of BrF3 was dissolved in 10 mL of CFCl3, cooled to 0 ◦C
and added dropwise (about 1 min) at the same temperature
using a glass dropping funnel. The reaction mixture was then
washed with aqueous Na2SO3 until colorless, the aqueous layer
extracted three times with CH2Cl2 and the combined organic layers
dried over MgSO4. Evaporation of the solvent followed by flash
chromatography yielded the desired fluorinated compounds.
s). As with the previous cases, the usual MS methods fail to show
any molecular peak. However, by using Amirav’s method, we were
able to detect a strong molecular ion peak of m/z 193 (M)+ with
an isotope abundance analysis matching factor of 995 out of 999.
Anal. calc. for C6H2ClF2NO2: Cl, 18.32; F, 19.63; N, 7.24. Found:
Cl, 18.33; F, 18.87; N, 6.86.
Acknowledgements
5,6-Dibromo-2,2-difluoro-4-methylbenzo-1,3-dioxole (15). Pre-
pared from 4-methylbenzo-1,3-dioxole-2-thione (14) (1 g), as
descr◦ibed above, in 75% yield: 1.5 g, yellow crystals, m.p. = 52.9–
This work was supported by the USA–Israel Binational Science
Foundation (BSF), Jerusalem, Israel. Y. H. thanks the Israel
Ministry of Science and Technology for a scholarship.
1
53.7 C; H NMR 7.20 (1 H, s), 2.37 ppm (3 H, s); 13C NMR
142.6, 131.8 (t, J = 254 Hz), 128.9, 123.2, 121.9, 118.8, 112.0,
17.3 ppm; 19F NMR -50.1 ppm (2 F, s). The usual MS methods
failed to show any molecular peak. Amirav’s supersonic GC-
MS revealed a strong molecular ion peak of m/z 328 (M)+. It
should be mentioned that along with 15, some traces of mono-
and tribrominated difluoromethylenedioxo derivatives were also
observed and identified by their respective MS spectra.
Notes and references
1 (a) F. Leroux, P. Jeschke and M. Schlosser, Chem. Rev., 2005, 105, 827–
856; (b) J. Su, H. Tang, B. A. McKittrick, D. A. Burnett, H. Zhang, A.
Smith-Torhan, A. Fawzi and J. Lachowicz, Bioorg. Med. Chem. Lett.,
2006, 16, 4548–4553.
2 C. Brennan, C. E. Kluender, P. Wickens, I. J. Enyedy, Z. Hong, B.
Jones, E. S. Kumarasinghe, C. Chuang, B. Phillips and J. Dixon, PCT
Int. Appl., 2006, 79, WO 2006023707.
5-Bromo-2,2-difluoro-6-(fluoromethyl)benzo-1,3-dioxole
(18).
Prepared from 4-methylbenzo-1,3-dioxole-2-thione (17) (1.8 g), as
described above, in 80% yield: 1.3 g, colorless oil; 1H NMR 7.36
(1 H, s), 7.29 (1 H, s), 5.50 ppm (2 H, d, JHF = 47 Hz); 13C NMR
144.7, 144.3, 132.6, 132.4 (t, J = 260 Hz), 114.9, 114.5, 110.1,
83.8 ppm (d, J = 172 Hz); 19F NMR -48.3 (2 F, s), -214.3 ppm
(1 F, t, JHF = 47 Hz). The usual MS methods failed to show any
molecular peak. Amirav’s method revealed a strong molecular
ion peak of m/z 267.9 (M)+ with an isotope abundance analysis
matching factor of 998 out of 999. Anal. calc. for C8H4BrF3O2:
C, 35.72; H, 1.50; Br, 29.70; F, 21.19. Found: C, 35.54; H, 1.41;
Br, 30.13; F, 21.31.
3 M. Shimizu and T. Hiyama, Angew. Chem., Int. Ed., 2005, 44, 214–231.
4 L. Saint-Jalmes, J. Fluorine Chem., 2006, 127, 85–90.
5 M. Kuroboshi, K. Kanie and T. Hiyama, Adv. Synth. Catal., 2001, 343,
235–250.
6 Y. Hagooly and S. Rozen, J. Org. Chem., 2008, 73, 6780–6783.
7 R. S. Michalak, S. R. Wilson and J. C. Martin, J. Am. Chem. Soc., 1984,
106, 7529–7539.
8 K. Ramig, Synthesis, 2002, 2627–2631.
9 (a) S. Rozen, E. Mishani and A. Bar-Haim, J. Org. Chem., 1994, 59,
2918; (b) S. Rozen and M. Brand, J. Org. Chem., 1986, 51, 222–225.
10 R. Sasson, A. Hagooly and S. Rozen, Org. Lett., 2003, 5, 769–
771.
11 R. R. Soelch, G. W. Mauer and D. M. Lemal, J. Org. Chem., 1985, 50,
5845–5852.
12 Y. Hagooly, R. Sasson, M. J. Welch and S. Rozen, Eur. J. Org. Chem.,
2008, 2875–2880.
2,2-Difluoro-1,3-dioxolo-4,5-pyridine (21). Prepared from 1,3-
dioxolo-4,5-pyridine-2-thione (20) (865 mg), as described above, in
95% yield: 856 mg, colorless oil; 1H NMR 7.89 (1 H, dd, J1 = 5 Hz,
J2 = 1.5 Hz), 7.33 (1 H, dd, J1 = 8 Hz, J2 = 1.5 Hz), 7.06 ppm (1 H,
dd, J1 = 8 Hz, J2 = 5 Hz); 13C NMR 153.1, 141.2, 136.7, 129.5 (t,
J = 269 Hz), 119.7, 116.7 ppm; 19F NMR -50.5 ppm (2 F, s). This
compound is very volatile and unstable, meaning that the usual
MS methods failed to show any molecular peak. The supersonic
GC-MS method revealed a strong molecular ion peak of m/z
159 (M)+.
13 Y. Hagooly, O. Cohen and S. Rozen, Tetrahedron Lett., 2009, 50, 392–
394.
14 S. Rozen and O. Lerman, J. Org. Chem., 1993, 58, 239–240.
15 S. Rozen, Acc. Chem. Res., 2005, 38, 803–812.
16 R. Sasson and S. Rozen, Tetrahedron, 2005, 61, 1083–1086.
17 T. L. Ho, Chem. Rev., 1975, 75, 1–20.
18 This compound is commercially available.
19 S. Rozen and I. Ben-David, J. Fluorine Chem., 1996, 76, 145–147.
20 (a) A. Amirav, A. Gordin, M. Poliak and A. B. Fialkov, J. Mass
Spectrom., 2008, 43, 141–163; (b) T. Alon and A. Amirav, Rapid
Commun. Mass Spectrom., 2006, 20, 2579–2588; (c) A. B. Fialkov and
A. Amirav, J. Chromatogr., 2004, 1058, 233–242.
6-Chloro-2,2-difluoro-1,3-dioxolo-4,5-pyridine (24). Prepared
from 1,3-dioxolo-4,5-pyridine-2-thione (23) (1.1 g), as described
above, in 95% yield: 1.1 g, colorless oil; 1H NMR 7.96 (1 H, d, J =
2 Hz), 7.43 ppm (1 H, d, J = 2 Hz); 13C NMR 152.3, 140.8, 137.7,
130.6 (t, J = 260 Hz), 128.1, 118.3 ppm; 19F NMR -49.9 ppm (2 F,
21 F. R. Leroux, B Manteau, P. Genix, F. Giornal, J.-P. Vors, S Pazenok,
Book of Abstracts, 16th European Symposium on Fluorine Chemistry,
2010, 63.
22 L. Stein, J. Am. Chem. Soc., 1959, 81, 1269–1273.
23 I. Garcia-Alvarez, L. Garrido and A. Fernandez-Mayoralas, Chem.
Med. Chem., 2007, 2, 496–504.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 902–905 | 905
©