Next Article in Journal
Previous Article in Journal
7-{[2-(4-Hydroxyphenyl)methylidene]amino}-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Short Note

tert-Butyl 1-(Furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate

Department of Studies in Chemistry, Mangalore University, Mangalagangotri-574 199, Karnataka, India
Aurigene Discovery Technologies Limited, Electronics city, Phase-II, Bangalore-560 100, Karnataka, India
Research Department of Chemistry, P. A College of Engineering, Nadupadavu, Mangalore 574153, Karnataka, India
Author to whom correspondence should be addressed.
Molbank 2012, 2012(2), M757;
Original submission received: 27 February 2012 / Accepted: 11 May 2012 / Published: 24 May 2012


A simple and novel route for synthesis of new spirocyclic compound is developed. The present work involves condensation of ethyl nipecotate with 2-furaldehyde followed by the MnO2 oxidation to give the β-keto ester which upon reaction with hydrazine hydrate gives the spiro pyrazolone.

Graphical Abstract


Spirocyclic compounds have attracted the attention of organic chemists due to their unique structural and reactivity pattern. These compounds represent an important class of naturally occurring substances characterized by their highly pronounced biological activities [1,2]. The spiro functionality shown in countless phytochemicals, such as in alkaloids, lactones, terpenoids, and clinically valuable compounds has been known for a long time. Arguably among the most challenging structural motifs to synthesize, all-carbon spirocyclics have inspired chemists for decades [3]. At present, spirocyclic compounds play a very important role in many fields such as chiral medicine, chiral LCD materials, macromolecule bulking agent and biological pesticides [4,5,6]. Because of the promising biological activity of spirocyclic compounds it was decided to prepare a new spiro-heterocyclic compound.

Results and Discussion

The title compound, tert-butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate (3), was prepared by the condensation of 1-tert-butyl 3-ethyl 3-(furan-2-carbonyl)piperidine-1,3-dicarboxylate (2) with hydrazine hydrate in acidic medium (Scheme 1). The intermediate 2 was in turn prepared by the condensation of ethyl nipecotate (1) with furfuraldehyde in presence of lithium diisopropyl amide (LDA) followed by MnO2 oxidation [7,8,9]. The final product was well characterized by using NMR, IR and mass spectral data.
The IR spectrum of compound (3) showed a wide absorption band at 3,412 cm−1 due to the presence of NH in the molecule. Two sharp bands at 1,693 and 1,624 cm−1 was due to Boc carbonyl and carbonyl group respectively. In 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 broad singlet observed at δ 11.4 ppm was due to the proton of pyrazolone NH. Nine protons of three methyl groups in Boc side chain resonated at δ 1.3 ppm as a doublet. The eight protons of piperidine ring resonated in the region at δ 1.4–3.75 ppm as different signals due to chemical non-equivalence of these protons. The three protons of furan ring resonated at δ 6.65, 7.06 and 7.84 ppm as a multiplet and two singlets respectively. The mass spectrum showed a peak at m/z 220 corresponding to M+-Boc group as the Boc group gets cleaved during the mass spectral conditions. Elemental analysis and 13C-NMR spectrum also gave satisfactory results for the title compound.


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 (mmax in cm−1). 1H-NMR (400 MHz) spectrum was recorded on a Bruker AMX 400 spectrometer, with 5 mm PABBO BB -1H TUBES and 13C-NMR (100 MHz) spectrum was recorded for approximately 0.03 M solutions in DMSO-d6 at 100 MHz with TMS as internal standard. 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 condensation of ethyl nipecotate (1) with furfuraldehyde in THF in the presence of lithium diisopropyl amide (LDA) at −78 °C yielded 1-tert-butyl 3-ethyl 3-(furan-2-yl(hydroxy)methyl)piperidine-1,3-dicarboxylate [7,8] which on oxidation by MnO2 yielded the intermediate, 1-tert-butyl 3-ethyl 3-(furan-2-carbonyl)piperidine-1,3-dicarboxylate (2) [9].
To a solution of 2 (3.79 g, 10.78 mmole) in ethanol (20 mL), hydrazine hydrate, (99%, 5.0 mL, 100 mmole) was added followed by 0.3 mL of acetic acid. The reaction mixture was stirred at the ambient temperature for 6 h. After the completion of reaction as indicated by TLC, the reaction mixture was cooled to 0–5 °C and filtered. The product was washed with chilled ethanol (10 mL) followed by ether (10 mL) and dried to afford the title compound. Yield was 3.0 g, 87.2%.
Melting point: 229–232 °C.
LCMS: m/z = 220, (M+-Boc) + 1.
IR (KBr): νmax (cm−1), 3412 (NH), 3097 (Furyl C-H), 2927 (aliphatic CH), 1693 (Boc C=O), 1624 (amide C=O), 1595 (C=N).
1H-NMR (400 MHz, DMSO-d6): δ ppm, 1.3 (s, 9H, Boc-CH3), 1.4 (d, 2H, Piperidine-H, J = 12.4 Hz), 1.95 (m, 2H, Piperidine-H), 2.95 (m, 1H, Piperidine-H), 3.45 (d, 1H, Piperidine-H, J = 13.6 Hz), 3.75 (m, 2H, Piperidine-H), 6.65 (m, 1H, Furyl-H), 7.06 (s, 1H, Furyl-H), 7.84 (s, 1H, Furyl-H),11.4 (s, broad, 1H, pyrazolone –NH).
13C-NMR (100 MHz, DMSO-d6): δ ppm, 17.95 (CH2 of piperidine), 27.96 (t-butyl-CH3), 43.29, 45.53, 46.74, 47.63 (Piperidine C’s), 78.58 (Boc-CMe3), 111.18, 111.57, 145.81, 144.63 (Furyl), 150.65 (Pyrazolone-C), 153.35 (Boc-CO),177.05 (pyrazolone CO).
Elemental analysis: Calculated for C16H21N3O4, C, 60.17%; H, 6.63%; N, 13.16%; Found: C, 60.13%; H, 6.64%; N, 13.13%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3


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


  1. Mead, K.T.; Brewer, B.N. Strategies in spiroketal 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. Sannigrahi, M. Stereocontrolled synthesis of spirocyclics. Tetrahedron 1999, 55, 9007–9071. [Google Scholar] [CrossRef]
  4. Zhang, Z.-H. Synthesis and application of chiral spiro ligands in asymmetric catalysis. Chin. J. Org. Chem. 2005, 25, 355–363. [Google Scholar]
  5. 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]
  6. Pan, C.-Y.; Wang, Y.; William, J.B. The investigation of polymerization mechanism of 7-methylene-2-methyl-1,4,6-triox-aspiro(4,4)nonane. Acta Polym. Sin. 1989, 1, 18–24. [Google Scholar]
  7. Aslanian, R.G; Bennett, C.E.; Burnett, D.A.; Chan, T.-Y.; Kiselgof, E.Y.; Knutson, C.E.; Harris, J.M.; Mc Kittrick, B.A.; Palani, A.; Smith, E.M.; Vaccaro, H.M.; Xiao, D.; Kim, H.M. Azetidinone derivatives and methods of use thereof. WO2008033464(A2), 20 March 2008. [Google Scholar]
  8. Theodoridis, G.; Rosen, D.; Zhang, S.; Yeager, W.H.; Henrie, I.R.N.; Ahmed, S.Z.; Men, H.; Donovan, S.F. N-Substituted azacycles. WO2005036961(A2), 28 April 2005. [Google Scholar]
  9. Corey, E.J.; Gilman, N.W.; Ganem, B.E. New methods for the oxidation of aldehydes to carboxylic acids and esters. J. Am. Chem. Soc. 1968, 90, 5616–5617. [Google Scholar] [CrossRef]
Scheme 1. Synthesis of tert-butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate.
Scheme 1. Synthesis of tert-butyl 1-(furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate.
Molbank 2012 m757 sch001

Share and Cite

MDPI and ACS Style

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.

AMA Style

Srinivasan R, Narayana B, Samshuddin S, Sarojini BK. tert-Butyl 1-(Furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate. Molbank. 2012; 2012(2):M757.

Chicago/Turabian Style

Srinivasan, Rajagopalan, Badiadka Narayana, Seranthimata Samshuddin, and Balladka Kunhanna Sarojini. 2012. "tert-Butyl 1-(Furan-2-yl)-4-oxo-2,3,7-triazaspiro[4.5]dec-1-ene-7-carboxylate" Molbank 2012, no. 2: M757.

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