A Convenient Synthesis of Functionalized 2,3-Diazaspiro[4.4]nona-1,6,8-trienes

Issa Yavari; Jamil Sheykhahmadi; Samira Bahemat; Mohammad Reza Halvagar

doi:10.1055/s-0037-1610549

Synlett, Table of Contents

Synlett 2018; 29(15): 2019-2022
DOI: 10.1055/s-0037-1610549

letter

A Convenient Synthesis of Functionalized 2,3-Diazaspiro[4.4]nona-1,6,8-trienes

Issa Yavari*

^aDepartment of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran Email: yavarisa@modares.ac.ir

,

Jamil Sheykhahmadi

^aDepartment of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran Email: yavarisa@modares.ac.ir

,

Samira Bahemat

^bDepartment of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran, PO Box 14335-186, Tehran, Iran

,

Mohammad Reza Halvagar

^bDepartment of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran, PO Box 14335-186, Tehran, Iran

› Author Affiliations

Abstract

All articles of this category

Abstract

A convenient Michael addition/cyclization sequence of alkyl isocyanide–acetylenic ester zwitterionic adducts with various pyrazolone derivatives, leading to the formation of dialkyl 6-(alkylamino)-1-methyl-4-oxo-3-phenyl-9-aryl-2,3-diazaspiro[4.4]nona-1,6,8-triene-7,8-dicarboxylates in moderate to good yields, is described. The structure of the target compounds was confirmed by an X-ray diffraction study.

Key words

spiro compounds - 4-arylidenepyrazolones - alkyl isocyanides - acetylenic esters - domino reaction

Full Text

References

References and notes

For selected reviews, see:

1a Chauhan P. Mahajan S. Enders D. Chem. Commun. 2015; 51: 12890
1b Schmidt A. Dreger A. Curr. Org. Chem. 2011; 15: 1423
1c Varvounis G. Adv. Heterocycl. Chem. 2009; 98: 143
1d Horton DA. Bourne GT. Smythe ML. Chem. Rev. 2003; 103: 893

For selected examples, see:

2a Li J. -H. Wen H. Liu L. Du D. -M. Eur. J. Org. Chem. 2016; 2492
2b Yang S. Shen L.-l. Kim Y.-J. Jeong J.-H. Org. Biomol. Chem 2016; 14: 623
2c Yetra SR. Mondal S. Mukherjee S. Gonnade RG. Biju AT. Angew. Chem. Int. Ed. 2016; 55: 268
2d Bao X. Wang B. Cui L. Zhu G. He Y. Qu I. Song Y. Org. Lett. 2015; 17: 5168

For selected examples, see:

3a Han B. Huang W. Ren W. He G. Wang J.-h. Peng C. Adv. Synth. Catal. 2015; 357: 561
3b Li JH. Du DM. Chem. Asian J. 2014; 9: 3278
3c Liang J. Chen Q. Liu L. Jiang X. Wang R. Org. Biomol. Chem. 2013; 11: 1441
3d Zhang JX. Li NK. Liu ZM. Huang XF. Geng ZC. Wang XW. Adv. Synth. Catal. 2013; 355: 797
3e Liu L. Zhong Y. Zhang P. Jiang X. Wang R. J. Org. Chem. 2012; 77: 10228

4 Bondock S. Rabie R. Etman HA. Fadda AA. Eur. J. Med. Chem. 2008; 43: 2122

5a Janin YL. Bioorg. Med. Chem. 2007; 15: 2479
5b Gutierrez-Lugo MT. Bewley CJ. J. Med. Chem. 2008; 51: 2606

6a Nicolaou KC. Snyder SA. Proc. Natl. Acad. Sci. USA 2004; 101: 11929
6b Mohr JT. Krout MR. Stoltz BM. Nature 2008; 455: 323
6c Sorensen EJ. Davies HM. L. Chem. Soc. Rev. 2009; 38: 2969

7a Deng JC. Chan FW. Kuo CW. Cheng CA. Huang CY. Chuang SC. Eur. J. Org. Chem. 2012; 5738
7b Zea A. Alba AN. R. Mazzanti A. Moyano A. Rios R. Org. Biomol. Chem. 2011; 9: 6519

8a Han Y. Sheng YJ. Yan CG. Org. Lett. 2014; 16: 2654
8b Gong H. Sun J. Yan CG. Synthesis 2014; 46: 2327
8c Vuluga D. Legros J. Crousse B. Bonnet-Delpon D. Green Chem. 2009; 11: 156
8d Tinarelli A. Righi P. Rosini G. Andreotti D. Profeta R. Spada S. Tetrahedron 2011; 67: 612

9a Yavari I. Naeimabadi M. Sheykhahmadi J. Bahemmat S. Halvagar MR. ChemistrySelect 2018; 3: 11370
9b Yavari I. Hojati M. Azad L. Halvagar MR. Synlett 2018; 26: 1024
9c Diyanatizadeh MH. Yavari I. J. Sulfur Chem. 2016; 37: 54
9d Yavari I. Nematpour M. Sodagar E. Monatsh. Chem. 2015; 146: 2135
9e Yavari I. Mirzaei A. Moradi L. Khalili G. Tetrahedron Lett. 2010; 51: 396

10 Typical Procedure for the Preparation of Compounds 4To a stirred mixture of 2 (1 mmol) and 3 (1.2 mmol) in dry toluene (3 mL) was added 1 (1.0 mmol). The mixture was heated at 80 °C for 4 h. After completion (TLC monitoring), the solvent was removed under reduced pressure and the residue was puriﬁed by column chromatography (SiO₂; n-hexane/EtOAc 4:1) to aﬀord the products 4a–m.Dimethyl 6-(cyclohexylamino)-1-methyl-4-oxo-3,9-diphenyl-2,3-diazaspiro[4.4]nona-1,6,8-triene-7,8-dicarboxylate (4a)Yellow powder; yield: 0.38 g (70%); mp 142–144 °C. IR (KBr): 3443, 2930, 1725, 1658, 1588, 1450, 1351, 1253, 1209 cm⁻¹. ¹H NMR (500 MHz, CDCl₃): δ = 0.88–0.91 (m, 2 H, CH₂), 1.10–1.13 (m, 2 H, CH₂), 1.22–1.31 (m, 2 H, CH₂), 1.46–1.58 (m, 2 H, CH₂), 1.61–1.79 (m, 2 H, CH₂), 2.06 (s, 3 H, Me), 2.85 (br s, 1 H, N-CH), 3.71 (s, 3 H, MeO), 3.75 (s, 3 H, MeO), 7.16 (d, ³ J = 8.6 Hz, 2 H, Ar-H), 7.20 (t, ³ J = 8.7 Hz, 2 H, Ar-H), 7.20 (t, ³ J = 8.7 Hz, 1 H, Ar-H), 7.23 (t, ³ J = 7.4 Hz, 1 H, Ar-H), 7.41 (t, ³ J = 7.7 Hz, 2 H, Ar-H), 7.72 (d, ³ J = 8.5 Hz, 2 H, Ar-H), 8.29 (br s, 1 H, NH) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 14.1 (Me), 24.5 (CH₂), 24.6 (CH₂), 24.8 (CH₂), 34.5 (CH₂), 34.6 (CH₂), 51.0 (MeO), 52.1 (MeO), 54.1 (N-CH), 73.1 (C), 100.7 (C), 119.3 (2 CH), 123.3 (C), 125.9 (CH), 127.5 (2 CH), 128.1 (CH), 128.6 (2 CH), 129.0 (2 CH), 131.9 (C), 137.3 (C), 138.8 (C), 157.2 (C), 161.6 (C), 165.4 (C=O), 166.5 (C=O), 168.0 (C=O) ppm. MS (EI, 70 eV): m/z (%) = 513 (100) [M⁺], 482 (4), 399 (13), 367 (22), 340 (18), 312 (12), 232 (15), 129 (13), 105 (10), 77(20), 55 (25). Anal. Calcd for C₃₀H₃₁N₃O₅ (513.59): C, 70.16; H, 6.08; N, 8.18. Found: C, 70.44; H, 6.10; N 8.21.
11 X-Ray Crystal Structure Determination of 4aThe X-ray diffraction measurement was carried out with a STOE IPDS 2T diffractometer with graphite-monochromated Mo-K_α radiation. A crystal suitable for X-ray analysis was obtained from EtOH solution, mounted on a glass fiber and used for data collection. Compound 4a crystallized in the monoclinic crystal system and P 21/c space group. For the unit cell a = 7.9800(16) Å, b = 12.750(3) Å, c = 26.360(5) Å, α = 90°, β = 94.07(3)°, γ = 90°, Z = 4, cell volume = 2675.2(10) Å³ and orientation matrixes for data collection were obtained by least-square refinement of the diffraction data from 4237 reflections for compound 4a. Diffraction data were collected in a series of ω scans in 1° oscillations and integrated by using the STOE X-AREA software package (see ref.¹³). The structure was solved by direct methods and subsequent difference Fourier maps and then refined on F ² to final R ₁ = 0.0508 and wR ₂ (all data) = 0.1176 by a full-matrix least-squares procedure by using anisotropic displacement parameters. Atomic factors are from the International Tables for X-ray Crystallography. All non-hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were placed in ideal positions and refined as riding atoms with relative isotropic displacement parameters. All refinements were performed with use of the X-STEP32, SHELXL-2014, and WinGX-2013.3 programs (see ref.¹⁴).
12 CCDC-1822520 contains the supplementary crystallographic data for compound 4a in this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
13 X-AREA: Program for the Acquisition and Analysis of Data, Version 1.30; STOE & Cie GmbH: Darmstadt, 2005;

For details, see:

14a Farrugia LJ. J. Appl. Cryst. 1999; 32: 837
14b Allen FH. Johnson O. Shields GP. Smith BR. Towler M. J. Appl. Cryst. 2004; 37: 335
14c Macrae CF. Edgington PR. McCabe P. Pidcock E. Shields GP. Taylor R. Towler M. van der Streek J. J. Appl. Cryst. 2006; 39: 453
14d Burnett M. N., Johnson C. K.; ORTEP-III Report ORNL-6895; Oak Ridge National Laboratory: Tennessee USA, 1996;
14e Spek AL. J. Appl. Cryst. 2003; 36: 7
14f Sheldrick GM. Acta Crystallogr. Sect. A 2008; 64: 112

Supplementary Material

Supporting Information