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CAS No. : | 37687-57-3 | MDL No. : | MFCD03425852 |
Formula : | C8H7ClO3 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | DTMJGFBJQBQOIA-UHFFFAOYSA-N |
M.W : | 186.59 | Pubchem ID : | 603956 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* 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 |
---|---|---|
92% | With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In dichloromethane; at 20℃; for 12h; | General procedure: Following an adaptation of the procedure of McKillop et al.7, anaqueous solution of 1.20 g of NaOH (30 mmol, 3.0 eq.) in 50 mL of deionized water was added to astirring solution of 2.31 g (10 mmol) of 2-bromo-isovanillin (2-bromo-3-hydroxy-4-methoxybenzaldehyde)in 50 mL of dichloromethane. Next, phase transfer catalyst was added, as 3.40 g of eithertetrabutylammonium hydrogen sulfate (TBAHS, 10.0 mmol, 1.0 eq.) or recycled catalyst (assuming thatthe recovered catalyst is tetrabutylammonium hydroxide, 2.6 g is 10 mmol, 1.0 eq). Once dissolved, 17g (120 mmol, 12 eq.) of methyl iodide was then added to the mixture and the reaction was allowed tostir at room temperature. Reaction progress was monitored by HPLC. As monitored by HPLC, reactionprogress generally showed complete turnover to product with no side products by 3 hours, however thesolution was typically allowed to stir overnight for convenience. The reaction mixture was extracted with3 x 50 mL portions of CH2Cl2. The combined organic extracts were washed with brine and deionizedwater, dried over MgSO4, filtered, and concentrated by evaporation under reduced pressure to yield aeither a white or yellow solid. To remove catalyst, the solid was first ground to a fine powder with amortar and pestle. This solid was poured on top of a 2 ? 3 cm layer of dry silica gel in a 3 ? 4 cm (I.D.)sintered glass fritted Buchner funnel. The solid was extracted with 1:5 ethyl acetate:hexanes in 75 mLportions by pouring the solvent mixture over the dry solids with vacuum suction to collect the solutionin a round bottom flask. Allow the solids to dry between solvent portions for best separation. The first1250 mL typically contained 85 - 95percent of pure product. The combined eluent was evaporated to drynessunder reduced pressure to afford a dense, white, flakey solid (2.06 g, 90percent). If the product was found tocontain non-halogenated contaminants from the previous step, pure halogenated product was easilyobtained by recrystallization from hexanes. The phase transfer catalyst, presumably a mixture oftetrabutylammonium salts, was recovered by either scooping it out of the filter or by eluting with ethylacetate. |
8.5 g (42 mmol, 98%) | With potassium carbonate; In acetonitrile; | Step 2--Formation of 2-Chloro-3,4-dimethoxybenzaldehyde To 8.03 g (43 mmol) of 2-Chloro-3-hydroxy-4-methoxybenzaldehyde in 100 mL of acetonitrile was added 7.7 g (55 mmol) of powdered potassium carbonate followed by 8.3 mL (0.13 mol) of iodomethane. The reaction was slowly warmed to reflux where it was stirred for 24 h. After cooling to room temperature the suspension was filtered and the filtrate evaporated to dryness in vacuo to give 8.5 g (42 mmol, 98percent) of a white solid shown to be desired product by 1 H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
189.49 g (96%) | With sodium hydroxide; In chloroform; water; acetonitrile; | Step 2 Synthesis of 2-chloro-3,4-dimethoxybenzaldehyde 184 g (0.986 mol) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde was dissolved in 2 l of CH3 CN. 204 g (1.476 mol) of K2 CO3 and 298 g (2.096 mol) of CH3 I were added to the solution, which was heated under reflux for 4 hours. After cooling, the crystals were separated by filtration and the mother liquor was concentrated under reduced pressure. 800 ml of water and 600 ml of CHCl3 were added to the residue to conduct extraction. The CHCl3 layer was washed with 500 ml of 10percent NaOH and a saturated Nacl aqueous solution. It was dehydrated over MgSO4 and concentrated to dryness under reduced pressure to obtain 189.49 g (96percent) of 2-chloro-3,4-dimethoxybenzaldehyde. mp 70°~72° C. NMR (90 MHz, CDCl3) delta:3.88 (3H, s), 3.96 (3H, s), 6.92 (1H, d), 7.72 (1H, d), 10.28 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N-methyl-acetamide; tetrachloromethane; ethanol; acetonitrile; | EXAMPLE 1 Chlorine (25.6 g, 0.362 mole) was bubbled into a slurry of isovanillin (50.0 g, 0.328 mole) in 500 ml of carbon tetrachloride over a period of 25 minutes while maintaining an internal temperature of 15°-20°. Upon completion of the chlorine addition the slurry was stirred for 1 hour at room temperature; the precipitate filtered, washed with carbon tetrachloride and dried to 57.8 g (94.5percent crude yield), mp: 181°-196°. Recrystallization of 34.5 g of the crude produce from 600 ml of ethanol gave 17.3 g of white fibrous crystals, mp: 199°-203°; concentrating the mother liquors yielded a second crop of 6.3 g, mp: 196-202.5 (68percent recovery for two crops). Recrystallization of 11.4 g of crude 2-chloroisovanillin from 170 ml of acetonitrile afforded 7.4 g, mp: 200°-204.5° (65percent recovery for one crop). This compound (189.3 g) was methylated using dimethylformamide solution with potassium carbonate and dimethylsulfate to give 2-chloro-3,4-dimethoxybenzaldehyde, m.p. 69°-70°. |
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