Subscribe to RSS
DOI: 10.1055/s-2007-983811
Unprecedented One-Pot Stereoselective Synthesis of Knoevenagel-Type Derivatives via in situ Condensation of N-Methyleniminium Salts of Ethylenethiourea and Ethyleneurea with Active Methylene Reagents
Publication History
Publication Date:
09 August 2007 (online)
![](https://www.thieme-connect.de/media/synthesis/200716/lookinside/thumbnails/10.1055-s-2007-983811-1.jpg)
Abstract
A facile stereoselective synthesis of Knoevenagel-type compounds 8 and 9 was accomplished through a one-pot two-step procedure. The reaction of ethylenethiourea (1) and ethyleneurea (2) with benzoyl chloride-N,N-dimethylformamide complex in N,N-dimethylformamide gave the corresponding isolable ternary N-methyleniminium chlorides 3 and 4, along with benzoic acid (5) as a byproduct. Hydrolysis of salts 3 and 4 yielded the N-formyl derivatives 6 and 7, thus confirming the N-methyleniminium structure. Salts 3 and 4 condensed in situ at 120 °C with a variety of acyclic active methylene reagents Y-CH2-Z (Y = or ≠ Z), in the presence of 5 (Procedure A) or of 5 and triethylamine (1.5 equiv) (Procedure B), afforded α,β-unsaturated compounds 8 and 9. The overall yields ranged from poor to good. Mechanistic hypotheses concerning the formation of 3 and 4 and the origin of the stereoselectivity are also discussed.
Key words
ternary iminium salts - active methylene reagents - stereoselective synthesis - Knoevenagel reaction
-
1a
Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry
Part 1, Vol. 9:
Böhme H.Vieche HG. Wiley; New York: 1976. -
1b
Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry
Part 2, Vol. 9:
Böhme H.Vieche HG. Wiley; New York: 1979. - 2
Westerwelle U.Keuper R.Risch N. J. Org. Chem. 1995, 60: 2263 - 3
Leonard NL.Paukstelis JV. J. Org. Chem. 1963, 28: 3021 ; and references cited therein - 4
Alt GH.Gallegos GA. J. Org. Chem. 1971, 36: 1000 - 5 Clemens D. H., Shropshire E. Y., Emmons W. D.; J. Org. Chem.; 1962, 27: 3664
- 6
Jutz C. The Vilsmeier-Haack-Arnold Acylations. C-C Bond-Forming Reactions of Chloromethyleniminium Ions, Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry Part 1, Vol. 9:Böhme H.Vieche HG. Wiley; New York: 1976. p.225-342 - 7
Marson CM. Tetrahedron 1992, 48: 3659 - 8
Selvi S.Perumal PT. Synth. Commun. 1999, 29: 73 - 9
Church R.Trust R.Albright JD.Powell DW. J. Org. Chem. 1995, 60: 3750 - 10
Meth-Cohn O.Tarnowski B. Adv. Heterocycl. Chem. 1982, 31: 207 - 11
Tramontini M. Synthesis 1973, 703 - 12
Speckamp WN.Moolenaar MJ. Tetrahedron 2000, 56: 3817 - 13
Arend M.Wetermann B.Risch N. Angew. Chem. Int. Ed. 1998, 37: 1045 - 14
House HO. Modern Synthetic Reactions W. A. Benjamin; California: 1972. p.646-653 - 15
Lehnert W. Tetrahedron Lett. 1970, 11: 4723 - 16
Jones G. Organic Reactions Vol. 15: Wiley & Sons; New York: 1967. p.204-599 - 17
Tietze LF.Beifuss U. Comprehensive Organic Synthesis Vol. 2:Trost BM.Fleming I. Pergamon; New York: 1991. p.341-394 - 18
Reeves RL. The Chemistry of the Carbonyl GroupPatai S. Interscience; London: 1966. p.593-598 - 19
Larock RC. Comprehensive Organic Transformations VCH; New York: 1989. p.170-171 - 20
Smith MB.March J. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure 5th ed.: Wiley & Sons; New York: 2001. Chap. 16. p.1225-1228 ; and references cited therein - 21
Prout FS.Beaucaire VD.Dyrkacz GR.Koppes WM.Kuznicki RE.Marlewski TA.Pienkowski JJ.Puda JM. J. Org. Chem. 1973, 38: 1512 - 22
Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry
Part 2, Vol. 9:
Böhme H.Vieche HG. Wiley; New York: 1979. p.144-147 ; and references cited therein - 23
Bredereck H.Bredereck K. Chem. Ber. 1961, 94: 2278 - 24
Gavin DF.Schabel WJ.Kober E.Robinson MA. J. Org. Chem. 1967, 32: 2511 - 25
Pruszynski P. Can. J. Chem. 1987, 65: 626 - 26
Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry
Part 2, Vol. 9:
Böhme H.Vieche HG. Wiley; New York: 1979. p.103-104 ; and references cited therein - 27
Zemlicka J.Arnold Z. Collect. Czech. Chem. Commun. 1961, 26: 2852 - 28
Arnold Z. Collect. Czech. Chem. Commun. 1961, 26: 1113 - 29
Csuros Z.Soos R.Bitter I.Karpati-Adam E. Acta Chim. Hung. 1972, 73: 239 ; Chem. Abstr. 1972, 77, 101082y - 30
Barton DHR.Elliott JD.Géro SD. J. Chem. Soc., Perkin Trans. 1 1982, 2085 - 31
Beyer K.-H,Eilingsfeld H, andWeidinger H. inventors; DE 1110625. ; Chem. Abstr. 1962, 56, 3363 - 32
Hall HK. J. Am. Chem. Soc. 1956, 78: 2717 - 33
Gompper R.Klemn K.Rempfer H. Chem. Ber. 1959, 92: 837 - 34
Finkbeiner H. J. Org. Chem. 1965, 30: 2861 - 35
Ranise A.Schenone S.Bruno O.Bondavalli F.Filippelli W.Falcone G.Rivaldi B. Farmaco 2001, 56: 647 - 36
Ranise A.Spallarossa A.Bruno O.Schenone S.Fossa P.Menozzi G.Bondavalli F.Mosti L.Capuano A.Mazzeo F.Falcone G.Filippelli W. Farmaco 2003, 58: 765 - 37
Ranise A.Bondavalli F.Bruno O.Schenone S.Losasso C.Costantino M.Cenicola ML.Donnoli D.Marmo E. Farmaco 1991, 46: 317 - 38
Ranise A.Bondavalli F.Bruno O.Schenone S.Donnoli D.Parrillo C.Cenicola ML.Rossi F. Farmaco 1991, 46: 1203 - 39 From part of
Palenzona MG. Ph.D. Thesis University of Genova; Italy: 1999. - 40
Duus F. Comprehensive Organic Chemistry Vol. 3:Barton DHR.Ollis WD. Pergamon; Oxford: 1979. p.452 - 41
Iminium Salts in Organic Chemistry, In Advances in Organic Chemistry
Part 1, Vol. 9:
Böhme H.Vieche HG. Wiley; New York: 1976. p.74 - 42
Hammond GS.Neuman RC. J. Phys. Chem. 1963, 67: 1655 - 43
Satchell DPN.Satchell RS. Acid-Base Behaviour and Complex Formation, In The Chemistry of Acyl HalidesPatai S. Interscience; New York: 1972. Chap. 4. p.122 - 44
Kohn H.Cravey MJ.Arceneaux JH.Cravey RL.Willcott MR. J. Org. Chem. 1977, 42: 941 ; and references cited therein - 45
Dixon AE.Hawthorne J. J. Chem. Soc. 1907, 122 - The pK a values are taken from
-
46a DBU:
Hofle G.Steglich W.Vorbruggen H. Angew. Chem., Int. Ed. Engl. 1978, 17: 569 -
46b DABCO:
Hine J.Kaufmann JC.Cholod MS. J. Am. Chem. Soc. 1972, 94: 4590 -
46c DABCO:
Hine J.Chen Y.-J. J. Org. Chem. 1987, 52: 2091 -
46d Triethylamine and pyridine:
Arnett EM.Mitchell EJ.Murty TSSR. J. Am. Chem. Soc. 1974, 96: 3875 -
46e Triethylamine:
Kuna S.Pawlak Z.Tusk M. J. Chem. Soc., Faraday Trans. 1 1982, 78: 2685 -
46f DIPEA:
Fujii T.Nishida H.Abiru Y.Yamamoto M. Chem. Pharm. Bull. 1995, 43: 1872 - 47
Smith MB.March J. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure 5th ed.: Wiley & Sons; New York: 2001. p.232 - 48
Inokawa S.Gomyo T.Yoshida H.Ogata T. Synthesis 1973, 365 - 49
Reetz MT.Peter R.von Itzstein M. Chem. Ber. 1987, 120: 121 - 50
Tanikaga R.Konya N.Tamura T.Kaji A. J. Chem. Soc., Perkin Trans. 1 1987, 825 - 51 The Merck Index 11th ed.: Merck & Co.; Rahway NJ: 1989.
- 52
Koenig H.-B,Schroeck W, andMetzger K.-G. inventors; DE 2152967. ; Chem. Abstr. 1973, 79, 32047t - 53
Corfield GC.Crawshaw A.Monks HH. J. Macromol. Sci., Chem. 1975, 9: 1085 - 54 MacroModel Version 5.5 Columbia University; New York, NY: 1996.