3-Methoxybenzyl chloride

3-Methoxybenzyl chloride Property

Melting point:

101.67°C

Boiling point:

124 °C13 mm Hg(lit.)

Density 

1.078 g/mL at 25 °C(lit.)

refractive index 

n20/D 1.544(lit.)

Flash point:

215 °F

storage temp. 

2-8°C

solubility 

Chloroform, Methanol (Slightly)

form 

clear liquid

color 

Colorless to Light yellow

Specific Gravity

1.157 (20/4℃)

Sensitive 

Moisture Sensitive

BRN 

636684

InChIKey

VGISFWWEOGVMED-UHFFFAOYSA-N

CAS DataBase Reference

824-98-6(CAS DataBase Reference)

NIST Chemistry Reference

«alpha»-Chloro-3-methoxytoluene(824-98-6)

Safety

Hazard Codes 

C

Risk Statements 

34

Safety Statements 

26-36/37/39-45

RIDADR 

UN 3265 8/PG 2

WGK Germany 

1

F 

19-21

HazardClass 

8

PackingGroup 

III

HS Code 

29093090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H314Causes severe skin burns and eye damage

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P330+P331IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P363Wash contaminated clothing before reuse.

3-Methoxybenzyl chloride Chemical Properties,Usage,Production

Chemical Properties

clear colorless to light yellow liquid

Uses

3-Methoxybenzyl chloride was used to alkylate 8-benzyloxy-2(1H)-quinolinone in the presence of DMF and NaH. It was also used in the synthesis of diarylmethanes via in situ organozinc-mediated, palladium-catalyzed cross-coupling between benzyl and aryl halide.

Application

3-Methoxybenzyl chloride is used for protection of alcohols, thiols, phenols, amides, amines, and carboxylic acids.

Synthesis

General procedure for the synthesis of 3-methoxybenzyl chloride from m-methoxybenzyl alcohol: 3-methoxybenzyl alcohol (248 μL, 2.0 mmol) and triethylamine (335 μL, 2.4 mmol) were dissolved in dichloromethane (DCM, 7 mL). Thionyl chloride (218 μL, 3.0 mmol) was added slowly. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was washed with 1N HCl aqueous solution. The organic phase was dried with anhydrous magnesium sulfate (MgSO?). The solvent was removed under reduced pressure to give the target product 3-methoxybenzyl chloride (313 mg, 100%) as a yellow oil. Next, 4-(4-chlorophenyl)-1-(2-methoxyethyl)-6-methyl-2-oxo-3,4-dihydropyridine-5-carboxylic acid (Example 74, 85 mg, 0.26 mmol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 1 mL), followed by addition of cesium carbonate (169 mg, 0.52 mmol) and 3-methoxybenzyl chloride ( 81 mg, 0.52 mmol). The reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (EtOAc) and water. The aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine and dried with anhydrous magnesium sulfate (MgSO?). The solvent was removed under reduced pressure. The crude product was purified by fast chromatography using a mixture of cyclohexane/ethyl acetate (8:2) as eluent to afford the target product (3-methoxyphenyl)methyl 4-(4-chlorophenyl)-1-(2-methoxyethyl)-6-methyl-2-oxo-3,4-dihydropyridine-5-carboxylate as a pale yellow oil (11 mg, 9%). Product characterization data: 1H NMR (300 MHz, CDCl?) δ 2.62 (s, 3H), 2.71 (dd, J = 15.8, 2.2 Hz, 1H), 2.92 (dd, J = 15.8, 7.5 Hz, 1H), 3.31 (s, 3H), 3.37 (ddt, J = 10.0, 8.5, 3.6 Hz, 1H). 3.46 (dt, J = 10.0, 4.1 Hz, 1H), 3.70-3.79 (m, 4H), 4.13-4.23 (m, 2H), 5.04 (d, J = 12.7 Hz, 1H), 5.11 (d, J = 12.7 Hz, 1H), 6.64 (s, 1H), 6.70 (d, J = 7.5 Hz, 1H), and 6.81 (dd, J = 8.2, 2.5 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 7.16-7.23 (m, 3H). Mass spectrum (MS): [M + H]? m/z 444. high-resolution mass spectrum (HRMS): calculated value of C??H??N?Cl, [M + H]? 444.1578, measured value 444.1579.

storage

3-Methoxybenzyl chloride is stored over K2CO3 to stabilize it.

References

[1] Patent: WO2016/16238, 2016, A1. Location in patent: Page/Page column 126-127
[2] Organic Process Research and Development, 2016, vol. 20, # 2, p. 568 - 573
[3] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 19, p. 8889 - 8895
[4] Journal of Organic Chemistry, 1998, vol. 63, # 25, p. 9565 - 9568
[5] Australian Journal of Chemistry, 1992, vol. 45, # 1, p. 71 - 97