Phthalazine nitration

Upon nitration of phthalazines a nitro group is introduced only into the carbocyclic ring. Side reactions occur frequently. For example, nitration of phthalazine or its 1-methyl analog with potassium nitrate in concentrated sulfuric acid gives the 5-nitro derivative (100) as the main product together with 5-nitrophthalazin-l(2H)-one (101) as a by-producf (Scheme 27). 

Phthalazine-1,4-diones reactions, 3, 39 Phthalazines applications, 3, 56 isoindoles from, 4, 152 mass spectra, 2, 21 metabolism, 1, 233 N-oxidation, 3, 20 nitration, 3, 22 nucleophilic attack, 3, 25 oxidation, 3, 31... 

JOC3221). Nitration of 6-methyl-[l,2,4]triazolo[3,4-a]phthalazine in fuming nitric acidconcentrated sulfuric acid produced the 8-nitro compound (190). On the other hand, attempted nitration of (17) with copper nitrate-acetic anhydride gave only the 3-acetyl compound. The Vilsmeier formylation failed on (17) (69JOC3221) however, deuterium exchange occurred at C-3. The 3-carbaldehyde (see synthesis section) underwent the benzoin condensation and was oxidized to the 3-carboxylic acid. 

Nitration of phthalazine gave only 5-nitrophthalazine (substrate, 96% H2SO4, KNOsi slowly, 0 C, then 55°C, 48 h 79% or likewise but KNOai at 20°C, then 100°C, 132h 20%). ... 

Many nuclear and extranuclear nitrophthalazines have been made by primary synthesis (see Chapter 8). The remainder have been made by passenger introduction (examples in most chapters) or by direct nitration of phthalazine substrates, as illustrated in the following examples. 

Note The nitration of unsubstimted phthalazine to give 5-nitrophthalazine has been described in Section 9.1.3. 

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