Structure of 58966-34-0
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CAS No. : | 58966-34-0 |
Formula : | C8H7ClO |
M.W : | 154.59 |
SMILES Code : | CC1=C(C=O)C=C(Cl)C=C1 |
MDL No. : | MFCD11111042 |
InChI Key : | DDYTVUGYXUWXGN-UHFFFAOYSA-N |
Pubchem ID : | 12347565 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
With titanium tetrachloride; In dichloromethane; at 20℃; for 15.0h; | To a solution of 4-chlorotoluene (25.0 g) and dichloromethylmethylether (45.4 g) in dichloromethane (160 ml) was added dropwise at room temperature a solution of titanium tetrachloride (74.9 g) in dichloromethane (40 ml), and the mixture was stirred at the same temperature for 15 hours. The reaction solution was poured into ice, and the organic layer was washed with water, sodium hydrogen carbonate solution, water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (ethyl acetate-hexane) to give oil of crude 2-chloro-5-methylbenzaldehyde (18.3 g) and 5-chloro-2-methylbenzaldehyde (4.1 g), respectively. To a mixture of acetone (160 ml), sodium hydroxide (2.6 g) and water (160 ml) was added dropwise at 0 C. a solution of crude 2-chloro-5-methylbenzaldehyde (18.3 g) in acetone (30 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g) as oil. To a solution of 20% sodium ethoxide in ethanol (4.3 g) was added at room temperature diethyl malonate (10.1 g), and then added little by little 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (33 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (33 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(2-chloro-5-methylphenyl)cyclohexane-1,3-dione (7.8 g) as colorless crystals. mp 186-188 C. 1H-NMR(CDCl3) delta: 2.33 (3H, s), 2.38-2.72 (4H, m), 3.2-5.4 (1H, br), 3.73-3.93 (1H, m), 5.55 (1H, s), 7.01 (1H, d, J=8 Hz), 7.03 (1H, s), 7.26 (1H, d, J=8 Hz). To a mixture of acetone (80 ml), sodium hydroxide (1.2 g) and water (80 ml) was added dropwise at 0 C. a solution of 5-chloro-2-methylbenzaldehyde (4.1 g) in acetone (10 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g) as oil. To a solution of 20% sodium ethoxide in ethanol (9.5 g) was added at room temperature diethyl malonate (4.5 g) and then added little by little 4-(5-chloro-2-methylphenyl)-3-buten-2-one (5.5 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (15 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (15 ml) for 15 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(5-chloro-2-methylphenyl)cyclohexane-1,3-dione (2.9 g) as colorless crystals. mp 180-181 C. 1H-NMR(CDCl3-DMSO-d6) delta: 2.31 (3H, s), 2.35-2.84 (4H, m), 3.37-3.73 (1H, m), 5.56 (1H, s), 6.9-7.43 (1H, br), 7.08-7.26 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide;titanium tetrachloride; In dichloromethane; water; acetone; | Synthesis of (+-)-7-(5-chloro-2-methylphenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline [Compound 6] Reference Example 20 To a solution of 4-chlorotoluene (25.0g) and dichloromethylmethylether (45.4g) in dichloromethane (160ml) was added dropwise at room temperature a solution of titanium tetrachloride (74.9g) in dichloromethane (40ml), and the mixture was stirred at the same temperature for 15 hours. The reaction solution was poured into ice, and the organic layer was washed with water, sodium hydrogen carbonate solution, water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was subjected to silica gel column chromatography (ethyl acetate-hexane) to give oil of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3g) and 5-chloro-2-methylbenzaldehyde (4.1g), respectively. To a mixture of acetone (160ml), sodium hydroxide (2.6g) and water (160ml) was added dropwise at 0C a solution of crude <strong>[14966-09-7]2-chloro-5-methylbenzaldehyde</strong> (18.3g) in acetone (30ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-methylphenyl)-3-buten-2-one (18.9g) as oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; | Step 1 5-chloro-2-methylbenzaldehyde To a solution of <strong>[27139-97-5]2-bromo-4-chlorotoluene</strong> (20.0 g; 97.3 mmol) in 300 mL of THF at -78° C. was added dropwise a 2.5 M solution of n-BuLi (102.2 mmol). After 30 min of stirring at that temperature, 1-formylpiperidine (11.4 mL) in 10 mL of THF was added and the solution left for 1 h. It was brought to 0° C., quenched with NH4OAc (25percent) and diluted with EtOAc. The organic phase was dried over Na2SO4, filtered and the solvent removed to yield 13.3 g of the title compound. 1H NMR (CDCl3) delta2.6 (3H, s), 7.15 (1H, d), 7.4 (1H, d), 7.75 (1H, s) and 10.2 (1H, s). | |
13.3 g (89%) | With n-butyllithium; In tetrahydrofuran; | Step 1 Ethyl (E)-3-(5-chloro-2-methylphenyl)-2-propenoate To 2-bromo-4-chloro toluene (20.0 g; 97.3 mmol) in 300 mL of THF at -78° C. was added n-BuLi 2.5M (40.8 mL) dropwise. After 20 min. 1-formylpiperidine (11.4 mL; 103.0 mmol) in 10 mL of THF was added dropwise. After 30 min the reaction mixture was brought to 0° C. and quenched with HCl (10percent) and diluted with EtOAc. The organic phase was collected, dry and the solvent evaporated to yield 13.3 g (89percent) of 5-chloro-2-methylbenzaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | 5-Chloro-2-methylbenzaldehyde Into a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2 was added <strong>[27139-97-5]2-bromo-4-chlorotoluene</strong> (10.0 mL, 75.0 mmol) in anhydrous THF (150 mL). The clear sol. was cooled to -78° C. and BuLi (36.6 mL, 82.4 mmol, 2.25 M sol. in hexanes) was added dropwise over 20 min. The resulting light orange sol. was stirred at -78° C. for 1 h, and DMF (30 mL, 375 mmol) was added in a single addition. The resulting mixture was allowed to warm to rt over 4 h. The reaction was quenched by addition of aq. 1M HCl (20 mL), and stirred at rt overnight. The reaction mixture was poured into a 500 mL separatory funnel containing aq. 1M HCl (200 mL). The mixture was extracted with Et2O (3*100 mL). The combined org. layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to a yellow oil. Purification by short-path distillation under reduced pressure (1 mm Hg) yielded the title compound as a light yellow oil (7.99 g, 69percent). bp=70-72° C. at 1 mm Hg. 1H NMR (CDCl3, 500 MHz) delta 10.23 (1H, s), 7.77 (1H, d, J=2.5 Hz), 7.45 (1H, dd, J=8.0, 2.5 Hz), 7.22 (1H, d, J=8.0 Hz), 2.65 (3H, s). | |
69% | 5-Chloro-2-methylbenzaldehyde. Into a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2 was added <strong>[27139-97-5]2-bromo-4-chlorotoluene</strong> (10.0 mL, 75.0 mmol) in anhydrous THF (150 mL). The clear sol. was cooled to -78 0C and BuLi (36.6 rnL, 82.4 mmol, 2.25 M sol. in hexanes) was added dropwise over 20 min. The resulting light orange sol. was stirred at -78 0C for 1 h, and DMF (30 mL, 375 mmol) was added in a single addition. The resulting mixture was allowed to warm to rt over 4 h. The reaction was quenched by addition of aq. IM HCl (20 mL), and stirred at rt overnight. The reaction mixture was poured into a 500 mL separatory funnel containing aq. IM HCl (200 mL). The mixture was extracted with Et2O (3 x 100 mL). The combined org. layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to a yellow oil. Purification by short- path distillation under reduced pressure (~ 1 mm Hg) yielded the title compound as a light yellow oil (7.99 g, 69percent). bp = 70-72 0C at 1 mm Hg.1H NMR (CDCl3, 500 MHz) delta 10.23 (IH, s), 7.77 (IH, d, J = 2.5 Hz), 7.45 (IH, dd, J = 8.0, 2.5 Hz), 7.22 (IH, d, J= 8.0 Hz), 2.65 (3H, s). |
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