Recent Advances in the Chemistry of Benzo[b]thiophenes

Iddon, B.; Scrowston, R. M.

doi:10.1016/s0065-2725(08)60776-x

Cited by 77 publications

(16 citation statements)

References 412 publications

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“…The sequence of events that occurs following attack at the 2,3 position of the thiophene ring is less clear, but it is proposed that 2,3 dioxygenation yields a product that is both a cis-dihydrodiol and a thiohemiacetal, which as a result of this structure undergoes two competing reactions: either spontaneous opening of the ring, yielding 2'-mercaptomandelaldehyde, or oxidation by the dihydrodiol dehydrogenase to another thiohemiacetal, 2-hydroxy-3-oxo-2,3-dihydrobenzothiophene, which is not a substrate for the ring cleavage dioxygenase but which spontaneously opens to form 2-mercaptophenylglyoxaldehyde and subsequently 2-mercaptophenylglyoxalate. The yellow product, trans4[3-hydroxy-2-thienylJ-2-oxobut-3-enoate, is a structural analog of nins-o-hydroxybenzylidenepyruvate, an intermediate of the naphthalene catabolic pathway; extracts of recombinant bacteria containing zns-o-hydroxybenzylidenepyruvate hydratase-aldolase catalyzed the conversion of ans-4-[3-hydroxy-2-thienyl]-2-oxobut-3-enoate to 3-hydroxythiophene-2-carboxaldehyde, which could then be further acted on, in the presence of NAD+, by extracts of recombinant bacteria containing the subsequent enzyme of the naphthalene pathway, salicylaldehyde dehydrogenase.Sulfur-containing heterocyclic chemicals, including benzothiophene (benzo-[b]-thiophene, thianaphthene), comprise a relatively small but significant fraction of petroleum, coal, and shale (5,9,26,30,42). …”

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Biotransformation of benzothiophene by isopropylbenzene-degrading bacteria

Eaton

Nitterauer

1994

J Bacteriol

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Isopropylbenzene-degrading bacteria, including Pseudomonas putida RE204, transform benzothiophene to a mixture of compounds. Induced strain RE204 and a number of its TnS mutant derivatives were used to accumulate these compounds and their precursors from benzothiophene. These metabolites were subsequently identified by 1H and 13C nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. When strain RE204 was incubated with benzothiophene, it produced a bright yellow compound, identified as trans-4-[3-hydroxy-2-thienylJ-2-oxobut-3-enoate, formed by the rearrangement of cis-4-(3-keto-2,3-dihydrothienyl)-2-hydroxybuta-2,4-dienoate, the product of 3-isopropylcatechol-2,3-dioxygenase-catalyzed ring cleavage of 4,5-dihydroxybenzothiophene, as well as 2-mercaptophenylglyoxalate and 2'-mercaptomandelaldehyde. A dihydrodiol dehydrogenase-deficient mutant, strain RE213, converted benzothiophene to cis-4,5-dihydroxy4,5-dihydrobenzothiophene and 2'-mercaptomandelaldehyde; neither trans-4-[3-hydroxy-2-thienyl]-2-oxobut-3-enoate nor 2-mercaptophenylglyoxalate was detected. Cell extracts of strain RE204 catabzed the conversion of cis-4,5-dihydroxy-4,5-dihydrobenzothiophene to trans-4-[3-hydroxy-2-thienyl]-2-oxobut-3-enoate in the presence of NAD+. Under the same conditions, extracts of the 3-isopropylcatechol-2,3-dioxygenasedeficient mutant RE215 acted on cis-4,5-dihydroxy-4,5-dihydrobenzothiophene, forming 4,5-dihydroxybenzothiophene. These data indicate that oxidation of benzothiophene by strain RE204 is initiated at either ring. Transformation initiated at the 4,5 position on the benzene ring proceeds by three enzyme-catalyzed reactions through ring cleavage. The sequence of events that occurs following attack at the 2,3 position of the thiophene ring is less clear, but it is proposed that 2,3 dioxygenation yields a product that is both a cis-dihydrodiol and a thiohemiacetal, which as a result of this structure undergoes two competing reactions: either spontaneous opening of the ring, yielding 2'-mercaptomandelaldehyde, or oxidation by the dihydrodiol dehydrogenase to another thiohemiacetal, 2-hydroxy-3-oxo-2,3-dihydrobenzothiophene, which is not a substrate for the ring cleavage dioxygenase but which spontaneously opens to form 2-mercaptophenylglyoxaldehyde and subsequently 2-mercaptophenylglyoxalate. The yellow product, trans4[3-hydroxy-2-thienylJ-2-oxobut-3-enoate, is a structural analog of nins-o-hydroxybenzylidenepyruvate, an intermediate of the naphthalene catabolic pathway; extracts of recombinant bacteria containing zns-o-hydroxybenzylidenepyruvate hydratase-aldolase catalyzed the conversion of ans-4-[3-hydroxy-2-thienyl]-2-oxobut-3-enoate to 3-hydroxythiophene-2-carboxaldehyde, which could then be further acted on, in the presence of NAD+, by extracts of recombinant bacteria containing the subsequent enzyme of the naphthalene pathway, salicylaldehyde dehydrogenase.Sulfur-containing heterocyclic chemicals, including benzothiophene (benzo-[b]-thiophene, thianaphthene), comprise a relatively sm...

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“…Sulfur-containing heterocyclic chemicals, including benzothiophene (benzo-[b]-thiophene, thianaphthene), comprise a relatively small but significant fraction of petroleum, coal, and shale (5,9,26,30,42).…”

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confidence: 99%

Biotransformation of benzothiophene by isopropylbenzene-degrading bacteria

Eaton

Nitterauer

1994

J Bacteriol

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“…Benzo[b]thiophene can be synthesized 21 either from substituted benzene or from substituted thiophene. We have developed expedient synthesis of benzo[b]thiophene derivatives using DoM methodology via both the routes.…”

Section: Synthesis Of Benzo[b]thiophene Using Dommentioning

confidence: 99%

Certain applications of heteroatom directed ortho-metalation in sulfur heterocycles

Pradhan¹,

Ghosh²,

De³

2004

Arkivoc

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Manifold uses of heteroatom directed ortho-metalation which is responsible for its wide application in aromatic and heteroaromatic chemistry include regiocontrolled introduction of substitutents in aromatic or heteroaromatic ring and manipulation of introduced functionalities leading to chain extension and ring annulation. Metalated compounds also undergo a variety of anionic rearrangements providing synthetic strategies to target molecules. In this article work carried out in the authors' laboratory on the application of this methodology in the field of sulfur heterocycles is reviewed.

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“…It has been described that Friedel-Crafts acylation of 5-substituted benzo [b]thiophene derivatives gives different isomers depending on the susbstituent; benzo[b]-thiophene derivatives with weakly activating or deactivating substituents such as chloro or acetoxy, mainly give the 3-acylated product [5]. Acetylation of 5-methylbenzo [b]thiophene gives a mixture of the 2-and 3-ketone derivatives in which the 3-isomer predominates [6].…”

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“…A very similar mixture of isomers is obtained when the starting material is benzo [b]thiophene itself [7]. Finally, although we also needed 3-acylbenzo [b]thiophenes with activating substituents at the 5-position, they could not be obtained directly from the acetylation of their corresponding benzo [b]thiophenes: the acylation of benzo[b]thiophenes containing 5-hydroxy, 5-methoxy or 5-amino groups at the 5 position occurs mainly on the benzene ring [5]. For this reason, these types of derivatives had to be obtained from benzo [b]thiophenes already acylated at the 3 position.…”

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Synthesis of new 5‐substitutedbenzo[b]thiophene derivatives

Pérez‐Silanes¹,

Martínez-Esparza²,

Oficialdegui³

et al. 2001

Journal of Heterocyclic Chem

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Previous works of our group have dealt with the synthesis of 1-(aryl)-3-[4-(aryl)piperazin-1-yl]propane derivatives in the search for new and efficient antidepressants with a dual mode of action: serotonin reuptake inhibition and 5-HT 1A receptor afinity [1][2][3][4]. From these studies we concluded that the 3-[4-(aryl)piperazin-1-yl]-1-(benzo [b]thiophen-3-yl)propane derivatives led to the best results. The continuation of this research project required the preparation of some new 3-acyl-5-substituted benzo [b]thiophenes with a wide variety of substituents at the 5 position, ranging from nitro to hydroxyl derivatives. To obtain these derivatives we acylated the corresponding 5-substituted benzo [b]thiophenes when it was possible. In this paper we describe the synthesis of 3-acyl-5-substitutedbenzo[b]thiophenes by Friedel-Crafts acylation of 5-substitutedbenzo [b]thiophenes. The starting compounds for the acylating reactions were synthesized according to described methods, which in most cases, were modified in order to optimize the yields and to facilitate the isolation of the product. 5-Nitrobenzo[b]thiophene was synthesized according to the literature [8,9], with slight modifications. In the first step, 5-nitro-2-chlorobenzaldehyde was treated with sodium sulfide nonahydrate and ethyl bromoacetate in basic medium, yielding ethyl 5-nitrobenzo[b]thiophene-2-carboxylate 1 (Scheme 1). Alkaline hydrolysis of this compound gave the corresponding acid 2, which was decarboxylated in copper-quinoline to 5-nitrobenzo[b]-thiophene 3 following described methods [8].

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Recent Advances in the Chemistry of Benzo[b]thiophenes

Cited by 77 publications

References 412 publications

Biotransformation of benzothiophene by isopropylbenzene-degrading bacteria

Biotransformation of benzothiophene by isopropylbenzene-degrading bacteria

Certain applications of heteroatom directed ortho-metalation in sulfur heterocycles

Synthesis of new 5‐substitutedbenzo[b]thiophene derivatives

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