Heterocyclic compounds benzofurans

Benzofuran derivatives are rare in petroleum, where sulfurated heterocycles predominate among heterocyclic compounds. Benzofurans and 2,3-dihydrobenzofurans are found, however, in the 200°-270° fraction of the distillate of California crude oil, with dibenzofurans and naphthobenzofurans.123 Alkyl-dibenzofurans have been traced in the 275°-305° fraction of petroleum with alkylnaphthalenes, 4-methyl-dibenzofuran among others.124 The distillation of humic acids with zinc powder is said to give benzofuran and hydrobenzofuran derivatives.125... 

A. Mustafa, The Chemistry of Heterocyclic Compounds, Benzofurans , ed. A. Weissberger and E. C. Taylor, Wiley-lnterscience, New York, 1974. 

While the simultaneous presence of benzofuran and benzothiophene is established in some fractions from coal pyrogenation and from the distillation of some petroleums, benzothiophene is entirely absent in heterocyclic compounds extracted from natural substances of vegetable origin. However, numerous benzofuran or hydrobenzofuran derivatives of biogenetic or metabolic origin have been isolated. 

D. Formation of the Benzofuran Nucleus from Other Heterocyclic Compounds... 

Similar elimination reactions are employed in the synthesis of the benzologs of five-membered heterocyclic compounds. For example, /3-phenylethyl alcohols having hydroxyl, sulfhydryl, and amino groups in the ortbo position ate cyclized to the dihydro derivatives of benzofuran, benzothiophene, and benzopyrrole, respectively. Likewise, dehydro-halogenation of /3-(o-hydroxyphenyl)-ethyl bromide gives dihydtobenzo-furan in 72% yield. ... 

Preparation of an appropriately disubstituted aromatic compound is the first step in the synthesis of fused aromatic heterocyclic compounds. Thus a method for the synthesis of benzofurans, coumarins etc. involves the preparation of the salicyl aldehydes as the first step. Standard methods are then used to add one or more carbon atoms and to effect cyclisation to complete the synthesis. 

A variety of heterocyclic compounds of the indole and benzofuran type can be made via photoaddition of alkenes to 2-amino- or 2-hydroxy-1,4-naphthoquinone. These products, described by H. Suginome probably derive from an intramolecular trapping reaction of the intermediary 1,4-biradicals or 1,4-zwitterions. 

Y zeolites also show promising activity in the acylation of heterocyclic compounds. Acylation of benzofurans by AAN was extensively studied, and some good S mthetic results have been achieved. Benzofuran and 2-methylbenzofuran undergo acylation with AAN under mild conditions, giving 2-acetylbenzofuran 13 and 2-methyl-3-acetylbenzofuran 14 respectively, as the main products over Y(32) zeolite (Scheme 4.8). 

Richard, F, Carreyre, H., and Perot, G. 1995. Zeolite catalyzed acylation of heterocyclic compounds. Part 111. Comparison between benzofuran and... 

The ASE values correlate with magnetic susceptibility for the five-membered heteroaromatic compounds. Magnetic and polarizability criteria put the order of aromaticity as thiophene > pyrrole > furan. The other criteria of aromaticity discussed in Section 8.2 are also applicable to heterocyclic compounds. HOMO-LUMO gaps and Fukui functions (see Topic 1.5) have been calculated for compounds such as indole, benzofuran, and benzothiophene and are in accord with the known reactivity patterns of these heterocycles. 

In addition to the above, a number of other heterocyclic compounds, for example, 2-aroylbenzofurans, 1,3-benzoxathioles, dihydropyrans, 1,4-benzoxazines, hydantoin derivatives, piperazine-2,5-diones, thioethenes, 1-arylbenzimidazoles, benzofuran-1-oxides, piperazinones, thiazoles, 5-thiacyclohexanecarboxaldehyde, pyrroles, triazines, fused napthoquinone derivatives and P-lactams have been synthesised using PTC technique." ... 

Benzo-annulated heterocyclic compounds such as oxindole and benzofuran derivatives were prepared in high yields by a novel cy-clization reaction of ethenetricarboxylate derivatives of aromatic compounds via Friedel-Crafts intramolecular Michael addition... 

As might be anticipated from the behaviour of the parent heterocycles, C-2 of indole, benzo[i]furan and benzo[i]thiophene (Table 13) is shifted to lower field than C-3. However, the shifts for C-2 (O, 144.8 Se, 128.8 S, 126.1 NH, 124.7 Te, 120.8) and C-7a (O, 155.0 Se, 141.3 S, 139.6 NH, 135.7 Te, 133.0) in the benzo[i] heterocycles vary irregularly (80OMR(l3)3l9), and the sequence is different to that observed for C-2 in the parent heterocycles, namely 0>Se>Te>S>NH. Also noteworthy is the upheld position of C-7, especially in indole and benzofuran, relative to the other benzenoid carbons at positions 4, 5 and 6. A similar situation pertains in the dibenzo heterocycles (Table 14), where not only are C-1 and C-8 shifted upheld in carbazole and dibenzofuran relative to the corresponding carbons in dibenzothiophene and fluorene, but similar, though smaller, shifts can be discerned for C-3 and C-6 in the former compounds. These carbon atoms are of course ortho and para to the heteroatom and the shifts reflect its mesomeric properties. Little variation in the carbon-hydrogen coupling constants is observed for these dibenzo compounds with V(qh) = 158-165 and V(c,h) = 6-8 Hz. 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

Finally, the Hammett equation has been applied in a few instances to heterocycles of the indole-benzofuran type. The double p method of Eq. (3) was first designed for this type of system and was here applied. When this approach was originally proposed, the only truly hetero-cychc system to which it was apphed was the substituted phthahds 14, and pertinent data on the hydrolysis of these compounds are included in Table IX. 

This review of furan chemistry is meant to continue the earlier survey by Bosshard and Eugster1 and concentrates upon the period 1968 to the end of 1979. Like the earlier review, this one is limited to the chemistry of the monocyclic furan nucleus and does not deal, except incidentally, with fused rings such as benzofuran or its quinones. Nor does it deal in detail with dihydro- or tetrahydrofurans, nor with compounds like furylpyridine that contain some other heterocyclic nucleus as well. Some butenolides and tetronic acids are admitted to consideration since they are the carbonyl equivalents of hydroxyfurans regarded as enols, but side-chain reactions are wholly excluded unless the furan nucleus clearly affects them in some important way. 

Furans and benzofurans continue to play an important role in the field of heterocyclic chemistry because their skeletons are present in many naturally occurring molecules, and they serve also as extremely useful precursors or intermediates towards the realization of many complex molecules. The authors of the present chapter have placed their attention on the more interesting applications and syntheses of these families of compounds, instead of executing an exhaustive literature search of all the relevant papers that were recorded in 2000. 

The chemistry of fiiians and benzofurans was a Held of lively research in the last year. There are a number of reasons for this activity. The furan ring system - both in its native as well as in its reduced form - occurs in a great number of natural products and a wide variety of these compounds has been isolated from natural sources. This subject is treated regularly with care and accuracy in Heterocycles and will not be repeated here. Therefore only a few examples will be given in this chapter. Several new furan derivatives were isolated from natural sources (-)-wistarin 1 from the marine sponge Ircinia sp. <99TA3869>,... 

The chromenes and benzofurans are rather simple compounds built from acetate and Isoprene metabolites. Heterocyclic ring formation gives rise to 2,2-dlmethyl chromene or 2-isoprophenyl benzofurans. The majority of known chromenes and benzofurans exhibit a methyl ketone moiety at a position para to the oxygen of the heterocyclic ring. Constituents esterified with phenolic acids or lacking methyl ketones are rare. 

Although not fitting exactly into the scope of this book, the iridium catalyzed borylation of five membered heterocycles through C-H bond activation also deserves mentioning. A recent report by Miyaura disclosed the reaction of bis(pinacolato)diboron with heteroaromatic systems, where thiophene, fiirane and pyrrole were converted to their 2-boryl derivatives with good selectivity (6.86.), The yields presented refer to the diboron compound since the heterocycles were used in excess in all cases. Indole, benzofurane and benzothiophene were monoborylated with similar efficiency.116... 

Mannich condensation of o-hydroxyphenylacetylene (227, R = H) leads to compound 228 heterocyclic ring closure of the latter gives the basic 2-substituted benzofuran 229. The diacetylenic derivative (227, R = C=CH) gives the corresponding 5-ethynylbenzofuran (229, R = C=CH).488... 

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