5,6-Dihydro-4H-imidazo[4,5,1-i,j]quinoline derivatives

The oxidation of 2-hydroxymethyl and 2-methyl derivatives of 5,6-dihydro-4H-imidazo[4,5,1-i,j] quinoline with active manganese dioxide and selenium dioxide gave 2-formyl derivatives of this heterocycle. Some transformations of these compounds are realized.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 967–969, July, 1971.     

5,6-Dihydro-4h-imidazole[4,5,1-i,j]quinoline derivatives

2-Alkyl(dialkyl)amino derivatives of I and their respective cyclic ammonium salts were obtained by reaction of the 2-chloro derivative of 5,6-dihydro-4H-imidazole [4,5,1-i,j ]quinoline (I) and its methiodide with amines. The eycloammonium salt was converted into 2-amino(alkylimino)-l,2-dihydro derivatives of 5. Methoxy- and methyl-substituted I readily formed 2-amino derivatives by reaction with sodium amide. Comparison of the UV spectra of the 2-amino derivative of I and its fixed tautomeric form indicates that the 2-amino derivative of I exists primarily in the amino form in dioxane and CC14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1410–1413, October, 1970.     

Synthesis and Properties of 1,3-Diaryl-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium Bromides

It has been established that the condensation of 3-(4-methoxyphenylamino)-5,6-dihydro-2H-1,4-oxazine with substituted phenacyl bromides occurs at the exocyclic nitrogen atom with formation of 3-aryl-3-hydroxy-1-(4-methoxyphenyl)-2,5,6,8-tetrahydro-3H-imidazo[2,1-c]-1,4-oxazinium bromides. By treatment of the latter with acetic anhydride 3-aryl-1-(4-methoxyphenyl)-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium bromides are formed. The structures of the compounds synthesized were determined via ¹H NMR spectroscopy and X-ray diffraction.     

Syntheses of Examples of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline, 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine,and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine ring systems

Lithiation of 1-vinylbenzotriazole 9 with n-BuLi (2 equiv) generates dianion 10, which upon subsequent reaction with 1,2- and 1,4-diketones affords 14 and 13, representatives of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline 1 and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine 2 ring systems, respectively. Reactions of dianion 10 with isocyanates give 15a,b, which contain the 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine 3 ring system.     

4-hydroxy-2-quinolones. 94. Improved synthesis and structure of 1-hydroxy-3-oxo-5,6-dihydro-3h-pyrrolo[3,2,1-i,j]-quinoline-2-carboxylic acid ethyl ester

A modified method is proposed for preparation and purification, and the special features of the spatial structure have been studied for the ethyl ester of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-i,j]-quinoline-2-carboxylic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 718–723, May, 2006.     

Synthesis of 5,6-dihydro-8-methoxy-4H-imidazo[4,5,1-ij]quinolines and some related ring systems

Reduction of amides of 8-amino-6-methoxyquinoline over platinum oxide in glacial acetic acid at room temperature affords 2-substituted-5,6-dihydro-8-methoxy-4H-imidazo [4,5,1-ij]-quinolines (I). The method could not be utilized for urea or carbamate derivatives of 8-amino-6-methoxyquinoline. 2-Amino derivatives of I were prepared through the chloro compound obtained from 5,6-dihydro-8-methoxy-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one, (IV). Several related ring systems have also been prepared.     

HETEROCYCLIC SYSTEMS CONTAINING BRIDGE HEAD NITROGEN ATOM: REACTION OF 5-MERCAPTO-4H-IMIDAZO[4,5-e]- [2,1,3]BENZOTHIADIAZOLES AND 5,6-DIAMINO[2,1,3]BENZOTHIAZOLE WITH 3-(2-BROMOACETYL)COUMARINS

Condensation of 5-mercapto-4H-imidazo[4,5-e][2,1,3]benzothiadiazole (I) with various 3-(2-bromoacetyl)coumarins, followed by PPA cyclization of the intermediate ketones II, yielded 3-(2,8-dithia 1,3,5b, 9-tetraaza cyclopenta(b)-as-indacen-6-yl)chromen-2-ones III. Reaction of 5,6-diamino[2,1,3]benzothiadiazole with 3-(2-bromoacetyl)- coumarin in anhydrous ethanol containing fused sodium acetate gave the corresponding 2-coumarinyl 3,4-dihydro-1,4-pyrazino[5,6-e][2,1,3]benzothiadiazoles IV.     

Synthesis of aminomethyl derivatives of 3-methyl-4,7-dihydro-3H-imidazo[4,5-d][1,2,3]triazin-4-one

New aminomethyl derivatives of 3-methyl-4,7-dihydro-3H-imidazo[4,5-d][l,2,3]triazin-4-one were synthesized by Mannich reaction. These Mannich bases is also possible to prepare by reaction of 7(5)-hydroxymethyl-3-methyl-4,7(5)dihydro-3H-imidazo[4,5-d][l,2,3]triazin-4-one with amines. The compounds obtained exist in solutions as mixtures of N⁵ and N⁷ isomers, and the fraction of the latter grows with the polarity of the solvent.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.     

Synthesis of substituted 1,4-diazepino[5,6,7-kl]acridines and imidazo[4,5,1-de][1,4]diazepino[5,6,7-mn]acridines

The synthesis of some substituted ll-methoxy-7-nitro-4H,8H-2,3-dihydro-1,4-diazepino[5,6,7-kl]acridines 4 with more diversified chains at position 4 is described. A convenient method for transformation of these compounds into the corresponding 4-substituted 12-methoxy-4H-2,3-dihydroimidazo[4,5,1-de][1,4]diazepino-[5,6,7-mn]acridine (5) is reported.     

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,molecular structure,and applications of 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate to the synthesis of novel heterocyclic ring systems

2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate (1) has been prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Deprotonated compound 1a containing both the nucleophilic endocyclic nitrogen atoms and electrophilic exocyclic nitrogen was used for the syntheses of 3-substituted 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]oxadiazoles 2-9 and 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]thiadiazole-3-thione (10) by tandem nucleophilic addition-electrophilic amination reaction. The method promises utility in the synthesis of a variety of other heterocycles. On the other hand, the convenient routes to 7,8-dihydroimidazo[1,2-c][1,3,5]thiadiazine-2,4(6H)-dithione (16) and 2,6,7,8-tetrahydroimidazo[1,2-a][1,3,5]triazine-4(3H)-thione derivative (17) are reported starting from compound 1. The structures of the compounds prepared were established by elemental analyses, IR, NMR, and MS spectra, and in some instances X-ray analyses.     

Arene imine derivatives of nitrogen heterocycles: 1a,9b-dihydrobenz[h]-azirino[f]quinoline, 1a,9b-dihydrobenz[f]azirino[h]quinoline and 1a,9b-dihydroazirino[f][1,10]phenanthroline

The syntheses of the K-imine derivatives of benzo[h]quinoline ( 1 ), benzo[f]quinoline ( 2 ) and 1,10-phenanthroline ( 3 ) are described. The parent nitrogen heterocycles were oxidized with sodium hypochlorite to the corresponding K-oxides, 4, 6 and 8 , which in turn were reacted with sodium azide. The resulting azido alcohols were then cyclized with triethyl phosphite to the title compounds 5, 7 and 9 . The oxirane ring cleavage in benzo[h]quinoline 5,6-oxide ( 4 ) and in benzo[f]quinoline 5,6-oxide ( 6 ) by sodium azide proceeded by the predicted regioselectivity: 4 gave trans-5-azido-5,6-dihydro-6-benzo[h]quinolinol ( 11 ) and trans-6-azido-5,6-dihydro-5-benzo[h]quinolinol ( 10 ) as the major and minor products respectively, and 6 yielded solely trans-6-azido-5,6-dihydro-5-benzo[f]quinolinol ( 12 ). The latter compound proved by X-ray analysis to crystallize as a hydrogen bonded dimer.     

Synthesis and cyclic AMP phosphodiesterase 4 isoenzyme inhibitory activity of heterocycle condensed purines

To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP phosphodiesterase 4 (PDE4), a series of heterocycle [a]-, [b]-, [c,d]-, and [i]-condensed purines were designed and synthesized. Although all compounds did not display PDE1 and PDE3 inhibitory activities, several heterocycle [i]-condensed purines strongly inhibited PDE4. Especially, dl-3,4-dipropyl-8-methyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (dl-7c) exhibited comparable PDE4 inhibitory activity (IC(50)=1.9 microM) to rolipram and denbufylline (DBF).     

Conformational effects on photophysical characteristics of C5-C5'-linked dihydrothymine dimers in solution

Photophysical characteristics of N-substituted C5-C5'-linked dihydrothymine dimers (1a,b[meso], meso compounds of [5R,5'S]-bi-5,6-dihydrothymines; 1a,b[rac], racemic compounds of [5R,5'R]-bi-5,6-dihydrothymines and [5S,5'S]-bi-5,6-dihydrothymines) in aqueous solution with varying contents of less-polar aprotic solvent such as tetrahydrofuran or dioxane have been investigated by UV-absorption, and steady-state and time-resolved fluorescence spectroscopies. Among the C5-C5'-linked dimers, (5R,5'S)-bi-5,6-dihydro-1-methylthymine (1a[meso]) showed a red-shifted weak UV-absorption band at 270-350 nm and excimer fluorescence emission at lambda max = 370 nm with a quantum yield (phi F) of approximately 0.1 in phosphate buffer (pH < 10) at 293 K. Racemic compound of 5,6-dihydro-1-methylthymine dimer (1a[rac]), meso and racemic compounds of 5,6-dihydro-1,3-dimethylthymine dimers (1b[meso] and 1b[rac]) in phosphate buffer were nonfluorescent under similar conditions. The UV-absorption and fluorescence spectral characteristics of 1a[meso] in aqueous solution were interpreted in terms of intramolecular stacking interactions between the dihydropyrimidine chromophores leading to a preferential "closed-shell" conformation both in the ground state and the excited singlet state. In basic solutions at pH > pKa = 11.7, the fluorescence quantum yield of 1a[meso] decreased due to a dominant "open-shell" conformation resulting from the electrostatic repulsion between the deprotonated dihydrothymine chromophores of 1a[meso] in a dianion form.     

Reaction of α,α-, α,α′-dihalothiones with 8-mercaptoquinolinium halides as a route to tetrahydro-1,4-thiazinoquinolinium halides

The reaction of 8-mercaptoquinolinium bromide with 1,3-dibromopropane-2-thione or 3,3-dibromobutane-2-thione in methanol gave the 2-bromomethyl-2-mercaptotetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium and 3-bromo-2-mercapto-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium bromides which readily exchanged the Br⁻ anion for ClO ₄ ⁻ upon treatment with sodium perchlorate in methanol. Oxidation of the 3-bromo-2-mercapto-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]-quinolinium bromide by selenium dioxide gave 2,2-dithiobis(3-bromo-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium) bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1720–1723, November, 2006.     

Reaction of ethyl γ-bromo-β-methoxycrotonate with carbonyl compounds. Synthesis of 4-methoxy-6-substituted-5,6-dihydro-2H-pyran-2-ones and 3-substituted 3-pyrazolin-5-ones

Ethyl β-methoxycrotonate I reacts with substituted carbonyl compounds II in benzene to give 4-methoxy-6-substituted-5,6-dihydro-2H-pyran-2-ones III. The reaction of IIIa and j with hydrazine hydrate in ethanol leads to 3-[(1′-thienyl-1-hydroxy)methyl]-5-hydroxy-1H-pyrazole (IVa) and 3-[1′-styryl-1′-hydroxy)methyl]-5-hydroxy-1H-pyrazole (IVj) in good yields. The structure of the products were assigned and confirmed on the basis of their elemental analysis and the electronic absorption, infrared and nmr spectra.     

Electrochemical oxidation of 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d] pyrimidine-4,6-dione (oxipurinol) at the pyrolytic graphite electrode

The electrochemical oxidation of 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d] pyrimidine-4,6-dione (oxipurinol) at the pyrolytic graphite electrode (PGE) has been studied. Oxipurinol exhibits up to three voltammetric oxidation peaks at the PGE between pH 1–12. The first pH-dependent peak (peak I_a) is proposed to be an initial, irreversible 2e-2H⁺ reaction to give 5,6-dihydro-4H-pyrazolo[3,4-d] pyrimidine-4,6-dione. This primary product further reacts by two routes. The major route, accounting for ca. 90% of the latter compound, involves a Michael addition of water followed by further electrochemical oxidation and hydrolysis to give 5,6-dihydro-5,6-dihydroxy-5-carboxy-6-diazenouracil. The minor route involves further electrochemical oxidation of 5,6-dihydro-4H-pyrazolo[3,4-d]-pyrimidine-4,6-dione in a 2e-2H⁺ reaction to give 4,5,6,7-tetrahydro-3H-pyrazolo[3,4-d]-pyrimidine-3,4,6-trione.Decomposition and, generally, additional electrochemical reactions of 5,6-dihydro-5,6-dihydroxy-5-carboxy-6-diazenouracil result in the formation of alloxan, parabanic acid, 6-diazo-isobarbituric acid and 5′-hydroxy-5-carboxy-6,6′-azouracil. The two latter compounds have never previously been reported. Decomposition of 4,5,6,7-tetrahydro-3H-pyrazolo[3,4-d]pyrimidine-3,4,6-trione results in formation of uracil-5-carboxylic acid.Detailed reaction schemes have been proposed to explain the observed electrochemistry and the formation of the observed products.     

Transformations of substituted tetrahydro-8h-indeno[1,2-d]imidazoles in concentrated sulfuric acid

The five-membered ring of the indene system in 2,8-dioxo-3a-hydroxy-8a-R-1,2,3a,8a-tetrahydro-8H-indeno[1,2-d]imidazoles is hydrolytically cleaved in concentrated sulfuric acid solutions. Depending on the reaction conditions, compounds for which substituted 4-(o-carboxyphenyl)imidazol-2-one (II), 1,8-dioxo-1,2-dihydro-8H-imidazo[4,3-a]isoindole (III), and spiro[imidazolidine-4,3′-phthalide] structures were assumed were isolated.     

Synthesis in the phenothiazine series

Quaternary salts of imidazo[4,5,1-k,l]phenothiazine were reduced with potassium borohydride to 1,2-dihydro-2-methylimidazo[4,5,1-k,l]phenothiazine, which was converted to 1,2 dihydro-2-methylimidazo[4,5,1-k,l]phenothiazine-1-thione and 1-methylamino-10-formylphenothiazine. The latter was hydrolyzed to 1-methylaminophenothiazine, which was also obtained by reduction of methyl phenothiazine-1-carbamate. The PMR and IR spectra of some of the derivatives are discussed.See [1] for communication XXXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372–374, March, 1974.