[70591-20-7]  · C15H12N2  · N-(Diphenylmethylene)aminoacetonitrile  · (MW 220.29)

(glycine anion equivalent for amino acid synthesis by phase transfer catalysis)

Alternate Names: aminoacetonitrile benzophenone imine; O'Donnell's Schiff base.

Physical Data: mp 81-82 °C; pKa (DMSO) = 17.8.1

Form Supplied in: commercially available.

Preparative Method: by transimination of benzophenone imine with aminoacetonitrile hydrochloride.2,3 The crude product can often be used as it is or it can be recrystallized (Et2O/hexane or CCl4).

Handling, Storage, and Precautions: stable to flash chromatography and stable at rt. It is best stored under argon to avoid contact with moisture. The hydrolysis product, benzophenone, can be detected either by TLC (EtOAc/hexane) or by NMR.

Amino Acid Synthesis by Alkylation using Phase Transfer Catalysis.

The benzophenone imine of aminoacetonitrile is a versatile glycine anion equivalent4 for the synthesis of higher amino acid derivatives by alkylation of a variety of alkyl halides (methyl, benzylic, allylic, primary, secondary) under phase transfer catalysis (PTC) conditions.5 The PTC method involves a simple reaction procedure, mild conditions, inexpensive and safe reagents and solvents, and the ability to easily scale-up the reaction. Typically the substrate is stirred at rt in a two-phase system (liquid-liquid (with aqueous base)5 or solid-liquid (with solid base)6 PTC) in the presence of the alkyl halide and the phase transfer catalyst, a tetraalkylammonium salt. The monoalkylated product is readily hydrolyzed to the racemic higher amino acid (eq 1).7,8 Combination with enzymatic resolution provides optically active amino acids.9 Labeled amino acids for various biochemical studies are prepared from deuterio-substituted alkyl halides10-12 or by a-deuteration with 50% aq. NaOD.13 Boronation of the propargylated derivative and hydrolysis leads to o-carboranylalanine (eq 2), a boron-containing amino acid of use in the treatment of melanoma by boron neutron capture therapy (BNCT).14 Palladium-catalyzed allylation leads to g,d-unsaturated amino acids.15

1-Aminocyclopropane-1-carboxylic acid (ACC), the biosynthetic precursor of ethylene in plants, can be prepared by PTC alkylation with 1,2-Dibromoethane followed by hydrolysis (eq 3).16 Reduction of the initial alkylation product gives 1-amino-1-(aminomethyl)cyclopropane, which can be differentially protected.17 Alkylation with 1,3-dibromopropane and modified stoichiometry yields 2,6-diaminopimelic acid (DAP), a key structural component of bacterial cell walls.16

Other Reactions.

Michael addition to phenyl vinyl sulfoxide under solid-liquid PTC conditions in the absence of solvent followed by thermolysis gives the a,b-dehydroamino acid derivative by double bond migration.18 Reaction with aromatic aldehydes results in 1,2-carbonyl addition followed by elimination of water,19 while reaction with imines gives the 1,2-adduct.20 Arylation by nucleophilic aromatic substitution occurs with either (halobenzene)tricarbonylchromium complexes21 or cationic arenetricarbonylmanganese complexes.22

Related Reagents.

Benzophenone Imine; t-Butyl 2-t-Butyl-3-methyl-4-oxo-1-imidazolidinecarboxylate; N,N-Diethylaminoacetonitrile; 2-(2,6-Dimethylpiperidino)acetonitrile; N-(Diphenylmethylene)methanamine; Ethyl N-(Diphenylmethylene)-2-acetoxyglycinate; Ethyl N-(Diphenylmethylene)glycinate; Methyl N-Benzylidenealaninate.

1. O'Donnell, M. J.; Bennett, W. D.; Bruder, W. A.; Jacobsen, W. N.; Knuth, K.; LeClef, B.; Polt, R. L.; Bordwell, F. G.; Mrozack, S. R.; Cripe, T. A. JACS 1988, 110, 8520.
2. O'Donnell, M. J.; Polt, R. L. JOC 1982, 47, 2663.
3. Sayer, J. M.; Conlon, P. JACS 1980, 102, 3592.
4. Beak, P.; Zajdel, W. J.; Reitz, D. B. CRV 1984, 84, 471.
5. O'Donnell, M. J.; Eckrich, T. M. TL 1978, 4625.
6. O'Donnell, M. J.; Bruder, W.; Wojciechowski, K.; Ghosez, L.; Navarro, M.; Sainte, F.; Antoine, J.-P. Pept.: Struct. Funct., Proc. Am. Pept. Symp., 8th 1983, 151.
7. Leduc, R.; Bernier, M.; Escher, E. HCA 1983, 66, 960.
8. Müller, W.; Lowe, D. A.; Neijt, H.; Urwyler, S.; Herrling, P. L.; Blaser, D.; Seebach, D. HCA 1992, 75, 855.
9. Knittel, J. J.; He, X. Q. Pept. Res. 1990, 3, 176.
10. Okamoto, T.; Shimada, M.; Shinzaburo, O. CL 1987, 817.
11. Baldwin, J. E.; Adlington, R. M.; Bird, J. W.; Schofield, C. J. CC 1989, 1615.
12. Baldwin, J. E.; Bradley, M.; Turner, N. J.; Adlington, R. M.; Pitt, A. R.; Sheridan, H. T 1991, 47, 8203.
13. Baldwin, J. E.; Adlington, R. M.; Crouch, N. P.; Schofield, C. J.; Turner, N. J.; Aplin, R. T. T 1991, 47, 9881.
14. Wyzlic, I. M.; Soloway, A. H. TL 1992, 33, 7489.
15. Genet, J.-P.; Juge, S.; Achi, S.; Mallart, S.; Ruiz Montes, J.; Levif, G. T 1988, 44, 5263.
16. O'Donnell, M. J.; Bruder, W. A.; Eckrich, T. M.; Shullenberger, D. F.; Staten, G. S. S 1984, 127.
17. Vergne, F.; Aitken, D. J.; Husson, H.-P. JOC 1992, 57, 6071.
18. Opio, J. O.; Labidalle, S.; Galons, H.; Miocque, M.; Zaparucha, A.; Loupy, A. SC 1991, 21, 1743.
19. Dryanska, V. SC 1990, 20, 1055.
20. Dryanska, V.; Tasheva, D. SC 1992, 22, 63.
21. Rose-Munch, F.; Aniss, K.; Rose, E.; Vaisserman, J. JOM 1991, 415, 223.
22. Rose-Munch, F.; Aniss, K. TL 1990, 31, 6351.

Martin J. O'Donnell

Indiana University-Purdue University at Indianapolis, IN, USA

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