Identification of alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines in roasted meat flavor. Model reaction used as basis for natural product formation and new synthesis (author's transl)]

Identification of alkyl-5H-6,7-dihydrococyclopenta[b]pyrazines in roasted meat flavor. Model reaction used as basis for natural product formation and new synthesis. Seven alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines have been identified in a roasted meat aroma obtained by thermolysis of the hydrosoluble flavor precursors of raw meat. Formation of these heterocyclics by condensation of hydroxycyclopentenones with aliphatic α-dicarbonyl compounds in the presence of ammonia has been confirmed by a model reaction. Alkyl-5H-cyclopenta[b]pyrazines and dicyclopenta [b,e]pyrazines are also obtained from this reaction, but have not yet been identified in roasted flavors. Preparation of the intermediates of the model reaction enabled development of an economical synthesis of 2,3,5-trimethyl-5H-6,7-dihydrocyclopenta[b]pyrazine.     

Pyrazines. 2ème communication [1]. II. Synthèse de dihydro-6,7-5H-cyclopenta[b]pyrazines alkylées

Alkyl-5H-6,7-dihydrocyclopenta[b]pyrazines are prepared by condensation of cyclopentenolones with alkylenediamines or of aliphatic α-diketones with 1,2-diaminocyclo pentanes. Products so obtained were dehydrogenated using palladium on activated charcoal, or copper chromite. NMR. and mass spectra are given for 21 bicyclic pyrazines and intermediates, and their IR. spectra are compared.     

An efficient synthesis of benzylidene-2-alkoxy-4-aryl-2,3-cycloalkenopyridine-3-carbonitrile derivatives

An efficient procedure for the synthesis of a novel class of benzylidene-2-alkoxy-4-aryl-6,7-dihydro-5H-cyclopenta[b]pyridine-, -5,6,7,8-tetrahydroquinoline and/or -6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile was introduced through the one-pot multi-component reaction of cyclopentanone, cyclohexanone, and/or cycloheptanone with different aromatic aldehydes and malononitrile. The same products were also produced by classical route by the two-component reaction of dibenzylidine cyclopentanone, cyclohexanone, and/or cycloheptanone derivatives with malononitrile. The reactions were achieved using sodium alkoxide solution as catalyst and reagent.     

Inhibitors of platelet aggregation. 4. [1,2,5]Thiadiazolo[3,4-c]acridines, 7,8,9,10-Tetrahydro[1,2,5] thiadiazolo[3,4-c]acridities,and 8,9-Dihydro-7H-cyclopenta[b][1,2,5] thiadiazolo[3,4-H]quinolines

The condensation of 4-amino-2,1,3-benzothiadiazole (IV) with diphenyliodonium-2-earboxylate gave N-(2,1,3-benzothiadiazoI-4-yl)anthranilic acid (V) (28%), which was cyclized with phosphorus oxychloride to 6-chloro[1,2,5]thiadiazolo[3,4-c]acridine (VI) (84%). Treatment of VI with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol afforded 6-[ [3-(dimethylamino)-propyl]thio] [1,2,5]thiadiazolo[3,4-c]acridine (VII) (65%). The reaction of IV with a mixture of methyl and ethyl 2-oxocyclohexanecarboxylate gave the adduct, which was ring closed in Dowtherm to 7,9,10,1 1-tetrahydro[1,2,5] thiadiazolo[3,4-c]acridin-6(8H)one (VIII) (70%). Chlorination of VIII with phosphorus oxychloride gave 6-chloro-7,8,9,10-tetrahydro[1,2,5]thiadiazolo[3,4-c]acridine (IX) (84%), which was condensed with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol yielding 6-[ [3-(dimethylamino)propyl]thio]-7,8,9,10-tetrahydrof 1,2,5]-thiadiazolo[3,4-c]acridine (X) (27%). 6-[ [3(1)imethylamino)propyl]thio]-8,9-dihydro-7H-cyclopenta[b] [1,2,5]thiadiazolo[3,4-h]quinoline (XIII) (25%) was prepared similarly from IV and a mixture of methyl and ethyl 2-oxocyclopentanecarboxylate via 7,8,9,10-tetrahydro-6H-cyclopenta[b][1,2,5]thiadiazolo[3,4-h]quinolin-6-one (XI) (85%) and 6-chloro-8,9-dihydro-7H-cyclopenta[b][1,2,5]thiadiazolof3,4-h]quinoline (XII) (56%). The effects of compounds VII-XIII as inhibitors of platelet aggregation are discussed.     

Synthesis of new thienocyclopenta[3,2-d]-oxazole and thiazole derivatives

Synthesis of thieno[2′,3′:5,4]cyclopenta[3,2-d]oxazole and thiazole derivatives are achieved by insertion of carbon dioxide and disulfide into 4-amino-5-chloro-5,6-dihydro-4H-cyclopenta[b]thiophen-6-one.     

Cross-recyclization of 4-aryl-2,6-diamino-4<Emphasis Type="Italic">H</Emphasis>-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene: New route to 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-[1]pyrindine-3-carbonitriles and their derivatives

Reaction of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene led to the formation of 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-3-carbonitriles used in the synthesis of substituted 2-alkylsulfanyl-4-aryl-6,7-dihydro-5H-[1]pyrindine-3-carbonitriles and 3-amino-4-aryl-6,7-dihydro-5H-cyclopenta[bthieno[3,2-e]pyridines.     

A Convenient Synthetic Approach to Newly Condensed Pyrazoloazines Based on Pyrazolo[3,4-b]pyridine

The reaction of 6-amino-5-cyano-3-methyl-1H-1-phenylpyrazolo[3,4-b]pyridine ( 2 ) and 6,7-dihydro-3-methyl-6-oxo-1H-1-phenylpyrazolo[3,4-b)]pyridine-5-carbonitrile ( 3 ) and 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]-1H-pyrazolo[4′,3′-e]pyridine ( 12 ) with different reagents have been conducted to give newly condensed pyrazoloazines.     

Cyclopenta[b]thienyl ligand in organometallic chemistry. Studies of the regioselectivity of the synthesis of new σ-element-substituted cyclopenta[b]thiophene derivatives

Reactions of 2-ethyl-5-methylcyclopenta[b]thienyllithium (thiopentalenyllithium) (2) with various electrophilic reagents afford σ-element-substituted thiopentalenes. However, the reaction with Ph₃SnCl yields only one of two possible isomers,viz, triphenyl(4H-cyclopenta[b] thiophen-4-yl)stannane (4c), whereas the reactions with Me₃SiCl, Me₃SiCl, or Ph₂PCl give both possible isomers,viz., trimethyl(6H-cyclopenta[b]thiophen-6-yl)silane (3a) and trimethyl(4H-cyclopental[b]thiophen-4-yl)silane (4a), trimethyl(6H-cyclopenta[b]thiophen-6-yl)stannane (3b) and trimethyl(4H-cyclopental[b]thiophen-4-yl)stannane (4b), or diphenyl(6H-cyclopenta[b]thiophen-6-yl)phosphine (3d) and diphenyl(4H-cyclopenta[b]thiophen-4-yl)phosphine (4d) in ratios of 1∶2, 1∶2, or 1∶1, respectively. The structure of compound4c was established by X-ray diffraction analysis. The observed regioselectivity of formation of compound4c is attributed to the specific precoordination of the tin atom by the sulfur atom of the thiopentalenyl ligand and to the steric overcrowding of the Sn atom in organotin electrophiles. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1285–1289, July, 2000.     

Synthesis of new fluorine-containing pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridinones as promising drug precursors

Methods for the synthesis of 4-R-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones (R = CF₂SAr and 4-CFHSAr) were developed. The derivatives with R = CF₂SAr were obtained by both heterocyclization of 1-substituted 5-aminopyrazoles with ethyl 4,4-difluoro-3-oxo-4-phenylsulfanylbutanoate and replacement of the Br atom in 4-bromodifluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. The fragment 4-CF-HSAr was introduced by replacement of the Cl atom in 4-chlorofluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. Oxidation of 4-CF₂SPh-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones gave the corresponding sulfoxides; their structures were confirmed by X-ray diffraction data.     

Aza-2-dienes-1,3. Partie 5. Préparation de N-aminoimidazoles, 3H-pyrroles,triazolo[1,2,4][1,5-a]pyrazines et imidazo[1,2-a]pyrazines

2-Aza-1,3-dienes. Access to N-Aminoimidazoles, 3H-Pyrroles, [1,2,4]Triazolo[1,5-a]pyrazines, or Imidazo[1,2-a]pyrazines Nucleophilic attack of 5-(dialkylamino)-2-aza-1,3-diene-1,1-dicarbonitriles (or their 1-methoxycarbonyl analogous) by hydrazines or hydrazdes gives substituted N-aminoimidazoles, [1,2,4]triazolo-[1,5-a]pyrazines, or α-dihydrazino derivatives. With α-amino esters (or analogous), imidazo[1,2-a]pyrazines are produced. Addtion of cyanide anions occurs also with formation of substituted 3H-pyrroles. Structures and rationalisation of this nucleophilic attack are discussed.     

Single-crystal X-ray diffraction analysis of arylamine-containing 2,2′-bipyridine derivatives

The structures of six 2,2′-bipyridine derivatives containing aromatic amine moieties, namely N-aryl-4-aryl-1-(pyridin-2-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-3-amines, were studied by single-crystal X-ray diffraction. The molecular structures and the effect of the substituents of these compounds on the crystal packing are discussed.

     

Synthesen mit Nitrilen, 20. Mitt.: Untersuchungen über den Farbstoff aus Acenaphthenchinon und Malonitril

Zusammenfassung Malonitril und Acenaphthenchinon reagieren bei Anwesenheit von Basen zum blau gefärbten 6b-Hydroxy-8-imino-7,8-dihydro-6bH-cyclopenta [a]acenaphthylen-7,7,9-tricarbonsäurenitril (5). Kondensation mit Acenaphthenon führt zum 1-Dicyanmethylen-acenaphthen (7) bzw. zum 8-Amino-acenaphtho-[2,1—j]fluoranthen-7-carbonsäurenitril (9).

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The reaction of malononitrile and acenaphthenequinone in the presence of bases yields a blue compound, 6b-hydroxy-8-imino-7, 8-dihydro-6bH-cyclopenta[a]acenaphthylene-7,7,9-tricarbonitrile (5). Condensation with acenaphtenone gives 1-dicyanomethyleneacenaphtene (7) and 8-aminoacenaphtho[2,1—j]fluoranthene-7-carbonitrile (9), resp.

     

Synthesis of 3-alkyl-1,4-dihydrocyclopenta[b]indoles: unexpected formation of dimeric compounds

Acid-catalyzed dehydration of 3-alkyl(aryl)-4-methyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-ols gives dimeric derivatives of 3-alkyl(aryl)-4-methyl-1,4-dihydrocyclopenta[b]indole.     

Synthesis of cyclopentathiophenacetic acid derivatives. Reactivity of methyl 6-oxo-4,5-dihydro-6H-cyclopenta[b]thiophen-4-acetate

Oxodihydrocyclopentathiophenacetic acids 4 , 5 and 6 were synthesized from suitable 2- or 3-formylthiophenes. Reactivity of the carbonyl group or the carboxylic group of these bicyclic systems was investigated. The Beckmann rearrangement of methyl 6-oximino4,5-dihydro-6H-cyclopenta[b]thiophen-4-acetate 12 is an interesting route to methyl 7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-acetate ( 13 ).     

Synthesis of new hetero[1,2,4]thiadiazin‐3‐one S,S‐dioxides and oxazolo[3,2‐b]hetero[1,2,4]thiadiazine S,S‐dioxides as potential psychotropic drugs

A series of 2‐substituted 2H‐thieno[3,4‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 2 ), 2‐substituted 2H‐thieno[2,3‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 3 ), 2‐substituted 4,6‐dihydropyrazolo[4,3‐e]‐[1,2,4]thiadiazin‐3(2H)‐one 1,1‐dioxides ( 4 ), 2‐substituted 2,3‐dihydrooxazolo[3,2‐b]thieno[3,4‐e]‐[1,2,4]thiadiazine 5,5‐dioxides, ( 5 ), 6‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thia‐diazine 9,9‐dioxides ( 6 ) and 7‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thiadiazine 9,9‐dioxides ( 7 ) were synthesized as potential psychotropic agents.     

Synthesis of some 3-alkenyl-4-oxo-6,7-dihydro-4H-pyrano[3,4-d]isoxazoles

A series of 3-alkenyl-4-oxo-6,7-dihydro-4H-pyrano[3,4-d]isoxazole derivatives was prepared by reaction of hydroxylamine with 4,5-dioxo-2,3,7,8-tetrahydro-4H,5H-pyrano[4,3-b]pyran derivatives.     

Studies on sulphur heterocycles. Reactions of 6,7-dihydrobenzo[b]thiophen-4(5H)one derivatives and their conversion to 7-substituted thieno[2,3-h][1]benzopyran-8-ones

Cyclization of γ-(2-thienyl)butryic acid with acid anhydrides gives 2-acyl derivatives as well as the expected 6,7-dihydrobenzo[b]thiophen-4(5H)one. Several reactions of these ketones have been studied including their conversion to 0,0-diethyl thiophosphonohydrazones. 7-Substituted thieno[2,3-h][1]benzopyran-8-ones have been prepared via 4-hydroxybenzo[b]thiophen-5-carbaldehydes.     

Organische photochemie XXI. 9H-cyclopenta[b] [1]benzoselenin -ein neues heterocydisches ringsystem

By way of a photo-induced selenolester-seleninone rearrangement, the derivative 5 of a new heterocyclic ring system, 9H-cyclopenta[b][1]benzoselenin, has been formed. This rearrangement occurs via a new photosubstitution reaction of S-aryl- in competition with Se-aryl-groups, followed by photocyclization using 2-p -tolythiocyclopentene -1 - selenocarbonic acid Se-p-tolylester (1a) as starting materials. As a competing product in this photo-rearrangement, a second heterocycle, 7-methylcyclopenta[b] [1]benzothiopyrone (4) (9) has been formed via an intramolecular photochemical Friedel Crafts reaction.     

Synthesis of tricyclic and tetracyclic thieno[3,2-f]-1,4-thiazepines

Treatment of 5-methylthio-2,3-dihydrothieno[3,2-f]-1,4-thiazepine ( 9 ) with acylhydrazines gave 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepines 10, 11 , and that of 9 with ethyl anthranilate gave 5,6-dihydrothieno[3′,2′:6,7][1,4]thiazepino[5,4-b]quinazolin-8-one ( 14 ). Reaction of 9 with hydrazine hydrate or 4-chlorophenylhydrazine afforded 5-hydrazino compounds 12, 15 , which were subsequently cyclized to ethyl 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepine-3-carboxylate ( 13 ), 2-(4-chlorophenyl)-5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepin-3(2H)-one ( 16 ) and 2-(4-chlorophenyl)-6,7-dihydro-2H-thieno[3,2-f][1,2,4]triazino[4,3-d][1,4]thiazepine-3,4-dione ( 17 ). New thieno-anellated heterocycles were prepared with the aim of studying their affinity for the benzodiazepine receptors.     

A process for the preparation of 1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole

A synthesis of 1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole is described exemplifying a new synthetic route to medicinally interesting compounds. The key step involves a cyclization of 2-(2,3,3a,8b-tetrahydrocyclopenta[b]indol-4(1H)-yl)-ethanamine with aqueous formaldehyde in the presence of trifluoroacetic acid.