Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.     

Die molekulare und kristalline Struktur von 9,10-Dihydro-4-(3-dimethylamino-propyliden)-4H-benzo[4,5] cyclohepta[1,2-b]thiophen-hydrochlorid. Untersuchungen über synthetishe Arzneimittel, 19. Mitteilung [1]

The α-isomer of 9,10-dihydro-4-(3-dimethylamino-propylidene)-4 H-benzo[4,5] cyclohepta [1, 2-b] thiophen is shown to have the trans configuration by means of an X-ray analysis of its hydrochloride.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene 3. Synthesis of 2,3,6,7-tetrahydro-3-oxobenzo[1,2]cyclohepta[3,4,5-hi]thieno[3,4-c]pyridine and 2,3,7,8-tetrahydro-3-oxothieno[2,1-b]cyclohepta[5,6,7-de]isoquinoline

The title compounds 3 and 4 were synthesized by cyclization via isocyanate of the Z and E-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene-4-ylidenacetic acids 8 and 9 , which in turn were prepared by the Wadsworth-Emmons reaction of ketone 5 with triethyl phosphonacetate followed by separation and independent hydrolysis of the corresponding esters 6 and 7 . The structures of these new compounds as well as the configurations of their isomeric precursors are described.     

The preparation of the benzo[4,5]cyclohepta[1,2-b]pyrazine and benzo[4,5]cyclohepta[1,2-b]quinoxaline systems

Benzo[4,5]cyclohepta[1,2-b]quinoxaIine 2 , benzo[4,5]cyclohepta[1,2-b]pyrazine 3a and benzo[4,5]cyclohepta[1,2-b]quinoxaline 4 were prepared from 4,5-benzotropolone and 1,2-phenylenediamine, ethylenediamine and 1,2-diaminocyclohexane, respectively. Compound 3a was methylated to 3b .     

Synthesis of 2-(1-methyl-4-piperylid-3-ene)-9,10-dihydro-4H-benzo[4,5]- cyclohepta[1,2-b]thiophen-10-one,a new potential antiasthmatic analogue of zaditene

The title compound has been prepared in four steps from readily available starting material. The key reaction is the metallation of 10-methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophene, which occurs exclusively at the desired 2 position.     

Imino-bridged heterocycles. I. A derivative of benzo[5,6]cyclohepta[1,2-b]pyridin-5,11-imine

The current interest in structures that contain a tricyclic framework with a nitrogen bridged central ring has prompted us to examine the synthesis of imino-bridged benzocycloheptapyridines. Treatment of 5,6-trans-dibromobenzo[5,6]cyclohepta[1,2-b]pyridin-11-one with anhydrous methyl amine in THF produced 6-β-bromo-5,6-dihydro-11α-hydroxy-12-methyl-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-5,11-imine, the first example of the desired bridged derivatives.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene. 1. Synthesis and cyclization of N-(9,10-dihydro-4H-benzo[4,5]cyclohepta-[1,2--6]thiophene-4-ylmethyl)amides

Starting from ketone III several acyl derivatives of 4-aminomethyl-9,10-dihydro-4H-benzo[4,5]cyclohepta-[1,2--6]thiophene (VII) have been synthesized. The intramolecular cyclization of some of these new amides through the Bischler-Napieralski reaction is described.     

Polycyclic N-hetero compounds. XXXV. Syntheses and anti-platelet aggregation activity of 5,6-Dihydro-4H-benzo[3,4]cyclohept[1,2-e]imidazo[1,2-c]pyrimidines with an oxygen function at the 1-position

Various 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d][pyrimidines bearing amino acid group at the 4-position of the skeleton were synthesized by the reaction of 4-chloro-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]-pyrimidine with some amino acid, which were cyclized to 5,6-dihydro-4H-benzo[3,4]cyclohept[1,2-e]imidazo-[1,2-c]pyrimidines, corresponding to B-homo-11,13,15-triazasteroids. Their inhibitory activities against platelet aggregation induced by collagen were also investigated.     

Beiträge zur Chemie des 4,5-Dihydro-10H-benzo [5, 6]cyclohepta[1,2-b]thiophens

Several syntheses of 4,5-dihydro-10 H-benzo[5,6]-cyclohepta[1, 2-b]thiophen-10-one (I b) are described. The pharmacological properties of the compounds XIII, which derive from IB through basic substitution on position 10, are briefly mentioned.     

Synthesis of two new heterocyclic ring systems: Benzo[3,4] cyclohepta[1,2-d]-pyrimidines and benzo[3,4]cyclohepta[2,1-d] pyrimidines

Three 2,4-diamino-l(), 11-dihydro-9H-benzo[3,4]cyclohepta[ 1,2-d]pyrimidines (6a-6c) representing the first examples of a new ring system were synthesized from 2-benzosuberones and cyanoguanidine. Similarly, 2,4-diamino-6,7-dihydro-5H-benzo[3,4]cyelohepta[2,1-d]pyrimidine ( 24 ) was prepared from 1-benzosuberone. The ultraviolet spectral properties of these compounds were examined with reference to those of the analogs in which the central ring is five- and six-mernbered.     

Reaction of dichloroketene and sulfene with N,N-disubstituted 6-amino-methylene-b,7,8,9 -tetrahydro-5H-benzocyclohepten-5-ones. Synthesis of 6-(2,2-Dichloroethylidene)-b,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and of 5H-benzo[3,4]cyclohepta[2,l-b]pyran and 5H-Benzo[3,4]cyclo-hepta[1,2-e]-1,2-oxathiin derivatives

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-b,7,8,9-tetra-hydro-5H-benzocyclohepten-5-ones afforded N,N-disubstituted 4-amino-3,3-dichloro-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones only in the case of aromatic or strong hindering aliphatic N-substitution. The adducts gave N,N-disubstituted 4-amino-3-chloro-b,7-dihydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones by dehydrochlorination with collidine. Upon chromatography on neutral alumina, two products were instead isolated in the case of usual aliphatic N-substitution (diethylamine, piperidine), namely 6-(2,2-dichloroethylidene)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and the dehydrochlorinated 2-pyrone; this latter was the sole product in the case of pyrrolidine substitution. The 1,4-cycloaddition of sulfene occurred readily to give N,N-disubstituted 4-amino-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta-[1,2-e]-1,2-oxathiin 2,2-dioxidesin the case of both aliphatic and partially aromatic N-substitution.     

Polycyclic N-hetero compounds. XXXIII. Syntheses of 4-substituted 6,7-dihydro-5H-benzo[6,7]-cyclohepta[1,2-d]pyrimidines and their inhibitory activities on platelet aggregation and on reserpine-induced hypothermia

Various 4-substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidines were synthesized by the reaction of 4-chloro-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidine with amines. Their inhibitory activities against collagen-induced platelet aggregation and also against reserpine-induced hypothermia in mice were investigated.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.     

A novel construction of quino-fused tropone skeleton: first synthesis of 12H-benzo[4,5]cyclohepta[1,2-b]quinolin-12-one derivatives

In the present investigation, the incorporation of both quinoline moiety and tropone ring in a molecule frame work in fused form leading to a series of structurally novel and biologically intriguing quinoline/tropone hybrids 12H-benzo[4,5]cyclohepta[1,2-b]quinolin-12-one derivatives has been first achieved through a simple, and economical two-step procedure, involving the one-pot synthesis of (E)-2-(arylvinyl)quinoline-3-carboxylic acids followed by intramolecular Friedel–Crafts acylation reaction using polyphosphoric acid (PPA).     

Furannes et pyrroles disubstitues en 2,3—XVIII : Synthese et rearrangement de 4H-dihydro-9,10 benzo[4,5]cyclohepta[1,2-b]furannones-4

Cyclisation of 2-arylethyl 3-furancarboxylic acid chlorides gives 4H-9,10-dihydro benzo[4,5]cyclohepta[1,2-b]furan-4-ones 8 only when the aryl moiety is activated by a m-methoxy group or when the 5-position of furyl acid chlorides is blocked by a substituent. If the Friedel-Crafts reaction is performed with an excess of aluminium chloride, 4H-5,6-dihydro benzo[3,4]cyclohepta[2,1-b]furan-4-ones 13 appear in lower yields probably through isomerisation of 8. The rearrangement 8 → 13 also occurs by treatment of 8 in boiling hydrated pyridine hydrochloride.     

Stereoselektive Synthesen von (Z)-(10-Methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yliden)essigsäure

Stereoselective Syntheses of (Z)-(10-Methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)acetic Acid Two stereoselective syntheses for the antiinflammatory compound 1 ((Z)-isomer) are described. In the first approach (Strategy A, Scheme 1) the stereoselective synthesis of 1 was realized via the bicyclic compound 11 under thermodynamic conditions, followed by a thiophene annelation with retention of the double-bond geometry (Schemes 2–4). Optimized conditions were necessary to avoid (E/Z)-isomerization during annelation. In the second approach (Strategy B, Scheme 1), diastereoisomer 17b was obtained selectively from a mixture of the diastereoisomers 17b and 18b by combining thermodynamic epimerization and solubility differences (Scheme 5). Diastereoisomer 17b was converted into the tricyclic compound 23 using a novel thiophene annelation method which we described recently (Scheme 6). In a final step, a stereospecific ‘syn’-elimination transformed the sulfoxide 24 into the target compound 1 (Scheme 7). To avoid (E/Z)-isomerization, it was necessary to trap the sulfenic acid liberated during the reaction. The key reactions of both approaches are highly stereoselective (> 97:3).     

Synthesis of 4,10-dihydro-4,10-dioxo-1H-[1]-benzopyrano[3,2-b]pyridine, 4,5-Dihydro-4,5-dioxo-1H-[1]-benzopyrano[2,3–6]pyridine and 1,5-Dihydro-1,5-dioxo-4H-[1]-benzopyrano[3,4-b]pyridine derivatives from aminobenzopyrones

3-Aminochromone and 3-aminocoumarin were condensed with diethyl ethoxymethylenemalonate and with dimethyl acetylenedicarboxylate to give intermediates, which were thermally cyclized to give 4,10-dihydro-4,10-dioxo-lH-[1]-benzopyrano[3,2-b]pyridinecarboxylates and 1,5-dihydro-1,5-dioxo-4H-[1]-benzopyrano-[3,4-b]pyridinecarboxylates. 2-Aminochromone was converted to 4,5-dihydro-4,5-dioxo-1H-[1]-benzopyrano-[2,3-b]pyridinecarboxylate via an intermediate condensation product with diethyl ethoxymethylenemalonate. These esters were hydrolyzed to the corresponding carboxylic acids (21, 30, 36, 50, and 60). Attempts to prepare 4,5-dihydro-4,5-dioxo-1H-[1]-benzopyrano[4,3-b]pyridinecarboxylates from 4-aminocoumarin were unsuccessful.     

Heterocyclic fused tropylium ions VII. On the synthesis of 9H-dithieno[2,1 -b:4,5-c′]tropylium fluoborate and 4H-dithieno[1,2-b:4,5-c′]tropylium fluoborate

9H-Dithieno[2,1 -b:4,5-c′]tropylium ion (III) and 4ii-dithieno[1,2-b:4,5-c′]tropylium ion (IV) have been synthesized by ring-closure of 1-(4-carboxy-3-thienyl)-2-(3′-thienyl)ethane (IX) and 1-(4-carboxy-3-thienyl)-2-(2′-thienyl)ethane (XVI), respectively, followed by bromination-debrom-ination to 9H-cyclohepta[2,1-b:4,5-c′] dithiophen-9-one (XI) and 4H-cyclohepta[1,2-b:4,5-c′]-dithiophen-4-one (XVIII), and finally by reduction and hydride transfer. The tropylium ions III and IV were less stable than the [b,b′]-fused isomers previously studied.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are described.     

Synthesis of 1H-[1,2]diazepino[4,5-b]indole derivatives

A synthesis of four 1H-[1,2]diazepino[4,5-b]indole derivatives and some preliminary information about their biological activity are presented. The starting materials were 2-ethoxycarbonylindoles and 2-ethoxy-carbonyl-3-formylindoles, la, b and 2a, b, respectively. 2-Ethoxycarbonyls la, b reacted with 1-dimethylamino-2-nitroethylene and -2-ethoxycarbonyl-3-formylindoles 2a, b in the presence of nitroalkanes (nitromethane or nitroethane) giving 3-(2-nitrovinyl)indoles 3a, b. Reduction of 3a, b yielded β-(2-oxoalkyl)indoles 4. On reaction with an excess of hydrazine hydrate, compounds 4 gave satisfactory yields of 5-oxo-1H-[1,2]diazepino[4,5-b]indoles 5.