E
S. J. Barraza, S. E. Denmark
Letter
Synlett
tion, use of soluble bases under single-phase reaction con-
ditions, or the alternative use of alkyl chlorides, is recom-
mended.
(6) (a) Fischer, O.; Hepp, E. Ber. Dtsch. Chem. Ges. 1886, 19, 2991.
(b) Glazer, J.; Hughes, E. D.; Ingold, C. K.; James, A. T.; Jones, G.
T.; Roberts, E. J. Chem. Soc. 1950, 2657. (c) Neber, P. W.;
Rauscher, H. Justus Liebigs Ann. Chem. 1942, 550, 182.
(7) (a) Bender, G. Ber. Dtsch. Chem. Ges. 1886, 19, 2272.
(b) Armstrong, H. E. J. Chem. Soc. Trans. 1900, 77, 1047.
(c) Chattaway, F. D.; Orton, K. J. P. J. Chem. Soc. 1899, 75, 1046.
(8) Mellor, M.; Osbourn, S. E. Tetrahedron 1991, 47, 2255.
(9) Chromatographic methods could not adequately separate the
products, as their properties were too similar.
Funding Information
This work is generously supported by Janssen Research and Develop-
ment LLC, San Diego.
)(
(10) Cella, J. A.; Bacon, S. W. J. Org. Chem. 1984, 49, 1122.
(11) (a) McMillen, D. F.; Golden, D. M. Ann. Rev. Phys. Chem. 1982, 33,
493. (b) Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36,
255.
(12) (a) O’Bara, E. J.; Balsley, R. B.; Starer, I. J. Org. Chem. 1970, 35, 16.
(b) Effenberger, F.; Menzel, P. Angew. Chem., Int. Ed. Engl. 1970,
10, 493. (c) Effenberger, F.; Menzel, P. Chem. Ber. 1977, 110,
1342. (d) Effenberger, F. Angew. Chem. Int. Ed. 2002, 41, 1699.
(13) Winemiller, M. D.; Kopach, M. E.; Harman, W. D. J. Am. Chem.
Soc. 1997, 119, 2096.
Acknowledgment
We are grateful the expert support services of the mass spectrometry
and NMR laboratories of the University of Illinois at Urbana-Champaign.
Supporting Information
Supporting information for this article is available online at
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(14) General Procedure for Rearrangement Experiments
The relevant aniline (0.5 mmol) was weighed into an oven-
dried, threaded dram vial, followed by the sequential addition
of anhydrous DMF (1 mL), an additional reagent (if required),
and an alkyl halide (if required) last. The vial was tightly capped
and placed in a pre-heated aluminum block (80 °C or 120 °C).
After 24 h, the vial was removed from the block and allowed to
cool to ambient temperature (23 °C), at which point it was cau-
tiously opened (may be pressurized). The most common reac-
tion colors are: colorless, black, amber, green, and blue. The
reaction mixture was diluted with 1:1 hexanes/EtOAc (20 mL)
and washed with 10% aq NaHCO3 (30 mL), 10% aq LiCl (30 mL),
and brine (30 mL), dried over anhydrous Na2SO4 (1 g), decanted,
and concentrated on a rotovap (30 °C, 15 mm Hg). The crude
product was then dried further under high vacuum (0.1 mm Hg)
for 1 h before being diluted with a solution of a known quantity
of tetramethylurea (TMU) in CDCl3 (1 mL). The targeted quan-
tity was 0.05 mmol TMU/1 mL CDCl3, prepared as stock solu-
tions in 10 mL volumetric flasks at 23 °C. TMU was measured by
mass, and the actual quantity per mL CDCl3 is reported. The
solution was then transferred to a 5 mm NMR tube and ana-
lyzed by 1H NMR and 13C NMR spectroscopy (600 MHz, 1H).
References and Notes
(1) Excepting reactions (e.g., certain Smiles rearrangements) in
which the defining structure of aniline is lost.
(2) (a) Bamberger, E. Ber. Dtsch. Chem. Ges. 1894, 27, 1347.
(b) Bamberger, E. Ber. Dtsch. Chem. Ges. 1894, 27, 1548.
(c) Bamberger, E. Justus Liebigs Ann. Chem. 1912, 390, 131.
(d) Bamberger, E. Justus Liebigs Ann. Chem. 1921, 424, 233.
(3) (a) Fries, K.; Oehmke, G. Justus Liebigs Ann. Chem. 1928, 462, 1.
(b) Fries, K.; Boeker, R.; Wallbaum, F. Justus Liebigs Ann. Chem.
1934, 509, 73. (c) Miller, B. Tetrahedron Lett. 1962, 2, 55.
(d) Boduszek, B.; Shine, H. J. J. Am. Chem. Soc. 1988, 110, 3247.
(4) (a) Hofmann, A. W.; Martius, C. A. Ber. Dtsch. Chem. Ges. 1871, 4,
742. (b) Hofmann, A. W. Ber. Dtsch. Chem. Ges. 1872, 5, 720.
(5) (a) Reilly, J.; Hickenbottom, W. J. J. Chem. Soc. 1920, 117, 103.
(b) Rhee, E. S.; Shine, H. J. J. Am. Chem. Soc. 1986, 108, 1000.
(c) Wright, G. E. J. Org. Chem. 1980, 45, 3128.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E