The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

Chemistry of 1,2,3-thiadiazole. IV. Synthesis of [1]benzoxepino-[3,4-d][1,2,3]thiadiazole, [1]benzothiepino-[3,4-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d]oxazole and [1]benzoxepino[4,3-d]oxazole. Four novel heterocycles

Starting from the readily available 4-bromomethy-5-carbethoxy 1,2,3-thiadiazole (V), 5-bromomethy-4-carbethoxy-1,2,3-thiadiazole (IX) and ethyl 2-aryl-5-bromomethyloxazole-4-carboxylate (XIV), 4,10-dihydro-10-oxo[1]benzoxepino[3,4-d][1,2,3]thiadiazole (Ia), 4,10-dihydro-10-oxo[1]benzothiepino[3,4-d][1,2,3]thiadiazole (Ib), 4,10-dihydro-4-oxo[1]benzothiepino[4,3-d] [1,2,3]thiazole (II), 2-aryl-4,10-dihydro-4-oxo[1]benzoxepino[4,3-d]oxazoles (XIXa-XIXc) and 2-aryl-4,10-dihydro-4-oxo[1]benzothiepino[4,3-d]oxazoles (XIXd-XIXf) were prepared.     

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.     

Selenium heterocycles. XXXII . Synthesis of [1]benzoxepino[3,4-d]-thiazole, [1]benzothiepino[3,4-d]thiazole, [1]benzoxepino[3,4-d]selenazole,and [1]benzothiepino[3,4-d]selenazole. four novel heterocycles

Starting from the readily available ethyl 2-phenyl-4-methyl-thiazole-5-carboxylate (III), 2-phenyl-4-chloromethyl-thiazole (VIII) and 2-aryl-4-chloromethylselenazole (XIV), 2-phenyl-4,10-dihydro-10-oxo-[1]benzoxepino[3,4-d]thiazole (Ia), 2-phenyl-4,10-dihydro-10-oxo[1]benzothiepino[3,4-d]thiazole (Ib), 2-aryl-4,10-dihydro-10-oxo[1]benzoxepino[3,4-d]selenazoles (IIa-IIe) and 2-aryl-4,10-dihydro-10-oxo[1]benzothiepino[3,4-d]selenazoles (IIf-IIj) were prepared.     

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.     

Chiral Calix[3]pyrrole Derivatives: Synthesis,Racemization Kinetics,and Ring Expansion to Calix[9]- and Calix[12]pyrrole Analogues

Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole-based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene ( 1 ), synthesized from an oligoketone. Macrocycle 1 adopts a partial cone conformation in the solid state, and undergoes racemization via ring inversion. Molecular dynamics simulations revealed that inversion of the thiophene is the rate determining step. Pyrrole N-methylation suppressed racemization and permitted chiral resolution. Enantioselective N-methylation also occurred in the presence of a chiral ammonium salt, although the stereoselectivity is modest. A unique feature of 1 is that it acts as a useful synthetic precursor to yield several calix[n]furan[n]pyrrole[n]thiophene products (n=2–4), including a calix[12]pyrrole analogue that to our knowledge constitutes the largest calix[n]pyrrole-like species to be structurally characterized.     

The synthesis of monomethoxy[1]benzothieno[2,3-c]quinolines

A series of monomethoxy[1]benzothieno[2,3-c]quinolines 24-28 were prepared by photocylization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 9–13 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 14-18 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 19-23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24-28 with methyl iodide provided the corresponding N-methyl quaternary salts 29-33 . Also, conversion of 4-meth-oxy[1]benzothieno[2,3-c]quinolin-6(5H)-one 16 to 4-methoxy-6-methylthio[1]benzothieno[2,3-c]quinoline 35 and 4,6-dimethoxy[1]benzothieno[2,3-c]quinoline 36 is described.     

Synthesis of benzo[4,5]phenaleno[1,9-bc]thiophene and benzo[4,5]phenaleno[9,1–6c]thiophene

Two pentacyclic thiophenes, benzo[4,5]phenaleno[1,9–6c]thiophene ( 1 ) and benzo[4,5]phenaleno[9,1-bc]-thiophene (2) were synthesized via the corresponding 3-methylphenanthro[2,1-b]thiophene (7) and 1-methylanthra[2,1–6]thiphene ( 19 ).     

Synthesis of 1-azacycl[3.2.2]azine and 1-azabenzo[h]cycl[3.2.2]azine

1-Azacycl[3.2.2]azines were synthesized from 2-methylthioimidazo[1,2-a]pyridines, 2a and 2b , by using [2 + 8] cycloaddition reaction with dimethyl acetylenedicarboxylate as the key step. Synthesis of 1-azabenzo-[h]cycl[3.2.2]azine was also described.     

Synthese von [1]Benzothieno[2,3—c]pyrazol-Derivaten

Derivatives of [1]benzothieno[2.3-c]pyrazole, a new heterocyclic ring system, were synthesized by 1.3-dipolar cycloadditions: benzo[b]thiophene-1.1-dioxide and derivatives thereof reacted with diazomethane and diazoethane to yield substituted [1]benzothieno[2.3-c]pyrazolines. A similar reaction with ethyl diazoacetate gave the corresponding cyclopropa[b][1]benzothiophene-2.2-dioxide derivative.     

Mass spectrometric investigation of some [1]benzopyrano[3,4-c]pyrazole and [1]benzopyrano[4,3-d]isoxazole derivatives

The fragmentation behaviour of some [1]benzopyrano[3,4-c]pyrazole and [1]benzopyrano[4,3-d]isoxazole derivatives under electron impact is described.     

[1] Benzofuro [2,3-d] pyridazines II. Etude des benzofuropyridazones

The synthesis of 1,2-dihydro[1]benzofuro[2,3-d]pyridazin-1-one and 3,4-dihydro [1]benzofuro[2,3-d]pyridazin-4-one was accomplished by the eyclization of appropriately carbonyl-substituted benzofuran derivatives. Another successful synthetic route was provided using 1,2,3,4-tetrahydro[1]benzofuro[2,3-d]pyridazine-1,4 dione and 1,2,3,4-tetrahydro[1]benzofuro[2,3-d]pyridazin-4-one. The structure of a nitrobenzofuropyridazin-4-one was established using nmr and the nuclear Overhauser effect.     

Electron ionization mass spectra and crystal structures of some [1,2,4]triazolo[1,2-b]- and [1,3,4]thiadiazolo[3,4-b]phthalazines

The mass spectra of ten 1,3-dithioxo[1,2,4]triazolo[1,2,-b]phthalazines, five 3-iminosubstituted 1-thioxo-[1,3,4]thiadiazolo[3,4-b]phthalazines, three 3-iminosubstituted-1-thioxo[1,2,4]triazolo[1,2-b]phthalazines, and 1,3-dithioxo-5,10-dihydro[1,3,4]thiadiazolo[3,4-b]phthalazine were recorded under electron ionization. The fragmentation pathways were elucidated by metastable ion analysis and exact mass measurements. The changes in the ring-system had little effect on the fragmentation mechanism, but the effect on peak intensities was considerable. The most important fragmentations began with the opening of the triazole ring. Substituents at nitrogen atoms also had a marked effect on the mass spectral behavior. The aryl substituents prompted a whole new fragmentation. The X-ray crystal structure was determined for a few compounds. Two of the three structures of the 1,3-dithioxo[1,2,4]triazolo[1,2-b]phthalazines that were studied proved to be relatively planar, whereas the structure of 1,3-dithioxo-5,10-dihydro[1,3,4]thiadiazolo[3,4-b]phthalazine was considerably bent similarly to the 2-(4-chlorophenyl)-1,3-dithioxo-2,3,5,10-tetrahydro[1,2,4]triazolo[1,2-b]-phthalazine. The triazole and the thiadiazole rings had a strong double bond nature.     

CHEMICAL BEHAVIOR OF SOME BENZ[b] INDENO[1,2-e] [1,4] THIAZINE DERIVATIVES

Abstract

The study of the chemical behavior of some benz[b] indeno[1,2-e] [1,4] thiazine derivatives was accomplished. Different reactivities were observed for 4b,5-dihydrobenz[b]-indeno[1,2-e] [1,4] thiazine-10α(11H)-ol (3) and 5-ethyl-4b,5-dihydrobenz[b] indeno[1,2-e]-[1,4] thiazine-10α(11H)-ol (5); 3 is reoxidated to benz[b] indeno[1,2-e] [1,4] thiazine-10α(11H)-ol (2), while 5 undergoes transposition and oxidation to spiro[3-ethylbenzo-thiazol-2(3H), 1′-indan-2′-one] (6). Possible pathways for these transformations are discussed.     

[1]Benzothienopyrimidines. II. Study of the electrophilic substitutions of [1]benzothieno[3,2-d]pyrimidine and [1]benzothieno[3,2-d]pyrimidin-4-(3H)one

The nitration and bromination of both [1]benzothieno[3,2-d]pyrimidin-4(3H)one ( 1 ) and [1]benzothieno-[3,2-d]pyrimidine ( 2 ) has been studied. Nitration of 1 at ?30° afforded a mixture of 8-nitro[1]benzothieno-[3,2-d]pyrimidin-4(3H)one ( 7b ) (70%) and 6-nitro[1]benzothieno[3,2-d]pyrimidin-4(3H)one ( 7a ) (30%). However when the nitration was carried out at 60°, the 6,8-dinitro derivative 8 was the result. On the contrary, the nitration of 2 at ?30° gave a single nitration product, 8-nitro[1]benzothieno[3,2-d]pyrimidine ( 11 ). The bromination of both 1 and 2 gave the corresponding 8-bromo derivatives 10 and 13 . Assignment of structure of all the products was based on ir and nmr spectral studies and on unequivocal syntheses.     

Polycyclic systems: Synthesis of isoindolo[2,1-b]-pyrrolo[1,2-d][2,4]benzodiazocine and isoindolo-[1,2-d]pyrrolo[1,2-a] [1,5]benzodiazocine

The synthesis of isoindolo[2,1-b]pyrrolo[1,2-d][2,4]benzodiazocine 7 and isoindolo[1,2-d]pyrrolo[1,2-a]-[1,5]benzodiazocine 13 are described starting from 2-(2-methoxycarbonyl)benzylphthalimide 1a and ethyl α-bromohomophthalate 9 respectively.     

The synthesis of benzo[b]phenanthro[d]thiophenes and anthra[b]benzo[d]thiophenes

The synthesis of benzo[b]phenanthro[2, 3-d]thiophene ( 5 ), benzo[b]phenanthro[4, 3-d]thiophene ( 6 ), benzo-[b]phenanthro[2, 1-d]thiophene ( 9 ), benzo[b]phenanthro[3, 2-d]thiophene ( 14a ), anthra[1, 2-b]benzo[d]thiophene ( 24 ), anthra[2, 3-b]benzo[d]thiophene ( 29 ) and anthra[2, 1-b]benzo[d]thiophene ( 30 ) is described as well as the preparation of 13-methylbenzo[b]phenanthro[3, 2-d]thiophene ( 14b ).     

[1,3,5]Triazino[1,2-a] azepines: A new ring system

The reaction of 2-pyrrolidino-1-aza-1-cycloheptene with aryl isocyanates leads, via 1,4-dipolar cycloaddition, to 1,3-diaryl-10a-pyrrolidinoperhydro[1,3,5]triazino[1,2-a]azepine-2,4-diones. The reaction provides a facile route to the novel [1,3,5]triazino[1,2-a]azepine ring system.     

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.