J. Wilamowski

Synthesis of standards of the most important markers of Leuckart p-methoxymethamphetamine (PMMA): Examination of the influence of experimental conditions and a drug diluent on SPE/TLC profiling

The synthesis of characteristic markers of PMMA obtained by Leuckart method was described. The effectiveness of a procedure of SPE/TLC screening profiling of impurities was studied on the basis of selected impurities. The influence of glucose (a drug diluent) on the profile quality was investigated. The intermediate product (characteristic for the Leuckart synthesis) N-formyl-p-methoxymethamphetamine (1) and by-products: N-formyl-p-methoxyamphetamine (2), p-methoxyamphetamine (3), N,N-dimethyl-p-methoxyamphetamine (4), (RS) and (RR/SS) diastereoisomers of bis(1-methyl-2-(4-methoxyphenyl)ethyl)amine (meso-5 and rac-5), (RS) and (RR/SS) diastereoisomers of N-methyl-bis(1-methyl-2-(4-methoxyphenyl)ethyl)amine (meso-6 and rac-6), N-methyl-1,3-bis(4-methoxyphenyl)propane-2-amine (7) were synthesized. The substrate p-methoxyphenylacetone and the impurities 1 and 4 were used in the study of influence of experimental conditions and glucose on the profiling process and results. The experiments were carried out according to a 2(4) factorial design. The proposed criterions of the profile quality are based on matrix presentation of TLC patterns. They take into account the number of spots revealed, differences between R(f) values and intensity of fluorescence, simultaneously.

Synthesis of alkylphenanthrenes from naphthylalkylidenemalonodinitriles. A route to 1-methyl-, 2-methyl-, and 1,2-dimethylphenanthrene

Abstract The study has been carried out to evaluate the feasibility of synthesis of 1-methyl-, 2-methyl-, 1,2-dimethyl-, and 1-ethyl-2-methylphenanthrene through the annulation of the naphthalene system with the exploitation of the dicyanovinyl moiety of 2-naphthylalkylidenemalonodinitriles as an active electrophile in cold solutions of concentrated sulfuric acid. 2-(2-Naphthyl)propanal ( 3 ), 1-(2-naphthyl)propan-2-one ( 9 ), 3-(2-naphthyl)butan-2-one ( 14 ), and 3-(2-naphthyl)pentan-2-one ( 19 ) had been condensed with malonodinitrile to afford 2-naphthylalkylidenemalonodinitriles which were then cyclised to give 4-amino-1-methylphenanthrene-3-carbonitrile ( 5 ), 4-amino-2-methylphenanthrene-3-carbonitrile ( 11 ), 4-amino-1,2-dimethylphenanthrene-3-carbonitrile ( 16 ), and 4-amino-1-ethyl-2-metylphenanthrene-3-carbonitrile ( 21 ). The nitrile function has been removed from the aminonitriles, with the exception of 21 , through hydrolysis and decarboxylation in alkaline ethanolic solutions under elevated pressure (∼3 MPa) and temperature 220–230°C to give the respective 4-amino-methylphenanthrenes. Diazotisation of the phenanthreneamines and the reaction with hypophosphorus acid has lead to the methylphenanthrenes in moderate yields (50–52%).

New aromatic rearrangement accompanying ring closure of 2-arylpropylidenemalonodinitriles to 1-aminonaphthalene-2-carbonitriles

Cyclization and a rearrangement in concentrated sulfuric acid of 2-(4-substituted-phenyl)propylidenemalonodinitriles (1) into 1-amino-4-methyl-6-substituted-naphthalene-2-carbonitriles (5) appears to involve a series of steps such as ipso electrophilic attack of the protonated nitrile function on the para position of the phenyl group, opening of a spirobenzenium cation or its transformation, and ring reclosure to the naphthalene framework with participation of the secondary alkyl carbocation as an active electrophile.

Novel synthesis of α-arylnaphthalenes from diphenylacetaldehydes and 1,1-diphenylacetones

Abstract A two-step synthesis of 1-amino-4-arylnaphthalene-2-carbonitriles from diphenylacetaldehydes and 1,1-diphenylacetones involves condensation of the carbonyl compounds with malonodinitrile and cyclization of the aryl-ylidenemalonodinitriles obtained in concentrated sulfuric acid. The benzannulation reaction is accompanied with a quasi-aromatic rearrangement. Some of synthesized aminonitriles reveal considerable biological activity against phytopathogenic fungi.

Profiling of impurities in p-methoxymethamphetamine (PMMA) by means of SPE/TLC method: Examination of the influence of experimental conditions according to 24 factorial

In the present paper profiling of impurities in p-methoxymethamphetamine (PMMA) by means of SPE/TLC is reported. PMMA was synthesised by Leuckart procedure. The influence of experimental conditions on the profile quality was investigated. The experiments were carried out according to a 2(4) factorial. The proposed characteristics of the profile quality (optimisation criterions) are based on a matrix presentation of TLC patterns. They take into account, simultaneously, the number of spots revealed, differences between R(f) values and intensity of fluorescence.

TLC profiling of impurities of 1-(3,4-methylenedioxyphenyl)-2-nitropropene an intermediate in MDMA synthesis. Influence of sample preparation methods and conditions

Abstract Thin‐layer chromatography (TLC) was employed for screening profiling of impurities of 1‐(3,4‐methylenedioxyphenyl)‐2‐nitropropene, an intermediate product of (3,4‐methylenedioxy)methamphetamine (MDMA) synthesis (from piperonal). Liquid–liquid extraction (LLE) and solid phase extraction (SPE) were applied to isolate impurities from the drug matrix. The SPE extraction process was performed on C8 columns and LLE was carried out using n‐heptane. The influence of buffer solutions (pH 1, 4, 5, 6, 7, 8, 10, 11, 13, and 14) on the extraction efficiency was investigated. The chromatograms were developed with the use of chloroform:ethyl acetate (98:2) mixture. The spots of separated impurities were observed under UV light at λexc = 254 and 366 nm. The proposed semiquantitative criterion of profile (chromatogram) quality has been based on a matrix presentation of TLC patterns. It takes into account the number of spots revealed, differences between R f values, and intensity of fluorescence, simultaneously.

SPE/TLC Profiling of the Impurities of MDMA: The Influence of an Agglutinant, Diluents, and Adulterants

Abstract The SPE/TLC method has been used in the screening profiling of impurities extracted (SPE) from MDMA (3,4‐methylenedioxymethamphetamine), the main active component of Ecstasy tablets. Sought for, was the optimum buffer solution used in sample dissolution and optimum composition of eluent used in TLC separation. The spots of impurities were observed under UV light at λexc=366 nm. The influence of magnesium stearate, used as an agglutinant in preparation of drug tablets, as well as adulterants (aspirin, paracetamol and caffeine) and diluents (glucose and citric acid) on the TLC profile of impurities was examined. The composition of the above additives was varied in accordance with an unsymmetrical 32 factorial design. The quality of TLC profiles was estimated by means of semiquantitative criteria, which are based on matrix presentation of TLC patterns. The number of spots revealed, differences between Rf values, and intensity of fluorescence are taken into account, simultaneously.

TLC Screening Method for Identification of Active Components of “Ecstasy” Tablets. Influence of Diluents and Adulterants

Abstract The possibility of TLC screening identification of active components of “ecstasy”: MDMA, PMA, PMMA, and ephedrine has been studied. For sample dissolution, methanol and phosphate buffer have been used and the results were compared. The usefulness of several multicomponent eluents for TLC has been tested. The simplex method has been employed to find the optimum composition of eluent∶chloroform∶dioxane∶methanol∶ammonia∶acetonitrile (3.5∶15∶2∶1.5∶15 v/v/v/v/v). The influence of adulterants and diluents: magnesium stearate, acetylsalicylic acid (aspirin), p‐hydroxyacetanilide (paracetamol), procaine, 1‐phenylethylamine, caffeine, glucose, powdered sugar, citric acid, starch, plaster, and chalk on TLC chromatograms of the above drugs was tested.