A. Guirado et al. / Tetrahedron Letters 48 (2007) 9137–9139
9139
Table 1. Synthesis of 4-chloro-1-hydroxyphenazines
reaction of 3,3,6,6-tetrachloro-2,2-dihydroxycyclohexanone
o-phenylenediamines 2
3
from the
with
3. McCullough, K. J. In Rodd’s Chemistry of Carbon
Compounds; Ansell, M. F., Ed.; Elsevier: Amsterdam,
1989; Vol. 4, Part I J, pp 354–416.
1
4. Urleb, U., 4th ed. In Methods of Organic Chemistry
(Houben-Weyl); Schaumann, E., Ed.; Thieme: Stuttgart,
1998; Vol. E9b/Part 2, pp 266–303.
5. Bolton, R. In Rodd’s Chemistry of Carbon Compounds;
Sainsbury, M., Ed.; Elsevier: Amsterdam, 2000; Vol. 4,
Part I J, pp 162–171.
Entry
1
Diamine
Product
Yield (%)
90
OH
H2N
N
H2N
N
2a
Cl
6. Laursen, J. B.; Nielsen, J. Chem. Rev. 2004, 104, 1663.
7. Beifuss, U.; Tietze, M. Top. Curr. Chem. 2005, 244, 77.
8. Olah, G. A. Friedel–Craft and Related Reactions; Inter-
science: New York, 1964.
3a
OH
H2N
H2N
Me
Me
N
Me
Me
´
9. Guirado, A.; Cerezo, A.; Ramırez de Arellano, C.
2
3
4
78
58
59
Tetrahedron 1997, 53, 6183.
10. (a) Guirado, A.; Cerezo, A.; Andreu, R. Tetrahedron Lett.
2000, 41, 6579; (b) Guirado, A.; Cerezo, A.; Andreu, R.;
N
Cl
2b
2c
2d
3b
´
´
Lopez-Sanchez, J. I.; Bautista, D. Tetrahedron 2004, 60,
6747.
OH
H2N
H2N
Cl
Cl
11. Sucrow, W.; Wanzlick, H. W. Chem. Ber. 1959, 92, 2516.
N
Cl
Cl
´
12. De Buyck, L.; Vanslembrouck, J.; De Kimpe, N.; Verhe,
R.; Schamp, N. Bull. Soc. Chim. Belg. 1984, 93, 913.
13. For example: (a) Usher, L. R.; Lawson, R. A.; Geary, I.;
Taylor, C. J.; Bingle, C. D.; Taylor, G. W.; Whyte, M. K.
B. J. Immunol. 2002, 168, 1861; (b) Kerr, J. R.; Taylor, G.
W.; Rutman, A.; Hoiby, N.; Cole, P. J.; Wilson, R. J. Clin.
Pathol. 1999, 52, 385; (c) Lauredo, I. T.; Sabater, J. R.;
Ahmed, A.; Botvinnikova, Y.; Abraham, W. J. Appl.
Physiol. 1998, 85, 2298; (d) Kitahara, T.; Kinoshita, Y.
Tetrahedron Lett. 1997, 38, 4993; (e) Kinoshita, Y.;
Watanabe, H.; Kitahara, T.; Mori, K. Synlett 1995, 186;
(f) Muller, M. Biochim. Biophys. Acta 1995, 185; (g)
Kitahara, T.; Kinoshita, Y.; Aono, S.; Miyake, M.;
Hasegawa, T.; Watanabe, H.; Mori, K. Pure Appl. Chem.
1994, 66, 2083; (h) Watson, D.; MacDermot, J.; Wilson,
R.; Cole, P. J.; Taylor, G. W. Eur. J. Biochem. 1986, 159,
309.
N
Cl
3c
OH
H2N
H2N
Br
Br
N
Br
Br
N
Cl
3d
In conclusion, an effective new method on phenazine
synthesis is provided. Good yields, easy availability of
starting materials and the mild reaction conditions are
valuable advantages of the reported procedure, which
give access to the previously unattainable 4-chloro-1-
hydroxyphenazines.
14. Typical procedure: a mixture of 3,3,6,6-tetrachloro-2,2-
dihydroxycyclohexanone 1 (3.8 mmol), the correspond-
ing o-phenylenediamine
2 (3.8 mmol), triethylamine
(14 mmol), and chloroform (50 mL) was stirred for 5 h
at 45 ꢁC. After evaporation to dryness under reduced
pressure, water (150 mL) was added and the mixture was
extracted with chloroform (3 · 60 mL). The combined
extracts were washed with water and dried over anhydrous
magnesium sulfate. The solvent was evaporated under
reduced pressure giving a solid residue that provided
highly pure phenazines 3 by either direct crystallization in
the appropriate solvent (3a,b) or by column chromato-
graphy (3c,d; silica gel/ethyl acetate–hexane, ratio 3:1).
15. The procedure followed by us to prepare this compound is
reported as Supplementary data.
Acknowledgments
We gratefully acknowledge the financial support of the
´
Ministerio de Educacion y Ciencia (project CTQ2004-
´
´
06427) and the Fundacion Seneca of the Comunidad
´
´
Autonoma de la Region de Murcia (project 03035/PI/
05).
Supplementary data
16. Tables of fractional atomic coordinates, thermal para-
meters, bond lengths and angles have been deposited at
the Cambridge Crystallographic Center (CCDC 607589).
17. Mousseron, M.; Jacquier, R. Bull. Soc. Chim. Fr. 1950, 17,
698.
Detailed experimental procedures and spectroscopic and
analytical data for compounds 1, 3a–d, and 12. Supple-
mentary data associated with this article can be found,
18. McDonald, R. N.; Tabor, T. E. J. Org. Chem. 1968, 33,
2934.
19. (a) McDonald, R. N.; Schwab, P. A. J. Am. Chem. Soc.
1963, 85, 820; (b) McDonald, R. N.; Schwab, P. A. J. Org.
Chem. 1964, 29, 2459; (c) Dufraise, Ch. C. R. Acad. Sci.
1921, 172, 162; (d) McDonald, R. N.; Tabor, T. E. J. Am.
Chem. Soc. 1967, 89, 6573; (e) McDonald, R. N.; Steppel,
R. N. J. Org. Chem. 1970, 35, 1250.
References and notes
1. Swan, G. A.; Felton, D. G. I. In Phenazines, The
Chemistry of Heterocyclic Compounds; Weissberger, A.,
Ed.; Interscience: New York, 1957; Vol. 11.
20. The starting material 1 was recovered unaltered from
experiments under the same preparative experimental
conditions but in the absence of o-phenylenediamine.
2. Porter, A. E. A. In Comprehensive Heterocyclic Chemistry;
Katritzky, A., Rees, C., Potts, K., Eds.; Pergamon Press:
Oxford, 1984; Vol. 3, pp 157–197.