Fragmentation of the metastable molecular ion of methyl lactate: The formation of oxygen-protonated methanol [CH3OH2]+ involving double hydrogen atom transfers

The spontaneous unimolecular dissociation reaction of methyl lactate (1) ionized by electron impact was investigated by a combination of mass-analyzed ion kinetic energy spectrometry and deuterium labeling. The metastable ions 1^+· decompose in a variety of ways: four fragment peaks are observed at m/z 89, 76, 61, and 45, which correspond to the losses of ?H₃, CO, CH₃?O, and ?OOCH₃, respectively. Double hydrogen atom transfer occurs in the third reaction. The source-generated m/z 61 ions decompose into oxygen-protonated methanols at m/z 33 ([CH₃OH ₂ ⁺ ]) by the loss of CO with double hydrogen atom migration. Both hydroxyl and methyne hydrogen atoms in 1 ^+· are present in the resultant protonated methanols.     

Stereospecific synthesis of eight- and nine-membered cyclic ethers by Eu(fod)3-mediated cyclization of hydroxy epoxides

An efficient and versatile method for the stereospecific construction of α,ω-cis- and α,ω-trans-disubstituted eight- and nine-membered cyclic ethers was developed. Cyclization of the hydroxy epoxides promoted by Eu(fod)₃ proceeded via an S_N2 process and exo mode to provide the corresponding cyclic ethers in excellent yields.     

Unambiguous Determination of the Absolute Configurations of Acetylene Alcohols by Combination of the Sonogashira Reaction and the CD Exciton Chirality Method – Exciton Coupling between Phenylacetylene and Benzoate Chromophores

The CD exciton chirality method was applied to various phenylacetylene alcohols to determine their absolute configurations; the long axis polarized –^* transition (_max=252nm) of the 4-methoxyphenylacetylene chromophore couples with the transition (_max=257nm) of the 4-methoxybenzoate group to generate intense exciton split CD Cotton effects, from the signs of which the absolute configurations of phenylacetylene alcohols were unambiguously determined. As an extension of the results, a new methodology for determining the absolute configurations of acetylene alcohols having the HCCCH(OH)-moiety by combination of the Sonogashira reaction and the CD exciton chirality method has been developed and applied. Since the –^* transition of acetylene triple bond is located below 180nm, it is difficult to observe ideal bisignate CD Cotton effects due to the exciton coupling between acetylene and benzoate chromophores. To observe the ideal exciton split Cotton effects necessary for the unambiguous determination of absolute configuration, the terminal acetylene group was converted, by the Sonogashira reaction, to the 4-methoxyphenylacetylene moiety, which exhibits an intense –^* absorption band polarized along the long axis of the chromophore at 252nm. As a partner of exciton coupling, 4-methoxybenzoate showing a –^* band at 257nm was introduced into the alcohol moiety, and the benzoates formed showed intense bisignate CD Cotton effects, from the signs of which the absolute configurations of original acetylene alcohols could be determined in an unambiguous manner.     

Tetrahedranyllithium: synthesis, characterization, and reactivity

The first representative of stable tetrahedranyl anion, tris(trimethylsilyl)tetrahedranyllithium (3), has been synthesized by the reaction of tetrakis(trimethylsilyl)tetrahedrane (2) with methyllithium in tetrahydrofuran. The structural characterization of the tetrahedranyllithium has been achieved by X-ray crystallography, showing that the structure of 3.(TMEDA)1.5 represents a stretched tetrahedron. The endocyclic C(Li)-C(SiMe3) bond lengths range from 1.5408(15) to 1.5441(15) A (av 1.5425(15) A), and are longer than the endocyclic C(SiMe3)-C(SiMe3) bond lengths, which range from 1.4961(15) to 1.5009(15) A (av 1.4986(15) A). Methyl- and hydrogen-substituted tetrahedranes have also been prepared by the reaction of 3 with dimethyl sulfate and cyclopentadiene, respectively.     

Derivatives Of ditraizinylamine and tritriazinylamine

2-Arylamino-4,6-dichloro-s-triazine reacts with cyanuric chloride in the presence of alkali to yield N,N-bis(4,6-dichloro-s-triazin-2-yl)-arylamine. In like manner, 2-substituted o-chloro-, p-chloro-, o-nitro- and p-carbomethoxyphenylamino-4,6-dimethoxy-s-triazines react with cyanuric chloride to yield the corresponding 4,6-dichloro-s-triazin-2-yl-4′,6′-dimethoxy-s-triazin-2′-ylaryl-amine, while anilino-, p-toluidino, o- and p-methoxyphenylamino and o-carbomethoxyphenylamino derivatives did not. The reaction of cyanuric chloride with 2,4-dichloro-6-ethylamino-s-triazine in the presence of alkali yields the condensation product of the ditriazinylamine type and the reaction of cyanuric chloride with ammonia yields N,N-bis(4,6-dichloro-s-triazin-2-yl)- or tris(4,6-dichloro-s-triazin-2-yl)amine.     

Stereoselective analysis of flecainide enantiomers using reversed‐phase liquid chromatography for assessing CYP2D6 activity

Stereoselective analyses of flecainide enantiomers were performed using reversed‐phase high‐performance liquid chromatography (HPLC) equipped with a polysaccharide‐based chiral column (Chiralpak AS‐RH) and fluorescence detector. Excitation and emission wavelengths were set at 300 and 370 nm, respectively. Flecainide enantiomers in serum and urine were extracted using diethyl ether. The mobile phase solution, comprising 0.1 m potassium hexafluorophosphate and acetonitrile (65:35, v/v), was pumped at a flow rate of 0.5 mL/min. The recoveries of flecainide enantiomers were greater than 94%, with the coefficients of variation (CVs) <6%. The calibration curves of flecainide enantiomers in serum and urine were linear in the concentration range 5–500 ng/mL and 0.75–15 µg/mL (r > 0.999), respectively. CVs in intra‐day and inter‐day assays were 1.8–5.8 and 3.4–7.5%, respectively. In a pharmacokinetic study, the ratios of (S)‐ to (R)‐flecainide (S/R ratio) in the area under the curve and the amount of flecainide enantiomers excreted in urine were lower in a subject carrying CYP2D6*10/*10 than in subjects carrying CYP2D6*1/*2. The S/R ratio of trough serum flecainide concentration ranged from 0.79 to 1.16 in patients receiving oral flecainide. The present HPLC method can be used to assess hepatic flecainide metabolism in a pharmacokinetic study and therapeutic drug monitoring. Copyright © 2014 John Wiley & Sons, Ltd.     

Multiple Mechanism of NCA Polymerization: Effect of N-Acetylglycine NCA and Related Additives

Polymerization of α-aminoisobutyric acid NCA by alkaline salts of various basicity as well as amines has been investigated. The study was focused on the effect on the initial polymerization rate of additives such as N-acetylglycine NCA and some other less electrophilic additives (l-acetyl-2-pyrrolidone, 3-acetyl-2-oxazolidone, 1-acetyl-3-methylhydantoin) which are all models of the growing chain end produced by the NCA anion pathway. The acetyl endgroup was detected by 250 MHz ¹H-NMR in all the polymers of α-aminoisobutyric acid NCA obtained in the presence of l-acetyl-3-methylhydantoin and triethyl amine or sodium methoxide initiators, whereas the additives influenced variously the kinetics of polymerization according to the nature of the initiator used. The results were interpreted in the light of a multiple mechanism supposing the simultaneous presence of the initiator anion, its conjugate acid, and NCA anion for basic salt initiation. Thus, the observed effect has to be considered as the sum of an elementary acceleration due to NCA anion and of an elementary deceleration due to the initiator anion. Predominance of the pathways involving NCA anion could be shown this way. This conclusion could be extended to γ-benxyl-L-glutamate NCA which is a more reactive NCA. However, the deceleration observed with some additives led us to believe that a nonnegligible participation of initiator anion during initiation cannot be excluded.     

(Tetragermacyclobutadiene)ruthenium tricarbonyl [η4-(But 2MeSi)4Ge4]Ru(CO)3

Tetrakis(di-tert-butylmethylsilyl)tetragermacyclobutadiene]ruthenium tricarbonyl [η⁴-(Bu^t ₂MeSi)₄Ge₄]Ru(CO)₃ is synthesized. This analogue of well-known cyclobutadiene transition metal complexes bears a tetragermacyclobutadiene derivative as ligand. The structure and spectroscopic parameters of the complex are compared with those of its iron-containing analogue [η⁴-(Bu^t ₂MeSi)₄Ge₄]Fe(CO)₃. Based on experimental data and results of quantum chemical calculations, it is shown that the π-donating ability of ligands increases upon replacement of carbon atoms in the cyclobutadiene moiety by silicon or germanium atoms, tetrasilacyclobutadiene and tetragermacyclobutadiene being comparable in π-donating activity.