Formamide → Formamide, N-(diphenylmethyl)-N-methyl-

HRID 1722429Notes

Reaction equation

HRID 1722429 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][C:4](C(Cl)=O)=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH:15]([O-:17])=O.[NH4+].[CH:19]([NH2:21])=O.[N+]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([O-])=O>ClC(Cl)C.C(O)=O>[CH:15]([N:21]([CH3:19])[CH:10]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:17]

Participants

8

Reactant 5

HCID 713FormamideHCID 7416NitrobenzeneHCID 134054-Methylbenzoyl ChlorideHCID 2723923Ammonium formateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 4321794Formamide, N-(diphenylmethyl)-N-methyl-

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 63651,1-DichloroethaneSolvent

Procedure

15.5 g of p-toluoyl chloride and 13.3 g of aluminum chloride were mixed in 250 ml of dichloroethane in a dropping funnel. The solution was added dropwise to the cooled, stirred suspension of the resin beads over a period of about 40 min., care being taken not to allow the reaction to warm up above 5° C. The stirring was continued for 4 hours at room temperature when the resin was washed sequentially with isopropanol, isopropanol-water (1:1 mixture), isopropanol and dried to give 53.8 g of p-toluoyl resin. This resin was then mixed with 168 g of ammonium formate, 201 ml of formamide, 134 ml of formic acid and 350 ml of nitrobenzene. The mixture was gradually heated up to 165°-170° C. under reflux and maintained for 1 day during which time about 115 ml of the aqueous phase was collected into a Dean-Stark trap. The resin was washed and dried as above to yield 55.5 g of N-formyl methylbenzhydrylamine resin. The product was hydrolyzed in a mixture of 300 ml each of 12N HCl and isopropanol under reflux for 3 hr. Washing and drying the resulting resin provided 54.9 g of the hydrochloride form of methylbenzhydrylamine resin. It showed a very strong positive reaction to ninhydrin reagent and incorporated 0.4 mmol of Boc-Ala-OH when neutralized and coupled with Boc-Ala-OH in the presence of dicyclohexylcarbodiimide.

Workup

  1. additionThe solution was added dropwise to the cooled
  2. additionsuspension of the resin
  3. customthe reaction
  4. temperatureto warm up above 5° C
  5. waitThe stirring was continued for 4 hours at room temperature
  6. washwhen the resin was washed sequentially with isopropanol, isopropanol-water (1:1 mixture), isopropanol
  7. customdried
  8. customto give 53.8 g of p-toluoyl resin
  9. temperatureThe mixture was gradually heated up to 165°-170° C.
  10. temperatureunder reflux
  11. customwas collected into a Dean-Stark trap
  12. washThe resin was washed
  13. customdried as above

Sources & evidence

ORD record
ord-2c611b5f47b04d07aa168a7651fd66e2
Source dataset
uspto-grants-1989_08
Patent number
US04855407

Reaction notes

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