Phosphorus oxychloride → Thieno[3,2-b]pyrrolizin-4-one
Reaction equation
P(Cl)(Cl)(Cl)=O.[N:6]1([C:11]2[S:12][CH:13]=[CH:14][C:15]=2[C:16]([OH:18])=O)[CH:10]=[CH:9][CH:8]=[CH:7]1.N1(C2C=CSC=2C(O)=O)C=CC=C1>>[S:12]1[C:11]2[N:6]3[C:10](=[CH:9][CH:8]=[CH:7]3)[CH2:16][C:15]=2[CH:14]=[CH:13]1.[S:12]1[C:11]2[N:6]3[C:7](=[CH:8][CH:9]=[CH:10]3)[C:16](=[O:18])[C:15]=2[CH:14]=[CH:13]1Participants
Procedure
The triheterocyclic substrates thieno[2,3-b]pyrrolizine and thieno[2,3-b]pyrrolizin-4-one; thieno[3,2-b]pyrrolizine and thieno[3,2-b]pyrrolizin-4-one are prepared exactly according to Rault et al., Heterocycles, 20 (1983) 477. The process involves the cyclization in boiling phosphoryl chloride of amide derivatives of 2-(1-pyrrolyl)-3-thienylcarboxylic acid and 3-(1-pyrrolyl)-2-thienylcarboxylic acid to yield thieno[2,3-b]pyrrolizin-4-one and thieno[3,2-b]pyrrolizin-4-one respectively. These ketones in accordance with Method I can be derivatized to the corresponding spiro-hydantoins: spiro-(thieno[3,2-b]pyrrolizin-4,4'-imidazolidine)-2',5'-dione and spiro-(thieno[3,2-b]pyrrolizin-4,4'-imidazolidine)-2',5'-dione. Both thieno[2,3-b]pyrrolizin-4-one and thieno[3,2-b]pyrrolizin-4-one can be reduced with 1.75 equivalents of lithium aluminum hydride in the presence of 3.5 equivalents aluminum chloride to yield the corresponding 4H-thieno-pyrrolizines quantitatively. The resulting thieno[2,3-b]pyrrolizine and thieno[3,2-b]pyrrolizine can be derivatived according to Methods II, III and IV into the corresponding spiro-thiazolidinediones, spiro-oxazolidinediones and spiro-succinimides, such as spiro-(thieno[3,2-b]pyrrolizin-4,5'-thiazolidine)-2',4'-dione, spiro-(thieno[2,3-b]pyrrolizin-4,5'-oxazolidine)-2',4'-dione and spiro-(thieno[3,2-b]pyrrolizin-4,3'-succinimide).
Sources & evidence
- ORD record
- ord-eb5ae89e14dc48deab8eb480b340624e
- Source dataset
- uspto-grants-1992_10
- Patent number
- US05153211
Reaction notes
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