Polar Effects. Part 14. Inductive Charge Dispersal in Bicyclo[2.2.2]oct-1-yl Cations

The rate constants (log k) for solvolysis of 2-, 3-, and 4-substituted bicyclo[2.2.2]octyl p-nitrobenzenesulfonates 10, 11 and 12 , respectively, correlate linearly with the corresponding inductive substituent constants s?. The formation of the ion pairs 9 is, therefore, controlled by the I effect of neighboring substituents. It follows from the corresponding reaction constants ρ₁ of ?1.54, ?1.12, and ?1.22 that inductivity is highest at the positions α to C(1). It is lower and practically equal at the β- and γ-positions. Therefore, charge dispersal is similar to that previously observed in the quinuclidinium ion 7 .     

Structural Factors Affecting the Basicity of ω-Pyridylalkanols, ω-Pyridylalkanamides and ω-Pyridylalkylamines

The present paper describes the preparation by conventional methods (when not available commercially) and the pK_a-determination of the α-, β- and γ-isomers of pyridylethanamide, 3-pyridylpropanamide. 4-pyridylbutanamide, 5-pyridyl-pentanamide, pyridylmethanol, 2-pyridylethanol, 3-pyridylpropanol, 4-pyridyl-butanol, 5-pyridylpentanol, pyridylmethylamine, 2-pyridylethylamine, 3-pyridyl-propylamine, 4-pyridylbutylamine, and 5-pyridylpentylamine. While a field effect accounts for many variations in pK_a as a function of chain length, marked inductive effects are operative in some methyl and ethyl homologs. The pK_a-decreasing influence of an intramolecular H-bond is also apparent in some lower homologs belonging to the α-series.     

A Reexamination of Inductive Substituent Constants Derived from pKa Values of 4-Substituted Quinuclidines. Polar effects. Part VIII

pK_a Values of 42 quinuclidinium perchlorates I have been measured in 0.1 M aqueous KCl-solution. In a few cases small corrections of earlier thermodynamic pK_a values are indicated. These measurements, in conjunction with recent X-ray structure determinations, confirm the reliability of the inductive substituent constants σ_I^q derived from them.     

Thermoanalytical behavior of cadmium(II) oxide—alkali persulfate binary systems

The non-isothermal behavior of two binary CdO—persulfate systems has been investigated. The molar ratios and T_i—T_f are established. The temperatures for the α- to β-Na₂SO₄ phase transition, as well as for α- to β- to γ-CdSO₄ of the CdONa₂S₂O₈ system have been fixed. No evidence for the occurrence of the β- to γ-CdSO₄ polymorphic trans-formation has been obtained from the reaction of the CdOK₂S₂O₈ system. This is because of the formation of a CdSO₄/K₂SO₄ eutectic mixture which melts at 653°C, i.e., before the β- to γ-phase change transition, which usually occurs later. No basic cadmium sulfate has been identified. The excess cadmium oxide acts as a p-type semiconductor which accelerates the thermal decomposition of pyrosulfates.     

The Derivation of Inductive Substituent Constants from pKa Values of 4-Substituted Quinuclidines. Polar effects. Part I

Thermodynamic pK_a-values have been determined for 38 4-substituted quinuclidinium perchlorates. They are remarkably sensitive to the polar effect of the substituent and cover a range of 3.63 pK_a units. Furthermore, they vary linearly and almost equally with temperature since the contribution of the TΔS° term to the free energy of ionization is relatively small and constant. The magnitude of the polar effect of the 4-cyano group varies with the solvent and appears to depend on its ability to form hydrogen bonds to the substituent rather than its dielectric constant. New inductive substituent constants σ_I^q are derived from the pK_a values. Their correlation with known inductive constants is only fair or unsatisfactory, especially as regards the relative order of hydrogen and the alkyl groups. The discrepancies can be ascribed mainly to the different models used to derive the substituent constants.     

Direct palladium-catalyzed allylic alkylations of alcohols with enamines: Synthesis of homoallyl ketones

An efficient, direct nucleophilic allylic substitution of α-, β- and γ-substituted alcohols with enamines, using the Pd(OAc)_2/PPh₃ catalyst system and ZnBr₂ as a promoter in CH₂Cl₂ at reflux, is reported. The reaction course was dependent on the steric hindrance at the α- or γ-positions with respect to the functionalized α-carbon, selectively affording in moderate to good yields, α- or γ-homoallyl ketones, the so-called “linear” and “branched” products, respectively.     

Stereoselective synthesis and 2D NMR study of S-D-glucopyranoside

2, 3, 4-Tri-O-benzyl-6-O trimethylsilyl-α-D-glucopyranosyl bromide reacted with RSH compounds (R = Et, t-Bu, PhCH₂, p-PhBu^t, Ph, 2-benzoxazole, 2-benzothiazole), with diisopropylethylamine as base, to give S-D-glucosides. The α- and β- anomeric ratio was dependent on the pKa. value of the thiol compound. If pKa value was less than or equal to 7, β-anomer was obtained. If pKa value was equal to or more than 11, α anomer was obtained. If pKa value was between 9 and 10.6, a mixture of α- and β-anomer was obtained. The probable mechanism was discussed. The chemical shifts of proton and carbon in these S-D-glucosides were measured and verified by 2D NMR (cosy and hetcor).     

Thermodynamic study on salt effects on complex formation of α-, β- and γ-cyclodextrins with p-aminobenzoic acid

The aim of this work was to gain a deeper understanding of salt effects in the inclusion complex formation of cyclodextrins. For this purpose, thermodynamic study of complex formation of α-, β- and γ-cyclodextrins with p-aminobenzoic acid was carried out in water and solutions of KCl, KBr, KH₂PO₄ and K₂SO₄ (0.2 mol/kg). Stability constants were calculated from the binding isotherms obtained on the basis of ¹H NMR measurements. Enthalpy and entropy of complex formation were estimated from the van’t Hoff plots. It was found that effects of KCl, KH₂PO₄ and K₂SO₄ are insignificant, while the influence of KBr on complex formation of cyclodextrins with p-aminobenzoic acid is more pronounced and results in a decrease of the stability constants. Specific action of Br⁻ is caused by the ability of these anions to penetrate into macrocyclic cavity. Coexistence of two complexation equilibria in KBr solution is accompanied by significant solvent reorganization originated from more intensive dehydration of the interacting species. This results in an increase of the enthalpy and entropy of complex formation. Manifestation of Br⁻ effect was found to be the same in the binding of p-aminobenzoic acid with α-, β- and γ-cyclodextrins.     

Experimental and theoretical study on the substitution reactions of aryl 2,4-dinitrophenyl carbonates with quinuclidines

The reactions of quinuclidines with phenyl, 4-methylphenyl, and 4-chlorophenyl 2,4-dinitrophenyl carbonates are kinetically evaluated in aqueous solution. The Brønsted-type plots (log k_N vs pK_a of quinuclidinium ions) are linear. The magnitude of the slopes and validated theoretical scales of electrophilicity and nucleophilicity confirm the concerted nature of these reactions.     

Reactions of transition metal carbonyl anions with 2-(1-bromoalkylidene)thiazolidin-4-ones: halogenophilic attack or deprotonation

Bromophilic attack by the transition metal carbonyl anion, [Re(CO)₅]Na (pK_a = 21.1), on 2-(1-bromoalkylidene)thiazolidin-4-ones is significantly faster than abstraction of an acidic lactam hydrogen (pK_a ∼17-18), when the generated carbanion is stabilized by an α-CN or α-PhCO group. The bromophilic reaction of 2-(1-bromoalkylidene)thiazolidin-4-one, having an α-CN electron-withdrawing group, resulted in formation of a new metallacyclic anionic complex. With less reactive vinyl bromides, containing an α-CONHPh or α-CO₂Et group, only deprotonation is observed. The role of the metal carbonyl anion is highlighted by a comparison with the 9-methylfluorenide carbanion (pK_a of 9-methylfluorene is 22.3), which reacts exclusively via a deprotonation pathway.     

Epoxidation of phosphinoyl alkenes with hydrogen peroxide

The epoxidation of alkenylphosphorus compounds with hydrogen peroxide was systematically studied, revealing that while alkenylphosphine oxides failed to produce the corresponding epoxides, alkenylphosphonates, or phosphinates having a phenyl group at α-position reacted with H₂O₂/K₂CO₃ or alkenylphosphonic acids or phosphinic acids having an aliphatic group at α- or β-positions reacted with H₂O₂/Na₂WO₄/Et₃N to produce high yields of the corresponding epoxides.     

The synthesis and structural analysis of cis -β-{(1,6-di(2′-pyridyl)(2,5-dibenzyl-2,5-diazahexane O(1,2-diazahexane))(1,2-benzoquinone diimine))ruthenium(II)} and related complexes

Several isomers are possible when N₄-tetradentate ligands coordinate to form metal complexes. Here we report the synthesis and structural analysis of cis-β-{[1,6-di(2′-pyridyl)(2,5-dibenzyl-2,5-diazahexane)(1,2-benzoquinone diimine)]ruthenium(II)} formed exclusively from the β-precusor, β-{[1,6-di(2′-pyridyl)(2,5-dibenzyl-2,5-diazahexane) (dimethylsulfoxide)chloride] ruthenium(II)} hexaflourophosphate. Ruthenium(II) complexes synthesised from 1,6-di(2′-pyridyl)-2,5-dibenzyl-2,5-diazahexane, produce only two isomers which can be separated by recrystallisation into α- and β-[Ru(picenbz₂)(dmso)Cl]PF₆ (where picenbz₂ is 1,6-di(2′-pyridyl)-2,5-dibenzyl-2,5-diazahexane). The distinctively different proton NMR spectra of the isomers are an especially convenient feature with which to assess separation. Isomeric structure of the precursor, α or β, is conserved upon coordination of a bidentate ligand, such as benzene-1,2-diamine, 4,5-dimethyl-benzene-1,2-diamine, naphthalene-2,3-diamine, 2,2′-bipyridine, 1,10-phenanthroline or dipyrido[3,2-d:2′3′-f] quinoxaline, to produce complexes of the type α- or β-[Ru(picenbz₂)(bidentate)](PF₆)₂. The synthesis, separation and characterisation of the α- and β-precursors and the α- and β-[Ru(picenbz₂)(bidentate)](PF₆)₂ complexes are reported. Moreover, the crystal structures have been determined for β-[Ru(picenbz₂)(dmso)Cl]PF₆.0.5H₂O (C₃₀H₃₇N₄O_1.5F₆PSClRu); it is triclinic, space group P 1, a?=?9.987, b?=?12.883, c?=?14.287?Å, α?=?72.11, β?=?78.65, γ?=?88.39° and Z?=?2 and β-[Ru(picenbz₂)(bqdi)](PF₆)₂, (C₃₄H₃₈N₆F₁₂P₂Ru) which is triclinic, space group P 1, with a?=?10.129, b?=?10.338, c?=?19.587?Å, α?=?104.42, β?=?93.36, γ?=?92.00° and Z?=?2. The structures were determined at room temperature and refined by least-squares methods to R?=?0.044 for 5109 and R?=?0.075 for 3057 non-zero diffractometer data, respectively, for the dmso and bqdi species above.     

Formation and phase transition of cobalt molybdate in cobalt oxide-molybdenum trioxide-alumina system

In the cobalt oxide-molybdenum trioxide-alumina system with a molar ratio of 1:1:1, the amounts of the high-temperature modification (a) of CoMoO₄ formed during heating from 500 to 800°C and the low-temperature modification (b) formed by phase transition during the subsequent cooling to room temperature are influenced by the kinds of alumina used, such as α-, γ- and calcined γ-aluminas. Powder X-ray diffraction analysis revealed that in an α-alumina system formation of a-CoMoO₄ is most favorable at a calcination temperature of 500°C and phase transition from a- to b-CoMoO₄ during cooling is enhanced by higher calcination temperatures. In the γ-alumina system, formation of a-CoMoO₄ is slight at 500°C but increases with increase in the calcination temperature, as does slightly the degree of phase transition from a- to b-CoMoO₄ upon cooling. In a system containing calcined γ-alumina, formation of a-CoMoO₄ similar to α- and γ-alumina systems was observed to occur at 500°C and 800°C, respectively, together with phase transition to b-CoMoO₄ during cooling. The degree of dispersion in the CoOMoO₃ coexistent system is affected by the particle size of aluminas, such as coarse α-, fine amorphous γ- and calcined γ-alumina consisting of both sizes, as observed with electron microscopy. Presence of finer γ-alumina is considered to suppress or retard the solid state reaction and phase transition.     

β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α-difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α-oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro-β-phenylalanine derivatives (4). Enantiomerically pure β,β-difluorophenylalanine (l-4a) was obtained when α,α-difluoro-α-phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pK_a values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (K_i 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.     

NMR assignments and the acid–base characterization of the pomegranate ellagitannin punicalagin in the acidic pH-range

In exploring the capability of nuclear magnetic resonance (NMR) spectroscopy for pomegranate juice analysis, the eight aromatic singlet resonances of α- and β-punicalagin were clearly identified in the ¹H NMR spectra of juice samples. The four downfield resonances were found to be sensitive to small pH changes around pH 3.50 where the NMR spectra of the juice samples were recorded. To understand this unusual behavior, the ¹H and ¹³C resonance assignments of the punicalagin anomers were determined in aqueous solution and pH titrations with UV and ¹H NMR detection carried out to characterize the acid–base properties of punicalagin over the pH range 2–8. Simultaneous fitting of all of the pH-sensitive ¹H NMR signals produced similar but significantly different pK _a values for the first two deprotonation equilibria of the gallagic acid moiety of the punicalagin α- (pK _a1?=?4.57?±?0.02, pK _a2?=?5.63?±?0.03) and β- (pK _a1?=?4.36?±?0.01, pK _a2?=?5.47?±?0.02) anomers. Equivalent pK _a values, (α?:?6.64?±?0.01, β?:?6.63±?0.01) were measured for the third deprotonation step involving the ellagic acid group, in good agreement with a prior literature report. The punicalagin anomer equilibrium readjusts in parallel with the proton dissociation steps as the pH is raised such that β-punicalagin becomes the most abundant anomer at neutral pH. The unusual upfield shifts observed for the glucose H3 and H5 resonances with increasing pH along with the shift in the α/β anomer equilibrium are likely the consequence of a conformational rearrangement.

Correlation between Absorption and Substitution of Photochromic 1,2-Bis(thienyl)ethenes (BTEs) Using Modified Spectroscopic Hammett Equations

Series of photochromic 1,2-bis(thienyl)ethenes possessing perfluorocyclopentene backbones, either hydrogen or methyl groups at the β-positions of the thiophenes, and a variety of substituents in their α'-positions were prepared, which cover the range from electron-donating to electron-withdrawing (Me, −CH₂OH, −OTBS, −TMS, −Br, 1,3-dioxan-2-yl, pyridin-4-yl, −CH₂OH, −COOH). As a linear free energy relationship the spectroscopic Hammett equation gives fair to excellent fits to the excitation energy of the absorption maxima of the ring-opened as well as the ring-closed forms of the BTEs, when Hammett substituent constants σ_p were replaced by Brown's modified substituent constants σ_p⁺ and σ_p⁻. Vice versa, hitherto unknown Hammett-Brown substituent constants can be estimated from the UV spectra. Furthermore, we compared the experimentally measured absorption maxima with values which we calculated by three different methods (DFT STEOM-DLPNO-CCSD/def2-TZVPP, TD-DFT ωB97X-D3/6-31G*, TD-DFT ωB97X-D3/6-311++G**).     

β- and α-lithiaton of methyl β-methoxyacrylate: efficient synthesis of α,γ-substituted methyl tetronates - structure of aspertetronins and gregatins

Methyl β-methoxyacrylate ($\text{1}$) can be lithiated successively in β- and α-positions. Reaction with two electrophiles (at first a carbonyl compound) leads to α, γ-substituted methyl tetronates in a two step synthesis. Application of this method to the synthesis of methyl tetronate whose structure was assigned as that of gregatin B indicates that the gregatins and aspertetronins have the isomeric structures $\text{17}$.     

Polynuclear Branched Tetrazole Systems. 2. New 2-(5-Tetrazolyl)ethylpodands and Their NH-Acidity

Nine new polynuclear 2-(5-tetrazolyl)ethyl podands have been obtained by the azidation of the corresponding nitriles. Using Bjerrum distribution functions, the values of pK _a ¹, pK _a ², pK _a ³, and pK _a ⁴ have been determined by a potentiometric method for 14 polynuclear tetrazoles in aqueous and aqueous methanolic solution. The found values lie in the range from 3.5 to 7.5 pH units. The overall rules and the sequence of the ionization of the spatially separated tetrazole fragments in these podand systems are discussed.     

EFFECT OF THE BROMINE ATOM UPON THE DISSOCIATION CONSTANTS OF BROMOPYRIDINES,BROMOQUINOLINES AND 4-BROMOISOQUINOLINE IN THEIR LOWEST EXCITED SINGLET AND TRIPLET STATES*

Abstract— The lowest excited singlet-state dissociation constants (pK^S_a) of bromosubstituted pyridines, quinolines, and isoquinolines were determined from the pH-dependent shifts in their electronic absorption spectra. The lowest excited triplet-state dissociation constants (pK^T_a) of bromosubstituted quinolines and 4-bromoisoquinoline were obtained from the shifts of the 0–0 phosphorescence bands measured in rigid aqueous solution at 77 K. The pK^S_a values indicate that the basicity of these brominated nitrogen heterocycles is increased in the lowest excited singlet state by 2 to 10 orders of magnitude as compared with the ground state. The pK^T_a values are found to be significantly different from the corresponding ground-state pK_a values, indicating that the basicity of bromoquinolines is increased in the lowest excited triplet state by 1.7 to 3.0 pK units. The enhancement of the excited singlet-and triplet-state basicity of brominated nitrogen heterocycle derivatives as compared with the unsuhstituted parent compounds is attributed to the increased electron-donor conjugative interactions of the bromine atom pπ orbitals with π orbitals in the lowest excited singlet and triplet state.     

Heterylation of 3-R1-5-R2-1,2,4-Triazoles with Derivatives of 3,5-Dinitro-1,2,4-Triazole

Heterylation of 3-R¹-5-R²-1'2'4-triazoles (pK _a 3-12) with N-alkyl-, N-alkenyl-, N-alkoxy-carbonyl-, N-oxoalkyl-, N-nitroxyalkyl, N-nitroaminoalkyl-3'5-dinitro-1'2'4-triazoles results insubstitution of a nitro group in 5 position of the dinitro compound yielding 1-R-methyl-3-nitro-5-(3-R¹-5-R²-1,2,4-triazolyl)-1,2,4-triazoles. The side processes: Hydroxide-ion attack on C⁵ and (or) N¹ of the ring both in the substrate and in the target compound afford 1-R-methyl3-nitro-1,2,4-triazol-5-ones, 3,5-dinitro-1,2,4-triazole and NH-acids of N-C-bitriazole series. Optimal reaction media are aprotic dipolar substances, and for compounds prone to heterolysis ethyl acetate-water systems. The azole pK _a is the decisive factor controlling the composition and the ratio of reaction products. The process is promising for azoles with pK _a > 5, and the optimal range of pK _a is 8-10.