Amines diazotization with metal halides

Primary alkyl amines RNHi can be convertedto alkyl halides by (1) conversion to RNTs2 (p. 447) and treatment of this with I or Br in DMF, or to N(Ts)—NH2 derivatives followed by treatment with NBS under photolysis conditions, (2) diazotization with terr-butyl nitrite and a metal halide such as TiCU in DMF, or (3) the Katritzky pyrylium-pyridinium method (pp. 447,489). Alkyl groups can be cleaved from secondary and tertiary aromatic amines by concentrated HBr in a reaction similar to 10-71, for example,... 

In summary, sulfonamides are most commonly prepared by the reaction of amines with sulfonyl halides. Aryl sulfonyl chlorides may be accessed from C-H bonds by chlorosulfonylation, from C-S bonds by oxidation, from C-N bonds by diazotization, or from C-X bonds by metalation. Approaches to all l sulfonamides are more limited as they are typically prepared by either oxidative chlorination of thiols or addition of organometallic nucleophiles to sulfur electrophiles. Traditional sulfonamide preparation has frequently necessitated harsh reagents and conditions, but the development of Pd-catalysed approaches and discovery of new sulfur dioxide sources allow for operationally simple sulfonamide synthesis under mild conditions. Future directions in sulfonamide synthesis will likely involve the direct C-H installation of sulfonamides without the use of hazardous reagents. 

There are three common approaches to the displacement of amine substituents from purines. First, diazotization and dediazoniation have been used to replace amine substituents, primarily with hydrogen or hydroxyl, carboxyl, and halide functionalities. Second, the S Ar reactions of quaternary ammonium substituents have provided useful synthetic adjuncts to the displacement reactions of halopurines. Finally, of increasing importance has been the conversion of aminopurines (or oxopurines) to N-linked 1,2,4-triazoles (and other azoles), which function as pseudohalogens and can be displaced by nucleophiles or take part in transition metal-catalyzed reactions. 

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