An expedient synthesis of novel [1,2,4]triazolo[3,2- d][1,5]benzothiazepine derivatives

Article abstract of DOI:10.1055/s-2000-6335

The synthesis of a series of unprecedented tricyclic heterocycles, 1,2,4-triazolo[3,2-d][1,5]benzothiazepine 6-oxides (5a-i), was accomplished via cycloaddition of the allene-like cations 3, derived from thiochroman-4- one arylhydrazones, to the triple bo

Full text of DOI:10.1055/s-2000-6335

PAPER
435
An Expedient Synthesis of Novel [1,2,4]Triazolo[3,2-d][1,5]Benzothiazepine
Derivatives
Xianjun Liu, Quanrui Wang,* Yi Liu, Yubo Fan, Zongbiao Ding
Department of Chemistry, Fudan University, 200433 Shanghai, P. R. China
Fax +86(21)65641740; E-mail: qrwangb@online.sh.cn
Received 17 September 1999; revised 4 November 1999
polar cycloaddition of the more sophisticated 1-aza-2-
azoniaallene cations19 3 derived from thiochroman-4-one
with nitriles.
Abstract: The synthesis of a series of unprecedented tricyclic het-
erocycles, 1,2,4-triazolo[3,2-d][1,5]benzothiazepine 6-oxides (5a-
i), was accomplished via cycloaddition of the allene-like cations 3,
derived from thiochroman-4-one arylhydrazones, to the triple bond
of nitriles and ensuing ring expansion annulation. The structure of
one product (5h) has been unambiguously determined by X-ray dif-
fraction analysis.
The hydrazones 1 prepared from thiochroman-4-one were
subjected to chlorination with 3.5 equivalents of hy-
pochlorous acid 1,1-dimethylethyl ester at low tempera-
tures (-10 ~ -5 ∞C). Workup afforded the geminal
chloroazo compounds 2 in almost quantitative yields. This
method, which was introduced by Moon,20 has been suc-
cessfully exploited for chlorination of a variety of carbo-
nyl compounds.19,21 Slightly unexpectedly, we observed
that the sulfur atom in the thiazepine ring was concurrent-
ly oxidized to the respective sulfoxide. Similar results
have been published by Bartsch13 when he prepared a tri-
azolo- fused benzothiazepine by treatment of 2,3-dihydro-
1,5-benzothiazepine-4-amine with triethyl orthoacetate /
ammonia followed by oxidative cyclization with sodium
hypochlorite. However, the sulfur atom was oxidized to
the corresponding sulfone in the event. The structural as-
signments of compounds 2 are based on their spectromet-
ric data. In the 1H NMR spectra of 2, absorption for N-H
is absent. The signals of the CH2-CH2 unit appear as a
multiplet centered at 3.0 ppm in 2a, and at 2.9 ppm in 2b.
In the 13C NMR spectra, the signals due to the tetrahedral
C-Cl lie at 91.12 ppm for 2a and 90.38 ppm for 2b. The
azo groups show weak IR-bands around 1570 cm-1,
whereas the strong absorptions at about 1050 cm-1 are at-
tributable to the S=O double bond.
Key words: allene-like cations, cycloaddition, nitriles, ring expan-
sion, 1,2,4-triazolo[3,2-d][1,5]benzothiazepine 6-oxides
Various benzoheteroazepine derivatives containing O, N
or S atoms are continuously being investigated due to
their significant contributions as therapeutic agents.1-3 For
example, chlordiazepoxide (Librium) and diazepam (Va-
lium) have become the well-known prototypes of 1,4-ben-
zodiazepines which are used primarily for treatment of
anxiety disorders.4 1,5-Benzothiazepines such as dictiaz-
em, nictiazem and tiazesime have been found to exhibit
coronary vessel dilation and anti-depressive activity, re-
spectively.5 Furthermore, 1,5-benzothiazepine 1-oxides
are promising candidates for use in medicine, especially
in the prophylaxis and treatment of hyperlipidemic condi-
tions and associate diseases such as atherosclerosis.6
Recent investigations have demonstrated that attachment
of a triazolo ring to the heptatomic ring can enhance the
pharmacological activity and/or offer other diverse prop-
erties.7-10 During the last decade, considerable efforts have
been made in order to synthesize new members of this
family.5,11-17 Among the newly developed 6-7-5 tricyclic
heterocycles, derivatives of benzothiazepines and also the
oxa-analogues with incorporation of an additional triazolo
ring have received a growing amount of attention owing
to their unique pharmaceutical values.5,9-13 However, the
ring systems studied so far are restricted to those either
with fusion of the 3,4-bond of a triazole ring at the [d]-
bond of a 1,5-benzoheteroazepine or with fusion of the
4,3-bond of a triazole ring at the [d]-bond of a 1,4-benzo-
heteroazepine. The reason for that is almost certainly the
apparent lack of facile procedures for the construction of
other rings. Therefore, it seemed interesting to develop s-
triazolo fused benzoheteroazepines with different fusion
modes that could modify the activity profile.
Although compounds 2 were stable at ambient conditions,
all attempts to purify them led to decomposition. There-
fore, compounds 2 were employed for further transforma-
tion as obtained. Following the previously well
documented method,19,21,22 a solution of the a-chloroazo
compound 2a in dichloromethane was allowed to react
with antimony pentachloride at low temperature (-40 ∞C).
Upon departure of the chloride ion, the allene-like cation
3a was generated as a highly reactive intermediate. The
allene-like cation 3a can be reasonably viewed as a cat-
ionic four-electron component for polar [3++2] cycloaddi-
tions.23,24 Although the extremely moisture-sensitive salts
3 have not yet been isolated, they can undergo smooth cy-
cloaddition to the triple bond of nitriles. Thus, in the pres-
ence of a slight excess amount of acetonitrile, 3a was
trapped cleanly to give firstly the 3-spiro substituted 3H-
1,2,4-triazolium salts 4a. On elevation of the temperature
to about 30 ∞C, 4a underwent spontaneous rearrangement
with insertion of the nitrogen atom into the S-containing
After finishing the synthesis of several [1,2,4]triazo-
lo[3,2-d][1,5]benzoxazepine heterocycles,18 we describe
herein an expedient approach to novel [1,2,4]triazolo[3,2-
d][1,5]benzothiazepine 6-oxide derivatives via the 1,3-di-
Synthesis 2000, No. 3, 435–441 ISSN 0039-7881 © Thieme Stuttgart · New York

436
X. Liu et al.
PAPER
Scheme
ring producing the tricyclic product 5a as white crystals in the starting material in order to facilitate the final rear-
89% yield. Likewise, other tricyclic products, 5b-i were rangement 4 Æ 5. In fact, other hydrazones worked equal-
synthesized in high yields (Scheme). It is noteworthy that ly well in the reaction sequence provided that the R1 group
heterocycles 5f-i contain a perfluorinated phenyl group at (Scheme) is inert to oxidation by hypochlorous acid 1,1-
N(1) which is expected to be of additional importance for dimethylethyl ester. If the corresponding ethyl cycloalky-
pharmaceutical values.
lidenecarbazate (R1 = CO2Et, Scheme) was used as the
starting hydrazone, the N(1)-unsubstituted neutral tricy-
clic ring could be produced by removal of the ester group
with aqueous base, thus demonstrating the wide applica-
bility of this methodology.26 As expected, the ring en-
largement proceeded smoothly under mild conditions
with exclusive selectivity of the aromatic side of the ring
giving the tricyclic compounds 5 as sole products. No
traces of the isomeric compounds 6 that would have re-
sulted from migration of the aliphatic side of the ring
could be detected in the crude reaction mixture.
The assigned 1H and 13C NMR spectral parameters and the
physical data of compounds 5 are compiled in Table 1.
The NMR data are complicated by the fact that com-
pounds 5a-c as well as 5f-h with R2 = Me, Et, or n-Pr ex-
hibit two distinct sets of signals for each proton and each
carbon, suggesting the occurrence of these molecules in
two solution forms at ambient temperature. Integration of
Aside from antimony pentachloride, another Lewis acid
such as AlCl3 or TiCl4 can also be employed for the gen-
eration of the allene-like cations 3. However, silver salts
as a Lewis acid (e.g. CF3CO2Ag, AgClO4) did not give a
definite product. Antimony pentachloride was preferen-
tially used throughout this work because the final products
are well-crystallized salts and could be obtained analyti-
cally pure.
Theoretical studies as well as experimental data have re-
vealed that the 1,2-rearrangement of carbon to electron-
deficient nitrogen in 3H-1,2,4-triazolium ions takes place
with complete selectivity.19,25 Given two different substit-
uents, the one that accommodates a positive charge more
effectively migrates. Further, an electron-withdrawing
group at N(1) in the 3H-triazolium rings accelerates the
rate of the rearrangement. In the present examination, we
chose the polyhalogenated arylhydrazones 1a and 1b as
Synthesis 2000, No. 3, 435–441 ISSN 0039-7881 © Thieme Stuttgart · New York

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An Expedient Synthesis of Novel [1,2,4]Triazolo[3,2-d][1,5]Benzothiazepine Derivatives
437
Table 1 Selected NMR, IR Data and Mps of Compounds 1, 2 and 5
Prod- Yieldb Mp
Appearance 1H NMR (CD3CN/TMS)
13C NMR (CD3CN/TMS)
d
IR(KBr)
ucta
(%)
(°C)
d, J (Hz)
n (cm–1)
1a
93
146–147 colorless
2.85–2.89 (m, 4 H, SCH2- CH2), 6.67
(NH), 6.95–7.92 (m, 6 H, ArH)c
–
3320, 1650,
1534, 1320
crystals
1b
2a
95
162–163 white
2.86–3.00 (m, 4 H, SCH2- CH2), 6.62
(NH), 7.02–7.95 (m, 4 H, ArH)c
–
3310, 1645,
1540, 1310
crystals
96d
–
red oil
red oil
2.89–3.02 (m, 4 H, SCH2- CH2),
6.95–7.92 (m, 6 H, ArH)c
34.02 (CH2), 35.13 (SOCH2), 91.12
(CCl), 124.40, 124.77, 125.23, 125.32,
126.01, 126.61, 129.43, 129.78, 130.18,
131.06 (Ar)c
1710, 1645,
1314, 1050e
2b
5a
97d
89
–
2.87–2.93 (m, 4 H, SCH2- CH2),
7.02–7.95 (m, 4 H, ArH)c
32.89 (CH2), 35.01 (SOCH2), 90.38
(CCl), 125.31, 125.93, 126.14, 126.72,
128.87, 129.35, 130.06, 131.23, 131.76,
132.05 (Ar)c
1705, 1663,
1321, 1050e
186–188 white
2.71 (s, 3 H, CH3), 3.80–3.86 (m, 2 H, 12.47 (CH3), 25.80 (CH2), 37.81
CH2), 4.63 (t, 2 H, J = 6.4, SOCH2) (SOCH2), 121.08, 129.06, 131.06,
(A2XY system), 8.04–8.16 (m, 6 H, 133.25, 133.44, 134.34, 135.98, 136.26,
2960, 1560,
1475, 1050
(dec)
crystals
ArH)f
141.87, 145.20, 159.21, 161.35
(Ar, C = N)f
5b
5c
87
90
198–199 white
1.51 (t, 3 H, J = 7.5, CH3), 2.93 (q,
9.54 (CH3), 20.20 (CH2), 25.80 (CH2),
2962, 1559,
(dec)
crystals
2 H, J = 7.5, CH2), 3.80–3.86 (m, 2 H, 36.99 (SOCH2), 123.15, 125.93, 127.52 1480, 1049
CH2), 4.62 (t, 2 H, J = 6.4, SOCH2) 128.36, 130.28, 131.30, 132.02, 133.36,
(A2XY system), 8.04–8.18 (m, 6 H, 137.17, 141.30, 161.30, 163.21
ArH)f
(Ar, C = N)f
200–201 pale yellow 1.13 (t, 3 H, J = 7.4, CH3), 1.97 (m, 12.25 (CH3), 19.84 (CH2), 26.02 (CH2), 2965, 1560,
(dec)
crystals
2 H, CH2), 2.84–2.91 (m, 1 H), 2.97– 27.91 (CH2), 37.19 (SOCH2), 123.10,
3.05 (m, 1 H) (C(2)-CH2) (AB sys- 125.34, 128.01, 130.12, 131.23, 132.10,
1490, 1380
tem), 3.15–3.23 (m, 1 H), 3.60–3.67 133.48, 133.65, 134.50, 137.24, 163.25,
(m, 1 H) (CH2), 3.75–3.83 (m, 1 H), 165.32 (Ar, C = N)f
3.87–3.92 (m, 1 H) (SOCH2) (ABMX
system), 7.21–8.07 (m, 6 H, ArH)f
5d
5e
85
83
203–204 pale yellow 3.86–3.90 (m, 2 H, CH2), 4.71 (t, 2 H, 26.30 (CH2), 36.81 (SOCH2), 123.10,
2960, 1561,
(dec)
crystals
J = 6.5, SOCH2) (A2XY system),
7.67–8.10 (m, 11 H, ArH)
123.45, 125.72, 126.23, 126.78, 128.34, 1475, 1051
129.02, 129.43, 130.31, 131.33, 132.24,
133.56, 136.70, 141.65, 160.24, 164.01
(Ar, C = N)
182–183 white
3.13–3.22 (m, 1 H), 3.58–3.66 (m,
26.31 (CH2), 32.79 (CH2), 36.80
2962, 1565,
1480, 1048
(dec)
crystals
1 H) (CH2), 3.74–3.82 (m, 1 H), 3.86– (SOCH2), 123.02, 124.28, 125.47,
3.92 (m, 1 H) (SOCH2) (ABMX sys- 126.16, 128.24, 129.06, 129.45, 130.24,
tem), 4.30 (d, 1 H, J = 16.4,), 4.56 (d, 130.88, 131.23, 133.53, 136.67, 137.54,
1 H, J = 16.4,) (AB system, CH2),
7.22–8.07 (m, 11 H, ArH)
141.50, 162.37, 164.01 (Ar, C = N)
5f
85
89
158–160 brown
2.81 (s, 3 H, CH3), 3.31–3.39 (m,
1 H), 3.74–3.77 (m, 1 H) (CH2), 3.81– (SOCH2), 122.31, 127.56, 129.45,
3.84 (m, 1 H), 3.87–3.91 (m, 1 H) 131.37, 133.30, 134.51, 136.06, 136.33,
12.70 (CH3), 25.84, (CH2), 37.86
2961, 1560,
1469, 1046
(dec)
crystals
(SOCH2) (ABMX system), 7.37–8.09 137.54, 141.60, 162.10, 164.34
(m, 4 H, ArH)f
(Ar, C = N)f
5g
174–176 yellow
(dec) crystals
1.52 (t, 3 H, J = 7.5, CH3), 3.03 (q,
2 H, J = 7.5, CH2), 3.08–3.17 (m,
9.53 (CH3), 20.17 (CH2), 25.80 (CH2),
36.99 (SOCH2),
2963, 1562,
1472, 1050
1 H), 3.59–3.69 (m, 1 H) (CH2), 3.75– 122.72, 125.93, 128.34, 131.30, 131.85,
3.82 (m, 1 H), 3.90–3.93 (m, 1 H)
(SOCH2) (ABMX system), 7.31–
8.07 (m, 4 H, ArH)f
132.02, 133.36, 134.75, 137.18, 143.20,
164.20, 165.03 (Ar, C = N)f
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438
X. Liu et al.
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Table 1 (continued)
Prod- Yieldb Mp
Appearance 1H NMR (CD3CN/TMS)
13C NMR (CD3CN/TMS)
d
IR(KBr)
n (cm–1)
ucta
(%)
(°C)
d, J (Hz)
5h
90
178–179 yellow
(dec) crystals
1.12 (t, 3 H, J = 7.4, CH3), 1.99 (m,
2 H, CH2), 3.00 (t, 2 H, J = 7.2, CH2), 27.91 (CH2), 37.21 (SOCH2), 126.18,
3.08–3.17 (m, 1 H) (3.58–3.65 (m, 128.06, 130.09, 130.47, 131.56, 132.20,
12.49 (CH3), 19.84 (CH2), 26.02 (CH2), 2967, 1565,
1480, 1055
1 H) (CH2), 3.74–3.79 (m, 1 H), 3.81– 133.52, 133.67, 134.30, 137.40 164.38,
3.92 (m, 1 H) (SOCH2) (ABMX
165.06 (Ar, C = N)f
system), 7.32–8.06 (m, 4 H, ArH)f
5i
84
192–194 yellow
(dec) crystals
3.13–3.25 (m, 1 H), 3.64–3.74 (m,
1 H) (CH2), 3.84–3.91 (m, 1 H), 3.96– 126.18, 126.74, 127.56, 128.34, 129.05, 1479, 1050
26.30 (CH2), 37.00 (SOCH2), 125.51,
2964, 1561,
3.98 (m, 1 H) (SOCH2) (ABMX
system), 7.38–8.10 (m, 9 H, ArH)
129.54, 130.26, 130.83, 131.25, 131.42,
133.63, 137.56, 141.52, 162.47, 164.01
(Ar, C = N)
a Satisfactory microanalysis obtained: C 0.13, H 0.10, N 0.14, except for 2a, b which are oily products and used as afforded.
b After recrystallization.
c In CDCl3.
d Without further purification.
e In CCl4.
f Main component.
the proton resonances showed that the two forms exist in
an approximate 3:1 ratio. On the contrary, compounds 5d,
5e and 5i bearing a more sterically demanding substituent
at C(2) (R2 = Ph or PhCH2) are present in a single solution
form as disclosed by observation of their NMR spectra.
This may reflect the effect of the substituents located at
the fused triazole ring on the height of the activation ener-
gy for ring inversion. Increasing the size of the substituent
can enhance the energy barrier to conformer interconver-
sion and hence prevent the occurrence of the products as
a conformer mixture.
Because of the dissymmetrical arrangement of the ring
system, the four methylene protons of the CH2CH2 units
in the seven-membered ring show either A2XY (in 5a, 5b,
Figure Molecular Structure of Compound 5h
5d) or ABMX (in 5c, 5e-5i). In comparison to the sub-
strates 2a and 2b, the chemical shifts of the CH2CH2 units
in compounds 5 exhibit remarkable downfield shifts. It
shown that the molecules occur in most cases as a mixture
may be further noted that the two benzylic protons in com-
of two slowly interconverting conformers and obtained a
pound 5e as well as the two methylene protons directly
linked to C(2) in the propyl substituted 5c are not equiva-
lent. They appear as a characteristic AB system centered
value of 70-80 kJ.mol-1 for the energy barrier for ring in-
version by variable temperature NMR studies.
at 4.30 ppm and 4.56 ppm in 5e, and as the AB part of an Since we found it difficult to preclude the structure of ring
ABX2 system centered at about 3.0 ppm and 2.9 ppm in isomeric compounds 6, a crystal of salt 5h was submitted
5c. Evidently, the rotation about the C(2)-substituent and to X-ray diffraction analysis confirming the structural as-
the fused s-triazole ring in molecules 5c and 5e are hin- signment made. A perspective drawing of 5h is shown in
dered.
the Figure.
In the 13C NMR spectra of compounds 5, the chemical The thiazepine ring adopts a rigid boat configuration
shifts at about 26 and 37 ppm for the CH2-CH2 group and which can be described in terms of the dihedral angles be-
two signals between 159 and 165 ppm arising from the tween four least-squares planes: plane 1, the five atoms of
C=N carbons together with other signals are in conformity the fused triazole ring; plane 2, four atoms N1, C2, C3,
with the assigned structure.
C8; plane 3, four atoms S, C2, C9, C10 of the thiazepine
ring; plane 4, the fused phenyl ring C3, C4, C5, C6, C7,
C8. The dihedral angles between these planes are as fol-
lows: p.1-p.2 43.43; p.1-p.3 61.07; p.1-p.4 120.89; p.2-p.3
49.90; p.2-p.4 154.79; p.3-p.4 107.10∞.
Similar NMR complexity was observed by Grandolini
and his co-workers27 in the NMR and conformational
analysis of a closely related structure of 4,5-dihydro-s-tri-
azolo[3,4-d][1,5]benzothiazepines. The authors have
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An Expedient Synthesis of Novel [1,2,4]Triazolo[3,2-d][1,5]Benzothiazepine Derivatives
439
Table 2 Selected Bond Lengths [pm], Bond Angles, and Torsion Angles (deg) for 5h
Atoms
X-ray
AM1
159.2
138.8
140.2
136.7
151.1
103.0
105.5
107.4
105.7
125.2
127.3
122.4
117.0
120.2
177.1
−34.6
4.5
Atoms
X-ray
AM1
174.2
142.0
142.4
147.4
152.0
100.5
124.0
122.5
110.0
111.3
118.9
116.3
112.2
120.3
−176.4
142.9
−176.9
−5.1
Atoms
X-ray
AM1
178.3
143.5
136.7
149.5
150.7
101.3
122.8
129.6
124.8
121.9
120.8
111.3
112.9
−6.5
S-O
144.8(9)
138.2(4)
133.9(5)
133.4(6)
151.0(8)
107.9(4)
105.5(3)
107.0(3)
105.8(4)
125.5(4)
127.5(4)
121.6(3)
116.3(3)
121.4(4)
177.1(3)
−41.7(6)
1.3(5)
S-C8
178.5(5)
132.8(5)
142.6(5)
147.9(6)
150.2(8)
104.0(4)
124.4(3)
122.6(3)
110.0(4)
111.6(4)
120.4(4)
120.7(4)
112.4(4)
119.2(4)
−174.5(4)
132.9(5)
179.4(4)
−2.1(5)
S-C10
181.2(6)
143.1(5)
133.7(5)
148.4(6)
146.2(9)
101.9(2)
128.1(3)
130.0(3)
124.5(4)
120.8(4)
117.2(4)
110.1(4)
114.5(5)
−4.5(5)
N1-N2
N1-C2
N1-C3
N2-C1
N2-C14
N3-C1
N3-C2
C1-C11
C2-C9
C9-C10
C11-C12
C12-C13
O-S-C8
O-S-C10
C8-S-C10
N2-N1-C2
N1-N2-C1
C1-N3-C2
N3-C1-C11
N3-C2-C9
S-C8-C3
N2-N1-C3
C2-N1-C3
N1-N2-C14
N2-C1-N3
C1-N2-C14
N2-C1-C11
N1-C2-C9
N1-C2-N3
N1-C3-C4
N1-C3-C8
S-C8-C7
C2-C9-C10
C11-C12-C13
S-C8-C3-N1
S-C10-C9-C2
O-S-C10-C9
N1-N2-C14-C15
N1-C2-C9-C10
N2-N1-C2-C3
N2-C1-C11-C12
N3-C1-N2-C14
N3-C2-C9-C10
C1-N2-C14-C19
C2-N1-N2-C14
C2-N3-C1-C11
C3-C8-S-C10
C11-C1-N2-C14
S-C10-C9
N2-C14-C15
S-C8-C3-C4
O-S-C8-C3
N1-N2-C1-N3
N1-N2-C14-C19
N1-C3-C4-C5
N2-N1-C3-C8
C1-C11-C12
N2-C14-C19
S-C8-C7-C6
O-S-C8-C7
N1-N2-C1-C11
N1-C2-N3-C1
N1-C3-C8-C7
N2-C1-N3-C2
N2-C14-C19-C18
N3-C2-N1-C3
C1-N2-C14-C15
C1-C11-C12-C13
C2-N1-C3-C8
C3-N1-C2-C9
C8-S-C10-C9
−38.0(5)
71.7(5)
−32.2
61.0
−86.5(5)
80.9(5)
−103.8
84.1
92.4(5)
76.3
178.4(4)
114.0(4)
−177.3
110.4
−177.6
99.3
−179.3(4)
0.4(5)
176.1
0.3
2.9(4)
−150.5
−78.1
170.4
−97.5
−87.9
−174.2
−178.2
69.1
−76.0(6)
174.3(4)
−94.8(6)
−79.8(6)
−176.2(4)
−177.7(4)
67.4(4)
N2-C14-C15-C16 −179.6(4)
179.8(4)
167.5(4)
101.4(5)
−53.6(7)
−48.0(6)
−8.9(6)
177.6
158.4
92.0
N3-C1-C11-C12
C1-N2-N1-C3
C1-N3-C2-C9
C2-N1-C3-C4
C3-N1-N2-C14
C7-C8-S-C10
101.8(6)
−167.8(4)
174.0(4)
130.4(4)
18.5(6)
−157.3
176.3
140.8
35.8
−59.2
−35.6
−23.0
−44.7
−118.0(4)
−113.3
−40.4(4)
−7.5(7)
−10.7
Pennini28 has reported that the seven-membered ring, Å in pyridine.30 For a N=N+double bond in a 1,2,4-triazo-
which is unstable, can be converted to two conformations lium salt 1.243(5) Å and for C-N single bonds values of
in the crystal. The pentatomic ring is essentially planar. about 1.48 Å have been published by other research
The ring contains an apparently long N1-N2 distance of groups.31-33 These bond lengths indicate a delocalization
1.382(4) Å characteristic for a single N-N bond; howev- of electron density in the pentatomic ring supporting our
er, it is slightly shorter than a N-N single bond with a val- view that the dominant contribution to the structure comes
ue of 1.401 Å as reported by Allen.29 On the other hand, from the two resonance hybrids 5h and 5h’ (Scheme). It
the other four bond lengths in the triazole ring are nearly follows that the positive charge is predicted to distribute
equal with values between 1.328(5) to 1.339(5) Å which mainly over the N1 and N2 atoms. All the bond lengths
refer to partial double bond length 1.332(3) Å and coin- and bond angles in the two aryl rings are normal as both
cide well with those of delocalized systems such as 1.338 rings are planar. Due to hindered rotation about the N2-
Synthesis 2000, No. 3, 435–441 ISSN 0039-7881 © Thieme Stuttgart · New York

440
X. Liu et al.
PAPER
1h while maintaining the temperature under -5 ∞C, the resulted so-
lution was dried (CaCl2). Thorough removal of volatiles by rotary
evaporation left the a-chloroazo compound as a red oil, which was
a relatively clean product as shown by NMR analysis (Table 1).
C14 bond, the pentafluorophenyl ring at N2 is perpendic-
ularly oriented to the triazolo ring with a dihedral angle of
96.51∞. Together with the rather long N2-C14 bond dis-
tance [1.426(5) Å] which is indicative of a C(sp2)-N sin-
gle bond, the conclusion can be made that there is no
conjugation between the two rings. The S-C10 bond
length of 1.812(6) Å is slightly longer than the S-C8 bond
length of 1.785(5) Å, however, both data are normal and
compete well with the bond distance of 1.809 Å for a C-
S(=O)-C system and that of 1.790 Å for a Caromatic-S(=O)-
C system provided by Allen.29 Finally, the octahedral ori-
Reaction of the a-Chloroazo Compounds 2 with Nitriles; Gen-
eral Procedure
To a solution of 2 (10 mmol) and the appropriate nitrile (16 mmol)
in anhyd CH2Cl2 (15 mL) was added dropwise a solution of SbCl5
(3.60 g, 12 mmol) in CH2Cl2 (10 mL) at -40 ∞C. The mixture was
allowed to react under stirring at the same temperature for an addi-
tional 1h. Subsequently, the reactants were warmed up gradually to
30 ∞C (oil bath temperature) and kept at this temperature for 10-15
min to make sure that the ring expansion has proceeded completely.
To the resulting deep colored mixture was added Et2O (120 mL) and
the precipitate separated to furnish the heterocycles 5. Recrystalli-
zation from MeOH gave analytically pure 5 (Table 1).
–
entation of the counter ion SbCl6 is not exceptional.
The X-ray results may be compared with the data
achieved by AM1 calculations (Table 2).34,35 While com-
parison between most of the calculated and measured pa-
rameters is in good accordance, the O-S bond length was
calculated too long (approx. 15 pm). In addition, the pen-
tafluorophenyl position was calculated to be deformed by
approximately 17∞, as can be seen from the deviations be-
tween calculated and measured torsion angles: N1-N2-
C14-C19 [found 92.4(5)∞, calculated 76.3∞], N1-N2-C14-
C15 [found -86.5(5)∞, calculated -103.8∞], C3-N1-N2-
C14 [found 18.5(6)∞, calculated 35.8∞]. Packing effects in
the crystal may account for the discrepancies between the
calculated and measured torsion angles.
X-Ray diffraction analysis of 5h
The suitable crystal for an X-ray diffraction analysis was obtained
from MeOH (Table 2). [C19H15F5N3OS]SbCl6, yellow prismatic,
size about 0.20 × 0.20 × 0.30 mm. FW = 762.88; triclinic, space
group P1(#2), a = 11.606(3), b = 11.911(3), c = 9.972(3) Å;
a = 100.32(2)∞, b = 90.50(2)∞, g = 96.36(2)∞; V = 1347.3(6) Å3;
Z = 2; Dcalc = 1.880 g/cm3, w-2q scan, scan width (1.84+0.30 tan
q)∞; 18.72 < 2q < 24.20∞; F (000) = 744.00; mMo-Ka = 17.49 cm-1;
T = 293 K. A total of 5001 reflections were measured on a Rigaku
AFC7R diffractometer with graphite monochromated Mo-Ka radi-
ation (l = 0.71069 Å); 4746 independent reflections, 4124 observed
reflections (I > 3.00s (I)). The structure was solved by heavy-atom
Patterson methods and expanded using Fourier techniques. The re-
finement converged at R = 0.041 and Rw = 0.054 for all data.
In summary, we have defined an expedient synthetic entry
to a new [1,2,4]triazolo[3,2-d][1,5]benzothiazepine het-
erocyclic ring system based on a cationic [3++2] polar cy-
cloaddition. The ready availability of the starting
materials, the simplicity of the performance and the op- Acknowledgement
portunity for incorporation of a reasonably diverse range
The authors are grateful for financial support by National Natural
Science Foundation of China (Project No. 29872007).
of substituents render this chemistry especially profitable
to the ever-present quest for novel pharmaceutical and re-
lated compounds.
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Synthesis 2000, No. 3, 435–441 ISSN 0039-7881 © Thieme Stuttgart · New York