Brønsted acidic ionic liquids and their zwitterions: synthesis, characterization and pKa determination

Imidazolium chlorides with one or two carboxylic acid substituent groups, 1-methyl-3-alkylcarboxylic acid imidazolium chloride, [Me[(CH2)nCOOH]im]Cl (n=1, 3), and 1,3-dialkylcarboxylic acid imidazolium chloride, [[(CH2)nCOOH]2im]Cl (n=1, 3), have been synthesized via their corresponding acid esters. Deprotonation of the carboxylic acid functionalized imidazolium chlorides with triethylamine affords the corresponding zwitterions [Me[(CH2)nCOO]im] (n=1, 3) and [[(CH2)nCOOH][(CH2)nCOO]im] (n=1, 3). Subsequent reaction of the zwitterions with strong acids gives the new imidazolium salts [Me[(CH2)nCOOH]im]X (n=1, 3; X=BF4, CF3SO3) and [[(CH2)nCOOH]2im]X (n=1, 3; X=BF4, CF3SO3), which exhibit melting points as low as -61 degrees C. The solid-state structures of two of the carboxylic acid functionalized imidazolium salts have been determined by single-crystal X-ray diffraction analysis. Extensive hydrogen bonding is present between the chloride and the imidazolium, with eight Cl.H interactions below 3 A. The pK(a) values of all the salts, determined by potentiometric titration, lie between 1.33 and 4.59 at 25 degrees C.     

Hydrogen‐Bonding Interactions and Properties of Energetic Nitroamino[1,3,5]triazine‐Based Guanidinium Salts: DFT‐D and QTAIM Studies

The intramolecular hydrogen‐bonding interactions and properties of a series of nitroamino[1,3,5]triazine‐based guanidinium salts were studied by using the dispersion‐corrected density functional theory method (DFT‐D). Results show that there are evident LP(N or O; LP=lone pair)→σ*(N? H) orbital interactions related to O???H? N or N???H? N hydrogen bonds. Quantum theory of atoms in molecules (QTAIM) was applied to characterize the intramolecular hydrogen bonds. For the guanidinium salts studied, the intramolecular hydrogen bonds are associated with a seven‐ or eight‐membered pseudo‐ring. The guanylurea cation is more helpful for improving the thermal stabilities of the ionic salts than other guanidinium cations. The contributions of different substituents on the triazine ring to the thermal stability increase in the order of ? NO₂23 (? ONO₂)2. Energy decomposition analysis shows that the salts are stable owing to electrostatic and orbital interactions between the ions, whereas the dispersion energy has very small contributions. Moreover, the salts exhibit relatively high densities in the range of 1.62–1.89 g cm^?3. The detonation velocities and pressures lie in the range of 6.49–8.85 km s^?1 and 17.79–35.59 GPa, respectively, which makes most of them promising explosives.     

Anisotropic local motions and location of amide protons in proteins

A new method has been developed to obtain dynamic and structural information about peptide planes in proteins by a combination of measurements of weak short-range cross-correlation rates R(H(N)N/NC') that are due to concerted fluctuations of the H(N)-N and N-C' dipole-dipole interactions and stronger long-range cross-correlation rates R(C'H(N)/H(N)N) and R(NH(N)/H(N)C(alpha)). The rates were interpreted using the axially symmetric Gaussian axial fluctuation model (GAF). The oscillation amplitudes as well as the positions of H(N) atoms with respect to peptide planes in ubiquitin were determined. Most N-H(N) bonds were found not to lie exactly along the bisector of the N-C' and N-C(alpha) bonds but to be slightly tilted toward the carbon-terminal side of the peptide.     

Structural studies of metabolic products of dopamine. III. Crystal and molecular structure of (--)-adrenaline.

The crystal structure of (--)-adrenaline has been determined by X-ray methods, using 831 observed reflections collected by counter methods. The crystals are monoclinic, space group P2-1 with a=7.873(2), b=6.790(2), c=8.638(2) A and beta=98.01(2) degrees. Least-squares refinements yielded a conventional R-factor of 0.053. Standard deviations in bond lengths are 0.005-0.006 A and in bond lengths aree 0.005-0.006 A and in bond angles 0.4 degrees. The adrenaline molecules were found to exist as zwitterions in the crystals. The conformation of the adrenaline molecule corresponds closely to that usually encountered among the salts of the sympathomimetic amines. The crystals consist of molecular double layers parallel to (100). The molecules within a layer are linked through hydrogen bonds of the types N--H...O and O--H...O, whereas the layers are connected by van der Waals interactions.     

The thiazolium-catalyzed Sila-Stetter reaction: conjugate addition of acylsilanes to unsaturated esters and ketones

A new acyl anion addition reaction between acylsilanes and alpha,beta-unsaturated conjugate acceptors promoted by a nucleophilic organic catalyst has been disclosed. The 1,4-dicarbonyl products produced in this reaction are highly useful synthons. Neutral carbenes (or zwitterions) generated in situ from commercial thiazolium salts are used as effective catalysts for the reaction which is in contrast to established anionic catalysts typically employed to promote the required Brook rearrangement (1,2-silyl shift from carbon to oxygen) involved in the reported reaction. This process successfully utilizes acylsilanes as tunable acyl anion progenitors and is tolerant of a wide range of structural diversity on the acylsilane or the conjugate acceptor.     

Catalytic additions of acylsilanes to imines: an acyl anion strategy for the direct synthesis of alpha-amino ketones

The addition of acylsilanes to imines catalyzed by neutral carbenes (or zwitterions) generated in situ from readily available thiazolium salts is described. The general reaction successfully utilizes acylsilanes as carbonyl anion precursors and is tolerant of a range of structural diversity on the acylsilane or imine electrophile. The overall reaction utilizes easily available precursors and directly accesses protected alpha-amino ketones in the correct oxidation state.     

Electrophilicity Scale of Activated Amides: 17O NMR and 15N NMR Chemical Shifts of Acyclic Twisted Amides in N−C(O) Cross-Coupling

The structure and properties of amides are of tremendous interest in organic synthesis and biochemistry. Traditional amides are planar and the carbonyl group non-electrophilic due to n_N→π*_C=O conjugation. In this study, we report electrophilicity scale by exploiting ¹⁷O NMR and ¹⁵N NMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selective oxidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acid anhydrides and acid chlorides. Furthermore, a wide range of electrophilic amides is possible with gradually varying carbonyl electrophilicity by steric and electronic tuning of amide bond properties. Overall, the study quantifies for the first time that steric and electronic destabilization of the amide bond in common acyclic amides renders the amide bond as electrophilic as acid anhydrides and chlorides. These findings should have major implications on the fundamental properties of amide bonds.     

Molecular and crystal structure of quinoline-2-aldehyde thiosemicarbazone

The molecular and crystal structure of quinoline-2-aldehyde thiosemicarbazone is determined. The thiosemicarbazide fragment has cis-arrangement of terminal nitrogen atoms relative to the central N-C bond. The structure is based on a centrosymmetric dimer formed by hydrogen bonds between NH groups and sulfur atoms of thiosemicarbazide fragments of the neighboring molecules. In the crystal, the dimers are joined with each other through a system of hydrogen bonds and intermolecular π-π interactions.     

Phosphonioalkylthiosulfate zwitterions--new masked thiol ligands for the formation of cationic functionalised gold nanoparticles

We report the synthesis and structural characterisation of a new family of stable phosphonioalkylthiosulfate zwitterions, R3P+ (CH2)nS2O3- (R = Ph or Bu, n = 3,4,6, 8 or 10) which behave as cationic masked thiolate ligands with applications in the functionalisation of gold nanoparticles, having potential as new diagnostic biorecognition systems. The ligands were prepared by treatment of omega-bromoalkylphosphonium salts with sodium thiosulfate. The crystal and molecular structures of the zwitterions (R = Ph, n = 3) and (R = Bu, n = 3) were determined. A series of phosphonioalkanethiolate-capped gold nanoparticles dispersed in water was prepared by borohydride reduction of potassium tetrachloroaurate in the presence of the zwitterions in a dichloromethane-water system. UV-visible spectroscopy and scanning transmission electron-microscopy indicated that capped nanoparticles of ca. 5 nm diameter were present.     

Hydrogen bonds and geometry of amide groups in 2- [2-acyl-(2-isoquinolinyl)] cycloalkan-1,3-diones

The geometry of the amide groups and hydrogen bonds (formed by the enol protons and amide oxygen atoms) in 2-[2-acyl-(2-isoquinolinyl)]cycloalkan-1,3-diones has been studied by X-ray diffraction analysis. The correlation between the C=O and N-C(O) distances, the parameters characterizing the nonplanarity of these groups, and the relative directions of the hydrogen bonds have been found.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 107–109, January, 1995.     

Dicarba-closo-dodecaborane(12) derivatives of phosphonium salts: easy formation of nido-carborane phosphonium zwitterions

The first examples of arylphosphonium salts containing a dicarba-closo-dodecaborane(12) (closo-carborane) are reported; in contrast to the 1,12-carborane derivative, the 1,2- and 1,7-isomers undergo a facile deboronation reaction in polar solvents to afford the corresponding nido-carborane phosphonium zwitterions.     

Analysis of endoproteinase Arg C action on adrenocorticotrophic hormone by capillary electrophoresis and reversed-phase high-performance liquid chromatography.

The specificity and rate of cleavage of adrenocorticotrophic hormone (ACTH) peptide bonds by endoproteinase Arg C were analyzed using capillary electrophoresis (CE) and reversed-phase (C18) high-performance liquid chromatography (HPLC). Acidic cleavage products were readily resolved by CE in uncoated capillaries using low ionic strength electrolytes. However, products predicted to have a net positive charge greater than 2 or more than 4 positively charged groups per peptide did not migrate out from the capillary at low ionic strength. Addition of salts and zwitterions to the electrolyte decreased capillary-peptide interactions such that all of the ACTH peptides examined were eluted with high efficiency separation by CE. Commercially obtained endoproteinase Arg C preparations exhibited peptidase activity at Lys-15-Lys16 and at Lys16-Arg17 in addition to the expected cleavage at Arg-X bonds. ACTH peptide bond cleavage rates for Arg8-Trp9, Arg17-Arg-18, Lys15-Lys16, and Lys16-Arg17 were 1.46, 0.096, 0.57, and 0.029 mumol min-1 mg-1 respectively. CE separations generally exhibited better resolution and were accomplished in shorter times than C18 HPLC separations. These properties make CE a particularly appropriate method for kinetic analysis of proteolytic enzyme action on peptide substrates.     

新的氨基酸受体的合成和分子识别性质研究

从双氨基甲基手性双环胍出发,经三步反应合成了由稳定的共价键桥联双环胍、氮杂冠醚和萘环的氨基酸受体1.液-液竞争萃取和^1HNMR实验表明受体对氨基酸两性离子具有较好的侧链选择性和对映选择性,能够选择性地将L-芳香族氨基酸从水相转移到二氯甲烷有机相。     

Polysiloxane zwitterionomers and related model compounds. I. Synthesis

Polymers containing zwitterions were prepared by reacting γ-propanesultone with polydimethylsiloxane-co-(4,7-diazaheptylmethylsiloxane), which generated substituted di(ammonium-3-propane-sulfonate) groups pendant from the siloxane chain. Their concentration in the polymers varied from 0.5 to 10 mole %. Two model compounds were also prepared in order to (1) characterize the reaction leading to the formation of these zwitterions and (2) characterize the ionic forces in solutions (tetrahydrofuran and benzene were used as solvents). The degree of aggregation of these model compounds was higher in tetrahydrofuran and increased in both solutions with the concentration. No rearrangements of siloxane bonds were observed in the presence of these zwitterions or γ-propanesultone.     

Structural motifs in secondary ammonium halides: ring-stacking and ring-laddering in the organic solid state

The ring-stacking and ring-laddering concepts of structural inorganic chemistry may be applied to rationalize motifs observed for secondary ammonium halides R(2)NH(2)X (X = Cl, Br) in the organic solid state. General examination of the directional preferences of N(+)...X(-) contacts in 166 crystal structures confirms that the shortest contacts (3.0-3.2 and 3.2-3.4 A, X = Cl, Br) are N(+)-H...X(-) hydrogen bonds lying approximately along the directions of the N(+)-H bond vectors. The next shortest N(+)...X(-) contacts display two preferred directions of approach: i) contacts in the distance range 3.2-3.5 (X = Cl) and 3.2-3.9 A (X = Br) lie close to the H-N(+)-H plane, along the direction of the bisector of the H-N(+)-H angle; ii) contacts in the distance range 4.0-4.2 (X = Cl) and 4.0-4.4 A (X = Br) lie close to the H-N(+)-H plane, along the direction of an axis extending to the rear of one of the N(+)-H bonds. Both directions of approach lead frequently to association of R(2)NH(2) (+)X(-) ion pairs into laddered motifs. Stacking association is also observed, giving rise in one case to discrete cubanes and in several other cases to extended stacked-cube arrangements. In each case, the distribution of N(+)...X(-) contacts reflects a balance between the directional properties of the N(+)-H...X(-) hydrogen bonds and (primarily steric) interactions between the R groups of the organic moieties. The ladder and stack motifs of the organic ammonium halides are in many cases directly comparable to those in alkali metal amides, [R(2)NM](n), and information derived from the extensive organic sample provides insight into the motifs adopted by the inorganic complexes.     

Synthesis and properties of 4,6-diamino-3-cyano-2(1H)-pyridineselenone: Molecular and crystal structure of 2-allylseleno-4,6-diamino-3-cyanopyridine

Self-condensation of cyanoselenoacetamide gives 4,6-diamino-3-cyano-2(1H)pyridineselenone, which is regioselectively alkylated at the exocyclic heteroatom. The cisoid position of the Se-C bonds of the selenoallyl substituent relative to the N-C bond of the pyridine ring in the N¹C²SeC⁸ fragment favors cyclization into selenazolo[3,2-a]pyridinium salts.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2585–2590, November, 1989.     

Role of the cocatalyst in the copolymerization of CO2 and cyclohexene oxide utilizing chromium salen complexes

The mechanism of the copolymerization of cyclohexene oxide and carbon dioxide to afford poly(cyclohexylene)carbonate catalyzed by (salen)CrN3 (H2salen = N,N,'-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylene-diimine) in the presence of a broad range of cocatalysts has been studied. We have previously established the rate of copolymer formation to be very sensitive to both the electron-donating ability of the salen ligand and the [cocatalyst], where N-heterocyclic amines, phosphines, and ionic salts were effective cocatalysts. Significant increases in the rate of copolymerization have been achieved with turnover frequencies of approximately 1200 h(-1), thereby making these catalyst systems some of the most active and robust thus far uncovered. Herein we offer a detailed explanation of the role of the cocatalyst in the copolymerization of CO2 and cyclohexene oxide catalyzed by chromium salen derivatives. A salient feature of the N-heterocyclic amine- or phosphine-cocatalyzed processes is the presence of an initiation period prior to reaching the maximum rate of copolymerization. Importantly, this is not observed for comparable processes involving ionic salts as cocatalysts, e.g., PPN+ X-. In these latter cases the copolymerization reaction exhibits ideal kinetic behavior and is proposed to proceed via a reaction pathway involving anionic six-coordinate (salen)Cr(N3)X- derivatives. By way of infrared and 31P NMR spectroscopic studies, coupled with in situ kinetic monitoring of the reactions, a mechanism of copolymerization is proposed where the neutral cocatalysts react with CO2 and/or epoxide to produce inner salts or zwitterions which behave in a manner similar to that of ionic salts.     

Nitrogen inversion in cyclic amines and the bicyclic effect

The hitherto unsolved problem of the origin of the unusually high nitrogen inversion-rotation (NIR) barriers in 7-azabicyclo[2.2.1]heptanes (the bicyclic effect) was examined using the natural bond orbital (NBO) approach. Reinvestigating the NIR barrier for tropane by DNMR, we found that NIR barriers increase smoothly on going from nitrogen-bridged bicyclic systems of a larger ring size to the smaller ring homologous systems. The experimental NIR barriers are reproduced with good accuracy using the MP2/6-31G level of theory. The NBO analysis for these and other azabicycles led to the conclusion that the height of these barriers is mostly determined by the energy of the sigma-orbitals of the C(alpha)(-)C(beta) bonds as well as the nitrogen lone pair. Thus, the bicyclic effect is actually an extreme case of a common C(alpha-)N-C(alpha) tripyramid geometry-NIR barrier dependence for N-bridged bicyclic amines. By establishing the rate-determining role of the C(alpha-)N-C(alpha) tripyramid fragment for NIR, we have derived the first sufficiently accurate quantitative correlations amine geometry-NIR barrier for monocyclic as well as bicyclic N-H and N-Me amines (i.e., for an amine set which also includes the bicyclic effect systems).     

Mono and double polar [4 + 2(+)] Diels-Alder cycloaddition of acylium ions with O-heterodienes

Gas-phase reactions of acylium ions with alpha,beta-unsaturated carbonyl compounds were investigated using pentaquadrupole multiple-stage mass spectrometry. With acrolein and metacrolein, CH(3)-C(+)(double bond)O, CH(2)(double bond)CH-C(+)(double bond)O, C(6)H(5)-C(+)(double bond)O, and (CH(3))(2)N-C(+)(double bond)O react to variable extents by mono and double polar [4 + 2(+)] Diels-Alder cycloaddition. With ethyl vinyl ketone, CH(3)-C(+)(double bond)O reacts exclusively by proton transfer and C(6)H(5)-C(+)(double bond)O forms only the mono cycloadduct whereas CH(2)(double bond)CH-C(+)(double bond)O and (CH(3))(2)N-C(+)(double bond)O reacts to great extents by mono and double cycloaddition. The positively charged acylium ions are activated O-heterodienophiles, and mono cycloaddition occurs readily across their C(+)(double bond)O bonds to form resonance-stabilized 1,3-dioxinylium ions which, upon collisional activation, dissociate predominantly by retro-addition. The mono cycloadducts are also dienophiles activated by resonance-stabilized and chemically inert 1,3-dioxonium ion groups, hence they undergo a second cycloaddition across their polarized C(double bond)C ring double bonds. (18)O labeling and characteristic dissociations displayed by the double cycloadducts indicate the site and regioselectivity of double cycloaddition, which are corroborated by Becke3LYP/6-311++G(d,p) calculations. Most double cycloadducts dissociate by the loss of a RCO(2)COR(1) molecule and by a pathway that reforms the acylium ion directly. The double cycloadduct of the thioacylium ion (CH(3))(2)N-C(+)(double bond)S with acrolein dissociates to (CH(3))(2)N-C(+)(double bond)O in a sulfur-by-oxygen replacement process intermediated by the cyclic monoadduct. The double cycloaddition can be viewed as a charge-remote type of polar [4 + 2(+)] Diels-Alder cycloaddition reaction.     

Single-crystal studies of peptide prolyl and glycyl 15N shielding tensors

15N shielding tensors were determined for the central peptide groups in GGV, AGG, and APG by single-crystal NMR. We find that the angle between the downfield component (delta11) and the N-H or the N-C(delta) (pro) bonds is in the range of 20-23 degrees and in accord with previous solid-state NMR measurements. However, AGG, unlike APG or GGV, has a distorted peptide plane, and delta11 lies approximately in the plane of N, C(alpha), and H rather than in the peptide plane defined by heavy atoms. Accurate orientations of delta22 and delta33 were determined, and the usual assumption that delta22 is along the peptide normal was found only in APG which has a highly nonaxial tensor. More generally, delta22 and delta33 are rotated about the delta11 axis (36 degrees in GGV). These results are compared with DFT calculations to gain a structural understanding of the effects of intermolecular interactions on shielding tensor principal components and orientations. Trimeric clusters containing H-bonded neighbors predict the orientations of the principal components within 2-3 degrees, but calculated principal components are less quantitative. Possible reasons for this disagreement are explored.