Phenol → Coumarin

HRID 642842Notes

Reaction equation

HRID 642842 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)[C:10](=O)[CH2:11][C:12](OCC)=[O:13].CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:7]1[C:1]2[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:10]=[CH:11][C:12]1=[O:13]

Participants

5

Reactant 3

HCID 996Phenol2×HCID 6101p-Toluenesulfonic acidHCID 67793Ethyl 4,4,4-trifluoroacetoacetate

Product 1

HCID 323Coumarin

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Scheme VIII describes the synthesis of 6-alkylaminocoumarins, as demonstrated by Structure 45, from phenol through a similar route as that described in Schemes I and II. A mixture of a phenol compound and a 3-ketoester such as ethyl 4,4,4-trifluoroacetoacetate are heated in refluxing toluene in the presence of TsOH to afford a coumarin compound e.g., Structure 43. Nitration of coumarin compounds (e.g., Structure 43) followed by hydrogenation give aminocoumarin compounds such as Structure 44. Sequential reductive alkylation provides dialkylamino-coumarin compounds as shown in Structure 45. Hydrogenation of a dialkylamino-coumarin compound (e.g., Structure 45) affords compounds Structure 46.

Sources & evidence

ORD record
ord-dd421e523c9e48b6b7346ff729e75e87
Source dataset
uspto-grants-2010_04
Patent number
US07696246B2

Reaction notes

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