Synthesis and Study of 1-Aryl-1H-4,5-dihydroimidazoles

Abstract

An easy synthesis of 1-aryl-1H-4,5-dihydroimidazoles 1 by cyclocondensation of N-aryl-N′-formylethylenediamines 2 is described. Such precursors were synthesized by selective formylation of N-arylethylenediamines 3 with p-nitrophenyl formate. Cyclizations were performed using trimethylsilyl polyphosphate. Chemical properties of compounds 1, typical of amidine system, were studied. Reaction of 1 with methyl iodide leads to the corresponding 1-aryl-3-methyl-1H-4,5-dihydroimidazolium salts 5. Reduction of dihydroimidazoles 1 with sodium cyanoborohydride provides a convenient access to N-aryl-N′-methylethylenediamines 4.

heterocycles - nitrogen - cyclization - reductions - alkylations

References

<A NAME="RM00304SS-1">1</A> Faust JA. Yee LS. Sahyun M. J. Org. Chem.  1961,  26:  4044 

<A NAME="RM00304SS-2A">2a</A> Ishikawa F. Chem. Pharm. Bull.  1980,  28:  1394 

<A NAME="RM00304SS-2B">2b</A> McFarland JW. Conover LM. Howes HL. Lynch JE. Chisholm DR. Austin WC. Cornwell RL. Danilewicz JC. Courtney W. Morgan DH. J. Med. Chem.  1969,  12:  1066 

<A NAME="RM00304SS-3">3</A> inventors; Tanabe Seiyaku Co., Ltd., Jpn. Kokai Tokkyo Koho JP 60  51176.  ; Chem. Abstr. 1985, 103, 141951

<A NAME="RM00304SS-4">4</A> Le Bian G. Rondu F. Pelé-Tounian A. Wang X. Lidy S. Toubout E. Lamouri A. Dive G. Huet J. Pfeiffer B. Renard P. Guardiola-Lemaitre B. Manéchez D. Penicaud L. Ktorza A. Godfroid J.-J. J. Med. Chem.  1999,  42:  1587 ; and references cited therein

<A NAME="RM00304SS-5">5</A> Szabo B. Pharmacol. Ther.  2002,  93:  1 ; and references cited therein

Dehydrogenation to imidazoles. Among others:

<A NAME="RM00304SS-6A">6a</A> Martin PK. Matthews HR. Rapaport H. Thyagarajan G. J. Org. Chem.  1968,  33:  3758 

<A NAME="RM00304SS-6B">6b</A> Hughey JL. Knapp S. Schugar H. Synthesis  1980,  489 

<A NAME="RM00304SS-6C">6c</A> Klem RE. Skinner HF. Walba H. Isensee RH. J. Heterocycl. Chem.  1970,  7:  403 

<A NAME="RM00304SS-6D">6d</A> Matsuura T. Ito Y. Saito I. Bull. Chem. Soc. Jpn.  1973,  46:  3805 

<A NAME="RM00304SS-7">7</A> Jones RCF. Howard KJ. Snaith JS. Tetrahedron Lett.  1997,  38:  1647 

<A NAME="RM00304SS-8">8</A> Salerno A. Ceriani V. Perillo IA. J. Heterocycl. Chem.  1992,  29:  1725 ; and references cited therein.

<A NAME="RM00304SS-9">9</A> Salerno A. Ceriani V. Perillo IA. J. Heterocycl. Chem.  1997,  34:  709 ; and references cited therein

<A NAME="RM00304SS-10">10</A> Fernández BM. Reverdito AM. Paolucci GA. Perillo IA. J. Heterocycl. Chem.  1987,  24:  1717 

<A NAME="RM00304SS-11">11</A> Anderson HW. Jones RCF. Saunders J. J. Chem. Soc., Perkin Trans. 1  1986,  1995 ; and references cited therein

<A NAME="RM00304SS-12">12</A> Pandit UK. Pure Appl. Chem.  1994,  66:  759 ; and references cited therein

<A NAME="RM00304SS-13A">13a</A> Seefelder M, and Jentzsch W. inventors; Badische Anilin & Soda-Fabrik A.-G., German Patent  1189998.  ; Chem. Abstr. 1965, 63, 610

<A NAME="RM00304SS-13B">13b</A> Jentzsch W. Seefelder M. Chem. Ber.  1965,  98:  1342 

<A NAME="RM00304SS-14">14</A> Bieraugel H. Plemp R. Hiemstra HC. Pandit UK. Tetrahedron  1983,  39:  3971 

<A NAME="RM00304SS-15">15</A> Vecerková J. Ve cerek B. Chundela B. Chem. Listy  1953,  47:  1680 ; Chem. Abstr. 1955, 49, 1019

<A NAME="RM00304SS-16A">16a</A> Grundmann C. Kreutzberger A. J. Am. Chem. Soc.  1955,  77:  6559 

<A NAME="RM00304SS-16B">16b</A> Grundmann C, and Kreutzberger A. inventors; US Patent  2841585.  ; Chem. Abstr. 1958, 52, 20211

<A NAME="RM00304SS-17">17</A> Docker T, Frank A, and Krug H. inventors; Ger. Offen.  2728976.  ; Chem. Abstr. 1979, 90, 121603

<A NAME="RM00304SS-18">18</A> Becke F, Paessler P, and Swoboda OP. inventors; Ger. Offen.  1922802.  ; Chem. Abstr. 1971, 74, 22840

<A NAME="RM00304SS-19">19</A> Hagen H, and Becke F. inventors; Ger. Offen.  2040502.  ; Chem. Abstr. 1972, 76, 140862

<A NAME="RM00304SS-20A">20a</A> Poindexter GS. Owens DA. Dolan PL. Woo E. J. Org. Chem.  1992,  57:  6257 ; and references cited therein

<A NAME="RM00304SS-20B">20b</A> Fourneau J.-P. Lestrange MY. Bull. Soc. Chim. Fr.  1947,  827 

<A NAME="RM00304SS-21">21</A> Chung TF. Wu YM. Cheng CH. J. Org. Chem.  1984,  49:  1215 

<A NAME="RM00304SS-22">22</A> Hedrera ME. Perillo IA. Trends Heterocycl. Chem.  2002,  8:  105 

<A NAME="RM00304SS-23">23</A> García MB. Orelli LR. Magri ML. Perillo IA. Synthesis  2002,  2687 

<A NAME="RM00304SS-24">24</A>

It is well known that N-1 and/or N-3 unsubstituted imidazolidines exhibit ring (imidazolidine)-chain (imine) tautomerism, [25] and usually both species can be spectroscopically identified.

<A NAME="RM00304SS-25">25</A> Göblyös A. Lázár L. Evanics F. Fülöp F. Heterocycles  1999,  51:  2431 ; and references cited therein

<A NAME="RM00304SS-26">26</A> Yokohama M. Yoshida S. Imamoto T. Synthesis  1982,  591 

<A NAME="RM00304SS-27">27</A> Pollmann W. Schramm G. Biochim. Biophys. Acta  1964,  80:  1 

<A NAME="RM00304SS-28">28</A> Salerno A. Caterina C. Perillo IA. Synth. Commun.  2000,  30:  3369 

<A NAME="RM00304SS-29">29</A> Wright WB. Brabander HJ. J. Org. Chem.  1961,  26:  2120 

<A NAME="RM00304SS-30">30</A> Perillo IA. Lamdan S. J. Chem. Soc., Perkin Trans. 1  1975,  894