3-Ethoxyacrylonitrile

[61310-53-0]  · C5H7NO  · 3-Ethoxyacrylonitrile  · (MW 97.12) (E)

[58243-08-6]

(bifunctional three-carbon electrophile; C3N building block in various condensation reactions/cytosine synthesis;1,2 polarized alkene for cycloaddition reactions3)

Alternate Name: 3-ethoxy-2-propenenitrile.

Physical Data: bp 188-190 °C, 90-91 °C/19 mmHg; d 0.944-0.947 g cm-3; n20D 1.454.

Form Supplied in: colorless liquid; commercially available.

Handling, Storage, and Precautions: keep cold; 3-ethoxyacrylonitrile is a lachrymator. Use in a fume hood.

Cyclocondensations.

One important condensation reaction of 3-ethoxyacrylonitrile involves a base-catalyzed cyclization with Urea to give cytosine (eq 1).1 3-Ethoxyacrylonitrile is obtained by fragmentation of isoxazole and subsequent ethylation.

No catalyst is needed when 3-ethoxyacrylonitrile is condensed with aromatic (or aliphatic) amidines, affording 2-amino-2-arylpyrimidines.2,4 The alternate 2-Chloroacrylonitrile gives lower yields.2

The introduction of substituents in position 5 of the cytosine ring can be achieved by metalation of 3-ethoxyacrylonitrile and subsequent alkylation.5 Metalation with n-Butyllithium takes place regioselectively at the a-position.6 The 2-lithio derivative reacts with activated primary bromides (Allyl Bromide or Benzyl Bromide) or straight chain primary alkyl iodides. Condensation with urea affords 5-alkylcytosines in moderate yields (eq 2).5

Other Cyclizations.

A benzimidazolium N-ylide undergoes 1,3-dipolar cycloaddition with 3-ethoxyacrylonitrile to give a benzopyrrolo[1,2-a]pyrazine derivative (eq 3).7

In a formal [3 + 2] cycloaddition, acylcarbenes add to conjugated nitriles. The acylcarbenes are produced from a-diazoaldehyde esters and can react, e.g. with 3-ethoxyacrylonitrile in the presence of catalytic amounts of Dirhodium(II) Tetraacetate, to give a 2-substituted 4-ethoxycarbonyl-1,3-oxazole (eq 4).8

Photocycloadditions.

Ortho photocycloaddition with 4-cyanoanisole as the arene component and 3-substituted acrylonitriles are regiospecific. (E)-3-Ethoxyacrylonitrile yields predominantly a 1:1 adduct, a bicyclo[4.2.0]octa-2,4-diene derivative, after 24 h irradiation with 4-cyanoanisole in acetonitrile (eq 5).3 No azocine is formed.

Ethylenes undergo photocycloadditions to 1,4-benzoquinone, yielding spiro-oxetanes (Paterno-Büchi reaction). Investigations were made with a variety of alkenes and electron-donor and -acceptor dienes.9 While electron-donor dienes such as Ethyl Vinyl Ether give only very small yields of oxetane, the captodative alkene (E)-3-ethoxyacrylonitrile adds to 1,4-benzoquinone in 30% yield (equal amounts of the cis and trans isomer) (eq 6).

Similar photocycloaddition of (E)-3-ethoxyacrylonitrile to 1,4-naphthoquinone affords both cis and trans adducts and a small amount of a second cis isomer.10

Other Addition Reactions.

3-Ethoxyacrylonitrile can be used as the starting material for the synthesis of glyoxal mono(diethyl acetal). The nitrile is brominated to the bromo acetal with N-Bromosuccinimide, which is converted into the cyano ester and the glyoxal acetal (eq 7).11

Related Reagents.

3-Ethoxyacrolein; Ethoxymethylenemalonitrile; Ethyl 3-Ethoxyacrylate; Ethyl Ethoxymethylenecyanoacetate.


1. Tarsio, P. J.; Nicholl, L. JOC 1957, 22, 192.
2. Singh, B.; Lesher, G. Y. JHC 1977, 14, 1413.
3. Al-Jalal, N.; Gilbert, A. RTC 1990, 109, 21.
4. Singh, B.; Laskowski, S. C.; Lesher, G. Y. SL 1991, 2, 549.
5. Smirnow, D.; Hopkins, P. B. SC 1986, 16, 1187.
6. Schmidt, R. R.; Speer, H. TL 1981, 22, 4259.
7. Matsuda, Y.; Yamashita, M.; Takahashi, K.; Ide, S.; Torisu, K.; Furuno, K. H 1992, 33, 295.
8. Connell, R. D.; Tebbe, M.; Helquist, P. TL 1991, 32, 17.
9. Bryce-Smith, D.; Evans, E. H.; Gilbert, A.; McNeill, H. S. JCS(P2) 1991, 1587.
10. Bryce-Smith, D.; Evans, E. H.; Gilbert, A.; McNeill, H. S. JCS(P1) 1992, 485.
11. Babler, J. H. SC 1987, 17, 77.

Roswitha M. Böhme

University of Bonn, Germany



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