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.     

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.

     

The structure of thiophene sesquioxide: Syn,endo-3a,4,7,7a-tetrahydro-4,7-epithiobenzo[b] thiophene 1,1,8-trioxide

Thiophene sesquioxide is shown to be syn, endo-3a,4,7,7a-tetrahydro-4,7-epithiobenzo[b]-thiophene 1,1,8-trioxide (I) by ¹ H and ¹³ C nmr evidence. Assignment of the ¹³ C spectrum was facilitated by a cross-ring long-range ¹³ C-¹ H coupling. The mass spectrum of I is dominated by an unusual break-down to give benzene radical cation.     

Furopyridines. VI. Preparation and reactions of 2- and 3-substituted furo[2,3-b]pyridines

This paper describes the synthesis and chemical properties of some 2- and 3-substituted furo[2,3-b]pyridines. Reaction of ethyl 2-chloronicotinate 1 with sodium ethoxycarbonylmethoxide or 1-ethoxycarbonyl-1-ethoxide gave β-keto ester 2 or ketone 5 , respectively. Ketonic hydrolysis of 2 afforded ketone 3, from which furo[2,3-b]pyridine 4 was obtained by the method of Sliwa. While, 2-methyl derivative 7 was prepared from 5 by reduction, O-acetylation and the subsequent pyrolysis. Reaction of ketone 3 with methyllithium gave tertiary alcohol 8 which was O-acetylated and pyrolyzed to give 3-methyl derivative 9 . Formylation of 4 , via lithio intermediate, with DMF yielded 2-formyl derivative 10 , from which 7 , was obtained by Wolff-Kishner reduction. Dehydration of the oxime 11 of 10 gave 2-cyano derivative 12 , which was hydrolyzed to give 2-carboxylic acid 13 . Reaction of 3-bromo compound 14 with copper(I) cyanide gave 3-cyano derivative 15 . Alkaline hydrolysis of 15 afforded compound 16 and 17 , while acidic hydrolysis gave carboxamide 18 . Reduction of 15 with DIBAL-H afforded 3-formyl derivative 19 . Wolff-Kishner reduction of 19 gave no reduction product 9 but hydrazone 20 . Reduction of tosylhydrazone 21 with sodium borohydride in methanol afforded 3-methoxymethylfuro[2,3-b]pyridine 22 .     

Synthesis of aromatic polyethers by Scholl reaction. V. Synthesis and polymerization of 1,3-bis[4-(1-naphthoxy) benzoyl]benzene, 1,4-bis[4-(1-naphthoxy)benzoyl]benzene,bis[4-(1-naphthoxy)phenyl]methane, 1,3-bis[4-(1-naphthoxy) phenylmethyl]benzene,and 1,4-bis-[4-(1-naphthoxy)phenylmethyl]benzene

This article describes the synthesis and the cation-radical polymerization (Scholl reaction) of 1,3-bis[4-(1-naphthoxy) benzoyl] benzene ( 6 ) and 1,4-bis[4-(1-naphthoxy) benzoyl]- benzene ( 7 ) initiated by FeCI₃. This polymerization produced poly(ether ether ketone ketone)s (PEEKK) of number average molecular weight (M?_n) up to 5400 g/mol. The synthesis of bis[4-(1-naphthoxy) phenyl] methane ( 8 ), 1,3-bis[4-(1-napthoxy) phenylmethyl] benzene ( 9 ), and 1,4-bis[4-(1-naphthoxy) phenylmethyl] benzene ( 10 ) are also described. Polyethers of M?_n up to 15400 g/mol at a FeCl₃/monomer molar ratio of 2/1 were obtained. An increased polymerizability of the monomers 9 and 10 containing two CH₂ groups versus that of the corresponding monomers containing two carbonyl groups ( 6 and 7 ) was observed. This enhanced polymerizability was explained based on the increased nucleophilicity of monomers 9 and 10 .     

Nitro derivatives of the thiophene series. 3. Study of the nitration of thiophene α,β-unsaturated ketones in the presence of protic and aprotic acids

The nitration of 4-(5-R-2-thienyl) but-3-en-2-ones (R = H, CH₃, C₂H₅) with a nitrating mixture and group I and III metal nitrates in concentrated sulfuric and trifluoroacetic acids, as well as in the presence of aluminum chloride, was investigated. Nitration with a nitrating mixture and potassium, sodium, lithium, copper, and aluminum nitrates in sulfuric acid takes place in the heterocyclic ring to give a mixture of nitro ketones. Nitration in trifluoroacetic acid and in the presence of aluminum chloride proceeds with the formation of a single -nitro ketone. The structures of the substances obtained were proved by means of the IR and PMR spectra. A possible mechanism of the reaction is discussed.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–757, June, 1981.     

Dichloro[TADDOLato(2−)-O,O′]titanium/Dichlorobis[1-methylethoxy]titanium-Mediated,Highly Diastereo- and Enantioselective Additions of Silyl Enol Ethers to Nitro Olefins and [3+2] Cycloadditions of Primary Adducts to Acetylenes

The diastereoselective, Ti-Lewis-acid-mediated, low-temperature addition of silyl enol ethers to 1-aryl-2-nitroethenes (Scheme 1) occurs enantioselectively with dichloro[TADDOLato(2−)-O,O′]titanium 3 (TADDOL=α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol) (Scheme 2). At least 3 equiv. of Lewis acid are required for high conversions (yields). However, the chiral Lewis acid 3 can be `diluted' with the achiral Cl₂Ti(OCHMe₂)₂ analog (ratio 1 : 2.5), with hardly any loss of enantioselectivity! Both, the primary (4+2) cycloadducts ( B , 9 ) and the γ-nitro ketones ( A , 1a – h , 5 , 7 ), formed by hydrolysis, can be isolated in good yields and with high configurational purities (Schemes 3 and 4, and Table 1). The relative and absolute configurations (2S,1′R) of the products 1 from cyclohexanone silyl enol ether and 1-aryl(including 1-heteroaryl)-2-nitroethenes (obtained with (R,R)-TADDOLate) are assigned by NMR spectroscopy, and optical comparison and correlation with literature data, as well as by anomalous-dispersion X-ray crystal-structure determination (nitro ketone 1c ; Fig.). The nitro ketone 7 from cyclohex-2-enone and 4-methoxy-β-nitrostyrene was cyclized (via a silyl nitronate C ; Scheme 5) to the nitroso acetal 8 , and one of the bicyclic nitronate primary adducts 9 underwent a [3+2] cycloaddition to phenylacetylene and to ethyl 2-butynoate to give, after a ring-contracting rearrangement, tricyclic aziridine derivatives with five consecutive stereocenters ( 10 , 11 ; Scheme 5 and Table 2), in enantiomerically pure form. With an aliphatic nitro olefin, the Ti-TADDOLate-mediated reaction with (silyloxy)cyclohexene led to a moderate yield, but the product 4 was isolated in a high configurational purity.     

A facile synthesis of benzo[b]thiophene derivatives

Lithiation of S-(2-methylphenyl) N,N,N',N'-tetramethylphosphorodiamidothioate with sec-BuLi at -105° gave the corresponding benzylic anion which was acylated with various aromatic esters to give various deoxybenzoin derivatives in moderate to high yields. Acidic treatment of these products in refluxing formic acid gave 2-arylbenzo[b]thiophene derivatives. 2-Methylbenzo[b]thiophene and benzo[b]thiophen-2(3H)-one were also prepared using the similar procedure.     

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.

     

Study of the reactivity of ketone enolates with 3-halo-2-amino derivatives of benzo[b]thiophene under photostimulated sRN1 reaction conditions

Reactivity of the 3-halo-2-amino derivatives of benzo[6]thiophene 1a-c and 2 with several ketone enolates 3–5 have been studied under photostimulated S_RN1 reaction conditions. The normal substitution product 6 only was obtained in low yields using potassioacetophenone 3 as the enolate ion and 2-(tert-butoxycarbonylamino)-3-chlorobenzo[b]thiophene ( 1a ) and 2-(tert-butoxycarbonylamino)-3-iodobenzo[b]thiophene ( 1c ) as substrates. In all reactions the main product was the corresponding dehalogenated substrate 7a-b , thus indicating that reduction of the substrate strongly competes with the desired substitution reaction.     

Synthese von 15-Hydroxy[9]metacyclophan

Synthesis of 15-Hydroxy[9]metacyclophane 3-(1-Nitro-2-oxocyclododecyl)propanal ( 1 ) was converted to 15-hydroxy[9]metacyclophane ( 3 ) on two different routes. In the first case the internal aldol reaction product of 1 was treated with K₂CO₃/THF to give 3 in 29 % yield with regard to cyclododecanone. Alternatively, the aldehyde 1 reacted with a primary amine to form e.g. 4 which gave 3 in the presence of CH₃I/K₂CO₃ in 48 % yield.     

Reactivity patterns in the reactions of [Rh(CO)2Cl]2 with chelating ketones

A survey is made of the reactions of chelating ketones and aldehydes with [(CO)₂RhCl]₂. With the enolizable ketone 8-quinolinyl benzyl ketone a rhodium(I)-vinyl alcohol π-complex forms, whose crystal structure was determined (C₁₈H₁₃NO₂ClRh, monoclinic space group C2/c, a 14.531(3), b 18.038(3), c 15.257(3) Å, β 111.48(1)°, V 3721 ų, Z = 8, final R_w 4.16%). The non-enolizable ketone 8-quinolinyl phenyl ketone gives oxygen atom transfer to CO, producing CO₂ and a 1,3-dirhodiametallacyclobutane complex. Oxygen atom transfer is also seen from 8-nitroquinoline to give a chelating nitroso ligand. Finally 8-quinoline carboxaldehyde undergoes CH activation followed by loss of H₂ to give a dimeric acylrhodium(II), whose crystal structure was determined (C₂₆H₁₂N₂O₈Cl₄Rh₄, orthorhombic space group Pccn, a 9.466(5), b 13.648(9), c 24.124(14) Å, V 3119 ų, Z = 4 final R_w 5.68%).     

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.

     

Crystal structures of functional building blocks derived from bis(benzo[b]thiophen‐2‐yl)methane

The syntheses of three bis(benzo[b]thiophen‐2‐yl)methane derivatives, namely bis(benzo[b]thiophen‐2‐yl)methanone, C₁₇H₁₀OS₂, (I), 1,1‐bis(benzo[b]thiophen‐2‐yl)‐3‐(trimethylsilyl)prop‐2‐yn‐1‐ol, C₂₂H₂₀OS₂Si, (II), and 1,1‐bis(benzo[b]thiophen‐2‐yl)prop‐2‐yn‐1‐ol, C₁₉H₁₂OS₂, (III), are described and their crystal structures discussed comparatively. The conformation of ketone (I) and the respective analogues are rather similar for most of the compounds compared. This is true for the interplanar angles, the C_aryl—C_bridge—C_aryl angles and the dihedral angles. The best resemblance is found for a bioisotere of (I), viz. 2,2′‐dinaphthyl ketone, (VII). By way of interest, the crystal packings also reveal similarities between (I) and (VII). In (I), the edge‐to‐face interactions seen between two napthyl residues in (VII) are substituted by S…π contacts between the benzo[b]thiophen‐2‐yl units in (I). In the structures of the bis(benzo[b]thiophen‐2‐yl)methanols, i.e. (II) and (III), the interplanar angles are also quite similar compared with analogues and related active pharmaceutical ingredients (APIs) containing the dithiophen‐2‐ylmethane scaffold, though the dihedral angles show a larger variability and produce unsymmetrical molecules.     

Synthesis of Benzo[c]thiophene Analogs Containing Benzimidazole,Benzothiazole, and Oxazole

Iodine-mediated cyclization of benzo[c]thiophene aldehyde with 1,2-diphenylamine/2-aminophenylthiol led to the formation of benzimidazole/benzothiazole-incorporated benzo[c]thiophenes. Similarly, reaction of benzo[c]thiophene aldehyde with p-toluenesulfonylmethyl isocyanide (TOSMIC) reagent in the presence of K₂CO₃ as a base furnished oxazole-containing benzo[c]thiophene analogs.     

Die Cyclopropylcarbinyl-Cyclobutyl-Homoallyl-Umlagerung. I. Teil. Synthese von Tricyclo[3.2.1.02,7]octan-3-ol,endo- und exo-Tricyclo[3.2.1.03,6]octan-4-ol und exo-Bicyclo[3.2.1]-oct-2-en-7-ol

Tricyclo[3.2.1.0^2,7]octan-3-ol ( 1 ) and its 4-isomer 7 were obtained by hydroboration of tricyclo[3.2.1.0^2,7]oct-3-ene ( 5 ). The former alcohol 1 is quantitatively converted to the isomeric alcohol exo-bicyclo[3.2.1]oct-2-en-7-ol ( 3 ) by treatment with aqueous acid. Photolysis of 1-diazo-3-(cyclopent-3-enyl)-propan-2-one ( 12c ) gave a high yield of tricyclo[3.2.1.0^3,6]octan-4-one ( 10a ). Reduction of the latter ketone produced a mixture of endo- and exo-tricyclo[3.2.1.0^3,6]octan-4-ol 2 and 9 , respectively. Oxidation of these secondary alcohols with silver carbonate in benzene furnished a mixture of the ketone 10a and the lactone 14 of 6-hydroxy-bicyclo[2.1.1]heptane-2-carboxylic acid. The latter is thought to be formed by oxydation of the hydrate of the strained ketone 10a .     

Tetraazadibora[3, 3]paracyclophane

Starting from the para‐phenylenediamine derivative HN(SiMe₃)‐C₆H₄‐NH(SiMe₃), a lithiation and subsequent borylation give [(MeO)₂B]N(SiMe₃)‐C₆H₄‐N(SiMe₃)[B(OMe)₂] ( 1 ), the hydridation of which yields Li₂[(H₃B)N(SiMe₃)‐C₆H₄‐N(SiMe₃)(BH₃)] ( 2 ). Applying ZrCl₄ upon 2 initiates a condensation to give the title compound [‐N(SiMe₃)‐p‐C₆H₄‐N(SiMe₃)‐BH‐]₂, a hetero[3, 3]paracyclophane with two N‐B‐N chains that connect the para‐phenylene units. The product 3 crystallizes in the orthorhombic space group P2₁2₁2₁.     

Synthesis of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-imidazo[4,5-b]pyridin-2-amine. An aza analogue of enviroxime

6-[[(Hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-imidazo[4,5-b]pyridin-2-amine ( 1 ), an aza analogue of enviroxime, was synthesized in eight steps from 6-hydroxynicotinic acid ( 2 ). Acid 2 was nitrated, chlorinated with phosphorus pentachloride, and subjected to Friedel-Crafts aroylation to give 6-chloro-5-nitro-3-pyridyl phenyl ketone ( 5 ). Amination of 5 was followed by reduction of the nitro group and condensation with ethoxycarbonylisothiocyanate to give 6-benzyl-2-ethoxycarbonylamino-1H-imidazo[4,5-d]pyridine ( 8 ). The ethoxycarbonyl moiety of 8 was cleaved, N-1 was isopropylsulfonylated, and the carbonyl moiety was condensed with hydroxylamine to give 1 . Compound 1 was inactive against rhinovirus 1B and poliovirus type 1 .     

Dimethylenebicyclo[1.1.1]pentanone

The highly strained and reactive dimethylenebicyclo[1.1.1]pentanone (I), was prepared as follows. Treatment of 1,5-bis(chloromethyl)tricyclo[2.1.0.0^{2, 5}]pentan-3-one diethyl ketal (III) with di-t-butyl hydrazodicarboxylate (VII), followed by pyridinium p-toluenesulfonate and trifluoroacetic acid, yielded the keto hydrazine X which was oxidized to the desired ketone I. The ketone I decomposes very rapidly above −30°C.     

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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Mit 1 Abbildung