Allylamine

[107-11-9]  · C3H7N  · Allylamine  · (MW 57.11)

(used in synthesis of secondary or tertiary allylamines and -amides and heterocyclic compounds1)

Alternate Name: 2-propen-1-amine.

Physical Data: bp 56.6 °C/756 mmHg; d 0.762 g cm-3; mp -88 °C; fp -28 °C;n 20D 1.4205; dipole moment 1.31 D (benzene; 25 °C); pKa 9.49 (H2O; 25 °C).

Solubility: miscible with water, alcohol, ether, chloroform.

Form Supplied in: colorless liquid, commercially available.

Handling, Storage, and Precautions: corrosive. Highly toxic. Lachrymator. Use only in a chemical fume hood. Use chemical resistant gloves, safety goggles. Do not breathe vapor. Avoid contact with eyes, skin, and clothing. Wash thoroughly after handling. Keep tightly closed. Store in a cool dry place. Extremely flammable.

Allylamine acts as a typical amine towards acylating and alkylating agents and in the formation of imines with aldehydes and ketones. The double bond is also unremarkable in its chemical behavior.

N-Acylation.

Acylations of the amino function can be performed with the usual reagents, such as acid anhydrides,2 acid chlorides,3 enol esters,4 lactones,5 and carboxylic acids in the presence of molecular sieves6 or other activating agents (e.g. eq 1).7 N-Allylcarbamates are obtained upon acylation of allylamine with reagents like Benzyl Chloroformate or Di-t-butyl Dicarbonate in the presence of base.8 Another route to carbamates consists of saturation of an allylamine solution with carbon dioxide and reaction of the ionic carbamate thus obtained with Benzyl Chloride or dimethyl carbonate (eq 2).9 Iodolactonization of the ionic carbamates leads to oxazolidinones (eq 3).10 Diacylations of allylamine to N-allylimides are known;2a an interesting application is the facile preparation of 1,4-disubstituted piperazine-2,4-diones with iminodiacetic acid derivatives (eq 4).11

N-Alkylation.

Allylamine can be converted under mild conditions into secondary amines with functionalized alkyl chlorides, bromides, and tosylates.12 Alkylations through conjugate addition to a,b-unsaturated nitriles13 and a,b-unsaturated ketones are known (eq 5).14

In connection with the search for efficient routes to b-lactam antibiotics, N-allylazetidines have been prepared by dialkylation of allylamine. Thus t-butyl 2,4-dibromobutyrate led to the azetidine derivative in moderate yield (eq 6).15 Allylamine attacks the readily available (R*,R*)-bromobenzyloxirane (1) at the less substituted oxirane carbon and then at the benzylic bromide to give the trans-azetidine derivative in reasonable yield (eq 7).16

Imine Formation.

Reaction of allylamine with aldehydes17 (eq 8)17a and ketones18 gives rise to imines. Addition of Lewis acids or molecular sieves may be necessary (eq 9).18b Reductive aminations of ketones with allylamine can be performed in the presence of reducing agents like zinc-modified cyanoborohydride (eq 10).19

An important route to b-lactam antibiotics proceeds via condensation of imines with ester enolates to form the b-lactam ring. Allylimines are used in this condensation because the N-allyl protecting group from b-lactams can be easily removed by standard methods, thus providing access to b-lactams with a variety of other N-substituents. In a highly interesting example of this condensation, the chiral (S,S)-diazaborolidine (2) is used in the asymmetric synthesis of b-lactams from achiral esters and allylimines. Reaction of the (Z)-boron enolate, prepared from S-t-butyl thiopropionate with triethylamine, with N-allylimines derived from various aldehydes at -78 °C proceeds with high diastereoselectivity and high enantioselectivity to afford the b-amino acid esters. Treatment of these esters with t-Butylmagnesium Chloride results in ring closure to the trans-substituted b-lactam derivatives (eq 11).20 In another approach to b-lactams, the allylimines are treated with DBU to afford 2-aza-1,3-dienes which react with acid chlorides to provide the cis-substituted b-lactams (eq 12).21

Reactions at the C=C-Bond.

The double bond shows the usual reactions, such as addition of bromine22 or hydrogen halides,23 Friedel-Crafts reaction (eq 13),24 Diels-Alder reaction (eq 14),25 or Pd-catalyzed cyclopropanation with Diazomethane (eq 15).26

Related Reagents.

O-Allylhydroxylamine; O-Benzylhydroxylamine Hydrochloride; t-Butylamine.


1. (a) Gladych, J. M. Z.; Hartley, D. Comprehensive Organic Chemistry; Barton, D. H. R., Ed.; Pergamon Press: Oxford, 1979; Vol. 2, pp 71-73. (b) Ullmann's Encyclopedia of Industrial Chemistry, 5th ed.; VCH: Weinheim, 1985; Vol. A1, pp 439, 441.
2. (a) Stille, J. K.; Becker, Y. JOC 1980, 45, 2139. (b) Hubert, A. J.; Moniotte, P.; Goebbels, G.; Warin, R.; Teyssié, P. JCS(P2) 1973, 1954.
3. (a) Newcomb, M.; Marquardt, D. J.; Deeb, T. M. T 1990, 46, 2329. (b) Fisher, L. E.; Muchowski, J. M.; Clark, R. D. JOC 1992, 57, 2700.
4. Kabouche, Z.; Bruneau, C.; Dixneuf, P. H. TL 1991, 32, 5359.
5. (a) Späth, E.; Lintner, J. CB 1936, 69, 2727. (b) Walters, M. A.; McDonough, C. S.; Brown, Jr., P. S.; Hoem, A. B. TL 1991, 32, 179.
6. Cossy, J.; Pale-Grosdemange, C. TL 1989, 30, 2771.
7. Nomura, R.; Nakano, T.; Yamada, Y.; Matsuda, H. JOC 1991, 56, 4076.
8. Bischofberger, N.; Waldmann, H.; Saito, T.; Simon, E. S.; Lees, W.; Bednarski, M. D.; Whitesides, G. M. JOC 1988, 53, 3457.
9. Aresta, M.; Quaranta, E. T 1991, 47, 9489; 1992, 48, 1515.
10. Toda, T.; Kitagawa, Y. AG(E) 1987, 26, 334.
11. Kruse, C. G.; Troost, J. J.; Cohen-Fernandes, P.; Linden, H. van der; Loon, J. D. van RTC 1988, 107, 303.
12. (a) Costa, B. R. de; Radesca, L.; Di Paolo, L.; Bowen W. D. JMC 1992, 35, 38. (b) Garst, M. E.; Bonfiglio, J. N.; Marks, J. JOC 1982, 47, 1494. (c) Martin, S. F.; Williamson, S. A.; Gist, R. P.; Smith, K. M. JOC 1983, 48, 5170. (d) Brown, S. W.; Pauson, P. L. JCS(P1), 1990, 1205.
13. Becking, L.; Schäfer, H. J. TL 1988, 29, 2797.
14. Ireland, R. E.; Willard, A. K. JOC 1974, 39, 421.
15. Wasserman, H. H.; Lipshutz, B. H.; Tremper, A. W.; Wu, J. S. JOC 1981, 46, 2991.
16. Toda, T.; Karikomi, M.; Ohshima, M.; Yoshida, M. H 1992, 33, 511.
17. (a) Bergmann, M.; Miekeley, A. CB 1924, 57, 662. (b) Cook, G. R.; Barta, N. S.; Stille, J. R. JOC 1992, 57, 461.
18. (a) Govindan, C. K.; Taylor, G. JOC 1983, 48, 5348. (b) Welch, J. T.; De Corte, B.; De Kimpe, N. JOC 1990, 55, 4981.
19. Kim, S.; Oh, C. H.; Ko, J. S.; Ahn, K. H.; Kim, Y. J. JOC 1985, 50, 1927.
20. Corey, E. J.; Decicco, C. P.; Newbold, R. C. TL 1991, 32, 5287.
21. Georg, G. I.; Kant, J.; He, P.; Ly, A. M.; Lampe, L. TL 1988, 29, 2409.
22. Paal, C.; Hermann, C. CB 1889, 22, 3076.
23. (a) Abderhalden, E.; Eichwald, E. CB 1918, 51, 1312. (b) Gabriel, S.; Weiner, J. CB 1888, 21, 2669.
24. Weston, A. W.; Ruddy, A. W.; Suter, C. M. JACS 1943, 65, 674.
25. Alder, K.; Windemuth, E. CB 1938, 71, 1939.
26. Tomilov, Yu. V.; Kostitsyn, A. B.; Shulishov, E. V.; Nefedov, O. M. S 1990, 246.

Henk de Koning & W. Nico Speckamp

University of Amsterdam, The Netherlands



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