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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Guaiacol is a phenolic natural product first isolated from Guaiac resin and the oxidation of lignin. Guaiacol is readily oxidized by the heme iron of peroxidases including the peroxidase of cyclooxygenase (COX) enzymes.
Synonyms: 2-Methoxyphenol; 2-hydroxyanisole; O-methylcatechol
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Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh
Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.
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Purchased from AmBeed: 27916-43-4 ; 2438-05-3 ; 501-89-3 ; 42287-94-5 ; 776-79-4 ; 53473-36-2 ; 7251-61-8 ; 42287-97-8 ; 1621-91-6 ; 37718-11-9 ; 288-13-1 ; 86-73-7 ; 104-53-0 ; 2018-90-8 ; 87-66-1 ; 135-19-3 ; 1664-57-9 ; 289-80-5 ; 693-95-8 ; 55-22-1 ; 102-93-2 ; 1477-50-5 ; 1632-76-4 ; 4780-79-4 ; 16642-79-8 ; 3581-89-3 ; 501-97-3 ; 771-50-6 ; 98-98-6 ; 619-64-7 ; 100-51-6 ; 402-45-9 ; 59-67-6 ; 93-60-7 ; 273-53-0 ; 2084-13-1 ; 51-17-2 ; 2459-09-8 ; 2459-07-6 ; 95-16-9 ; 459-31-4 ; 90-05-1 ; 150-76-5 ; 103-25-3 ; 271-44-3 ; 6293-56-7 ; 2550-26-7 ; 288-32-4 ; 501-52-0 ; 2001-32-3 ; 1592-38-7 ; 95-15-8 ; 91-19-0 ; 1122-61-8 ; 3724-19-4 ; 20173-24-4 ; 118-31-0 ; 6125-24-2 ; 60-12-8 ; 90-15-3 ; 120-72-9 ; 822-36-6 ; 288-47-1 ; 288-42-6 ; 2038-57-5 ; 38628-51-2 ; 1929-29-9 ; 15009-91-3 ; 1505-50-6 ; 581-40-8 ; 616-47-7 ; 1571-33-1
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CAS No. : | 90-05-1 |
Formula : | C7H8O2 |
M.W : | 124.14 |
SMILES Code : | OC1=CC=CC=C1OC |
Synonyms : |
2-Methoxyphenol; 2-hydroxyanisole; O-methylcatechol
|
MDL No. : | MFCD00002185 |
InChI Key : | LHGVFZTZFXWLCP-UHFFFAOYSA-N |
Pubchem ID : | 460 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H332-H313-H315-H319-H336-H412 |
Precautionary Statements: | P501-P261-P273-P270-P271-P264-P280-P302+P352-P312-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P304+P340+P312-P403+P233-P405 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In isopropyl alcohol; at 150℃; for 17.0h; | Step B: 2- (2-Methoxy-phenoxy)-lH-benzoimidazole; Cesium carbonate (3.965 g, 12.17 mmol) was added to a solution of 2-chloro- benzoimidazole-1-carboxylic acid tert-butyl ester (1.500 g, 5.936 mmol) and 2- methoxyphenol (5.90 g, 5.20 mL, 47.5 mmol) in isopropanol (25 mL). The mixture was heated at 150 C for 17 h and was then cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and 2.0 N sodium hydroxide solution. The aqueous phase was separated and extracted with ethyl acetate and dichloromethane. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford an off-white solid. Trituration with ethyl acetate and filtering afforded 2- (2-methoxy-phenoxy)- 1H-benzoimidazole as a white solid. MS (MH+) 240. 8 ; Calculated 240.09 for Ct4Hi2N202. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
528 mg of sodium hydride was added to a tetrahydrofuran (30 ml) solution of 1.64 g of 2-methoxyphenol with cooling with ice, and the reaction liquid was stirred for 30 minutes at the same temperature. Next, 1.91 g of <strong>[361-72-8]3,5-difluoro-2-nitroaniline</strong>, which had been produced according to the method described in , was added to it, and the reaction liquid was stirred for 2 days at room temperature. The reaction liquid was poured into water, extracted with ethyl acetate, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate = 5/1 to 4/1) to obtain the entitled compound as an orange solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With potassium phosphate; copper(l) iodide; 2-((2-isopropylphenylimino)methyl)phenol; In 1,4-dioxane; at 20 - 101℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: 2-((2-Isopropylphenylimino)methyl)phenol (15mol%), CuI (5mol%), phenol (1.5mmol, 141mg) and K3PO4 (2.0mmol, 425mg) were added to a screw-capped Schlenk tube under argon. The tube was then evacuated and backfilled with argon (three cycles). Iodobenzene (1mmol, 0.11mL) and dry dioxane (0.5mL) were added by syringe at room temperature. The reaction mixture was stirred at needed temperature (101C) for 24h. The reaction mixture was allowed to reach room temperature and then diluted with dichloromethane (10mL). The slurry was filtered, and the filter cake was washed with 10mL of dichloromethane. The solvent was removed in vacuo, and the residue was purified by column chromatography on silica gel to afford the desired product (3aa). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 80℃; for 3h; | General procedure: To a stirred solution of 6 (0.100 g, 0.433 mmol), appropriate substituted phenol (0.649 mmol) and PPh3 (0.182 g,0.693 mmol) in anhydrous toluene (5 mL) was added DIAD(0.14 mL, 0.693 mmol) at 80 C. After 3 h, EtOAc (40 mL)was added to the resulting solution. The organic layer was washed with 0.5 M aqueous NaOH (40 mL) and water (2 X40 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash silica gel column chromatography eluting with Hexanes/EtOAc (9:1) or (95:5) to afford compounds 7a-s. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Gas phase; Large scale; | Example 1 The catechol is reacted continuously in the vapor phase with methanol after vaporization. The resulting mixture comprises catechol, guaiacol, veratrole, 6-methylguaiacol, unreacted methanol, and tars (compound of high molecular weight compared with the other surrounding compounds, for example molecular weight multiplied by 2 or more). Depending on the operating conditions adhered to, the proportions of veratrole, 6-methylguaiacol and tars may be more or less significant in the condensed liquid stream exiting the reaction. Typically, this reaction can be carried out according to patent EP 914 854 B1. The abovementioned resulting mixture was subjected to a continuous distillation using the distillation system shown in FIG. 1 comprising a first distillation column (A) 10, a second distillation column (E) 20 and a third distillation column (F) 30, successively connected in series. The liquid mixture 1 containing catechol, guaiacol, veratrole, 6-methylguaiacol, unreacted methanol, and tars was fed into the central part of the first distillation column 10 comprising, in its lower part 12, a falling liquid film boiler. The evaporation temperature was 242 C. on average. The first distillation column 10 was operated under conventional conditions so as to separate according to two distinct streams or fractions: the top stream or fraction 15 drawn off from the upper part 14 of column 10, comprising essentially methanol, and the bottom stream or fraction 21 drawn off from the lower part 12 of column 10, comprising essentially the other heavy compounds. The top stream or fraction 15 from the upper part 14 of column 10 was cooled using a condenser so as to at least partially condense the top stream or fraction 15. A part of the top stream or fraction 15 can be introduced, according to a stream or fraction 17, into the upper part 14 of column 10. The output stream 15 from the upper part 14 of column 10 can be purified separately, for example again by distillation using one or more distillation columns. Advantageously, the unreacted methanol is recycled to the reagents of the O-alkylation reaction, after purification. In the lower part 12, a part of the bottom stream or fraction 21 drawn off can be partially reintroduced into the lower part of column 10 according to a stream or fraction 23. It is thus typically possible to obtain a bottom stream or fraction 21 exiting from the lower part 12 of this first distillation column 10, comprising: Catechol (PC): 400 to 600 kg; Guaiacol (GA): 400 to 600 kg; Veratrole (VER): 10 to 50 kg; 6-methylguaiacol (MEGA): 5 to 50 kg; Tars: 5 to 100 kg. The bottom stream 21 conveyed from the lower part 12 of the first distillation column 10 and having a temperature of approximately 115 C. was fed into a central part 28 of a second distillation column 20 and a falling liquid film boiler. In the second distillation column 20, a top fraction 25 comprising essentially guaiacol and a bottom fraction 31 comprising essentially catechol were generated from the liquid stream 21 that was fed in. The evaporation temperature in the boiler was 155 C. on average, and the temperature in the upper part 24 of column 20 was approximately 110 C. In the lower part 22, a part of the bottom stream or fraction 31 drawn off can be reintroduced into the lower part of the column 20 according to a stream or fraction 33. A part of the top stream 25 drawn off can be introduced, according to a stream or fraction 27, into the upper part 24 of the second column 20. The distillation in the column 20 is carried out so as to remove from the upper part 24 of the column a maximum amount of guaiacol and, at the bottom, a maximum amount of catechol, of veratrole and of MEGA-6. The bottom liquid stream 31 drawn off from the lower part 22 of the second distillation column 20 was recovered at an average flow rate of approximately 650 kg/hour. The top stream 25 drawn off from the upper part 24 of the second distillation column 20 was recovered at an average flow rate of approximately 570 kg/hour. The top stream 25 recovered from the upper part 24 of column 20 advantageously comprises: Catechol (PC): approximately 0 kg; Guaiacol (GA): 400 to 600 kg; Veratrole (VER): 0 to 5 kg; 6-methylguaiacol (MEGA): 0 to 5 kg; Tars: approximately 0 kg. The bottom stream 31 recovered from the lower part 22 of column 20 advantageously comprises: Catechol (PC): 400 to 600 kg; Guaiacol (GA): 0 to 50 kg; Veratrole (VER): 5 to 50 kg; 6-methylguaiacol (MEGA): 0 to 50 kg; Tars: 5 to 100 kg. The bottom stream 31 conveyed from the lower part 22 of the second distillation column 20 was fed into a central part 38 of a third distillation column 30 and a falling liquid film boiler. The distillation in the third column 30 is carried out so as to draw off, from the upper part 34 of the column, a top stream 35 comprising guaiacol, veratrole, MEGA-6 and catechol, so as to draw off, in the central part 38, a side stream 36 comprising essentially catechol, and ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With molybdenum(VI) oxide; In ethanol; at 280℃; for 4h;Inert atmosphere;Catalytic behavior; | General procedure: 2.0 g of guaiac acid (purchased in Tianjin Guangfu Technology Co., Ltd.), 0.5 g of MOS catalyst and 100 ml of ethanol were placed in a 300 ml reaction vessel, and the air in the reaction vessel was replaced with nitrogen. The temperature was raised to 280 C, and the reaction was stirred for 4 h. After the reaction was completed, the mixture was filtered under suction and rotary evaporated. The liquid product was subjected to qualitative analysis on a gas chromatography-mass spectrometer (GC6890-MS5973, Agilent), and the internal standard was added. Quantitative analysis by gas chromatography. The chromatogram was performed on an HP-5ms, 30m X 0.25mm X 0.25mum capillary column. The conversion of the raw guaiacol is calculated by (initial guaiacol moles - residual guaiacol moles) / (initial guaiacol moles) X100%, and the selectivity of the product hydrocarbyl phenol is (hydrocarbyl phenol) The number of moles / (molar guaiacol moles) X 100 % was calculated. Among the guaiacol conversion products, ethyl phenols include o-ethyl phenol, 2,5-diethyl phenol, 3,5-diethyl phenol, and propyl phenols include 2,6-diisopropyl phenol. , 2,4-diisopropylphenol, 2,4,6-triisopropylphenol, butyl phenols including 2,5-di-sec-butylphenol, 2,6-di-tert-butylphenol, 2, 4-di-tert-butylphenol, 2,6-di-tert-butyl-p-ethylphenol, pentanols include 2,4-di-tert-amylphenol, others include o-ethoxyphenol, o-ethoxybenzene Methyl ether, p-ethyl guaiacol, 2,6-diisopropylanisole). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With perrhenic acid anhydride; at 320℃; for 6h;Inert atmosphere; Sealed tube; | General procedure: The catalytic reactions were carried out in a batch reactor (ParrInstruments, 300 mL). In a typical model compound conversion experiment,the reactor was loaded with 0.1 g catalyst, 1 g substrate,60 mL solvent, sealed and purged with N2 five times. The reactor wasthen heated to the desired reaction temperature within 1.5 h and kept atthis temperature for the desired reaction time with stirring at 550 rpm.The reaction time was denoted as 0 h when the prescribed reactiontemperature was reached. After the reaction, the reactor was firstlycooled in air by removing the heating jacket. On reaching below 150 C,the reactor was further cooled by immersing it into cold-water. Thepost-reaction solution and the spent catalyst were separated by filtration.The solution mixture was analyzed with an Agilent Technologies6890 N gas chromatograph (GC) equipped with a HP-5 MS capillarycolumn (Agilent, 30m ×0.25mm ×0.25 mum) and a FID detector withanisole as the internal standard. However, when the substrate was anisole,tridecane was chosen as the internal standard. The GC parameterswere: inlet temperature 280 C, detector temperature 300 C, split ratio1:50. The oven temperature ramped from 45 C to 105 C at 15 Cmin-1, and then ramped to 280 C at 6 C min-1. Products wereidentified with a gas chromatograph-mass spectroscopy (GC-MS,Agilent Technologies, model 5973). The mass spectrum acquired withthe GC-MS was retrieved in the NIST Mass Spectral Library to identifythe structure of each product. |
Tags: 90-05-1 synthesis path| 90-05-1 SDS| 90-05-1 COA| 90-05-1 purity| 90-05-1 application| 90-05-1 NMR| 90-05-1 COA| 90-05-1 structure
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Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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The concentration of the dissolution solution you need to prepare is mg/mL