The Journal of Organic Chemistry
Article
4
-Acetamido-2,3,5,6-tetrafluorobenzoic Acid (7). To a solution of
-azido-2,3,5,6-tetrafluorobenzoic acid (103 mg, 0.44 mmol) in water
1 mL) was added NaOH (35 mg, 0.88 mmol). When the azide was
CD OD (0.4 mL) in an NMR tube at 25 °C was added thioacetic acid
3
1
9
4
(
(1 equiv in 0.4 mL of CD OD). The reaction was monitored by F
3
NMR, and the rate constants were estimated by nonlinear curve fitting
8b
completely dissolved after sonication, thioacetic acid (46 mg, 0.6
mmol) was added, and the mixture was stirred for 20 min. After this,
the reaction was quenched with 1 M HCl (10 mL), and the solvent
was evaporated. The residue was purified by flash column
following a second-order kinetic model.
Chemoselectivity Studies. The functional group tolerance was
19
evaluated with the strategy suggested by Glorius and co-workers.
The azide (0.22 mmol) was dissolved in the solvent (0.5 mL) to which
chromatography (3:1 DCM/MeOH, R = 0.25) to yield the product
NEt (39 μL) was added (except for buffer systems). The additive
f
3
1
as white crystals (98 mg, 88%). H NMR (400 MHz, D O): δ 2.21 (s,
(0.28 mmol) and the thioacid (0.28 mmol) were premixed in the
solvent; the solution was added to the azide solution, and the resulting
mixture was stirred at room temperature until complete conversion of
2
3
1
1
2
2
1
H). 13C NMR (100 MHz, DMSO): δ 22.5, 116.4 (m), 117.0 (m),
42.0 (dm, 2C, J = 248 Hz), 142.7 (dm, 2C, JCF = 245 Hz), 160.5,
CF
68.6. 19F NMR (376 MHz, D O): δ −144.12 (m, 2F), −145.56 (m,
the azide was recorded. The products were analyzed by F and H
NMR before and after reaction to determine the percentage of each
component in the reaction mixture.
19
1
2
+
F). ESI-HRMS Calcd for C H F NO [M + H] : 252.0284. Found:
9
6
4
3
52.0282. IR (ATR): 3189.8, 2499.5, 1686.2, 1624.7, 1473.7, 1400.1,
−1
362.9, 1247.3, 1013.5, 983.8, 950.6, 848.7, 827.7, 741.8 cm .
2
2
4
-Azido-2,3,5,6-tetrafluorobenzonitrile (9). Light yellow liquid.
ASSOCIATED CONTENT
Supporting Information
1
3
■
C NMR (100 MHz, CDCl ): δ 89.1 (t, 1C, CN, J = 18 Hz), 107.2 (t,
3
*
S
1
C, J = 4 Hz), 126.7 (m, 1C), 140.3 (dm, 2C, J
= 252 Hz), 147.5
1
13
19
C−F
dm, 2C, JC−F = 262 Hz). 1 F NMR (376 MHz, CDCl ): δ −132.05
9
Characterization data including H, C, and F NMR spectra;
(
(
3
m, 2F), −148.68 (m, 2F).
N-(4-Cyano-2,3,5,6-tetrafluorophenyl)acetamide (10). The com-
pound was synthesized following the protocol of compound 3 from 4-
azido-2,3,5,6-tetrafluorobenzonitrile (184 mg, 0.85 mmol) and thio-
acetic acid (84 mg, 1.1 mmol). The reaction mixture was evaporated
under reduced pressure, and the residue was purified by flash column
AUTHOR INFORMATION
Author Contributions
S.X. and R.F. contributed equally to this paper.
Notes
■
*
*
chromatography (2:1 hexane/EtOAc, R = 0.14) to give the product as
f
1
a pale yellow solid (165 mg, 88%). H NMR (400 MHz, CDCl ): δ
3
2
1
.30 (s, 3H), 7.12 (s, 1H). 13C NMR (100 MHz, CDCl ): δ 23.3, 91.5,
3
07.4 (m), 122.6 (m), 141.8 (dm, 2C, J = 246 Hz), 147.5 (dm, 2C,
CF
JCF = 262 Hz), 167.6. 19F NMR (376 MHz, CDCl ): δ −132.27 (m,
3
+
2
2
1
9
F), −141.50 (m, 2F). ESI-HRMS Calcd for C H F N O [M + H] :
9
5
4
2
The authors declare no competing financial interest.
33.0338. Found: 233.0339. IR (ATR): 3296.6, 2243.2, 1686.1,
647.5, 1542.2, 1504.9, 1482.5, 1371.4, 1320.6, 1282.3, 1259.1, 1141.2,
−1
ACKNOWLEDGMENTS
99.8, 963.2, 924.2, 706.9 cm .
■
1
-Azido-2,3,4,5,6-pentafluorobenzene (11). Amber liquid. 13
2
4
C
This study was supported in part by the Royal Institute of
Technology, the National Institutes of Health
(R01GM080295), and the National Science Foundation
CHE-1112436). S.X. thanks the China Scholarship Council
for a special scholarship award.
NMR (100 MHz, CDCl ): δ 115.9 (dt, J = 4.63, 12.5 Hz), 138.1 (dm,
3
19
J = 261 Hz), 141.0 (dm, J = 250 Hz). F NMR (376 MHz, CDCl ): δ
3
−
151.48 (m, 2F), −159.62 (m, 1F), −161.11 (m, 2F).
(
N-(Perfluorophenyl)acetamide (12). The compound was synthe-
sized following the protocol of compound 3 from pentafluorophenyl
azide (167 mg, 0.8 mmol) and thioacetic acid (76 mg, 1.0 mmol).
Purification was done by flash column chromatography (2:1 hexane/
REFERENCES
(1) Curtius, T. Ber. Dtsch. Chem. Ges. 1902, 35, 3226.
(2) (a) Saxon, E.; Armstrong, J. I.; Bertozzi, C. R. Org. Lett. 2000, 2,
141. (b) Nilsson, B. L.; Kiessling, L. L.; Raines, R. T. Org. Lett. 2000,
■
EtOAc, R = 0.29) to give the product as white crystals (121 mg, 86%).
f
1
13
H NMR (400 MHz, CDCl ): δ 6.79 (br, 1H), 2.25 (s, 3H). C NMR
3
2
(
100 MHz, CDCl ): δ 23.0, 111.9 (m), 137.9 (dm, 2C, J = 253 Hz),
40.4 (dm, 1C, JCF = 235 Hz), 143.1 (dm, 2C, JCF = 253 Hz), 168.9.
3
C
F
1
2, 1939.
1
9
F NMR (376 MHz, CDCl ): δ −144.81 (m, 1F), −156.24 (m, 2F),
(3) (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596. (c) Rasmussen,
L. K.; Boren, B. C.; Fokin, V. V. Org. Lett. 2007, 9, 5337.
3
+
−
162.18 (m, 2F). ESI-HRMS Calcd for C H F NO [M + H] :
8
5 5
2
1
7
26.0291. Found: 226.0293. IR (ATR): 3215.3, 1689.1, 1523.4,
493.0, 1461.9, 1378.4, 1274.8, 1160.7, 1033.8, 1007.4, 980.6, 942.0,
−
1
(
4) (a) Saxon, E.; Bertozzi, C. R. Science 2000, 287, 2007. (b) Kohn,
35.0, 666.8 cm .
-Azido-2,3,5,6-tetrafluoropyridine (13). Colorless liquid. 13
2
5
M.; Breinbauer, R. Angew. Chem., Int. Ed. 2004, 43, 3106. (c) Lutz, J. F.
Angew. Chem., Int. Ed. 2007, 46, 1018. (d) Manova, R.; van Beek, T.
A.; Zuilhof, H. Angew. Chem., Int. Ed. 2011, 50, 5428.
4
C
NMR (100 MHz, CDCl ): δ 132.2 (m), 135.4 (dm, 2C, J
= 262
3
3
C−F
Hz), 143.6 (dm, 2C, JC−F = 244 Hz). 19F NMR (376 MHz, CDCl ): δ
−
89.59 (m, 2F), −152.91 (m, 2F).
(5) (a) Huisgen, R. Angew. Chem., Int. Ed. 1963, 2, 565. (b) Agard, N.
J.; Prescher, J. A.; Bertozzi, C. R. J. Am. Chem. Soc. 2004, 126, 15046.
(c) Ess, D. H.; Houk, K. N. J. Am. Chem. Soc. 2007, 129, 10646.
(6) (a) Yoshida, S.; Shiraishi, A.; Kanno, K.; Matsushita, T.; Johmoto,
K.; Uekusa, H.; Hosoya, T. Sci. Rep. 2011, 1, 82. (b) Dommerholt, J.;
van Rooijen, O.; Borrmann, A.; Guerra, C. F.; Bickelhaupt, F. M.; van
Delft, F. L. Nat. Commun. 2014, 5, 5378.
N-(Perfluoropyridine-4-yl)acetamide (14). The compound was
synthesized following the protocol of compound 3 from 4-azido-
,3,5,6-tetrafluoropyridine (163 mg, 0.85 mmol) and thioacetic acid
84 mg, 1.0 mmol). Purification was done by flash column
2
(
chromatography (2:1 hexane/EtOAc, R = 0.23) to give the product
as a white solid (151 mg, 91%). H NMR (400 MHz, DMSO): δ 2.17
f
1
(
(
1
2
2
1
6
s, 3H), 10.77 (br, 1H). 13C NMR (100 MHz, CDCl ): δ 23.4, 128.2
(7) Rosen, T.; Lico, I. M.; Chu, D. T. W. J. Org. Chem. 1988, 53,
1580.
3
m), 136.6 (dm, 2C, J = 261 Hz), 143.7 (dm, 2C, JCF = 245 Hz),
CF
67.3. 19F NMR (376 MHz, CDCl ): δ −145.67 (m, 2F), −89.44 (m,
(8) (a) Shangguan, N.; Katukojvala, S.; Greenberg, R.; Williams, L. J.
J. Am. Chem. Soc. 2003, 125, 7754. (b) Kolakowski, R. V.; Shangguan,
N.; Sauers, R. R.; Williams, L. J. J. Am. Chem. Soc. 2006, 128, 5695.
(c) Muhlberg, M.; Siebertz, K. D.; Schlegel, B.; Schmieder, P.;
Hackenberger, C. P. Chem. Commum. 2014, 50, 4603.
3
+
F). ESI-HRMS Calcd for C H F N O [M + H] : 209.0338. Found:
7
5
4
2
09.0338. IR (ATR): 3220.4, 2979.4, 1694.6, 1643.7, 1524.4, 1461.8,
420.7, 1372.9, 1279.8, 1248.1, 1088.7, 1012.3, 985.9, 924.6, 723.6,
89.6, 613.8 cm .
−
1
Kinetic Studies. Rate constants were measured with the following
(9) Rijkers, D. T.; Merkx, R.; Yim, C. B.; Brouwer, A. J.; Liskamp, R.
protocol. To a mixture of azide (2 equiv) and NEt (1 equiv) in
M. J. Pept. Sci. 2010, 16, 1.
3
E
J. Org. Chem. XXXX, XXX, XXX−XXX