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

<A NAME="RZ15406SS-1">1</A>

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.

<A NAME="RZ15406SS-2">2</A> Merrifield RB. J. Am. Chem. Soc.  1963,  85:  2149 

<A NAME="RZ15406SS-3A">3a</A> Gravert DJ. Janda KD. Chem. Rev.  1997,  97:  489 

<A NAME="RZ15406SS-3B">3b</A> Toy PH. Janda KD. Acc. Chem. Res.  2000,  33:  546 

<A NAME="RZ15406SS-4">4</A> Horvath IT. Acc. Chem. Res.  1998,  31:  641 

<A NAME="RZ15406SS-5A">5a</A> Fraga-Dubreuil J. Bazureau JP. Tetrahedron Lett.  2001,  42:  6097 

<A NAME="RZ15406SS-5B">5b</A> Fraga-Dubreuil J. Bazureau JP. Tetrahedron  2003,  59:  6121 

<A NAME="RZ15406SS-6A">6a</A> Welton T. Chem. Rev.  1999,  99:  2071 

<A NAME="RZ15406SS-6B">6b</A> Holbrey D. Seddon KR. Clean Prod. Process  1999,  1:  223 

<A NAME="RZ15406SS-6C">6c</A> Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3772 

<A NAME="RZ15406SS-6D">6d</A> Dupont J. de Souza RF. Suarez PAZ. Chem. Rev.  2002,  102:  3667 

See for example:

<A NAME="RZ15406SS-7A">7a</A> Handy ST. Okello M. Tetrahedron Lett.  2003,  44:  8399 

<A NAME="RZ15406SS-7B">7b</A> Miao W. Chan TH. Org. Lett.  2003,  5:  5003 

<A NAME="RZ15406SS-7C">7c</A> Anjaiah S. Chandrasekhar S. Grée R. Tetrahedron Lett.  2004,  45:  569 

<A NAME="RZ15406SS-7D">7d</A> de Kort M. Tuin AW. Kuiper S. Overkleeft HS. van der Marel GA. Buijsman RC. Tetrahedron Lett.  2004,  45:  2171 

<A NAME="RZ15406SS-7E">7e</A> Miao W. Chan T.-H. J. Org. Chem.  2005,  70:  3251 

<A NAME="RZ15406SS-7F">7f</A> Yi F. Peng Y. Song G. Tetrahedron Lett.  2005,  46:  3931 

See for example:

<A NAME="RZ15406SS-8A">8a</A> Mi X. Luo S. Cheng J.-P. J. Org. Chem.  2005,  70:  2338 

<A NAME="RZ15406SS-8B">8b</A> Song G. Cai Y. Peng Y. J. Comb. Chem.  2005,  7:  561 

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

<A NAME="RZ15406SS-9A">9a</A> Nair V. Bindu S. Sreekumar V. Angew. Chem. Int. Ed.  2004,  43:  5130 

<A NAME="RZ15406SS-9B">9b</A> Handy ST. Okello M. J. Org. Chem.  2005,  70:  1915 

<A NAME="RZ15406SS-10">10</A> Casaschi A. Grigg R. Sansano JM. Tetrahedron  2001,  57:  607 

<A NAME="RZ15406SS-11">11</A> Fraga-Dubreuil J. Famelart M.-H. Bazureau JP. Org. Process Res. Dev.  2002,  6:  374 

<A NAME="RZ15406SS-12">12</A> 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 

<A NAME="RZ15406SS-13">13</A> 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 

<A NAME="RZ15406SS-14">14</A> Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 

<A NAME="RZ15406SS-15">15</A>

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

<A NAME="RZ15406SS-16">16</A> 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 

<A NAME="RZ15406SS-17">17</A> Fantauzzi PP. Yager KM. Tetrahedron Lett.  1998,  39:  1291 

<A NAME="RZ15406SS-18">18</A> 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 

<A NAME="RZ15406SS-19">19</A> Fayol A. Housseman C. Sun X. Janvier P. Bienaymé H. Zhu J. Synthesis  2005,  161 

<A NAME="RZ15406SS-20">20</A> Misaki T. Nagase R. Matsumoto K. Tanabe Y. J. Am. Chem. Soc.  2005,  127:  2854 

<A NAME="RZ15406SS-21">21</A> Prasad ASB. Stevenson TM. Citineni JR. Nyzam V. Knochel P. Tetrahedron  1997,  53:  7237