Chemistry Letters Vol.33, No.7 (2004)
917
Table 1. Microwave-assisted NBS reactions without radical
initiator and solvent
important because of their subsequent facile hydrolytic conver-
sion to the corresponding dialdehydes. The synthesis of pterin-
6-carbaldehyde is important by this method as no other dibromo
or tetrabromo heterocyclic compounds studied here, yield the
corresponding aldehyde under the similar condition of the reac-
tion or isolation.
Starting Material
MW Conditionsa
Watt, min
Products
Yield
450, 9
N
N
N
N
4
R1
R2
We thank DST, Govt. of India for financial support, Dr.
(Mrs.) B. Goswami for help, and the referees for valuable sug-
gestion. S. J. and A. K. A acknowledge CSIR for fellowships.
4a: R = R = CH Br (40%)
4b: R = R = CHBr (25%)
1
2
2
1
2
2
N
N
N
R1
300, 6
450, 6
N
5
5a: R = CH Br (25%)
1
2
References and Notes
5b: R = CHBr (20%)
1
2
N
N
CHBr2
1
a) Y. Yamada and D. Momose, Chem. Lett., 1981, 1277. b) S. P.
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N
6
N
6a (30%)
450, 9
450, 3
Br
2
3
N
7
N
7a (40%)
R2
R1
O
O
N
N
N
H
N
H
8
8a: R = CH Br, R = H (25%)
1
2
2
8b: R = CH , R = Br (70%)
1
3
2
R2
O
O
450, 6
N
N
9
N
H
N
R1
H
9a: R = CH Br, R = H (30%)
1
2
2
9b: R = CH , R = Br (33%)
1
3
O
2
O
4
N
N
450, 9
N
N
R
O
O
10
10a: R = CH Br (40%)
2
10b: R = CHBr (40%)
2
Parry, J. Org. Chem., 30, 304 (1965). d) K. Gyorgy, Synthesis,
1993, 931.
¨
R
5
6
a) C. Djerassi, Chem. Rev., 43, 217 (1948). b) L. Horner and
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a) For a most recent book and reviews on microwave-assisted
organic reactions, see: B. L. Hayes in ‘‘Microwave Synthesis:
Chemistry at the Speed of Light,’’ CEM publishing, Matthews,
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J. Westman, Tetrahedron, 57, 9225 (2001). c) M. Larhed, C.
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(2001).
450, 9
Br
11: o-isomer
12: m-isomer
13: p-isomer
11a: R = CH (45%) 11b: R = CH Br (40%)
12a: R = CH (40%) 12b: R = CH Br (42%)
13a: R = CH (43%) 13b: R = CH Br (40%)
3
2
3
3
2
2
NO2
NO2
450, 9
450, 6
R
14: o-isomer
15: m-isomer
16: p-isomer
14a: R = CH Br (30%)
2
15a: R = CH Br (70%)
2
2
7
8
16a: R = CH Br (70%) 16b: R = CHBr (20%)
2
NHAc
NHAc
CHBr2
17a (45%)
17
a1:1 Molar ratios of NBS per methyl group of the substrate were
used.
16 along with the major mono bromomethyl product 16a. Only
the dibromo derivatives 6a and 17a were obtained in the case of
pyrazine and acetyl protected o-toluidine,13 respectively.
Thus this method of side chain bromination is more straight-
forward and environmentally friendlier as no solvent or initiator
like AIBN are necessary compared to those reported earlier.12
Interestingly, when a mixture of 9 (1 mmol) and NBS (1 mmol)
in CCl4 is refluxed for a period of 4 h without using AIBN, the
products are different compared to the microwave heating where
the nuclear bromination (9b) results without any side chain bro-
mination. Though it is difficult to predict the exact reaction
mechanism under this condition, microwave irradiation may
help easy cleavage of N–Br bond to generate bromine radical
for benzylic bromination in the solid phase.
9
10 All these heteroaromatic and aromatic bromo compounds are
separable by chromatography. The products are well character-
1
ized by H NMR, MS, Elemental Analysis, and by comparison
of melting points with the authentic samples when available.
11 S. D. Ross, M. Finkelstein, and R. C. Petersen, J. Am. Chem.
Soc., 80, 4327 (1958).
We have thus developed a new method for the side chain
bromination of aromatic as well as heteroaromatic methyl
groups by microwave-assisted solid phase NBS reaction without
radical initiator. The isolation of the tetrabromo compounds is
12 C. H. M. Amijs, G. P. M. van Klink, and G. van Koten, Green
Chem., 5, 470 (2003).
13 2-N-Acetylaminotoluene 17 (mp 92–94 ꢀC) was obtained by
acetylation of o-toluidine with acetic anhydride at 60 ꢀC.
Published on the web (Advance View) June 21, 2004; DOI 10.1246/cl.2004.916