Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol.

1) 2011 ISSN: 2231-2560

Research Article

Asian Journal of Biochemical and Pharmaceutical Research

One-pot Synthesis of Fluorescent 4-Amino-naphthalimide Dyes in Dioxane Ghasem R. Bardajee
Department of Chemistry, Payame Noor University, 19395-4697, Tehran, I. R. of Iran

Received: 24 February 2011; Revised: 1 March 2011; Accepted: 4 March 2011

Abstract: In this report, we described the one-pot synthesis of a group of fluorescent naphthalimide dyes in 1, 4-dioxane as a polar aprotic solvent. The interested derivatives were prepared via the condensation reaction of amines and 4-Br-1, 8-naphthalic anhydride, followed by the aromatic nucleophilic substitution reaction of 4bromo-N-alkylnaphthalimides with excess amines in the reaction mixture. Keywords: Amines; Dioxane; Naphthalimide dyes; One-pot; Synthesis

INTRODUCTION: Naphthalimide fluorescent dyes are widely used class of dyes due to their multipurpose submissions in various fields [1-2]. As they have strong fluorescence and good photo-stability, this family of compounds have found applications in polymer materials [3], laser active media, fluorescent markers in biology, anticancer agents, analgesics in medicine, fluorescence switchers and sensors, light emitting diodes, electroluminescent materials, liquid crystal displays and ion probes [4-5]. The 4-amino-1,8-naphthalimide dyes are one of the most important members of naphthalimide derivatives. For example, they are the most important yellow components for day light fluorescent pigments. Most applications of 4-amino-1, 8-naphthalimide dyes are as fluorescent in detergents, textiles, paper, plastics and paints [6]. More recently, 1,8-naphthalimide derivatives have been studied as DNA intercalators [7]. Due to the importance of naphthalimide dyes, several approaches have been developed for their syntheses which often consist of limited practical applicability, involving harsh reaction conditions, toxic reagents, and multistep syntheses. Here, a one-pot and simple procedure for the preparation of fluorescent naphthalimide dyes in refluxing 1, 4-dioxane (DOX) is described (Scheme 1).

Scheme 1: General route for the one-pot synthesis of naphthalimide derivatives

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Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011

MATERIALS AND METHODS: Materials: All amines, 4-bromo-1,8-naphtalic anhydride and DOX were purchased from Merck or Sigma- Aldrich companies. The course of the synthesis and purity of the products were followed by TLC on silica gel plates (Merck, silica gel 60 F254, ready to use), using n-hexane-acetone (3:1) as eluent. The eluent for column chromatography was the same as TLC eluent. Instrumentation: Melting points were recorded using a Buchi B540 melting point apparatus and are uncorrected. 1H and 13C NMR spectra were obtained using a bruker (DRX-500 Avance) NMR spectrometers at ambient temperature. 1H NMR spectra are referenced to tetramethylsilane (0.00 ppm) and 13C NMR spectra are referenced from the solvent central peak (for example, 77.23 ppm for CDCl3). Chemical shifts are given in ppm. IR spectra were taken as KBr pellets on an ABB Bomem MB-100 FTIR spectrophotometer. IR is reported as characteristic bands (cm-1) at their maximum intensity. General procedure for the synthesis of the 4-amino-1, 8-naphthalimide derivatives: To a solution of 4-bromo-1, 8-naphtalic anhydride 1 (1 mmol, 1 equiv) in DOX (10 mL), butylamine (10 mmole, 10 equiv) was added. The resulting mixture was heated in an oil bath at 105 C for overnight as required for completion of the reaction. The course of the reaction was monitored using TLC on silica gel with n-hexane-acetone (3:1) as eluent. The solvent was evaporated under vacuum and the product was separated by column chromatography on silica gel or crystallization from methanol. Finally, the product was dried under vacuum at 50 C for 10 hrs. Selected data for compound 3b: Yield: 83%; m.p. = 128-129 C; IR (film) max cm-1: 3392; 1687; 1648; 1579; 1365. 1H NMR (500 MHz, CDCl3): 0.96 (d, J = 6.6 Hz, 6H); 1.15 (d, J = 6.6 Hz, 6H); 2.22 (m, 2H); 3.20 (d, J = 6.2 Hz, 2H); 4.02 (d, J = 6.8 Hz, 2H); 5.31 (s, 1H); 7.27 (d, J = 8.1 Hz, 1H); 7.69 (dd, J = 7.4 Hz, 8.4 Hz, 1H); 8.49 (d, J = 8.1 Hz, 1H); 8.57 (dd, J = 1.2 Hz, 7.4 Hz, 1H); 8.61 (dd, J = 1.2 Hz, 8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): 20.3; 20.6; 27.4; 27.7; 45.9; 51.2; 111.5; 112.3; 123.1; 125.5; 125.8; 130.1; 130.5; 131.2; 132.2; 155.5; 164.4; 164.8. Anal. Calcd for C20H24N2O2 (324.42): C, 74.04; H, 7.46; N, 8.64. Found: C, 74.17; H, 7.55; N, 8.78. RESULTS AND DISCUSSION: Survey literature shows that the interesting compounds, with the general structure 3, are commonly prepared according to a two steps reaction procedure (Scheme 2). The first stage of the reaction involves the reaction of 4-Br-1, 8-naphthalic anhydride 1 with an appropriate primary amine to yield the corresponding 4-bromo-1, 8-naphthalimide derivative 2. In the second step of the synthesis, the reaction of the isolated compound 2 and a nucleophile like amine or thiol promote the corresponding 1,8-naphthalimide dyes 3 [8-9]. Herein, our protocol involves the synthesis of 4-amino1,8-naphthalimide dyes from the reaction of 4-Br-1,8-naphthalic anhydride 1 and an excess of primary amines via a one-pot procedure in DOX solvent (Scheme 1).

Scheme 2: The mechanism for the preparation of naphthalimide dyes. 26

Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011

To test the feasibility of this reaction, we initially investigated the reaction of 4-Br-1,8-naphthalic anhydride 1 and butylamine in different solvents. Different solvents like 1,4-dioxane (DOX), dimethylformamide, ethanol and water were tested as the reaction medium. Gratifyingly, the desired product was obtained in 88% GC yield in DOX as a reaction medium (83% isolated yield). In a typical procedure, when the 4-Br-1,8-naphthalic anhydride 1 (1 mmol, 1 equiv) was treated with butylamine (10 mmol, 10 equiv) in refluxing DOX (10 mL) for overnight, the 4-amino-1,8-naphthalimide dyes 3a was obtained in 83% yield (Table 1, entry 1). The completion of reactions was followed by thin-layer chromatography (TLC) on silica gel using n-haxane-acetone (3:1) as eluent. The dyes were characterized by m.p., IR, 1H-NMR, 13C-NMR and elemental analysis. Table 1: Synthesis of 4-amino-1,8-naphthalimide dyes in DOX solvent.
Entry 1
HN 3a

Amine

Product 3a
O N O

Yield [%]b

83

2
HN 3b

O N O

80

3
HN

O N O

82

3c

4
HN

O N O

75

3c

a b

All products were characterized by m.p., IR, and 1HNMR, and their physical data were similar to those reported in the literature [4-9]. All reactions were run under the following conditions: compound 1 (1 mmol) and amine (10 mmol) in DOX (10 mL) were reflux for overnight.

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Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011

In the second step, the generality of the reaction was examined by using several primary amines (Table 1). As one can see from Table 1, different primary like hexylamine, octylamine and isobutylamine showed high yields (Table 1, entries 1-4). More effort for the synthesis of naphthalimide dyes via using hindered amines such as tert-butylamine failed and no product was observed. This phenomenon can be attributed to the competition of nucleophilicity strength of amines versus their steric effects. The possible mechanism for this one-pot conversion can be summarized in Scheme 2. The first step involves the condensation reaction of 4-Br-1, 8-naphthalic anhydride 1 and corresponding amine along with elimination of 2 water molecules to give the intermediate 2. In the next step, the reaction of the intermediate 2 and excess amine leads to the naphthalimide dyes 3 via an aromatic nucleophilic substitution mechanism CONCLUSION: In summary, we have described the synthesis of a series of fluorescent naphthalimide dyes, which can be prepared from the one-pot reaction of 4-Br-1,8-naphthalic anhydride 1 and primary amines in refluxing DOX. The entitled products were obtained in good to excellent yields. The use of a simple procedure, clean, and easily available reagents under essentially neutral reaction conditions make this protocol practical and economically attractive.

REFERENCES: 1. A.A. Fadda, H. A. Etmen, F. A. Amer, M. Barghout, K. S. Mohammed; J. Chem. Tech. Biotechnol; 1994, 61, 343. 2. F. Karci, I Sxener, Z.H. Deligo; Dyes and Pigments; 2003, 59, 53. 3. I. Grabchev, T. Konstantinova; Dyes and Pigments; 1997, 33, 197. 4. I. Grabchev, I. Moneva, V. Bojinov, S. Guittonneau; J. Mater. Chem; 2000, 10, 1291. 5. F. Cosnard, V. Wintgens; Tetrahedron Lett; 1998, 39, 2751. 6. H Gold, The chemistry of synthetic dyes; New York: Academic Press; 1971, 535. 7. Z.F. Tao, X. Qian, J. Tang; Dyes and Pigments; 1996, 30, 247. 8. S. C. Chang, E. R. Utecht, D. E. Lewis; Dyes and Pigments; 1999, 43, 83. 9. G. R. Bardajee, A.Y. Li, J. C. Haley, M. A. Winnik; Dyes and Pigments; 2008, 79, 24.

*Correspondence Author: Ghasem R. Bardajee Department of Chemistry, Payame Noor University, 19395-4697, Tehran, I. R. of Iran

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