Synthesis of thiazoles and benzothiazoles
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.
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 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.
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.
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.
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.
A simple, green, and efficient method enables the synthesis of benzoxazoles and benzothiazoles from o-amino(thio)phenols and aldehydes using samarium triflate as a reusable acid catalyst under mild reaction conditions in aqueous medium.
P. B. Gorepatil, Y. D. Mane, V. S. Ingle, Synlett, 2013, 24, 2241-2244.
A copper-catalyzed condensation of 2-aminobenzenethiols with nitriles enables an efficient and convenient synthesis of 2-substituted benzothiazoles. The developed method is applicable to a wide range of nitriles containing different functional groups furnishing excellent yields of the corresponding products.
Y. Sun, H. Jiang, W. Wu, W. Zeng, X. Wu, Org. Lett., 2013, 15, 1598-1601.
The use of elemental sulfur as traceless oxidizing agent enables a remarkably simple solvent-free and catalyst-free synthesis of benzazoles from alkylamines and o-hydroxy/amino/mercaptan anilines.
T. B. Nguyen, L. Ermolenko, W. A. Dean, A. Al-Mourabit, Org. Lett., 2012, 14, 5948-5951.
A decarboxylative redox cyclization strategy enables the synthesis of 2-substituted benzothiazoles from o-chloronitroarenes and arylacetic acids in the presence of elemental sulfur/N-methylmorpholine under metal- and solvent-free conditions.
T. Guntreddi, R. Vanjari, K. N. Singh, Org. Lett., 2015, 17, 976-978.
An external oxidant-free oxidative coupling for aromatic C-H thiolation using visible-light photoredox cobalt-catalysis affords benzothiazoles in good to excellent yields with only H2 as a side product. When catalytic TBAOH was used as the base, not only 2-aryl but also 2-alkylbenzothiazoles could be obtained.
G. Zhang, C. Liu, H. Yi, Q. Meng, C. Bian, H. Chen, J.-X. Jian, L.-Z. Wu, A. Lei, J. Am. Chem. Soc., 2015, 137, 9273-9280.
Copper-catalyzed double C-S bond formation enables a highly efficient synthesis of benzothiazoles from easily available N-benzyl-2-iodoanilines and potassium sulfide via a traditional cross-coupling and an oxidative cross-coupling reaction.
X. Zhang, W. Zeng, Y. Yang, H. Huang, Y. Liang, Org. Lett., 2014, 16, 876-879.
The use of K2S2O8 enables a nontransition metal-catalyzed synthesis of 2-aryl benzothiazoles was achieved through oxidative condensation of benzothiazoles with aryl aldehydes or phenylglyoxylic acids.
Z. Yang, X. Chen, S. Wang, J. Liu, K. Xie, A. Wang, Z. Tan, J. Org. Chem., 2012, 77, 7086-7091.
Brønsted acid catalyzed cyclization reactions of 2-amino thiophenols and anilines with β-diketones under oxidant- and metal-free conditions give 2-substituted benzothiazoles and benzimidazoles in good yields, respectively. Various groups such as methyl, chloro, nitro, and methoxy linked on benzene rings were tolerated under the optimized reaction conditions.
M. S. Mayo, X. Yu, X. Zhou, X. Feng, Y. Yamamoto, M. Bao, Org. Lett., 2014, 16, 764-767.
The reaction of ortho-substituted anilines with functionalized orthoesters yields benzoxazole, benzothiazole, and benzimidazole derivatives in an efficient and connective methodology. The versatility of this approach enables the development of new libraries of heterocycles containing multifunctional sites.
G. Bastug, C. Eviolitte, I. E. Markó, Org. Lett., 2012, 14, 3502-3505.
Various 2-bromoanilides were reacted with 2-ethylhexyl 3-mercaptopropionate in high yields using a palladium catalyst. Subsequent generation of thiols and condensation under basic or acidic conditions allows a convenient synthesis of substituted benzothiazoles.
T. Itoh, T. Mase, Org. Lett., 2007, 9, 3687-3689.
A convenient method for the synthesis of 2-substituted benzimidazoles and benzothizoles offers short reaction times, large-scale synthesis, easy and quick isolation of the products, excellent chemoselectivity, and excellent yields as main advantages.
K. Bahrami, M. M. Khodaei, F. Naali, J. Org. Chem., 2008, 73, 6835-6837.
A one-pot tandem reaction of benzyl halides and o-aminobenzenethiol gives benzothiazoles in high chemical yields under mild conditions in DMSO in the absence of an additional oxidant. Both benzyl chlorides and bromides bearing a range of substituents proved to be suitable substrates.
C. Zhu, T. Akiyama, Synlett, 2010, 2345-2351.
An aerobic visible-light driven photoredox catalytic formation of 2-substituted benzothiazoles through radical cyclization of thioanilides features C-H functionalization and C-S bond formation with no direct metal involvement except the sensitizer. In this reaction, visible-light is the driving force, molecular oxygen the terminal oxidant, and water the only byproduct.
Y. Cheng, J. Yang, Y. Qu, P. Li, Org. Lett., 2012, 14, 98-101.
Dess-Martin periodinane (DMP) efficiently mediates the intramolecular cyclization of phenolic azomethines at ambient temperature leading to substituted benzoxazoles and benzothiazoles. Treatment of the reaction mixtures sequentially with Amberlyst A-26 thiosulfate resin and diisopropylaminomethyl resin (PS-DIEA) removes excess reagent and byproducts, to give pure products.
D. S. Bose, M. Idrees, Synthesis, 2010, 398-402.
Various benzothiazoles were synthesized by the intramolecular cyclization of thioformanilides using 2,6-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ) in dichloromethane at ambient temperature in high yields.
D. S. Bose, M. Idrees, B. Srikanth, Synthesis, 2007, 819-823.
The use of Pd/C as catalyst enables a ligand-free and additive-free synthesis of 2-substituted benzothiazoles via cyclization of o-iodothiobenzanilide derivatives at room temperature. The protocol is high-yielding and involves very mild conditions.
Y. Cheng, Q. Peng, W. Fan, P. Li, J. Org. Chem., 2014, 79, 5812-5819.
A copper-catalyzed, one-pot, three-component reaction of 1-iodo-2-nitroarenes with sodium sulfide and an aldehyde gives 2-substituted 1,3-benzothiazoles in good yields.
J. Liu, Q. Gui, Z. Yang, Z. Tan, R. Guo, J.-C. Shi, Synthesis, 2013, 45, 943-951.
In the presence of CuI and 1,10-phen, and n-Pr3N as the base, (2-iodobenzyl)triphenylphosphonium bromide and (2-iodophenylimino)triphenylphosphorane reacted efficiently with thiocarboxylic acids to give benzo[b]thiophenes and benzothiazoles in good yields via sequential Ullmann-type C-S bond coupling and subsequent Wittig reaction.
H. Yu, M. Zhang, Y. Li, J. Org. Chem., 2013, 78, 8898-8899.
A wide range of 2-aroylbenzothiazoles can be obtained in high yields by simply heating o-halonitrobenzenes, acetophenones, elemental sulfur, and N-methylmorpholine. This three-component coupling occurs in an excellent atom-, step-, and redox-efficient manner with elemental sulfur as nucleophile building block and redox moderating agent.
T. B. Nguyen, K. Pasturaud, L. Ermolenko, A. Al-Mourabit, Org. Lett., 2015, 17, 2562-2565.
An iron-catalyzed oxidative cyclization of 1-acyl-3-(phenyl)thioureas in the presence of sodium persulfate gave various N-benzothiazol-2-yl-amides selectively in good yields through C(sp2)-H functionalization and C-S bond formation.
J. Wang, Y. Zong, X. Zhang, Y. Gao, Z. Li, G. Yuo, Z. Quan, X. Wang, Synlett, 2014, 25, 2143-2148.
A catalytic amount of iodine enables a metal-free synthesis of 2-aminobenzothiazoles from cyclohexanones and thioureas in the presence of molecular oxygen as the oxidant under mild conditions. Various 2-aminobenzothiazoles, 2-aminonaphtho[2,1-d]thiazoles, and 2-aminonaphtho[1,2-d]thiazoles were prepared in satisfactory yields.
J. Zhao, H. Huang, W. Wu, H. Chen, H. Jiang, Org. Lett., 2013, 15, 2604-2607.
A multipathway coupled oxidation/heterocyclization domino strategy enables an efficient synthesis of 2-acylbenzothiazoles from various substrates including arylethenes, arylacetylenes, 2-hydroxy-aromatic ketones and carbinols via four distinct pathways free of metal in one pot.
Y.-p. Zhu, F.-c. Jia, M.-c. Liu, A.-x. Wu, Org. Lett., 2012, 14, 4414-4417.
N-Arylthioureas are converted to 2-aminobenzothiazoles via intramolecular C-S bond formation/C-H functionalization in the presence of an unusual cocatalytic Pd(PPh3)4/MnO2 system under an oxygen atmosphere at 80°C. This method eliminates the need for an ortho-halo substituted precursor, instead achieving direct functionalization of the ortho-aryl C-H bond.
L. L. Joyce, R. A. Batey, Org. Lett., 2009, 11, 2792-2795.
2-Aminobenzthiazole is a privileged scaffold with a range of biological activities. Using anilines as starting materials, a highly efficient and mild protocol enables the synthesis of 2-aminiobenzthiazoles in the presence of NaICl2.
V. N. Telvekar, H. M. Bachhav, V. K. Bairwa, Synlett, 2012, 23, 2219-2222.
Various aromatic and heteroaromatic compounds have been efficiently thiocyanated by using a combination of bromodimethylsulfonium bromide (BDMS) and ammonium thiocyanate.
D. S. Bhalerao, K. G. Agamanchi, Synlett, 2007, 2952-2956.
An efficient strategy for the synthesis of various 2-mercaptobenzothiazole derivatives proceeds from o-haloaniline derivatives and carbon disulfide via a tandem reaction in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford the corresponding 2-mercaptobenzothiazole derivatives in good yields.
F. Wang, S. Cai, Z. Wang, C. Xi, Org. Lett., 2011, 13, 3202-3205.
Lawesson’s reagent is an efficient promoter in the solvent-free microwave-assisted synthesis of 2-substituted benzoxazoles and benzothiazoles from carboxylic acids and 2-aminophenol or 2-aminothiophenol, respectively. Various aromatic, heteroaromatic and aliphatic carboxylic acids react under the conditions developed with good yields.
J. A. Seijas, M. P. Vázquez-Tato, M. R. Carballido-Reboredo, J. Crecente-Campo, L. Romar-López, Synlett, 2007, 313-316.
A general method for the formation of benzoxazoles and benzothiazoles via a copper-catalyzed cyclization of ortho-haloanilides is reported. Optimal conditions for cyclization used a catalyst combination of CuI and 1,10-phenanthroline as ligand. The mechanism is believed to proceed via an oxidative insertion/reductive elimination pathway through a Cu(I)/Cu(III) manifold. The rate of reaction of ortho-haloanilides follows the order I > Br > Cl, consistent with oxidative addition being the rate-determining step.
G. Evindar, R. A. Batey, J. Org. Chem., 2006, 71, 1802-1808.
A set of benzimidazoles, 3H-imidazo[4,5-b]pyridines, purines, xanthines and benzothiazoles was readily prepared from (hetero)aromatic ortho-diamines or ortho-aminothiophenol and aldehydes using chlorotrimethylsilane in DMF as a promoter and water-acceptor agent, followed by oxidation with air oxygen.
S. V. Ryabukhin, A. S. Plaskon, D. M. Volochnyuk, A. A. Tolmachev, Synthesis, 2006, 3715-3726.
A new, mild, and efficient method for the synthesis of 2-substituted benzothiazoles proceeds via the intramolecular cyclization of thioformanilides by using hypervalent iodine reagents in CH2Cl2 at ambient temperature.
D. S. Bose, M. Idrees, J. Org. Chem., 2006, 71, 8261-8263.
A novel metal-free iodine-mediated intramolecular oxidative cyclization protocol allows the preparation of various 2-substituted benzothiazoles.
D.-Y. Zhao, X.-K. Guo, J.-H. Li, R.-Y. Zang, Synthesis, 2012, 44, 927-933.
A transition-metal-free, DDQ-mediated method enables the intramolecular S-arylation of o-halobenzothiaoureas to yield 2-aminobenzothiazole derivatives. The reactions are performed at room temperature under base-free conditions with very good yields.
R. Wang, W.-j. Yang, L. Yue, W. Pan, H.-y. Zeng, Synlett, 2012, 23, 1643-1648.
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 Cu(II)-catalyzed oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids enables the synthesis of various 2-aryl benzothiazoles in good yields from 2-unsubstituted benzothiazoles in the presence of oxygen as the sole oxidant. The reaction proceeds via Cu(II)-catalyzed decarboxylation, C-H bond oxidation, ring-opening, and condensation steps in one-pot and tolerates various functional groups.
Q. Song, Q. Feng, M. Zhou, Org. Lett., 2013, 15, 5990-5993.
A highly efficient Pd/Cu-catalyzed C-H arylation method for a range of heterocycles has been discovered. The efficiency and low loading of a combination of a palladium catalyst and a well-defined copper cocatalyst together with the mild reaction conditions demonstrate this method to be practically useful and mechanistically interesting.
J. Huang, J. Chan, Y. Chen, C. J. Borths, K. D. Baucom, R. D. Larsen, M. M. Faul, J. Am. Chem. Soc., 2010, 132, 3674-3675.
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 simple and straightforward method for the direct carboxylation of aromatic heterocylces such as oxazoles, thiazoles, and oxadiazoles using CO2 as the C1 source requires no metal catalyst and only Cs2CO3 as the base. A good functional group tolerance is achieved.
O. Vechorkin, N. Hirt, X. Hu, Org. Lett., 2010, 12, 3567-3569.