Categories: Synthesis of N-Heterocycles, Synthesis of S-Heterocycles >
Synthesis of thiazoles
Recent Literature
Treatment of N,N-diformylaminomethyl aryl ketones with phosphorus
pentasulfide and triethylamine in chloroform gives 5-arylthiazoles in good yield.
The 5-aryl-1,3-thiazole core has been successfully functionalised at the
2-position to yield, over two steps, a large array of
5-aryl-2-arylsulfonyl-1,3-thiazoles.
P. W. Sheldrake, M. Matteucci, E. McDonald, Synlett,
2006, 460-462.
A copper-catalyzed [3+1+1]-type condensation of oximes, anhydrides and
potassiumthiocyanate (KSCN) provides thiazoles in very good yields under mild
reaction conditions. The transformation has good functional group tolerance.
X. Tang, J. Yang, Z. Zhu, M. Zheng, W. Wu, H. Jiang, J. Org. Chem.,
2016, 81, 11461-11466.
Practical Cu-catalyzed oxidative, multiple Csp3-H bond cleavage
processes achieve a synthesis of thiazoles from simple aldehydes, amines, and
element sulfur in the presence of molecular oxygen as a green oxidant.
X. Wang, X. Qiu, J. Wei, J. Liu, S. Song, W. Wang, N. Jiao, Org. Lett.,
2018, 20, 2632-2636.
Ligand-free Pd(OAc)2 catalyzes very efficiently the direct arylation
of thiazole derivatives under very low catalyst concentration. Reactions with
activated aryl bromides can be performed employing as little as 0.1-0.001 mol %
catalyst, whereas some strongly deactivated or highly congested aryl bromides
only give disappointing results.
J. Roger, F. Pogan, H. Doucet, J. Org. Chem., 2009,
74, 1179-1186.
Conditions for the palladium-catalyzed direct arylation of a wide range of
heterocycles with aryl bromides employ a stoichiometric ratio of both coupling
partners, as well as a substoichiometric quantity of pivalic acid, which results
in significantly faster reactions. An evaluation of the influence of the nature
of the aryl halide has also been carried out.
B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem., 2009,
74, 1826-1834.
Base-induced cyclization of active methylene isocyanides such as tosylmethyl
isocyanide, ethyl isocyanoacetate, and arylmethyl isocyanides with methyl arene-
and hetarenecarbodithioates enables an efficient synthesis of 4,5-disubstituted
thiazoles. This synthesis is simple, rapid, and often avoids purification steps.
G. S. Lingaraju, T. R. Swaroop, A. C. Vinayaka, K. S. S. Kumar, M. P. Sadashiva,
K. S. Ragappa, Synthesis, 2012, 44,
1373-1379.
1-sulfonyl-1,2,3-triazoles react with thionoesters in the presence of a
rhodium(II) catalyst providing 3-sulfonyl-4-thiazolines, which subsequently
aromatize into the corresponding 2,5-disubstituted thiazoles by elimination of
the sulfonyl group.
T. Miura, Y. Funakoshi, Y. Fujimoto, J. Nakahashi, M. Murakami, Org. Lett.,
2015,
17, 2454-2457.
A small library of compounds with oxazole and thiazole scaffolds and structural
diversity in both positions 2 and 5 has been synthesized. Double acylation of a
protected glycine affords intermediate α-amido-β-ketoesters, which in turn can
be dehydrated to afford 1,3-oxazoles or reacted with Lawesson’s reagent to
furnish 1,3-thiazoles.
J. F. Sanz-Cervera, R. Blasco, J. Piera, M. Cynamon, I. Ibáñez, M. Murguía, S. Fustero, J. Org. Chem., 2009,
74, 8988-8996.
Three-component reactions of enaminoesters, fluorodibromoiamides/ester, and
sulfur provide thiazoles and isothiazoles via two C-F bond cleavages
along with the formation of new C-S, C-N, and N-S bonds. Both methods offer
high selectivity for the synthesis of thiazoles/isothiazoles, which have vital
applications in drug discovery and development.
X. Ma, X. Yu, H. Huang, Y. Zhou, Q. Song,
Org. Lett., 2020, 22, 5284-5288.
Synthesis of 2-Alkoxy-Substituted Thiophenes, 1,3-Thiazoles, and Related S-Heterocycles via Lawesson's Reagent-Mediated Cyclization under Microwave
Irradiation: Applications for Liquid Crystal Synthesis
A. A. Kiryanov, P. Sampson, A. J. Seed, J. Org. Chem., 2001,
66, 7925-7929.
Hantzsch condensation of 2-bromoacetophenones with thiourea or selenourea
enables a simple, fast, and eco-friendly solvent-free synthesis of
2-aminothiazoles and 2-amino-1,3-selenazoles without the use of a catalyst.
Reactions proceed to completion in a few seconds and products are obtained in
good yields after easy workup.
V. Facchinetti, M. M. Avellar, A. C. S. Nery, C. R. B. Gomes, T. R. A.
Vasconcelos, M. V. N. de Souza,
Synthesis, 2016, 48, 437-440.
Palladium(II) acetate catalyzes a highly selective construction of 4-substituted
2-aminothiazoles from vinyl azides and potassium thiocyanate, whereas iron(III)
bromide promotes the formation of 4-substituted 5-thiocyano-2-aminothiazoles.
Use of readily available starting materials, high selectivity, as well as mild
reaction conditions make these practical methods particularly attractive.
B. Chen, S. Guo, X. Guo, G. Zhang, Y. Yu, Org. Lett.,
2015,
17, 4698-4701.
A library of thiazoles and selenothiazoles were synthesized via Ir-catalyzed
ylide insertion chemistry. The reaction was applied to the synthesis of
fanetizole, an anti-inflammatory drug, and a thiazole-containing drug fragment
that binds to the peptidyl-tRNA hydrolase (Pth) in Neisseria gonorrheae
bacteria.
S. Hassell-Hart, E. Speranzini, S. Srikwanjai, E. Hossack, S. M. Roe, D.
Fearon, D. Akinbosede, S. Hare, J. Spencer, Org. Lett.,
2022, 24, 7924-7927.
A copper-catalyzed coupling of oxime acetates with isothiocyanates provides
various 4-substituted and 4,5-disubstituted 2-aminothiazoles under mild reaction
conditions via copper-catalyzed N-O bond cleavage, activation of vinyl sp2
C-H bonds, and C-S/C-N bond formations. The oxime acetates serve not only as
substrate but also as single oxidant.
X. Tang, Z. Zhu, C. Qi, W. Wu, H. Jiang, Org. Lett., 2016, 18, 180-183.
A one-pot three-component reaction of α-nitro epoxides, potassium thiocyanate,
and primary amines provides polysubstituted 2-aminothiazoles in a smooth, highly
efficient, and eco-friendly manner with good yields.
Y. Zhu, W. Chen, D. Zhao, G. Zhang, Y. Yu, Synthesis, 2019, 51,
2023-2029.
The use of tribromoisocyanuric acid enables a simple and efficient one-pot
protocol for the synthesis of 2-aminothiazoles from readily available β-keto
esters via α-monohalogenation in aqueous medium and a subsequent reaction with
thiourea and DABCO. Extension of the reaction to thioacetamide and o-phenylenediamine
led to 2-methylthiazole and quinoxalines, respectively.
V. S. C. de Andrade, M. C. S. de Mattos, Synthesis, 2018, 50,
4867-4874.
A domino alkylation-cyclization reaction of propargyl bromides with thioureas
and thiopyrimidinones allows the synthesis of 2-aminothiazoles and
5H-thiazolo[3,2-a]pyrimidin-5-ones, respectively. Domino reactions were
performed under microwave irradiation leading to desired compounds in a few
minutes and high yields.
D. Castagnolo, M. Pagano, M. Bernardini, M. Botta, Synlett, 2009,
2093-2096.
2-Amino-4-alkyl- and 2-amino-4-arylthiazole-5-carboxylates and their selenazole
analogues were synthesized by α-halogenation of β-keto esters with N-bromosuccinimide,
followed by cyclization with thiourea or selenourea, respectively, in the
presence of β-cyclodextrin in water at 50°C.
M. Narender, M. S. Reddy, V. P. Kumar, B. Srinivas, R. Sridhar, Y. V. D.
Nageswar, K. R. Rao, Synthesis, 2007, 3469-3472.
Thiazoles were obtained in good yields by the reaction of 1H-1-(1′-alkynyl)-5-methyl-1,2,3-benziodoxathiole
3,3-dioxides with thioamides. The co-product, potassium
2-iodo-5-methylbenzenesulfonate, was recovered quantitatively by simple
filtration of the reaction mixture, and was regenerated to 1H-1-(1′-alkynyl)-5-methyl-1,2,3-benziodoxathiole
3,3-dioxides to be reused.
Y. Ishiwata, H. Togo, Synlett, 2008,
2637-2641.
A cyclization of tosylmethyl isocyanide with α-oxodithioesters in the presence
of KOH provides 4-methylthio-5-acylthiazoles, whereas ethyl isocyanoacetate underwent cyclization with α-oxodithioesters to form
4-ethoxycarbonyl-5-acylthiazoles in the presence of DBU/EtOH.
K. R. Kiran, T. R. Swaroop, N. Rajeev, S. M. Anil, J. S. Rangappa, M. P.
Sadashiva, Synthesis, 2020, 52,
1103-1112.
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.
Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, and N,N'-acylhydrazines
with the use of a fluorous Lawesson's reagent leads to thioamides, thiophenes,
1,3-thiazoles, and 1,3,4-thiadiazoles in high yields. The isolation of the final products is achieved in most cases by a
simple filtration.
Z. Kaleta, B. T Makowski, T. Soos, R. Dembinski, Org. Lett.,
2006, 8, 1625-1628.
A new method for a direct, copper-catalyzed arylation of heterocycle C-H bonds
by aryl iodides allows the conversion of electron-rich five-membered
heterocycles and electron-poor pyridine oxides. The best results are obtained by
using a combination of lithium tert-butoxide as base and copper iodide as
catalyst.
H.-Q. Do, O. Daugulis, J. Am. Chem. Soc.,
2007,
129, 12404-12405.
A Regel-type transition-metal-free direct C-2 aroylation of (benzo)oxazoles, (benzo)thiazoles
and 1,3,4-oxadiazoles with acid chlorides is catalyzed by N,N-dimethyl-4-aminopyridine
(DMAP) and affords the corresponding 2-ketoazoles in good yields.
P. Lassalas, F. Marsais, C. Hoarau, Synlett, 2013, 24,
2233-2240.
A "bulky-yet-flexible" Pd-PEPPSI-IPentAn complex catalyzes a highly efficient
amination of sterically hindered (hetero)aryl chlorides with a variety of
aliphatic and aromatic amines. The operationally simple protocol smoothly
proceeded under mild conditions without the exclusion of air and moisture to
provide the desired products.
F.-D. Huang, C. Xu, D.-D. Lu, D.-S. Shen, T. Li, F.-S. Liu, J. Org. Chem., 2018, 83,
9144-9155.
A one-pot three-component cascade cyclization of enaminones, cyanamide, and
elemental sulfur provides 2-amino-5-acylthiazoles in good yields with good
functional group tolerance. This method offers an effective way for accessing
valuable and potentially bioactive 2-amino-5-acylthiazole derivatives.
R.-G. Fu, Y. Wang, F. Xia, H.-L. Zhang, Y. Sun, D.-W. Yang, Y.-W. Wang, P. Yin, J. Org. Chem., 2019, 84,
12237-12245.
A metal-free synthesis of thiocyanated aminonitroalkenes and
2,4,5-trisubstituted thiazoles/selenazoles from β-aminonitroalkenes and N-thio/selenocyanatosaccharin
offers simple operation, mild reaction conditions, short reaction time, and good
functional group compatibility.
H. Yang, Y. Chen, X. Xu, Z. Li, Synlett, 2023,
34,
176-182.
A cyclization of tosylmethyl isocyanide with α-oxodithioesters in the presence
of KOH provides 4-methylthio-5-acylthiazoles, whereas ethyl isocyanoacetate underwent cyclization with α-oxodithioesters to form
4-ethoxycarbonyl-5-acylthiazoles in the presence of DBU/EtOH.
K. R. Kiran, T. R. Swaroop, N. Rajeev, S. M. Anil, J. S. Rangappa, M. P.
Sadashiva, Synthesis, 2020, 52,
1103-1112.