The synthesis of novel polycyclic heterocyclic ring systems.. Benzo[e][1]benzothieno[3,2-g][1]benzothiophenes

The novel polycyclic heterocyclic ring system compound, methyl 3-chlorobenzo[e][1]benzothieno-[3,2-g][1]benzothiophene-2-carboxylate was synthesized. The assignment of its ¹H and ¹³C nmr spectra was also accomplished by utilizing two-dimensional nmr methods.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 5. [1]Benzothieno[2,3-c]naphtho[2,1-f]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline

Two previously unknown heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[2,1-f]quinoline ( 4 ) and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline ( 5 ) were synthesized via photocyclization of 3-chloro-N-(2-phenanthryl)benzo[b]thiophene-2-carboxamide ( 8 ) followed by chlorination and dechlorination. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing inverse-detected HMQC and HMBC two-dimensional nmr spectroscopic methods.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine

s-Triazolo[4,3-b]pyridazine (I) photochemically reacted with cyclooctene, cyclododecene, bicyclo[2.2.2]oct-2-ene, bicyclo[2.2.1]hept-2-ene and indene to form tri and tetracyclic triazoles (II-X). Generally, two or more products were formed. For example the reaction with cyclooctene gave 4a,5,7,8,9,10,10a,11-octahydro-11-methylene-6H-cycloocta[4,5]-pyrrole[1,2-b]-s-triazole (II) and the corresponding 11-cyanomethyl product (III). When I was reacted with open chain alkenes, various isomers of the substituted pyrrolo[1,2-b]triazoles (XI-XV) were formed. Since the reaction was not stereospecific, cycloaddition must be a two step process.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 7. [1]Benzothieno[2,3-c]naphtho[2,1-h]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-h][1,2,4]triazolo[4,3-a]quinoline

The synthesis of two novel polycyclic heterocyclic ring systems via photocyclization is described. These are [1]benzothieno[2,3-c]naphtho[2,1-h]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-h][1,2,4]triazolo[4,3-α]-quinoline. In the ¹H nmr spectrum the proton at position 6 is strongly deshielded in the first ring system while the proton at position 6 in the second ring system is shifted considerably upfield while the proton at position 8 in the second ring system is the most deshielded proton in that ring system. The bay regions in both ring systems are severely congested.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo [4,3-b] pyridazine,III

s-Triazolo[4,3-b]pyridazine (I) reacted photochemieally with bieyélo[2.2.1] hepla-2,5-diene, 1,5-cyclooctadiene, 1,3-cyclooctadiene, methylene cyclohexane, diethyl cis-1,2,3,6-tetrahydro-phthalate and ethyl 2-cyclopentene-1-acetate to givt: the following products: the endo and exo isomers of 4a, 5, 8a, 9-tetrahydro-9-rnethylene-5,8-rnethano-8H-s-triuzolo[1, 5-a]indole (II) and the endo and exo-9-cyanometliyl products (III and IV) from bicyclo[2.2.1] hepta-2,5-diene; 4a,5,-9, 10, 10a, 11-huxahydro-11-methylene-6H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole (V) and the 11-cyanomethyl product VI from 1,5-cyclooctadiene: 4a,7,8,9,10,10a-hexahydro-11 -inethylene-11H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole(VII),4a, 5, 7, 8, 10a, 11-hexahydro-11-methylene-6H-cycloocta[4,5]pyrroIo[1,2-b]-s-triazole (VIII) and their respective 9-cyanomethyl products (X and 1X) from 1,3-cyclooctadiene; 6′, 7′ -dihydro-7′ -methylenespiro[cyclohexane-1, 5′-[5H] pyr-rolo[1,2-b]-s-triazole] (XI), 6′, 7′-dihydro-7′-meth) lene. spiro cyclohexane-1, 6′-[5H]pyrrolo[1,2-b]-s-triazole] (XII) and their respective 7 -eyanomethyl products (XIII and XIV) from melhylene cyclohexane; 6,7-dicarbethoxy-9-cyanomelhyl-4a, 5, 7, 8, 8a, 9-hexahydro-6H-s-triazolo[1,5-a]indole (XV) from diethyl cis-1, 2, 3, 6-tetrahydrophlhalate: and 5-earl)elhoxymethyl-8-eyanomethyl-4a, 5, 6, 7, 7a, 8-hexahydrocyclopenta[4,5]pyrrolo( 1, 2-b]-s-triazole (XVI) from ethyl 2, 2-cyclo-pentene-1-acetate. Many other alkenes, particularly the phenyl ethylenes, did not react with compound 1. In general, more than one product was isolated for each reaction except in the case of the two ester alkenes where a single eyanomethyl product was observed.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine (II)

s-Triazolo[4,3-b Jpyridazine (I) photochemically reacted with dihydropyran; 2,3-dihydro-p-dioxin; 2,5-dihydrofuran; 2,5-dimethoxy-2,5-dihydrofuran; and 1,3-dioxep-5-ene to give a new series of substituted pyrrolo[1,2-b]-.s-triazoles (II-IX). In most reactions, two or more products were formed. The following compounds have been prepared from I: 9-methylene-4a,5,6,7,8a,9-hexahydropyrano[2,3 :4,5]pyrrolo[1,2-b]-s-triazole (Ha), the corresponding 9-cyanomethyl product (III), and 9-methylene-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3′,2′:4,5]pyrrolo[1,2-b]-s-triazole (IIb) from dihydropyran; 9-methylene-4a,6,7,8a-tetrahydro-9H-p-dioxino[2′,3′:4,5]-pyrrolo[1,2-6]-s-triazole (IV) from 2,3-dihydro-p-dioxin; 8-methylene-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]pyrrolo[1,2-b]-s-triazole (V) and the corresponding 8-cyanomethyl product (VI) from 2,5-dihydrofuran; 8-cyanomethyl-5,7-dimethoxy-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]-pyrrolo[1,2-6]-s-lriazole (VII) from 2,5-dimethoxy-2,5-dihydrofuran; and 10-methylene-4a,5,9a,10-tetrahydro-9H-[1,3]dioxepino[5′,6′:4,5]pyrrolo[1,2-b]-s-triazole (VIII) and the corresponding 10-cyanomethyl product (IX) from 1,3-dioxep-5-ene. The addition of several other compounds (1,2,3,6-tetrahydropyridine, 1-acetylimidazole, 3-sulfolene, 2,3-dihydro-p-dithiin, and vinylene carbonate) was attempted, but no reactions were observed.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 6. Naphthothienonaphthyridines

Five novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: naphtho[1′,2′:4,5]thieno[2,3-c][1,8]naphthyridin-6(5H)-one ( 5 ), naphtho-[1′,2′:4,5]thieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 6 ), naphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 9 ), naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]-1,5-naphthyridine ( 12 ), and naphtho[2′,1′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 17 ). The direction of photocyclization to produce 9 was established from a zero quantum two-dimensional nmr spectroscopy experiment (ZQCOSY) using 6-chloronaphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 8 ) as the model compound.     

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 of bridgeheaded nitrogen systems. s-triazolo[4,3-b]-as-triazine,s-triazolo[4,3-d]-as-triazine and s-triazolo[3,4-b]-1,3,4-Thiadiazole ring systems

By the reactions of hydrazino-as-triazines ( 1a-d and 5 ) with cyanogen bromide were synthesized s-triazolo-as-triazines ( 2a-d ) and ( 6 ). Likewise, similar reactions of amino-s-triazolethiols ( 7a-e ) gave s-triazolo-1,3,4-thiadiazoles ( 8a-e ). Compound 2a was brominated to 2g.     

Studies on polycyclic thiaarenes: Part II. An improved synthesis of phenanthro[1,2-b]thiophene and a synthesis of acenaphtho[1,2-b]naphtho-[2,3-d]thiophene,a novel polynuclear thiaarene

An improved synthesis of phenanthro[1,2-b]thiophene ( 6 ) from 1-chloro-3,4-dihydrophenanthrene-2-aldehyde ( 2 ) by condensation with thioglycolate followed by hydrolysis, decarboxylation and dehydrogenation is described. A new polycyclic thiophene derivative 14 has also been prepared from acenaphthothiophene ( 7 ) by Friedel-Craft's reaction with phthalic anhydride followed by lactonisation of the keto carboxylic acid 9 and then reduction and finally cyclisation of the resultant aldehyde 13 .     

The synthesis of the monomethyl isomers of benzo[b]naphth[2,1-d]thiophene

All isomers of the monomethylbenzo[b]naphth[2,1-d]thiophenes were synthesized using photocyclization of 3-styrylbenzo[b]thiophenes. The 1-, 3-, 4-, and 5-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by irradiation of the corresponding methylated 3-styrylbenzo[b]thiophenes which were prepared by the Wadsworth-Emmons reaction of diethyl benzo[b]thenylphosphonate with o-, m-, p-tolualdehyde and acetophenone. The 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by decarboxylation of 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophene-6-carboxylic acid with copper in quinoline. These carboxylic acids were prepared by photocyclization of the corresponding 2-(benzo[b]thiophen-3-yl)-3-phenylpropenoic acids which were prepared by the condensation of the methylated benzo[b]thiophene-3-ylacetic acids with benzaldehyde in the presence of triethylamine in acetic anhydride.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 3 . 12-Methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridine

The synthesis of the 12-methyl derivative of a novel heterocyclic ring system, namely benzo[h][1]benzothieno[2,3-c][1,6]naphthyridine ( 8 ) was prepared by photocyclization of 3-chloro-N-(2′-methyl-4′-quinolyl)benzo-[6]thiophene-2-carboxamide ( 5 ) to 12-methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 6 ). Chlorination of 6 afforded 6-chloro-12-methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridine ( 7 ) which upon dechlorination provided the novel title compound 8 .     

Research on heterocyclic compounds. XXI. Synthesis of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]thiazole derivatives

The reaction of some 2-aminobenzothiazoles and 2-aminothiazoles with ethyl 3-bromo-4-oxopentanoate was investigated with the aim to obtain the corresponding imidazo[2,1-b]benzothiazole and imidazo[2,1-b]-thiazole derivatives, respectively. In some cases, two unexpected side products were obtained together with the required compound and their structures were elucidated: e.g., 2-aminobenzothiazole reacted with ethyl 3-bromo-4-oxopentanoate to give ethyl 2-methylimidazo[2,1-b]benzothiazole-3-acetate together with ethyl imi-dazo[2,1-b]benzothiazole-2-propionate and ethyl 3-(benzothiazol-2-yl)amino-4-oxopentanoate.     

Cascade transformation of 4-hydroxymethyl-2-carene into novel cage methanopyrano[4,3-b]thieno[3,2-g]benzofuran derivative

Reaction of trans-4-hydroxymethyl-2-carene with thiophene- 2-carbaldehyde under heterogeneous catalysis by K10 clay affordsubstitutedmethanopyrano[4,3-b]thieno[3,2-g]- benzofuran, a complex 5-membered chiral cage heterocyclic compound containing two thiophene moieties. Its structure was determined by 1D and 2D NMR experiments (HSQC, HMBC, COSY, NOESY) and HRMS.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 8 . [1]Benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline

The previously unknown polycyclic heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-h]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were synthesized via photocyclization of 3-chloro-N-(1′-phenanthryl)benzo[b]thiophene-2-carboxamide.     

Facile synthesis of some novel triazolo[3,4-b]thiadiazines and triazolo[4,3-b]tetrazines

4-Amino-5-ethyl-4H-1,2,4-triazole-3-thiol was used as a key intermediate for the synthesis of triazolo[3,4-b][1,3,4]thiadiazines, triazolo[4,3-b][1,2,4,5]tetrazines and Schiff’s base via reactions with various hydrazonoyl halides and salicyaldehyde, respectively. Moreover triazolyl-N-N′-triazole derivatives were prepared from reaction of Schiff’s base with various hydrazonoyl halides. The structures of all the newly synthesized heterocyclic compounds were established by considering elemental analysis and spectral data.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 2 . Benzo[h][1]benzothieno[2,3-c]quinoline and benzo[h][1]benzothieno[2,3-c]quinoline

The synthesis of two previously unknown unsubstituted heterocyclic ring systems namely, benzo[h][1]benzothieno[2,3-c]quinoline ( 6 ) and benzo[f][1]benzothieno[2,3-c]quinoline ( 12 ) is reported. These two novel ring systems have been assembled by photocyclization of the appropriate amides.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 23 . Naphtho[2′,1′:4,5]thieno‐[2,3‐c]naphtho[2,1‐f]quinoline

A previously unknown heterocyclic ring system, naphtho[2′,1′:4,5]thieno[2,3‐c]naphtho[2,1‐f]quinoline ( 14 ), was synthesized via oxidative photocyclization of 3‐chloro‐N‐(2‐phenanthryl)naphtho[1,2‐b]‐thiophene‐2‐carboxamide ( 9 ). Further elaboration of the lactam 10 yielded the unsubstituted ring system 14 . Structural confirmation of compound 14 was accomplished by a total assignment of its ¹H and ¹³C nmr spectra utilizing the concerted two‐dimensional nmr spectroscopic methods.     

Heteropolycyclic molecules. Part IX. Synthesis of some new benzo[b]thiophene,oxofluoreno[4,3-b]thiophene,cyclic hydrazides and acridine compounds

p-Tolyl 2-thienyl ketone (I) condensed with dimethyl succinate in the presence of potassium t-butoxide to give the trans (SC₄H₃/CO₂Me) half-ester (IIIa) whose configuration was deduced by cyclization to the corresponding benzo[b]thiophene derivatives. Carbamates, esters, cyclic hydrazides and substituted phenolic and acetic acids useful as antibacterial and antiinflamatory agents were obtained. The reaction of ketone I with malononitrile to give ylidenemalononitrile II was also considered.