491-11-2Relevant academic research and scientific papers
Compound containing FXR agonist, and preparation method and application thereof
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Paragraph 0229-0232, (2020/03/25)
The invention belongs to the technical field of medicines, and concretely relates to a compound containing an FXR agonist, represented by general formula (I), or a pharmaceutically acceptable salt thereof, a preparation method of the compounds, a pharmaceutical composition and a pharmaceutical preparation containing the compounds, and an application of the compounds in the preparation of drugs used for treating and/or preventing FXR mediated diseases. R, R, R, R, m, n, p, q, T, L1-L2 and A ring or B ring in the formula (I) are defined in the description.
Kinetics and mechanism of trichloroisocyanuric acid/NaNO2-triggered nitration of aromatic compounds under acid-free and Vilsmeier-Haack conditions
Bhooshan,Rajanna,Govardhan,Venkanna,Satish Kumar
, p. 445 - 462 (2019/04/10)
Kinetics and mechanism of nitration of aromatic compounds using trichloroisocyanuric acid (TCCA)/NaNO2, TCCA-N,N-dimethyl formamide (TCCA-DMF)/NaNO2, and TCCA-N,N-dimethyl acetamide (TCCA-DMA)/NaNO2 under acid-free and Vilsmeier-Haack conditions. Reactions followed second-order kinetics with a first-order dependence on [Phenol] and [Nitrating agent] ([TCCA], [(TCCA-DMF)], or [(TCCA-DMA)] >> [NaNO2]). Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups, but did not fit well into the Hammett's theory of linear free energy relationship or its modified forms like Brown-Okamoto or Yukawa-Tsuno equations. Rate data were analyzed by Charton's multiple linear regression analysis. Isokinetic temperature (β) values, obtained from Exner's theory for different protocols, are 403.7?K (TCCA-NaNO2), 365.8?K (TCCA-DMF)/NaNO2, and 358?K (TCCA-DMA)/NaNO2. These values are far above the experimental temperature range (303-323?K), indicating that the enthalpy factors are probably more important in controlling the reaction.
Method for hydrolyzing nitroaniline substances into phenol
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Paragraph 0085-0087; 0098-0101, (2019/07/04)
The invention discloses a method for hydrolyzing nitroaniline substances into phenol. The method comprises the following steps: mixing the nitroaniline substances, a catalyst and inorganic base whichare used as raw materials with water used as a solvent, adding the mixture to a reactor, sealing the reactor, and heating the reactor to 100-190 DEG C for a reaction for 2-8 h; cooling an obtained reaction solution to room temperature, then, adjusting pH to 1-2, and washing and drying obtained precipitates to obtain the product, namely, nitrophenol substances. The nitrophenol substances are synthesized with the method, the utilization rate of the raw materials is high, expensive catalysts are not used, emission of three wastes is reduced, the production cost is reduced, and the product has high purity, high yield and good industrial application values.
Sodium perborate/NaNO2/KHSO4-triggered synthesis and kinetics of nitration of aromatic compounds
Rajanna,Muppidi, Suresh,Pasnoori, Srinivas,Saiprakash
, p. 6023 - 6038 (2018/09/21)
Sodium perborate (SPB) was used as efficient green catalyst for NaNO2/KHSO4-mediated nitration of aromatic compounds in aqueous acetonitrile medium. Synthesis of nitroaromatic compounds was achieved under both conventional and solvent-free microwave conditions. Reaction times were comparatively shorter in the microwave-assisted than conventional reaction. The reaction kinetics for nitration of phenols in aqueous bisulfate and acetonitrile medium indicated first-order dependence on [Phenol], [NaNO2], and [SPB]. Reaction rates accelerated with introduction of electron-donating groups but retarded with electron-withdrawing groups. Kinetic results did not fit well quantitatively with Hammett’s equation. Observed deviations from linearity were addressed in terms of exalted Hammett’s constants (σˉ or σeff), para resonance interaction energy (ΔΔGp) parameter, and Yukawa–Tsuno parameter (r). This term provides a measure of the extent of resonance stabilization for a reactive structure that builds up charge (positive) in its transition state. The observed negative entropy of activation (?ΔS#) suggests greater solvation and/or cyclic transition state before yielding products.
Potassium Periodate/NaNO2/KHSO4-Mediated Nitration of Aromatic Compounds and Kinetic Study of Nitration of Phenols in Aqueous Acetonitrile
Sriram, Y. Hemanth,Fatima, Touheeth,Rajanna,Kumar, M. Satish,Raju, R. Madhusudan
supporting information, p. 622 - 632 (2017/06/30)
Synthesis and kinetics of potassium periodate(KIO4)/NaNO2/KHSO4)-initiated nitration of aromatic compounds have been studied in aqueous acetonitrile medium. Synthesis of nitroaromatic compounds is achieved under conventional and solvent-free microwave conditions. Reaction times in microwave-assisted reaction are comparatively less than in conventional reaction. The reaction kinetics for the nitration of phenols in aqueous bisulfate and acetonitrile medium indicated first-order dependence on [phenol], [NaNO2], and [KIO4]. An increase in [KHSO4] accelerated the rate of nitration under otherwise similar conditions. The rate of nitration increased in the solvent of high dielectric media (solvents with high dielectric constant (D)). Observed results were in accordance with Amis and Kirkwood plots [log k′ vs. (1/D) and [(D ? 1)/(2D + 1)]. These observations probably indicate the participation of anionic species and molecular or (dipolar) species in the rate-determining step. In addition, the plots of (log k′) versus volume% of organic solvent were also linear, which probably indicate the importance of both electrostatic and nonelectrostatic forces, solvent–solute interactions during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups, but results could not be quantitatively correlated with Hammett's equation and depicted deviations from linearity. These deviations could probably be attributed to cumulative effects arising inductive, resonance, and steric effects. Leffler's plot (ΔH# vs. ΔS#) was found linear indicating the compensation (cumulative) effect of both enthalpy and entropy parameters in controlling the mechanism of nitration.
Tertiary Butyl Nitrite Triggered Nitration of Phenols: Solvent- and Structure-Dependent Kinetic Study
Kumar, M. Satish,Rajanna,Venkateswarlu,Rao, K. Lakshman
supporting information, p. 171 - 196 (2016/04/09)
Nitration of phenols with tertiary butyl nitrite (TBN) obeyed second-order kinetics with a first-order dependence on [TBN] and [phenol] under acid-free conditions. Reaction rates were significantly altered by a change in the dielectric constant and other physical properties of solvent. The rate of nitration increased with an increase in temperature (303-323 K) in different solvent media (acetonitrile, dichloroethane, CCl4, dimethyl formamide (DMF), and toluene). The rates of nitration (log k) could not fit into either Amis or Kirkwood plots [log k' vs. (1/D) or [(D - 1)/(2D + 1)], but the trends were better explained by the basic form of multivariate linear solvent energy relationships (MLSER) suggested by the Koppel and Palm approach on the one hand and the Kamlet and Taft approach on the other hand. These observations probably substantiate that cumulative contributions of basic solvent parameters (equilibrium as well as frictional solvent effects) and solvent-solute interactions for solvation of transition state during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups. Accordingly, the reactivity of structurally different phenols was found to follow the following sequence: p-OH > p-MeO > p-Me > H > m-Me > p-Cl > p-Br > m-Cl > p-NO2 > m-OH. The results are interpreted by Hammett's theory of linear free energy relationship. The reaction constant (Hammett's ρ) is a measure of the sensitivity of the reaction toward the electronic effects of the substituent. The rho (ρ) values obtained from the present experiments are fairly large negative values (ρ CH3) versus σ? or, Es or combined Taft's relationship. However, Charton's MLRA of the log k with polar, resonance, steric, hydrophobicity, and molar refractivity showing a very good linear relationship was obtained. It is of interest to note that when log kexp values are correlated with log kcal a perfect linearity is obtained with a correlation coefficient of unity, indicating the consonance between experimental and calculated rate constants in the present work.
Production method of 3-ethoxy-4-nitrophenol
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Paragraph 0036, (2017/05/26)
The invention discloses a production method of 3-ethoxy-4-nitrophenol. The low-price m-dichlorobenzene is used instead of the high-price resorcinol as the raw material, and the methoxy is converted into the hydroxy; and a simple alkaline process is used instead of the conventional hydrogen bromide/acetic acid system to prepare the 3-ethoxy-4-nitrophenol. By using low-price m-dichlorobenzene instead of the high-price resorcinol as the raw material to prepare the 3-ethoxy-4-nitrophenol, the method has the advantages of simple synthesis steps, low pollution, environment friendliness, high product quality, high yield, low production cost and normal-pressure operation, and can implement industrial production.
A practical approach for regioselective mono-nitration of phenols under mild conditions
Chen, Ling-Yan,Liu, Tao,Zhou, Xiaokun,Sun, Zhihua
, p. 64 - 71 (2014/07/22)
Cu(NO3)2.3H2O was demonstrated to be an efficient, regioselective and inexpensive nitrating reagent for the synthesis of mono-nitro substituted phenolic compounds. 12 examples of different phenols were examined. Good yields (67-90%) have been achieved. ARKAT-USA, Inc.
Nitration of phenolic compounds and oxidation of hydroquinones using tetrabutylammonium chromate and dichromate under aprotic conditions
Pourali, Ali Reza,Goli, Arezou
scheme or table, p. 63 - 67 (2012/01/13)
In this work, we have reported a mild, efficient and selective method for the mononitration of phenolic compounds using sodium nitrite in the presence of tetrabutylammonium dichromate (TBAD) and oxidation of hydroquinones to quinones with TBAD in CH2Cl2. Using this method, high yields of nitrophenols and quinones were obtained under neutral aprotic conditions. Tetrabutylammonium chromate (TBAC) can also be used as oxidant at same conditions. Indian Academy of Sciences.
A probable hydrogen-bonded meisenheimer complex: An unusually high S NAr reactivity of nitroaniline derivatives with hydroxide ion in aqueous media
Imoto, Mitsutaka,Matsui, Yasunori,Takeda, Motonori,Tamaki, Akihiro,Taniguchi, Hisaji,Mizuno, Kazuhiko,Ikeda, Hiroshi
experimental part, p. 6356 - 6361 (2011/10/05)
Observations show that nitroanilines exhibit an unusually high S NAr reactivity with OH- in aqueous media in reactions that produce nitrophenols. SNAr reaction of 4-nitroaniline (2a) in aqueous NaOH for 16 h yields 4-nitrophenol (4a) quantitatively, whereas a similar reaction of 4-nitrochlorobenzene (1a) gave 4a in 2% yield together with recovered 1a in 97%, suggesting that the leaving ability of the NH2 group far surpasses that of Cl under these conditions. An essential feature of SNAr reactions of nitroanilines is probably that the NH2 leaving group participates in a hydrogen-bonding interaction with H 2O. Density functional theory (DFT) calculations for a set of 4-nitroaniline, OH-, and H2O suggest a possible formation of a Meisenheimer complex stabilized by hydrogen-bonding interactions and a six-membered ring structure. The results obtained here contrast with conventional SNAr reactivity profiles in which nitroanilines are nearly unreactive with nucleophiles in organic solvents.
