Design and Synthesis of Three Naphtol Derivatives using the Three Component System

Introduction

Several methods have been reported for synthesis of aromatic-condensed derivatives; for example, the synthesis of naphtyl ketone by the reaction of o-alkynylbenzaldehydes with alkynes using AuCl₃ as catalyst¹. Other reports indicate the tandem pummerer Diels-Alder sequence for the preparation of α-thio substituted naphthalene derivatives². Additionally, other studies³ showed the synthesis of 1,8-diphenylnaphtalene and 1-Iodo-8-phenylnaphtalene by the reaction of lithium diphenylcuprate and aryl halides. Other studies reported by Ganapathy and Viswanathan⁴ shown the synthesis of polysubstituted naphthalene derivatives through gallium trichloride catalyzed by alkyne-aldehyde coupling. In addition, some carbamato-alkyl-naphtol derivatives⁵ have been synthetized by condensation of β-naphtol, aromatic aldehyde and methyl carbamate in ionic liquid media. Other studies indicate that the compound N-(2,4-Dibromonaphthyl)benzamide was prepared by benzoylation of 2,4-Dibromonaphthylamine in pyridine⁶. Additionally, other naphtalen benzamide derivative (N-(3-mercapto-5-(naphthalen-1-yl)-4H-1,2,4-triazol-4-yl)benzamide) was synthetized by the reaction of potassium 2-(2-naphthoyl)hydrazinecarbodithioate with N-amino-arylcarboxamides in ethanol to reflux⁷. Recently, was synthetized a naphthalene-benzamide derivative (N-(3-(1-Methoxy-naphthalen-2-yl)-2,2-dimethylpropyl)-2-benzamide) by the reaction of benzoic acid with   3-(1-1 Methoxy-naphtalen-2-yl)-2,2-dimethyl-propylamine in methanol at room temperature⁸. All these experimental results show several procedures which are available for synthesis of naphthalene derivatives; nevertheless, expensive reagents and special conditions are required. Therefore, in this study three naphthol derivatives were synthetized using the three component system.

Material and Methods

General methods

The compounds evaluated in this study were purchased from Sigma-Aldrich Co., Ltd. The melting points for the different compounds were determined on an Electrothermal (900 model). Infrared spectra (IR) were recorded using KBr pellets on a Perkin Elmer Lambda 40 spectrometer. ¹H and ¹³C NMR spectra were recorded on a Varian VXR-300/5 FT NMR spectrometer at 300 and 75.4 MHz in CDCl₃ using TMS as internal standard. EIMS spectra were obtained with a Finnigan Trace GCPolaris Q. spectrometer. Elementary analysis data were acquired from a Perkin Elmer Ser. II CHNS/0 2400 elemental analyzer.

Synthesis of 1-[(2-Amino-ethylamino)-phenyl-methyl]-naphthalen-2-ol. (4)

A solution of β-naphtol (100 mg, 0.69 mmol), benzaldehyde (105 µl, 1.03mmol), ethylenediamine (92 µl, 1.38 mmol) in 10 ml of ethanol was stirring for 72 h to room temperature. The reaction mixture was evaporated to a smaller volume. After the mixture was diluted with water and extracted with chloroform. The organic phase was evaporated to dryness under reduced pressure, the residue was purified by crystallization from methanol:water (4:1) yielding 75 % of product, m.p. 52-54 ^oC; IR ṽ = 3530, 3330, 3310  cm^-1; ¹H NMR (300 MHz, CDCl3) d_H: 2.88 (t, 2H, J = 11 6.0 Hz), 3.08 (t, 2H, J = 6.0 Hz), 3.72 (broad, 3H), 5.75(s, 1H), 6.88 (m, 12 2H), 7.05 (m, 1H), 7.11 (m, 2H), 7.20 (m, 1H), 7.41-7.54 (m, 3H), 7.68-7.75 (m, 2H) ppm. ¹³C NMR (75.4 Hz, CDCl3) d_C: 42.20 (C-15), 52.98 (C-14), 55.53 (C-12), 114.39 (C-9), 121.17 (C-8), 123.57 (C-6), 125.65 (C-2), 126.21 (C-7), 127.39 (C-20), 128.01 (C-4), 128.22 (C-10), 130.02 (C-18, C-22), 130.06 (C-5), 130.88 (C-19, C-21), 137.07 (C-17), 138.35 (C-3), 152.11 (C-1) ppm. EI-MS m/z: 292.07 (M+, 11). Anal. Calcd for: C₁₉H₂₀N₂O : C, 78.05; H, 6.89; N, 9.58; O, 5.47. Found: C, 78.02; H, 6.85.

{[2-Hex-1-ynyl-phenyl-amino)-ethylamino]-phenyl-methyl}-naphtalen-2-ol (6).

A solution of 4 (100 mg, 0.34 mmol), 1-hexyne (42 µl, 0.36 mmol), benzaldheyde (50 µl, 0.51 mmol) and cupric chloride anhydrous (90 mg, 0.67 mmol) in 10 ml of ethanol was stirring for 48 h to room temperature. The reaction mixture was evaporated to a smaller volume. After the mixture was diluted with water and extracted with chloroform. The organic phase was evaporated to dryness under reduced pressure, the residue was purified by crystallization from methanol:water (4:1) yielding 70 % of product, m.p. 72-74 ^oC; IR (V_max, cm^-1): 3530, 3320, 2190 and 1170; ¹H NMR (300 Hz, CDCl₃) d_H: 0.91 (t, 3H, J = 6.3 Hz), 1.42 (m, 2H), 1.47 (m, 2H), 2.32 (t, 2H, J = 6.83 Hz), 2.88 (t, 2H, J = 6.9 Hz), 3.14   (t, 3H, J = 6.3 Hz), 4.70 (broad, 2H), 5.02 (s, 1H), 6.61 (d, 3H, J = 8.0 Hz), 6.87 (d, 2H,  J = 7.8 Hz), 7.10-7.12 (m, 4H), 7.20 (m, 1H), 7.42-7.54 (m, 3H), 7.69-7.75 (m, 2H) ppm.   ¹³C NMR (75.4 Hz, CDCl₃) d_C: 13.54 (C-34), 16.78 (C-31), 21.98 (C-33), 31.88 (C-32), 47.34 (C-14), 55.22 (C-12), 59.10 (C-15), 59.38 (C-30), 82.28 (C-29), 113.82(C-18,  C-22), 114.02 (C-9), 120.18 (C-20), 121.10 (C-8), 123.57 (C-6), 125.16 (C-2), 126.60  (C-7), 127.38 (C-26), 128.01 (C-4), 128.14 (C-10), 128.90 (C-24, C-28), 129.28(C-5), 129.60 (C-19, C-21), 130.08 (C-25, C-27), 135.78 (C-25), 138.14 (C-3), 144.60 (C-17), 152.08 (C-1) ppm. EI-MS (70 eV): m/z = 448.18 (M + 17), 262.19, 155.17, 105.14. Anal. Calcd. for C₃₁H₃₂N₂O: C, 83.00; H, 7.19; N, 6.24, O, 3.57. Found. C, 82.97; H, 7.16.

di(naphtyl-2-ol)-1,10-diphenyl-4,7-diaza-deca-1,9-diene (8)

A solution of cinamaldehyde (87 µl, 0.69 mmol), β-naphtol (100 mg, 0.69 mmol), and ethylenediamine (67 µl 1.00 mmol) in 10 ml of ethanol was stirring for 72 h to room temperature. The reaction mixture was evaporated to a smaller volume. After the mixture was diluted with water and extracted with chloroform. The organic phase was evaporated to dryness under reduced pressure, the residue was purified by crystallization from methanol:water (4:1) yielding 70 % of product, m.p. 54-56 ^oC; IR (V_max, cm^-1): 3526, 3314, 1586 and 1164; ¹H NMR (300 Hz, CDCl₃) d_H: 2.51 (m, 2H) 2.8 (m, 2H), 5.22 (d, 2H, J = 7.5 Hz), 6.07 (d, 2H, J = 7.5 Hz), 6.57 (d, 2H, J = 15.70 Hz), 6.92 (broad), 7.14-7.28 (m, 6H), 7.40-7.52 (m, 12H), 7.59-7.73 (m, 4H) ppm. ¹³C NMR (75.4 Hz, CDCl₃) d_C: 49.27 (C-14, C-15), 57.34 (C-12, C-17), 115.52 (C-9, C-20), 120.62 (C-8, C-24), 123.82 (C-6, C-26), 125.11 (C-2, C-18), 126.43 (C-7, C-25), 126.62 (C-31, C-35, C-39, C-43), 127.28 (C-33, C-41), 127.41 (C-4, C-22), 127.91 (C-10, C-21), 128.76 (C-32, C-34, C-40, C-42), 129.53 (C-5, C-27), 131.26 (C-29, C-37), 135.71 (C-28, C-36), 139.95 (C-3, C-23, C-30, C-38), 151.02 (C-1, C-19) ppm. EI-MS (70 eV): m/z = 576.17 (M⁺, 3), 331.00 (100), 302.00 (63), 159.17 (38), 90.05 (57), Anal. Calcd. for C₄₀H₃₆N₂O₂: C, 83.30; H, 6.29; N, 4.86, O, 5.55. Found. C, 83.28; H, 6.24.

Results and Discussion

In this study were synthetized some naphtol derivatives using the three components system; it is important to mention, that many procedures have used this method in order to synthesize several compounds. The most widely practiced method employs boric acid⁹, silica sulfuric acid¹⁰, poly(4-vinylpyridine-codivynylbenzene)-Cu(II) complex¹¹, H₂SO₄¹¹, silica triflate¹² and phosphorus pentoxide¹³. Nevertheless, despite its wide scope, the former protocols suffer from several drawbacks e.g., some reagents have a limited stability and its preparation can be dangerous. Analyzing these data, in this study several straightforward routes are reported for the synthesis of three naphtol-derivatives. The first step involves preparation of 4 using the three-component system (β-naphtol, benzaldehyde and ethylenediamine) in ethanol. The ¹H NMR spectrum of 4 shows signals at 2.88 and 3.08 ppm for protons involved in the arm present in the compound 4; at 5.75 ppm for hydrogen of methylene which is bound to both phenyl and naphtol groups. Other signal at 3.72 ppm for both amino and hydroxyl groups were found. Finally, the spectrum contains several signals at 6.88, 7.11 and 7.20 ppm for phenyl group; at 7.05, 7.41-7.75 ppm for naphtol group. The ¹³C NMR spectrum contains peaks at chemical shifts of 42.20 and 52.98 ppm for the carbons of the methylenes involved in the arm of 4. A signal at 55.53 ppm for methylene bound to phenyl group and naphtol group was found. In addition, several signals at 114.39-126.21, 128.01-128.22, 130.06 and 138.35-152.11 ppm for carbons involved in the naphtol group; at 127.39, 130.02, 130.88-137.07  ppm for carbons of phenyl group were found. In addition, the presence of 4 was further confirmed from mass spectrum which showed a molecular ion at m/z 292. 07.

In the second stage, the compound 6 was developed using the three-component system (compound 4, benzaldehyde and 1-hexyne) in presence of cupric chloride. It is important to mention that cupric chloride was used as catalyst because there are several reports which indicate that copper(I) reagent has been found to be an efficient catalyst for an enantioselective one-pot three-component synthesis between aldehydes, amines and alkynes^14,15. The results indicate that ¹H NMR spectrum of 6 showed several signals at 0.91 ppm corresponding to methyl presents in the alkyne fragment; at 1.42-2.32 ppm for methylenes bound to alkyne group; at 2.88-3.14 ppm for methylenes bound to amino groups; at 4.70 ppm for both amino and hydroxyl groups; at 5.02 ppm for the methylene bound to both amino and phenyl groups. Finally, other signals at 6.61-7.75 ppm for protons involved in phenyl groups were found. The ¹³C NMR spectra display chemical shifts at 13.54 ppm for the carbon of methyl present in the alkyne fragment; at 16.78-31.88 ppm for methylenes involved in the alkyne fragment; at 47.34 and 59.10 ppm for methylenes bound to both amine groups; at 55.22 ppm for carbon bound to both amine and phenyls groups; at 59.38-82.28 ppm for alkyne group. Finally, other signals at 113.82-152.08 ppm for phenyl groups were found. Additionally, the presence of the compound 6 was further confirmed from mass spectrum which showed a molecular ion at m/z 448.18.

In the third stage, the compound 8 was synthetized by the reaction of using the three components system (cinamaldehyde, β-naphtol and ethylenediamine) in ethanol. The ¹H NMR spectrum of 8 shows signals at 2.51 and 2.80 ppm for methylenes bound to amine groups; at 5.22 ppm for methylene bound to phenyl, amine and alkene groups; at 6.07-6.57 ppm for protons of alkene group; at 6.92 ppm for both amine and hydroxyl groups. Finally, other signals at 7.14-7.73 ppm for phenyls groups were found. The ¹³C NMR spectrum contains peaks at chemical shifts of 49.27 ppm for the carbons of the methylenes involved in the arm bound to amine groups. Other signals at 131.26-135.71 ppm for alkene groups; at 115.52-129.53 and 139.95-151.02 ppm for phenyls groups were found. Finally, the presence of 8 was further confirmed from mass spectrum which showed a molecular ion at m/z 576.17. In conclusion, in this study are reported several strategies for the synthesis of some naphthol derivatives. It is important to mention that the methods used are highly versatile and the yield is good.

Figure 1: Synthesis of 1-[(2-Amino-ethylamino)-phenyl-methyl]-naphthalen-2-ol. (4). Click here to View figure

 

Figure 2: Synthesis of 1-{[2-Hex-1-ynyl-phenyl-amino)-ethylamino]-phenyl-methyl}-naphtalen-2-ol (6). Click here to View figure

 

Figure 3: Synthesis of 1-{[2-Hex-1-ynyl-phenyl-amino)-ethylamino]-phenyl-methyl}-naphtalen-2-ol (6).  Click here to View figure

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