Microwave Assisted Solvent-Free Synthesis of Some Imine Derivatives

Bekdemir, Yunus; Efil, Kürşat

doi:https://doi.org/10.1155/2014/816487

Organic Chemistry International

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Research Article | Open Access

Volume 2014 | Article ID 816487 | https://doi.org/10.1155/2014/816487

Microwave Assisted Solvent-Free Synthesis of Some Imine Derivatives

Yunus Bekdemir¹and Kürşat Efil^1,2

Academic Editor: Joseph E. Saavedra

Received02 Jan 2014

Revised23 Feb 2014

Accepted24 Feb 2014

Published26 Mar 2014

Abstract

Some imine derivatives (1a–7d) were synthesized using a rapid and an environmentally friendly method with reaction of aromatic aldehydes (a–d) and aromatic amines (1–7) (in 1 : 1 molar ratio) in the presence of -ethoxyethanol as a wetting reagent (2 drops) under solvent-free conditions using microwave heating.

1. Introduction

Compounds containing the –C=N– (azomethine group) structure are known as Schiff bases, usually synthesized from the condensation of primary amines and active carbonyl groups [1]. The reaction is acid-catalyzed and is generally carried out by refluxing the carbonyl compound and amine, with an azeotroping agent if necessary, and separating the water as formed [2]. Schiff bases are well known for their biological applications as antibacterial, antifungal, anticancer, and antiviral agents; furthermore, they have been used as intermediates in medical substrates and as ligands in complex formation with some metal ions [1, 3]. The synthesis of imines was firstly reported by Hugo Schiff in 1864 and they have been known since then [4]. The imine compounds have been prepared using molecular sieves [5, 6], infrared irradiation [7], Mg(ClO₄)₂ [8], P₂O₅/SiO₂ [9], ZnCl₂ [10], CaO under microwave power [11], ethyl lactate as a tunable solvent [12], K10 clay [13], TiCl₄ [14], alumina [15], CeCl₃7H₂O [16], ultrasound irradiation [17], polymer-supported [18], nanotube TiO₂ (in sunlight) [19], and Ti(OEt)₄ [20, 21].

The present work reveals the comparative aspects of condensation of some aromatic amines with aldehyde derivatives using microwave and conventional methods. The amine and aldehyde compounds as starting materials, -ethoxyethanol (-EE) as wetting reagent and microwave power as an effective source of heating are used in this study. The corresponding imine compounds were prepared in high yields and short reaction times using this effective and environment friendly method.

2. Results and Discussion

In this work, we synthesized quickly and efficiently a series imine derivatives (1a–7d) by condensation of some aromatic amines (1–7) and aldehyde derivatives such as salicylaldehyde (a), p-chlorobenzaldehyde (b), p-methoxybenzaldehyde (c) and cinnamaldehyde (d) under microwave-assisted solvent-free conditions using -EE as wetting reagent. -EE that is a polar molecule quickly absorbs microwaves and therefore heats up and heats around effectively. As a result, -EE, which increases the polarity of the reaction medium, has an active role in the heating of the reaction medium by microwaves.

The general reaction was summarized in Scheme 1. In addition, we tested the effect of different microwave power such as 180, 360, 600, 900 W and detected the microwave power of 180 W and 360 W are more appropriate choices for the reaction. Hence, the optimum microwave reaction conditions were determined using 180 and 360 W microwave power and neat and wetting with β-EE for compound 1a. The highest reaction yield (94%) and shorter reaction time (1.5 min.) were obtained at 360 W microwave power with -EE. In the absence of wetting reagent, the reaction yields are 81% for 1.5 minutes and 88% for 5 minutes. It is understood that the reaction yield was increased by wetting reagent that increases the polarity of the reaction medium. The optimization of microwave-assisted conditions was given in Table 1.

In addition, we have synthesized some imine derivatives (1a, 4a, 1b, 4b, 1c, 4c, 1d, 4d) under classical conditions using a solvent (azeotropic) and traditional heating source (hot plate) for comparison with microwave conditions. Firstly, synthesis of compound 1a under the classical reaction conditions was tested at various periods of time (30, 60, 120, 240, 1300 min) to determine the optimum reaction time, which was determined as 120 minutes. Information on the optimization of the reaction time of compound 1a for classic conditions was presented in Table 2.

The compounds 1a, 4a, 1b, 4b, 1c, 4c, 1d, and 4d were obtained at 76%, 73%, 63%, 79%, 67%, 73%, 67%, and 75% yields, respectively, in 120 minutes under the classical reaction conditions, whereas in microwave conditions, the corresponding reaction yields were 94%, 97%, 95%, 98%, 91%, 97%, 95%, and 96%, respectively, in 1.0–1.5 minutes. All the results such as reactions time, yields, and melting points of the compounds were presented in Table 3. In addition, the yields of microwave and conventional reaction conditions for some imines were expressed graphically in Figure 1.

3. Conclusion

In conclusion, we have developed a simple microwave assisted solvent-free method for the synthesis of imines using a wetting reagent (-ethoxyethanol). The method works well for the reaction of this type amines and aldehydes. Because, we have synthesized imine compounds for good yields and fast reaction times in our method. Our method has some advances such as higher reaction yields, shorter reaction times, and green reaction conditions than classical requirements used of a solvent and conventional heat source (like hot plate) and other some microwave methods used of catalyst and solid supports. In addition, some imines were synthesized for the first time by us with this study.

4. Experimental

All of the chemicals were obtained from commercial sources or prepared according to standard methods. Melting points were determined with an Electrothermal 9100 apparatus. The infrared absorption spectrum of the compounds has been recorded in the region at 4000 and 400 cm⁻¹ range using a Bruker Vertex 80/80 v spectrophotometer using KBr pressed pellet technique at room temperature. The ¹H NMR and ¹³C NMR spectra were recorded using a Bruker AC 200 NMR 200 MHz spectrometer in CDCl₃- and DMSO- using TMS as the internal standard. Elemental analyses were conducted at the METU Central Laboratory using a LECO, CHNS-932. All syntheses were carried out in A Bosh HMT 812 C modified microwave oven.

General Procedure for Preparation of 1a–7d. Aldehyde (1 mmoL), amine (1 mmoL) and two drops of -ethoxyethanol as a wetting reagent were mixed in a beaker. Then the beaker was placed in the microwave oven and was exposed to microwave irradiation (360 W). The product obtained by reaction was washed with cold ethanol. Then, it was recrystallized in ethanol. The physical and spectra data of the compounds 3a, 2b, 3b, 2c, 3c, 2d, and 3d are as follows.

N-(Salicylidene)-2-hydroxy-4-methylaniline (3a). M.p. 199-202°C. IR: 3033, 2965, 2916, 2858, 1612 (C=N), 1592, 1527, 1486, 1422, 1278, 1221, 1141, 1113, 1012, 869, 788, 754, 720, 622, 587, 556 cm⁻¹. ¹H NMR (DMSO-d₆): δ 8.94 (s, 1H, N=CH), 13.90 (s, 1H, OH), 9.65 (s, 1H, OH). ¹³C NMR (DMSO-d₆): δ 160.54, 160.36, 150.82, 137.56, 132.36, 132.25, 131.92, 120.17, 119.46, 119.14, 118.46, 116.93, 116.48. Elemental Anal. Calcd. for C₁₄H₁₃NO₂: C, 73.99; H, 5.77; N, 6.16. Found: C, 72.81; H, 5.64; N, 6.16%.

N-(p-Chlorobenzylidene)-2-hydroxy-5-chloroaniline (2b). M.p. 123–125°C. IR: 3367, 3086, 3071, 3059, 2910, 2894, 1626 (C=N), 1588, 1569, 1478, 1424, 1370, 1274, 1234, 1194, 1154, 1087, 1011, 911, 857, 815, 799 (C–Cl), 697, 658, 608, 548, 533 cm⁻¹. ¹H NMR (CDCl₃): δ 8.66 (s, 1H, N=CH), 7.91 (d, J = 8.4 Hz, 2H, Ar), 7.54 (d, J = 8.4 Hz, 2H, Ar), 7.34 (s, 1H, Ar), 7.24 (d, J = 8.6 Hz, 1H, Ar), 7.02 (d, J = 8.6 Hz, 1H, Ar). ¹³C NMR (CDCl₃): δ 156.75 (N=C), 150.94, 138.21, 135.86, 133.87, 130.06, 129.28, 128.77, 125.07, 116.19, 116.16. Elemental Anal. Calcd. for C₁₃H₉Cl₂NO: C, 58,67; H, 3,41; N, 5,26. Found: C, 57.74; H, 3.42; N, 5.26%.

N-(p-Chlorobenzylidene)-2-hydroxy-4-methylaniline (3b). M.p. 134–137°C. IR: 3367, 3063, 3049, 3028, 2907, 2857, 1629 (C=N), 1576, 1569, 1497, 1370, 1344, 1295, 1242, 1169, 1154, 1080, 1011, 947, 874, 857, 828, 808 (C–Cl), 793, 733, 687, 610, 591, 579 cm⁻¹. ¹H NMR (CDCl₃): δ 8.72 (s, 1H, N=CH), 7.92 (d, J = 8.3 Hz, 2H, Ar), 7.53 (d, J = 8.4 Hz, 2H, Ar), 7.29 (d, J = 8.1 Hz, 1H, Ar), 6.92 (s, 1H, Ar), 6.80 (d, J = 8.0 Hz, 1H, Ar), 2.42 (s, 3H, CH₃). ¹³C NMR (CDCl₃): δ 154.09 (N=C), 152.34, 139.81, 137.40, 134.54, 132.60, 129.72, 129.16, 120.93, 115.67, 115.36, 21.48. Elemental Anal. Calcd. for C₁₄H₁₂ClNO: C, 68.44; H, 4.92; N, 5.70. Found: C, 67.64; H, 4.89; N, 5.69%.

N-(p-Methoxybenzylidene)-2-hydroxy-5-chloroaniline (2c). M.p. 86–88°C. IR: 3323, 3017, 2970, 2954, 2927, 2840, 1626 (C=N), 1599, 1569, 1511, 1453, 1312, 1250, 1165, 1027, 804, 650, 594 cm⁻¹. ¹H NMR (CDCl₃): δ 9.88 (s, 1H, OH), 8.55 (s, 1H, N=CH), 7.85 (d, J = 8.5 Hz, 2H, Ar), 7.23 (s, 1H, Ar), 7.11 (d, J = 8.6 Hz, 1H, Ar), 6.99 (d, J = 8.5 Hz, 2H, Ar), 6.90 (d, J = 8.6 Hz, 1H, Ar), 3.88 (s, 3H, OCH₃). ¹³C NMR (CDCl₃): δ 162.92, 157.76 (N=C), 150.70, 136.69, 130.85, 128.49, 127.81, 124.91, 116.08, 115.77, 114.33, 55.49. Elemental Anal. Calcd. for C₁₄H₁₂ClNO₂: C, 64.25; H, 4.62; N, 5,35. Found: C, 62.92; H, 4.57; N, 5.45%.

N-(p-Methoxybenzylidene)-2-hydroxy-4-methylaniline (3c). M.p. 86–87°C. IR: 3344, 3066, 3018, 2974, 2934, 2907, 2840, 1622 (C=N), 1593, 1567, 1509, 1481, 1423, 1378, 1245, 1162, 1026, 969, 909, 861, 835, 809, 761, 666, 617, 559 cm⁻¹. ¹H NMR (CDCl₃): δ 8.59 (s, 1H, N=CH), 7.83 (d, J = 8.7 Hz, 2H, Ar), 7.16 (d, J = 8.1 Hz, 1H, Ar), 6.97 (d, J = 8.7 Hz, 2H, Ar), 6.81 (s, 1H, Ar), 6.68 (d, J = 7.8 Hz, 1H, Ar), 3.86 (s, 3H, OCH₃), 2.31 (s, 3H, CH₃). ¹³C NMR (CDCl₃): δ 162.52, 155.25 (N=C), 152.02, 138.71, 133.68, 130.36, 129.13, 120.74, 115.34, 115.26, 114.30, 55.45, 21.41. Elemental Anal. Calcd. for C₁₅H₁₅NO₂: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.63; H, 6.41; N, 6.21%.

N-(Cinnamylidene)-2-hydroxy-5-chloroaniline (2d). M.p. 91–93°C. IR: 3344, 3064, 3013, 2964, 2911, 2881, 2839, 1621 (C=N), 1577, 1501, 1483, 1445, 1366, 1240, 1154, 1082, 979, 837, 804, 742, 683, 661, 593 cm⁻¹ ¹H NMR (CDCl₃): δ 8.41 (d, J = 8.2 Hz, 1H, N=CH), 7.54 (d, J = 5.2, 2H, Ar), 7.43–7.00 (m, 5H, Ar & CH=CH), 7.29 (s, 1H, Ar), 7.22 (d, J = 8.1 Hz, 1H, Ar), 6.90 (d, J = 8.6 Hz, 1H, Ar). ¹³C NMR (CDCl₃): δ 159.36, 150.95 (N=C), 145.23, 136.47, 135.35, 129.99, 128.99, 128.36, 128.11, 127.69, 124.94, 115.99, 115.86. Elemental Anal. Calcd, for C₁₅H₁₂ClNO: C, 69.91; H, 4.69; N, 5.43. Found: C, 68.80; H, 4.72; N, 5.36%.

N-(Cinnamylidene)-2-hydroxy-4-methylaniline (3d). M.p. 97-98°C. IR: 3350, 3061, 3012, 2963, 2912, 2880, 2840, 1624 (C=N), 1577, 1541, 1498, 1447, 1368, 1257, 1157, 1092, 975, 836, 804, 749, 686, 630, 552 cm⁻¹ ¹H NMR (CDCl₃): δ 8.57 (d, J = 6.6 Hz, 1H, N=CH), 7.66 (dd, J = 6.0, 1.9 Hz, 2H, Ar), 7.54–7.12 (m, 5H, Ar & CH=CH), 7.30 (d, J = 7.9 Hz, 1H, Ar), 6.93 (s, 1H, Ar), 6.80 (d, J = 8.1 Hz, 1H, Ar), 2.43 (s, 3H, Ar).¹³C NMR (CDCl₃): δ 156.85, 152.28 (N=C), 143.26, 139.38, 135.71, 133.20, 129.53, 128.92, 128.73, 127.46, 120.75, 115.48, 115.04, 21.46. Elemental Anal. Calcd, for C₁₆H₁₅NO: C, 80.98; H, 6.37; N, 5,26. Found: C, 79.22; H, 6.18; N, 5.90%.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

The authors would like to thank the Middle East Technical University analysis Center (Türkiye) for elemental analyses and Özgür Özdamar (Assistant Professor) and Hasan Saral (Assistant Professor) for the analysis, NMR, and IR of some imine compounds.

References

A. M. Asiri and S. A. Khan, “Synthesis and anti-bacterial activities of some novel schiff bases derived from aminophenazone,” Molecules, vol. 15, no. 10, pp. 6850–6858, 2010.
View at: Publisher Site | Google Scholar
R. W. Layer, “The chemistry of imines,” Chemical Reviews, vol. 63, pp. 489–510, 1963.
View at: Publisher Site | Google Scholar
H.-K. Fun, R. Kia, A. M. Vijesh, and A. M. Isloor, “5-Diethylamino-2-[(E)-(4-methyl-3-nitrophenyl)iminomethyl]phenol: a redetermination,” Acta Crystallographica E: Structure Reports Online, vol. 65, no. 2, pp. o349–o350, 2009.
View at: Publisher Site | Google Scholar
H. Schiff, “Sur quelques dérivés phéniques des aldéhydes,” Annali Di Chimica, vol. 131, p. 118, 1864.
View at: Google Scholar
K. Taguchi and F. H. Westheimer, “Catalysis by molecular sieves in the preparation of ketimines and enamines,” Journal of Organic Chemistry, vol. 36, no. 11, pp. 1570–1572, 1971.
View at: Publisher Site | Google Scholar
M. E. Kuehne, “The application of enamines to a new synthesis of β-ketonitriles,” Journal of the American Chemical Society, vol. 81, no. 20, pp. 5400–5404, 1959.
View at: Publisher Site | Google Scholar
M. Á. Vázquez, M. Landa, L. Reyes, R. Miranda, J. Tamariz, and F. Delgado, “Infrared irradiation: effective promoter in the formation of N-benzylideneanilines in the absence of solvent,” Synthetic Communications, vol. 34, no. 15, pp. 2705–2718, 2004.
View at: Publisher Site | Google Scholar
A. K. Chakraborti, S. Bhagat, and S. Rudrawar, “Magnesium perchlorate as an efficient catalyst for the synthesis of imines and phenylhydrazones,” Tetrahedron Letters, vol. 45, no. 41, pp. 7641–7644, 2004.
View at: Publisher Site | Google Scholar
H. Naeimi, H. Sharghi, F. Salimi, and K. Rabiei, “Facile and efficient method for preparation of Schiff bases catalyzed by P₂O₅/SiO₂ under free Solvent conditions,” Heteroatom Chemistry, vol. 19, no. 1, pp. 43–47, 2008.
View at: Publisher Site | Google Scholar
J. H. Billman and K. M. Tai, “Reduction of Schiff bases. II: benzhydrylamines and structurally related compounds,” Journal of Organic Chemistry, vol. 23, no. 4, pp. 535–539, 1958.
View at: Publisher Site | Google Scholar
M. Gopalakrishnan, P. Sureshkumar, V. Kanagarajan, and J. Thanusu, “New environmentally-friendly solvent-free synthesis of imines using calcium oxide under microwave irradiation,” Research on Chemical Intermediates, vol. 33, no. 6, pp. 541–548, 2007.
View at: Publisher Site | Google Scholar
J. S. Bennett, K. L. Charles, M. R. Miner et al., “Ethyl lactate as a tunable solvent for the synthesis of aryl aldimines,” Green Chemistry, vol. 11, no. 2, pp. 166–168, 2009.
View at: Publisher Site | Google Scholar
R. S. Varma, R. Dahiya, and S. Kumar, “Clay catalyzed synthesis of imines and enamines under solvent-free conditions using microwave irradiation,” Tetrahedron Letters, vol. 38, no. 12, pp. 2039–2042, 1997.
View at: Publisher Site | Google Scholar
W. A. White and H. Weingarten, “A versatile new enamine synthesis,” Journal of Organic Chemistry, vol. 32, no. 1, pp. 213–214, 1967.
View at: Publisher Site | Google Scholar
F. Texier-Boullet, “A simple, convenient and mild synthesis of imines on alumina surface without solvent,” Synthesis, vol. 1985, no. 6-7, pp. 679–681, 1985.
View at: Publisher Site | Google Scholar
L. Ravishankar, S. A. Patwe, N. Gosarani, and A. Roy, “Cerium(III)-catalyzed synthesis of schiff bases: a green approach,” Synthetic Communications, vol. 40, no. 21, pp. 3177–3180, 2010.
View at: Publisher Site | Google Scholar
K. P. Guzen, A. S. Guarezemini, A. T. G. Órfão, R. Cella, C. M. P. Pereira, and H. A. Stefani, “Eco-friendly synthesis of imines by ultrasound irradiation,” Tetrahedron Letters, vol. 48, no. 10, pp. 1845–1848, 2007.
View at: Publisher Site | Google Scholar
R. Annunziata, M. Benaglia, M. Cinquini, and F. Cozzi, “Poly(ethylene glycol)-supported 4-alkylthio-substituted aniline: a useful starting material for the soluble polymer-supported synthesis of imines and 1,2,3,4-tetrahydroquinolines,” European Journal of Organic Chemistry, no. 7, pp. 1184–1190, 2002.
View at: Google Scholar
M. Hosseini-Sarvari, “Nano-tube TiO₂ as a new catalyst for eco-friendly synthesis of imines in sunlight,” Chinese Chemical Letters, vol. 22, no. 5, pp. 547–550, 2011.
View at: Publisher Site | Google Scholar
G. Dutheuil, S. Couve-Bonnaire, and X. Pannecoucke, “Diastereomeric fluoroolefins as peptide bond mimics prepared by asymmetric reductive amination of α-fluoroenones,” Angewandte Chemie: International Edition, vol. 46, no. 8, pp. 1290–1292, 2007.
View at: Publisher Site | Google Scholar
J. F. Collados, E. Toledano, D. Guijarro, and M. Yus, “Microwave-assisted solvent-free synthesis of enantiomerically pure N-(tert-Butylsulfinyl)imines,” Journal of Organic Chemistry, vol. 77, Article ID 300919, pp. 5744–5750, 2012.
View at: Google Scholar
E. Tauer and K. H. Grellmann, “Photochemical and thermal reactions of aromatic Schiff bases,” Journal of Organic Chemistry, vol. 46, no. 21, pp. 4252–4258, 1981.
View at: Publisher Site | Google Scholar
R. J. Argauer and C. E. White, “Effect of substituent groups on fluorescence of metal chelates,” Analytical Chemistry, vol. 36, no. 11, pp. 2141–2148, 1964.
View at: Google Scholar
J. D. Margerum and J. A. Sousa, “Spectroscopic studies of substituted benzalanilines,” Applied Spectroscopy, vol. 19, pp. 91–97, 1965.
View at: Google Scholar
J. E. Kuder, H. W. Gibson, and D. Wychick, “Electrochemical characterization of salicylaldehyde anils,” Journal of Organic Chemistry, vol. 40, no. 7, pp. 875–879, 1975.
View at: Publisher Site | Google Scholar
F. F. Stephens and J. D. Bower, “The preparation of benziminazoles and benzoxazoles from Schiff's bases. Part I,” Journal of the Chemical Society, pp. 2971–2972, 1949.
View at: Publisher Site | Google Scholar
J. Schmeyers, F. Toda, J. Boy, and G. Kaupp, “Quantitative solid-solid synthesis of azomethines,” Journal of the Chemical Society: Perkin Transactions 2, no. 4, pp. 989–993, 1998.
View at: Publisher Site | Google Scholar
W. Xu, S. Zhang, S. Yang et al., “Asymmetric synthesis of α-aminophosphonates using the inexpensive chiral catalyst 1,1′-binaphthol phosphate,” Molecules, vol. 15, no. 8, pp. 5782–5796, 2010.
View at: Publisher Site | Google Scholar
Y. M. S. A. Al-Kahraman, H. M. F. Madkour, D. Ali, and M. Yasinzai, “Antileishmanial, antimicrobial and antifungal activities of some new aryl azomethines,” Molecules, vol. 15, no. 2, pp. 660–671, 2010.
View at: Publisher Site | Google Scholar

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Copyright © 2014 Yunus Bekdemir and Kürşat Efil. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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