Ionic-Liquid-Supported Synthesis of Amines and Derivatives

Abstract

Amine precursors such as glycines protected at nitrogen with a Boc or formyl group were grafted by esterification on the hydroxylated arms of 1-(2-hydroxyethyl)-3-methylimidazolium hexafluorophosphates or tetrafluoroborates. The cleavage of the Boc group was then realized at room temperature by successively treating acetonitrile solutions of the thus formed glycinates with methanol and acetyl chloride (two equivalents each). Interestingly, the resulting glycinate hydrochlorides were converted into the corresponding amines during the removal of the solvent. Ugi reaction of one of these ionic-liquid-grafted amines with phthalaldehydic acid and tert-butyl isocyanide, followed by cleavage, furnished a phthalimidine.

ionic liquids - amines - glycine derivatives - esters - Ugi reaction

References

1

Present address: Sciences Chimiques de Rennes, UMR 6226, CNRS, Bâtiment 10A, Université de Rennes 1, Campus de Beaulieu, Avenue du Général Leclerc, 35042 Rennes Cedex, France.

2 Merrifield RB. J. Am. Chem. Soc.  1963,  85:  2149 

3a Gravert DJ. Janda KD. Chem. Rev.  1997,  97:  489 

3b Toy PH. Janda KD. Acc. Chem. Res.  2000,  33:  546 

4 Horvath IT. Acc. Chem. Res.  1998,  31:  641 

5a Fraga-Dubreuil J. Bazureau JP. Tetrahedron Lett.  2001,  42:  6097 

5b Fraga-Dubreuil J. Bazureau JP. Tetrahedron  2003,  59:  6121 

6a Welton T. Chem. Rev.  1999,  99:  2071 

6b Holbrey D. Seddon KR. Clean Prod. Process  1999,  1:  223 

6c Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3772 

6d Dupont J. de Souza RF. Suarez PAZ. Chem. Rev.  2002,  102:  3667 

See for example:

7a Handy ST. Okello M. Tetrahedron Lett.  2003,  44:  8399 

7b Miao W. Chan TH. Org. Lett.  2003,  5:  5003 

7c Anjaiah S. Chandrasekhar S. Grée R. Tetrahedron Lett.  2004,  45:  569 

7d de Kort M. Tuin AW. Kuiper S. Overkleeft HS. van der Marel GA. Buijsman RC. Tetrahedron Lett.  2004,  45:  2171 

7e Miao W. Chan T.-H. J. Org. Chem.  2005,  70:  3251 

7f Yi F. Peng Y. Song G. Tetrahedron Lett.  2005,  46:  3931 

See for example:

8a Mi X. Luo S. Cheng J.-P. J. Org. Chem.  2005,  70:  2338 

8b Song G. Cai Y. Peng Y. J. Comb. Chem.  2005,  7:  561 

Concerning the reactivity of the imidazolium rings, see for example:

9a Nair V. Bindu S. Sreekumar V. Angew. Chem. Int. Ed.  2004,  43:  5130 

9b Handy ST. Okello M. J. Org. Chem.  2005,  70:  1915 

10 Casaschi A. Grigg R. Sansano JM. Tetrahedron  2001,  57:  607 

11 Fraga-Dubreuil J. Famelart M.-H. Bazureau JP. Org. Process Res. Dev.  2002,  6:  374 

12 The solution was prepared by mixing equimolar amounts of acetyl chloride and methanol in ethyl acetate; see: Nudelman A. Bechor Y. Falb E. Fischer B. Wexler BA. Nudelman A. Synth. Commun.  1998,  28:  471 

13 Thermal dehydrochlorination from crystalline solids such as pyridinium salts of chlorometallates has been described; see: Adams CJ. Crawford PC. Orpen AG. Podesta TJ. Salt B. Chem. Commun.  2005,  2457 

14 Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 

15

Ugi reactions are generally performed in methanol at room temperature or 40 °C (see ref. 14).

16 For an example of a reaction between a π-deficient aza-aromatic and an isocyanide, see: Ugi I. Böttner E. Liebigs Ann. Chem.  1963,  670:  74 

17 Fantauzzi PP. Yager KM. Tetrahedron Lett.  1998,  39:  1291 

18 For a similar Ugi reaction between aliphatic amines, phthalaldehydic acid, and tert-butyl isocyanide, see: Hanusch-Kompa C. Ugi I. Tetrahedron Lett.  1998,  39:  2725 

19 Fayol A. Housseman C. Sun X. Janvier P. Bienaymé H. Zhu J. Synthesis  2005,  161 

20 Misaki T. Nagase R. Matsumoto K. Tanabe Y. J. Am. Chem. Soc.  2005,  127:  2854 

21 Prasad ASB. Stevenson TM. Citineni JR. Nyzam V. Knochel P. Tetrahedron  1997,  53:  7237