Acrylonitrile

[107-13-1]  · C3H3N  · Acrylonitrile  · (MW 53.06)

(electrophile in 1,4-addition reactions; radical acceptor; dienophile; acceptor in cycloaddition reactions)

Physical Data: mp -83 °C; bp 77 °C; d 0.806 g cm-3; nD 1.3911.

Solubility: miscible with most organic solvents; 7.3 g of acrylonitrile dissolves in 100 g of water at 20 °C.

Form Supplied in: colorless liquid (inhibited with 35-45 ppm hydroquinone monomethyl ether); widely available.

Purification: the stabilizer can be removed prior to use by passing the liquid through a column of activated alumina or by washing with a 1% aqueous solution of NaOH (if traces of water are allowed in the final product) followed by distillation. For dry acrylonitrile, the following procedure is recommended. Wash with dilute H2SO4 or H3PO4, then with dilute aqueous Na2CO3 and water. Dry over Na2SO4, CaCl2, or by shaking with molecular sieves. Finally, fractional distillation under nitrogen (boiling fraction of 75-75.5 °C) provides acrylonitrile which can be stabilized by adding 10 ppm t-butyl catechol or hydroquinone monomethyl ether. Pure acrylonitrile is distilled as required.1a

Handling, Storage, and Precautions: explosive, flammable, and toxic liquid. May polymerize spontaneously, particularly in the absence of oxygen or on exposure to visible light, if no inhibitor is present. Polymerizes violently in the presence of concentrated alkali. Highly toxic through cyanide effect. Use in a fume hood.

Deuterioacrylonitrile.

Deuterium-labeled acrylonitrile can be obtained by reduction of propiolamide-d3 with Lithium Aluminum Hydride, followed by D2O workup. The resulting acrylamide can then be dehydrated with P2O5.1b

Reactions of the Nitrile Group.

Various functional group transformations have been carried out on the nitrile group in acrylonitrile. Hydration with concentrated Sulfuric Acid at 100 °C yields acrylamide after neutralization.2 Secondary and tertiary alcohols produce N-substituted acrylamides under these conditions in excellent yield (Ritter reaction).3 Heating in the presence of dilute sulfuric acid or with an aqueous basic solution yields acrylic acid.4 Imido ethers have been prepared by reacting acrylonitrile with alcohols in the presence of anhydrous hydrogen halides.5 Anhydrous Formaldehyde reacts with acrylonitrile in the presence of concentrated sulfuric acid to produce 1,3,5-triacrylylhexahydrotriazine.6

Reactions of the Alkene.

Reduction with hydrogen in the presence of Cu,7 Rh,8 Ni,9 or Pd10 yields propionitrile. Acrylonitrile can be halogenated at low temperature to produce 2,3-dihalopropionitriles. For example, reaction with Bromine leads to dibromopropionitrile in 65% yield.11 Also, treatment of acrylonitrile with an aqueous solution of Hypochlorous Acid, gives 2-chloro-3-hydroxypropionitrile in 60% yield.12 a-Oximation of acrylonitrile has been achieved using CoII catalysts, n-Butyl Nitrite and phenylsilane.13

Nucleophilic Additions.

A wide variety of nucleophiles react with acrylonitrile in 1,4-addition reactions. These Michael-type additions are often referred to as cyanoethylation reactions.14 The following list illustrates the variety of substrates which will undergo cyanoethylation: ammonia, primary and secondary amines, hydroxylamine, enamines, amides, lactams, imides, hydrazine, water, various alcohols, phenols, oximes, sulfides, inorganic acids like HCN, HCl, HBr, chloroform, bromoform, aldehydes, and ketones bearing an a-hydrogen, malonic ester derivatives, and other diactivated methylene compounds.15 Stabilized carbanions derived from Cyclopentadiene and fluorene and 1-5% of an alkaline catalyst also undergo cyanoethylation. The strongly basic quaternary ammonium hydroxides, such as Benzyltrimethylammonium Hydroxide (Triton B), are particularly effective at promoting cyanoethylation because of their solubility in organic media. Reaction temperatures vary from -20 °C for reactive substrates, to heating at 100 °C for more sluggish nucleophiles. The 1,4-addition of amines has recently been used in the synthesis of poly(propyleneimine) dendrimers.16

Phosphine nucleophiles have been reported to promote nucleophilic polymerization of acrylonitrile.17

Addition of organometallic reagents to acrylonitrile is less efficient than to conjugated enones. Grignard reagents react with acrylonitrile by 1,2-addition and, after hydrolysis, give a,b-unsaturated ketones.18 Lithium dialkylcuprate (R2CuLi) addition in the presence of Chlorotrimethylsilane leads to double addition at the alkene and nitrile, giving a dialkyl ketone.19 Yields of only 23-46% are obtained in the conjugate addition of n-BuCu.BF3 to acrylonitrile.20 An enantioselective Michael reaction has been achieved with titanium enolates derived from N-propionyloxazolidone (eq 1).21

Acrylonitrile fails to react with trialkylboranes in the absence of oxygen or other radical initiatiors. However, secondary trialkylboranes transfer alkyl groups in good yield when oxygen is slowly bubbled through the reaction mixture.22 Primary and secondary alkyl groups can be added in excellent yields using copper(I) methyltrialkylborates.23 Reaction of acrylonitrile with an organotetracarbonylferrate in a conjugate fashion provides 4-oxonitriles in moderate (25%) yields.24

Transition Metal-Catalyzed Additions.

Palladium-catalyzed Heck arylation and alkenylation occurs readily with acrylonitrile (eq 2).25 Double Heck arylation is observed in the PdII/montmorillonite-catalyzed reaction of aryl iodides with acrylonitrile.26

PdII catalyzed oxidation of the double bond in acrylonitrile in the presence of an alcohol (Wacker-type reaction) produces an acetal in high yield.27 When an enantiomerically pure diol such as (2R,4R)-2,4-Pentanediol is used, the corresponding chiral cyclic acetal is produced (eq 3).28

Hydrosilation29a of acrylonitrile with MeCl2SiH catalyzed by nickel gives the a-silyl adduct. The b-silyl adduct is obtained when copper(I) oxide is used.29b The regioselectivity of the cobalt catalyzed hydrocarboxylation to give either the 2- or 3-cyanopropionates can also be controlled by the choice of reaction conditions.30 Hydroformylation of acrylonitrile has also been described.31

Cyclopropanation of the double bond has been achieved upon treatment with a CuI oxide/isocyanide or Cu0/isocyanide complex. Although yields are low to moderate, functionalized cyclopropanes are obtained.32,33 Photolysis of hydrazone derivatives of glucose in the presence of acrylonitrile provides the cyclopropanes in good yield, but with little stereoselectivity.34 Chromium-based Fischer carbenes also react with electron deficient alkenes including acrylonitrile to give functionalized cyclopropanes (eq 4).35

Radical Additions.

Carbon-centered radicals add efficiently and regioselectively to the b-position of acrylonitrile, forming a new carbon-carbon bond.36,37 Such radicals can be generated from an alkyl halide (using a catalytic amount of Tri-n-butylstannane, alcohol (via the thiocarbonyl/Bu3SnH), tertiary nitro compound (using Bu3SnH), or an organomercurial (using NaBH4). The stereochemistry of the reaction has been examined in cyclohexanes and cyclopentanes bearing an a-stereocenter.36 CrII complexes, vitamin B12, and a Zn/Cu couple have been shown to mediate the intermolecular addition of primary, secondary, and tertiary alkyl halides to acrylonitrile.38 Acyl radicals derived from phenyl selenoesters and Bu3SnH also give addition products with acrylonitrile (eq 5).39

Radical additions with acrylonitrile have been used to prepare C-glycosides36,37b and in annulation procedures.37c Acrylonitrile has also been used in a [3 + 2] annulation based on sequential radical additions (eq 6).40

Alkyl and acyl CoIII complexes add to acrylonitrile and then undergo b-elimination to give a product corresponding to vinylic C-H substitution.41 This methodology is complementary to the Heck reaction of aryl and vinyl halides, which fails for alkyl and acyl compounds.25

Radicals other than those based on carbon also add to acrylonitrile. Heating acrylonitrile and tributyltin hydride in a 2:3 molar ratio in the presence of a catalytic amount of Azobisisobutyronitrile yields exclusively the b-stannylated adduct in excellent yield.42 Hydrostannylation in the presence of a Pd0 catalyst gives only the a-adduct (eq 7).42c

Treatment of ethyl propiolate with Bu3SnH in the presence of acrylonitrile results in addition of a tin radical to the b-site of the alkyne followed by addition to acrylonitrile. Use of excess acrylonitrile results in trapping of the radical followed by an annulation reaction, providing trisubstituted cyclohexenes.43

Thioselenation of the alkene using Diphenyl Disulfide, Diphenyl Diselenide, and photolysis gives the a-seleno-b-sulfide in 75% yield by a radical addition mechanism.44 Similarly, Tris(trimethylsilyl)silane adds to acrylonitrile at 80-90 °C using AIBN to give the b-silyl adduct in 85% yield.45

Pericyclic Reactions.

In the presence of a suitable alkene, the double bond in acrylonitrile undergoes a thermally induced ene reaction in low to moderate yield. For example, when (+)-limonene and acrylonitrile are heated in a sealed tube, the corresponding ene adduct is produced in 25% yield.46

The thermal [2 + 2] dimerization of acrylonitrile has been known for many years. Good regioselectivity is observed but the yield is low and a mixture of stereoisomers is produced.47 Cis-1,2-dideuterioacrylonitrile was used in this reaction to study the stereochemical outcome of the cycloaddition. It was concluded that a diradical intermediate was involved.1b

Other [2 + 2] reactions have been reported. Regioselective cycloaddition between a silyl enol ether and acrylonitrile yields a cyclobutane in the presence of light and a triplet sensitizer.48a Reaction between acrylonitrile and a ketene silyl acetal in the presence of a Lewis acid gives either substituted cyclobutanes or g-cyanoesters depending on the Lewis acid and solvent (eq 8).48c

Dihydropyridines undergo stereoselective cycloaddition with acrylonitrile under photolytic conditions.48c The combination of a Lewis acid (Zinc Chloride) and photolysis promotes cycloaddition between benzene and acrylonitrile.48d Allenyl sulfides undergo Lewis acid catalyzed [2 + 2] cycloaddition with electron deficient alkenes including acrylonitrile with good regioselectivity but little stereoselectivity (eq 9).49

Metal catalysts promote [3 + 2] cycloaddition reactions with acrylonitrile, leading to carbocyclic compounds. Reaction of acrylonitrile with a trimethylenemethane (TMM) precursor in the presence of Pd0 provides an efficient route to methylenecyclopentanes in moderate yield (40%).50 A similar yield is obtained when a Ni0 or Pd0 catalyzed cycloaddition is employed starting from methylenecyclopropane.51 Moreover, a variety of substituted methylenecyclopropanes have also been used to furnish substituted methylenecyclopentanes (eq 10).51b

Five-membered heterocycles can be prepared from acrylonitrile by dipolar cycloadditions. Acrylonitrile undergoes efficient cycloaddition with 1,3-dipolar species52 including nitrile oxides, nitrones, azomethine ylides, azides, and diazo compounds.53 Cycloaddition of acrylonitrile with an oxopyrilium ylide generates stereoisomeric oxabicyclic compounds with excellent regioselectivity (eq 11).54

The dipolar cycloaddition of acrylonitrile with a hydroxypyridinium bromide is also highly regioselective.55

The [2 + 2 + 2] homo Diels-Alder cycloaddition between acrylonitrile and norbornadiene, substituted norbornadienes, or quadricyclane, has also been described under thermal and metal catalyzed conditions.56 The effect of ligands and substituents on the stereo- and regioselectivity of the nickel catalyzed process has been investigated (eq 12).56c,d

Cobalt catalysts (Octacarbonyldicobalt) also promote the cycloaddition of 1,6-diynes with acrylonitrile, yielding cyclohexadienes which are readily aromatized.57

Diels-Alder reactions using acrylonitrile have been widely reported with many different dienes. These include alkyl, aryl, alkoxy, alkoxycarbonyl, amido, phenylseleno, phenylthio, and alkoxyboranato substituted butadienes.58 Reactions between acrylonitrile and furans, thiophenes, and thiopyrans have been reported. In some instances, Lewis acids accelerate the reaction.59 Heterodienes including 2-azabutadienes and the 4-(oxa, aza, and thio) derivatives also undergo cycloaddition. Reactive dienes such as o-quinodimethanes,60 benzofurans,61 and dimethylbenzodioxanes react efficiently with acrylonitrile (eq 13).62


1. (a) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: Oxford, 1988. (b) von Doering, W. E.; Guyton, C. JACS 1978, 100, 3229.
2. Adams, R.; Jones, V. V. JACS 1947, 69, 1803.
3. Plaut, H.; Ritter, J. J. JACS 1951, 73, 4076.
4. Mamiya, Y. J. Soc. Chem. Ind. Jpn. 1941, 44, 860 (CA 1948, 42, 2108).
5. Price, C. C.; Zomlefer, J. JOC 1949, 14, 210.
6. Wegler, R.; Ballauf, A. CB 1948, 81, 527.
7. Reppe, W.; Hoffmann, U. U.S. Patent 1 891 055, 1932.
8. Hernandez, L. Experienta 1947, 3, 489.
9. Bruson, H. A. U.S. Patent 2 287 510, 1942.
10. Ali, H. M.; Naiini, A. A.; Brubaker Jr., C. H. TL 1991, 32, 5489.
11. Moureau, C.; Brown, R. L. BSF(2) 1920, 27, 901.
12. Tuerck, K. H. W.; Lichtenstein, H. J. U.S. Patent 2 394 644, 1946.
13. Kato, K.; Mukaiyama, T. BCJ 1991, 64, 2948.
14. (a) This reaction has been thoroughly reviewed, see: Bruson, H. A. OR, 1949, 5, 79. (b) The Chemistry of Acrylonitrile, 2nd ed.; American Cyanamid Co: 1959.
15. For some recent examples, see: (a) Thomas, A.; Manjunatha, S. G.; Rajappa, S. HCA 1992, 75, 715. (b) Fredriksen, S. B.; Dale, J. ACS 1992, 46, 574. (c) Nowick, J. S.; Powell, N. A.; Martinez, E. J.; Smith, E. M.; Noronha, G. JOC 1992, 57, 3763. (d) Genet, J. P.; Uziel, J.; Port, M.; Touzin, A. M.; Roland, S.; Thorimbert, S.; Tanier, S. TL 1992, 33, 77. (e) Kubota, Y.; Nemoto, H.; Yamamoto, Y. JOC 1991, 56, 7195.
16. (a) Buhleier, E.; Wehner, W.; Vögtle, F. S 1978, 155. (b)Wörner, C.; Mülhaupt, R. AG(E) 1993, 32, 1306 (c) de Brabander-van den Berg, E. M. M.; Meijer, E. W. AG(E) 1993, 32, 1308.
17. Horner, L.; Jurgeleit, W.; Klüpfel, K. LA 1955, 591, 108.
18. (a) Kharash, M. S.; Reinmuth, O. Grignard Reactions of Nonmetallic Substances; Prentice Hall: New York, 1954; pp 782, 814. (b) Mukherjee, S. M. JIC 1948, 25, 155.
19. Alexakis, A.; Berlan, J.; Besace, Y. TL 1986, 27, 1047.
20. Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. JOC 1982, 47, 119.
21. Evans, D. A.; Bilodeau, M. T.; Somers, T. C.; Clardy, J.; Cherry, D.; Kato, Y. JOC 1991, 56, 5750.
22. Brown, H. C.; Midland, M. M. AG(E) 1972, 11, 692.
23. Miyaura, N.; Itoh, M.; Suzuki, A. TL 1976, 255.
24. Yamashita, M.; Tashika, H.; Uchida, M. BCJ 1992, 65, 1257.
25. (a) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic Press: London, 1985 and references therein. (b) Bumagin, N. A.; More, P. G.; Beletskaya, I. P. JOM 1989, 371, 397.
26. Choudary, B. M.; Sarma, R. M.; Rao, K. K. T 1992, 48, 719.
27. Lloyd, W. G.; Luberoff, B. J. JOC 1969, 34, 3949.
28. Hosokawa, T.; Ohta, T.; Kanayama, S.; Murahashi, S.-I. JOC 1987, 52, 1758.
29. For reviews, see: (a) Speier, J. L. Adv. Organomet. Chem. 1979, 17, 407. (b) Ojima, I. The Chemistry of Organic Silicon Compounds; Patai, S.; Rappoport, Z. Eds.; Wiley: New York, 1989; Part 2, Chapter 25. For the specific examples described, see: (c) Boudjouk, P.; Han, B.-H.; Jacobsen, J. R.; Hauck, B. J. CC 1991, 1424 and references therein. (d) Bank, H. M. CA 1992, 116, 255808a.
30. Pesa, F.; Haase, T. J. Mol. Catal. 1983, 18, 237.
31. Kollar, L.; Consiglio, G.; Pino, P. C 1986, 40, 428 and references therein.
32. (a) Saegusa, T.; Yonezawa, K.; Murase, I.; Konoike, T.; Tomita, S.; Ito, Y. JOC 1973, 38, 2319. (b) Saegusa, T.; Ito, Y. S 1975, 291.
33. While the reactions of some copper complexes with substituted acrylonitriles give good yields, unsatisfactory yields were obtained using acrylonitrile; see: Saegusa, T.; Murase, I.; Ito, Y. BCJ 1972, 45, 830.
34. Somsak, L.; Praly, J.-P.; Descotes, G. SL 1992, 119.
35. Wienand, A.; Reissig, H.-U. OM 1990, 9, 3133.
36. (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon Press: Oxford, 1986. (b) Curran, D. P. COS 1991, 4, 715.
37. (a) Giese, B.; González-Gómez, J. A.; Witzel, T. AG(E) 1984, 23, 69 and references therein. (b) Dupuis, J.; Giese, B.; Hartung, J.; Leising, M.; Korth, H.-G, Sustmann, R. JACS 1985, 107, 4332. (c) Angoh, A. G.; Clive, D. L. J. CC 1985, 980.
38. (a) For a recent example using CrII, see: Tashtoush, H. I.; Sustmann, R. CB 1992, 125, 287. (b) Scheffold, R.; Abrecht, S.; Orlinski, R.; Ruf, H.-R.; Stamouli, P.; Tinembart, O.; Walder, L.; Weymuth, C. PAC 1987, 59, 363. (c) Sarandeses, L. A.; Mourino, A.; Luche, J.-L. CC 1992, 798. (d) Blanchard, P.; El Kortbi, M. S.; Fourrey, J.-L.; Robert-Gero, M. TL 1992, 33, 3319.
39. Boger, D. L.; Mathvink, R. J. JOC 1992, 57, 1429.
40. (a) Curran, D. P.; Chen, M.-H. JACS, 1987, 109, 6558. (b) For a recent example, see: Journet, M.; Malacria, M. JOC 1992, 57, 3085.
41. Pattenden, G. CSR 1988, 17, 361.
42. (a) Leusink, A. J.; Noltes, J. G. TL 1966, 335. (b) Pereyre, M.; Colin, G.; Valade, J. BSF(2) 1968, 3358. (c) Four, P.; Guibe, F. TL 1982, 23, 1825.
43. Lee, E.; Uk Hur, C. TL 1991, 32, 5101.
44. Ogawa, A.; Tanaka, H.; Yokoyama, H.; Obayashi, R.; Yakoyama, K.; Sonoda, N. JOC 1992, 57, 111.
45. Kopping, B.; Chatgilialoglu, C.; Zehnder, M.; Giese, B. JOC 1992, 57, 3994.
46. (a) Albisetti, C. J.; Fisher, N. G.; Hogsed, M. J.; Joyce, R. M. JACS 1956, 78, 2637. (b) Mehta, G.; Reddy, A. V. TL 1979, 2625.
47. Coyner, E. C.; Hillman, W. S. JACS 1949, 71, 324.
48. (a) Mizuno, K.; Okamoto, H.; Pac, C.; Sakurai, H.; Murai, S.; Sonoda, N. CL 1975, 237. (b) Adembri, G.; Donati, D.; Fusi, S.; Ponticelli, F. JCS(P1) 1992, 2033. (c) Quendo, A.; Rousseau, G. SC 1989, 19, 1551. (d) Ohashi, M.; Yoshino, A.; Yamazaki, K.; Yonezawa, T. TL 1973, 3395.
49. (a) Hayashi, Y.; Niihata, S.; Narasaka, K. CL 1990, 2091. For other [2 + 2] cycloadditions of allenes, see: Pasto, D. J.; Sugi, K. D. JOC 1991, 56, 3795.
50. (a) Trost, B. M.; Chan, D. M. T. JACS 1983, 105, 2315. (b) Trost, B. M. AG(E) 1986, 25, 1.
51. (a) Noyori, R.; Odagi, T.; Takaya, H. JACS 1970, 92, 5780. (b) For a review, see: Binger, P.; Buch, H. M. Top. Curr. Chem. 1987, 135, 77.
52. For reviews, see: (a) Confalone, P. N.; Huie, E. M. OR 1988, 36, 1. (b) Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; Vols. 1 and 2. (c) Advances in Cycloaddition, Curran, D. P., Ed.; JAI Press: Greenwich, CT, 1988-1993; Vols. 1-3.
53. Katritsky, A. R.; Hitchings, G. J.; Zhao, X. S 1991, 863.
54. Wender, P. A.; Mascarenas, J. L. TL 1992, 33, 2115.
55. Jung, M. E.; Longmei, Z.; Tangsheng, P.; Huiyan, Z.; Yan, L.; Jingyu, S. JOC 1992, 57, 3528.
56. (a) Schrauzer, G. N.; Eichler, S. CB 1962, 95, 2764. (b) Yoshikawa, S.; Aoki, K.; Kiji, J.; Furukawa, J. BCJ 1975, 48, 3239. (c) Noyori, R.; Umeda, I.; Kawauchi, H.; Takaya, H. JACS 1975, 97, 812. (d) Lautens, M.; Edwards, L. E. JOC 1991, 56, 3761.
57. Zhou, Z.; Costa, M.; Chiusoli, G. P. JCS(P1) 1992, 1399. For a review, see: Vollhardt, K. P. C. AG(E) 1984, 23, 539.
58. (a) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; Wiley: New York, 1990. (b) Ward, D. E.; Gai, Y.; Zoghaib, W. M. CJC 1991, 69, 1487 and references therein.
59. (a) Moore, J. A.; Partain, E. M. III JOC 1983, 48, 1105. (b) Brion, F. TL 1982, 23, 5299.
60. (a) Ito, Y.; Amino, Y.; Nakatsuka, M.; Saegusa, T. JACS 1983, 105, 1586. (b) For reactions of chromium complexed species, see: Kundig, E. P.; Bernardinelli, G.; Leresche, J. CC 1991, 1713.
61. Rodrigo, R.; Knabe, S. M.; Taylor, N. J.; Rajapaksa, D.; Chernishenko, M. J. JOC 1986, 51, 3973 and references therein.
62. Ruiz, N.; Pujol, M. D.; Guillaumet, G.; Coudert, G. TL 1992, 33, 2965.

Mark Lautens & Patrick H. M. Delanghe

University of Toronto, Ontario, Canada



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