Benzophenone Imine

[1013-88-3]  · C13H11N  · Benzophenone Imine  · (MW 181.24)

(reagent for protection of primary amines)

Alternate Name: diphenylketimine.

Physical Data: bp 151-153 °C/10 mmHg.

Form Supplied in: commercially available.

Preparative Methods: prepared by the addition of phenylmagnesium bromide to benzonitrile followed by hydrolysis with MeOH1 or by reaction of benzophenone with ammonia.2

Protected Primary Amines.

Benzophenone imine, a useful protecting group for primary amines (eq 1), is introduced by reaction with the amine salt (CH2Cl2, room temperature).3 The resulting Schiff bases are stable to flash chromatography and have been used in conjunction with other anion-stabilizing groups, especially in the field of amino acid chemistry, to provide activation for proton abstraction.4 Reaction of protected derivatives with base followed by alkylation with an alkyl halide (cases a (R = H)5 and d6,7), an alkynyl(phenyl)iodonium triflate (case b),8 or intramolecular alkylation (case c)9 establish new carbon-carbon bonds at the indicated center.

Benzophenone imine can also serve as a simple protecting group to allow acylation (case e)10 or formylation (case f)11 at a remote site. Removal is accomplished with either mild acid or catalytic hydrogenolysis.

Other Reactions.

Michael addition to acceptor-substituted alkenes gives protected b-amino acids, nitriles, and ketones (eq 2).12

Reaction of oxalyl chloride with 1 equiv of t-BuOH followed by Ph2C=NH results in a protected a-keto amino ester (starting material in eq 3). This compound can be reacted with nonstabilized, semistabilized, stabilized, or heteroatom-substituted phosphonium ylides to give a,b-dehydroamino acid derivatives (eq 3).13,14 Other reactions of these products have been reported.15

A stereoselective synthesis of b-amino alcohols from the benzophenone Schiff base of a-amino esters has been reported (eq 4).16 Other reactions from similar protected a-amino acid derivatives include preparations of a- or b-O-serine or -threonine glycopeptides,17 unsymmetrical disulfides of cysteine,18 and several methods for transesterification12,19 or related reactions20 of the benzophenone imines of amino esters.

Related Reagents.

N-(Diphenylmethylene)aminoacetonitrile; Ethyl N-(Diphenylmethylene)-2-acetoxyglycinate; Ethyl N-(Diphenylmethylene)glycinate; Phthalimide; Sodium Azide; Isocyanic Acid.

1. Pickard, P. L.; Tolbert, T. L. OSC 1973, 5, 520.
2. Verardo, G.; Giumanini, A. G.; Strazzolini, P.; Poiana, M. SC 1988, 18, 1501.
3. O'Donnell, M. J.; Polt, R. L. JOC 1982, 47, 2663.
4. Beak, P.; Zajdel, W. J.; Reitz, D. B. CRV 1984, 84, 471.
5. O'Donnell, M. J.; Bennett, W. D.; Wu, S. JACS 1989, 111, 2353.
6. Genet, J.-P.; Uziel, J.; Touzin, A. M.; Juge, S. S 1990, 41.
7. Peyman, A.; Budt, K.-H.; Spanig, J.; Stowasser, B.; Ruppert, D. TL 1992, 33, 4549.
8. Bachi, M. D.; Bar-Ner, N.; Crittell, C. M.; Stang, P. J.; Williamson, B. L. JOC 1991, 56, 3912.
9. Salaün, J.; Marguerite, J.; Karkour, B. JOC 1990, 55, 4276.
10. Hoekstra, W. J.; Press, J. B. H 1993, 35, 89.
11. Hvidt, T.; Szarek, W. A.; Maclean, D. B. CJC 1988, 66, 779.
12. Wessjohann, L.; McGaffin, G.; de Meijere, A. S 1989, 359.
13. Bazureau, J. P.; Person, D.; Le Corre, M. TL 1989, 30, 3065.
14. O'Donnell, M. J.; Arasappan, A.; Hornback, W. J.; Huffman, J. C. TL 1990, 31, 157.
15. Balsamini, C.; Spadoni, G.; Bedini, A.; Tarzia, G.; Lanfranchi, M.; Pellinghelli, M. A. JHC 1992, 29, 1593.
16. Polt, R.; Peterson, M. A.; DeYoung, L. JOC 1992, 57, 5469.
17. Polt, R.; Szabó, L.; Treiberg, J.; Li, Y.; Hruby, V. J. JACS 1992, 114, 10249.
18. Polt, R.; Li, Y.; Fernando, Q.; Rivera, M. TL 1992, 33, 2961.
19. O'Donnell, M. J.; Cook, G. K.; Rusterholz, D. B. S 1991, 989.
20. Josien, H.; Martin, A.; Chassaing, G. TL 1991, 32, 6547.

Martin J. O'Donnell

Indiana University-Purdue University at Indianapolis, IN, USA

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