Ammonia → 4-(Bicyclo[2.2.1]hept-1-yl)-3,6-dichloropyridazine

HRID 380317Notes

Reaction equation

HRID 380317 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[N:8]=[N:9][C:10]([Cl:13])=[CH:11][CH:12]=1.[C:14]12(C(O)=O)[CH2:20][CH:17]([CH2:18][CH2:19]1)[CH2:16][CH2:15]2.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].N>O.[N+]([O-])([O-])=O.[Ag+]>[C:14]12([C:12]3[CH:11]=[C:10]([Cl:13])[N:9]=[N:8][C:7]=3[Cl:6])[CH2:20][CH:17]([CH2:18][CH2:19]1)[CH2:16][CH2:15]2

Participants

8

Reactant 5

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 62648Ammonium PersulfateHCID 673313,6-DichloropyridazineHCID 140414Bicyclo(2.2.1)heptane-1-carboxylic acid

Product 1

HCID 183649464-(Bicyclo[2.2.1]hept-1-yl)-3,6-dichloropyridazineYield 98.7%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent3×

Conditions

Temperature
70 °C

Procedure

Concentrated sulphuric acid (2.17 ml, 40 mM) was added carefully to a suspension of 3,6-dichloropyridazine (2.11 g, 14.3 mM) in water (50 ml). This mixture was then heated to 70° C. and bicyclo[2.2.1]heptane-1-carboxylic acid (Org. Synth., 59, 85; 2.0 g, 14.3 mM) was added. After ten minutes a solution of silver nitrate (0.48 g, 2.8 mM) in water (5 ml) was added dropwise over two minutes. A solution of ammonium persulphate (9.8 g, 43 mM) in water (20 ml) was added over 20 minutes. The reaction was heated at 70° C. for a further 40 minutes and then allowed to cool to room temperature. The mixture was poured onto ice and basified with concentrated aqueous ammonia; the temperature was kept below 10° C. by addition of more ice. The aqueous phase was extracted with dichloromethane (3×200 ml) and the combined extracts were dried (MgSO4), filtered and evaporated to give the crude product, which was purified by column chromatography using ethyl acetate/hexane mixtures as the eluent to give the title compound (3.4 g). 1H NMR (250 MHz, CDCl3) δ1.49-2.00 (8H, m), 2.17 (2H, m), 2.43 (1H, m), 7.45 (1H, s); MS (ES+) m/e 244 [MH]+.

Workup

  1. temperatureThe reaction was heated at 70° C. for a further 40 minutes
  2. temperatureto cool to room temperature
  3. additionthe temperature was kept below 10° C. by addition of more ice
  4. extractionThe aqueous phase was extracted with dichloromethane (3×200 ml)
  5. dry with materialthe combined extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product, which
  9. customwas purified by column chromatography

Sources & evidence

ORD record
ord-f136de486a904972a2deea84bad56575
Source dataset
uspto-grants-2001_10
Patent number
US06303597B1

Reaction notes

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