Download PDF
Synlett 2005(7): 1129-1132  
DOI: 10.1055/s-2005-865217
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Facile Regioselective Decomposition of Tosylhydrazones: An Application towards the Synthesis of α-Lipoic Acid

Subhash P. Chavan*, Ramesh R. Kale, K. Pasupathy
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune, 411 008, India
e-Mail: spchavan@dalton.ncl.res.in;
Further Information

Publication History

Received 1 February 2005
Publication Date:
14 April 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

A facile regioselective decomposition of tosylhydrazones using NaOH as a base in refluxing isopropyl alcohol is described. This finding has been successfully applied towards the synthesis of (±)-α-lipoic acid (1).

Key words

tosylhydrazones - regioselectivity - olefins - α-lipoic acid

    References

  • 1 Shapiro RH. Org. React.  1976,  23:  405 
    Google Scholar
  • 2a Shapiro RH. Duncan JH. Clopton JC. J. Am. Chem. Soc.  1967,  89:  1442 
    CrossrefGoogle Scholar
  • 2b Shapiro RH. Heath MJ. J. Am. Chem. Soc.  1967,  89:  5734 
    CrossrefGoogle Scholar
  • 3 Bamford WR. Stevens TS. J. Chem. Soc.  1952,  4735 
    Google Scholar
  • 4 Gianturco MA. Friedel P. Flanagan V. Tetrahedron Lett.  1965,  6:  1847 
    CrossrefGoogle Scholar
  • 5 Johnson PY. Koza E. J. Org. Chem.  1973,  38:  2967 
    Google Scholar
  • 6 Ogata T. Kawata K. Oshikawa T. Yoshida H. Inokawa S. Nippon Kagaku Kaishi  1987,  7:  1370 
    Google Scholar
  • 7 Happman A. Weyerstahl P. Zummack W. Justus Liebigs Ann. Chem.  1977,  9:  1547 
    Google Scholar
  • 8 von Luttringhaus A. Prinzbach H. Justus Liebigs Ann. Chem.  1959,  624:  79 
    CrossrefGoogle Scholar
  • 9a Brandstrom A. Junggern U. Acta Chem. Scand.  1969,  23:  3585 
    Google Scholar
  • 9b Ruzicka J. Koutek B. Streinz L. Saman D. Leseticky L. Tetrahedron: Asymmetry  1999,  10:  3521 
    Google Scholar
  • 9c Matsuama H. Takei Y. Kobayashi M. Bull. Chem. Soc. Jpn.  1986,  59:  2657 
    Google Scholar
  • 10a Krapcho AP. Synthesis  1982,  805 
    Article in Thieme ConnectGoogle Scholar
  • 10b Krapcho AP. Synthesis  1982,  893 
    Article in Thieme ConnectGoogle Scholar
  • 11 van der Eycken E. De Wilde H. Deprez L. Vandewalle M. Tetrahedron Lett.  1987,  28:  4759 
    CrossrefGoogle Scholar
  • Reviews:
  • 12a Schmidt U. Grafen P. Altland K. Goedde HW. Adv. Enzymol.  1969,  32:  423 
    CrossrefGoogle Scholar
  • 12b Sigel H. Angew. Chem., Int. Ed. Engl.  1982,  21:  389 
    CrossrefGoogle Scholar
  • 13a Yadav JS. Mysorekar SV. Garyali K. J. Sci. Ind. Res.  1990,  49:  400 
    CrossrefGoogle Scholar
  • 13b Brookes MH. Golding BT. Howes DA. Hudson AT. J. Chem. Soc., Chem. Commun.  1983,  1051 
    CrossrefGoogle Scholar
  • 13c Brookes MH. Golding BT. Hudson AT. J. Chem. Soc., Perkin Trans. 1  1988,  9 
    CrossrefGoogle Scholar
  • 14a Fadanavis NW. Babu RL. Vadivel SK. Deshpande AA. Bhalerao UT. Tetrahedron: Asymmetry  1998,  9:  4109 
    CrossrefGoogle Scholar
  • 14b Chavan SP. Praveen C. Ramakrishna G. Kalkote UR. Tetrahedron Lett.  2004,  45:  6027 ; and the references cited therein
    CrossrefGoogle Scholar
  • 15a Christian F, Walther S, and Hans S. inventors; Ger. Offen. DE  10150063/18. 
  • 15b Klatt M, and Niebel M. inventors; PCT Int. Appl. WO  2003048102/17. 
  • 16 Kawai M. Rev. Int. Serv. Sante Armees Terre, Mer Air  1966,  39:  861 ; Chem. Abstr. 1966, 66, 93545g
    Google Scholar
  • 17 Natraj CV. Gandhi VM. Menon KKG. J. Biosciences  1984,  6:  37 
    Google Scholar
  • 18 Wagh SS. Natraj CV. Menon KKG. J. Biosciences  1987,  11:  59 
    Google Scholar
  • 19 Baur A. Harrer T. Peukert M. Jahn G. Kalden JR. Fleckenstein B. Klin. Wochenschr.  1991,  69:  722 ; Chem. Abstr. 1992, 116, 207360
    CrossrefGoogle Scholar
  • 20 Bingham PM, and Zachar Z. inventors; PCT Int. Appl. WO  0024/734.  ; Chem. Abstr. 2000, 132, 3081921
  • 21 Yasuaki O. inventors; Jpn. KoKai Tokkyo Koho, JP  63,08,315.  ; Chem. Abstr. 1988, 109, 196909qP
  • 22 Kyotaro H. inventors; Jpn. KoKai Tokkyo Koho, JP  62,175,417.  ; Chem. Abstr. 1988, 108, 62465nP
  • 23a Kursanov DN. Parnes ZN. Loim NM. Synthesis  1974,  633 
    Google Scholar
  • 23b Parnes ZN. Bolestova GI. Belenkiy LI. Kursanov DN. Izv. Akad. Nauk SSSR, Ser. Khim.  1973,  1918 ; Chem. Abstr. 1974, 80, 14800
    Google Scholar
  • 24 Menon RB. Ph. D. Thesis   University of Pune; Maharashtra, India: 1987. 
    Google Scholar
  • Data for Selected Compounds.
  • 25a

    Methyl 4-(4-methoxycarbonyl-butyl)-2,2-dimethyl-5-oxo-(1,3)-dithiane-4-carboxylate (8c): molecular formula: C14H22O5S2; yield 70%; viscous liquid. IR (CHCl3): 3021, 2953, 2925, 1748, 1713, 1439, 1160, 765 cm-1. 1H NMR (200 MHz, CDCl3 + CCl4): δ = 3.76 (d, J = 18.6 Hz, 1 H), 3.75 (s, 3 H), 3.60 (s, 3 H), 3.30 (d, J = 18.6 Hz, 1 H), 2.24 (t, J = 7.3 Hz, 2 H), 1.64-1.85 (m, 5 H), 1.72 (s, 3 H), 1.64 (s, 3 H), 1.17-1.27 (m, 2 H). 13C NMR (125 MHz, CDCl3 + CCl4): δ = 197.1 (s), 173.5 (s), 170.0 (s), 61.7 (s), 53.1 (q), 51.4 (q), 50.6 (s), 36.6 (t), 33.6 (t), 32.7 (q), 32.6 (t), 32.2 (q), 25.0 (t), 24.2 (t). MS (EI): m/z (%) = 334 (26), 303 (6), 270 (15), 260 (10), 237 (2), 228 (18), 212 (14), 197 (27), 180 (36), 169 (23), 159 (27), 155 (39), 141 (32), 127 (81), 123 (68), 115 (100), 99 (94), 87 (51), 73 (76), 59 (25). HRMS (ESI+ mode): m/z calcd for C14H22O5NaS2 [M + Na]+: 357.0806; found: 357.0811.

    Google Scholar
  • 25b

    Methyl 5-[2,2-dimethyl-5-oxo-(1,3)-dithian-4-yl]pentanoate (9c): molecular formula: C12H20O3S2; yield 81%; viscous liquid. IR (CHCl3): 3020, 1732, 1711, 772, 744 cm-1. 1H NMR (200 MHz, CDCl3 + CCl4): δ = 3.98 (dd, J = 6.8, 5.9 Hz, 1 H), 3.64 (s, 3 H), 3.63 (d, J = 16.6 Hz, 1 H), 3.25 (d, J = 16.6 Hz, 1 H), 2.29 (t, J = 7.3 Hz, 2 H), 1.76-1.92 (m, 1 H), 1.84 (s, 3 H), 1.56-1.71 (m, 2 H), 1.66 (s, 3 H), 1.34-1.49 (m, 3 H). 13C NMR (125 MHz, CDCl3 + CCl4): δ = 204.0 (s), 173.6 (s), 51.4 (q), 50.4 (s), 47.1 (d), 37.1 (t), 33.7 (t), 32.8 (q), 31.9 (q), 27.2 (t), 26.6 (t), 24.7 (t). MS (EI): m/z (%) = 276 (57), 262 (3), 243 (13), 225 (6), 211 (8), 202 (11), 179 (8), 170 (100), 153 (24), 142 (28), 127 (36), 111 (16), 93 (21), 73 (68), 56 (11). HRMS (ESI+ mode): m/z calcd for C12H20O3NaS2 [M + Na]+: 299.0752; found: 299.0742.

    Google Scholar
  • 25c

    5-[5-(p-Toluenesulfonyl)hydrazono-2,2-dimethyl-(1,3)-dithian-4-yl]pentanoic acid methyl ester (2c): molecular formula: C19H28O4N2S3; yield 87%; white solid, mp 120 °C. IR (CHCl3): 3020, 2400, 1731, 757 cm-1. 1H NMR (200 MHz, CDCl3 + CCl4): δ = 8.53 (s, 1 H), 7.58 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 8.3 Hz, 2 H), 3.74 (dd, J = 7.8, 6.4 Hz, 1 H), 3.61 (s, 3 H), 3.56 (d, J = 15.6 Hz, 1 H), 3.21 (d, J = 15.6 Hz, 1 H), 2.37 (s, 3 H), 2.19 (t, J = 7.8 Hz, 2 H), 1.76-1.84 (m, 1 H), 1.68 (s, 3 H), 1.46 (s, 3 H), 1.20-1.61 (m, 5 H). 13C NMR (50 MHz, CDCl3 + CCl4): δ = 173.6 (s), 155.7 (s), 143.9 (s), 135.4 (s), 129.3 (d), 128.1 (d), 51.2 (q), 49.7 (s), 45.1 (d), 33.6 (t), 32.2 (q), 31.0 (q), 28.9 (t), 26.1 (t), 25.6 (t), 24.4 (t), 21.3 (q). MS (ESI, solvent: MeCN + H2O + CH3COONH4): m/z = 445.04 [M + 1]. HRMS (ESI+ mode): m/z calcd for C19H29N2O4S3 [M + H]+: 445.1289; found: 445.1271.

    Google Scholar
26

General Procedure for Decomposition of Tosylhydra-zones to Olefins.
A mixture of tosylhydrazone (1 mmol) and NaOH (2 mmol) in i-PrOH (10 mL) was refluxed for 2-3 h. The reaction was monitored by TLC, and after the completion of the reaction, i-PrOH was removed under vacuum and the residue was extracted with Et2O. The ether layer was dried over anhyd Na2SO4 and filtered. Then Et2O was removed under vacuum and the residue was purified by column chromatography.

27

Typical Procedure for Entry 3 in Table 2 (3c and 4c). The mixture of tosylhydrazone 2c (200 mg, 0.450 mmol) and NaOH (40 mg, 2 mmol) in i-PrOH (10 mL) was refluxed for 2-3 h. The reaction was monitored by TLC and after the completion of the reaction, i-PrOH was removed under vacuum and H2O was added to the reaction mixture. Then aqueous layer was washed with Et2O and then acidified with dilute HCl. Finally, the aqueous layer was extracted with Et2O (3 × 15 mL). The ether layer was dried over anhyd Na2SO4, filtered and Et2O was removed under vacuum. The residue was purified by column chromatography to give 93 mg (84%) of pure product (3c and 4c).
Data for 5-(2,2-dimethyl-6H-[1,3]dithiin-4-yl)pentanoic acid(3c): molecular formula: C11H18O2S2; yield 84%; viscous liquid. IR (CHCl3): 2985, 1709, 1216, 1167 cm-1. 1H NMR (200 MHz, CDCl3 + CCl4): δ = 10.06 (br s, 1 H), 5.75 (t, J = 4.4 Hz, 1 H), 3.44 (d, J = 4.4 Hz, 2 H), 2.34 (t, J = 7.3 Hz, 2 H), 2.20 (t, J = 6.4 Hz, 2 H), 1.67 (s, 6 H), 1.42-1.74 (m, 4 H). 13C NMR (50 MHz, CDCl3 + CCl4): δ = 179.2 (s), 136.5 (s), 111.4 (d), 47.3 (s), 38.2 (t), 33.8 (t), 31.0 (q), 28.3 (t), 26.4 (t), 23.7 (t). MS (ESI, solvent: MeCN + H2O + CH3COONH4): m/z = 263.05 [M + NH3], 245.05 [M - 1].