Ammonia → 3,6-Dichloro-4-cyclobutylpyridazine

HRID 1369417

Reaction equation

HRID 1369417 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.[CH:14]1(C(O)=O)[CH2:17][CH2:16][CH2:15]1.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].N>O.[N+]([O-])([O-])=O.[Ag+]>[Cl:6][C:7]1[N:8]=[N:9][C:10]([Cl:13])=[CH:11][C:12]=1[CH:14]1[CH2:17][CH2:16][CH2:15]1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 19494Cyclobutanecarboxylic acidHCID 62648Ammonium PersulfateHCID 673313,6-Dichloropyridazine

Product 1

HCID 219732193,6-Dichloro-4-cyclobutylpyridazineYield 82%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent3×

Conditions

Temperature
70 °C

Procedure

Concentrated sulphuric acid (53.6 ml, 1.0 mol) was added carefully to a stirred suspension of 3,6-dichloropyridazine (50.0 g, 0.34 mol) in water (1.25 l). This mixture was then heated to 70° C. (internal temperature) before the addition of cyclobutane carboxylic acid (35.3 ml, 0.37 mol). A solution of silver nitrate (11.4 g, 0.07 mol) in water (20 ml) was then added over approximately one minute. This caused the reaction mixture to become milky in appearance. A solution of ammonium persulphate (230 g, 1.0 mol) in water (0.631) was then added over 20-30 minutes. The internal temperature rose to approximately 85° C. During the addition the product formed as a sticky precipitate. Upon complete addition the reaction was stirred for an additional 5 minutes, then allowed to cool to room temperature. The mixture was then poured onto ice and basified with concentrated aqueous ammonia, with the addition of more ice as required to keep the temperature below 10° C. The aqueous was extracted with dichloromethane (×3). The combined extracts were dried (MgSO4), filtered and evaporated to give the title compound (55.7 g, 82%) as an oil. 1H nmr (CDCl3) indicated contamination with approximately 5% of the 4,5-dicyclobutyl compound. However, this material was used without further purification. Data for the title compound: 1H NMR (360 MHz, d6-DMSO) δ1.79-1.90 (1H, m), 2.00-2.09 (1H, m), 2.18-2.30 (2H, m), 2.33-2.40 (2H, m), 3.63-3.72 (1H, m), 7.95 (1H, s); MS (ES+) m/e 203 [MH]+, 205 [MH]+, 207 [MH]30 .

Workup

  1. customrose to approximately 85° C
  2. additionDuring the addition the product
  3. customformed as a sticky precipitate
  4. additionUpon complete addition the reaction
  5. temperatureto cool to room temperature
  6. customthe temperature below 10° C
  7. extractionThe aqueous was extracted with dichloromethane (×3)
  8. dry with materialThe combined extracts were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-9488acc872e54dae966afc5b5c138db4
Source dataset
uspto-grants-2003_06
Patent number
US06579875B1

Linked notes

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