Ethyl 3-Ethoxyacrylate1

[1001-26-9]  · C7H12O3  · Ethyl 3-Ethoxyacrylate  · (MW 144.17) (E)

[5941-55-9] (Z)

[40648-44-0]

(mono- and bifunctional three-carbon electrophile in acylation reactions;2 various condensation reactions;3 building block for heterocycles1 and nucleoside synthesis4)

Alternate Name: 3-ethoxy-2-propenoic acid, ethyl ester.

Physical Data: bp 195-196 °C, 85.5-86.5 °C/19 mmHg; d 0.993-0.998 g cm-3; nD20 1.444-1.448.

Form Supplied in: colorless, sweet-smelling liquid, stabilized with 0.01% hydroquinone monomethyl ether; commercially available.

Handling, Storage, and Precautions: should be stored at 0-4 °C. It is a slight lachrymator and irritant. Use in a fume hood.

Reactions at the Double Bond.

Transetherification.

Ethyl 3-ethoxyacrylate and 3,3-diethoxypropionate undergo reversible interconversion in the presence of some acidic-type catalysts.5 Thus the acrylate is converted into the propionate in the presence of Boron Trifluoride Etherate; the propionate distilled with ethanol and a catalytic amount of sodium bisulfate affords the acrylate. Replacing ethanol by less volatile alcohols yields ethyl 3-alkoxyacrylates or ethyl 3,3-dialkoxypropionates5 (eq 1). Similarly, thiols5 and thiophenols6 undergo transetherification reactions with ethyl 3-ethoxyacrylate and sodium bisulfate to give alkylthioacrylates.

Addition.

Addition of allyl alcohols to ethyl 3-ethoxyacrylate using N-Bromosuccinimide as bromine donor yields ethyl 3-allyloxy-2-bromopropionates, which can be cyclized reductively to 3-ethoxycarbonyltetrahydrofurans with Chromium(II) Acetate (eq 2).7

Other Substitutions.

b-Ethoxycinnamates are obtained in moderate yields by cross-coupling reaction of iodobenzenes with ethyl 3-ethoxyacrylate in the presence of Palladium on Carbon (eq 3).8 3-Iodopyridine and 3-iodoquinoline react similarly.8

Carboxy Reactions and Subsequent Cyclization.

Ethyl 3-ethoxyacrylate is an important starting material in the synthesis of uracil nucleosides. In a three-step synthesis the ester is converted into the acid chloride, then to the acyl isocyanate which reacts with ammonia,2a aliphatic2a or aromatic amines2a,9 to give b-ethoxyacryloylureas (cf. eq 4). These acylureas are cyclized in alkaline solution to the corresponding uracils. With acyl isothiocyanates, thiopyrimidones2b are obtained, while for the synthesis of thymines, 3-methoxy-2-methylacrylic acid is used.2a Carbocyclic analogs of uracil nucleosides are obtained when the amine component is a hydroxycyclopentylamine (eq 4).4,10 The cyclization is catalyzed by acid.4 Tetrahydroxycyclopentylamines may be also used.11

Other Cyclizations.

Aminoarabinose containing a 2-amino-1,2-oxazoline ring reacts with ethyl 3-ethoxyacrylate directly to give the O2,2-anhydrouridine, although the yield is poor (24%).12

2-Substituted 4(3H)-pyrimidinones are obtained by reaction of ethyl 3-ethoxyacrylate with orthoesters and ammonia.3 Ethoxyacrylate alone reacts with ammonia (mol ratio 2:1) to give ethyl 2(1H)-pyridone-5-carboxylate (eq 5);3 excess of ammonia gives additional pyridine-3,5-dicarboxylate.

Condensation of 4,6-diamino-2-methylthiopyrimidine with ethyl 3-ethoxyacrylate in acetic acid yields 4-amino-2-methylthio-7-oxopyrido[2,3-d]pyrimidine, whereas a complex mixture is obtained with ethyl propiolate.13

Related Reagents.

Diethyl Ethoxymethylenemalonate; Ethyl 3,3-Diethoxypropanoate; Ethyl Hydroxymethyleneacetate, Sodium Salt; Methyl Diformylacetate; Methyl Propiolate.


1. Aldrichim. Acta 1982, 15, 68.
2. (a) Shaw, G.; Warrener, R. N. JCS 1958, 157. (b) Shaw, G.; Warrener, R. N. JCS 1958, 153.
3. Adams, V. D.; Anderson, R. C. S 1974, 286.
4. Shealy, Y. F.; O'Dell C. A. JHC 1976, 13, 1015.
5. Croxall, W. J.; Van Hook, J. O.; Luckenbaugh, R. JACS 1949, 71, 2736.
6. Croxall, W. J.; Freimiller, L. R.; Shropshire E. Y. JACS 1950, 72, 4275.
7. Lübbers, T.; Schäfer, H. J. SL 1990, 1, 44.
8. Sakamoto, T.; Kondo, Y.; Kashiwagi, Y.; Yamanaka, H. H 1988, 27, 257.
9. Miller, M. W.; Chappel, L. R. JMC 1983, 26, 1075.
10. Hronowski, L. J. J.; Szarek, W. A. CJC 1985, 63, 2787.
11. Tadano, K.; Horiuchi, S.; Suami, T. BCJ 1978, 51, 897.
12. Holy, A. CCC 1974, 39, 3177.
13. Anderson, G. L.; Richardson, S. G. JHC 1985, 22, 1735.

Roswitha M. Böhme

University of Bonn, Germany



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