Benzyne anions

Scheme 3.37 describes gas-phase generation of m-benzyne anion (the distonic anion-biradical) from m-bis(trimethylsilyl) benzene (Wenthold et al. 1994, 1996 Wenthold and Squires 1998). The same anion-biradical is formed from isophthalic acid under the same conditions (Reed et al. 2000). Particularly, the reaction of m-bis(trimethylsilyl) benzene with fluoride ion, followed by treatment of the formed trimethylsilyl phenyl anion with fluorine in helium, produces the anion-biradical mentioned. The latter is transformed into the corresponding nitro benzoate anion through the addition of CO2 and NO2 (Scheme 3.37). 

Theoretical studies on the m-benzyne anion led to the inference that it holds a pair of weakly interacting orbitals. One orbital contains the odd spin density, whereas another contains two electrons that are responsible for the negative charge of this species (Nash and Squires 1996). 

A way forward might be to form the imine 7.3 [and hence its enamine tautomer 7.4] by reacting the phenylamine 7.2 with cyclohexanone (Scheme 7.18). Then to generate the benzyne anion 7.5 by treating the tautomers with sodamide and sodium fcr/-buloxide in THF. Cydization to the required indole 7.1 occurs through nucleophilic addition to the benzyne, followed by protonation during work-up. 

FIGURE 1. Electronic structure of singlet and triplet neutral 0-benzyne and doublet 0-benzyne anion... 

The neat resin preparation for PPS is quite compHcated, despite the fact that the overall polymerization reaction appears to be simple. Several commercial PPS polymerization processes that feature some steps in common have been described (1,2). At least three different mechanisms have been pubUshed in an attempt to describe the basic reaction of a sodium sulfide equivalent and -dichlorobenzene these are S Ar (13,16,19), radical cation (20,21), and Buimett s (22) Sj l radical anion (23—25) mechanisms. The benzyne mechanism was ruled out (16) based on the observation that the para-substitution pattern of the monomer, -dichlorobenzene, is retained in the repeating unit of the polymer. Demonstration that the step-growth polymerization of sodium sulfide and /)-dichlorohenzene proceeds via the S Ar mechanism is fairly recent (1991) (26). Eurther complexity in the polymerization is the incorporation of comonomers that alter the polymer stmcture, thereby modifying the properties of the polymer. Additionally, post-polymerization treatments can be utilized, which modify the properties of the polymer. Preparation of the neat resin is an area of significant latitude and extreme importance for the end user. 

The addition-elimination mechanism involves two intermediates, a chlorophenyl anion and benzyne. A simple displacement mechanism can be ruled out because reaetion of ort/io-chlorotoluene gives not only ort/io-methylphenol but also meto-methylphenol. 

Halobenzenes undergo nucleophilic aromatic substitution through either of two mechanisms. If the halobenzene has a strongly electron-withdrawing substituent in the ortho or para position, substitution occurs by addition of a nucleophile to the ring, followed by elimination of halide from the intermediate anion. If the halobenzene is not activated by an electron-withdrawing substituent, substitution can occur by elimination of HX to give a benzyne, followed by addition of a nucleophile. 

A variation of the halide affinity approach was used by Riveros et al. in the investigation of the enthalpy of formation of o-benzyne. Reaction of bromo- or iodobenzene with base in an ICR leads predominantly to the formation the expected M-1 anion, but also leads to the formation of solvated halide ions (Eq. 5.15). By using substrates with known halide affinities, it was possible to assign limits to the enthalpy of formation of the benzyne product. Ultimately, the experiment is comparable to that outlined in Eq. 5.14, although the acidity and halide affinity measurements are made in a single step. 

Dehydrobenzene or benzyne 158 can be trapped by all manner of species. 1,2-Dehydro-o-carborane 159 has been shown to undergo many of the same reactions as its two-dimensional relative, 1,2-dehydrobenzene. Although dehydroaromatic molecules can be formed in a variety of ways, synthetic pathways to 1,2-dehydro-o-carborane are quite limited. An effective procedure reported so far78 first forms the dianion by deprotonation of o-carborane with 2 equiv. of butyllithium. Precipitated dilithium carborane is then treated with 1 equiv. of bromine at 0°C to form the soluble bromo anion 160. Thermolysis of 160 with anthracene, furan, and thiophene as substrates leads to the adducts 161-164.79 80 1,2-Dehydro-o-carborane reacts with norbomadiene to give both homo 2+4 and 2+2 addition, leading to three products 165-167, in a 7 1 ratio79. An acyclic diene, 2,3-dimethyl-... 

Synthesis of Functionalized Indole- and Benzo-Fused Heterocyclic Derivatives through Anionic Benzyne Cyclization... 

Scheme 2. Anionic cyclization of A/-(2-lithioallyl)-/V-2-fluoroanilines 1 via benzyne intermediates 7.

Scheme 4. Anionic cyclization of benzyne-tethered organolithiums from 2-chloroanilines 12 and 15. Synthesis of the serotonin analogue 16.i) fBuLi (3.3 equiv), THF, -110 20°C ii) H20, -78 20°C iii) CH2N+Me2I, THF, 67 °C.

Intra-complex TMS+ abstraction by F yields the trimethylenemethane radical anion 33. Similarly, a number of other (mostly aromatic) distonic radical anions have been generated. Using the same approach, several other highly unsaturated distonic negative ions, such as the benzyne radical anions, were also studied164. 

Strong base treatment of the spiro salt 49 gives a benzyne (107) from which the isolated products were produced by further reaction. For example, with n-butyllithium and furan in tetrahydrofuran, 108 is produced after hydrogenation and acid treatment via 109. Reaction with phenyllithium gives 110 (R == Ph and Me) by subsequent addition of phenyl or methyl anion to the benzyne, respectively, and 110 (R = I) by subsequent reaction with iodine anion. Similarly the 9,9-diphenyl salt 111 gives 112 with phenyllithium. Pyrolysis of the spiro salt 49 gives 50. 

The distonic radical anions of o-, m-, and p-benzyne were crucial intermediates in an elegant determination of the S,T splitting of the corresponding benzynes. The ions are accessible by well-estabhshed (routine) gas-phase reactions o-benzyne... 

Intramolecular addition to benzyne generated from the Schiff base of aniline and o-chlorobenzaldehyde is thought to involve addition of an amide anion to the C=N bond [163]. This mechanism indicates donor accentuation of the ortho carbon. 

However, this achievement was then marred by an unfortunate error. The calcium salt of 4-fluorobenzoic acid was heated in admixture with calcium hydroxide, and fluorobenzene was claimed to be formed by decarboxylation. Later, it was shown16 that the product, a solid, was phenol. It had been analyzed only for carbon and hydrogen content an early warning to all workers in fluorine chemistry of the need for quantitative assays for fluorine in their products. Being more activated than fluorobenzene towards nucleophilic attack, the fluorobenzoate anion itself probably lost fluorine before decarboxylation occurred. A benzyne-type process seems to be a less likely reaction pathway. 

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