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. 4. Synthesis of 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines

Thirteen 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines 11 have been synthesized in three steps from 4-amino-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene ( 6 ), which was obtained from the reduction of either 4-azido 4 or 4-hydroxyimino 5 derivatives. All the compounds have been evaluated as potential antidepressive agents.     

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 .     

Beiträge zur Chemie der 4-Hydroxyindol-Verbindungen 10. Mitteilung über synthetische indolverbindungen [1]

Catalytic hydrogenation of 4-benzyloxyindoles does not stop at the hydroxyindole stage, but slowly leads to the 4,5,6,7-tetrahydro-4-ox-indoles 3 . Some procedures for the selective preparation of 4-hydroxyindoles 2 are described. When 4-benzyloxy-3-(1-hydroxyimino-ethyl)-indole ( 4c ) is warmed with trifluoroacetic acid, cleavage of the ether results as well as partial benzylation of the free hydroxyindole in the position 5 ( 5a, 5b ); no Beckmann rearrangement is observed. Esters of 4-benzyloxy-indole-2-carboxylic acid are formylated with POCl₃/dimethylformamide in the 7-position to give 7a ; in the corresponding dimethylamide, on the other hand, the formyl group enters the 3-position to give 8 . Both 4- and 7-hydroxyindole are oxidized with Frémy's salt to the 4, 7-quinone 13 ; on reduction this yields 4, 7-dihydroxyindole 14 , which is tautomerized by base-catalysis to 5, 6-dihydro-4, 7-dioxo-indole 15 . The course of the etherification of 4-hydroxyindoles with epichlorohydrin and related compounds is described, and the resulting side-chains are characterized by their NMR. spectra.     

Synthesen von Mannich-Basen von Hydroxy-indolen. 3. Mitteilung über synthetische Indol-Verbindungen [1]

The reactivity of hydroxy-indoles under the conditions of the Mannich-reaction has been studied. The electrophilic side-chain enters in each case in a position ortho to the phenolic group. 4-Hydroxy-indole is substituted in the 5-, 5-hydroxy-indole in the 4-, 6-hydroxy-indole in the 7-, and 7-hydroxy-indole probably in the 6-position. The structures of the Mannich bases from 4-, 5- and 6-hydroxy-indole have been confirmed by comparison of the hydroxy-methyl-indoles obtained by reductive desamination with hydroxy-methyl-indoles prepared by unambiguous total synthesis.     

Der FISCHER'sche Indolringschluss mit 1, 3-disubstituierten 4-Piperidonen. 7. Mitteilung über synthetische Indolverbindungen [1]

Treatment of the arylhydrazones of 1, 3-disubstituted 4-piperidones with ethanolic hydrogen chloride (FISCHER reaction conditions) affords 1, 2, 3, 4-tetrahydropyrimido [3, 4-a]-indoles in good yields. During catalytic hydrogenation in the presence of protons these tetrahydropyrimido-indoles are split into 2-(2-methylamino-ethyl)-indoles. The formation of these tricyclic products can be explained by rearrangement immediately following the normal FISCHER reaction. If the substituent at the piperidine nitrogen is an acyl group, normal or rearranged products are formed, depending on the nature of the 3-substituent.     

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.     

Präparative Verwendung von Mannich-Basen von Hydroxy-indolen als Alkylierungsmittel. 4. Mitteilung über synthetische Indol-Verbindungen [1]

The MANNICH bases 4-dimethylaminomethyl-5-hydroxy-indole and 7-dimethylaminomethyl-6-hydroxy-indole are suitable agents for alkylating C-acidic compounds such as nitroalkanes and ethyl formamido-malonate. The products obtained have been transformed into (substit.) aminoethyl derivatives or amino-acids containing the basic side-chain in the benzene nucleus and which are, therefore, isomeric to tryptamines and tryptophans.     

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.     

New heterocyclic systems. Benzo[4,5]cyclohepta[1,2-b]pyrrole and benzo[5,6]cyclohepta[1,2-f]pyrrolizidine derivatives

The synthesis of the polycyclic pyrrole acetic acids 9e, 13e and 13g by multistep processes from 1-bromo-4-phenylbutan-2-one ( 6c ) is reported. An instance of the use of the 2-chloroethyl moiety as a pyrrole nitrogen protecting group is described. The α-methylaminoketone ( 6e ) was synthesised by a novel two step process from 6c and methyl N-methylformimidate ( 12 ).     

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.     

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.     

Chemische und pharmakologische Studien über Derivate des Benzo[de]chinolins. II. 10.Mitteilung über natürliche und synthetische Isochinolinderivate

Chemical and Pharmacological Studies on Derivatives of Benzo[de]quinoline, II Spirocompounds of type V ( 12–18 ) were synthesized by a carbenium ion cyclization reaction of the intermediates 7 and 11 , respectively. 7 was prepared from 2-oxocyclopentanepropionic acid via 1, 2 , and 4–6; 11 from the same starting material via 1, 2 , and 8–10 . - The spiro[7H-benzo[de]quinolin-7,1′-cyclohexan]-2′-one 27 and other compounds of type VI could be synthesized from the (1-isoquinolinyl)ethyl-cyclohexanone 25: 25 is hydroxylated to the hydroxyketone 26 ; treatment of 26 with a mixture of sulfuric acid and oleum gives 27 . The structure of 27 has been proved by transformation into the known spirocyclohexane 33 . - Aporphine analogues of type VII ( 38, 39 ) were synthesized from the cyclic ketone 34 via either the formylketone 35 and its methyl vinyl ketone adducts 36 and 37 or the methyl ethynyl ketone adduct 40 . Compound 40 has also been cyclized to the 10-hydroxy-aporphine 42 . 9 compounds of the types mentioned have been screened for hypotensive action in rats, and partly in cats and dogs. Only compound 13 · HCl proved to be (moderately) active in rats and dogs.     

Synthese von 1, 2-Dimethyl-phenanthro[1,2-b]furan und 1-Äthyl-2-methyl-phenanthro[1,2-b]furan. Furanabkömmlinge, 26. Mitteilung

We describe here the synthesis of 1,2-dimethyl-phenanthro [1,2-b] furan ( 11 ) and 1-ethyl-2-methyl-phenanthro [1,2-b] furan ( 13 ). The starting material was the known ethyl 2-methyl-phenanthro [1,2-b] furan-1-carboxylate ( 4 ). The two synthetized substances were characterized by their UV.-, IR.-, NMR.- and mass spectra, and identified with two products obtained by selenium dehydrogenation of anhydrohirundigenin.     

A new route to benzo[4,5]cyclohepta[1,2-b]naphthalenes: synthesis of radermachol

[formula: see text] Condensation of 3-phenylsulfonyl-1,3-isobenzofuranone (3) with benzocyclohept-6,7-en-5-ones such as 4 and 15 provides a straightforward, general method for synthesis of functionalized benzo[4,5]cyclohepta[1,2-b]naphthalenes (e.g., 5 and 16). This finding was used to achieve a brief and efficient preparation of 6,7-benzo-3,4-(1,4-dimethoxy-2,3-naphtho)-1,5-dioxosuberane (2), an established intermediate to the naturally occurring red pigment radermachol (1).     

Notiz über Methoden zur Umwandlung von 1,2-Dicarbonsäuren in konjugiert ungesättigte Monocarbonsäuren. Über synthetische Methoden, 12.Mitteilung

A Note on Methods for the Transformation of 1,2-Dicarboxylic Acids into α, β-Unsaturated Monocarboxylic Acids. A model study using the Diels-Alder adduct of maleic anhydride and butadiene (see scheme 3) exemplifies the conversion of the succinic acid type of structure into α, β-unsaturated carboxylic acids via two complementary fragmentations of 3,6-dioxo-perhydro-1,2-oxazine derivatives.