Pyrrolo[3,2-c]piperidines

The heterocyclization reaction of oximes derived from aliphatic ketones with acetylene has been applied to piperidone oximes. Pyrrole[3,2-c]piperidines substituted on the six-membered ring have been prepared in this manner. Assumptions have been made concerning their conformational and configurational properties. These reactions have been demonstrated to lead to the formation of condensed systems containing a pyrrolenine fragment.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 973–977, July, 1987.     

Synthesis of some 3-substituted [1,8]naphthyrido[3,2-c][1,8]naphthyridines. A new heterocyclic ring system

Some 3-substituted-5,6-dihydro[1,8]naphthyrido[3,2-c][1,8]naphthyridines (V) were obtained by the condensation of 7-substituted-2,3-dihydro-1,8-naphthyridin-4-(1H)ones (IV) with 2-aminonicotinaldehyde. All of the 5,6-dihydro derivatives V were transformed into the fully aromatic compounds VI by refluxing with nitrobenzene.     

Synthesis of some 3-substituted quino[3,2-c][1,8]naphtyridines. A new heterocyclic ring system

Isatoic acid reacts with 7-mcthyl-2,3-dihydro-1,8-naphthyridin-4(1H) one ( 8 ) to give 3-methyl-5,6-dihvdroquino[3,2-c][1,8]naphthyriclin-7-carboxylic acid ( 9a ), which was transformed into the 3-methylquino[3,2-c][1,8]naphthyridine ( 7a ) by refluxing with copper chromite in quinoline. The same product ( 7a ) was also obtained by aromatization of the 3-methyl-5,6-dihydroquino-[3,2-c][1.8]naphthvridine ( 10a ), prepared by condensation of the ketone ( 8 ) and o-aminobenzaldehyde. Other 3-substituted quino[3,2-c][1,8]naphthyridines ( 7b,c,d,e ), which contain a new heterocyclic, ring structure, have been prepared using o-aminobenzaldehyde and 7-sub-stituted-2,3-dihv dro-1,8-naphthyridin-4(1H) ones ( 12 and 13 ) as starting materials. Also, the preparation of the parent nucleus ( 7f ) is described.     

A new derivative of 1,5-dihydropyrazolo[4,3-c][1,2,5]benzotriazepine

A new compound, 1,5-dihydro-3-methyl-7-nitro-propylpyrazolo[4,3-c][1,2,5]benzotriazepine, was synthesized by intramolecular cyclization of 5-amino-4-[(2-bromo-5-nitrophenyl) azo]-3-methyl-1-isopropylpyrazole, and it was established on the basis of the spectral data that the triazepine ring in the synthesized compound exists in two tautomeric forms — amino-azo- and hydrazone. The structure of the compound synthesized was confirmed by the data of the PMR, IR, electronic, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1136–1139, August, 1984.     

Beiträge zur Chemie der Pyrrolo[3,2-c]azepine und der Pyrrolo [3,2-b]azepine

Some chemical transformations in the series of the pyrrolo [3,2-b]azepines and the pyrrolo[3,2-c]azepines are reported: alkylation at the pyrrolo nitrogen and/or the azepino nitrogen, reduction of the lactam group by means of LiAlH₄, preparation of lactim ethers and amidines, substitution in position 2 by MANNICH reaction, bromination and condensation with oxalyl chloride or chloral hydrate, and the cyclocondensation with dimethylmalonyl chloride. The structures of the 2-substitution products have been evaluated by NMR.-spectroscopy.     

Nitration studies of naphtho[2,3-c][1,2,5]thiadiazole

Nitration of naphtho[2,3-c][1,2,5]thiadiazole gives the 5-nitro derivative in 61–66% yield. Chlorination of this product apparently gives an unstable addition product which loses hydrogen chloride on recrystallization to give 4-chloro-8-nitronaphtho[2,3-c][1,2,5]thiadiazole. Thus, naphtho[2,3-c][1,2,5]thiadiazole under nitrating conditions behaves as a 2-substituted naphthalene rather than as an anthracene analog.     

Synthesis of thieno[3,4-c] and thieno[3,2-c][2,1]benzothiazepines

Starting from [4,3-c] and [3,2-c] methyl chlorosulfonylthiophenecarboxylates the synthesis of ketones 7 and 8 is described. These compounds are the first two representatives of the new thieno[3,4-c] and thieno-[3,2-c][2,1]benzothiazepine ring systems. The formation of methyl 3-chlorosulfonylthiophene-2-carboxy-late is also revised.     

1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazolidyl: a long-lived radical anion and its stable salts

[1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazole (1) is synthesized in 62% yield by fluoride ion-induced condensation of 3,4-difluoro-1,2,5-thiadiazole with (Me(3)SiN=)(2)S. The reversible electrochemical reduction of 1 leads to the long-lived [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazolidyl radical anion (2) and further to the dianion (3). The radical anion 2 is also obtained by the chemical reduction of the precursor 1 with t-BuOK in MeCN. The radical anion 2 is characterized by ESR spectroscopy in solution and in the crystalline state. The stable salts [K(18-crown-6)][2] and [K(18-crown-6)][2].MeCN (8 and 9, respectively) are isolated from the spontaneous decomposition of the [K(18-crown-6)][PhXNSN] (6, X = S; 7, X = Se) salts in MeCN solution followed by XRD characterization. The radical anion 2 acts as a bridging ligand in 8 and as chelating ligand in 9. The structural changes observed by XRD in going from 1 to 2 are explained by means of DFT/(U)B3LYP/6-311+G calculations.     

Halogenation and nitration of naphtho[1,2-c][1,2,5]thiadiazole

Bromination of naphtho[1,2-c][1,2,5]thiadiazole ( I ) gives either an addition product, 4,5-dibromo-4,5-dihydronaphtho[1,2-c][1,2,5]thiadiazole ( II ), or a substitution product, 5,6-dibromonaphtho[1,2-c][1,2,5]thiadiazole ( III ), depending on the reaction conditions. Dehydrobromination of II gives 5-bromonaphtho[12-c][1,2,5]thiadiazole ( IV ). Chlorination of I gives the corresponding addition product V or 5-chloronaphtho[1,2-c][1,2,5]thiadiazole ( VI ). Compound VI can also be obtained by dehydrochlorination of V. The nitration of I produces a mixture of isomeric substitution products, 9-nitro VIII and 6-nitronaphtho[1,2-c][1,2,5]thiadiazoles ( VII ).     

Synthesis and rearrangements of 7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]-and 7h-pyrrolo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines

7H-Pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines were synthesized by the reactions of 2-ethoxymethyleneamino-1H-pyrrole-3-carbonitriles with acid hydrazides and by the reactions of aminoiminopyrimidines (prepared based on the above-mentioned carbonitriles) with acid chlorides. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1438–1443, August, 2006.     

A new synthesis of benzofuro[3,2-c]pyridines

The condensation of O-phenylhydroxylamine with piperidin-4-one and 3-methylpiperidin-4-one has given 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine and 4-methyl-1,2,3,4-tetrahydro-benzofuro [3,2-c]pyridine, and these have been dehydrogenated to the corresponding heteroaromatic system of benzofuro[3,2-c]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.7, pp. 908–909, July, 1973.     

Synthesis of pyrido[3,2-e]pyrrolo[2,1-c][1,2,4]triazines from pyrido[3,2-e][1,2,4]triazine derivatives

In carrying on our interest in heteropolycyclic structures with biological activities, we projected the preparation of compounds containing the pyrido[3,2-e][1,2,4]triazine or pyrido[2,3-b][1,4]triazepine systems. The established synthetic approach for the preparation of latter system led to the triazine derivatives 5a-f while a new bicyclic triazepine structure 6 is accomplished with difficulty. In expanding the pyridotriazine structure, we obtained derivatives of a new tricyclic structure, 5-substituted-6a-ethyloxycarbonyl-5,6,6a,7-tetrahydropyrido[2,3-e]pyrrolo[2,1-c][1,2,4]triazin-9(8H)-ones 8 in which the triazine ring is fused with a pyrrole nucleus. Compounds 5a-f and 8a,b will be tested as potential CNS depressant, antiinflammatory, analgesic and antibacterial agents.     

New Facile Route to Synthesize Furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives

A new facile route for synthesis of 3-(aryl)-8,9-diphenylfuro[3,2-e][1,2,4]triazolo pyrimidines derivative from the same starting material, 2-amino-4,5-diphenylfuran-3-carbonitrile, has been developed through heterocyclization of the corresponding arylidene-hydrazono-5,6-diphenylfuro[2,3-d]pyrimidine and N-(arylmethylene)-4-imino-5,6-diphenylfuro[2,3-d]pyrimidin-3(4H)-amine under refluxing condition with acetic anhydride followed by air oxidation. The products were obtained in good yield with an easy workup along with the purification of products by a nonchromatographic method. This general synthetic procedure can be extended to the preparation of a wide range of isomeric triazoles using 2-amino 3-carbonitrile bifunctional derivatives.     

Synthesis of substituted furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines and furo[3,2-e]tetrazolo[1,5-c]pyrimidines

A series of substituted furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines and furo[3,2-e]tetrazolo[1,5-c]pyrimidines were obtained from reactions of substituted 2-dimemylamino-4-hydrazmofuro[2,3-d]pyrimidines with orthoesters or sodium nitrite in acetic acid, respectively.     

Studies on mechanisms of the rearrangement of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines into thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines

Recyclization of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines was studied experimentally and theoretically by B3LYP/6-31G** calculations in the gas phase and in solution (EtOH). The experimentally observed characteristic features of the isomerization (the possibility of the Dimroth rearrangement occurring by the ANRORC mechanism and high energy barriers in acid-catalyzed reactions) were confirmed by quantum chemical calculations. Substituents in the triazole ring were found to play the principal role in the rearrangement. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2164–2171, December, 2006.     

A new synthesis of 2,3-dihydrofuro[2,3-b], [2,3-c] and [3,2-c]quinolines

A new synthesis of three isomeric dihydrofuroquinolines is described. This route via ortholithiation of O-quinolyl carbamates is considerably more effective than that which proceeds via lithiation of alkoxyquinolines.     

Synthesis of some 3-Methyl-11H-indolo[3,2-c] [1,8]naphthyridines. A New heterocyclic ring system

Some derivatives of 11H-indolo[3,2-c] [1,8]naphthyridine, a new heterocyclic system, have been prepared using the Fischer indole synthesis on the appropriately phenylhydrazones. The preparation of some substituted 5,6-dihydro-11H-indolo[3,2-c][1,8]naphthyridines is also described.     

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.