Benzoxazoles aldehydes

Benzoxazoles are produced in high yield from a-acylphenol oximes by a Beckmann rearrangement using zeolite catalysts <95SC3315>. The reaction of the o-benzoquinone 40 with aromatic aldehyde oximes produces the benzoxazoles 41 <95ZOR1060>. The fused oxazolium salts 43 (R = Me, Et, Pr , or Ph R2 = Me or Pr ) are formed from tropone and nitrilium hexachloroantimonates 42 <96JPR598>. 

Remote steric effects have also been noted to play an unanticipated role in the sense of asymmetric induction. This is apparent from related condensations carried out on aldehydes 106 (26) and 107 (eqs. [76]-[78]) (26,92). Other examples illustrating the influence of remote structural perturbations on the carbonyl addition process have been observed in these laboratories. The addition of the lithio benzoxazole 110 to aldehyde 108 proceeded with good Cram diastereoface selection (95a), whereas the same nucleophilic addition to aldehyde 109 was stereorandom (95b). 

Unsaturated 5(4//)-oxazolones derived from aromatic and heterocyclic aldehydes including phthalic anhydride/ antipyrine/ " chromone/ indoles/ pyridines/" ° quinolines/" diazines/" benzoxazoles/" and benzimidazoles " " have been prepared. Reaction with nitrogen nucleophiles and subsequent cycliza-tion leads to the expected 5(477)-imidazolones. 

Beispielsweise liefert die Kupplung von Phenylamino-methansulfonsaure mit diazotiertem 2-(4-Amino-phenyl)-l, 3-benzoxazol einen Monoazofarbstoff, der hydrolysiert und mit ein-em aromatischen Aldehyd umgesetzt wird. Dabei entstehen typische Farbstoffe fur Flus-sigkristalle vom Guest-Host-Typ3 ... 

Similar reaction has also been carried out with benzoxazoles substituted in the benzo ring with up to three substituents, such as chloro, alkyl, alkoxy,48 phenoxy,49 phenyl, cycloalkyl, or sulfamoyl10 groups. By employing anils of substituted aromatic aldehydes, varying groups may also be introduced into the stilbene part of the molecule.50 Water-soluble derivatives have also been obtained by the use of sulfonic acid-substituted p-tolylbenzoxazoles and also aromatic aldehyde anils.51... 

A further series of styryl derivatives from benzoxazoles and hetero-aromatic aldehyde anils are shown in Tables VIII, XI, XV, and XVII. 

Condensation of the aldehyde 175 with the lithiated derivative of benzoxazole 176 gave an 88 12 mixture of chromatographically separable diastereomeric al-... 

The oxazole ring of benzoxazoles, in which the 4,5-bond is masked by incorporation in a benzene ring, survives many oxidation reactions. 2-Methylbenzoxazole (100), for example, can be oxidized to benzoxazole-2-carboxylic acid, and 2-methylnaphth[2,1 -d ]oxazole (101) forms the corresponding aldehyde by the action of selenium dioxide. 

Nitrated orf/to-aminophcnols react with aldehydes to form Schiff s bases, which are easily oxidized into the corresponding benzoxazoles (Scheme 2.72) [481],... 

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],... 

Condensation of 2-hydrazinobenzoxazoles (286) with aromatic aldehydes in glacial acetic acid yields 3-aryl[l,2,4]triazolo[3,4-Z>]benzoxazoles (288) <88BCJ1339). Similarly, 3-aryl-9/7-[ 1,2,4]tri-azolo[4,3-Z>]benzimidazoles (287) are obtained from 2-hydrazinobenzimidazoles (289) (Equation (80)) <88BCJ1339>. 

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] ... 

N-1 benzoxazolyl 3,4-dihydropyrimidinones/thiones 33 have been obtained by reacting carbomethoxy benzoxazole 30 with semicarbazide/ thiosemicarbazide 31 (X = O, S) in refluxing ethanol using a catalytic amount of piperidine to obtain intermediate 2-(2- alkylbenzoxazole-5-car-bonyl)hydrazine carboaxo/thioamide 32 (R = H, Me X = O, S), which upon cyclocondensation with an aromatic aldehyde and p-ketoester in the presence of tiifluoromethane sulfonic acid at room temperature afforded benzoxazolyl 3,4-dihydropyrimidin-2(lH)-ones/thiones 33 (R = H, Me R = Me, CF3), in excellent yield (Scheme 12) (09M16). 

When benzoxazole-substituted urea/thiourea 140 was used in a Biginelli condensation with an aldehyde and a (3-ketoester in the presence of alumina-supported trifluoromethane sulfonic add as a heterogenous catalyst under solvent-free reaction conditions, N-3 benzoxazole-substituted 141 (X = S, O) was obtained in good yield (Scheme 54) (09JHC119, 09M17). 

Very recently, Mandal and coworkers reported that CuO nanoparticles supported on silica (Cu0-NPs/Si02) could be utilized as a heterogeneous and recyclable catalyst for the one-pot synthesis of benzimidazoles, benzothiazoles, and benzoxazoles (Scheme 4.46) (Inamdar et al., 2013). The Cu-NPs/Si02-catalyzed cyclization of o-phenylenediamines, o-aminothiophenols, and o-aminophenols with various aldehydes efficiently delivered the corresponding heterocycles. 

By analogy to the standard synthesis of benzoxazoles (cf. p. 180), benzothiazoles are synthesized [360] by cyclocondensation of (2-amino)thiophenols with carboxylic acids or esters, with orthoesters in the presence of the acidic montmorillonite KSF clay catalyst, practicable also for the synthesis of benzoxazoles and benzimidazoles [361] or with aldehydes in the presence of an oxidant [362] ... 

It was reported [134] that treatment of o-aminophenol with various aldehydes in aqueous glycerol led to the formation of 2-substituted benzoxazoles 154 (X=0) (Scheme 90). A similar reaction of o-phenylenediamine with aldehydes afforded 2-substituted benzimidazoles 154 (X=NH) with satisfactory yields. 

Rokade BV, Prabhu JR (2012) Chemoselective Schmidt reaction mediated by triflic acid selective synthesis of nitriles from aldehydes. J Org Chem 77(12) 5364-5370 Nimnual P, Tummatorn J, Thongsornkleeb C, Ruchirawat S (2015) Utility of nitrogen extmsion of azido complexes for the synthesis of nitriles, benzoxazoles, and benzisoxazoles. J Org Chem 80(17) 8657-8667... 

A simple and efficient method has also been developed for the synthesis of benzoxazoles from 2-aminophenol and substituted aldehydes in the presence of a cataljdic amount of zinc triflate (Equation (8.34)) [68]. Benzoxazoles are an important class of heterocyclic compounds that have many applications in medicinal chemistry, amyloidogenesis inhibitors, kinase inhibitors, and antitumor agents. 

Very recently. Song, Yang, and coworkers described a domino Mannich reaction catalyzed by a chiral thiourea derivative of a cinchona alkaloid (111 in Figure 42.5). They showed how amino-benzoxazoles 128 are viable amine components for the imine formation with aldehydes 127 in three-component Mannich reactions (Scheme 42.28) [70]. 

The open-and-close valence isomerization is very fast. Therefore, even an extreme position of the equilibrium does not necessarily prejudice the outcome of electrophilic trapping. Chlorotrialkylsilanes and acyl chlorides seek to get linked to the heteroatom, in other words, tend to intercept the ring-opened species. In contrast, chlorotrialkylstannanes and aldehydes preferentially bind to the electron-rich carbon center of the metalated heterocycle.The behavior of benzoxazol-2-ylIithium (228a) and its alter ego lithium 2-isonitrilophenolate (228b) toward chlorotrimethylsilane and chlorotrimethylstannane nicely illustrates this dichotomy (Scheme 1-175). ... 

Dehydrogenative condensations have also been utilised for the synthesis of bicyclic heteroaromatic systems. The reaction of alcohols with o-aminoani-lines in the presence of a ruthenium catalyst and a hydrogen acceptor was shown to provide benzimidazoles. Mechanistically, this transformation requires dehydrogenation to form an aldehyde, condensation to generate an imine/dihydrobenzimidazole, which is likely followed by a second dehydrogenation to afford the benzimidazole products (Scheme 12.38). Two equivalents of crotonitrile are employed as the hydrogen acceptor. The authors also note that the coupling of aldehydes with o-aminophenols under modified conditions enables the synthesis of benzoxazoles. 

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