Visible-light-mediated synthesis of helicenes in batch and continuous flow systems

Le présent mémoire décrit le développement d’une méthode de synthèse des hélicènes catalysée par la lumière visible. Les conditions pour la formation de [5]hélicène ont été établies par une optimisation du photocatalyseur, du solvant, du système d’oxydation et du temps réactionnel. Suite aux études mécanistiques préliminaires, un mécanisme oxydatif est proposé. Les conditions optimisées ont été appliquées à la synthèse de [6]hélicènes pour laquelle la régiosélectivité a été améliorée en ajoutant des substituants sur la colonne hélicale. La synthèse de thiohélicènes a aussi été testée en utilisant les mêmes conditions sous irradiation par la lumière visible. La méthode a été inefficace pour la formation de benzodithiophènes et de naphtothiophènes, par contre elle permet la formation du phenanthro[3,4-b]thiophène avec un rendement acceptable. En prolongeant la surface-π de la colonne hélicale, le pyrène a été fusionné aux motifs de [4]- et [5]hélicène. Trois dérivés de pyrène-hélicène ont été synthétisés en utilisant les conditions optimisées pour la photocyclisation et leurs caractéristiques physiques ont été étudiées. La méthode de cyclisation sous l’action de la lumière visible a aussi été étudiée en flux continu. Une optimisation du montage expérimental ainsi que de la source lumineuse a été effectuée et les meilleures conditions ont été appliquées à la formation de [5]hélicène et des trois dérivés du pyrène-hélicène. Une amélioration ou conservation des rendements a été observée pour la plupart des produits formés en flux continu comparativement à la synthèse en batch. La concentration de la réaction a aussi été conservée et le temps réactionnel a été réduit par un facteur de dix toujours en comparaison avec la synthèse en batch.The present work describes the development of a visible-light-mediated method for the synthesis of helicenes. The conditions for the formation of [5]helicene were established in a batch process as a result of an extensive optimization of the photosensitizer, solvent, oxidant system and reaction time. Following preliminary mechanistic studies, an oxidative reaction mechanism was proposed. The optimized conditions were applied to the synthesis of [6]helicenes and the regioselectivity of the reaction was improved through substitution along the helicene backbone. Synthesis of thiohelicenes was also explored under the same conditions and although ineffective for the formation of benzodithiophenes and naphthothiophene, it did provide phenanthro[3,4-b]thiophene in a moderate yield. In an effort to extend the π-surface of the helical backbone, a pyrene moiety was fused to the [4]- and [5]helicene core. Three pyrene-helicene hybrid derivatives were synthesized under the visible-light-mediated cyclization conditions and their physical properties investigated. The visible-light-mediated method for the formation of helicenes was also explored using the continuous flow method. An optimization of the reaction set up, the reaction medium as well as the light source was conducted with the [5]helicene model system. The optimal conditions were applied to the formation of various pyrene-helicene derivatives. In most cases the reaction yields were maintained or significantly improved when compared with the batch process. Also, the reaction concentration was conserved while the reaction time was decreased tenfold from the batch method to the continuous flow process

Do drug advertisements in Russian medical journals provide essential information for safe prescribing?

Objective To examine pharmaceutical advertisements in medical journals for their adequacy of information. Methods We selected a convenience sample of 5 major Russian medical journals covering different fields of medicine and different types of publications. We evaluated all the ads in all the issues of the selected journals published during 1998. We counted the number of appearances of trade, chemical, and generic names; indication and contraindication; pharmacologic group; safety warnings; and references. Counts in all categories were aggregated for each advertiser. Results There were 397 placements of 207 distinct advertisements. Only 154 placements (40%) mentioned the generic name, 177 (45%) mentioned any indication, 42 (11%) mentioned safety warnings and contraindications, 21 (5%) warned about drug interactions, and 8 (2%) provided references. The 6 companies responsible for the most ads on average provided less information than the other companies. Conclusions Almost none of the drug ads published in Russian medical journals provide the basic information required for appropriate prescribing. This is despite the fact that in Russia, ads that omit essential information and that could lead consumers to misunderstandings about an advertised product are illegal. The arrival of drug advertising in Russia has brought little information and has been potentially damaging

Toward a Visible Light Mediated Photocyclization: Cu-Based Sensitizers for the Synthesis of [5]Helicene

A photochemical synthesis of [5]helicene employing a copper-based sensitizer <b>7</b> has been developed that avoids the disadvantages associated with the traditional UV light mediated method. The visible light mediated synthesis uses common glassware and a simple household light bulb without the competing formation of [2 + 2] cycloadducts, regioisomers, or the overoxidation product benzo[<i>ghi</i>]perylene <b>3</b>. Preliminary results show that the reaction time can be significantly reduced through the use of a continuous flow strategy

Сравнительная характеристика различных вариантов количественного хроматографического анализа способами внешнего и внутреннего стандартов

Chromatographic analysis of a series of two-component samples (solutions of a target analyte and a standard) allows simultaneous comparison of the possibilities and features of six variants of quantitative analysis using the external and internal standards techniques according to the criteria of results precision and repeatability (random and systematic errors values). These variants include the simplest version of the external standard method (I); its modified version (II) that implies the application of an additional standard and averaging not the absolute, but relative peak areas; the commonly used version of the internal standard method (III); and its version modified in a similar manner (IV). Besides, two variants of using a homologue of the target analyte as the internal standard without determining the calibration coefficients are considered (V) and (VI). This topic is of interest for optimization of practical works on chromatography and teaching the subject in general.The requirements to the additional and internal standards are not identical. Any compound (both present in the samples or added to them) can be selected as the additional standards, and precise setting of their concentrations is not required. It is only necessary to ensure their equal concentrations in the analyzed and reference solutions. It is shown that the modified versions of the external and internal standard methods are characterized by the equal relative standard deviations of the results.The minimal relative standard deviations of the results are typical for the variants implying the use of an additional (II) or an internal (IV) standard and the averaging the ratio of peak areas of target analytes and such standards. The systematic errors of determinations appeared to be minimal for the same variants. Controlling the values of the calibration coefficients is informative for revealing the possible distortions of the composition of samples due to the partial evaporation of volatile constituents in the course of handling such samples.Keywords:  Gas chromatography, quantitative analysis, methods of external and internal standards, comparison of different variantsХроматографический анализ серии характеризуемых и гра дуировочных двух компонентныхобразцов (растворы ана лита и стандарта) позволяет сопо ста вить возможности и особенностиодновременно шести вариантов количест вен ных опреде ле ний способами внешнего и внутреннегостандарта по критериям точности результатов (значениям случайных и систематичес ких погрешностей).Они включают про стейший вариант способа внешнего стан дарта (I), модифициро ван ный вариант,предполагающий использование дополни тельного стандарта и ус ред нение не абсо лютных, аотносительных площадей пиков (II), обы ч но используе мый способ внут реннего стандарта (III) и егомодифициро ван ную аналогичным об разом версию (IV). Кро ме этого рас смо т рены два вариантаис пользования гомолога ана лита в качестве внутрен него стандарта без учета градуировочныхкоэффициентов (V) и (VI). Это пред ста в ляет интерес для оп ти ми зации практических работ похро матографии и процес са обуче ния предмету.Требования к дополнительным и внутренним стандартам не идентичны. В каче стве дополни-тельных стандартов можно выбирать любые соединения, как введен ные в образцы искусственно,так и уже присутствующие в них, причем точ ное за да ние их концентраций не требуется. Необходимолишь обеспечить их ра вен ство в характеризуемом и градуировочном растворах. Показано, чтомо ди фициро ван ные варианты методов внешнего и внутреннего стандартов характе ри зу ютсяоди нако вы ми относительными стандартными отклонениями результатов.Показано, что минимальными случайными составляющими погрешностями ха рак теризуютсява ри анты, предполагающие применение дополнитель ного (II) или внутреннего стан дарта (IV) иусреднение отношений площадей пиков целевых ана литов и таких стандартов. Для них же мини-мальны систематические погрешности определений. Для выявления возможных искаже ний составаанализируемых образ цов, обуслов ленных час тичным ис парением летучих компонентов в процессерабо ты с такими образцами, информативен контроль значений градуировочных коэф фи циентов.Ключевые слова: Газовая хроматография, количественный анализ, способы внеш него ивнутреннего стандарта, сравнение различных вариантов