The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 16. [1]benzothieno[2′,3′:4,5]thieno[2,3-c]quinoline and [1]benzothieno[2′,3′:4,5]thieno[2,3-c]naphtho[1,2-f]quinoline

The synthesis of two previously unknown polycyclic heterocyclic ring systems via photocyclization is described. The unequivocal assignment of their proton and carbon spectra was achieved by utilizing two-dimensional nmr techniques.     

Synthesis of new guanidine derivatives from 2′,3′,4′,9′-tetrahydrospiro[piperidine-4,1′-[1H]pyrido[3,4-b]indole]

The reaction of the isothiourea derivative 2 with methylaminc or pyrrolidine resulted in guanidines 3a-3b . Using hydrazine under the same conditions the tetrazole derivative 4 was obtained. On reacting 2 with piperidine, morpholine, methylhydrazine, phenylhydrazine, hydroxylamine or sodium hydroxide, cycliza-tion took place leading to the novel 4-cyanimino-1,2,3,4,6,7,12,12b-octahydro-3,12b-ethanopyrim-ido[1′,6′:1,2]pyrido[3,4-b]indole ( 5 ). Some structural aspects of 5 and other model compounds were analysed mainly by ¹³C nmr spectroscopy.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 19. Thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-f]quinoline,thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[1,2-f][1,2,4]triazolo[4,3-a]quinoline and thieno[3′,2′:4,5]-thieno[2,3-c]naphtho[1,2-f]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-(3-phenanthryl)thieno[2,3-b]thiophene-2-carboxamide ( 5 ) yielded only one of the two possible structural isomers, thieno[3′,2′:4,5]thieno[2,3-c]naphtho[1,2-f]quinolin-6(5H)-one ( 6 ), which was further elaborated to afford the unsubstituted ring system 10 , its triazole 11 and tetrazole 12 . The structural confirmation of 10 was achieved by the total assignment of its ¹H and ¹³C nmr spectra by the concerted utilization of two-dimensional nmr spectroscopic methods.     

Synthesis of thieno[2′,3′(3′,4′ or 3′,2′):5,6]azepino[2,1-a]isoindolediones from N-Thienyl-2(3)-ylmethylphthalimides

Reduction of N-thienybnethylphthalimides 5a-e followed by the Wittig reaction gave the substituted acetic acids 8a-e . Their corresponding acyl chlorides where cyclized in the presence of aluminium trichloride to furnish the cyclic ketones 9a-e . Treatment of these ketones with bromine followed by triethylamine, or with selenium dioxide led to the thienoazepinoisoindolediones 1a-e .     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 17. Thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[2,1-f]quinoline and thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-g]quinoline

The synthesis of two previously unknown novel polycyclic heterocyclic ring systems via photocyclization is described. The structural assignment of the isomeric ring systems, 4 and 5 , was achieved by the total assignment of their ¹H and ¹³C nmr spectra by the concerted usage of two-dimensional nmr methods.     

Synthesis and reduction of thieno[2′,3′(3′,2′ or 3′,4′):5,6]-azocino[2,1-a]isoindole-7, 13-diones

A synthesis of the thieno[2′,3′(3′,2′ or 3′,4′):5,6]azocino[2,1-a]isoindole-7,13-diones 6a-c was developed from N-thienylethylphthalimides 3a-c using a Wittig reaction followed by a Friedel-Crafts cyclization of acetic acid derivatives 5a-c . Reduction of ketones 6a-c into alcohols 7a-c was stereo specific.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 1. Thieno[3′,2′:4,5]thieno[2,3-c]quinoline and thieno[2′,3′:4,5]thieno[2,3-c]quinoline

The synthesis of two previously unknown heterocyclic ring systems, namely, thieno[3′,2′:4,5]thieno[2,3-c]-quinoline and thieno[2′,3′:4,5]thieno[2,3-c]quinoline is reported. These two novel ring systems were assembled by photocyclization of the appropriate anilides.     

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.     

Nitration of dithieno[3,4-b:3′,2′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

The nitration of dithieno[3,4-b:3′,2′-d]pyridine ( 2 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 3 ) has been studied. Nitration of 2 occurred in both positions of the c-fused thiophene ring, while 3 was predominantly substituted in the 2-position. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Nitration of dithieno[3,2-b:3′,2′-d]pyridine and dithieno[3,2-b:3′,4′-d]pyridine

Nitration of dithieno[3,2-b:3′,2′-d]pyridine ( 4 ) and dithieno[3,2-b:3′,4′-d]pyridine ( 5 ) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4-fused ring. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Tricyclic heterocyclic systems: Pyrazolo[5′,4′:4,5]-and pyrazolo-[3′,4′:4,5]pyrano[2,3-b]pyridine derivatives

By reacting 2-chloronicotinoyl chloride with acetyl or benzoyl acetate, ethyl 2-methyl- or 2-phenyl-4-oxopyrano[2,3-b]pyridine-3-carboxylates were prepared. The nucleophilic rearrangement of the latter with hydrazines gave rise to the title compounds.     

Synthesis of 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-thiopyrans] and 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro-[isobenzofuran-1,4′-pyrans]

The 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-thiopyran] ring system ( 2a ) has been prepared from o-bromobenzoic acid. The 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-pyran] ring system ( 3a ) has been prepared from 2-bromobenzhydrol methyl ether. Several 3-(dimethylaminoalkyl) derivatives of both 2a and 3a were prepared by lithiation followed by alkylation.     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

Synthesis of pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidine derivatives

Pyrido [3′,2′:4,5]thieno[3,2-d] pyrimidine and several of its derivatives have been synthesized.     

Synthesis of 7,8,9,10-tetrahydropyrido[3′,4′:4,5]pyrrolo[2,3-c]quinolines

A series of structurally novel 7,8,9,10-tetrahydropyrido[3′,4′:4,5]pyrrolo[2,3-c,]quinolines, 4a-c , were synthesized via a facile Fischer indole cyclization from the appropriately substituted hydrazinoquinolines 2a-c . Acetamides 4a,c were hydrolyzed to 5a,b and further converted to tertiary amines 6a-c . Potent antihypertensive activity has been observed with a number of the title compounds as well as the intermediate 3a .     

The stereochemistry of 1,6,7,12b-Tetrahydro-2H,4H-[1,2] oxazino[3′,4′:1,2]-pyrido[3,4-b]indole and of 1,2,3,6,7,12b-Hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2]pyrido[3,4-6] indole

From an analysis of nmr spectral data, 1,6,7,12b-tetrahydro-2H,4H-[1,3 ]oxazino[3′, 4′ :1,2]-pyrido[ 3,4-b ]indole is shown to exist in solution at room temperature almost entirely in the cis-fused ring conformation with the nitrogen lone pair bisecting the C4 methylene group whereas under the same conditions 1,2,3,6,7,12b-hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2] pyrido-[3,4-b ]indole exists as an approximately 50:50 equilibrium mixture of the cis and trans-fused ring conformations.     

Direct bromination of dithieno[3,4-b:3′,4′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

Bromination of dithieno[3,4-b:3′,4′-d]pyridine ( 1 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 2 ) has been studied. Disubstitution occurred at both positions of the C ring. The substitution pattern is found to be similar to that of the nitration reaction. The structures of bromo derivatives were established by ¹H and ¹³C nmr spectroscopy.     

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 ).