From bromobenzene

Phenylmagnesium bromide (2.8 mol) was prepared in anhydrous ether (21) from bromobenzene (440 g, 2.9 mol) and magnesium turnings (68.0 g 2.8 g-atom). To this solution was added dropwise a solution of indole (328 g, 2.8 mol) in benzene (8(X)ml). The resulting solution was stirred for 10 min and then a solution of cyclopentanoyl chloride (322 g, 2.4 mol) in benzene (800 ml) was added dropwise. The solution was stirred for 1 h and then water (11) was added carefully. The precipitate which formed was collected by filtration and dried to give 169 g of crude product. Additional product (97 g) was obtained by evaporation of the organic layer of the filtrate. The combined products were recrystallized from toluene to give 250 g (49% yield) of pure product. 

For the synthesis of a suitable arylboron compound, usually an aryl halide is converted to an aryllithium or aryl Grignard derivative, and then reacted with a trialkoxyborane to yield an arylboronic ester, e.g. the phenylboronic acid diisopropyl ester 13 from bromobenzene 11 ... 

Further mechanistic evidence comes from trapping experiments. When bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction (Section 14.5) occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene. Ben-zyne is too reactive to be isolated as a pure compound but, in the presence of water, addition occurs to give the phenol, in the presence of a diene, Diels-Alder cycloaddition takes place. 

Benzocyclobutenone was first prepared from 1 -bromobenzocyclobutene by hydrolysis followed by chromium trioxide oxidation.3 More recent procedures involve hydrolysis of 1,1-dichloro- or 1,1-dimethoxybenzocyclobutene which in turn have been obtained through cycloaddition of the appropriate 1,1-disubstituted ethylenes to benzyne generated either from anthranilic acid through diazotization5 6 or from bromobenzene through sodium amide treatment.7.3 Benzocyclobutenone has... 

The atom economy of the cross-coupling reaction and the Heck reaction for making styrene from bromobenzene and vinyl bromide (cross), and bromobenzene and ethene (Heck) respectively are in favour of the Heck reaction, as that produces only one equivalent of salt. 

Nickel(O) triphenylphosphine can be used to couple aryl halides and alkenes to synthesize substituted olefins [149], 1,2-bis[(di-2-propylphosphino)benzene]nick-el(0) can be used to couple aryl halides [150], and l,2-bis[(diphenylphos-phino)ethane]nickel(0) can be used to prepare benzoic acid from bromobenzene in the presence of carbon dioxide [151]. 

A detailed investigation of the Ni-dppe catalyzed formation of biphenyl from bromobenzene has resulted in the proposal of a catalytic cycle (Scheme 1) in which the tr-aryl-nickel intermediate is first reduced into the corresponding ArNi then transformed into a diaryl-nickel(III) complex. This complex then undergoes a reductive elimination leading to the product and Ni, followed by the regeneration of the Ni system [32, 34],... 

The synthesis of phenylbromosilanes from bromobenzenes and silicon, catalyzed by copper 142) at 411°C, could be correlated by the Hammett equation (series 113, seven points, slope 0.63). 

This reaction sequence illustrates how the rates of many base-catalyzed reactions can be enhanced greatly by substitution of dimethylsulfoxide for the usual hydroxylic solvents. Other examples of the enhanced reactivity of anions in dimethylsulfoxide are found in Wolff-Kishner reductions and Cope elimination reactions. The present reaction illustrates the generation of an aryne intermediate from bromobenzene. ... 

The formation of bromophenylmercapturic acid from bromobenzene and cystine in the organism, if it had the formula given it by Baumann now seemed scarcely possible, unless an isomeric a-thio-y8-aminopropionic acid were also present in the protein molecule together with the di-/8-thio-a-aminopropionic acid or cystine. The investigation of their constitution was therefore taken up by Friedmann in 1904, who succeeded in showing that they were also derived from -thio-a-aminopropionic acid and not from the isomeric a-thio-/8-aminopropionic acid. 

Subsequently, a copper-catalyzed cross-coupling [with substoichiometric amounts of copper(l) iodide and N,N -dimethylethylenediamine (DMEDA)] between aryl halides and sulfoximines was developed [52]. In this case, both aryl bromides and aryl iodides reacted well. For the conversion of the former substrates an in-situ copper-catalyzed aryl Finkelstein reaction [53] had to be performed first, as shown in Scheme 2.1.1.22 for the preparation of 64 starting from bromobenzene (62). 

Alkanamines have acid strengths corresponding to Ka values of about 10 33, which means that their conjugate bases are powerfully basic reagents. Therefore they are very effective in causing elimination reactions by the E2 mechanism (Section 8-8) and aromatic substitution by the aryne mechanism (Section 14-6C). The following example illustrates this property in a useful synthesis of a benzenamine from bromobenzene ... 

An interesting case is provided by the nitration of aryl halides where the effect of the halogen is to deactivate the aromatic nucleus (by the -I effect) but to direct the incoming nitronium ion to the ortho and para positions as a result of the mesomeric interaction of the halogen lone electron pair with the charge developed in the corresponding intermediates [e.g. (5), in the formation of p-bromonitrobenzene from bromobenzene, Expt 6.20],... 

The role of molecular dimensions is well demonstrated by complex formation with halogen-ated benzenes. 1 1 complexes may be prepared from chloro-, bromo-, and iodobenzenes but from chlorobenzene only witto-CD, from bromobenzene witb- andp-CDs, and from iodobenzene with P- andy-CDs. 

On treatment with sodium bis (2-methoxyethoxy)aluminium hydride (Scheme 16), 122 gave the aldehyde 123, which was converted by standard synthetic operations, into the methyl-O-benzylester 124. Acid hydrolysis of 124 followed by allylic epoxidation of the diol furnished the p-oxirane 125. On heating 125 in water containing sodium benzoate a remarkable chain of chemical events took place that resulted in the generation of (+)-pancratistatin (94) in 2% overall yield starting from bromobenzene. 

In each part of this problem in which there is a change in the carbon skeleton, disconnect the phenyl group of the product to reveal the aldehyde or ketone precursor that reacts with the Grignard reagent derived from bromobenzene. Recall that reaction of a Grignard reagent with formaldehyde (H2C=0) yields a primary alcohol, reaction with an aldehyde (other than formaldehyde) yields a secondary alcohol, and reaction with a ketone yields a tertiary alcohol. 

Treatment of TV-methyl-4-piperidone with the Grignard reagent derived from bromobenzene gives a tertiary alcohol that can be dehydrated to an alkene. Hydrogenation of the alkene completes the synthesis. 

The reaction of the sodium derivative of methylpyrazine with alkyl halides in liquid ammonia gives good yields (44-81%) of mono-alkylated products phenylation has been achieved by reaction with benzyne (generated from bromobenzene and sodamide in liquid ammonia) and gives 53% benzylpyrazine.178 The alkylation of the sodio derivative of 2-methoxy-3-methylpyrazine with methyl iodide, and of the product with ethyl bromide, gives 2-methoxy-3-sec-butylpyrazine (25) a constituent of galbanum oil.31... 

Starting from bromobenzene and any other reagents and solvents you need, show how you would synthesize the following compounds. Any of these products may be used as starting materials in subsequent parts of this problem. 

The arynic condensation of 1,2-diketone monoacetal enolates with aryne (from bromobenzene and sodium amide) lead to IV/114. Depending on the reaction conditions, compound IY/1I4 can be transformed to two different enlargement products, IV/115 and IV/117. The mechanisms involved in these transformations are obvious [63] [64], Scheme IV/18. 

The simplest and most obvious nucleophilic substitutions on an aromatic ring, such as the displacement of bromide from bromobenzene with hydroxide ion, do not occur. 

At the start of the section on Nucleophilic aromatic substitution we said that the displacement of bromide from bromobenzene with hydroxide ion does not occur . That statement is not quite correct. Substitution by hydroxide on bromobenzene can occur but only under the most vigorous conditions—such as when bromobenzene and NaOH are melted together (fused) at very high temperature. A similar reaction with the very powerful reagent NaNH2 (which supplies NH2 ion) also happens, at rather lower temperature. 

Notice the symmetry in this mechanism. Benzyne is formed from an ortho carbanion and it gives an ortho carbanion when it reacts with nucleophiles. The whole mechanism from bromobenzene to aniline involves an elimination to give benzyne followed by an addition of the nucleophile to the triple bond of benzyne. In many ways, this mechanism is the reverse of the normal addition-elimination mechanism for nucleophilic aromatic substitution and it is sometimes called the elimination-addition mechanism, the elimination step... 

Toward this end, halo-spacers 41, 42, 45 and 46 were synthesized (Scheme 2), and the appropriate chromophores were attached [56, 57], Tweezers 27 and 28 are synthesized in only 7 and 8 steps, respectively, from bromobenzene and succinic anhydride. The synthesis of 29 required 13 steps from cyclohexanone, pyrrolidine, and acrylonitrile. Although this synthesis is two steps longer than an alternative... 

Fluorobenzene [5] A solution of phenylmagnesium bromide (from bromobenzene (1.57 g, 10 mmol) in ether (50 ml)) is added dropwise during 30 min to a stirred slurry of /V-fluoroquinuclidinium fluoride (1.49 g, 10 mmol) in ether (15 ml), under an inert atmosphere. An immediate reaction gives a fine white precipitate. The mixture is stirred for 2 h, filtered, and the filtrate added to chloroform, resulting in further precipitation. The mixture is filtered, and the filtrate is concentrated under reduced pressure, and filtered to remove solid quinuclidine. The filtrate is carefully concentrated and the residual liquid is carefully fractionally distilled to give fluorobenzene (0.249 g, 23%), b.p. 84°. 

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