Acetophenone → 2-Bromophenyl methyl phenyl carbinol

HRID 2101529Notes

Reaction equation

HRID 2101529 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[Br:8].[Li]CCCC.[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])[CH3:15]>C1COCC1.CCCCCC>[Br:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([OH:16])[CH3:15]

Participants

6

Reactant 3

HCID 7410AcetophenoneHCID 114141,2-DibromobenzeneHCID 178418339Butyllithium

Product 1

HCID 129377442-Bromophenyl methyl phenyl carbinolYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A microsystem composed of three T-shaped micromixers (M1, M2 and M3) and two microtube reactors (R1 and R2) was used. The whole microsystem was dipped in a cooling bath (−78° C.). A solution of o-dibromobenzene (0.27 M) in THF (flow rate: 6 mL/min, 1.62 mmol/min) and a solution of n-BuLi (1.5 M) in n-hexane (flow rate: 1.2 mL/min, 1.8 mmol/min) were introduced to the first T-shaped mixer M1 (inner diameter: 250 μm) by using syringe pumps. The resulting solution was passed through the tube reactor R1 and was mixed with acetophenone (0.65 M) in THF (flow rate: 3 mL/min, 1.95 mmol/min) in the second T-shaped mixer M2 (inner diameter: 500 μm). The solution was introduced to the third T-shaped mixer M3 (inner diameter: 500 μm), where the solution was quenched with methanol (neat, flow rate=3.0 mmol/min). The residence time of the tube reactor R1 (inner diameter: 500 μm, length=50 cm) was 0.82 second. The residence time of the tube reactor R2 (inner diameter: 1,000 μm, length=75 cm) was 3.46 second. After finishing the reaction, an aliquot of the product solution was taken (15 sec) and was analyzed by GC (column, CBP1; 0.25 mm×25 m; initial oven temperature, 50° C.; rate of temperature increase, 10° C./min). As a result, 1-(2-bromophenyl)-1-phenylethanol (GC retention time: 23.5 min) was obtained in 81% yield. 1H NMR (400 MHz, CDCl3) δ: 1.95 (s, 3H), 3.49 (s, 1H), 7.16 (dt, J=7.6, 1.6 Hz, 1H), 7.20-7.30 (m, 5H), 7.38 (dt, J=7.6, 1.2 Hz, 1H), 7.52 (dd, J=8.0, 1.2 Hz, 1H), 7.80 (dd, J=7.6, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 30.4, 77.4, 122.2, 125.4, 126.7, 127.2, 128.0, 128.3, 129.0, 134.7, 144.7, 147.4. HRMS (EI) m/z: calcd. for C14H13BrO 276.0150, found 276.0155.

Workup

  1. customThe whole microsystem was dipped in a cooling bath
  2. custom(−78° C.)
  3. additionThe solution was introduced to the third T-shaped mixer M3 (inner diameter: 500 μm), where the solution
  4. customwas quenched with methanol (neat, flow rate=3.0 mmol/min)
  5. waitThe residence time of the tube reactor R2 (inner diameter: 1,000 μm, length=75 cm) was 3.46 second
  6. customthe reaction
  7. custom(15 sec)
  8. customtemperature, 50° C.
  9. temperaturerate of temperature increase

Sources & evidence

ORD record
ord-088930ca2d404b65ba7a3c943309ff33
Source dataset
uspto-grants-2009_08
Patent number
US07572927B2

Reaction notes

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