Phenetole → (2-Chloro-5-iodophenyl)(4-ethoxyphenyl)methanone

HRID 913346Notes

Reaction equation

HRID 913346 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[CH2:5]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:6].[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:16]=1[C:17](Cl)=[O:18]>ClCCl>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:16]=1[C:17]([C:11]1[CH:12]=[CH:13][C:8]([O:7][CH2:5][CH3:6])=[CH:9][CH:10]=1)=[O:18]

Participants

5

Reactant 3

HCID 7674PhenetoleHCID 47693022-Chloro-5-iodobenzoyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 57432783(2-Chloro-5-iodophenyl)(4-ethoxyphenyl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
6 °C

Procedure

A jacketed 2 L three-necked round bottom flask with mechanical stirrer, rubber septum with temperature probe and pressure-equalized addition funnel with gas bubbler was charged with aluminum chloride (97.68 g, 0.733 mol, 1.04 equiv), dichloromethane (0.65 L, KF=0.003 wt % water) and the suspension was set stirring under nitrogen and was cooled to about 6° C. Then ethoxybenzene (90 mL, 0.712 mol, 1.01 equiv) was added over 7 minutes keeping internal temperature below 9° C. The resulting orange solution was diluted with dichloromethane (75 mL) and was cooled to −7° C. Then a solution of 2-chloro-5-iodobenzoyl chloride (<0.706 mol) in 350 mL dichloromethane was added over 13 minutes keeping the internal temperature below +3° C. The reaction mixture was warmed slightly and held at +5° C. for 2 hours. HPLC analysis suggested the reaction was complete and the reaction was quenched into 450 mL pre-cooled (˜5° C.) 2N aq. HCl with stirring in a jacketed round bottom flask. This quench was done in portions over 10 min with internal temperature remaining below 28° C. The quenched biphasic mixture was stirred at 20° C. for 45 min and the lower organic phase was washed with 1 N aq. HCl (200 mL), twice with saturated aq. sodium bicarbonate (200 mL per wash), and with saturated aq. sodium chloride (200 mL). The washed extract was concentrated on a rotary evaporator to afford crude (2-chloro-5-iodophenyl)(4-ethoxyphenyl)methanone as an off-white solid (268.93 g, 99.0 area % by HPLC at 220 nm, 1.0 area % regioisomer at 200 nm, 98.5% “as-is” yield).

Workup

  1. customtemperature below 9° C
  2. temperaturewas cooled to −7° C
  3. customthe internal temperature below +3° C
  4. temperatureThe reaction mixture was warmed slightly
  5. customthe reaction was quenched into 450 mL
  6. temperaturepre-cooled (˜5° C.) 2N aq. HCl
  7. stirringwith stirring in a jacketed round bottom flask
  8. waitThis quench was done in portions over 10 min with internal temperature
  9. customremaining below 28° C
  10. stirringThe quenched biphasic mixture was stirred at 20° C. for 45 min
  11. washthe lower organic phase was washed with 1 N aq. HCl (200 mL), twice with saturated aq. sodium bicarbonate (200 mL per wash)
  12. extractionThe washed extract
  13. concentrationwas concentrated on a rotary evaporator
  14. customto afford

Sources & evidence

ORD record
ord-3a1bbaa4cd2c4ccb800e3085c6576d2f
Source dataset
uspto-grants-2011_09
Patent number
US08026347B2

Reaction notes

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