N-Iodosuccinimide → Psoralen

HRID 1383423Notes

Reaction equation

HRID 1383423 reaction equation
[NH+]1C=CC=CC=1.F[C:8]1[C:9](=[O:22])[O:10][C:11]2[C:16]([CH:17]=1)=[CH:15][C:14]([CH2:18][CH:19]=C)=[C:13]([OH:21])[CH:12]=2.C1C(=O)N(I)C(=O)C1>N1C=CC=CC=1>[CH:18]1[C:14]2=[CH:15][C:16]3[CH:17]=[CH:8][C:9](=[O:22])[O:10][C:11]=3[CH:12]=[C:13]2[O:21][CH:19]=1

Participants

5

Reactant 3

HCID 120273N-IodosuccinimideHCID 4989215PyridiniumHCID 21187799HCID 21187799, compound

Product 1

HCID 6199Psoralen

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Similarly the fluorine atom was introduced during the formation of the pyrone moiety through a Pechmann reaction with ethyl 2-fluoro-acetoacetate as the fluorine carrier. Thus, 3-fluoro-4,8-dimethyl-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) was prepared in 3 steps from 2-methylresorcinol (36% overall yield). Then, ring closure was achieved in two steps in a 66% overall yield following the same route employed with the 3-cyano derivatives giving a mixture 89:11 of (5, R═F, T═Br) and its pyrano isomer (6, R═F) in favor of the expected psoralen. Finally, this 89:11 mixture was reacted with refluxing anhydrous pyridine affording pure target compound (5, R═F, T═pyridinium, Br salt) in 73% yield. Alternatively, the 3-fluoro-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) could be ring closed with NIS in 91% yield to give 3-fluoro-4,8-dimethyl-4′,5′-dihydro-5′-iodomethylpsoralen (5, R═F, T═I). The resulting 3-fluoro-4,8-dimethyl-4′,5′-dihydro-5′-iodomethylpsoralen was reacted with pyridine to form the pyridinium iodine salt (5, R═F, T═pyridinium iodide). Ring closure of 3-fluoro-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) with mercury acetate in ethanol gave the 5′-acetomercurimethyl-4,8-dimethyl-4′,5′-dihydropsoralen (5, R═F, T═HgOAc) in 92% yield.

Sources & evidence

ORD record
ord-c81be58072d7410ebffa32b59c348397
Source dataset
uspto-grants-2001_07
Patent number
US06255324B1

Reaction notes

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