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Synlett 2007(10): 1529-1532  
DOI: 10.1055/s-2007-982530
LETTER
© Georg Thieme Verlag Stuttgart · New York

Thia-Michael Addition Using Cheap and Odorless S-Alkylisothiouronium Salts as Thiol Equivalents in Water

Yan Zhaoa, Ze-Mei Ge*a, Tie-Ming Chenga, Run-Tao Li*a,b
a School of Pharmaceutical Sciences, Peking University, Beijing 100083, P. R. of China
b State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, P. R. of China
Fax: +86(10)82716956; e-Mail: zmge@bjmu.edu.cn;
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Publication History

Received 2 February 2007
Publication Date:
06 June 2007 (online)

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Abstract

S-Alkylisothiouronium salt has been found to be a nontoxic, odorless and simply operational alternative of thiol for the thia-Michael addition with electron-deficient olefins. The reactions were carried out under alkaline conditions in water at room temperature within 5-20 minutes to afford the expected products in good to excellent yields.

Key words

thia-Michael addition - thiol equivalent - S-alkylisothiouronium salts - electron-deficient olefins - green chemistry

    References and Notes

  • 1a Organosulfur Chemistry   Vols. 1-2:  Page PCB. Springer; Berlin: 1999. 
    Google Scholar
  • 1b Shono T. Matsumura Y. Kashimura S. Hatanaka K. J. Am. Chem. Soc.  1979,  101:  4752 
    Google Scholar
  • 2a Khan AT. Ghosh S. Choudhury LH. Eur. J. Org. Chem.  2006,  2226 
    Google Scholar
  • 2b Fetterly BM. Jana NK. Verkade JG. Tetrahedron  2006,  62:  440 
    Google Scholar
  • 2c Li BJ. Jiang L. Liu M. Chen YC. Ding LS. Wu Y. Synlett  2005,  603 
    Google Scholar
  • 2d Firouzabadi H. Iranpoor N. Jafari AA. Synlett  2005,  299 
    Google Scholar
  • 2e Chaudhuri MK. Hussain S. Kantam ML. Neelima B. Tetrahedron Lett.  2005,  46:  8329 
    Google Scholar
  • 2f Caupène C. Boudou C. Perrio S. Metzner P. J. Org. Chem.  2005,  70:  2812 
    Google Scholar
  • 2g Alam MM. Varala R. Adapa SR. Tetrahedron Lett.  2003,  44:  5115 
    Google Scholar
  • 2h Bandini M. Cozzi PG. Giacomini M. Melchiorre P. Selva S. Umani RA. J. Org. Chem.  2002,  67:  3700 
    Google Scholar
  • 2i Abrouki Y. Zahouily M. Rayadh A. Bahlaouan B. Sebti S. Tetrahedron Lett.  2002,  43:  8951 
    Google Scholar
  • 2j Zahouily M. Abrouki Y. Rayadh A. Tetrahedron Lett.  2002,  43:  7729 
    Google Scholar
  • 2k Cheng S. Comer DD. Tetrahedron Lett.  2002,  43:  1179 
    Google Scholar
  • 2l Kobayashi S. Ogawa C. Kawamura M. Sugiura M. Synlett  2001,  983 
    Google Scholar
  • 2m Mori Y. Kakumoto K. Manabe K. Kobayashi S. Tetrahedron Lett.  2000,  41:  3107 
    Google Scholar
  • 2n Saito M. Nakajima M. Hashimoto S. Tetrahedron  2000,  56:  9589 
    Google Scholar
  • 2o Emori E. Arai T. Sasai H. Shibasaki M. J. Am. Chem. Soc.  1998,  120:  4043 
    Google Scholar
  • 2p Nishimura K. Ono M. Nagaoka Y. Tomioka K. J. Am. Chem. Soc.  1997,  119:  12974 
    Google Scholar
  • 2q Kimura M. Matsubara S. Sawaki Y. Iwamura H. Tetrahedron Lett.  1986,  27:  4177 
    Google Scholar
  • 2r Mukaiyama T. Ikegawa A. Suzuki K. Chem. Lett.  1981,  2:  165 
    Google Scholar
  • 2s Cohen T. Mura AJ. Shull DW. Fogel ER. Ruffner RJ. Falck JR. J. Org. Chem.  1976,  41:  3218 
    Google Scholar
  • 3a Chu CM. Gao S. Sastry MNV. Kuo CW. Lu C. Liu JT. Yao CF. Tetrahedron  2007,  63:  1863 
    Google Scholar
  • 3b Khatik GL. Sharma G. Kumar R. Chakraborti AK. Tetrahedron  2007,  63:  1200 
    Google Scholar
  • 3c Firouzabadi H. Iranpoor N. Jafarpour M. Ghaderi A. J. Mol. Catal. A: Chem.  2006,  249:  98 
    Google Scholar
  • 3d Pore DM. Soudagar MS. Desai UV. Thopate TS. Wadagaonkar PP. Tetrahedron Lett.  2006,  47:  9325 
    Google Scholar
  • 3e Gao S. Tzeng T. Sastry MNV. Chu CM. Liu JT. Lin C. Yao CF. Tetrahedron Lett.  2006,  47:  1889 
    Google Scholar
  • 3f Chu CM. Gao S. Sastry MNV. Yao CF. Tetrahedron Lett.  2005,  46:  4971 
    Google Scholar
  • 3g Rajabi F. Saidi MR. J. Sulfur Chem.  2005,  26:  251 
    Google Scholar
  • 3h Moghaddam FM. Bardajee GR. Veranlou ROC. Synth. Commun.  2005,  35:  2427 
    Google Scholar
  • 3i Srivastava N. Banik BK. J. Org. Chem.  2003,  68:  2109 
    Google Scholar
  • 3j Sreekumar R. Rugmini P. Padmakumar R. Tetrahedron Lett.  1997,  38:  6557 
    Google Scholar
  • 3k Trost BM. Keeley DE. J. Org. Chem.  1975,  40:  2013 
    Google Scholar
  • 4 Meèiarová M. Toma S. Kotrusz P. Org. Biomol. Chem.  2006,  4:  1420 
    Google Scholar
  • 5a Garg SK. Kumar R. Chakraborti AK. Tetrahedron Lett.  2005,  46:  1721 
    Google Scholar
  • 5b Firouzabadi H. Iranpoor N. Jafari AA. Adv. Synth. Catal.  2005,  347:  655 
    Google Scholar
  • 6a Yadav JS. Reddy BVS. Baishya G. J. Org. Chem.  2003,  68:  7098 
    Google Scholar
  • 6b Ranu BC. Dey SS. Hajra A. Tetrahedron  2003,  59:  2417 
    Google Scholar
  • 7 Khatik GL. Kumar R. Chakraborti AK. Org. Lett.  2006,  8:  2433 
    Google Scholar
  • 8 Nishide K. Miyamoto T. Kumar K. Ohsugi S. Node M. Tetrahedron Lett.  2002,  43:  8569 
    Google Scholar
  • 9 Singh H. Batra MS. Indian J. Chem., Sect B: Org. Chem. Incl. Med. Chem.  1987,  26:  1111 
    Google Scholar
  • 10 Ranu BC. Mandal T. Synlett  2004,  1239 
    Google Scholar
  • 11a Dong DW. Yu HF. Ouyang Y. Liu Q. Bi XH. Lu YM. Synlett  2006,  283 
    Google Scholar
  • 11b Yu HF. Dong DW. Ouyang Y. Liu Q. Wang Y. Lett. Org. Chem.  2005,  2:  755 
    Google Scholar
  • 11c Dong DW. Ouyang Y. Yu HF. Liu Q. Liu J. Wang M. Zhu J. J. Org. Chem.  2005,  70:  4535 
    Google Scholar
  • 11d Liu Q. Che GB. Yu HF. Liu YC. Zhang JP. Zhang Q. Dong DW. J. Org. Chem.  2003,  68:  9148 
    Google Scholar
  • 11e Ouyang Y. Yu HF. Dong DW. Liu Q. Dongbei Shida Xuebao (Ziran Kexueban)  2006,  38:  67 
    Google Scholar
  • 12a Lutz GA. Bearse AE. Leonard JE. Croxton FC. J. Am. Chem. Soc.  1948,  70:  4135 
    Google Scholar
  • 12b Frank RL. Smith PV. J. Am. Chem. Soc.  1946,  68:  2103 
    Google Scholar
  • 13a Zorin VV. Nikolaeva SV. Zlotskii DL. Zh. Org. Khim.  1985,  21:  660 
    Google Scholar
  • 13b Srivastava N. Banik BK. J. Org. Chem.  2003,  68:  2109 
    Google Scholar
  • 13c Dickschat JS. Helmke E. Schulz S. Chem. Biodiversity  2005,  2:  318 
    Google Scholar
  • 13d Anderson MB. Ranasinghe MG. Palmer JT. Fuchs PL. J. Org. Chem.  1988,  53:  3125 
    Google Scholar
  • 13e Kaptein B. Barf G. Kellogg RM. Bolhuis FV. J. Org. Chem.  1990,  55:  1890 
    Google Scholar
  • 13f Goda S. Yamada K. Yamamoto Y. Mackawa H. Nishiguchi I. J. Electroanal. Chem.  2003,  545:  129 
    Google Scholar
  • 13g Tokmurzin KK. Kozhabekov ZE. Zhangutov NR. Kuanyshkaliev KA. Zh. Org. Khim.  1981,  17:  443 
    Google Scholar
  • 14 Bell R. Cottam PD. Davies J. Jones DN. J. Chem. Soc., Perkin. Trans. 1  1981,  2106 
    Google Scholar
15

Typical Procedure for the Thia-Michael Addition of S -Alkylisothiouronium Salts to Electron-Deficient Olefins: To a magnetically stirred solution of an S-alkylisothio-uronium salt (3 mmol) and an electron-deficient olefin (3 mmol) in H2O (5 mL) was slowly added an aq NaOH solution (7.5 mmol NaOH in 2 mL H2O), and then the mixture was stirred at r.t. for the indicated time in Table [1] . Then, the reaction mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using EtOAc-PE as eluent to afford the corresponding product. All the new compounds were characterized on the basis of 1H NMR and elemental analysis and the structures of the known compounds were confirmed by 1H NMR spectra, which were consistent with literature data.

16

Spectroscopic data of the selected compound:
3-Methylthiopropanenitrile 14 (3j; Table 1, entry 10): colorless liquid. 1H NMR (300 MHz, CDCl3): δ = 2.20 (s, 3 H), 2.67 (t, J = 6.9 Hz, 2 H), 2.78 (t, J = 6.9 Hz, 2 H).
3-Cyclopentylthiopropanenitrile (3u; Table 1, entry 21): colorless liquid. 1H NMR (300 MHz, CDCl3): δ = 1.48-1.62 (m, 4 H), 1.73-1.77 (m, 2 H), 1.97-2.05 (m, 2 H), 2.64 (t, J = 7.2 Hz, 2 H), 2.81 (t, J = 7.2 Hz, 2 H), 3.13-3.23 (m, 1 H). Anal. Calcd for C8H13NS: C, 61.89; H, 8.44; N, 9.02. Found: C, 61.92; H, 8.274; N, 8.902.
3-Phenyl-3-benzylthiopropanenitrile (3v; Table 1; entry 22): colorless oil. 1H NMR (300 MHz, CDCl3): δ = 2.80 (dd, J = 2.5, 7.5 Hz, 2 H), 3.52 (d, J = 13.8 Hz), 3.66 (d, J = 13.8 Hz, 1 H), 3.90 (t, J = 7.2 Hz, 1 H), 7.21-7.41 (m, 10 H). Anal. Calcd for C16H15NS: C, 75.8; H, 5.91; N, 5.53. Found: C, 75.70; H, 6.04; N, 5.41.