Benzyne kinetics

In connection with the substituent effects, the kinetic stability of benzyne is suggested to be increased by electron withdrawal (-/) and decreased by electron release (+/).73 However, the inference cannot be extrapolated to selectivity of substituted arynes in general. For example, in additions involving competition between phenyllithium and lithium piperidide, the methyl substituents (+/) on benzyne increase its selectivity, whereas methoxy groups (-/) decrease it (Scheme 6). On the other hand, in reactions of car-banions derived from acetonitrile in alkylamine solvents both +/ and -/ benzyne substituents lower selectivity and cause predominant amination. Thus, the method was found unsuitable for preparation of many substituted benzyl nitriles.74 In symmetrically disubstituted arynes there is partial cancellation of polarization, and in fact acceptable yields of acetonitrile adducts could be obtained from 3,6-dimethoxy-benzyne.75 The selectivity of substituted arynes varies with the set of nucleophiles in the competition and no comprehensive theory or simple generalization is available on this point. 

A tetrakis(trimethylphosphine)ruthenium complex of benzyne has been prepared6 26 by a reaction similar to that used for the Group 4 and 5 metals thermally induced /3-hydride elimination of methane or benzene from 1 or 2, respectively [Eq. (3)]. A careful study of the kinetics of the elimination of methane from 1 revealed that dissociation of trimethylphosphine pre-... 

Furan reacts as a diene with powerful dienophiles such as maleic anhydride, maleimide, and benzyne to give Diels Alder adducts. The kinetically favored products are the undo adducts but the exo adducts are thermodynamically preferred (Scheme 95). Thus, on prolonged reaction at room temperature, or on heating, the proportion of exo to endo adduct is increased. 

Benzyne was shown to react with a variety of monocyclic and fused-ring thiiranes to produce vinyl thiophenyl ethers <84TL2679>. Initial reaction gives an intermediate betaine, which abstracts the most acidic (kinetic) ring proton, with concomitant C=C bond formation and C—S bond scission, to give excellent yields of products (illustrated for (2) in Scheme 3). The stereochemistry of the starting thiiranes is preserved in the product vinyl sulfides. 

An attempt to prepare triplet benzyne by the triplet-sensitized (benzophenone) decomposition of the peroxide (254) has shown that a singlet benzyne is produced.150 This conclusion was reached even though a kinetic study showed that the decomposition occurred from the triplet state of the peroxide. The two products (255), obtained in the ratio 82 18 by trapping the benzyne with trans-cyclo-octene, could be produced in identical yield using benzyne formed by a variety of paths. The absence of other products which might have arisen from a biradical such as (256) is thought to be conclusive evidence for the absence of triplet benzyne in these experiments. 

For processes in the gas phase, static systems (constant volume and temperature) have been mostly used, and the manometric method has been widely employed for Diels-Alder reactions and for 1,2-cycloadditions " pressure measurements were associated with gravimetric, infrared or gas-chromatographic analyses whenever required by the presence of more than one product. For Diels-Alder reactions only nonmanometric methods were used, either weighing the producF or chemical analysis of iF, or gas chromatography of reactants and product. 1,2-Cyclo self-addition of gaseous benzyne has been kinetically followed by uv spectroscopy-" -. ... 

The kinetics of benzyne dimerisation to biphenylene have been the object of two studies. In the first a limit was determined for the rate coefficient (k > 7x 10 I.mole". see" ) , while the authors of the second arrived at a more accurate value (/ = (4.6 1.2) X 10 l.mole". sec" ) and checked its in-variancy over the range 90-200°C (benzyne was obtained in situ by decomposition of aromatic derivatives). 

At Caltech Robert G. Bergman (1942- ) investigated 1,4-benzyne, an even less stable isomer of 1,2-benzyne. Synthesizing the deuterated compound (shown above), he heated it and observed it rearrange. A fairly simple combination of kinetic measurements and energy estimates indicated that 1,4-benzyne (see the structure a singlet having the two electrons paired) is a true chemical intermediate. This pure research study would have totally unexpected applications to cancer treatment in future decades (see chapter 9). 

The practice of using an insoluble polymer to isolate and kinetic-ally stabilize a reactive intermediate has been addressed in several reports, most commonly using DVB cross-linked polystyrene as a support. In these cases, the three dimensional structure of the polymer and rigidity of the polymer backbone diminish intramolecular reactivity between two sites on the same polymer bead. Physical constraints preclude any significant reaction between two different polymer beads. Similar, less dramatic reduced intramolecular reactivity has also been noted for reactive intermediates bound to linear polystyrene. For example, o-benzyne bound to linear polystyrene has been shown by Mazur to have enhanced stability relative to non-polymer-bound -benzyne (35). In this case, o-benzyne was generated by lead tetraacetate oxidation of a 2-aminobenzotriazole precursor, 1. Analysis of the reaction products after cleaving the benzyne derived products from the polymer by hydrolysis showed a 60% yield of aryl acetates was obtained (Equation 11). In contrast, the monomeric aryne forms only coupled products under similar conditions. Further comparisons of the reactivity of -benzyne bound to insoluble 2% or 20%... 

Kinetic investigations of the lifetimes of polymer-bound benzyne (7.81 and of an N-deprotected amino acid active ester (2) put the concept of site isolation into voper po qi ve. Polymra -bound reactive intermediates have substantially longer lifetimes than the analogous micromolecular species, but they arc not completely isolated, and in time react with othra- polymer-bound species. Several reviews summarize the field as of 1978-82 (10-171. 

The seeming contradiction between these various experiments may be resolved if site isolation is considered to be partially a kinetic phenomenon. For slow reversible reactions, such as anhydride formation or condensation reactions, the polymer chains have sufficient time to exercise several degrees of freedom, permitting site-site interaction. For reactions that occur over shorter periods, such as the decomposition of benzynes, the probability of close contact between reactive centers is greatly reduced. Metal dimer formation was obviated simply because there was no important thermodynamic driving force. 

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