Three useful bromimetric methods for the determination of salbutamol sulfate

Three different methods developed for the determination of salbutamol sulfate (SBS), in pure drug form and in dosage forms, are discussed. The methods are based on the oxidation–bromination reaction of the drug by bromine generated in-situ by the interaction of bromate with bromide in acid medium. In titrimetry the drug is titrated directly with bromate in the presence of a large excess of bromide and in sulfuric acid medium using methyl red as indicator. Spectrophotometry is based on addition of a measured excess of bromate–bromide mixture to the sample solution in sulfuric acid medium followed by the estimation of surplus bromine by reacting it with a definite amount of methyl orange dye and measuring the absorbance at 510 nm. The amount of bromate reacting corresponds to the sample content. The kinetic method depends on the linear relationship between the concentration of the drug and time for oxidation and bromination as indicated by the bleaching of the methyl orange acid colour by the bromine generated in situ. Titrimetry is applicable in the 2–20 mg range. In spectrophotometry, Beer's law is obeyed in the 0.5–5.0 g mL^–1 range whereas concentrations in the 5.0–25.0 g mL^–1 range can be determined by the kinetic method. The effect of common excipients and additives in tablets is discussed. The procedures have been successfully applied to dosage forms; the results agree well with those obtained by use of a reference method. The methods can be used to determine SBS at mg or g levels.     

Oxidative bromination of aniline and its derivatives

Oxidative bromination of aniline and its derivatives containing various substituents (CH₃, Cl, NO₂, COOH) in ortho, meta, and para positions with a brominating mixture of NaBr (KBr) and 20–22% hydrogen peroxide in 6–8% hydrochloric acid at the molar ratio aniline : NaBr (KBr) : H₂O₂ : HCl = 1 : 3.5 : 3.2 : 4.5 is described.     

Bestimmung der Geschwindigkeitskonstante der Bromierungsreaktion von Acetanilid mittels Titrationsmethode in diffuser Schicht an der rotierenden Ring-Scheiben-Elektrode

The kinetics of the bromination of acetanilide has been studied with the diffusion layer titration method. The results have been obtained using the apparatus which consists of the ring-disc electrode and an amperostat-potentiostat system. Dependence of the ring current on the disc current has been determined as a function of rotation speeds of the electrode, of the solution concentration and temperature. It has been shown the bromination reaction of acetanilide exhibits by first order kinetics. In that case Br₂ and Br₃ ^? are the brominating species. The rate of bromination changes with the concentration of the Br^? ions. This reaction rate depends on reactions of molecular bromine with acetanilide. For 0.033<[Br^?]<0.173M the rate constant changes in the following range: $$17530M^{ - 1} s^{ - 1}< k< 6400M^{ - 1} s^{ - 1} ([H + ] = 1,34;T = 298K)$$      

高立体选择性地合成薄荷基溴和新薄荷基溴

薄荷基溴和新薄荷基溴是一类非常有用的不对称合成中间体。以L-薄荷醇为原料,通过与不同的溴化剂反应高立体选择性地得到薄荷基溴和和新薄荷基溴。当L-薄荷醇与盐酸和无水溴化锌反应时高立体选择性地得到薄荷基溴,当L-薄荷醇与三溴化磷反应时高立体选择性地得到新薄荷基溴.     

Determination of Some Catecholamines Based on Their Reaction with Periodate

An indirect kinetic-spectrophotometric method is proposed for the determination of trace amounts of levodopa, methyldopa, dopamine, and adrenaline based on their reaction with periodate in acidic media. The excess periodate that is related to the amount of catecholamines is determined by its reaction with iodide in the presence of methylene blue. The reaction is monitored spectrophotometrically by measuring the decrease in the absorbance of the solution at 665 nm with a fixed time method of 3.0 min. The relative standard deviation for seven replicate determinations of 0.5 gmL^–1 of L-dopa, methyldopa, dopamine and adrenaline was 1.80, 1.20, 0.92 and 1.35%, respectively. The method was successfully applied to the determination of catecholamines in pure form and in pharmaceutical preparations.     

Bromination of emodin

Using emodin as an example, it has been shown that in the bromination of hydroxyanthraquinones the qualitative composition and quantitative ratio of the reaction products depend on the nature of the brominating agent and the solvent, the ratio of the rea Lants, and the temperature regime. In order to obtain bromo-3-methyl-1,6,8-trihydroxyanthraquinone it is recommended to use dioxane dibromide in acid solution as the brominating agent, and to obtain 5-bromo-3-methyl-1,6,8-trihydroxyanthraquinone the same reagent in dioxane solution. The optimum conditions for obtaining 3-bromomethyl-1,6,8-trihydroxyanthraquinone by the methods of initiated bromination and photobromination have been selected. S. M. Kirov Kazakh State University, Alma-Ata. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 618–621, September–October, 1990.     

A new chromatographic method for the separation of food dye mixtures on thin MgO layers

Summary A new effective TLC method has been developed for the separation of the five main watersoluble food dyes such as indige carmin, cochineal red, acid amaranth I, orange yellow S and tartrazine G. The chromatograms are developed by the ascending technique on thin MgO layers applied onto glass plates, previously activated at 130°C. A 82 mixture of 15% sodium citrate and methanol is used as the developing phase. This composition was selected on the basis of Snyder's theory and the polarity index which for this mixture is 8.3. The proposed method permits the full separation of the dye mixture from a 0.3l sample solution with concentrations of 1×10^–6 mole/liter.     

A green bromination process for synthesis of a novel drug candidate

A bromination process has been developed using a salt-based brominating reagent and a non-chlorinated solvent system. The process affords enhanced selectivity and enables product isolation by simple filtration of the reaction mixture, resulting in a substantially reduced waste stream.     

Bromination of emodin

Using emodin as an example, it has been shown that in the bromination of hydroxyanthraquinones the qualitative composition and quantitative ratio of the reaction products depend on the nature of the brominating agent and the solvent, the ratio of the rea Lants, and the temperature regime. In order to obtain bromo-3-methyl-1,6,8-trihydroxyanthraquinone it is recommended to use dioxane dibromide in acid solution as the brominating agent, and to obtain 5-bromo-3-methyl-1,6,8-trihydroxyanthraquinone the same reagent in dioxane solution. The optimum conditions for obtaining 3-bromomethyl-1,6,8-trihydroxyanthraquinone by the methods of initiated bromination and photobromination have been selected.S. M. Kirov Kazakh State University, Alma-Ata. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 618–621, September–October, 1990.     

Utilization of oxidation reactions for the spectrophotometric determination of captopril using brominating agents

Three simple, accurate and sensitive methods (A–C) for the spectrophotometric assay of captopril (CPL) in bulk drug, in dosage forms and in the presence of its oxidative degradates have been described. The methods are based on the bromination of captopril with a solution of excess brominating mixture in hydrochloric acid medium. After bromination, the excess brominating mixture is followed by the estimation of surplus bromine by three different reaction schemes. In the first method (A), the determination of the residual bromine is based on its ability to bleach the indigo carmine dye and measuring the absorbance at 610 nm. Method B, involves treating the unreacted bromine with a measured excess of iron(II) and the remaining iron(II) is complexed with 1,10-phenanthroline and the increase in absorbance is measured at 510 nm. In method (C), the surplus bromine is treated with excess of iron(II) and the resulting iron(III) is complexed with thiocyanate and the absorbance is measured at 478 nm. In all the methods, the amount of bromine reacted corresponds to the drug content. The different experimental parameters affecting the development and stability of the color are carefully studied and optimized. Beer's law is valid within a concentration range of 0.4–6.0, 0.4–2.8 and 1.2–4.8 μg mL^?1 for methods A, B and C, respectively. The calculated apparent molar absorptivity was found to be 5.16 × 10⁴, 9.95 × 10⁴ and 1.74 × 10⁵ L mol^?1 cm^?1, for methods A, B and C, respectively. Sandell's sensitivity, correlation coefficients, detection and quantification limits are also reported. No interference was observed from common additives found in pharmaceutical preparations. The proposed methods are successfully applied to the determination of CPL in the tablet formulations with mean recoveries of 99.94–100.11% and the results were statistically compared with those of a reference method by applying Student's t- and F-test.     

Bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline

Depending on the substituent, the bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline takes place in the 5 position of the thiophene or thiazole ring. When an amino group is present in the 2 position of the thiazole ring, bromination takes place in the 5 position of the thiazole ring. When excess brominating agent is present, a second bromine atom enters the 5 position of the free ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 35–38, January, 1982.     

Complexometric determination of copper(II) in ores,alloys and complexes using 2-mercaptoethanol as indirect masking reagent

A complexo-titrimetric method for the determination of copper(II) in the presence of other metal ions is described, based on the selective masking ability of 2-mercaptoethanol towards copper(II). Copper and other ions in a given sample solution are initially complexed with an excess of EDTA and the surplus EDTA is titrated with zinc sulfate solution at pH 5.0–6.0 (hexamine), using xylenol orange as indicator. A known excess of 2-mercaptoethanol solution (10%) is then added, the mixture is shaken well and the released EDTA from the Cu-EDTA complex is titrated against standard zinc sulfate solution. The interferences of various ions are studied and the method is applied to the determination of copper in its ores, alloys and complexes. Reproducible and accurate results are obtained for 2.5–40 mg of Cu with relative errors 0.4% and standard deviations 0.04 mg.     

Indirect complexometric determination of palladium(II) using sodium nitrite as a selective masking reagent

A selective complexometric method is described for the determination of palladium, sodium nitrite being used as masking reagent. Palladium(II) in a given sample solution is initially cornplexed with an excess of EDTA and the surplus EDTA is titrated with zinc sulfate solution at pH 4.5–5.5 (acetic acid-sodium acetate buffer), using xylenol orange as indicator. An excess of sodium nitrite is then added, the mixture is shaken well and the EDTA released from the Pd-EDTA complex is titrated with a standard zinc sulfate solution. Results are obtained for 2.5–27.5 mg of Pd with relative errors 0.5% and standard deviations 0.05 mg. The interferences of various ions are studied. The method is applied for the determination of palladium(II) in alloys and complexes.     

Complexometric determination of cadmium using 2-Mercaptoethanol as masking reagent

A complexometric method for the determination of cadmium(II) in presence of other metal ions is described based on the selective masking ability of 2-mercaptoethanol towards cadmium(II). Cadmium and other ions in a given sample solution are initially complexed with excess of EDTA and the surplus EDTA is titrated with lead nitrate solution at pH 5.0–6.0 (hexamethylentetramine), using xylenol orange as indicator. A known excess of 2-mercaptoethanol solution (10% alcoholic) is then added, the mixture is shaken well and the released EDTA from the Cd-EDTA complex is titrated against standard lead nitrate solution. The interferences of various ions are studied and the method is applied to the determination of cadmium in its complexes. Reproducible and accurate results are obtained for 3.5–25mg of Cd with relative errors 0.65% and standard deviations 0.06 mg.     

3-α-Halocarbonyl derivatives of pyrazolo[1,5-a] benzimidazole and their reactions

3-(-haloacyl)-2,4-dialkylpyrazolo[1,5-a]benzimidazoles can be obtained either by brominating 3-acetylpyrazolo[1,5-a]benzimidazoles with bromine in acetic acid, or by acylating the 3-unsubstituted pyrazolobenzimidazoles with haloacetic halides. Halogenation of 3-acetylpyrazolo[1,5-a]benzimidazoles with bromine in acetic acid in the presence of sodium acetate, and bromination with N-bromosuccinimide or 1-chlorobenzotriazole, result in deacylation to give 3,6(7)-dibromo- and 3-chloropyrazolo[1,5-a]benzimidazoles. The mono- and trihaloketones obtained have been used to prepare the corresponding aminoketones, the 3-carboxylic acid, and its derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 43–48, January, 1988.     

Coordination chemistry of perhalogenated cyclopentadienes and alkynes. XXVIII new high-yield synthesis of monobromoferrocene and simplified procedure for the synthesis of pentabromoferrocene. Molecular structures of 1,2,3-tribromoferrocene and 1,2,3,4,5-pentabromoferrocene

Monobromoferrocene (1) was obtained in 95% yield from ferrocene via lithiation with tert-BuLi/KO-tert-Bu and bromination with dibromotetrachloroethane. Starting from 1 mixtures of 1,2-dibromoferrocene (2) and apparently unreacted 1 (ranging from 80:20 to 50:50, depending on the reaction conditions) can be obtained via a lithiation- zincation- bromination sequence. These mixtures can be transferred directly with a tenfold excess of Lithium-tetramethylpiperidinide, followed by bromination with 1,1,2,2-tetrabromoethane to pentabromoferrocene (3), in an overall yield of 36% starting from ferrocene. The molecular structures of 3 and of 1,2,3-tribromoferrocene (4) have been determined by X-Ray diffraction.     

Highly Efficient Oxidative Bromination of Alkanes with the HBr-H2O2 System in the Presence of Catalyst

Various cycloalkanes and straight‐chain alkanes were efficiently brominated with an aqueous HBr‐H₂O₂ system. This oxidative brominating process was promoted by catalysis and irradiation with light. The cycloalkanes were converted to the corresponding bromo‐cycloalkanes in moderate yields and the straight‐chain alkanes produced dominantly secondary bromides. This simple but effective bromination method of alkanes is characterized by high atom efficiency, inexpensive reagents and the absence of organic waste, which make it a good alternative to the existing method for C? H activation through bromination.     

室温下二氧化氮催化带有给电子取代基的苯和萘的氧化溴化

在室温下,以8.2%的二氧化氮为催化剂,反应管中残留的空气为氧化剂,分子溴为溴化试剂,研究了带有给电子取代基的苯和萘的氧化溴化.使用的低沸点非金属催化剂易于从产物中去除,很少玷污最终产品;但反应后有少量的苯环硝化副产物生成,这会造成催化剂二氧化氮的损耗.反应具有较高的原子经济性,大部分溴原子被转化到产物中.反应产物具有可控性:可通过改变溴源的用量,分别得到单溴化和二溴化产物.初步的机理分析结论为:反应可能经历分子溴和芳环的反应,生成溴代芳烃和溴化氢;然后在氧化氮类物种催化下,生成的溴化氢被氧气氧化为具有反应活性的溴.     

Preparation of new nitrogen-bridged heterocycles. 55. Reinvestigation of the bromination/dehydrobromination of ethyl 3-[2-(methylthio)indolizin-3-yl]acrylate derivatives

The bromination/dehydrobromination reactions of ethyl 3-[1-alkoxycarbonyl-2-(methylthio)indolizin-3-yl]acrylates were reinvestigated. Reactions of the title compounds with two equivalents of bromine, followed by heating of the resulting reaction mixture and then treatment with a base gave the unexpected dialkyl 7-bromothieno[2,3-b]indolizine-2,9-dicarboxylates, while similar reactions using benzyltrimethylammonium tribromide as a brominating agent afforded only non-brominated thieno[2,3-b]indolizine derivatives, which were converted to the corresponding 7-bromo derivatives upon further treatment with bromine.     

Environmentally benign electrophilic and radical bromination ‘on water’: H2O2-HBr system versus N-bromosuccinimide

A H₂O₂-HBr system and N-bromosuccinimide in an aqueous medium were used as a ‘green’ approach to electrophilic and radical bromination. Several activated and less activated aromatic molecules, phenylsubstituted ketones and styrene were efficiently brominated ‘on water’ using both systems at ambient temperature and without an added metal or acid catalyst, whereas various non-activated toluenes were functionalized at the benzyl position in the presence of visible light as a radical activator. A comparison of reactivity and selectivity of both brominating systems reveals the H₂O₂-HBr system to be more reactive than NBS for benzyl bromination and for the bromination of ketones, while for electrophilic aromatic substitution of methoxy-substituted tetralone it was higher for NBS. Also, higher yields of brominated aromatics were observed when using H₂O₂-HBr ‘on water’. Bromination of styrene reveals that not just the structure of the brominating reagent but the reaction conditions: amount of water, organic solvent, stirring rate and interface structure, play a key role in defining the outcome of bromination (dibromination vs bromohydroxylation). In addition, mild reaction conditions, a straightforward isolation procedure, inexpensive reagents and a lower environment impact make aqueous brominating methods a possible alternative to other reported brominating protocols.