(S)-(+)-2-(2,4,5,7-Tetranitro-9-fluorenylideneaminooxy)propionic Acid


[50996-73-1]  · C16H9N5O11  · (S)-(+)-2-(2,4,5,7-Tetranitro-9-fluorenylideneaminooxy)propionic Acid  · (MW 447.30) (R)-(-)


(used as a p-acidic resolving agent for racemic p-bases, especially carbohelicenes1 and heterohelicenes,1a,2 and also for resolving certain types of amines3)

Alternate Name: TAPA.

Physical Data: mp 195 °C (dec.); [a]25 +92° (c = 1.6, dioxane).

Solubility: sol CHCl3, dioxane, hot acetic acid; slightly sol CH2Cl2, toluene.

Form Supplied in: available as the neat solid.

Analysis of Reagent Purity: NMR,4 mp, [a].

Preparative Methods: prepared from acetone oxime, ethyl 2-bromopropionate, and 2,4,5,7-tetranitrofluorenone.4 The intermediate racemic 2-(isopropylideneaminooxy)propionic acid is resolved with (1R,2S)-Ephedrine.

Handling, Storage, and Precautions: should be stored under protection from light. No reported toxicity.

Resolving Agent for p-Bases.

The title reagent was originally designed as an agent for resolving hexahelicene, through formation of diastereomeric charge-transfer complexes.5 It has subsequently been used for resolution of several different types of chiral, racemic p-bases not containing any of the functional groups usually needed to effect resolution by conventional reagents. Carbohelicenes1 and heterohelicenes (e.g. 1),1a,2 [2,2]paracyclophanes,6 naphthalenophanes,7 highly substituted alkenes,8 derivatives of polycyclic aromatic hydrocarbons (e.g. 2),9 porphyrin derivatives,10 an alkyl aryl ether,11 and an a-aryl ester11 have been successfully resolved using this reagent, either by chromatographic separation on columns coated with TAPA or by fractional crystallization. Analytical determination of the enantiomeric purity of hexahelicene and several of its derivatives is also possible using HPLC.12

Resolution of helicenes has been effected using chromatography on other types of chiral stationary phases, including columns derivatized with analogs of TAPA containing larger alkyl groups at the stereocenter, but TAPA is generally the most effective agent.1

Resolving Agent for Certain Types of Amines.

TAPA has also been used as resolving agent for some amines that formed either unstable, insoluble, or noncrystalline salts with common resolving acids. Compounds (3) and (4) were among those resolved with TAPA, whereas camphor-10-sulfonic acid, 3-bromo-8-camphorsulfonic acid, O,O-di-p-toluoyl-(+)-tartaric acid, (+)-tartaric acid, and (+)-camphoric acid could not be used.3

1. (a) Laarhoven, W. H.; Prinsen, W. J. C. Top. Curr. Chem. 1984, 125, 86. (b) Newman, M. S.; Mentzer, R. G.; Slomp, G. JACS 1963, 85, 4018. (c) Goedicke, C.; Stegemeyer, H. TL 1970, 937. (d) Laarhoven, W. H.; Cuppen, T. J. H. M.; Nivard, R. J. F. T 1974, 30, 3343. (e) Mikes, F.; Boshart, G.; Gil-Av, E. CC 1976, 99. (f) Mikes, F.; Boshart, G.; Gil-Av, E. J. Chromatogr. 1976, 122, 205.
2. (a) Numan, H.; Helder, R.; Wynberg, H. RTC 1976, 95, 211. (b) Nakagawa, H.; Ogashiwa, S.; Tanaka, H.; Yamada, K.; Kawazura, H. BCJ 1981, 54, 1903. (c) Nakagawa, H.; Yamada, K.; Kawazura, H. CC 1989, 1378.
3. Carroll, F. I.; Berrang, B.; Linn, C. P. JMC 1978, 21, 326.
4. Block, P., Jr.; Newman, M. S. OSC 1973, 5, 1031.
5. (a) Newman, M. S.; Lutz, W. B.; Lednicer, D. JACS 1955, 77, 3420. (b) Newman, M. S.; Lednicer, D. JACS 1956, 78, 4765.
6. (a) Longone, D. T.; Reetz, M. T. CC 1967, 46. (b) Rebafka, W.; Staab, H. A. AG 1973, 85, 831; AG(E) 1973, 12, 776 (CA 1974, 80, 47 529w).
7. Meurer, K.; Luppertz, F.; Vögtle, F. CB 1985, 118, 4433.
8. Feringa, B.; Wynberg, H. JACS 1977, 99, 602.
9. (a) Kim, Y. H.; Tishbee, A.; Gil-Av, E. CC 1981, 75. (b) Newman, M. S.; Wotring, Jr., R. W.; Pandit, A.; Chakrabarti, P. M. JOC 1966, 31, 4293.
10. Risch, N.; Reich, H. TL 1979, 4257.
11. Newman, M. S.; Lutz, W. B. JACS 1956, 78, 2469.
12. Prinsen, W. J. C.; Laarhoven, W. H. J. Chromatogr. 1987, 393, 377.

Tobias Rein

The Royal Institute of Technology, Stockholm, Sweden

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