GC-MS and GC-IRD studies on the ring isomers of N-methyl-2-methoxyphenyl-3-butanamines (MPBA) related to 3,4-MDMA

The mass spectra of the controlled substance 3,4-MDMA and its regioisomer 2,3-MDMA are characterized by an imine fragment base peak at m/z 58 and additional fragments at m/z 135/136 for the methylenedioxybenzyl cation and radical cation, respectively. Three positional ring methoxy isomers of N-methyl-2-(methoxyphenyl)-3-butanamine (MPBA) have an isobaric relationship to 2,3- and 3,4-MDMA. All five compounds have the same molecular weight and produce similar EI mass spectra. This lack of mass spectral specificity for the isomers in addition to the possibility of chromatographic co-elution could result in misidentification. The lack of reference materials for the potential imposter molecules constitutes a significant analytical challenge. Perfluoroacylation of the amine group reduced the nitrogen basicity and provided individual fragmentation pathways for discrimination among these compounds based on unique fragment ions and the relative abundance of common ions. Studies using gas chromatography with infrared detection provided additional structure-IR spectra relationships. The underivatized amines and the perfluoroacylated derivatives (PFPA and HFBA) were resolved by capillary gas chromatography on a 100% dimethylpolysiloxane stationary phase. The perfluoroacylated derivatives showed better resolution on a cyclodextrin modified stationary phase.     

Differentiation of methylenedioxybenzylpiperazines and ethoxybenzylpiperazines by GC-IRD and GC-MS

The substituted benzylpiperazines, 3,4-methylenedioxybenzylpiperazine, its regioisomer 2,3-methylenedioxybenzylpiperazine and three isobaric ring substituted ethoxybenzylpiperazines have equal mass and many common mass spectral fragment ions. The mass spectra of the three ethoxybenzylpiperazines yield a unique fragment at m/z 107 that allows the discrimination of the three ring substituted ethoxybenzylpiperazines from the two methylenedioxy isomers. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions, but acylation does not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. Gas chromatography coupled with infrared detection provides direct confirmatory data for the structural differentiation between the five isomers. The mass spectra in combination with the vapor phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The perfluoroacyl derivatives of the ring substituted benzylpiperazines were resolved on a stationary phase of 50% phenyl and 50% methylpolysiloxane. Gas chromatography coupled with time-of-flight mass spectrometric detection provides an additional means of differentiating between the isobaric compounds 3,4-methylenedioxybenzylpiperazine and 4-ethoxybenzylpiperazine, which have similar nominal masses but are different in their calculated exact masses.     

GC-MS analysis of acylated derivatives of the side-chain regioisomers of 4-methoxy-3-methyl-phenethylamines related to methylenedioxymethamphetamine

The five side-chain regioisomers of 4-methoxy-3-methylphenethylamine constitute a unique set of compounds having an isobaric relationship with the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA or Ecstasy). These isomeric forms of the 4-methoxy-3-methylphenethylamines have mass spectra essentially equivalent to 3,4-MDMA, and all have a molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. Mass spectral differentiation of 2,3- and 3,4-MDMA from primary and secondary amine regioisomeric side chains of 4-methoxy-3-methylphenethylamines was possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides and heptafluorobutyrylamides. The mass spectra for these derivatives are significantly individualized, and the resulting unique fragment ions allow for specific side-chain identification. The individualization is the result of fragmentation of the alkyl carbon-nitrogen bond, which yielded unique hydrocarbon fragments. The heptafluorobutyrylamide derivatives offer more fragment ions for molecular individualization among these regioisomeric substances. Gas chromatographic separation on relatively non-polar stationary phases successfully resolves these derivatives.     

GC-MS analysis of ring and side chain regioisomers of ethoxyphenethylamines

Mass spectral differentiation of 3,4-methylenedioxymethamphetamine (3,4-MDMA), a controlled drug, and its 2,3-regioisomer from the ring substituted ethoxyphenethylamines is possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides (PFPA), and heptafluorobutyrylamides (HFBA). The ring substituted ethoxyphenethylamines constitute a unique set of compounds having an isobaric relationship with 3,4-MDMA. These isomeric forms of the 2-, 3-, and 4-ethoxy phenethylamines have mass spectra essentially equivalent to 3,4-MDMA; all have molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. All the side chain regioisomers of 2-ethoxy phenethylamine having equivalent mass spectra to 3,4-MDMA are synthesized and compared via gas chromatography-mass spectrometry to 2,3- and 3,4-methylenedioxymethamphetamine. The mass spectra for the perfluoroacyl derivatives of the primary and secondary amine regioisomers are significantly individualized, and the side chain regioisomers yield unique hydrocarbon fragment ions at m/z 148, 162, and 176. Additionally, the substituted ethoxymethamphetamines are distinguished from the methylenedioxymethamphet-amines via the presence of the m/z 107 ion. Gas chromatographic separation on relatively non-polar stationary phases successfully resolves these derivatives.     

Inelastic neutron scattering (INS) studies on 2,5-dihydroxy-1,4-benzoquinone (DHBQ)

Inelastic neutron scattering (INS) spectra of solid 2,5-dihydroxy-1,4-benzoquinone were measured and compared with IR and Raman data. The INS spectrum is very well reproduced in the region below 1000 cm(-1) by DFT calculations on the B3LYP/6-311++G** level using Gaussian and Climax programs. To get a better agreement one should take into account additional interactions of OH groups in the solid state leading to an increase of the gamma(OH) frequency and to a decrease of frequencies for modes in which the delta(OH) participates. The studies of the deuterated compound in IR enabled to correct the assignment of gamma(OH) vibrations. Highly asymmetric nu(OH) band observed in IR spectrum with sharp maximum at about 3300 cm(-1) is discussed in terms of a stochastic approach to the analysis of hydrogen bonded systems.     

GC-MS studies on the regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines related to MDEA, MDMMA, and MBDB

Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in forensic studies in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N-N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). The mass spectra of the regioisomers (2,3-methylenedioxyphenethylamines) are essentially equal to the three compounds reported as drugs of abuse. This paper reports the synthesis, mass spectral characterization, and chromatographic analysis of these six regioisomeric amines. The six regioisomeric methylenedioxyphenethylamines are synthesized from commercially available starting materials. The electron impact mass spectra of these regioisomers show some variation in the relative intensity of the major ions with only a couple of minor ions that may indicate side chain specific fragments. Differentiation by mass spectrometry is only possible after the formation of the perfluoroacyl derivatives, pentafluoropropionylamides (PFPA) and heptafluorobutrylamides (HFBA). Gas chromatographic separation on non-polar stationary phases (Rtx-1 and Rtx-5) is not successful at resolving the three 3,4-methylenedioxyphenethylamines from the three 2,3-methylenedioxyphenethylamines as the underivatized amines. The six underivatized amines are resolved on the more polar trifluoropropylmethyl polysiloxane Rtx-200 stationary phase as well as a permethylated beta-cyclodextran Rtx-bDEX stationary phase. Gas chromatographic separation is successful at resolving the four PFPA and the four HFBA derivatives on the Rtx-200 stationary phase as well as the permethylated beta-cyclodextran stationary phase. The 2,3-methylenedioxyphenethylamine derivatives (compounds 4 and 6) eluted before the 3,4-methylenedioxyphenethylamine derivatives (compounds 1 and 3) as both the PFPA and HFBA derivatives.     

GC-MS analysis of acylated derivatives of the side chain and ring regioisomers of methylenedioxymethamphetamine

The perfluoroacyl derivatives (pentafluoropropionylamides and heptafluorobutrylamides) of the primary and secondary regioisomeric amines, related to the controlled drug substance 3,4-methylenedioxymethamphetamine, are prepared and evaluated in GC-MS studies. These derivatives show excellent resolution on nonpolar stationary phases, such as RTX-1 and RTX-5, with elution order differences from those of the underivatized amines. The mass spectra for these derivatives are significantly individualized, and the resulting unique fragment ions allow for specific side-chain identification. The individualization is the result of fragmentation of the alkyl carbon-nitrogen bond, yielding hydrocarbon fragments and other unique ions. The heptafluoro butrylamides derivatives offer more fragment ions for molecular individualization among these regioisomeric substances.     

Quantum chemical studies on structures and spectra of 2,5-distyrylpyrazine (DSP) laser dye

Semiempirical (MNDO and PM3) molecular orbital calculations have been undertaken to study the structures of the ground and excited states of 2,5-distrylpyrazine dye to assess its activity as a laser dye. In the ground and first excited singlet states, the trans-trans structure of C_2h symmetry is the most stable structure in the gas phase and in DMSO, which agrees with the experimental findings. Upon excitation, the flexibility of the molecule decreases, leading to a subsequent decrease in the radiationless deactivation pathway and this increases the fluorescence efficiency of DSP. The absorption, excitation, and emission spectra have been calculated at the MNDO level using the PM3 optimized geometries in DMSO. At this level the agreement between theory and experiment is quite good. An estimated absorption band at 377 nm (expt 380 nm) is assigned to the S₀→S₁ transition. The excited state absorption band at 457 nm (expt 460 nm) is assigned to the S₁→S₁₂ transition. The emission band at 458 nm (expt 460 nm) is assigned to the S′₁→S′₀ transition. The overlap between the emission and the excited-state absorption spectra is presumably the main reason behind the reduced laser activity of the investigated dye. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 585–592, 1998     

Palladium (II) and platinum (II) complexes with 2,5-dimethylbenzoxazole and 2,5-diphenyloxazole

Some 2,5-diphenyloxazole (PPO) and 2,5-dimethylbenzoxazole (Me₂BO) complexes of palladium (II) and platinum (II) have been prepared and their molar conductivities, i.r. and electronic spectra are reported and discussed. The PPO generally acts as monodentate N-bonded, while the Me₂BO behaves as monodentate O-bonded. The complexes are generally trans-square planar.     

Gas chromatographic optimization studies on the side chain and ring regioisomers of methylenedioxymethamphetamine

Gas chromatographic (GC) optimization studies are conducted for the 10 methylenedioxyphenethylamine regioisomeric substances related to the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). These 10 compounds, having the same molecular weight and equivalent major mass spectral fragments, are not completely resolved using typical GC-mass spectrometry screening methods for illicit drugs. MDMA coelutes with at least one nondrug regioisomer under standard drug screening conditions. Separation of the 10 regioisomers is studied using stationary phases of varying polarities. Resolution optimization shows that very slow program rates give the best separation for the nonpolar stationary phases, requiring analysis times of as much as 85 min. Narrow-bore columns containing the same nonpolar stationary phases improve the analysis time to approximately 29 min. The polar stationary phase DB-35MS allows high-temperature programming rates, yielding complete resolution of all 10 compounds in less than 7 min. Temperature program optimization studies on the DB-35MS phase allow the separation time to be reduced to approximately 4.5 min.     

Total synthesis of (-)-spirotryprostatin B: synthesis and related studies

The total synthesis of spirotryprostatin B, a cytostatic spiro[pyrrolidine-3,3'-oxindole] alkaloid, is described. The key step of the synthetic approach consists of the application of the MgI2-mediated ring-expansion reaction of a spiro[cyclopropane-1,3'-oxindole] with an aldimine, leading to rapid assembly of the spirotryprostatin core. The route documents the installation of the prenyl side chain by Julia-Kocieński olefination of a key aldehyde precursor, a transformation that ultimately allows for facile synthesis of analogues and facilitates structure-activity relationships studies.     

Ab initio studies on the reaction of O2 with Ba(n) (n=2,5) clusters

Ab initio theoretical calculations have been performed to study the reaction of O(2) with Ba(n) (n=2,5) clusters. Our results show that O(2) can easily chemisorb and dissociate on small Ba(n) clusters and there is no obvious energy barrier in the process of the dissociation. The local magnetic moment contributed by oxygen must vanish during the intermediate states before the O(2) dissociation. Correspondingly, local magnetic moment only decreases from 2 mu(B) to about 1 mu(B) if O(2) molecularly adsorbs onto Ba(5) cluster. The electronic structure analysis indicates that the charge transfer from Ba(n) cluster to O(2) as well as the orbital hybridization between the cluster and the oxygen molecule may play a key role in O(2) dissociation.     

Phenylbismuth Bis(2,5-dimethylbenzenesulfonate): Structure and properties

Phenylbismuth bis(2,5-dimethylbenzenesulfonate) (I), a coordination polymer in which a bismuth atom has a distorted square pyramidal coordination to an axial carbon atom (Bi-C, 2.247(5) Å) and basal oxygen atoms (Bi-O, 2.390(9)–2.403(10) Å), has been synthesized by the reaction between triphenylbismuth and 2,5-dimethylbenzenesulfonic acid (1: 2 mol/mol) in toluene and structurally characterized. Pentaphenylbismuth and pentaphenylantimony phenylate compound I to triphenylbismuth.     

Designer drugs 2,5-dimethoxy-4-bromo-amphetamine (DOB) and 2,5-dimethoxy-4-bromo-methamphetamine (MDOB): studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques

Studies are described on the metabolism and the toxicological analysis of the amphetamine-derived designer drug 2,5-dimethoxy-4-bromo-amphetamine (DOB) and its corresponding N-methyl analogue 2,5-dimethoxy-4-bromo-methamphetamine (MDOB) in rat urine using gas chromatographic/mass spectrometric techniques. The identified metabolites indicated that DOB was metabolized by O-demethylation followed by oxidative deamination to the corresponding ketone as well as deamination followed by reduction to the corresponding alcohol. Other metabolic pathways were O,O-bisdemethylation or hydroxylation of the side chain followed by O-demethylation and deamination to the corresponding alcohol. The expected oxo compound after deamination could not be detected. All metabolites carrying hydroxy groups were found to be partly excreted in the conjugated form. MDOB underwent O-demethylation, O,O-bisdemethylation, or hydroxylation of the side chain followed by O-demethylation. Additional N-demethylation to DOB occurred, including the above-mentioned metabolites. Again, all metabolites carrying hydroxy groups were found to be partly excreted in the conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation allowed the detection of an intake of a dose of DOB and MDOB in rat urine that corresponds to a common drug user's dose. Assuming a similar metabolism, the described STA procedure in human urine should be suitable as proof of an intake of DOB and MDOB.     

2,5-Dimethoxy-2,5-dihydrofuran chemistry: a new approach to 2(5H)-furanone derivatives

2,5-Dimethoxy-2,5-dihydrofuran is a synthetic equivalent of 2(5H)-furanone or 2-trimethylsilyloxyfuran, useful C₄ synthons in the preparation of 5-substituted-2(5H)-furanone derivatives. The reaction conditions adopted allow to obtain different classes of complex and biologically interesting compounds, in only one step, with high yields.     

Structures of substituted di-aryl-1,3,4-oxadiazole derivatives: 2,5-bis(pyridyl)- and 2,5-bis(aminophenyl)-substitution

Crystal structures of four different di-aryl-1,3,4-oxadiazole compounds (aryl = 2-pyridyl-, 3-pyridyl-, 2-aminophenyl-, 3-aminophenyl-) are determined. Crystallization of di(2-pyridyl)-1,3,4-oxadiazole yielded monoclinic and triclinic polymorphs. The structures are characterized by the occurrence of π–π interactions. Additionally, in case of the aminophenyl compounds intra- as well as intermolecular hydrogen bonds are found that influence the packing motif as well. Since these molecules are often used as ligands in metal–organic complexes similarities and differences of the molecular conformation between the molecules in the pure crystals and that of the ligands in the complexes are discussed.     

Synthesis, characterization and computational studies of zinc(II)-halide complexes with a bidentate schiff base ligand (2,5-MeO-ba)2En: The crystal structure of (2,5-MeO-ba)2En

In this study four coordinated complexes of zinc(II) halides with a new symmetrical bidentate Schiff base ligand (2,5-MeO-ba)₂En are synthesized and characterized. The metal to ligand ratio of the complexes is found to be 1:1 with the formula of Zn((2,5-MeO-ba)₂En)X₂ (X = Cl (1), Br (2), I (3)). The crystal structure of the Schiff base ligand (2,5-MeO-ba)₂En is determined by X-ray crystallography from single crystal data. Also, the optimized geometries of the Schiff base ligand (2,5-MeO-ba)₂En and its zinc(II) complexes are calculated using the density functional theory method (B3LYP/6-31G). The obtained structural parameters of (2,5-MeO-ba)₂En are in agreement with the experimental data.     

Asymmetric synthesis of rubiginones A(2) and C(2) and their 11-methoxy regioisomers

Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.     

Synthesis and some properties of poly-(2,5-trimethylene benzimidazole) and poly-(2,5-trimethylene benzimidazole hydrochloride)

A polymer, poly(2,5-trimethylene benzimidazole), the first of a new family of nonsymmetrical polymers, was synthesized via an eight-step synthetic route. The polymer, obtained by melt polymerization, is amorphous and in its neutral form behaves as a moderate insulator. It forms 1 : 1 HCl adducts. When cast from formic acid solution, it forms 1 : 1 formic acid adducts. The acid adducts are semiconductors with resistivities in the 10⁶–10⁸ ohm-cm range. Space-charge effects are generated in the adducts as carrier mobility rises.