Ammonia → 5-(Aminomethyl)nicotinonitrile

HRID 359681ノート

反応式

HRID 359681 の反応式
O[CH2:2][C:3]1[CH:4]=[C:5]([C:9]#[N:10])[CH:6]=[N:7][CH:8]=1.Cl.S(Cl)(Cl)=O.[NH3:16]>C(OCC)C.C1C=CC=CC=1.CO>[NH2:16][CH2:2][C:3]1[CH:4]=[C:5]([C:9]#[N:10])[CH:6]=[N:7][CH:8]=1

参加物

8

反応物 4

HCID 222Ammonia2 回HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 224165405-(Hydroxymethyl)nicotinonitrile

生成物 1

HCID 200639425-(Aminomethyl)nicotinonitrile収率 64%

試薬・触媒・溶媒 3

HCID 241Benzene溶媒HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
23 °C

実験手順

A solution of 5-hydroxymethyl-3-pyridinecarbonitrile (4.39 g, 32.7 mmol) in diethyl ether (250 mL) at 23° C. was saturated with gaseous HCl. Solvent was then removed in vacuo and the residue was suspended in thionyl chloride (14.3 mL, 196 mmol). The mixture was then heated at reflux for 2 hours, cooled to 23° C., and diluted with benzene (150 mL). The tan precipitate was isolated by filtration, transferred to a pressure reactor, and dissolved in methanol (30 mL). The methanolic solution was saturated with gaseous ammonia, sealed in the reaction vessel, and heated with stirring at 80° C. for 2.5 hours. After cooling to 23° C., the solution was again saturated with gaseous ammonia, sealed in the vessel, and heated at 80° C. for 5 hours. The reaction mixture was then concentrated in vacuo, and the residue was diluted with aqueous 0.5M NaOH (60 mL). The aqueous layer was extracted with chloroform (3×60 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to provide 5-aminomethyl-3-pyridinecarbonitrile (2.79 g, 21.0 mmol, 64% yield): Rf 0.19 (20% MeOH in EtOAc); 1H NMR (DMSO-D6, 200 MHz)δ8.88 (dd, J=7,2 Hz, 1H), 8.79 (m, 1H), 8.25 (d, J=7 Hz), 3.75 (s, 2H), 2.8 (br s, 2H).

後処理

  1. customat 23° C.
  2. customSolvent was then removed in vacuo
  3. temperatureThe mixture was then heated
  4. temperatureat reflux for 2 hours
  5. customThe tan precipitate was isolated by filtration
  6. customtransferred to a pressure reactor
  7. customsealed in the reaction vessel
  8. temperatureheated
  9. temperatureAfter cooling to 23° C.
  10. customsealed in the vessel
  11. temperatureheated at 80° C. for 5 hours
  12. concentrationThe reaction mixture was then concentrated in vacuo
  13. additionthe residue was diluted with aqueous 0.5M NaOH (60 mL)
  14. extractionThe aqueous layer was extracted with chloroform (3×60 mL)
  15. dry with materialThe combined organic extracts were dried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-82c6a667f236419fb21e13ca1a8d9513
出典データセット
uspto-grants-1991_03
特許番号
US05002949

反応ノート

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