Download PDF
Synlett 2009(12): 1964-1968  
DOI: 10.1055/s-0029-1217539
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Syntheses of Amidines from Thioamides, Mediated by the N-Heterocyclic Carbene Indazol-3-ylidene

Swetlana Scherbakowa, Jan C. Namysloa, Mimoza Gjikajb, Andreas Schmidt*a
a Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
Fax: +49(5323)723861; e-Mail: schmidt@ioc.tu-clausthal.de;
b Institute of Inorganic Chemistry, Clausthal University of Technology, Paul-Ernst-Str. 4, 38678 Clausthal-Zellerfeld, Germany
Further Information

Publication History

Received 14 April 2009
Publication Date:
03 July 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

On decarboxylation, 1,2-dimethylindazolium-3-carboxylate forms the N-heterocyclic carbene 1,2-dimethylindazol-3-ylidene in situ, which proved to be a suitable reagent for amidinations of the mono-thiolactams of succinimide and phthalimide.

Key Words

thiolactam - mesomeric betaine - decarboxylation

    References and Notes

  • 1 Dunn PJ. In Comprehensive Organic Functional Group Transformations   Vol. 5:  Katritzky AR. Meth-Cohn O. Rees CW. Pergamon Press; Cambridge: 1995.  p.741 
    Google Scholar
  • 2 Fleischhauer J. Beckert R. Günther W. Kluge S. Zahn S. Weston J. Berg D. Goerls H. Synthesis  2007,  2839 
    Article in Thieme ConnectGoogle Scholar
  • 3a Yang D. Fu H. Hu L. Jiang Y. Zhao Y. J. Org. Chem.  2008,  73:  7841 
    Google Scholar
  • 3b Gao X. Fu H. Qiao R. Jiang Y. Zhao Y. J. Org. Chem.  2008,  73:  6864 
    Google Scholar
  • 3c Attanasi OA. Giorgi G. Favi G. Filippone P. Lillini S. Perrulli FR. Santeusanio S. Synlett  2007,  1691 
    Google Scholar
  • 4a Joannesse C. Simal C. Concellon C. Thomson JE. Campbell CD. Slawin AMZ. Smith AD. Org. Biomol. Chem.  2008,  6:  2900 
    Google Scholar
  • 4b Ahmad SM. Braddock DC. Cansell G. Hermitage SA. Redmond JM. White AJP. Tetrahedron Lett.  2007,  48:  5948 
    Google Scholar
  • 5 Tanaka K, and Wakatsuki S. inventors; JP  2008156542.  ; Chem. Abstr. 2008, 149, 105547
  • 6a Kowai K, Sakaguchi N, and Kono K. inventors; JP  2008120718.  ; Chem. Abstr. 2008, 148, 569011
  • 6b Giordani A, Mandelli S, Zanzola S, Tarchino F, Caselli G, Fiorentino TS, Mazzari S, Makovec F, and Rovati LC. inventors; WO  2008014815.  ; Chem. Abstr. 2008, 148, 239229
  • 7a Deng Y. Liu J. Zhang Q. Li F. Yang Y. Li P. Ma J. Inorg. Chem. Commun.  2008,  11:  433 
    Google Scholar
  • 7b Wanniarachchi YA. Slaughter LM. Chem. Commun.  2007,  31:  3294 
    Google Scholar
  • 8 Anthony NG. Breen D. Clarke J. Donoghue G. Drummond AJ. Ellis EM. Gemmell CG. Helesbeux J.-J. Hunter IS. Khalaf AI. Mackay SP. Parkinson JA. Suckling CJ. Waigh RD. J. Med. Chem.  2007,  50:  6116 
    CrossrefGoogle Scholar
  • 9 Al Ashry SH. Abdel-Rahman AA.-H. El Kilany Y. Schmidt RR. Tetrahedron  1999,  55:  2381 
    CrossrefGoogle Scholar
  • 10a Barker PL. Gendler PL. Rapoport H. J. Org. Chem.  1981,  46:  2455 
    Google Scholar
  • 10b Stanek J. Caravatti G. Capraro H.-G. Furet P. Mett H. Schneider P. Regenass U. J. Med. Chem.  1993,  36:  460 
    Google Scholar
  • 10c Nii Y. Okano K. Kobayashi S. Ohno M. Tetrahedron Lett.  1979,  2517 
    Google Scholar
  • 10d Nakayama Y. Senokuchi K. Sakaki K. Kato M. Maruyama T. Miyazaki T. Ito H. Nakai H. Kawamura M. Bioorg. Med. Chem.  1997,  5:  971 
    Google Scholar
  • 11a Avalos M. Babiano R. Cintas P. Durán CJ. Jiménez JL. Palacios JC. Tetrahedron  1995,  51:  8043 
    Google Scholar
  • 11b Foloppe MP. Rault S. Thurston DE. Jenkins TC. Robba M. Eur. J. Med. Chem.  1996,  31:  407 
    Google Scholar
  • 11c Suzuki K. Fujii T. Sato K.-I. Hashimoto H. Tetrahedron Lett.  1996,  37:  5921 
    Google Scholar
  • 11d Barin CT. Brunton SA. Tetrahedron Lett.  2002,  43:  1893 
    Google Scholar
  • 11e Dobashi Y. Kobayashi K. Dobashi A. Tetrahedron Lett.  1998,  39:  93 
    Google Scholar
  • 11f Panday N. Vasella A. Synthesis  1999,  1459 
    Google Scholar
  • 11g Marchand-Brynaert J. Moya-Portuguez M. Huber I. Ghosez L. J. Chem. Soc., Chem. Commun.  1983,  818 
    Google Scholar
  • 12 Schmidt A. Merkel L. Eisfeld W. Eur. J. Org. Chem.  2005,  2124 
    Google Scholar
  • 13 Schmidt A. Beutler A. Habeck T. Mordhorst T. Snovydovych B. Synthesis  2006,  1882 
    Article in Thieme ConnectGoogle Scholar
  • 14 Schmidt A. Habeck T. Snovydovych B. Eisfeld W. Org. Lett.  2007,  9:  3515 
    CrossrefPubMedGoogle Scholar
  • 15 Schmidt A. Snovydovych B. Hemmen S. Eur. J. Org. Chem.  2008,  4313 
    CrossrefGoogle Scholar
  • 16 Schmidt A. Snovydovych B. Synthesis  2008,  2798 
    Article in Thieme ConnectGoogle Scholar
  • 17 Lindner AS. Schmidt A. Synlett  2008,  2961 
    Article in Thieme ConnectGoogle Scholar
  • 18 Yde B. Yousif NM. Pedersen U. Thomsen I. Lawesson SO. Tetrahedron Lett.  1984,  40:  2047 
    CrossrefGoogle Scholar
  • 21 Dorokhov VA. Cherkasova KL. Rozhkova TI. Bogdanov VS. Tananykin NI. Smirnov VY. Semenov SY. Metalloorg. Khim.  1988,  1:  1411 
    Google Scholar
  • 22a Spiessens LI. Anteunis MJO. Bull. Soc. Chim. Belg.  1982,  91:  763 
    Google Scholar
  • 22b Spiessens LI. Anteunis MJO. Bull. Soc. Chim. Belg.  1983,  92:  965 
    Google Scholar
  • 23 This compound was mentioned in a mechanistic study but was not fully characterized, see: Okubo M. Sakata M. Iwatsu Y. Tsurusaki N. Nakashima S. Iwamoto Y. Nonaka H. Yamauchi A. Matsuo K. Phys. Org. Chem.  1997,  10:  242 
    CrossrefGoogle Scholar
  • 25 Sheldrick GM. SHELXS-97, SHELXL-97, A program package for crystal structure solution and refinement   University of Göttingen; Germany: 1997. 
    Google Scholar
19

Synthesis of 3-Methyl-2-(p-tolylimino)-pyrrolidin-1-one (13b); Typical Procedure: Samples of 2-methyl-3-thioxopyrrolidin-1-one (12; 77 mg, 0.60 mmol), p-toluidine (64 mg, 0.60 mmol) and 1,2-dimethylindazolium-3-carboxylate (1; 114 mg, 0.60 mmol) were suspended in toluene (3 mL) and heated for 3 h at reflux. The solvent was then distilled off, and the resulting residue was purified by chromatography on silica gel (petroleum ether-EtOAc, 4:1). The amidine 13b was obtained as a yellow solid (70 mg, 58%). ¹H NMR (200 MHz, CDCl3): δ = 7.10 (d, J = 8.0 Hz, 2 H, H-3′), 6.72 (d, J = 8.0 Hz, 2 H, H-2′), 3.12 (s, 3 H,
H-6), 2.60-2.53 (m, 4 H, H-4, H-5), 2.30 (s, 3 H, H-5′); ¹³C NMR (50 MHz, CDCl3): δ = 176.7, 160.8, 146.3, 133.1, 129.7, 120.5, 28.3, 26.0, 22.8, 21.0; IR (KBr): 2936, 1898, 1744, 1659, 1507, 1429, 1382, 1322, 1292, 1215, 1134, 946, 837, 745, 648, 563 cm-¹; MS: m/z (%) = 202 (100) [M+], 173 (40) [M - 2CH3], 159 (40) [M - 2CH3 - O]; Anal. Calcd for C12H14N2O: C, 71.26; H, 6.98; N, 13.85. Found: C, 70.60; H, 6.75; N, 13.61.

20

3-(12-Methoxyphenylimino)isoindolin-1-one (15g); Typical Procedure: Samples of 3-thioxoisoindolinone (14a; 98 mg, 0.60 mmol), p -anisidine (74 mg, 0.60 mmol) and 1,2-dimethylindazolium-3-carboxylate (1; 114 mg, 0.60 mmol) were suspended in toluene (3 mL) and heated for 3 h at reflux. The solvent was then distilled off in vacuo, and the resulting residue was purified by chromatography (silica gel; petroleum ether-EtOAc, 4:1). The product was obtained as yellow needles (75 mg, 50% yield). mp 150 ˚C; ¹H NMR (400 MHz, CDCl3): δ (Z-isomer) = 8.02 (s, 1 H, NH), 8.01 (d, J = 7.4 Hz, 1 H, H-4), 7.85 (d, J = 7.4 Hz, 1 H, H-7), 7.73 (ddd, J = 7.5, 7.5, 1.1 Hz, 1 H, H-5), 7.66 (ddd, J = 7.5, 7.5, 1.1 Hz, 1 H, H-6), 7.00 (d, J = 8.5 Hz, 2 H, H-3′), 6.92 (d, J = 8.5 Hz, 2 H, H-2′), 3.81 (s, 3 H, H-5′); ¹³C NMR (100 MHz, CDCl3): δ (Z-isomer) = 168.6, 157.1, 148.7, 140.8, 136.2, 132.9, 132.2, 131.2, 123.5, 122.5, 122.5, 114.8, 55.6. ¹H NMR (400 MHz, CDCl3): δ (E-isomer) = 8.57 (br s, 1 H, NH), 7.82 (m, 1 H, H-7), 7.55 (m, 1 H, H-6), 7.35 (ddd, J = 7.5, 7.5, 1.1 Hz, 1 H, H-5), 6.94-6.90 (m, 4 H, H-2′,
H-3′), 6.75 (d, J = 7.7 Hz, 1 H, H-4), 3.85 (s, 3 H, H-5′); ¹³C NMR (100 MHz, CDCl3): δ (E-isomer) = 168.2, 156.9, 151.6, 141.2, 133.3, 133.3, 132.3, 130.0, 125.7, 123.7, 121.1, 114.6. IR (KBr): 2996, 2784, 1732, 1669, 1504, 1472, 1361, 1290, 1249, 1192, 1111, 1032, 837, 778, 702, 622

cm-¹. MS: m/z (%) = 252 (100) [M+], 237 (75) [M - CH3]; Anal. Calcd for C15H12N2O2: C, 71.41; H, 4.79; N, 11.11. Found: C, 70.41; H, 4.29; N, 11.19.

24

X-ray structure analysis for 15d: Empirical formula: C15H12N2O; M = 236.27 g/mol. A suitable single crystal of the title compound (grown in DMSO) was selected under a polarization microscope and mounted in a glass capillary (d = 0.3 mm). The crystal structure was determined by X-ray diffraction analysis using graphite monochromated Mo-K α radiation [0.71073 Å; T = 223 (2) K], whereas the scattering intensities were collected with a single crystal diffractometer (STOE IPDS II). The crystal structure was solved by Direct Methods using SHELXS-97 and refined using alternating cycles of least squares refinements against F ² (SHELXL-97). ²5 All non-H atoms were located in Difference Fourier maps and were refined with anisotropic displacement parameters. The H positions were determined by a final Difference Fourier Synthesis. 15d crystallized in the space group P21/c(monoclinic), lattice parameters a = 5.489 (1) Å, b = 8.684 (1) Å, c = 24.851 (5) Å, β = 98.29 (2)˚, V = 1172.2 (3) ų, Z = 4, d (calcd.) = 1.339 g cm-³, F(000) = 496 using 2066 independent reflections and 208 parameters. R1 = 0.0722, wR2 = 0.0983 [I >2σ(I)], goodness of fit on F ²  = 1.104, residual electron density = 0.575 and -0.397 e Å-³.

26

Details of the crystal structure investigations have been deposited with the Cambridge Crystallographic Data Center, CCDC 727259. Copies of this information may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: +44 (1223)336033; e-mail: fileserv@ccdc.ac.uk or http://www.ccdc.cam.ac.uk)