Benzoxazole, 2- synthesis

In the standard form of this route, a carboxylic acid is heated with the orffto-disubstituted benzene orf/to-amino-phenol, -thiophenol or -aniline. An iminoether will react at a much lower temperature and iminochlorides, generated in situ using the acid, triphenylphosphine and hot carbon tetrachloride, can be used for benzimidazole or benzoxazole synthesis. Orthoesters with a KSF clay is a highly recommended variant and can be used for the synthesis of all three unsubstituted benzo-l,3-azoles. ... 

Original method of benzoxazole synthesis starting from 2,5-difluoroaniline is based on the aryne mechanism [54], Boc-protected difluoroaniline 50 undergoes base-induced aryne formation via ortho directed Uthiation. Subsequent intramolecular cychzation produced a mixture of benzoxazole derivatives 51 and 52, which could be converted into 52 exclusively by heating. 

Sun et al. have also reported microwave-assisted S5mthetic process for bis-benzimidazolyl benzoxazole synthesis. IL-grafted 3-amino-4-hydroxy benzimidazolyl 100 was subjected with thiocarbonyl diimidazole under micro-wave irradiation followed by S-alkylation by various alkyl bromides at ambient temperature to afford IL-bound bis-benzimidazolyl benzoxazole 108 and subsequently basic methanolysis to remove IL support (Scheme 12) [45]. Present strategy is useful to obtain IL-intermediate and final product by simple operation, and short reaction time is observed under microwave dielectric heating. 

Phenylstilben-4-yl)benzoxazoles are prepared by means of the anil synthesis from 2-(4-methylphenyl)benzoxazoles and 4-biphenylcarboxaldehyde anil, and used for brightening polyester fibers (24,25). An example is (3) [16143-18-3]. 

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

Benzoxazole, 2-carbonamidomethyl-5-methyl-, 1, 333 Benzoxazole, 2,3-dihydroring-chain tautomerism, 6, 186 structure, 6, 179 synthesis, 6, 227-228 Benzoxazole, 2-dimethylamino-synthesis, 5, 128 Benzoxazole, 2-mercapto-... 

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]. 

Formation of the oxazole ring is not always the last step in synthesis of the brightener. Unsymmetrical compounds that contain both a benzoxazole group and an ethene linkage can be prepared by the anil synthesis [51], in which a compound possessing an activated methyl group reacts with a Schiff base. The preparation of brightener 11.31 is an illustration of this method (Scheme 11.12). 

Some interesting organic chemistry is involved in the synthesis of chlorite-resistant brighteners for acrylic fibres. None of these compounds is easy to make and methods for preparation of the starting materials can be complex. Much manufacturing know-how is involved. One route for introduction of the benzimidazole nucleus into structure 11.55 is shown in Scheme 11.22. Preparation of the chemically rather simpler benzoxazole grouping in product 11.56 is shown in Scheme 11.23. 

Cu-catalyzed domino reactions have been used for the synthesis of carbocycles, as well as for heterocycles such as indoles, benzoxazoles, and quinoxalines. A very useful process is also the combination of the formation of allyl vinyl ethers, followed by a Claisen rearrangement. 

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

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

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... 

TABLE 7.1. Synthesis of a Small Benzoxazoles Library, the Yields and Mass Spectra (M+l)+ (note 6)... 

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

Cashin, C. H., Dawson, W. and Kitchen, E.A. (1977). The pharmacology of benoxaprofen (2-[4-chlorophynl]-a-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. J. Pharm. Pharmacol. 29 330-336. 

Figure 35. Synthesis of sulfonated poly (benzimidazole) and poly(benzoxazole).

For the synthesis of base-sensitive oxazoles (Scheme 52), /3-acyloxyvinyl azides (130) react with triethyl phosphite via an aza-Wittig-cyclization. Phosphorimidate 131 is converted to 1,3-oxazole 132 with spontaneous elimination of triethyl phosphate (89JOC431). Benzoxazoles are also available by this synthetic route (71CC1608). 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

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