The Willgerodt-Kindler Reaction in Water
65
General Experimental Procedure for the Synthesis of 2 in Water
Caution: Experiments should be carried out in an efficient hood to avoid exposure to noxious hydrogen
sulfide vapors.
The aldehyde or aldimine (1mmol), 2 mmol sulfur, 3 mmol morpholine, and 5 cm3 H2O are placed
in a flask fitted with an air-cooled reflux condenser and stirrer. The mixture is heated at 80ꢁC for 3 h.
The dark-brown mixture is cooled to room temperature and the solid product is isolated by suction, and
recrystallized from hot ethanol to remove the unreacted sulfur. Further purification (if necessary) can
be achieved by recrystallization from n-hexane. The products 2 were generally pure as judged by TLC,
1
GC-MS and H NMR analysis.
References
[1] Brown EV (1975) Synthesis 358–375 and references cited therein
€
[2] Asinger F, Schafer W, Halcour K, Saus A, Triem H (1964) Angew Chem Engl Int Ed 3: 19
[3] a) Padwa A, Beall LS, Heidelbaugh TM, Liu B, Sheehan SM (2000) J Org Chem 65: 2684; b) May
PJ, Bradley M, Harrowven DC, Pallin D (2000) Tetrahedron Lett 41: 1627; c) Harrowven DC,
Lucas MC, Howes PD (1999) Tetrahedron Lett 40: 4443; d) Metzner P (1992) Synthesis 1185
[4] Spatola AF (1983) Chemistry and Biochemistry of Amino acids, Peptides and Proteins. In:
Weinstein B (ed) vol 7. Marcel Dekker, New York, pp 267–357 and references cited therein
[5] Hoeg-Jensen T, Olsen CE, Holm A (1994) J Org Chem 59: 1257
[6] Katritzky AL, Moutou JL, Yang Z (1995) Synlett 99
[7] Murguia MC, Rossi RA (1997) Tetrahedron Lett 38: 1355
[8] a) Nooshabadi M, Aghapoor K, Darabi HR, Mojtahedi MM (1999) Tetrahedron Lett 40: 7549;
b) Aghapoor K, Darabi HR, Tabar-Heydar K, Nakhshab L (2002) Sulfur Lett25: 259; c) Darabi HR,
Aghapoor K, Tabar-Heydar K (2002) Phosphorus, Sulfur and Silicon 177: 1189; d) Darabi HR,
Aghapoor K, Tajbakhsh M (2004) Tetrahedron Lett 45: 4167
€
[9] Asinger F, Schafer W, Halcour K, Saus A, Triem K (1963) Angew Chem 75: 1050
[10] a) Moghaddam FM, Ghaffarzadeh M, Dakamin MG (2000) J Chem Res Synop 228;
b) Poupaert JH, Bouinidane K, Renard M, Lambert D, Isa M (2001) Org Prep Proc Int 33:
335; c) Moghaddam FM, Ghaffarzadeh M (2001) Synth Commun 31: 317; d) Moghaddam FM,
Hojabri L, Dohendou M (2003) Synth Commun 33: 4279
[11] Darabi HR, Aghapoor K, Nakhshab L (2004) Z Naturforsch 59b: 601
[12] Kanyonyo MR, Ucar H, Isa M, Carato P, Lesieur D, Renard P, Poupaert JH (1996) Bull Soc Chim
Belg 105: 17
[13] Zbruyev OI, Stiasni N, Kappe CO (2003) J Comb Chem 5: 145
[14] Aghapoor K, Darabi HR, Nooshabadi M, Tabar-Heydar K (2002) Phosphorus, Sulfur and Silicon
177: 1183
[15] Poupaert JH, Duarte S, Colacino E, Depreux P, McCurdy CR, Lambert DL (2004) Phosphorus,
Sulfur, and Silicon 179: 1959
[16] Carmack M, Behforouz M, Berchtold GA, Berkowitz SM, Wiesler D, Barone R (1989)
J Heterocycl Chem 26: 1305
[17] Carmack M (1989) J Heterocycl Chem 26: 1319
[18] Stauffer SR, Sun J, Katzenellenbogen BS, Katzenellenbogen JA (2000) Bioorg Med Chem 8:
1293
´
´ ´ ´
[19] Waisser K, Gregor G, Kubicova L, Klimec°ova V, Kumes J, Machacek M, Kaustova J (2000) Eur J
Med Chem 35: 733
[20] Matysiak J, Niewiadomy A, Mac°ik-Niewiadomy G, Korniowicz T (2000) Eur J Med Chem 35: 393
[21] Kazimir S, Bellini F, Fung S, Nedumrambil A, Tresaurywala A, Humber L (1984) J Med Chem
27: 255
ꢀ
[22] Woitrin-Dutron F, Merenyi R, Viehe HG (1985) Synthesis 79