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Synthesis of thioamides
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.
O. I. Zubruyev, N. Stiasni, C. O. Kappe, J. Comb. Chem., 2003, 5, 145-148.
A convenient method for the synthesis of aryl thioamides from aryl aldehydes and tetramethylthiuram disulfide (TMTD) in the presence of CuI and di-tert-butyl peroxide (DTBP) avoids the use of a sulfurating reagent. The protocol offers broad substrate scope, very good yields, operability and uses commercially available and inexpensive raw materials.
M.-T. Zeng, M. Wang, H.-Y. Peng, Y. Cheng, Z.-B. Dong, Synthesis, 2018, 50, 644-650.
In an efficient aqueous synthesis of thioamides from aldehydes and N-substituted formamides, sodium sulfide serves as the sulfur source in water, which makes this method very practical and efficient. Furthermore, late-stage modifications of bioactive molecules are demonstrated.
J. Wei, Y. Li, X. Jiang, Org. Lett., 2016, 18, 340-343.
O-Ethyl thioformate has been synthesized from triethylorthoformate and hydrogen sulfide gas using sulfuric acid as Brønsted acid catalyst. The product can be isolated as a neat liquid in 83% overall yield. Both the crude and purified thiolate can be used to thioformylate various amines in good to excellent yields.
C. J. Borths, J. Chan, B. J. Burke, R. D. Larsen, Synlett, 2009, 3139-3142.
A nucleophilic activation of elemental sulfur by thiols enables a mild and chemoselective thioacylation of amines with α-keto acids and elemental sulfur. The reaction tolerates a broad range of functional groups, including unprotected hydroxyl, carboxyl, amide, sulfide, and tertiary amine moieties.
M. Saito, S. Murakami, T. Nanjo, Y. Kobayashi, Y. Takemoto, J. Am. Chem. Soc., 2020, 142, 8130-8135.
A three-component reaction of alkynes, elemental sulfur, and aliphatic amines allows a general, straightforward, and atom-economical synthesis of thioamides.
T. B. Nguyen, M. Q. Tran, L. Ermolenko, A. Al-Mourabit, Org. Lett., 2014, 16, 310-313.
Base-controlled three component reactions of styrenes, amines, and sulfur provide thioamides. Depending on the base, 2-phenylethanethioamides and benzothioamides were obtained selectively.
P. Zhang, W. Chen, M. Liu, H. Wu, J. Org. Chem., 2018, 83, 14269-14276
A metal- and additive-free reaction of 1,2-dibenzyldisulfanes with amines using iodine as oxidant and DMSO as solvent at 100°C provides various thioamides in high yields.
S. Chen, Y. Li, J. Chen, X. Xu, L. Su, Z. Tang, C.-T. Au, R. Qiu, Synlett, 2016, 27, 2339-2344.
In an environmentally friendly, atom-economical, and step-economical oxidation, thiols are used as a synthon for the preparation of thioamides without the use of exogenous sulfur reagents.
X. Wang, M. Ji, S. Lim, H.-Y. Jang, J. Org. Chem., 2014, 79, 7258-7260.
An efficient and selective multicomponent oxidative coupling of two different aliphatic primary amines allows the synthesis of thioamides in the presence of elemental sulfur under solvent-free conditions.
T. B. Nguyen, L. Ermolenko, A. Al-Mourabit, Org. Lett., 2012, 14, 4274-4277.
A decarboxylative strategy for the synthesis of thioamides involves a three-component reaction of arylacetic or cinnamic acids, amines and elemental sulfur powder, without the need of a transition metal and an external oxidant.
T. Guntreddi, R. Vanjari, K. N. Singh, Org. Lett., 2014, 16, 3624-3625.
A transition-metal-free cleavage of C-C triple bonds in aromatic alkynes in the presence of S8 and amides furnishes aryl thioamides in good yields. The method offers mild reaction conditions, as well as wide substrate scope that is particularly compatible with some internal aromatic alkynes and acetamides.
K. Xu, Z. Li, F. Cheng, Z. Zuo, T. Wang, M. Wang, L. Liu, Org. Lett., 2018, 20, 2228-2231.
A metal-free oxidative-amidation strategy enables the synthesis of α-ketothioamides and amides from α-azido ketones. The C-H bond thionation of α-azido ketones with elemental sulfur could form α-ketothioacyl azide, which was then nucleophilically attacked by amines, while amides could be formed with the release of nitrogen gas and cyano anion in the presence of PhI(OAc)2.
P. Yu, Y. Wang, Z. Zeng, Y. Chen, J. Org. Chem., 2019, 84, 14883-14891.
Endothiopeptides can easily be obtained via Ugi reaction using thio acids as acid components. If isonitriles with an acetal group are applied, the endothiopeptides can directly be converted into thiazoles using TMSCl-NaI under microwave irradiation.
U. Kazmaier, S. Ackermann, Org. Biomol. Chem., 2005, 3, 3184-3187.