256-96-2Relevant academic research and scientific papers
Stability indicating spectrophotometric methods for quantitative determination of carbamazepine and its degradation product, iminostilbene, in pure form and pharmaceutical formulations
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A stressed study on the stability and degradation behavior under ICH forced degradation conditions of most widely used antiepileptic drug; carbamazepine (CMZ) is presented in this work. The research also includes studying spectrophotometric nature of CMZ and assaying it with mostly used spectrophotometric techniques. Six simple and sensitive spectrophotometric methods are introduced as stability indicating methods for quantitative determination of CMZ and its degradation product, one of its reported potential impurities; iminostilbene (IMS). Dual wavelength is method I where two wavelengths (215 and 270 nm for CMZ and 258 and 307 nm for IMS) were chosen for each component while absorbance difference is zero for the second one. Method II is isoabsorptive point method where the absorbance of CMZ at A225 nm was measured in the range of 0.5–20 μg mL?1. Method III is second derivative method which allows simultaneous determination of CMZ at 247 nm and IMS at 273 nm without any interference. Method IV based on measuring the peak amplitude of first derivative of ratio spectra (1DD) at 280.5 and 253 nm for determination of CMZ and IMS, respectively. Method V is mean centering of the ratio spectra with good linearity for CMZ and IMS over 200–330 nm. Ratio difference method is method VI where good linearity was achieved for determination of CMZ and IMS by measuring differences in the amplitude of ratio spectra at 285, 258 nm and 258, 285 nm, respectively. The proposed methods show successful application in CMZ's pharmaceutical formulations.
High temperature polymorphic conversion of carbamazepine in supercritical CO2: A way to obtain pure polymorph I
Oparin, Roman D.,Vaksler, Yevhenii A.,Krestyaninov, Michael A.,Idrissi, Abdenacer,Kiselev, Michael G.
, (2021)
In this work, we studied the high-temperature polymorphic conversion of carbamazepine (CBZ) in a high-density supercritical CO2 (scCO2) medium in the temperature range of 110–200°C. In order to understand the mechanism of transformation we performed a detailed IR analysis of the supercritical fluid (SCF) phase being in permanent contact with an excess of CBZ. We studied the conformational equilibrium of CBZ molecules in scCO2 phase under isochoric heating conditions. Three temperature ranges, where different types of CBZ–scCO2 equilibria are realized, were considered: i. ?CBZ solid – SCF solution?; ii. phase transition region related to the melting of CBZ in high-density scCO2; iii. ?CBZ melt – SCF solution?. An analysis of the IR spectroscopy data on CBZ dissolved in the scCO2 phase obtained for the third temperature range shows that when ?CBZ melt – SCF solution? equilibrium exists, the scCO2 phase contains only one CBZ conformer. Relying on this finding, we hypothesized that it is possible to obtain pure CBZ polymorph I by the crystallization from CBZ solution in scCO2. This statement has been proven by the micro-Raman analysis of the crystalline substance being obtained from such fluid solution.
Method for synthesizing iminostilbene
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Paragraph 0018-0033, (2021/03/11)
The invention discloses a method for synthesizing iminostilbene, which comprises the following steps: by using 1-phenylindole as a starting raw material, carrying out intramolecular rearrangement reaction on 1-phenylindole under the action of a composite acidic catalytic system to generate iminostilbene; wherein the composite acidic catalytic system is formed by mixing a phosphorus-containing acidic substance and a sulfur-containing acidic substance, the phosphorus-containing acidic substance is one or more of polyphosphoric acid, phosphoric acid and phosphorus pentoxide, and the sulfur-containing acidic substance is one or more of sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid. The phosphorus-containing acidic substance and sulfur-containing acidic substance are used together to form the composite acidic catalytic system, the catalytic system is used in a reaction for catalytic synthesis of iminostilbene, corresponding reaction conditions are optimized, reaction time is shortened, side reactions are reduced, and therefore the method has the advantages of being high in product yield, short in reaction time and the like. The highest yield of the product reaches 83.4%, the purity is 99%, and a good technical effect is achieved.
Combined KOH/BEt3Catalyst for Selective Deaminative Hydroboration of Aromatic Carboxamides for Construction of Luminophores
Li, Jinshan,Wang, Jiali,Yang, Jianguo,Yao, Wubing,Zhong, Aiguo
, p. 8086 - 8090 (2020/11/03)
The selective catalytic C-N bond cleavage of amides into value-added amine products is a desirable but challenging transformation. Molecules containing iminodibenzyl motifs are prevalent in pharmaceutical molecules and functional materials. Here we established a combined KOH/BEt3 catalyst for deaminative hydroboration of acyl-iminodibenzyl derivatives, including nonheterocyclic carboxamides, to the corresponding amines. This novel transition-metal-free methodology was also applied to the construction of Clomipramine and luminophores.
Hydride-catalyzed selectively reductive cleavage of unactivated tertiary amides using hydrosilane
Yao, Wubing,Li, Rongrong,Yang, Jianguo,Hao, Feiyue
, p. 3874 - 3878 (2019/08/07)
The first hydride-catalyzed reductive cleavage of various unactivated tertiary amides, including the biologically active aryl-phenazine carboxamides and the challenging non-heterocyclic carbonyl functions, using low-cost hydrosilane as a reducing reagent has been developed. The novel catalyst system exhibits high efficiency and exclusive selectivity, providing the desired amines in useful to excellent yields under mild conditions. Overall, this transition metal-free process may offer a versatile alternative to currently employed expensive reducing reagents, high-pressure hydrogen or metal systems for the selective reductive cleavage of amides.
Chemical synthesis, spectroscopic studies, chemical reactivity properties and bioactivity scores of an azepin-based molecule
Kollur, Shiva Prasad,Castro, Joaquín Ortega,Frau, Juan,Glossman-Mitnik, Daniel
, p. 300 - 306 (2018/12/13)
Azepines derived molecules are of great interest because of their multi-drug like properties and thus advantageous in biomedical field. Herein, a novel route is described for the synthesis of an azepine-based molecule, 10,11-Dibromo-10,11-dihydro- 5H-dibenzo[b,f]azepine-5-carbonyl chloride (DACC) by using dibutyltin dilaurate (DBTDL) as catalyst. The structure of DACC was elucidated by using FT-IR, NMR, and mass spectroscopic techniques. Several density functionals were considered for the study of the molecular properties of the synthesized compound. The global and local reactivity descriptors were estimated by using Conceptual Density Functional Theory (CDFT). The active sites suitable for the nucleophilic and electrophilic attacks were selected by linking them with the Fukui indices, Parr functions and condensed Dual Descriptor Δf(r). Finally, the bioactivity scores for the studied molecule were predicted through different methodologies.
Intermediate compound, carbamazepine and derivative thereof as well as preparation method of oxcarbazepine and derivative thereof
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Paragraph 0134; 0135, (2019/12/25)
The invention provides an intermediate compound, carbamazepine and a derivative thereof as well as a preparation method of oxcarbazepine and a derivative thereof. 2-substituted aminophenylacetate or 2-substituted aminophenylacetonitrile and 2-halobenzonitrile are used as raw materials, substitution reaction, intramolecular condensation reaction, hydrolysis and hydrochloric acid acidification are carried out to obtain the oxcarbazepine and the derivative 5-substituent-10-oxa-10, 11-dihydro-5H-dibenzo [b, f] aza thereof, and the derivative of the oxcarbazepine can be used as a raw material to prepare the carbamazepine and the derivative 5-substituted iminostilbene thereof, an intermediate compound iminostilbene and intermediate compounds 5-substituted-10-methoxyiminostilbene and 10-methoxyiminostilbene. The raw materials used in the method are cheap and easy to obtain, and the cost is low; the preparation method is simple, conditions are easy to realize, the method is simple, convenientand safe to operate, and the process flow is short; the production amount of three wastes is small, and thus, the method is environmentally friendly; and a target product has high yield and purity, and is suitable for industrial production.
A disubstituted amide derivatives decarbonylation hydrogenation green new method (by machine translation)
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Paragraph 0038; 0039; 0040; 0041, (2018/02/04)
The invention relates to a high efficiency, high selectivity of the disubstituted amide derivatives of decarbonylation hydrogenation reaction green new method. For the first time to the metallic compound triethylborane as catalyst, under mild conditions can be conveniently catalytic N, N - di-aryl substituted amide and its derivative and cheap and easy to obtain organic silicon reagent selective preparation of secondary organic amine product. Compared with the traditional method, the new method generally has the wide substrate universality, functional group compatibility outstanding, simple operation and the like. For the first time in order to realize the organic silicon reagent as reducing agent and amide compounds decarbonylation hydrogenation reaction, is the reduction of amides and derivatives thereof, in particular the organic light-emitting diodes (OLEDs) material unit - diaryl amine compound of the laboratory preparation or industrial production provides a brand-new "green" response strategies. (by machine translation)
One-step synthesis method of iminostilbene
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Paragraph 0016; 0017; 0018; 0019; 0020; 0021, (2017/05/06)
The invention discloses a one-step synthesis method of iminostilbene, and belongs to the field of drug synthesis. Under the argon protection condition, 2-aminostilbene is added; under the stirring condition, the temperature is slowly increased to 100-105 DEG C, at the moment, 2-aminostilbene is molten, anhydrous phosphorus acid is slowly dropped, after dropping is complete, the temperature is increased to continue the reaction, after the reaction is completed, the product is poured into an ice-water mixture, a 10% sodium hydroxide solution is used for adjusting the pH to be neutral, filtering is performed, a filtrate is extracted through dichloromethane, organic layers are combined and washed three times through saturated salt solutions and water, the organic layers are dried through anhydrous magnesium sulfate, filtering is performed, decompression and rotary evaporation are performed, and dichloromethane is recycled to obtain iminostilbene. According to the method, many defects in the prior art are overcome, iminostilbene can be obtained through the one-step reaction, the yield reaches 95% or above, and a solvent can be recycled. According to the synthesis method of iminostilbene, the iminostilbene synthesis cost can be greatly lowered on the whole, and the industrial application prospect is achieved.
An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine
Ravinder,Rajeshwar Reddy,Sridhar,Murali Mohan,Srinivas, Katkam,Panasa Reddy,Bandichhor, Rakeshwar
supporting information, p. 2841 - 2844 (2013/06/26)
Efficient methods have been developed for the synthesis of three active pharmaceutical ingredients (APIs) carbamazepine (Tegretol) 1, oxcarbazepine (Trileptal) 2, and eslicarbazepine acetate (Exalief) 3 by employing enantioselective reduction and carboxamidation reaction.
