Thionyl Chloride → 2-(3-Methoxy-4-methyl-phenyl)vinylisocyanate

HRID 651602Notes

Reaction equation

HRID 651602 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11]C(O)=O)[CH:6]=[CH:7][C:8]=1[CH3:9].S(Cl)(Cl)=O.[N-:19]=[N+]=[N-].[Na+].O.[O:24]1[CH2:29]COCC1>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][N:19]=[C:29]=[O:24])[CH:6]=[CH:7][C:8]=1[CH3:9]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 218864351,4-Dioxane--water (1/1)HCID 534017143-Methoxy-4-methylcinnamic acid

Product 1

HCID 538573922-(3-Methoxy-4-methyl-phenyl)vinylisocyanate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

3-(3-Methoxy-4-methylphenyl)propenoic acid (5.33 g, 27.7 mmol) (prepared according to the procedure described in J. Med. Chem. 1991, 34, 1662-1668) is suspended in benzene (30 mL) and treated dropwise with thionyl chloride (2.22 mL, 30.5 mmol) at 0° C. The reaction is heated to reflux and it is maintained for 1 hour. The volatiles are removed in vacuo and the resulting solid is dissolved in dioxane and added dropwise to a mixture of sodium azide (3.6 g, 55.4 mmol) in water/dioxane (30 mL, 1:5) at 0° C. After stirring 1 hours, the solution is poured over ice-water, the precipitate is collected and washed with water. The solid is dried under vacuum over P2O5 (24 hours), dissolved in benzene (30 mL) and heated to reflux slowly over about 4 hours. The benzene is removed to give 2-(3-methoxy-4-methyl-phenyl)vinylisocyanate as a brown oil. The oil is taken up in o-dichlorobenzene, treated with iodine and heated to reflux for 3.5 hours. The volatiles are removed and the residue is mixed with 2.5% MeOH/CH2Cl2(10 mL), then allowed to stand overnight at room temperature. The resulting solid is collected washed with hexane and ether, and dried to give the title compound (2.67 g, 14.1 mmol).

Workup

  1. temperatureThe reaction is heated
  2. temperatureto reflux
  3. temperatureit is maintained for 1 hour
  4. customThe volatiles are removed in vacuo
  5. dissolutionthe resulting solid is dissolved in dioxane
  6. customthe precipitate is collected
  7. washwashed with water
  8. dry with materialThe solid is dried under vacuum over P2O5 (24 hours)
  9. dissolutiondissolved in benzene (30 mL)
  10. temperatureheated
  11. temperatureto reflux slowly over about 4 hours
  12. customThe benzene is removed

Sources & evidence

ORD record
ord-91f4f22a578849d4b480361704db53de
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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