title: Short and scalable synthesis of an anhydride precursor of the environment-sensitive fluorophore 6-dimethylaminonaphthalimide.
abstract: Environment-sensitive fluorophores have different quantum yields in different solvents. 6-Dimethylaminonaphthalimide (6-DMN), for example, has a low quantum yield in aqueous solutions, but is highly fluorescent in nonpolar solvents or when bound to hydrophobic sites in proteins or membranes. 6-DMN has been used to investigate protein-protein interactions, as well as the in-tissue distribution and internalization of δ-receptors. This protocol describes a highly efficient three-stage synthesis of 6-dimethylamino-2,3-naphthalenedicarboxylic anhydride (compound 1), which is a stable precursor that can be converted to 6-DMN. The three stages are (i) photo-bromination of 4-nitro-o-xylene (yield 82%), (ii) Diels-Alder reaction followed by base hydrolysis, resulting in 6-nitro-2,3-naphthalenedicarboxylic acid (yield 87%) and (iii) reductive amination followed by dehydration (yield 76.5%) to form compound 1. The synthesis can be performed on a gram scale (in 55 h over 3 d) with an overall yield of about 55%. It can easily be modified to prepare related compounds by, for example, performing different reactions using 6-nitro-2,3-naphthalenedicarboxylic acid.
authors: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Kishore
authors: K
authors: Baathulaa
authors: Yufang
authors: Y
authors: Xu
authors: Xuhong
authors: X
authors: Qian
mesh_terms: D005456:Fluorescent Dyes; D006868:Hydrolysis; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D053644:Naphthalimides / Q000737:chemistry*
chemical_list: C499819:6-N,N-dimethylamino-2,3-naphthalimide; C574292:6-dimethylamino-2,3-naphthalenedicarboxylic anhydride; D005456:Fluorescent Dyes; D009281:Naphthalenes; D053644:Naphthalimides