LETTER
O. A.; Giorgi, G.; Favi, G.; Filippone, P.; Lillini, S.; Perrulli,
Syntheses of Amidines from Thioamides
1967
H-6), 2.60–2.53 (m, 4 H, H-4, H-5), 2.30 (s, 3 H, H-5¢); 13
NMR (50 MHz, CDCl3): d = 176.7, 160.8, 146.3, 133.1,
C
F. R.; Santeusanio, S. Synlett 2007, 1691.
(4) (a) Joannesse, C.; Simal, C.; Concellon, C.; Thomson, J. E.;
Campbell, C. D.; Slawin, A. M. Z.; Smith, A. D. Org.
Biomol. Chem. 2008, 6, 2900. (b) Ahmad, S. M.; Braddock,
D. C.; Cansell, G.; Hermitage, S. A.; Redmond, J. M.; White,
A. J. P. Tetrahedron Lett. 2007, 48, 5948.
(5) Tanaka, K.; Wakatsuki, S. JP 2008156542, 2008; Chem.
Abstr. 2008, 149, 105547.
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): d (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): d (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): d (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): d (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.
(21) Dorokhov, V. A.; Cherkasova, K. L.; Rozhkova, T. I.;
Bogdanov, V. S.; Tananykin, N. I.; Smirnov, V. Y.;
Semenov, S. Y. Metalloorg. Khim. 1988, 1, 1411.
(22) (a) Spiessens, L. I.; Anteunis, M. J. O. Bull. Soc. Chim. Belg.
1982, 91, 763. (b) Spiessens, L. I.; Anteunis, M. J. O. Bull.
Soc. Chim. Belg. 1983, 92, 965.
(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.
(6) (a) Kowai, K.; Sakaguchi, N.; Kono, K. JP 2008120718,
2008; Chem. Abstr. 2008, 148, 569011. (b) Giordani, A.;
Mandelli, S.; Zanzola, S.; Tarchino, F.; Caselli, G.;
Fiorentino, T. S.; Mazzari, S.; Makovec, F.; Rovati, L. C.
WO 2008014815, 2008; Chem. Abstr. 2008, 148, 239229.
(7) (a) Deng, Y.; Liu, J.; Zhang, Q.; Li, F.; Yang, Y.; Li, P.; Ma,
J. Inorg. Chem. Commun. 2008, 11, 433.
(b) Wanniarachchi, Y. A.; Slaughter, L. M. Chem. Commun.
2007, 31, 3294.
(8) Anthony, N. G.; Breen, D.; Clarke, J.; Donoghue, G.;
Drummond, A. J.; Ellis, E. M.; Gemmell, C. G.; Helesbeux,
J.-J.; Hunter, I. S.; Khalaf, A. I.; Mackay, S. P.; Parkinson,
J. A.; Suckling, C. J.; Waigh, R. D. J. Med. Chem. 2007, 50,
6116.
(9) Al Ashry, S. H.; Abdel-Rahman, A. A.-H.; El Kilany, Y.;
Schmidt, R. R. Tetrahedron 1999, 55, 2381.
(10) (a) Barker, P. L.; Gendler, P. L.; Rapoport, H. J. Org. Chem.
1981, 46, 2455. (b) Stanek, J.; Caravatti, G.; Capraro, H.-G.;
Furet, P.; Mett, H.; Schneider, P.; Regenass, U. J. Med.
Chem. 1993, 36, 460. (c) Nii, Y.; Okano, K.; Kobayashi, S.;
Ohno, M. Tetrahedron Lett. 1979, 2517. (d) Nakayama, Y.;
Senokuchi, K.; Sakaki, K.; Kato, M.; Maruyama, T.;
Miyazaki, T.; Ito, H.; Nakai, H.; Kawamura, M. Bioorg.
Med. Chem. 1997, 5, 971.
(11) (a) Avalos, M.; Babiano, R.; Cintas, P.; Durán, C. J.;
Jiménez, J. L.; Palacios, J. C. Tetrahedron 1995, 51, 8043.
(b) Foloppe, M. P.; Rault, S.; Thurston, D. E.; Jenkins, T. C.;
Robba, M. Eur. J. Med. Chem. 1996, 31, 407. (c) Suzuki,
K.; Fujii, T.; Sato, K.-I.; Hashimoto, H. Tetrahedron Lett.
1996, 37, 5921. (d) Barin, C. T.; Brunton, S. A. Tetrahedron
Lett. 2002, 43, 1893. (e) Dobashi, Y.; Kobayashi, K.;
Dobashi, A. Tetrahedron Lett. 1998, 39, 93. (f) Panday, N.;
Vasella, A. Synthesis 1999, 1459. (g) Marchand-Brynaert,
J.; Moya-Portuguez, M.; Huber, I.; Ghosez, L. J. Chem. Soc.,
Chem. Commun. 1983, 818.
(12) Schmidt, A.; Merkel, L.; Eisfeld, W. Eur. J. Org. Chem.
2005, 2124.
(13) Schmidt, A.; Beutler, A.; Habeck, T.; Mordhorst, T.;
(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-Ka
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 F2 (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, b = 98.29 (2)°, V = 1172.2
(3) Å3, Z = 4, d (calcd.) = 1.339 g cm–3, F(000) = 496 using
2066 independent reflections and 208 parameters.
Snovydovych, B. Synthesis 2006, 1882.
(14) Schmidt, A.; Habeck, T.; Snovydovych, B.; Eisfeld, W. Org.
Lett. 2007, 9, 3515.
(15) Schmidt, A.; Snovydovych, B.; Hemmen, S. Eur. J. Org.
Chem. 2008, 4313.
(16) Schmidt, A.; Snovydovych, B. Synthesis 2008, 2798.
(17) Lindner, A. S.; Schmidt, A. Synlett 2008, 2961.
(18) Yde, B.; Yousif, N. M.; Pedersen, U.; Thomsen, I.;
Lawesson, S. O. Tetrahedron Lett. 1984, 40, 2047.
(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): d = 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,
R1 = 0.0722, wR2 = 0.0983 [I >2s(I)], goodness of fit on
Synlett 2009, No. 12, 1964–1968 © Thieme Stuttgart · New York