MODIFIED COUMARINS. 3. PSORALEN AND ALLOPSORALEN ANALOGS

1,2,3,4-Tetrahydro-5H-benzo[c]furo[3,2-g]chromen-5-ones and 8,9,10,11-tetrahydro-7H-benzo[c]furo[2,3-f]chromen-7-ones, analogs of psoralen and allopsoralen, were synthesized from 1-hydroxy- and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-ones.     

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.     

Über die Synthese von 1-Aryl-und 1-Alkyl-2, 3-dimethyl-chinoxalinium-perchloraten. 2. Mitteilung. Synthese und 1H-NMR.-Spektren von 2,3-Dimethyl-1-phenyl-6-X-chinoxalinium-perchloraten

On the Synthesis of 1-Aryl- and-1-Alkyl-2, 3-dimethyl-quinoxalinium Perchlorates. 2nd Communication

1 1. Mitt.: [1].

. Synthesis and ¹ H-NMR. Spectra of 2, 3-Dimethyl-1-phenyl-6-X-quinoxlinium Perchlorates The synthesis of the title compounds ( 5 ) which have been useful as precursors for a lot of conventional and new-type dyes [2-8] has yet been limited to examples with X?H [2] [3] [11] [15] and with electron-donating [4] [12] or at best slightly electron-accepting [1] [6] substituents X and R. We now describe a method suitable even for compounds 5 with strongly electron-accepting substituents: N-monosubstituted o-phenylendiamines 4 , were condensed with 2, 3-butanedione and perchloric acid in mixed solvents containing an excess of diethyl ether. The products - mostly substituted at position 6 of the quinoxalinium ring - are chracterized by ¹H-NMR. spectra, elemental analyses and in most cases by isolation of the corresponding bases 6 . Correlations of chemical shifts with Hammett's σ_p [18] are given by equations (1)-(5).     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 3. The benzo[b]-1,4-diazabicyclo [2.2.2]-octene system

Benzo[b]-1,4-diazabicyclo[2.2.2]octene and 4′-methylbenzo[1′,2′-b]-1,4-diazabicyclo[2.2.2]octene were synthesized by the reaction of N-acetyl-6-H- and 6-methyl-1,2,3,4-tetrahydroquinoxalines with ethylene oxide and subsequent cyclization of the N-(β-hydroxyethyl)-N'-acetyl derivatives in refluxing HBr. The errors of the published data on the benzo[b]-1,4-diazabicyclo[2.2.2]octene system are demonstrated. See [1] for communication 2. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 827–830.     

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 .     

1,2,4-triazines. 7. Regioselective n2-amination of 3-methylthio-1,2,4-triazin-5(2H)-ones.A novel synthesis of [1,2,4]triazolo[2,3-b][1,2,4]triazinones and -triazine

A regioselective synthesis of 2-aminotriazinones 6a-d is reported, by reaction of 3-methylthio-1,2,4-triazinones 5a-d with O-(2,4-dinitrophenyl)hydroxylamine (2) as an amino-transfer agent. A spectroscopic study and an unequivocal synthesis of 2-amino-4-methyl-6-phenyl-1,2,4-triazinedione ( 11a ) has shown the site of amination to be N2 of the 1,2,4-triazinone ring. Subsequent reaction of 2-amino-1,2,4-triazinones 6a-b with amines, followed by ring closure with aliphatic acids provided [1,2,4]triazolo[2,3-b][1,2,4]triazine-7(1H)ones 13a-e. Conversion of [1,2,4]triazolo[2,3-b][1,2,4]triazinone 13c to unsubstituted [1,2,4]triazolo[2,3-6][1,2,4]triazine (15) was attained.     

珠子参化学成分分析

从珠子参根茎中分离得到7个化合物. 利用核磁共振、 质谱和红外等手段, 并结合其理化性质, 鉴定了其结构, 它们分别是24(R)-珠子参苷R1, 6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇、 6″-乙酰基-人参皂苷Rd、 人参皂苷Rf、 竹节参皂苷Ⅳa、 人参皂苷Rd和竹节参皂苷Ⅴ. 其中, 24(R)-珠子参苷R1和6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇为2个新化合物, 6″-乙酰基-人参皂苷Rd 和人参皂苷Rf为首次从珠子参根茎中得到.     

Reaction of nitrenes with strained olefins. Preparation and reactions of some 6-azabicyclo[3.1.0]hexanes

A number of examples of the 6-azabicycIo[3.1.0]hexane ring system have been prepared by the oxidation of N-aminophthalimide or 3-amino-2-methyl-4-quinazoIone with lead tetraacetate in the presence of variously substituted cyclopentenes. Thus, 6-phthalimidyl-6-azabicyclo[3.1.0]hexane, dimethy 1–6-phthalimidyl-6-azabicyclo[3.1.0]-hexane-1,5-dicarboxylate, 2,3-benzo-6-phthalimidyl-6-azabicycIo[3.1.0]hexane and N-3-(2-methyl-4-quinazolyl)-6-azabicyclo [3.1.0]hexane were prepared for the first time. All of the new compounds were found to be stable in refluxing carbon tetrachloride and chlorobenzene. Refluxing 6-phthalimidyl-6-azabieyclo[3,1.0]hexane in acetic acid for 24 hours resulted in quantitative rearrangement to a phthalohydrazide, 8 .     

Investigation of nitrogen- and sulfur-containing heterocycles. 38. Reactions of 2-mercapto-3-ureidopyridines with halo β-diketones

The reaction of 2-mercapto-3-ureido-6-chloropyridine with chlorodibenzoylmethane in the presence of alkali leads to 2-(benzoylmethylthio)-3-benzamido-6-chloropyridine, whereas the reaction in the absence of alkali leads to 2-chloro-6-phenyl-7-benzoylpyrido[2,3-b] [1,4]thiazine. Under similar conditions 2-(diacetylmethylthio)-3-ureido-6-chloropyridine, 2-(acetylmethylthio)-3-ureido-6-chloropyridine, and 2-chloro-6-methyl-7-acetylpyrido[2,3-b][1,4]thiazine were obtained from 2-mercapto-3-ureido-6-chloropyridine and chloroacetylacetone. Treatment of 2-(diacetylmethylthio)-3-ureido-6-chloropyridine with alcoholic alkali leads to 2-(acetylmethylthio)-3-ureido-6-chloropyridine. 2-Chloro-6-phenyl-7-acetylpyrido-[2,3-b] [1,4]thiazine and 2-(benzoylmethylthio)-3-ureido-6-chloropyridine are formed in the reaction of 2-mercapto-3-ureido-6-chloropyridine with chlorobenzoylacetone in the presence of an equimolar amount of alkali, while 2-(benzoylmethylthio)-3-acetamido-6-chloropyridine is formed when excess alkali is used. See [1] for communication 37. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–790, June, 1980.     

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.     

Chemistry of Thienopyridines. XXIV. Two Transformations of Thieno[ 2,3-b] pyridine 7-Oxide

Refluxing thieno[2,3-b ]pyridine 7-oxide ( 1 ) with aeetic anhydride plus subsequent hydrolysis produced a mixture of thieno[2,3-b]pyrid-6(7H)one ( 2 ) (13%) and 5-hydroxythieno[2,3-b]-pyridine ( 4 ) (4%). Refluxing 1 with phosphorus oxychloride yielded a mixture of 4- and 6-chloro-thieno[2,3-b]pyridines, ( 5 ) (54%) and ( 6 ) (31%), respectively. Compound 6 was also obtained directly from 2 (31%). A mechanistic rationalization for the isomerization of 1 to form 2 and 4 is presented. Marked differences in the mass spectral fragmentations of these three isomeric compounds are noted.     

Furanverbindungen, 14. Mitt.

Zusammenfassung Eine für die Synthese linearer Furoxanthone ohne Substituenten am Furanring geeignete Methode ist dieUllmann-Kondensation von 6-Hydroxycumaran mit verschiedenen o-Chlorbenzoesäuren mit anschließender Cyclisierung und Dehydrierung. Als Beispiele werden die Synthesen von Furo[3,2-b]-, 7-Methylfuro-[3,2-b]-und 8-Methylfuro[3,2-b]xanthon beschrieben.

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A method for the synthesis of linear furoxanthones carrying no substituent in the furan ring is achieved by theUllmann condensation of 6-hydroxycoumaran with various o-chlorobenzoic acids, followed by cyclisation and subsequent dehydrogenation. This is illustrated by the synthesis of furo[3,2-b]-, 7-methylfuro[3,2-b]-and 8-methylfuro[3,2-b]xanthones.

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Diese Veröffentlichung ist ein Teil der Dissertation, dieC. S. Angadiyavar an der Karnatak University zur Erlangung des Titels eines Ph. Dr. einreichen wird.

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10. Mitt.:Y. S. Agasimundin undS. Rajagopal, Chem. Ber.100, 383 (1967).     

Pyrroloindoles. 2. Some electrophilic substitution reactions in the 1H, 6H-pyrrolo[2, 3-e] indole series

As expected, the 3 and 8 positions are the reaction centers of 1H, 6H-pyrrolo-[2, 3-e] indole in the Vilsmeier-Haack and Mannich reactions. Diazo coupling takes place primarily in the 3 position and leads primarily to monosubstitution products. 6,8-Diacetyl-1H,6H-pyrrolo [2,3-e]indole and 1,8-diacetyl-1H, 6H-pyrrolo-[2,3-e] indole were isolated from the acetylation products.See [1] for communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 639–644, May, 1980.     

Condensed isoquinolines. 37.* Heterocyclization using 3-(arylamino)- and 3-(hetarylamino)isoquinolin-1(2H)-ones

The reaction of 3-NHR-isoquinolin-1(2H)-ones (R = Ar) with aromatic aldehydes in the presence of Me3SiCl or in acetic acid leads to the formation of derivatives of dibenzo[b,f][1, 8]naphthyridin-5(6H)- one and benzo[f]isoquino[3,4-b][1, 8]naphthyridine-5,9(6H,7H)-dione. The reaction for R = Het in the presence of Me3SiCl gives derivatives of 5H-pyrido[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, benzo[f]isoquinoline[3,4-b][1,8]naphthyridine-5,9[6H,7H]-dione, and derivatives of new heterocyclic systems, 5H-pyrazino[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, 5H-[1,3]thiazolo[3',2':1,2]pyrimido- [4,5-c]isoquinolin-5-one, 5-H-benzo[f]pyrazolo[3,4-b][1,8]naphthyridin-5-one, and isoquino[3,4-b]- [1,5]naphthyridin-5(6H)-one. The effect of the structure of substituent R and nature of the substituent in the benzaldehydes on the structure of the reaction products was studied.     

Benzo[b] thiophene derivatives. XVIII. The sulfur isosteres of harmaline,harmine and related isomers

The sulfur analogs of harmaline, 7-methoxy-3,4-dihydro-1-methyl[1]benzothieno[2,3-c]-pyridine (Ib), harmine, 7-methoxy-1-methyl[1]benzothieno[2,3- c ]pyridine (IIb), and corresponding 6-methoxy isomers (Ic and IIc) have been synthesized for pharmacological evaluation as monoamine oxidase inhibitors.     

Polycyclic nitrogen compounds. Part II. Tricyclic quinoxalinones and their 4- or 6-aza analogues

1,2,3,3a-Tetrahydro-9-nitropyrrolo[1,2-α]quinoxalin-4-one and 7,8,9,10-tetrahydro-3-nitropyrido[1,2-α]quin-oxalin-6-one (V-VI) were reduced and deaminated to give new parent tricyclic quinoxalinone skeletons I-II. The latter compounds were identical with the tricycles obtained by an unambiguous independent synthesis. New 6-aza-1,2,3,3a-tetrahydropyrrolo[1,2-α]quinoxalin-4-one (III) and 4-aza-7,8,9,10-tetrahydropyrido[1,2-α]-quinoxalin-6-one (IV) were prepared by selective hydrogen transfer reductive cyclisation of esters of N-(2-nitro-3-pyridyl)pyrrolidine-2-carboxylic acid and N-(2-nitro-3-pyridyl)piperidine-2-carboxylic acid (Xb and XIb) respectively.     

Modified Coumarins. 6. Synthesis of Substituted 5,6-Benzopsoralens

Substituted 5H-benzo[c]furo[3,2-g]chromen-5-ones, modified analogs of psoralen that contain a benzene ring annelated at the 5,6-position of a furo[3,2-g]chromen-7-one system, were synthesized from 3-hydroxy- 6H-benzo[c]chromen-6-ones.     

Heterocyclic derivatives of purines. 3. Synthesis and mass spectrometric study of imidazo[1,2-]purine

A mixture containing 65% 1-methyl-2-phenyl-5,7-dichloro- and 35% 1-methyl-2-phenyl-3,5,7-trichloroimidazo [1,2-f] purine (the percentages of the components were established by means of Chromatographic mass-spectrometric analysis) was obtained by refluxing 1,8-dimethyl-2-phenylimidazo [1,2-f]xanthine in POCl₃ in the presence of excess PCl₅. Reduction of this mixture with concentrated HCl in the presence of red phosphorus leads to 1-methyl-2-phenylimidazo[1,2-f] purine, while heating with piperidine gives a mixture consisting of 55% 1-methyl-2-phenyl-6-piperidino-8-chloroimidazo [1,2-f] purine and 45% 1-methyl-2-phenyl-3, 8-dichloro-6-piperidino-imidazo [1,2-f] purine. The IR, PMR, and mass spectra of the compounds obtained are discussed.See [1] for communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125–1129, August, 1980.     

Modified Coumarins. 17. Synthesis and Anticoagulant Activity of 3,4-Cycloannelated Coumarin D-Glycopyranosides

3,4-Cyclocondensed coumarin O-glycopyranosides containing glucose, galactose, xylose, and arabinose were synthesized by condensation of potassium salts of hydroxycoumarins and acetobromosugars. 7-(β-D-Galactopyranosyloxy)-2,3-dihydrocyclopenta[c]chromen-4-one, 3-(β-D-xylopyranosyloxy)-7,8,9,10-tetrahydrobenzo[c]chromen-6-one, and 3-(α-D-arabinopyranosyloxy)benzo[c]chromen-6-one exhibited distinct anticoagulant activity. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 416–419, September–October, 2005.     

2-Azabicyclo[2.1.1]hexanes. 2. Substitutent effects on the bromine-mediated rearrangement of 2-azabicyclo[2.2.0]hex-5-enes

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 have been prepared by photoirradiation of appropriately substituted 1,2-dihydropyridines. Torquoselectivity is observed in the synthesis of the 3-endo-methyl- and 3-endo-phenyl-2-azabicyclo[2.2.0]hexenes 6c-e from 2-methyl- and 2-phenyl-1,2-dihydropyridines 5c-e. Products formed upon addition of bromine to 3-endo-, 4-, and 5-methyl- and 3-endo-phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6a-f were substituent dependent. For 6a,b, which lack substituents at C(3) or C(5), mixtures of unrearranged dibromides 8a,b and rearranged dibromides 9a,b were obtained. With the 3-endo-substituents in 6c-e, only rearranged dibromides 9c-e were formed; 5-methyl substitution afforded mainly unrearranged dibromide 8f and some allylic bromide 10. Both unrearranged 5-endo,6-exo-dibromo-2-azabicyclo[2.2.0]hexanes 8 and rearranged 5-anti-6-anti-dibromo-2-azabicyclo[2.1.1]hexanes 9 are formed stereoselectively. The dibromoazabicyclo[2.1.1]hexanes 9 have been reductively debrominated to afford the first reported 2-azabicyclo[2.1.1]hexanes 11 with alkyl or aryl substituents at C-3.