Synthesis Of 4- Amino-1,8- Naphthalimide And Its Analogues

As fluorescent dyes, fluorescent probes and anti-tumor drugs, 1,8- naphthalimide are widely studied and reported. Imide portion of these compounds and naphthalene ring structure can be modified by derivatization to obtain new derivatives,exhibiting structural diversity.The naphthalimide with different structure have a variety of drug activity or different spectral properties, so the study of naphthalimide compounds has attracted the attention of many researchers. PARP(Poly(ADP-ribose)polymerase) inhibitors combined with chemotherapeutic drugs or radiotherapy drugs can improve the efficacy of chemotherapy drugs or radiotherapy. PARP inhibitors can be used alone in the treatment of BRCA deficient tumors, so PARP inhibitor anticancer drugs in recent years become a popular research. 4- amino-1,8-naphthalimide is a PARP inhibitor with moderate intensity, which has been widely used in the study of the function of PARP protein and the activity of PARP as a new inhibitor. One aspect of the study is to explore, improve the synthetic route of 4-amino-1,8-naphthalimide in order to develop more efficient and green synthesis methods; on the other hand the development of new 4-amino-1,8-naphthalene imide derivatives, naphthalimide derivatives to expand the type and provide a reference for future study.The traditional synthetic route of 4- amino- 1,8- naphthalimide is starting from acenaphthene as raw material, throughing nitration, oxidation, reduction and ammoniated four step reaction to get the product.The synthesis uses the dilute nitric acid and acetic acid to be nitrifyed, the sodium dichromate and acetic acid to be oxidized. These materials will pollute the environment, and has strong causticit to the equipment. We explore a new synthetic route, that is to put industrial products 4-bromo- 1, 8-naphthalic anhydride as raw materials,and then aminate and azide it, so we reduce three steps for the preparation of 4- amino- 1, 8-naphthalimide. The method of relationship synthetic reaction steps, improves total yield, and avoid the use of sodium dichromate, dilute nitric acid,so the route is much more environmental protection, and is suitable for mass production of 4- amino- 1. 8 naphthalimide. We use SnCl2 /HCl to reduce azide group.The method is efficient, and cost less,so we think it is a beneficial exploration to put azide group into amino.In order to expand the naphthalimide compounds, and provide the basic train of thought for following study, we designed and synthesized four 4- amino- 1,8-naphthalimide structure analogues x, y, A1, A2, and these compounds were characterized by IR, NMR hydrogen spectrum and carbon spectrum), to determine the correctness of the structure. In addition, we also explored the synthetic routes of the four compounds M3, M1, M2 and A3, which providing the basis for further theoretical research.