Benzofurans derivatives

Amiodarone. Amiodarone, an iodinated benzofuran derivative that has stmctural similarities to the thyroid hormones (qv), was originally... 

Chemical composition and perspectives of using in medicine of lactones and benzofuran derivatives from Cetraria islandica (L) ACH 99MI15. 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

For the preparation of the benzo[fc]cyclopropa d pyran 2-599, Ohta and coworkers have treated 3-ethoxycarbonylcoumarin (2-597) with dimethylsulfoxonium methylide (2-598), derived from the corresponding trimethylsulfoxonium iodide and NaH (Scheme 2.136) [307]. The isolated product was not 2-599, however, but an unexpected eye lope nia[fc]benzofuran derivative 2-600 probably formed through 2-599. 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

When the alkynyl substrate possesses a nucleophilic functionality, intramolecular solvomercuration reactions can sometimes be observed. These reactions, which result in the formation of a heterocycle, have been used in the total synthesis of natural products. For example, reaction of 114 with Hg(OAc)2 affords the benzofuran derivative 115, which is an important intermediate for the synthesis of various neolignans (Equation (42)).154 155... 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

Benzofuran derivatives and enolethers are offered as chemical antiozonants for light coloured rubber compounds. Benzofuran derivatives are used in CR and its blends with other rubbers and give ageing protection in addition to ozone protection. 

An intramolecular Heck cyclization strategy was developed for the construction of indole and benzofuran rings on solid support [82], enabling rapid generation of small-molecular libraries by simultaneous parallel or combinatorial synthesis. Sn2 displacement of resin-bound y-bromocrotonyl amide 97 with o-iodophenol 96 afforded the cyclization precursor 98. A subsequent intramolecular Heck reaction using Jeffery s ligand-free conditions furnished, after double bond tautomerization, the resin-bound benzofurans, which were then cleaved with 30% TFA in CH2CI2 to deliver the desired benzofuran derivatives 99 in excellent yields and purity. 

Several antimicrobial benzofuran derivatives including dihydropyrida-zinone-substituted congeners of type (118, R = H, Ac, Ph, cycloaminomethyl) have been prepared in Egypt [335, 336], The triazinylpyridazinedione (119) has also been reported to have antibacterial properties [337],... 

In order to determine whether or not these and similar reactions proceed through radical species, 2-(3,3-diphenylprop-2-enyloxy)phenyllead triacetate, a compound containing an internal radical trap, was prepared, and its behavior in base-catalyzed C-arylation reactions investigated. The absence of benzofuran derivatives among the products excluded the participation of radical species in these processes.35... 

Cycloaddition Reactions with Other Nucleophiles The anodic two-electron oxidation of catechol affords o-quinone that may react with the enolates of 4-hydroxycoumarine or 5,5-dimethyl-1,3-cyclohexanedione (dimedone). The resulting adducts undergo a second anodic oxidation leading to benzofuran derivatives in good yields (90-95%) (Scheme 53) [75, 76]. 

Amiodarone (11), a benzofuran derivative, was initially developed as a coronary vasodilator in the early 1960 s [11,12]. Several years later, the efficacy of the compound as an antiarrhythmic agent began to be exploited. The first clinical trials with amiodarone were reported in 1974 [13]. Amiodarone was effective in controlling the tachyarrhythmias of eleven patients with Wolff-Parkinson-White syndrome. Since that time the compound has been studied extensively [14,15]. Recently, in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT), amiodarone was shown to reduce mortality during a mean 18 month period following myocardial infarction (13.8% deaths in placebo group vs. 2.1 % deaths in the treatment group) [16]. 

The second alcohol toxin of significance is tremetol, the toxin found in white snakeroot in the midwest and ray less goldenrod in the southwest. Tremetol is an oily extract of the plant and was first associated with the toxic effects, and named appropriately by Couch in 1927. Tremetol is a mixture of methyl ketone benzofuran derivatives, including tremetone, dehydrotremetone, and hydroxytremetone (Beier and Norman, 1990). 

One potential approach for the preparation of benzofuran derivatives involves the acid-catalyzed cyclization of O-aryl oximes 1193. 39 (equation 36). The transformation is analogous to well-known Fisher indole synthesis. The reaction proceeds through a [3,3]-sigmatropic rearrangement of enehydroxylamine 120 to compound 121 followed... 

Brand Name(s) Cordarone, Cordarone IV, Pacerone Chemical Class lodinated benzofuran derivative... 

Hakim, E.H. et al., Artoindonesianins N and O, new prenylated stilbene and prenylated aryl-benzofuran derivatives from Artocarpus gomezianus, Fitoterapia, 13, 597, 2002. 

For further work in the field of benzofurans see <99TA1521> (synthesis of TAK-218 using (i )-2-methylglycidyl tosylate as a chiral building block), <99SL495> (heterocyclic rubicene analogues) and <99S751> (synthesis of benzofuro[2,3-b]benzofuran derivatives under Hoesch reaction conditions). 

A series of the regioisomeric benzofuran derivatives are produced from a base-catalyzed cyclization/dehydration sequence of dihydroxydibenzoylbenzenes (Equation 89) <2002HC0179, 2005T545>. The cyclization of the related derivatives containing benzyl or bromoalkyl substituents (R = benzyl or Br(CH2) -i, where = 8 or 12) has been reported to occur in benzene under photochemical conditions <1995JOC1303, 2002J(P1)310>. 

Benzannulation reactions of Fischer carbene complexes have proved a useful route for the synthesis of benzene rings fused to one furan ring and one additional heteroaromatic ring (Equation 96) <2005TL2211>. Thus, reaction of chromium carbene complex 168 with the conjugated dienyne systems produces benzofuran derivatives (Table 7). 

Analysis of the stems of Encella ventorum from Baja California showed the presence of a number of benzopyran and benzofuran derivatives and two stereo Isomers of a novel euparln-encecalln (XII) dimer (25). A closely related euparln-encecalln dimer (XIII), was previously Isolated from farlnosa (26). Although the dimer Is not photoactive, preliminary studies Indicate that It Is a feeding deterrent to Hellothls zea. 

Phthalides are lactones of 2-hydroxymethyl benzoic acid. They are also called as benzofuran derivatives. Phthalides are found in some oils of Apiaceae, such... 

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

Members of the retinoid natural product class, containing a quaternary benzylic stereocenter, were prepared by the ring closure of allyl-arylethers. The palladium catalysed process in the presence of sodium formate led to the formation of a partially reduced benzofurane derivative through an insertion-hydride capture reaction sequence (3.24.), The coupling, which was run in the presence of a silver-zeolite, showed acceptable enantioselectivity when... 

The same reaction, the conversion of 2-iodophenol to 2-arylbenzofuranes was also accomplished in the presence of a copper-phenantroline catalyst and caesium carbonate. Different arylacetylenes and iodophenols were coupled to give the corresponding benzofurane derivatives in good to excellent yield (3.55.)71... 

The same reaction, run in the presence of carbon monoxide, led to the incorporation of an acyl moiety into the 3-position. Ring closure of the ethynylphenol derivative shown in 3.61. in the presence of iodobenzene and carbon monoxide gave the corresponding 3-anisoyl-benzofurane derivative in excellent yield.78... 

F. R., Astruc-Diaz, F., Thompson, . M., Cavasotto, C. N., Naguib, M. (2009) 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists design, synthesis, and binding mode prediction through ligand-steered modeling. ChemMedChem 4, 1615-1629. 

Iantherans A (516) and B (517) are dimeric tetrabrominated benzofuran derivatives that were isolated from an Australian Ianthella species. The structures were determined by spectroscopic and chemical methods. Iantheran A (516) includes a (Z,Z)-1,3-butadiene moiety, whereas iantheran B (517) is the geometric isomer possessing a (Z, )- 1,3-butadiene moiety. Both compounds were Na+/K+-ATPase inhibitors [434,435]. Ianthesines C (518) and D (519) showed potent Na+/K+-... 

Effect of Heteroelements in Modifying Some Cyclizations — Benzofuran Derivatives Formed by Cyclization of Current Trends in Heterocyclic Chemistry , ed. A. Albert, G. M. Badger and C. W. Shoppee, Academic Press, New York, 1958, pp. 58-64. 

---