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DOI: 10.1055/s-0031-1290605
Friedel-Crafts Alkylation of Indoles by tert-Enamides in Acetic Acid
Publikationsverlauf
Publikationsdatum:
28. Februar 2012 (online)
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Abstract
In acetic acid, Friedel-Crafts alkylation of indoles by tert-enamides proceeded effectively in the absence of any catalyst to afford the pharmacologically and biologically active 2-oxo-1-pyrrolidine derivatives in moderate to good yields. The mechanistic study based on the NMR and HRMS analysis shows that the reaction was promoted by acid catalysis. The hydrogen-bond interaction between tert-enamides and AcOH may also be responsible for the reaction.
Key words
acetic acid - Friedel-Crafts alkylation - tert-enamide - indole
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
General Procedure
for the Reaction of
N
-Vinyl Compound with Nucleophile (Take the Reaction
of 1-Vinylpyrrolidin-2-one with Indole as Example)
To
a mixture of 1-vinylpyrrolidin-2-one (0.1111g, 1.0 mmol) and indole
(0.1171g, 1.0 mmol), AcOH (1.0 mL) was added. The reaction system
was stirred vigorously at r.t. until the starting materials were
completely consumed as indicated by TLC analysis. Then the mixture
was poured into H2O, neutralized by NaHCO3,
and extracted by CH2Cl2 (2 × 15 mL).
The combined organic layer was washed with brine, dried with anhyd
Na2SO4, and evaporated under the reduced pressure.
The residue was purified by flash column chromatography with EtOAc
and PE as eluents to afford pure product 3aa (0.194
g, yield 85%).
1-[1-(2-Methyl-1
H
-indol-3-yl)ethyl]pyrrolidin-2-one (3ab)
White
solid; mp 176-177 ˚C. IR (KBr): 3317, 2974, 2933, 2876,
1656, 1491, 1435, 1287, 1198, 1051, 749 cm-¹. ¹H NMR
(300 MHz, CDCl3): δ = 1.72
(d, J = 6.9
Hz, 3 H), 1.82-2.00 (m, 2 H), 2.32-2.41 (m, 2
H), 2.48 (s, 3 H), 3.11-3.19 (m, 1 H), 3.53-3.61
(m, 1 H), 5.75 (q, J = 7.2
Hz, 1 H), 7.05-7.12 (m, 2 H), 7.27 (t, J = 1.8
Hz, 1 H), 7.70 (d, J = 7.5 Hz,
1 H), 8.07 (br s, 1 H). ¹³C NMR (75
MHz, CDCl3): δ = 174.3,
135.6, 133.9, 128.3, 121.3, 119.9, 119.6, 111.0, 110.8, 44.0, 44.0,
31.9, 18.1, 18.0, 13.0. HRMS (EI):
m/z calcd
for C15H18N2O: 242.1419; found:
242.1420.