International Journal of Inorganic Chemistry

International Journal of Inorganic Chemistry / 2010 / Article

Research Article | Open Access

Volume 2010 |Article ID 621376 | 4 pages | https://doi.org/10.1155/2010/621376

Facile Access to Aldol Products from Aromatic and Heteroaromatic Aldehydes Using Ruthenium Catalyst

Academic Editor: Hakan Arslan
Received02 Nov 2009
Accepted22 Feb 2010
Published04 May 2010

Abstract

A new method for the synthesis of aldol products is described. The reaction of aromatic and heteroaromatic aldehydes with 1-(thiophen-2-yl)ethanone in the presence of ruthenium chloride hydrate combined with ligand provided the related aldol adducts, in a short time at room temperature in good yields (77–84%).

1. Introduction

Lewis acid catalyzed reactions belong to one of the most powerful methods in modern synthetic chemistry. Among the many Lewis acids developed so far, ruthenium has received growing attention because of the unique combinations of their strong Lewis acidity mixed with mildness and usually high selectivity [13]. On the other hand, there has been great demand to develop one-pot procedures for successive reactions for the formation of several C–C bonds. The aldol reaction is generally regarded as one of the most powerful and efficient C–C bond forming reactions [46]. Aldol reactions can be catalyzed by bases. The reactions catalyzed by bases are not easily controlled, and the dehydration of the product is often unavoidable [7]. Organic molecules have also been used as the catalysts. However the byproduct from dehydration was still existed. Therefore, many efforts have been devoted to the development of catalytic aldol reactions [812].

In this research, cross-aldol reactions were carried out in a one-pot reaction by mixing the reaction components at room temperature. In the presence of catalytic quantities of RuCl3 nH2O with triphenylphosphine, the reaction of 1-(thiophen-2-yl)ethanone with aldehydes resulted aldol adducts in good yields without the formation of any side product. Although a large number of catalytic and organocatalytic reactions exist, this work adds new knowledge to the field because to the best of our knowledge R combined with ligand had never been used as a catalyst in catalytic cross aldol reactions of 1-(thiophen-2-yl)ethanone with aromatic and heteroaromatic aldehydes.

2. Results and Discussion

As part of our continuing studies toward ruthenium catalyzed aldol reactions [13], it was found that R in the presence of triphenylphosphine would be a more suitable catalyst for the mild formation of aldol adducts. In this method, the aldol products produced a shorter reaction times and simple experimental procedures. On the other hand, amount of PPh3 ligand used in this work was lower than when R [14] was used. Here we report our new findings on the application of this catalytic system for the synthesis of aldol products at room temperature.

At the outset of this research, in order to optimize the reaction condition, the reaction of 1-(thiophen-2-yl)ethanone 1 (3 mmol) and 4-(Methylthio)benzaldehyde 2a (1 mmol) as model substrates, in the presence of ruthenium chloride hydrate in dioxane (1 mL) at room temperature was carried out and the effect of PPh3 to Ru mole ratio on the aldolization was studied (Table 1). Among the catalytic systems examined, commercial ruthenium trichloride hydrate was an efficient catalyst (Table 1, entry 1), but the yield of 3a could be greatly increased by adding PPh3. Addition of an equal amount of PPh3 ligand with the RuCl3 nH2O enhanced the catalytic activity to give 3a in yield of 67% (Table 1, entry 2). Moreover, when the amount of PPh3 was increased to 0.057 mmol (Table 1, entry 4), the formation of the 3a became the predominant product and no byproduct was detected. On the other hand, more addition of PPh3 ligand did not improve the reaction. Thus, PPh3 to Ru ratio was kept at 3 in the following experiments.


621376.Table.001

Entr Catalyst (0.019 mmol)Temp. C)Time (h)Yield (%

1RuCl3.nH2ORT355
2RuCl3 nH2O PPh3RT467
3RuCl3 nH2O 2PPh3RT370
4RuCl3 nH2O 3PPh3RT382
5RuCl3 nH2O 4PPh3RT372
6RuCl3 nH2O 5PPh3RT377
7RuCl3 nH2O 6PPh3RT479
8RuCl3 nH2O 3PPh3Reflux5.562
9RuCl3 nH2O 6PPh3805.576
10RuCl3 nH2O 6PPh3Reflux665

ll products were characterized by 1H NMR, 13C NMR, and IR data. ields after purification by chromatography.

Therefore, when aldehydes (1 mmol), RuCl3 nH2O (0.019 mmol), PPh3 (0.057 mmol), and 1-(thiophen-2-yl)ethanone (3 mmol) were added at room temperature in dioxane (1 mL) (Scheme 1), the aldol products 3ai were generated within (3-4 hours) (Table 2).


Entr AldehydeProductTime (h)Yield (%

14-(Methylthio)benzaldehyde3a382
23-Methylthiophen-2-carbaldehyde3b3.578
35-Methylthiophen-2-carbaldehyde3c480
4Thiophen-2-carbaldehyde3d3.584
5Furan-2-carbaldehyde3e3.577
64-Methoxybenzaldehyde3f380
74-Methylybenzaldehyde3g3.581
82-Methoxybenzaldehyde3h3.577
9Benzaldehyde3i383

ll products were characterized by 1H NMR, 13C NMR, and IR data. ields after purification by chromatography.
621376.sch.001

Considering the results described above, the most plausible mechanism is illustrated in Scheme 2. The mechanism involves activation of the substrates within the coordination sphere of the metal.

621376.sch.002

3. Conclusions

Prompted by our findings and intrigued by diverse reactivities of ruthenium compounds [1518], we have found that the coupling of aldehydes with 1-(thiophen-2-yl)ethanone is achieved in a short time under the influence of RuCl3 nH2O combined with PPh3 to give aldol products in good yields. We were pleased to find that catalytic amounts of ruthenium at room temperature cleanly produced aldol products. More importantly, there was no side product produced and the estimated molar waste was small.

4. Experimental

4.1. General Methods

All solvents, organic, and inorganic compounds were purchased from Merck and used without further purification. All reactions were followed by TLC with detection by UV light.

IR spectra were recorded on Shimadzu FTIR-8400S spectrometer. 1H NMR spectra were obtained on a Bruker DRX-500 Avance spectrometer, and 13C NMR were obtained on a Bruker DRX-125 Avance spectrometer. Samples were analyzed in CDCl3, and the chemical shift values are reported in ppm relative to (tetramethylsilane) TMS as the internal reference. Elemental analyses were made by a Carlo-Erba EA1110 CHNO-S analyzer and agreed with the calculated values. The isolation of pure products was carried out via preparative thin layer chromatography (silica gel 60 GF254, Merck).

Excess of solvent was evaporated under reduced pressure at a bath temperature of 50 and 6 C.

4.2. Typical Experimental Procedure for Synthesis of Aldol Products (3a–i)

A mixture of aldehyde (1 mmol), 1-(thiophen-2-yl)ethanone (3 mmol), RuCl3 nH2O (4 mg, 0.019 mmol), and PPh3 (15 mg, 0.057 mmol) in dioxane (1 mL) was stirred at room temperature and monitored by TLC. After the indicated reaction time (Table 2), the reaction mixture was purified by thin layer chromatography (EtOAc/petroleum ether 1 : 4 v/v), providing the aldol adduct. In this method, no other products were observed.

3-Hydroxy-3-(4-(methylthio)phenyl)-1-(thiophen-2-yl)propan-1-one (3a): yellow oil, IR (neat): 3400, 2920, 1700, 1645, 1465 cm-1.1H NMR (500 MHz, CDCl3): 2.53 (m, 3H), 3.30 (dd, J = 16.0, 6.9 Hz, 1H), 3.43 (dd, J = 16.0, 6.9 Hz, 1H), 3.57 (d, J = 3.0 Hz, OH), 5.33 (m, 1H), 7.41–7.14 (m, 4H), 7.79–7.65 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): 16.4, 45.7, 70.3, 127.3, 127.5, 128.4, 128.6, 132.6, 133.1, 134.2, 144.6 and 214.2 ppm. (Found: C, 60.42; H, 5.07; S, 23.03. Calc. for C14H14O2S2: C, 60.43; H, 5.03; S, 23.02%.)

3-Hydroxy-3-(3-methylthiophen-2-yl)-1-(thiophen-2-yl)propan-1-one (3b): yellow oil, IR (neat): 3578, 3118, 2965, 1674, 1564, 1465 cm-1. 1H NMR (500 MHz, CDCl3): 2.40 (s, 3H), 3.45 (m, 2H), 4.01 (d, J = 3.4 Hz, OH), 5.30 (m, 1H), 6.70 (d, J = 3.3 Hz, 1H), 6.87 (d, J = 3.3 Hz, 1H), 7.21 (m, 1H), 7.72 (d, J = 4.8 Hz, 1H) and 7.81 (d, J = 3.7 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): 15.9, 52.4, 67.5, 125.3, 125.9, 128.6, 134.7, 135.5, 138.6, 141.7, 142.0 and 192.1 ppm. (Found: C, 57.16; H, 4.80; S, 25.40. Calc. for C12H12O2S2: C, 57.14; H, 4.76; S, 25.39%.)

3-Hydroxy-3-(5-methylthiophen-2-yl)-1-(thiophen-2-yl)propan-1-one (3c): yellow oil, IR (neat): 3589, 3088, 2960, 1675, 1575, 1466 cm-1. 1H NMR (500 MHz, CDCl3): 2.51 (s, 3H), 3.48 (m, 2H), 3.59 (d, J = 3.5 Hz, OH), 5.50 (m, 1H), 6.66 (d, J = 3.3 Hz, 1H), 6.86 (d, J = 3.3 Hz, 1H), 7.20 (m, 1H), 7.74 (d, J = 4.9 Hz, 1H) and 7.79 (d, J = 3.7 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): 15.7, 50.2, 68.9, 125.6, 126.4, 128.4, 133.3, 134.5, 138.5, 141.5, 141.8 and 192.0 ppm. (Found: C, 57.18; H, 4.80; S, 25.41. Calc. for C12H12O2S2: C, 57.14; H, 4.76; S, 25.39%.)

3-Hydroxy-1,3-di(thiophen-2-yl)propan-1-one (3d): yellow oil, IR (neat): 3400, 3095, 2925, 1651, 1601, 1515, 1413 cm-1. 1H NMR (500 MHz, CDCl3): 3.41 (dd, J = 16.0, 6.0 Hz, 1H), 3.53 (dd, J = 16.0, 6.0 Hz, 1H), 3.54 (d, J = 3.5 Hz, OH), 4.45 (m, 1H), 6.95–6.91 (m, 2H), 7.17 (m, 2H), 7.67 (m, 1H) and 7.81 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ 50.2, 69.0, 125.4, 126.1, 126.6, 128.6, 133.3, 134.5, 141.9, 142.9 and 192.2 ppm. (Found: C, 55.50; H, 4.24; S, 26.92. Calc. for C11H10O2S2: C, 55.46; H, 4.20; S, 26.89%.)

3-(Furan-2-yl)-3-hydroxy-1-(thiophen-2-yl)propan-1-one (3e): yellow oil, IR (neat): 3400, 3382, 2925, 1656, 1517, 1465 cm-1. 1H NMR (500 MHz, CDCl3): 3.40 (dd, J = 16.0, 6.0 Hz, 1H), 3.47 (dd, J = 16.0, 6.0 Hz, 1H), 3.70 (d, J = 3.5 Hz, OH), 4.21 (m, 1H), 6.12 (m, 1H), 6.27 (m, 1H), 7.32–7.15 (m, 2H), 7.67 (m, 1H) and 7.82 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): 47.5, 63.2, 105.8, 110.0, 128.5, 133.3, 134.2, 141.5, 141.8, 152.8 and 192.2 ppm. (Found: C, 59.43; H, 4.54; S, 14.43. Calc. for C11H10O3S: C, 59.45; H, 4.50; S, 14.41%.

3-Hydroxy-3-(4-methoxyphenyl)-1-(thiophen-2-yl)propan-1-one (3f): yellow oil, IR (neat): 3450, 2925, 1700, 1635, 1455 cm-1.1H NMR (500 MHz, CDCl3): 3.55 (m, 3H), 3.33 (dd, J = 16.0, 6.8 Hz, 1H), 3.40 (dd, J = 16.0, 6.8 Hz, 1H), 3.56 (d, J = 3.1 Hz, OH), 5.38 (m, 1H), 7.45–7.15 (m, 4H), 7.83–7.67 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): δ 42.7, 50.3, 70.3, 117.3, 117.5, 128.6, 128.7, 132.6, 133.1, 134.2, 154.6 and 214.1 ppm. (Found: C, 64.14; H, 5.31; S, 12.25. Calc. for C14H14O3S: C, 64.12; H, 5.34; S, 12.21%.)

3-Hydroxy-1-(thiophen-2-yl)-3-p-tolylpropan-1-one (3g): yellow oil, IR (neat): 3450, 2925, 1700, 1635, 1455 cm-1.1H NMR (500 MHz, CDCl3): δ 3.50 (m, 3H), 3.30 (dd, J = 16.0, 6.8 Hz, 1H), 3.49 (dd, J = 16.0, 6.8 Hz, 1H), 2.50 (s, OH), 5.29 (m, 1H), 7.41–7.25 (m, 4H), 7.80–7.66 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): 42.7, 50.3, 70.3, 117.3, 117.5, 128.6, 128.7, 132.6, 133.1, 134.2, 154.6 and 214.1 ppm. (Found: C, 68.28; H, 5.73; S, 13.02. Calc. for C14H14O2S: C, 68.29; H, 5.69; S, 13.00%.)

3-Hydroxy-3-(2-methoxyphenyl)-1-(thiophen-2-yl)propan-1-one (3h): yellow oil, IR (neat): 3452, 2935, 1700, 1615, 1445 cm-1.1H NMR (500 MHz, CDCl3): 3.55 (m, 3H), 3.31 (dd, J = 16.0, 6.8 Hz, 1H), 3.44 (dd, J = 16.0, 6.8 Hz, 1H), 3.54 (d, J = 3.2 Hz, OH), 5.35 (m, 1H), 7.46–7.12 (m, 4H), 7.81–7.69 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): 42.9, 55.3, 72.3, 117.1, 117.4, 128.6, 128.7, 132.6, 133.3, 134.2, 154.5 and 214.2 ppm. (Found: C, 64.11; H, 5.32; S, 12.23. Calc. for C14H14O3S: C, 64.12; H, 5.34; S, 12.21%.)

3-Hydroxy-3-phenyl-1-(thiophen-2-yl)propan-1-one (3i): yellow oil, IR (neat): 3460, 2950, 1700, 1625, 1475 cm-1.1H NMR (500 MHz, CDCl3): 3.35 (dd, J = 16.0, 6.8 Hz, 1H), 3.45 (dd, J = 16.0, 6.8 Hz, 1H), 2.50 (s, OH), 4.80 (m, 1H), 7.25–7.19 (m, 5H), 7.59–7.20 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): 42.9, 72.3, 117.1, 117.4, 128.6, 128.7, 132.6, 133.3, 134.2, 154.5 and 214.2 ppm. (Found: C, 67.28; H, 5.18; S, 13.80. Calc. for C13H12O2S: C, 67.24; H, 5.17; S, 13.79%.)

Acknowledgment

The authors are grateful to the Research Council of Guilan University for the support of this study.

References

  1. S.-I. Murahashi, Ruthenium in Organic Synthesis, Wiley-VCH, New York, NY, USA, 2004.
  2. C. S. Yi, S. Y. Yun, and Z. He, “Conjugate addition of alcohols to acrylic compounds catalyzed by a bifunctional ruthenium-acetamido complex,” Organometallics, vol. 22, no. 15, pp. 3031–3033, 2003. View at: Publisher Site | Google Scholar
  3. P.-B. Ilan and B. Ouri, “Transformation of carbinols by RuCl2(PPh3)3 and by some other transition-metal catalysts,” The Journal of Organic Chemistry, vol. 45, pp. 4418–4428, 1980. View at: Google Scholar
  4. T. Mukaiyama, “Explorations into new reaction chemistry,” Angewandte Chemie International Edition, vol. 43, no. 42, pp. 5590–5614, 2004. View at: Publisher Site | Google Scholar
  5. T. D. Machajewski and C.-H. Wong, “The catalytic asymmetric aldol reaction,” Angewandte Chemie International Edition, vol. 39, no. 8, pp. 1352–1374, 2000. View at: Publisher Site | Google Scholar
  6. R. Mahrwald, “Diastereoselection in Lewis-acid-mediated aldol additions,” Chemical Reviews, vol. 99, no. 5, pp. 1095–1120, 1999. View at: Google Scholar
  7. J. March, Advanced Organic Chemistry: Reactions, Mechanisms and Structure, Wiley-Interscience, New York, NY, USA, 4th edition, 1992.
  8. H.-X. Wei, R. L. Jasoni, H. Shao, J. Hu, and P. W. Paré, “Anti-selective and regioselective aldol addition of ketones with aldehydes using MgI2 as promoter,” Tetrahedron, vol. 60, no. 51, pp. 11829–11835, 2004. View at: Publisher Site | Google Scholar
  9. M. Wang and C.-J. Li, “Aldol reaction via in situ olefin migration in water,” Tetrahedron Letters, vol. 43, no. 19, pp. 3589–3591, 2002. View at: Publisher Site | Google Scholar
  10. S. Matsunaga, T. Ohshima, and M. Shibasaki, “Linked-BINOL: an approach towards practical asymmetric multifunctional catalysis,” Advanced Synthesis & Catalysis, vol. 344, no. 1, pp. 3–15, 2002. View at: Google Scholar
  11. B. M. Trost, E. R. Silcoff, and H. Ito, “Direct asymmetric aldol reactions of acetone using bimetallic zinc catalysts,” Organic Letters, vol. 3, no. 16, pp. 2497–2500, 2001. View at: Publisher Site | Google Scholar
  12. N. Yoshikawa, N. Kumagai, S. Matsunaga et al., “Direct catalytic asymmetric aldol reaction: synthesis of either syn-or anti-a,ß-dihydroxy ketones,” Journal of the American Chemical Society, vol. 123, no. 10, pp. 2466–2467, 2001. View at: Publisher Site | Google Scholar
  13. K. Tabatabaeian, M. Mamaghani, N. O. Mahmoodi, and E. Keshavarz, “Ruthenium-catalyzed cross aldol reaction with aldehydes and ketones,” Arkivoc, vol. 2009, no. 2, pp. 68–75, 2009. View at: Google Scholar
  14. T. A. Stephenson and G. Wilkinson, “New complexes of ruthenium (II) and (III) with triphenylphosphine, triphenylarsine, trichlorostannate, pyridine and other ligands,” Journal of Inorganic and Nuclear Chemistry, vol. 28, no. 4, pp. 945–956, 1966. View at: Google Scholar
  15. K. Tabatabaeian, M. Mamaghani, N. O. Mahmoodi, and A. Khorshidi, “Ultrasonic-assisted ruthenium-catalyzed oxidation of aromatic and heteroaromatic compounds,” Catalysis Communications, vol. 9, no. 3, pp. 416–420, 2008. View at: Publisher Site | Google Scholar
  16. K. Tabatabaeian, M. Mamaghani, N. O. Mahmoodi, and A. Khorshidi, “RuIII-catalyzed double-conjugate 1,4-addition of indoles to symmetric enones,” Journal of Molecular Catalysis A, vol. 270, no. 1-2, pp. 112–116, 2007. View at: Publisher Site | Google Scholar
  17. K. Tabatabaeian, M. Mamaghani, N. Mahmoodi, and A. Khorshidi, “Efficient RuIII-catalyzed condensation of indoles and aldehydes or ketones,” Canadian Journal of Chemistry, vol. 84, no. 11, pp. 1541–1545, 2006. View at: Publisher Site | Google Scholar
  18. K. Tabatabaeian, M. Mamaghani, N. O. Mahmoodi, and A. Khorshidi, “Solvent-free, ruthenium-catalyzed, regioselective ring-opening of epoxides, an efficient route to various 3-alkylated indoles,” Tetrahedron Letters, vol. 49, pp. 1450–1454, 2008. View at: Publisher Site | Google Scholar

Copyright © 2010 Khalil Tabatabaeian et al. 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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