Synthesis of substituted α,β-unsaturated ketones, pyrazoles, isoxazoles and 2,4,6-triarylpyrylium chlorophosphates via β-lithiation of benzotriazolylvinyl ethyl ether

Article abstract of DOI:10.1055/s-2004-837293

Quenching the β-lithiated benzotriazolylvinyl ethyl ether 2 with aldehydes, acid chlorides and chalcones provided the corresponding β-hydroxyalkyl derivatives 4a-f, β-keto vinyl ethers 7a,b, and Michael adducts 8a,b, respectively. The alkylated product 4 was converted into α,β-unsaturated ketones 5a-f upon treatment with bromine. β-Keto vinyl ethers 7a,b cyclocondensed with hydrazines to afford pyrazoles 9a-d, and with hydroxylamine hydrochloride to give isoxazoles 10a,b. Treatment of 8 with phosphorus pentachloride resulted in the formation of 2,4,6-triarylpyrylium chlorophosphates 12.

Full text of DOI:10.1055/s-2004-837293

PAPER
245
Synthesis of Substituted a,b-Unsaturated Ketones, Pyrazoles, Isoxazoles and
2,4,6-Triarylpyrylium Chlorophosphates via b-Lithiation of Benzotriazolyl-
vinyl Ethyl Ether
b
-Lithiation of Ben
s
zotriazoly
h
lvinyl Ethyl
rEther af A. A. Abdel-Fattah*
Chemistry Department, Faculty of Science, Benha University, Benha, Egypt
E-mail: ashraf25894@yahoo.com
Received 28 July 2004; revised 14 October 2004
properties can facilitate metalation. We report herein the
Abstract: Quenching the b-lithiated benzotriazolylvinyl ethyl ether
2 with aldehydes, acid chlorides and chalcones provided the corre-
sponding b-hydroxyalkyl derivatives 4a–f, b-keto vinyl ethers 7a,b,
and Michael adducts 8a,b, respectively. The alkylated product 4
b-lithiation of benzotriazolylvinyl ethyl ether 2 and the
subsequent reactions with various electrophiles provide a
method of producing substituted derivatives (e.g. a,b-un-
was converted into a,b-unsaturated ketones 5a–f upon treatment saturated ketones, pyrazoles, and isoxazoles) and 2,4,6-
with bromine. b-Keto vinyl ethers 7a,b cyclocondensed with hydra-
zines to afford pyrazoles 9a–d, and with hydroxylamine hydrochlo-
ride to give isoxazoles 10a,b. Treatment of 8 with phosphorus
pentachloride resulted in the formation of 2,4,6-triarylpyrylium
chlorophosphates 12.
triarylpyrylium chlorophosphates (Schemes 1 and 2).
R
Bt
Li
O
Bt
Ph
Bt
Ph
OH
n-BuLi
RCHO
Br2
O
Ph
Key words: heteroatom, b-lithiation, vinyl ethyl ether, benzotri-
azole, electrophile
O
2
4a–f
3
t-BuOK
Br2
Et2SO4
Heteroatom-assisted metalations are important tool for
the functionalization of carbocyclic-aromatic and het-
eroaromatic compounds, and regioselective ortho-lithia-
tion at an sp2-hybridized ring carbon directed by
heteroatom bearing substituent.1 Recently, the generation
and reaction of sp2 carbanionic centers in the proximity of
heterocyclic nitrogen atom have been reported.2 The met-
alation without the assistance of an activating group is of-
ten difficult to achieve due to charge repulsion of the
heteroatom lone pair, and low acidity of the hydrogen to
be abstracted. Repulsion between the lone pair of nitrogen
atom and negative charge considerably reduces the ther-
modynamic stability.
R
O
R
O
Bt
Bt
Bt
Ph
OH
Br
Ph
Br
Ph
1
O
Bt = Benzotriazol-1-yl
6
5a–f
For designation of R in 4 and 5 see Table 1
Scheme 1
a-Benzotriazolyl-substituted ketones have been used as a
precursor for the synthesis of various useful organic com-
pounds.13–15 Thus, simply mixing benzotriazol-1-ylaceto-
phenone (1) with diethyl sulfate in dimethyl sulfoxide in
the presence of t-BuOK at room temperature afforded a-
phenyl-b-benzotriazolylvinyl ethyl ether (2) in excellent
yield (Scheme 1). The 1H NMR spectrum showed a char-
acteristic signal at approximately 7.10 ppm, which was as-
signed to the proton attached to the double bond. The cis
orientation of the ethoxy group and the vinylic proton was
established by NOE: irradiation of the vinylic proton of 2
at 7.10 ppm showed NOE effects on the methylene pro-
tons at 3.68 ppm.
Regioselective metalation of vinyl ethers has received
considerable attention. McDougal and Rico reported the
b-lithiation by sec-butyllithium of methoxymethyl vinyl
ether, which was then reacted with a variety of electro-
philes.3,4 cis-2-Ethoxyvinyl lithium has been synthesized
by transmetalation from the corresponding tin deriva-
tive.5,6 Lithiation of vinyl ethers is known to proceed
smoothly at the a-position upon treatment with organo-
lithium compounds at low temperature,7,8 and the pressure
of additional directing groups such as halogens or thioaryl
groups generally assist and stabilize the lithiation product
by intramolecular interaction.
Compound 2 was used to study the effect of the nitrogen
atom in the assisted b-lithiation of vinyl ether. Treatment
of compound 2 with 1.3 equivalents of n-butyllithium at
–78 °C followed by quenching with a variety of electro-
philes such as aldehydes, acid chlorides and chalcones
gave the corresponding b-hydroxyalkyl derivatives 4a–f,
b-keto vinyl ethers 7a,b, and Michael adducts 8a,b, re-
spectively, in good yields. The structures of the alkyated
product 4, 7 and 8 were confirmed on the basis of their
Benzotriazole is a good activating group for a-lithia-
tions,9–12 serving as both a strong electron-withdrawing
and coordinative group during the lithiation. These two
SYNTHESIS 2005, No. 2, pp 0245–0249
x
x
.
x
x
.2
0
0
5
Advanced online publication: 16.12.2004
DOI: 10.1055/s-2004-837293; Art ID: P08604SS
© Georg Thieme Verlag Stuttgart · New York

246
A. A. A. Abdel-Fattah
PAPER
Table 1 Synthesis of Novel Benzotriazole Derivatives 4,5,7–10, and
Pyrylium Salts 12
spectral data as summarized in the experimental section.
The alkylated products 4 were subsequently treated with
bromine in CH2Cl2 at 0–25 °C to give only the corre-
sponding a,b-unsaturated ketones 5a–f in 62–76% instead
of the expected products of type 6 (Scheme 1, Table 1).
The reactivity of the b-keto vinyl ether 7 towards certain
nitrogen nucleophiles was also investigated. Thus, treat-
ment of compound 7 with hydrazines, and hydroxylamine
hydrochloride in refluxing ethanol provided pyrazoles
9a–d, and isoxazoles 10a,b, respectively, in good yields
(Scheme 2, Table 1).
Entry
R
Yield Entry
(%)
R
Yield
(%)
4a
4b
4c
4d
4e
4f
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
pyridin-4-yl
(CH3)2CH
C2H5
69
82
65
71
65
60
76
71
75
62
67
73
7a
7b
C6H5
83
72
78
65
77
84
82
79
82
75
77a
71
4-CH3C6H4
C6H5
8a
8b
4-CH3C6H4
C6H5
9a
An alternative route for the synthesis of 2,4,6-triarylpyry-
lium salts utilizing enol ethers 8 was investigated for
R = Ph. Thus, treatment with perchloric acid at 70–90 °C
or heating with p-TsOH in boiling toluene for 24 hours
gave the diketone 11, whereas heating in toluene with 3
equivalents of phosphorus pentachloride at 80–100 °C
gave the pyrylium salts 12a,b in good yields (Scheme 2,
Table 1).
9b
4-CH3C6H4
C6H5
5a
5b
5c
5d
5e
5f
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
pyridin-4-yl
(CH3)2CH
C2H5
9c
9d
4-CH3C6H4
C6H5
10a
10b
12a
12b
4-CH3C6H4
C6H5
In summary, a-phenyl-b-benzotriazolylvinyl ethyl ether
underwent facile b-lithiation, most likely due to coordina-
tion of nitrogen of the benzotriazole moiety towards lithi-
um via a four-membered ring complex. Quenching the b-
lithiated vinyl ethyl ether 3 with a variety of electrophiles
provided the corresponding alkylated products, which
were used as precursors for the synthesis of various useful
organic compounds.
4-CH3C6H4
a Lit.16 yield = 36%.
2-Benzotriazol-1-yl-1-ethoxy-1-phenylethene (2)
A mixture of a-benzotriazol-1-ylacetophenone (1; 3.6 g, 15 mmol),
diethyl sulfate (4.6 g, 30 mmol) and t-BuOK (3.4 g, 30 mmol) was
stirred in DMSO (20 mL) at r.t. for 3 h. The mixture was poured into
ice water (50 mL) and extracted with EtOAc (3 × 20 mL). The com-
bined organic extracts were washed several times with H2O and
dried (MgSO4, 5 g). The solvent was removed in vacuo and the re-
sulting oil was purified by column chromatography (silica gel,
All mps are uncorrected. 1H and 13C NMR spectra were recorded on
a Varian Gemini (300 MHz) spectrometer in CDCl3 with TMS as
the internal standard. Microanalyses were performed on a Carlo
Erba 1106 elemental analyzer.
Scheme 2
Synthesis 2005, No. 2, 245–249 © Thieme Stuttgart · New York

PAPER
b-Lithiation of Benzotriazolylvinyl Ethyl Ether
247
CH2Cl2–hexanes, 2:1) to afford 2; yield: 3.82 g (96%); mp 67–
69 °C.
(E)-2-(Benzotriazol-1-yl)-3-ethoxy-3-phenyl-1-pyridin-4-yl-
prop-2-en-1-ol (4d)
Yield: 1.32 g (71%); mp 91–93 °C.
1H NMR: d = 8.07 (d, J = 8.4 Hz, 1 H), 7.69–7.55 (m, 8 H), 7.10 (s,
1 H), 3.68 (q, J = 7.0 Hz, 2 H), 1.07 (t, J = 7.0 Hz, 3 H).
13C NMR: d = 153.1, 145.2, 133.2, 133.1, 129.6, 128.6, 127.3,
126.7, 123.8, 119.5, 111.5, 106.3, 67.2, 14.9.
1H NMR: d = 7.92 (d, J = 8.5 Hz, 1 H), 7.77–7.19 (m, 7 H), 6.89 (d,
J = 8.5 Hz, 2 H), 6.49 (d, J = 8.7 Hz, 2 H), 5.64 (d, J = 7.9 Hz, 1 H),
4.37 (d, J = 7.9 Hz, 2 H), 3.49–3.38 (m, 2 H), 0.77 (t, J = 7.0 Hz, 3
H).
13C NMR: d = 158.3, 154.8, 144.3, 134.5, 132.6, 131.2, 129.4,
128.7, 127.0, 126.1, 123.4, 119.2, 119.2, 113.1, 111.3, 71.7, 65.6,
14.6.
Anal. Calcd for C16H15N3O (265.32): C, 72.43; H, 5.70. Found C,
72.65; H, 6.01.
Reaction of Lithiated 2-Benzotriazol-1-yl-1-ethoxy-1-phenyl-
ethene (2) with Electrophiles; Compounds 4, 7, and 8; General
Procedure
Anal. Calcd for C22H20N4O2 (372.43): C, 70.95; H, 5.41; N, 15.04.
Found: C, 71.14; H, 5.49; N, 15.32.
To a solution of 2 (1.3 g, 5 mmol) in anhyd THF (20 mL) was added
a 1.6 M solution of n-BuLi in pentane (1.3 equiv, 4 mL, 6.5 mmol)
at –78 °C. The mixture was stirred at –78 °C for 2 h, and a solution
of the electrophile (7 mmol, 1.4 equiv) in THF (5 mL) was added.
The reaction mixture was then stirred at –78 °C for 4 h and further
12 h at r.t. The mixture was then poured into aq sat. NH4Cl solution
and extracted with EtOAc (3 × 20 mL). The combined organic lay-
ers were washed with H2O (25 mL), dried (MgSO4) and concentrat-
ed in vacuo. The products were isolated by column chromatography
(eluent: EtOAc–hexanes, 1:30, then 1:10).
(E)-2-(Benzotriazol-1-yl)-1-ethoxy-4-methyl-1-phenylpent-1-
en-3-ol (4e)
Yield: 1.10 g (65%); oil.
1H NMR: d = 8.10 (d, J = 8.5 Hz, 1 H), 7.68–7.30 (m, 8 H), 3.97
(dd, J = 9.6, 9.9 Hz, 1 H), 3.71 (d, J = 9.9 Hz, 1 H), 3.58–3.31 (m,
2 H), 1.13–1.04 (m, 1 H), 0.85 (d, J = 6.4 Hz, 3 H), 0.78 (t, J = 7.0
Hz, 3 H), 0.66 (d, J = 6.4 Hz, 3 H).
13C NMR: d = 154.1, 144.6, 134.3, 131.6, 129.8, 129.6, 128.7,
127.3, 123.7, 119.6, 118.8, 112.3, 76.9, 65.4, 32.1, 19.4, 19.1, 14.7.
(E)-2-(Benzotriazol-1-yl)-3-ethoxy-1-(4-methylphenyl)-3-phe-
nylprop-2-en-1-ol (4a)
Anal. Calcd for C20H23N3O2 (337.43): N, 12.45. Found: N, 12.13.
Yield: 1.32 g (69%); mp 87–89 °C.
(E)-2-(Benzotriazol-1-yl)-1-ethoxy-1-phenylpent-1-en-3-ol (4f)
1H NMR: d = 8.00 (d, J = 8.2 Hz, 1 H), 7.67 (d, J = 8.0 Hz, 1 H),
7.58–7.12 (m, 11 H), 6.18 (d, J = 10.1 Hz, 1 H), 4.56 (d, J = 10.1
Hz, 1 H), 3.55 (q, J = 7.2 Hz, 2 H), 2.17 (s, 3 H), 0.93 (t, J = 7.0 Hz,
3 H).
Yield: 0.97 g (60%); oil.
1H NMR: d = 8.10 (d, J = 8.5 Hz, 1 H), 7.68–7.37 (m, 8 H), 4.36 (d,
J = 8.7 Hz, 1 H), 3.64–3.34 (m, 3 H), 1.33–1.07 (m, 2 H), 0.82 (t,
J = 7.0 Hz, 3 H), 0.73 (t, J = 7.3 Hz, 3 H).
13C NMR: d = 145.1, 140.5, 136.7, 132.9, 132.7, 128.6, 128.5,
128.4 (2 C), 128.3, 127.9, 124.7, 123.9, 119.7, 110.2, 108.0, 70.4,
66.3, 20.4, 14.6.
13C NMR: d = 153.3, 144.8, 134.6, 130.9, 129.9, 129.2, 128.7,
127.3, 124.1, 120.4, 119.0, 109.7, 72.5, 65.8, 28.0, 14.7, 10.6.
Anal. Calcd for C19H21N3O2 (323.40): C, 70.57; H, 6.55; N, 12.99.
Found: C, 70.28; H, 6.23; N, 12.75.
Anal. Calcd for C24H23N3O2 (385.47): C, 74.78; H, 6.01; N, 10.90.
Found: C, 74.55; H, 6.24; N, 10.63.
(E)-2-(Benzotriazol-1-yl)-3-ethoxy-1,3-diphenylpropenone (7a)
Yield: 1.53 g (83%); mp 143–145 °C.
(E)-2-(Benzotriazol-1-yl)-3-ethoxy-1-(4-methoxyphenyl)-3-phe-
nylprop-2-en-1-ol (4b)
Yield: 1.65 g (82%); mp 93–95 °C.
1H NMR: d = 8.08 (d, J = 8.2 Hz, 1 H), 7.65 (d, J = 7.4 Hz, 2 H),
7.51–7.11 (m, 11 H), 3.76 (q, J = 7.0 Hz, 2 H), 1.09 (t, J = 7.0 Hz,
3 H).
13C NMR: d = 191.0, 166.1, 145.4, 137.7, 134.0, 132.3, 131.7,
131.0, 129.8, 128.7 (2 C), 128.0, 127.9, 123.9, 120.1, 1165.8, 109.9,
67.9, 15.1.
1H NMR: d = 8.03 (d, J = 8.2 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 1 H),
7.51 –7.08 (m, 11 H), 6.13 (d, J = 5.8 Hz, 1 H), 4.62 (d, J = 5.8 Hz,
1 H), 3.84 (s, 3 H), 3.61 (q, J = 7.2 Hz, 2 H), 0.93 (t, J = 7.2 Hz, 3
H).
13C NMR: d = 159.8, 146.1, 136.2, 132.9, 132.7, 130.0, 128.6,
128.5, 128.2 (2 C), 127.8, 124.9, 124.0, 120.2, 113.8, 109.9, 70.6,
65.9, 55.7, 14.3.
Anal. Calcd for C23H19N3O2 (369.43): C, 74.78; H, 5.18; N, 11.37.
Found: C, 75.02; H, 4.97; N, 11.15.
Anal. Calcd for C24H23N3O3 (401.47): C, 71.80; H, 5.77; N, 10.47.
Found: C, 72.03; H, 5.49; N, 10.36.
(E)-2-(Benzotriazol-1-yl)-3-ethoxy-1-(4-methylphenyl)-3-phe-
nylpropenone (7b)
Yield: 1.38 g (72%); mp 158–160 °C.
1H NMR: d = 8.03 (d, J = 8.2 Hz, 1 H), 7.69–7.14 (m, 12 H), 3.81
(q, J = 7.0 Hz, 2 H), 2.37 (s, 3 H), 1.03 (t, J = 7.0 Hz, 3 H).
13C NMR: d = 190.5, 161.2, 144.6, 136.2, 133.8, 132.0, 131.6,
130.4, 130.0, 128.8, 128.5, 127.9, 127.4, 124.6, 120.3, 118.0, 109.8,
67.6, 21.4, 14.6.
(E)-2-(Benzotriazol-1-yl)-1-(4-chlorophenyl)-3-ethoxy-3-phe-
nylprop-2-en-1-ol (4c)
Yield: 1.32 g (65%); mp 112–114 °C.
1H NMR: d = 8.10 (d, J = 8.2 Hz, 1 H), 7.70 (d, J = 8.2 Hz, 1 H),
7.61–7.15 (m, 11 H), 5.40 (s, 1 H), 4.09 (s, 1 H), 4.03 (q, J = 7.2 Hz,
2 H), 1.39 (t, J = 7.2 Hz, 3 H).
Anal. Calcd for C24H21N3O2 (383.45): C, 75.18; H, 5.52; N, 10.96.
Found: C, 75.22; H, 5.19; N, 10.75.
13C NMR: d = 149.9, 145.6, 139.9, 133.8, 132.7, 132.5, 129.9,
129.6, 128.2, 127.6, 126.3, 125.1, 124.2, 119.8, 113.4, 110.0, 70.1,
65.4, 14.3.
(E)-4-(Benzotriazol-1-yl)-5-ethoxy-1,3,5-triphenylpent-4-en-1-
one (8a)
Yield: 1.85 g (78%); mp 152–154 °C.
Anal. Calcd for C23H20ClN3O2 (405.89): C, 68.06; H, 4.97. Found:
C, 67.88; H, 5.17.
1H NMR: d = 7.97 (d, J = 8.2 Hz, 1 H), 7.88 (d, J = 7.3 Hz, 2 H),
7.68 (d, J = 5.8 Hz, 2 H), 7.57–6.77 (m, 14 H), 4.83 (t, J = 7.3 Hz,
Synthesis 2005, No. 2, 245–249 © Thieme Stuttgart · New York

248
A. A. A. Abdel-Fattah
PAPER
(E)-2-Benzotriazol-1-yl-1-phenyl-3-pyridin-4-yl-propenone
1 H), 3.76 (q, J = 6.9 Hz, 2 H), 3.36 (dd, 2JAB = 7.0 Hz, 3J = 3.0 Hz,
1 H, A part of AB system), 3.32 (dd, 2JAB = 6.8 Hz, 3J = 2.5 Hz, 1
H, B part of AB system), 0.69 (t, J = 6.9 Hz, 3 H).
(5d)
Yield: 0.61 g (62%); mp 138–140 °C.
13C NMR: d = 197.6, 154.1, 144.7, 141.1, 136.8, 135.2, 133.0,
132.3, 129.8, 129.7, 128.9, 128.4, 128.3, 128.0, 127.3, 126.8, 126.6,
123.2, 119.7, 119.1, 110.9, 65.3, 41.4, 41.3, 14.7.
1H NMR: d = 8.10 (d, J = 8.5 Hz, 1 H), 8.05 (d, J = 8.3 Hz, 1 H),
7.92–7.35 (m, 11 H).
13C NMR: d = 192.0, 151.0, 149.2, 145.8, 137.2, 133.8, 131.7,
129.1, 128.9, 127.8, 126.4, 123.6, 119.8, 118.5, 114.0, 110.2.
Anal. Calcd for C31H27N3O2 (473.58): C, 78.62; H, 5.75. Found: C,
78.94; H, 5.61.
Anal. Calcd for C20H14N4O (326.36): C, 73.61; H, 4.32; N, 17.17.
Found: C, 73.54; H, 4.08; N, 16.96.
(E)-4-(Benzotriazol-1-yl)-5-ethoxy-1-(4-methylphenyl)-3,5-
diphenylpent-4-en-1-one (8b)
Yield: 1.59 g (65%); mp 136–138 °C.
(E)-2-Benzotriazol-1-yl-4-methyl-1-phenylpent-2-en-1-one (5e)
Yield: 0.59 g (67%); mp 110–112 °C.
1H NMR: d = 8.01 (d, J = 8.5 Hz, 1 H), 7.70 (d, J = 7.3 Hz, 2 H),
7.50–7.19 (m, 6 H), 6.83 (d, J = 10.5 Hz, 1 H), 2.41–2.31 (m, 1 H),
1.03 (d, J = 6.7 Hz, 6 H).
13C NMR: d = 190.4, 154.3, 145.3, 136.5, 133.9, 132.8, 132.0,
129.1, 128.5, 128.1, 124.0, 120.0, 109.7, 28.4, 22.1.
1H NMR: d = 8.08 (d, J = 8.2 Hz, 1 H), 7.78 (d, J = 7.2 Hz, 2 H),
7.62–7.30 (m, 11 H), 7.29 (d, J = 7.7 Hz, 2 H), 7.03 (d, J = 8.3 Hz,
2 H), 4.79 (t, J = 7.3 Hz, 1 H), 3.89 (q, J = 6.9 Hz, 2 H), 3.43 (dd,
3
2JAB = 7.2 Hz, J = 2.8 Hz, 1 H, A part of AB system), 3.43 (dd,
2JAB = 6.8 Hz, 3J = 2.3 Hz, 1 H, B part of AB system), 2.44 (s, 3 H),
0.86 (t, J = 6.9 Hz, 3 H).
13C NMR: d = 198.1, 156.2, 145.0, 140.8, 136.5, 135.0, 133.8,
132.1, 130.1, 129.9, 128.8, 128.2, 128.0, 127.6, 126.9, 126.7, 124.0,
123.6, 119.8, 118.6, 110.4, 66.2, 42.2, 41.9, 24.0, 15.1.
Anal. Calcd for C18H17N3O (291.36): C, 74.21; H, 5.88. Found: C,
73.93; H, 5.74.
(E)-2-Benzotriazol-1-yl-1-phenylpent-2-en-1-one (5f)
Yield: 0.61 g (73%); colorless microcrystals; mp 105–107 °C.
1H NMR: d = 8.02 (d, J = 8.5 Hz, 1 H), 7.67–7.21 (m, 8 H), 6.73 (t,
J = 7.9 Hz, 1 H), 2.13–1.99 (m, 2 H), 0.96 (t, J = 7.0 Hz, 3 H).
13C NMR: d = 191.2, 154.1, 144.8, 136.1, 133.5, 132.4, 131.3,
129.6, 129.0, 128.2, 123.6, 119.7, 110.1, 24.8, 17.3.
Anal. Calcd for C32H29N3O2 (487.61): C, 78.83; H, 5.99; N, 8.62.
Found: C, 78.46; H, 5.95; N, 8.85.
Substituted a,b-Unsaturated Ketones 5a–f; General Procedure
A mixture of compound 4 (3 mmol) and Br2 (0.3 mL, 6 mmol) in
CH2Cl2 (15 mL) was stirred for 30 min at 0 °C. The resultant mix-
ture was allowed to attain r.t. and stirred for an additional 3 h. Then
the solvent was evaporated in vacuo. The residue was subjected to
column chromatography on silica gel, and eluted with a mixture of
EtOAc–hexanes (1:10, then 1: 5) to give the desired product 5.
Anal. Calcd for C17H15N3O (277.33): C, 73.63; H, 5.45; N, 15.15.
Found: C, 73.42; H, 5.68; N, 15.02.
3-Substituted 1-(5-Phenylpyrazol-4-yl)benzotriazoles 9; Gener-
al Procedure
(E)-2-Benzotriazol-1-yl-3-(4-methylphenyl)-1-phenylprope-
none (5a)
Yield: 0.77 g (76%); mp 158–160 °C.
1H NMR: d = 8.10 (d, J = 8.5 Hz, 1 H), 7.83–7.18 (m, 13 H), 2.37
(s, 3 H), 2.17 (s, 3 H).
13C NMR: d = 189.9, 154.3, 146.0, 145.6, 133.8, 132.0, 131.5,
129.7, 128.9, 128.3, 127.9 127.6, 124.1, 119.9, 118.5, 111.7, 109.6,
21.0.
To a solution of b-keto vinyl ethers 7 (3 mmol) in EtOH (20 mL)
was added hydrazine hydrate or phenyl hydrazine (3.6 mmol). After
refluxing the mixture until the complete conversion of the starting
material (TLC control), it was concentrated under vacuum. The ob-
tained residue was purified by column chromatography on silica gel
(hexanes–EtOAc) to give 9a–d as pure products.
1-(3,5-Diphenyl-1H-pyrazol-4-yl)-1H-benzotriazole (9a)
Yield: 0.78 g (77%); mp 154–156 °C.
1H NMR: d = 12.33 (br s, 1 H), 7.99 (d, J = 8.2 Hz, 1 H), 7.75 (d,
J = 8.2 Hz, 1 H), 7.57–7.18 (m, 12 H).
Anal. Calcd for C22H17N3O (339.40): C, 77.86; H, 5.05; N, 12.38.
Found: C, 78.08; H, 5.13; N, 12.47.
13C NMR: d = 155.4, 149.3, 146.0, 140.2, 133.4, 132.7, 130.3,
(E)-2-Benzotriazol-1-yl-3-(4-methoxyphenyl)-1-phenylprope-
none (5b)
Yield: 0.76 g (71%); mp 175–177 °C.
1H NMR: d = 8.11–8.06 (m, 3 H), 7.55–7.12 (m, 9 H), 7.03 (d,
J = 8.8 Hz, 2 H), 3.93 (s, 3 H).
130.1, 129.2, 128.4 (2 C), 128.0, 127.5, 123.9, 123.2, 119.8, 109.8.
Anal. Calcd for C21H15N5 (337.39): C, 74.76; H, 4.48. Found: C,
74.66; H, 4.57.
13C NMR: d = 190.3, 156.1, 145.9, 133.8, 132.5, 131.7, 130.6,
129.7, 128.6, 128.3, 127.9, 127.0, 124.1, 120.6, 119.4, 114.2, 110.1,
55.0.
1-[3-(4-Methylphenyl)-5-phenyl-1H-pyrazol-4-yl]-1H-benzotri-
azole (9b)
Yield: 0.89 g (84%); mp 147–149 °C.
1H NMR: d = 11.98 (br s, 1 H), 8.05 (d, J = 8.2 Hz, 1 H), 7.87 (d,
J = 8.2 Hz, 1 H), 7.47–7.33 (m, 5 H), 7.29 (d, J = 7.5 Hz, 2 H), 7.18
(d, J = 8.2 Hz, 2 H), 7.08 (d, J = 8.0 Hz, 2 H), 2.27 (s, 3 H).
Anal. Calcd for C22H17N3O2 (355.40): C, 74.35; H, 4.82. Found: C,
74.02; H, 4.73.
13C NMR: d = 162.0, 156.6, 155.5, 146.3, 140.1, 133.3, 131.1,
129.9, 129.1, 128.5, 128.0, 127.6, 126.7, 124.2, 123.6, 119.8, 110.5,
21.2.
(E)-2-Benzotriazol-1-yl-3-(4-chlorophenyl)-1-phenylprope-
none (5c)
Yield: 0.81 g (75%); mp 189–191 °C.
1H NMR: d = 8.11 (dd, J = 2.1, 7.3 Hz, 1 H), 7.80–7.18 (m, 9 H),
7.13 (d, J = 7.1 Hz, 2 H), 6.77 (d, J = 7.0 Hz, 2 H).
Anal. Calcd for C22H17N5 (351.41): C, 75.19; H, 4.88; N, 19.93.
Found: C, 74.98; H, 4.52; N, 19.76.
13C NMR: d = 190.7, 145.6, 140.1, 137.2, 136.3, 132.9 (2C), 131.5,
1-(1,3,5-Triphenyl-1H-pyrazol-4-yl)-1H-benzotriazole (9c)
Yield: 1.02 g (82%); mp 168–170 °C.
131.2, 129.6, 129.1, 129.0, 128.6, 128.5, 124.4, 120.1, 109.8.
Anal. Calcd for C21H14ClN3O (359.82): C, 70.10; H, 3.92; N, 11.68.
Found: C, 70.43; H, 4.22; N, 11.41.
Synthesis 2005, No. 2, 245–249 © Thieme Stuttgart · New York

PAPER
b-Lithiation of Benzotriazolylvinyl Ethyl Ether
249
1H NMR: d = 8.11 (d, J = 8.5 Hz, 1 H), 7.89 (d, J = 8.5 Hz, 1 H),
ene (50 mL) was stirred for 3 h at 80–100 °C. On cooling reaction
mixture to r.t., yellow crystals were precipitated. The crystals were
collected by filtration, washed with anhyd Et2O (3 × 10 mL), and
dried in vacuo over P2O5. Compounds 12a,b are extremely hygro-
scopic.
7.80–7.18 (m, 17 H).
13C NMR: d = 165.4, 163.8, 152.2, 146.3, 144.3, 141.0, 133.7,
129.1, 128.9, 128.2 (2 C), 127.8, 127.4 (2 C), 126.9, 126.1, 124.3,
123.9, 120.1, 118.3, 109.8.
Anal. Calcd for C27H19N5 (413.49): C, 78.43; H, 4.63; N, 16.94.
Found: C, 78.79; H, 4.46; N, 16.81.
2,4,6-Triphenylpyrylium Chlorophosphate (12a)
Yield: 0.69 g (77% calculated assuming y = 0.5); mp 214–218 °C
(dec.) (Lit.16 mp 210–215 °C).
1H NMR: d = 9.20 (s, 2 H), 8.82–8.68 (m, 6 H), 7.75 (s, 6 H), 7.44
(s, 3 H).
1-[3-(4-Methylphenyl)-1,5-diphenyl)-1H-pyrazol-4-yl]-1H-ben-
zotriazole (9d)
Yield: 1.01 g (79%); mp 177–179 °C.
13C NMR: d = 169.9, 165.9, 135.4, 135.3, 131.8, 131.4, 130.3,
129.9, 129.2, 128.7, 115.7.
1H NMR: d = 8.06 (d, J = 8.5 Hz, 1 H), 7.57–7.13 (m, 17 H), 2.29
(s, 3 H).
13C NMR: d = 161.1, 158.4, 153.6, 146.8, 141.9, 133.6, 132.1,
131.5, 129.9 (2 C), 129.3, 129.0, 128.2 (2 C), 127.7, 127.0, 126.7,
124.0, 123.6, 119.6, 111.0, 21.7.
2-(4-Methylphenyl)-4,6-diphenylpyrylium Chlorophosphate
(12b)
Yield: 0.66 g (71% calculated assuming y = 0.5); mp 190–194 °C
Anal. Calcd for C28H21N5 (427.51): C, 78.67; H, 4.95; N, 16.38.
Found: C, 78.35; H, 4.67; N, 16.51.
(dec.).
1H NMR: d = 8.92 (s, 2 H), 8.65–8.45 (m, 6 H), 7.85 (s, 6 H), 7.54
(s, 3 H), 2.45 (s, 3 H).
13C NMR: d = 168.6, 166.2, 137.8, 135.9, 133.7, 132.6, 132.4,
132.0, 131.5, 131.0, 130.3, 129.9, 129.6, 129.0, 128.7, 128.5,
128.1,127.7, 127.3, 115.7, 23.9.
3-Substituted-1-(5-Phenylisoxazol-4-yl)benzotriazoles 10; Gen-
eral Procedure
A mixture of b-keto vinyl ether 7 (3 mmol) and hydroxylamine hy-
drochloride (0.2 g, 3 mmol) in EtOH (20 mL) was stirred for 16 h at
65–80 °C and left to cool down to r.t. The product was precipitated
by addition of H2O (10 mL), the precipitate was filtered off, washed
with toluene and recrystallized from benzene.
Acknowledgment
The author gratefully acknowledges Professor Alan R. Katritzky for
his generous help and discussion during this work. We wish also to
express our sincere appreciation to Dr. Novruz G. Akhmedov who
most graciously undertook the NOE experiments.
1-(3,5-Diphenylisoxazol-4-yl)-1H-benzotriazole (10a)
Yield: 0.83 g (82%); mp 156–158 °C.
1H NMR: d = 8.22 (d, J = 8.2 Hz, 1 H), 7.63–7.18 (m, 13 H).
13C NMR: d = 168.0, 155.1, 148.3, 144.8, 138.1, 133.6, 132.4,
131.8, 129.9, 129.1, 128.0, 127.8, 127.3, 126.6, 124.1, 120.3, 109.8.
References
Anal. Calcd for C21H14N4O (338.37): C, 74.54; H, 4.17; N, 16.56.
Found: C, 74.67; H, 4.22; N, 16.43.
(1) Geschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26,
1.
(2) Rewcastle, G. W.; Katritzky, A. R. Adv. Heterocycl. Chem.
1993, 56, 155.
(3) McDougal, P. G.; Rico, J. G. Tetrahedron Lett. 1984, 25,
5977.
(4) McDougal, P. G.; Rico, J. G.; VanDerveer, D. J. Org. Chem.
1986, 51, 4492.
(5) Wollenberg, R. H.; Albizati, K. F.; Peries, R. J. Am. Chem.
Soc. 1977, 99, 7365.
(6) Lau, F. S. Y.; Schlosser, M. J. Org. Chem. 1978, 43, 1595.
(7) Kraus, G. A.; Krolski, M. E. Synth. Commun. 1982, 12, 521.
(8) Baldwin, J. E.; Hofle, G. A.; Lever, W. O. J. Am. Chem. Soc.
1974, 96, 7125.
1-[3-(4-Methylphenyl)-5-diphenylisoxazol-4-yl]-1H-benzotri-
azole (10b)
Yield: 0.79 g (75%); mp 139–141 °C.
1H NMR: d = 8.14 (d, J = 8.5 Hz, 1 H), 7.75–7.36 (m, 8 H), 7.31 (d,
J = 7.5 Hz, 2 H), 7.11 (d, J = 7.5 Hz, 2 H), 2.21 (s, 3 H).
13C NMR: d = 166.1, 156.3, 151.0, 146.2, 137.6, 133.2, 132.7,
131.4, 130.1, 129.0, 128.3, 127.9, 127.0, 126.9, 123.8, 119.6, 109.9,
22.3.
Anal. Calcd for C22H16N4O (352.40): C, 74.98; H, 4.58; N, 15.90.
Found: C, 75.21; H, 4.81; N, 15.66.
2-Benzotriazol-1-yl-1,3,5-triphenylpenta-1,5-dione (11)
Compound 8a (0.95 g, 2 mmol) was heated with either 57% HClO4
(10 mL) at 70–90 °C for 1.5 h or refluxed in toluene with p-TsOH
(0.52 g, 3 mmol) for 5 h. The mixture was cooled, and the crystals
of pentadione derivative 11 was filtered off, washed with EtOH
(3 × 10 mL) and recrystallized from hexanes; yield: 0.83 g (93%);
mp 176–178 °C (Lit.16 mp 177–179 °C).
1H NMR: d = 8.12 (d, J = 7.7 Hz, 1 H), 7.90 (d, J = 7.8 Hz, 2 H),
7.84 (d, J = 8.5 Hz, 1 H), 7.54–7.10 (m, 11 H), 6.98 (s, 5 H), 4.87
(q, J = 6.5 Hz, 1 H), 3.61 (d, J = 6.5 Hz, 2 H).
(9) Katritzky, A. R.; Lang, H.; Lan, X. Tetrahedron 1993, 49,
2829.
(10) Katritzky, A. R.; Lan, X.; Lam, J. N. Chem. Ber. 1991, 124,
1809.
(11) Katritzky, A. R.; Lan, X.; Lam, J. N. Chem. Ber. 1991, 124,
1819.
(12) Katritzky, A. R.; Yang, Z.; Lam, J. N. J. Org. Chem. 1991,
56, 6917.
(13) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org.
Chem. 2002, 67, 7526.
(14) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Tymoshenko, D.
O.; Essway, S. A. Synthesis 1999, 2114.
(15) Katritzky, A. R.; Zhang, S.; Fang, Y. Org. Lett. 2000, 2,
3789.
13C NMR: d = 197.5, 192.6, 146.0, 138.1, 136.6, 135.0, 134.2,
133.3, 132.2, 129.0, 128.9, 128.6, 128.5, 128.3, 128.2, 127.6, 127.4,
123.8, 119.8, 111.0, 66.5, 41.7, 41.2.
(16) Drevko, B. I.; Zhukov, O. I.; Kharchenko, V. G. Russ. J.
Org. Chem. 1995, 31, 1401.
2,4,6-Triarylpyrylium Chlorophosphates 12; General Proce-
dure
A solution of 4-benzotriazol-1-yl-5-ethoxy-1,3,5-triarylpent-4-en-
1-one (8; 0.95 g, 2 mmol) and PCl5 (1.25 g, 6 mmol) in anhyd tolu-
Synthesis 2005, No. 2, 245–249 © Thieme Stuttgart · New York