408
M. Cibian et al.
LETTER
23.21 ppm. Anal. Calcd (%) for C19H24N2: C, 81.38; H, 8.63;
N, 9.99. Found: C, 81.62; H, 9.27; N, 10.17.
(9) General Procedure – N-Oxidation of Amidines with
MCPBA
References and Notes
(1) (a) Srivastava, R. M.; Brinn, I. M.; Machuca-Herrera, J. O.;
Faria, H. B.; Carpenter, G. B.; Andrade, D.; Venkatesh,
C. G.; de Morais, L. P. F. J. Mol. Struct. 1997, 406, 159.
(b) Clement, B. Drug Metab. Rev. 2002, 34, 565.
(2) (a) Durust, N.; Akay, M. A.; Durust, Y.; Kilic, E. Anal. Sci.
2000, 16, 825. (b) Dueruest, Y.; Akcan, M.; Martiskainen,
O.; Siirola, E.; Pihlaja, K. Polyhedron 2008, 27, 999.
(3) (a) Kharsan, R. S.; Mishra, R. K. Bull. Chem. Soc. Jpn. 1980,
53, 1736. (b) Kharsan, R. S.; Patel, K. S.; Mishra, R. K.
Indian J. Chem., Sect. A: Inorg., Bio-inorg., Phys., Theor.
Anal. Chem. 1980, 19, 499. (c) Agarwal, C.; Patel, K. S.;
Mishra, R. K. Asian Environ. 1990, 12, 29. (d) Deb, M. K.;
Mishra, N.; Patel, K. S.; Mishra, R. K. Analyst 1991, 116,
323.
A solution of MCPBA (1 equiv) in CH2Cl2 was added
dropwise by addition funnel to a solution of amidine (1
equiv) and NaHCO3 (1.0–1.5 equiv) in the same solvent, at
0 °C (ice bath) to r.t. The reaction mixture was stirred for
other 30–60 min at r.t. and was washed with an aq solution
of K2CO3 (5%; 2 × 25 mL). The combined organic fractions
were dried over anhyd MgSO4 or Na2SO4 and filtered. The
solvent was removed by evaporation, to afford solids or oils
that were further purified by recrystallization or flash
chromatography on silica gel.
(10) Compound 3f: Compound 2f (2.0 g, 7.1 mmol, 1 equiv) and
NaHCO3 (0.61 g, 7.1 mmol, 1 equiv) in CH2Cl2 (50 mL) and
MCPBA (1.6 g, 7.1 mmol, 1 equiv) in CH2Cl2 (50 mL) were
reacted following the general procedure described in ref. 9,
and modified as specified in Table 1 (footnote k). After
purification by flash chromatography on silica gel [gradient
of eluants: hexane–EtOAc (2:8), EtOAc–MeOH (9:1),
CH2Cl2 100%] and recrystallization in hot hexane, a
colorless solid was obtained; yield 0.92 g, 58%. 1H NMR
(300 MHz, CDCl3): d = 7.93 (s, 1 H, NHCH=N), 7.45–7.39
(m, 2 H, C6H4), 7.34–7.31 (m, 2 H, C6H4), 7.28–7.08 (m, 3
H, C6H4), 6.96 (d, J = 8 Hz, 1 H, C6H4), 3.67 (br s, OH), 3.40
[sept, J = 7 Hz, 1 H, CH(CH3)2], 3.27 [sept, J = 7 Hz, 1 H,
CH(CH3)2], 1.33–1.29 [m, 12 H, CH(CH3)2] ppm. 13C NMR
(75 MHz, CDCl3): d = 145.0, 142.1, 137.4, 136.2, 135.4,
130.1, 127.1, 127.0, 126.7, 126.6, 125.5, 124.3, 116.2,
28.12, 27.61, 24.27 (2 C), 23.08 (2 C) ppm. MS (ESI-
HRMS, CH2Cl2): m/z [M + H]+ calcd for C19H25N2O:
297.1961; found: 297.1971. Anal. calcd (%) for C19H24N2O:
C, 76.99; H, 8.16; N, 9.45. Found: C, 76.80; H, 8.23; N, 9.40.
(11) Compound 3g: Compound 2g (1.5 g, 4.3 mmol, 1 equiv) and
NaHCO3 (0.38 g, 4.3 mmol, 1 equiv) in CH2Cl2 (50 mL) and
MCPBA (0.96 g, 4.3 mmol, 1 equiv) in CH2Cl2 (50 mL)
were reacted following the general procedure described in
ref. 9, and modified as specified in Table 1 (footnote k).
After purification by flash chromatography on silica gel
[gradient of eluants: hexane–EtOAc (2:8), EtOAc–MeOH
(9:1), CH2Cl2 100%] and recrystallization in CH2Cl2–hexane
(1:1), a colorless solid was obtained; yield 0.93 g, 59%.
1H NMR (400 MHz, CDCl3): d = 7.85–7.78 (m, 1 H, C6H4),
7.55–7.32 (m, 14 H, C6H5, C6H4, NHCH=N), 7.21 (dd, J = 7,
2 Hz, 1 H, C6H4), 7.11 (td, J = 8, 2 Hz, 1 H, C6H4), 7.05 (td,
J = 7, 1 Hz, 1 H, C6H4), 6.17 (d, J = 8 Hz, 1 H, C6H4), 3.67
(br s, OH) ppm. 13C NMR (75 MHz, CDCl3): d = 142.0,
138.2, 137.5, 136.9, 135.7, 135.2, 131.7, 131.40, 130.7,
129.4 (2 C), 129.24 (2 C), 129.19 (2 C), 129.1 (2 C), 128.8,
128.6, 128.5 (2 C), 128.3, 128.1, 126.1, 123.7, 115.4 ppm.
MS (ESI-HRMS, CH2Cl2): m/z [M + H]+ C25H21N2O calcd
for: 365.1648; found: 365.1655. Anal. Calcd (%) for
C25H20N2O: C, 82.39; H, 5.53; N, 7.69. Found: C, 82.33; H,
5.52; N, 7.73.
(4) (a) Desjardins, S. Y.; Cavell, K. J.; Jin, H.; Skelton, B. W.;
White, A. H. J. Organomet. Chem. 1996, 515, 233. (b) Lee,
A. V.; Schafer, L. L. Eur. J. Inorg. Chem. 2007, 2243.
(c) Batten, M. P.; Canty, A. J.; Cavell, K. J.; Ruether, T.;
Skelton, B. W.; White, A. H. Inorg. Chim. Acta 2006, 359,
1710. (d) John, A.; Katiyar, V.; Pang, K.; Shaikh, M. M.;
Nanavati, H.; Ghosh, P. Polyhedron 2007, 26, 4033.
(e) Ding, F.; Sun, Y.; Monsaert, S.; Drozdzak, R.; Dragutan,
I.; Dragutan, V.; Verpoort, F. Curr. Org. Synth. 2008, 5,
291. (f) Ledoux, N.; Allaert, B.; Schaubroeck, D.; Monsaert,
S.; Drozdzak, R.; Van Der Voort, P.; Verpoort, F.
J. Organomet. Chem. 2006, 691, 5482.
(5) (a) Briggs, L. H.; Cambie, R. C.; Dean, I. C.; Rutledge, P. S.
Aust. J. Chem. 1976, 29, 357. (b) Krajete, A.; Steiner, G.;
Kopacka, H.; Ongania, K.-H.; Wurst, K.; Kristen, M. O.;
Preishuber-Pfluegl, P.; Bildstein, B. Eur. J. Inorg. Chem.
2004, 1740. (c) Tian, L.; Xu, G.-Y.; Ye, Y.; Liu, L.-Z.
Synthesis 2003, 1329. (d) Kamm, O.; Marvel, C. S. Org.
Synth. 1941, 1, 445.
(6) General Procedure14 – Method A
The EtOH was distilled from a mixture of aniline,
triethylorthoformate (2:1), and a catalytic amount of glacial
AcOH at 120–160 °C. The reactions times ranges from 1 h
for compound 2h to overnight. Solids were formed which
were further purified as described in ref. 7.
(7) General Procedure15 – Method B
A mixture of aniline, triethylorthoformate (2:1), and a
catalytic amount of glacial AcOH (MS 4 Å were also added)
was microwave activated at 130 °C for 10 min. At the end of
the reactions, oily solids were obtained, which were taken in
CH2Cl2 (2a–e and 2g–i) or hexane(2f). The solvents were
evaporated under vacuum to afford solids or oils that were
further purified by recrystallization in CH2Cl2–hexane (1:1;
2a–e,g), boiling hexane (2f,i) or by trituration/sonication
with hexane(2h). Colorless solids were obtained in all
cases.8
(8) Except for compound 2f, all of the formamidines are known
compounds, and their characterization is similar to reported
data.14
Compound 2f: Compound 1f (7.5 mL, 51 mmol, 2 equiv),
triethylorthoformate (4.0 mL, 25 mmol, 1 equiv) and a
catalytic amount of glacial AcOH (0.30 mL, 5.1 mmol, 0.2
equiv) were reacted following the general procedure
described in ref. 7. After purification by trituration with cold
pentane and recrystallization in hot hexane, colorless
crystals were obtained; yield 5.56 g, 78%. 1H NMR (300
MHz, CDCl3): d = 8.00 (s, 1 H, NHCH=N), 7.29 (d, J = 8
Hz, 2 H, C6H4), 7.20–7.08 (m, 4 H, C6H4), 7.02 (d, J = 8 Hz,
2 H, C6H4), 3.29 [sept, J = 7 Hz, 2 H, –CH(CH3)2], 1.26 [d,
J = 7 Hz, 12 H, CH(CH3)2] ppm. 13C NMR (75 MHz,
CDCl3): d = 148.6, 139.5, 126.7, 125.9, 124.0, 118.7, 27.73,
(12) Compound 3h: Compound 2h (1.0 g, 4.0 mmol, 1 equiv) in
CH2Cl2 (20 mL) and MCPBA (0.89 g, 4.0 mmol, 1 equiv) in
CH2Cl2 (20 mL) were reacted following the general
procedure described in ref. 9, and modified as specified in
Table 1 (footnote l). After recrystallization in CH2Cl2–
hexane (1:1) at –10 °C, a colorless solid was obtained; yield
0.98 g, 92%. 1H NMR (400 MHz, CDCl3): d = 7.34 (s, 1 H,
NHCH=N), 7.20 (t, J = 8 Hz, 1 H, C6H3), 7.15–7.06 (m, 5 H,
C6H3), 3.51 (br s, OH), 2.38 (d, J = 3 Hz, 12 H, CH3). 13
C
NMR (75 MHz, CDCl3): d = 142.1, 140.4, 135.8, 134.8 (2
C), 133.4, 129.3, 129.0 (2 C), 128.6 (2 C), 126.7, 18.81 (2
C), 17.26 (2 C) ppm. ESI-MS (CH2Cl2): m/z (%) = 269.2
Synlett 2011, No. 3, 405–409 © Thieme Stuttgart · New York