Cyclodimerization of the 1-methyl-1,3-diferrocenylallyl cation into 1,3,5-triferrocenyl-4-(1-ferrocenylethenyl)cyclohexene

An unusual cyclodimerization reaction of the 1-methyl-1,3-diferrocenylallyl cation into 1,3,5-triferrocenyl-4-(1-ferrocenylethenyl)cyclohexene has been studied. Two isomeric compounds were isolated and their structures were established as 1,r3,c5-triferrocenyl-4-t-(1-ferrocenylethenyl)cyclohexene and 1,r3, t5-triferrocenyl-4-c-(1-ferrocenylethenyl)cyclohexene on the basis of ¹H NMR and ¹³C NMR spectral data.     

呋喃并呫吨酮衍生物的合成与生物活性研究

以水杨酸、间苯三酚为原料合成了1,3-二羟基呫吨酮, 经醚化、环化反应得到1-羟基呋喃并呫吨酮3a和3b, 再经Mannich反应合成了10个呋喃并呫吨酮衍生物4和5, 接着通过季铵化反应得到相应的10个季铵盐6和7. 运用IR、一维和二维NMR、MS、元素分析等对化合物进行了结构表征, 考察了化合物4～7对乙酰胆碱酯酶的抑制作用及化合物6, 7的抗癌活性. 结果表明: 化合物4～7对乙酰胆碱酯酶具有较好的抑制活性, IC50＝2.0～12.4 μmol/L; 化合物6, 7对肝癌(HepG2)、肺癌(SPC-A)、口腔上皮癌(KB)、乳腺癌(MCF-7)这四种癌细胞株的增殖均有抑制作用, 其中化合物6c对癌细胞株HepG2、化合物7d对癌细胞株MCF-7的抑制作用最强, IC50分别为0.82和0.77 μmol/L.     

2-氰基-2,3-二甲基-3-甲基羰甲基-5-硫酮-吡咯烷的合成

2-氰基-2;3-二甲基-3-甲基羰甲基-5-硫酮-吡咯烷的合成;双甲基环并内酯;双甲基环并内酰胺-内酯;氰基吡咯烷酮;氰基吡咯烷硫酮     

Preparation and steric structures of saturated or partially saturated cyclopentane-and cyclohexane[b]pyrrolo[1,2-a][3,1]benzoxazine isomers [1]

The reactions of 2-ethoxycarbonylmethyleyclopentanone (1) with cis- (3a) and trans-2-hydroxymethylcyclohex-4-enyl-1-amine (3b) and of 2-ethoxycarbonylmethylcyclohexanone (2) with stereoisomeric 2-hydroxymethyl-1-cyclohexylamines (4a,b) yield the isomeric cyclopentane-(5a,b) and cyclohexane[b] pyrrolo[1,2-a][3,1]benzoxazinones (6a,b) with unsaturated (5) or saturated (6) ring A. The steric structures were elucidated by means ¹H, ¹³C NMR and X-ray measurements.     

NMR and Molecular Mechanics Studies on Configurational Isomerism and Conformational Equilibrium of Chiral Cyclohexenones

Chiral diastereomers of 2-isopropyl-5-methyl-6-(4-phenyl)benzylcyclohex-2-enone and their isomer 2-(4-phenylbenzyl)-3-methyl-6-isopropylcyclohex-2-enone, which are products of an acid-catalyzed intramolecular rearrangement of 3R,6R-2-(4-phenylbenzylidene)-3-methyl-6-isopropylcyclohexanone, were investigated to show that conformational analysis by molecular mechanics and ¹H NMR spectroscopy permits an integrated solution of three structural problems: double bond location in an aliphatic ring for isomeric products; determination of the stereochemical configuration for the two diastereomers; evaluation of the conformational equilibrium between the diastereomers. Based on the results of calculations, this is achieved by estimating the configuration- and conformation-sensitive proton spin–spin coupling constants of the cyclohexenone ring for alternative structures and correlating them with ¹H NMR data.     

The spatial structure of the isomeric dimethyl esters of 4-hydroxypiperidine-2, 6-dicarboxylic acid

Three isomeric dimethyl esters of 4-hydroxypiperidine-2, 6-dicarboxylic acid have been isolated. The spatial structures of all three isomeric esters and of the acids corresponding to them have been established on the basis of NMR spectra. It has been shown that while the isomers I and II exist in the form of only one conformation each, isomer III in neutral and acid media apparently consists of an equilibrium mixture of two (or more) conformers. The information obtained on the spatial structure of the isomeric esters shows that the cyclization of these compounds with benzylamine and p-nitrobenzaldehyde takes place with the inversion of the piperidine ring.     

Phosphacarborane chemistry: the 7,8,9,11-, 7,9,8,10- and 7,8,9,10-isomers of nido-P2C2B7H9--diphosphadicarbaborane analogues of 7,8,9,10-C4B7H11

The reaction between the carborane arachno-4,6-C2B7H13 (1) and PCl3 in dichloromethane in the presence of a "proton sponge" (PS = 1,8-dimethylaminonaphthalene) resulted in the isolation of the eleven-vertex nido-diphosphadicarbaboranes 7,8,9,11-P2C2B7H, (2) and 3-Cl-7,8,11-P2C2B7H, (3-Cl-2) in yields of 54 and 7%, respectively. Replacement of the PS by NEt3 in the same reaction gave diphosphadicarbaboranes 2 and 3-CI-2 together with the isomeric species nido-7,9,8,10-P2C2B7H, (3) in yields of 28, 15 and 3%, respectively. The reaction between the isomeric carborane arachno-4,5-C2B7H13 (4) and PCl3 in dichloromethane in the presence of PS gave the asymmetrical isomer, nido-7,8,9,10-P2C2B7H, (5). along with the chloro derivatives 4-Cl-7,8,9,10-P2C2B7H8 (4-Cl-5) and 11-Cl-7,8,9,10-PC2B7,H8 (11-Cl-5) (yields of 21, 1 and 13%, respectively). The structures of the chlorinated derivatives 3-Cl2 and 11 -Cl-5 were determined by X-ray diffraction analysis. In addition, the structures of all compounds isolated were geometry-optimised and confirmed by comparison of experimental 11B chemical shifts with those calculated by the GIAO-SCF/II//RMP2(fc)/6-31G* method. The calculations also include the structure and 11B NMR shifts of the isomer nido-7,10,8,9-P2C2B7H9 (6) which has not yet been isolated.     

Base catalyzed intramolecular cyclization of dialkycrotyl(3-alkenylpropyn-2-yl)ammonium salts and aqueous base fission of 2,2-dialkyl-4-methyl-and 2,2-dialkyl-4,6-dimethyl-2,6,7,7a-tetrahydro-1H-isoindolium bromides

Cyclization of dimethylcrotyl(3-vinyl-or-3-isopropenylpropyn-2-yl)ammonium bromides in the presence of base gave a mixture of the isomeric 2,2-dialkyl-4-methyl-and 2,2-dialkyl-4,6-dimethyl-2,6,7,7a-tetrahydro-1H-isoindolium bromides. Basic fission of the salts obtained at increased temperature gave a mixture of the isomeric N,N-disubstituted di-and trimethylbenzylamines whose structures were confirmed by their IR, ¹H NMR, and ¹³C NMR spectra. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 841–846, June, 2008.     

Pyrazolo-N-hydroxyuracils from the modified lossen rearrangement of vicinal pyrazoledicarbohydroxamates

The reaction of 1-phenyl-3,4- and 4,5-pyrazoledicarbohydroxamates, II and VIII, with benzene- and methanesulfonyl chlorides is reported. Each hydroxamate yielded two isomeric N-phenyl-N-hydroxypyrimidinediones whose structures were established. The NMR spectra of a number of isomeric pyrazole derivatives are discussed.     

First synthesis and isolation of the E- and Z-isomers of some new Schiff bases. Reactions of 6-azido-5-formyl-2-pyridone with aromatic amines

Some novel Schiff bases have been prepared by reacting 6-azido-5-formyl-2-pyridone 1 with a series of aromatic amines 2a-f. 5-Arylaminomethylene-6-(E)-aryl-iminopyridones 3a-e were obtained by reaction of 1 with 2a-e at room temperature, whereas with 2f, the 6-azido-5-naphthalen-2-yl-iminomethylpyridone derivative 4 was formed. On the other hand, heating 1 with 2a-d at 140-150 degrees C yielded two sets of isomeric products, (E)-3a-d and (Z)-5a-d. Refluxing compounds (Z)-3a,c with hydroxyl-amine in methanol gave the corresponding hydroxyliminopyridones 8a,c. Heating of (E)-3a-d with excess POCl3 at reflux did not give the expected tricyclic compound 9, but rather the isomeric products (Z)-5a-d were obtained. The structures of all these products have been characterized using IR and 1H- and 13C-NMR spectroscopy.     

Thallophilic interactions in aryloxide compounds: the [Tl2(mu2-OAr)4] structural motif in (TlOAr)4 and Tl2Cu(OAr)4 compounds

Two thallium aryloxide compounds TlOC6F5 (TlOAr(F)) and bis-3,5-TlOC6H3(CF3)2 (TlOAr') have been recrystallized from THF and crystallographically characterized in different isomeric forms. The latter compound forms a solvated tetrameric cubane, [TlOAr']4.THF, 1. The TlOAr(F) compound crystallized with a similar stoichiometry, [TlOAr(F)]4.2 THF, 2, but contains a [Tl2(mu2-OAr(F))4] unit that includes a thallophilic interaction at a distance of 3.5943(15) angstroms. Solution 205Tl and 203Tl NMR studies of 1 and 2 support the retention of a cubane structure for 1 in solution and suggest a similar structure for 2 with coupled thallium centers down to -90 degrees C. Fluorescence spectroscopy data for both compounds 1 and 2 in THF are consistent with LMCT. DFT calculations of 1, 2, and three models of the [Tl2(mu2-OAr(F))4] unit show a bonding overlap of the bridged thallium atoms in 2 and are also used to describe the bonding in 1. The structures of two heterobimetallic compounds, Tl2Cu(OAr(F))4, 4, and Tl2Cu(OAr')4, 5, with the [Tl2(mu2-OAr(F))4] structural motif and thallophilic contacts of 3.86(6) and 3.564(1) angstroms, respectively, are described. The crystal structures of the unsolvated of TlOAr(F), 2b, solvated heterobimetallic derivative Tl2Cu(OAr')4.2THF, 5b, and the monomeric (18-crown-6)TlOAr(F), 3, and 205Tl NMR spectra of TlOC6H5, 6, are also reported for comparison purposes.     

Isomeric Squaraine‐Based [2]Pseudorotaxanes and [2]Rotaxanes: Synthesis,Optical Properties,and Their Tubular Structures in the Solid State

On the basis of formation of [2]pseudorotaxane complexes between triptycene‐derived tetralactam macrocycles 1 a and 1 b and squaraine dyes, construction of squaraine‐based [2]rotaxanes through clipping reactions were studied in detail. As a result, when two symmetrical squaraines 2 d and 2 e were utilized as templates, two pairs of isomeric [2]rotaxanes 3 a – b and 4 a – b as diastereomers were obtained, owing to the two possible linking modes of triptycene derivatives. It was also found, interestingly, that when a nonsymmetrical dye 2 g was involved, there existed simultaneously three isomers of [2]rotaxanes in one reaction due to the different directions of the guest threading. The ¹H NMR and 2D NOESY NMR spectra were used to distinguish the isomers, and the yield of [2]rotaxane 5 a with the benzyl group in the wider rim of the host 1 a was found to be higher than that of another isomer 5 b with an opposite direction of the guest, which indicated the partial selection of the threading direction. The X‐ray structures of 3 b and 4 a showed that, except for the standard hydrogen bonds between the amide protons of the hosts and the carbonyl oxygen atoms of the guests, multiple π???π stacking and C? H???π interactions between triptycene subunits and aromatic rings of the guests also participated in the complexation. Crystallographic studies also revealed that the [2]rotaxane molecules 3 b and 4 a further self‐assembled into tubular structures in the solid state with the squaraine dyes inside the channels. In the case of 4 a , all the nonsymmetrical macrocyclic molecules pointed in one direction, which suggests the formation of oriented tubular structures. Moreover, it was also found that the squaraines encapsulated in the triptycene‐derived macrocycles were protected from chemical attack, and subsequently have potential applications in imaging probes and other biomedical areas.     

Synthesis and isolation of homeomorphous isomers of P-containing cryptands

The novel isomeric phosphite cryptands 2, 3, and 4 could be synthesized by a simple one-pot tripod capping method starting from bisphenol 1 and PCl3. The assembling of five components led to the formation of a macrobicyclic structure, which probably requires an appropriate preorganization of the reactants. In contrast to the NMR spectra of 2, 3, and 4 in solution, the X-ray structures of 2 and 3 reveal that these molecules have no C3 symmetry in the solid state. In the 31P NMR spectra, both in- and out-P atoms have remarkably different chemical shifts due to a distorted geometry around the in-phosphorus. Phosphorus atoms in the inposition have a decreased reactivity. They are, therefore, more slowly oxidized by cumene hydroperoxide than out-P atoms. A stepwise synthesis was developed for phosphite/phosphatecryptands (5, 7, 9, and 15) via the monoprotected bisphenol 11 and the phosphate 14. In addition, the cylindrical macrotricycle 16 was isolated as a mixture of diastereomers from the crude product of this reaction.     

Study of the reaction products of flavonols with 2,2-diphenyl-1-picrylhydrazyl using liquid chromatography coupled with negative electrospray ionization tandem mass spectrometry

The products obtained after the reaction between flavonols and the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) in both methanol and acetonitrile were characterized using liquid chromatography coupled with negative electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) and NMR spectroscopy. The flavonols studied were quercetin, kaempferol and myricetin. In methanol, two reaction products of oxidized quercetin were identified using LC/ESI-MS/MS and NMR. Quercetin was oxidized through a transfer of two H-atoms to DPPH(*) and subsequently incorporated either two CH(3)OH molecules or one CH(3)OH- and one H(2)O molecule giving the products 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dimethoxy-2,3-dihydrochromen-4-one and 2-(3,4-dihydroxyphenyl)-3,3,5,7-tetrahydroxy-2-methoxy-2,3-dihydrochromen-4-one, respectively. LC/ESI-MS/MS analysis revealed that in methanol, kaempferol and myricetin also gave rise to methoxylated oxidation products similar to that identified for quercetin. Kaempferol, in addition, also exhibited products where a kaempferol radical, obtained by a transfer of one H-atom to DPPH(*), reacted with CH(3)OH through the addition of CH(3)O(*), yielding two isomeric products. When the reaction took place in acetonitrile, LC/ESI-MS/MS analysis showed that both quercetin and myricetin formed stable isomeric quinone products obtained by a transfer of two H-atoms to DPPH(*). In contrast, kaempferol formed two isomeric products where a kaempferol radical reacted with H(2)O through the addition of OH(*), i.e. similar to the reaction of kaempferol radicals with CH(3)OH.     

Synthesis and spectroscopy of N3P3X5OCH=CH2 (X = Cl, F, OCH3, OCH2CF3, N(CH3)2) and N3P3X4(OCH=CH2)2 (X = Cl, N(CH3)2). Correlations of ultraviolet photoelectron spectroscopy and nuclear magnetic resonance data to electronic and geometrical structure

The syntheses of the vinyloxycyclotriphosphazene derivatives N3P3X5OCH=CH2 (X = OMe, OCH2CF3) and the N3P3(NMe2)4(OCH=CH2)2 isomeric mixture along with improved preparations of N3P3X5OCH=CH2 (X = F, NMe2) are reported. The interactions between the vinyloxy function and the cyclophosphazene in these and the previously reported N3P3Cl5 (OCH=CH2) and N3P3F6-n(OCH=CH2)n (n = 1-4) have been examined by ultraviolet photoelectron spectroscopy (UPS) and NMR spectroscopy. The UPS data for the chloro and fluoro derivatives show a strong electron-withdrawing effect of the phosphazene on the olefin that is mediated with decreasing halogen substitution. The 1H and 13C NMR data for N3P3X5OCH=CH2 (X = F, Cl, OMe, OCH2CF3, NMe2) show significant changes as a function of the phosphazene substituent. There is a linear correlation between the beta-carbon chemical shift on the vinyloxy unit and the phosphorus chemical shift at the vinyloxyphosphorus centers. The chemical shifts of the different phosphorus centers on each ring are also related in a linear fashion. These relationships may be understood in terms of the relative electron donor-acceptor abilities of the substituents on the phosphazene ring. The 1H NMR spectra of the N3P3(NMe2)4(OCH-CH2)2 isomeric mixture allow for assignment of the relative amounts of cis and trans isomers. A model for the observed cis preference in the formation of N3P3Cl4(OCH=CH)2 is presented.     

Electronic localization versus delocalization determined by the binding of the linker in an isomer pair

By using stoichiometric amounts of (C5H5)2FePF6, the isomeric neutral diamidate-bridged molecules, alpha- and beta-(DAniF)3Mo2(ArN(O)CC(O)NAr)Mo2(DAniF)3, with Ar = p-MeOC6H4, have been oxidized to give the PF6 salts of the four cations alpha1+, alpha2+, beta1+, and beta2+. All four structures have been accurately determined and, together with supporting evidence from near-IR, EPR, NMR and magnetic susceptibility measurements, it clearly establishes that in the mixed-valent alpha+ species the unpaired electron is localized over only one of the Mo2 units while the alpha2+ cation behaves as a diradical having two Mo25+ units that are essentially uncoupled. However, the beta+ species is fully delocalized, in the time scale of the experiments, with the unpaired electron being equally shared by the two Mo2 units. It displays a HOMO-1 --> SOMO transition at 4700 cm-1 (Deltanu1/2 = 2300 cm-1). Because of strong coupling, the beta2+ species is diamagnetic.     

Zur-Reaktionsweise von Enaminen mit Cyclopropenonen III. Isolierung eines Produktes der «C,C-Insertion»

From the reaction of the N-(2-Methylpropenyl)-pyrrolidin 6 with diphenylcyclopropenone 7 we isolated as a byproduct 5-Methyl-2, 4-diphenyl-1-pyrrolidino-hexa-1, 4-diene-3-one 9 . The structure was proven by an interpretation of the IR.-, NMR.- and MS.-spectra. This result is of importance since it represents the first case of a direct ‘C, C-insertion’ product 4 from the reaction of an enamine 1 and a cyclopropenone 2 and because structures of type 4 (including 9 ) have previously been postulated for the main products of this reaction, which were later shown to be amides 3 (including 8 ). Acid hydrolysis of the β-amino-dienone 9 yielded the dihydropyrone 10 and the cyclopentenone 11 . These isomeric products are considered to be the result of two electrocyclic reactions, one of a hexa-2,4-diene-al 12 and the other of a hexadienylium ion 14 .     

Lipophilic G-quadruplexes are self-assembled ion pair receptors,and the bound anion modulates the kinetic stability of these complexes

With an eye toward the eventual selective modification of noncovalent structures, we used ESI-MS, X-ray crystallography, and NMR spectroscopy to study the anion's influence on the structure and dynamics of self-assembled ion pair receptors formed from guanosine G 1. We compared five complexes of formula (G 1)(16).2Ba(2+).4A(-) containing different organic anions: 2,4,6-trinitrophenolate (2), 2,6-dinitrophenolate (3), 4-methyl-2,6-dinitrophenolate (4), 4-methoxy-2,6-dinitrophenolate (5), and 2,5-dinitrophenolate (6). Crystallography reveals that anion-nucleobase hydrogen bond geometry is sensitive to both phenolate basicity and structure. For the 2,6-substituted anions 2-5, progressive shortening of anion-nucleobase hydrogen bonds is correlated with increased phenolate basicity. Lipophilic G-quadruplexes with different anions also have much different kinetic stabilities in CD(2)Cl(2) solution. Proton NMR shows that free 6 exchanges faster with G-quadruplex-bound anion than do the 2,6-dinitrophenolates 2-5. The increased lability of 6 is probably because, unlike the 2,6-dinitrophenolates, this anion cannot effectively chelate separate G(8).M(2+) octamers via anion-nucleobase hydrogen bonds. In addition to these structural effects, the anion's basicity modulates the anion exchange rate between its free and bound states. 2D EXSY NMR shows that 3 and 5 exchange about 7 times slower than the less basic picrate (2). The use of 3, a relatively basic dinitrophenolate that hydrogen bonds with the amino groups of the two "inner" G(4)-quartets, resulted in extraordinary kinetic stabilization of the G-quadruplex in CD(2)Cl(2). Thus, no isomerization product (G 1)(8).Ba(2+).(G 1)(8).Sr(2+).4(3) was observed even 2 months after the separate G-quadruplexes (G 1)(16).2Ba(2+).4(3) and (G 1)(16).2Sr(2+).4(3) were combined in CD(2)Cl(2). In sharp contrast, G-quadruplexes containing the isomeric 6 anion have isomerization half-lives of approximately t(1/2) = 30 min under identical conditions. All the evidence indicates that the structure and electronics of the organic anions, bound to the assembly's periphery, are crucial for controlling the kinetic stability of these cation-filled G-quadruplexes.     

Study of the characteristics of rearrangements of 5-amino-1,2,3-thiadiazole-4-carbothioamides

Using NMR spectroscopy, we have determined the relative stability and the effect of the solvent on the ratio of isomeric NN-disubstituted 5-amino-1,2,3-thiadiazole-4-carbothioamides in a mixture. We carried out chromatographic separation of a mixture of 5-benzylamino-1, 2, 3-thiadiazole-4-N-methylcarbothioamide and 5-methylamino-1, 2, 3-thiadiazole-4-N-benzylcarbothioamide and we show that when each compound dissolves, it rapidly isomerizes with formation of the initial composition. We conclude that the orientation of the rearrangement process is thermodynamically controlled.     

Structural distinction between sabandins A and B from Artemisia scoparia waldst. (Asteraceae)

The three possible isomeric structures of the sabandin coumarin were published by Reyes and Gonzalez in 1970. We have isolated two of these isomers sabandins A and B from Artemisia scoparia (Asteraceae) and distinguished by NOE difference NMR measurements.