[25186-34-9]  · C3H5NO  · (Z)-b-Aminoacrolein  · (MW 71.08)

(pyridine synthesis, Friedländer synthon, b-amino aldehyde)

Alternate Name: 3-amino-2-propenal.

Physical Data: yellow solid, mp 105-106 °C.

Solubility: sol alcohol and water.

Preparative Methods: the reagent is highly reactive towards self-condensation and is best when freshly prepared. One method of preparation involves the reaction of Ammonia with Propargyl Aldehyde (propynal) in the presence of ethanol in a sealed tube.1 This method is somewhat erratic, propargaldehyde is not commercially available, and the stereochemistry of the resulting double bond is most likely trans. A modified route, proceeding through 1,1,3,3-tetraethoxypropane, has also been reported.2 The most satisfactory preparation of b-aminoacrolein involves the partial hydrogenation of isoxazole.3,4 A solution of commercially available isoxazole (5 g, 0.073 mol) in anhyd MeOH (100 mL) containing 1.0 g of Raney Nickel was hydrogenated at 40 psi until one equivalent of hydrogen had been absorbed and hydrogen uptake had ceased (eq 1). The mixture was filtered to remove the catalyst and the solvent was evaporated to give 4.2 g (82%) of a yellow solid, mp 96-97 °C. Recrystallization from chloroform-petroleum ether (1:1) gave crystals, mp 104-105 °C.

Handling, Storage, and Precautions: the reagent should be used immediately although it can be stored under inert atmosphere at 0 °C in the dark for several days. Analysis by NMR (D2O) shows three equal area peaks at d 5.41 (dd), 7.50 (d), and 8.70 (d). Repurification can be effected by sublimination if necessary. Use in a fume hood.

Pyridine Synthesis.

In a series of three papers, Breitmaier and Bayer demonstrated that the reagent was effective in the preparation of 2,3-substituted pyridines.5 For example, the Friedländer condensation of b-aminoacrolein with cyclohexanone leads to 5,6,7,8-tetrahydroquinoline in moderate yield (eq 2). The reaction works well for other cyclic ketones but unfortunately fails with cyclobutanone.

This same approach has been extrapolated to the preparation of 3,3-polymethylene bridged derivatives of 2,2-bipyridine, albeit in relatively low yields (eq 3).6

The reaction may be employed with appropriate diketones to create two pyridine rings simultaneously and represents a direct route to doubly bridged derivatives of 2,2;6,2-terpyridine (eq 4). As expected, the yields are even lower and other routes to these same compounds have been developed.7

Related Reagents.

Acrolein; 2-Aminobenzaldehyde; O-Allylhydroxylamine; 3-Ethoxyacrolein.

1. Terpinski, J.; Dabrowski, J. J. Mol. Struct. 1969, 4, 285.
2. Breitmaier, E.; Gassenmann, S. CB 1971, 104, 665.
3. Thummel, R. P.; Kohli, D. K. JOC 1977, 42, 2742.
4. D'Alcontres, G. S. G 1950, 80, 441 (CA 1951, 3837g).
5. (a) Breitmaier, E.; Gassenmann, S.; Bayer, E. T 1970, 26, 5907. (b) Breitmaier, E.; Bayer, E. AG(E) 1969, 8, 765. (c) Breitmaier, E.; Bayer, E. TL 1970, 3291.
6. Thummel, R. P.; Lefoulon, F.; Mahadevan, R. JOC 1985, 50, 3824.
7. Thummel, R. P.; Jahng, Y. JOC 1985, 50, 2407.

Randolph P. Thummel

University of Houston, TX, USA

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