Iodine → Benzo[b]thiophene-6-sulfonic acid benzhydrylamide

HRID 1986205Notes

Reaction equation

HRID 1986205 reaction equation
[Mg].II.Br[C:5]1[CH:6]=[CH:7][C:8]2[CH:12]=[CH:11][S:10][C:9]=2[CH:13]=1.[S:14](=[O:16])=[O:15].ClN1C(=O)CCC1=O.[NH2:25][CH:26]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1.ClCCl.O.C1(C)C=CC=CC=1>[CH:26]([NH:25][S:14]([C:5]1[CH:6]=[CH:7][C:8]2[CH:12]=[CH:11][S:10][C:9]=2[CH:13]=1)(=[O:16])=[O:15])([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

11

Reactant 6

HCID 807IodineHCID 1119Sulfur Dioxide2×HCID 7036BenzhydrylamineHCID 31398ChlorosuccinimideHCID 5462224MagnesiumHCID 127444006-Bromo-benzo[b]thiophene

Product 1

HCID 68857528Benzo[b]thiophene-6-sulfonic acid benzhydrylamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
68 °C

Procedure

To a suspension of magnesium (1.14 g, 46.9 mmol) in dry THF (50 mL) is added iodine (100 mg) followed by slow addition of 6-bromobenzo[b]thiophene (5.00 g, 23.5 mmol) in dry THF (100 mL) at 64° C. (internal temperature) under a nitrogen atmosphere. During the addition, dry toluene (20 mL) is added to the mixture. When addition is completed, the mixture is heated at 68° C. (internal temperature) for 3 hours then cooled to −60° C. where a stream of sulfur dioxide is passed through the solution for 10 minutes. The mixture is allowed to warm to room temperature, the sulfur dioxide bubbling continues for an additional 5 minutes, and the mixture is stirred for 45 minutes. After filtration and concentration, a reddish solid is obtained (8.0 g), which is diluted with dichloromethane (235 mL), treated with N-chlorosuccinimide (3.45 g, 25.8 mmol) at room temperature, and stirred for 2 hours. After filtration and concentration, a reddish solid is obtained (5.8 g), which is diluted with dichloromethane (234 mL), treated with aminodiphenylmethane (20.2 mL, 117 mmol) at 0° C. and the mixture is stirred for 1 hour. Water (200 mL) is added and the mixture is extracted with dichloromethane (3×200 mL). The organic layers are dried (MgSO4) and concentrated. The crude product is suspended in dichloromethane/hexane before it is filtered to give the title compound as a white solid. The filtrate is concentrated and the residue is chromatographed on silica gel (dichloromethane) to give a second crop of title compound (total 2.52 g). ES+(m/z) 378 [M−H].

Workup

  1. additionis added to the mixture
  2. additionWhen addition
  3. temperatureto warm to room temperature
  4. filtrationAfter filtration and concentration
  5. customa reddish solid is obtained (8.0 g), which
  6. stirringstirred for 2 hours
  7. filtrationAfter filtration and concentration
  8. customa reddish solid is obtained (5.8 g), which
  9. stirringthe mixture is stirred for 1 hour
  10. extractionthe mixture is extracted with dichloromethane (3×200 mL)
  11. dry with materialThe organic layers are dried (MgSO4)
  12. concentrationconcentrated
  13. filtrationis filtered

Sources & evidence

ORD record
ord-a07a2b91fb6c4f6a991d2ccb59ded157
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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