Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethyleneketones. XI. Synthesis of 1,2-oxathiino[5,6-d]-1-benzoxepin derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones gave, generally in excellent yield, N,N-disubstituted 4-amino-3,4,5,6-tetrahydro-1,2-oxathiino-[5,6-d)-1-benzoxepin 2,2-dioxides, which are derivatives of the new heterocyclic system 1,2-oxathiino[5,6-d]-1-benzoxepin. This reaction did not occur only with the N,N-diphenylenaminone.     

Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethvlene ketones V. Synthesis of 1,2-oxatliiino[5.6-c] pyridine and 1,2-oxathiino[5,6-c] quinoline derivatives

Reaction of sulfene with N,N-disubstituted 3-aminomethylene-1-(methyl, methylphenyl, phenyl)-4-piprridones and 3-aminomethylene-2,3-dihydro-1-plumy 1–4(1H) quinolones gave N,N-disubstituted 4-amino-3,4,5,6,7.8-hexahydro-6-(methyl, methylphenyl, phenyl)-1,2-oxathiino-[5,6-c] pyridine 2,2-dioxides and 4-amino-6-phenyl-3,4,5,6-tetrahydro-1,2-oxathiino[5,6-c]quinoline 2,2-dioxides, respectively, whereas N,N-disubstituted 3-aminomethylene-2,3-dihydro-1-methyl-4(1H) quinolones did not react. Slow air oxidation in the cold of intermediates 2,3-dihydro-3-hydroymethyIene-1-(methyl, phenyl)-4(1H) quinolones gave the corresponding 1-substituted 1,4-dihydro-4-oxo-3-quinolinecarboxyaldehydes.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XI. Synthesis of 2H-pyrano[3,2-g]benzothiazole derivatives

Cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-5,6-dihydro-2-phenylbenzothiazol-7-(4H)ones gave in good yield N,N-disubstituted 4-amino-3,3-dichloro-3,4,5,6-tetrahydro-8-phenyl-2H-pyrano[3,2-g]benzothiazol-2-ones II, which are derivatives of the new heterocyclic system 2H-pyrano[3,2-g]benzothiazole. Dehydrochlorination with triethylamine of II afforded N,N-disubstituted 4-amino-3-chloro-5,6-dihydro-8-phenyl-2H-pyrano[3,2-g]benzothiazol-2-ones III in good to moderate yield. The dimethylamino adduct was dehydrochlorinated in high yield by refluxing in toluene, whereas the diisopropylamino adduct gave in low yield 6-(2,2-dichloroethylidene)-5,6-dihydro-2-phenylbenzothiazol-7-(4H)one with the triethylamine treatment. The dehydrochlorinated product IIId (NR₂ = pyrrolidino) was obtained directly in low yield by cycloaddition of dichloroketene to the corresponding enaminone. Full aromatisation of IIIa,g [NR₂ = N(CH₃)₂ and N(CH₃)C₆H₅, respectively] to the corresponding N,N-disubstituted 4-amino-3-chloro-8-phenyl-2H-pyrano-[3,2-g]benzothiazol-2-ones was accomplished with DDQ in refluxing benzene.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVIII. Synthesis of N,N-disubstituted 4-amino-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones

1,4-Cycloaddition of phenylchloroketene to N,N-disubstituted 2-aminomethylene-3,4-dihydro-1(2H)naphthalenones gave the corresponding adducts, namely N,N-disubstituted 4-amino-3-chloro-3,4,5,6-tetrahydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones II, in the case of aliphatic N,N-disubstitution or aromatic N-monosubstitution. Apart from IIf (NR₂ = NMePh), adducts II were unstable and were dehydrochlorinated in situ with DBN to give N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones III in fair overall yields. Compounds III were dehydrogenated with Pd/C in boiling p-cymene to afford the title compounds generally in high yields.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XIII. Synthesis of 2H-pyrano[3,2-d]-1-benzoxepin derivatives

Cycloaddition of dichloroketone to N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones gave N,N-disubstituted 4-amino-3,3-dichloro-3,4,5,6-tetrahydro-2H-pyrano[3,2-d]-1-benzoxepin-2-ones II, which are derivatives of the new heterocyclic system 2H-pyrano[3,2-d]-1-benzoxepin. Dehydrochlorination with triethylamine of II afforded N,N-disubstituted 4-amino-3-chloro-5,6-dihydro-2H-pyrano-[3,2-d]-1-benzoxepin-2-ones III in good to moderate yields. In the triethylamine treatment of IIh (NR₂ = diphenylamino), 3-chloro-5,6-dihydro-2H-pyrano[3,2-d]-1-benzoxepin-2-one was isolated in low yield near to IIIh, whereas IIc (NR² = diisopropylamino) gave in low yield 4-diisopropylamino-5,6-dihydro-2H-pyrano(3,2-d)-1-benzoxepin-2-one.     

Reaction of sulfenes with heterocyclic N,N-disubstituted α-aminomethyleneketones. XIII. Synthesis of 1,2-oxathiino[6,5-f]quinazoline derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted (E)-6-aminomethylene-7,8-dihydro-(2-methyl)-(2-phenyl)quinazolin-5(6H)-ones I gave N,N-disubstituted 4-amino-3,4,5,6-tetrahydro-(8-methyl) (8-phenyl)-1,2-oxathiino[6,5-f]quinazoline 2,2-dioxides II , which are derivatives of the new heterocyclic system 1,2-oxathiino[6,5-f]quinazoline. With 2-phenylenaminones Id-h , the cycloaddition occurred, generally in satisfactory yields, both in the case of aliphatic N,N-disubstitution and aromatic N-monosubstitution, whereas with 2-methyl enaminones Ia-c the reaction took place in low yields only in the case of aliphatic N,N-disubstitution. Also the reaction of 2-phenyl enaminones Id-g with chlorosulfene occurred as with sulfene, giving a mixture of cycloadducts which were dehydrochlorinated in situ with DBN to afford N,N-di-substituted 4-amino-5,6-dihydro-8-phenyl-1,2-oxathiino[6,5-f]quinazoline 2,2-dioxides III generally in satisfactory yields. Compounds III could not be dehydrogenated either by DDQ in boiling benzene or by palladium on carbon in boiling p-cymene.     

Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethyleneketones. VIII. Synthesis of furo[2,3-h]-1,2-benzoxathiin derivatives

Cycloaddition of sulfene to N,N-disubstituted (E)5-aminomethylene-6,7-dihydrobenzo[b]furan-4(5H)ones I gave, only in the case of aliphatic N-substitution and generally in satisfactory yields, N,N-disubstituted 4-amino-3,4,5,6-tetrahydrofuro[2,3-h]-1,2-benzoxathiin 2,2-dioxides II, which are derivatives of the new heterocyclic system furo[2,3-h]-1,2-benzoxathiin. The 4-dimethylamino and 4-piperidino cycloadducts IIa,e were dehydrogenated with DDQ to the corresponding 4-dialkylamino-3,4-dihydrofuro[2,3-h]-1,2-benzoxathiin 2,2-dioxides IIIa,e in low yield. Compounds IIIa,e were tested for photobiological activity and found to be inactive.     

Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethyleneketones. X. Synthesis of thieno[2,3-h]-1,2-benzoxathiin derivatives

The polar 1,4-cycloaddition of sulfene to N,N-disubstituted (E)5-aminomethylene-6,7-dihydrobenzo[b]-thiophen-4(5H)ones II gave in excellent yield and only in the case of aliphatic N-substitution, N,N-disubstituted 4-amino-3,4,5,6-tetrahydrothieno[2,3-h]-1,2-benzoxathiin 2,2-dioxides III, which are derivatives of the new heterocyclic system thieno[2,3-h]-1,2-benzoxathiin. Dehydrogenation with DDQ of cycloadducts IIIa-d was successful only in the case of IIIa (NR₂ = dimethylamino) to give in low yield 4-dimethylamino-3,4-dihydrothieno[2,3-h]-1,2-benzoxathiin 2,2-dioxide.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVII. Synthesis of 2H-[1]benzothiepino[5,4-b]pyran derivatives

1,4-Cycloaddition of dichloroketene to a number of N,N-disubstituted (E)-4-amino methylene-3,4-dihydro-[1]benzothiepin-5(2H)-ones gave in excellent yield N,N-disubstituted 4-amino-3,3-dichloro-3,4,5,6-tetrahydro-2H-[1]benzothiepino[5,4-b]pyran-2-ones III, which are derivatives of the 2H-[1]benzothiepino[5,4-b]pyran system. Dehydrochlorination of III with DBN afforded N,N-disubstituted 4-amino-3-chloro-5,6-dihydro-2H-[1]-benzothiepino[5,4-b]pyran-2-ones, generally in excellent yield.     

Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethyleneketones. IX. Synthesis of 1,2-oxathiino[6,5-e]indole derivatives

The polar 1,4-cycloaddition of sulfene to N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-1-methylindol-4-ones occurred only in the case of aliphatic N-substitution to give, generally in good yield, 4-dialkylamino-3,4,5,6-tetrahydro-7-methyl-7H-1,2-oxathiino[6,5-e]indole 2,2-dioxides IV. Full aromatization of IVa (4-NR₂ = dimethylamino) with DDQ in refluxing benzene gave in low yield 7-methyl-7H-1,2-oxathiino-[6,5-e]indole 2,2-dioxide, whereas the same reaction of IVe (4-NR₂ = morpholinyl) with excess DDQ afforded in low yield 7-methyl-4-morpholinyl-7H-1,2-oxathiino[6,5-e]indole 2,2-dioxide.     

Reaction of sulfenes with heterocyclic N,N-disubstituted α-aminomethyleneketones. XII. Synthesis of [1]benzothiepino[4,5-e][1,2]oxathiin derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro[1]benzothiepin-5(2H)-ones I occurred only in the case of aliphatic N,N-disubstitution to give in good yield 4-dialkylamino-3,4,5,6-tetrahydro[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides, which are derivatives of the new heterocyclic system [1]benzothiepino[4,5-e][1,2]oxathiin. Also the reaction of I with chlorosulfene occurred only in the case of aliphatic N,N-disubstitution to afford chiefly trans-4-dialkylamino-3-chloro-3,4,5,6-tetrahydro-[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides III in satisfactory yield. Adducts III were dehydrochlorinated with DBN to 4-dialkylamino-5,6-dihydro[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides in good yield.     

Reaction of dichloroketene and sulfene with N,N-disubstituted α-aminomethyleneketones. Synthesis of pyrano[2,3-e]indazole and 1,2-oxathiino[6,5-e]indazole derivatives

The polar 1,4-cycloaddition of dichloroketene to N,N-disubstituted (E)-5-aminomethylene-1,5,6,7-tetrahydro-(1-methyl)(1-phenyl)-4H-indazol-4-ones V, prepared from 1,5,6,7-tetrahydro-(1-methyl)(1-phenyl)-4H-indazol-4-ones via the 5-hydroxymethylene derivatives, gave in good yield N,N-disubstituted 4-amino-3,3-dichloro-4,5,6,7-tetrahydro-(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-(3H)ones VI, which are derivatives of the new heterocyclic system pyrano[2,3-e]indazole. Dehydrochlorination of VI with DBN afforded N,N-disubstituted 4-amino-3-chloro-6,7-dihydro(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-2(5H]-ones VII generally in satisfactory yield. Full aromatization with DDQ of VII was tried only in the case of dimethylamino derivatives, giving a moderate yield of 3-chloro-4-dimethylamino(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-2(7H)-ones. Cycloaddition of sulfene to V occurred only in the case of aliphatic N-substitution to give in moderate yield 4-dialkylamino-4,5,6,7-tetrahydro-(7-methyl)(7-phenyl)-3H-1,2-oxathiino[6,5-e]indazole 2,2-dioxides, which are derivatives of the new heterocyclic system 1,2-oxathiino[6,5-e]indazole.     

The reaction of ethyl 4H-pyran-4-one-2-carboxylate with 1,2-diaminobenzene

Ethyl 4H-pyran-4-one-2-carboxylate was allowed to react with 1,2-diaminobenzene and related diamines. The resulting products were found to be 8H-5,6-dihydro-6,8-dioxopyrido[1,2-a]quinoxaline and derivatives. The synthesis 3H-5,6-dihydrobenzo[g]pyrido[1,2-a]quinoxaline-3,5-dione ( 2c ) constitutes the synthesis of a derivative of previously unknown benzo[g]pyrido[1,2-a]quinoxaline ring system.     

Reaction of dichloroketene and sulfene with N,N-disubstituted 6-amino-methylene-b,7,8,9 -tetrahydro-5H-benzocyclohepten-5-ones. Synthesis of 6-(2,2-Dichloroethylidene)-b,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and of 5H-benzo[3,4]cyclohepta[2,l-b]pyran and 5H-Benzo[3,4]cyclo-hepta[1,2-e]-1,2-oxathiin derivatives

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-b,7,8,9-tetra-hydro-5H-benzocyclohepten-5-ones afforded N,N-disubstituted 4-amino-3,3-dichloro-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones only in the case of aromatic or strong hindering aliphatic N-substitution. The adducts gave N,N-disubstituted 4-amino-3-chloro-b,7-dihydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones by dehydrochlorination with collidine. Upon chromatography on neutral alumina, two products were instead isolated in the case of usual aliphatic N-substitution (diethylamine, piperidine), namely 6-(2,2-dichloroethylidene)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and the dehydrochlorinated 2-pyrone; this latter was the sole product in the case of pyrrolidine substitution. The 1,4-cycloaddition of sulfene occurred readily to give N,N-disubstituted 4-amino-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta-[1,2-e]-1,2-oxathiin 2,2-dioxidesin the case of both aliphatic and partially aromatic N-substitution.     

Synthesis of 4,8-disubstituted 4H,8H-bis[1,2,5]oxadiazolo[3,4–6:3′,4′-e]pyrazines

The dilithio anion of 3,4-N,N′-disubstituted diamino[1,2,5]oxadiazole ( 4a R = benzyl, 4b R = p-methoxybenzyl, 4c R = isopropyl) and cyanogen oxide gave 4,7-disubstituted 5,6-dioximino[1,2,5]oxadiazolo[3,4-b]-pyrazines 5a,b,c. Ring closure to the title compound 1 was accomplished upon heating 5 with sodium hydroxide in ethylene glycol at 150°.     

Etude de la décomposition thermique d'azido dithiényl-1,2 éthènes et éthanes

Thermal decomposition of azido-1,2-dithienylethenes 1 gave thienyl 4H-thieno[3,2-b]pyrroles 3 . For the 3,4-disubstituted thiophene derivatives 2 , the same reaction led to the amino-1,2-dithienylethenes 4 . In contrast, only azido-1,2-dithienylethanes 7 led to thienyl-5,6-dihydro-4H-thieno[3,4-b]pyrroles 8 . The structure of the obtained derivatives was established on the basis of ¹H nmr, ir, and mass spectral data.     

Reaction of Sulfene wild Heterocyclic N,N-Disubstituted α-Aminomethylene Ketones IV. Synthesis of 3,4-Dihydro-5H-[1]benzothiopyratio [3,4-e]-1,2-oxathiin and 2,3,6,7-Tetrahydro-5H-thiopyrano[3,4-e]-1,2-oxathiin Derivatives

The reaction of sulfene with N,N-disubstituted 3-aminomethylene-2,3-dihydro-4-thiochromanones and-2,3,5,6-tetrahydro-4-thiopyranones gave 1,4-cycloadducts which are derivatives of new heterocyclic systems, namely 3,4-dihydro-5H-[1]benzothiopyrano[3,4-e]-1,2-oxathiin and 3,4,7,8-tetrahydro-5H-thiopyrano[3,4-e]-1,2-oxathiin, respectively. Furthermore, some pyrazole derivatives VII and VIII were prepared from 3-hydroxymethylene-2,3-dihydro-4-thiochromanone or 2,3,5,6-tetrahydro-4-thiopyranone and hydrazines.     

Reaction of sulfene and dichloroketene with N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones. Synthesis of 1,2-oxathiino[6,5-E] indole and of pyrano[2,3-e] indole derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones afforded N,N-disubstituted 3,4,5,6-tetrahydro-8-methyl-7-phenyl-7H-1,2-oxathiino[6,5-e]indol-4-amine 2,2-dioxides only in the case of aliphatic N-substitution. The 1,4-cycloaddition of dichloroketene occurred normally only in the case of 1,5,6,7-tetrahydro-2-methyl-1-phenyl-5-piperidinomethyleneindol-4-one to give 3,3-dichloro-3,4,5,6-tetrahydro-8-methyl-7-phenyl-4-piperidino-7H-pyrano[2,3-e]indol-4-one. Attempted recrystallisation, dehydro-chlorination or treatment with palladium on carbon of this adduct, as well as reaction of similar enaminoketones with dichloroketene, gave instead the same product, namely 3-chloro-8-methyl-7-phenyl-7H-pyrano[2,3-e]indol-4-one, as a result of dehydrochlorination, dehydrogenation and subsequent hydrogenolysis of the C-NR₂ bond in the primary adduct.     

Polycyclic N-hetero compounds. XIX. Synthesis of novel meso-ionic benz[h]imidazo[1,2-c]quinazoline and benzo[h]pyrrolo[1′,2′:3,4]imidazo[1,2-c]quinazoline derivatives

Benz[h]imidazo[1,2-c]quinazolinium-l-olate (5) and benzo[h]pyrrolo[1′,2′:3,4]imidazo[1,2-c]quinazolinium-8-olate (9) having novel meso-ionic ring systems were synthesized by the reaction of N-(5,6-dihydrobenzo[h]-quinazolin-4-yl)amino acids with acetic anhydride.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XIX. Synthesis of N,N-disubstituted 4-amino-3-phenyl-2H-furo[2,3-h]-1-benzopyran-2-ones (4-amino-3-phenylangelicins). Crystal and molecular structure of 3-Phenylangelicin

1,4-Cycloaddition of phenylchloroketene to N,N-disubstituted 5-aminomethylene-6,7-dihydrobenzo[b]- furan-4(5H)-ones gave the corresponding adducts, namely N,N-disubstituted 4-amino-3-chloro-3,4,5,6-tetra- hydro-3-phenyl-2H-furo[2,3-h]-l-benzopyran-2-ones II , which were dehydrochlorinated with DBN to N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-furo[2,3-h]-1-benzopyran-2-ones III . Compounds III afforded the title compounds IV by dehydrogenation with DDQ. In the cycloaddition step, 3-phenylangelicin V , whose structure was confirmed by ¹H-nmr shift reagents data and by X-ray crystal structure determination, was almost always formed, probably starting from II by dehydrochlorination, dehydrogenation and hydrogenolysis of the disubstituted amino group. Separation of V was achieved by alumina chromatography either in the cycloaddition step or, in most cases, in the dehydrochlorination step. 3-Phenylangelicin crystallizes in the trigonal system, space group R3, with cell parameters (hexagonal axes) a = b = 41.021(10), c = 3.888(2) Å. The angelicin moiety forms a dihedral angle of 42.1(1)° with the phenyl substituent. Disordered solvent molecules of ethyl acetate are clathrated in channels in the direction of the crystallographic axis c.