Oxygen → N-[4-(3-Amino-4-nitrophenoxy)phenyl]acetamide

HRID 1294051Notes

Reaction equation

HRID 1294051 reaction equation
O=O.[C:3]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:5])[CH3:4].Cl[C:15]1[CH:16]=[CH:17][C:18]([N+:22]([O-:24])=[O:23])=[C:19]([CH:21]=1)[NH2:20].[H-].[Na+]>CN(C=O)C>[C:3]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:15]2[CH:16]=[CH:17][C:18]([N+:22]([O-:24])=[O:23])=[C:19]([CH:21]=2)[NH2:20])=[CH:9][CH:8]=1)(=[O:5])[CH3:4]

Participants

6

Reactant 4

HCID 977OxygenHCID 1983AcetaminophenHCID 24758Sodium hydrideHCID 742185-Chloro-2-nitroaniline

Product 1

HCID 13705240N-[4-(3-Amino-4-nitrophenoxy)phenyl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compounds of Formula (I), wherein R3 is —C(O)OCH3, A is phenyl, and X and Z are oxygen, D and T are CH, M is C, Q is N(R7)p, either p or q is 1, and the other is 0, can be prepared according to the synthetic sequence shown in Scheme 1 and further detailed in the Examples section following. 4-Acetamidophenol (1) in DMF is reacted with 5-chloro-2-nitroaniline (2) in the presence of 60% NaH to provide 5-(4-acetamidophenoxy)-2-nitroaniline (3). The nitroaniline (3) is then refluxed with Na2S2O4 to provide 4-(4-acetamidophenoxy)phenylene-1,2-diamine (4). (It is understood that reduction of nitro group of (3) can be effected in many ways, for example by use of H2, Pd/C; Raney Nickel with hydrazine; SnCl4 in HCl; etc.) Diamine (4) is refluxed with 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea in ethanol and the acetylated carbamate (5) is obtained. HCl is added to deacetylate the carbamate (5) to give methyl (5-(4-aminophenoxy)-1H-benzimidazol-2-yl)carbamate (7). Alternatively, carbamate (7) may be prepared by refluxing 3,4,4′-triaminodiphenylether (6) with 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea and then treating with conc. HCl to give carbamate (7). Carbamate (7) is then reacted with the appropriate phenyl isocyanate (8) to give the resultant benzimidazole (9) of the present invention. It is understood that R1 and R2 are as described above. When X of Formula (I) is sulfur and Z of Formula (I) is oxygen, the final compounds are obtained by following the same procedure using a phenylthiol derivative of 1. When X of Formula (I) is sulfur, the compound thus obtained can be oxidized with MCPBA (metachloroperbenzoic acid) to give compounds containing sulfone (SO2) or sulfine (SO) as X. Also, when 3-(3-substitutedphenyl)aminocarbonylamino)phenoxy derivatives of Formula 1 are prepared, 3-acetamidophenol is utilized instead of 4-acetamidophenol.

Workup

  1. customcan be prepared

Sources & evidence

ORD record
ord-a9d9abf345964295afaba69909efd13a
Source dataset
uspto-grants-2007_07
Patent number
US07238813B2

Reaction notes

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