Synthesis of benzothiazoles
A straightforward synthesis of 2-arylbenzothiazoles from 2-aminothiophenol and aryl aldehydes in air/DMSO oxidant system is operationally simple, proceeds without catalysts, tolerates a wide range of functionalities, and provides desired products in good to excellent yields.
R. Hu, X. Li, Y. Tong, D. Miao, Q. Pan, Z. Jiang, H. Gan, S. Han, Synlett, 2016, 27, 1387-1390.
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.
Triggered by alkyl radicals, varieties of 2-isocyanoaryl thioethers containing aliphatic, aryl, and heteroaromatic groups can be cleaved and precisely reinstalled to give benzothiazole derivatives. Mechanistic studies reveal that the cascade reaction undertakes an intermolecular pathway.
K. Luo, W.-C. Yang, K. Wei, Y. Liu, J.-K. Wang, L. Wu, Org. Lett., 2019, 21, 7851-7856.
A highly efficient reaction of readily available aromatic amines, benzaldehydes, and NH4SCN as a sulfur source provides 2-arylbenzothiazoles with wide functional group compatibility in good yields via an iodine-mediated oxidative annulation.
A. Dey, A. Hajra, Org. Lett., 2019, 21, 1686-1689.
A copper-promoted [3 + 1 + 1]-type cyclization reaction enables a selective construction of 2-aryl or 2-benzyl substituted benzothiazoles from o-iodoaniline derivatives, S8, and N-tosylhydrazones depending on the reaction system.
Y. Huang, P. Zhou, W. Wu, H. Jiang, J. Org. Chem., 2018, 83, 2460-2466.
A selective, TBHP/KI-promoted C-O bond cleavage of ethers followed by annulation with anilines and elemental sulfur provides a wide range of 2-aryl-, 2-heteroaryl-, and 2-alkyl-substituted benzothiazoles with satisfactory yields and good functional group compatibility under transition-metal-free conditions.
J. Zhang, X. Zhao, P. Liu, P. Sun, J. Org. Chem., 2019, 84, 12596-12605.
A three-component reaction of nitroarenes, alcohols, and sulfur powder provided 2-substituted benzothiazoles in good yield with a good functional group tolerance via nitro reduction, C-N condensation, and C-S bond formation.
Q. Xing, Y. Ma, H. Xie, F. Xiao, F. Zhang, G.-J. Deng, J. Org. Chem., 2019, 84, 1238-1246.
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.
A synthesis of 2-substituted benzothiazoles in good yields from o-iodoanilines, arylacetic acids, and elemental sulfur is catalyzed by cheap copper metal. This S8-mediated directed decarboxylative redox-cyclization strategy is operationally simple, ligand-free, and compatible with a wide range of functional groups.
X. Wang, X. Li, R. Hu, Z. Yang, R. Gu, S. Ding, P. Li, S. Han, Synlett, 2018, 29, 219-224.
A visible-light-driven, intramolecular C(sp2)-H thiolation without addition of a photosensitizer, metal catalyst, or base induces the cyclization of thiobenzanilides to benzothiazoles. The substrate undergoes a reverse hydrogen-atom transfer (RHAT) in its excited state with TEMPO to form a sulfur radical, which adds to the benzene ring followed by a rearomatization via RHAT.
Z.-M. Xu, H.-X. Li, D. J. Young, D.-L. Zhu, H.-Y. Li, J.-P. Lang, Org. Lett., 2019, 21, 237-241.
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 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.
Brřnsted 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.
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.
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 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 tandem approach enables a facile and efficient synthesis of various 2-aminobenzothiazoles from 2-chloroanilines and dithiocarbamates in excellent yields in the presence of Pd(PPh3)4 and t-BuOK.
W. Xu, M.-T. Zeng, M. Liu, S.-S. Liu, Y.-S. Li, Z.-B. Dong, Synthesis, 2017, 49, 3084-3090.
A ruthenium catalyzed intramolecular C-S coupling reaction of N-arylthioureas enables the synthesis of 2-aminobenzothiazoles via an electrophilic ruthenation pathway instead of a direct C-H activation. In case of meta-substituents on the N-arylthiourea, stereoelectronic effects dictate the final regioselective outcome of the reaction.
S. Sharma, R. S. Pathare, A. K. Maurya, K. Gopal, T. K. Roy, D. M. Sawant, R. T. Pardasani, Org. Lett., 2016, 18, 356-359.
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.
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.
A cascade reaction of isothiocyanatobenzenes with primary or secondary amines provides 2-aminobenzothiazoles using iodine as a catalyst and oxygen as an oxidant via formation of a benzothiourea intermediate followed intramolecular cross dehydrogenative coupling. This method eliminates the use of ortho-halo-substituted precursors, expensive transition-metal catalysts, and hazardous oxidants.
Y. Xu, B. Li, X. Zhang, X. Fan, J. Org. Chem., 2017, 82, 9637-9646.
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.
The use of alkyl diacyl peroxides and alkyl tert-butyl peresters, which are readily accessible from carboxylic acids, enables an efficient, iron-catalyzed C-H alkylation of benzothiazoles. This reaction is environmentally benign and compatible with a broad range of functional groups. Various primary, secondary, and tertiary alkyl groups can be efficiently incorporated.
K. R. Babu, N. Zhu, H. Bao, Org. Lett., 2017, 19, 46-49.
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 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.