Next Article in Journal
2-[(4-Bromophenylimino)methyl]-5-pentadecylphenol
Previous Article in Journal
2-[3-(Aziridin-1-yl)-2-hydroxypropyl]-5,5-dimethyl-2,5-dihydro-4H-benzo[e]isoindol-4-one (Cytotoxic Oxonaphthalene-Pyrroles, Part III)
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

4-[5-(3,5-Difluorophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one Hydrochloride

1
Department of Studies in Chemistry, Mangalore University, Mangalagangotri-574 199, Karnataka, India
2
Aurigene Discovery Technologies Limited, Electronics city, Phase-II, Bangalore-560 100, Karnataka, India
3
Research Department of Chemistry, P. A College of Engineering, Nadupadavu, Mangalore 574153, Karnataka, India
*
Author to whom correspondence should be addressed.
Molbank 2012, 2012(3), M773; https://doi.org/10.3390/M773
Submission received: 3 July 2012 / Accepted: 21 August 2012 / Published: 24 August 2012

Abstract

:
A novel route for the synthesis of new spirocyclic derivative is developed. The present work involves the synthesis of title compound 3 by Suzuki coupling of 3,5-difluorophenyl boronic acid with tert-butyl 1-(5-bromofuran-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate (2), which in turn prepared from the ethyl nipecotate (1). Newly prepared spirocyclic derivative (3) is characterized by IR, NMR and mass spectral data.

Graphical Abstract

Introduction

The spiro framework is an important subunit in a vast number of natural products such as alkaloid: (−)-sibirine, fused tetracyclic lycopodium alkaloid: nankakurine-A, several spongistatins: β-vetivone, acorenone B, fredericamycin and Shizuca-acordienol [1,2]. Many spirocyclic compounds have been found to display inter alia antiinflammatory [3] and herbicidal activity [4] or act as aromatase inhibitors [5]. Moreover, the unique structural features of spirocyclics have been used for the synthesis of new ligands and catalysts such as spirobisoxazolines, SPINOL, SPINOL-derived phosphoric acids etc. [6,7,8]. Due to their unique structural properties, several methodologies have been reported for the synthesis of spiro compounds [9,10,11]. In view of the biological importance of spirocycles and in continuation of our effort on the synthesis of new spirocyclic derivatives [12,13], a new spirocyclic derivative was synthesized and characterized.

Results and Discussion

The title compound, 4-[5-(3,5-diflurophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one hydrochloride (3), was prepared by the PdCl2 (dppf) catalyzed Suzuki coupling of tert-butyl 1-(5-bromofuran-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate (2) with 3,5-difluorophenyl boronic acid followed by deprotection of Boc group (Scheme 1). The intermediate 2, a bromo substituted derivative of tert-butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate, was prepared by using 5-bromo-2-furaldehyde as described in our earlier work [12]. The final product 3 was well characterized by using NMR, IR and mass spectral data.
The IR spectrum of compound (3) showed a wide absorption band at 3425 cm−1 due to the presence of NH in the molecule. The absorption band at 1708 cm−1 is due to the stretching of amide carbonyl group. In the 1H-NMR spectrum, the signals of the respective protons of the title compound (3) were verified on the basis of their chemical shifts, multiplicities and coupling constants. A singlet observed at δ 12.18 ppm was due to the proton of piperidine NH. Another singlet observed at δ 9.70 ppm was due to the proton of pyrazolone NH. The two furyl protons appeared as two doublets at δ 7.43 and 7.46 ppm. The eight protons of piperidine ring resonated in the region δ 1.8–3.6 ppm as different signals due to chemical non-equivalence of these protons. The mass spectrum showed a molecular ion peak at m/z 332 corresponding to (M+−HCl)+1 as the HCl gets instantly dissociated in the mass spectral conditions. Elemental analysis and 13C-NMR spectrum also gave satisfactory results for the title compound.

Experimental

Melting point was taken in open capillary tube and was uncorrected. The purity of the compound was confirmed by thin layer chromatography using Merck silica gel 60 F254 coated aluminium plates. IR spectrum was recorded on Shimadzu-FTIR Infrared spectrometer in KBr (νmax in cm−1). 1H-NMR (400 MHz) spectrum was recorded on a Varian 400 spectrometer, with 5 mm PABBO BB-1H TUBES and 13C-NMR (100 MHz) spectrum was recorded for approximately 0.03 M solutions in CD3OD at 100 MHz with TMS as internal standard. All exchangeable protons were confirmed by addition of D2O. LCMS was obtained using Agilent 1200 series LC and Micromass zQ spectrometer. Elemental analysis was carried out by using VARIO EL-III (Elementar Analysensysteme GmBH).
The synthesis of tert-butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate was described in our earlier work [12]. Intermediate (2) was prepared by following the same procedure using 5-bromo-2-furaldehyde instead of 2-furaldehyde.
To a solution of 2 (0.3 g, 0.755 mmol) in 1,2-dimethoxyethane (2 mL), 3,5-difluorophenyl boronic acid (0.143 g, 0.9 mmol) was added followed by Na2CO3 solution (0.24 g, 2.264 mmol). After passing nitrogen to the reaction mass for 30 min, PdCl2 (dppf) (0.124 g, 0.152 mmol) was added and heated to 80 °C and maintained for 4 h. After the completion of reaction as indicated by TLC, the reaction mixture was concentrated to afford the crude material which was purified by column chromatography. The isolated product was reacted with HCl in 1,4-dioxane [14] to afford the title compound. Yield was 123 mg, 44%.
Melting point: 193–200 °C.
LCMS: m/z = 332, (M+−HCl)+1.
IR (KBr): νmax (cm−1), 3424 (NH), 3087 (Ar-H), 1708 (pyrazolone C=O), 1588 (C=N), 1213 (C-F).
1H-NMR (400 MHz, DMSO-d6): δ ppm, 1.76 (d, 1H, Piperidine-H, J = 14 Hz), 1.88 (d, 1H, Piperidine-H, J = 13.6 Hz), 2.20 (m, 3H, Piperidine-H), 3.61 (d, 1H, Piperidine-H, J = 13.2Hz), 7.24 (m, 2H, 3,5-Difluorophenyl-H), 7.43 (d, 2H, Furyl-H, J = 4 Hz), 7.46 (d, 2H, Furyl-H, J = 3.6 Hz), 7.51 (d, 1H, 3,5-Difluorophenyl-H), 7.74 (broad s, 1H, HCl, D2O exchangeable), 9.70 (s, 1H, Pyrazolone-NH, D2O exchangeable), 12.18 (s, 1H, Piperidine-NH, D2O exchangeable).
13C-NMR (100 MHz, CD3OD): δ ppm, 15.62, 26.84, 43.1, 44.48, 66.2 (Piperidine C’s), 102.5, 106.1, 108.9, 113.5, 132.1, 145.1, 149.1 (Ar-C), 152.9 (C=N), 161.91 (C-F), 164 (C-F), 177.6 (Pyrazolone C=O).
Elemental analysis: Calculated for C17H16ClF2N3O2, C, 55.52%; H, 4.38%; N, 11.43%; Found: C, 55.49%; H, 4.42%; N, 11.38%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgments

RS thanks Aurigene Discovery Technologies Limited and Mangalore University for research facilities.

References

  1. Mead, K.T.; Brewer, B.N. Strategies in spiro ketal synthesis revisited: Recent applications and advances. Curr. Org. Chem. 2003, 7, 227–256. [Google Scholar] [CrossRef]
  2. Shi, Z.-J.; Zhang, S.-L.; Cao, W.-G.; Deng, H.-M. Facile synthesis of a series of perfluoroalkyl-containing tetra-spirocyclic compounds and their spectral analysis. Chin. J. Chem. 2008, 26, 2103–2106. [Google Scholar] [CrossRef]
  3. Yang, L.; Qin, L.-H.; Bligh, S.W.A.; Bashall, A.; Zhang, C.-F.; Zhang, M.; Wang, Z.-T.; Xu, L.-S. A new phenanthrene with a spirolactone from Dendrobium chrysantum and its antiinflammatory activities. Bioorg. Med. Chem. 2006, 14, 3496–3501. [Google Scholar] [CrossRef] [PubMed]
  4. Gates, P.S.; Baldwin, D.; Wilson, C.A.; Gillon, J. Herbicidal 5-cyano-2,3-dihydrobenzofuran-2-ones. U.S. Patent 4263037, 1982. [Chem. Abstr. 1982, 97, 215978]. [Google Scholar]
  5. Edwards, P.N.; Large, M.S. Preparation of 8-(triazolylmethyl)naphtho[2,1-b]furanones and analogs as aromatase inhibitors. EP Patent 316079, 1989. [Chem. Abstr. 1989, 111, 232794]. [Google Scholar]
  6. Zhang, Z.-H. Synthesis and application of chiral spiro ligands in asymmetric catalysis. Chin. J. Org. Chem. 2005, 25, 355–363. [Google Scholar]
  7. Arai, M.A.; Kuraishi, M.; Arai, T.; Sasai, H. A new asymmetric Wacker-type cyclization and tandem cyclization promoted by Pd(II)-spiro bis(isoxazoline) catalyst. J. Am. Chem. Soc. 2001, 123, 2907–2908. [Google Scholar] [CrossRef] [PubMed]
  8. Ding, K.; Han, Z.; Wang, Z. Spiro skeletons: A class of privileged structure for chiral ligand design. Chem.–Asian J. 2009, 4, 32–41. [Google Scholar] [CrossRef] [PubMed]
  9. Rios, R. Enantioselective methodologies for the synthesis of spiro compounds. Chem. Soc. Rev. 2012, 41, 1060–1074. [Google Scholar] [CrossRef] [PubMed]
  10. Zea, A.; Alba, A.N.R.; Mazzanti, A.; Moyano, A.; Rios, R. Highly enantioselective cascade synthesis of spiropyrazolones. Org. Biomol. Chem. 2011, 9, 6519–6523. [Google Scholar] [CrossRef] [PubMed]
  11. Alba, A.N.R.; Zea, A.; Valero, G.; Calbet, T.; Font-Bardía, M.; Mazzanti, A.; Moyano, A.; Rios, R. Highly stereoselective synthesis of spiropyrazolones. Eur. J. Org. Chem. 2011, 2011, 1318–1334. [Google Scholar] [CrossRef]
  12. Srinivasan, R.; Narayana, B.; Samshuddin, S.; Sarojini, B.K. tert-Butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate. Molbank 2012, 2012, M757. [Google Scholar]
  13. Srinivasan, R.; Narayana, B.; Samshuddin, S.; Sarojini, B.K. N-(3,4-Dimethoxyphenyl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-1-carboxamide hydrochloride. Molbank 2012, 2012, M769. [Google Scholar]
  14. Han, G.; Tamaki, M.; Hruby, V.J. Fast, efficient and selective deprotection of the tert-butoxycarbonyl (Boc) group using HCl/dioxane (4 M). J. Pept. Res. 2001, 58, 338–341. [Google Scholar]
Scheme 1. Synthesis of 4-[5-(3,5-diflurophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one hydrochloride.
Scheme 1. Synthesis of 4-[5-(3,5-diflurophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one hydrochloride.
Molbank 2012 m773 sch001

Share and Cite

MDPI and ACS Style

Srinivasan, R.; Narayana, B.; Samshuddin, S.; Sarojini, B.K. 4-[5-(3,5-Difluorophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one Hydrochloride. Molbank 2012, 2012, M773. https://doi.org/10.3390/M773

AMA Style

Srinivasan R, Narayana B, Samshuddin S, Sarojini BK. 4-[5-(3,5-Difluorophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one Hydrochloride. Molbank. 2012; 2012(3):M773. https://doi.org/10.3390/M773

Chicago/Turabian Style

Srinivasan, Rajagopalan, Badiadka Narayana, Seranthimata Samshuddin, and Balladka Kunhanna Sarojini. 2012. "4-[5-(3,5-Difluorophenyl)furan-2-yl]-2,3,7-triazaspiro[4.5]dec-3-en-1-one Hydrochloride" Molbank 2012, no. 3: M773. https://doi.org/10.3390/M773

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop