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Volume 2012
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Short Note

5-(tert-Butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol

by
Linda Bouarata
1,
Dahmane Tebbani
1,* and
Paul Mosset
2
1
Département de chimie, Faculté des sciences, Université de Constantine 1, Constantine 25000, Algeria
2
Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France
*
Author to whom correspondence should be addressed.
Molbank 2012, 2012(4), M790; https://doi.org/10.3390/M790
Submission received: 30 October 2012 / Accepted: 4 December 2012 / Published: 14 December 2012
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Abstract

:
Novel 5-(tert-butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol (7) was prepared via allylation of 2-chloro-5,8-dimethoxyquinoline-3-carbaldehyde (6) with functionalized allylic iodide as tert-butyl-(3-(iodomethyl)but-3-enyloxy)dimethylsilane (5), in the presence of metallic indium in anhydrous DMF as solvent at ambient temperature. The structure of the synthesized compound was assigned on the basis of elemental analysis and spectral data.

Graphical Abstract

Introduction

Quinoline and its derivatives form an important class of organic compounds due to their structural chemistry and biological activities as antifungal [1,2], antibacterial [2,3,4,5,6,7], antiviral [3,8,9,10,11,12], and anticancer [9,13,14,15,16] properties. Compounds possessing the quinoline moiety exhibit significant activity against several diseases such as malaria [17], and cardiovascular pathologies [18,19]. In continuation to develop synthesis of compounds possessing biological activities, we report in this paper the synthesis of homoallylic alcohol 7 by allylation [20] of 2-chloro-5,8-dimethoxyquinoline-3-carbaldehyde (6) with functionalized allylic iodide 5 using metallic indium. The synthesized homoallylic alcohol 7 is an intermediate for the synthesis of heterocyclic compounds. Tetrahydrofurans and tetrahydropyrans are important moieties of natural biologically active compounds such as antibiotics (Monensine, Lasalocide A) and antimicrobial (Milbemycine, Avermectines). It was also found that spiroacetals obtained by allylation of cycloalkanones, are contained in many natural compounds produced by insects having pheromonal activity.

Result and Discussion

We have synthesized the allylic iodide 5 according to a known method [21] (scheme 1), in three steps starting from dimethyl itaconate (1). The iodide was prepared in small quantities because it was unstable and was stored in darkness.
Molbank 2012 m790 sch001 550
Scheme 1. Synthesis of allylic iodide 5.
Scheme 1. Synthesis of allylic iodide 5.
Molbank 2012 m790 sch001
We first studied the addition of allylic bromide 3 with aldehyde 6 in the presence of metallic indium in different solvents. Compared to acetonitrile, methanol and dichloromethane, DMF was found to be a good solvent. Allylic iodide 5 and bromide 3 were equally reactive. However, the reactivity of allylic chloride 4 was markedly diminished.
Molbank 2012 m790 sch002 550
Scheme 2. Synthesis of 5-(tert-butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol (7).
Scheme 2. Synthesis of 5-(tert-butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol (7).
Molbank 2012 m790 sch002

Experimental

All reactions were carried out under nitrogen atmosphere. DMF was dried on BaO and distilled under reduced pressure and stored on molecular sieves 4Å. Progress of the reactions and purity of the compounds were monitored by thin layer chromatography (TLC) using ethyl acetate/n-hexane as eluting system on silica gel (60–120 mesh), UV apparatus and anisaldehyde solution as visualizing agents.
1H (400 MHz) and 13C (100 MHz) spectra were recorded on a Bruker FT-ARX 400 spectrometer in CDCl3 using TMS as internal standard. The IR spectra were recorded on a Nicolet 205 FT spectrometer as KBr pellets. Elemental analysis was performed by the regional center of analysis of Rennes, CRMPO (Centre régional de mesures physiques de l’Ouest), Rennes, France.
To a suspension of indium powder (345 mg, 3 mmol) in dry DMF (3 mL) was added allylic iodide 5 (977.7 mg, 3 mmol) in DMF (1 mL) and 2-chloro-5,8-dimethoxyquinoline-3-carbaldehyde (6) (503.0 mg, 2 mmol) in DMF (1 mL). An exothermic reaction occurred immediately, the mixture was stirred at room temperature for 1 h and the mixture was quenched by addition of diluted hydrochloric acid. The product was extracted with ether and purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:50) to afford homoallylic alcohol 7 as yellow oil.
Yield: 0.76 g (84%).
IR (KBr, cm−1) ν 3415 (OH), 1647 (C=C).
1H-NMR (400 MHz, CDCl3) δ 8.90 (s, 1H, H-C4), 7.04 (d, 1H, J = 8.6 Hz, H-C7), 6.83 (d, 1H, J = 8.6 Hz, H-C6), 5.27 (ddd, 1H, J = 9.9, 2.4, 2.3 Hz, CHOH), 5.10 (m, 1H, C=CH2), 5.08 (broad ddd, 1H, J = 1.8, 1.6, 1.2 Hz, C=CH2), 4.03 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 3.94–3.83 (m, 2H, CH2OSi), 3.39 (d, 1H, J = 2.4 Hz, OH), 2.86 (ddd, 1H, J = 14.0, 2.4, 1.4 Hz, CH2CHOH), 2.44 (pseudo broad tt, 2H, J = 6.4, 1.0 Hz, CH2CH2OSi), 2.20 (ddd, 1H, J = 14.0, 9.9, 0.5 Hz, CH2CHOH), 0.92 (s, 9H, t-Bu), 0.10 (s, 6H, Si(CH3)2).
13C-NMR (100 MHz, CDCl3) δ 148.81 (Cquat, C8), 148.40 (Cquat, C5), 146.86 (Cquat, C8a), 143.59 (Cquat, C=CH2), 142.52 (Cquat, C2), 135.87 (Cquat, C3), 135.65 (CH, C4), 130.0 (CH, C7), 127.57 (Cquat, C4a), 127.06 (CH, C6), 115.89 (C=CH2), 68.71 (CHOH), 62.44 (CH2OSi), 56.24 (OCH3), 55.98 (OCH3), 45.65 (CH2CHOH), 38.58 (CH2CH2OSi), 25.96 (3C, C(CH3)3), 18.42 (Cquat, C(CH3)3), −5.29 (Si-CH3), −5.33 (Si-CH3).
Elemental analysis: Calculated for C23H34ClNO4Si: C, 61.13%; H, 7.53%; O, 14.17%; found: C, 61.05%; H, 7.47%; O, 14.08.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References

  1. Musiol, R.; Serda, M.; Hensel-Bielowka, S.; Polanski, J. Quinoline-Based Antifungals. Curr. Med. Chem. 2010, 17, 1960–1973. [Google Scholar] [CrossRef] [PubMed]
  2. Kumar, S.; Bawa, S.; Gupta, H. Biological Activities of Quinoline Derivatives. Mini Rev. Med. Chem. 2009, 9, 1648–1654. [Google Scholar] [CrossRef] [PubMed]
  3. Richter, S.; Parolin, C.; Palumbo, M.; Palu, G. Antiviral Properties of Quinolone-based Drugs. Curr. Drug Targets Infect. Disord. 2004, 4, 111–116. [Google Scholar] [CrossRef] [PubMed]
  4. Segev, S.; Rubinstein, E. Future aspects [of quinoline antibacterials]. In Handbook of Experimental Pharmacology; Kuhlmann, J., Dalhoff, A., Zeiler, H.-J., Eds.; Springer: Berlin, Germany, 1998; Volume 127, pp. 454–475. [Google Scholar]
  5. Rosen, T. 6 The fluoroquinolone antibacterial agents. Prog. Med. Chem. 1990, 27, 235–295. [Google Scholar] [PubMed]
  6. Lontie, M. Les nouvelles quinolones. J. Pharm. Belg. 1989, 44, 292–301. [Google Scholar] [PubMed]
  7. Fernandes, P.B.; Chu, D.T.W. Quinolone antibacterial agents. Annu. Rep. Med. Chem. 1988, 23, 133–140. [Google Scholar]
  8. Kaushik, S.; Gupta, S.P.; Sharma, P.K. Design and development of anti-hepatitis B virus agents. Curr. Med. Chem. 2010, 17, 3377–3392. [Google Scholar] [CrossRef] [PubMed]
  9. Das, B.; Krishnaiah, M.; Venkateswarlu, K.; Das, R. Camptothecins: Review on the bioactive natural products. Part XVIII. Some recent chemical studies. Nat. Prod. Commun. 2006, 1, 255–263. [Google Scholar]
  10. Okamoto, H.; Cujec, T.P.; Okamoto, M.; Peterlin, B.M.; Baba, M.; Okamoto, T. Inhibition of the RNA-Dependent Transactivation and Replication of Human Immunodeficiency Virus Type 1 by a Fluoroquinoline Derivative K-37. Virology 2000, 272, 402–408. [Google Scholar] [CrossRef] [PubMed]
  11. Baba, M.; Okamoto, M.; Makino, M.; Kimura, Y.; Ikeuchi, T.; Sakaguchi, T.; Okamoto, T. Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives. Antimicrob. Agents Chemother. 1997, 41, 1250–1255. [Google Scholar] [PubMed]
  12. Wentland, M.P.; Perni, R.B.; Dorff, P.H.; Brundage, P.; Castaldi, M.J.; Carlson, J.A.; Bailey, T.R.; Aldous, S.C.; Carabateas, P.M.; Bacon, E.R.; et al. Antiviral properties of 3-quinolinecarboxamides: A series of novel non-nucleoside antiherpetic agents. Drug Des. Discov. 1997, 15, 25–38. [Google Scholar] [PubMed]
  13. Solomon, V.R.; Lee, H. Quinoline as a privileged scaffold in cancer drug discovery. Curr. Med. Chem. 2011, 18, 1488–1508. [Google Scholar] [CrossRef] [PubMed]
  14. Khan, M.T.H. Quinoline analogs as antiangiogenic agents and telomerase inhibitors. Top. Heterocycl. Chem. 2007, 11, 213–229. [Google Scholar]
  15. Joseph, B.; Darro, F.; Behard, A.; Lesur, B.; Collignon, F.; Decaestecker, C.; Frydman, A.; Guillaumet, G.; Kiss, R. 3-Aryl-2-Quinolone Derivatives: Synthesis and Characterization of In Vitro and In Vivo Antitumor Effects with Emphasis on a New Therapeutical Target Connected with Cell Migration. J. Med. Chem. 2002, 45, 2543–2555. [Google Scholar] [CrossRef] [PubMed]
  16. Bergh, J.C.S.; Toetterman, T.H.; Termander, B.C.; Strandgarden, K.A.-M.P.; Gunnarsson, P.O.G.; Nilsson, B.I. The first clinical pilot study of roquinimex (Linomide) in cancer patients with special focus on immunological effects. Cancer Invest. 1997, 15, 204–211. [Google Scholar] [CrossRef] [PubMed]
  17. Kaur, K.; Jain, M.; Reddy, R.P.; Jain, R. Quinolines and structurally related heterocycles as antimalarials. Eur. J. Med. Chem. 2010, 45, 3245–3264. [Google Scholar] [CrossRef] [PubMed]
  18. Feldman, A.M.; Strobeck, J.E. Quinolinone derivatives in the management of congestive heart failure. Coronary Artery Dis. 1994, 5, 107–111. [Google Scholar] [CrossRef]
  19. Javed, T.; Baker, N.R. Synthesis and biological activity of quinoline analogues in cardiovascular disease. In Pharmacological Aspects of Cardiovascular Medicine; Javed, T., Ed.; Research Signpost: Trivandrum, India, 2002; pp. 55–83. [Google Scholar]
  20. Araki, S.; Ito, H.; Butsugan, Y. Indium in organic synthesis: Indium-mediated allylation of carbonyl compounds. J. Org. Chem. 1988, 53, 1831–1833. [Google Scholar] [CrossRef]
  21. Hughes, R.C.; Dvorak, C.A.; Meyers, A.I. An Asymmetric Approach to Spirocylic Systems: A Formal Synthesis of Zizaene. J. Org. Chem. 2001, 66, 5545–5551. [Google Scholar] [CrossRef] [PubMed]

Share and Cite

MDPI and ACS Style

Bouarata, L.; Tebbani, D.; Mosset, P. 5-(tert-Butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol. Molbank 2012, 2012, M790. https://doi.org/10.3390/M790

AMA Style

Bouarata L, Tebbani D, Mosset P. 5-(tert-Butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol. Molbank. 2012; 2012(4):M790. https://doi.org/10.3390/M790

Chicago/Turabian Style

Bouarata, Linda, Dahmane Tebbani, and Paul Mosset. 2012. "5-(tert-Butyldimethylsilyloxy)-1-(2-chloro-5,8-dimethoxyquinolin-3-yl)-3-methylenepentan-1-ol" Molbank 2012, no. 4: M790. https://doi.org/10.3390/M790

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