Methyl 2- benzofuran-5-carboxylate

The reaction of 2-vinylfuran la with methyl propiolate (MP) did not proceed at room temperature owing to the lower reactivity of this dieno-phile and at 80°C, although two isomeric benzofurans are possible, only methyl benzofuran-4-carboxylate 6a was obtained. This regioselectivity is not unexpected, considering electronic and substituent effects (67AG 16). 

Methyl ejco-cyclopropa[fc]benzofuran-3-carboxylate (27) was converted to methyl benzofuran-3-acetate (28) and -2-acetate (29) in a ratio of 4 1 upon treatment with methanolic hydrogen chloride. Due to the stability of the aromatic benzofuran system, rearrangement, rather than addition of methanol, occurred. 

The Chi group further developed a highly enantioselective formal [4 + 2] cycloaddition of a-branched indole 3-carboxaldehydes with trifluoromethyl ketones or isatins to give polyeyelic and spiro lactones, respectively. The reaction is postulated to undergo a catalytic cycle of NHC-eatalyzed aetiva-tion of the C(sp )—H bond of 2-methyl indole 3-carboxaldehydes to produee ort/ o-quinodimethane intermediates. Notably, 2-methyl benzofuran and ben-zothiophene aldehydes are also suitable substrates for this reaction, while 2-methylbenzaldehyde gives the partially oxidized carboxylic acid under these conditions without the observation of the desired lactone product (Scheme 7.115). 

Isotubaic acid — see Benzofuran-5-carboxylic acid, 4-hydroxy-2-isopropyl-Isouramil occurrence, 3, 144 5-Isoxalones potentiometry, 6, 11 Isoxanthopterin, 6-acetonyl-structure, 3, 276 Isoxanthopterin, 3,8-dimethyl-rearrangements, 3, 309 Isoxanthopterin, 6-methoxy-3,8-dimethyl-synthesis, 3, 297 Isoxanthopterin, 6-methyl-bromination, 3, 301 Isoxanthopterin, 8-methyl-synthesis, 3, 319 Isoxanthopterin, 6-phenacyl-structure, 3, 276... 

Benzofuran-2-carbaldehydes readily undergo Wittig reactions in tetra-hydrofuran at room temperature with the resonance-stabilized ylide 2-car-boxy-l-methoxycarbonylethyltriphenylphosphorane, affording high yields of ( )-4-(2-benzofuranyl)-3-methoxycarbonylbut-3-enoic acids. This method is preferable to the Stobbe condensation. The Stobbe-type intermediates undergo quantitative cyclization to methyl l-acetoxydibenzofuran-3-carboxylates on exposure to acetic anhydride at 100 C. Examples are shown in Scheme 27. The intermediate 109 has been used in a synthesis of cannabifuran (110), and the intermediate 111 has been used in a synthesis of the lichen metabolite schizopeltic acid (112). ... 

Compound 408 with 3% KOH/ethanol forms benzofuran 409,853 with decarboxylation of the nonisolated intermediate. Alkaline degradation (KOH/ethanol) of compounds 410 leads to 2-phenylbenzofuran-3-carboxylic acids (411, R = H), then, by methylation, to compounds 411 (R = Me)398 or by decarboxylation to 2-phenylbenzofuran... 

As 2-vinylfuran rapidly polymerizes even in a nitrogen atmosphere in the presence of a stabilizer, yields obtained for these Diels-Alder reactions were very low. In fact, when the more stable 5-(4-nitrophenyl)-2-vinylfuran lb reacted with DMAD, the yield of the aromatized cycloadduct, dimethyl 2-(4-nitrophenyl)benzofuran-4,5-dicarboxylate 4b, was 50%. The 4-nitrophenyl group not only deactivated the vinylfuran for oxidation and polymerization, but also deactivated the diene system toward cycloadditions, and the reaction was successful only when conducted in boiling xylene. The decrease in reactivity of the reactive diene may account for the relatively low yield of methyl 2-(4-nitrophenyl)benzo-furan-4-carboxylate 6b obtained in a similar reaction with MP (73-AJC1059). 

Amongst other examples of pharmacologically active seven-membered heterocyclic ring compounds the following are of interest 5-(2-morpholin-4-yl-ethoxy)-benzofuran-2-carboxylic acid (,S)-3-methyl-1 - 3-oxo-1 -[2-(3-pyridin-2-yl-phenyl)-ethenoyl]azepan-4-... 

Benzofuran, 2-phenyl -, nitration, 58, 224 Benzofuran, 4,5,6,7-tetrafluoro-2-fluoromethyl-, 60, 28 Benzofuran-3-carboxylate, 4,5,6,7-tetrafluoro-2-methyl-, 60, 18 Benzofuran-2-carboxylic acid, esters, bromination, 59, 250... 

The reaction of alkyl sulfates with alkoxide ions is quite similar to 10-8 in mechanism and scope. Other inorganic esters can also be used. Methyl ethers of alcohols and phenols are commonly formd by treatment of alkoxides or aroxides with methyl sulfate. The alcohol or phenol can be methylated directly with dimethyl sulfate under various conditions. Carboxylic esters sometimes give ethers when treated with alkoxides (Bal2 mechanism, p. 1403) in a very similar process (see also, 16-64). A related reaction heated 111 with alumina to give the corresponding benzofuran, 112. ... 

The rhodium- or copper-catalyzed cyclopropanation of furan and its derivatives with diazo-acetic esters,300-302 or ethyl 2-diazopropanoate300 usually leads to a mixture of the 2-oxa-bicyclo[3.1.0]hex-3-ene-e co-6-carboxylate, ring-opened (4Z)-6-oxohexa-2,4-dienoates, and ring-substituted furans. Only with electron-deficient furans methyl furan-2-carboxylates, 2-[( )-2-methoxycarbonylvinyl]furan300 and with benzofuran,301,303 was the cyclopropane product obtained exclusively. Examples 37-40 are representative.300... 

Phenylbenzofuran (282) was used to protect polyphenylene ether resins against damage from UV radiation <87USP4665ii2>. As a nucleating agent, benzofuran-2-carboxylic acid (283) was found to improve the properties of an ethylene/4-methyl-l-pentene copolymer <84JAP(K)59197446). 

Carboxylic acid 125 was coupled with ethanolamine or L-serine methyl ester hydrochloride in the presence of EDCI, HOBt, and EtsN to afford the corresponding p-hydroxy amides, which were cyclized using bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) to afford oxazolines (149 and 150, Scheme 24) [56, 57]. Oxazoline 150 was converted to oxazole 151 in 80% yield by treatment with bromotrichloromethane and DBU, conditions which did not lead to epimerization at C-8 [57], A variety of oxadiazoles (152-158) have been produced in 10-56% yield by treating carboxylic acid 125 with appropriate amidoximes in the presence of EDCI and HOBt followed by heating in toluene (Scheme 24) [44, 57, 58]. These conditions led to some epimerization at C-8, necessitating purification by HPLC. Carboxylic acid 125 was treated with either (2-hydroxybenzyl)triphenyl- or (2-thiobenzyl)triphenyl phosphonium bromide in the presence of CDMT and EtsN to afford the benzofuran (159) and benzothiophene (160) products in 26 and 35% yield, respectively (Scheme 24) [58]. 

An example of an asymmetric induction from optically inactive monomers is an anionic polymerization of esters of butadiene carboxylic acids with (/ )-2-methylbutyUithium or with butyUithium complexed with (—)methyl ethyl ether as the catalyst. (This type of polymerization reaction is described in Chap. 4) The products, tritactic polymers exhibit small, but measurable optical rotations [78]. Also, when benzofuran, that exhibits no optical activity, is polymerized by cationic catalysts like aluminum chloride complexed with an optically active co catalyst, like phenylalanine, an optically active polymer is obtained [77]. 

The DA behavior of methyl 5-nitrofuran-3-carboxylate 29a with isoprene was studied under similar conditions than before (Figure 8).3o These reactions yielded the mixture of isomeric cycloadducts 30a and 30b, as principal products (60%) and a mixture of double addition adducts 31a-d (10%) and 32a-d (10%), in both cases as regioisomer mixtures. When l-N-acetyl-N-propyl-l,3-butadiene (6) reacted with 29a, it afforded benzofuran 33. Meanwhile, exposure of 29a to 7 and 8 yielded benzofurans 34 and 35, respectively. In these reactions, only 1 1 adducts whose structure revealed site selectivity and regioselectivity were obtained. 

Bromo-6-hydroxy-3-methyl-7-(l-oxopropyl)benzofuran-2-carboxylic acid... 

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