Acid-Mediated Amine Exchange of N,N-Dimethylformamidines: Preparation of Electron-Rich Formamidines

David D. Díaz; Warren G. Lewis; M. G. Finn

doi:10.1055/s-2005-872249

LETTER

Acid-Mediated Amine Exchange of N,N-Dimethylformamidines: Preparation of Electron-Rich Formamidines

David D. Díaz, Warren G. Lewis, M. G. Finn*
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA
Fax: +1(858)7848850; e-Mail: mgfinn@scripps.edu;

Abstract

All articles of this category

Abstract

The effect of acid in the amine exchange of N,N-dimethylformamidines has been revisited, allowing the preparation of highly electron-rich compounds that are difficult to obtain under standard conditions. The use of propargylamine as nucleophile led to the formation of substituted imidazoles.

Key words

formamidine - acid - amine exchange - imidazole

Full Text

References

1a Ziegleskylakakis K. Nill S. Pan JF. Andrae U. Environ. Mol. Mutagen. 1998, 31: 362

1b Leung VKS. Chan TYK. Yeung VTF. J. Toxicol., Clin. Toxicol. 1999, 37: 513

1c Goto T. Sakashita H. Murakami K. Sugiura M. Kondo T. Fukaya C. Chem. Pharm. Bull. 1997, 45: 305

2a Böhme F. Kunert C. Klinger C. Komber H. Macromol. Symp. 1998, 128: 183

2b Böhme F. Klinger C. Komber H. Haussler L. Jehnichen D. J. Polym. Sci., Part A: Polym. Chem. 1998, 36: 929

2c Wulff G. Schönfeld R. Adv. Mater. 1998, 10: 957

2d Marchildon L. Daneault C. Leduc C. Sain MM. Cellulose Chem. Technol. 1996, 30: 473

2e Rillich M. Haussler L. Jehnichen D. Böhme F. Polym. Bull. 1995, 34: 43

2f Meier J. Papier 1994, 48: 677

3 Taylor EC. Ehrhart WA. J. Org. Chem. 1963, 28: 1108

4 For a synthesis of unsymmetrically substituted formamidinium salts using orthoformates and acetic acid, see: Wicherink SC. Scheeren JW. Nivard RJF. Synthesis 1977, 273

5a The Chemistry of Amidines and Imidates Vol. 2: Patai S. Rappoport Z. J. Wiley and Sons; New York: 1991.

5b Granik VG. Russ. Chem. Rev. 1983, 52: 377

6a Ripka AS. Díaz DD. Sharpless KB. Finn MG. Org. Lett. 2003, 5: 1531

6b Díaz DD. Finn MG. Chem.-Eur. J. 2004, 10: 303

6c Díaz DD. Finn MG. Org. Lett. 2004, 6: 43

6d Díaz DD. Finn MG. Chem. Commun. 2004, 2514

7

See ref. 6d and ref. 3-6 cited therein.

For examples using non-protic solvents such as toluene, particularly with secondary amines, see:

8a Meyers AI. Edwards PD. Rieker WF. Bailey TR. J. Am. Chem. Soc. 1984, 106: 3270

8b Beeley LJ. Rockell JM. Tetrahedron Lett. 1990, 31: 417

8c Meyers AI. Millar DB. White FH. J. Am. Chem. Soc. 1988, 110: 4778

9a Harnden MR. Parkin A. Wyatt PG. Tetrahedron Lett. 1988, 29: 701

9b Harnden MR. Jarvest RL. J. Chem. Soc., Perkin Trans. 1 1989, 2207

9c Harnden MR. Jennings LJ. McKie CMD. Parkin A. Synthesis 1990, 893

10 Eilingsfeld H. Chem. Ber. 1965, 98: 1308

11a Katritzky AR. Huang T.-B. Voronkov MV. J. Org. Chem. 2000, 65: 2246

11b Guillot N. Viehe HG. Tinant B. Declercq JP. Tetrahedron 1990, 46: 3897

11c Jones SD. Kennewell PD. Tulley WR. Westwood R. J. Chem. Soc., Perkin Trans. 1 1990, 447

11d Maquestiau A. Eynde J.-JV. Tetrahedron 1987, 43: 4195

11e Bátori S. Sándor P. Messmer A. Heterocycles 1990, 31: 289

12a Shallop AJ. Gaffney BL. Jones RA. J. Org. Chem. 2003, 68: 8657

12b Alarcon K. Martelli A. Demeunynck M. Lhomme J. Tetrahedron Lett. 2000, 41: 7211

12c Sternfeld F. Guiblin AR. Jelley RA. Matassa VG. Reeve AJ. Hunt PA. Beer MS. Heald A. Stanton JA. Sohal B. Watt PA. Street LJ. J. Med. Chem. 1999, 42: 677

12d Zelenin KN. Khrustalev VA. Sergutina VP. Zh. Org. Khim. 1980, 16: 276

12e Khrustalev VA. Zelenin KN. Sergutina VP. Zh. Org. Khim. 1979, 15: 2288 ; and ref. 2 cited therein

13 Stocks MJ. Cheshire DR. Reynolds R. Org. Lett. 2004, 6: 2969

All the starting N,N-dimethylformamidines were synthesized by the usual methods reported previously in the literature, see:

14a Abdulla RF. Brinkmeyer RS. Tetrahedron 1979, 33: 1675

14b

ref. 11a.

15 For studies concerning the site of protonation of N,N-dimethylformamidines, see: Raczynska ED. Maria P.-C. Gal J.-F. Decouzon M. J. Org. Chem. 1992, 57: 5730 ; and references therein

16a N,N′-Dipropargylformamidine is mentioned in passing in: Dötz KH. Kroll F. Harms K. J. Organomet. Chem. 1993, 459: 169

16b

We find that at least some cyclization to the corresponding imidazole cannot be prevented when the synthesis of the formamidine is attempted either from orthoformate or from propargyldimethylformamidine at elevated temperatures; at r.t. the required exchange reaction is prohibitively slow.

17a Jezewski A. Jurczak J. Lidert Z. Tice CM. J. Heterocycl. Chem. 2001, 38: 645

17b Taylor EC. Zhou P. Tetrahedron Lett. 1997, 38: 4339

17c Eloy F. Deryckere A. Maffrand JP. Eur. J. Med. Chem. 1974, 602

17d Iwai I. Hiraoka T. Chem. Pharm. Bull. 1964, 12: 813