Reactions of Benzyne with Benzene

Arynes from Aromatic Anhydrides A. Reactions of Benzyne with Benzene 

The partial mass spectrum (McLafferty and Gohlke, 1959 Meyerson, 1965) of phthalic anhydride and tentative structures of the ions in the main reaction sequence are  

The large amount of C6Ht formed, most simply formulated as benzyne, although the structure is not established, prompted us to try to duplicate this reaction thermally. 

Accordingly, a 0-1 molar solution of phthalic anhydride in benzene (100 ml.) was pyrolyzed at 690° under nitrogen at a steady rate of 30 ml/hr (Fields and Meyerson, 1965). The pyrolysis tube was Vycor, filled with Vycor beads contact time was 11 5 sec, which gave a 58% conversion of the phthalic anhydride. Acetylene was steadily evolved, along with carbon dioxide and carbon monoxide in a 1 1 ratio these were identified in the gas stream by mass-spectral analysis of samples taken at regular intervals. The benzene was distilled off and the products boiling over 180° (2 g) were analyzed by mass spectrometry on a Consolidated Model 

The major portion of the pyrolysate, apart from 0-62 g of unconverted phthalic anhydride, was 1-05 g of a mixture of naphthalene (15%) and biphenyl (85 %). Benzene (100 ml), pyrolyzed under identical conditions, gave no acetylene, and only 0-18 g of high-boiling product, which consisted of about 96% (0-17 g) biphenyl and 4% (0-072 g) terphenyl. Only a trace of naphthalene (about 0-2%, 0-0004 g) was found. 

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Although benzobarrelene has been used in a number of recent studies, the best available published synthesis" starts with the Diels-Alder reaction of j8-naphthol and maleic anhydride, affording benzobarrelene in ca. 1% yield after five further steps. Minor improvements allow small quantities of benzobarrelene to be prepared in an overall yield of ca. 10%. The reaction of benzyne with benzene is relatively inefficient, giving benzobarrelene in ca. 2% yield. When benzyne is generated by decomposition of benzenediazonium-2-carboxylate at high dilution in benzene, the yield of benzobarrelene is raised to 14%. The reactions of benzyne with other aromatic substrates are equally inefficient. 

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 analogues of the other products formed in the reaction of benzyne with benzene, 2,3,4,5-tetrafhiorobiphenyl (23), octafluorobiphenylene, and tetrafluorobenzocydo-octatetraene (26), have not been detected in the reactions of tetrafluorobenzyne with benzene. 

Triptycene is the Diels-Alder cycloaddition product from the reaction of benzyne with anthracene (compound A). Although anthracene is aromatic, it is able to undergo cycloaddition at the center ring with a dienophile because the adduct retains the stabilization energy of two benzene rings. 

The reaction of benzyne with hexachlorobenzene was tried (Fields and Meyerson, 1967d). This compound, in spite of steric crowding, is stable to heat (Krynitzky and Carhart, 1949) and to electron impact in the mass spectrometer (Meyerson and Fields, 1966c), as well as inert chemically. At 690° for 35 sec. it was recovered unchanged. With phthalic anhydride in a 2 1 mole ratio, under the same conditions, it gave about a 5% conversion to hexaehlorobiphenyl, the benzyne insertion product. Absence of any chlorinated naphthalene indicates the difficulty of forming a 1,4- or 1,2-adduct of benzyne with the completely shielded benzene ring. 

Cycloaddition reactions were illustrated in CHEC-I by, for example, reactions of benzyne with pyridazine A -oxides and A -acetylimides (to give 2-hydroxy- and 2-acetylaminophenylpyridazines), inverse electron demand cycloaddition reactions of pyridazinecarboxylates with electron rich acetylenes (to give pyridines and benzenes) and dipolar cycloaddition reactions of a pyridazinone with... 

AMI studies of the 2 - - 2-cycloaddition of ketenimines with imines show that the reaction involves a stepwise mechanism via an intermediate and two transition states. A computational investigation of the thermal 2 - - 2-cycloaddition between imines and ketiminium cations finds that the reaction takes place via a stepwise mechanism.The reaction of benzyne with Schiff bases, diimines, yields l,4-bis(2-substituted acridin-10-yl)benzene via an initial double 2 - - 2-cycloaddition. 

Whereas only one dehydrobenzene, benzyne, has been detected, two pyridynes are possible. Thus, the scheme we can write ab initio for the action of a nucleophile on the isomeric monosubstituted derivatives of pyridine involving 2,3- (26) and/or 3,4-pyridyne (31) is more complicated than that for the analogous reaction of the corresponding benzene derivative. The validity of this scheme can be checked using data available in the hterature on reactions of halogenopyridines with potassium amide and hthium piperidide involving pyridynes. 

The reactions of benzyne and carbenes with phosphabenzenes and of carbenes with phospholes have been investigated. Whereas benzyne reacted in the anticipated manner with (27) to give (28), carbenes, or their precursors, reacted in a curious manner to give substituted benzenes (30). Good evidence for the intermediacy of the phosphepin (29) came from the finding that closely related compounds, such as (31), also decomposed to give substituted benzenes. The nature of the eliminated phosphorus entity has still to be determined. 

Another surprising feature appears in the reactions of certain alkyl-benzenes with tetrabromo- and tetraiodo-benzyne generated by the aprotic diazotisation of the corresponding anthranilic acids S9K While only one product (41, X = Br or I, R = H or Me) was obtained in the reactions with benzene or -xylene, three products, (42, X = Br or I, R = Me, Pr1, or But), (43, X = Br or I, R = Me, Pr1, or But) and a naphthalene derivative a> were obtained in reactions with toluene, cumene (isopropylbenzene), and f-butylbenzene. 

Scheme 2.7 Non-benzyne mechanism to account for rearrangement in the reaction of 4-bromomethoxy-benzene (15) with lithium diethylamide.

Biphenyl, benzocyclooctatetraene (9), and benzobicyclo[2,2,2]octatriene (10) resulted from the reaction of benzyne (by decomposition of benzene-diazonium carboxylate) with benzene at 45° (Miller and Stiles, 1963). Both 9 and 10 have been found to go to naphthalene and acetylene 9 on photolysis (Fonken, 1963), and 10 in a sealed tube at 300° (Miller and Stiles, 1963). 

We propose rather that thiophyne is formed by intramolecular dehydrogenation, and that the minor pyrolysis products of thiophene arise from the reaction of thiophyne with thiophene (Scheme 22). Phenylthiophene is a major product from benzyne and thiophene, and therefore suggests the intervention of benzyne in thiophene pyrolysis. A likely source of benzyne in this system is the 1,4-addition of thiophyne to thiophene followed by loss of acetylene and sulfur (Scheme 23). Such a scheme parallels the behavior of benzene, which at 690° gives a small amount of naphthalene, arising presumably from intramolecular... 

In one of the first contributions to the field, Friedman reported on the ability of silver to influence the reactivity of benzyne toward benzene (Scheme 2.1). In the absence of silver, benzyne 2, generated in situ from 1, reacted with benzene in a [4+2] manner to afford adduct 3 in addition to small amounts of dimerization product 4.6 However, in the presence of substochiometric amounts of silver ions, the course of the reaction was altered, leading to formation of biphenyl 5 and benzocycloctatriene 6. A contingent of other metal ions including T1+, Cu +, Cu2 +, Hg22 +, and Hg2 + were unable to influence product formation in a similar manner. 

We reported that the palladium-catalyzed reaction of arynes with bis-jr-allyl palladium complex afforded 1,2-diallylated derivatives of benzene in good yields (Scheme 32) [77]. The reaction of 104 with allyltributylstan-nane 3a and allyl chloride 11 in acetonitrile in the presence of 2.5 mol % Pd2(dba)3.CHCl3/dppf catalyst at 40 °C for 12 h afforded 1,2-diallyl benzene 105 in 76% yield. The generation of benzyne 106 takes place presumably first from 104 under the conditions of the palladium catalysis, which reacts with the complex 2 in a manner similar to the diallylation of activated olefins (refer Scheme 29). 

An organocopper intermediate was detected by Lewin and Cohen in the reaction of / -iodotoluene with copper in a good complexing solvent (184). Analysis of protonated aliquots from a reaction performed in quinoline indicated an accumulation of />-tolylcopper to a maximum of 43% after 95 hours, at which point the iodide was consumed, and then a slow decrease to by dimerization. Other experiments also indicate the formation of an arylcopper compound in Ullmann reactions (127,141, 210). The isolation of deuterated products, presumably from the decomposition of an intermediate organocopper species in deuterated benzene and cyclohexane, suggested decomposition to free radicals (127). Decompositions of certain o-haloarylcopper intermediates by a benzyne mechanism cannot be totally excluded. The formation of a dichlorobenzene and by-products such as dibenzofuran and triphenylene from only the ortho isomer of the chloroiodobenzenes in Ullmann coupling reactions (210)... 

Polyfluoroaryl-lithiums and, to a lesser extent, the Grignard reagents will decompose by a (3-elimination of metal fluoride, leaving an aryne whose properties are considerably affected by the remaining fluorine atoms. The highly electrophilic nature of these species leads to some reactions, e.g. with benzene derivatives, that are not shown by benzyne itself [228] (Figure 9.88). 

Benzyne complex 58 (L = PMes) reacts with AcR (R = Me, Ph) to afford the cyclo-metalated complex 59 plus methane or benzene, respectively , and with MesNHCl and KOC(=CH2)Me to give 60a, for which intermediate 61a has been isolated. Complex 60a rearranges in solution at room temperamre to give the oxametalacyclobutane 62, which at 45 °C leads to 59 and methane, providing strong evidence that 60a and 62 are intermediates in the reaction of 58 with AcMe to give 59 . Furthermore, 62 reacts with... 

Benzyne. 1 -N itrosobenzotriazole (1), prepared by the reaction of benzotriazole with nitrosyl chloride, reacts vigorously with the reagent at room temperature in benzene solution with evolution of nitrogen. Reaction in the presence of tetra-phenylcyclopentadienone (I, 1149-1150) gives the benzyne adduct, 1,2,3,4-tetraphenylnaphthalene (3), in 23% yield. Presumably the nitrene (2) is formed initially. ... 

Since considerable trimethylamine was observed, the fate of the phenyl group was examined. It was determined by carbon-14 labeling, that biphenyl results from the reaction of phenyllithium with 5. However, it is most unlikely that the phenyl group can be displaced by phenyllithium in an 5 2 reaction. Therefore, it was suggested 157> that proton abstraction occurs at the ortho carbon of the benzene ring to give benzyne which subsequently reacts with phenyllithium to give biphenyl. 

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