Methyl Acrylate

(1; R = Me)

[96-33-3]  · C4H6O2  · Methyl Acrylate  · (MW 86.10) (2; R = Et)

[140-88-5]  · C5H8O2  · Ethyl Acrylate  · (MW 100.13) (3; R = n-Bu)

[141-32-2]  · C7H12O2  · Butyl Acrylate  · (MW 128.19) (4; R = t-Bu)

[1663-39-4]  · C7H12O2  · t-Butyl Acrylate  · (MW 128.19)

(electrophile in conjugate addition reactions; dienophile or dipolarophile in cycloaddition reactions; acceptor in radical addition reactions; used in ene reactions)

Alternate Name: methyl propenoate.

Physical Data: (1) mp -75 °C; bp 80 °C. (2) mp -71 °C; bp 99 °C. (3) bp 145 °C. (4) bp 61-63 °C/60 mmHg.

Solubility: sol most organic solvents; slightly sol water.

Purification: wash repeatedly with aqueous NaOH to remove inhibitors, wash with H2O, dry over CaCl2, and distill under reduced pressure.

Handling, Storage, and Precautions: store at 0 °C in the dark (material will polymerize if exposed to light). Inhibited with up to 200 ppm hydroquinone monomethyl ether. Lachrymator and potential vesicant. Use in a fume hood. The ethyl ester (2) is a cancer suspect agent.

Conjugate Additions.

Acrylic acid esters have been used as Michael acceptors for a variety of nucleophiles. A typical example using an amino alcohol is shown in eq 1.1 This example illustrates chemoselectivity (amine over alcohol) and demonstrates that primary amines can undergo multiple additions.2 This reaction has been performed with anilines,3 imines,4 guanidines,5 hydrazones,6 xanthines,7 and pyrrolopyrimidines.8 Other heteroatomic nucleophiles have also been used, including alcohols,9 thiols,10 halides,11 and phosphorus reagents.12

A variety of carbon nucleophiles have also been used with acrylates in conjugate additions. An example using an enamine is shown in eq 2.13,14 This reaction has been extended to the synthesis of optically active esters through the use of chiral amines (eq 3).15,16

Stabilized azaallyl anions have also been used in asymmetric conjugate additions with methyl acrylate, as shown in eq 4.17,18 Other stabilized anions used in this reaction include hydrazones,19 malonates,20 a-cyano anions,21 ester enolates,22 a-nitro anions,23 a-sulfonyl anions,24 phosphorus ylides,25 and organozinc reagents.26

Enolates formed upon Michael addition of nucleophiles to acrylates have been trapped with a variety of electrophiles. An example of an intermolecular trapping with an aldehyde is shown in eq 5.27,28 Other traps have included ketones,29 N-tosyl imines,30 and Michael acceptors.31

Intramolecular variants of these reactions are also well known. For example, eq 6 shows an intramolecular trapping with an enone to produce a bicyclic ring system.32 Both chiral enolates33 and chiral acrylates34 have been used in this reaction. Other intramolecular traps have included esters35 and ketones.36

Cycloaddition Reactions.

Acrylates are commonly used as dienophiles in Diels-Alder reactions. Endo products predominate when stereochemistry is involved. A simple example is shown in eq 7.32b,37

A wide variety of attempts at asymmetric induction have been reported for this reaction. Chiral acrylate esters have been used in the cycloaddition process (eq 8),38,39 as well as chiral catalysts.40

Acrylates have further utility as dipolarophiles and have been used to trap nitrile oxides (eq 9),41 nitrones,42 azomethine ylides,43 and azomethine imines.44 They have also been used in hetero Diels-Alder reactions45 and [2 + 2] cycloadditions.46

Radical Trap.

Acrylates have been used as traps for alkyl radicals in radical chain processes.47 A variety of radical precursors may be used and intramolecular cyclization often precedes intermolecular trapping. Frequently, it is necessary to use a large excess of the acrylate to enhance trapping. The example in eq 10 shows the reaction of cyclohexyl iodide with methyl acrylate in the presence of Tris(trimethylsilyl)silane.48

Curran has developed atom transfer cycloaddition as a means of forming new rings and maintaining high levels of functionality in the final products (eq 11).49 Acyl radicals have also been trapped by acrylates to produce 1,4-dicarbonyl compounds.50 Ketones reduced with Samarium(II) Iodide have been trapped with ethyl acrylate to give the corresponding lactones (eq 12).51

Arylations and Vinylations.

Aryl and vinyl halides and triflates have been coupled to acrylates in the presence of palladium catalysts to produce the corresponding unsaturated esters. This method is very versatile and stereospecific when substituted vinyl halides are used. Coupling reactions with an aryl bromide,52 a vinyl triflate,53 and a vinyl halide54 are shown in eqs 13-15.

Acrylates have also been oxidatively coupled to indoles and furans using palladium salts (eq 16). These reactions appear to proceed via p-complexation to the heterocyclic double bond, conversion to the s-complex, addition to the acrylate, and subsequent reductive elimination of the palladium species.55,56

An interesting extension of this palladium chemistry, shown in eq 17, involves the vinylation of an imino iodide.57 Under the same conditions, the corresponding imino chlorides are recovered unchanged.

Ene Reactions.

Acrylates have been used in Lewis acid catalyzed ene reactions. Methyl acrylate reacts with (-)-b-pinene (eq 18) at rt with catalysis by Aluminum Chloride.58 This reaction can be stereoselective and may proceed better if a salt mixture is present.59

Transesterifications.

The transesterification of acrylates is best carried out using p-Toluenesulfonic Acid in the presence of hydroquinone as an inhibitor of polymerization. A representative example is shown in eq 19.60

Related Reagents.

Ethyl Acrylate.


1. Wadsworth, D. H. OSC 1988, 6, 75.
2. (a) Baltzly, R.; Phillips, A. P. JACS 1949, 71, 3419. (b) Baldwin, J. E.; Harwood, L. M.; Lombard, M. J. T 1984, 40, 4363. (c) Mozingo, R.; McCracken, J. H. OSC 1955, 3, 258. (d) Jones, R. A. Y.; Katritzky, A. R.; Trepanier, D. L. JCS(B) 1971, 1300.
3. (a) Braunholtz, J. T.; Mann, F. G. JCS 1957, 4166. (b) Barluenga, J.; Villamaña, J.; Yus, M. S 1981, 375.
4. Wessjohann, L.; McGaffin, G.; de Meijere, A. S 1989, 359.
5. Kim, Y. H.; Lee, N. J. H 1983, 20, 1769.
6. Barluenga, J.; Palacios, F.; Viña, S.; Gotor, V. JHC 1986, 23, 447.
7. Kalcheva, V.; Stoyanova, D.; Simova, S. LA 1989, 1251.
8. West, R. A. JOC 1963, 28, 1991.
9. Rehberg, C. E.; Dixon, M. B.; Fisher, C. H. JACS 1946, 68, 544.
10. (a) Kharasch, M. S.; Fuchs, C. F. JOC 1948, 13, 97. (b) Bakuzis, P.; Bakuzis, M. L. F. JOC 1981, 46, 235. (c) Fehnel, E. A.; Carmack, M. OSC 1963, 4, 669. (d) Mukaiyama, T.; Izawa, T.; Saigo, K.; Takei, H. CL 1973, 355.
11. Mozingo, R.; Patterson, L. A. OSC 1955, 3, 576.
12. (a) Boyd, E. A.; Corless, M.; James, K.; Regan, A. C. TL 1990, 31, 2933. (b) Green, K. TL 1989, 30, 4807. (c) Thottathil, J. K.; Ryono, D. E.; Przybyla, C. A.; Moniot, J. L.; Neubeck, R. TL 1984, 25, 4741. (d) Beer, P. D.; Edwards, R. C.; Hall, C. D.; Jennings, J. R.; Cozens, R. J. CC 1980, 351.
13. Fritz, H.; Fischer, O. T 1964, 20, 1737.
14. (a) Kinney, W. A.; Coghlan, M. J.; Paquette, L. A. JACS 1985, 107, 7352. (b) Borne, R. F.; Fifer, E. K.; Waters, I. W. JMC 1984, 27, 1271. (c) Barluenga, J.; Jardón, J.; Gotor, V. S 1988, 146.
15. Desmaële, D.; Pain, G.; D'Angelo, J. TA 1992, 3, 863.
16. (a) Matsuyama, H.; Fujii, S.; Kamigata, N. H 1991, 32, 1875. (b) Stetin, C.; De Jeso, B.; Pommier, J.-C. JOC 1985, 50, 3863. (c) Ito, Y.; Sawamura, M.; Kominami, K.; Saegusa, T. TL 1985, 26, 5303.
17. Schollkopf, U.; Pettig, D.; Busse, U.; Egert, E.; Dyrbusch, M. S 1986, 737.
18. (a) Minowa, N.; Hirayama, M.; Fukatsu, S. TL 1984, 25, 1147. (b) Belokon, Y. N.; Bulychev, A. G.; Ryzhov, M. G.; Vitt, S. V.; Batsanov, A. S.; Struchkov, Y. T.; Bakhmutov, V. I.; Belikov, V. M. JCS(P1) 1986, 1865. (c) Kanemasa, S.; Tatsukawa, A.; Wada, E. JOC 1991, 56, 2875. (d) achiral 1-azaallyl anion: Hua, D. H., Bharathi, S. N.; Takusagawa, F.; Tsujimoto, A.; Panangadan, J. A. K.; Hung, M.-H.; Bravo, A. A.; Erpelding, A. M. JOC 1989, 54, 5659.
19. Baldwin, J. E.; Adlington, R. M.; Jain, A. U.; Kolhe, J. N.; Perry, M. W. D. T 1986, 42, 4247.
20. Floyd, D. E.; Miller, S. E. JOC 1951, 16, 882.
21. (a) Kubota, Y.; Nemoto, H.; Yamamoto, Y. JOC 1991, 56, 7195. (b) Cheng, A.; Uyeno, E.; Polgar, W.; Toll, L.; Lawson, J. A.; DeGraw, J. I.; Loew, G.; Camerman, A.; Camerman, N. JMC 1986, 29, 531.
22. (a) Kraus, G. A.; Roth, B. TL 1977, 3129. (b) asymmetric synthesis: Aoki, S.; Sasaki, S.; Koga, K. TL 1989, 30, 7229. (c) Luthman, K.; Orbe, M.; Waglund, T.; Claesson, A. JOC 1987, 52, 3777.
23. (a) Moffett, R. B. OSC 1963, 4, 652. (b) Chasar, D. W. S 1982, 10, 841. (c) White, D. A.; Baizer, M. M. TL 1973, 3597.
24. Trost, B. M.; Schmuff, N. R. JACS 1985, 107, 396.
25. Wanner, M. J.; Koomen, G. J. S 1988, 325.
26. (a) Caronna, T.; Citterio, A.; Clerici, A. OPP 1974, 6, 299. (b) Sustmann, R.; Hopp, P.; Holl, P. TL 1989, 30, 689.
27. Brown, J. M.; Evans, P. L.; James, A. P. OS 1989, 68, 64.
28. For attempted asymmetric induction in this process, see (a) Basavaiah, D.; Gowriswari, V. V. L.; Sarma, P. K. S.; Rao, P. D. TL 1990, 31, 1621. (b) Drewes, S. E.; Emslie, N. D.; Karodia, N.; Khan, A. A. CB 1990, 123, 1447.
29. Basavaiah, D.; Gowriswari, V. V. L. SC 1989, 19, 2461.
30. (a) Bertenshaw, S.; Kahn, M. TL 1989, 30, 2731. (b) Perlmutter, P.; Teo, C. C. TL 1984, 25, 5951.
31. (a) Barco, A.; Benetti, S.; Casolari, A.; Pollini, G. P.; Spalluto, G. TL 1990, 31, 4917. (b) Posner, G. H.; Shulman-Roskes, E. M. T 1992, 23, 4677.
32. (a) White, K. B.; Reusch, W. T 1978, 34, 2439. (b) Lee, R. A. TL 1973, 3333.
33. Zhao, R.-B.; Zhao, Y.-F.; Song, G.-Q.; Wu, Y.-L. TL 1990, 31, 3559.
34. Spitzner, D.; Wagner, P.; Simon, A.; Peters, K. TL 1989, 30, 547.
35. Wada, A.; Yamamoto, H.; Ohki, K.; Nagai, S.; Kanatomo, S. JHC 1992, 29, 911.
36. Marino, J. P.; Katterman, L. C. CC 1979, 946.
37. (a) Narayama, Y. V. S.; Pillai, C. N. SC 1991, 21, 783. (b) Hashimoto, Y.; Saigo, K.; Machida, S.; Hasegawa, M. TL 1990, 31, 5625. (c) Cativiela, C.; Fraile, J. M.; Garcia, J. I.; Mayoral, J. A. Pires, E.; Figueras, F.; de Mènorval, L. C. T 1992, 48, 6467.
38. (a) Oppolzer, W.; Chapuis, C.; Dao, G. M.; Reichlin, D.; Godel, T. TL 1982, 23, 4781. (b) Oppolzer, W.; Chapuis, C.; Bernardinelli, G. TL 1984, 25, 5885.
39. (a) Corey, E. J.; Cheng, X.-M.; Cimprich, K. A. TL 1991, 32, 6839. (b) Stähle, W.; Kunz, H. SL 1991, 260. (c) Poll, T.; Metter, J. O.; Helmchen, G. AG(E) 1985, 24, 112.
40. (a) Hawkins, J. M.; Loren, S. JACS 1991, 113, 7794. (b) Ketter, A.; Glahsl, G.; Herrmann, R. JCR(M) 1990, 2118.
41. (a) Olsson, T.; Stern, K.; Westman, G.; Sundell, S. T 1990, 46, 2473. (b) Zhang, R.; Chen, J. S 1990, 817.
42. Padwa, A.; Fisera, L.; Koehler, K. F.; Rodriguez, A.; Wong, G. S. K. JOC 1984, 49, 276.
43. (a) Allway, P.; Grigg, R. TL 1991, 32, 5817. (b) Padwa. A.; Haffmanns, G.; Tomas, M. JOC 1984, 49, 3314.
44. Zlicar, M.; Stanovnik, B.; Tisler, M. T 1992, 48, 7965.
45. (a) Chehna, M.; Pradere, J. P.; Guingant, A. SC 1987, 17, 1971. (b) Sainte, F.; Serckx-Poncin, B.; Hesbain-Frisque, A.-M.; Ghosez, L. JACS 1982, 104, 1428.
46. Guerry, P.; Neier, R. CC 1989, 1727.
47. (a) Giese, B. AG(E) 1983, 22, 753. (b) Curran, D. P. S 1988, 417, 489.
48. Giese, B.; Kopping, B; Chatgilialoglu, C. TL 1989, 30, 681.
49. Curran, D. P.; Chen, M.-H. JACS 1987, 109, 6558.
50. Schwartz, C. E.; Curran, D. P. JACS 1990, 112, 9272.
51. Fukuzawa, S.-I.; Nakanishi, A.; Fujinami, T.; Sakai, S. CC 1986, 624.
52. Spencer, A. JOM 1983, 258, 101.
53. Hirota, K.; Kitade, Y.; Isobe, Y.; Maki, Y. H 1987, 26, 355.
54. Dieck, H. A.; Heck, R. F. JOC 1975, 40, 1083.
55. (a) Murakami, Y.; Yokoyama, Y.; Aoki, T. H 1984, 22, 1493. (b) Itahara, T.; Ikeda, M.; Sakakibara, T. JCS(P1) 1983, 1361.
56. Itahara, T.; Ouseto, F. S 1984, 488.
57. Uneyama, K.; Watanabe, H. TL 1991, 32, 1459.
58. Snider, B. B. JOC 1974, 39, 255.
59. &AAring;kermark, B.; Ljungqvist, A. JOC 1978, 43, 4387.
60. Rehberg, C. E. OSC 1955, 3, 146.

Duane A. Burnett & Margaret E. Browne

Schering-Plough Research Institute, Kenilworth, NJ, USA



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