Benzyne reaction intermediate

A C2gH,4 hydrocarbon was recently prepared, also by flash vacuum pyrolysis. This interesting reaction, which may involve a benzyne type intermediate, represents the first synthesis of a benzocorannulene. ... 

When potassium amide, with added potassium metal in liquid ammonia, was substituted in the benzyne reaction, further cleavage of C—bonds of the intermediate dibenzopyrrocolines was often observed. The indoline 41 (32) and... 

Special iodonium salts. A range of o-trimethylsilyl-phenyliodonioarenes [111] and heteroarenes [112] as well as some similar Wc-compounds coming from norbornadiene [113] and o-carborane [114] have been obtained from the corresponding bis trimethylsilyl precursors upon reaction with one equivalent of (diacetoxyiodo)benzene. These compounds are useful for their facile in situ conversion into benzyne-type intermediates for benzyne itself the whole procedure is available in Organic Syntheses [115]. A recent improvement involved the synthesis of a new benzyne precursor illustrated in Scheme 38 [116]. 

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. 

Chapter 2 includes complete discussion on reaction intermediates including carboca-tions, carbanions, free radicals, carbenes, nitrines and benzynes. The structure, methods of generation and important reactions of all the intermediates are discussed in this chapter. The author has emphasized on their applications in the asymmetric synthesis. 

This phenol synthesis is different from the nucleophilic aromatic substitutions discussed in the previous section because it takes place by an elimination addition mechanism rather than an addition/elimination. Strong base first causes the elimination of HX from halobenzene in an E2 reaction, yielding a highly reactive benzyne intermediate, and a nucleophile then adds to benzyne in a second step to give the product. The two steps are similar to those in other nucleophilic aromatic substitutions, but their order is reversed elimination before addition for the benzyne reaction rather than addition before elimination for the usual reaction. 

A MINDO/3 study of the singlet and triplet forms of the isomeric bisdehydro-benzenes shows that the singlet state of (1) is the more stable, but that the singlet of (2) is at least comparable in stability, and such intermediates merit consideration in benzyne reaction mechanisms.71... 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

An early case in which the existence of benzyne as a reaction intermediate was... 

The preceding explanation would seem to explain most of the data in Table 8.21, but there is one apparent discrepancy. We might have expected the methoxy substituent to be electron-donating, but it gives the same product orientation as does trifluoromethyl. This intuitive expectation of the substituent effect of methoxy is based primarily on its influence on electrophilic aromatic substitution (SeAr) and on nucleophilic aromatic substitution (SwAr) reactions, both of which involve attachment of a species to an aromatic ring to form a cr complex. In contrast, the carbanionic intermediates presumed to be formed in the benzyne reaction have the nonbonded pair of electrons in... 

Also during the 1940s, the formation of biphenyl (24) from fluorobenzene (26) and phenyl hthium (25) in an uncatalyzed reaction (Scheme 1.9) led Wittig to propose a dehydrobenzene, specifically an ortho-benzyne, as intermediate [39, 40], the formation of which was confirmed by Roberts in 1953 [41]. Modem arylation methodologies based on arynes as key intermediates are reviewed by Yu Chen and Richard Larock in Chapter 12. 

Sol 12. (i) The first equivalent of LDA creates an intermediate as a diene component by deprotonation of nitrogen and the second equivalent induces an E2 elimination to generate a benzyne. The intermediate benzyne is then trapped by an intramolecular Diels—Alder reaction to give the enolate, which after protonation and oxidation by air gives the observed aromatic product. 

Following the development of the MINDO/3 method, which is considerably more successful than MINDO/2 in taking account of strain factors, the possibility of collapse of bisdehydrobenzenes (3) to bicyclic structures has been examined. The most striking conclusion was that (3a) should have a stability comparable to that of o-benzyne, and this suggests that m-benzynes may be viable reaction intermediates. ... 

An early case in which the existence of benzyne as a reaction intermediate was established was in the reaction of chlorobenzene with potassium amide. Carbon-14 label in the starting material was found to be distributed in the aniline as expected for a benzyne intermediate. ... 

Eliminations to create alkenes can occur from neutral structures, or they can involve car-benium ions, carbanions, or radical intermediates. We look at all these possibilities below within the context of aliphatic systems. Although eliminations can occur on alkenes to make alkynes and on arenes (see the benzyne reaction. Section 10.20), we concentrate our discussion on aliphatics, because this is the most common type of system to undergo elimination. Before looking at the details, let s review the E2 and El mechanisms and electron pushing, and define the terms "1,2-elimination", "1,4-elimination", and "p-elimination". 

Elimination of H and Cl produces a very high energy intermediate called benzyne. This intermediate does not survive long because it is quickly attacked by the nucleophile, producing an addition reaction. Nucleophilic attack can take place at (a) the position of the isotopic label or (b) the other end of the triple bond. 

PROBLEM 14.79 The Chapter 14 benzyne reaction is also animated. Benzyne is an intermediate in the elimination—addition version of the Sf Ar reaction, and is a very reactive intermediate. Observe the reaction several times. What are the most acidic hydrogens in the reaction mixture What are the second most acidic hydrogens The animation shows benzene without double bonds. Why are the double bonds left out The animation shows the amide ion ( NH2) attacking one carbon of the benzyne. Observe the LUMO of the benzyne. Could the "NHj attack either carbon of the benzyne Remember that the LUMO tells us about cationic character. How can both carbons of the benzyne have equal cationic character ... 

Benzyne is formed as a reactive intermediate in the reaction of aryl halides with very strong bases such as potassium amide... 

Preparation of phlorogluciaol or its monomethyl ether by reaction of a halogenated phenol with an alkaU metal hydroxide in an inert organic medium by means of a benzyne intermediate has been patented (142). For example, 4-chlororesorcinol reacts with excess potassium hydroxide under nitrogen in refluxing pseudocumene (1,2,4-trimethylbenzene) with the consequent formation of pure phlorogluciaol in 68% yield. In a version of this process, the solvent is omitted but a small amount of water is employed (143). 

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