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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.
1,2-Dimethoxybenzene is an aromatic ether commonly found in secondary metabolites of plants, showing some antioxidant and antimicrobial activities. It protects cells from oxidative stress by inhibiting ROS production and enhancing cellular antioxidant enzyme activity.
Synonyms: Veratrole
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Pd/C promotes C–H bond activation and oxidation of p-hydroxybenzoate during hydrogenolysis of poplar
Canan Sener ; Vitaliy I. Timokhin ; Jan Hellinger ; John Ralph ; Steven D. Karlen ;
Abstract: Hydrogenolysis of lignin generates a portfolio of products, the yields of which are generally calculated using a subset of phenolic monomers that are dependent on the lignin composition, product distribution, and analytical technique. Some lignins are naturally γ-acylated; poplar lignins, for example, have p-hydroxybenzoate groups on 1–15% of their syringyl subunits. Upon hydrogenolysis, it is generally assumed that the p-hydroxybenzoate is cleaved before the deacylated lignin is depolymerized. Hydrogenolysis of model γ-p-hydroxybenzoylated β-aryl ethers do not, however, produce the deacylated β-aryl ether intermediates, as was previously conjectured; products instead derive from palladium-assisted reactions on the cinnamyl p-hydroxybenzoates resulting in initial β-ether cleavage. The p-hydroxybenzoate moiety itself also undergoes carboxylate-assisted palladium-catalyzed C–H bond activation to form the 2,4-dihydroxybenzoate, that subsequently converts to the 2,4-dihydroxycyclohex-1-enoate. These details underscore previously unrec_x0002_ognized pathways and products that are key to understanding the different hydrogenolysis product distributions from naturally acylated lignins that are prevalent biomass-conversion feedstocks.
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CAS No. : | 91-16-7 |
Formula : | C8H10O2 |
M.W : | 138.16 |
SMILES Code : | COC1=CC=CC=C1OC |
Synonyms : |
Veratrole
|
MDL No. : | MFCD00008357 |
InChI Key : | ABDKAPXRBAPSQN-UHFFFAOYSA-N |
Pubchem ID : | 7043 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
90.1% | at 25℃; for 24 h; | A type B crystal of 2,3,6,7,10,11-hexahydroxytriphenylene monohydrate was synthesized according to the process described in Synthesis, 477, 1994 and JP-A-8-119894. Namely, 1,2-dimethoxybenzene (31.78 g, 0.23 moles) and anhydrous ferric chloride (120 g, 0.74 moles) were dissolved in 70percent sulfuric acid, and the solution was reacted at 25°C for 24 hours with stirring. After completion of the reaction, the solution was poured into ice water (500 g), and the precipitated crystal was collected by filtration. After the resultant crystal was washed with water (1 L), and then dried to give pale purple colored 2,3,6,7,10,11-hexamethoxytriphenylene (28.2 g, theoretical yield from 1,2-dimethoxybenzene: 90.1percent) (the method of Synthesis, 477, 1994). |
85.4% | at 10 - 15℃; for 6 h; | 600 ml of ethyl acetate was added into a 1000ml four-necked flask, sodium peroxydisulfate 102.4g (0.43 mol) and o-xylene 45.7 g (0.43 mol) were added, stirred and cooled at internal temperature of 10 degrees C. Anhydrous iron(III) chloride 345.4g (2.10 mol) was added little by little, reacted at an internal temperature of 10-15 degrees C for 6 hours. After completion of the reaction, reaction mixture was cooled, 2000 ml of water was added and stirred for 10minutes. The aqueous layer of the solution was separated, and the organic layer was washed with 800 ml of salt solution. 600 ml of methanol was added to the organic layer and crystallized at 15-25 degrees C for 1 hour, the crystals were filtered, and dried to obtain 19.5 g (43.6percent of yield) of objects as gray crystal. |
82% | With trifluorormethanesulfonic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 20℃; for 10 h; Inert atmosphere | General procedure: An oven-dried 20 mL scintillation vial, equipped with a magnetic stir-bar, was charged with the starting material (1.0 equiv), DDQ (1.0 equiv), trifluoromethanesulfonic acid (1.4percent v/v, 3.0 equiv), and 1,2-dichloroethane (0.05 M). The reaction mixture was then allowed to stir at ambient temperature for 10 h. After this time, methanol (0.05M) was added, and the solution was then allowed to stir at ambient temperature for an additional hour. Upon addition of the methanol, some solids precipitated out of the solution. Then, the solvent was removed from the heterogeneous mixture under reduced pressure. The crude material was purified by either recrystallization (methanol/DCM) or silica-gel column chromatography (hexanes/DCM) to give the title compounds. |
80% | With iron(III) chloride; sulfuric acid In dichloromethane at 20℃; for 3 h; | A solution of 1,2-dimethoxybenzene (10 g, 72.4 mmol) in dichloromethane(50 ml) was added dropwise to a suspension of anhydrous FeCl3 (35.22 g, 217.2 mmol) in dichloromethane (100 ml) and concentrated sulphuric acid (0.5 ml). After complete addition (15 min), the reaction mixture was further stirred for 3 h at room temperature. 200 ml of methanol were then slowly added under vigorous stirring. The obtained mixture was further stirred for additional 30 min. And the precipitate was filtered off, washed with methanol (5 × 100 ml) and dried under reduced pressure to give a purple solid. Yield: 80percent, 1HNMR (CDCl3) δ/ppm: 4.10 (s, 18H, OCH3), 7.80 (s, 6H, ArH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-iodo-succinimide; trifluoroacetic acid; In acetonitrile; at 80℃; for 2h; | To a stirred solution of 1,2-dimethoxybenzene 7 (1mL, 7.85mmol) in acetonitrile (5mL) was added N-iodosuccinimide (NIS) (1.94g, 8.63mmol) and trifluoroacetic acid (TFA) (0.18mL, 2.35mmol). The mixture was stirred for 2hat 80C. After that period the resulting mixture was poured into ice (20g) and water (100mL) and a saturated solution of sodium thiosulfate was added. The aqueous layer was extracted with dichloromethane (3×100mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane as eluent to give the desired 4-iodo-1,2-dimethoxybenzene 8 in excellent yield (1.97g, 95%). This compound showed spectroscopic and analytical data identical to one previously reported [37]. |
85% | With 3-iodo-4,4-dimethyloxazolidin-2-one; In acetonitrile; for 15h;Reflux; | [00274] A mixture of veratrole (0.22 g, 1.63 mmol), 3-iodo-4,4- dimethyloxazolidin-2-one (0.6 g, 2.44 mmol) and MeCN (10 mL) was stirred under reflux conditions for 15 h and concentrated in vacuo. The residue was treated with 1 M aq Na2S03 (5 mL), extracted with hexane (3 x 10 mL) and then with DCM (3 x 10 mL). The combined DCM extracts were dried over Na2S04, filtered and concentrated in vacuo to give 0.27 g (95%) of 4,4-dimethyl-2- oxazolidinone. The combined hexane extracts were washed with 1 M aq Na2S03 (10 mL), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent hexane/DCM 100:0 to 0:100 v/v) to give 0.36 g (85%) of 4-iodo- 1,2-dimethoxybenzene. 1H NMR: δ 7.19 (dd, J = 1.5 Hz, J = 8.5 Hz, 1H), 7.09 (d, J = 1.5 Hz, 1H), 6.59 (d, J = 8.5 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H) ppm; 13C NMR: δ 149..8, 149.1, 129.7, 120.3, 113.2, 82.3, 56.1, 55.9 ppm. |
68% | With N-iodosaccharine; at 20℃;Ionic liquid; Darkness; | General procedure: To a solution of 54 mg (0.5 mmol) of anisole in 1 mL of BMIM BF4 was added 158 mg (0.51 mmol) of N-iodosaccharin. The reaction was stirred at room temperature protected from light for 8-12 h. The product was then isolated by extraction with ether (3 × 3 mL), followed by evaporation of the solvent to afford the desired iodinated product. In some cases, the product was contaminated with small amounts of BMIM BF4. This could be removed via filtration with ether through a short plug of silica. Alternatively, it could be avoided entirely by extraction of the product from the reaction using 1:1 ether/hexanes in place of pure ether. The identity of all products were confirmed by comparison (spectral and mp) with either commercially available samples or data reported in the literature as indicated in Table 1. |
61% | With 1-iodo-3,5,5-trimethylhydantoin; In acetonitrile; at 20℃; for 48h; | [00276] A mixture of veratrole (0.22 g, 1.63 mmol), l-iodo-3,5,5- trimethylhydantoin (0.53 g, 1.97 mmol) and MeCN (10 mL) was stirred for 48 h at rt and concentrated in vacuo. The residue was treated with 1 M aq Na2S03 (5 mL), extracted with hexane (3 x 10 mL) and then with DCM (3 x 10 mL). The combined DCM extracts were dried over Na2S04, filtered and concentrated in vacuo to give 0.25 g (90%) of 3,5,5-trimethylhydantoin (3,5,5-TMH). The combined hexane extracts were washed with 1 M aq Na2S03 (10 mL), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent hexane/DCM 100:0 to 0: 100 v/v) to give 0.31 g (61%) of 4-iodo-l,2-dimethoxybenzene. |
With N-iodo-succinimide; trifluoroacetic acid; In acetonitrile;Reflux; | General procedure: To a solution of the appropriate benzene derivative 6a,b (1.0 mmol) in acetonitrile (20 mL) were added NIS (0.247 g, 1.1 mmol) and a catalytic amount of TFA (0.023 mL, 0.3 mmol). The reaction mixture was stirred at reflux overnight. After this time, it was poured onto ice (50 g) and H2O (100 mL) and then, it was treated with a saturated solution of Na2S2O3. The obtained precipitate was filtered off, taken in CH2Cl2 and dried over anhydrous Na2SO4. The solvent was evaporated to dryness and the obtained residue was purified by silica gel column chromatography using CH2Cl2/C6H14 (1:1) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; trifluoroacetic anhydride;AlCl3; In hexane; dichloromethane; ethyl acetate; | 18.1: 2,2,2-Trifluoro-1-(3,4-dimethoxyphenyl)-ethanone 13.8 g (0.10 mol) of 1,2-dimethoxybenzene and 12.2 g (0.10 mol) of 4-dimethylaminopyridine are mixed in 75 ml of CH2Cl2 and cooled in an ice bath. To the solution are added dropwise 21.0 g (0.10 mol) of trifluoroacetic anhydride, followed by 32.0 g (0.24 mol) of AlCl3 by portions. The reaction mixture is stirred at room temperature overnight, poured into ice water, and extracted with CH2Cl2. The organic phase is washed with water, dried over MgSO4, and concentrated. The residue is purified by flash chromatography on silica gel with ethyl acetate and hexane (1:9), yielding 2.9 g of product as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90%Chromat. | With trifluorormethanesulfonic acid; at 20℃; for 1h;Neat (no solvent); | General procedure: 430 muL of anisyl acetate (2.5 mmol, 1 equiv) and 2.2 mL of anisole (12.25 mmol, 5 equiv) were placed into a 10 mL round-bottom flask equipped with a magnetic stir-bar. Then 11 muL 5% of pure triflic acid (0.125 mmol) was added and the solution was stirred for 20 min. The crude was analyzed by 1H NMR and GC-MS. Purification by column chromatography gave 484 mg (85% yield) of bis(4-methoxyphenyl)methane, which was identical to an authentic sample. |
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 |
---|---|---|
17 mg; 61% | With hydrogenchloride; iodine; sodium nitrite; In 2,2,2-trifluoroethanol; water; at 20℃; for 1h; | General procedure: To a 25 mL round-bottom flask equipped with a magnetic stir bar was added ground iodine (127 mg, 0.5 mmol) and solvent (1.0 mL). Under agitation, this mixture was treated with hydrochloric acid (37% aqueous, 12.5 L, 0.15 mmol), sodium nitrite (40% aqueous, 6.7 L, 0.05 mmol), and the aromatic substrate (1.0 mmol). A balloon inflated with air was attached and the mixture was stirred at room temperature for 1-72 h, after which the reaction was quenched by the addition of saturated sodium thiosulfate (ca. 2 mL) and saturated sodium bicarbonate (ca. 2 mL). The mixture was partitioned between dichloromethane (ca. 15 mL) and deionized water (ca. 25 mL). The organic layer was collected, dried over sodium sulfate, and concentrated. The residue was purified by silica gel chromatography. |
Tags: 1,2-Dimethoxybenzene | Veratrole | Benzene Compounds | Aryls | Ethers | Organic Building Blocks | 91-16-7
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H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
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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