Ethyl Acrylate1

[140-88-5]  · C5H8O2  · Ethyl Acrylate  · (MW 100.13) (Me ester)

[96-33-3]  · C3H6O  · Methyl Acrylate  · (MW 58.09)

(two- and three-carbon alkylating and annulating reagent commonly used in cycloadditions,2 conjugate additions,3 tandem vicinal dialkylation reactions,4 and Heck reactions5)

Physical Data: mp -71 °C; bp 98-100 °C; d204 0.924 g cm-3; n20D 1.4049.

Solubility: 2 g 100 mL-1 H2O (20 °C); forms 45% aqueous azeotrope, bp 81 °C; sol EtOH, ether; forms 57% ethanol azeotrope, bp 76 °C.

Form Supplied in: &egt;99%; typically stabilized with 15-200 ppm hydroquinone monomethyl ether; widely available.

Purification: 6 commercial material should be washed repeatedly with aq dil NaOH to free it from stabilizers; alternatively, stabilizers can be extracted using inhibitor removal columns (commercially available). Follow by washing with saturated aq CaCl2. Dry using CaCl2, and distill under reduced pressure. Store the purified ester tightly capped in an amber container, refrigerated below 0 °C.

Handling, Storage, and Precautions: the compound is a cancer suspect agent. A highly flammable irritant, it has an acrid, lachrymatory, penetrating odor. It polymerizes upon standing; polymerization is accelerated by heat, light, or peroxides. Additionally, polymerization occurs upon distillation at atmospheric pressure. Pure material can be stored below -10 °C without polymerization. This toxic reagent should be handled in a fume hood and skin contact should be scrupulously avoided.

Introduction.

The chemical reactivity of the alkyl acrylates is dominated by the electron-deficient nature of the carbon-carbon double bond. The lower alkyl acrylates readily polymerize, and the resulting polymers find commercial application in surface coatings, varnishes, and printing inks.7

Cycloaddition Reactions.

Alkyl acrylates probably rival maleic anhydride as the most common dienophiles in Diels-Alder chemistry.2 They undergo [4 + 2] cycloadditions with a wide variety of dienes and 1,3-dipoles such as nitrones8 and S-methylides,9 providing entry to functionalized carbocyclic and heterocyclic systems. Eq 1 illustrates the use of methyl acrylate in a sequential Diels-Alder-decarboxylative retrocycloaddition-Diels-Alder preparation of a bornene diester intermediate, which can be converted to barrelene.10 Certain bulky Lewis acids preferentially coordinate to alkyl acrylates with sterically undemanding alkyl groups, activating them towards reactions with dienes and substantially increasing the stereoselection of the reaction for endo adducts (eq 2).11 Lewis acid-catalyzed ene reactions2 of acrylates can be used in stereoselective, three-carbon chain homologations, such as in the synthesis of chenodeoxycholic acid (eq 3).12

Conjugate Addition Reactions.

A large number of carbon nucleophiles undergo conjugate additions with alkyl acrylates, including cyanide, enolates, nitro-, sulfinyl-, and sulfonyl-stabilized carbanions, organocopper reagents, Grignard reagents, enamines, amines, thiols, and radicals.3a,13 Performed under protic conditions, monobasic nucleophiles such as 2-Nitropropane provide high chemical yields of b-substituted propionates (eq 4).14 If the nucleophile is dibasic, 1:2 nucleophile:acrylate adducts form efficiently:15 3-amino-1-propanol provides a 1:2 adduct with ethyl acrylate (eq 5) that can be used to prepare azetidine.16

In aprotic solvents the ester enolate formed upon conjugate addition can be alkylated in the a-position; a large number of these tandem vicinal dialkylation reactions are known.4 Most such reactions are initiated by Michael addition of an enolate to the acrylate substrate; in contrast, organocopper reagents have been used relatively rarely. This may be because of a lack of reactivity with lithium dialkylcuprates: the situation is substantially improved when higher order cyanocuprates are employed.17 With proper choice of nucleophile, both 1:1 and 1:2 conjugate adducts can participate in subsequent annulation reactions, illustrated by the [3 + 3] annulation synthesis of glutethimide (eq 6).18 In aprotic media, these Michael-ring closure (MIRC)4 reactions can afford cyclized products directly, as in the [1 + 2 + 3]19 cyclohexanone synthesis of eq 7,20 or upon workup, illustrated by the [3 + 3] synthesis of 6-methoxytetralone (eq 8).21

Radical conjugate additions are relatively straightforward to perform;3a,22 typically, Samarium(II) Iodide is used as a one-electron transfer reagent to form the radical conjugate donor.23 A simple MIRC-type synthesis of g-lactones is initiated by conjugate addition of various ketyls to ethyl acrylate (eq 9).24

Vinylations of Organohalogen Compounds.

The Heck reaction provides a convenient route to various substituted acrylate derivatives.5 While the substituting reagent may simply be a second molecule of alkyl acrylate, resulting in tail-to-tail dimerization for formation of dialkyl (E)-2-hexenedioates,25 sp2- and sp-hybridized halides are more commonly used.26 A rapid, two-step, stereospecific synthesis of pellitorine is indicative of the efficiency of the method (eq 10).27 The process is reliable and quite general, although anomalous products can form: the reaction of methyl acrylate and 2-bromobenzaldehydes provides, in addition to the expected b-substituted acrylate, unusual doubly substituted products (eq 11).28

Other Reactions.

The carbon-carbon double bond of alkyl acrylates undergoes predictable electrophilic addition reactions:29 the addition of Hydrogen Bromide to provide alkyl b-bromopropionates is typical (eq 12).30 Transesterification31 and hydrolysis32 are accomplished via acid catalysis; concomitant polymerization can cause yields to be variable. Pyrolysis of ethyl acrylate at 590 °C yields ethylene and acrylic acid.33


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Martin Hulce

Creighton University, Omaha, NE, USA



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