Propionaldehyde t-Butylimine1

(R = t-Bu)

[7020-81-7]  · C7H15N  · Propionaldehyde t-Butylimine  · (MW 113.23) (R = t-Bu, Li salt)

[75261-61-9]  · C7H14LiN  · 2-Lithiopropionaldehyde t-Butylimine  · (MW 119.16) (R = Cy)

[6898-80-2]  · C9H17N  · Propionaldehyde Cyclohexylimine  · (MW 139.27)

(two-carbon nucleophile in enolate alkylations, conjugate addition reactions, and directed aldol condensations; especially useful for a-monoalkylations and three-carbon homologations1)

Physical Data: R = t-Bu: bp 103 °C,2 48-50 °C/115 mmHg,3 47-49 °C/95 mmHg.4 R = Cy: bp 63-64 °C/15 mmHg,4 62-63 °C/12 mmHg;5 n16D 1.4450.

Solubility: sol THF, ether, CCl4, pentane, benzene, toluene.

Form Supplied in: colorless liquid when freshly distilled; darkens on prolonged standing

Analysis of Reagent Purity: NMR or IR.

Preparative Methods: the general method adapted by Stork and Dowd from the procedure developed earlier by Tiollais is said to be highly efficient for the synthesis of aldimines from low-boiling aldehydes.2 Quantitative yields have also been reported when propanal is added to a preformed amine-Titanium(IV) Chloride complex.6 Lithiopropionaldehyde t-butylimine is usually prepared by reaction with a slight excess of a hindered nonnucleophilic base like Lithium Diethylamide in THF or ether at -78 °C under N2 or argon.7,8 A variation of this method calls for addition of Hexamethylphosphoric Triamide to the reaction mixture.8b

Handling, Storage, and Precautions: best used when freshly prepared. Imines can be distilled, but they tend to polymerize upon long standing. Stored samples are distilled over KOH to remove high-boiling condensation products prior to use. Storage as neat liquids is not recommended for long periods, but solutions in dry THF (0.4 M) can be stored at -20 to -30 °C with minimal deterioration.9 In acidic solutions, the imine reverts to propanal and the amine. The lithiated imine is generally prepared in situ under N2 or argon. Use in a fume hood.

Condensation Reactions.

The synthetic value of these reagents lies in their facile conversion to imine anions and their low propensity for self-aldol condensation. These characteristics favor their use over propionaldehyde in directed crossed-aldol condensation reactions. (E)-a,b-Unsaturated aldehydes are stereoselectively formed upon hydrolysis and dehydration of the a-methyl-b-hydroxy aldehyde adducts. This strategy is illustrated in the synthesis of nuciferal (eq 1) and sinensal,7 and in a variety of intermediates for the synthesis of natural products,1,10

These reagents can tolerate the presence of other functional groups in the electrophile (eq 2).10 Phosphonates11 and trialkylsilyl groups3,8,12 have been used to stabilize the lithio imine anions in these reactions.

g-Diketones have been prepared by Michael-type additions of the t-Bu imine anion and by alkylation with allylic halides followed by ozonolysis.13


The ease with which metalloenamines undergo a-monoalkylation in the presence of alkyl halides extends the usefulness of these reagents. Yields are usually high and no rearrangement is observed even with allyl halides. In contrast, propionaldehyde tends to undergo self-aldol condensation in the presence of base and is not alkylated by primary and secondary alkyl halides. Enamines, on the other hand, tend to undergo N-alkylation.14 With dihalides as alkylating agents, subsequent intramolecular reactions can be utilized to effect ring closure. Nitrogen heterocycles like tetrahydropyridines (eq 3)15 and substituted azetidines (eq 4)16 have been synthesized in this manner. Other ring closure reactions using these imines have afforded 2-amino-5-cyanopyrroles,17 azaphosphorines,18 azaphospholenes,18 substituted 4-methylpyrrolidines,19 and substituted 3-pyridinecarboxylic acids and their derivatives.20

Other Reactions.

Functionalization at the a-position can be achieved using a variety of reagents. N-Chlorosuccinimide can be used for a-chlorination. A stereoselective reaction with a chiral sulfinate ester affords (Z)-b-enamino sulfoxides,4 while nitration with an alkyl nitrate yields 1-alkylamino-2-nitro-1-alkenes (eq 5).21 The (Z) stereochemistry is preferred due to stabilization by intramolecular H-bonding. These reagents also provide a useful route for the synthesis of vinyl isocyanates by reaction with Phosgene22 and secondary propanamines by chemical reduction using Sodium Cyanoborohydride23 or catalytic hydrogenation with Raney Nickel.24 Hydrolysis of the elaborated imines is often a final step in a reaction sequence involving these reagents. Such hydrolyses are facile and are often carried out using cold, aqueous acid, e.g. NaOAc-HOAc-H2O (1:2:2),25 Oxalic Acid,7 NH4Cl,16 and Zinc Chloride.3 Cold 10% oxalic acid is most commonly used.

Related Reagents.

Acetaldehyde N-t-Butylimine; Acetone Cyclohexylimine; Acetone Hydrazone; t-Butylamine; 2-Chloro-2-methylpropanal N-Isopropylimine; 1-(N,N-Dimethylamino)-2-methyl-1-propene.

1. For general reviews on imines, see: (a) Layer, R. W. CRV 1963, 63, 489. (b) Wagner-Jauregg, T. S 1976, 349. (c) Viehe, H. G. CI(L) 1977, 386. (d) Whitesell, J. K.; Whitesell, M. A. S 1983, 517. (e) Mukaiyama, T. OR 1981, 29, 203. (f) Martin, S. F. COS 1991, 2, 475.
2. (a) Stork, G.; Dowd, S. R. OSC 1988, 6, 526. (b) Tiollais, R. BSB 1947, 14, 708. (c) Suydam, F. H. Anal. Chem. 1963, 193.
3. Bellassoued, M.; Majidi, A. JOC 1993, 58, 2517.
4. Annunziata, R.; Cinquini, M.; Restelli, A. JCS(P1) 1982, 1183.
5. Wittig, G.; Frommeld, H. D.; Suchanek, P. AG 1963, 75, 978.
6. Carlson, R.; Larrson, U.; Hansson, L. ACS 1992, 46, 1211.
7. (a) Buchi, G.; Wuest, H. JOC 1969, 34, 1122. (b) Buchi, G.; Wuest, H. HCA 1967, 50, 2440.
8. (a) Corey, E. J.; Enders, D.; Bock, M. G. TL 1976, 7. (b) Cuvigny, T. Normant, H. BSF 1970, 3976.
9. Meyers, A. I.; Poindexter, G. S.; Brich, Z. JOC 1978, 43, 892.
10. Henke, B. R.; Kouklis, A. J.; Heathcock, C. H. JOC 1992, 57, 7056.
11. Nagata, W.; Hayase, Y. JCS(C) 1969, 460.
12. Schlessinger, R. H.; Poss, M. A.; Richardson, S.; Lin, P. TL 1985, 26, 2391.
13. (a) Ahlbrecht, H.; Von Daacke, A. S 1987, 24. (b) Molander, G. A.; Cameron, K. O. JACS 1993, 115, 830.
14. Stork, G.; Dowd, S. R. JACS 1963, 85, 2178.
15. (a) Stevens, C.; De Kimpe, N. SL 1991, 5, 351. (b) Sulmon, P.; De Kimpe, N.; Schamp, N. S 1989, 8.
16. De Kimpe, N.; Stevens, C. S 1993, 89.
17. Verhe, R.; De Kimpe, N.; De Buyck, L.; Tilley, M.; Schamp. N. T 1980, 36, 131.
18. (a) Bourdieu, C.; Foucaud, A. TL 1986, 27, 4725. (b) Wai, T.; Wai, H. L.; Bourdieu, C.; Foucaud, A. T 1990, 46, 6715.
19. Trost, B. M.; Bonk, P. J. JACS 1985, 107, 1778.
20. Ito, K.; Yokokura, S.; Miyajima, S. JHC 1989, 26, 773.
21. Fetell, A. I.; Feuer, H. JOC 1978, 43, 497.
22. Koenig, K. H.; Reitel, C.; Mangold, D.; Feuerherd, K. H.; Oiser, G. AG 1979, 91, 334.
23. Borch, R. F.; Bernstein, M. D.; Durst, H. D. JACS 1971, 93, 2897.
24. Campbell, K. N.; Sommers, A. H.; Campbell, B. K. JACS 1944, 66, 82.
25. Stork, G.; Benaim, J. JACS 1971, 93, 5938.

Milagros M. Peralta

University of the Phillipines at Los Banos, Laguna, Phillipines

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.