Nitrogen bridgehead compounds,part 68. Studies on quinolizine derivatives. Part 2. Synthesis of 1,3-disubstituted-4H-quinolizine derivatives

Quinolizine compounds 1 and 2 or their monocyclic tautomers 3 and 4 have been synthesized using 2-pyri-dineacetic acid derivatives 6a, b, A, B and ethoxymethylenemalonic acid derivatives 7a, b, c in base catalyzed or thermic reaction. In the 6-unsubstituted series, both the 4-oxo and 4-imino derivatives could have been obtained, in the 6-substituted series, however the 4-oxo ones only, whereas instead of the 4-imino derivatives, their monocyclic tautomers 3, 4 have been isolated. In the 6-unsubstituted series, the primarily formed 4-imino compounds have been rearranged into 4-oxo ones under stronger conditions. The structure of the isolated compounds have been proved by ultraviolet, infrared and ¹H nmr spectra, that of 3B=C by X-ray analysis as well.     

Nitrogen bridgehead compounds. Part 69. Studies on quinolizine derivatives. Part 3. Infrared and 1H NMR spectroscopic studies of quinolizine derivatives and their monocyclic tautomers

Infrared and ¹H nmr spectra of 4-oxo, 1 , and 4-imino, 2 , quinolizine derivatives or their monocyclic tautomers 3, 4 have been comparatively studied. The number of ethoxycarbonyl groups, the signals of the hetero proton, the C(9)-H, and the C(6)-CH₃ group in the ¹H nmr spectrum, moreover the N-H stretching vibration bands proved to be diagnostically important for monocyclic or bicyclic as well as for 4-oxo or 4-imino structures. A weak intramolecular hydrogen bridge in compounds 2b and 2f , a strong chelate type hydrogen bridge in 4E and 4F=G could have been demonstrated as well.     

Solvation of the bismuth(III) ion by water, dimethyl sulfoxide, N,N'-dimethylpropyleneurea, and N,N-dimethylthioformamide. An EXAFS, large-angle X-ray scattering, and crystallographic structural study

The structure of the solvated bismuth(III) ion in aqueous, dimethyl sulfoxide, N,N'-dimethylpropyleneurea, and N,N-dimethylthioformamide solution has been studied by means of EXAFS and large-angle X-ray scattering (LAXS). The crystal structures of the solid compounds octakis(dimethyl sulfoxide)bismuth(III) perchlorate, [Bi(OS(CH3)2)8](ClO4)3, hexakis(N,N'-dimethylpropyleneurea)bismuth(III) perchlorate, [Bi(OCN2(CH2)3(CH3)2)6](ClO4)3, and nonaaquabismuth(III) trifluoromethanesulfonate, [Bi(H2O)9](CF3SO3)3 (redetermination), have been determined. The aqueous solutions must be strongly acidic, since the hydrated bismuth(III) ion starts to hydrolyze into Bi6O4(OH)4(6+) complexes already at an excess of strong acid at 1.0 mol.dm-3. For very acidic aqueous perchlorate solutions, the LAXS and EXAFS data gave a satisfactory fit for eight-coordination of the bismuth(III) ion, with a mean Bi-O bond distance of 2.41(1) A. The crystal structure of octakis(dimethyl sulfoxide)bismuth(III) perchlorate shows that the bismuth(III) ion coordinates eight dimethyl sulfoxide molecules via the oxygen atoms in a distorted square antiprismatic configuration. The mean Bi-O bond distance is 2.43 A and the mean Bi...S distance 3.56 A. For the dimethyl sulfoxide solution, the corresponding mean distances were found to be 2.411(6) and 3.535(12) A. The N,N'-dimethylpropyleneurea-solvated bismuth(III) ion is octahedrally coordinated in both solid state and solution with the Bi-O bond distances of 2.324(5) and 2.322(3) A, respectively. The bismuth(III) ion is six-coordinated in the sulfur donor solvent N,N-dimethylthioformamide with a mean Bi-S bond distance of 2.794(8) A. A comparison with the structure of the solvated lanthanum(III) ion shows that the bismuth(III) ion is smaller for all coordination numbers. New effective ionic radii for the bismuth(III) ion in different coordination numbers are proposed, based on results in this study and in the literature.     

Development of optimum conditions for the synthesis of sodium polymethylsiliconates

A procedure was suggested for preparing soluble polymethylsilsesquioxane by partial butoxylation of the initial methyltrichlorosilane. The possibility of synthesizing linear sodium methylsiliconates by reaction of polymethylsilsesquioxane with sodium hydroxide in aqueous ethanol or in the presence of dimethyl sulfoxide was demonstrated. Sodium methylsiliconates prepared in aqueous alcohol or as suspension in dimethyl sulfoxide are polymeric products structurally similar to poly(sodiumoxy)methylsilsesquioxane. The suggested procedure considerably simplifies the synthesis of the target compounds as compared to the previously developed methods.     

Bilirubin acidity. Titrimetric and 13C NMR studies.

Acidimetric titration of bilirubin IX-alpha, dissolved in excess aqueous sodium hydroxide, showed that two protons are dissociated with pK values well below 7 and that one or several additional acidic groups titrate with pK around 12.9. Precipitation of the nearly insoluble acid precluded determination of the two lower pK values by titration in aqueous solution. In dimethyl sulfoxide solution, four acidic protons were demonstrated, titrating two by two without precipitation. 13C NMR spectra of bilirubin IX-alpha were recorded and complete assignments were made by comparison with the spectra of bilirubin XIII-alpha and mesobilirubin etc. Such spectra, recorded after addition of 2 and 4 mol of base per mol of bilirubin IX-alpha, showed that both carboxyl groups are titrated by the first 2 mol of base, and both lactams by the following 2 mol of base. Cotitrations of bilirubin IX-alpha with other acids, o- and m-hydroxybenzoic acid and 2-pyridone, were used to determine relative pK values in dimethyl sulfoxide solution, and pK values for the four acidic protons of bilirubin IX-alpha in aqueous solution were calculated from the Born equation. Both carboxyl groups exhibited pK = 4.4, and both lactams pK = 13.0, in good agreement with values expected from the chemical structure of the bilirubin molecule. The implications of these findings for understanding the mechanism of bilirubin neurotoxicity are discussed.     

含嘧啶环的双冠醚（Ⅱ）

由4，6－二氯－5－硝基嘧啶、2，4－二氯－5－硝基－6－甲基嘧啶分别与4′-氨基苯并冠醚反应合成了6种以嘧啶环为桥链的新双冠醚，其中分别含有苯并－12－冠－4（Al,Bl)、苯并－15－冠－5（A2，B2）和苯并－18－冠－6（A3，B3）单元。用这些双冠 氯仿溶液绎碱金属苦味酸盐水溶液进行了萃取，计算了萃取平衡常数Kc。结果表明双冠醚（A1，B1）、（A2，B2）和（A3，B3）分别对钠、钾和铯具有较高的萃取能力，其选择性显著优于相应的单冠醚。     

Quantum chemical studies on some potentially tautomeric oxazolidin-4-one derivatives and their thio and azo anologs

The basicities and nucleophilicities along with prototautomerism of biologically active oxazolidin-4-one and its thio and azo analogs were investigated by semi-empirical methods. The oxo and thion protonation were found to be easier than that of azo protonation for 4-oxo and 4-thion derivatives whereas amino protonation was found to be easier than imino and azo protonation in 4-imino derivative. The preferred tautomeric form for 4-oxo and 4-thion derivatives were found to be the keto and thion forms, respectively, whereas the amino form was found to be preferred in 4-imino derivatives. An acceptable correlation between gas phase proton affinities and aqueous phase acidity constants as well as the correlation between nucleophilicity and acidity constants was observed.     

Pyrazolo [1,5-a]indole. 10. Mitteilung über metallogranische reaktionen und folgeprodukte

Pyrazolo[1,5- a ]indoles Treatment of 1-(2-heteroaroyl or aroyl-phenyl)-pyrazoles ( 3 ) with potassium hydroxide in 95% ethanol or with sodium ethanolate in ethanol produces a novel ring closure to new 4-hydroxy-4-(4-heteroaryl or aryl)-4H-pyrazolo [1,5-a]indoles 5 and 6 (Table 1). A 2, 3, or 4-pyridyl at position 4 is easily reduced yielding the 4-(2, 3, or 4-piperidyl)-derivatives 7 and 8 (Table 2). Water is split off from these piperidyl-derivatives 7 or 8 to give the piperidylidene derivatives 9 or 10 (Table 3) which may be considered as heterocyclic analogues to known tricyclic psychopharmaceuticals with antidepressant or neuroleptic activities.     

Tautomerism in side-chain derivatives of n-heterocycles NMR and UV spectra—I

NMR and UV spectra of some (ψ)cyano-, carbethoxy-, and acylmethyl derivatives of 2-oxo-1,2-dihydroquinoxaline, 2-oxo-1,2-dihydro-6,7-benzoquinoxaline, 3,4-dihydro-1,4,2H-benzoxazone, quinaxoline, and quinoline, were recorded in chloroform, dimethyl sulfoxide, and trifluoro- acetic acid. The results indicate the existence of tautomeric equilibria, with noticeable contribution of the enaminic structures B or D, depending on the solvent and the nature of the heterocycle. Relationhips between some NMR parameters and tautomeric structures were observed.     

Synthesis and ring-opening polymerization of novel bicyclic oxalactams: 2-oxa-5-azabicyclo[2.2.2]octan-6-one

A novel bicyclic oxalactam 2-oxa-5-azabicyclo [2.2.21 octan-6-one (2,5-BOL) was synthesized from sodium 3,4-dihydro-2H-pyran-2-carboxylate through a seven-step reaction sequence. Anionic ring-opening polymerization of 2,5-BOL was carried out in bulk at 12OOC or in dimethyl sulfoxide at 40, 60, and 80°C by using potassium pyrrolidonate and the N-benzoyl derivative of 2,5-BOL as catalyst and activator, respectively. The polymerization gave a new polyamide containing cis- and trans-2,5-linked tetrahydropyran rings in the main chain. The cis/trans ratio varied from 70/30 to 95 /5 depending on the reaction conditions. The polyamide having number average molecular weights of 3000–8000 was soluble in a variety of solvents including methanol, ethanol, dimethyl sulfoxide, dimethylformamide, chloroform, and dichloromethane. It began to decompose at 280–32OOC depending on the compositions of the cis- and trans-2,5-linked structural units. The anionic ring-opening polymerizability of 2,5-BOL was found to be much lower than its structural isomer, 8-oxa-6-azabicyclo[ 3.2.11 octan-7-one (8,6-BOL).     

Saturated heterocycles. Part 209. Synthesis of 1-cyclohexyl-substituted isoquinoline derivatives

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l-methyl-3,4-dihydroisoquinolines 1-4 to yield the diesters 5-9 or the dinitrile 10 , respectively. Compounds 5-10 were converted by Claisen condensation to 1-[(3′-methoxycarbonyl- or 1-[(3′-ethoxycarbonyl-4′-oxo)-l'-cyclohexyl]-3,4-dihydroisoquinoline derivatives 11-16 . Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.     

Tautomeric structure of dihydropyrazolo[1,5-a]-pyrimidin-7-one in a solution. A facile synthesis of novel 6-quinoxalinyldihydropyrazolo[1,5-a]pyrimidin-7-ones by ring transformation

6-Quinoxalinyldihydropyrazolo[1,5-a]pyrimidin-7-ones 4a-d were synthesized by the ring transformation of 3-(N,N-dimethylcarbamoyl)furo[2,3-b]quinoxaline hydrochloride 5 . Compounds 4a-d were found to exist as the 4,7-dihydro-7-oxo form E in dimethyl sulfoxide based on the nmr spectral data.     

A facile method for 2-thiophenacylidenethiazoline derivatives

The reactions of 2-alkyl-5-phenylisothiazole-3-thiones with 2-chloro-1,3-dicarbonyl compounds in chloroform gave the corresponding isothiazolium chlorides which, upon treatment at room temperature with sodium borohydride in a mixture of chloroform and ethanol, underwent S? N bond cleavage to give 3-alkyl-4,5-disubstituted-2-thiophenacylidenethiazolines. Similarly, treatment of the isothiazolium chlorides with triphenylphosphite in chloroform at 60° afforded the same thiazoline derivatives.     

Ring transformations of heterocyclic compounds. XVII, 2-(2,4,6-Triarylphenyl) substituted dihydro-1H-imidazolium,dihydrothiazolium and thiazolium salts from 2-methyl derivatives by pyrylium and thiopyrylium ring transformations

The synthesis of hitherto unknown 2-(2,4,6-triarylphenyl) substituted 4,5-dihydro-1H-imidazolium perchlorates 6 , 4,5-dihydrothiazolium perchlorates 8 and thiazolium perchlorates 9 from their 2-methyl derivatives 2 , 4 and 5 , respectively, by a 2,6-[C₅+C] ring transformation of 2,4,6-triarylpyrylium and -thiopyrylium salts 1/10 in ethanol in the presence of an appropriate base ( 6 : sodium ethanolate; 8,9 : anhydrous sodium acetate) is reported. Spectroscopic data of the transformation products and structural influences on their formation via anhydrobases of the salts 2 , 4 and 5 are discussed.     

Synthesis and reaction of 6-substituted 3-methoxycarbonyl-4-methylthio-2H-pyran-2-one derivatives

Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate ( 2 ) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3a-m . 6-Aryl derivatives 3a-d,g were treated with sodium methoxide in methanol to give the corresponding 6-aryl-4-methoxy-2H-pyran-2-ones 8a-d and 9. Phenylcoumalin ( 7a ) and paracotoin ( 7b ) were synthesized by the desulfurization of 6-aryl-4-methylthio-2H-pyran-2-ones 4a,b. Similarly, anibine ( 8e ) was also synthesized from 3g . Treatment of 3 with hydrogen peroxide or 3-chloroperoxybenzoic acid gave the corresponding 4-methylsulfiny-2H-pyran-2-ones 10a-f in good yields. Displacement reactions of 10a-f with nucleophilic reagents are also described.     

Subtle ring-constraint effects on the formation of metallacycles. Cyclodimer versus cyclotrimer of bis(chloro)-1,4-bis(dimethyl-3 or 4-pyridylsilyl)benzenepalladium(II) complexes

Stepwise modulation of the ring size of metallacyclic compounds via subtle ring-constraint effects has been established. The reactions of (COD)PdCl 2 with p- or m-psb ligand [COD = 1,5-cyclooctadiene; p-psb = 1,4-bis(dimethyl-4-pyridylsilyl)benzene; m-psb = 1,4-bis(dimethyl-3-pyridylsilyl)benzene] in a mixture of acetone and ethanol at room temperature produce the metallacyclodimers [PdCl 2( p- or m-psb)] 2. The cyclodimeric species of [PdCl 2( p-psb)] 2 at the boiling temperature or via the sonication of the chloroform solution is completely converted to the cyclotrimer [PdCl 2( p-psb)] 3. Direct reaction of (COD)PdCl 2 with p-psb in a mixture of acetone and ethanol at reflux temperature yields the same trimer, [PdCl 2( p-psb)] 3. Furthermore, equilibria between the kinetic product, [PdCl 2( p-psb)] 2, and the thermodynamic product, [PdCl 2( p-psb)] 3, have been observed in N, N-dimethylformamide as well as in dimethyl sulfoxide. In contrast, the cyclodimeric structure of [PdCl 2( m-psb)] 2 is retained under the same treatment conditions for 40 h; that is, the trimeric species, [PdCl 2( m-psb)] 3, is not formed. Such a notable difference between [PdCl 2( p-psb)] 2 and [PdCl 2( m-psb)] 2 might be explained by their different angle constraints.     

Chemotherapeutical agents. VII. Synthesis and pesticidal activities of sulphides and sulphones derived from bis[4-aryl-1,2,4-triazoline-5-thione-3-yl]alkane and 5-phenyl-1,3,4-oxadiazole-2-thione

The bis[4-aryl-3-alkylthio-1,2,4-triazol-5-yl]alkanes 4 were prepared by the action of alkyl halides on bis[4-aryl-1,2,4-triazoline-5-thione-5-yl]alkanes in aqueous sodium hydroxide (5%). The prepared sulphides 4 were oxidised to give the corresponding sulphones 5 either with acidic potassium permanganate or hydrogen peroxide. Similarly, sulphides 8 were prepared from 5-phenyl-1,3,4-oxadiazole-2-thione by reaction with different alkylhalides in alkaline medium. Mannich bases 9 from 5 -phenyl-1,3,4-oxadiazole-2-thione (7) were also prepared by stirring an equimolar solution of 6 in ethanol with formaldehyde (38%) and an amine in an ice-cold bath. All the compounds were screened for their pesticidal activities but none showed any significant activity.     

The problem of the tautomerism of 2-iminothiazolidin-4-one and some of its derivatives

IR spectroscopy is used to investigate imino-amine tautomerism of 2-iminothiazoliin-4-one and 2-phenyl (p-tolyl, benzyl)imino derivatives of thiazolidin-4-one. It is shown that in the crystalline state 2-iminothiazolidin-4-one exists in the 2-imino form, while in solution (chloroform) it exists in the amino form. 2-Phenyl- and 2-p-tolylimino derivatives of thiazolidin-4-one exist in the imino form, while 2-benzyl-iminothiazolidin-4-one exist in the amino form.     

Design,synthesis and in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antitubercular and antimalarial agents

A series of 5-substituted-3-[{5-(6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl}-imino] -1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-tubercular and antimalarial activity.     

DFT, ab initio, NMR, and NBO analyses of N-substituted hydrazino acetamides: Experimental vs theoretical values

We studied the DFT (B3LYP) and HF at 6-31+G/6-31+G^∗∗ levels of theory in order to throw light on the conformation, structure, intramolecular hydrogen bond network, as well as proton and nitrogen NMR (GIAO method) of a series of model primary amides in the gas phase and/or in solution (chloroform, methanol, water, dimethyl sulfoxide, and heptane). In this manner, it was possible to show that the amidic group of these model compounds acts as the H-bond donor and interacts with two different H-bond acceptors, thus stabilizing the C₈ pseudocycle. The study was conducted to gain a better understanding of the conformation (both experimentally and theoretically) adopted by hydrazino acetamides (model compounds for aza-β³-peptides). In the light of this, we were able to explain why aza-β³-peptides develop a different H-bond network in comparison to their isosteric β³-peptide analogues (an extension of the β-peptide concept).