Synthesis of Benzoxazoles

A route involving generation of the o-halobenzanilide substructure in situ has also been described. Viirre et al. found that the combination of o-bromoanilines and acyl chlorides with a copper catalyst under microwave irradiation resulted in an efficient one-pot formation of benzoxazoles [126], 

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As in the case of benzimidazole, a parallel synthesis of benzoxazoles was described. The authors report that mixing directly differently substituted o-amino phenols 193 with acylating agents 194 and heating at 200 °C for 10-15 min under microwave irradiation, a collection of benzoxazoles 195 was obtained (Scheme 70). With this reaction, a 48-member library of benzoxazoles with different substituents on the aromatic rings was obtained [125]. 

Scheme 7.18. Chromium-manganese redox couple-mediated domino process for the synthesis of benzoxazoles.

For the synthesis of benzoxazoles, Player and coworkers have developed a simple method that involves microwave heating of a 2-aminophenol with 1.1 equivalents of an acid chloride in dioxane or xylene (Scheme 6.213) [384]. The best results were... 

A simple montmorillonite K 10 clay surface is one among numerous acidic supports that have been explored for the Beckmann rearrangement of oximes (Scheme 6.27) [54]. However, the conditions are not adaptable for the aldoximes that are readily dehydrated to the corresponding nitriles under solventless conditions. Zinc chloride has been used in the above rearrangement for benzaldehyde and 2-hydroxyacetophe-none, the later being adapted for the synthesis of benzoxazoles. 

SOLID-PHASE SYNTHESIS OF BENZOXAZOLES VIA MITSUNOBU REACTION... 

Solid-Phase Synthesis of Benzoxazoles via Mitsunobu Reaction... 

Pottorf, R.S., Chadha, N.K., Katkevics, M., Ozola, V., Suna, E., Ghane, H., Regberg, T. and Player, M.R., Parallel synthesis of benzoxazoles via microwave-assisted dielectric heating, Tetrahedron Lett., 2003, 44, 175-178. 

Suschitzky et al. have proposed an original synthesis of benzoxazole nitro derivatives in a mixture of carboxylic and polyphosphoric acids by heating aromatic aldehydes containing the nitro group in the para-position [471],... 

Wang Y, Sarris K, Sauer DR et al (2006) A simple and efBcient one step synthesis of benzoxazoles and benzimidazoles from carboxylic acids. Tetrahedron Lett 47 4823 826... 

Pottorf RF, Chadha NK, Katkevics M et al (2003) Parallel synthesis of benzoxazoles via microwave-assisted dielectric heating. Tetrahedron Lett 44 175-178... 

Bimolecular trapping of phenoxonium ions by nucleophilic yr-bonds can lead to cyclized products when attack occurs at the or /io-position. For instance, a Ritter-type reaction occurs when MeCN is used as solvent in the absence of other nucleophiles, leading to a useful synthesis of benzoxazoles (XLV) [48] ... 

By analogy to the synthesis of benzoxazoles, benzothiazoles Eire obtained by cyclocondensation of o-aminothiophenols or their salts with carboxylic acids, their derivatives or with aldehydes [101] ... 

The synthesis of heterocycles by means of Lewis bases has been carried out using the reactions described above. For instance, the dipole resulting from the reaction of pyridine with DMAD was intercepted with phenylisocyanate giving a 1,4 dipole that ultimately led to pyrimidindione derivatives. Wang and coworkers have described the synthesis of benzoxazoles by reaction of ynals with N-protected-2-aminophenols using pyrrolidine as catalyst. Salicylaldehyde has been the starting material for the synthesis of many benzoheterocycles. When using DBU as catalyst, it was transformed into benzopyran derivatives by reaction with 2,2-disubstituted allene esters. When DABCO is used as catalyst, the reaction of AT-tosylimines with ethyl... 

Benzisoxazoles and benzoxazoles appear as scaffolds in many pharmaceutical products, and the benzoxazole moiety is also present in natural products. Chen et al. reported a synthesis of benzoxazoles and benzisoxazoles that allows the synthesis of both isomers from the same substrate tScheme In both synthetic routes, the authors propose that an N-... 

There has been considerable interest in benzoxazole and benzothiazole derivatives, not least because of their value for a variety of industrial (Belhouchet et al., 2012 Eshghi et al, 2012), biological (Fukuzawa et al., 2009), and medicinal chemistry uses (Praveen et al, 2012 Wen et al., 2012). In continuation of the interest in the use of heterogeneous solid catalysts (Karami et al., 2008, 2013b), a very simple procedure for the synthesis of benzoxazole and benzothiazole derivatives using TSA as a superior solid acid catalyst was reported (Scheme 3.16) (Farahi et al., 2013). 

Farahi, M., Karami, B. and Azari, M. 2013. Tungstate sulfuric acid as an efficient catalyst for the synthesis of benzoxazoles and benzothiazoles under solvent-free conditions. C. R. Chimie. 16(11) 1029-1034. 

Kantam, M. L., Venkanna, G. T., S. Kumar, K. B., Balasuhrahmanyam, V., and Bhargava, S. 2009b. Synthesis of benzoxazoles via intramolecular cychzation of orf/io-halobenzani-lides using copper fluorapatite catalyst. Synlett. (11) 1753-1756. 

Mohammadpoor-Baltorka, I., Moghadama, M., Tangestaninejad, S., Mirkhania, V., Zolfigolb, M.A. and Hojatia, S.F. 2008. SUica sulfuric acid catalyzed synthesis of benzoxazoles, benzimidazoles and oxazolo[4,5-h]pyridines under heterogeneous and solvent-free con-dihons. J. Iran. Chem. Soc. 5 S65-S70. 

Kumar, K.R., Satyanarayana, P.V.V. and Reddy, B.S. 2013. NaHS04-Si02 promoted solvent-free synthesis of benzoxazoles, benzimidazoles, and benzothiazole derivatives. J. Ghent. 2013 (151273). 

Moghaddam, F. M. Bardajee, G. R. Ismaili, H. Taimoory, S. M. D. Facile and efficient one-pot protocol for the synthesis of benzoxazole and benzothiazole derivatives using molecular iodine as catalyst. Synth. Commun. 2006, 36, 2543-2548. 

Oxazoles were used in the Kondrat eva reaction for the synthesis of pyridine-based compounds (13OL2530, 13OL3550). A continuous flow procedure was reported for a scalable synthesis of benzoxazoles 137 starting form 3-halo-N-acyl anilines 136 (130L5546). The reaction proceeded via a base-mediated elimination of the 3-halo substituents to give an aryne intermediate that underwent intramolecular cyclization to provide lithiated benzoxazoles that were quenched in-line by addition of electrophiles (E ). 

Scheme 2.8 Cu-catal3ized synthesis of benzoxazoles from amides.

Scheme 2.9 Cu-catalyzed synthesis of benzoxazoles from nitriles.

In 2010, Bao and Shen reported a novel and efficient procedure for the synthesis of benzoxazole and benzimidazole derivatives. The one-pot cascade process is based on Cul under ligand-free conditions. A variety of carbodiimides coupled with o-halophenols or o-haloanilines to give the products in moderate to excellent yields under the mild conditions (Scheme 2.134). 

The original limited scope with regard to the isocyanide was soon overcome. Lang et al. adapted this methodology for the synthesis of benzoxazoles 8 and oxazolines 9 by using... 

SCHEME 3,8 Synthesis of benzoxazoles and oxazohnes by palladium-catalyzed isocyanide reactions. 

The use of three Keggintype of HPAs including, H [PMo VO, H5[PMo,qV20, and H3[PMOj20 ] in the synthesis of benzoxazole derivatives from reaction of 2-aminophenol with benzaldehydes and benzoic acids and the effects of reaction parameters such as the type, amount of HPA, and solvent on the yield of reaction has been recently reported [93], The comparison of these two methods for the synthesis of benzoxazole derivatives showed that condensation of 2-aminophenol with benzoic acids using HPAs under refluxing condition led to better yields than benzaldehydes. In addition, higher amount of HPA and more reaction time was required for the latter (Scheme 3.34). 

Peddinti also reported a simple and efficient one-pot synthesis of benzoxazolic bicyclo[2.2.2]octenones 29-31 by subjecting 2-methoxy-substituted phenolic aldimines of type 26 to a similar treatment with DIB in the presence of the same kind of dienophiles 24, or furans, in MeOH [47], This clever domino reaction starts with a DIB-mediated oxidative cychzation of the phenolic aldimines into the phenolic benzoxazoles 27, which are then converted, with a second equivalent of DIB, into the MOBs 28 that are finally trapped with excess of dienophile to furnish selectively the expected [4+2] cycloadducts 29-31 (Fig. 11) [47]. 

The range of oxidative heterocyclizations was successfully extended to the construction of intramolecular C-O bonds. Zheng et al. [26] showed that enamides 29 can be oxidatively cyclized to functionalized oxazoles 30 using PIDA as an oxidant and BF3-OEt2 as a Lewis acid (Scheme 7 (1)). A similar strategy was adopted by Yu and coworkers portraying the synthesis of benzoxazoles in high... 

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