April 1998
SYNLETT
421
8.
9.
Wolfe, J.P.; Wagaw, S.; Buchwald, S.L. J. Am. Chem. Soc. 1996,
118, 7215.
2-PhCH(OH) (48%) N-t-Boc diphenylamines.
19. 8b may be a useful intermediate for acridones related to Glaxo
France pharmaceutical GF120918. See Dodic, N.; Dumaitre, B.;
Daugan, A.; Pianetti, P. J. Med. Chem. 1995, 38, 2418.
Driver, M.S.; Hartwig, J.F. J. Am. Chem. Soc. 1996, 118, 217.
Review: Hartwig, J.F. Synlett 1997, 329.
20. Clark, R.D.; Jahangir, A. Org. React. 1995, 47, 1.
10. Vitale, A.A.; Chiocconi, A.A. J. Chem. Res. (S), 1996, 336.
21. This constitutes a variant of a Madelung result in which the
11. Typical Coupling Procedure: A thick-walled screw cap glass tube
was charged with a mixture of N,N-diethyl 2-bromobenzamide
(505 mg, 1.97 mmol), aniline (0.21 mL, 2.30 mmol), NaOt-Bu
carbonyl carbon originates from external CO , see Clark, R.D.;
2
Muchowski, J.M.; Fisher, L.E.; Flippin, L.A.; Repke, D.B.;
Souchet, M. Synthesis, 1991, 871.
(266 mg, 2.77 mmol), Pd (dba) (5 mg, 0.006 mmol), BINAP (11
2
3
mg, 0.017 mmol) and toluene (5 mL) under N atmosphere. The
22. For
analogous
formation
of
dibenzooxepinone,
2
tube was sealed and heated (90-100°C) with stirring for 21 h, and
dibenzophosphorinone, and dibenzothiepinone systems, see refs.
4 and 5, and footnote 11 in ref. 4, respectively.
cooled to rt. Addition of aq NH Cl and standard workup, followed
4
by flash column chromatography (10% EtOAc/hexane) afforded
23. Richelson, E. In Antidepressants: Neurochemical, Behavioral,
and Clinical Perspectives Enna, S. J.; Malick, J. B.; Richelson, E.
(Eds.), Raven Press, New York, 1981, p53; Sulser, F. In
Antidepressants: Thirty Years On Leonard, B. and Spencer, P.
(Eds.), CNS Publishers, London, 1990, p23.
N, N-diethyl N-phenylanthranilamide (426 mg, 81%), mp 74-76°C
-1
1
(hexane); IR (neat) 1622 cm ; H NMR (CDCl , 250 MHz) δ
3
7.40 (d, 1H, J = 0.8 Hz), 7.37-7.16 (m, 4H), 7.10-7.05 (m, 2H),
13
6.96-6.84 (m, 3H), 3.45 (bs, 4H), 1.17 (bs, 6H); C NMR
(CDCl , 62.9 MHz) δ 170.1, 142.1, 141.1, 129.5, 128.9, 126.9,
3
24. Beak, P.; Meyers, A.I. Acc. Chem. Res. 1986, 19, 356.
+
125.0, 120.9, 119.4, 118.2, 116.8, 29.3, 13.3; m/z (EI) 268 (M ).
25. All new compounds show analytical and spectral (IR, NMR, MS)
data in full agreement with the depicted structures.
Anal. Calcd for C
H N O: C, 76.09; H, 7.51; N, 10.44. Found:
17 20 2
C, 76.08; H, 7.43; N, 10.70.
26. Typical Cyclization Procedure: A solution of N,N-diethyl N-
methyl-N-phenylanthranilamide (0.1145 g, 0.41 mmol) in THF (3
mL) was cooled to 0 °C under argon atmosphere and treated with
12. Compare with the corresponding Friedel-Crafts method (32%
yield, see ref 7).
13. See, inter alia, Vieira, P.C.; Kubo, I. J. Nat. Prod. 1992, 55, 1112;
Su, T.-l.; Dziewiszek, K.; Wu, T.-s. Tetrahedron Lett. 1991, 32,
1541.
a solution of LDA (1.42 mmol) [n-BuLi, 0.85 mL, 1.67 M, 1.42
i
mmol; HN Pr , 0.19 mL, 1.42 mmol], in THF (2 mL) precooled to
2
0 °C. The reaction mixture was maintained at 0 °C for 1.5 h and
14. For general effects of m-EDG on Friedel-Crafts chemistry, see
Taylor, R. In Electrophilic Aromatic Substitution Wiley, New
York, 1990, p236. For examples, see Sargent, M.V. J. Chem. Soc.,
Perkin Trans. 1 1987, 2553; Sharp, M.J. MSc. Thesis, University
of Waterloo, 1986.
warmed to rt. Addition of aq NH Cl and standard workup,
followed by silica gel flash column chromatography (30% EtOAc/
4
hexane eluent) afforded N-methylacridone (0.0680 g, 79% yield),
27
mp 221.5-222°C (MeOH/H O), lit mp 210-211°C (abs EtOH);
2
1
H NMR (250 MHz, CDCl ) δ 8.51 (dd, J = 8.0, 1.5 Hz, 1H),
3
15. Svoboda, G.H. Lloydia 1966, 29, 206; Svoboda, G.H.; Poore,
G.A.; Simpson, P.J.; Boder, G.B. J. Pharm. Sci. 1966, 55, 758.
Review on acridone alkaloids: Su, T.-l. and Watanabe, K.A. In
Studies in Natural Product Chemistry, Atta-ur-Rahman, Ed.,
Elsevier, Amsterdam, 1993, 13, 347.
7.70-7.63 (m, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.27 - 7.21 (m, 1H),
3.81 (s, 3H).
27. Maskiewicz, R.; Sogah, D.; Bruice, T.C. J. Am. Chem. Soc. 1979,
101, 5355.
28. We are grateful to NSERC Canada and Monsanto/Searle for
support of our synthetic programs under the Industrial Research
Chair award. S. MacNeil is an NSERC Postgraduate Scholar.
Professors Steve Buchwald and John Hartwig and their students
graciously provided experimental details of their diarylamine
synthesis and valuable advice. VS thanks the Dipartimento di
Chimica, University of Pisa and Professors P. Salvadori and D.
Pino for a Visiting Professorship and cultural hospitality during
the preparation of this paper.
16. Sibi, M.P.; Snieckus, V. J. Org. Chem. 1983, 48, 1935. Snieckus,
V. Chem. Rev. 1990, 90, 879. For a recent list of citations, see
James, C.A.; Snieckus, V. Tetrahedron Lett. 1997, 38, 8149.
17. For similar reactions, see Hellwinkel, D.; Lammerzahl, F.;
Hofmann, G. Chem. Ber. 1983, 116, 3375; Hallberg, A.;
Svensson, A.; Martin, A.R. Tetrahedron Lett. 1986, 27, 1959;
Billedeau, R. M.Sc. Thesis, University of Waterloo, 1983.
18. Metalation of 7a under these conditions for 60 min followed by
electrophile quench afforded 2-TMS (58-77%), 2-Me (59%), and