Kinetic Studies upon the Influence of Cyclodextrin on the Polymerization of Methacrylamides in Homogenous Aqueous Solution

Summary: N‐methacryloyl‐1‐aminopropane ( 1 ), N‐methacryloyl‐1‐aminobutane ( 2 ), N‐methacryloyl‐1‐aminopentane ( 3 ), and N‐methacryloyl‐1‐aminohexane ( 4 ) are synthesized and treated with an aqueous solution of randomly methylated β‐cyclodextrin (Me‐β‐CD) to form the water‐soluble host‐guest complexes 1a – 4a . In case of the aqueous polymerization of the free monomers 1 – 4 the initial polymerization rate increases with increasing water solubility. The opposite effect is observed in the case of the polymerizations of the Me‐β‐CD‐complexed methacrylamide monomers 1a – 4a . The polymerization rates are increased with increasing alkyl chain length of the complexed monomers 1a – 4a and decreasing water solubility of the free monomers 1 – 4 .

Initial polymerization rate v₀ of CD‐complexed monomers 1a – 4a (○) vs. water solubilities of monomers 1 – 4 (▪).     

Diazo Strategy for the Synthesis of Pyridazines: Pivotal Impact of the Configuration of the Diazo Precursor on the Process

Phosphazenes of vinyldiazocarbonyl compounds having cis stereochemistry of the functional groups on the vinyl bond readily produce pyridazines by a diaza‐Wittig process, whereas their counterparts with trans configuration remain intact under similar reaction conditions. Upon UV irradiation trans‐phosphazenes furnish pyridazines through a tandem trans‐to‐cis isomerization followed by intramolecular cyclization. At elevated temperatures trans‐(triphenyl)phosphazenes dissociate to give the initial vinyldiazo compounds, which produce pyrazoles in high yields. The first theoretical study on the mechanism of the diaza‐Wittig process by DFT calculations at the M06‐2X/6‐31G(d) level of theory suggest that for the cis‐phosphazenes a rapid tandem [2+2] cycloaddition/cycloelimination process with low energy barriers is preferred over trans isomers.     

Application of high‐performance countercurrent chromatography for the isolation of steroidal saponins from Liriope plathyphylla

High‐performance countercurrent chromatography (HPCCC) with electrospray light‐scattering detection was applied for the first time to isolate a spirostanol and a novel furostanol saponin from Liriope platyphylla. Due to the large differences in K_D values between the two compounds, a two‐step HPCCC method was applied in this study. The primary HPCCC employed methylene chloride/methanol/isopropanol/water (9:6:1:4 v/v, 4 mL/min, normal‐phase mode) conditions to yield a spirostanol saponin ( 1 ). After the primary HPCCC run, the solute retained in the stationary phase (SP extract) in HPCCC column was recovered and subjected to the second HPCCC on the n‐hexane/n‐butanol/water system (1:9:10 v/v, 5 mL/min, reversed‐phase mode) to yield a novel furostanol saponin ( 2 ). The isolated spirostanol saponin was determined to be 25(S)‐ruscogenin 1‐O‐β‐d ‐glucopyranosyl (1→2)‐[β‐d ‐xylopyranosyl (1→3)]‐β‐d ‐fucopyranoside (spicatoside A), and the novel furostanol saponin was elucidated to be 26‐O‐β‐d ‐glucopyranosyl‐25(S)‐furost‐5(6)‐ene‐1β‐3β‐22α‐26‐tetraol‐1‐O‐β‐d ‐glucopyranosyl (1→2)‐[β‐d ‐xylopyranosyl‐(1→3)]‐β‐d ‐fucopyranoside (spicatoside D).     

Characteristics of the biodegradability and physical properties of stereocomplexes between poly(L‐lactide) and poly(D‐lactide) copolymers

Random and block copolymerizations of L ‐ or D ‐lactide with ε‐caprolactone (CL) were performed with a novel anionic initiator, (C₅Me₅)₂SmMe(THF), and they resulted in partial epimerization, generating D ,L ‐ or meso‐lactide polymers with enhanced biodegradability. A blend of PLLA‐r‐PCL [82/18; PLLA = poly(L ‐LA) and PCL = poly(ε‐caprolactone)] and PDLA‐r‐PCL [79/21; PDLA = poly(D ‐LA)] prepared by the solution‐casting method generated a stereocomplex, the melting temperature of which was about 40 °C higher than that of the nonblended copolymers. A blend of PLLA‐b‐PCL (85/15) and PDLA‐b‐PCL (82/18) showed a lower elongation at break and a remarkably higher tensile modulus than stereocomplexes of PLLA‐r‐PCL/PDLA‐r‐PCL and PLLA/PDLA. The biodegradability of a blend of PLLA‐r‐PCL (65/35) and PDLA‐r‐PCL (66/34) with proteinase K was higher than that of PLLA‐b‐PCL (47/53) and PDLA‐b‐PCL (45/55), the degradability of which was higher than that of a PLLA/PDLA blend. A blend film of PLLA‐r‐PDLLA (69/31)/PDLA‐r‐PDLLA (68/32) exhibited higher degradability than a film of PLLA/PDLLA [PDLLA = poly(D ,L ‐LA)]. A stereocomplex of PLLA‐r‐PCL‐r‐PDMO [80/18/2; PDMO = poly(L ‐3,D ,L ‐6‐dimethyl‐2,5‐morpholinedion)] with PDLA‐r‐PCL‐r‐PDMO (81/17/2) showed higher degradability than PLLA‐r‐PDMO (98/2)/PDLA‐r‐PDMO (98/2) and PLLA‐r‐PCL (82/18)/PDLA‐r‐PCL (79/21) blends. The tensile modulus of a blend of PLLA‐r‐PCL‐r‐PDMO and PDLA‐r‐PCL‐r‐PDMO was much higher than that of a blend of PLLA‐r‐PDMO and PDLA‐r‐PDMO. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 438–454, 2005     

Examining the kinetics of the thermal polymerization of commercial aromatic bis‐benzoxazines

Three commercial bis‐benzoxazine monomers based on the aniline derivatives of bisphenol A (BA‐a), bisphenol F (BF‐a), and 3,3′‐thiodiphenol (BT‐a) are examined using a variety of spectroscopic, chromatographic, and thermomechanical techniques. The kinetics of the polymerization of BA‐a were found to be well described using an autocatalytic model for which values of n = 1.39 and m = 2.49 were obtained for the early and later stages of reaction respectively (activation energy = 81–88 kJ/mol.). Following recrystallization the same monomer yielded values of n = 1.80, m = 0.92, and E_a = 94–97 kJ/mol. BF‐a and BT‐a were also found to be well described using an autocatalytic model for which values of n = m = 2.11 (BF‐a) and n = 2.10, m = 1.47 (BT‐a) were obtained for the early and later stages of reaction (activation energy = 80–84 kJ/mol. for BF‐a and 88–95 kJ/mol. for BT‐a). The kinetic data are compared with parallel studies involving chemically initiated benzoxazine monomers. Molecular simulation is used to examine the rotational freedom of the central bridging units and this is related to the degree of conversion achieved. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2068–2081     

An acrylic acid modified polypropylene as a compatibilizing agent for the intercalation/exfoliation of an organically modified montmorillonite in polypropylene

This work dealt with the effect of using an acrylic acid modified polypropylene (PP‐g‐AA) as a compatibilizing agent for the intercalation/exfoliation of an organically modified montmorillonite (o‐MMT) in a polypropylene matrix (PP). Two PP‐g‐AA containing the same AA content (6 wt %) and having different molar masses were used. The o‐MMT content was 0, 1, or 5 wt % of total mass and the PP‐g‐AA/o‐MMT mass ratio was 0/1, 1/1, 2/1, or 5/1. Results of wide angle X‐ray scattering (WAXS) and transmission electronic microscopy (TEM) showed that without the PP‐g‐AA, the o‐MMT was dispersed in the PP/o‐MMT in a micrometer scale, similar to a conventional microcomposite. With the PP‐g‐AA, the o‐MMT was much better dispersed and its interlayers were intercalated and partly exfoliated by the polymer chains. Compared with the neat PP, some PP/PP‐g‐AA/o‐MMT systems exhibited higher G′ values and a yield stress at low frequencies, indicating that the PP‐g‐AA promoted the intercalation/exfoliation of the o‐MMT. The compatibilizing efficiency of those two PP‐g‐AA was very similar. Generally speaking, the higher the PP‐g‐AA/o‐MMT mass ratio, the better the state of dispersion and the degree of intercalation/exfoliation. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1811–1819, 2008     

Synthesis of the indole core structures of conophylline

Conophylline is a bisindole alkaloid of unique structure that shows anti‐cancer and anti‐diabetic activities. Two indole core structures of conophylline, namely 6,7‐dimethoxy‐5‐methoxymethoxy‐1H‐indole ( 1 ), and N‐benzoyl‐N‐[2‐(6‐methoxymethoxy‐2‐vinyl‐1H‐indol‐3‐yl)ethyl]amine ( 2 ) has been synthesized starting with substituted benzene derivatives.     

A fast isocratic liquid chromatography method for the quantification of xanthophylls and their stereoisomers

A fast isocratic liquid chromatography method was developed for the simultaneous quantification of eight xanthophylls (13‐Z‐lutein, 13’‐Z‐lutein, 13‐Z‐zeaxanthin, all‐E‐lutein, all‐E‐zeaxanthin, all‐E‐canthaxanthin, all‐E‐β‐apo‐8’‐carotenoic acid ethyl ester and all‐E‐β‐apo‐8’‐carotenal) within 12 min, compared to 90 min by the conventional high‐performance liquid chromatography method. The separation was achieved on a YMC C₃₀ reversed‐phase column (100 mm x 2.0 mm; 3 μm) operated at 20°C using a methanol/tert‐butyl methyl ether/water solvent system at a flow rate of 0.8 mL/min. The method was successfully applied to quantify lutein and zeaxanthin stereoisomers in egg yolk, raw and cooked spinach, and a dietary supplement. The method can be used for the rapid analysis of xanthophyll isomers in different food products and for quality control purposes.     

High‐performance countercurrent chromatography separation of Peucedanum cervaria fruit extract for the isolation of rare coumarin derivatives

For the first time, rare major and minor compounds from fruits of Peucedanum cervaria were isolated. High‐performance countercurrent chromatography with two different solvent systems, heptane/ethyl acetate/methanol/water (3:2:3:2 and 2:1:2:1, v/v), was successfully used in the reversed‐phase mode. A scale‐up process from analytical to semipreparative in a very short time was developed. The structures of isolated compounds were evaluated by high‐performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry, gas chromatography with mass spectrometry, and one‐ and two‐dimensional NMR spectroscopy. (8S,9R)‐9‐(3‐Methylbutenoyloxy)‐O‐acetyl‐8,9‐dihydrooroselol (compound B), (8S,9R)‐9‐(2‐methyl‐Z‐butenoyloxy)‐O‐acetyl‐8,9‐dihydrooroselol (edultin, compound C), and (8S,9R)‐9‐acetoxy‐O‐(2α‐methylbutyryl)‐8,9‐dihydrooroselol (compound D) were obtained using heptane/ethyl acetate/methanol/water (2:1:2:1, v/v) in <40 min. The method yielded 4.6 mg of a mixture of compounds B and C (11:89) and 3.7 mg of compound D. These amounts were obtained from the crude extract (0.5 g) in a single run. Although the compounds are known, their isolation by countercurrent chromatography and the analysis of their relative stereochemistry by two‐dimensional NMR spectroscopy have been performed for the first time. Additionally, heptane/ethyl acetate/methanol/water (3:2:3:2, v/v) led to the isolation of oxypeucedanin (1.2 mg; compound A). This is the first time that angular dihydrofuranocoumarin was isolated from plant extract by countercurrent chromatography.     

Crystallographic evidence of Gly‐d,l‐Met oxidation to its sulfoxide in the presence of gold(III): solid solution of the racemic mixture of two diastereoisomers

Crystallographic analysis of a solid solution of two diastereoisomers, i.e. ({(1S,R)‐1‐carboxy‐3‐[(R,S)‐methylsulfinyl]propyl}aminocarbonyl)methanaminium tetrachloridoaurate(III) and ({(1S,R)‐1‐carboxy‐3‐[(S,R)‐methylsulfinyl]propyl}aminocarbonyl)methanaminium tetrachloridoaurate(III), (C₇H₁₅N₂O₄S)[AuCl₄], has shown that in the presence of gold(III), the methionine part of the Gly‐d ,l ‐Met dipeptide is oxidized to sulfoxide, and no coordination to the Au^III cation through the S atom of the sulfoxide is observed. In view of our observation, literature reports that methionine acts as an N,S‐bidentate donor ligand forming stable gold(III) complexes require verification. Moreover, it has been demonstrated that crystallization of the oxidation product leads to a substantial 77:23 excess of both S‐methionine/R‐sulfoxide and R‐methionine/S‐sulfoxide over S‐methionine/S‐sulfoxide and R‐methionine/R‐sulfoxide. The presence of two different diastereoisomers at the same crystallographic site is a source of static disorder at this site.     

Microemulsion polymerization of acrylamide and styrene: Effect of the structures of reaction media

Isothermal phase diagrams of the system cetyltrimethylammonium bromide (CTAB)/n‐butanol/n‐octane/water were constructed, and the effect of the oil (n‐octane) contents on the microemulsions was studied at 40 °C. We determined the microemulsion structures of two systems, CTAB/n‐butanol/10% n‐octane/water and sodium dodecyl sulfonate (As)/n‐butanol/20% styrene/water, by conductivity measurements to investigate the polymerization of acrylamide and styrene in the two microemulsion systems. The polymerization kinetics of the water‐soluble monomer acrylamide in CTAB micelles and the different CTAB/n‐butanol/10% n‐octane/water microemulsion media [water‐in‐oil (W/O), bicontinuous (BC), and oil‐in‐water (O/W)] were studied with water‐soluble sodium bisulfite as the initiator. The maximum polymerization rate in CTAB micelles was found at the second critical micelle concentration. A mechanism of polyacrylamide formation and growth was proposed. A connection between the structures of the microemulsions and the polymerization rates was observed; the maximum polymerization rate occurred at two transition points, from W/O to BC and from BC to O/W, and the polyacrylamide molecular weights, which depended on the structures of the microemulsions, were also found. A square‐root dependence of the polymerization rates on the initiator concentrations was obtained in CTAB micelles and O/W microemulsion media. The polymerization of the oil‐soluble monomer styrene in different As/n‐butanol/20% styrene/water microemulsion media (W/O, BC, and O/W) was also investigated with different initiators: water‐soluble potassium persulfate and oil‐soluble azobisisobutyronitrile. A similar connection between the structures of the microemulsions and the conversions of styrene in CTAB/n‐butanol/10% n‐octane/water for the polymerization of acrylamide was observed again. The structures of the microemulsions had an important role in the molecular weights and sizes of polystyrene. The polystyrene particles were 10–20 nm in diameter in BC microemulsion media and 30–60 nm in diameter in O/W microemulsion media according to transmission electron microscopy. We determined the solubilization site of styrene in O/W microemulsion drops by ¹H NMR spectra to analyze the results of the microemulsion polymerization of styrene. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3320–3334, 2001     

Prelandrine,the Key‐Step Intermediate in the Biosynthesis of the Macrocyclic Spermine Alkaloid Aphelandrine

By means of the high sensitive on‐line‐coupled high‐performance liquid chromatography and atmospheric‐pressure chemical‐ionization mass spectrometry (HPLC/APCI‐MS and HPLC/APCI‐MS/MS) techniques, the new macrocyclic spermine alkaloid prelandrine ( 5 ) was detected in the roots of Aphelandra squarrosa (Acanthaceae), and its structure was elucidated as 4′‐hydroxyprotoverbine (=8‐(4‐hydroxyphenyl)‐1,5,9,13‐tetraazacycloheptadecan‐6‐one). It was further demonstrated that protoverbine ( 6 ) is enzymatically hydroxylated to prelandrine ( 5 ) in a reaction catalyzed by microsomes from the roots of A. squarrosa. The chemical synthesis of (−)‐(S)‐prelandrine is also described. The possible key role of prelandrine ( 5 ) as an intermediate in the biosynthesis of aphelandrine ( 1 ) is discussed.     

On the Influence of the Carbohydrate Moiety on Chromophore Formation during Food‐Related Maillard Reactions of Pentoses,Hexoses, and Disaccharides

The influence of the carbohydrate moiety on the formation of 2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]furan‐3(2H)‐one chromophores during food‐related Maillard reactions from pentoses, hexoses, and disaccharides is reported. The orange compounds 1a , b and 2a , b , detected in a roasted xylose/ L ‐proline mixture, were identified as (2E)/(2Z)‐4‐hydroxy‐5‐methyl‐2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐ene‐1‐ylidene]furan‐3(2H)‐one and (2E)/(2Z)‐5‐methyl‐2‐[4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]‐4‐(pyrrolidin‐1‐yl)furan‐3(2H)‐one, respectively, by 1D‐ and 2D‐NMR, LC/mass, and UV/VIS spectroscopy, as well as by synthetic experiments. Studies on their formation revealed that 1a , b and 2a , b are formed upon condensation of pentose‐derived 4‐hydroxy‐5‐methyl‐ ( 3 ) and 5‐methyl‐4‐(pyrrolidin‐1‐yl)furan‐3(2H)‐one ( 4 ), respectively, with 2‐hydroxycyclopenta‐2,4‐dien‐1‐one ( 5 ) and L ‐proline (Scheme 1). Further condensation reaction of 1a , b with furan‐2‐carbaldehyde yielded the red (2Z)‐2‐{(5Z)‐5‐[(2‐furyl)methylidene]‐4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene}‐4‐hydroxy‐5‐methylfuran‐3(2H)‐one ( 6 ) as an additional novel Maillard chromophore. Replacement of the pentose by glucose in the mixture with L ‐proline led, after dry‐heating, to the identification of the structurally related colored (2Z)/(2E)‐2‐[5‐hydroxy‐5‐methyl‐4‐oxo‐3‐(pyrrolidin‐1‐yl)cyclopent‐2‐en‐1‐ylidene]‐4‐hydroxy‐5‐methylfuran‐3(2H)‐one ( 7a / 7b ) and to the characterization of 2,4,5‐trihydroxy‐5‐methylcyclopent‐2‐en‐1‐one ( 10 ) and 5‐hydroxy‐5‐methylcyclopent‐3‐ene‐1,2‐dione ( 11 ) as key intermediates in chromophore formation from hexoses. Comparative studies on disaccharides revealed that not 7a / 7b , but the colorless 4‐(α‐D ‐glucopyranosyloxy)‐2‐hydroxy‐2‐methyl‐6H‐pyran‐3(2H)‐one ( 8 ) and 2‐(α‐D ‐glucopyranosyloxy)‐4,5‐dihydroxy‐5‐methylcyclopent‐2‐en‐1‐one ( 9 ) were formed amongst the major degradation products of maltose (Scheme 4). The aglycons of 8 and 9 could not be liberated under food‐related heating conditions, thus, inhibiting the formation of the color precursors 10 and 11 and, in consequence, of 7a / 7b (Scheme 6). These data strongly suggest that the 1,4‐glycosidic linkage of disaccharides is responsible for their lower efficiency in browning development compared to pentoses or hexoses.     

Reaction of 3‐Hydroxyquinoline‐2,4‐diones with Inorganic Thiocyanates in the Presence of Ammonium or Alkylammonium Ions: the Unexpected Replacement of a Hydroxy Group by an Amino Group

3‐Hydroxyquinoline‐2,4‐diones react with KSCN in the presence of the NH$\rm{{_{4}^{+}}}$ ions to generate 2,3‐dihydro‐3‐thioxoimidazo[1,5‐c]quinazolin‐5(6H)‐ones, 2,3‐dihydro‐2‐thioxo‐1H‐imidazo[4,5‐c]quinolin‐4(5H)‐ones, and products of molecular rearrangement of the 3‐aminoquinolinedione intermediates. Starting compounds with a benzyl (Bn) group at C(3) afford 3‐aminoquinolinediones, even when only AcONH₄ is used. The results of the reaction between 3‐hydroxyquinoline‐2,4‐diones and KSCN in the presence of BuNH₂ show that replacing a OH group with a secondary NH₂ group is also possible.     

Toughening modification of PLLA with PCL in the presence of PCL‐b‐PLLA diblock copolymers as compatibilizer

To obtain an effective compatibilizer for the blends of poly(L‐lactide) (PLLA) and poly(ε‐caprolactone) (PCL), the diblock copolymers PCL‐b‐PLLA with different ratios of PCL/PLLA (CL/LA) and different molecular weights (M_n) were synthesized by ring‐opening polymerization (ROP) of L‐lactide with monohydric poly(ε‐caprolactone) (PCL‐OH) as a macro‐initiator. These copolymers were melt blended with PLLA/PCL (80/20) blend at contents between 3.0 and 20 phr (parts per hundred resin), and the effects of added PCL‐b‐PLLA on the mechanical, morphological, rheological, and thermodynamic properties of the PLLA/PCL/PCL‐b‐PLLA blends were investigated. The compatibility between PLLA matrix and PCL phase was enhanced with decreasing in CL/LA ratios or increasing in M_n for the added PCL‐b‐PLLA. Moreover, the crystallinity of PLLA matrix increased because of the added compatibilizers. The PCL‐b‐PLLA with the ratio of CL/LA (50/50) and M_n ≥ 39.0 kg/mol were effective compatibilizers for PLLA/PCL blends. When the content of PCL‐b‐PLLA is greater than or equal to 5 phr, the elongations at break of the PLLA/PCL/PCL‐b‐PLLA blends all reached approximately 180%, about 25 times more than the pristine PLLA/PCL(80/20) blend.     

Synthesis of Amphiphilic ABC Triblock Copolymers with PEO as the Middle Block

Summary: Stepwise anionic polymerization, catalytic hydrogenation, and atom transfer radical polymerization were performed to synthesize an amphiphilic ABC triblock copolymer, poly(ethylene‐alt‐propylene)‐block‐poly(ethylene oxide)‐block‐poly(hexyl methacrylate) (PEP‐b‐PEO‐b‐PHMA), with hydrophilic PEO as the middle block. The resulting block copolymers have well‐defined molecular weights and narrow molecular weight distributions as revealed by ¹H NMR spectroscopy and gel permeation chromatography.

GPC chromatograms of an ABC triblock copolymer, PEP‐b‐PEO‐b‐PHMA, and its intermediate precursors exhibiting narrow polydispersities.     

Theoretical Study of Ammonolysis of Monobactams: Kinetic Role of the N‐Sulfonate Group

The ammonolysis reaction of 3‐(formylamino)‐4‐methyl‐2‐oxoazetidine‐1‐sulfonate is investigated by quantum‐chemical methods (B3LYP/6‐31+G*) as a model system of the aminolysis reaction of monobactam antibiotics involved in the allergic reaction to these drugs. The influence of the N‐sulfonate group on the β‐lactam ring, reaction intermediates, and transition states is characterized in terms of the geometries and relative energies of the corresponding critical structures located on the B3LYP/6‐31+G* potential‐energy surface. It is shown that the N‐sulfonate group, which has only a moderate impact on the structure and charge distribution of the β‐lactam ring, reduces the rate‐determining ΔG barrier by ca. 20 kcal/mol with respect to a purely uncatalyzed ammonolysis of the unsubstituted system, azetidin‐2‐one. This intramolecular catalytic effect occurs through a −NH−SO↔[−N−SO₃H]⁻ isomerization process, which is involved in the proton relay from the attacking ammonia molecule to the β‐lactam N‐atom. Our theoretical results predict that, in aqueous solution, monobactams will show an intrinsic reactivity against amine nucleophiles more important than that of penicillins.     

Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP)

In 2013, the new psychoactive substance methoxypiperamide (MeOP) was first reported to the European Monitoring Centre for Drug and Drug Addiction. Its structural similarity to already controlled piperazine designer drugs might have contributed to the decision to offer MeOP for online purchase. The aims of this work were to identify the phase I/II metabolites of MeOP in rat urine and the human cytochrome P450 (CYP) isoenzymes responsible for the initial metabolic steps. Finally, the detectability of MeOP in rat urine by gas chromatography–mass spectrometry (GC‐MS) and liquid chromatography coupled with multistage mass spectrometry (LC‐MSⁿ) standard urine screening approaches (SUSAs) was evaluated. After sample preparation by cleavage of conjugates followed by extraction for elucidating phase I metabolites, the analytes were separated and identified by GC‐MS as well as liquid chromatography‐high resolution‐tandem mass spectrometry (LC‐HR‐MS/MS). For detection of phase II metabolites, the analytes were separated and identified after urine precipitation followed by LC‐HR‐MS/MS. The following metabolic steps could be postulated: hydrolysis of the amide, N‐oxide formation, N‐ and/or O‐demethylation, oxidation of the piperazine ring to the corresponding keto‐piperazine, piperazine ring opening followed by oxidation of a methylene group to the corresponding imide, and hydroxylation of the phenyl group. Furthermore, N‐acetylation, glucuronidation and sulfation were observed. Using human CYPs, CYP1A2, CYP2C19, CYP2D6, and/or CYP3A4 were found to catalyze N‐oxide formation and N‐, O‐demethylation and/or oxidation. Mostly MeOP and N‐oxide‐MeOP but to a minor degree also other metabolites could be detected in the GC‐MS and LC‐MSⁿ SUSAs. Copyright © 2015 John Wiley & Sons, Ltd.     

A novel synthesis of indole derivatives by the reaction of N‐arylhydroxamic acids with malononitrile

An approach to indole derivatives from N‐arylhydroxamic acids and malononitrile via a [3,3]‐sigmatropic rearrangement and intramolecular cyclization is described. Reactions of N‐arylhydroxamic acids 1a‐c, 2a‐c and 3a‐c with malononitrile in the presence of triethylamine at room temperature gave the corresponding α‐cyanoacetamide derivatives 4a‐c, 5a‐c, 6a‐c, 7a‐c and 8a‐c . Thermal treatment of 4a‐c, 5a‐c and 7a‐c with a base, e.g. triethylamine and sodium methoxide, caused intramolecular cyclization and deacylation to afford the corresponding indole derivatives 9‐11 .     

Studies on the Middle-phase Microemulsion of Lauric-N-methylglucamide

The phase behaviour of the middle-phase microemulsion for the quaternary system lauric-N-methylglucamide （MEGA-12）/n-butanollalkane/water has been studied with Winsor type, δ-γ, fishlike and novel ε-β fishlike phase diagrams. A series of phase inversions Winsor I （2）→Ⅲ（3）→Ⅱ （ 2 ） were observed for the three kinds of phase diagrams. The phase types, the phase volumes and the range of alcohol concentrations from the beginning to the end of the middle-phase microemulsion were obtained from Winsor phase diagram. From δ-γ, fishlike phase diagram, the physicochemical parameters, such as the mass fraction of n-butanol in the hydrophile-lipophile balanced inteffacial layer, A^s, the coordinates of the start and end points of the middle-phase microemulsion, and the solubilities of MEGA-12 and n-butanol in alkane phase were calculated. The novel ε-β fishlike phase diagram was also presented. From this kind of diagram, the above experimental phenomena were observed and the physicochemical parameters were calculated precisely. The novel fishlike phase diagram has advantages over the Winsor and δ-γ fishlike phase diagrams in the evaluation of the solubilization power of the microemulsion and calculation of the related physicochemical parameters.