218
Can. J. Chem. Vol. 83, 2005
stirred at 35 °C for an additional 10 min and then transferred
to a solution containing K2CO3 (5 g) in 100 mL ice water.
The reaction mixture was then taken up in ether, and the
ethereal extracts were washed with water and dried over an-
hydrous magnesium sulfate. Removal of the solvent under
reduced pressure gave the crude product.
General procedure for microscale production — Use of
bromodimethylsulfonium bromide prepared by HBr
and DMSO
A solution of 48% aq. HBr (2.49 mL, 20.0 mmol) dis-
solved in DMSO (25 mL) was added dropwise to a solution
of aminoarene (5 mmol) in a mixture of 25 mL of DMSO
and KNO2 (1.70 g, 20.0 mmol) at 35 °C with stirring. The
added mixture was stirred at 35 °C for the time given in Ta-
ble 2 and then transferred to a solution of K2CO3 (5 g) in
100 mL of ice water. The reaction mixture was then taken up
in ether, and the ethereal extracts were washed with water
and dried over anhydrous magnesium sulfate. Removal of
the solvent under reduced pressure gave the crude product.
The crude product was further purified by column chroma-
tography (or recrystallization) to give the product, the mp,
and spectral data (1H NMR and GC–MS) all of which were
in full agreement with those of an authentic sample.
Acknowledgments
This work was supported by the Regional Research Cen-
ter program of the Ministry of Science and Technology
(MOST) and KOSEF-Kyungkido.
References
1. (a) E.B. Merkushev. Synthesis, 923 (1988); (b) R.C. Larock.
Comprehensive organic transformations. 2nd ed. Wiley, New
York. 1999. pp. 619–626.
General procedure for preparative-scale production
A mixture of 2.5 L of DMSO and KNO2 (85.1 g, 1.0 mol)
was vigorously stirred at 60 °C to rapidly dissolve KNO2,
and aminoarene (0.25 mol) was then added.3 The resulting
solution was then cooled to room temperature. Aqueous HBr
solution (48%, 124.5 mL, 1.0 mol) diluted with 2.0 L of
DMSO was added dropwise at a rate of 20 mL/min, and the
mixture was then warmed to 35 °C. The DMSO solution of
HBr added to the reaction mixture can be carried off through
a long condenser tube. After the usual workup, the crude
product was purified by recrystallization.
2. (a) D.S. Wulfman. The chemistry of diazonium and diazo
groups. Edited by S. Patai. Wiley, New York. 1978. Chap. 8;
(b) R.C. Larock. Comprehensive organic transformations. 2nd
ed. Wiley, New York. 1999. pp. 678–679; (c) J.K. Kochi. J.
Am. Chem. Soc. 79, 2942 (1957); (d) S.C. Dickerman, D.J.
Desouza, and N. Jacobson. J. Org. Chem. 34, 710 (1969);
(e) C.J. Galli. J. Chem. Soc. Chem. Perkin Trans. 2, 897 (1984).
3. (a) H.H. Hodgen. Chem. Rev. 40, 251 (1947); (b) L.A.
Bigelow. In Organic syntheses, collective volumes. Vol. 1.
Wiley, New York. 1941. p. 135; (c) W.W. Hartman and M.R
Brethen. In Organic syntheses, collective volumes. Vol. 1.
Wiley, New York. 1941. p. 162; (d) J.L Hartwell. In Organic
syntheses, collective volumes. Vol. 3. Wiley, New York. 1955.
p. 185.
4. (a) M.P. Dolye, B. Siegried, and J.F. Dellaria. J. Org. Chem.
42, 2426 (1977); (b) M.P. Dolye, M.A. Van Lente, R. Mowat,
and W.F. Fobare. J. Org. Chem. 45, 2570 (1980); (c) M.P.
Dolye and W.J. Bryker. J. Org. Chem. 44, 1572 (1979);
(d) W.B. Smith and O.C. Ho. J. Org. Chem. 55, 2543 (1990);
(e) V. Nair and S.G. Richardson. J. Org. Chem. 45, 3969
(1980); (f) L. Friedman and J.F. Chlebowski. J. Org. Chem. 33,
1636 (1967); (g) J.G. Lee and H.T. Cha. Tetrahedron Lett. 33,
3167 (1992); (h) H. Suzuki and N. Nonoyama. Tetrahedron
Lett. 39, 4533 (1998); (i) C. Giordano, L. Coppi, and M.
Paiocchi. US Patent 5 142 093, 1992; (j) M.J. Evers, L.E.
Christiaens, M.R. Guillaume, and M.J. Renson. J. Org. Chem.
50, 1779 (1985); (k) M.S. Newman and W. Fones. J. Am.
Chem. Soc. 69, 1221 (1947).
5. (a) G. Majetich, R. Hicks, and S. Reister. J. Org. Chem. 62,
4321 (1997); (b) K. Mislow, T. Simmons, J. Melillo, and A.
Ternary. J. Am. Chem. Soc. 86, 1452 (1964); (c) D. Landini
and F. Montari. J. Chem. Soc. Chem. Commun. 86 (1968).
6. S.K. Srivastava, P.M.S. Chauhan, and A.P. Bhaduri. J. Chem.
Soc. Chem. Commun. 2679 (1996).
7. (a) G. Megyeri and T. Keve. Synth. Commun. 19, 3415
(1989); (b) T. Fletcher and H. Pan. J. Am. Chem. Soc. 78,
4812 (1956).
8. W.W. Hartman and M.R. Brethen. Organic syntheses, collec-
tive volumes. Vol. 1. Wiley, New York. 1941. pp. 162.
9. For reviews, see: (a) P.E. Fanta. Synthesis, 9 (1974); (b) M.
Goshaev, O.S. Otroshchenko, and A.S. Sadykov. Russ. Chem.
Rev. 41, 1046 (1972); (c) G. Bringmann, R. Walker, and R.
Weirich. Angew. Chem. Int. Ed. Engl. 29, 977 (1990).
10. (a) T.D. Nelson and A.I. Meyers. J. Org. Chem. 59, 2655
(1994); (b) J.C. Salfeld and E. Baume. Tetrahedron Lett. 7,
Preparation of 4-bromoanisole
A mixture of 4-methoxyaniline (0.25 mol, 30.75 g),
KNO2 (85.1 g, 1.0 mol), HBr solution (48%, 124.5 mL,
1.0 mol), and 4.5 L of DMSO was stirred at 60 °C for 2 h.
The product was recovered by the standard procedure, yield-
ing 37.87 g of pure 4-bromoanisole (81%).
General procedure for microscale production — Use of
iododimethylsulfonium iodide prepared by HI and
DMSO
Aminoarene (5.0 mmol) was added to a solution of KNO2
(1.70 g, 20.0 mmol) in DMSO (25 mL) at 35 °C. Aqueous
HI (57%, 2.64 mL, 20 mmol) in DMSO (25 mL) was added,
and the reaction mixture was stirred for the time given in Ta-
ble 4. After the reaction was completed, the cooled reaction
mixture was neutralized with 10% aq. Na2CO3 and extracted
with methylene chloride (3 × 10 mL). The combined methy-
lene chloride extracts were washed with brine and dried over
magnesium sulfate. The solvent was removed in vacuo and
the residue was chromatographed to give the product, the
mp, and spectral data (1H NMR and GC–MS) all of which
were in full agreement with those of an authentic sample.
General procedure for microscale production — Use of
bromodimethylsulfonium iodide prepared by HBr, KI,
and DMSO
To a solution of aminoarene (5.0 mmol) in a mixture of
25 mL of DMSO and KNO2 (1.70 g, 20 mmol) was added
dropwise a solution of 47% HBr (2.49 mL, 20 mmol) and KI
(4.15 g, 25 mmol) dissolved in DMSO (25 mL) at 35 °C.
When the addition was complete, the mixture was further
© 2005 NRC Canada