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Bull. Chem. Soc. Ethiop. 2012, 26(3), 473-478. Printed in Ethiopia DOI:


ISSN 1011-3924 © 2012 Chemical Society of Ethiopia

SHORT COMMUNICATION SYNTHESIS OF 1-AMIDOALKYL-2-NAPHTHOLS BASED ON A THREECOMPONENT REACTION CATALYZED BY BORIC ACID AS A SOLID HETEROGENEOUS CATALYST UNDER SOLVENT-FREE CONDITIONS Zahed Karimi-Jaberi* and Hadi Fakhraei Department of Chemistry, Firoozabad Branch, Islamic Azad University, Firoozabad, Fars, Iran (Received December 09, 2011; revised June 18, 2012)
ABSTRACT. An efficient method for the preparation of 1-amidoalkyl-2-naphthols has been described using a multi-component, one-pot condensation reaction of 2-naphthol, aldehydes and amides in the presence of boric acid under solvent-free conditions. KEY WORDS: 1-Amidoalkyl-2-naphthols, Boric acid, 2-Naphthol, Solvent-free synthesis

INTRODUCTION One-pot, multi-component processes have recently gained considerable economic and ecological interest as they have proved to be remarkably successful in generating molecular complexity in a single synthetic operation [1]. The use of heterogeneous catalysts in different areas of the organic synthesis has now reached significant levels, not only for the possibility to perform environmentally benign synthesis, but also for the good yields [2]. It is noteworthy that 1-amidomethyl-2-naphthols can be converted to important biologically active 1-aminomethyl-2-naphthol derivatives by amide hydrolysis reaction. The hypotensive and bradycardiac effects of these compounds have been evaluated [3-4]. The preparation of 1amidoalkyl-2-naphthols can be carried out by multi-component condensation of aryl aldehydes, 2-naphthol and acetonitrile or amide in the presence of Lewis or Brønsted acid catalysts [5-16]. However, some of these catalysts suffer from the drawback of green chemistry such as prolonged reaction times, low yields and toxicity of the catalyst. Therefore, introducing clean processes and utilizing eco-friendly and green catalysts which can be simply recycled at the end of reactions have been under permanent attention. The demand for environmentally benign procedure with heterogeneous and reusable catalyst promoted us to develop a safe alternate method for the synthesis of amidoalkyl naphthols. As a consequence of our interest in the application of solid acid catalysts in organic synthesis [17-20], herein, we describe an efficient method for the synthesis of 1-amidoalkyl-2naphthols by one-pot condensation reaction of 2-naphthol, aldehydes and amides using catalytic amounts of boric acid under solvent-free conditions (Scheme 1).




H3BO3 NH2 neat, 120 oC R O




Scheme 1
__________ *Corresponding author. E-mail:

dihydroquinazolinones [19] and benzimidazoles [20]. the aza Michael addition [26]. It offers milder conditions relative to common mineral acids. Boric acid is a readily available and inexpensive reagent and can conveniently be handled and removed from the reaction mixture. RESULTS AND DISCUSSION To optimize the reaction conditions. the Mannich reaction [29] and by our group in the synthesis of dibenzoxanthenes [17]. Table 1. benzaldehyde and acetamide was used as a model reaction. transesterification of ethyl acetoacetate [28].474 Zahed Karimi-Jaberi and Hadi Fakhraei Boric acid (H3BO3) is a useful and environmentally benign catalyst which has been successfully utilized in numerous reactions [21-29]. Synthesis of 1-amidoalkyl-2-naphthols. the remarkable catalytic activities together with its operational simplicity make it the most suitable catalyst for the synthesis of 1-amidoalkyl 2-naphthols. Reactions at different conditions and various molar ratios of substrates in the presence of boric acid revealed that the best conditions were solvent-free at 120 o C. the Biginelli reaction [27].5-(OMe)2 CH3 OH MeO NHCOCH3 OMe 71 251-256 4 3-NO2 CH3 OH O 2N NHCOCH3 76 241-243 OH 5 4-NO2 CH3 NHCOCH3 O 2N 75 248-249 Bull. the catalyst (boric acid) can be separated from the reaction mixture by washing the product with water. the reaction of 2-naphthol. Ethiop. 26(3) . 2012. After completion of the reaction. Soc. Entry R R′ Product Yield (%) m. α-aminophosphonates [18]. (oC) 1 H CH3 OH NHCOCH3 73 244-245 OH 2 4-CH3 CH3 NHCOCH3 H3C 71 221-222 3 2. for example.p. Chem. Thus.

2012. Ethiop. Soc.Short Communication 475 Entry R R′ Product Yield (%) m. The results are summarized in Table 1. (oC) 6 3-F CH3 OH F NHCOCH3 72 248-249 7 4-Cl CH3 Cl OH NHCOCH3 72 223-225 8 2-Cl CH3 Cl OH NHCOCH3 71 214-215 9 2.p. 26(3) . Various Bull.4-Cl2 CH3 Cl Cl OH NHCOCH3 73 199-201 OH 10 4-NMe2 CH3 NHCOCH3 Me2N 68 124-126 11 H Ph OH NHCOPh 75 234-236 OH 12 4-NO2 Ph NHCOPh O2N 76 238-240 13 2-Cl Ph Cl OH NHCOPh 72 285-286 To show the generality of this method the optimized system was used for the synthesis of other amidoalkyl naphthol derivatives. Chem.

the reactions of aliphatic aldehydes would fail to give the desired products as well as the known catalysts. such as chloro. and it follows along the line of green chemistry. which are normally observed under the influence of strong acids. such as montmorillonite K10 [5]. 10]. low reaction times. As has been suggested earlier [7. 26(3) . Ethiop. The catalyst is readily available and inexpensive and can conveniently be handled and removed from the reaction mixture. aldehyde (1 mmol). In all these cases. K5CoW12O40. After completion of the reaction. Chem. flouro. solvent-free condition. we have developed a very simple and efficient method for the high-yielding synthesis of 1-amidoalkyl-2-naphthols by one-pot three-component coupling of 2-naphthol. Soc. the reaction mixture was diluted with water and extracted with ethylacetate.05 g) at 120 oC was stirred for 15 min. entries 11-13). low cost. 2012. aromatic aldehydes and amides is shown in Scheme 2. the corresponding 1-amidoalkyl-2-naphthols were obtained in good yields at 120 °C without formation of any side products such as dibenzoxanthenes. the reaction of 2-naphthol with aromatic aldehydes in the presence of acid catalyst is known to give ortho-quinone methides (O-QMs).3H2O [8]. EXPERIMENTAL Typical procedure for the preparation of 1-amidoalkyl 2-naphthols. and Fe(HSO4)3 [9].476 Zahed Karimi-Jaberi and Hadi Fakhraei functionalities present in the aryl aldehydes. IR. various aromatic aldehydes and amides using boric acid as a heterogeneous acid catalyst. This method offers some advantages in terms of simplicity of performance. In conclusion. methyl and methoxy groups were tolerated under these conditions at 120 oC (Table 1).2 mmol) and H3BO3 (0. Further. The reaction can also proceed with benzamide instead of acetamide (Table 1. It is important to note that the synthesis of 1amidoalkyl-2-naphthols could not be achieved in the absence of catalyst (boric acid). concentrated under vacuum and the crude mixture was purified by recrystalization from ethanol to afford pure products. nucleophilic conjugate addition of amide on o-quinone methide intermediate leads to the formation of amidoalkyl naphthol as a product. Bull. and mass spectroscopic methods and the results were confirmed by comparison with those available in the literature. The proposed mechanism for the boric acid catalyzed preparation of 1-amidoalkyl-2naphthols from the reaction of 2-naphthol. 13C NMR. However. ArCHO OH H3BO3 O Ar O OH H 2N H3BO3 H O-QMs R' Ar R' NH O Scheme 2 All the products were identified by 1H NMR. A mixture of 2-naphthol (1 mmol). The progress of reactions was monitored by TLC (ethyl acetate/n-hexane = 1/3). amide (1. dried over Na2SO4.

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