Preparation of Thioamide Building Blocks via Microwave-Promoted Three-Component Kindler Reactions

Oleksandr I. Zubruyev, Nikola Stiasni and C. Oliver Kappe*

*Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria, Email: oliver.kappeuni-graz.at

O. I. Zubruyev, N. Stiasni, C. O. Kappe, J. Comb. Chem., 2003, 5, 145-148.

DOI: 10.1021/cc0200538

Abstract

A microwave-enhanced Kindler thioamide synthesis is introduced. The three-component condensations of aldehydes, amines, and elemental sulfur were carried out using 1-methyl-2-pyrrolidone (NMP) as solvent employing microwave flash heating at 110-180°C for 2-20 min. A simple workup protocol allows the isolation of synthetically valuable thioamide building blocks in good yield and purity.

R	R', R''	Aldehyde/Amine/S* (mmol, *S: 32 g/mol)	T (°C)	t (min)	Yield (%, isol.)

Ph	-(CH₂)₅-	4/6/5	110	3	95
4-(NO₂)Ph	-(CH₂)₅-	4/6/5	130	2	94
PhCH₂	-(CH₂)₅-	4/5/4.5	100	3	73
3-indolyl	-(CH₂)₅-	4/5/4.5	100	8	72
Ph	H, PhCH₂CH₂	4/5/4.5	180	4	99
3,4-(MeO)Ph	H, PhCH₂CH₂	4/5/4.5	140	10	99
4-(NMe₂)Ph	H, PhCH₂CH₂	4/5/4.5	140	12	99
3-(Cl)Ph	H, PhCH₂CH₂	4/5/4.5	140	12	97
3-(NO₂)Ph	H, PhCH₂CH₂	4/5/4.5	150	10	99
2-(Me)Ph	H, PhCH₂CH₂	4/5/4.5	160	20	43
2-thiophenyl	H, PhCH₂CH₂	4/5/4.5	140	14	99
pentyl	H, PhCH₂CH₂	4/5/4.5	140	12	39
4-(NMe₂)Ph	H, 2-(MeO)PhCH₂CH₂	4/5/4.5	140	12	99
3-(Me)Ph	H, 2-(MeO)PhCH₂CH₂	4/5/4.5	140	12	99
3-indolyl	H, 2-(MeO)PhCH₂CH₂	4/5/4.5	140	10	99
Ph	H, propyl	4/5/4.5	150	5	93
4-(NMe₂)Ph	H, propyl	4/5/4.5	170	7	97
3-(Cl)Ph	H, propyl	4/5/4.5	140	12	90
3-(NO₂)Ph	H, propyl	4/5/4.5	150	12	95
pentyl	H, propyl	4/5/4.5	140	10	54
Ph	H, H	4/6/4.5	180	20	44
4-(Me)Ph	H, H	4/6/4.5	170	20	36
3-(Cl)Ph	H, H	4/6/4.5	170	20	46
4-(NMe₂)Ph	H, H	4/6/4.5	160	20	38

see article for more examples

Key Words

Kindler Reaction, Kindler Thioamide Synthesis, Thioamides, Microwave Synthesis, Multicomponent Reactions

ID: JXX-Y2003-1230