A Zwitterionic Phosphonio‐1, 2, 4‐Diazaphospholide and Neutral 1, 2, 4‐Diazaphosphole — A Comparative Study of Molecular Structures and Co‐ordination Properties

The bis‐phosphonio‐1, 2, 4‐diazaphospholide salt ( 1 [Cl]) reacts with complex boron hydrides under selective extrusion of one PPh₃ moiety to give borane adducts of a novel zwitterionic phosphonio‐1, 2, 4‐diazaphospholide. Both the Et₃B adduct 2b and the free zwitterionic heterocycle 3 , which was liberated by further reaction of 2b with NEt₃, were characterized by spectroscopic data and 2b , as well, by a single crystal X‐ray diffraction study. The comparison of the structural data with those of a neutral 1, 2, 4‐diazaphosphole and a lithium‐1, 2, 4‐diazaphospholide which was formed by deprotonation of the parent 1, 2, 4‐diazaphosphole 4a discloses trends in endocyclic bonding distances which can be rationalized in terms of a charge dependent shift in the π‐electron distribution. First studies of the co‐ordination properties reveal for both 2b and 4a a marked preference to bind two M(CO)₅‐fragments (M = Cr, W) via the lone‐pairs of the phosphorus and one nitrogen atom; mononuclear complexes with P‐co‐ordinated heterocycles are formed as intermediates. A single crystal X‐ray diffraction study of the dinuclear complex [Cr₂(CO)₁₀(μ₂‐C₂H₃N₂P‐κP, κN)] ( 10a ) together with spectroscopic studies (including ¹⁸³W NMR studies of tungsten complexes) suggests that M→L back donation is more efficient for P‐ than for N‐bound metal fragments. No evidence for π‐co‐ordination of the 1, 2, 4‐diazaphosphole ring to a Cr(CO)₃ fragment was obtained.     

Three polymorphic forms of the co-crystal 4,4'-bipyridine/pimelic acid and their structural, thermal, and spectroscopic characterization

Three crystal forms of the co-crystal 4,4'-bipy/pimelic acid (bipy: bipyridine), [NH(4)C(5)-C(5)H(4)N][HOOC(CH(2))(5)COOH], have been prepared and their relationship investigated by single-crystal X-ray diffraction, variable-temperature X-ray powder diffraction, differential scanning calorimetry and solid-state NMR spectroscopy. Both X-ray and NMR spectroscopic results indicate that no proton transfer takes place, that is, the three crystal forms are true co-crystals of neutral molecules. Forms I and II both convert into Form III at high temperature, Forms II and III being the thermodynamically stable forms at room and high temperature, respectively.     

Chemical modulation of peptoids: synthesis and conformational studies on partially constrained derivatives

The high conformational flexibility of peptoids can generate problems in biomolecular selectivity as a result of undesired off-target interactions. This drawback can be counterbalanced by restricting the original flexibility to a certain extent, thus leading to new peptidomimetics. By starting from the structure of an active peptoid as an apoptosis inhibitor, we designed two families of peptidomimetics that bear either 7-substituted perhydro-1,4-diazepine-2,5-dione 2 or 3-substituted 1,4-piperazine-2,5-dione 3 moieties. We report an efficient, solid-phase-based synthesis for both peptidomimetic families 2 and 3 from a common intermediate. An NMR spectroscopic study of 2a,b and 3a,b showed two species in solution in different solvents that interconvert slowly on the NMR timescale. The cis/trans isomerization around the exocyclic tertiary amide bond is responsible for this conformational behavior. The cis isomers are more favored in nonpolar environments, and this preference is higher for the six-membered-ring derivative 3a,b. We propose that the hydrogen-bonding pattern could play an important role in the cis/trans equilibrium process. These hydrogen bonds were characterized in solution, in the solid state (i.e., by using X-ray studies), and by molecular modeling of simplified systems. A comparative study of a model peptoid 10 containing the isolated tertiary amide bond under study outlined the importance of the heterocyclic moiety for the prevalence of the cis configuration in 2a and 3a. The kinetics of the cis/trans interconversion in 2a, 3a, and 10 was also studied by variable-temperature NMR spectroscopic analysis. The full line-shape analysis of the NMR spectra of 10 revealed negligible entropic contribution to the energetic barrier in this conformational process. A theoretical analysis of 10 supported the results observed by NMR spectroscopic analysis. Overall, these results are relevant for the study of the peptidomimetic/biological-target interactions.     

The Richest Collection of Tautomeric Polymorphs: The Case of 2‐Thiobarbituric Acid

Five new polymorphs and one hydrated form of 2‐thiobarbituric acid have been isolated and characterised by solid‐state methods. In both the crystalline form II and in the hydrate form, the 2‐thiobarbituric molecules are present in the enol form, whereas only the keto isomer is present in crystalline forms I (reported in 1967 by Calas and Martinex), III , V and VI . In form IV , on the other hand, a 50:50 ordered mixture of enol/keto molecules is present. All new forms have been characterised by single‐crystal X‐ray diffraction, 1D and 2D (¹H, ¹³C, and ¹⁵N) solid‐state NMR spectroscopy, Raman spectroscopy and X‐ray powder diffraction at variable temperature. It has been possible to induce keto–enol conversion between the forms by mechanical methods. The role of hydrogen‐bond interactions in determining the relative stability of the polymorphs and as a driving force in the conversions has been ascertained. To the best of the authors’ knowledge, the 2‐thiobarbituric family of crystal forms represents the richest collection of examples of tautomeric polymorphism so far reported in the literature.     

The first silicon-based cationic clathrate III with high thermal stability: Si172-xPxTey (x=2y, y>20)

A new representative of a very rare clathrate III family, Si130P42Te21, has been synthesized from the elements. It crystallizes in the tetragonal space group P4(2)/mnm (no. 136) with the unit cell parameters a=19.2632(3) angstroms, c=10.0706(2) angstroms. Single crystal X-ray diffraction and solid state 31P NMR revealed a non-random distribution of phosphorus atoms over the framework positions. The crystal structure features a peculiar packing of large polyhedra Te@(Si/P)(n) never observed before for cationic clathrates. Despite the structural complexity, the composition of the novel clathrate Is in accordance with the Zintl rule, which was confirmed by a combination of optical metallography, scanning electron microscopy (SEM) and wavelength dispersive X-ray spectroscopy (WDXS), as well as by diamagnetic and semiconducting behavior of the synthesized phase. Clathrate Si130P42Te21 exhibits the highest reported thermal stability for this class of materials, it decomposes at 1510 K. This opens new perspectives for the creation of clathrate-based materials for high-temperature applications.     

Monometallic Ni0 and Heterobimetallic Ni0/AuI Complexes of Tripodal Phosphine Ligands: Characterization in Solution and in the Solid State and Catalysis

The tridentate chelate nickel complexes [(CO)Ni{(PPh₂CH₂)₃CMe}] ( 2 ), [(CO)Ni{(PPh₂CH₂CH₂)₃SiMe}] ( 6 ), and [Ph₃PNi{(PPh₂CH₂CH₂)₃SiMe}] ( 7 ), as well as the bidentate complex [(CO)₂Ni{(PPh₂CH₂)₂CMeCH₂PPh₂}] ( 3 ) and the heterobimetallic complex [(CO)₂Ni{(PPh₂CH₂)₂CMeCH₂Ph₂PAuCl}] ( 4 ), have been synthesized and fully characterized in solution. All ¹H and ¹³C NMR signal assignments are based on 2D‐NMR methods. Single crystal X‐ray structures have been obtained for all complexes. Their ³¹P CP/MAS (cross polarization with magic angle spinning) NMR spectra have been recorded and the isotropic lines identified. The signals were assigned with the help of their chemical shift anisotropy (CSA) data. All complexes have been tested regarding their catalytic activity for the cyclotrimerization of phenylacetylene. Whereas complexes 2 – 4 display low catalytic activity, complex 7 leads to quantitative conversion of the substrate within four hours and is highly selective throughout the catalytic reaction.     

Assignment of chemical shifts in benzohydroxamic acid and structure of its silylated derivatives by 15N enrichment

¹⁵N isotopic enrichment was necessary for the unequivocal assignment of the ¹H NMR lines to the protons in the NH–OH fragment of benzohydroxamic acid, BHXA, C₆H₅CONHOH, in dry dimethyl sulfoxide solutions. The assignment [δ(NH) = 11.21, δ(OH) = 9.01, ¹J(¹⁵N,¹H) = 102.2 Hz, ²J(¹⁵N,¹H) <1.5 Hz], which is opposite to that used by other authors, confirms the assignment extended to BHXA by Brown and co‐workers from the spectra of acetohydroxamic acid. The enrichment allowed also assignment of the ²⁹Si lines in the spectra of disilylated benzohydroxamic acid, (Z)‐tert‐butyldimethylsilyl N‐tert‐butyldimethylsilyloxybenzoimidate (2) and (Z)‐tert‐butyldiphenylsilyl N‐tert‐butyldiphenylsilyloxybenzoimidate (3), and confirmed structure of the monosilylated products, N‐tert‐butyldiphenylsilyloxybenzamide (4) and N‐tert‐butyldiphenylsilyloxy benzoimidic acid (5). Copyright © 2003 John Wiley & Sons, Ltd.     

Stereochemical analysis of N-cyclohexylidene-N-(1-phenylethyl)amine derivatives

The configurational properties of a series of cyclohexylidene imines are discussed on the basis of their 1H, 13C and 15N NMR spectral data.     

Structural study of 2,6-bis[(dimethylaminomethyl)phenyl]butyl stannanes: nonconventional behaviour of triorganotin(IV) halides

The four organotin (IV) compounds ([2,6-bis(dimethylaminomethyl)phenyl](n-butyl)R(1)R(2)stannane, with R(1)=R(2)=nBu (1), R(1)=nBu, R(2)=Cl (2), R(1)=nBu, R(2)=Br (3) and R(1)=R(2)=Br (4)), have been prepared and their structures have been investigated in various solvents and at various temperatures (NMR). The structures of these compounds in solution are solvent- and temperature-dependent. The solid state structures of 2 and 3 were studied using CP/MAS NMR spectroscopy and Xray diffraction techniques. The tetraorganotin compound 1 exhibits tetrahedral geometry with very weak Sn-N coordination. The dynamic process of Sn-N bond(s) association/dissociation was observed using low-temperature NMR measurements. The tin central atom in 2 and 3 is [4+2]-coordinated in toluene solutions and the NMR low-temperature measurements reveal the same dynamic behavior as for 1 in this solution, with retention of the covalent halogen-tin bond. However, this bond is dissociated in methanol solutions, yielding ionic species, where the tin atom is only [3+2]-coordinated, and the halogen atom lies outside of the primary coordination sphere of the tin atom. In addition, while the same ionic structure as in methanol was found in the whole measured temperature range in the chloroform solution of 3, the structure of 2 varies in this solvent. In this compound, the covalent Sn-Cl bond (similar structure as in toluene solution), which is retained at room temperature in chloroform solution, is continuously dissociated with a decrease in temperature, leading to ionic bonding (a similar structure as in methanol solution). All the above-mentioned processes are reversible in all the solvents and at all temperatures. In the solid state, the covalent Sn-Cl bond is observed for 2, while an ionic bond was found in 3.     

Stabilization of a Diphosphagermylene through pπ–pπ Interactions with a Trigonal‐Planar Phosphorus Center

N‐Heterocyclic carbenes and their heavier homologues are, in part, stabilized by delocalization of the N lone pairs into the vacant p‐orbital at carbon (or a heavier Group 14 element center). These interactions are usually absent in the corresponding P‐substituted species, owing to the large barrier to planarization of phosphorus. However, judicious selection of the substituents at phosphorus has enabled the synthesis of a diphosphagermylene, [(Dipp)₂P]₂Ge, in which one of the P centers is planar (Dipp=2,6‐diisopropylphenyl). The planar nature of this P center and the correspondingly short P? Ge distance suggest a significant degree of P? Ge multiple bond character that is due to delocalization of the phosphorus lone pair into the vacant p‐orbital at germanium. DFT calculations support this proposition and NBO and AIM analyses are consistent with a Ge? P bond order greater than unity.     

Reaction of o-phenylenediamine with diacetyl monoxime: characterisation of the product by solid-state 13C and 15N MAS NMR

2,3-dimethylquinoxaline (DMQ) and dimethylglyoxime (DMGH2) form a 1:1 hydrogen-bonded complex in the solid state, which is completely dissociated in methanol solution. There are small differences in solid-state 13C shifts between the separated components DMQ and DMGH2 and the complex. The changes in 15N solid-state chemical shifts are more significant: the hydrogen bond imparting a low frequency shift of ca 19 ppm. The effect of direct protonation on the DMQ solid-state 15N shifts was measured, and the experimental 15N data correlated with those from GIAO molecular orbital (MO) calculations.     

Rapid Acquisition of 14N Solid‐State NMR Spectra with Broadband Cross Polarization

Nitrogen is an element of utmost importance in chemistry, biology and materials science. Of its two NMR‐active isotopes, ¹⁴N and ¹⁵N, solid‐state NMR (SSNMR) experiments are rarely conducted upon the former, due to its low gyromagnetic ratio (γ) and broad powder patterns arising from first‐order quadrupolar interactions. In this work, we propose a methodology for the rapid acquisition of high quality ¹⁴N SSNMR spectra that is easy to implement, and can be used for a variety of nitrogen‐containing systems. We demonstrate that it is possible to dramatically enhance ¹⁴N NMR signals in spectra of stationary, polycrystalline samples (i.e., amino acids and active pharmaceutical ingredients) by means of broadband cross polarization (CP) from abundant nuclei (e.g., ¹H). The BR oadband A diabatic IN version C ross‐ P olarization ( BRAIN–CP ) pulse sequence is combined with other elements for efficient acquisition of ultra‐wideline SSNMR spectra, including W ideband U niform‐ R ate S mooth‐ T runcation ( WURST ) pulses for broadband refocusing, C arr– P urcell M eiboom– G ill ( CPMG ) echo trains for T₂‐driven S/N enhancement, and frequency‐stepped acquisitions. The feasibility of utilizing the BRAIN–CP/WURST–CPMG sequence is tested for ¹⁴N, with special consideration given to (i) spin‐locking integer spin nuclei and maintaining adiabatic polarization transfer, and (ii) the effects of broadband polarization transfer on the overlapping satellite transition patterns. The BRAIN–CP experiments are shown to provide increases in signal‐to‐noise ranging from four to ten times and reductions of experimental times from one to two orders of magnitude compared to analogous experiments where ¹⁴N nuclei are directly excited. Furthermore, patterns acquired with this method are generally more uniform than those acquired with direct excitation methods. We also discuss the proposed method and its potential for probing a variety of chemically distinct nitrogen environments.     

Unambiguous assignment of trifluoromethylpyrazole regioisomers by 19F-15N correlation spectroscopy

Analysis of the 19F chemical shifts of trifluoromethylpyrazole regioisomers has shown that while chemical shift is in general a reliable predictor of regiochemistry in this series, there is a narrow chemical shift range in which the two isomers overlap and the regiochemistry cannot be assigned with certainty. We have examined the usage of 19F--15N correlation spectroscopy as a method to provide a second unambiguous confirmation of regiochemistry of 3- and 5-trifluoromethylpyrazole regioisomers. In the case of 3-trifluoromethyl analogs, one expects a three-bond coupling to the pyridine type nitrogen (N-2). In the case of the 5-trifluoromethyl pyrazole the situation is exactly reversed, with the fluorines of the trifluoromethyl moiety being 3-bonds from the pyrrole type nitrogen (N-1). We have observed that 3-trifluromethyl analogs follow the expected pattern of readily observable 3-bond coupling. However, 19F--15N couplings in 5-trifluromethyl analogs do not follow the normal pattern of 3-bond coupling. Using this information we have been able to develop unambiguous methods to distinguish the isomers.     

Synthetic and Mechanistic Aspects of the Immortal Ring‐Opening Polymerization of Lactide and Trimethylene Carbonate with New Homo‐ and Heteroleptic Tin(II)‐Phenolate Catalysts

Several new heteroleptic Sn^II complexes supported by amino‐ether phenolate ligands [Sn{LOⁿ}(Nu)] (LO¹=2‐[(1,4,7,10‐tetraoxa‐13‐azacyclopentadecan‐13‐yl)methyl]‐4,6‐di‐tert‐butylphenolate, Nu=NMe₂ ( 1 ), N(SiMe₃)₂ ( 3 ), OSiPh₃ ( 6 ); LO²=2,4‐di‐tert‐butyl‐6‐(morpholinomethyl)phenolate, Nu=N(SiMe₃)₂ ( 7 ), OSiPh₃ ( 8 )) and the homoleptic Sn{LO¹}₂ ( 2 ) have been synthesized. The alkoxy derivatives [Sn{LO¹}(OR)] (OR=OiPr ( 4 ), (S)‐OCH(CH₃)CO₂iPr ( 5 )), which were generated by alcoholysis of the parent amido precursor, were stable in solution but could not be isolated. [Sn{LO¹}]⁺[H₂N{B(C₆F₅)₃}₂]^? ( 9 ), a rare well‐defined, solvent‐free tin cation, was prepared in high yield. The X‐ray crystal structures of compounds 3 , 6 , and 8 were elucidated, and compounds 3 , 6 , 8 , and 9 were further characterized by ¹¹⁹Sn Mössbauer spectroscopy. In the presence of iPrOH, compounds 1 – 5 , 7 , and 9 catalyzed the well‐controlled, immortal ring‐opening polymerization (iROP) of L ‐lactide (L ‐LA) with high activities (ca. 150–550 mol_L?LA mol_Sn^?1 h^?1) for tin(II) complexes. The cationic compound 9 required a higher temperature (100 °C) than the neutral species (60 °C); monodisperse poly(L ‐LA)s were obtained in all cases. The activities of the heteroleptic pre‐catalysts 1 , 3 , and 7 were virtually independent of the nature of the ancillary ligand, and, most strikingly, the homoleptic complex 2 was equally competent as a pre‐catalyst. Polymerization of trimethylene carbonate (TMC) occurs much more slowly, and not at all in the presence of LA; therefore, the generation of PLA‐PTMC copolymers is only possible if TMC is polymerized first. Mechanistic studies based on ¹H and ¹¹⁹Sn{¹H} NMR spectroscopy showed that the addition of an excess of iPrOH to compound 3 yielded a mixture of compound 4 , compound [Sn(OiPr)₂]_n 10 , and free {LO¹}H in a dynamic temperature‐dependent and concentration‐dependent equilibrium. Upon further addition of L ‐LA, two active species were detected, [Sn{LO¹}(OPLLA)] ( 12 ) and [Sn(OPLLA)₂] ( 14 ), which were also in fast equilibrium. Based on assignment of the ¹¹⁹Sn{¹H} NMR spectrum, all of the species present in the ROP reaction were identified; starting from either the heteroleptic ( 1 , 3 , 7 ) or homoleptic ( 2 ) pre‐catalysts, both types of pre‐catalysts yielded the same active species. The catalytic inactivity of the siloxy derivative 6 confirmed that ROP catalysts of the type 1 – 5 could not operate according to an activated‐monomer mechanism. These mechanistic studies removed a number of ambiguities regarding the mechanism of the (i)ROPs of L ‐LA and TMC promoted by industrially relevant homoleptic or heteroleptic Sn^II species.     

Deuterium isotope effects on 15N chemical shifts of double Schiff bases in the solid state and solution

The proton transfer equilibrium in a series of double Schiff base derivatives of trans‐1,2‐diaminocyclohexane in solution and the solid state was studied by means of ¹⁵N NMR spectroscopy and analysis of the deuterium isotope effect on the chemical shifts Δ¹⁵N(D). The presence of a proton transfer equilibrium in the N‐2‐hydroxynaphthylidene moieties of the Schiff bases studied in the solid state at room temperature was evidenced. The results confirmed the interrelation of the two hydrogen bonds in double Schiff base derivatives of trans‐1,2‐diaminocyclohexane. Copyright © 2003 John Wiley & Sons, Ltd.     

Highly Stable Water‐Soluble Platinum Nanoparticles Stabilized by Hydrophilic N‐Heterocyclic Carbenes

Controlling the synthesis of stable metal nanoparticles in water is a current challenge in nanochemistry. The strategy presented herein uses sulfonated N‐heterocyclic carbene (NHC) ligands to stabilize platinum nanoparticles (PtNPs) in water, under air, for an indefinite time period. The particles were prepared by thermal decomposition of a preformed molecular Pt complex containing the NHC ligand and were then purified by dialysis and characterized by TEM, high‐resolution TEM, and spectroscopic techniques. Solid‐state NMR studies showed coordination of the carbene ligands to the nanoparticle surface and allowed the determination of a ¹³C–¹⁹⁵Pt coupling constant for the first time in a nanosystem (940 Hz). Additionally, in one case a novel structure was formed in which platinum(II) NHC complexes form a second coordination sphere around the nanoparticle.