Application of sulfinyl bis(2,4-dihydroxythiobenzoyl) in the synthesis of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles

Article abstract of DOI:10.1080/00397910600591896

One-stage synthesis of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles is described. The compounds were prepared by the reaction of the sulfinyl bis(2,4-dihydroxythiobenzoyl) (STB) with 4-substituted 3-thiosemicarbazides. STB was obtained

Full text of DOI:10.1080/00397910600591896

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Application of Sulfinyl
bis(2,4‐dihydroxythiobenzoyl) in
the Synthesis of N‐Substituted
2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazo
Joanna Matysiak a & Andrzej Niewiadomy a
a Department of Chemistry, Agricultural University, Lublin, Poland
Published online: 21 Aug 2006.
To cite this article: Joanna Matysiak & Andrzej Niewiadomy (2006) Application
of Sulfinyl bis(2,4‐dihydroxythiobenzoyl) in the Synthesis of N‐Substituted
2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 36:11, 1621-1630
To link to this article: http://dx.doi.org/10.1080/00397910600591896
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Synthetic Communicationsw, 36: 1621–1630, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600591896
Application of Sulfinyl bis(2,4-
dihydroxythiobenzoyl) in the Synthesis
of N-Substituted 2-Amino-5-(2,4-
dihydroxyphenyl)-1,3,4-thiadiazoles
Joanna Matysiak and Andrzej Niewiadomy
Department of Chemistry, Agricultural University, Lublin, Poland
Abstract: One-stage synthesis of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-
1,3,4-thiadiazoles is described. The compounds were prepared by the reaction of the
sulfinyl bis(2,4-dihydroxythiobenzoyl) (STB) with 4-substituted 3-thiosemicarbazides.
STB was obtained from 2,4-dihydroxybenzenecarbodithioic acid and thionyl dichloride.
The structure of compounds was confirmed by IR, 1H NMR, 13C NMR, and EI-MS data.
Keywords: 2-Amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles, Cyclization, Sulfinyl-
bis(2,4-dihydroxythiobenzoyl), Thiosemicarbazides
Among 2,5-disubstituted 1,3,4-thiadiazoles there are derivatives that pos-
sess valuable biological properties, such as antitumor,[1,2] anticonvulsant,[3]
antibacterial,[3] antifungal,[4] anti-inflammatory,[5] antihypertensive,[6] anes-
thetic,[7] and cardiotonic.[8] 2-Aminoderivatives are a very important group
of these substitution patterns.[1–3] Some of them were entered in phase II
clinical trials in patients with different tumors.[2]
There is a large number of methods for 2-amino-5-substituted 1,3,4-
thiadiazoles synthesis with variations among them. The most universal is a
two-stage method consisting of acylation of thiosemicarbazide using car-
boxylic acid chlorides and subsequent cyclization of the intermediate
acylthiosemicarbazides. Various dehydrating agents are used in commonly
Received in Poland October 10, 2005
Address correspondence to Joanna Matysiak, Department of Chemistry, Agricul-
tural University, Akademicka 15, 20-950 Lublin, Poland. Fax: 48 81 5333752;
E-mail: joanna.matysiak@ar.lublin.pl
1621

1622
J. Matysiak and A. Niewiadomy
applied methods: sulfuric acid, phosphorus oxychloride, benzoyl chloride, and
acetyl chloride. Not all of these substances are readily available and con-
venient to use; moreover, they often take part in side reactions that
significantly lower the yield of the products and complicate their separ-
ation.[3,4,9–15] Acylthiosemicarbazides can be also obtained in the reaction of
acenylhydrazine from isothiocyanates. Ring closure to thiadiazole occurs by
heating with sulfuric or methanesulfonic acid.[16,17] Specific substitutions
were obtained from 5-nitro-2-furfurilidene diacetate and thiosemicarbazides.[18]
2-Amino-5-substituted 1,3,4-thiadiazoles were prepared in a one-
step reaction of thiosemicarbazides with arylthio- and arylsulfonylacetic
(-propionic) acids or their nitriles in the polyphosphoric acid medium,[19] or
with benzonitrile in trifluoroacetic acid.[20] Recently, based on the typical
reagents for preparation of 1,3,4-thiadiazoles, new techniques have been
developed: cyclization of linear structures under microwave irradiation in
the presence of glacial acetic acid[21,22] and solid-phase synthesis.[23]
The conversion of 4-amino-D2-1,2,4-oxadiazolines into 2-arylamino-
1,3,4-thiadiazoles was described by Hussein and coworkers.[24] Oxi-
dative cyclization of 1-thioaroylsemicarbazides by bromine (hydrogen
peroxide)[25] or thiosemicarbazones and A-CH55N-NR-CX-B system by
iron(III) chloride gave also the described compounds.[26,27]
For the synthesis of 1,3,4-thiadiazole ring substituted in another way than
by the amine group, there are commonly applied thiohydrazides[28] and thioa-
cylamidrazones.[29] Sulfur-containing reagents are used for analogues cycliza-
tion of amidrazones.[30] 1,4-Dicarbonyl compounds are converted to the
described heterocyclic nucleus under the microwave irradiation conditions
in the presence of Lawesson’s reagent.[31]
The electrophilic reagent sulfinyl bis(2,4-dihydroxythiobenzoyl) (STB)
prepared in our laboratory gives thiobenzanilides[32] or thiobenzamides[33]
in the reactions with primary or secondary aryl- and heterocyclic amines. In
the reaction of STB with N3-substituted amidrazones, the linear products,
N1-thioacyl derivatives, and the cyclic products, 2,5-disubstituted 1,3,4-thia-
diazoles, with a considerably higher fungistatic activity, were obtained.[34]
These investigations show that this compound can also act as an endogenous
cyclizing reagent. Endocyclizing properties were next confirmed in the case of
some transition products of SE reaction using STB and compounds with amine
nitrogen atoms of different electron density.[35]
In this work we report the preparation of a new series of N-substituted
2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles as continuation of the
studies connected with searching for biologically active derivatives. The
compounds were prepared in one-stage synthesis from sulfinyl bis(2,4-dihy-
droxythiobenzoyl) (STB) and commercially available 3-thiosemicarbazides.
STB was synthesized from 2,4-dihydroxybenzenecarbodithioic acid and
thionyl dichloride.[36] 2,4-Dihydroxybenzenecarbodithioic acid was prepared
from 1,3-dihydroxybenzene in the electrophilic substitution reaction of CS2 in
ethanol (alkaline medium) according to the modified Kolbe–Schmidt

Application of Sulfinyl bis(2,4-dihydroxythiobenzoyl)
1623
reaction.[36] The process of 2,4-dihydroxybenzenecarbodithioic acid with SOCl2
in diethyl ether gave sulfinyl bis(2,4-dihydroxythiobenzoyl) (STB) (Scheme 1).
The strongly reducing character of acid and tendency toward desulfhydrylation
(EI-MS, [M-SH8]þ ! (HO)2C6H3Cþ55S, 153 m/z, B ¼ 100) allow us to
explain the course of the SOCl2 reduction forming a specific reagent of electro-
philic properties. In the reaction of acid with SOCl2, -SH groups split off from the
acid reduce chlorine from thionyl dichloride to HCl, forming elementary sulfur
and [(HO)2C6H3C55S)]2SO (STB). Properties of 2,4-dihydroxybenzenecarbo-
dithioic acid that allow STB to be obtained are also due to the stability of -OH
groups bonded with ring and resistance to oxidation processes of meta- substi-
tuted dihydroxyphenol system. Anhydrousethyl ether used as solvent is
capable of stabilizing of (HO)2C6H3Cþ55S cations released in the desulfhydryla-
tion reaction and other transient forms.
STB as an electrophilic reagent makes the course of the reaction with
various 4-substituted 3-thiosemicarbazides as organic bases and selective
endocyclization of thioacylderivatives possible. After the SE reaction of
STB and thiosemicarbazide, the process is due to stabilization of the linear
structure by the thiol form and then oxidative bonding of H2S by the excess
of electrophylic reagent takes place (Scheme 2). The proposed mechanism
is considerably different from that described for acylthiosemicarbazides
(cyclization and elimination of H2O).[19] It promotes a tendency of
compounds with thioamide moiety for transition into the imidothiol forms
compared with the analogous ones with oxygen.[37]
The compounds were obtained with high efficiency and chromatographic
purity: RP-HPLC and RP-OPLC; methanol–water mobile phases. Their
characterization is based on the IR (KBr), 1H NMR, 13H NMR, EI-MS
spectra, and elemental analyses. The molecular peak was found to be
present in all the derivatives, although their relative intensity is differentiated.
The 1H NMR spectral data show bands in the range 9.9–7.9 ppm characteristic
of NH proton and in about 11.1–10.8 and 10.6–9.8 ppm of 2C-OH and 4C-
OH protons in the resorcinol moiety respectively. There are characteristic
signals at 165–163 and 155–156 ppm for C-2 and C-5 respectively of 2-ami-
nothiadiazole ring in 13C NMR spectra. The IR spectra exhibit characteristic
strong absorption at 1650–1610 cm21 for C55N and weak band at 1050–
1010 cm21 for N55C-S-C55N.
Scheme 1.

1624
J. Matysiak and A. Niewiadomy
Scheme 2.
In conclusion, the simple synthesis method of 1,3,4-thiadiazoles has been
presented. The methodology described herein is expected to be quite general
for the synthesis of N-differently substituted 2-amino-5-(2,4-dihydroxyphe-
nyl)-1,3,4-thiadiazoles. The synthesis methods reported in literature do not
describe preparation of hydroxyl derivatives. The studies of various groups
of compounds with 2,4-dihydroxyphenyl moiety indicate favorable
influence of this fragment on biological effect with simultaneous relatively
low level of toxicity. Therefore, work will be undertaken to prepare a large
number of derivatives as compounds with diverse biological activity.
EXPERIMENTAL
The melting point (mp) was determined on a Buchi B-540 (Switzerland)
melting-point apparatus. The elemental analysis was performed in order to
determine C, H, and N contents (Perkin-Elmer 2400). Analyses of C, N, and
H were within +0.4% of the theoretical values. The vibrational spectra were
recorded with a Perkin-Elmer FT-IR 1725X spectrophotometer using KBr
pellets in the range of 600–4000 cm21. 1H NMR and 13C NMR spectra were
recorded in DMSO-d6 or CDCl3 on a Varian Mercury 400 or Bruker DRX
500 instrument. Chemical shifts (d, ppm) were given in with tetramethylsilane
(TMS). The spectra MS (EI, 70 eV) were run on a AMD-604 apparatus.
Preparation of Compounds
2,4-Dihydroxybenzenecarbodithioic Acid
Resorcinol (0.1 mol) was dissolved in solution of KOH (2 M, 50 ml). Ethanol
(50 ml) was added, CS2 (0.1 mol) was dropped in, and the mixture was heated

Application of Sulfinyl bis(2,4-dihydroxythiobenzoyl)
1625
(3 h). After cooling, the solution was acidified with small portions of HCl
(2 M). The evolved product was doubly crystallized from ethanol. Yield:
82%, mp: 132–1338C. EI-MS (m/z, rel. intens.): 186 (Mþ, 36), 153 (100),
141 (12), 124 (9), 97 (12), 69 (5), 65 (14). Anal. Calcd. for C7H6O2S2
(186.25): C, 45.14; H, 3.25; N, 17.18. Found: C, 45.10; H, 3.23; N, 17.21.
Sulfinyl bis(2,4-dihydroxythiobenzoyl) (STB)
2,4-Dihydroxybenzenecarbodithioic acid (0.35 mol) was dissolved in
anhydrous diethyl ether (250 mL). At 208C the solution was saturated with
dry CO2; SOCl2 (0.7 mol) was slowly dropped in and then heated over the
water bath (4 h). A red product was removed from the solution. The solvent
and SOCl2 remains were separated by distillation under reduced pressure.
The obtained compound was washed with DMSO. Amorphous red powder,
1
mp 259–2608C. H NMR (DMSO-d6): d 8.19–7.54 (m, 2H, 6,60-CH),
6.92–6.27 (m, 4H, 3,5,30,50-CH), (in the range of absorption of -OH
protons there are blurred, not distinct bands). IR (KBr, cm21): 3392 (OH),
2960, 1614 (C55C), 1542, 1507, 1457 (C55C), 1396, 1372, 1237 (C-OH),
1135, 1048 (S55O), 1019 (C55S), 976, 948, 902, 876, 845. EI-MS (m/z,
rel. intens.): 200 (15), 184 (94), 154 (42), 153 (60) 137 (15), 136 (16), 124
(32), 110 (11), 108 (11), 97 (10), 96 (25), 69 (20), 64 (89), 33 (100). Anal.
calcd. for C14H10O5S3 (354.42): C, 47.44; H, 2.84; S, 27.14. Found: C,
47.57; H, 2.83; S, 27.24.
Compounds 1–10
STB (0.0075 mol) and corresponding commercially available 4-substituted
3-thiosemicarbazide (0.01 mol) were put into methanol (50 ml) and heated
to boiling (3 h). During the synthesis the compounds was (9, 5) removed;
the mixture was hot filtered and the filtrate was concentrated to 20 ml (1).
The filtrate was concentrated to dry (2, 4, 6, 7); water (50 ml) was added to
the filtrate (3, 8, 10). The removed compound was filtrated, washed with
water, and crystallized from methanol (30 ml) (1, 3, 4, 5, 9) or from
methanol-water solutions (50 ml) (2, 6, 7, 8, 10).
2-Isopropylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (1). Yield:
63%, mp: 124–1268C. 1H NMR (500 MHz, DMSO-d6, d, ppm): 11.11
(s, 1H, 2-COH), 9.93 (s, 1H, 4-COH), 7.95 (m, 1H, NH), 3.80 (m, 1H, CH),
1.23–1.12 (m, 6H, CH3). 13C NMR (100 MHz, DMSO-d6, d, ppm): 165.97
(Cthia-2), 160.99 (C-2), 156.36 (C-4), 153.00 (Cthia-5), 128.20 (C-6), 108.40
(C-1), 107.30 (C-5), 102.42 (C-3), 47.57 (CH), 21.93 (CH3). IR (KBr,
cm21): 3417 (OH, NH), 1613 (C55N, C55C), 1534, 1213 (C-OH), 1119,
807, 675 (C-S-C). EI-MS (m/z, rel. intens.): 251 (Mþ, 100), 236 (39), 209
(40), 207 (7), 192 (10), 163 (13), 161 (35), 153 (25), 150 (9), 149 (10), 145
(8), 137 (23), 136 (45), 135 (29), 121 (9), 120 (19), 117 (26), 64 (65), 58

1626
J. Matysiak and A. Niewiadomy
(28), 44 (61), 40 (89). Anal. calcd. for C11H13N3O2S (251.30): C, 52.57; H,
5.21; N, 16.72. Found: C, 52.74; H, 5.19; N, 16.78.
2-Butylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (2). Yield: 62%,
1
mp: 135–1368C. H NMR (500 MHz, CDCl3, d, ppm): 11.05 (broad band,
1H, 2-COH), 9.93 (s, 1H, 4-COH), 8.35 (s, 1H, NH), 1.61–1.24 (m, 6H,
CH2), 0.93-0.87 (m, 3H, CH3). IR (KBr, cm21): 3438 (OH, NH), 2923
(CH2), 1617 (C55N, C55C), 1532, 1218 (C-OH), 1121, 838. EI-MS (m/z,
rel. intens.): 265 (Mþ, 75), 256 (40), 222 (28), 209 (40), 192 (20), 170 (32),
160 (24), 135 (41), 111 (15), 91 (39), 69 (19), 64 (100), 40 (73). Anal.
calcd. for C12H15N3O2S (265.33): C, 54.32; H, 5.70; N, 15.84. Found: C,
54.52; H, 5.72; N, 15.89.
2-Cyclohexylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (3). Yield:
1
80%, mp: 107–1088C. H NMR (500 MHz, CDCl3, d, ppm): 11.03 (s, 1H,
2-COH), 9.90 (s, 1H, 4-COH), 2.65–2.51 (m, 1H, CH), 1.99–1.57 (m, 4H,
CH2), 1.36–1.15 (m, 6H, CH2). IR (KBr, cm21): 3431 (OH, NH), 2924,
2854 (CH2), 1616 (C55N, C55C), 1535, 1420, 1320, 1263 (C-OH), 1114,
1046 (N55C-S-C55N), 809, 670 (C-S-C). EI-MS (m/z, rel. intens.): 291
(Mþ, 48), 256 (9), 248 (5), 210 (12), 209 (100), 192 (4), 168 (3), 167 (6),
160 (7), 157 (10), 156 (17), 153 (9), 150 (10), 137 (6), 136 (32), 123 (5),
113 (8), 94 (6), 83 (5), 74 (11), 64 (17), 55 (19). Anal. calcd. for
C14H17N3O2S (291.37): C, 57.71; H, 5.88; N, 14.42. Found: C, 57.29; H,
5.86; N, 14.48.
2-Phenylamino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (4). Yield: 81%,
1
mp: 238–2408C. H NMR (500 MHz, DMSO-d6, d, ppm): 10.91 (s, 1H,
2-COH), 10.39 (s, 1H, 4-COH), 9.94 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6, d, ppm): 163.51 (Cthia-2), 160.25 (C-2), 155.71 (C-4), 154.79
(Cthia-5), 140.89 (C-10), 129.03 (C-30,50), 128.57 (C-6), 121.48 (C-40),
117.22 (C-20,60), 108.50 (C-1), 108.09 (C-5), 102.44 (C-3). IR (KBr, cm21):
3367, 3251, 3198 (OH, NH), 1623 (C55N), 1601 (C55C), 1576, 1531, 1501,
1456, 1434, 1410, 1325, 1240, 1218 (C-OH), 1184, 1111, 1032 (N55C-S-
C55N), 986, 968, 875, 841, 803, 672 (C-S-C). EI-MS (m/z, rel. intens.):
285 (Mþ, 100), 256 (2), 150 (63), 118 (17), 91, 77 (18), 40 (12). Anal.
calcd. for C14H11N3O2S (285.32): C, 58.93; H, 3.89; N, 14.73. Found: C,
59.15; H, 3.72; N, 14.90.
2-(2-Ethylphenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (5).
Yield: 65%, mp: 253–2548C. 1H NMR (500 MHz, DMSO-d6, d, ppm)
10.85 (broad band, 1H, 2-COH), 9.87 (s, 1H, 4-COH), 9.43 (s, 1H, NH),
2.70–2.66 (q, 2H, CH2), 1.16–1.13 (t, 3H, CH3). IR (KBr, cm21): 3437
(OH, NH), 2920 (CH2), 1626 (C55N, C55C), 1532, 1454, 1211 (C-OH),
1021 (N55C-S-C55N), 845. EI-MS (m/z, rel. intens.): 313 (Mþ, 78), 284
(19), 280 (11), 195 (6), 178 (34), 177 (4), 163 (25), 153 (19), 151 (18), 146

Application of Sulfinyl bis(2,4-dihydroxythiobenzoyl)
1627
(10), 145 (100), 144 (47), 136 (10), 135 (8), 131 (20), 119 (17), 106 (17), 94
(10), 91 (11), 77 (26), 39 (12). Anal. calcd. for C16H15N3O2S (313.33): C,
61.32; H, 4.82; N, 13.41. Found: C, 60.20; H, 4.80; N, 13.46.
2-(5-Chloro-2-methylphenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thia-
1
diazole (6). Yield: 65%, mp: 257–2588C. H NMR (500 MHz, CDCl3, d,
ppm): 10.88 (broad band, 1H, 2-COH), 9.88 (s, 1H, 4-COH), 9.58 (s, 1H,
NH), 2.27 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, d, ppm): 164.23
(Cthia-2), 160.45 (C-2), 155.79 (C-4), 155.63 (Cthia-5), 140.25 (C-10), 131.83
(C-50), 130.60 (C-20), 128.43 (C-6), 125.90 (C-30), 122.01 (C-40), 118.86
(C-60), 108.42 (C-1), 108.18 (C-5), 102.44 (C-3), 17.65 (CH3). IR (KBr,
cm21): 3267, 3089 (OH, NH), 2965 (CH3), 1634 (C55N), 1597 (C55C),
1537, 1402, 1320, 1224 (C-OH), 1234, 1211, 1169, 1140, 1110, 1105
(C-Cl), 1052 (N ¼ C-S-C55N), 987, 971, 849, 672 (C-S-C). EI-MS (m/z,
rel. intens.): 333 (Mþ, 100), 318 (13), 302 (6), 299 (22), 284 (4), 200 (18),
199 (8), 198 (50), 184 (5), 183 (7), 171 (12), 167 (24), 153 (35), 149 (10),
136 (21), 135 (17), 131 (19), 121 (12), 94 (22), 77 (18), 39 (20). Anal.
calcd. for C15H12ClN3O2S (333.79): C, 53.97; H, 3.62; N, 12.59. Found
C, 53.81; H, 3.61; N, 12.53.
2-(2,5-Dichlorophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole
(7). Yield: 82%, mp: 255–2568C. 1H NMR (500 MHz, CDCl3, d, ppm): 10.88
(s, 1H, 2-COH), 9.91 (s, 1H, 4-COH), 9.84 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6, d, ppm): 163.38 (Cthia-2), 160.52 (C-2), 156.57 (C-4), 155.77
(Cthia-5), 138.45 (C-10), 132.11 (C-50), 130.80 (C-20), 128.43 (C-6), 122.41
(C-30), 119.94 (C-40), 119.50 (C-60), 108.55 (C-1), 108.21 (C-5), 102.44
(C-3). IR (KBr, cm21): 3287 (OH, NH), 1632 (C55N), 1588 (C55C), 1537,
1402, 1320, 1265 (C-OH), 1234, 1212, 1169, 1134, 1110, 1099 (C-Cl),
1046 (N ¼ C-S-C55N), 987, 967, 848, 670 (C-S-C). EI-MS (m/z, rel.
intens.): 354 (Mþ, 18), 353 (94), 321 (96), 320 (38), 319 (18), 318 (100),
220 (7), 218 (10), 186 (5), 185 (9), 183 (22), 153 (4), 136 (3), 135 (4), 94
(3), 69 (3), 66 (3), 39 (5). Anal. calcd. for C14H9Cl2N3O2S (354.21): C,
47.47; H, 2.56; N, 11.86. Found: C, 47.28; H, 2.57; N, 11.81.
2-(4-Iodophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole
(8).
1
Yield: 61%, m. p.: 206-2088C. H NMR (500 MHz, CDCl3, d, ppm): 10.80
(broad band, 1H, 2-COH), 10.39 (s, 1H, 4-COH), 9.90 (s, 1H, NH). 13C
NMR (100 MHz, DMSO-d6, d, ppm): 163.14 (Cthia-2), 160.40 (C-2), 155.71
(C-4), 154.96 (Cthia-5), 140.62 (C-1), 137.51 (C-20,60), 128.51 (C-6), 119.56
(C-30,50), 108.39 (C-1), 108.15 (C-5), 102.42 (C-3), 84.47 (C-40). IR (KBr,
cm21): 3176 (OH, NH), 1620 (C55N), 1560 (C55C), 1526, 1486, 1435,
1397, 1318, 1211 (C-OH), 1181, 1119, 1063, 1005, 986, 968, 807, 669
(C-S-C). EI-MS (m/z, rel. intens.): 411 (Mþ, 100), 285 (6), 276 (23), 244
(6), 153 (9), 150 (9), 149 (19), 142 (4), 136 (4), 135 (9), 128 (6), 122 (9),

1628
J. Matysiak and A. Niewiadomy
94 (10), 90 (8), 76 (10), 66 (6), 63 (7). Anal. calcd. for C14H10IN3O2S
(411.22): C, 40.89; H, 2.45; N, 10.22. Found: C, 40.61; H, 2.46; N, 10.20.
2-(4-Ethoxycarbonylphenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadia-
1
zole (9). Yield: 69%, m. p.: 246–2478C. H NMR (500 MHz, DMSO-d6, d,
ppm): 10.86 (s, 1H, 2-COH), 10.57 (s, 1H, 4-COH), 4.31-4.27 (q, 2H, CH2),
1.34–1.31 (t, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, d, ppm): 165.42
(C55O), 162.79 (Cthia-2), 160.90 (C-2), 156.02 (C-4), 155.80 (Cthia-5),
144.84 (C-10), 130.65 (C-30,50), 128.50 (C-6), 122.33 (C-40), 116.62 (C-
20,60), 108.33 (C-1), 107.99 (C-5), 102.46 (C-3), 60.30 (CH2), 14.29 (CH3).
IR (KBr, cm21): 3313, 3186 (OH, NH), 2985 (CH3), 1686 (C55O), 1608
(C55N, C55C), 1553, 1471, 1415, 1370, 1286, 1180 (C-OH), 1112, 1019
(N55C-S-C55N), 887, 966, 850, 811, 670 (C-S-C). EI-MS (m/z, rel.
intens.): 357 (Mþ, 100), 312 (8), 222 (9), 194 (10), 178 (3), 177 (17), 162
(3), 156 (8), 153 (5), 150 (9), 145 (5), 121 (3), 94 (6), 66 (3), 65 (3). Anal.
calcd. for C17H15N3O4S (357.38): C, 57.13; H, 4.23; N, 11.76. Found: C,
57.43; H, 4.21; N, 11.81.
2-(4-Morpholinoethylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole
(10). Yield: 60%, mp: 301–3038C. 1H NMR (400 MHz, DMSO-d6, d, ppm):
10.89 (s, 1H, 2-COH), 9.99 (s, 1H, 4-COH), 9.84 (s, 1H, NH), 3.59 (t, 4H,
OCH2), 3.45–3.41 (m, 2H, CH2NH, m), 3.34 (s, 6H, NCH2). IR (KBr,
cm21): 3268 (OH, NH), 2942, 2874 (CH2), 1602 (C55N), 1529 (C55C),
1474, 1419, 1332, 1252, 1192 (C-OH), 1131, 1110, 1068, 1019 (N55C-S-
C55N), 1003, 985, 960, 911, 851, 803, 675 (C-S-C). EI-MS (m/z, rel.
intens.) 322 (Mþ, 1.4), 302 (38), 222 (3), 209 (9), 167 (12), 153 (5), 135
(8), 113 (47), 100 (100), 56 (6). Anal. calcd. for C14H18N4O3S (322.38): C,
52.16; H, 5.63; N, 17.38. Found: C, 52.49; H, 5.48; N, 17.52.
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