Benzynes, reactions

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. 

When potassium amide, with added potassium metal in liquid ammonia, was substituted in the benzyne reaction, further cleavage of C—bonds of the intermediate dibenzopyrrocolines was often observed. The indoline 41 (32) and... 

Benzo[/)]thiophene chemistry, recent advances in, 11, 177 29, 171 Benzo[c]thiophenes, 14, 331 1,2,3-Benzotriazines, 19, 215 Benzyne, reactions with heterocyclic compounds, 28, 183 Betaines, heterocyclic derivatives of alternant hydrocarbons,... 

In the course of discovery research, reexamination of the benzyne chemistry led to an easily and safely operated benzyne reaction (Scheme 4).38 Solvent was found to affect the rate of halogen-metal exchange processes and the basicity of RLi reagents toward cyclopentadiene, a compound with a low pKa ( 14). Noncoordinating solvents... 

This phenol synthesis is different from the nucleophilic aromatic substitutions discussed in the previous section because it takes place by an elimination addition mechanism rather than an addition/elimination. Strong base first causes the elimination of HX from halobenzene in an E2 reaction, yielding a highly reactive benzyne intermediate, and a nucleophile then adds to benzyne in a second step to give the product. The two steps are similar to those in other nucleophilic aromatic substitutions, but their order is reversed elimination before addition for the benzyne reaction rather than addition before elimination for the usual reaction. 

All the elimination reactions listed in Review Table 2 occur by the same E2 mechanism. Though they appear different, the elimination of an alkyl halide to yield an alkene (reaction 1), the elimination of a vinylic halide to yield an alkyne (reaction 2), and the elimination of an aryl halide to yield a benzyne (reaction 3) are ail E2 reactions,... 

The third compound studied is the 4-thio analog of mescaline, 4-methylthio-3,5-dimethoxyphenethylamine. This was prepared (see scheme II) by the reaction, of lithiated m-dimethoxybenzene with dimethyldisulfide to form 2,6-dimethoxythioanisole. This underwent bromination uniquely adjacent to the methoxy group, and the resulting bromodimethoxythioanisole underwent a smooth benzyne reaction with acetonitrile to form the benzyl cyanide shown, which was reduced to the desired end product (3) with aluminum hydride in THF. 

Immonium salts can also be used in the benzyne reaction. Treatment of salt (32) with dimsyl sodium in DMSO gave a 25% yield of dehydrodomesticine which was reduced to domesticine. Similarly, salt (33) furnished 1-hydroxy-2,10-dimethoxydehydroaporphine which was readily reduced to the corresponding aporphine. ... 

An interesting synthesis of the lycorine-type alkaloids (46) and (47) using the photocyclization of an enamido-ketone (44) as the key step has been reported (Scheme 5). Benzyne reaction of the phenethylamine (41) provided the indoline... 

Benzyne. Reactions of acetanilide in dry benzene with PCBN in the presence of tetraphenylcyclopentadienone, anthracene, 9,10-dimethoxyanthracene, and methyl methacrylate as trapping agents give the corresponding benzyne adducts, 1,2,3,4-... 

The benzyne reaction of the bromoisoquinoline 140 was examined by using sodium methylsulfinylmethanide, and dibenz[6,g]azecine 141 was obtained (80,81). An attractive modification appeared to be the expansion of the central ring of ( )-homoargemonine (143), since it seemed possible that 143 could be a representative of a new, as yet undiscovered alkaloid class originating from a 1-phenethyltetrahydroisoquinoline precursor. The synthesis of 143 was accomplished by reaction of the 1,2-dihydroisoquinoline 142 and formic acid-phosphoric acid (82). 

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