Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH12528
RESEARCH ARTICLE
Contents Vol 66(6)

Improving the Yield of the Exhaustive Grignard Alkylation of N-Benzylphthalimide

Viraj C. Jayawardena A , Kathryn E. Fairfull-Smith A and Steven E. Bottle A B
+ Author Affiliations
- Author Affiliations

A ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Faculty of Science and Engineering, Queensland University of Technology, 2 George Street, Brisbane, Qld 4001, Australia.

B Corresponding author. Email: s.bottle@qut.edu.au

Australian Journal of Chemistry 66(6) 619-625 https://doi.org/10.1071/CH12528
Submitted: 28 November 2012  Accepted: 6 February 2013   Published: 25 March 2013

Abstract

The tetraalkylation of N-benzylphthalimide is the major yield limiting step in the common synthetic route to isoindoline nitroxides. The progress of this reaction was found to be limited by the formation of previously unobserved mono- and dialkyl side products that do not lead to the desired product. The yield for the tetraalkylation of N-benzylphthalimide with ethylmagnesium iodide could be increased (60 % over two steps) when a stepwise addition sequence was employed. The new two-step synthesis offers a practical preparative scale alternative to the current approach.


References

[1]  G. Likhtenshtein, J. Yamauchi, S. Nakatsuji, A. I. Smirnov, R. Tamura, Nitroxides: Applications in Chemistry, Biomedicine, and Materials Science 2008 (Wiley-VCH: Weinheim).

[2]  J. P. Blinco, K. E. Fairfull-Smith, B. M. Morrow, S. E. Bottle, Aust. J. Chem. 2011, 64, 373.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXkvVCrs7g%3D&md5=ecd27680137b4ef4a66b8bb2fbffa137CAS |

[3]  L. Tebben, A. Studer, Angew. Chem. Int. Ed. 2011, 50, 5034.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmtFymu78%3D&md5=0835abddf586f947cfc241f7c318b081CAS |

[4]  G. Gryn’ova, K. U. Ingold, M. L. Coote, J. Am. Chem. Soc. 2012, 134, 12979.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xltl2hsLg%3D&md5=fd84619d4be09b6010ceb62cae6ea0bbCAS |

[5]  G. Moad, E. Rizzardo, D. H. Solomon, Macromolecules 1982, 15, 909.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XktVKrtrw%3D&md5=e48693cd192f0c3d1eff95b8ccfba697CAS |

[6]  P. G. Griffiths, E. Rizzardo, D. H. Solomon, Tetrahedron Lett. 1982, 23, 1309.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38Xlt1Kls7g%3D&md5=e89afae71358e1410318cc5d05663824CAS |

[7]  J. Shen, S. E. Bottle, N. Khan, O. Grinberg, D. Reid, A. Micallef, H. Swartz, Appl. Magn. Reson. 2002, 22, 357.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnvVeru7s%3D&md5=8acd6c7f86b06fe622b28506e9bdd1e8CAS |

[8]  N. Khan, J. P. Blinco, S. E. Bottle, K. Hosokawa, H. M. Swartz, A. S. Micallef, J. Magn. Reson. 2011, 211, 170.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXptlWgsbo%3D&md5=a9e83654b55dc2cab2172717b8e8e99dCAS |

[9]  A. S. Micallef, R. C. Bott, S. E. Bottle, G. Smith, J. M. White, K. Matsuda, H. Iwamura, J. Chem. Soc., Perkin Trans. 2 1999, 2, 65.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  H.-Y. Ahn, K. E. Fairfull-Smith, B. J. Morrow, V. Lussini, B. Kim, M. V. Bondar, S. E. Bottle, K. D. Belfield, J. Am. Chem. Soc. 2012, 134, 4721.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjtVGhsb0%3D&md5=b65c46dac1dd70efd8935825d4f915f3CAS |

[11]  L. Marx, A. Rassat, Angew. Chem. Int. Ed. 2000, 39, 4494.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhs1yntQ%3D%3D&md5=8b0066ce6cf4deddbe63fdc168722af0CAS |

[12]  T. K. Kálai, M. Lakshmi, M. Balog, K. Selvendiran, B. K. Rivera, P. Kuppusamy, K. Hideg, J. Med. Chem. 2011, 54, 5414.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  J. R. Walker, K. E. Fairfull-Smith, K. Anzai, S. Lau, P. J. White, P. J. Scammells, S. E. Bottle, Med. Chem. Commun. 2011, 2, 436.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXls1Kht7Y%3D&md5=0ddc8123ef4063acdcbb89a14b8c018eCAS |

[14]  S. P. Cresidio, F. Aldabbagh, W. K. Busfield, I. D. Jenkins, S. H. Thang, C. Zayas-Holdsworth, P. B. Zetterlund, J. Polym. Sci. Part A 2001, 39, 1232.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXit1Omt7g%3D&md5=e3ed92a62252d680f83d5a1794abbd39CAS |

[15]  W. Huang, B. Charleux, R. Chiarelli, L. Marx, A. Rassat, J.-P. Vairon, Macromol. Chem. Phys. 2002, 203, 1715.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmsVSlsrs%3D&md5=117d97a79de5e5094c61a9cdd54e4d1aCAS |

[16]  J. C. Colwell, J. P. Blinco, C. Hulbert, K. E. Fairfull-Smith, S. E. Bottle, Aust. J. Chem. 2011, 64, 426.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXkvVCrsL0%3D&md5=bdd67e5400cab8eaa03b20957d699dd9CAS |

[17]  J. P. Blinco, K. E. Fairfull-Smith, A. S. Micallef, S. E. Bottle, Polym. Chem. 2010, 1, 1009.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtl2ms7bJ&md5=d49a85717dbf8d7da65fc16d4a35d759CAS |

[18]  K. E. Fairfull-Smith, S. E. Bottle, Eur. J. Org. Chem. 2008, 5391.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFWmtLjN&md5=6ab0e42ab754683ef4024dd17e964f53CAS |

[19]  J. C. Morris, J. C. McMurtrie, S. E. Bottle, K. E. Fairfull-Smith, J. Org. Chem. 2011, 76, 4964.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmt1Giu7Y%3D&md5=08bd1cc7a7c2e3364ce51ef97cfc91e2CAS |

[20]  N. Barhate, P. Cekan, A. P. Massey, S. T. Sigurdsson, Angew. Chem. Int. Ed. 2007, 46, 2655.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksVWru7w%3D&md5=2038eddbe9174f13830e8f1c89195678CAS |

[21]  B. Miljevic, M. F. Heringa, K. A. Keller, N. K. Meyer, J. Good, A. Lauber, P. F. DeCarlo, K. E. Fairfull-Smith, T. Nussbaumer, H. Burtscher, A. S. H. Prevot, U. Baltensperger, S. E. Bottle, Z. R. Ristovski, Environ. Sci. Technol. 2010, 44, 6601.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpslWjsrw%3D&md5=0143e28d0a2f9385c9044ccc8f8ef5a7CAS |

[22]  S. Stevanovic, B. Miljevic, G. K. Eaglesham, S. E. Bottle, Z. D. Ristovski, K. E. Fairfull-Smith, Eur. J. Org. Chem. 2012, 2012, 5908.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtlaiu77O&md5=007ac15c0c5a6f9989b20264cbdf8000CAS |

[23]  K. E. Fairfull-Smith, J. P. Blinco, D. J. Keddie, G. A. George, S. E. Bottle, Macromolecules 2008, 41, 1577.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhvV2ntrw%3D&md5=c151a27ac2e989b341a26fe417f2a9c7CAS |

[24]  B. J. Morrow, D. J. Keddie, N. Gueven, M. F. Lavin, S. E. Bottle, Free Radic. Biol. Med. 2010, 49, 67.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmsVGgs7Y%3D&md5=79d4db8455e09efce9189c50e9169b9cCAS |

[25]  S. A. Shelke, S. T. Sigurdsson, Eur. J. Org. Chem. 2012, 2291.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xnt1yjsw%3D%3D&md5=3dce0cc65aba60ca7a84a4eb28a3a048CAS |

[26]  S. E. Bottle, D. G. Gillies, D. L. Hughes, A. S. Micallef, A. I. Smirnov, L. H. Sutcliffe, J. Chem. Soc., Perkin Trans. 2 2000, 7, 1285.
         | Crossref | GoogleScholarGoogle Scholar |

[27]  G. Gryn’ova, J. M. Barakat, J. P. Blinco, S. E. Bottle, M. L. Coote, Chem. – Eur. J. 2012, 18, 7582.
         | 1:CAS:528:DC%2BC38XmtFeku74%3D&md5=409f2698a1190cd4efd7eec842e1ecc0CAS |

[28]  T. Kálai, M. Balog, J. Jekő, K. Hideg, Synthesis 1999, 973.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  T. Kálai, J. Jekő, K. Hideg, Synthesis 2009, 15, 2591.

[30]  P. G. Griffiths, G. Moad, E. Rizzardo, D. H. Solomon, Aust. J. Chem. 1983, 36, 397.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3sXkt1ahtL8%3D&md5=09243da1ee0c1709537d9ebd9b51c337CAS |

[31]  R. C. Foitzik, S. E. Bottle, J. M. White, P. J. Scammells, Aust. J. Chem. 2008, 61, 168.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjslSqs70%3D&md5=32a6deccf6c7a50f8c10c2c0c9138a6aCAS |

[32]  Caldararo  M.Po  R.Riccci  M.2007, PCT Int. Appl. WO2007093452.

[33]  R. Braslau, V. Chaplinski, J. Org. Chem. 1998, 63, 9857.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXns1ymtbo%3D&md5=aea3c4f9d0fbb6ab1c85c9e78a798d73CAS |

[34]  R. C. Fuson, J. Am. Chem. Soc. 1926, 48, 2681.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaB28XivF2rtQ%3D%3D&md5=16264561d74fa0afdefe96a644d535e9CAS |

[35]  E. C. Ashby, A. B. Goel, J. Am. Chem. Soc. 1981, 103, 4983.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3MXksl2ksL0%3D&md5=3d43a5bdd633b4659d89b34f4124f851CAS |

[36]  C. Blomberg, Mechanisms of Reactions of Grignard Reagents, in Handbook of Grignard Reagents (Eds G. S. Silverman, P. E. Rakita) 1996, pp. 243 (Marcel Dekker: New York, NY).

[37]  R. H. F. Manske, Org. Synth. 1932, 12, 10.

[38]  K. R. Heidenbluth, H. Tonjes, R. Scheffler, J. Prakt. Chem. 1965, 30, 204.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF28XktlKmug%3D%3D&md5=747afda18e7563a04ce5938525ef14a7CAS |

[39]  H. Tonjes, K. R. Heidenbluth, R. Scheffler, J. Prakt. Chem. 1964, 26, 218.
         | Crossref | GoogleScholarGoogle Scholar |

[40]  D. Augner, D. C. Gerbino, N. Slavov, J.-M. Neudorfl, H.-G. Schmalz, Org. Lett. 2011, 13, 5374.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFCgsLvN&md5=ab569497e15074153454a34af6574c6fCAS |