0-Aminophenols benzoxazoles

Bis(benZoxaZol-2-yl) Derivatives. Bis(benzoxazol-2-yl) derivatives (8) (Table 3) aie prepared in most cases by treatment of dicaiboxyhc acid derivatives of the central nucleus, eg, stilbene-4,4Cdicarboxyhc acid, naphthalene-l,4-dicarboxyhc acid, thiophene-2,5-dicarboxyhc acid, etc, with 2 moles of an appropriately substituted o-aminophenol, followed by a ring-closure reaction. These compounds are suitable for the brightening of plastics and synthetic fibers. 

Oxazole. DaB nicht nur NH2-, sondem auch phenolische OH-Gruppen mit s-Triazin zu reagieren vermogen, laBt sich an dem zu Benzoxazol (XLI) ftihrenden RingschluB des o-Aminophenols demon-strieren (25). 

Those polyester FBAs containing a benzoxazole group are usually prepared from the appropriate o-aminophenol and carboxylic acid (11.45 Y = OH) or one of its derivatives, as shown in Scheme 11.10. The reaction proceeds via an intermediate amide and it can be advantageous to start from an acid derivative such as the acid chloride (11.45 Y = Cl) or ester (11.45 Y = OEt), which are both more effective acylating agents. The preparation of compound 11.36, shown in Scheme 11.11, illustrates this process, but the optimum conditions for ring closure vary considerably from one structure to another. The article by Gold contains a valuable and detailed summary [4]. 

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... 

Reaction of 2-mercaptomethyl-l,3,4-oxadiazolin-5-one 321 with o-aminophenol 322 and glycine, in refluxing isopropanol, gives 3-mercaptomethyl-[l,2,4]triazole[3,4-A benzoxazole 71, via intermediate 323 (Scheme 31), and 3-mercaptomethyl-6-oxo-oxazolo[2,3-c][l,2,4]triazole 324, respectively <1996M549>. 

Mamyama et al.25 have obtained high-molecular-weight poly(benzoxazole)s by the low-temperature solution polycondensation of A,A 0,0 -tetrais(trimethyl-silyl)-substituted 2,2-bis(3-amino-4-hydroxyphenyl)-l,l,l,3,3,3-hexafluoro-propane (25) with aromatic diacids and subsequent thermal cyclodehydration of the resulting poly(o-hydroxy amide)s in vacuo. In this method, aromatic diamines with low nucleophilicity are activated more positively through the conversion to the /V-silylated diamines, and the nucleophilicity of the fluorine-containing bis(o-aminophenol) can be improved by silylation. 

As described above, a small library containing 27 benzoxazoles was synthesized by using three diamines, three dicarboxylic anhydrides, and three 2-aminophenols (Table 7.1). Wang resin... 

The preparation of 1,3-azoles (benzoxazoles, benzimidazoles and benzothiazoles) from oximes using oxidants on mineral supports such as Ca(0Cl)2/Al203 or Mu02/Si02 or by fusion in dry media has been described. Eor instance, benzoxazoles 232 can be obtained by reaction of o-aminophenols (R, R = H, N02,C1) with substituted beuzaldehyde oximes 231 in the presence of Ca(0Cl)2/Al203 under microwave irradiation (equation 100). ... 

The furo[3,4-ri]oxazoie 54, constracted by cyclisation of a rhodium carbenoid, is a useful compound for the production of unusual benzoxazoles for example, cycloaddition of Al-phenylmaleimide gave the benzoxazole 55 <98JOC7680>. Simpler benzoxazole syntheses include the base catalysed cyclizsation (with loss of the trifluoromethyl anion) of the imines 56 <99TL4119> and the acid catalysed cyclisation of diacylated aminophenols 57 <99H(51)979>. ... 

Poly(arylene ether benzoxazole)s were also synthesized from the reaction of bis[(4-hydroxyphenyl)benzoxazole]s and activated aromatic difluoro monomers as shown in Eq. (7) [28,29]. The bis[(4-hydroxyphenyl)benzoxazole]s were readily prepared by condensation of the appropriate bis(o-aminophenol) (e.g. 3,3 -dihydroxy-4,4 -diaminobiphenyl) with phenyl-4-hydroxybenzoate in diphenyl sulfone at 260°C. Under proper conditions, the less expensive 4-hydroxybenzoic acid can be used in place of the phenyl ester to provide high yields of the desired bis[(4-hydroxyphenyl)benzoxazole]s. As presented in Table 9, the hexafluoroisopropylidene (6F) containing polymers were amorphous. These polymers were prepared in DMAc. However, the polymers derived from 6,6 -bis[2-(4-hydroxyphenyl)benzoxazole] were prepared in diphenyl sul-... 

A few other PAEH have been reported. One disclosure concerned PAE containing pendent benzoxazole and benzothiazole units [49]. The activated difluoro benzazole monomers, 2-(2,6-difluorophenyl)benzoxazole or benzothiazole, were prepared from the reaction of 2,6-difluorobenzoyl chloride with 2-aminophenol or 2-aminothiophenol in polyphosphoric acid. By H NMR, the benzazole unit was shown to have a greater electron-withdrawing effect on the 2-phenyl group than on the benzo ring [49]. Only a few polymers were reported. As an example, the polymer of structure 12 had an intrinsic viscosity of 0.45 (NMP at 30 °C) and Tg of 170°C [49],... 

Benzoxazoles, as in (99), are prepared by condensation of two molecules of an o-aminophenol with a dicarboxylic acid such as terephthalic acid, or by condensation of the o-aminophenol with a dialdehyde such as terephthalaldehyde followed by oxidation of the Schiff base (50JCS1722). Pendant heterocycles, such as benzotriazoles, are also commonly incorporated. 

Fused oxygen and nitrogen-containing rings may also be prepared in reactions with thioureas thus, dihydrobenzoxazine products are obtained on treatment of salicyloyl chloride with thioureas371 or on fusion of salicylate esters with thiopseudoureas.320 When the thio-pseudoureas are treated with o-aminophenol, the products are benzoxa-zoles.320 A naphthyl analog of a benzoxazole is produced on treatment of l-(2-hydroxy-l-naphthyl)-2-thiourea with dimethyl sulfate.372... 

The microwave-assisted synthesis of a benzoxazole derivative by the same approach was also described starting from 2-aminophenol (Scheme 3.17)29. 

In a closely related publication, carboxylic acids were employed instead of acid chlorides in a microwave-assisted direct synthesis of 2-substituted benzoxazoles [79]. The reactions with 2-aminophenol were performed in a household microwave oven and worked well with aromatic, heteroaromatic, aj/i-unsalurated and arylalkyl carboxylic acids (35-82% yields). Phthalic acid formed only mono-benzoxazoles, while the use of succinic acid led to a mixture of mono- and bis-benzoxazoles. Phthalic and succinic anhydrides could... 

Phenylenediamine and 2-aminophenol initially give N-arylimidoyl fluoride. Elimination of hydrogen fluoride from the product and further intramolecular nucleophilic cyclization lead to perfluoroalkyl derivatives of benzimidazole and benzoxazole, respectively. In the case of 2-aminothio-phenol, the reaction occurs at the sulfur atom and forms a carbanion. If RF is fluorine, then the carbanion is destabilized by the interaction of the lone electron pairs of fluorine with the center, and the stabilization reactions occur with participation of the proton. If, however, RF is the trifluoro-methyl group, the negative charge is stabilized by it. The fluoride ion is eliminated with further intramolecular nucleophilic cyclization. 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

Mono- or diacyl derivatives that undergo cyclization to benzoxazoles on heating or under the influence of dehydrating agents are formed as intermediates in this reaction [134, 452, 453, 459, 461 173], Phosphorus oxychloride [453, 457], boric anhydride [455, 461, 462], or polyphosphoric acid [134, 471] are used as condensing agents. In particular, 2-hydroxy-5-nitrobenzoxazole, used for the synthesis of antivirus medicines, has been obtained by the reaction of condensation of 4-nitro-2-aminophenol with (NH2)2CO in pyridine [474],... 

Like perfluorocarboxylic acid fluorides, perfluoroalkyl chlorosulfonates react with 2-aminophenols, 2-aminothiophenols, and 1,2-diaminobenzene to give A -acylated products. On subsequent heating ring closure occurs with formation of 2-perfluoroalkyl-substituted benzoxazoles, benzothiazoles, and benzimidazoles [90JFC(49)197] (Scheme 44). 

The heterocyclic ring of benzoxazoles (156) can be cleaved by exposure to diborane giving borazoles (157 possibly as shown in Scheme 8). Treatment of these products with hydrochloric acid leads to the formation of 2-aminophenols (158). Catalytic hydrogenation of the parent compound (156 R = H) over molybdenum sulfide has a similar end result although, since the conditions of the reaction are quite severe, phenol and 2-toluidine can form as by-products. ... 

Benzoxazoles are found in a variety of natural products and routinely find use in pharmaceutical research. They are generally made by condensation of a 2-aminophenol with a carboxylic acid or oxidative cylization of an imine intermediate. A mild copper-catalyzed cyclization of o/t/ o-haloanilides to give benzoxazoles 209 has been reported (Scheme 62) <2006JOC1802>. This route is conceptually different to the aforementioned methods in that the starting material is a 2-haloaniline rather than a 2-aminophenol. The reaction conditions tolerate various functional groups in the amide portion of the molecule. 

The preparation of 3-H-benzoxazol-2-one from o-ami-nophenol and urea is well known but the reaction is accompanied by the formation of tars and other side reactions. In contrast, phosgene reacts cleanly with o-aminophenol. We have devised a simple process without any acid scavenger which affords pure benzoxazolone in excellent yield as depicted in scheme 183 (Ref. 236). 

The special type of carbonyl-group derivatization is aimed for gas chromatography-mass spectrometry (GC-MS) determination of double-bond C = C positions in the unsaturated long-chain acids. The analytical derivatives for the solution of this problem are nitrogen-containing heterocycles. These compounds can be synthesized by condensation of carboxylic acids with 2-amino-2-methyl-l-propanol (2-substituted 4,4-dimethyloxazolines), 2-aminophenol (2-substituted benzoxazoles), and so forth. 

Aryl- and 2-heteroaryl-benzoxazoles (112, 113) were prepared by Pd-catalyzed three-component condensation of aryl halides with o-aminophenols and carbon monoxide followed by dehydrative cyclization [63, 64]. A variant of such methodology using o-fluorophenylamines in place of o-am 1 nophenols was used to synthesize arylbenzoxazoles. 

Benzoxazoles. Benzoxazoles can be prepared in 45-75% yield by heating an o-aminophenol and a carboxylic acid with the reagent for 30 minutes at 100°.8 An example is the synthesis of 2-phenylbenzoxazole (1). Use of o-aminothiophenols gives benzthiazoles. 

An anhydride [2309, 2323] (catalysed by mineral acid) or ethyl hippurate (ethyl 2-benzoylglycinate) [2186] cyclizes an o-aminophenol on prolonged refluxing. Chloral hydrate and hydroxylamine convert an aminophenol into a benzoxazole-2-carboxaldehyde oxime [2104]. 

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