Benzyne methods

The method described is that of Hampton, Harris, and Hauser6 and is an improvement over the benzyne method, which gives poor yields.6,7 This /J-diketone has been prepared by Claisen condensation of ethyl phenylacetate with acetone,8 but the yield is poorer and the product has been shown by gas chromatography to be impure.6 The j8-diketone has also been prepared by the hydrolysis of 4-methoxy-5-phenyl-3-penten-2-one and by hydrolysis and decarboxylation of ethyl a-acetyl-/3-oxo-y-phenylbutyrate10 but these compounds are more difficult to obtain than the starting materials used in the present synthesis. 

Alternative methods for its generation have made it possible to use benzyne as an intermediate m a number of synthetic applications One such method involves treating o bromofluorobenzene with magnesium usually m tetrahydrofuran as the solvent... 

A method for the generation of benzyne involves heating the diazonium salt from o aminobenzoic acid (benzenediazonium 2 carboxylate) Using curved arrows show how this sub stance forms benzyne What two inorganic compounds are formed in this reaction" ... 

There are several methods for generation of benzyne in addition to base-catalyzed elimination of hydrogen halide from a halobenzene, and some of these are more generally applicable for preparative work. Probably the most convenient method is diazotization of o-aminobenzoic acid. Concerted loss of nitrogen and carbon dioxide follows diazotization and generates benzyne. Benzyne can be formed in this manner in the presence of a variety of compounds with which it reacts rapidly. 

It should be noted that CASSCF methods inherently tend to give an unbalanced description, since all the electron correlation recovered is in die active space, but none in the inactive space, or between the active and inactive electrons. This is not a problem if all the valence electrons are included in the active space, but this is only possible for small systems. If only part of die valence electrons are included in the active space, the CASSCF methods tend to overestimate the importance of biradical structures. Consider for example acetylene where the hydrogens have been bent 60° away from hnearity (this may be considered a model for ort/zo-benzyne). The in-plane jt-orbital now acquires significant biradical character. The true structure may be described as a hnear combination of the three configurations shown in Figure 4.11. 

In the case of 1,3-diphenylisoindole (29), Diels-Alder addition with maleic anhydride is readily reversible, and the position of equilibrium is found to be markedly dependent on the solvent. In ether, for example, the expected adduet (117) is formed in 72% yield, whereas in aeetonitrile solution the adduet is almost completely dissociated to its components. Similarly, the addition product (118) of maleic anhydride and l,3-diphenyl-2-methjdi.soindole is found to be completely dissociated on warming in methanol. The Diels-Alder products (119 and 120) formed by the addition of dimethyl acetylene-dicarboxylate and benzyne respectively to 1,3-diphcnylisoindole, show no tendency to revert to starting materials. An attempt to extrude carbethoxynitrene by thermal and photochemical methods from (121), prepared from the adduct (120) by treatment with butyl-lithium followed by ethyl chloroform ate, was unsuccessful. 

Benzyne, intermediate in preparation of phenyl t butyl ether, 46, 90 methods for generation of, 46, 112 trapping by tetraphenylcyclopenta-dienone, 46,112... 

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

However, in a re-investigation of the reaction of benzyne with benzene 39>, it was shown that the original method of isolating benzene-diazonium-2-carboxylate resulted in the contamination of the zwitter-ion with silver salts 40>41). In the absence of silver ions biphenylene, and... 

The same compound has been obtained by a number of other research groups, using a number of different methods of generating tetrafluoro-benzyne. These include the loss of magnesium halide from pentafluorophenylmagnesium halides 44 46>, the loss of lithium fluoride from penta-fluorophenyl-lithium 47>48), and the aprotic diazotisation of tetrafluoro-anthranilic acid 49>. 

A very convincing demonstration of the existence of benzyne by physical methods involves the introduction into the heated inlet of a mass spectrometer of the zwitterion ion (106), a salt of diazotised o-aminobenzoic(anthranilic) acid. The mass spectrum is found to be a very simple one exhibiting m/e peaks at 28, 44, 76 and 152 ... 

It has been shown e that two mechanisms, elimination-addition (benzyne) and SN2 displacement, are operative in the liquid-phase hydrolysis of halogenatcd aromatic compounds. The formation of isomeric phenols as a result of the availability of the benzyne route makes the reaction of limited synthetic value. The incorporation of the copper-cuprous oxide system suppresses reaction via the benzyne route, so that the present method has general utility for the preparation of isomer-free phenols. For example, >-cresol is the only cresol formed from -bromotoluene under the conditions of this preparation. 

Abstract The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or... 

The influence of substituents on the stability of singlet m-benzynes is weak, and small variations have been rationalized on the basis of electrostatic arguments. The triplet states are even less affected by substimtion. Note that high structural flexibility is obviously characteristic for all m-benzynes. It can therefore not be taken for granted that calculated tendencies (and in particular those obtained with DFT methods) represent actual physical trends instead of just reflecting the deficiencies of the respective level of theory. 

In contrast to benzynes and benzdiynes (cf. Section 6.2), knowledge of tridehy-droarenes is scarce. According to calculations by Bettinger et al. 1,2,4-tridehy-drobenzene (121) and 1,3,5-tridehydrobenzene (122) are less stable than the 1,2,3-isomer 123 by 4.0 and 11.8 kcal/mol, respectively. In contrast to didehydrophenyl cation 111 (Section 5), 122 possesses C2v symmetry the calculated Cl—C3 and Cl—C5 distances are different (194 and 230 pm, respectively, at the CCSD/DZP level of theory). For the 1,2,3-isomer 123 a significantly shorter Cl—C3-distance ( 170 pm) is predicted by various methods. 

Amidst all the enthusiasm about this versatile new tool that quantum chemistry has put at the hands of practioners of IR spectroscopy in matrices, one should not forget its limitations. First, a valid prediction can only come from a calculation based on a correct structure. In the case of reactive intermediates, this is not always as evident as one might wish. A famous example is given in Chapter 16 in this volume Much of the recent discussion on the correct assignment of the IR spectrum of m-benzyne was caused by the fact that different theoretical methods predict different structures, with more or less bonding between the radical centers, for this species. The DFT methods appear to overestimate this bonding, and hence are unsuitable for the prediction of the IR spectrum of m-benzyne. 

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