on intermediates 4. Compounds 5a-l were obtained after
purification in moderate to good yields depending essentially
on the solvent used (Table 1).
Scheme 1
Table 1. Preparation of N-Imidoylbenzotriazoles 5
yield (%)
product
R1
R2
benzene toluene xylenes
5a
5b
5c
5d
5e
5f
5g
5h
5i
-(CH2)5-
-(CH2)4-
55
50
37
20
60
70
20
50
15
60
30
20
35
64
C6H5
C6H5
CH3
CH3
C6H5
CH3
15
87
84
45
2-pyridyl
C6H5
-(CH2)4CHCH3
C(CH3)3
C2H5
CH3
CH3
5j
CH2C6H5
CH(CH3)2
CH2C6H5
CH(CH3)2
5k
5l
-CH(CH2CH2)- -CH(CH2CH2)-
For the less reactive oximes 2e and 2i, the yield is
dramatically improved by using a higher boiling solvent for
the reaction. On the other hand, highly reactive oximes (2a,
2b, and 2g) require a low reaction temperature to avoid
decomposition. A solvent effect study suggested that non-
polar solvents are more efficient since use of THF gave only
starting material. Additionally, the type of base influenced
the course of the reaction. Thus, alkylamines (Et3N), alkyl-
lithiums (n-BuLi), or hydrides (NaH) did not permit the
synthesis of the desired compounds, while heterogeneous
systems using t-BuOK or K2CO3 were effective.
yield by condensation of benzotriazole with p-toluenesulfonyl
chloride in toluene in the presence of triethylamine as
previously reported.14 Compound 1 is stable and can be
stored for months at room temperature.
N-Imidoylbenzotriazoles 5a-l were then prepared by one-
pot reactions of the corresponding oximes 2a-l (com-
mercially available or prepared according to known proto-
cols15 for 2c, 2g, 2k, and 2l) with BtTs in the presence of
t-BuOK as the base. The mechanism probably involves first
oxime sulfonates 3 and then iminocarbocations of type 4
which are trapped by the nucleophilic benzotriazole anion
(Scheme 1). To the best of our knowledge, these reactions
are the first examples of nucleophilic attack of a heterocycle
N-Imidoylbenzotriazoles 5a-j were obtained as single
1
E-isomers and as only Bt1 isomers on the basis of their H
and 13C NMR data. Interestingly, when oximes 2k and 2l,
bearing a single hydrogen atom on the R position of bulky
substituents, were used as starting materials, the correspond-
ing N-imidoylbenzotriazoles 5k and 5l were obtained as
mixtures of E- and Z-isomers (E/Z ) 75/25 for both
compounds) perhaps because steric effects cause partial
isomerization of the intermediates. The regio- and stereo-
chemistry of the unsymmetrical compounds 5f,c16 were
determined by extensive NMR investigations.17 The regio-
chemistry for the unsymmetrical N-imidoylbenzotriazoles 5h
and 5i was deduced from the 13C NMR shifts of the methyl
groups.
(14) Ried, W.; Schon, M. Chem. Ber. 1965, 3142.
(15) Hutchins, R. O.; Su, W.-Y.; Sivakumar, R.; Cistone, F.; Stercho,
Y. P. J. Org. Chem. 1983, 48, 3412.
(16) Compound 5c was already described.10
(17) The protons on the phenyl group have been identified based on their
intensity and multiplicity as 7.38 (d, 2H) ortho and 7.32 (t, 2H) meta. The
para proton is at 7.39, as demonstrated by the intensity of the cluster around
7.38 and by the lack of couplings of 7.38-7.39 and 7.32 to any other protons
but themselves. The long-range coupling between 7.32 and 130.4 identified
the quaternary carbon on the phenyl ring, and the long-range coupling of
7.38 to 156.0 identified the imine carbon and demonstrated that the phenyl
is attached to the carbon of the imine group. The quaternary carbon at 146.4
was assigned to position 3a of benzotriazole on the basis of its chemical
shift. Long-range couplings identified the protons meta to this carbon as
8.53 (d, position 7) and 7.50 (t, position 5). The protons in positions 4 and
6 were identified as 8.14 and 7.62, correspondingly, on the basis of their
couplings to the other protons on the Bt. Long-range couplings of 8.14 and
7.62 allowed the assignment of the quaternary carbon in position 7a as
131.8. The CH at 8.34/148.8 was assigned to position 6 of the pyridine,
based on the chemical shifts. The tocsy spectrum revealed the sequence
8.34-6.94-7.53-6.73. The H-C long-range couplings confirmed this
assignment and revealed the quaternary carbon in position 2 as 159.7.
(18) General Procedure for the Preparation of Compounds 5. The
corresponding oxime 2 (1 mmol), BtTs (1 mmol), t-BuOK (1 mmol), and
crown ether 18C6 (0.1 mmol) were stirred and heated in the adequate solvent
(10 mL) (see Table 1). After completion of the reaction (TLC), the mixture
was allowed to reach room temperature and hydrolyzed by H2O (10 mL).
After extraction, the organic layers were dried over MgSO4, and the solvent
was removed under reduced pressure. The residue was subjected to
purification (method A, extraction with hot hexanes; method B, flash column
chromatography).
In conclusion, a new method for the synthesis of N-
imidoylbenzotriazoles has been presented. This approach
allows the preparation of such compounds in modest to good
yields (average yield in the optimal solvent for twelve
compounds is 56%) by using mild reaction conditions.18
Acknowledgment. We thank Dr. Ion Ghiviriga for the
NMR experiments on compound 5f.
Supporting Information Available: Full characterization
for compounds 5a-l. This material is available free of charge
OL990090G
578
Org. Lett., Vol. 1, No. 4, 1999