A recent synthesis in our drug discovery program required access to 4,7-diaminoisoindoline-1,3-dione (1, also 3,6-diaminophthalimide) in 250–500 mg quantities. This compound has been previously reported from the known 4,7-dichloroisobenzofuran-1,3-dione (also 3,6-dichlorophthalic anhydride). The preparation of this anhydride involved zinc promoted hydrodechlorination of 3,4,5,6-tetrachlorophthalic anhydride under basic conditions to initially give 3,4,6-trichlorophthalic acid. Further dechlorination with zinc generated 3,6-dichlorophthalic acid, and boiling in toluene with azeotropic removal of water gave 3,6-dichlorophthalic anhydride. We repeated this sequence on a small scale to get all of these compounds with physical and spectral properties identical to those reported. Subsequent reaction of 3,6-dichlorophthalic anhydride with excess aq NH3 and CuI (sealed tube, 120–130 C, 8 h) according to the literature procedure, however, gave a product that melted at 273–275 C, which did not match the reported value. Spectral analysis of this material suggested that it was 4-amino-7-chloroisoindoline-1,3dione rather than the diamino compound. The H NMR spectrum displayed a singlet at d 11.1 (1H) for the imide proton, two doublets at d 7.38 and d 7.02 (1H each) for the coupled protons at C6 and C7, and a broad singlet at d 6.53 (2H) for the amino protons. Additionally, the C NMR showed eight carbons rather than four carbons expected for the symmetrically substituted phthalimide, and the mass spectrum gave parent ion peaks at 196 and 198 in an approximate 3:1 ratio. Though the original work apparently did yield the correct product from 3,6-dichlorophthalimide, problems were documented when 3,6-dichlorophthalic anhydride was used as the starting material. Since the 4-amino-7chloro derivative did not meet our needs and the procedure was rather labor intensive, this approach was not repeated, but instead, we opted to develop our own route to the 4,7diamino compound. Our findings are reported below. The successful synthesis required two steps and was more straightforward than the

中文翻译：

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4,7-Diaminoisoindoline-1,3-dione

我们的药物发现计划中最近的一项合成需要获得 250-500 毫克的 4,7-二氨基异吲哚啉-1,3-二酮（1，也是 3,6-二氨基邻苯二甲酰亚胺）。该化合物先前已由已知的 4,7-二氯异苯并呋喃-1,3-二酮（也称为 3,6-二氯邻苯二甲酸酐）报道。这种酸酐的制备涉及锌促进 3,4,5,6-四氯邻苯二甲酸酐在碱性条件下的加氢脱氯，最初得到 3,4,6-三氯邻苯二甲酸。用锌进一步脱氯生成 3,6-二氯邻苯二甲酸，在甲苯中沸腾，共沸除去水，生成 3,6-二氯邻苯二甲酸酐。我们在小范围内重复了这个序列，以获得所有这些化合物的物理和光谱特性与报告的相同。3的后续反应，然而，根据文献程序，使用含有过量 NH3 和 CuI 水溶液的 6-二氯邻苯二甲酸酐（密封管，120-130 C，8 小时），得到的产物在 273-275 C 下熔化，这与报告值不符。该物质的光谱分析表明它是 4-amino-7-chloroisoindoline-1,3dione 而不是二氨基化合物。1H NMR 光谱显示酰亚胺质子在 d 11.1 (1H) 处有一个单峰，C6 和 C7 处的耦合质子在 d 7.38 和 d 7.02 处有两个双峰（各 1H），在 d 6.53 (2H) 处有一个宽单峰氨基质子。此外，C NMR 显示八个碳，而不是对称取代的邻苯二甲酰亚胺预期的四个碳，并且质谱在 196 和 198 处以大约 3:1 的比例给出母离子峰。虽然最初的工作显然确实从 3 中产生了正确的产品，6-二氯邻苯二甲酰亚胺，当使用 3,6-二氯邻苯二甲酸酐作为起始原料时出现问题。由于 4-氨基-7 氯衍生物不能满足我们的需要，而且该过程相当费力，所以没有重复这种方法，而是选择开发我们自己的 4,7 二氨基化合物路线。我们的发现报告如下。成功的合成需要两个步骤，并且比