Metallation at a ring carbon atom

Another possibility to introduce a substituent E at position 5 (E = Me, TMS, CH2Ph, C02Me, I) is to use the tosyl substituent as protecting group. For example, 1-arylpyrazoles can undergo ortho-lithiation on either the aryl substituent or the pyrazole 5 position 92CL357 . 

2 Hydrogen exchange at ring carbon in neutral pyrazoles 

Progress has not been made on the base-catalyzed hydrogen exchange of pyrazoles since the early 1980s 84CHEC-I(5)I67 . Begtrup 92ACS1096 reports that H3 and H are more acidic in 1-benzylpyrazole-2-oxide than in the parent 1-benzylpyrazole. 

The carbanion can usually be masked or trapped as a more metalloid derivative and be released in the presence of an electrophile. Trialkylsilane and trialkylstannane derivatives are most often used (81T4069, 88G211), for example in ipso substitution with acyl halides. 

In pyridazines, base-catalyzed hydrogen-deuterium exchange takes place at positions 4 and 5 more easily than at positions 3 and 6. Pyridazine 1-oxide reacts first at positions 5 and 6 and then at positions 

3 and 4. Pyrimidine exchanges as expected most readily at the 5-position, next at the 4-, and least readily at the 2-position. In pyrimidine 1-oxide, the reactivity order is2 6 4 5. 1,2,4-Triazines easily undergo base-catalyzed hydrogen exchange in the 3-position. 

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Reduction by complex hydrides Azide ions and nitrite ions Nucleophilic Attack at Hydrogen. 6.1 Metalation at a ring carbon atom... 

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