Benzene derivatives, halogen chloro

Plazek [28,28b] and Plazek and Talik [28a] stated recently that the reactivity of halogens in nitro derivatives of pyridine is much higher than in the similar benzene derivatives. Thus, at 20°C where only 0.5% of chloro-2,4-dinitrobenzene was subjected to nucleophilic displacement of chlorine by the amino group, the figure was 98.3% for 2-chloro-3,5-dinitropyridine. 

Benzimidazoles are generally synthesized from ortho-diamino-benzenes and carboxylic acid derivatives. The antihistaminic agent, clemizole (60), for example, can be prepared by first reacting ortho-diaminobenzene (57) with chloroacetic acid to form 2-chloro-methylbenzimidazole (58). Displacement of the halogen with pyro-... 

Schlosser and co-workers have reported the shift of lithium in lithiated l-bromo-3-(tri-fluoromethyl)benzene 2,fa Quenching at — 100 C gives exclusively the product derived from 2, whereas after 2 hours at — 75 C, arene 2 is completely converted into less basic 3. A lithium-iodine exchange takes place in lithiated 2-chloro-3-iodo-6-(trifluoromethyl)pyridine 4, which at —85 C is totally converted into the less basic isomer 5.7 These rearrangements have been discussed in terms of a base-catalyzed halogen dance or halogen-shuffling mechanism. 

The halogenation of benzothiazinotropones 361 and 362 as depicted in Scheme 97 affords 7- and/or 9-substituted derivatives like 363 and 364 (66BCJ1980). Chlorination of 362 additionally gives the 9-chloro compound or, on treating the tropone with thionyl chloride in excess (2.5 molar equivalents), a 7,9,Jc-trichloro derivative, presumably substituted at the benzene ring. 

Just as in benzene chemistry, all types of halogen atom are activated toward nucleophilic displacement by the presence of other electron-withdrawing substituents. This is illustrated by the conversion of 2-chloro-5-nitropyridine 938 to the 2-hydrazine derivative (N2H4, 20 C) or the 2-thione 939 under relatively mild conditions. 

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