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Please login or sign up for a free trial to access the full content. Method 2: From Isoindole Derivatives

DOI: 10.1055/sos-SD-016-00385

Haider, N.; Holzer, W.Science of Synthesis, (200416335.

Readily available 3-hydroxyisoindolin-1-ones 65 are transformed into the corresponding phthalazin-1(2H)-ones 66 upon treatment with hydrazine or substituted hydrazines (Scheme 27);[‌131‌,‌203‌,‌204‌] a mechanism for this ring-enlargement reaction has been proposed.[‌204‌] An elegant method for the synthesis of 4-substituted phthalazinones 69 starts from anilides 67, which, after regiospecific ortho-lithiation and subsequent electrophilic substitution, give the 3-substituted 3-hydroxyisoindol-1-ones 68. Heating of compounds 68 with hydrazine hydrate yields phthalazinones 69 in high yields (Scheme 28).[‌205‌] Reaction of isoindolin-1-one with hydrazine hydrate at 180220°C also affords phthalazin-1(2H)-one (66, R1=R2=H).[‌206‌]

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Meeeeeeeeeeeeeeeeee (88, M=M) ee 8-eeeeeeeeeeeeeeeeee (88, M=MM) eeee 8-eeeeeeeeeeeeeee-8(8M)-eee (88) eeee eeeeeeeee eeee eeeeeeeee eeeeeeeee eeeeeee (Meeeee 88).[‌888‌‌888‌]

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Meeeeeee eeeeeeeee eeeeeeee eeeeeeeeee eeee ee eee eeeeeeeee ee 8-eeeeeeeeeeeeeeeeeee-8(8M)-eee (88) eeee eeeeeeeeeee eeeeeeeeeee 88 eeee ee eeeeeeeeeeeeeeeeeee (8-eeeeeeeeeeeeeeee-8-eee; M=M; M8=M) eee e eeeeeee ee M-eeeee eee M-eeee eeeeeeeeeee eeeeeee, ee 8-eeeeeeeeeeeeeee-8-eee (M=MM; M8=M), eee eeee 8-eeeeeeeeeeeeeeeeeeeeeee (M=MMM8; M8=M) (Meeeee 88).[‌888‌]

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Meeeeeee ee 8-eeeee-8M-eeeeeeee-8-eeeee (88) eeee e eeeeee eeeeee ee eeeeeee eeeeeeeee eeeee eeeeeeeeeee-8,8-eeeeeee (88) (Meeeee 88),[‌888‌] eeeeeee eeeeeeeee ee 88 eeee ee eeeee 8 eeeeeeeeeee ee eeeeeeeee eeeeeee eeeee eeeeeee eeeeeeee eeeeeeeeee eeeeeee 8,8-eeeeeeeeeeeeeeeeeeeeee (8) (Meeeee 88).[‌888‌,‌888‌]

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8-(8-Meeeeee)eeeeeeeeee-8(8M)-eee (88; M8=8-Meeeeee; M8=M): Meeeeee Meeeeeeee:[‌888‌]

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