Ethylenimine1

[151-56-4]  · C2H5N  · Ethylenimine  · (MW 43.08)

(aminoalkylating agent1)

Alternate Name: aziridine

Physical Data: mp -74 °C; bp 56.7 °C; d 0.829 g cm-3.

Solubility: miscible with H2O and virtually all organic solvents.

Form Supplied in: colorless liquid.

Handling, Storage, and Precautions: highly toxic; causes inhalation hazard and skin burns. Use a laboratory hood and wear goggles and gloves. Aziridine is also highly flammable (flash point -11.1 °C, similar to that of benzene). Stable at rt if acid impurities are excluded. Usually stored over solid sodium hydroxide.

Introduction.

Many reactions of aziridines are similar to other cyclic amines. However, the strain present (113 kJ mol-1) results in much easier ring-opening reactions by cleavage of C-N and occasionally C-C bonds.

Aziridines form quaternary ammonium salts with protons and Lewis acids, but these salts are usually reactive towards nucleophiles present in the reaction mixture. They are isolable using weakly nucleophilic solvents (like H2O) and counterions2 (perchlorate,2a tetrafluoroborate,2b trinitrophenylsulfonate,2c hydrogen sulfate, etc.). Aziridinium salts were formed at low temperatures from salicylic, glycolic, formic, acetic, benzoic, and dichloroacetic acids, but decomposed within a very short time.1 Stable salts are obtained from dicarboxylic acids (oxalic,3a adipic, terephthalic, isophthalic, tetrachlorophthalic3b).

Aziridine forms coordination compounds by the donation of the unshared pair of electrons on the nitrogen atom to molecules or metal ions capable of accepting such electron pairs. The complex with BMe3 is stable at 100 °C for several hours.4 Boron Trifluoride Etherate cleaves aziridine rings readily,5 but adducts with Trimethyl Borate and B(OPh)3 are reasonably stable.6 Labile metal ion-aziridine complexes have been made with CuII, HgII, MnII, CoII, and NiII.7 Some salts like CrIII, CoIII, PdII, PtII, RhI, and RhIII give inert complexes with aziridine.7

Nucleophilic Attack of the Aziridine Nitrogen on Carbon.

Stable HBF4 salts are formed when trialkyloxonium fluoroborates are used for alkylation of aziridine.1a Problems with ring cleavage arise in the reaction of aziridine with alkyl or aryl halides (alkylation) and formation of quaternary ammonium salts. Ring cleavage can be avoided or reduced by using an excess of aziridine over alkyl halide.

Nucleophilic addition to b-alkenic carbons depends on the presence of acceptor groups to stabilize the transient partial negative charge on the a-carbon in the transition state. The reaction of aziridine with activated vinylic chlorides proceeds with retention of configuration.8,9 Addition to activated alkynes is stereoselective (eq 1).8 Only esters of alkyne mono-9 and dicarboxylic acids10 yield an excess of (E)-isomer. Other acceptor groups prefer the formation of (Z)-isomer.

Ring Expansion of Aziridines.

Carbonylation gives b-lactams (eqs 2 and 3).11 The insertion occurs with net retention of configuration and is quite regioselective. Carbon Monoxide inserts into either the more (catalyst Tetracarbonyl(di-m-chloro)dirhodium)11a or the less (catalyst Tetracarbonylnickel)11b substituted C-N bond. The (E)-amidine formed by addition of aziridine to isocyanides (eq 4) rearranges to the imidazolines.12

Aziridine is an excellent starting material for the synthesis of various heterocycles: 1,3-oxazolidines,13 1,3-thiazolidines,13 dihydro-1,4-thiazines,14 bicyclic pyrrolidines,15 D1-pyrrolines.16 Moreover, it is a building block for various alkaloids: crinine, sendaverine, corgoine, reframidine, a-dihydrocaranone, and g-lycorane.1c

Other Reactions.

N-Chloroaziridine is prepared by gas/solid chlorination17 and used to prepare azirine by dehydrohalogenation. The larger cyclic imines (4-6 membered) are more stable and obtained in higher yields (eq 5).17b Various aza macrocycles can be formed by using aziridine as a construction unit, either by ring cleavage,18a or with aziridine in the side chain.18b


1. (a) Dermer, O. C.; Ham, G. E. Ethylenimine and Other Aziridines; Academic: New York, 1969. (b) Deyrup, J. A. Chem. Heterocycl. Comp. 1983, 42, 1. (c) Kametani, T.; Honda, T. Adv. Heterocycl. Chem. 1986, 39, 181.
2. (a) Jones, G. D. The Chemistry of Cationic Polymerization; Plesch, P. H., Ed.; Macmillan: New York, 1963; p 513. (b) Harder, U.; Pfeil, E.; Zenner, K.-F. CB 1964, 97, 510. (c) Clark, R. D.; Helmkamp, G. K. JOC 1964, 29, 1316.
3. (a) Avetisyan, A. A.; Ovsepyan, V. V.; Kostyanovskii, R. G. IZV (Engl. Transl.) 1983, 32, 167. (b) Christena, R. C.; Johnston, E. L. U.S. Patent 3 676 424, 1972 (CA 1972, 77, 102 619r.)
4. Brown, H. C.; Gerstein, M. JACS 1950, 72, 2926.
5. Eis, M. J.; Ganem, B. TL 1985, 26, 1153.
6. Fedotova, L. A.; Voronkov, M. G. KGS (Engl. Transl.) 1965, 1, 573.
7. (a) Jackson T. B.; Edwards J. O. JACS 1961, 83, 355. (b) Jackson, T. B.; Edwards, J. O. IC 1962, 1, 398.
8. Truce, W. E.; Gorbaty M. L. JOC 1970, 35, 2113.
9. Truce, W. E.; Brady, D. G. JOC 1966, 31, 3543.
10. El'natanov, Yu. I.; Kostyanovskii R. G. IZV (Engl. Transl.) 1988, 37, 1661.
11. (a) Chamcaang, W.; Pinhas A. R. CC 1988, 710. (b) Alper, H.; Urso, F. JACS 1983, 105, 6737.
12. Hegarty, A. F.; Chandler, A. TL 1980, 21, 885.
13. Sasaki, T.; Yoshioka, T.; Shoji K. JCS(C) 1969, 1086.
14. Asinger, F.; Stalschus, J.; Saus, A. M 1979, 110, 425.
15. (a) Hudlicky, T.; Frazier, J. O.; Seoane, G.; Tiedje, M.; Seoane, A.; Kwart, L. D.; Beal, C. JACS 1986, 108, 3755. (b) Pearson, W. H.; Celebuski, J. E.; Poon, Y.-F.; Dixon, B. R.; Glans, J. H. TL 1986, 27, 6301.
16. (a) Whitlock, H. W., Jr.; Smith, G. L. TL 1965, 1389. (b) Heine, H. W. JACS 1963, 85, 2743.
17. (a) Guillemin, J. C.; Denis, J. M. S 1985, 1131. (b) Guillemin, J.-C.; Denis, J.-M.; Lasne, M.-C.; Ripoll, J.-L. T 1988, 44, 4447.
18. (a) Garcia-Espana, E.; Micheloni, M.; Paoletti, P. G 1985, 115, 399. (b) Bogatsky, A. V.; Lukyanenko, N. G.; Pastushok, V. N.; Kostyanovsky, R. G. S 1983, 992.

Peteris Trapencieris

Institute of Organic Synthesis, Riga, Latvia



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