Synthesis, Structure, and Properties of the 2-[5-(Aryloxyacetyl)-Amino-1,3,4-Thiadiazol-2-Ylthio] Propionate Derivatives

Article abstract of DOI:10.1080/10426507.2013.858251

A series of novel 2-[5-(aryloxyacetyl)-amino-1,3,4-thiadiazol-2-ylthio] propionate derivatives were synthesized in high yield, and their structures were characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis, coupled with one selected single-crystal X-ray structure determination. The herbicidal activities of target compounds were assessed. The preliminary bioassay results showed that some compounds exhibited moderate to strong herbicidal symptoms in preemergence and postemergence tests. At 150 g/ha, S. tritici. show tolerance, while E. crus-galli L., E. Dahuricus, A. retroflexus, and C. glaucum L. were killed or severely injured. The activity of some compounds was comparable to the commercial herbicide 2,4-D. A suitable electron-withdrawing substituent at the 2-and/or 4-position of the phenyl ring was essential for high herbicidal activity. Moreover, the antifungal activities of the compounds have also been studied. The compounds were found to possess broad-spectrum antifungal activity.

Full text of DOI:10.1080/10426507.2013.858251

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Phosphorus, Sulfur, and Silicon and the
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Synthesis, Structure, and Properties of
the 2-[5-(Aryloxyacetyl)-Amino-1,3,4-
Thiadiazol-2-Ylthio] Propionate
Derivatives
Bing Huab, Yue-Yuan Zhaia, Ling Zhanga, You-Ming Zhanga & Tai-Bao
Weia
a Key Laboratory of Eco-Environment-Related Polymer Materials,
Ministry of Education of China; Key Laboratory of Polymer Materials
of Gansu Province; College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu, 730070, P. R. China
b College of Science, Gansu Agricultural University, Lanzhou, Gansu,
730070, P. R. China
Accepted author version posted online: 13 Mar 2014.Published
online: 21 Aug 2014.
To cite this article: Bing Hu, Yue-Yuan Zhai, Ling Zhang, You-Ming Zhang & Tai-Bao Wei (2014)
Synthesis, Structure, and Properties of the 2-[5-(Aryloxyacetyl)-Amino-1,3,4-Thiadiazol-2-Ylthio]
Propionate Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 189:9, 1337-1345,
DOI: 10.1080/10426507.2013.858251
To link to this article: http://dx.doi.org/10.1080/10426507.2013.858251
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Phosphorus, Sulfur, and Silicon, 189:1337–1345, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.858251
SYNTHESIS, STRUCTURE, AND PROPERTIES OF THE
2-[5-(ARYLOXYACETYL)-AMINO-1,3,4-THIADIAZOL-2-
YLTHIO] PROPIONATE DERIVATIVES
Bing Hu,1,2 Yue-Yuan Zhai,1 Ling Zhang,1 You-Ming Zhang,1
and Tai-Bao Wei1
1Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of
Education of China; Key Laboratory of Polymer Materials of Gansu Province;
College of Chemistry and Chemical Engineering, Northwest Normal University,
Lanzhou, Gansu, 730070, P. R. China
2College of Science, Gansu Agricultural University, Lanzhou, Gansu, 730070, P. R.
China
GRAPHICAL ABSTRACT
Abstract A series of novel 2-[5-(aryloxyacetyl)-amino-1,3,4-thiadiazol-2-ylthio] propionate
derivatives were synthesized in high yield, and their structures were characterized by IR,
1H NMR, 13C NMR, and elemental analysis, coupled with one selected single-crystal X-
ray structure determination. The herbicidal activities of target compounds were assessed.
The preliminary bioassay results showed that some compounds exhibited moderate to strong
herbicidal symptoms in preemergence and postemergence tests. At 150 g/ha, S. tritici. show
tolerance, while E. crus-galli L., E. Dahuricus, A. retroflexus, and C. glaucum L. were killed or
severely injured. The activity of some compounds was comparable to the commercial herbicide
2,4-D. A suitable electron-withdrawing substituent at the 2- and/or 4-position of the phenyl ring
was essential for high herbicidal activity. Moreover, the antifungal activities of the compounds
have also been studied. The compounds were found to possess broad-spectrum antifungal
activity.
Keywords 1,3,4-thiadiazole; phenoxy acid; crystal structure; biological activity
Received 1 July 2013; accepted 17 October 2013.
Address correspondence to Tai-Bao Wei, College of Chemistry and Chemical Engineering, Northwest
Normal University, Lanzhou, Gansu 730000, P. R. China. E-mail: weitaibao@126.com
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
1337

1338
B. HU ET AL.
INTRODUCTION
Heterocyclic compounds, as the main sources of lead molecules, play an important
role in agrochemicals. In the 1960s, Merck & Co. Int. discovered and developed thiaben-
dazole as a fungicide.1 Afterward, many thiazoles including a number of widely used
fungicides (e.g., tricyclazole, probenazole, and trifluzamide) and herbicides (e.g., buthi-
uron, thiazfluron, and tebuthiuron) have been introduced into the pesticide market.2 1,3,4-
Thiadiazoles, as an important class of sulfur-containing compounds with various interesting
properties, are becoming a rapidly growing and independent branch of the chemistry of thi-
azoles.3,4 They displayed a wide range of biological and pharmaceutical activities and have
attracted considerable attention. Some of them exhibited anti-HIV, insecticidal, fungicidal,
antiviral activities, and herbicidal activity.5–9
A variety of substituted phenoxy acids exhibit plant growth regulating and herbicidal
activity. Substituents that are most effective in enhancing these activities are halogens
and methyl groups.10 The development of phenoxyalkanoic acid herbicides dates from the
1940s. 2,4-D (2,4-dichlorophenoxy acetic acid) is the successful representative, which is a
readily systemic herbicide. The toxicity, herbicidal effects and environmental persistence
have been studied in detail.11 The presence of an alkyl ester often leads to increased lipid
solubility and the 2-substituted ethyl propionate as a reactive group is widely used in
pesticides (e.g., Fenoxaprop-ethyl, Fentiaprop-ethyl, and Quizalofop-ethyl).12
In order to continue the research in thiadiazoles and aryloxycarboxylic acid biological
interests,13,14 we decided to introduce the phenoxy acid and propionate as active groups
into the thiadiazole molecule to improve their herbicidal activity, in this paper. Thus, a
series of 2-[5-(aryloxyacetyl)-amino-1,3,4-thiadiazol-2-ylthio] propionate derivatives were
synthesized, characterized and their herbicidal activity was evaluated. Surprisingly, several
compounds also exhibit favorable fungicidal activities. The synthetic route of compounds
is shown in Scheme 1.
RESULTS AND DISCUSSION
Syntheses and Characterization
A number of aryloxyacetic acid analogues have been reported as herbicides, which
provided a guide to here synthesis. As a first step, 2 were prepared by the reaction of
2-amino-5-mercapto-1,3,4-thiadiazole and ethyl 2-bromopropionate in aqueous media.
Then, aryloxyacetic acid was acylated with thionyl chloride to provide acyl chloride 5
in high yield. Finally, 5 upon further reaction with 2 gave 2-[5-(aryloxyacetyl)-amino-
1,3,4-thiadiazol-2-ylthio] propionate derivatives 6a to 6i in moderate reaction yields. The
synthetic route is shown in Scheme 1.
A characteristic feature of IR spectra in the 6 series is the strong absorption by N H
and C O groups. For example, 6a shows strong stretching vibration of the C O group at
1730 cm−1 and of the N H group at 3173 cm−1. In the 1H NMR spectra, a characteristic
feature in the 6 series is the presence of singlet signals in low fields belonging to an NH
proton. Taking 6a as an example, the protons of NH groups appear as one singlet signal at
10.63 ppm (Figure S1 Supplemental Materials).
The structure of 6f was further identified by a single-crystal X-ray diffraction analysis
(Figure 1). The heterocyclic ring is planar within experimental error and the heterocyclic
bond distances compare well with those of related molecules.15,16 The dihedral angle formed
by the trichlorobenzene and the thiadiazole ring is 12.24(129)◦. In the crystal structure,

SYNTHESIS, STRUCTURE, AND PROPERTIES
1339
Scheme 1
intermolecular N1–H1···N6, N4–H4···N2 hydrogen bonds form centrosymmetric dimers
(Figure S3). Selected bond lengths and angles are listed in Table 1. Hydrogen bonding
parameters are shown in Table S1.
Biological Activity
Herbicidal Studies. As an initial evaluation, all of the title compounds were tested
at a dosage of 150 g ai/ha for preemergence and postemergence herbicidal activities on
E. dahuricus, E. crus-galli L., A. retroflexus, C. glaucum L., Brassica chinensis L., and
Figure 1 Molecular structure of the title compound 6f, with 50% probability thermal ellipsoids. Color code: Cl,
green; O, red; N, blue; S, yellow; C, gray. H atoms are omitted for clarity.

1340
B. HU ET AL.
Table 1 Selected bond distances (Å) and angles (◦) for 6f
C1–Cl1
1.737(5)
C3–Cl2
1.759(5)
Bond lengths
C4–Cl3
1.720(5)
C6–O1
C8–O2
C9–N1
C10–S2
C11–C12
C13–O4
N2–N3
1.384(5)
1.181(5)
1.382(5)
1.738(5)
1.496(7)
1.333(6)
1.396(5)
C7–O1
C8–N1
C9–S1
C10–S1
C11–S2
C14–O4
1.447(5)
1.409(5)
1.711(5)
1.790(5)
1.866(5)
1.346(7)
C7–C8
C9–N2
C10–N3
C11–C13
C13–O3
C14–C15
1.529(6)
1.347(5)
1.298(6)
1.373(7)
1.137(6)
1.513(11)
Bond angles
C2–C1–Cl1
C4–C3–Cl2
O1–C6–C5
O2–C8–N1
N2–C9–N1
N3–C10–S2
C13–C11–C12
O3–C13–O4
O4–C14–C15
C10–N3–N2
C9–S1–C10
118.5(3)
123.2(4)
125.3(4)
121.1(4)
123.1(4)
123.3(4)
108.7(5)
129.7(5)
111.2(7)
109.5(3)
86.4(2)
C6–C1–Cl1
C5–C4–Cl3
O1–C6–C1
O2–C8–C7
N2–C9–S1
N3–C10–S1
C13–C11–S2
O3–C13–C11
C9–N1–C8
C6–O1–C7
C10–S2–C11
118.3(3)
119.1(4)
118.0(4)
122.2(4)
113.3(3)
115.9(4)
109.1(4)
122.8(5)
124.0(4)
121.0(4)
102.9(2)
C2–C3–Cl2
C3–C4–Cl3
O1–C7–C8
N1–C8–C7
N1–C9–S1
S2–C10–S1
C12–C11–S2
O4–C13–C11
C9–N2–N3
C13–O4–C14
119.3(4)
118.9(4)
106.4(4)
116.7(4)
123.5(3)
120.8(3)
111.6(4)
107.3(5)
114.9(4)
116.9(5)
S. tritici. Compounds 2,4-D was selected as control. In general, the compounds were
more active on monocotyledonous than dicotyledonous species with the difference being
most apparent in postemergence evaluations (Table S1). Especially, the title compounds
6f displayed notable herbicidal activity higher than commercial herbicide 2,4-D in some
cases.
It’s particularly worth noting that most compounds showed a high degree of selectivity
with wheat in both preemergence and postemergence assays. For example, compound 6e
Table 2 Crystallographic and data collection parameters for 6f
Compound
6f
Empirical formula
Formula weight
Crystal system
Space group
C15H14Cl3N3O4S2
470.76
triclinic
P-1
11.233(9), 13.327(8), 14.317(2)
100.88(4)◦, β=98.50(5)◦, 113.95(7)◦
1862.4(19), 4
1.679
a, b, c (Å)
α βγ (◦)
V (Å3), Z
Calculated density(g cm−3
F(000)
)
960
Absorption coefficient (mm−1
Reflections collected/unique
θ range for data collection (O)
Data/restraints/parameters
Goodness-of-fit on F2
)
0.745
12342,6524
3.11–25.00
6524 / 12 / 491
1.034
R indices [I > 2σ(I)] R1, wR2
R indices (all data) R1, wR2
0.06551, 0.1419
0.0996, 0.1593

SYNTHESIS, STRUCTURE, AND PROPERTIES
1341
displayed remarkable promoting activity (41% in postemergence tests) on the wheat’s
growth, thus indicating that compound 6e might selectively control weeds in wheat fields.
The structure-activity relationship is as follows:
Compound 6a with the no para substituent on the phenyl ring had little inhibitory
effect on weed development as compared with compound 6b–g with chlorine or methoxy
(most at the 2- and/or 4-position), indicating that the herbicidal activity was critically de-
pendent on the combined effect of the suitable group(s) (chlorine or methoxy) substituents.
The replacement of chlorine by an alkoxy group did not affect the herbicidal activity obvi-
ously. Meanwhile, the structures of ester moiety also played a role in activity of compounds
6. In our previous work, the 2-substituted ethyl propionate group modified by the replace-
ment of ethyl acetate, those good activities prompted the authors to synthesize a series of
propanoate analogues as shown in Scheme 1. We found that the introduction of propanoate
to 1,3,4-thiadiazole increased the herbicidal activity, which is consistent with previous re-
ports.17 Additionally, di-substituted compounds 6h and 6i were significantly more active
than most of mono-substituted derivatives 6a–e, these changes may be attributable to the di-
substituted compounds are more lipophilic than the mono-substituted ones. The observed
results conform to the superposition principle of reinforcement of biological activities.18
Experimental details and the activities (Table S1) are presented in the Supplemental
Materials.
Antifungal Studies. The antifungal activities of the compounds 6a–i were per-
formed by the poisoned food technique against the fungi viz., Alternaria alternata, Fusar-
ium oxysporum, Alternaria soluni, Botrytis Cinerea, and Fusarium sulphureum cultured on
potato dextrose agar as medium.19 The fungal activity of each compound was compared
with 2,4-D and the commercial fungicide griseofulvinas as standard drug.
Investigation of antifungal activity of the compounds 6a-i showed that all compounds
displayed a degree of fungicidal activity against the test fungi, and relatively more active
at the given dilutions against the fungi chosen in comparison to the 2,4-D, but less than
that of the commercial fungicide griseofulvinas. Among them, compounds 6c, 6d, and 6f
displayed high fungicidal activity against Alternaria alternata and Fusarium sulphureum
(Table S2).
Experimental details and the activities (Table S2) are presented in the Supplemental
Materials.
CONCLUSION
In conclusion, as part of continuous efforts to search for new herbicides with high
efficacy, broad-spectrum activity, and safety to crops, 1,3,4-thiadiazoles and phenoxy acid
were used as lead compounds for further optimization. A new series of 2-[5-(aryloxyacetyl)-
amino-1,3,4-thiadiazol-2-ylthio] propionate analogues were synthesized by a simple, rapid,
and cost-effective method, and their structures were confirmed by IR, 1H NMR, 13C NMR,
elementary analysis, and X-ray diffraction analysis. Preliminary bioassay data showed
that some of them possess commercial levels of herbicidal activity comparable to the
commercial herbicide 2,4-D, while S. tritici. show tolerance. These compounds could be
lead compounds for further discovery of herbicides. At the same time, some compounds had
interesting fungicidal activity even at 50 ppm. The title compounds have a broad prospect
of application in agriculture as novel pesticides.

1342
B. HU ET AL.
EXPERIMENTAL
All of the chemicals are commercially available and used without further purification.
Melting points were measured on an X-4 digital melting-point apparatus (uncorrected). Ele-
mental analyses were performed with a Perkin-Elmer 2400 elemental analyzer. The IR (KBr
pellet) spectra were recorded on a Perkin-Elmer FT-IR spectrometer in the 4000–400 cm−1
range. NMR spectra were recorded on a Varian Mercury Plus-400 MHz spectrometer.
Compounds 1and 4 were prepared according to the literature methods.20,21
General Synthetic Procedure for Target Compounds 6a–i
The 2-amino-5-mercapto-1,3,4-thiadiazole 1 (5 mmol) was dissolved in NaOH
(5 mmol, 15 mL) at room temperature. Ethyl 2-bromopropionate (5 mmol) was added
to the solution obtained and the mixture was stirred for 20 min. After that, the solid precipi-
tate was filtered off, washed with cold water, air dried, and then recrystallized from ethanol
to give 2-(5-amino-1,3,4-thiadiazol-2-ylthio) propanoate 2 in 78% yield as pale yellow
solid. Mp 79–80◦C; 1H NMR(CDCl3, 400 MHz) δH: 1.25–1.28 (t, 3H, CH3, J = 6.0 Hz),
1.57–1.59 (d, 3H, CH3, J = 8.0 Hz), 4.03–4.08 (q, 1H, SCH, J = 12.0 Hz), 4.16–4.22
(q, 2H, OCH2, J = 16.0 Hz).4.35 (s, 2H, NH2); 13C NMR (CDCl3, 400 MHz) δC: 14.0,
17.5, 46.0, 61.8, 150.0, 170.9, 171.4; IR (KBr) ν: 3266 (NH2), 1736 (OC O), 1501,
1449, 1321, 1094 (C N N C S) cm−1; Anal. calcd for C7H11N3O2S2: C36.04, H 4.75,
N 18.01; found C 36.10, H 4.77, N 17.93.
To a 50 mL round-bottom flask was added phenoxyalkanoic acid 4 (5 mmol) and
SOCl2 (5 mL). The mixture was refluxed for 4 h, and the excess SOCl2 was removed
under vacuum. The crude diacyl chloride was dissolved in CH3CN (5 mL) and added
dropwise through a dropping funnel to the mixture of 2-(5-amino-1,3,4-thiadiazol-2-ylthio)
propanoate 2 (4.5 mmol) and Et3N (4.2 mL, 30 mmol) in CH3CN (15 mL) on an ice bath.
This mixture was vigorously stirred at room temperature for an additional 12 h after
completion of the addition. The product was evaporated under reduced pressure washed
with water and brine, dried and recrystallized from ethanol to give the title compounds 6.
Ethyl 2-[5-(2-phenoxyacetamido)-1,3,4-thiadiazol-2-ylthio]propanoate
1
(6a). Colorless crystals, yield 81%, mp 115–117◦C; H NMR(CDCl3, 400 MHz) δH:
1.25–1.28 (t, 3H, CH3, J = 6.2 Hz), 1.63–1.65 (d, 3H, CH3, J = 7.2 Hz), 4.20–4.23 (q,
2H, OCH2, J = 7.2 Hz), 4.30–4.36 (q, 1H, SCH, J = 14.4 Hz), 4.79–4.80 (s, 2H, COCH2),
6.96–7.37 (m, 5H, ArH), 10.63 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz) δC: 14.0, 17.8,
45.7, 61.8, 66.7, 114.7, 122.5, 129.8, 156.8, 158.1, 159.5, 166.7, 171.2; IR (KBr) ν: 3173
(NH), 1730 (OC O), 1583, 1497, 1306, 1072 (C N N C S) cm−1; Anal. calcd for
C15H17N3O4S2: C 49.03, H 4.66, N 11.44; found C 49.08, H 4.72, N 11.54.
Ethyl 2-{5-[2-(2-chlorophenoxy)acetamido]-1,3,4-thiadiazol-2-ylthio}po-
opanoate (6b). White crystals, yield 86%, mp 138–139◦C; 1H NMR (CDCl3, 400 MHz)
δH: 1.22–1.24 (t, 3H, CH3, J = 4.0 Hz), 1.61–1.63 (d, 3H, CH3, J = 7.2 Hz), 4.15–4.20 (q,
2H, OCH2, J = 10.0 Hz), 4.26–4.32 (q, 1H, SCH, J = 14.4 Hz), 4.79–4.88 (s, 2H, COCH2),
6.59–7.28 (m, 4H, ArH), 11.63 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz) δC: 14.0, 17.8,
45.6, 61.9, 67.0, 116.1, 127.6, 129.7, 155.5, 158.3, 159.5, 166.3, 171.0; IR (KBr) ν: 3186
(NH), 1725 (OC O), 1587, 1495, 1306, 1077 (C N–N = C–S) cm−1; Anal. calcd for
C15H16N3O4S2Cl: C 44.83, H 4.01, N 10.46; found C 44.88, H 3.89, N 10.51.
Ethyl 2-{5-[2-(4-chlorophenoxy)acetamido]-1,3,4-thiadiazol-2-ylthio}pr-
opanoate (6c). White crystals, yield 87%, mp 126–127◦C; 1H NMR (CDCl3, 400 MHz)

SYNTHESIS, STRUCTURE, AND PROPERTIES
1343
δH: 1.25–1.28 (t, 3H, CH3, J = 6.0 Hz), 1.65–1.67 (d, 3H, CH3, J = 7.2 Hz), 4.19–4.24
(q, 2H, OCH2, J = 14.0 Hz), 4.35–4.40 (q, 1H, SCH, J = 14.4 Hz), 4.82 (s, 2H, COCH2),
6.96–7.47 (m, 4H, ArH), 10.22 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz) δC: 14.0, 17.8,
45.6, 61.9, 68.0, 114.7, 123.6, 128.1, 130.7, 152.5, 158.6, 165.9, 171.1; IR (KBr) ν: 3141
(NH), 1714 (OC O), 1551, 1484, 1306, 1079 (C N N C S) cm−1; Anal. calcd for
C15H16N3O4S2Cl: C 44.83, H 4.01, N 10.46; found C 45.01, H 4.02, N 10.52.
Ethyl 2-{5-[2-(2,4-dichlorophenoxy)acetamido]-1,3,4-thiadiazol-2-ylthio}
1
propanoate (6d). White crystals, yield 82%, mp 145–146◦C; H NMR (CDCl3, 400
MHz) δH: 1.26–1.29 (t, 3H, CH3, J = 7.2 Hz), 1.64–1.66 (d, 3H, CH3, J = 6.8 Hz),
4.19–4.24 (q, 2H, OCH2, J = 14.4 Hz), 4.33–4.39 (q, 1H, SCH, J = 14.8 Hz), 4.81 (s,
2H, COCH2), 6.90–7.46 (m, 3H, ArH), 10.32 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz)
δC: 14.1, 17.8, 45.7, 61.9, 68.2, 115.5, 124.5, 128.1, 130.5, 151.3, 158.5, 165.4, 171.1;
IR (KBr) ν: 3149 (NH), 1714 (OC O), 1558, 1481, 1307, 1080 (C N N C S) cm−1
;
Anal. calcd for C15H15N3O4S2Cl2: C 41.29, H 3.47, N 9.63; found C 41.38, H 3.42,
N 9.57.
Ethyl 2-{5-[2-(4-methoxyphenoxy)acetamido]-1,3,4-thiadiazol-2-ylthio}
propanoate (6e). White crystals, yield 83%, mp 105–106◦C; 1H NMR (CDCl3,
400 MHz) δH: 1.25–1.29 (t, 3H, CH3, J = 7.2 Hz), 1.64–1.65 (d, 3H, CH3, J = 7.2 Hz),
3.76–3.78 (s, 3H, OCH3), 4.20–4.25 (q, 2H, OCH2, J = 11.2 Hz), 4.32–4.37 (q, 1H, SCH,
J = 14.4 Hz), 4.73 (s, 2H, COCH2), 6.86–7.27 (m, 4H, ArH), 10.45 (s, 1H, NH); 13C
NMR (CDCl3, 400 MHz) δC: 14.0, 17.8, 45.6, 55.6, 61.9, 67.6, 114.9, 115.8, 150.8, 155.0,
158.1, 159.1, 166.8, 171.1; IR (KBr) ν: 3192 (NH), 1733 (OC O), 1578 1508, 1304, 1075
(C N N C S) cm−1; Anal. calcd for C16H19N3O5S2: C 48.35, H 4.82, N 10.57; found
C 48.44, H 4.75, N 10.48.
Ethyl 2-{5-[2-(2,4,5-trichlorophenoxy)acetamido]-1,3,4-thiadiazol-2-ylt-
1
hio}propanoate (6f). White crystals, yield 81%, mp 148–149◦C; H NMR (CDCl3,
400 MHz) δH: 1.25–1.27 (t, 3H, CH3, J = 4.8 Hz), 1.63–1.65 (d, 3H, CH3, J = 7.2 Hz),
4.18–4.23 (q, 2H, OCH2, J = 14.4 Hz), 4.29–4.35 (q, 1H, SCH, J = 14.8 Hz), 4.85 (s, 2H,
COCH2), 7.10–7.55 (m, 2H, ArH), 10.85 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz) δC:
14.0, 17.7, 45.6, 61.9, 68.2, 116.3, 122.8, 126.6, 131.3, 131.6, 151.7, 158.6, 159.3, 165.1,
171.0; IR (KBr) ν: 3170 (NH), 1742 (OC = O), 1569, 1477, 1306, 1084 (C = N–N =
C–S) cm−1; Anal. calcd for C15H14N3O4S2Cl3: C 38.27, H 3.00, N 8.93; found C 38.41, H
3.12, N 8.82.
Ethyl 2-{5-[2-(2,4,6-trichlorophenoxy)acetamido]-1,3,4-thiadiazol-2-ylt-
1
hio}propanoate (6g). Pale yellow crystals, yield 78%, mp 138–140◦C; H NMR
(CDCl3, 400 MHz) δH: 1.24–1.28 (t, 3H, CH3, J = 7.6 Hz), 1.64–1.66 (d, 3H, CH3, J =
7.6 Hz), 4.19–4.23 (q, 2H, OCH2, J = 8.8 Hz), 4.32–4.37 (q, 1H, SCH, J = 14.4 Hz),
4.78 (s, 2H, COCH2), 7.39 (s, 2H, ArH), 10.50 (s, 1H, NH); 13C NMR (CDCl3, 400 MHz)
δC: 14.0, 17.9, 45.6, 61.9, 70.6, 129.0, 129.5, 131.2, 148.5, 158.2, 158.7, 165.5, 171.1; IR
(KBr) ν: 3068 (NH), 1728 (OC O), 1557, 1456, 1309, 1051 (C N N C S) cm−1
;
Anal. calcd for C15H14N3O4S2Cl3: C 38.27, H 3.00, N 8.93; found C 38.38, H 3.04, N
8.88.
Diethyl 2,2’-{[5,5’-((2,2’-(1,3-phenylenebis(oxy))bis(acetyl))bis(azanediyl))
bis(1,3,4-thiadiazole-5,2-diyl)]bis(sulfanediyl)}dipropanoate (6h). Yellow crys-
tals, yield 80%, mp 126–128◦C; 1H NMR (CDCl3, 400 MHz) δH: 1.27–1.29 (t, 6H, CH3,
J = 4.8 Hz), 1.63–1.65 (d, 6H, CH3, J = 7.6 Hz), 4.20–4.24 (q, 4H, OCH2, J = 10.4 Hz),
4.30–4.35 (q, 2H, SCH, J = 14.4 Hz), 4.79–4.82 (s, 4H, COCH2), 6.90–7.33 (m, 4H,
ArH), 10.77 (s, 2H, NH); 13C NMR (CDCl3, 400 MHz) δC: 14.0, 17.8, 45.6, 61.9, 66.8,

1344
B. HU ET AL.
102.6, 108.4, 130.6, 158.2, 159.6, 166.5, 171.1; IR (KBr) ν: 3181 (NH), 1732 (OC O),
1571, 1491, 1300, 1069 (C N N C S) cm−1; Anal. calcd for C24H28N6O8S4
C 43.89, H 4.30, N 12.80; found C 43.82, H 4.25, N 12.77.
:
Diethyl 2,2’-{[5,5’-((2,2’-(1,4-phenylenebis(oxy))bis(acetyl))bis(azanediyl))
bis(1,3,4-thiadiazole-5,2-diyl)]bis(sulfanediyl)}dipropanoate (6i). Yellow crys-
tals, yield 82%, mp 168–170◦C; 1H NMR (CDCl3, 400 MHz) δH: 1.25–1.28 (t, 6H, CH3,
J = 4.8 Hz), 1.63–1.65 (d, 6H, CH3, J = 7.6 Hz), 4.17–4.23 (q, 4H, OCH2, J = 10.0 Hz),
4.30–4.35 (q, 2H, SCH, J = 14.4 Hz), 4.74–4.78 (s, 4H, COCH2), 6.82–7.27 (m, 4H, ArH),
10.82 (s, 2H, NH); 13C NMR (CDCl3, 400 MHz) δC: 14.1, 17.9, 45.7, 61.9, 67.4, 116.2,
152.2, 158.4, 158.9, 166.3, 171.1; IR (KBr) ν: 3182 (NH), 1730 (OC O), 1574,1506,
1305, 1071 (C N N C S) cm−1; Anal. calcd for C24H28N6O8S4: C 43.89, H 4.30, N
12.80; found C 43.72, H 4.36, N 12.69.
X-Ray Diffraction
A single light yellow crystal of compound 6f having approximate dimensions of
0.24 mm × 0.22 mm × 0.20 mm was mounted on the top of a glass fiber in a random
orientation. All X-ray crystallographic data were collected on a Bruker SMART APEX
II CCD diffractometer equipped with a graphite-monochromatized Mo Ka radiation (λ =
0.71073 Å) radiation using ϕ/ω scan technique at 293 K. The structures were solved by
a direct method and refined by a full-matrix least-squares procedure based on F2 using
the SHELXTL program package. The molecular structure of compound 6f is shown in
Figure 1, and a summary of the crystallographic data and refinement parameters are given
in Table 2. CCDC 946566 contains the supplementary crystallographic data for this article.
These data can be obtained free of charge via www.ccdc.cam.ac.uk/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge B2 1EZ, UK;
fax +44 1223 336033; or deposit@ccdc.cam.ac.uk).
FUNDING
This work was supported by the National Natural Science Foundation of China
(NSFC) (Nos. 21064006, 21161018 and 21262032), the Natural Science Foundation of
Gansu Province (1010RJZA018) and the Program for Changjiang Scholars and innovative
Research Team in University of Ministry of Education of China (IRT1177).
SUPPLEMENTAL MATERIAL
Supplementary data for this article can be accessed on the publisher’s website,
www.tandfonline.com/gpss
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