Benzyne formation

Halogen Reactions. Hydrolysis of chlorotoluenes to cresols has been effected by aqueous sodium hydroxide. Both displacement and benzyne formation are involved (27,28). o-Chlorotoluene reacts with sodium in Hquid ammonia to afford a mixture of 67% of o-toluidine [95-53-4] and 33% of yW-toluidine [108-44-1], C H CIN, as shown in equation 3 (29). 

Other examples of the ElcB pathway are benzyne formation from C6HsF (cf. p. 174), reversal of simple nucleophilic addition to 0=0, e.g. base-induced elimination of HCN from cyanohydrins (20 cf. p. 212),... 

Chlorobenzene is lithiated more slowly and cannot be lithiated completely at temperatures where benzyne formation is slow. With 1,2,3,4-tetrachlorobenzene 165, MeLi leads to ortholithiation f-BuLi, on the other hand, leads to halogen-metal exchange (Scheme 83). ... 

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °C . 

Usutani H, Tomida Y, Nagaki A et al (2007) Generation and reactions of o-bromophenyl-lithium without benzyne formation using a microreactor. J Am Chem Soc 129(11) 3046-3047... 

Ortho-lithiated halobenzenes, prepared by lithium-bromide exchange, undergo rapid benzyne formation at -30, -40, and -50°C for bromo, chloro, and fluoro derivatives [57JA(79)2625]. They normally require... 

Attempted anodic bis-decarboxylation of o-phthalic acid (as its dianion) failed to give any evidence for benzyne formation 174h... 

With the discovery of benzyne formation by pyrolysis of phthalic anhydride, a new field was opened for the investigation of aryne reactions at high temperatures. A first concern was to determine the generality of aryne formation from aromatic acid anhydrides. Such syntheses could be of considerable significance because of the enormous quantities of aromatic mono- and polyanhydrides available from petroleum aromatics by oxidation. 

Finally, if the two-step mechanism is confirmed for benzyne formation in the case of 5, this may be the sole example of aryne formation by such a mechanism, although it is also a possibility for a rhenium-benzyne complex prepared by Arnold el al.30... 

Thermolysis of 6 at 60°C gives the benzyne complex 7. This reaction is significantly retarded by excess trimethylphosphine, which indicates that benzyne formation occurs from a 16-e intermediate. An X-ray crystal structure of 7 was reported. Bond lengths for the benzyne unit are given in Table III. No reactions of 7 have been reported. 

Behydrohalogenation of aiyl halides benzyne formation (Section 16.9)... 

Here benzyne formation involves abstraction of a proton (reaction 5) by the base QH5 to form a carbanion which loses fluoride ion (reaction 6) to give benzyne. 

Each ring contains 6 rr electrons. 20. (a) Via an aryne (b) direct displacement accompanies elimination-addition. Fluoride least reactive toward benzyne formation (p. 838), most reactive toward direct displacement (Sec. 25.12). Piperidine shifts equilibrium (1) toward left, tends to inhibit benzyne formation. 21. UU is aromatic, with 14 n electrons. Methyl protons are insii/e aromatic ring see Fig. 13.4, p. 419. 

For halobenzenes, halogen-Li exchanges and benzyne formation become easier in the sequence I > Br > Cl > F indeed, for iodides and bromides, the most probable reactions are halogen-lithium exchanges (see 5.5.2.3.3.). Halogenoanisoles,... 

Benzyne is able to add nucleophiles very easily7,8 to give anions 3 which after quenching by a proton leads to substituted products 4. It is very important to note that in these condensations nucleophiles operate only after the benzyne formation. 

One of the simplest routes to benzyne starts with aniline which is converted to benzenediazonium ion. Benzyne is liberated when this ion is deprotonated by acetate base in solvents such as benzene, Eq. (20). Detracting from this approach, however, are competing reactions in which phenyl radicals and phenyl cations are formed. Presently it is possible to minimize the importance of radical chain side reactions and thereby to favor benzyne formation by adding a radical trapping agent such as 1,1-diphenylethylene. 8S ... 

Scheme 5.6.21 Three-component cascade with i n situ benzyne formation terminating with allenylstannane capture...

Scheme 5.6.22 Three-component cyclization cascade with in situ benzyne formation terminating in thienyl-...

Cyclopropyllithium may engage itself in various types of reactions depending on the properties of the aromatic compound. When fluorobenzene is the aromatic substrate, benzyne formation followed by hydride transfer is believed to take place, but if the aromatic compound is a diazine or a substituted or annulated pyridine, the first step is nucleophilic addition of cyclopropyllithium to the nitrogen-containing ring of the aromatic nucleus. The predominance... 

As profiled in Figure 6.24, the yield is very low at temperatures higher than —60°C, presumably because of the decomposition of the o-bromophenyllithium intermediate to benzyne. At lower temperatures, the yield increases with a decrease in the temperature because of slower benzyne formation. A further decrease in temperature, however, results in a decrease in the yield, because the bromine-lithium exchange reaction does not complete at such low temperatures within the residence time. 

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