5,6-Dimethoxy- und [4,5,6-Trimethoxy-benzo[b]-thienyl-(3)]-acylamine

Zusammenfassung Umsetzung von 5,6-Dimethoxy- und [4,5,6-Trimethoxy-benzo[b]thienyl-(3)]-essigsäure mit PCl₅ lieferte die methoxysubstituierten [Benzo[b]thienyl-(3)]-essigsäurechloride, die mit sekundären Aminen zu den entsprechenden Amiden reagierten.Die homologen Verbindungen mit einer C₃-Brücke wurden durchArndt-Eistert-Reaktion des Diazomethylketons in Gegenwart der entsprechenden sekundären Amine erhalten.

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Reaction of 5.6-dimethoxy- and [4.5.6-trimethoxybenzo[b]-thienyl-(3)]-acetic acid with PCl₅ gave the methoxy-substituted [benzo[b]thienyl-(3)]-acetic acid chlorides, which reacted with secondary amines to the corresponding amides.The homologous compounds with a C₃-bridge were synthesized viaArndt-Eistert reaction of the diazomethyl ketone in presence of the corresponding secondary amines.

     

Benzo[b]thiophene derivatives. XXIII. Derivatives of 5,6-dihydroxy-3-benzo[b] thienylacetic acid

A series of 5,6-disubstituted benzo[b]thiophenes have been synthesized for biological evaluation. These include analogs of tryptamine, melatonin and harmaline types, having hydroxy, methoxy, methoxymethyloxy, or isopropylidenedioxy groups at both the 5- and 6- positions. In order to synthesize these, the appropriate mercaptoguaiacols were prepared, and condensed with chloroacetoacetic esters to the 4-arylthioacetoacetic esters. Cyclization of these ketones was best accomplished when the free phenolic groups were masked by methoxymethyl groups. The benzo[b] thienylacetic esters were then converted to corresponding amides, reduced to tryptamine analogs, acetylated to melatonin analogs, and cyclized to harmaline analogs. N-Acetyltryptamine and 1-methylmelatonin were also synthesized for comparison. Preliminary bioassay results on the melatonin analogs, which showed activity, are reported.     

Benzo[b]thiophene derivatives. XX. The sulfur isostere of 5,6-Dihydroxytryptamine

3β-Aminoethyl-5,6-dihydroxybenzo[b]thiophene, the sulfur bioisostere of 5,6-dihydroxytryptamine, a selective neurotoxin, has been synthesized and shown to have significant effect on biogenic amine levels both centrally and peripherally. A derivative, 3β-aminoethyl-5,6-isopropylidenedioxybenzo[b]thiophene, showed significant but opposite activity. The syntheses and preliminary pharmacology are reported.     

Benzo[b] thiophene derivatives XVII. Electrophilic substitution of 4-hydroxybenzo[b] thiophene derivatives

A variety of eleclrophilic substitution reactions have been carried out on 4-methoxybenzo[b]-thiophene (IIIa) and 4-benzoyloxybenzo[b ] thiophene (IVa). Substitution occurs in the 7-position of IIIa and, with the exception of bromination, in the 7-position of IVa. Bromination of IVa occurs in the 3-position. Bromination of 4-hydroxybenzo[b] thiophene (IIa) occurs in the 5-position. The nmr spectra of eleven disubstituted benzo[b] thiophenes have been tabulated.     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

Benzo[b]thiophene derivatives I. 6-methoxybenzo[b]thiophene analogs of plant growth regulators

The acid catalyzed ring closure of an appropriately substituted phenyl ketoester sulfide served as the initial reaction in the synthesis of several 3,4- and 3,6-disubstituted benzo[b]thiophenes. One of these compounds, 4-methoxybenzo[b]thienyl-3-acetic acid, showed marked plant growth enhancement.     

N-Substituierte 2-Methyl-3-aminoacetyl-benzo[b]thiophene und 2-Methyl-3-(α-hydroxy-β-amino-äthyl)-benzo[b]thiophene

Zusammenfassung Bromierung von 2-Methyl-3-acetyl-benzo[b]thiophen ergab 2-Methyl-3-bromacetyl-benzo[b]thiophen, das beim Umsetzen mit Dimethylamin, Morpholin und N-Methylpiperazin die entsprechend basisch substituierten 3-Acetylverbindungen lieferte. Diese wurden mit LiAlH₄ zu den -Hydroxyverbindungen reduziert.In ähnlicher Weise wurde auch 3-Diäthylaminoacetyl-benzo[b]thiophen dargestellt.

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Bromination of 2-methyl-3-acetyl-benzo[b]thiophene gave 2-methyl-3-bromacetyl-benzo[b]thiophene, which reacted with dimethylamine, morpholine and N-methylpiperazine to give the corresponding base-substituted 3-acetyl derivatives. These were reduced by LiAlH₄ to the -hydroxy compounds.Similarily 3-diethylaminoacetyl-benzo[b]thiophene was synthesized.

     

3-Aminoalkyl-5-methyl-benzo[b]thiophene

Zusammenfassung Ausgehend von -[5-Methyl-benzo[b]thienyl-(3)]-propionsäure wurde eine Reihe von 5-Methyl-benzo[b]thiophenen mit einer Aminoalkylsubstitution in 3-Stellung dargestellt: 3-(-Aminoäthyl)-5-methyl-benzo[b]thiophen durchCurtius-Abbau des Azids und 3-(-Aminopropyl)-5-methyl-benzo[b]thiophen sowie N-Substitutionsprodukte davon durch LiAlH₄-Reduktion der entsprechenden Amide.

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5-Methyl-benzo[b]thiophenes having an aminoalkyl substituent in position 3 were prepared from -[5-methyl-benzo[b]-thienyl-(3)]-propionic acid: 3-(-aminoethyl)-5-methyl-benzo[b]-thiophene byCurtius rearrangement of the azide, and 3-(-aminopropyl)-5-methyl-benzo[b]thiophene as well as some of its N-derivatives by reduction of the corresponding amides with LiAlH₄.

     

New reaction of benzo[b]thieno[3,2-b]benzo[b]thiophene disulfone

A new reaction of benzo[b]thieno[3,2-b]benzo[b]thiophene disulfone with amines that takes place with opening of one of the thiophene rings and nucleophilic substitution in the heteroaromatic ring at the site of cleavage of the S-C bond was observed. The molecular structures of the products of amination of the disulfone were determined by x-ray diffraction analysis. Hydrolysis and dehydration of the amination products gave derivatives of a new heterocyclic system, viz., benzo[b]-thieno[3,2-e]benzo[c]-1,2-oxathiin. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 320–323, March, 1980.     

Benzo[b] thiophene derivatives. XIV. Derivatives of naphtho[1,8-c] thiophene

In the course of our efforts to synthesize the sulfur isostere of lysergic acid, we have prepared a number of derivatives of the little known naphtho[1,8-bc]thiophene ring system. Two previously reported compounds, 2-bromo-3,4-dihydro-5-oxo-5H-naphtho[1,8-bc]thiophene and 2-bromo-5-hydroxy-3,4-dihydro-5H-naphtho[1,8-bc] thiophene have been obtained pure for the first time, and the syntheses and spectral data of eighteen new compounds are presented. The new compounds include alcohols, ketones, and halogen derivatives of partially reduced naphtho-[1,8-bc] thiophene, as well as the sulfones of several of these compounds.     

N-Substituierte Benzo [b]thiophen-3-acetamide und 3-(β-Aminoäthyl)-benzo [b]thiophene

Zusammenfassung Die Synthese der Titelverbindungen erfolgte über die Benzo[b]thiophen-3-essigsäure, deren Chlorid mit Diäthylamin und N-Methylpiperazin zu den entsprechenden N-substituierten Benzo[b]thiophen-3-acetamiden reagierte; diese wurden mit LiAlH₄ zu tertiären Aminen reduziert.Die Synthese der homologen 2-Methylverbindungen ging vom 2-Methyl-3-acetyl-benzo[b]thiophen aus: Haloformreaktion gab 2-Methyl-benzo[b]thiophen-3-carbonsäure;Wolff-Umlagerung des entsprechenden Diazomethylketons in Gegenwart von sekundären Aminen lieferte verschiedene N-substituierte 2-Methyl-benzo[b]thiophen-3-acetamide, von denen drei mit LiAlH₄ zu tertiären Aminen reduziert wurden.

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The title substances were synthesized using benzo[b]thiophene-3-acetic acid as an intermediate, the acid chloride of which reacted with diethylamine and N-methylpiperazine to give the corresponding N-substituted benzo[b]thiophene-3-acetamides; these were reduced by LiAlH₄ to tertiary amines.The synthesis of the homologous 2-methyl compounds started from 2-methyl-3-acetyl-benzo[b]thiophene: haloform reaction gave 2-methyl-benzo[b]thiophene-3-carboxylic acid;Wolff-rearrangement of the corresponding diazomethyl ketone in the presence of secondary amines yielded various N-substituted 2-methyl-benzo[b]thiophene-3-acetamides; three of them were reduced by LiAlH₄ to tertiary amines.

     

Benzo[B]thiophene derivatives XXIV. Oxidation of o-dihydroxybenzo[b]thiophene methyl ethers

The attempted oxidative demethylation of a series of o-dihydroxybenzo[b]thiophene methyl ethers with cerium (IV), argentic oxide, periodale and thallate usually led to intractable mixtures. However, in one ease, use of ceric ammonium nitrate resulted in nitration of the benzo[b]-thiophene ring. In another example, treatment with aqueous periodate or thallate resulted in oxidative hydroxylation of benzo[b]thiophene.     

Synthesis of 6-aminobenzo[b]naphtho[2,1-d]thiophene

6-Aminobenzo[b]naphtho[2,1-d]thiophene has been prepared by two different routes, one, a one-pot synthesis.     

2,2′‐Bi[benzo[b]thiophene]: an unexpected isolation of the benzo[b]thiophene dimer

The crystal structure of 2,2′‐bi[benzo[b]thiophene], C₁₆H₁₀S₂, at 173 K has triclinic (P) symmetry. It is of interest with respect to its apparent mode of synthesis, as it is a by‐product of a Stille cross‐coupling reaction in which it was not explictly detected by spectroscopic methods. It was upon crystal structure analysis of a specimen isolated from the mother liquor that this reaction was determined to give rise to the title compound, which is a dimer arising from the starting material. Two independent half‐molecules of this dimer comprise the asymmetric unit, and the full molecules are generated via inversion centers. Both molecules in the unit cell exhibit ring disorder, and they are essentially identical because of their rigidity and planarity.     

Benzo[b]thiophene mit Halogensubstitution in 5-Stellung

Zusammenfassung Cyclisierung von -(p-Chlor-phenylthio)-acetessigester und -(p-Brom-phenylthio)-acetessigester mit Polyphosphorsäure und anschließende Hydrolyse gab 5-Chlor- und 5-Brom-benzo[b]-thiophen-3-essigsäure. Deren Säurechloride wurden mit verschiedenen sekundären Aminen zu den entsprechenden N-substituierten 5-Chlor-und 5-Brom-benzo[b]thiophen-3-acetamiden umgesetzt. Diese wurden mit LiAlH₄ zu den tertiären Aminen reduziert.Ähnlich wie im Fall des -(p-Methoxy-phenylthio)-acetessigesters konnte auch die entsprechende Fluorverbindung nicht zu einem Benzo[b]thiophen-Derivat ringgeschlossen werden.

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Cyclization reactions of -(p-chloro-phenylthio)-acetoacetate and -(p-bromo-phenylthio)-acetoacetate withPPA followed by hydrolysis gave 5-chloro- and 5-bromobenzo[b]thiopheneacetic acid. The acid chlorides reacted with various secondary amines to give the corresponding N-substituted 5-chloro- and 5-bromo-benzo[b]thiophene-3-acetamides. These were reduced by LiAlH₄ to tertiary amines.Similar to -(p-methoxy-phenylthio)-acetoacetate the fluoro compound gave no cyclization to a benzo[b]thiophene derivative.

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