(4-BROMOBENZYL)DIMETHYLAMINE

(4-BROMOBENZYL)DIMETHYLAMINE Property

Melting point:

165-167 °C

Boiling point:

121-122 °C(Press: 20 Torr)

Density 

1.320±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

form 

liquid

pka

8.56±0.28(Predicted)

color 

Clear, colourless

Safety

Hazard Codes 

Xi

Hazard Note 

Irritant

HS Code 

2921490090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

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

(4-BROMOBENZYL)DIMETHYLAMINE Chemical Properties,Usage,Production

Synthesis

1. In a flask containing 50% aqueous diethylamine (500 mmol) and K2CO3 (50 mmol), a solution of 4-bromobenzyl bromide (50 mmol) in THF (90 mL) was added slowly and dropwise. The reaction mixture was stirred at 60 °C under Ar atmosphere for 24 hours. After completion of the reaction, water (60 mL) was added and extracted with CHCl3 (100 mL x 3). The organic layers were combined, dried with Na2SO4, filtered and concentrated under reduced pressure to give 4-bromobenzyl dimethylamine in 99% yield (boiling point 55 °C/1 mmHg). 2. Mg (40 mmol) was dried with a vacuum pump at 70 °C for 20 min. To the dried Mg was added a solution of 4-bromobenzyldimethylamine (30 mmol) in anhydrous THF (70 mL) and stirred for 1 h at room temperature under Ar atmosphere. Subsequently, anhydrous THF (30 mL) solution of chlorodiphenylphosphine (30 mmol) was slowly added at 0°C and stirred at room temperature for 2 hours. At the end of the reaction, the mixture was filtered and washed with dichloromethane. To the filtrate was added a 30% aqueous solution of H2O2 (60 mmol) at 0 °C and stirred for 1 h at room temperature. After completion of the reaction, the reaction was quenched with water (100 mL) and extracted with chloroform (50 mL x 3). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. To the residue, diethyl ether (300 mL) was added, stirred for 0.5 h to dissolve the product, filtered and concentrated under reduced pressure to give 4-(diphenylphosphinyl)benzyldimethylamine in 95% yield. 3. To a flask containing anhydrous 1,2-dimethoxyethane (200 mL) solution of 4-(diphenylphosphinoyl)benzyldimethylamine (60 mmol) was added dimethyl sulfate (120 mmol) at 0 °C. The mixture was mixed with a mixture of 2,2-dimethoxyethane (200 mL) and 4-(diphenylphosphinoyl)benzyldimethylamine (60 mmol). The mixture was stirred at 50 °C under Ar atmosphere for 1 hour. Subsequently, LiAlH4 (180 mmol) was added at 0 °C and stirred at room temperature for 2 hours. Upon completion of the reaction, it was quenched with ice, then quenched with 1 M aqueous HBr solution (200 mL) and washed with ether (200 mL x 2). The aqueous phase was extracted with dichloromethane (100 mL x 3), the organic layers were combined, dried with Na2SO4, filtered and concentrated under reduced pressure. To the residue, diethyl ether (300 mL) was added, stirred under Ar atmosphere for 0.5 h. 4-(Diphenylphosphino)benzyltrimethylammonium bromide was obtained by filtration in 79% yield.

References

[1] Tetrahedron, 2010, vol. 66, # 19, p. 3421 - 3426
[2] Tetrahedron, 2013, vol. 69, # 19, p. 3971 - 3977
[3] Chemical Communications, 2012, vol. 48, # 63, p. 7823 - 7825
[4] Journal of Organic Chemistry, 2016, vol. 81, # 18, p. 8520 - 8529
[5] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2667 - 2677