rXXXX American Chemical Society A dx.doi.org/10.1021/jo200177s | J. Org. Chem. XXXX, XXX, 000–000 ARTICLE pubs.acs.org/joc Microwave-Assisted Synthesis of Naphthalenemonoimides and N-Desymmetrized Naphthalenediimides Koujiro Tambara, †,|| Nandhini Ponnuswamy, †,|| Gunther Hennrich, ‡ and G. Dan Pantos - * ,†,§ † University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom ‡ Departamento de Quimica Organica, Universidad Autonoma de Madrid, 28049 Cantoblanco, Spain § Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom b S Supporting Information ’ INTRODUCTION We report herein the stepwise and high-yielding synthesis of naphthalenemonoimides (NMIs) and N-desymmetrized naphtha- lenediimides (NDIs). We also investigate the factors which influ- ence the efficiency of this microwave-assisted process, such as the steric crowding at the R-carbon, the solubility of the amine reactant, and the noncovalent interaction between the reagents. The main benefits of this method are the straightforward synthesis and purification of NMIs, the ability to control the reactivity of naphthalene dianhydride (NDA), and the produc- tion of N-desymmetrized NDIs with a broad range of structural variety. Furthermore, the observed selectivity for the monofunc- tionalization of NDA was rationalized using molecular modeling at the ab initio level. The NDIs represent a class of compounds with an electron- deficient π-system whose electronic and spectroscopic proper- ties have led to their extensive study in the field of supramolecular chemistry. 1 As an electron-acceptor motif, their ability to form donoracceptor interactions has been widely exploited in the construction of molecular devices and machines. 2 The electronic properties of the π-surface, however, may be altered by core substitution: the π-acidity of unsubstituted NDIs has facilitated the development of transmembrane anion transport systems, 3 while the attachment of electron-donating substituents at the naphthyl core can be employed in the synthesis of electroopti- cally active molecular materials. 4 Water-soluble NDI derivatives have been employed by the Iverson group as DNA intercalators, 5 while the Sanders group has used them as building blocks in dynamic combinatorial libraries, leading to the formation of a wide variety of catenanes. 6 Organic-soluble amino acid-functio- nalized NDI derivatives have been shown to spontaneously self- assemble into hydrogen-bonded helical nanotubes with a well- defined interior cavity capable of complexing various guests, including fullerenes, ion pairs, and polyaromatic hydrocarbons. 7 Mild stepwise functionalization of NDA (1) using R-amino acids and microwave dielectric heating was previously reported by the Sanders group as an efficient one-pot method for the synthesis of NDIs. This method is particularly suitable for symmetrically substituted NDIs and has found limited applica- tion to N-desymmetrized derivatives. 8 The literature regarding efficient synthesis and isolation of NMIs 2, however, is scant due to the difficulty involved in controlling the reaction of 1 equiv of an amine with a cross-conjugated molecule containing two equivalent electrophilic sites such as NDA. ’ RESULTS AND DISCUSSION All reactions were run in a dedicated microwave reactor in pressure-resistant, tightly sealed tubes. The reactions were carried out in two stages, first a mild heating at 40 °C (amino acids and their derivatives) or 75 °C (alkylamines) for 5 min followed by heating for 515 min at 140 °C. The microwave maximum power input was set to 300 W, and the temperature was held at 75 °C by 520 W pulses. In the second step, the temperature was set to 140 °C and was maintained by pulses of 3050 W. The synthesis of NMIs 2ag using alkylamines is outlined in Scheme 1 with the reaction conditions and yields reported in Table 1, entries 17. The data from this study suggest that the steric bulk at the R- carbon influences significantly the outcome of the reaction: amines attached to a secondary carbon gave consistently higher yields than when connected to a tertiary carbon. Furthermore, amines with tertiary R-carbons required longer reaction times (up to 15 min at 140 °C) to force the condensation to completion. For 1-adamantanamine, where the nucleophile is attached to a quaternary carbon, the 1 H NMR spectrum of the product Received: February 8, 2011 ABSTRACT: Naphthalenemonoimides and N-desymmetrized naphtha- lenediimides were synthesized using a stepwise microwave-assisted protocol. The steric and electronic properties of aliphatic amines determined the outcome of the reactions, while in the amino acid series their ability to solubilize the naphthalene dianhydride starting material was crucial. Molecular modeling was used to rationalize the observed selectivity.