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Structure of 4-Methylbenzyl chloride
CAS No.: 104-82-5
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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.
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| CAS No. : | 104-82-5 |
| Formula : | C8H9Cl |
| M.W : | 140.61 |
| SMILES Code : | CC1=CC=C(CCl)C=C1 |
| MDL No. : | MFCD00000919 |
| InChI Key : | DMHZDOTYAVHSEH-UHFFFAOYSA-N |
| Pubchem ID : | 7722 |
| GHS Pictogram: |
|
| Signal Word: | Danger |
| Hazard Statements: | H302-H312-H314-H332 |
| Precautionary Statements: | P280-P305+P351+P338-P310 |
| Class: | 8 |
| UN#: | 3265 |
| Packing Group: | Ⅱ |
* 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 |
|---|---|---|
| General procedure: Various substituted BnCl 9a?k (2.5 mmol) and thiourea (0.19 g,2.5 mmol) were refluxed together in EtOH (2.5 mL) for 1 h. After removalof EtOH at reduced pressure, the obtained solid was slowly added to a mixture of NCS (1.33 g, 10 mmol), 2M HCl (0.68 mL) and MeCN (4 mL) over 30 min. After completion of the reaction, the MeCN was removed on a rotary evaporator. Then H2O (3 mL) was added, and the white solid was filtered and dried under an infrared lamp to afford 10a?k (70percent?93percent), respectively, which did not require further purification.Then, 10a?k were treated with ammonia solution (1 mL) inacetone (2 mL) at 0 °C for 4 h. After removal of acetone at reducedpressure, the crude was extract with EtOAc, and the combined organiclayers were washed with H2O, and brine. After drying over Na2SO4,filtering, and concentrating of the organic phase, the resulting yellowsolid 11a?k was used directly in the next step. Finally, 11a?k and ethylchloroformate (1.2 eq) were refluxed together in the presence K2CO3(1.5 eq) in acetone (5.0 mL) for 4 h obtained 12a?k. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 51 g (46%) | With sodium hydroxide; thionyl chloride; sodium sulfite; In N-methyl-acetamide; ice-water; Petroleum ether; | EXAMPLE 1 Synthesis of p-methylbenzylsulfonyl chloride In a 10percent aqueous solution of sodium hydroxide (250 ml) is dissolved sodium sulfite (67 g, 0.53 mol), followed by the addition of p-methylbenzyl chloride (75 g, 0.53 mol). The mixture is refluxed with stirring for 4 hours. The reaction mixture is diluted two-fold with water and filtered when hot. The filtrate is cooled. The crystals of sodium p-methylbenzylsulfonate are collected by filtration. Yield 51 g (46percent). In dimethylformamide (90 ml) is dispersed sodium p-methylbenzylsulfonate (30 g, 0.145 mol) which is sufficientry dry. The dispersion is cooled to -10° C. and under stirring, thionyl chloride (19.2 ml, 0.29 mol) is added dropwise. The mixture is stirred at room temperature for 3 hours and poured in ice-water (500 g) and extracted with ether (3 times, 150 ml each). The ethereal layers are combined, washed twice with cold water and dried over sodium sulfate. The ether is distilled off and petroleum ether is added to the crystalline residue, followed by cooling. The crystals are collected by filtration. Yield 23.5 g (78percent), m.p. 80°-81° C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 55% | In 1-methyl-pyrrolidin-2-one; at 100℃; for 2h; | To a solution of 4-methylbenzyl chloride (3.1 g, 20.0 mmol) in 50 mL of NMP, 2-aminobenzenethiol (3.1 g, 20.0 mmol) was added. The mixture was heated to 100 C. for 2 hours. The mixture was cooled down to rt, and saturated Na2CO3 solution was added, followed by 20 mL of water. The resulting white solid was filtered, washed by water and dried over high vacuum. (3.6 g, 55% yield) LC-MS (ESI): [M+1]+=226.13, tR=4.59 min. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J=8.1 Hz, 1H), 7.97 (d, J=8.1 Hz, 2H), 7.87 (d, J=7.9 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H), 7.35 (t, J=7.5 Hz, 1H), 7.28 (d, J=7.9 Hz, 2H), 2.41 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 168.27, 154.18, 141.45, 134.96, 130.96, 129.75, 127.50, 126.27, 125.02, 123.06, 121.60, 21.56. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 84% | With NHC-Pd(II)-Im; lithium tert-butoxide; In toluene; at 130℃; for 3h;Inert atmosphere; Sealed tube; | Under N2 atmosphere, LiOtBu (1.0 mmol), benzoxazole 2a (0.6 mmol), NHC-Pd(II)-Im complex 1 (2.0 mol %), dry toluene (2.0 mL) and benzyl chloride 3a (0.5 mmol) were successively added into a sealed tube. The mixture was stirred vigorously at 130 C for 3 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel to afford pure product 4a. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With copper(II) acetate monohydrate; sodium carbonate; sulfur; In dimethyl sulfoxide; at 130℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: 2-Iodoaniline 1a (0.5 mmol), benzyl chloride 2a (1 mmol, 126 mg), sulfur powder (2 mmol, 64 mg), Cu(OAc)2·H2O (20 mg) and Na2CO3 (1 mmol, 106 mg) in DMSO (3 mL) were put into a Schlenk tube. The reaction mixture was stirred at 130 C for 24 h and cooled to room temperature, filtered and extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography on silica gel (300-400 mesh) to afford desired product 3aa as a light yellow solid; yield : 102 mg (97%); |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | With N-methylcyclohexylamine; sulfur; at 110℃; for 24h;Sealed tube; Inert atmosphere; | General procedure: A mixture of o-chloronitrobenzene (0.5 mmol), benzyl chloride (1.0 mmol), elemental sulfur (1.5 mmol) and N-methylpiperidine (1.5 mL) was placed in a sealed pressure vessel (25 mL) containing a magnetic stirring bar. The The tube was purged with nitrogen three times, and then capped and stirred in a preheated oil bath at 110 C for 24 h. After the mixture was cooled to room temperature, concentrated in vacuum and purified by silica gel column chromatography by using petroleum ether and ethyl acetate (PE:EA=1:500) as eluent. |

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