Benzyne and thiophene

A report of 2 + 2- and 4 + 2-cycloadditions of benzyne and thiophene provides several reaction paths to account for the 1-naphthyl and 2-naphthyl phenyl sulfide products. A DFT study of these paths shows that some presumed reaction intermediates are not stable entities. A new reaction path adapting a portion of the literature paths but with a lower activation free energy, is described.2 The 4 + 2 path crosses over from (5) and joins the 2 + 2 path with structure (6). The paths appear to proceed by both 2 + 2 and 2 + 4-additions with equal facility. 

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... 

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-... 

A DFT study of the 2 + 2/4 + 2-cycloaddition of benzyne with thiophene to produce 1-naphthyl- and 2-naphthyl phenyl sulfides led to a modification of the originally proposed reaction pathway.1 The reaction of an E-Z mixture of 7-benzylidenecycloocta-1,3,5-triene (1) with TCNE yields a mixture of 2 + 2- [(2) and (3)], 4 + 2- [(4) and (5)], and 8 + 2- (6) cycloadducts. The presence of pentadienyl and homotropylium zwitterions accounts for the products isolated (Scheme l).2... 

Tetrachloronaphthalene (26) and tetrachlorobenzothiophene (27) from tetrachlorophthalic anhydride formed by addition of tetrachloro-benzyne to thiophene and subsequent loss of sulphur and acetylene, respectively (Fields and Meyerson, 1967e) ... 

As benzothiophene was a product of both the reaction of benzyne with thiophene and the pyrolysis of thiophene alone (Fields and Meyerson, 1966d), we investigated the reaction of benzyne with benzothiophene. Pyrolysis of a mixture of phthalic anhydride and benzothiophene gave the products shown in Table 11. Anthracene and dibenzothiophene probably arose via 1,2-, and phenanthrene via 1,4-addition to the thiophene ring ... 

Aryne interconversion, involving the transfer to benzyne of two hydrogen atoms from adjacent positions of another aromatic compound, is apparently possible at high temperatures (see discussion of thiophen, Section V,B). 1,4-Abstraction of hydrogen atoms by benzyne is the most probable explanation of the aromatization of the Diels-Alder adducts of benzyne and some styrene derivatives under the relatively mild conditions used for benzyne generation from o-bromofluorobenzene or benzenediazonium-2-carboxylate (4) (Scheme 4).24... 

Vinylbenzo[b]thiophen and benzyne (from o-bromofluorobenzene) afford 62 (13%) dehydrogenation of the 1 1 adduct 61 is possibly induced by attack of benzyne.60 Formation of the 1 1 adduct 45 (14%), from benzyne and l,3-diphenylbenzo[c]thiophen (143) is accompanied by some desulfurization to give 9,10-diphenylanthracene (9%)48 45 also loses sulfur at 250°C. 

Benzoselenadiazole (128) behaves as a heterodiene toward dimethyl acetylenedicarboxylate, with which it gives the quinoxaline 124 and selenium. But 128 reacts differently with benzyne (generated from 4 or from 9) to give the 1,2-benzisoselenazole derivative 132 (88%) and a small amount of a cis,trans stereoisomer of 132.82 The analogous adduct 131 is obtained in lower yield from benzyne and 2,1,3-benzothiadiazole (127). The structure of these benzyne adducts is strikingly reminiscent of 135, which is obtained from a photochemical addition of dimethyl acetylenedicarboxylate to 126 via a nitrile oxide intermediate.84 However, for reasons given elsewhere,82 a nitrile selenide is unlikely to be an intermediate in the formation of 132, which is better explained by the mechanism outlined in Scheme 16. As in the case of thiophen (Section V,B), this is a 1,3-cycloaddition (in one or two steps) of benzyne to the heterocycle, enabled by the use of d orbitals on the sulfur or selenium atom. 

Benzyne and substituted benzynes, generated by thermal decomposition of 2-carboxybenzenediazonium chloride or by aprotic diazotization of appropriate anthranic acids, reacted with a variety of thiophene dioxides to produce naphthalene derivatives generally in moderate yields (Scheme 56) [34,159]. In two cases, the naphthalenes so produced further reacted with benzyne to give benzobarrelene derivatives. 

Only one example of an ene reaction is reported [40]. As already described, ben-zyne and thiophene dioxides undergo [4+2] cycloaddition. However, the reaction of 3,4-dineopentylthiophene 1,1-dioxide with benzyne affords compound 98, the product of an ene reaction. The other two products, 99 and 100, result from [4+2] cycloaddition (Scheme 59). 

The question that we should answer now is not only one concerning the relative reactivity of these dienes and dienophiles, but additionally, whether the addition of these dienophiles (ethylene, benzene, and benzyne) to furan and thiophene is experimentally feasible. That can only be properly addressed by computing activation barriers. Semiempirical methods tend to produce very similar and very narrow differences in activation barriers for different diene-dienophile reactant... 

Arynes, such as benzyne (1,2-dehydrobenzene), also undergo Diels-Alder cycloaddition reactions. Benzyne, CelTj, is a highly reactive species and can be prepared by elimination of a suitably substituted benzene derivative. It reacts in situ with various dienes such as furan, cyclopentadiene, cyclohexadiene and even benzene and naphthalene to give bicyclic or polycyclic cycloadducts (3.15). Analogous addition reactions are shown by dehydroaromatics in the pyridine and thiophene series. 

The 4-hydroxy-THISs react with electron-deficient alkynes to give cycloadducts (3) that spontaneously eliminate sulfur, producing 2-pyridones (3). Bulky 5-substituents lead to a decrease in the addition rate, and elimination of isocyanate with formation of thiophenes becomes favored (3, 12, 13). Benzyne yields an isolable adduct that exclusively extrudes isocyanate on thermolysis, but sulfur on irradiation (Scheme 7)... 

Benzyne, generated from diphenyliodonium 2-carboxyIate, reacts with various thiophenes by addition to the sulfur and /3-carbon to give, after loss of an acetylene moiety, benzo[Z)]thiophenes in low (<4%) yield (Scheme 52) (81CC124). 

Despite the fact that the history of hetarynes is older than that of the benzynes (cf. 2), physical data on these compounds are scarce. Numerous trapping experiments furnished evidence for the formation of brradicaloid intermediates in the field of five-membered heterocycles (didehydrofurans, -thiophenes, and -pyrroles)." Direct spectroscopic data on these species, however, do not exist, which may be attributable to the increased ring strain in the five-membered o-arynes, associated with a strong tendency to undergo ring-opening reactions. 

The first successful Diels-Alder addition of thiophene appears to have been with tetrafluorobenzyne (66CC143). The adduct apparently loses sulfur, resulting in the isolation of the tetrafluoronaphthalene in 40% yield (Scheme 78). Other thiophene derivatives (69T25) and fluorinated benzynes <71JCS(C)604) have been similarly reacted. Subsequently it was found (80H 14)647) that unsubstituted benzyne, generated from diphenyliodonium-2-carboxylate, could be trapped with thiophene to form naphthalene in 33% yield. The earlier failure to add thiophene to benzyne generated by other methods must have been due to intervention of side reactions. Thiophyne also has been similarly trapped to yield benzo[A]thiophene (see Section 3.14.2.2). 

Vinylbenzo[6]thiophene undergoes Diels-Alder reactions with benzyne,468 maleic anhydride,469 benzo[6]thiophene-1,1-dioxide,469 p-benzoquinone, and various 1,4-naphthaquinones.469,470 With quinones, the product depends on the reaction conditions. For... 

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