Acetaldehyde N-t-Butylimine

[7020-80-6]  · C6H13N  · Acetaldehyde N-t-Butylimine  · (MW 99.17) (E)

[62058-77-9]

(acetaldehyde equivalent; synthesis of a,b-unsaturated aldehydes)

Alternate Names: N-ethylidene-1,1-dimethylethylamine; N-(ethylidene)-t-butylamine; N-ethylidene-2-methyl-2-propaneamine.

Physical Data: bp 25-28 °C/95 mmHg; n19.2D 1.4005.

Solubility: sol most organic solvents.

Form Supplied in: colorless liquid; not commercially available.

Analysis of Reagent Purity: 1H NMR; GC.

Preparative Methods: condensation of freshly distilled Acetaldehyde with t-Butylamine without solvent.1-4 The way the reactants are mixed is crucial. t-Butylamine is added dropwise to 1 equiv of the aldehyde at -10 to 0 °C (eq 1). The reaction mixture is further stirred at rt for 10 min after which solid KOH is added (about 10 g per mol). After separation of the water layer, the imine is distilled over KOH using a Vigreux column. It was reported that azeotropic removal of the water, formed during the reaction, with an organic solvent, nonmixable with water, gave good results.5 However, it was found that this procedure with dichloromethane as solvent gave an end product which was always contaminated with the solvent.4

Handling, Storage, and Precautions: very sensitive to hydrolysis; store in closed vessels under an inert atmosphere in the refrigerator. Use of the freshly distilled reagent is recommended. Use in a fume hood.

Introduction.

Imines derived from acetaldehyde and lower alkylamines, e.g. ethylamine, are extremely difficult to handle under basic reaction conditions.6 More bulky derivatives such as acetaldimines derived from cyclohexylamine and preferably t-butylamine are much more stable and can be used as a ready acetaldehyde equivalent.

Reactions of Metalated Acetaldehyde N-t-Butylimine.

Lithiation of aldimines results in a change from (E) to (Z) configuration.7 A facile carbon-carbon bond rotation in 1-azaallyllithium reagents is readily observed by variable temperature 1H NMR spectroscopy.8 Lithiation is most frequently performed by Lithium Diisopropylamide or Lithium Diethylamide in THF or diethyl ether. Lithiated acetaldehyde t-butylimine is readily a-monoalkylated by alkyl bromides, but a,a-dialkylation is difficult to avoid.4 This acetaldimine has been used to prepare the alkaloid stenusine, the spreading agent of the beetle Stenus comma (eq 2).4,9 Attempts to perform the synthesis starting from acetaldehyde N-ethylimine failed.4

Similar a-deprotonations and a-alkylations of acetaldehyde cyclohexylimine have been performed with Potassium-Graphite and alkyl bromides, respectively.10 o-Halo aldehydes (eq 3),11 4-bromo-4-pentenal,12 and 5-chloro-4-alkenals12 are accessible from the same aldimine after deprotonation and reaction with a,o-dihaloalkanes, 2,3-Dibromopropene, and 3-chloroallyl chloride, respectively.

Acetaldehyde t-butylimine is an extremely versatile building block for the synthesis of a,b-unsaturated aldehydes by lithiation, subsequent reaction with diethyl chlorophosphate, further reaction with aldehydes or ketones, and final hydrolysis (eq 4).13 Examples include 3-cyclohexylpropenal (1),13 (E,E)-4-(phenylthiomethyl)-2,4-hexadienal (2),14 polyoxygenated cyclohexanes (3)15 and others.16,17 An alternative method consists of a-trimethylsilylation of acetaldehyde t-butylimine followed by deprotonation and reaction with a carbonyl compound (eq 5).17,18 a,a-Disilylation is accomplished similarly and leads also via condensation with aldehydes to a wide range of (E)-a,b-unsaturated aldehydes (eq 6).19,20 It should be pointed out also that directed aldol condensations between lithiated acetaldehyde imines and aldehydes or ketones have been frequently reported (eq 7).6,21 Other electrophiles, e.g. nitriles,22,23 carboxylic esters,6 and enones,6,24 lead to the expected reaction products.

Nitration can be accomplished after deprotonation and reaction with ethyl nitrate, but the reaction takes a partially different course with propyl nitrate (eq 8).25 In a similar way, b-enamino and b-iminosulfoxides are obtained by using menthyl p-toluenesulfinate.26 Lithiated acetaldehyde t-butylimine reacts with chlorophosphites to give a-phosphorylated imines, which are in equilibrium with their enamino form.27,28 Without the initial deprotonation step, N-phosphorylation takes place.29

a-Functionalization.

Acetaldehyde t-butylimine is a,a,a-trichlorinated with N-Chlorosuccinimide at room temperature (eq 9).30 The resulting chloral imine is a suitable substrate for conversion into a,a-dichloroacetimidates, a-cyano-b,b-dichloroenamines, a,b,b-trisulfenylated enamines, and b,b,b-trichloroamines.30 The reaction of acetaldehyde t-butylimine with aromatic nitroso compounds affords a-(N-hydroxy-N-aryl)aminoaldimines or a-diimines.31,32

Synthesis of Heterocycles.

Condensation of acetaldehyde t-butylimine with enamines at 150-220 °C affords rearranged 1-azabutadienes via cycloreversion of an azacyclobutene intermediate, formed by [2 + 2] cycloaddition of the reactants (eq 10).33 Further reaction of the 1-azabutadienes with enamines in the presence of p-toluenesulfonic acid produces pyridines (eq 10).33

A very convenient synthesis of the imidazole nucleus consists of the reaction of acetaldehyde t-butylimine with p-Tolylsulfonylmethyl Isocyanide (TosMIC) in the presence of t-butylamine (eq 11).34 The same aldimine is readily oxygenated by peroxy acids to the corresponding oxaziridine.35-37 Asymmetric oxidations have been performed with monoperoxycamphoric acid.35,36

Reactions at the Imino Bond.

Nucleophilic addition of dimethyl phosphite across the imino bond of acetaldehyde t-butylimine without any solvent delivers the addition product (eq 12).38 Functionalization at the nitrogen atom is accomplished with Phosgene, which gives the N-vinylcarbamoyl chloride (eq 13).39,40 Upon thermolysis, a,b-unsaturated isocyanates and t-butyl chloride are produced (eq 13).40 Functionalized N-nitrosodialkylamines are accessible from acetaldehyde t-butylimine via reaction with Nitrosyl Chloride and, for example, Ethanethiol (eq 14).41

Related Reagents.

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


1. Hurwitz, M. D. U.S. Patent 2 582 128 1952 (CA 1952, 46, 8146i).
2. Campbell, K. N.; Sommers, A. H.; Campbell, B. K. JACS 1944, 66, 82.
3. Wittig, G.; Hesse, A. OSC 1988, 6, 901.
4. Stevens, C.; De Kimpe, N. JOC 1993, 58, 132.
5. Beekhuis, G. E.; Thoma, J. A. Ger. Offen. 2 109 267, 1971 (CA 1971, 75, 140 353r).
6. Wittig, G.; Reiff, H. AG 1968, 80, 8.
7. (a) Fraser, R. R.; Chuaqui-Offermans, N. CJC 1981, 59, 3007. (b) For reviews on 1-azaallyl metal reagents (metalloenamines), see: Martin, S. F. COS 1991, 2, Chapter 1.16, p 475; Gawley, R. E. Rein, K. COS 1991, 3, 65; Whitesell, J. K.; Whitesell, M. A. S 1983, 517.
8. Lee, J. Y.; Lynch, T. J.; Mao, D. T.; Bergbreiter, D. E.; Newcomb, M. JACS 1981, 103, 6215.
9. Enders, D.; Tiebes, J.; De Kimpe, N.; Keppens, M.; Stevens, C.; Smagghe, G.; Betz, O. JOC 1993, 58, 4881.
10. Savoia, D.; Trombini, C.; Umani-Ronchi, A. JOC 1978, 43, 2907.
11. Leborgne, J.-F. JOM 1976, 122, 123.
12. Leborgne, J.-F. JOM 1976, 122, 129.
13. Meyers, A. I.; Tomioka, K.; Fleming, M. P. JOC 1978, 43, 3788.
14. Vedejs, E.; Campbell, J. B., Jr.; Gadwood, R. C.; Rodgers, J. D.; Spear, K. L.; Watanabe, Y. JOC 1982, 47, 1534.
15. Molin, H.; Pring, B. G. TL 1985, 26, 677.
16. Cregge, R. J.; Lentz, N. L.; Sabol, J. S. JOC 1991, 56, 1758.
17. Boger, D. L.; Wysocki, R. J., Jr. JOC 1988, 53, 3408.
18. Corey, E. J.; Enders, D.; Bock, M. G. TL 1976, 7.
19. Gaudemar, M.; Bellassoued, M. TL 1990, 31, 349.
20. Bellassoued, M.; Majidi, A. JOC 1993, 58, 2517.
21. Borch, R. F.; Evans, A. J.; Wade, J. J. JACS 1975, 97, 6282.
22. Wittig, G.; Hesse, A. OSC 1988, 6, 901.
23. Wittig, G.; Fischer, S.; Tanaka, M. LA 1973, 1075.
24. Weyerstahl, P.; Buchmann, B.; Marschall-Weyerstahl, H. LA 1988, 507.
25. Fetell, A. I.; Feuer, H. JOC 1978, 43, 497.
26. Annunziata, R.; Cinquini, M.; Restelli, A.; Cozzi, F. JCS(P1) 1982, 1183.
27. Novikova, Z. S.; Kabachnik, M. M.; Chadnaya, I. A.; Lutsenko, I. F. ZOB 1988, 58, 1663.
28. Chodnaya, I. A.; Potapova, E. L.; Kabachnik, M. M.; Borisenko, A. A.; Novikova, Z. S. ZOB 1991, 61, 1698 (CA 1992, 116, 129 076).
29. Novikova, Z. S.; Kabachnik, M. M.; Lutsenko, I. F. ZOB 1988, 58, 2031 (CA 1989, 111, 78 145).
30. Verhé, R.; De Kimpe, N.; De Buyck, L.; Tilley, M.; Schamp, N. BSB 1977, 86, 879.
31. Aurich, H. G.; Heinrich, J.-M.; Wassmuth, G. JCR(S) 1980, 222.
32. Aurich, H. G.; Heinrich, J.-M.; Wassmuth, G. JCR(S) 1980, 224.
33. Komatsu, M.; Takamatsu, S.; Uesaka, M.; Yamamoto, S.; Ohshiro, Y.; Agawa, T. JOC 1984, 49, 2691.
34. van Leusen, A. M.; Wildeman, J.; Oldenziel, O. H. JOC 1977, 42, 1153.
35. Pirkle, W. H.; Rinaldi, P. L. JOC 1977, 42, 2080.
36. Pirkle, W. H.; Rinaldi, P. L. JOC 1977, 42, 3217.
37. Black, D. S. C.; Watson, K. G. AJC 1973, 26, 2159.
38. Harger, M. J. P.; Williams, A. JCS(P1) 1989, 563.
39. König, K.-H.; Reitel, C.; Mangold, D. Ger. Offen. 2 601 542, 1977, (CA 1977, 87, 101 973).
40. König, K.-H.; Reitel, C.; Mangold, D.; Feuerherd, K.-H.; Oeser, H.-G. AG 1979, 91, 334.
41. Rugewitz-Blackholm, B.; Wiessler, M. LA 1987, 583.

Norbert De Kimpe

University of Gent, Belgium



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