Phthalazine, hydroxylation

Benzoylphthalazine with sodium hydroxide in dimethyl sulfoxide hydroxylates the phthalazine ring to give, after oxidation, 4-benzoyl-l(2H)phthalazinone (Scheme 16) (85CPB4193). 

This microwave-accelerated double alkylation reaction was applicable to a variety of aniline derivatives and dihalides, furnishing N-aryl azacycloalkanes in good to excellent yields [89]. The reaction was applicable to alkyl chlorides, bromides and iodides and was extended to include hydrazines [90]. This improved synthetic methodology provided a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted-2,3-dihydro-Iff-isoindoles, 4,5-dihydro-pyrazoles, pyrazolidines, and 1,2-dihydro-phthalazines [91]. The mild reaction conditions tolerated a variety of functional groups such as hydroxyls, carbonyls, and esters. 

Formation of the chiral 1,2-amido-alcohol 12 can be achieved in a single transformation by using the asymmetric amino-hydroxylation reaction (see Section 5.3.3). For the regioisomer 12, the linker anthraquinone (AQN) rather than the normal phthalazine (PHAL) is required. For the enantiomer 12, the cinchona alkaloid dihydroquinidine (DHQD) is required. Hence, the reagents and conditions effective for the formation of 12 are ... 

---