93-14-1Relevant articles and documents
Trapping of muscle relaxant methocarbamol degradation product by complexation with copper(II) ion: Spectroscopic and quantum chemical studies
Mansour, Ahmed M.,Shehab, Ola R.
, p. 263 - 271 (2014)
Structural properties of methocarbamol (Mcm) were extensively studied both experimentally and theoretically using FT IR, 1H NMR, UV-Vis., geometry optimization, Mulliken charge, and molecular electrostatic potential. Stability arises from hyper
Bitterless guaifenesin prodrugs—design, synthesis, characterization, in vitro kinetics, and bitterness studies
Thawabteh, Amin,Lelario, Filomena,Scrano, Laura,Bufo, Sabino A.,Nowak, Stefanie,Behrens, Maik,Di Pizio, Antonella,Niv, Masha Y.,Karaman, Rafik
, p. 262 - 271 (2019)
A respected number of drugs suffer from bitter taste which results in patient incompliance. With the aim of solving the bitterness of guaifenesin, dimethyl maleate, maleate, glutarate, succinate, and dimethyl succinate prodrugs were designed and synthesized. Molecular orbital methods were utilized for the design of the ester prodrugs. The density functional theory (DFT) calculations revealed that the hydrolysis efficiency of the synthesized prodrugs is significantly sensitive to the pattern of substitution on C=C bond and distance between the nucleophile and the electrophile. The hydrolysis of the prodrugs was largely affected by the pH of the medium. The experimental t1/2 for the hydrolysis of guaifenesin dimaleate ester prodrugs in 1N HCl was the least and for guaifenesin dimethyl succinate was the highest. Functional heterologous expression of TAS2R14, a broadly tuned bitter taste receptor responding to guaifenesin, and experiments using these prodrugs revealed that, while some of the prodrugs still activated the receptor similarly or even stronger than the parent substance, succinate derivatization resulted in the complete loss of receptor responses. The predicted binding modes of guaifenesin and its prodrugs to the TAS2R14 homology model suggest that the decreased activity of the succinate derivatives may be caused by a clash with Phe247.
Ligand-Free Copper-Catalyzed Ullmann-Type C?O Bond Formation in Non-Innocent Deep Eutectic Solvents under Aerobic Conditions
Capriati, Vito,García-álvarez, Joaquín,Marinò, Manuela,Perna, Filippo M.,Quivelli, Andrea Francesca,Vitale, Paola
, (2021/12/09)
An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.
Revisiting Hydroxyalkylation of Phenols with Cyclic Carbonates
Kao, Shih-Chieh,Lin, Yi-Ching,Ryu, Ilhyong,Wu, Yen-Ku
supporting information, p. 3639 - 3644 (2019/07/10)
Described is a tetrabutylammonium fluoride-mediated hydroxyalkylation reaction of phenols with cyclic carbonates. This operationally simple method enables the synthesis of a variety of aryl β-hydroxyethyl ethers in good to excellent yields with a very small amount of catalyst loading (0.1–1 mol%). Of particular note is the efficient conversion of aromatic diols and phloroglucinol to the corresponding bis- and tris-hydroxyethylated products. To further showcase the versatility of this protocol, guaifenesin was prepared with a single step by the condensation of guaiacol and glycerol carbonate. We also developed a flow ethoxylation process permitting the continuous synthesis of multiflorol. (Figure presented.).
Glycerol as a source of designer solvents: Physicochemical properties of low melting mixtures containing glycerol ethers and ammonium salts
Leal-Duaso, Alejandro,Pérez, Pascual,Mayoral, José A.,Pires, Elisabet,García, José I.
, p. 28302 - 28312 (2017/11/06)
In this work we report the preparation of mixtures of several alkyl glyceryl ethers, as hydrogen bond donor compounds, with two ammonium salts, choline chloride and N,N,N-triethyl-2,3-dihydroxypropan-1-aminium chloride. The stability of the mixtures at different molar ratios and temperatures has been evaluated in order to determine the formation of low melting mixtures. Liquid and stable mixtures have been characterized and their physico-chemical properties such as density, viscosity, refractive index, conductivity and surface tension have been measured in the temperature range of 293.15 K to 343.15 K. Comparison of the mixtures prepared herein with the ones containing glycerol and choline chloride evidences the possibility of tuning the physico-chemical properties by changing the substitution pattern in the hydrogen bond donor compound or in the ammonium salt, thus broadening the scope of application of these mixtures.
Activity and selectivity of different base catalysts in synthesis of guaifenesin from guaiacol and glycidol of biomass origin
Bhanawase, Shivaji L.,Yadav, Ganapati D.
, p. 213 - 222 (2017/06/21)
Guaiacol and glycidol can be obtained from biomass valorization. Guaiacol (2-methoxyphenol) and glycidol (2,3-epoxy-1-propanol) have been used for the efficient synthesis of guaifenesin ((RS)-3-(2-methoxyphenoxy) propane-1,2-diol). Different catalysts such as hydrotalcite (HT), calcined hydrotalcite (CHT), calcinated hydrotalcite supported on hexagonal mesoporous silica, magnesium oxide, alumina and, potassium promoted zirconium oxide were synthesized, out of which CHT was found to be the most active, selective and reusable catalyst. The catalyst characterization was done by different techniques. Both Oxide and hydroxide phases were observed on calcination of HT in air at 450?°C for 6?h. CHT possess both acidic and basic sites and basicity of CHT was the highest. Crystallite size, surface area and pore size of CHT play important role in catalytic activity and selectivity. Reaction was carried out in a batch reactor and influence of different parameters was systematically studied. The reaction mechanism involving two sites, acidic and basic, was proposed. A suitable kinetic model was developed and fitted against experimental data. A second order rate equation was derived on the basis of Langmuir–Hinshelwood–Hougen–Watson mechanism with weak adsorption of reactants, intermediates and products. Kinetics was used to predict reaction conditions to obtain guaifenesin selectively. Guaifenesin was efficiently obtained with 94.8% selectivity at guaiacol conversion of 38.2% over CHT at 80?°C after 4?h.
Chemoenzymatic Route for the Synthesis of (S)-Moprolol, a Potential β-Blocker
Ghosh, Saptarshi,Bhaumik, Jayeeta,Banoth, Linga,Banesh, Sooram,Banerjee, Uttam Chand
, p. 313 - 318 (2016/03/19)
A biocatalytic route for the synthesis of a potential β-blocker, (S)-moprolol is reported here. Enantiopure synthesis of moprolol is mainly dependent on the chiral intermediate, 3-(2-methoxyphenoxy)-propane-1,2-diol. Various commercial lipases were screened for the enantioselective resolution of (RS)-3-(2-methoxyphenoxy)propane-1,2-diol to produce the desired enantiomer. Among them, Aspergillus Niger lipase (ANL) was selected on the basis of both stereo- and regioselectivity. The optimized values of various reaction parameters were determined such as enzyme (15 mg/mL), substrate concentration (10 mM), organic solvent (toluene), reaction temperature (30 °C), and time (18 h).The optimized conditions led to achieving >49% yield with high enantiomeric excess of (S)-3-(2-methoxyphenoxy)propane-1,2-diol. The lipase-mediated catalysis showed regioselective acylation with dual stereoselectivity. Further, the enantiopure intermediate was used for the synthesis of (S)-moprolol, which afforded the desired β-blocker. Chirality 28:313-318, 2016.
Method for synthesizing guaifenesin pharmaceutical intermediate 3-(o-methoxyphenoxy)-1,2-propylene glycol
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Paragraph 0013; 0014, (2016/11/21)
A method for synthesizing a guaifenesin pharmaceutical intermediate 3-(o-methoxyphenoxy)-1,2-propylene glycol comprises the following steps: in a reaction vessel provided with a stirrer, a thermometer and a reflux condenser, adding 1.5 mol of sodium sulfite and 300 ml of a potassium chloride solution, controlling the stirring speed to be 130-160 rpm, slowly adding 1.3 mol of o-methoxyphenol, increasing the temperature of the solution to 45-50 DEG C, and maintaining for 2-3 h; adding 1.5-1.7 mol of 3-amino-1,2-propylene glycol (3), increasing the temperature of the solution to 85-90 DEG C, and maintaining a stirring state for 4-5 h; dropping the temperature of the solution to 10-15 DEG C, allowing to stand for 20-25 h, layering, then removing an aqueous layer, adding 200 ml of a sodium bromide solution into an oil layer, adding an oxalic acid, and adjusting the pH of the solution to maintain at 6-7; and cooling, then precipitating to obtain a solid, carrying out suction filtration, washing with a salt solution, washing with nitromethane, recrystallizing in propionitrile, and thus obtaining the crystal 3-(o-methoxyphenoxy)-1,2-propylene glycol, wherein the mass fraction of the potassium chloride solution in the steps is 15-20%, the mass fraction of the sodium bromide solution in the steps is 20%-25%, and the mass fraction of oxalic acid in the steps is 30-35%.
COMPOSITIONS AND METHODS FOR THE TREATMENT OF COUGH
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Paragraph 0113, (2015/05/26)
The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing cough may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of acute respiratory tract infections, asthma, gout, fibromyalgia, facilitating conception, promotes secondary mucosal secretions in the respiratory system, muscle relaxant, allergy, asthma, chronic obstructive pulmonary disorders, spasms, respiratory and neurological diseases.
Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols
Seth, Kapileswar,Roy, Sudipta Raha,Pipaliya, Bhavin V.,Chakraborti, Asit K.
supporting information, p. 5886 - 5888 (2013/07/25)
Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.
