Benzofuran ring hydroxy— from

Coumestans,21 although they have a fused benzofuran ring, will be surveyed as being 8-lactones of 2-(2-hydroxyphenyl)-3-benzofuran carboxylic acids [coumestrol (4)22 is the 8-lactone of 2-(2,4-dihydroxy-phenyl)-6-hydroxy-3-benzofurancarboxylic acid]. The synthesis of some rotenoids 23 from benzofuran derivatives will also be reviewed, but dibenzofuran derivatives, such as usnic acid and its derivatives, will not be treated. 

The synthesis of the (i) 4-hydroxy-6-methoxytetrahydrofuro[2,3-6]-benzofuran ring (116), a degradation product of natural substances of the sterigmatocystin series, is similar,318 as is the synthesis of the dihydro derivative (117) from the o-acetylated acetaldehyde (118), a nonisolated intermediate which is ring-closed to 119 and then heated in toluene to give 117. The last is the starting point for the synthesis of aflatoxin M4 (49).153... 

The fast fade rate shown by 2-(4-trifluoromethyl)-2-phenyl-5-trifluorophenyl-[l]benzofuran[2,3-(]naphtho[l,2-6]pyran is attributable to the bulky 5-substituent rather than to the fused benzofuran ring <01WOP36424>. Its synthesis follows from the preparation of 9-hydroxy-7-trifluoromethylbenzo[6]naphtho[ f]furan from 4-chloromethyldibenzofuran (Scheme 18). 

Hydroxy derivatives of benzofuran are also found in the phenolic fractions of shale oil tar such compounds are formed by thermal ring closure of phenol ethers with unsaturated side chains.113-115 2-(4-Methoxyphenyl)benzofuran has been isolated in small amounts from the depolymerization products of some tars (in the presence of phenol).114,115... 

An important extension of this method has made it possible to synthesize polycyclic benzofurans under the influence of various demethylating and dehydrating media.335 For such ring closures, pyridine hydrochloride is especially suitable thus coumestan has been synthesized from 4-hydroxy-3-(2-methoxyphenyl)coumarin.8 4,7-Di hydroxy-3-(2,4-dimethoxyphenyl)coumarin gives coumestol with aniline hydrochloride 336 other polymethoxycoumestans have been obtained with pyridine hydrochloride or with HBr (or HI) and acetic acid.337-339... 

V. Heterocyclic ring closure of o-hydroxylated aromatic compounds with acetylenic side chains. This method leads from acetylenic compounds 221 to 2-substituted benzofurans 222. Thus, l-(2-hydroxy-5-methyl)phenyl-2-phenylacetylene (221a), heated at 90° for 45 minutes in the presence of 2 iV NaOH, gives 5-methyl-2-phenylbenzofuran (222a) (90% yield). 

The benzene ring of benzofurans can also be built up by elimination reactions from suitably substituted precursors. Treatment of (78), which is available from l,3-diketo-5-phenylcyclohexane and ethyl a-chloroacetoacetate and subsequent bromination with base, yields a 4-hydroxy-benzofuran (Scheme 71) <76CHE733, 76KGS879). 

As shown in Scheme 1.46, a simple synthesis of complex fused 1,4-benzoxaz-epin-2-one derivatives 86 and 87 was aehieved via a three-component leaction of quinoline or isoquinoline, acetylene dicaiboxylic esters and l-(6-hydioxy-2-isopio-penyl-l-benzofman-yl)-l-ethanone in water, in the absence of aiy catalyst [68]. Presumably, this transformation proceeds via the initial formation of a 1 1 zwitter-ionic intermediate 88 from the Michael addition of isoquinohne (or quinolone) to the activated ester. A proton transfer reaction takes then place in which this species is protonatedby the phenol group in the l-(6-hydroxy-2-isopropenyl-l-benzofuran-yl)-l-ethanone substrate, and this is followed by a second Michael addition of the resulting phenoxide anion to the isoquinohnium ion to afford intermediate 88, containing benzofuryl and isoquinoline ring systems. This intermediate then undergoes... 

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