Synthèses dans la série des bis-indéno-fluorènes,VI [1] Dihydro-12, 15–6H-bis-indéno[1. 2-b; 2′.1′-h]fluorène et dihydro-14, 15–8H-bis-indéno[2. 1-a; 2′. 1′-h]fluoréne

Starting from cyclohexene and 2, 2′, 5, 5′-tetramethylbiphenyl the linear bisindenofluorene 12, 15-dihydro-6H-diindeno [1.2-b; 2′.1′-h] fluorene (XX) has been synthesized in 5 steps (overall yield 27%). As an intermediate product the 6, 12, 15-trioxo-derivative XIX (greyish green crystals, blue alcaline vat) was obtained. By a side way, the 6-oxo-derivative of XX and the already known monoangular bis-indenofluorene 14, 15-dihydro-8H-diindeno [2.1-a; 2′.1′ -h] fluorene (XXVII) were also obtained. XX can also be prepared in several steps starting from 3-methyl-fluorene or fluorene.     

Synthèses dans la série des bis-indéno-fluorénes III [1]. Dihydro-14, 15-13H-bis-indéno[2,1-a;1′,2′,-i]fluorène et dihydro-14, 15-8H-bis-indéno [2, 1-a;2′,1′-h]fluorène

Starting from 2-bromo-9-oxo-fluorene-1-carboxylic acid the biangular bis-indenofluorene 14, 15-dihydro-13H-diindeno[2, 1-a; 1′, 2′-1]fluorene (VIII) and the monoangular 14, 15-dihydro-8H-diindeno[2, 1-a; 2′, 1′-h]fluorene (XI) have been synthesised in 6 resp. 7 steps (overall yield 22% resp. 18%). As intermediate compounds the 14-oxoderivatives of VIII and XI were also obtained.     

Synthèses dans la série des bis-indéno-fluorènes I. Le dihydro-13, 15-5H-bis-indéno[1, 2-a;1′, 2′-h]fluorène

The synthesis of 13,15-dihydro-5H-diindeno[1,2-a;1′,2′-h] fluorene in six steps starting from flourenone 4-carboxylic acid and 2,4-dichlorotoluene is described. As an intermediate product the 5, 13, 15-trioxo-derivative is obtained.     

Synthèses dans la série des bis-indéno-fluorènes,VIII. Méthyl-6-dihydro-9,15-7H-bis-indéno[2.1-b;2′.1′-g]fluorène

Starting from 5-benzoyl-2,4-dibromobenzoic acid and 3-methyl-fluorene, the 6-methyl-9,15-dihydro-7H-diindeno[2.1-b; 2′,1′-g]fluorene, a derivative of a mono-angular diindenofluorene has been synthesized in 5 steps (overall yield 1,5%).     

Synthèses dans la série des bis-indéno-fluorènes,IX. Le dihydro-13,15-7H-bis-indéno[2.1-b; 2′.1′-h]fluorène et son dérivé méthylé en position 6

By condensation according Ullmann of 2-iodo-9-oxo-fluorene with 3-bromo-2-cyano-9-oxo-fluorene, followed by cyclisation and reduction, the new linear 13,15-dihydro-7H-diindeno[2.1-b; 2′.1′-h]fluorene (III) is synthesized in 3 steps. The 6-methyl-derivative of II is also obtained in a similar way.     

Synthèses dans ka série des bis-indéno-fluorènes II. Le dihydro-10,15-5H-bis-indéno [1, 2-a;2′,1′-i] fluorène

The biangular bis-indeno-fluorene 10,15-dihydro-5H-diindeno [l, 2-a; 2′, 1′-i]-fluorene (XII) has been synthesised in 6 steps starting from 1-(o-carboxyphenyl)-fluorenone (overall yield 21%). As an intermediate the 5,10,15-trioxoderivative of XII and, accessorily, its 5,10-dioxoderivative were also obtained.     

Synthèses dans la série des bis-indéno-fluorènes IV [1] Hydroxy-8-dihydro-9, 15-7H-bis-indéno[2, 1-b;2′, 1′-g]fluorène

8-Hydroxy-9, 15-dihydro-7H-diindeno [2, 1-b;2′, 1′-g] fluorene, a derivative of a new mono-angular diindenofluorene system, has been synthesised in 6 steps (overall yield 42%) starting from 9-oxo-fluorene-1-carbaldehyde and acetophenone. The corresponding hydrocarbon could not be obtained by reductive scission of the hydroxyl group.     

Nitrogen bridgehead compounds. Part 55 Synthesis of substituted 7,8-dihydro-5H,13H-indolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5-ones

Fischer indolization of 6-arylhydrazono-6,7,8,9-tetahydro-11H-pyrido[2,1-b]quinazolin-11-ones 1 afforded substituted 7,8-dihydro-5H,13H-indolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5-ones 3-12 in high yields.     

Synthesis of 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine

4-Methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 3 ) was synthetized from 2-acetylfuro[3,2-f]benzo[b]furan ( 4 ) or from 2-acetyl-5,6-dihydrofuro[3,2-f]benzo[b]furan ( 10 ). The key step involves a rearrangement-cyclization of azides 6 and 12 to form 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridin-1(2H) one ( 7 ) and 8,9-dihydro-4-methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin-1(2H)-one ( 13 ). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1-chloro-4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 8 ).     

Synthesis and proton NMR stereochemical study of 7,8,9-substituted-7,8-dihydro-4H,9H-furo[2′,3′,4′:4,4a,5]-naphth[2,1-e][1,3]oxazin-4-ones

7,8,9-Substituted-7,8-dihydro-4H,9H-furo[2′,3′,4′:4,4a,5]naphth[2,1-e][1,3]oxazin-4-ones were stereospecifically obtained as a single pair of enantiomers. Their relative trans configuration and the conformation of the dihydro oxazine ring were established by ¹H nmr 2D NOESY experiments.     

Simultaneous Formation of 8H-Isoquino[2,1-b][2,7]naphthyridin-8-ones and 13H-Pyrido[4′,3′:3,4]pyrrolo[2,1-b][3]benzazepin-13-ones,a Novel Potential Alkaloidal System

Condensation of 3,4-dihydro-6,7-dimethoxyisoquinoline ( 4 ) with 4-methylnicotinoyl chloride ( 12 ) in refluxing pyridine gives 5,6,13,13a-tetrahydro-2,3-dimethoxy-8H-isoquino[2,1-b][2,7] naphthyridin-8-one ( 11 ), along with some of its 13,13a-didehydro derivative 7 . A similar reaction of 4 with 4-(chloromethyl)nicotinoyl chloride ( 14 ) affords, in addition to 7 , the isomeric product 10,11-dihydro-7,8-dimethoxy-13H-pyrido[4′,3′:3,4]pyrrolo[2,1- b][3]benzazepin-13-one ( 3 ). Analogous pairs of products are obtained from 3,4-dihydro-6,7-(methylenedioxy)- and 3,4-dihydro-6,7,8-trimethoxy-isoquinolines ( 15 and 18 , resp.). The structure of 3 was established by extensive NMR data and confirmed by single-crystal X-ray studies. Structure 7 has the ring system of the Alangium alkaloids like alangimarinc ( 1 ), while the isomeric ring system 3 is predicted to be present in nature on biogenetic reasoning.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

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.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Polycyclic N-heterocyclic compounds. XLI. Synthesis of 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines, 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors

As a series of polyheterocyclic compounds for exploitation as anti-platelet agents, tricyclic heterocyclic compounds, 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines 3–6, 9, 12–14 , and 16–26 , having nitrogen, oxygen, or sulfur containing functional groups at the 4-position, were prepared. In addition, tetra-cyclic heterocyclic compounds, 3-methyl-1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzaze-pinium chloride ( 7 ), 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines 10a-e , 2,3,6,7-tetrahydro-1H 5H-pyrimido[1′,2′:1,6]pyrimido[5,4-d][1]benzazepine ( 11 ), and 1,2,5,6-tetrahydro-4H-thiazolo-[3′,2′:1,6]pyrimido[5,4-d][1]benzazepinium chloride ( 15 ) via ring closure of 4-(hydroxyalkylamino)- 6, 9a-e , and 3c , and 4-(2-hydroxyethylthio)-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepine ( 14 ) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen-induced aggregation of rabbit blood platelets in vitro were investigated. Among them, compound 5 having a morpholino group at the 4-position on the tricyclic nucleus, which enhanced the activity more than 14-fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.     

Research on nitrogen containing heterocyclic compounds. XVII. Synthesis of 8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine,a novel tetracyclic ring of pharmaceutical interest

The synthesis of 8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine 6 , a novel nitrogen-containing tetracyclic ring, is reported starting from 5H-imidazo[2,1-c][1,4]benzodiazepine 7. Reaction of this compound with nitromethane and subsequent reduction of the obtained nitromethyl derivative 8 afforded 11-aminomethyl-10,11-dihydro-5H-imidazo[2,1-c][1,4]benzodiazepine 9. Treatment of the latter compound with formaldehyde led to 1,2,3,3a-tetrahydro-8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine 10 , which was then oxidized to the title compound.     

The synthesis of novel polycyclic heterocyclic ring systems. 3. Synthesis and NMR spectroscopy of 15-chloro[1]benzo-thieno[2″,3″:3′,4′]naphtho[1′,2′:4,5]thieno[2,3-c]quinoline

The polycyclic heterocyclic compound with a novel ring system, 15-chloro[1]benzothieno[2″,3″:3′,4′]-naphtho[1′,2′:4,5]thieno[2,3-c]quinoline was synthesized via photocyclization of 3-chloro-N-phenyl[1]-benzothieno[2′,3′:3,4]naphtho[2,1-b]fhiophene-2-carboxamide followed by chlorination with phosphorus oxychloride. The assignment of its ¹H and ¹³C nmr spectra was accomplished by utilizing two-dimensional nmr methods.     

Naphtho[1′,2′:5,6]pyrano[2,3–6][1,5]benzodiazepine Derivatives

The reaction of 3-(dimethylamino)-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (Ia) with o-phenylenediamines or N-monosubstituted o-phenylenediamines in refluxing glacial acetic acid afforded the corresponding naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(8H)ones V in very good yields. A similar result was achieved when the reaction was carried out in refluxing pyridine, using N-monosubstituted o-phenylenediamine hydrochlorides. The isolation of a significant intermediate as well as the synthesis through a different univocal pathway confirmed the structure of the compounds V. Moreover the reaction of Ia with N-monosubstituted o-phenylenediamines in refluxing pyridine generally afforded only low yields of compounds V, sometimes together with naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(13H)ones VII, isomers of V.     

The synthesis and transformations of 2H-naphtho-[1,2-b]pyran-2-one derivatives. Naphtho[2′,1′:5,6]-pyrano[3,4-d][1,3]oxazines and naphtho[1′,2′:5,6]pyrano[3,4-d]-pyrimidines,derivatives of two new heterocyclic systems

1,4-Naphthoquinone ( 1 ) was transformed with alkyl 2-aminofumarates 2 into 2H-naphtho[1,2-b]pyran-2-ones 3 and 4 , which served as intermediates in the synthesis of 7, 8 and 13 , which are derivatives of two new heterocyclic systems: naphtho[2′,1′:5,6]pyrano[3,4-d][1,3]oxazine and naphtho[1′,2′:5,6]pyrano[3,4-d]pyrimidine.     

Synthesis of spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones,spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones and spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones via transannular reactions of eight membered ring intermediates

An auto oxidation-rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5-trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2-b]indol-10-ones 1–3 with sodium periodate to give isoindolo[2,1-a]-indole-6,11-diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones 8–10 , spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones 11–13 and isoindole[1,2-a:2′,1′-b]pyrimidine-5,15-diones 15, 16 in high yields. Analogous reactions were performed on 3-amino-5a, 10a-dihydroxybenzo[b]indeno[2,1-d]furan-10-one ( 17 ) to give a dibenzoxocintrione 18 , spiro-[benzofuran-2,1′-isobenzofuran]-3,3′-dione 19 and an isoindol-1-one 20 .