Sodium Cyanide → Mefenidil

HRID 839131Notes

Reaction equation

HRID 839131 reaction equation
Cl.Cl[CH2:3][C:4]1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][C:8]=1[CH3:9].[C-:16]#[N:17].[Na+]>CS(C)=O.O>[C:16]([CH2:3][C:4]1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][C:8]=1[CH3:9])#[N:17]

Participants

5

Reactant 2

HCID 8929Sodium Cyanide2×HCID 22563401HCID 22563401, compound

Product 1

HCID 65475Mefenidil

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

A solution of 48.6 g (0.2 mole) of 4-chloromethyl-5-methyl-2-phenylimidazole hydrochloride [see Cornforth & Huang, J. Chem. Soc., 731 (1948)] in 200 ml of DMSO is added (over 20 minutes) to a rapidly stirred solution of sodium cyanide, prepared by dissolving 29.4 g (0.6 mole) of sodium cyanide in 70 ml of water and adding 200 ml of DMSO, at 0° to 5° C. [slightly modified procedure of W. Schultze, J. Prakt. Chem. 19, 91-100 (1922)]. The reaction mixture is stirred in the cold for 2 hours and then poured onto a slight excess of cracked ice which causes a semicrystalline gum to separate (Crop A). The gum is quickly filtered off and to the filtrate is added sufficient aqueous sodium carbonate (10%) to give a volume of 2 liters. The mixture is allowed to stand overnight during which time a second crop (about 12-13 g) crystallizes (Crop B). Extraction of the mother liquor with ethyl acetate gives an aditional (about 2-3 g) yield (Crop C). Crop A is recrystallized from benzene-Norite B. Crop C is recrystallized from benzene. The resulting crystals are combined with Crop B. Repeated recrystallizations from benzene gives a pure product of 4-cyanomethyl-5-methyl-2-phenylimidazole, m.p., 132°-140° C. Treatment with a mineral acid, e.g., sulfuric, hydrobromic and the like, affords the corresponding acid addition salts.

Workup

  1. customprepared
  2. customat 0° to 5° C.
  3. additionpoured onto a slight excess of cracked ice which
  4. customto separate (Crop A)
  5. filtrationThe gum is quickly filtered off and to the filtrate
  6. additionis added sufficient aqueous sodium carbonate (10%)
  7. customto give a volume of 2 liters
  8. waitto stand overnight during which time
  9. customa second crop (about 12-13 g) crystallizes (Crop B)
  10. extractionExtraction of the mother liquor with ethyl acetate
  11. customgives an aditional (about 2-3 g)
  12. customyield (Crop C)
  13. customCrop A is recrystallized from benzene-Norite B
  14. customCrop C is recrystallized from benzene
  15. customrecrystallizations from benzene

Sources & evidence

ORD record
ord-b804102c620a4f2da4c3293dfe1d0596
Source dataset
uspto-grants-1978_06
Patent number
US04093811

Reaction notes

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