Scheme 2
methyl)benzotriazoles 3a-f were prepared according to the
1H-1,2,3-benzotriazole Z-6a (R ) Ph)8 as the minor product.
No regioisomers were detected. NOE experiments of E-6a
displayed positive NOE between OCH3 group and vinylic
proton when the vinylic proton at 6.11 ppm was irradiated.
The ratio of E/Z-6a is from 74:26 to 80:20.
The mixtures of E-6a,b and Z-6a,b were hydrolyzed with
concentrated HCl in methanol or ethanol yielding the
homologated methyl ester 7a or ethyl ester 7b in good yields,
respectively. In fact, the enol triflates 4a-c readily converted
into the desired esters 7a-c after treatment in situ with
NaOCH3 in acetonitrile followed by concentrated HCl in an
alcohol successively in excellent yields without the isolation
of the intermediates 5a-c and 6a-c (Table 1).
literature procedures in good yields.7 N-(Acylmethyl)ben-
zotriazoles 3a-f were each treated with triflic anhydride
(Tf2O) in the presence of 2,6-lutidine at 0-20 °C to afford
stereospecifically E-enol triflates 4a-f in excellent isolated
yields (>90%, see Table 1 and Scheme 2). No trans-isomers
Table 1. One-carbon Homologation of Carboxylic Acids 2 to
Esters 7
isolated yields, %
R
3
4
5
7
857
90
917
837
95
95
95
90
88
95
90
989
97
89a
98a
92a
55b
45b
49b
The procedure was modified for the aliphatic derivatives
4d-f: these compounds were treated with 2.2 equiv of
NaOCH3 in CH3CN (or with 2N NaOH in THF) at 20 °C
for 1 h. After workup, 1-alkynylbenzotriazoles (5d-f) were
obtained in quantitative yield (Table 1, entries 4-6). This
is the first synthesis of an 1-alkynylbenzotriazole, compounds
that cannot be obtained by direct alkynylation of benzotri-
azole.9 However, after further reflux of the reaction mixture,
none of the desired addition product analogous to 6a-c was
detected. Fortunately, treatment of 5d-f with p-toluene-
sulfonic acid monohydrate in acetonitrile at 65 °C for 4-6
h generated enol toluenesulfonates 8d-f in 62-75% yield
together with about 5-10% of the starting 3d-f and 5-10%
of the hydrolyzed product 7d-f. Hydrolysis of isolated 8d-f
with 1 equiv of TBAF in THF at 70 °C provided the
corresponding acids 7d-f (65-80%). This two-step proce-
dure could be carried out in one-pot by direct treatment of
5d-f with p-toluenesulfonic acid followed by the hydrolysis
of 8d-f with TBAF in THF without the isolation of the
intermediate 8d-f, but gave a lower yields of 7d-f (40-
55%).
2a
2b
2c
2d
2e
2f
C6H5
p-ClC6H4
p-CH3C6H4
CH3
(CH3)3CCH2
n-CH3(CH2)6
959
90
91
92
95
a Isolated yield from 4. b Yield from 5.
were detected in the NMR spectra of the crude products:
for instance, irradiation of the vinylic proton of 4a at 7.59
ppm showed no NOE between the phenyl group and the
vinylic proton, indicating that they are mutually trans.
Enol triflates 4a-f reacted with 2.5 equiv of NaOCH3 in
acetonitrile at 20 °C to give alkynyl-1H-1,2,3-benzotriazoles
5a-f which could be isolated in quantitative yields. The
effects of the base and solvent are small: use of 2 N NaOH/
THF or NaOCH3/CH3CN gave similar results. For aromatic
compounds 4a-c, further reflux of the reaction mixture at
65 °C followed by hydrolysis with concentrated HCl in an
alcohol afforded directly the corresponding homologated
esters 7a-c. The reaction sequence is shown in Scheme 2.
Treatment of 5a with 1.2 equiv of NaOCH3 in acetonitrile
at 65 °C for 2 h regioselectively generated 1-[(E)-1-methoxy-
2-phenylethenyl]-1H-1,2,3-benzotriazole E-6a (R ) Ph)8 as
the major product and 1-[(Z)-1-methoxy-2-phenylethenyl]-
In summary, a concise and practical procedure for the
transformation of acids into one-carbon homologated acid
derivatives has been developed using readily available,
versatile, and high-yielding reagent BtCH2TMS (1), and this
procedure is apparently applicable for both aromatic and
aliphatic carboxylic acid derivatives. This novel approach
(6) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Chem. ReV.
1998, 98, 409.
(7) Katritzky, A. R.; Lam, J. N. Heteroatom Chem. 1990, 21.
(8) Katritzky, A. R.; Zhao, X.; Shcherbakova, I. V. J. Chem. Soc., Perkin
Trans. 1 1991, 3295.
(9) (a) Kitamura, T.; Tashi, N.; Tsuda, K.; Fujiwara, Y. Tetrahedron
Lett. 1998, 3787. (b) Kitamura, T.; Tashi, N.; Tsuda, K.; Chen, H.; Fujiwara,
Y. Heterocycles 2000, 52, 303.
3790
Org. Lett., Vol. 2, No. 24, 2000