Arynes detection

Since heteroarynes are thus seen to be subject to strong orientation effects, the detection of the occurrence of the aryne mechanism and the evaluation of the extent of its participation require a special approach. Both the aryne and Sj Arl mechanisms can occur together, and variation of the leaving group on a substrate (e.g., 2-halonaphthalenes) can cause a complete shift from the aryne (2-chloro, -bromo, and -iodo) to the Sj Arl mechanism (2-fluoro) see also Section II, D, 1. 

The question of the occurrence of cine or aryne substitution in some of these reactions has been raised but not answered adequately. The normal product, 2-methoxynaphthalene was shown to be formed from 2-chloronaphthalene and methoxide ion, and the normal 6- and 8-piperidinoquinolines were proved to be products of piperidino-debromination of 6- and 8-bromoquinolines, all in unspecified yield. More highly activated compounds were then assumed not to react via the aryne mechanism. Even if the major product had been characterized, the occurrence of a substantial or predominant amount of aryne reaction may escape notice when strong orientation or steric effects lead to formation of the normal displacement product from the aryne. A substantial amoimt of concurrent aryne reaction may also escape detection if it yields an amount of cine-substituted material easily removed in purification or if the entire reaction mixture is not chromatographed Kauffman and Boettcher have demonstrated that activated compounds such as 4-chloropyridine do indeed react partially via the aryne mechanism (Section I,C,1). 

Most of the subsequent work on this reagent was concerned with the formation of aryl radicals (see review by Cadogan, 1971). However, 2-terf-butyl-A-nitrosoacet-anilide was found to decompose in benzene to give, instead of 2-tert-butylbiphenyl, as expected for a substitution of benzene by a 2-tert-butylphenyl radical, a mixture of isomeric tert-butylphenyl acetates. A careful reexamination (Cadogan and Hib-bert, 1964) suggested that the ratio of 2- and 3-tert-butylphenyl acetates was consistent with the involvement of 2-tert-butylbenzyne, i.e., the product of an ionic dediazoniation, as an intermediate. This was later confirmed by trapping experiments designed to detect aryne intermediates. 

We have also attempted to study the reactions of the tetrafluoro-o-phenylene di-radical (32) with benzene, by carrying out the photolysis of 1,2-di-iodotetrafluorobenzene in the presence of benzene. It is known that 1,2-di-iodoarenes give arynes on photolysis 70-72>. The only product derived immediately from o-dehydrotetrafluorobenzene was the 1,4-cyclo-adduct (24) which was, as expected, partially photoisomerised to (27) and a trace of (26) 73>. The photolysis resulted in the appearance of (24) and (27) before (26) was detected and hence we conclude that (26) was not a primary product. 

The reaction of benzyne with furan was the first example of a Diels-Alder reaction of benzyne to be studied b. No authenticated examples of arynes are known which fail to give cyclo-adducts with furan i38>. The tetrahalogenobenzynes all form the expected adducts 103, X = F 6), Cl 57>i39)j gr 59) or i 59)). d0 other highly fluorinated arynes i40,i4i>. The isomeric adducts (104) and (105) have been detected by 19F n.m.r. spectroscopy when the dilithio-compound (12) was allowed to decompose in the presence of furan 28 103). 

Brown et al. [36] attempted to approach pentalene (2) by a thermolytic ring-contraction-cyclization of 3-ethenylbenzyne 41, which, in turn, was generated by flash vacuum thermolysis of 3-ethenylphthalic anhydride 40. Indeed, the pentalene dimer 43 ( 50%) was formed along with phenylacetylene 44 ( 50%) in 80% overall yield (Scheme 6). The failure to detect monomeric pentalene (2) is in accord with the observation of de Mayo et al. that 1-methylpentalene (37) dimerizes above —140 °C [29]. The formation of phenylacetylene 44 was unexpected, and it is as yet unclear as to whether it arises by migration of two hydrogens in the aryne 41 or the intermediate carbene 42, or whether it is a secondary product formed from pentalene (2). 

To show an analogy between pyridine and nitrobenzene, the latter compound was heated with lithium amide in DMA. The only product, detected by vapor-phase chromatography, was about a 5% yield of m-nitroaniline. It was proposed that the presence of the meta isomer could be explained only by formation of nitrobenzyne intermediates (75CI(L)520). The aryne mechanism for the Chichibabin reaction with pyridine has been severely criticized (64CI(L)659). 

These cycloadditions can be highly regioselective, as in a recent synthesis of apomorphine analog 693 from 691 and 3,4-dimethoxybenzyne 693 was isolated in 34% yield, and none of its regioisomer could be detected in the reaction mixture. Thus initial attack is by the more nucleophilic site of the diene on the more electrophilic (and less hindered) site of the aryne. 

The C—N o-bond of N-aryltrifluoroacetamides and the S—N triple bond to afford l-[2-(arylamino)aryl]trifluoroethanones and (2-arylamino)aryl trifluoromethyl sulfoxides, respectively (Equations 12.19 and 12.20) [25]. The presence of the CF3 moiety in the substrates proved to be crucial for these insertion reachons to occur moreover, the reactions were limited to secondary amides or sulfinamides. No insertion product was detected in the case of the tertiary amide N-methyl-N-phenyltrifluoroacetamide. 

The Diels-Alder reaction is the most prominent reaction of arynes, providing not only a powerful tool to construct various carbocycles and heterocydes of synthetic importance, but also a useful method to detect the generation and existence of transient aryne spedes. Due to their high electrophilidty, arynes have been shown to react with a wide variety of dienes. 

By far the most common and historically oldest aryne generation method involves the elimination of hydrogen halides from aryl halides (32a) in the presence of strong bases (Table 1). " In many cases o-haloarylanions (33) can be trapped as intermediates, although often the elimination of halide ion to the aryne (1) is either too rapid to allow their detection or perhaps concerted. The effect of halogen, metal, and substituents on this reaction has been well studied. ... 

In the last aryne precursor to be discussed in this section the nitrogen to be eliminated is exclusively exocyclic to the cleaving cyclic system. Photolysis of the diazobenzofuranone (61) gives benzyne (1) by the sequential loss of Nj and CO as shown. Each of the numbered species was detected by infrared spectroscopy in an argon matrix at... 

Arynes are very reactive intermediates which enter into a large variety of bimolecular reactions including dimerization. With the exception of apparently slow reactions such as equation (13), no unimolecular decompositions of arynes are known. The direct detection of arynes, therefore, is possible in the gas phase or in dispersed, inert media. Utilizing such conditions the ultraviolet and infrared absorption spectra, ionization potential, enthalpy of formation, rate of dimerization, and approximate lifetimes of arynes have been measured. Most claims for the existence of... 

With selected aryne precursors it has been possible to demonstrate the intermediacy of free arynes in cyclojaddition reactions by other methods. The most convincing of these is the previously mentioned spectroscopic detection of benzyne (1) from the photolysis of phthaloyl peroxide (72) in an argon matrix at 8 K and its subsequent reaction with furan (146a) upon warming to give the adduct 148a. A conceptually similar technique is pseudodilution, in which... 

The formal Diels-Alder adduct (228) of anthracene and didehydromaleic anhydride (23) was subjected to flash vacuum thermolysis at 600°C in the hope that a retro-Diels-Alder reaction (Section II.1.E) might generate the aryne 23. Although the theoretical yield of anthracene was obtained, the aryne 23 could not be frozen out or indirectly detected by trapping experiments the only other identifiable products were CO and which could have arisen directly... 

CO, then the alleged aryne adduct (390) could be formed via an adduct such as 401 and hence without the intervention of the aryne (4). Although such dienophilic reactivity has not been detected for benzocyclopropenones (33), even in the presence of several traditional dienes (146), it has been observed for cyclopropenone itself (but not for diphenylcyclopropenone) and for benzocyclopropene (402). The second step of the proposed sequence 400 to... 

An attempt to detect the aryne 542 from the in situ diazotization of the amino acid 543 with isoamyl nitrite in the presence of furan (146a) or tetracyclone (151) failed to yield any of the aryne adducts 544 or 545, respectively. The only identifiable products isolated in low yield were the acids 546 and 547 and their corresponding nitro compounds 548 and 549. Although it was considered that the latter two compounds might arise via the unlikely dipolar form (542b) of the aryne, it was demonstrated that they were actually transformation products of the former two compounds, 546 and 547, under the diazotization conditions. Similar decarboxylative nitrations with isoamyl nitrite and nitric acid have been observed in related systems. The acids 546 and 547 were proposed to arise from the dipolar species 550,... 

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