127.7 (C3), 130.5 (C3ꢀ,5ꢀ), 136.3 (C2ꢀ,6ꢀ), 139.6 (C1ꢀ), 140.0 (C4),
152.9 (C6), 162.1 (C2), 167.4 (COOH); m/z (ESMS+) 246 [M +
H], 268 [M + Na].
mixture heated at 120 C for 4 hours under argon with stirring.
The resulting a brown liquid was cooled to room temperature
and then slowly poured onto cold concentrated aqueous sodium
hydroxide solution (300 cm3) with vigorous stirring and the light
grey precipitates that formed were removed via filtration. The
product was washed with water and dried thoroughly to yield a
◦
7-Methyl-1-azathioxanthone, 13. Polyphosphoric acid (60 cm3)
was added to 2-4ꢀ-methylthiophenoxy-nicotinic acid (5.50 g
22.4 mmol) and the mixture heated at 120 ◦C for 4 hours
under argon with stirring. The resulting a brown liquid was
cooled to room temperature and then slowly poured onto cold
concentrated aqueous sodium hydroxide solution (300 cm3) with
vigorous stirring and the light green precipitate that formed was
removed via filtration. The product was recrystallised from warm
EtOH. The crystals that formed upon standing were filtered
and dried thoroughly to yield the title compound as a yellow
microcrystalline solid (4.32 g, 87%), m.p. 139–41 ◦C. Found C,
68.6; H, 4.07; N, 5.89; S, 13.9%; C13H9NOS requires C, 68.7; H,
3.95; N, 6.17; S, 14.1%. dH (CDCl3) 8.85 (1H, d, J 7.9 Hz, H2),
8.72 (1H, d, J 7.9 Hz, H4), 8.50 (1H, s, H6), 7.78 (1H, d, J 8.2 Hz,
H9), 7.63 (2H, m, H3,8), 3.29 (3H, s, CH3); dc (CDCl3) 22.9 (CH3),
123.1 (C3), 127.5 (C9ꢀ), 128.2 (C7), 129.5 (C6ꢀ), 129.6 (C9), 130.0
(C8), 136.3 (C6), 138.7 (C4), 139.4 (C4ꢀ), 156.9 (C1ꢀ), 159.7 (C2),
179.8 (C5); m/z (ESMS+) 228 [M + H], 250 [M + Na].
1
1 : 1 mixture (obtained from H-NMR) of the title compounds
as a light yellow powder. Products were separated by column
chromatography (silica, toluene–CH2Cl2–EtOAc 45 : 45 : 10), Pure
fractions were combined together and the solvents removed by
reduced pressure. Products were recrystallised from warm EtOH,
to yield the given compound as a light yellow crystalline solid.
6-Methyl-1-azathioxanthone, 14. Yield 0.41 g (8%) m.p. 184–
186 ◦C. Found C, 69.1; H, 4.04; N, 6.02.; S, 13.8%; C13H9NOS
requires: C, 68.7; H, 3.95; N, 6.17; S, 14.1%. dH (CDCl3) 8.81 (1H,
dd, J 8 Hz, H2), 8.79 (1H, d, J 8 Hz, H4), 8.34 (1H, m, H9), 7.42
(2H, m, H2,7), 7.31 (2H, m, H3,8), 2.23 (3H, s, CH3); dc (CDCl3)
22.3 (CH3), 122.5 (C3), 126.2 (C8), 127.1 (C4ꢀ), 128.7 (C7), 129.8
(C9), 138.8 (C1ꢀ), 139.1 (C2), 142.3 (C6ꢀ), 152.7 (C4), 159.2 (C4ꢀ),
180.8 (C5); m/z (ESMS+) 228 [M + H], 250 [M + Na].
8-Methyl-1-azathioxanthone, 15b. Yield 0.56 g (11%) m.p.
126–128 ◦C. Found C, 68.7; H, 3.99; N, 5.81.; S, 14.1%; C13H9NOS
requires C, 68.7; H, 3.95; N, 6.17; S, 14.1%. dH (CDCl3) 8.72 (1H,
d, J 8 Hz, H2), 8.66 (1H, d, J 8 Hz, H4), 7.52 (1H, s, H9), 7.50 (1H,
d, J 7.9 Hz, H6), 7.41 (1H, t, J 8 Hz, H3), 7.30 (1H, d, J 7.9 Hz, H7)
2.88 (3H, s, CH3); dc (CDCl3) 24.5 (CH3), 121.8 (C3), 125.5 (C6),
128.3 (C1ꢀ), 130.7 (C7), 131.6 (C9), 131.8 (C9ꢀ), 138.3 (C4), 138.8
(C6ꢀ), 142.4 (C8), 153.3 (C2), 157.8 (C4ꢀ) 182.1 (C5); m/z (ESMS+)
228 [M + H], 250 [M + Na].
2-(2ꢀ-Methylthiophenoxy)nicotinic acid. This was prepared as
described above for the para isomer to yield the title compound as
a pale yellow, crystalline solid (6.02 g, 85%), m.p. 166–8 ◦C. Found
C, 64.1; H, 4.29; N, 5.39; S,12.8%; C13H11NO2S requires: C, 63.7;
H, 4.49; N, 5.73; S, 13.1%. dH (CDCl3) 13.55 (1H, br s, –OH), 8.36
(1H, d, J 7.2 Hz, H6), 8.22 (1H, d, J 7.2 Hz, H5), 7.45 (1H, d, J
7.6 Hz, H6ꢀ), 7.34 (2H, m, H3ꢀ,5ꢀ), 7.20 (2H, m, H4,4ꢀ) 2.20 (3H, s,
CH3); dc (CDCl3) 21.5 (CH3), 120.3 (C2ꢀ), 127.2 (C5), 131.1 (C3),
131.6 (C4ꢀ,5ꢀ), 137.0 (C6ꢀ), 137.2 (C3ꢀ), 143.2 (C1ꢀ), 143.7 (C4), 153.6
(C6), 162.0 (C2), 167.4 (COOH); m/z (ESMS+) 246 [M + H], 268
[M + Na].
Acknowledgements
9-Methyl-1-azathioxanthone, 16. This was prepared as de-
scribed for the isomer above yield the title compound as a light
yellow crystalline solid (4.73 g, 95%), m.p. 135–7 C. Found: C,
This paper is dedicated to Richard P. Wayne, who first introduced
the author to the benefits of excited state chemistry. We thank
Professor Judith Howard for access to crystallographic facilities.
Financial support from EPSRC, the Royal Society, ESF-COST
D18, the EC networks of excellence, EMIL and DiMI is gratefully
acknowledged.
◦
68.8; H, 3.97; N, 6.24; S, 13.9%; C13H9NOS requires: C, 68.7; H,
3.95; N, 6.17; S, 14.1%. dH (CDCl3) 8.92 (1H, dd, J 8, 1.8 Hz, H2),
8.74 (1H, dd, J 8, 1.8 Hz, H4), 8.34 (1H, dd, J 8, 2 Hz, H6), 7.76
(1H, dd, J 8, 2 Hz, H8), 7.67 (1H, t, J 8 Hz, H3), 7.54 (1H, t, J
8 Hz, H7), 2.52 (3H, s, CH3); dc (CDCl3) 20.1 (CH3), 123.8 (C3),
126.0 (C4ꢀ), 127.3 (C7), 127.8 (C6), 129.1 (C6ꢀ), 135.0 (C8), 135.2
(C9), 136.6 (C9ꢀ), 138.1 (C4), 157.2 (C2), 158.9 (C1ꢀ), 181.4 (C5);
m/z (ESMS+) 228 [M + H], 250 [M + Na].
References
1 E. Soini and I. Hemmila, Clin. Chem. (Washington, D. C.), 1979, 25,
353; I. Hemmila and V.-M. Mukkala, Crit. Rev. Clin. Lab. Sci., 2001,
38, 441; H. Sitari, I. Hemmila, K. Pettersson and T. Lo¨vgren, Nature,
1983, 301, 258.
2 G. Mathis, Clin. Chem. (Washington, D. C.), 1993, 39, 1953; G. Mathis,
Clin. Chem. (Washington, D. C.), 1995, 41, 1391.
3 D. Maurel, J. Kriazeff, G. Mathis, E. Trinquet, J. P. Pin and H. Ansanay,
Anal. Biochem., 2004, 329, 253; M. Gabourdes, V. Bourgine, G. Mathis,
H. Bazin and B. Alpha-Bazin, Anal. Biochem., 2004, 333, 105.
4 S. Pandya, D. Parker and J. Yu, Dalton Trans., 2006,
DOI: 10.1039/b514637b.
5 V. W. W. Yam and K. K. W. Lo, Coord. Chem. Rev., 1999, 184, 157.
6 D. Parker, Coord. Chem. Rev., 2000, 205, 109; D. Parker, R. S. Dickins,
H. Puschmann, C. Crossland and J. A. K. Howard, Chem. Rev., 2002,
102, 1977; D. Parker, K. P. Senanayake and J. A. G. Williams, J. Chem.
Soc., Perkin Trans. 2, 1998, 2129.
2-(3ꢀ-Methylthiophenoxy)nicotinic acid. This was prepared as
described above for the para isomer yielding the title compound as
a pale yellow crystalline solid (6.02 g, 85%), m.p. 160–2 ◦C. Found
C, 63.9; H, 4.45; N, 5.26; S, 13.3%; C13H11NO2S requires C, 63.7;
H, 4.49; N, 5.73; S, 13.1%. dH (CDCl3) 13.60 (1H, br s, –OH),
8.41 (1Hꢀ, d, J 7.9 Hz, H6), 8.20 (1H, d, J 7.9 Hz, H4), 7.28 (5H,
ꢀ
ꢀ
m, H5,2 ,3 ,4 ,6ꢀ) 2.23 (3H, s, CH3); dc (CDCl3) 21.7 (CH3), 120.1
(C5ꢀ), 122.0 (C5), 129.7 (C3ꢀ), 130.2 (C3,4ꢀ), 134.0 (C6ꢀ), 137.3 (C2ꢀ),
138.7 (C1ꢀ), 139.8 (C4), 153.2 (C6), 158.1 (C2), 167.4 (COOH); m/z
(ESMS+) 246 [M + H], 268 [M + Na].
7 P. R. Selvin, Annu. Rev. Biophys. Biomol. Struct., 2002, 31, 275.
8 S. Faulkner, S. J. A. Pope and B. P. Burton-Pye, Appl. Spectrosc. Rev.,
2005, 40, 1.
6-Methyl-1-azathioxanthone, 14 and 8-methyl-1-azathioxan-
thone, 15b. Polyphosphoric acid (60 cm3) was added to 2-3ꢀ-
methylthiophenoxy-nicotinic acid (5.50 g 22.4 mmol) and the
9 T. Gunnlaugsson and J. P. Leonard, Chem. Commun., 2005, 3114.
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 1707–1722 | 1721
©