RSS-Feed abonnieren
DOI: 10.1055/s-2003-42486
A Convenient Procedure for the Synthesis of Novel Modified 3-Substituted 1H-Quinoxaline-2-thiones via Side-Chain Lithiation of 3-Alkyl-1H-quinoxaline-2-thiones
Publikationsverlauf
Publikationsdatum:
17. November 2003 (online)
Abstract
3-Methyl-1H-quinoxaline-2-thione (1) has been doubly lithiated, at nitrogen and at the 3-methyl group, with n-butyllithium at -78 °C in THF. The resulting dilithium reagent obtained reacts with a variety of electrophiles (iodomethane, iodoethane, 1-bromobutane, D2O, benzaldehyde, anisaldehyde, 2-hexanone, cyclohexanone, benzophenone, phenyl isothiocyanate) to give the corresponding modified 3-substituted 1H-quinoxaline-2-thiones 4-13 in high yields. Similarly, double lithiation of 3-ethyl- (4) and 3-propyl-1H-quinoxaline-2-thiones (5), followed by reaction with some electrophiles gave the corresponding modified 3-substituted derivatives 15-19 in high yields. Treatment of some of the products with trifluoroacetic acid in dichloromethane at room temperature led to formation of substituted 2,3-dihydrothieno[2,3-b]quinoxalines in good yields.
Key words
quinoxalines - lithiation - electrophilic additions - cyclizations - heterocycles - sulfur
- See for example:
- 2a
Anctil EJ.-G.Snieckus V. J. Organomet. Chem. 2002, 653: 150 - 2b
Turck A.Plé N.Mongin F.Quéguiner G. Tetrahedron 2001, 57: 4489 - 2c
Monin F.Quéguiner G. Tetrahedron 2001, 57: 4059 - 2d
El-Hiti GA. Heterocycles 2000, 53: 1839 - 2e
Snieckus V. Chem. Rev. 1990, 90: 879 - 2f
Beak P.Zajdel WJ.Reitz DB. Chem. Rev. 1984, 84: 471 - See for example:
- 3a
Sato N. Tetrahedron Lett. 2002, 43: 6403 - 3b
Rohonnstad P.Wensbo D. Tetrahedron Lett. 2002, 43: 3137 - 3c
Geneste H.Schäfer B. Synthesis 2001, 2259 - 3d
Turck A.Plé N.Quéguiner G. Heterocycles 1994, 37: 2149 - 3e
Quéguiner G.Marsais F.Snieckus V.Epsztajn J. Adv. Heterocycl. Chem. 1991, 52: 187 - 3f
Narasimhan NS.Mali RS. Synthesis 1983, 957 - See for example:
- 4a
Li L.Martins A. Tetrahedron Lett. 2003, 44: 5987 - 4b
Lukás G.Porcs-Makkay M.Simig G. Tetrahedron Lett. 2003, 44: 3211 - 4c
Gros P.Choppin S.Fort Y. J. Org. Chem. 2003, 68: 2243 - 4d
Katritzky AR.Manju K.Steel PJ. J. Org. Chem. 2003, 68: 407 - 4e
Toudic F.Plé N.Turck A.Quéguiner G. Tetrahedron 2002, 58: 283 - 4f
Mukherjee C.De A.. Synlett 2002, 325 - 4g
Gros P.Louërat F.Fort Y. Org. Lett. 2002, 4: 1759 - 4h
Cuperly D.Gros P.Fort Y. J. Org. Chem. 2002, 67: 238 - 4i
Gros P.Fort Y. Eur. J. Org. Chem. 2002, 20: 3375 - 4j
Rebstock A.-S.Mongin F.Trécourt F.Quéguiner G. Tetrahedron Lett. 2002, 43: 767 - 5a
Smith K.El-Hiti GA.Hawes AC. Synthesis 2003, 2047 - 5b
Smith K.El-Hiti GA.Hawes AC. Synlett 1999, 945 - 5c
Smith K.El-Hiti GA.Shukla AP. J. Chem. Soc., Perkin Trans. 1 1999, 2305 - 5d
Smith K.El-Hiti GA.Pritchard GJ.Hamilton A. J. Chem. Soc., Perkin Trans. 1 1999, 2299 - 5e
Smith K.El-Hiti GA.Hamilton A. J. Chem. Soc., Perkin Trans. 1 1998, 4041 - 6a
Smith K.El-Hiti GA.Abdel-Megeed MF. Russ. J. Org. Chem. 2003, 39: 430 - 6b
Smith K.El-Hiti GA.Abdel-Megeed MF.Abdo MA. Collect. Czech. Chem. Commun. 1999, 64: 515 - 6c
Smith K.El-Hiti GA.Abdel-Megeed MF.Abdo MA. J. Org. Chem. 1996, 61: 656 - 6d
Smith K.El-Hiti GA.Abdel-Megeed MF.Abdo MA. J. Org. Chem. 1996, 61: 647 - 6e
Smith K.El-Hiti GA.Abdo MA.Abdel-Megeed MF. J. Chem. Soc., Perkin Trans. 1 1995, 1029 - 7
Smith K.El-Hiti GA.Mahgoub SA. Synthesis 2003, 2345 - 8
Parra S.Laurent F.Subra G.Deleuze-Masquefa C.Benezch V.Fabreguettes J.-R.Vidal J.-P.Pocock T.Elliott K.Small R.Escale R.Michel A.Chapat J.-P.Bonnet P.-A. Eur. J. Med. Chem. 2001, 36: 255 - 9
Chapoulaud VG.Salliot I.Plé N.Turck A.Quéguiner G. Tetrahedron 1999, 55: 5389 - 10
Turck A.Plé N.Tallon V.Quéguiner G. J. Heterocycl. Chem. 1993, 30: 1491 - 11
Ward JS.Merritt L. J. Heterocycl. Chem. 1991, 28: 765 - 12
Kaiser EM. Tetrahedron 1983, 39: 2055 - See for example:
- 13a
Seitz LE.Suling WJ.Reynolds RC. J. Med. Chem. 2002, 45: 5604 - 13b
Catarzi D.Colotta V.Varano F.Cecchi L.Filacchioni G.Galli A.Costagli C.Carla V. J. Med. Chem. 2000, 43: 3824 - 13c
Mollegaard NE.Bailly C.Waring MJ.Nielsen PE. Biochemistry 2000, 39: 9502 - 13d
Myers MR,He W, andSpada AP. inventors; PCT Int. Appl. WO 3151. ; Chem. Abstr. 2000, 133, 17479 - 13e
Myers MR,Spada AP,Persons PE, andMaguire MP. inventors; PCT Int. Appl. WO 3150. ; Chem. Abstr. 2000, 133, 17478 - 13f
Spada AP,He W, andMyers MR. inventors; PCT Int. Appl. WO 3149. ; Chem. Abstr. 2000, 133, 17477 - 13g
Nikam SS.Cordon JJ.Ortwine DF.Heimbach TH.Blackburn AC.Vartanian MG.Nelson CB.Schwarz RD.Boxer PA.Rafferty MF. J. Med. Chem. 1999, 42: 2266 - 14
Badr MZA.El-Naggar GM.El-Sherief HAH.Mahgoub SA. Bull. Chem. Soc. Jpn. 1984, 57: 1653 - 15
Watson SC.Eastham JF. J. Organomet. Chem. 1967, 9: 165 - 16
Asano K. Yakugaku Zasshi 1958, 78: 729 ; Chem. Abstr. 1958, 52, 18428
References
Current address: G. A. El-Hiti, Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK.