3-Nitrosalicylic acid → 3-Aminosalicylamide

HRID 379347

反応式

HRID 379347 の反応式
OC1C([N+]([O-])=O)=CC=CC=1C(O)=O.S(Cl)(Cl)=O.[N+:18]([C:21]1[CH:29]=[CH:28][CH:27]=[C:23]([C:24]([NH2:26])=[O:25])[C:22]=1[OH:30])([O-])=O.[S]>CN(C)C1C=CN=CC=1.[Ni].[Pd].C(N(CC)CC)C>[NH2:18][C:21]1[CH:29]=[CH:28][CH:27]=[C:23]([C:24]([NH2:26])=[O:25])[C:22]=1[OH:30]

参加物

9

反応物 4

HCID 68073-Nitrosalicylic acidHCID 24386Thionyl ChlorideHCID 5362487SulfurHCID 112753922-Hydroxy-3-nitrobenzamide

生成物 1

HCID 113785963-Aminosalicylamide

試薬・触媒・溶媒 4

HCID 935Nickel触媒HCID 142844-(Dimethylamino)pyridine触媒HCID 23938Palladium触媒HCID 8471Triethylamine溶媒

実験手順

A preferred synthesis of the desired product acylated aminosalicylamides (Formula I) is shown in the following Scheme 1. 2-Hydroxy-3-nitrobenzoic acid 1 was converted to the acid chloride 2 with excess thionyl chloride. After removal of the excess thionyl chloride, the crude acid chloride 2 was reacted with the desired cyclic amine 3 in dichloromethane solution containing triethylamine as an acid scavenger and 4-dimethylaminopyridine (DMAP) as a catalyst. Crude 3-nitrosalicylamide 4 could be isolated after washing the reaction mixture with dilute HCl solution, drying, and evaporation of the solvent. Usually 4 was of sufficient purity to carry forward to the final product 6, but if desired could be purified by recrystallization or chromatography or a combination of both. In some cases where the 3-nitrosalicylamide 4 is a mixture of diastereomers, one might choose to isolate the individual diastereomers at this stage. However, since all of the various diastereomers are fuigicidally active, this is not necessary. The 3-nitrosalicylamide (4) was subsequently reduced under catalytic hydrogenation conditions using Pd, Pt, or Ni catalysts either unpoisoned or poisoned with sulfur or lead. The 3-aminosalicylamide 5 usually was not isolated, but immediately reacted with excess acetic-formic anhydride. Isolation of the AASA product 6 was a simple matter of filtration, washing with sodium bicarbonate solution, drying and evaporation of the solvent The crude product 6, usually a solid foam or glass, often was of sufficient purity to be directly submitted for testing. However, if desired, it could be further purified by recrystallization or chromatography or a combination of both.

後処理

  1. customAfter removal of the excess thionyl chloride
  2. customthe crude acid chloride 2 was reacted with the desired cyclic amine 3 in dichloromethane solution
  3. customCrude 3-nitrosalicylamide 4 could be isolated
  4. washafter washing the reaction mixture with dilute HCl solution
  5. customdrying
  6. customevaporation of the solvent
  7. customif desired could be purified by recrystallization or chromatography
  8. additiona mixture of diastereomers, one
  9. customto isolate the individual diastereomers at this stage

出典と根拠

ORDレコード
ord-97bbca9c62ef4e11a7eb3d947be86904
出典データセット
uspto-grants-2001_10
特許番号
US06297401B1

関連ノート

読み込み中…