Roman Szostak

Quantitative determination of acetylsalicylic acid and acetaminophen in tablets by FT-Raman spectroscopyElectronic Supplementary Information available. See http://www.rsc.org/suppdata/an/b1/b108240j/

A procedure for quantitative determination of acetylsalicylic acid and acetaminophen in pharmaceuticals by PLS (partial least squares) and PCR (principal component regression) treatment of FT (Fourier transform)-Raman spectroscopic data is proposed. The proposed method was tested on powdered samples. Three chemometric models were built: the first, for samples consisting of an active substance diluted by lactose, starch and talc; the second, in which a simple inorganic salt was applied as an internal standard and additions were not taken into account; and the third, in which a model was constructed for a commercial pharmaceutical, where all constituents of the tablet were known. By utilising selected spectral ranges and by changing the chemometric conditions it is possible to carry out fast and precise analysis of the active component content in medicines on the basis of the simplified chemometric models. The proposed method was tested on five commercial tablets. The results were compared with data obtained by intensity ratio and pharmacopoeial methods. To appraise the quality of the models, the relative standard error of predictions (RSEPs) were calculated for calibration and prediction data sets. These were 0.7-2.0% and 0.8-2.3%, respectively, for the different PLS models. Application of these models to the Raman spectra of commercial tablets containing acetylsalicylic acid gave RSEP values of 1.3-2.0% and a mean accuracy of 1.2-1.7% with a standard deviation of 0.6-1.2%.

CX⋅⋅⋅O Halogen Bonding: Interactions of Trifluoromethyl Halides with Dimethyl Ether

The formation of weakly bound molecular complexes between dimethyl ether (DME) and the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I dissolved in liquid argon and in liquid krypton is investigated, using Raman and FTIR spectroscopy. For all halides evidence is found for the formation of C-X...O halogen-bonded 1:1 complexes. At higher concentrations of CF(3)Br, a weak absorption due to a 1:2 complex is also observed. Using spectra recorded at temperatures between 87 and 125 K, the complexation enthalpies for the complexes are determined to be -6.8(3) kJ mol(-1) (DME x CF(3)Cl), -10.2(1) kJ mol(-1) (DME x CF(3)Br), -15.5(1) kJ mol(-1) (DME x CF(3)I), and -17.8(5) kJ mol(-1) [DME(x CF(3)Br)(2)]. Structural and spectral information on the complexes is obtained from ab initio calculations at the MP2/6-311++G(d,p) and MP2/6-311++G(d,p)+LanL2DZ* levels. By applying Monte Carlo free energy perturbation calculations to account for the solvent influences, and statistical thermodynamics to estimate the zero-point vibrational and thermal influences, the ab initio complexation energies are converted into complexation enthalpies for the solutions in liquid argon. The resulting values are compared with the experimental data deduced from the cryosolutions.

N-Acylsaccharins: Stable Electrophilic Amide-Based Acyl Transfer Reagents in Pd-Catalyzed Suzuki-Miyaura Coupling via N-C Cleavage.

The development of efficient catalytic methods for N-C bond cleavage in amides remains an important synthetic challenge. The first Pd-catalyzed Suzuki-Miyaura cross-coupling of N-acylsaccharins with boronic acids by selective N-C bond activation is reported. The reaction enables preparation of a variety of functionalized diaryl and alkyl-aryl ketones with broad functional group tolerance and in good to excellent yields. Of general interest, N-acylsaccharins serve as new, highly reactive, bench-stable, economical, amide-based, electrophilic acyl transfer reagents via acyl-metal intermediates. Mechanistic studies strongly support the amide N-C(O) bond twist as the enabling feature of N-acylsaccharins in the N-C bond cleavage.

Ground-State Distortion in N-Acyl-tert-butyl-carbamates (Boc) and N-Acyl-tosylamides (Ts): Twisted Amides of Relevance to Amide N-C Cross-Coupling.

Amide N-C(O) bonds are generally unreactive in cross-coupling reactions employing low-valent transition metals due to nN → π*C═O resonance. Herein we demonstrate that N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts), two classes of acyclic amides that have recently enabled the development of elusive amide bond N-C cross-coupling reactions with organometallic reagents, are intrinsically twisted around the N-C(O) axis. The data have important implications for the design of new amide cross-coupling reactions with the N-C(O) amide bond cleavage as a key step.

Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.

Quantitative determination of diclofenac sodium in solid dosage forms by FT-Raman spectroscopy.

The FT-Raman quantification of diclofenac sodium in tablets and capsules was performed with the help of the partial least squares (PLS), principal component regression (PCR) and counter-propagation artificial neural networks (CP-ANN) methods. For the analysed tablets, calibration models were built using unnormalised spectra and spectra normalised by the intensity of a selected band of an internal standard. Different pre-processing methods were applied for the capsules. To compare the predictive ability of the models, the relative standard errors of prediction (RSEP) were calculated. The 5 x 5 CP-ANN and PLS methods gave models of comparable quality, which were usually more efficient than the PCR ones. The RSEP error values for the tablets were in the range of 2.4-3.8% for the calibration and 2.6-3.5% for the validation data sets and for the three procedures applied. For capsules, the RSEP errors were in the range of 0.8-1.9% and 1.4-1.7% for the calibration and validation samples, respectively. Five commercial products containing 25, 50 or 75 mg of diclofenac sodium per tablet/capsule were quantified. Concentrations found from the Raman data analysis agree with the results of the reference analysis and correlate strongly with the declared values with the recovery of 99.5-101.3%, 99.7-102.0% and 99.9-101.2% for the PLS, PCR and CP-ANN methods, respectively. The proposed procedure can be a fast and convenient alternative to the standard pharmacopoeial methods of diclofenac sodium quantification in solid dosage forms.

Quantification of atorvastatin calcium in tablets by FT-Raman spectroscopy.

The FT-Raman quantification of atorvastatin calcium in tablets was performed using the partial least squares (PLS), principal component regression (PCR) and counter-propagation artificial neural networks (CP-ANN) methods. To compare the predictive abilities of the elaborated models, the relative standard errors of prediction (RSEP) were calculated. The application of PLS, PCR and 6x6 CP-ANN provided models of comparable quality. RSEP error values in the range of 1.9-2.8% for calibration and validation data sets were obtained for the three procedures applied. Four commercial products containing 10, 20 or 40 mg of atorvastatin calcium per tablet were successfully quantified. Concentrations found from the Raman data analysis correlate strongly with the declared values, with a recovery of 98.5-101.3%, and with the results of reference analysis, with the recovery of 98.9-102.1%, for the different models. The proposed procedure can be a fast, precise and convenient method of atorvastatin calcium quantification in commercial tablets.

Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon-Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C–N Rotational Pathway

Twisted amides containing nitrogen at the bridgehead position are attractive practical prototypes for the investigation of the electronic and structural properties of nonplanar amide linkages. Changes that occur during rotation around the N-C(O) axis in one-carbon-bridged twisted amides have been studied using ab initio molecular orbital methods. Calculations at the MP2/6-311++G(d,p) level performed on a set of one-carbon-bridged lactams, including 20 distinct scaffolds ranging from [2.2.1] to [6.3.1] ring systems, with the C═O bond on the shortest bridge indicate significant variations in structures, resonance energies, proton affinities, core ionization energies, frontier molecular orbitals, atomic charges, and infrared frequencies that reflect structural changes corresponding to the extent of resonance stabilization during rotation along the N-C(O) axis. The results are discussed in the context of resonance theory and activation of amides toward N-protonation (N-activation) by distortion. This study demonstrates that one-carbon-bridged lactams-a class of readily available, hydrolytically robust twisted amides-are ideally suited to span the whole spectrum of the amide bond distortion energy surface. Notably, this study provides a blueprint for the rational design and application of nonplanar amides in organic synthesis. The presented findings strongly support the classical amide bond resonance model in predicting the properties of nonplanar amides.

Spectra and details of the structure of europium aliphatic carboxylates with 1,10-phenanthroline derivatives

Abstract Luminescence, excitation of luminescence, IR and Raman spectra of a variety of carboxylates Eu(RCOO) 3 .Phen (Phen–1,10-phenanthroline) consisting of acetate, propionate, lactate, capronate compounds, and Eu(CH 3 COO) 3 .Ph (Ph–six 1,10-phenanthroline derivatives) were examined. Crystal field parameters for model compounds were calculated. The crystal structure of the europium acetate Eu(CH 3 COO) 3 .Phen was solved by X-ray method. Dependence of the spectroscopic characteristics on variation of both types of ligands, indicating details of the structure of compounds, was examined. Reciprocal influence of inequivalent ligands in europium carboxylates was analysed. It was demonstrated that steric factors are as significant as the donor–acceptor properties of the ligands in creation of the structure of compounds under investigation.

Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of N-Mesylamides by N–C Cleavage: Electronic Effect of the Mesyl Group

A general Pd-catalyzed Suzuki-Miyaura cross-coupling of N-mesylamides with arylboronic acids by selective N-C cleavage has been developed. The presented results represent the first example of a transition-metal-catalyzed cross-coupling of amides activated by an atom-economic, cheap, and benign mesyl group. The reaction delivers arylated products featuring a range of useful functional groups by chemoselective cleavage of the amide N-C bond with high efficiency. Both the scope and the origin of high selectivity are discussed. A beneficial effect of the N-mesyl substituent on the bond activation in acyclic amides is presented.