Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones

Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones <b>9b</b>, <b>9i</b>–<b>9am</b>. Many of these hydroxyisoindolinones are converted to chlorophthalazines <b>1b</b>–<b>1v</b> via reaction with hydrazine, followed by chlorination with POCl₃. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) provided dihydrobenzoazepinediones <b>15a</b>–<b>15c</b> via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids <b>16a</b>–<b>16d</b> and 2-pyrazolyl benzohydrazides <b>17a</b>–<b>17g</b> rather than the expected alkynyl phthalazinones

Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones

Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones <b>9b</b>, <b>9i</b>–<b>9am</b>. Many of these hydroxyisoindolinones are converted to chlorophthalazines <b>1b</b>–<b>1v</b> via reaction with hydrazine, followed by chlorination with POCl₃. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) provided dihydrobenzoazepinediones <b>15a</b>–<b>15c</b> via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids <b>16a</b>–<b>16d</b> and 2-pyrazolyl benzohydrazides <b>17a</b>–<b>17g</b> rather than the expected alkynyl phthalazinones

Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones

Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones <b>9b</b>, <b>9i</b>–<b>9am</b>. Many of these hydroxyisoindolinones are converted to chlorophthalazines <b>1b</b>–<b>1v</b> via reaction with hydrazine, followed by chlorination with POCl₃. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) provided dihydrobenzoazepinediones <b>15a</b>–<b>15c</b> via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids <b>16a</b>–<b>16d</b> and 2-pyrazolyl benzohydrazides <b>17a</b>–<b>17g</b> rather than the expected alkynyl phthalazinones

Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones

Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones <b>9b</b>, <b>9i</b>–<b>9am</b>. Many of these hydroxyisoindolinones are converted to chlorophthalazines <b>1b</b>–<b>1v</b> via reaction with hydrazine, followed by chlorination with POCl₃. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) provided dihydrobenzoazepinediones <b>15a</b>–<b>15c</b> via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids <b>16a</b>–<b>16d</b> and 2-pyrazolyl benzohydrazides <b>17a</b>–<b>17g</b> rather than the expected alkynyl phthalazinones

Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones

Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones <b>9b</b>, <b>9i</b>–<b>9am</b>. Many of these hydroxyisoindolinones are converted to chlorophthalazines <b>1b</b>–<b>1v</b> via reaction with hydrazine, followed by chlorination with POCl₃. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to <i>N</i>,<i>N</i>-dimethylaminophthalimide (<b>8a</b>) provided dihydrobenzoazepinediones <b>15a</b>–<b>15c</b> via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids <b>16a</b>–<b>16d</b> and 2-pyrazolyl benzohydrazides <b>17a</b>–<b>17g</b> rather than the expected alkynyl phthalazinones