The synthesis and crystal structure of new 3,6-bis[1-(4-ethoxyphenyl)-5- methyl-1,2,3- triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole

Article abstract of DOI:10.1007/s10870-005-1155-6

The 3,6-bis[1-(4-ethoxyphenyl)-5-methyl-1,2,3-triazol-4-yl]-s-triazolo[3,4- b]-1,3,4-thiad- iazole was synthesized from p-ethoxyaniline to 8 with 1-(4-ethoxyphenyl)-5-methyl-1,2,3-triazol-4-caroxylic acid. The yielded product 9 was investigated with X-ray

Full text of DOI:10.1007/s10870-005-1155-6

Journal of Chemical Crystallography, Vol. 35, No. 1, January 2005 (ꢀC 2005)
DOI: 10.1007/s10870-005-1155-6
The synthesis and crystal structure of new
3,6-bis[1-(4-ethoxyphenyl)-5-methyl-1,2,3-
triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole
Heng-Shan Dong(1)∗ and Bin Wang(2)
Received April 5, 2004; accepted August 24, 2004
The 3,6-bis[1-(4-ethoxyphenyl)-5-methyl-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiad-
iazole was synthesized from p-ethoxyaniline to 8 with 1-(4-ethoxyphenyl)-5-methyl-1,2,3-
triazol-4-caroxylicacid. Theyieldedproduct9wasinvestigatedwithX-raycrystallographic,
NMR, MS, and IR techniques. Compound 9, C25H24N10O2S, Mr = 528.60, crystallizes in
¯
the triclinic space group P1 with unit cell parameters a = 6.4490(10), b = 11.481(2),
◦
3
˚
˚
c = 18.168(4) A, α = 72.08(3), β = 86.57(3), γ = 86.72(3) . V = 1276.6(4) A , Z = 2,
Dx = 1.375 Mgm−3. The final R was 0.0589.
KEY WORDS: Crystal structure; 1,2,3-triazole; s-triazolo[3,4-b]-1,3,4-thiadiazole; synthesis.
Introduction
components—thiosemicarbazide and biguanide,
which often display diverse biological activities.
Therefore, it is worthwhile to investigate the sys-
tem, combining these three biologically active
components in a compact system for screening
of their biologic activities.
We have reported the crystalline structure
of 2-(3-bromoanilino)-5-[5-amino-1-(4-chlorop-
henyl)-1,2,3-triazole-4-yl]-1,3,4-thiodiazole and
their derivatives.4–6 Recently, we obtained a novel
compound 3,6-bis[1-(4-ethoxyphenyl)-5-methyl-
1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadia-
zole. The route of syntheses is in Scheme 1.
It is reported that the 1,3,4-triazole nucleus,
1,2,3-triazole nucleus, some new 1,3,4-triazole
derivatives, and the 1,2,3-triazole derivatives
possess multiformity biological and medication
activities.1 Likewise the 1,3,4-thiadiazole nu-
cleus which incorporates an N C S linkage ex-
hibits a large number of biological activities.2
The fused 1,3,4-triazolo[3,4-b]-1,3,4-thiadiazole
derivatives show various biological effects, such
as antifungal,3 antibacterial, and CNS depressant
activities.4 A triazolo-thiadiazole system may be
viewed as a cyclic analog of two very important
Experimental section
(1) National Laboratory of Applied Organic Chemistry, Institute
of Organic Chemistry, College of Chemistry and Chemical
Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R.
China.
(2) College of Science and Engineering, Gansu Association
University, Lanzhou, Gansu 730000, P. R. China.
*To whom correspondence should be addressed; e-mail:
donghengshan@lzu.edu.cn.
All melting points were uncorrected and de-
termined on an XT4-100x microscopic melting
point apparatus. IR spectra were obtained in KBr
discs on a Shimadzu IR-435 spectrometer. MS
were performed on a HP-5988A spectrometer (EI
61
ꢀ
C
1074-1542/05/0100-0061/0 2005 Springer Science+Business Media, Inc.

62
Dong and Wang
Preparation of ethyl 1-(4-ethoxyphenyl)-5-
methyl-1,2,3-triazol-4-carboxyate 5 was follow-
ing method in the literature.1
The yield of 5 (a white crystalline solid,
1
mp 113–114◦C) was 23.4 g (85.0%). HNMR:
7.304–7.349 (d, 2H, J = 9.0 Hz, Ar1-3,5), 7.000–
7.045 (d, 2H, J = 9.0 Hz, Ar1-2,6), 4.399–
4.505 (q, 2H, J = 7.0 Hz, TRZ1CO2CH2-),
4.042–4.146 (q, 2H, J = 6.8 Hz, Ar1OCH2-),
2.540 (s, 3H, TRZ1-CH3), 1.417–1.487 (t,
3H, J = 7.0 Hz, TRZ1CO2CH2CH3), 1.402–
1.472 (t, 3H, J = 6.8 Hz, Ar1OCH2CH3). MS:
275(M†, 45), 247(M-28 N2 or CH2 CH2, 1),
230(M-45 CH3CH2O, 10), 218(M-57 N2
CH3CH2,− 17), 202 (M CH3CH2OCO, 10),
190(27), 174(58), 146(100), 121(10), 83(86),
65(68). IR: 3411, 3091, 2983, 2935, 2884, 1717,
1593, 1563, 1516, 1435, 1375, 1349, 1248, 1222,
1120, 1103, 1049, 1023, 983, 837, 786 cm−1.
1-(4-Ethoxyphenyl)-5-methyl-1,2,3-triazol-
4-carbonylhydrazine 6 was prepared from 5
following procedure method in the literature.1
The yield of compound is 93.0%, mp
1
222–223◦C. HNMR: 7.477–7.521 (d, 2H, J =
8.8 Hz, Ar1-3,5), 7.095–7.139 (d, 2H, J =
8.8 Hz, Ar1-2,6), 4.450–4.720 (broad peak, 3H,
NHNH2), 4.054–4.157 (q, 2H, J = 7.0 Hz,
Ar1OCH2−), 2.474 (s, 3H, TRZ1 CH3), 1.315–
1.385 (t, 3H, J = 7.0 Hz, Ar1OCH2CH3). MS:
261(M†, 72), 217(5), 204(42), 202(25), 174(49),
162(20), 146(86), 134(15), 121(16), 119(21),
83(31), 77(25), 69(50), 65(66), 57(77), 43(100).
IR: 3307, 3264, 3213 (N H), 2979, 2931, 1669
(C O), 1639, 1608, 1587, 1516, 1476, 1447,
1269, 1249 (Are O R), 1119, 1045, 959 (1,2,3-
triazole ring), 845, 658 cm−1.
Scheme 1
1
at 70 eV). H NMR spectroscopy (CDCl3) were
recorded on Avance Mercury plus-300 instrument
with TMS as an internal standard. Elemental anal-
yses were carried out on a Yanaco CHN Corder
MT-3 analyzer.
Phosphorus oxychloride was redistilled
(bp 105).
1-(4-ethoxyphenyl)-5-methyl-1,2,3-triazol-
4-caroxylic acid 4 were prepared following
methods in the literature.7,8 Mp166–167◦C.
1-Amino-5-[1-(4-ethoxyphenyl)-2-mercapto-
5-methyl-1,2,3-triazol-4-yl]-1,3,4-triazole 8 was
prepared from 6 via 7 following the method
reported in the literature.1
The compound 8 is white flak, 17.8 g (70%
1
yield), mp 204–205◦C. HNMR: 7.371–7.400(d,
2H, J = 8.7 Hz, Ar1-3,5), 7.047–7.076(d, 2H,
J = 8.7 Hz, Ar1-2,6), 4.080–4.150(q, 2H, J =
7.0 Hz, Ar1 OCH2 ), 2.525(s, 3H, TRZ1 CH3),
2.521(s, 1H, SH), 1.620–1.840(broad peak,

Synthesis and crystal structure
63
2H, NH2), 1.449–1.497(t, 3H, J = 7.0 Hz,
Ar1 OCH2CH3). MS: 317(M†, 16), 302(1),
285(1), 273(3), 260(5), 201(3), 194(17), 179(8),
173(3), 171(11), 151(11), 137(13), 121(100),
111(7), 105(23), 95(10), 83(10), 77(17), 69(16),
57(16), 55(20), 43(19). IR: 3449, 3281(N H),
3186, 3111, 2974, 2942, 2838, 2783(S H),
1632, 1610(C N), 1519, 1499, 1467, 1291,
1254(Ar O R), 1174, 1019, 949(1,2,3-triazole
ring), 840, 669.
crystal was obtained after 15 d by evaporation of
the solvent.
Single crystals were selected and mounted
on the tip of a glass fiber. Preliminary examination
and data collection were performed with MoKα
˚
radiation(λ = 0.71073 A) on an Enraf-Nonius
CAD4 computer controlled kappa axis diffrac-
tometer operating in the ω/2θ scanning mode.
The structure was determined by direct methods
(SHELXS-86) and refined by full covariance ma-
trix methods (SHELXL-97). The crystal data and
the refinement details are given in Table 1.
General procedure of preparation of 3,6-bis
[1-(4-ethoxyphenyl)-5-methyl-1,2,3-triazol-4-yl]-
s-triazolo[3, 4- b]-1, 3, 4-thiadiazole derivatives
9.
The structure of the title compound is shown
inFig. 1. Theunitcellparametersofthecompound
9 are shown in Fig. 2 (The coordinate of the unit
A mixture of 1-amino-5-[1-(4-ethoxyphenyl)-
5-methyl-1,2,3-triazol-4-yl]-2-mercapto-1,3,4-
triazole 8 (1 mmol). 1-(4-ethoxyphenyl)-5-methyl
-1,2,3-triazol-4-caroxylic acid (1 mmol) and
POCl3 (5 mL) was heated under refluxing for
6 h with stirring. The cooled reaction mixture
was poured into crushed ice and made alkaline
by adding potassium hydroxide, and then the
resulting solid was filtered and dried. The solid
was purified by chromatography on a column
of silica gel and eluted successively with 2:1
ethyl acetate–petroleum ether to give colorless
block of Compound 9 Yield 72%, mp 226–
227◦C. 1HNMR: 7.375–7.463 (2d, 4H, J =
8.1 Hz, Ar1, Ar2-2,6), 7.046–7.097 (d, 4H,
J = 8.1 Hz, Ar1, Ar2-3,5), 4.082–4.152 (2q,
4H, J = 7.2 Hz, Ar1, Ar2 OCH2 ), 2.726,
2.755 (2s, 6H, Ar1, Ar2 CH3), 1.448–1.495 (t,
6H, J = 7.2 Hz, Ar1, Ar2 OCCH3). MS M/z:
528(M†, 1.7%), 500(M-28, N2 or CH2 CH2,
57), 471(M-28-28, 25), 443(M-28-28-28, 2),
313(3), 285(3), 257(7), 245(10), 228(6), 215
cell is 1);
2);
) The selected bond
lengths are given in Table 2, selected bond angles
Table 1. Crystal Data and Structure Refinement Details
Empirical formula
CCDC deposit no
Formula weight
Temperature, K
C25H24N10O2S
235478
528.60
293(2)
˚
Wavelength, A
0.71073
25
Reflns. for cell determination
2θ range for above
Crystal system
Space group
Cell dimensions
10◦–20◦
triclinic
¯
P1
a = 6.4490(10)
b = 11.481(2)
˚
c = 18.168(4) A
α = 72.08(3)
β = 86.57(3)
γ = 86.72(3)◦
1276.6(4)
3
˚
Volume, A
Z
2
Density(calculated)
Absorption coefficient
F(000)
θ range for data collection
Index ranges
1.375 mg/m3
0.172 mµ−1
552.0
4.19◦–21.26◦
0 ≤ h ≤ 6;
−11 ≤ k ≤ 11;
−18 ≤ l ≤ 18
2820
(18), 200(39), 186(11), 172(
100),
171(91), 159(12), 146(31), 137(14), 129(12),
Reflections collected
123(17), 115(14), 111(27), 97(50), 91
(31), 83(57), 77(27), 71(56), 65(49), 57(75),
44(69). IR: 3067, 2981, 2920, 1608, 1584, 1516,
1462, 1303, 1255, 1172, 1115, 1045, 967, 947,
843, 782, 721.
Independent reflection
Data/Restrains/Parameters
Goodness-of-fit on F2
Final R indices [I > σ2(I)]
1614
2820/0/344
1.084
R1 = 0.0589,
wR2 = 0.1401
R1 = 0.1390,
wR2 = 0.1590
R indices
The purified product was dissolved in chlo-
roform, petroleum ether, and ethanol solvent. The
−3
˚
Largest diff. Peak and hole
0.282 and −0.206 eA

64
Dong and Wang
˚
Table 2. Selected Bond Lengths (A)
Atoms
Length
S1 C13
S1 C14
O1 C3
1.734(12)
1.752(11)
1.328(13)
1.389(15)
1.366(12)
1.438(13)
1.339(12)
1.351(11)
1.435(13)
1.287(11)
1.327(12)
1.292(12)
1.406(11)
1.297(12)
1.341(10)
1.356(12)
1.381(11)
1.300(11)
1.284(10)
1.385(11)
1.381(10)
1.396(11)
1.401(11)
1.491(17)
1.358(15)
1.387(15)
1.398(16)
1.395(15)
1.340(14)
1.351(14)
1.371(13)
1.474(15)
1.457(14)
1.438(13)
1.340(12)
1.455(12)
1.343(13)
1.398(13)
1.377(12)
1.368(12)
1.355(13)
1.400(13)
1.409(16)
O1 C2
O2 C23
O2 C24
N1 C9
N1 N2
N1 C6
Fig. 1. ORTEP diagram of the compound 9 showing 50%
thermal ellipsoids.
N2 N3
N3 C11
N4 C12
N4 N5
N5 C13
N6 N7
N6 C13
N6 C12
N7 C14
N8 N9
N8 C15
N9 N10
N10 C16
N10 C20
C1 C2
C3 C4
C3 C8
C4 C5
C5 C6
C6 C7
C7 C8
C9 C11
C9 C10
C11 C12
C14 C15
C15 C16
C16 C17
C18 C19
C18 C23
C19 C20
C20 C21
C21 C22
C22 C23
C24 C25
are given in Table 3. The geometric calculations
were performed using the program SHELX-97.
Results and discussion
The structure of the title compound is
shown in Fig. 1. In recent years the syn-
thesis and characteristics of s-triazolo[3,4-b]-
1,3,4-thiadiazoles have been investigated.1 These
heterocyclic compounds contain 1,2,4-triazole
and 1,3,4-thiadiazole rings condensed through
a C N bond. In a continuation of our earlier
studies,4 we now report the crystal structure
of 3,6-bis[1- (4-ethoxyphenyl) - 5 -methyl-1,2,3-
triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole9.
The bond lengths indicate a degree of delo-
calization around the ring system with the three
C N bonds ranging from N4 C12 1.292(12),
˚
N5 C13 1.297(12) to N7 C14 1.300(11)A and
Fig. 2. The unit cell parameters of the compound 9.

Synthesis and crystal structure
65
Table 3. Selected Bond Angles (◦)
the N N bond lengths ranging from N6 N7
1.341(10) to N4 N5 1.406(11)A.
˚
Atoms
Angle
The 1,2,3-triazole ring system is pla-
C13 S1 C14
C3 O1 C2
C23 O2 C24
C9 N1 N2
C9 N1 C6
N2 N1 C6
87.3(5)
118.4(11)
120.9(9)
111.7(8)
129.0(9)
119.3(9)
106.0(8)
110.2(8)
110.5(8)
103.7(8)
118.5(8)
136.8(8)
104.6(8)
108.7(8)
107.9(8)
109.2(7)
108.1(7)
120.5(7)
131.3(7)
109.1(13)
125.8(11)
116.0(12)
118.0(10)
119.5(11)
120.3(11)
119.3(10)
122.2(9)
118.4(10)
120.0(10)
122.8(11)
102.8(9)
123.5(10)
133.4(11)
109.3(9)
122.9(9)
127.9(10)
108.1(9)
129.3(9)
122.3(9)
113.0(9)
137.8(8)
109.1(8)
122.4(9)
116.4(7)
121.2(8)
110.5(8)
128.9(9)
120.4(9)
104.4(7)
132.9(9)
122.5(8)
119.9(9)
121.4(9)
119.1(9)
120.3(8)
120.6(8)
121.1(9)
119.7(9)
116.8(9)
124.6(9)
118.6(10)
108.6(11)
nar. The bond lengths N1 N2 1.351(11),
˚
N9 N101.381(10)A, N2 N31.287(11), N8 N9
˚
1.284(10)A are in agreement with the values re-
˚
ported for triazole, N N 1.352A by Fenean-
Dupont9 and Huang.10 The bond lengths C10 N3
N3 N2 N1
N2 N3 C11
C12 N4 N5
C13 N5 N4
N7 N6 C13
N7 N6 C12
C13 N6 C12
C14 N7 N6
N9 N8 C15
N8 N9 N10
N9 N10 C16
N9 N10 C20
C16 N10 C20
O1 C2 C1
O1 C3 C4
O1 C3 C8
C4 C3 C8
C3 C4 C5
C6 C5 C4
C7 C6 C5
C7 C6 N1
C5 C6 N1
˚
˚
1.359(6)A and C9 N1 1.343(6)A are between the
bond lengths of C N and C N.
There aren’t the strong interactions of hydro-
gen bond on the molecular stacking but weak in-
termolecular interaction of the pi–pi. The plane of
1,2,3-triazole ring, benzene ring, and fused 1,3,4-
triazolo[3,4-b]-1,3,4-thiadiazole ring system is
parallel to each other on intermolecular. It is
shown in Fig. 2.
The dihedral angle (◦) of 1,2,3-triazole and
benzene ring plane is between 50 and 90, there
isn’t the conjugate of the pi–pi. The dihedral angle
(◦) of 1,2,3-triazole and fused 1,3,4-triazolo[3,4-
b]-1,3,4-thiadiazole ring plane is between 165 and
180, there is the conjugate of the pi–pi.
C6 C7 C8
C7 C8 C3
N1 C9 C11
N1 C9 C10
C11 C9 C10
N3 C11 C9
N3 C11 C12
C9 C11 C12
N4 C12 N6
N4 C12 C11
N6 C12 C11
N5 C13 N6
N5 C13 S1
N6 C13 S1
N7 C14 C15
N7 C14 S1
C15 C14 S1
C16 C15 N8
C16 C15 C14
N8 C15 C14
C15 C16 N10
C15 C16 C17
N10 C16 C17
C19 C18 C23
C18 C19 C20
C21 C20 C19
C21 C20 N10
C19 C20 N10
C22 C21 C20
C21 C22 C23
O2 C23 C18
O2 C23 C22
C18 C23 C22
C25 C24 O2
Acknowledgments
The authors wish to acknowledge this project
is supported by NNSFC(chuangxin qunti) and
Lanzhou University SKLAOC.
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