1,3,4-Thiadiazoles. Regioselective O-demethylation on dehydrative cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted thiosemicarbazides with sulphuric acid

Article abstract of DOI:10.1080/10426500490485525

Cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted thiosemicarbazides 2a-g with sulphuric acid at ambient temperature afforded the selectively demethylated products 2-(4-hydroxy-3,5-dimethoxyphenyl)-5-substituted amino-1,3,4-thiadiazoles 4a-g. Meanw

Full text of DOI:10.1080/10426500490485525

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Phosphorus, Sulfur, and Silicon
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1,3,4-THIADIAZOLES.
REGIOSELECTIVE O-
DEMETHYLATION
ON DEHYDRATIVE
CYCLIZATION OF 1-(3,4,5-
TRIMETHOXYBENZOYL)4-
SUBSTITUTED
THIOSEMICARBAZIDES WITH
SULPHURIC ACID
Mohamed Al-Omar a , Omar A. Al-Deeb a , Hamad A.
Al-Khamees a & Ali A. El-Emam a
a Department of Pharmaceutical Chemistry, College
of Pharmacy, King Saud University , Riyadh, Saudi
Arabia
Published online: 16 Aug 2010.
To cite this article: Mohamed Al-Omar , Omar A. Al-Deeb , Hamad A. Al-Khamees
& Ali A. El-Emam (2004) 1,3,4-THIADIAZOLES. REGIOSELECTIVE O-DEMETHYLATION
ON DEHYDRATIVE CYCLIZATION OF 1-(3,4,5-TRIMETHOXYBENZOYL)4-SUBSTITUTED
THIOSEMICARBAZIDES WITH SULPHURIC ACID, Phosphorus, Sulfur, and Silicon and the
Related Elements, 179:12, 2509-2517, DOI: 10.1080/10426500490485525
To link to this article: http://dx.doi.org/10.1080/10426500490485525
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Phosphorus, Sulfur, and Silicon, 179:2509–2517, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485525
1,3,4-THIADIAZOLES. REGIOSELECTIVE
O-DEMETHYLATION ON DEHYDRATIVE
CYCLIZATION OF 1-(3,4,5-TRIMETHOXYBENZOYL)-
4-SUBSTITUTED THIOSEMICARBAZIDES WITH
SULPHURIC ACID
Mohamed Al-Omar, Omar A. Al-Deeb, Hamad A. Al-Khamees,
and Ali A. El-Emam
Department of Pharmaceutical Chemistry, College of Pharmacy,
King Saud University, Riyadh, Saudi Arabia
(Received April 18, 2004; accepted May 12, 2004)
Cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted thiosemicar-
bazides 2a–g with sulphuric acid at ambient temperature afforded the
selectively demethylated products 2-(4-hydroxy-3,5-dimethoxyphenyl)-
5-substituted amino-1,3,4-thiadiazoles 4a–g. Meanwhile, dehydrative
cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-(benzyl or t-butyl)thiosemi-
carbazides 2h,i with sulphuric acid yielded 2-(4-hydroxy-3,5-dimetho-
xyphenyl)-5-amino-1,3,4-thiadiazole 5. On the other hand, dehy-
dration of 2h,i by heating with phosphorus oxychloride yielded
2-(3,4,5-trimethoxyphenyl)-5-amino-1,3,4-thiadiazole 6.
Keywords: 1,3,4-Thiadiazoles; N-debenzylation; N-(t-debutylation);
selective O-demethylation
INTRODUCTION
1,3,4-thiadiazole nucleus constitutes the active part of several
biologically active compounds, including antibacterial,1–4 anti-
mycotic,5,6 antiviral,7,8 carbonic anhydrase inhibitor,9–11 and anti-
inflammatory12,13 activities. In view of these findings, and in
continuation to our interest in the synthesis of 2-substituted-
5-amino-1,3,4-thiadiazoles,14 we report our observations on the
dehydrative cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted
thiosemicarbazides with sulphuric acid and phosphorus oxychloride.
Address correspondence to Ali A. El-Emam, Department of Pharmaceutical Chem-
istry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. E-mail:
elemam5@hotmail.com
2509

2510
M. Al-Omar et al.
RESULTS AND DISCUSSION
The reaction of 3,4,5-trimethoxybenzoic acid hydrazide 1 with cer-
tain alkyl or arylisothiocyanates in ethanol yielded the corresponding
1-(trimethoxybenzoyl)-4-substituted thiosemicarbazides 2a–i in high
yields. Several procedures were reported for dehydrative cyclization
of 1,4-disubstituted thiosemicarbazides to their substituted amino-
1,3,4-thiadiazole analogues utilizing a variety of dehydrating agents,
including sulphuric acid,5,14,15 phosphorus oxychloride,14,16 polyphos-
phoric acid,17 and methane sulphonic acid.13 Attempted cyclization of
compounds 2a–g via stirring with sulphuric acid at ambient tempera-
ture for 24 h did not yield the expected 2-(3,4,5-trimethoxyphenyl)-5-
substituted amino-1,3,4-thiadiazoles 3a–g; the O-demethylated prod-
ucts 4a–g were obtained instead. On the other hand, compounds
3a–g were successfully obtained by cyclization of 2a–g via heating with
phosphorus oxychloride (Scheme 1).
SCHEME 1
Dehydrative cyclization of 1-(trimethoxybenzoyl)-4-benzyl or
t-butyl-thiosemicarbazides 2h, 2i using sulphuric acid yielded the
O-demethylated, N-debenzylated or de(t-butylated) product 5. Mean-
while, heating compound 2h or 2i with phosphorus oxychloride yielded
the N-debenzylated or de(t-butylated) product 6 (Scheme 2). The
structures of the O-demethylated and the N-debenzylated or de(t-
butylated) products were confirmed by the correct elemental analyses,
mass spectra, and NMR data. Although the literature are enriched

Regioselective O-Demethylation
2511
SCHEME 2
with several reports on the O- and N-dealkylation and debenzylation
under the influence of various reagents, to our knowledge the de-
scribed regioselective O-demethylation via the action of suphuric acid
is unusual and previously unreported. Nonselective O-demethylation
was reported to be conducted via the action of aqueous hydrobromic
acid,18 boron tribromide in dichloromethane,19,20 sodium ethanethi-
olate in dimethylformamide,21–23 and oxidative demethylation with
silver(II)oxide in the presence of nitric acid24 or cobalt trifluoride
in dioxane-water.25 Selective O-demethylation was achieved by the
action of diisobutylaluminium26 and magnesium iodide etherate.27
The cleavage of N-benzyl and alkyl bond has been reported to take
place via the action of catalytic hydrogenation,28 sodium or lithium
and ammonia,29,30 tert-butyllithium in tetrahydrofuran,31 aqueous
hydrobromic acid,32 95% formic acid,33 phenol and orthophosphoric
acid,34 trifluoroacetic acid,35,36 and diethyl azodicarboxylate.37
EXPERIMENTAL
Melting points (◦C, uncorrected) were recorded on a Fisher-Johns melt-
ing point apparatus. NMR spectra were recorded on a Bruker A 250 FT
instrument at 250 MHz for 1H NMR and 62.9 MHz for 13C NMR using
tetramethylsilane (TMS) as an internal standard and dimethylsulfox-
ide (DMSO)-d6 as solvent (Chemical shifts in δ ppm). Silica gel plates
60 F254 (Merck, Darmstadt, Germany) were used for monitoring the re-
action. Mass spectra were obtained on a Kratos MS 50-spectrometer at
70 eV. Analytical data (C, H, N, S) were within 0.4% of the theoretical
values.

2512
M. Al-Omar et al.
1-(3,4,5-Trimethoxybenzoyl)-4-substituted
Thiosemicarbazides 2a–i
A mixture of 3,4,5-trimethoxybenzoic acid hydrazide (2.26 g, 0.01 mol)
and the appropriate alkyl or arylisothiocyanate (0.01 mol) in ethanol
(20 ml) was heated under reflux for 1 h. On cooling, the precipitated
crystalline solid was filtered, washed with cold ethanol, and dried to
yield compounds 2a–i in 90–97% yields. The products were pure enough
to be used in the next step without further purification (Table I).
2a: 1H NMR: 2.87 (d, 3H, CH3), 3.71 (s, 3H, OCH3), 3.88 (s,
6H, OCH3), 7.25 (s, 2H, Ar H), 8.0 (s, 1H, NH, D2O-exchang.), 9.31
(s, 1H, NH, D2O-exchang.), 10.28 (s, 1H, NH, D2O-exchang.). 13C NMR:
31(CH3), 56 (2 × OCH3), 61 (OCH3), 106, 128, 152, 140, 167 (Ar C,
C O & C S).
2b: 1H NMR: 1.06 (t, 3H, CH3), 3.46 (q, 2H, CH2), 3.71 (s, 3H, OCH3),
3.83 (s, 6H, OCH3), 7.26 (s, 2H, Ar H), 8.06 (s, 1H, NH, D2O-exchang.),
9.25 (s, 1H, NH, D2O-exchang.), 10.26 (s, 1H, NH, D2O-exchang.). 13C
NMR: 13 (CH3), 36 (CH2), 56 (2 × OCH3), 60 (OCH3), 105, 128, 153,140,
166 (Ar C, C O, & C S).
2c: 1H NMR: 0.86 (t, 3H, CH3), 1.24 (q, 2H, CH2), 1.47 (q, 2H, CH2),
3.34 (q, 2H, CH2), 3.67 (s, 3H, OCH3), 3.83 (s, 6H, OCH3), 7.26 (s, 2H,
Ar H), 8.03 (s, 1H, NH, D2O-exchang.), 9.23 (s, 1H, NH, D2O-exchang.),
10.25 (s, 1H, NH, D2O-exchang.). 13C NMR: 14 (CH3), 20 (CH2), 31
(CH2), 43 (CH2), 56 (2 × OCH3), 59 (OCH3), 105, 127, 152, 140, 166
(Ar C, C O & C S).
1
2d: H NMR: 3.72 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 7.14–7.42 (m,
7H, Ar H), 9.76 (br s, 2H, NH, D2O-exchang.), 10.50 (s, 1H, NH, D2O-
exchang.).
TABLE I Melting Points, Yield Percentages, Molecular Formulae,
and Molecular Weights of Compounds 2a–i
Molecular formula
(mol. weight)
Comp. no.
R
m.p. (◦C)
Yield (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
CH3
C2H5
C4H9(n)
C6H5
4-FC6H4
4-ClC6H4
4-BrC6H4
C6H5CH2
(CH3)3C
210–212
205–207
188–190
185–187
210–212
204–206
234–236
200–202
160–162
94
90
90
95
94
96
97
92
90
C12H17N3O4S (299.34)
C13H19N3O4S (313.37)
C15H23N3O4S (341.42)
C17H19N3O4S (361.41)
C17H18FN3O4S (379.40)
C17H18ClN3O4S (395.86)
C17H18BrN3O4S (440.31)
C18H21N3O4S (375.44)
C15H23N3O4S (341.42)

Regioselective O-Demethylation
2513
1
2e: H NMR: 3.72 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 7.14 (s, 2H,
Ar H), 7.30 (d, 2H, Ar H), 7.43 (d, 2H, Ar H), 9.75 (br s, 2H, NH,
D2O-exchang.), 10.49 (s, 1H, NH, D2O-exchang.).
1
2f: H NMR: 3.71 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 7.29 (s, 2H,
Ar H), 7.37 (d, 2H, Ar H), 7.49 (d, 2H, Ar H), 9.82 (s, 2H, NH, D2O-
exchang.), 10.50 (s, 1H, NH, D2O-exchang.).
1
2g: H NMR: 3.72 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 7.29 (s, 2H,
Ar H), 7.45 (d, 2H, Ar H), 7.50 (d, 2H, Ar H), 9.83 (s, 2H, NH, D2O-
exchang.), 10.51 (s, 1H, NH, D2O-exchang.).
1
2h: H NMR: 3.70 (s, 3H, OCH3), 3.83 (s, 6H, OCH3), 4.73 (d, 2H,
CH2), 7.24–7.31 (m, 7H, Ar H), 8.62 (s, 1H, NH, D2O-exchang.), 9.45
(s, 1H, NH, D2O-exchang.), 10.36 (s, 1H, NH, D2O-exchang.).
2i: 1H NMR: 1.46 (s, 9H, CH3), 3.72 (s, 3H, OCH3), 3.83 (s, 6H, OCH3),
7.24 (s, 2H, Ar H), 8.21 (s, 1H, NH, D2O-exchang.), 9.12 (s, 1H, NH,
D2O-exchang.), 10.25 (s, 1H, NH, D2O-exchang.). 13C NMR: 29 (3 ×
CH3), 53 (C(CH3)3), 56 (2 × OCH3), 60 (OCH3), 105, 128, 131, 141, 153,
165 (Ar C, C O & C S).
2-(3,4,5-Trimethoxyphenyl)-5-substituted Amino-
1,3,4-thiadiazoles 3a–g
A mixture of the substituted thiosemicarbazide 2a–g (1.0 g) and phos-
phorus oxychloride (10 ml) was heated under reflux for 1 h, and the
mixture was then evaporated under reduced pressure. The resulting
residue was washed with saturated sodium hydrogen carbonate solu-
tion, then with water, dried and crystallized to yield compounds 3a–g
(Table II).
3a: 1H NMR: 2.91 (t, 3H, CH3), 3.68 (s, 3H, OCH3), 3.81 (s, 6H, OCH3),
7.01 (s, 2H, Ar H), 7.85 (br s, 1H, NH, D2O-exchang.). MS, m/z (Rel.
Int.): 281 (M+, 22), 267 (23), 266 (100), 194 (19), 180 (14), 88 (49), 74
(26).
TABLE II Melting Points, Yield Percentages, Crystallization Solvents,
Molecular Formulae, and Molecular Weights of Compounds 3a–g
Yield
(%)
Molecular formula
(mol. weight)
Comp. no.
R
Cryst. solv.
m.p. (◦C)
3a
3b
3c
3d
3e
3f
CH3
C2H5
C4H9(n)
C6H5
4-FC6H4
4-ClC6H4
EtOH
EtOH
EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
218–220
219–220
193–195
233–235
228–230
265–267
258–260
68
65
64
73
71
77
70
C12H15N3O3S (281.32)
C13H17N3O3S (295.35)
C15H21N3O3S (323.41)
C17H17N3O3S (343.40)
C17H16FN3O3S (361.39)
C17H16ClN3O3S (377.84)
C17H16BrN3O3S (422.29)
3g
4-BrC6H4 CHCl3/EtOH

2514
M. Al-Omar et al.
3b: 1H NMR: 1.19 (t, 3H, CH3), 3.33 (q, 2H, CH2), 3.69 (s, 3H, OCH3),
3.83 (s, 6H, OCH3), 7.0 (s, 2H, Ar H), 7.82 (br s, 1H, NH, D2O-exchang.).
13C NMR: 14 (CH3), 41 (CH2), 55 (2 × OCH3), 61 (OCH3), 103, 126, 138,
144, 154, 169 (Ar C & Thiadiazole-C). MS, m/z (Rel. Int.): 295 (M+, 8),
281 (12), 280 (100), 266 (25), 253 (9), 197 (18), 179 (64), 69 (46), 44 (58).
3c: 1H NMR: 1.12 (t, 3H, CH3), 1.40 (m, 2H, CH2), 1.53 (m, 2H, CH2),
3.45 (q, 2H, NHCH2), 3.70 (s, 3H, OCH3), 3.87 (s, 6H, OCH3), 7.0 (s, 2H,
Ar H), 8.22 (s, 1H, NH, D2O-exchang.).
1
3d: H NMR: 3.71 (s, 3H, OCH3), 3.86 (s, 6H, OCH3), 6.99–7.35 (s,
7H, Ar H), 7.81 (s, 1H, NH, D2O-exchang.).
1
3e: H NMR: 3.70 (s, 3H, OCH3), 3.85 (s, 6H, OCH3), 7.07 (s, 2H,
Ar H), 7.20 (d, 2H, Ar H), 7.66 (d, 2H, Ar H). 8.02 (s, 1H, NH,
D2O-exchang.). 13C NMR: 55 (2 × OCH3), 60 (OCH3), 104, 115, 119,
125, 137, 139, 148, 156, 164 (Ar C & Thiadiazole-C). MS, m/z (Rel.
Int.): 362 (M+ + 1, 11), 361 (M+, 58), 347 (13), 346 (22), 208 (5), 194 (7),
193 (16), 168 (15), 95 (16), 69 (65), 45 (100).
1
3f: H NMR: 3.71 (s, 3H, OCH3), 3.85 (s, 6H, OCH3), 7.01 (s, 2H,
Ar H), 7.34 (d, 2H, Ar H), 7.44 (d, 2H, Ar H). 8.05 (s, 1H, NH, D2O-
exchang.).
1
3g: H NMR: 3.72 (s, 3H, OCH3), 3.85 (s, 6H, OCH3), 7.11 (s, 2H,
Ar H), 7.51 (d, 2H, Ar H), 7.61 (d, 2H, Ar H). 8.46 (s, 1H, NH, D2O-
exchang.). MS, m/z (Rel. Int.): 423 (M+ + 2, 43), 422 (M+ + 1, 12), 421
(M+, 45), 409 (86), 407 (88), 393 (11), 377 (14), 363 (9), 228 (50), 230
(51), 194 (72), 179 (100), 45 (94).
2-(4-Hydroxy-3,5-dimethoxyphenyl)-5-substituted
Amino-1,3,4-thiadiazoles 4a–g
98% Sulphuric acid (6 ml) was added dropwise to the appropriate sub-
stituted thiosemicarbazide 2a–g (1.0 g), and the mixture was stirred
at ambient temperature for 24 h. The resulting homogenous mixture
was poured onto crushed ice (100 g), neutralized with ammonium hy-
droxide solution, and the separated yellowish orange precipitate was
filtered, washed with water, dried, and crystallized to yield compounds
4a–g (Table III).
1
4a: H NMR: 2.92 (d, 3H, CH3), 3.82 (s, 6H, OCH3), 7.01 (s, 2H,
Ar H), 7.86 (s, 1H, NH, D2O-exchang.), 8.81 (br s, 1H, OH, D2O-
exchang.). MS, m/z (Rel. Int.): 268 (M+ + 1, 21), 267 (M+, 100), 252
(9), 194 (22), 179 (38), 88 (69).
4b: 1H NMR: 1.18 (t, 3H, CH3), 3.70 (q, 2H, CH2), 3.82 (s, 6H, OCH3),
6.97 (s, 2H, Ar H), 7.85 (s, 1H, NH, D2O-exchang.), 8.82 (br s, 1H,
OH, D2O-exchang.). 13C NMR: 14 (CH3), 40 (CH2), 56 (2 × OCH3),
103, 121, 126, 148, 156, 168 (Ar C & Thiadiazole-C). MS, m/z (Rel.

Regioselective O-Demethylation
2515
TABLE III Melting Points, Yield Percentages, Crystallization Solvents,
Molecular Formulae, and Molecular Weights of Compounds 4a–g
Yield
(%)
Molecular formula
(mol. weight)
Comp. no.
R
Cryst. solv.
m.p. (◦C)
4a
4b
4c
4d
4e
4f
CH3
C2H5
EtOH/H2O
EtOH/H2O
MeOH
EtOH
EtOH
139–140
152–154
133–135
218–220
215–217
220–222
207–209
52
53
50
68
62
70
74
C11H13N3O3S (267.30)
C12H15N3O3S (281.32)
C14H19N3O3S (309.38)
C16H15N3O3S (329.37)
C16H14FN3O3S (347.36)
C16H14ClN3O3S (363.81)
C16H14BrN3O3S (408.26)
C4H9(n)
C6H5
4-FC6H4
4-ClC6H4
4-BrC6H4
EtOH
EtOH
4g
Int.): 282 (M+ + 1, 20), 281 (M+, 100), 266 (16), 253 (18), 197 (20),
179 (64).
4c: 1H NMR: 0.91 (t, 3H, CH3), 1.35 (m, 2H, CH2), 1.47 (m, 2H, CH2),
3.40 (q, 2H, NHCH2), 3.85 (s, 6H, OCH3), 6.99 (s, 2H, Ar H), 7.77 (br
s, 1H, NH, D2O-exchang.), 8,66 (br s, 1H, OH, D2O-exchang.).
1
4d: H NMR: 3.85 (s, 6H, OCH3), 7.05–7.24 (s, 7H, Ar H), 7.75 (br
s, 1H, NH, D2O-exchang.), 9.88 (br s, 1H, OH, D2O-exchang.).
1
4e: H NMR: 3.87 (s, 6H, OCH3), 7.07 (s, 2H, Ar H), 7.19 (d, 2H,
Ar H), 7.62 (d, 2H, Ar H), 7.88 (br s, 1H, NH, D2O-exchang.), 10.53 (s,
1H, OH, D2O-exchang.). 13C NMR: 56 (2 × OCH3), 105, 115, 119, 125,
137, 139, 148, 153, 158, 164 (Ar C & Thiadiazole-C). MS, m/z (Rel. Int.):
347 (M+ + 1, 28), 346 (M+, 47), 328 (9), 208 (11), 193 (33), 168 (32), 95
(35), 69 (100).
1
4f: H NMR: 3.86 (s, 6H, OCH3), 7.06 (s, 2H, Ar H), 7.41 (d, 2H,
Ar H), 7.72 (d, 2H, Ar H), 7.95 (s, 1H, NH, D2O-exchang.), 10.34 (s, 1H,
NH, D2O-exchang.). MS, m/z (Rel. Int.): 356 (M+ + 2, 41), 364 (M+ + 1,
23), 363 (92), 349 (8), 195 (47), 184 (49), 179 (55), 69 (54), 45 (100).
1
4g: H NMR: 3.85 (s, 6H, OCH3), 7.08 (s, 2H, Ar H), 7.52 (d, 2H,
Ar H), 7.61 (d, 2H, Ar H), 8.90 (s, 1H, NH, D2O-exchang.), 10.51 (s, 1H,
OH, D2O-exchang.). MS, m/z (Rel. Int.): 409 (M+ + 2, 97), 408 (M+ + 1,
30), 407 (M+, 97), 393 (6), 377 (7), 363 (19), 329 (4), 231 (48), 229 (47),
194 (82), 179 (100), 45 (98).
2-(4-Hydroxy-3,5-dimethoxyphenyl)-5-amino-
1,3,4-thiadiazole 5
Sulphuric acid (98%, 5 ml) was added to compound 2h or 2i (0.01 mol),
and the mixture was stirred at ambient temperature for 24 h. The
obtained yellowish green syrupy solution was then added cautiously
to crushed ice (100 g), neutralized with saturated sodium hydrogen

2516
M. Al-Omar et al.
carbonate solution, and stirred for 1 h. The separated yellowish white
precipitate was filtered, washed with water, dried, and crystallized from
ethanol to yield 1.04 g (41%) or 1.75 g (69%) of compound 5 in cases of
1
compounds 2h and 2i, respectively, m.p. 128–130◦C. H NMR: 3.82 (s,
6H, OCH3), 6.97 (s, 2H, Ar H), 7.46 (s, 2H, NH2, D2O-exchang.), 9.45
(br. s, 1H, OH, D2O-exchang.). 13C NMR: 56 (OCH3), 104, 121, 137, 148,
157, 168 (Ar C & Thiadiazole-C). MS, m/z (Rel. Int.), C10H11N3O3S
(253.27): 254 (M+ + 1, 13.9), 253 (M+, 100), 238 (11.6), 194 (4.1), 180
(29.1), 164 (14.8), 153 (5.9), 74 (29.1), 45 (36.2).
2-(3,4,5-Trimethoxyphenyl)-5-amino-1,3,4-thiadiazole 6
A mixture of phosphorus oxychloride (10 ml) and compound 2h or 2i
(0.01 mol) was heated under reflux for 2 h. The mixture was evaporated
in vacuo, and the residue was washed with diluted ammonia solution
and then with water, dried, and crystallized from CHCl3/EtOH to yield
0.91 g (34%) or 1.9 g (71%) of compound 6 in the cases of compounds 2h
and 2i, respectively, m.p. 122–124◦C. 1H NMR: δ 3.79 (s, 3H, OCH3), 3.81
(s, 6H, OCH3), 6.95 (s, 2H, Ar H), 7.55 (s, 2H, NH2, D2O-exchang.). 13
C
NMR: 56 (2 × OCH3), 60 (OCH3) 104, 107, 138, 147, 153, 169 (Ar C &
Thiadiazole-C). MS, m/z (Rel. Int.), C11H13N3O3S (267.30): 268 (M+ + 1,
11.3), 267 (M+, 56.9), 252 (18.24), 224 (9.51), 179 (6.10), 164 (5.39), 152
(6.74), 135 (12.22), 95 (18.25), 69 (85.03), 45 (100).
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