Benzoxazoles intermediates

Other aza-benzoxazole intermediates in the current invention were prepared by the author using 4-methyl-2-methylthiooxazolo[4,5-b] pyridine, (I), and 6-halo-4-methyl-thiooxazole pyridines, (II). 

Salicylonitrile is believed to arise by direct cleavage with subsequent hydrogen transfer, while the benzoxazoles were produced by an isocyanide intermediate (73JA919, 74HCA376). Photolysis in D2O tends to confirm this possibility and rule out an azirine intermediate (39), due to deuterium corporation into the molecule (Scheme 10) (74HCA376). 

The mechanism of thermolysis and photolysis of ethers of 3-hydroxy-1,2-benzisoxazole has also been studied. Heating of the allyl ether (43) gave minor amounts of (44) and two benzoxazoles. Photolysis of (45) in methanol gave a benzisoxazole and an iminoester, via intermediate (46). Thermolysis at 600 °C gave a benzoxazole, a benzoxazolone and cyano-phenol (Scheme 16) (71DIS(D)4483). 

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]. 

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>. 

The intramolecular trapping of a benzyne intermediate has been used as a novel route to 7-lithiated benzoxazoles (Scheme 89)(82JOC2804). 

The first step in the constmction of the terminal side chain in the first glitazones comprises a reaction of benzaldehyde (106-1) with the mono-oxime (106-2) from biacetyl to afford the benzoxazole Al-oxide (106-3). Reaction of that intermediate with phosphoms oxychloride leads the chlorination of the adjacent methyl group in a version of the Plonovski reaction to afford the choromethyl derivative (106-4). This is then used to alkylate the carbanion from the substimted acetoacetate... 

Electrocyclic ring opening of benzoxadiazines (56) is thought to be the first step in their ring contraction to benzoxazoles (75CC962). The benzoxadiazines are prepared by oxidation of the appropriate benzamidoximes, and ring-chain tautomerism between the intermediate nitrosoimine (57) and the oxadiazine (58) has been clearly demonstrated (75CC914). 

Reactions of 2-(3-hydroxy-3-phenylpropylseleno)benzoxazole with KH in tetrahydrofuran (THF) give selenetane 31. In the cases of /< rt-alcohols (R1 = C2H5 or CH2Ph), complex mixtures of products and no expected selenetane 31 are obtained because of steric hindrance at the reaction site. The formation of a selenetane is explained by a spiro intermediate which is converted into a selenolate anion. Intramolecular displacement of 30 gives the selenetane 31 (Scheme 7) <1998H633>. 

An entirely different reaction occurred when 2-(4-diazo-3-oxobutyl)-benzoxazole (239) was treated with Rh(II) octanoate. In addition to undergoing dipolar cycloaddition to produce cycloadduct 241 (20%), the highly stabilized dipole (i.e., 240) formed from the benzoxazole loses a proton to produce the cyclic ketene N,O-acetal 242. This compound reacts further with the activated 7t-bond of DMAD to give zwitterion 243. The anionic portion of 243 then adds to the adjacent carbonyl group, producing a new zwitterionic intermediate 244. In the presence of water, this species is converted to the observed phenolic lactam 245. 

As part of an examination of an oxidative coupling of methyl 6-hydroxyindole-2-carboxylate with primary amines which enabled the development of a facile preparation of 2-substituted methyl pyrrolo[2,3-e]benzoxazole-5-carboxylates, the reaction of this indole with 1,2-diaminoethane and excess Mn02 gave compound (83) in an apparent intramolecular interception of a transient intermediate o-quinone monoimine (Equation (46)) <88JOC5163>. 

Benzoxazoles are formed by the action of potassium amide in liquid ammonia on JV-aroyl derivatives of both o- and m-chloroaniline. The reaction does not proceed directly from an intermediate aryne (284), as was once thought, but via isolable o-hydroxyphenylamidines (285 Scheme 29) (81JOC3256). 

Formyl-l,2,3,3-tetramethylindoline (29) was converted to various 5-([3-heterocyclylvinyl) indolines (30) via condensation with heterocyclic quaternary salts and subsequent N-dealkylation by triphenylphosphine. The resultant indolines were oxidized with mercuric acetate to the 5-substituted Fischer s bases (31, R = benzoxazol-2-yl quinolin-2-yl quinolin-4-yl pyridin-4-yl 1,3,3-trimethylindo-len-2-yl). These were used as intermediates for cyanine dyes their conversion to spiropyrans was not recorded. 41... 

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],... 

When heated, benzoxadiazines give benzoxazoles in good yield [495,496]. The intermediate formation of ort/zo-quinonimine has been suggested on the basis of the proposed recyclization mechanism (Scheme 2.76). 

Benzoxazole, 2-trimethylsilyl-, -trimethylstannyl-, 56, 221 Benzoyl isocyanide, possible intermediate in fragmentation, 56, 80 Benzoylacetone, reaction with ethylenediamine, 56, 4 Benzoylation of uracils, photochemical, using diphenyl-l,3,4-oxadiazole, 55,... 

Substituted salicylaldehydes react with hydrazoic acid in sulfuric acid to give indoxazenes 50,51 up to 15% of the corresponding 2-aminobenzoxazole (32) may be obtained as a by-product. The reaction is a variant of the Schmidt reaction, in which the intermediate nitre-nium ion may cyclize at once to the indoxazene, or rearrange and react with more hydrazoic acid, ultimately providing the benzoxazole. 

Benzoxazoles have been prepared by intramolecular reaction of a phenolic —OH groiq) with a Beckmann intermediate (equation 30). A cyclic imidate was isolated in high yield from tosylation and in situ Beckmann reaction of the erythromycin-derived oxime (4[Pg.698]

Figure 2. Proposed intermediate products in the synthesis of PBO, showing (a) aminophenylbenzoate, (b) hydroxyphenylbenzamide, and (c) benzoxazole. (See page 4 of color insert.)...

Both benzoxazole hydrolysis and hydrolysis of intermediate products such as benzamide or benzoate potentially cause tensile strength degradation in PBO, by disrupting the conjugated rigid rod stmcture and by chain scission, respectively. The former mechanism appears to be the primary mode of degradation in the laboratory-aged armor the latter mechanism appears to be predominant in the case of the failed field body armor. 

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. 

Similar attack of methanol on the presumed oxaziridine intermediate in the photolysis of C,N-diphenylnitrone led to the formation of 2- and 4-methoxyazoben-zenes."" The reaction converting dibenz[b,f] [l,4]oxazepine 60 to 2-(2-hydroxy-phenyl)benzoxazole 62 seems better explained by a nucleophilic substitution on protonated 61 than by the electrophilic process suggested by the authors. ... 

A rare example of photochemical cycloaddition to a C=N group is provided by the formation of benzoxazole (19) from pentachloro-phenol in acetonitrile. The photoconversion of 2-methylbenzo-phenone into the anthrone (20) involves two sequential photoprocesses via the E-enol (21) which under the influence of high intensity laser light absorbs a second photon to give the cyclized intermediate (22) which undergoes air-oxidation to (20) (Wilson et al.). 

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