Benzophenone imine, a commonly used protective group reagenta

Benzophenone Imine


[Molecular formula] C13H11N


[Molecular weight]: 181.24


[CAS No.] 1013-88-3


[Physical Properties]: Colorless liquid, bp 151~153°C/1.33kPa, 1.080 g/cm3, refractive index 1.6169.


[Preparation and commercial products] Benzophenone oxime is decomposed by heating, and a mixture of benzophenone and benzophenone imine can be generated. Then, the benzophenone imine is precipitated as a salt by passing dry hydrogen chloride gas. The filtered imine salt is neutralized with alkali to obtain benzophenone imine.


Precautions] Greater toxicity has not been reported.


Benzophenone imine is a commonly used reagent, can be used as a protective group of primary amines. In particular, it is widely used in amino acid chemistry, and can also be used to prepare aryl amines by reacting with aryl halides.


Primary amine protection reaction This reagent is an effective primary amine protection reagent. It reacts with primary amine hydrochlorides (including amino acids) in dichloromethane solvent under mild conditions to give amine-protected products. As shown in formula 1 [1]:This N-protected amino acid is a very useful intermediate [2~4].


Synthesis of anilines In recent years, the palladium-catalyzed construction of carbon-nitrogen bonds has attracted much attention. Aryl halides have been employed to react with benzophenone imines in a coupling reaction, and then aryl amines can be obtained by hydrolyzing the imines under acidic conditions (Eq. 2) [5]. Similar reactions can occur with aryl trifluoromethanesulfonates [6-8], e.g., the reaction of this reagent with pyridine trifluoromethanesulfonate allows the preparation of aminopyridine derivatives (Eq. 3) with high optical purity [6].


Acylation of benzophenone imines The reaction of this reagent with methyl chloroformate gives the corresponding acylated product (Eq. 4) [9], which is an important organic intermediate.


Michael Addition Reaction The reagent can undergo Michael addition with olefins containing electron-withdrawing group substituents to give protected β-amino acids, nitriles and ketones (Eq. 5) [10].






References.


1. O'Donnell. m. J.; Polt, R. L. J. Org. Chem. 1982,47,2663.


2. O'Donnell, M. J.; Bennett, W. D.; Wu, S.-D. J. Am. Chem. Soc. 1989, 111, 2353.


3. Bachi, M. D.; Bar-Ner, N.; Crittell, C. M.; Stang, P. J.; Williamson, B. L. J. Org. Chem. 1991, 56, 3912.


3912.


4. Salaiin, J.; Marguerite, J.; Karkour, B. J. Org. Chem. 1990, 55,4276.


5. Grasa, G. A.; Viciu, M. S.; Huang, J.-K.; Nolan, S. P. J. Org. Chem. 2001, 66, 7729.


6. Langlotz, B. K.; Wadepohl, H.; Gade, L. H. Angew. Chem., Int. Ed. 2008, 47, 4670.


7. Liu, Y.; Sun, B.; Wang, B.; Wakem, M.; Deng, L. J. Am. Chem. Soc. 2009, 131, 418.


8. Agoston, G. E.; Shah, J. H.; Suwandi, L.; Hanson, A. D.; Zhan, X.; LaVallee, T. M.; Pribluda, V..


Treston, A. M. Bioorg. Med Chem. Lett. 2009,19, 6241.


9. Rainer, K.; Meier, S. Synthesis 1984,8,688.


10. Wessjohann, L.; McGaffm, G.; de Meijere, A. Synthesis 1989, 5, 359.