Ethyl b-(1-Pyrrolidinyl)acrylate

[53927-12-1]  · C9H15NO2  · Ethyl b-(1-Pyrrolidinyl)acrylate  · (MW 169.25) (E)


(precursor to b-vinyllithium derivative; reactions with electrophiles yield cyclopentenones, butenolides, maleic acid derivatives, and oxalacetic acid derivatives1,2)

Physical Data: mp 41-43 °C; bp 80-105 °C/10-3 mmHg.3

Solubility: sol most organic solvents (ethanol, ethyl acetate, dichloromethane, chloroform, THF).

Form Supplied in: colorless solid.

Analysis of Reagent Purity: 1H NMR (CDCl3) d 1.27 (t, J = 7 Hz, 3 H, CH3), 1.95 (m, 4 H, CH2CH2N), 3.30 (m, 4H, CH2N), 4.16 (q, J = 7 Hz, 2 H, CH2O), 4.50 (d, J = 12.5 Hz, 1 H, 2-H), 7.72 (d, J = 12.5 Hz, 1 H, 3-H); 13C NMR d 14.7 (CH3), 25.3 (CH2CH2N), 4.88 (CH2N), 58.5 (CH2O), 84.6 (2-C), 169.2 (1-C); IR (CHCl3) 1600 (C=C), 1665 (C=O) cm-1; UV (EtOH) 287 nm (ε = 2600).4

Preparative Method: reaction of ethyl propiolate with pyrrolidine in acetonitrile at rt yields ethyl b-(1-pyrrolidinyl)acrylate in 55% yield as a colorless solid.3,4

Purification: distillation under reduced pressure.

Handling, Storage, and Precautions: store under nitrogen protected from moisture.

Acrylates with functional groups (for instance, amino, hydroxy, mercapto moieties) in the b-position exhibit: (i) nucleophilic character at the a-position, permitting reactions with various electrophiles; (ii) electrophilic character at the b-position, enabling nucleophilic exchange reactions which can be employed for ring closure reactions; and (iii) CH acidity at the b-position (and/or a-position) which, for instance with strong lithiating agents, leads to direct b-lithiation, thus generating highly versatile functionally substituted vinyllithium derivatives.5,6 Typical examples for ethyl b-(1-pyrrolidinyl)acrylate are shown below.

Reaction with Diazonium Salts.

The reaction of ethyl b-(1-pyrrolidinyl)acrylate with diazonium salts as electrophiles leads to the formation of iminium hydrazone derivatives (1) which can be isolated in 65-90% yields (eq 1). These products can be converted into imidazole derivatives by action of base (eq 2) or into cinnoline derivatives (eq 3), depending on the substituents of the aromatic ring.7,8

Reaction with a-Amino Carbonyl Compounds.

The reaction of ethyl b-(1-pyrrolidinyl)acrylate with a-amino carbonyl compounds as nucleophiles in refluxing ethanol proceeds via 1,4-addition followed by elimination to give transamination intermediates which cyclize immediately to yield 3-substituted pyrroles (eq 4).9

Vinylcarbanion Generation.

Ethyl b-(1-pyrrolidinyl)acrylate can be converted by direct lithiation with t-Butyllithium below -100 °C into a b-vinyllithium derivative (2) (eq 5), which can be used as a C3 synthon for cyclization reactions. Reaction with acrylates, aldehydes, or ketones as electrophilic-nucleophilic species leads to functionally substituted cyclopentenones (eq 6) and butenolides (eq 7).1 Many examples involving reactions with heterocumulenes have been reported.2 For instance, addition of Phenyl Isothiocyanate or Phenyl Isocyanate yields, after cyclization, the thiomaleic anhydride derivative (eq 8) or the N-phenylmaleimide derivative (eq 9), respectively. Addition of alkyl isocyanates does not lead to cyclization, and oxalacetic acid derivatives are obtained (eq 10). Similarly, addition of Carbon Dioxide yields, after hydrolysis of the enamine, an oxalacetate derivative (eq 11).

1. Schmidt, R. R.; Talbiersky, J. AG 1978, 90, 220.
2. Schmidt, R. R.; Talbiersky, J.; Betz, R. CB 1982, 115, 2674.
3. Grinblat, E. I.; Postovskiï, I. Y. DOK 1960, 133, 847.
4. Kanner, C. B.; Pandit, U. K. T 1982, 38, 3597.
5. Schmidt, R. R. BSB 1983, 92, 825.
6. Jatzke, H.; Evertz, U.; Schmidt, R. R. SL 1990, 191.
7. Kanner, C. B.; Pandit, U. K. H 1978, 9, 757.
8. Kanner, C. B.; Pandit, U. K. T 1981, 37, 3513.
9. Alberola, A.; Andrés, J. M.; Gonzalez, A.; Pedrosa, R.; Vicente, M. JCS(P1) 1990, 2681.

R. R. Schmidt & K.-H. Jung

Universität Konstanz, Konstanz, Germany

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