Dopamine → N,N'-Dicyclohexylurea

HRID 1975225Notes

Reaction equation

HRID 1975225 reaction equation
[CH:1]1([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.NCCC1C=CC(O)=C([OH:22])C=1>CN(C)C1C=CN=CC=1.O1CCCC1.CCCCCC.C1C=CC=CC=1>[CH:10]1([NH:9][C:8](=[O:22])[NH:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

7

Reactant 2

HCID 681DopamineHCID 10868Dicyclohexylcarbodiimide2×

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 241BenzeneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

DHA is first converted to DHA anhydride in the presence of dicyclohexyl carbodiimide. This is then reacted with dopamine in the presence of 4-dimethylaminopyridine as the acid acceptor in tetrahydrofurane. In a typical experiment, 300 mg of DHA (0.009M) was dissolved in a mixture of 3 ml hexane and 4 ml benzene and stirred under nitrogen. Subsequently, a solution of 0.00615M of dicyclohexyl carbodiimide in 4 ml benzene (0.1267 g) was stirred together with the DHA for 3 hours at room temperature. A white precipitate of dicyclohexyl urea formed as the reaction proceeded. The dicyclohexyl urea was filtered off to give a clear solution of the anhydride in benzene. This solution was concentrated down to 2 ml in a rotary evaporator and diluted with 10 ml of tetrahydrofurane (dry). The freshly prepared anhydride was then added to a solution of dopamine hydrobromide (0.1053 g) (or 0.0005M) in the presence of 0.009M of 4-diethylaminopyridine (0.098 g). After stirring for thirty minutes at room temperature the initially cloudy mixture changed to a mixture of a clear liquid and a brown precipitate. At the end of the reaction, 0.2 ml of water was added to the mixture, and stirring was continued for an additional thirty minutes to completely hydrolyze any remaining unreacted anhydride. The liquid phase was isolated and evaporated to dryness to yield a brown viscous solid. This was then dissolved in a solution of 70% ethanol in water (25 ml), and the solution was then passed through a mixed-bed ion exchange resin containing a strong acidic resin based on polystyrene sulfonic acid and a strong basic resin based on quanternary ammonium substituents such as tetramethyl ammonium hydroxide (RG501, Fisher Scientific, Cambridge, Mass.) using 90% ethanol in water as the eluent. This resin removes from the mixture unreacted dopamine, dimethylaminopyridine, as well as the liberated DHA molecule. The effluent from the column (a pale yellow solution) was then evaporated in a rotary evaporator to give a solid. The product was recrystallized from aqueous ethanol (yield=75%).

Sources & evidence

ORD record
ord-1b3baaebd7864991bfc29becccc1cfe5
Source dataset
uspto-grants-1994_02
Patent number
US05284876

Reaction notes

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