Benzyne isolation

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)... 

Although neither benzyne nor any other aryne has been isolated, it appears from the foregoing that we are justifled in considering these intermediates to be short-lived substances, the properties of which can be described by the series of resonance structures 17 and 21-23. 

The aporphinoid alkaloid PO-3 (129) was also prepared by intermolecular benzyne cycloaddition between 1-methylene isoquinolines 148 and arynes derived from 147 (Scheme 53). The alkaloid was finally isolated by means of preparative thin layer chromatography (91JOC2984). 

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. 

The reaction of pyridazine 1-oxide or 3- and/or 6-substituted pyridazine 1-oxides with benzyne gives 1 -benzoxepins 2 in variable yield. As byproducts, the respective 3-(2-hydroxyphenyl)pyrid-azines 3 can be isolated in 0-20% yield.88... 

Species such as 5 and 6 are called benzynes (sometimes dehydrobenzenes), or more generally, arynes, and the mechanism is known as the benzyne mechanism. Benzynes are very reactive. Neither benzyne nor any other aryne has yet been isolated under ordinary conditions, but benzyne has been isolated in an argon matrix at 8 where its IR spectrum could be observed. In addition, benzynes can be trapped for example, they undergo the Diels-Alder reaction (see 15-58). It should be noted that the extra pair of electrons does not affect the aromaticity. The... 

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... 

Since the nitrogen in pyridine is electron attracting it seemed reasonable to predict that the trihalopyridynes would also show the increased electrophilic character necessary to form adducts with aromatic hydrocarbons under similar conditions to those employed with the tetra-halogeno-benzynes. The availability of pentachloropyridine suggested to us and others that the reaction with w-butyl-lithium should lead to the formation of tetrachloro-4-pyridyl-lithium 82 84>. This has been achieved and adducts obtained, although this system is complicated by the ease with which pentachloropyridine undergoes nucleophilic substitution by tetrachloro-4-pyridyl lithium. Adducts of the type (45) have been isolated in modest yield both in the trichloro- and tribromo- 58) series. 

As we had hoped, -dimethoxybenzene reacted with tetrafluoro-benzyne to form initially a mixture of the two adducts (74) and (75) in the approximate ratio of 1 2.2. The compound (65) was again isolated... 

The reactions of benzyne with enol-ethers and enol-acetates have been much studied very recently 115-118). We were not surprised therefore to isolate a product derived from the attack of tetrafluorobenzyne on the bis-enol-ether (75). This product is derived from a (2 + 2) n cycloaddition and the available evidence suggests that this product has the structure (78). 

Benzyne reacts with 7-dehydrocholesteryl methyl ether to form the ene products (110) and (111, X = H), while with tetrafluorobenzyne we isolated the anticipated cyclo-adduct (112) in addition to an ene product (111, X = F) 152>. We expected that less crowding would obtain in the transition states leading to cyclo-adducts from cholesta-2,4-diene, and obtained from a reaction with benzyne both the a- and 3-adducts (113, X = H) and (114). In a reaction with tetrafluorobenzyne we only obtained the a-adduct (113, X = F). 

It had been reported that, for example, 5.7.9(ll)-cholestatrienyl acetate shows a greater reactivity towards dienophiles than the corresponding 5,7-dienes 153>. We therefore investigated reactions with tetra-fluoro- and tetrachloro-benzyne 152>. The two isomeric adducts (115) and (116) were obtained in only modest yields with tetrafluorobenzyne, while with tetrachlorobenzyne no adducts or ene products were isolated. 

In view of our results obtained in reactions of the tetrahalogeno-benzynes with aromatic compounds we carried out a reaction of tetra-fluorobenzyne with the A-ring aromatic steroid 3,l7,fl-dimethoxy-oestra-l(10),2,4-triene (119) 154>. As we expected the initially formed enol-ethers were very rapidly hydrolysed and the adducts were isolated as the ketones (120) and (121). The mass spectra of the compounds (120) and (121) did not show molecular ion peaks and as anticipated the ketones were rapidly converted into the naphthalenes (122) and (123) photo-chemically. 

It is known that benzenediazonium-2-carboxylate decomposes to give benzyne via the zwitter-ion (128) 161>. We therefore checked that benzyne is involved in our reactions by carrying out reactions with cinnamaldehyde using benzyne generated from benzothiadiazole-1,1-dioxide 162), diphenyhodonium-2-carboxylate i 3,164)( weil as fr0m anthranilic acid165). Flavene was isolated from each reaction and hence our reactions do involve aiynes and are not arynoid 13 8). 

Benzyne itself has been isolated in solid argon at 8 K, and much evidence for the existence of arynes has come from trapping experiments and spectroscopy. Thus generation of benzyne (101) in the presence of furan (102) leads to the formation of the Diels-Alder (p. 197) adduct (103), which undergoes ready acid-catalysed... 

Benzyne generated in situ by diazotization of anthranilic acid adds readily to aminides 172 to provide cycloadducts 171. Introduction of a nitro group into para position of the phenyl ring on the nitrogen terminus of the 1,3-dipole (X2 = N02) stabilizes the system and results in higher yields of product 171 (70% vs. 50% forX2 = H). Electron-deficient imines react also with aminides 172, but the yields of isolated adducts 173 are relatively low (10-26%) (Scheme 19) <2003ARK(vii)110>. 

Dehydrophenol 20i is a tautomeric form of carbene la, and a [1,3]-H migration should in principal interconvert these species. However, under the conditions of matrix isolation the benzynes 201—1 are thermally and photochemically stable towards rearrangement to the corresponding carbenes. UV irradiation of 20i results in a ring-opening and formation of so far unidentified acetylenic products. 

Benzynes are highly strained molecules, which are recognized as useful intermediates in organic synthesis.44 They can be isolated by coordination to transition metals.45 Similar to the reaction of the cyclohexyne species 66, Ni-benzyne complex such as 85 reacted with C02 to give the corresponding five-membered oxanickelacyle complex 86 (Scheme 31).46... 

For the formation of indoles 2 and 3 we assumed that amines 1 first reacted with fBuLi at -110°C to give N-(2-lithioallyl)amines 4, through halogen-metal exchange 23 this was confirmed by deuteration and isolation of the deuteriated amine 5 a (Scheme 2). Intermediate 4, which is stable for several hours at —110 °C, probably undergoes proton-abstraction ortho to the fluorine atom by the additional equivalents of fBuLi when the temperature is raised to — 40 °C giving the intermediate 6. The subsequent elimination of LiF produces a benzyne intermediate 7, which is efficiently... 

Ortiz de Montellano, P.R. and Mathews, J.M. (1981) Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct. Biochemical Journal, 195 (3), 761-764. 

Species identified by matrix isolation include cyclobutadiene and benzyne, where products derived from these molecules are formed at higher temperatures. 

The matrix isolation and spectroscopic characterization of m- and p-benzynes and their derivatives have been reported. Fourier transform ion cyclotron resonance mass spectrometry has been employed to investigate the reactivity of w-benzyne biradical with a pyridinium charge site in the 5-position. The chemical properties of w-benzyne in the gas phase differ from those of the monoradical and... 

It should be noted that the 1 1 adducts of benzyne with pyrrylmag-nesium iodide, and A -methyl- and iV-benzylpyrrole were isolated and characterized only as the hydrobromide (113), the methiodide (115), and the picrate of 102, respectively. The low yields of all these derivatives are due in part to further reactions of thenaphthalen-l,4-imines with benzyne (see Section III, F and G). Yields are better where the starting pjnrole has an electron-withdrawing N-substituent. Some analogous naphthalen-l,4-imines expected from 1,2,5-trisubstituted pyrroles apparently rearrange spontaneously to j3-naphthylamine derivatives under the conditions for their formation (see Section III, F). The related adducts 107 and 108 are formed from tetrahalobenzynes and N-methy Ipyrrole. 

A variety of experiments have shown that benzyne is a real molecule. However, no one yet has been able to isolate this unstable substance. 

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