that PDC, similar to other chromium-based oxidants, operates via an intermediate chromate ester that evolves to a carbonyl compound in the rate-determining step.125... 

One molecule of Ru04 is able to oxidize two molecules of a secondary alcohol to the corresponding ketone, while Ru04 is transformed into Ru02. Mechanistic evidences show that the rate determining step involves a hydride transfer from the alcohol to the oxidant as in the following Equation.39... 

Fuchs JR, Funk RL (2005) Indol-2-one Intermediates Mechanistic Evidence and Synthetic Utility. Total Syntheses of ( )-Fhistramines A and C. Org Lett 7 677... 

Indium trichloride was identified as an efficient catalyst for the atom-transfer cyclization of allylic halides with an alkyne pendant [(42) (43)]. Mechanistic evidence... 

Mechanistic evidence from variations in reaction conditions... 

Case studies more detailed mechanistic evidence from product studies... 

In general, mechanistic evidence for a reactive intermediate from trapping experiments needs to be linked to arguments against the introduction of an alternative pathway from the reactant, i.e. to show that an intermediate really has been trapped, not the reactant. A classic case is the hydrolysis of 4-nitrophenyl acetate catalysed by imidazole. The mechanism is nucleophile catalysis and the intermediate (N-acetylimidazolium cation) was trapped by aniline (to give acetanilide) with no kinetic effect, i.e. the aniline does not react directly with the substrate [51]. 

Study of reactions in different solvents often provides crucial mechanistic evidence. This is the case in the reaction between thiolates and a -substituted nitroalkanes when changing from dipolar aprotic solvents to protic solvents. In contrast to the above reactions in dipolar aprotic solvents, where a mixture of disulfides and SRN1 products is obtained, disulfides are exclusively formed in methanol with no SRN1 products. Early studies had shown that SrnI substitution between a-substituted nitroalkanes and anions such as nitronates and arylsulfinates takes place at a slower rate in methanol. 

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