Benzynes relative reactivity

Elegant methods for determining the relative reactivity of transient intermediates have been developed.6 Consider the reactions of benzyne with water and hydroxide ions ... 

As mentioned in the introductory section, arynes behave as soft acids . Therefore, the relative reactivity of a nucleophile should be governed by basicity as well as polarizability. The following gradations, established through competitive reactions of arynes with different nucleophiles, are more or less in line with this expectation.1 (i) BuLi > PhSLi > PhNMeLi > PhGaCLi > ROLi > ArOLi, for 9,10-phe-nanthryne in ether (ii) PhS- > Ph3C > PhC=C > enolates > PhO- > RO" > I, CN, for benzyne in liquid ammonia (iii) I- > Br > Cl- > EtOH for benzyne in alcohol. 

The question that we should answer now is not only one concerning the relative reactivity of these dienes and dienophiles, but additionally, whether the addition of these dienophiles (ethylene, benzene, and benzyne) to furan and thiophene is experimentally feasible. That can only be properly addressed by computing activation barriers. Semiempirical methods tend to produce very similar and very narrow differences in activation barriers for different diene-dienophile reactant... 

This subject has been thoroughly reviewedand only the main features will be briefly summarized here in order to set the following sections in context. Nucleophiles generally exhibit a smaller range of reactivities toward arynes than toward other substrates. This is because of the extreme reactivity and electrophilicity of arynes. Even so, selectivities are evident with benzyne in liquid ammonia, for example, the nucleophilicity order is PhS > PhO" > RO" and with benzyne in alcohol the order is F > Br > CF EtOH. In water at 318 °C the relative reactivities toward 4-methylbenzyne are PhS (46), F (6.2), piperidine (3.0), Br (1.7), PhNH2 (1.3), PhO (1.0), CF (1.0), NH3 (0.5), F (0.2)229 this compressed... 

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%... 

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