Categories: Synthesis of N-Heterocycles, Synthesis of O-Heterocycles > benzo-fused N-Heterocycles, benzo-fused O-Heterocycles >
Synthesis of Benzoxazoles
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 sequential one-pot procedure for the synthesis of either 2-(hetero)aryl or 2-styryl benzoxazoles from aryl and vinyl bromides involves an initial aminocarbonylation with 2-aminophenols as nucleophiles followed by an acid mediated ring closure to generate the heterocycle. The methodology displays a broad substrate scope in good yields.
K. T. Neumann, A. T. Lindhardt, B. Bang-Andersen, T. Skrydstrup, Org. Lett., 2015, 17, 2094-2097.
Cyclization reactions of 2-aminophenols with β-diketones catalyzed by a combination of Brřnsted acid and CuI give various 2-substituted benzoxazoles. Different substituents such as methyl, chloro, bromo, nitro, and methoxy on 2-aminophenol are tolerated under the optimized reaction conditions.
M. S. Mayo, X. Yu, X. Zhou, X. Feng, Y. Yamamoto, M. Bao, J. Org. Chem., 2014, 79, 6310-6314.
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.
The combination of sulfur and DABCO efficiently promotes a reductive coupling/annulation of o-nitrophenols or o-nitroanilines with benzaldehydes. This method represents a simple, straightforward, and green approach to the construction of benzoxazoles and benzimidazoles.
M.-H. D. Dang, L. H. T. Nguyen, P. H. Tran, Synthesis, 2020, 52, 1687-1694.
An iron-catalyzed hydrogen transfer strategy for the redox condensation of o-hydroxynitrobenzenes with alcohols provides a wide range of 2-substituted benzoxazoles in very good yields. Furthermore, the reaction system was successfully extended to the synthesis of benzothiazoles and benzimidazoles.
R. R. Putta, S. Chun, S. H. Choi, S. B. Lee, D.-C. Oh, S. Hong, J. Org. Chem., 2020, 85, 15396-15405.
A N-heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of aldimines generated from 2-amino phenols and aromatic aldehydes provides 2-arylbenzoxazoles in good yields under mild conditions. The reaction tolerates a broad range of functional groups.
A. Patra, A. James, T. K. Das, A. T. Biju, J. Org. Chem., 2018, 83, 14820-14826.
Nitrogen extrusion reactions of azido complexes, generated in situ from the corresponding aldehydes or ketones with TMSN3 in the presence of ZrCl4 or TfOH, enable the synthesis of benzisoxazole, nitriles, benzoxazoles depending on the substrates.
P. Nimnual, J. Tummatorn, C. Thongsornkleeb, S. Ruchirawat, J. Org. Chem., 2015, 80, 8657-8667.
Efficient and convenient three-component couplings of aryl halides, amino alcohols and tert-butyl isocyanide under palladium catalysis provide a range of oxazolines in excellent yield. The use of 1,2-amino phenols instead of amino alcohols enables the synthesis of benzoxazoles.
P. J. Boissarie, Z. E. Hamilton, S. Lang, J. A. Murphy, C. J. Suckling, Org. Lett., 2011, 13, 6184-6187.
An experimentally simple, general, efficient, and ligand-free synthesis of substituted benzimidazoles, 2-aminobenzimidazoles, 2-aminobenzothiazoles, and benzoxazoles via intramolecular cyclization of o-bromoaryl derivatives is catalyzed by copper(II) oxide nanoparticles in DMSO under air. The heterogeneous catalyst can be recovered and recycled without loss of activity.
P. Saha, T. Ramana, N. Purkait, M. A. Ali, R. Paul, T. Punniyamurthy, J. Org. Chem., 2009, 74, 8719-8725.
A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N-H ketimines proceeds in two distinct pathways through a common N-Cl imine intermediate: (a) N-O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively.
C.-y Chen, T. Andreani, H. Li, Org. Lett., 2011, 13, 6300-6303.
A copper(II)-catalyzed conversion of bisaryloxime ethers to 2-arylbenzoxazoles involves a cascade C-H functionalization and C-N/C-O bond formation under oxygen atmosphere.
M. M. Guru, M. A. Ali, T. Punniyamurthy, Org. Lett., 2011, 13, 1194-1197.
An efficient method for the transformation of N-benzyl bisarylhydrazones and bisaryloxime ethers to functionalized 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles involves a copper(II)-mediated cascade C-H functionalization/C-N/C-O bond formation under neutral conditions. Substrates having either electron-donating or -withdrawing substituents undergo the cyclization at moderate temperature.
M. M. Guru, M. A. Ali, T. Punniyamurthy, J. Org. Chem., 2011, 76, 5295-5308.
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.
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.
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.
Elemental sulfur is an excellent oxidant for an oxidative rearranging coupling between o-aminophenols and ketones in the presence of N-methylpiperidine to provide a wide range of 2-alkylbenzoxazoles under mild conditions.
T. B. Nguyen, P. Retailleau, Org. Lett., 2017, 19, 3887-3890.
An efficient oxidative cyclization of 2-aminophenols or 2-iodoanilines with alkenes provides diverse benzoxazoles/benzothiazoles in good yields in the presence of elemental sulfur.
J. Zhang, L. Hu, Y. Liu, Y. Zhang, X. Chen, Y. Luo, Y. Peng, S. Han, B. Pan, J. Org. Chem., 2021, 86, 14485-14492.
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.
An atom-economical and eco-friendly electrochemical oxidation/cyclization of glycine derivatives through intramolecular Shono-type oxidative coupling provides a variety of 2-substituted benzoxazoles in good yields. This oxidative cyclization proceeded in transition metal- and oxidant-free conditions and generated H2 as only byproduct.
L. Liu, Z. Xu, T. Liu, C. Xu, W. Zhang, X. Hua, F. Ling, W. Zhong, J. Org. Chem., 2022, 87, 11379-11386.
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.
The reaction of o-aminophenols with α-oxodithioesters provides 2-acylbenzoxazoles in good yields in the presence of p-toluene sulfonic acid as catalyst, whereas the reaction of o-phenylenediamines with α-oxodithioesters gives 2-methylthio-3-arylquinoxalines.
K. R. Kiran, T. R. Swaroop, K. P. Sukrutha, J. B. Shruthi, S. M. Anil, K. S. Rangappa, Synthesis, 2019, 51, 4205-4214.
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.
Readily available, air-stable, recyclable copper(II) ferrite nanopartices serve as a catalyst in a sustainable synthesis of benzoxazoles from substituted N-(2-halophenyl)benzamides. The nanocatalyst can be completely recovered with an external magnet and can be used seven times without significant loss of catalytic activity.
D. Yang, X. Zhu, W. Wei, M. Jiang, N. Zhang, D. Ren, J. You, H. Wang, Synlett, 2014, 25, 729-735.
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 versatile one-pot domino acylation annulation reaction of 2-bromoanilines with acyl chlorides in the presence of Cs2CO3, catalytic CuI, and 1,10-phenanthroline under microwave conditions was applied to the synthesis of benzoxazoles. These copper-catalyzed approaches complement existing strategies for benzoxazole synthesis, which typically utilize 2-aminopheonls as precursors.
R. D. Viirre, G. Evindar, R. A. Batey, J. Org. Chem., 2008, 73, 3452-3459.
The direct C-H bond arylation of benzoxazoles and oxazoles with aryl chlorides is catalyzed by a well-defined NHC-Pd(II)-Im complex. Under optimized conditions, various aryl chlorides can be used to yield 2-aryloxazole derivatives in good yields.
X.-B. Shen, Y. Zhang, W.-X. Chen, Z.-K. Xiao, T.-T. Hu, L. X. Shao, Org. Lett., 2014, 16, 1984-1987.
A copper(I) complex catalyzes a direct alkylation of benzoxazoles using nonactivated secondary alkyl halides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether.
P. Ren, I. Salihu, R. Scopelliti, X. Hu, Org. Lett., 2012, 14, 1748-1751.
Palladium-catalyzed direct alkynylations of heteroarenes with inexpensive gem-dichloroalkenes as user-friendly electrophiles set the stage for a modular, step-economical synthesis of diversely decorated heteroaryl alkynes.
L. Ackermann, C. Kornhaass, Y. Zhu, Org. Lett., 2012, 14, 1824-1826.
The reaction of N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as nonhazardous electrophilic cyanating agent with various substituted 2-aminophenols and benzene-1,2-diamine enables a facile synthesis of 2-aminobenzoxazole and 2-aminobenzimidazole derivatives in the presence of lithium hexamethyldisilazide (LiHMDS). This protocol offers operational simplicity, short reaction time, and simple workup.
M. Kasthuri, H. S. Babu, K. S. Kumar, Ch. Sudhakar, P. V. N. Kumar, Synlett, 2015, 26, 897-900.
A Pd-catalyzed aerobic oxidation of o-aminophenols and isocyanides gives 2-aminobenzoxazoles and 3-aminobenzoxazines in good yields and a broad substrate scope. This methodology has the advantages of experimental simplicity, mild reaction conditions, and easily accessible starting materials. Furthermore, the synthesis of other types of useful nitrogen heterocycles has been achieved.
B. Liu, M. Yin, H. Gao, W. Wu, H. Jiang, J. Org. Chem., 2013, 78, 3009-3020.
The reaction of isothiocyanates with ortho-substituted anilines bearing N,N-, N,O-, and N,S-bis-nucleophiles, followed by an intramolecular, potassium periodate mediated oxidative cyclodesulfurization of the in situ generated monothioureas provides substituted 2-aminobenzazole derivatives in very good yields.
C. Duangkamol, W. Phakhodee, M. Pattarawarapan, Synthesis, 2020, 52, 1981-1990.
Visible light efficiently mediates a mild intramolecular oxidative cyclization of o-hydroxy-N-aryl-N,N-dialkylformamidines leading to 2-aminobenzoxazole derivatives in excellent yields in the presence of only 1 mol% tris(2,2′-bipyridine)ruthenium(II) as a photoredox catalyst and air as terminal oxidant.
V. P. Srivastava, L. D. S. Yadav, Synlett, 2013, 24, 2758-2762.
Copper-catalyzed C-H bond activation enables a facile, efficient, and simple protocol for direct oxidative C-H amination of benzoxazoles with primary amines using tert-butyl peroxide (TBP) as oxidant under air. Various substituted aminobenzoxazoles were synthesized with very good yields.
J. Gu, C. Cai, Synlett, 2015, 26, 639-642.
A convenient, copper-catalyzed C-H and C-N bond activation enables an efficient and conceptually new method for oxidative amination of azoles with tertiary amines. This protocol can be performed in the absence of external base and only requires atmospheric oxygen as oxidant.
S. Guo, B. Qian, C. Xia, H. Huang, Org. Lett., 2011, 13, 522-525.
A facile metal-free oxidative amination of benzoxazole by activation of C-H bonds with secondary or primary amines in the presence of catalytic iodine in aqueous tert-butyl hydroperoxide proceeds smoothly at ambient temperature under neat reaction condition to furnish products in high yields. This user-friendly method produces only tertiary butanol and water as byproducts.
M. Lamani, K. R. Prabhu, J. Org. Chem., 2011, 76, 7938-7944.
Simple azole substrates can be converted into N-substituted 2-aminoazole derivatives in the presence of nitrogen nucleophiles, lithium tert-butoxide as the base, and iodine to mediate carbon-nitrogen bond formation. This method proceeds at room temperature under an air atmosphere using a normal benchtop set-up, or can be performed conveniently using microwave irradiation.
S. Yotphan, D. Beukeaw, V. Reutrakul, Synthesis, 2013, 45, 936-942.
Catalytic amounts of tetrabutylammoniumiodide (TBAI), aqueous solutions of H2O2 or TBHP as co-oxidant enabled an efficient transition-metal-free amination of benzoxazoles under mild reaction conditions, to yield highly desirable 2-aminobenzoxazoles in good yields. First mechanistic experiments indicate the in situ iodination of the secondary amine as the putative mode of activation.
T. Froehr, C. P. Sindlinger, U. Kloeckner, P. Finkbeiner, B. J. Nachtsheim, Org. Lett., 2011, 13, 3754-3757.
An efficient copper-based catalytic system (Cu/PTABS) enables an amination of a chloroheteroarenes at ambient temperature in water as the sole reaction solvent. A wide variety of chloroheteroarenes could be coupled efficiently with primary and secondary amines as well as selected amino acid esters under mild reaction conditions.
U. Parmar, D. Somvanshi, S. Kori, A. A. Desai, R. Dandela, D. K. Maity, A. R. Kapdi, J. Org. Chem., 2021, 86, 8900-8925.
The combination of Pd/PTABS enables an exceptionally mild and highly efficient catalytic amination of chloroheteroarenes with secondary amines at ambient temperature.
S. S. M. Bandaru, S. Bhilare, N. Chrysochos, V. Gayakhe, I. Trentin, C. Schulzke, A. R. Kapdi, Org. Lett., 2018, 20, 473-476.
A catalyst-free amination of 2-mercaptobenzoxazoles on water under microwave irradiation provides 2-aminobenzoxazoles in good yields via direct amination. Key benefits of this process include an on-water reaction, short reaction time, being scalable and catalyst-free, and use of 2-mercaptobenzoxazoles as an inexpensive starting material.
T. Tankam, J. Srisa, M. Sukwattanasinitt, S. Wacharasindhu, J. Org. Chem., 2018, 83, 11936-11943.