On the reactivity of isoxazoles with Mo(CO)6

Article abstract of DOI:10.1002/jhet.5570410518

Ring opening with molybdenum hexacarbonyl of functionalized isoxazoles is a valuable synthetic process. Tetrazolopyridine 4 and pyrazolopyridine 9 were obtained from isoxazolopyridines 3 and 6, respectively, whereas the isoxazole 14 gave ketone 16 through

Full text of DOI:10.1002/jhet.5570410518

Sep-Oct 2004
761
On the Reactivity of Isoxazoles with Mo(CO)
6
Donato Donati, Serena Ferrini, Stefania Fusi and Fabio Ponticelli*
Department of Chemistry, University of Siena, via A. Moro, 53100 Siena, Italy
Fax 390577234278; E-mail: ponticelli@unisi.it
Received March 1, 2004
Ring opening with molybdenum hexacarbonyl of functionalized isoxazoles is a valuable synthetic
process. Tetrazolopyridine 4 and pyrazolopyridine 9 were obtained from isoxazolopyridines 3 and 6, respec-
tively, whereas the isoxazole 14 gave ketone 16 through the intermediate 17.
J. Heterocyclic Chem., 41, 761 (2004).
Recently we reported [1] that ring opening - ring closure
6-azido group and tetrazole formation by the 4-azido
group was observed (Scheme 2). The extensive delocaliza-
tion of the tetrazole ring electrons, as deduced from X-ray
structure [2], stabilizes the enaminic form of compound 4.
ii) Compound 6 (with a small quantity of 7) was
obtained by site-selective nucleophilic substitution of 4,6-
d i c h l o r o - 3 - m e t h y l i s o x a z o l [ 5 , 4 -b]pyridine 5 with 2-
aminobenzylamine (Scheme 3).
of suitably substituted 3-methylisoxazolopyridines in the
presence of Mo(CO)6 is an efficient and versatile proce-
dure for the preparation of functionalized pyrido-con-
densed heterocycles, an important class of biologically
active molecules. In this way, from compounds 1 we
Scheme 1
Reaction of Mo(CO)6 on 4-substituted amine 6 yielded
two compounds, which were separated by crystallization.
One of these was the expected acetylpyridone 8, but any
attempt to cyclize this compound to obtain the pyridoa-
zocine 10 was unsuccessful, only giving decomposition
material. The second product was identified as 1-(2-
a m i n o b e n z y l ) - 6 - c h l o r o - 3 - m e t h y l - 1 , 5 - d i h y d r o - p y r a -
zolo[4,3-c]pyridin-4-one 9, on the basis of X-ray structure
determination (Figure 1 and Tables 1 and 2) of the N-
methyl-derivative 11, obtained with the corresponding O-
methyl-derivative 12 by reaction of 9 with diazomethane.
obtained the heterocycles 2, containing from five to eight
atoms in the ring condensed to the pyridine moiety. All the
products are formed by NH2 attack on keto/imino group
obtained after the reductive ring opening of isoxazole by
the Mo(CO)6.
For a deeper insight of this reaction, we planned to con-
sider a series of isoxazole derivatives in which the final
condensation of the NH2 group is strongly prevented. In
this way other possible pathways may be opened, and the
synthetic potentiality of the reaction extended.
i) When 4,6-diazido-3-methylisoxazolo[4,5-c]pyridine 3
was heated with Mo(CO)6 we obtained the tetrazolopyri-
done 4, whose X-ray structural determination we recently
reported [2].
In this case, in addition to the expected reductive ring
opening of the isoxazole, chemoselective reduction of the
Figure 1. ORTEP plot of pyrazolopyridone 11.
Scheme 2
It is to be noted that the formation of the pyrazole 9
requires the attack of the nitrogen in position 4 onto the
isoxazole nitrogen, probably by way of a nitrene-like inter-
mediate [3]. This process was not found for the [4,5-c]
condensed system [1] and it was previously observed only

762
D. Donati, S. Ferrini, S. Fusi and F. Ponticelli
Vol. 41
Scheme 3
Table 1
Single Crystal X-Ray Crystallographic Analysis of 11
Table 1 (continued)
R1 = 0.0399, wR2 = 0.0941
Final R indices [I>2σ(I)]
R indices (all data)
R1 = 0.0548, wR2 = 0.1026
Empirical formula
Formula weight
Temperature
C H ClN O
15 15 4
302.76
-3
Largest diff. peak and hole
0.137 and -0.263 e.A
293(2) K
Wavelength
0.71073 Å
Monoclinic
Crystal system
Space group
in the course of photochemical rearrangement of isoxa-
zolopyridine derivatives [4] or when isothiazolopyridines
were formed by reaction of Mo(CO)6 with isoxazolopyri-
dine-4-thiols [5].
P2 /c
1
Unit cell dimensions
a = 7.366(1)Å alpha = 90°
b = 10.695(1)Å beta = 98.09(1)°
c = 18.500(2)Å gamma = 90°
3
Volume
1442.9(3) A
Considering that the analogous [4,5-c] derivative gave
the azocine in good yields with no trace of the correspond-
ing pyrido-pyrazole, this case shows that the ring junction
plays an important, but not easy explicable, role. Further
work is planned to rationalize this factor.
iii) Finally, we considered non condensed isoxazoles.
Compound 14 was chosen also as a part of our interest for
hindered phenols with potential antioxidant properties [6]
and it can be prepared from 4-bromomethylisoxazole 13
(Scheme 4) by electrophilic attack on the corresponding
phenol. In this case, reaction of Mo(CO)6 on 13 afforded,
as reported in the Scheme 4, the aromatic ketone 16. The
Z
4
3
Calculated density
Absorption coefficient
F(000)
1.394 Mg/m
-1
0.269 mm
632
Crystal size
Theta range for data collection
Limiting indices
0.4 x 0.2 x 0.15 mm
2.21 to 25.00 °
-1<=h<=8,-1<=k<=12,-21<=l<=21
3542
2543 [R(int) = 0.0216]
1987
Reflections collected
Indipendent reflections
Observed reflections [I>2σ(I)]
Completeness to theta = 25.00
Refinement method
Data/restraints/parameters
Goodness-of-fit on F^2
100.0 %
Full-matrix least-squares on F
2
2543/0/250
1.047

Sep-Oct 2004
On the Reactivity of Isoxazoles with Mo(CO)6
763
Table 2
Bond Lengths (A) and Angles (deg) for 11
Scheme 4
Cl-C(2)
N(1)-C(2)
N(1)-C(6)
N(1)-C(15)
N(2)-C(7)
N(2)-N(3)
N(3)-C(4)
N(3)-C(8)
N(4)-C(10)
O(1)-C(6)
C(2)-C(3)
C(3)-C(4)
C(4)-C(5)
C(5)-C(7)
C(5)-C(6)
C(7)-C(16)
C(8)-C(9)
C(9)-C(14)
C(9)-C(10)
C(10)-C(11)
C(11)-C(12)
C(12)-C(13)
C(13)-C(14)
1.722(2)
1.380(2)
1.408(3)
1.475(3)
1.328(3)
1.381(2)
1.347(2)
1.464(3)
1.391(3)
1.230(2)
1.346(3)
1.411(3)
1.386(3)
1.414(3)
1.432(3)
1.489(3)
1.498(3)
1.394(3)
1.400(3)
1.395(3)
1.369(3)
1.372(3)
1.375(3)
two triplets at 2.70 and 3.02 attributable to the -CH2-CH2-
C(2)-N(1)-C(6)
C(2)-N(1)-C(15)
C(6)-N(1)-C(15)
C(7)-N(2)-N(3)
C(4)-N(3)-N(2)
C(4)-N(3)-C(8)
N(2)-N(3)-C(8)
C(3)-C(2)-N(1)
C(3)-C(2)-Cl
N(1)-C(2)-Cl
C(2)-C(3)-C(4)
N(3)-C(4)-C(5)
N(3)-C(4)-C(3)
C(5)-C(4)-C(3)
C(4)-C(5)-C(7)
C(4)-C(5)-C(6)
C(7)-C(5)-C(6)
O(1)-C(6)-N(1)
O(1)-C(6)-C(5)
N(1)-C(6)-C(5)
N(2)-C(7)-C(5)
N(2)-C(7)-C(16)
C(5)-C(7)-C(16)
N(3)-C(8)-C(9)
C(14)-C(9)-C(10)
C(14)-C(9)-C(8)
C(10)-C(9)-C(8)
N(4)-C(10)-C(11)
N(4)-C(10)-C(9)
C(11)-C(10)-C(9)
C(12)-C(11)-C(10)
C(11)-C(12)-C(13)
C(12)-C(13)-C(14)
C(13)-C(14)-C(9)
121.8(2)
moiety. The 13C signals (experimental) confirmed the
structural assignment.
121.2(2)
117.1(2)
106.0(2)
111.0(2)
128.3(2)
120.3(2)
124.5(2)
119.1(2)
116.4(1)
115.4(2)
107.1(2)
130.3(2)
122.6(2)
105.6(2)
121.2(2)
133.3(2)
119.7(2)
125.7(2)
114.6(2)
110.3(2)
120.8(2)
128.8(2)
113.5(2)
118.7(2)
120.9(2)
120.4(2)
121.0(2)
120.4(2)
118.5(2)
121.3(2)
120.7(2)
118.9(2)
121.9(2)
The unexpected formation of compound 16 can be
explained according to the mechanism reported in Scheme
5. Isoxazole ring opening produces an intermediate dioxo-
compound 15, which undergoes intramolecular cyclization
by reversible attack of the phenolic hydroxyl on a carbonyl
group to give the intermediate emiketal 17. Finally, ring
opening of 17 forms the more stable compound 16 by a
retro-Claisen like mechanism.
Scheme 5
Conclusions.
Reaction of molybdenum hexacarbonyl with isoxazole
derivatives is a valuable synthetic procedure, allowing the
easy access to several heterocyclic systems. The opening
of the N-O bond bringing to a methyliminic intermediate,
is usually followed by hydrolysis to a keto group, which
may perform a ring closure if a NH2 group is located in a
suitable position. However, depending on the structure of
the starting materials, trapping of the nitrene intermediate,
or further rearrangement of the products can also be
involved. The trapping of nitrene-like intermediate
structure of this compound was assigned on the basis of
analytical and spectral properties. In particular, a useful
datum was the presence, in the H-nmr spectrum of the
1

764
D. Donati, S. Ferrini, S. Fusi and F. Ponticelli
Vol. 41
(brt, 1H, NH, D O-exchangeable), 6.44 (s, 1H, H-5), 6.79-7.22
2
appears particularly promising for the synthesis of new
heterocycles, and therefore factors affecting this pathway
are actually under investigation.
13
(m, 4H, C H ); C nmr (CDCl + DMSO-d ): δ 12.3 (3-Me),
6
4
3
6
43.7 (CH ), 98.6 (C-3a), 99.1 (C-5), 115.5, 116.9, 119.7, 128.0,
2
145.6 (C H ), 151.3, 152.7, 153.9, 170.1 (C-7a); ms: (70 ev, elec-
6
4
+
tron impact) m/z 288/290 (M ).
Anal. Calcd. for C ClN O: C, 58.24; H, 4.54; N, 19.40.
Found: C, 57.89; H, 4.36; N, 19.72.
EXPERIMENTAL
H
14 13
4
Melting points were determined on a Kofler hot stage and are
uncorrected. Infrared spectra were obtained for KBr discs with a
(2-Amino-benzyl)-(4-chloro-3-methyl-isoxazolo[5,4-b]pyridin-
6-yl)-amine (7).
1
13
Perkin Elmer 782 spectrophotometer. H and C NMR spectra
were recorded on a Bruker AC 200 spectrometer at 200.13 MHz
and 50.33 MHz, respectively. Chemical shifts are reported in
ppm from internal TMS. All reagents were of reagent grade and
were used without purification. EI ms spectra were recorded on a
VG 70 250S instrument; electrospray ms spectra were recorded
with an LCQ-DECA Thermo Finnigan instrument. TLC was per-
This compound was obtained as a white solid, yield 0.2 g,
10%. An analytical sample of compound 7 was obtained by crys-
tallization from ethanol; m.p. 186-187 °C; ir: 3435, 3360, 3325,
-1
1
1605 cm ; H nmr (CDCl ): δ 2.58 (s, 3H, Me), 4.16 (brs, 2H,
3
NH , D O-exchangeable), 4.59 (d, J = 5.6 Hz, 2H, CH ), 5.16
2
(brt, 1H, NH, D O-exchangeable), 6.32 (s, 1H, H-5), 6.68-7.20
2
2
2
13
(m, 4H, C H ); C nmr (CDCl ): δ 12.1 (3-Me), 43.1 (CH ),
formed on precoated 5x20 silica gel 60 F
plates (Macherey-
6
4
3
2
254
102.5 (C-3a), 106.1 (C-5), 115.5, 116.1, 118.5, 121.8, 129.3,
130.4, 145.4 (C H ), 139.3, 155.0, 159.7, 171.3 (C-7a); ms: (70
Nagel) with detection by UV light. Column chromatography was
carried out on Silica gel (E. Merck, 0.063-0.2 mm). Elemental
analyses were performed at the Department of Org a n i c
Chemistry, University of Florence, Italy.
6
4
+
ev, electron impact) m/z 288/290 (M ).
Anal. Calcd for C ClN O: C, 58.24; H, 4.54; N, 19.40.
Found: C, 58.02; H, 4.68; N, 19.22.
H
14 13
4
5-Amino-8-(1-amino-ethylidene)-8H-tetrazolo[1,5-a]pyridin-7-
one (4).
3-Acetyl-4-(2-amino-benzylamino)-6-chloro-1H-pyridin-2-one
(8) and 1-(2-Amino-benzyl)-6-chloro-3-methyl-1,5-dihydro-
pyrazolo[4,3-c]pyridin-4-one (9).
A solution of the diazide 3 [7] (1.08 g, 5 mmoles) in MeOH
(30 ml) was treated with molybdenum hexacarbonyl (1.32 g, 5
mmol) and refluxed for two hours. The insoluble material was
removed by filtration, washed with MeOH and the combined
solutions were evaporated in vacuo. The residue was chro-
To a solution of the amine 6 (0.6 g, 2.1 mmol) in MeOH
molybdenum hexacarbonyl (0.55 g, 2.1 mmol) was added and the
mixture was refluxed for 1 hour. Solvent was removed in vacuo,
the residue was treated with 2 N sodium hydroxide, filtered and
the solution acidified to pH 5-6 with concentrated hydrochloric
acid. On cooling a green solid was collected by filtration and
crystallised from MeOH to give compound 8 (yield 0.22 g, 36%).
The mother liquid was evaporated and the residue crystallised
from ethyl acetate to give compound 9 (yield 0.24 g, 39.5%).
matographed with CHCl - MeOH (95:5 v/v) on a short column
3
of silica gel to yield 0.57 g (50%) of 4 as white plates (CHCl ),
3
mp: after a partial modification around 90 °C, it decomposes at
-1
1
295 °C without melting; ir: 3650-2540 br, 1620 cm ; H nmr
(CDCl + DMSO-d ): δ 2.48 (s, 3H, Me), 5.37 (s, 1H, 6-H) 6.31
(brs, 2H, NH , D O-exchangeable), 8.73, 12.54 (2 brs, 2H, NH ,
3
6
2
2
2
13
D O-exchangeable); C nmr (CDCl + DMSO-d ): δ 21.8 (Me),
3-Acetyl-4-(2-amino-benzylamino)-6-chloro-1H-pyridin-2-one (8).
2
3
6
88.7 (C-6), 90.2, 142.6, 149.9, 169.8, 178.8; ms: (70 ev, electron
White needles (MeOH), mp 229-230 °C; ir: 3460, 3375, 3300-
+
impact) m/z 192 (M ).
Anal. Calcd. for C H N O•2H O: C, 36.84; H, 5.38; N, 36.83.
-1
2280, 1650, 1625 cm ; H nmr (DMSO-d ): δ 2.49 (s, 3H, Me),
1
6
4.36 (d, J = 5.2 Hz, 2H, CH ), 5.07 (brs, 2H, NH , D O-
7
Found: C, 36.57; H, 5.41; N, 36.64.
8
6
2
2
2
2
exchangeable), 6.16 (s, 1H, 5-H), 6.51-6.71 and 6.97-7.05 (m,
4H, C H ), 10.99 (brt, 1H, NH, D O-exchangeable), 11.88 (brs,
13
6
1H, NH, D O-exchangeable); C nmr (DMSO-d ): δ 32.7 (Me),
4
2
(2-Amino-benzyl)-(6-chloro-3-methyl-isoxazolo[5,4-b]pyridin-
4-yl)-amine (6) and (2-Amino-benzyl)-(4-chloro-3-methyl-isox-
azolo[5,4-b]pyridin-6-yl)-amine (7).
2
42.8 (CH ), 94.1 (C-5), 115.1, 116.1, 128.1, 128.2 (Aryl CH),
6
2
100.4, 119.9, 140.8, 146.1, 159.9, 163.4, 199.3; ms: (electro-
To a solution of dichloroderivative 5 (1.4 g, 6.9 mmol) in THF
(6 ml) 2-aminobenzylamine (2 g, 16.4 mmol) was added with
stirring. After 24 hours at room temperature the solvent was
removed in vacuo and the residue treated with water (10 ml) to
give a solid that was collected by filtration, dried and treated with
+
spray) m/z (M +1): 292/294.
Anal. Calcd. for C
H ClN O : C, 57.64; H, 4.84; N, 14.40.
14 14 3 2
Found: C, 57.89; H, 4.62; N, 14.68.
1 - ( 2 - A m i n o - b e n z y l ) - 6 - c h l o r o - 3 - m e t h y l - 1 , 5 - d i h y d r o - p y r a-
zolo[4,3-c]pyridin-4-one (9).
hot CHCl (10 ml). The insoluble material was collected by fil-
3
tration to give compound 6. Evaporation of the CHCl solution
This compound was obtained as white powder, m.p. 266-268
°C (decomp.), ir: 3425, 3350, 3240, 3130-2300 (broad), 1660
3
gave a residue that was column chromatographed with CHCl -
3
-1
cm ; H nmr (DMSO- d ): δ 2.42 (s, 3H, Me), 5.10 (brs, 2H,
1
MeOH (95:5 v/v) to give (in order of elution) compound 7 and a
second crop of compound 6.
6
NH , D O-exchangeable), 5.24 (s, 2H, CH ), 6.48-6.59, 6.65-
2
6.70 and 6.85-7.04 (m, 4H, C H ), 6.84 (s, 1H, 7-H); 11.91 (brs,
2
2
6
4
1H, NH, D O-exchangeable); C nmr (DMSO-d ): δ 12.6 (Me),
(2-Amino-benzyl)-(6-chloro-3-methyl-isoxazolo[5,4-b]pyridin-
4-yl)-amine (6).
13
2
49.0 (CH ), 92.0 (C-7), 115.4, 116.3, 128.6, 129.1 (Aryl CH),
6
2
109.3, 119.9, 132.3, 144.4, 145.7, 146.4, 158.6; ms: (electro-
This compound was obtained as a white solid, yield 1.35 g,
68%, m.p. 186-188 °C (ethanol/water); ir: 3440, 3360, 3220,
+
spray) m/z 289/291 (M +1).
-1
1
1605 cm ; H nmr (CDCl ): δ 2.53 (s, 3H, Me), 3.86 (brs, 2H,
Anal. Calcd. for C H ClN O: C, 58.24; H, 4.54; N, 19.40.
14 13 4
Found: C, 58.46; H, 4.43; N, 19.64.
3
NH , D O-exchangeable), 4.36 (d, 2H, J = 4.7 Hz, CH ), 5.13
2
2
2

Sep-Oct 2004
On the Reactivity of Isoxazoles with Mo(CO)6
765
1-(2-Amino-benzyl)-6-chloro-3, 5-dimethyl-1, 5-dihydropyra -
zolo[4,3-c]pyridin-4-one (11) and 2-(6-Chloro-4-methoxy-3-
methyl-pyrazolo[4,3-c]pyridin-1-ylmethyl)-phenylamine (12).
Benzoic Acid 4-Methoxy-2-(3-oxo-3-phenyl-propyl)-phenyl
Ester (16).
To a solution of compound 14 (0.18 g, 0.5 mmol) in MeOH
molybdenum hexacarbonyl (0.13 g, 0.5 mmol) was added and the
mixture was refluxed for 24 hours. The reaction mixture was fil-
tered and solvent was removed in vacuo, to give a residue that
was crystallised from cyclohexane to give compound 16 as white
To a suspension of compound 9 (0.29 g, 1 mmol) in MeOH (5
ml) ethereal diazomethane (0.13 g, 3 mmol) was added. After 2
hours solvent was removed in vacuo and the residue crystallised
from a 1:1 mixture of ether and cyclohexane to give the N-methyl
derivative 11. Evaporation of the mother liquors gave a residue
which was column chromatographed with 1:1 ether/cyclohexane.
The faster running fraction was identified as the methoxy-deriva-
tive 12 (yield 0.08 g, 26%) and the slower running compound
was a second crop of 11 (total yield 0.11 g, 36%).
-1
crystals, m.p. 73-76 °C (yield 0.15 g, 84%); ir: 1735, 1685 cm ;
1
H-nmr (CDCl ): δ 2.70 (t, J = 8.0 Hz, 2H, CH ), 3.02 (t, J = 8.0
3
2
Hz, 2H CH ), 3.52 (s, 3H, OMe), 6.53 (dd, J = 8.8, 2.9 Hz, 1H,
2
H3), 6.63 (d, J = 2.9 Hz, 1H, H5), 6.80 (d, J = 8.6 Hz, 1H, H2),
13
7.06-7.40, 7.59-7.63 and 7.87-7.92 (m, 10H, 2Ph); C nmr
(CDCl ): δ 25.27 (CH ), 39.08 (CH ), 55.57 (OMe), 112.58,
3
115.58, 123.23, 128.05, 128.55, 128.89, 129.35, 130.14, 133.05,
2
2
1-(2-Amino-benzyl)-6-chloro-3,5-dimethyl-1,5-dihydropyrazolo-
[4,3-c]pyridin-4-one (11).
133.63, 134.32, 136.76, 142.71, 157.54 (Aryl), 165.62, 199.02 (2
+
CO); ms: (70 ev, electron impact) m/z 360 (M ).
This compound was obtained as white crystals, m.p. 185-186
°C (from cyclohexane-benzene); ir: 3395, 3340, 3250, 3230,
Anal. Calcd. for C
76.89; H, 5.63.
H O : C, 76.65; H, 5.59. Found: C,
23 20 4
-1
1675 cm ; H nmr (CDCl ): δ 2.59 (s, 3H, Me), 3.61 (s, 3H,
1
3
NMe), 5.18 (s, 2H, NH , D O-exchangeable), 5.24 (s, 2H, CH ),
2
2
6.43 (s, 1H, 7-H), 6.64-6.76 and 7.11-7.15 (m, 4H, C H );
2
Crystal Structure Analysis of compound 11.
13
C
nmr (CDCl ): δ 13.0 (Me), 32.0 (NMe), 51.2 (CH ), 93.0 (C-7),
6
4
Siemens P4 four circle diffractometer. Mo-Kα radiation
λ=0.71073, graphite monochromated, ω-scan. Cell constants
from 25 centred reflections. Intensity of three standard reflections
checked every 97 reflections. Structure solutions by direct meth-
ods using SHELXL-97 [9] implemented in Wingx [10] package
program. Anisotropic temperature factors were used for non-
hydrogen atoms. The positions of hydrogen atoms were found by
difference Fourier map and refined isotropically. Selected data
are given in Table 1. Figure was made by Ortep-III for Windows
version 1.076, implemented in Wingx package program [11].
Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 228428. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [Fax: (internat.) +44-1223/336-
033; e-mail:deposit@ccdc.cam.ac.uk].
3
2
116.6, 118.1, 129.9, 130.2 (Aryl CH), 109.9, 119.8, 135.9, 142.6,
146.2, 147.3, 159.0; ms: (70 ev, electron impact) m/z 302/304
+
(M ).
Anal. Calcd. for C H ClN O: C, 59.51; H, 4.99; N, 18.51.
15 15 4
Found: C, 59.74; H, 4.74; N, 18.68.
2-(6-Chloro-4-methoxy-3-methyl-pyrazolo[4, 3- c]pyridin-1-
ylmethyl)-phenylamine (12).
This compound was obtained as white crystals, m.p. 130-132
-1
1
°C (cyclohexane); ir: 3390, 3340, 3260, 1630, 1610 cm ; H nmr
(CDCl ): δ 2.57 (s, 3H, Me), 4.03 (s, 3H, OMe), 4.40 (brs, 2H,
NH , D O-exchangeable), 5.26 (s, 1H, 7-H) 6.62-6.78 and 7.05-
3
2
2
13
7.19 (m, 4H, C H ); C nmr (CDCl ): δ 13.6 (Me), 51.2 (CH ),
6
4
3
2
54.0 (OMe), 98.3 (C-7), 116.6, 118.3, 129.8, 130.5 (Aryl CH),
108.4, 120.2, 143.0, 144.5, 146.1, 147.1, 158.3; ms: (70 ev, elec-
+
tron impact) m/z 302/304 (M ).
Anal. Calcd. for C H ClN O: C, 59.51; H, 4.99; N, 18.51.
15 15 4
Found: C, 59.30; H, 5.26; N, 18.29.
Acknowledgement.
The authors wish to thank the University of Siena for funding
(Quota servizi), and the "Centro di Analisi e Determinazioni
Strutturali" of the University of Siena for the availability of Mass
Spectrometer and of X-Ray Diffractometer.
2-(3,5-Diphenylisoxazol-4-ylmethyl)-4-methoxyphenol (14).
A mixture of 4-bromomethyl-3,5-diphenylisoxazole [8] (0.63
g, 2 mmol), 4-methoxyphenol (0.38 g, 3 mmol) and aluminum
chloride (0.03 g) was heated under nitrogen in a sealed tube at 60
°C for 48 hours. The solid was treated with dichloromethane,
washed with water and the organic layer evaporated in vacuo.
Column chromatography of the residue with light
petroleum/ether (from 3:1 to 1:1 v/v) gave compound 14 (yield
0.22 g, 62% based on the unrecovered starting material), white
powder, m.p. 152-155 °C (cyclohexane); ir: 3420-3050 br, 1510
REFERENCES AND NOTES
[1] D. Donati, S. Ferrini, S. Fusi and F. Ponticelli, Synthesis,
2003 (16), 2518.
[2] D. Donati, S. Fusi and F. Ponticelli, Acta Cryst., 2003,
E59, o1589.
[3] M. Nitta and T. Kobayashi, J. Chem. Soc., Perkin Trans. 1,
1985, 1401.
[4] D. Donati, S. Fusi and F. Ponticelli, Tetrahedron Lett., 43,
9527 (2002) and references cited therein.
[5] S. Chimichi, R. Nesi, F. Ponticelli and P. Tedeschi , J.
Chem. Soc., Perkin Trans. I, 1990, 1477.
[6] G. Giorgi, F. Ponticelli, L. Salvini, A. Trendafilova, M.
Valoti and F. Pessina, Eur. J. Org. Chem., 2003, 106.
[7] D. Donati, S. Fusi and F. Ponticelli, J. Chem. Research (S),
1997, 170.
-1
1
cm ; H-nmr (CDCl ): δ: 3.57 (s, 3H, OMe), 4.01 (s, 2H, CH ),
3
5.15 (brs, 1H, OH D O-exchangeable), 6.52 (d, J = 2.7 Hz, 1H,
2
2
H5), 6.63 (dd, J = 8.6, 2.7 Hz, 1H, H3), 6.73 (d, J = 8.6 Hz, 1H,
13
H2), 7.31-7.42, 7.46-7.56 and 7.63-7.68 (m, 10H, Ph); C nmr
(CDCl ): δ 23.08 (CH ), 55.43 (OMe), 110.61, 111.97, 114.34,
3
2
115.21, 126.15, 126.55, 127.65, 127.94, 128.49, 128.63, 128.78,
129.36, 129.61, 148.36, 152.93, 164.19, 167.07 (Aryl); ms: (70
+
ev, electron impact) m/z: 357 (M ).
Anal. Calcd. for C H NO : C, 77.29; H, 5.36; N, 3.92.
23 19 3
Found: C, 77.40; H, 5.18; N, 3.73.
[8] S. D. Sokolov and N. K. Kochetkov, Zh. Obsch. Khim., 33,
1192 (1963).

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Vol. 41
[9] G. M. Sheldrick, SHELXL-97. Program for the refinement
of crystal structure, University of Gottingen, Germany, 1997.
[10] L. J. Farrugia, J. Appl. Chryst., 30, 565 (1993).
[11] L. J. Farrugia, J. Appl. Chryst., 32, 837 (1999).