Journal of Chemical Crystallography

, Volume 40, Issue 4, pp 296–301 | Cite as

Synthesis and Crystal Structure Determination of Methyl 2-acetyl-5′-phenyl-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate and Methyl 2-acetyl-5′-(2-thienyl)-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate

  • Clyde R. Metz
  • John D. Knight
  • Anna C. Dawsey
  • William T. Pennington
  • Donald G. VanDerveer
  • Jordan B. Brown
  • Kevin J. Bigham
  • Charles F. Beam
Original Paper


Dilithiated C(α), N-carbomethoxyhydrazones were condensed with lithiated methyl 2-(aminosulfonyl)benzoate to afford intermediates that were isolated and not characterized but cyclized with acetic anhydride, which also resulted in N-acetylation. The X-ray crystal structure determinations of methyl 2-acetyl-5′-phenyl-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate and methyl 2-acetyl-5′-(2-thienyl)-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate products were a follow up for absorption spectra, and they confirmed their structures. Mechanistic intermediates to describe the reaction may include C-acylated intermediates that cyclize to spiro(N-benzoisothiazole dioxide-pyrazole) instead of N-carbomethoxypyrazole-ortho-benzenesulfonamides. Crystals of C19H17N3O5S 7 are monoclinic, P21/c, a = 11.899(2) Å, b = 17.562(4) Å, c = 9.484(2) Å, β = 111.03(3)°, Z = 4, V = 1849.9(6) Å3, R 1 = 0.0857 and wR 2 = 0.2216 for reflections with I > 2σ(I); crystals of C17H15N3O5S2 8 are orthorhombic, Pbca, a = 16.045(3) Å, b = 10.746(2) Å, c = 20.389(4) Å, Z = 8, V = 3516(1) Å3, R 1 = 0.0841 and wR 2 = 0.2179 for all reflections with I > 2σ(I).

Graphical Abstract

X-ray crystal analysis was important for determining the conformation of the structure of N-acetyl-N′-carbomethoxy-spiro(benzoisothiazole–pyrazole)dioxides prepared by the condensation and twofold cyclization of dilithiated C(α), N-carbomethoxyhydrazones and methyl 2-(aminosulfonyl)benzoate.


Spiro(benzoisothiazole-pyrazoles) Multiple anions Anion–anion condensations 



We wish to thank the following sponsors: the Research Corporation, the National Science Foundation Grants CHE # 9708014 and # 0212699 for Research at Undergraduate Institutions, the United States Department of Agriculture, NRICGP # 2003-35504-12853, and the Petroleum Research Fund, Administered by the American Chemical Society. The College of Charleston awarded summer grants through its Summer Undergraduate Research Forum (SURF-2006 and 2007) to J. D. Knight and (SURF-2007) A. C. Dawsey.


  1. 1.
    Martins MAP, Cunico W, Pereira CMP, Sinhorin AP, Flores AFC, Bonacorso HG, Zanatta N (2004) Current Org Synth 1:391CrossRefGoogle Scholar
  2. 2.
    Muniz-Miranda M, Cardini G, Schettino V (2004) Theor Chem Acc 111:264Google Scholar
  3. 3.
    Lipton AS, Wright TA, Bowman MK, Reger DL, Ellis PD (2002) J Am Chem Soc 124:5850CrossRefGoogle Scholar
  4. 4.
    Boyer G, Galy JP, Faure R, Barbe J (1994) Magn Res Chem 32:537CrossRefGoogle Scholar
  5. 5.
    Okafor EC, Uzoukwu BA (1991) Syn React Inorg Metal Org Chem 21:825CrossRefGoogle Scholar
  6. 6.
    Sanz D, Claramunt RM, Alkorta I, Elguero J (2007) Struct Chem 18:703CrossRefGoogle Scholar
  7. 7.
    Shi F-Q, Song B-A (2008) Int J Quantum Chem 108:1107CrossRefGoogle Scholar
  8. 8.
    Wang H, Wang X, Wang H, Wang L, Liu A (2007) J Mol Model 13:147CrossRefGoogle Scholar
  9. 9.
    Menegatti R, Silva GMS, Zapata-Sudo G, Raimundo JM, Sudo RT, Barreiro EJ, Fraga CAM (2006) Bioorgan Med Chem 14:632CrossRefGoogle Scholar
  10. 10.
    Elguero J, Goya P, Jagerovic N, Silva AMS (2002) Targets Heterocycl Syst 6:52Google Scholar
  11. 11.
    Akbas E, Berber I (2006) Eur J Med Chem 41:904CrossRefGoogle Scholar
  12. 12.
    Bajpai VK, Lee TJ, Kang SC (2009) J Sci Food Agriculture 89:109CrossRefGoogle Scholar
  13. 13.
    Stanovnik B, Svete J (2002) Sci Synth 12:15Google Scholar
  14. 14.
    Elguero J (1996) Comp Heterocycl Chem II 3:1, 817Google Scholar
  15. 15.
    Shcherbakova I, Elguero J, Katritzky AR (2000) Adv Heterocycl Chem 77:51CrossRefGoogle Scholar
  16. 16.
    Redkin RG, Shemchuk LA, Chernykh VP, Shishkin OV, Shishkina SV (2007) Tetrahedron 63:11444CrossRefGoogle Scholar
  17. 17.
    Khodairy A, El-Sayed AM, Salah H, Abdel-Ghany H (2007) Synth Commun 37:3245CrossRefGoogle Scholar
  18. 18.
    Holzer W, Claramunt RM, Perez-Torralba M, Guggi D, Brehmer TH (2003) J Org Chem 68:7943CrossRefGoogle Scholar
  19. 19.
    Raghunathan R, Shanmugasundaram M, Bhanumathi S, Malar EJP (1998) Heteroatom Chem 9:327CrossRefGoogle Scholar
  20. 20.
    Mishriky N, Girgis AS, Hosni HM, Farag H (2006) J Heterocycl Chem 43:1549CrossRefGoogle Scholar
  21. 21.
    Dawood KM (2005) Tetrahedron 61:5229CrossRefGoogle Scholar
  22. 22.
    Sammelson RE, Gurusinghe CD, Kurth JM, Olmstead MM, Kurth MJ (2002) J Org Chem 67:876CrossRefGoogle Scholar
  23. 23.
    Khalil S, Hossain MB, van der Helm D, Alam M, Sanduja R (1996) Acta Crystallographica C 52:1272Google Scholar
  24. 24.
    Grant BJ, Kramp CR, Knight JD, Meierhoefer MA, Vella JH, Sober CL, Jones SS, Metz CR, Beam CF, Pennington WT, VanDerveer DG, Camper ND (2007) J Heterocycl Chem 44:627CrossRefGoogle Scholar
  25. 25.
    Wrobel J, Dietrich A (1994) Heterocycles 38:1823CrossRefGoogle Scholar
  26. 26.
    Grant SP, Embree MC, Downs JR, Townsend JD, Beam CF (2003) Ind Eng Chem Res 42:5721CrossRefGoogle Scholar
  27. 27.
    Meierhoefer MA, Dunn SP, Hajiaghamohseni LM, Walters MJ, Embree MC, Grant SP, Downs JR, Townsend JD, Metz CR, Beam CF, Pennington WT, VanDerveer DG, Camper ND (2005) J Heterocycl Chem 42:1095CrossRefGoogle Scholar
  28. 28.
    Dunn SP, Walters MJ, Metz CR, Beam CF, Pennington WT, Krawiec M (2004) J Heterocycl Chem 41:1005CrossRefGoogle Scholar
  29. 29.
    Knight JD, Brown JB, Overby JS, Beam CF, Camper ND (2008) J Heterocycl Chem 45:189CrossRefGoogle Scholar
  30. 30.
    Mirone P, Vampiri M (1952) Atti Accad Nazl Lincei Rend Classe Sci Fis Mat e Nat 583 (Chem Abstr 46:9423)Google Scholar
  31. 31.
    Johnson AL, Sweetser PB (1976) J Org Chem 41:110CrossRefGoogle Scholar
  32. 32.
    Rigaku Corporation (1999) Crystal clear. Rigaku Corporation, Danvers. Google Scholar
  33. 33.
    Jacobson RA (1998) Absorption correction used REQABS v 1.1. Molecular Structure Corp, College StationGoogle Scholar
  34. 34.
    Sheldrick, GM (1997) SHELX-97, Crystallographic Computing System–Windows Version; University of Gottingen, GermanyGoogle Scholar
  35. 35.
    Cromer DT, Waber JT (1974) International tables for X-ray crystallography, Vol IV, Tables 2.2 B and 2.3.1. Kluwer Academic Publisher, DordrechtGoogle Scholar
  36. 36.
    Farrugia LJ (1997) ORTEP-3 for windows. J Appl Cryst 30:565CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Clyde R. Metz
    • 1
  • John D. Knight
    • 1
  • Anna C. Dawsey
    • 1
  • William T. Pennington
    • 2
  • Donald G. VanDerveer
    • 2
  • Jordan B. Brown
    • 1
  • Kevin J. Bigham
    • 1
  • Charles F. Beam
    • 1
  1. 1.Department of Chemistry and BiochemistryCollege of CharlestonCharlestonUSA
  2. 2.Department of ChemistryClemson UniversityClemsonUSA

Personalised recommendations