Benzimidazole 2-phenylsulfonyl

Phenylsulfonyl-1,3-dihydrospiro[2//-benzimidazole-2, l -cyclohexan]-5-amine (601) gave 7-phenylsulfonyl-6-quinoxalinamine (602) [Me0H-H20, 60°C, 20 min then (CH0)2-NaHS02i, 95°C, 5 min 55% clearly a two-stage one-pot synthesis via the unisolated intermediate shown] 7-morpholino-6-... 

Most fused benzene rings are stable toward nucleophilic attack but exceptions are known for highly electron-deficient benzazoles having o-quinonoid structures. Thus, sulfur nucleophiles attack 27/-benzimidazole-2-spirocyclohexane 556 via an initial Michael-type 1,4-conjugate addition, followed by a prototropic shift in the adduct 557. When the nucleophile is electron withdrawing (e.g., phenylsulfonyl), 1,3-dihydro products 558 are isolated. If the nucleophile is electron donating, the adducts are oxidized in situ to 559. 

The parent compound is so reactive towards thiols that up to four sulfur groups can be introduced. In isopropanol at — 10°C, however, the monosuhstituted compounds (109) (Nu = PhS) can be made in reasonable yield. Further nucleophilic substitution of 5-nitro and 5-phenylsulfonyl derivatives occurs at the 4- and 6-positions the 1,3-dihydro products are isolated <92JCS(PI)685>. Conditions have been devised for substitution of one or two chlorines in 5,6-dichloro-2Ff-benzimidazoles using amines, thiolate, or oxyanionic nucleophiles in ethanol <88S87i>. Indeed nucleophilic displacements of hydrogen are not uncommon (Scheme 57) <90HCA902>. 

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