Benzyne ortho

Ortho-benzyne. The generation of ortho-benzyne within a HC was recently reported by Warmuth.21 Like 1,3-cyclobutadiene, strained ortho-benzyne is a unstable,... 

Organic stractures can be determined accurately and quickly by spectroscopic methods. Mass spectrometry determines mass of a molecule and its atomic composition. NMR spectroscopy reveals the carbon skeleton of the molecule, whereas IR spectroscopy determines functional groups in the molecules. UV-visible spectroscopy tells us about the conjugation present in a molecule. Spectroscopic methods have also provided valuable evidence for the intermediacy of transient species. Most of the common spectroscopic techniques are not appropriate for examining reactive intermediates. The exceptions are visible and ultraviolet spectroscopy, whose inherent sensitivity allows them to be used to detect very low concentrations for example, particularly where combined with flash photolysis when high concentrations of the intermediate can be built up for UV detection, or by using matrix isolation techniques when species such as ortho-benzyne can be detected and their IR spectra obtained. Unfortunately, UV and visible spectroscopy do not provide the rich structural detail afforded by IR and especially H and NMR spectroscopy. Current mechanistic studies use mostly stable isotopes such as H, and 0. Their presence and position in a molecule can... 

The triple bond in ortHo-benzyne can be stabilized by complexation with transition metals. Aryne-metal complexes were originally proposed as intermediates in the decomposition of various aryl derivatives of early transition metals, and the first fuUy characterized mononuclear ortho-benzyne complex, TaMe2(q -C5Me5) (q -CjH4), was prepared. Although this method does not appear general for all transition metals, various complexes of zirconium, rhenium, and niobium have been characterized. More recently, complexes of nickel and platinum have also been... 

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

Scheme 7.5 summarizes the common methods of aryne generation, although the examples are limited to ortho-benzyne. Because of their extreme reactivity, arynes must be generated in situ. When an unactivated aryl halide is treated with a very strong base, an elimination reaction is possible, generating aryne. 

Benzyne is electron-deficient and will be attacked by nucleophiles in a reaction that opens the it bond not part of the aromatic cloud, and produces a new carbanion. Protonation completes the sequence to give the aromatic substitution product (Scheme 7.6). Irradiation of either benzocyclobutenedione or phthaloyl peroxide or 3-diazobenzofuranone at 8 K in an argon matrix led to eventual formation of ortHo-benzyne (Scheme 7.7). 

Scheme 7.7 Low-temperature photolytic generation of ortho-benzyne.

Scheme 7.8 Generation of ortho-benzyne from o-dihaloaromatics.

The C-labeling experiments of Roberts in 1953 put the existence of ortho-benzyne as an intermediate beyond doubt when it was found that treatment of 1-i C-chlorobenzene with potassium amide in liquid ammonia gave a 1 1 mixture of 1- and 2- C labeled aniline. The reaction had clearly proceeded through a symmetrical intermediate ortho-benzyne. The overall process whereby a nucleophile apparently enters ortho to the leaving group is referred to as cine substitution (Scheme 7.10). 

Scheme 7.10 Ipso and cine substitution through an ortho-benzyne intermediate.

Probably the most important of all precursors to ortho-benzyne is benzenediazonium-2-carboxylate. The compound is easily prepared by... 

Scheme 7.13 Decomposition of benzenediazonium-2-carboxylate to give ortho-benzyne.

Scheme 7.18 Decomposition of benzothiadiazole-1,1-dioxide to give ortho-benzyne.

There are many other reactions that possibly involve aryne intermediates. While some are of mechanistic curiosities, some have been studied in detail, although none are generally synthetically useful. Irradiation of 1,2-diiodobenzene can lead to ortho-benzyne, probably via an aryl radical intermediate resulting from cleavage of the weak C-1 bond (Scheme 7.19). Aryl cations, formed by the decomposition of diazonium salts are also possible intermediates to ortho-benzynes provided that a large ortho-substituent is present, loss of a proton to give an aryne becomes competitive with the normal nudeophihc addition to the cation. 

Scheme 7.19 Formation of ortho-benzyne from 1,2-diiodobenzene/phthalic anhydride.

AU the examples discussed to date have involved ortho-benzyne itself, and have simply served to illustrate the range of nucleophiles that react. However, one needs to know what happens when unsymmetrical arynes are attacked by nucleophiles. 

Scheme 7.23 Addition of tertiary amines, phosphines, and sulfides to ortho-benzyne.

Arynes with their reactive triple bond would be expected to participate readily in cycloaddition reactions. However, as demonstrated in the previous section, the addition of nucleophiles is extremely facile, and therefore reactions with non-nucleophilic reagents cannot usually be observed unless the aryne is generated in the absence of nucleophiles. In practice this usually means that routes involving the treatment of aryl halides with nucleophilic bases cannot be used. The first cycloaddition reaction of ortho-benzyne, the Diels-Alder reaction with furan was observed in 1955 by Wittig and used 2-fluorobromobenzene as the precursor. The cycloadduct was obtained in almost 90% yield, and the reaction has formed the basis for numerous synthetically useful Diels-Alder cycloadditions involving arynes. Tetrabromobenzene reacts with butyllithium to give the diaryne intermediate with furan to form a tetrahydroanthracene. The mixture of syn and anti conformers can be separated based on differences in methanol solubility (Scheme 7.26). 

As a reactive dienophile ortbo-benzyne also participates in the ene reaction. Thus, alkenes with allylic hydrogen can undergo concerted reaction to give substituted benzenes. However, the yields are rarely good. Cycloaddition of ortho-benzyne to alkynes should in principle give benzocyclobutadienes. Such intermediates are highly unstable and not surprisingly are not isolated. Instead, the products, formed in low yield, derive from further reaction with another molecule of ortho-benzyne or by dimerization (Scheme 7.32). 

The high reactivity of ortho-benzyne is also evident in 1,3-dipolar cycloadditions. The reaction is an extremely useful route to benzo-fused five-membered ring heterocydes. For example, azides give benzotriazoles, diazo compounds give (after... 

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