Benzyl Methyl Ketone Research Articles

Pursuing drug laboratories: Analysis of drug precursors with High Kinetic Energy Ion Mobility Spectrometry

High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS) is a technique for rapid and reliable detection of trace compounds down to ppbV-levels within one second. Compared to classical IMS operating at ambient pressure and providing the ion mobility at low electric fields, HiKE-IMS can also provide the analyte-specific field dependence of the ion mobility and a fragmentation pattern at high reduced electric field strengths. The additional information about the analyte obtained by varying the reduced electric field strength can contribute to reliable detection. Furthermore, the reduced number of ion-molecule reactions at the low operating pressure of 10 – 40 mbar and the shorter reaction times reduce the impact of competing ion-molecule reactions that can cause false negatives. In this work, we employ HiKE-IMS for the analysis of phenyl-2-propanone (P2P) and other precursor chemicals used for synthesis of methamphetamine and amphetamine. The results show that the precursor chemicals exhibit different behavior in HiKE-IMS. Some precursors form a single significant ion species, while others readily form a fragmentation pattern. Nevertheless, all drug precursors can be distinguished from each other, from the reactant ions and from interfering compounds. In particular, the field-dependent ion mobility as an additional separation dimension aids identification, potentially reducing the number of false positive alarms in field applications. Furthermore, the analysis of a seized illicit P2P sample shows that even low levels of P2P can be detected despite the complex background present in the headspace of real samples.

Selectivity in Catalytic Asymmetric Formal [3 + 3] Annulation of 2-Enoyl-pyridine N-Oxide with Benzyl Methyl Ketone

The asymmetric formal [3 + 3] annulation process of (E)-2-(3-phenylacryloyl)pyridine N-oxide with benzyl methyl ketone was investigated. The possibility of a stereoselective outcome was checked using salts of natural amino acids, as well as chiral bifunctional derivatives containing amino groups and thiourea or squaramide fragments as organocatalysts. Different types of organocatalysts applied led to opposite enantiomers of 2-(3-oxo-4,5-diphenyl-cyclohex-1-en-yl)pyridine 1-oxide (up to 60% ee). Spectroscopic analysis of the isolated product and analysis of the reaction course was carried out, taking into account the obtained regio- and stereoselectivity. In order to verify the postulated results, calculations of the energy of the intermediate reaction products and the final product using the Kohn–Sham Density Functional Theory (KS-DFT) were made.

Impurity profiling of an alternative pathway to ephedrine/pseudoephedrine and methamphetamine from the precursors benzaldehyde and nitroethane

Methamphetamine is produced using various routes from two predominant precursors, ephedrine/pseudoephedrine or phenyl-2-propanone (P2P). The multitude of synthetic routes results in many possible impurities (by-products or intermediates). Impurity profiling of methamphetamine by gas chromatography-mass spectrometry (GC–MS) is an important tool for the forensic chemist and investigators to assist in identification of the synthetic pathway and linking seizures. With the emergence of alternative routes, continued research into impurity profiles is important. One such alternative route is an ephedrine/pseudoephedrine-based pathway using the precursors typically associated with the phenyl-2-propanone (P2P) route, benzaldehyde and nitroethane. Benzaldehyde and nitroethane were condensed to form 2-nitro-1-phenyl-1-propanol. Subsequent reduction led to the corresponding 2-amino-1-phenyl-1-propanol. Cyclization-methylation with dimethyl carbonate to 3,4-dimethyl-5-phenyl-2-oxazolidinone, followed by catalytic hydrogenolysis or basic hydrolysis formed methamphetamine and ephedrine/pseudoephedrine, respectively. This paper presents the impurity profile of the alternative route. The conditions for the reduction of the intermediate 2-nitro-1-phenyl-1-propanol to 2-amino-1-phenyl-1-propanol was found to influence the by-products observed in the methamphetamine product. Notable by-products were amphetamine, N-ethylamphetamine and N-hydroxymethamphetamine.

Electrochemical sensing of amphetamine-type stimulants (pre)-precursors to fight against the illicit production of synthetic drugs

The illicit drug precursor market for the manufacture of amphetamine-type stimulants (ATS), mainly amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA), has emerged quickly in the last years. The evidence of a more complex and sophisticated drug market underlines the pressing need for new on-site methods to quickly detect precursors of synthetic drugs, with electrochemical analysis as a promising technique. Herein, the electrochemical fingerprints of ten common ATS precursors-3-oxo-2-phenylbutanenitrile (APAAN), 3-oxo-2-phenylbutanamide (APAA), methyl 3-oxo-2-phenylbutanoate (MAPA), benzyl methyl ketone (BMK), 1-(1,3-benzodioxol-5-yl)propan-2-one (PMK), ephedrine, pseudoephedrine, safrole, sassafras oil and piperonal- are reported for the first time. The electrochemical screening disclosed the redox inactivity of BMK, which is an essential starting material for the production of ATS. Therefore, the local derivatization of BMK at an electrode surface by reductive amination is presented as a feasible solution to enrich its electrochemical fingerprint. To prove that, the resulting mixture was analyzed using a set of chromatographic techniques to understand the reaction mechanism and to identify possible electrochemical active products. Two reaction products (i.e. methamphetamine and 1-phenylpropan-2-ol) were found and characterized using mass spectrometry and electrochemical methods. Subsequently, the optimization of the reaction parameters was carefully addressed to set the portable electrochemical sensing strategy. Ultimately, the analysis concept was validated for the qualitative identification of ATS precursors in seizures from a forensic institute. Overall, the electrochemical approach demonstrates to be a useful and affordable analytical tool for the early identification of ATS precursors to prevent trafficking and drug manufacture in clandestine laboratories.

Bio-Oil Production from Multi-Waste Biomass Co-Pyrolysis Using Analytical Py–GC/MS

Background: Bioenergy attracts much attention due to the global demand for renewable and sustainable energy resources. Waste biomass feedstocks—date pits, coffee waste, and cow dung—require efficient and environmentally friendly waste-management technologies such as pyrolysis. Fast pyrolysis occurs at fast heating rates (10–100 °C/s), generates high bio-oil yields, and is the most widely used process for biofuel generation. The aim of the study is to compare the effect of pyrolysis between single, binary, and ternary feeds on thermal degradation behavior and bio-oil composition. Methods: Thermogravimetric analysis (TGA) was conducted at 30 °C/min from room temperature to 850 °C to understand the thermal degradation behavior of the biomasses. A Pyroprobe® reactor—a micro-scale pyrolyzer—was used to conduct the fast pyrolysis at 500 °C with a heating rate of 10 °C/s, and the volatile contents were quantified using a gas chromatograph–mass spectrometer (GC/MS). Results: The (TGA) showed three main stages of decomposition following dehydration, devolatilization, and char degradation for the different single and multiple feeds. According to the identified compounds, the bio-oil components are broadly identified as aldehydes, amines, aliphatic, aromatics, alcohols, furans, ketones, and acids. The three single-biomass pyrolysis products have four compounds in common, acetic acid and ketone groups (acetic acid, 2-propanone, 1-hydroxy-, benzyl methyl ketone, and 1,2-cyclopentanedione). Conclusion: The bio-oil generated from the feeds comprises great potential for volatiles, diesel, and gasoline production with carbon atoms ranging from C2–C33. Future studies should focus on understanding the effect of procedural parameters, including blending ratio, temperature, and heating rates, on bio-oil composition. Additional molecular techniques should be employed to understand biomass components’ reaction mechanisms to produce useful bio-oil products.

Stability of selected substances related to the clandestine production of amphetamine-type stimulants in wastewater:Identification of transformation products

Environmental impact of toxic and corrosive synthesis waste generated by the clandestine production of amphetamine-type stimulants (ATS) is a known problem, which can even result in malfunction of wastewater treatment plants (WWTPs), e. g. in case of illegal discharge of large amounts of highly acidic chemical waste into the sewage system, which is generated in clandestine labs converting pre-precursors to the most prevalent ATS precursor benzyl methyl ketone (BMK). ATS synthesis-specific substances, precursor chemicals, intermediates and route-specific by-products may also support wastewater-based epidemiology (WBE) studies to explain abnormally high loads of drugs in wastewater by distinguishing whether these high loads were caused by consumption or disposal of synthesis waste into the sewage system. Although some of these synthesis-specific substances can be detected in traces in the final form of consumption of the product, these substances are removed from the drug product to a large extent during cleaning steps, e.g. the frequently applied steam distillation step to purify the amphetamine raw base after clandestine Leuckart synthesis. In contrast, these synthesis-specific by-products are very prominent in chemical synthesis wastes, whereby their detection in wastewater would prove a disposal of synthesis wastes instead of excretion after drug product consumption. As a prerequisite, such substances need to exhibit a certain chemical and biological stability in wastewater and, therefore, lab-scale experiments were performed in a mixture of WWTP effluent and activated sludge. Fourteen selected synthesis-specific substances, all related to the production of ATS, comprised pre-precursors (e.g. α-phenylacetoacetonitrile (APAAN) or α-phenylacetoacetamide (APAA)), precursors (e.g. BMK), intermediates (e.g. N-formylamphetamine (NFA)), synthesis by-products (e.g. N,N-di-(β-phenylisopropyl)amine (DPIA)) and final products (e.g. amphetamine (AMPH)). Stability of test substances was evaluated by targeted HPLC-MS/MS analysis, while HPLC-HRMS techniques were used for the identification of transformation products (TPs) of substances that have undergone primary degradation. All substances were detectable for five days minimum and seven out of 14 substances underwent at least primary degradation. A total of three TPs were identified: TP164 was formed by oxidation of ephedrine (EPHE) and was further transformed after maximum formation, while TP180-1 and TP180-2 were formed by reduction of APAA and both remained stable. This is the first study investigating the stability of ATS synthesis-specific substances in wastewater demonstrating sufficient stability for wastewater monitoring studies.

Nontarget screening of production waste samples from Leuckart amphetamine synthesis using liquid chromatography - high-resolution mass spectrometry as a complementary method to GC-MS impurity profiling.

The established approaches of suspect and nontarget screening (NTS) using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) are usually applied in the field of environmental and bioanalytical analysis. Herein, these approaches were employed on a forensic-toxicological application by analyzing different production waste samples from controlled amphetamine synthesis via Leuckart route to evaluate the suitability of this methodology for identification of route-specific organic substances in such waste samples. For analysis, two complementary LC techniques were used to cover a broad polarity spectrum. After data processing and peak picking using the enviMass software and further manual data restriction, 17 features were tentatively identified as suspects, three of which were subsequently identified with reference substances. All suspects had been previously identified in studies, in which gas chromatography-mass spectrometry (GC-MS) was successfully applied for synthesis marker assessment in waste and amphetamine samples. Remaining features with high signal intensity and assigned sum formula were selected for the attempt of structure elucidation. Seven potential synthesis markers were tentatively identified, which were not yet reported, except the sum formula of one compound, and which were partly also detected in real case waste samples afterward. The innovative application of the NTS approach using LC-HRMS for the analysis of aqueous amphetamine synthesis waste samples showed its suitability as extension to GC-MS analysis as it was possible to successfully identify seven new potential marker compounds, which are specific either for the conversion of the pre-precursors α-phenylacetoacetonitrile and α-phenylacetoacetamide to benzyl methyl ketone or for the subsequent Leuckart synthesis route after their conversion.

Capillary Sensor for Detection of Amphetamine Precursors in Sewage Water.

This paper deals with the problem of detecting benzyl methyl ketone (BMK), which is a precursor of amphetamine that can be synthesized in home labs. The focus of our work was to identify an improvement for the analysis of sewage introduced into the municipal sewage system. The sensors used to detect BKM in these systems are often clogged and therefore cannot function properly. In this article, a new method of detecting BMK and other chemicals in wastewater is presented. A system containing capillary polypropylene, hydrophobized with polysiloxane coating fibers was prepared. These solutions were used for continuous online measurements by ion mobility spectrometry. The use of pipes with a polysiloxane coating reduces the permeation of water and significantly increases the BMK permeation due to its high solubility in the polymer.

Novel multiplex capacitive sensor based on molecularly imprinted polymers: A promising tool for tracing specific amphetamine synthesis markers in sewage water

The development of a sensing system for amphetamine (AMP), N-formyl amphetamine (NFA), and benzyl methyl ketone (BMK) in sewage is a strict requirement for enabling the on-site detection and tracing of the consumption of AMP, and the production and/or transportation of these target analytes. The present research is therefore devoted to the development of an on-site capacitive sensing system, based on molecularly imprinted polymers (MIPs) as recognition elements.To this end, the commercially available CapSenze capacitive sensor system was miniaturized by implementing an application-specific integrated circuit (ASIC), dedicated to the bias and read-out of the chemical sensor. MIPs towards AMP were purchased, whereas the ones towards NFA and BMK were synthesized in house. Gold transducers, consisting of six working electrodes with their corresponding reference electrodes and one common auxiliary electrode, were designed together with a flow cell to enable analyses. The applied water samples were filtered through a 20 micron filter before application in the sensors’ flow cell. The limits of detection in filtered sewage water were determined to be 25 μM for NFA and BMK and 50 μM for AMP. The overall performance of the sensing system was tested by analysis of blind-coded sewage samples, provided by legal authorities.To the best of our knowledge, this is the first research presenting multiplex MIP-based detection of amphetamine synthesis markers using a capacitive sensor, miniaturized via ASIC technology. The presented technique is undoubtedly a potential solution for any analysis requiring constant reliable on-site monitoring of a substance of interest.

Investigations into the stable isotope ratios of 1-phenyl-2-propanone.

Stable isotope ratio mass spectrometry (IRMS) can be used to determine the precursor and precursor origin of methylamphetamine drug samples. Previous work has shown that methylamphetamine samples can be distinguished as derived from different sources of (pseudo)ephedrine or phenyl-2-propanone (P2P) through the use of IRMS alongside conventional chemical profiling techniques. To date, limited research has been conducted to investigate whether methylamphetamine samples of differing P2P origins can be distinguished through drug profiling. This was investigated by synthesising methylamphetamine in-house in a three-step process. Two 'preprecursors' were used in this study, phenylacetic acid (PAA) and α-phenylacetoacetonitrile (α-PAAN). Using a combination of profiling techniques, it was found that methylamphetamine samples of PAA preprecursor origin and methylamphetamine samples of α-PAAN preprecursor origin can be distinguished.

Capacitive sensing of an amphetamine drug precursor in aqueous samples: Application of novel molecularly imprinted polymers for benzyl methyl ketone detection

Highly selective molecularly imprinted polymers (MIPs) towards benzyl methyl ketone (BMK) were synthesized for application as recognition elements in a capacitive sensor. A computational approach was employed to select the most appropriate monomers and cross-linkers. Using the selected compounds, different polymerization techniques and protocols were compared in order to study the effect on the MIP performance and characteristics. MIPs synthesized by bulk polymerization using itaconic acid and 1-vinylimidazole as monomers and p-divinylbenzene as cross-linker possess the highest affinity towards the target analyte. Prior to capacitive analysis, the developed particles were immobilized on the surface of gold transducers using tyramine as a linker. The validity of the developed sensor was checked by the BMK detection in spiked tap water and real water samples. A linear working range from 50 to 1000 μM was found while the limit of detection (LOD) was determined to be 1 μM in tap water. To the best of our knowledge, both the developed MIPs towards BMK and the electrochemical sensor for its detection have not been published or marketed to date.

Micromechanics analysis of carbon fiber/epoxy microdroplet composite under UV light irradiation by micro‐Raman spectroscopy

AbstractEvaluation of the surface morphology, chemical groups, interfacial microstructure, and mechanical properties of carbon fiber/epoxy resin microdroplet composites during ultraviolet photodegradation was carried out. The axial stress distribution and interfacial shear stress (ISS) distribution of the carbon fiber/microdroplet composite at 0.25% and 0.62% strains with different UV irradiation times were obtained using micro‐Raman spectroscopy. The results showed that after 40 hours of UV irradiation, tiny particles appeared on the surface of the carbon fiber/microdroplet sample, and with prolonged irradiation, the tiny particles grew larger and more in number. Benzyl methyl ketone was observed after 40 hours of UV irradiation, and the formation of the quinone methide structure, which causes the discoloration of composite, appeared after 300 hours of UV irradiation, and the tiny particles formed on the composite might be benzyl methyl ketone. The maximum axial stress reduced to 53% and 37%, and maximum shear stress reduced to 67% and 66%, for the 0.25% and 0.62% strain samples, respectively, when the UV irradiation time was extended to 940 hours. A power‐law function of ISS with irradiation times was proposed and is represented by τ0.25 = 66.78 ‑ 8.296 × 10–6 t2.26 and τ0.62 = 81.24 ‑ 2.20 × 10–6 t2.49. It was further determined that the loss of mechanical properties was slow during the first 300 hours of UV irradiation. This work provides a new approach for studying the influence of UV irradiation on the interfacial properties of fiber/polymer composite.

Potential for the Remediation of Methamphetamine Contamination Using Ozone.

The deposition of methamphetamine within indoor environments due to illegal activities can pose a health risk for occupants. Current cleaning techniques are costly and inefficient, calling for the development of alternative remediation methods. In addition, the fate of methamphetamine in indoor environments is largely unknown, negatively impacting our knowledge on the health risks associated with contaminated dwellings. Under the conditions of this study, 97% of surface deposited methamphetamine on a paper substrate was consumed after 12min of exposure to ozone, thus demonstrating potential for its use as a remediation agent. The reaction had an effective second-order rate constant with an upper limit of 2.15±1×10-18 cm3 /molecule/s, and the main product observed was phenyl-2-propanone (P2P) at 8.3% yield, as determined using GC/MS. Several products observed in this study have also been reported as by-products of methamphetamine synthesis, including P2P-a known methamphetamine precursor, which indicates that their detection at a potential clandestine site is not necessarily evidence of manufacture.

Origins of N-formylmethamphetamine and N-acetylmethamphetamine in methamphetamine produced by the hydriodic acid and red phosphorus reduction of pseudoephedrine

N-Formylmethamphetamine (FMA) and N-acetylmethamphetamine (AMA) are suspected to be trace by-products in methamphetamine (MA) produced from pseudoephedrine using the Nagai reaction. However, these amides are not rational by-products of the Nagai reaction.FMA is an intermediate in the synthesis of MA using the Leuckart reaction. However, as there is the possibility that FMA is a by-product of the Nagai reaction, the significance of FMA as an indicator of the Leuckart reaction has been debated. It is therefore important to establish whether AMA and especially FMA are by-products of the Nagai reaction and thus establish their significance as synthetic route markers.From the work presented here, FMA is a by-product of the Nagai reaction but the mechanism by which FMA arises could be not determined.AMA was also shown to be a by-product of the Nagai reaction, most likely due to reaction between MA and phenyl-2-propanone (P-2-P), itself a by-product of the Nagai reaction. Furthermore, during GC analysis of Nagai reaction products, MA has been shown to react with P-2-P or ethyl acetate in the injector to form AMA.Caution is recommended if the relative abundance of AMA and/or FMA are used as a basis for determining whether MA samples have a common source or not. Furthermore, it is clear that FMA cannot be considered to be a route-specific by-product for the Leuckart reaction – it is the abundance of FMA in a reaction mixture or profile, not simply its presence, that points to the involvement of the Leuckart reaction.

Identyfikacja 2-acetylo-2-fenyloacetamidu (APAA) – prekursora do produkcji benzylometyloketonu (BMK, P2P)

The article presents the possibilities of using gas and liquid chromatography with MS detection (GC-MS, HPLC-Q-TOF) to identify 2-acetyl-2-phenylacetamide (APAA) – a precursor for the production of benzyl methyl ketone (BMK, P2P). In recent years, APAA has become very popular on the illegal drug market and its identification by the above-mentioned methods raises interpretation doubts. They are caused by BMK being present in small amounts and the ambiguous chromatographic image (GC and HPLC), which consists of two peaks with different retention times, but with the same mass spectrum. This is a consequence of APAA found in two tautomeric forms: ketone and enol. The phenomenon of keto-enol tautomerism occurring here is a particular case of isomerism.

A facile synthesis of highly fluorescent pyrido[2,3-d]pyrimidines and 1,8-naphthyridines via oxazine transformation and enaminic addition reactions

Abstract The synthesis and fluorescence properties of highly substituted bicyclic pryridine derivatives are described. 2-Substituted-4-oxo-pyrido[2,3-d]pyrimidines 2–8 resulted from the acylation reaction of α-aminonicotinonitrile 1 with aroyl chlorides, diethyl malonate, morpholine-4-carboxylate, acetic anhydride or formic acid under solvent-free conditions. [4 + 2] Cyclocondensation and cycloaddition reactions of compound type 1 with formamide and ammonium thiocyanate tolerated the fused pyrimidines 9 and 11, respectively. Finally, the Friedlander-like reaction was applied for the synthesis of 1,8-naphthyridines 12–15 via reaction of compound 1 with cyclohexanone, dimedone, acetyl acetone and benzyl methyl ketone, respectively, under AlCl3 catalysis. The fluorescence spectroscopic data of compounds 1–4, 6–8, 11, 12, 14 and 15 measured and significant results were observed.

Combined colorimetric and gravimetric CMUT sensor for detection of benzyl methyl ketone

The detection of benzyl methyl ketone (BMK) is of interest as it is a common precursor for the synthesis of (meth)amphetamine. Resonant gravimetric sensors can be used to detect the mass and hereby the concentration of a gas while colorimetric arrays typically have exceptional selectivities to a target analyte. We present a sensor system consisting of a capacitive micromachined ultrasonic transducer (CMUT) and a colorimetric array for detection of BMK. The CMUT is used as a resonant gravimetric gas sensor where the resonance frequency shift due to mass loading of the plate. A single local oxidation of silicon (LOCOS) step was used to define the cavities which were sealed with a Si3N4 plate with a thickness of 100 nm, resulting in a resonance frequency of 38.8 MHz and a mass sensitivity of 28.3zgHz×μm2 or 8.5 × 103 cm2/g This sensitivity is, to our knowledge, the best reported as compared with the state of the art of CMUTs. The CMUTs were functionalized with the same dyes used to fabricate the colorimetric arrays. While both the CMUT and the colorimetric array showed selectivity between BMK and acetone and water, the highest selectivity was achieved with the colorimetric array. Here the analyte BMK resulted in the only signal (color change), while acetone and water did not give any signal. Furthermore, the mass of the BMK was found as a function of time. Thus, the combination of a colorimetric array and a CMUT resulted in a sensor system with a selectivity between BMK, acetone and water and in addition a quantitative value for the mass.

Enantiomeric profiling of amphetamine and methamphetamine in wastewater: A 7-year study in regional and urban Queensland, Australia

Enantiomeric profiling was used in this study to investigate the consumption of amphetamine and methamphetamine in regional and urban Southeast Queensland, Australia over a period of seven years. S(+) methamphetamine was predominantly consumed in both urban and regional areas, showing a two and three fold increase in urban and regional catchments respectively between 2011 and 2017. The ratio of amphetamine to methamphetamine (AMP/METH) in wastewater reflected the expected excretion profile of methamphetamine consumption indicating the presence of amphetamine in this study was primarily the result of methamphetamine metabolism. However, the occasional occurrence of R(−) amphetamine in samples containing higher AMP/METH ratios, suggested the consumption of racemic amphetamine. The R(−) methamphetamine enantiomer was also identified in several samples, possibly indicative that the phenyl-2-propanone (P2P) synthesis process rather than the more typical reduction of ephedrines was also being used to manufacture methamphetamine. Furthermore, we identified two samples with a significantly different enantiomer ratio for the METH and AMP as well as a much lower AMP/METH concentration ratio suggesting contribution from direct disposal of methamphetamine into the sewer. This study demonstrated that enantiomeric profiling in wastewater-based epidemiology can provide valuable information for evaluating the origin of amphetamine in wastewater as either a metabolite of methamphetamine consumption or amphetamine itself.

The synthesis and investigation of impurities found in clandestine laboratories: Baeyer-Villiger route part II; synthesis of Phenyl-2-propanone (P2P) analogues from substituted benzaldehydes

We have previously reported phenylpropan-2-one (most commonly known as phenyl-2-propanone, P2P) and methamphetamine derived by-products formed in the Baeyer-Villiger route starting from benzaldehyde. This route is a three step synthesis to P2P; an aldol condensation of benzaldehyde and methyl ethyl ketone (MEK), a Baeyer-Villiger reaction and a subsequent ester hydrolysis. We now report on our investigations into the synthesis of P2P analogues from substituted benzaldehydes via the Baeyer-Villiger route. When strong electron donating substituents are present in the three position of a substituted benzaldehyde (e.g. 3-methoxy and 3,4-methylenedioxy), the resulting aldol reaction is very sensitive to the amount of hydrogen chloride present due to the occurrence of a competing cyclization side reaction yielding various indenes by-products. In contrast, substrates bearing electron-withdrawing substituents react poorly under the Baeyer-Villiger reaction conditions described in this paper. Several new compounds were identified, namely esters 4c, f and g, amongst the known P2P precursors and derivatives. In addition, this work identifies several new by-products in the Baeyer-Villiger route namely 6, 10, 13, 14, 15 and 21; we also report the analytical data for various analogues prepared by this method and this is of value to forensic analysts.

Chemometrics-assisted chromatographic fingerprinting: An illicit methamphetamine case study.

The volatile chemical constituents in complex mixtures can be analyzed using gas chromatography with mass spectrometry. This analysis allows the tentative identification of diverse impurities of an illicit methamphetamine sample. The acquired two-dimensional data of liquid-liquid extraction was resolved by multivariate curve resolution alternating curve resolution to elucidate the embedded peaks effectively. This is the first report on the application of a curve resolution approach for chromatogram fingerprinting to identify particularly the embedded impurities of a drug of abuse. Indeed, the strong and broad peak of methamphetamine makes identifying the underlying peaks problematic and even impossible. Mathematical separation instead of conventional chromatographic approaches was performed in a way that trace components embedded in methamphetamine peak were successfully resolved. Comprehensive analysis of the chromatogram, using multivariate curve resolution, resulted in elution profiles and mass spectra for each pure compound. Impurities such as benzaldehyde, benzyl alcohol, benzene, propenyl methyl ketone, benzyl methyl ketone, amphetamine, N-benzyl-2-methylaziridine, phenethylamine, N,N,α-trimethylamine, phenethylamine, N,α,α-trimethylmethamphetamine, N-acetylmethamphetamine, N-formylmethamphetamine, and other chemicals were identified. A route-specific impurity, N-benzyl-2-methylaziridine, indicating a synthesis route based on ephedrine/pseudoephedrine was identified. Moreover, this is the first report on the detection of impurities such as phenethylamine, N,α,α-trimethylamine (a structurally related impurity), and clonitazene (as an adulterant) in an illicit methamphetamine sample.