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CAS No. : | 17100-58-2 | MDL No. : | MFCD11847398 |
Formula : | C8H9BrO | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | IFKWLKCPUIQXPU-UHFFFAOYSA-N |
M.W : | 201.06 | Pubchem ID : | 22280088 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 | UN#: | |
Hazard Statements: | H302-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 |
---|---|---|
78% | [00281] 28B. 4-bromo-2-methylbenzaldehyde: To a solution of oxalyl chloride (249 mL, 497 mmol) in CH2CI2 (150 mL) at -78 C under argon was added a solution of DMSO (42.4 mL, 597 mmol) in CH2C12 (75 mL) dropwise with a venting needle (Note: gas was generated, slow addition was necessary). After the addition, the venting needle was removed. The reaction mixture was stirred at -78 C under argon for 30 min. Then, a solution of 28A (20.0 g, 99.0 mmol) in CH2C12 (203 mL) was added. The resulting solution was stirred at -78 C for 30 min and then TEA (166 mL, 1190 mmol) was added dropwise. The reaction mixture was warmed to rt and stirred for 12 h. The reaction mixture was diluted with water (20 mL) and CH2C12 (30 mL). The layers were separated and the aqueous layer was extracted with CH2C12 (3 x 50 mL). The combined organic extracts were washed with water and brine, dried (MgSC^), filtered, and concentrated. The crude product was purified by flash chromatography to provide 28B (15.4 g, 78 mmol, 78 % yield) as a yellow oil. lH NMR (400 MHz, CDC13) delta 10.22 (s, 1H), 7.66 (d, J= 8.28 Hz, 1H), 7.51 (dd, J= 8.28, 1.76 Hz, 1H), 7.45 (s, 1H), 2.65 (s, 3H). | |
73% | To a solution of ID (9.30 g, 46.3 mmol) in CH2CI2 (200 mL) under argon was added oxalyl chloride (10.1 mL, 116 mmol) at -78 C; then DMSO (9.85 mL, 139 mmol) was added dropwise with a venting needle. After the addition was complete, the venting needle was removed and the reaction mixture was stirred at -78 C under argon for 30 min. Then, NEt3 (38.7 mL, 278 mmol) was added dropwise. After stirring at the same temperature for 3 h, the reaction mixture was diluted with water (20 mL) and CH2C12 (50 mL) and the layers were separated. The aqueous layer was further extracted with CH2CI2 (3 x 100 mL) and the combined organic extracts were washed with water and brine, dried over MgS04, filtered, and concentrated. The crude product was purified by silica chromatography to give IE (yellow oil, 6.70 g, 33.7 mmol, 73% yield). 1H NMR (400 MHz, CDC13) delta 10.22 (1 H, s), 7.66 (1 H, d, J=8.28 Hz), 7.51 (1 H, dd, J=8.28, 1.76 Hz), 7.45 (1 H, s), 2.65 (3 H, s). | |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1h; | [0453] Experimental Details: A solution of 2.4g (11.9mmol) of compound 2 in20ml of DCM was added a slurry of 5.1g(23.8mmol) of PCC in 60ml of DCM. The reaction solution was stirred for lhour at r.t. diluted with 300ml OfEt2O and filtered. The filtrate was concentrated to give compound 3. |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1h; | Experimental Details: A solution of 2.4 g (11.9 mmol) of compound 2 in 20 ml of DCM was added a slurry of 5.1 g (23.8 mmol) of PCC in 60 ml of DCM. The reaction solution was stirred for 1 hour at r.t. diluted with 300 ml of Et2O and filtered. The filtrate was concentrated to give compound 3. | |
With manganese(IV) oxide; In dichloromethane; at 20℃; for 72h; | Manganese dioxide (360 g, 4.1 mol) was added to a solution of (4-bromo-2-methylphenyl)methanol (91.5 g, 455 mmol) in dichloromethane (500 mL) and the reaction was stirred at room temperature for 72 h. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified via chromatography (5% ethyl acetate/hex), providing the product, 4-bromo-2-methylbenzaldehyde, as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 2.64 (s, 3H), 7.43 (s, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.65 (d, J=8.3 Hz, 1H), 10.20 (s, 1H). | |
With Dess-Martin periodane; In dichloromethane; at 0 - 30℃; for 1h; | To the solution of (4-bromo-2-methylphenyl)methanol (1.8 g, 8.1 mmol) in CH2C12 (20 mL) was added Dess-Martin Periodinane (5,1 g, 12.1 mmol) at 0C. The mixture was stirred at RT for 1 h, then diluted with water, and the solid was removed by filtration. The filtrate was extracted with CH2C12. The combined organic layer was washed with brine, dried over Na2S04 and concentrated in vacuo. Purification by normal phase silica gel column provided 4-bromo-2- methylbenzaldehyde as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 5℃; | Step b intermediate 51 <n="63"/>1 -Bromo-4-(bromomethyl)-3 -methylbenzene(4-Bromo-2-methylphenyl) methanol (10.4 g, 51.6 mmol) is dissolved in anhydrous CH2Cl2 (150 mL) and CBr4 (18.8 g, 56.8 mmol) added. The reaction mixture is cooled to 0-50C and PPh3 (14.9 g, 56.8 mmol) is added. The reaction mixture is stirred overnight then hexane / EtOAc (9:1) (250 mL) is added with vigorous stirring. The triphenylphosphine oxide that forms during the reaction is filtered off and the filtrates are concentrated in vacuo. The resulting oil is purified on a silica gel pad with hexane / EtOAc (8:2). The solvent are removed on a rotary evaporator and the bromoform is removed by vacuum distillation (15 mm Hg, bp: 40-500C) to provide the expected product l-Bromo-4-(bromomethyl)-3-methylbenzene (13.23 g, 97 %) as a yellow oil. IH NMR (300 MHz, CHLOROFORM-D): delta 7.37-7.27 (2H, m), 7.17 (IH, d, /= 8.1 Hz), 4.45 (2H, s), 2.39 (3H,s). |
97% | With phosphorus tribromide; In dichloromethane; at 0 - 20℃; | Intermediate 13: 4-bromo-1-(bromomethvl)-2-methylbenzene; To a solution of (4-bromo-2-methylphenyl) methanol, intermediate 12, (100 g, 0. 5mol) in dicholoromethane (1 L) was added dropwise phosphorus tribromine (54.2 g, 0.2 mol) at 0 0C. After addition, the reaction mixture was stirred for 2 hours at RT. The mixture was adjusted to pH=7 with a saturated solution of NaHCO3. The separated organic layer was dried over sodium sulfate, filtered, concentrated in vacuo to give the title product (4-bromo-2- methylphenyl)methanol, (128 g, 97% yield). 1H NMR: (400 MHZ, CDCI3) delta 7.43 (t, 1 H), 7.32- 7.37 (m, 2H), 4.67 (s, 2H), 2.33 (s, 3H). |
95% | With phosphorus tribromide; In chloroform; at 0 - 20℃; for 3h;Inert atmosphere; | PBr3 (14.54 g, 53.7mmol, 1.2 eq) was added to the solution of (4-bromo-2-methylphenyl)methanol (9.0 g, 44.76mmol, 1.0 eq) in CHC13 (100 mL) at 0 C under nitrogen atmosphere and the solution wasallowed to warm up to ambient temperature. The solution was, then, stirred at ambienttemperature for 3 h. After complete consumption of starting material, the reaction mixture was diluted with chloroform and washed with saturated aq NaHCO3 and brine. The organic extract was then dried over anhydrous sodium sulfate, filtered, and solvents evaporated from the filtrate under reduced pressure to afford 4-bromo-1-(bromomethyl)-2-methylbenzene (11.2 g, 95%) asyellow solid. |
89% | With phosphorus tribromide; In dichloromethane; at 0 - 20℃; for 1h; | [0653j To a solution of (4-bromo-2-methylphenyl)methanol (1.3 g, 6.7 mmol) in CH2C12 (50 mL) was added PBr3 (0.95 mL, 10 mmol) at 0 C. The mixture was stirred at rt for 1 h, quenched with ice-water (50 mL) and the pH value was adjusted to 7.0 with 50% aqueous NaOH solution. The mixture was extracted with EtOAc (100 mL x 2) and the combined organic layers were washed with water (50 mL), dried (Na2SO4) and concentrated in vacuo to give 4-bromo-1- (bromomethyl)-2-methylbenzene (1.56 g, yield: 89%) as a white solid which was used in next step without further purification. |
81% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 5h; | Triphenylphosphine (11.35 g, 43.27 mmol) followed by carbon tetrabromide (14.35 g, 43.27 mmol) were added to a solution of (4-bromo-2-methyl-phenyl)-methanol (7.25 g, 36 mmol) in CH2CI2 (200 mL). The mixture was stirred at room temperature for 5 hours. The solution was concentrated to 15 ml. The residue was purified by flash column chromotography (1% to 10% EtOAc in Hexane) gave the product as brown oil (9.25 g, 81% yield). 1H NMR (400 MHz, CDCI3) 5: 2.39 (3 H, s) 4.45 (2 H, s) 7.17 (1 H, d, J=8.08 Hz) 7.29 (2 H, m) 7.30 (1 H, dd, J=8.08, 2.02 Hz) 7.34 (1 H, s) |
With N-Bromosuccinimide; triphenylphosphine; In dichloromethane; | 4-Bromo-1-bromomethyl-2-methyl-benzene (Intermediate 138) A solution of (4-bromo-2-methyl-phenyl)-methanol (Intermediate 133, 319.0 mg, 1.58 mmol) and triphenylphosphine (466.0 mg, 1.74 mmol) in 5 mL CH2Cl2 was cooled to 0 C. and N-bromosuccinimide (309.0 mg, 1.74 mmol) was added in 5 portions over 20 minutes. The solution was warmed to 25 C. and stirred for 17 hours. The reaction was quenched by the addition of dilute aqueous NaHCO3. The resulting mixture was extracted with Et2O and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (Na2SO4) and concentrated under reduced pressure. The title compound, 350.0 mg (84%), was isolated by column chromatography (2-3% EtOAc-hexanes) as a colorless oil. 1H NMR (CDCl3) delta: 7.32 (1H, d, J=2.0 Hz), 7.29 (1H, dd, J=2.0, 7.9 Hz), 7.15 (1H, d, J=7.9 Hz), 4.43 (2H, s), 2.37 (3H, s). | |
With triphenylphosphine; In N-Bromosuccinimide; | 4-Bromo-1-bromomethyl-2-methyl-benzene (Intermediate 138) A solution of (4-bromo-2-methyl-phenyl)-methanol (Intermediate 133, 319.0 mg, 1.58 mmol) and triphenylphosphine (466.0 mg, 1.74 mmol) in 5 mL CH2C12 was cooled to 0 C. and N-bromosuccinimide (309.0 mg, 1.74 mmol) was added in 5 portions over 20 minutes. The solution was warmed to 25 C. and stirred for 17 hours. The reaction was quenched by the addition of dilute aqueous NaHCO3. The resulting mixture was extracted with Et2O and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (Na2SO4) and concentrated under reduced pressure. The title compound, 350.0 mg (84%), was isolated by column chromatography (2-3% EtOAc-hexanes) as a colorless oil. 1H NMR (CDCl3) delta: 7.32 (1H, d, J=2.0 Hz), 7.29 (1H, dd, J=2.0, 7.9 Hz), 7.15 (1H, d, J=7.9 Hz), 4.43 (2H, s), 2.37 (3H, s). | |
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; | To a stirred solution of (4-Bromo-2-methyl-phenyl)-methanol (as obtained in preparation 25) (4.58 g, 22.8 mmol) in CH2CI2 (50 ml) is added , under Argon and at RT, carbon tetrabromide (9.27 g, 27.4 mmol) followed by thphenylphosphine (7.25 g, 27.4 mmol). The mixture is stirred overnight and then concentrated in vacuo. The crude residue is then purified by chromatography (silicagel, hexane: EtOAc 25:1) to afford the title compound as a clear oil. | |
With hydrogen bromide; acetic acid; In water; at 50℃; for 12h; | Step 2: 4-bromo-l-(bromomethyl)-2-methylbenzene; Hydrobromic acid (cone, 2 eq.) was added to a stirred solution of the alcohol from step 1 (1 eq.) in acetic acid (0.22M). The mixture was stirred at 50 C for 12 h, cooled down to room temperature, poured in water and extracted with Et2O. The organic extract was washed with <n="25"/>water, aqueous sodium hydrogen carbonate (3x), brine, dried over MgSO4, filtered and concentrated to afford the desired benzyl bromide as a light yellow solid. | |
With phosphorus tribromide; In dichloromethane; at 0 - 20℃; for 3h; | To a solution of (4-bromo-2-methylphenyl)methanol 132 (4 g) in DCM was added PBr3 (5.42 g) at 0 C. The mixture was stirred for 3 h at room temperature. DCM was added and washed with water and aq NaHC03 until pH ~ 7. The organic layer was separated, dried over Na2S04, and concentrated under reduced pressure to give 4-bromo- l -(bromomethyl)-2- methylbenzene 133 as a brown oil (3.8 g). The compound was used in the next reaction without further purification. ? NMR (400 MHz, CDC13) ppm: 7.37 (s, 1 H), 7.34 (d, J= 8 Hz, 1 H), 7.20 (d, J= 8 Hz, 1 H), 4.48 (s, 2H), 2.41 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Example 20 5-[4-(hydroxymethyl)-3-methylphenyl]-1-methyl-1H-pyrrole-2-carbonitrile To a solution of <strong>[24078-12-4]4-bromo-2-methylbenzaldehyde</strong> (1.0 g, 4.65 mmol) in THF (25 mL) at -78 C. was added diisobutylaluminum hydride (DIBAL-1.0M in dichloromethane, 20 mL, 20 mmol) over 15 minutes in a dropwise fashion. The solution was stirred overnight at room temperature and slowly poured into a saturated ammonium chloride solution (50 mL). The mixture was extracted with ethyl acetate (3*30 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to give (4-bromo-2-methylphenyl)-methanol (0.88 g, 95%). MS (ES) m/z 201. | |
65% | With sodium tetrahydroborate; ethanol; at 0 - 20℃; for 12.5h; | 4-bromo-2-methylphenyl methanol. To a solution of <strong>[24078-12-4]4-bromo-2-methylbenzaldehyde</strong> (1.99 g, 10 mmol) in ethanol (100 mL) was added sodium borohydride (0.76 g, 20 mmol) in portions at 0C. The mixture was stirred for 30 minutes and warmed to 20C and stirred at the same temperature for 12 hours. The mixture was concentrated in vacuo to give (4-bromo-2- methylphenyl) methanol (1.3 g, 65%). |
65% | With methanol; sodium tetrahydroborate; In ethanol; at 0 - 20℃; for 12.5h; | To a solution of <strong>[24078-12-4]4-bromo-2-methylbenzaldehyde</strong> (1.99 g, 10 mmol) in ethanol (100 mL) was added sodium borohydride (0.76 g, 20 mmol) in portions at 0 C. The mixture was stirred for 30 minutes and warmed to 20 C. and stirred at the same temperature for 12 hours. The mixture was concentrated in vacuo to give (4-bromo-2-methylphenyl)methanol (1.3 g, 65%). |
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