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.

     

Synthesis of anthra[b]thiophenes and benzo[b]naphtho[d]thiophenes

All isomers of the parent anthra[b]thiophenes and benzo[b]naphtho[d]thiophenes, namely anthra[2,3-b]thio-phene, anthra[2,1-b]thiophene, anthra[1,2-b]thiophene, benzo[b]naphtho[2,3-d]thiophene, benzo[b]naphtho[2,1-d]thiophene and benzo[b]naphtho[1,2-d]thiophene were synthesized using a new procedure.     

Basisch substituierte 5,6-Dimethoxy- und 4,5,6-Trimethoxy-benzo[b]thiophene

Zusammenfassung N-substituierte -{5,6-Dimethoxy-benzo[b]thienyl-(3)}-äthylamine, -{4,5,6-Trimethoxy-benzo[b]thienyl-(3)}-äthylamine und -{5,6-Dimethoxy-benzo[b]thienyl-(3)}-propylamine wurden mittels LiAlH₄-Reduktion der entsprechenden von uns schon früher synthetisierten Säureamide hergestellt.

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N-substituted -{5,6-dimethoxy-benzo[b]thienyl-(3)}-ethylamines, -{4,5,6-trimethoxy-benzo[b]thienyl-(3)}-ethylamines and -{5,6-dimethoxy-benzo[b]thienyl-(3)}-propylamines were prepared by LiAlH₄ reduction of the corresponding amides previously synthesized by us.

     

The synthesis of benzo[b]phenanthro[d]thiophenes and anthra[b]benzo[d]thiophenes

The synthesis of benzo[b]phenanthro[2, 3-d]thiophene ( 5 ), benzo[b]phenanthro[4, 3-d]thiophene ( 6 ), benzo-[b]phenanthro[2, 1-d]thiophene ( 9 ), benzo[b]phenanthro[3, 2-d]thiophene ( 14a ), anthra[1, 2-b]benzo[d]thiophene ( 24 ), anthra[2, 3-b]benzo[d]thiophene ( 29 ) and anthra[2, 1-b]benzo[d]thiophene ( 30 ) is described as well as the preparation of 13-methylbenzo[b]phenanthro[3, 2-d]thiophene ( 14b ).     

The synthesis of the monomethyl isomers of benzo[b]naphth[2,1-d]thiophene

All isomers of the monomethylbenzo[b]naphth[2,1-d]thiophenes were synthesized using photocyclization of 3-styrylbenzo[b]thiophenes. The 1-, 3-, 4-, and 5-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by irradiation of the corresponding methylated 3-styrylbenzo[b]thiophenes which were prepared by the Wadsworth-Emmons reaction of diethyl benzo[b]thenylphosphonate with o-, m-, p-tolualdehyde and acetophenone. The 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by decarboxylation of 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophene-6-carboxylic acid with copper in quinoline. These carboxylic acids were prepared by photocyclization of the corresponding 2-(benzo[b]thiophen-3-yl)-3-phenylpropenoic acids which were prepared by the condensation of the methylated benzo[b]thiophene-3-ylacetic acids with benzaldehyde in the presence of triethylamine in acetic anhydride.     

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.     

Synthesis of phenanthro[b]thiophenes

All isomers of the parent phenanthro[b]thiophenes, namely, phenanthro[1,2-b]thiophene, phenanthro-[2,1-b]thiophene, phenanthro[2,3-b]thiophene, phenanthro[3,4-b]thiophene, phenanthro[3,4-b]thiophene, phenanthro[4,3-b]thiophene and phenanthro[9,10-b]thiophene have been synthesized.     

Derivate des 3-Phenyl-benzo[b]thiophens

Zusammenfassung 2-Methylthio-benzophenon reagierte mit Chloressigsäure zu 3-Phenyl-benzo[b]thiophen-2-carbonsäure und mit -Chlorphenylessigsäure zu 2,3-Diphenyl-benzo[b]thiophen. 3-Phenyl-5-methoxy-benzo[b]thiophen-2-carbonsäure wurde aus 3-Phenyl-5-amino-benzo[b]thiophen-2-carbonsäure durch Verkochen des Diazoniumsalzes und Methylierung erhalten; ihr N-Methylpiperazid sowie 3 basisch substituierte Ester wurden dargestellt.

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Derivatives of 3-phenylbenzo[b]thiophene

2-Methylthio-benzophenone reacted with chloroacetic acid to 3-phenyl-benzo[b]thiophene-2-carboxylic acid and with -chloro-phenylacetic acid to 2,3-diphenyl-benzo[b]thiophene. 3-Phenyl-5-methoxy-benzo[b]thiophene-2-carboxylic acid was prepared by diazotation of 3-phenyl-5-amino-benzo[b]thiophene-2-carboxylic acid and hydrolysis to the hydroxy compound followed by methylation; its N-methylpiperazide and three esters with basic substituents were synthesized.

     

Benzo[b]thiophene. Derivatives. XXVIII. 5-bromo-3-benzo[b]thienylalanine and derivatives

A potential inhibitor of gelation of sickle hemoglobin, 5-bromo-3-benzo[b]thienylalanine, has been synthesized along with several derivatives. Several hydrolytic pathways from the intermediate ethyl 5-bromo-3-benzo[b]thienylformamidomalonate have been examined, and that involving alcoholysis to ethyl N-formyl-5-bromo-3-benzo[b]thienylalanine shown to be superior.     

Synthesis of 3-formylbenzo[b]furan and 1-methyl-3,4-dihydrobenzo[b]-furo[2,3-c]pyridine

Starting from the readily available 3-methylcoumarilate, 3-formylbenzo[b]furan was synthesized in high yield. The latter could be converted to 1-methyl-3,4-dihydrobenzo[b]furo-[2,3-c]pyridine in moderate yield.     

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.

     

Synthesis of benzo[b]phenanthro[d]thiophenes

The synthesis of benzo[b]phenanthro[1,2-d]thiphene ( 1 ), benzo[b]phenanthro[4,3-d]thiophene ( 2 ), benzo-[b]phenanthro[2,1-d]thiophene ( 3 ) and benzo[b]phenanthro[3,4-d]thiophene ( 4 ) from appropriately substituted olefines by photochemical cyclodehydrogenation is described. The photolysis of olefin 9 gave a mixture of 4 and anthra[1,2-b]benzo[d]thiophene ( 5 ).     

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.     

Beiträge zur Chemie schwefelhaltiger Heterocyclen, 4. Mitt.: 6H-Benz[b]indeno[1,2-d]thiophen und 10H-Benz[b]indeno-[2,1-d]thiophen

Zusammenfassung Intramolekulare Cyclisierungsreaktionen von 3-Phenyl-benzo[b]thiophen-2-carbonsäurechlorid und von 2-Phenyl-benzo[b]thiophen-3-carbonsäurechlorid lieferten 6-Oxo-6H-benz[b]indeno[1,2-d]thiophen bzw. 10-Oxo-10H-benz[b]indeno[2,1-d]thiophen.

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Contributions to the chemistry of sulfur containing heterocycles, IV.: 6H-Benzo[b]indeno[1,2-d]thiophene and 10H-benzo-[b]indeno[1,2-d]thiophene

Intramolecular cyclization reactions of 3-phenyl-benzo[b]thiophene-2-carbonyl chloride and of 2-phenyl-benzo[b]-thiophene-3-carbonyl chloride gave 6-oxo-6H-benz[b]indeno-[1,2-d]thiophene and 10-oxo-10H-benz[b]indeno[2,1-d]thiophene, respectively.

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3. Mitt.:F. Sauter, Mh. Chem.99, 2100 (1968).     

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.

     

Beiträge zur Chemie schwefelhaltiger Heterocyclen, 1. Mitt.: Synthesen von Benzo[b]thieno[2,3−d]pyrimidin-Derivaten

Zusammenfassung 4-Oxo-3,4,5,6,7,8-hexahydro-benzo[b]thieno[2,3–d]pyrimidin sowie die 2-Methyl- und 2-Phenyl-Derivate davon wurden durch Ringschlußreaktionen aus 2-Acylamino-4,5,6,7-tetrahydrobenzo[b]thienyl-(3)-carbonsäureamiden gewonnen; das 2-Phenyl-Produkt entstand auch durch thermische Cyclisierung von 2-Benzylidenamino-4,5,6,7-tetrahydro-benzo[b]-thienyl-(3)-carbonsäureamid.

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4-Oxo-3,4,5,6,7,8-hexahydro-benzo[b]thieno[2,3–d]pyrimidine as well as its 2-methyl and 2-phenyl derivatives were synthesized by cyclization of the corresponding 2-acylamino-4,5,6,7-tetrahydro-benzo[b]thienyl-(3)-carboxamides; the 2-phenyl compound was also prepared by thermal cyclization of 2-benzylideneamino-3-carbamoyl-4,5,6,7-tetrahydro-benzo[b]thienyl-(3)-carboxamide.

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Mit 1 Abbildung     

Synthesen und Reaktivität von 2,3,6,7,8-Pentachlorimidazo-[1,2—b]pyridazin und 3,6,7,8-Tetrachlor-s-triazolo-[4,3—b]pyridazin

Zusammenfassung 2,3,6,7,8-Pentachlorimidazo[1,2—b]pyridazin und 3,6,7,8-Tetrachlor-s-triazolo[4,3—b]pyridazin wurden aus unsubstituierten Verbindungen und einigen Chlor-Derivaten synthetisiert. Die Reihenfolge der Substitution von Wasserstoffatomen durch Chloratome konnte beim Imidazo[1,2—b]pyridazin als 3>2, 7>8>6 ermittelt werden, während beis-Triazolo-[4,3—b]pyridazin der Verlauf als 3>8>7>6 sichergestellt wurde. Nukleophile Substitutionen an diesen perchlorierten Systemen verlaufen am leichtesten in Stellung 8.

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Pyridazines. XLVIII: Syntheses and Reactivity of 2,3,6,7,8-Pentachloroimidazo[1,2—b]pyridazine and 3,6,7,8-Tetrachloro-s-triazolo[4,3—b]pyridazine

2,3,6,7,8-Pentachloroimidazo[1,2—b]pyridazine and 3,6,7,8-Tetrachloro-s-triazolo[4,3—b]pyridazine were synthesized from the parent compounds and some of their chloro derivatives. It could be established that in the case of the first condensed system the stepwise introduction of chlorine atoms followed the order of 3>2, 7>8>6 and in the case of the second system this appears to be 3>8>7>6. Nucleophilic substitutions on these perchloro compounds proceed most easily at position 8.

     

Reactions of 6‐aminopyrimidines with 2‐dimethylaminomethylenetetralone. Regiospecific Synthesis Of 5,6‐Dihydrobenzo [h]pyrimido [4,5‐b] quinolines

Benzo[h]pyrimido[4,5‐b]quinolines ( 3 ) have been synthesized via a regiospecific cyclocondensation reaction between 6‐aminopyrimidines ( 1 ) and 2‐dimethylaminomethylentetralone hydrochloride ( 2 ). The linear structure of the final compounds were determined by nmr measurements, especially by ¹H,¹H, ¹H,¹³C COSY and DEPT experiments.     

The syntheses of 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]oxirene and 4b,5a-dihydro-5H-dibenz[3,4:5,6]anthra[1,2-b]azirine

The syntheses of the K-oxide and K-imine derivatives of dibenz[a,j]anthracene ( 1 ) are described. The parent hydrocarbon 1 that was obtained as a side product in the Elbs pyrolysis of (2-methyl-1-naphthyl)-1′-naphthylmethanone ( 10 ) was oxidized to 3-(2-formylphenyl)-3-phenanthrenecarboxaldehyde ( 3 ). Treatment of the dialdehyde with tris(dimethylamino)phosphine gave 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]oxirene ( 4 ). Reaction of the oxirane with sodium azide followed by triethyl phosphite cyclization of the mixture of trans azido-alcohols so formed, yielded mainly 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]azirine ( 5 ).     

Synthesis of New Pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline Derivatives in One Step

As a continuation of our search for new heterocyclic compounds, the synthesis of pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline ring system is described. A series of new derivatives of this heterocyclic system ( 3a–d ) have been synthesized through the one‐pot heterocyclization of the appropriate 5‐amino6‐methylpyrimidine‐4‐thiols and 2,3‐dichloroquinoxaline in the presence of K₂CO₃ in dimethylformamide under reflux. N‐alkylation of the synthesized compounds with alkyl halides in KOH/dimethylformamide also gave the desired new derivatives of N‐alkylated pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxalines ( 4a–h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.