Ammonium Chloride → (2-Chloro-5-nitro-phenyl)-(4-chloro-phenyl)-methanol

HRID 2092380Notes

Reaction equation

HRID 2092380 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:12]=1[CH:13]=[O:14].C(=O)=O.CC(C)=O.[NH4+].[Cl-]>C1COCC1>[Cl:10][C:11]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:12]=1[CH:13]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[OH:14]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 729332-Chloro-5-nitrobenzaldehydeHCID 18522661Acetone cardiceHCID 178478191HCID 178478191, compound

Product 1

HCID 58438156(2-Chloro-5-nitro-phenyl)-(4-chloro-phenyl)-methanolYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (4-chlorophenyl)magnesium bromide (1M in Et2O, 81 ml, 81 mmol) in THF (200 ml) was added drop wise a solution of 2-chloro-5-nitrobenzaldehyde (10 g, 53.9 mmol) in THF (100 ml) at −78° C. (dry ice/acetone bath). After the addition, the reaction mixture was further stirred at −78° C. for 1 h then 10 min at 0° C. (ice bath). A saturated aqueous NH4Cl solution (400 ml) was added and the resulting mixture was extracted with AcOEt (2×400 ml). The combined organic layers were washed with brine then dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/TBME 95:5→6:4) to yield the title compound (14.4 g, 48.4 mmol, 90%) as a beige solid. TLC: RF=0.80 (heptane/DCM/TBME 1:1:2); HPLC: AtRet=2.43 min; LC-MS: m/z not detected; 1H NMR (400 MHz, CDCl3): 6.20 (s, 1H), 7.36 (s, 4H), 7.53 (d, J=8.6, 1H), 8.13 (dd, J=8.8, 2.9, 1H), 8.66 (d, J=2.7, 1H).

Workup

  1. additionAfter the addition
  2. custom10 min
  3. customat 0° C.
  4. extractionthe resulting mixture was extracted with AcOEt (2×400 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialthen dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/TBME 95:5→6:4)

Sources & evidence

ORD record
ord-1a76bb5a95a446efae763aba4db57377
Source dataset
uspto-grants-2013_05
Patent number
US08440693B2

Reaction notes

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