Synthesis of New 1,3,4-Thiadiazole Derivatives Containing of Morpholine Ring

Article abstract of DOI:10.14233/ajchem.2013.13227

The synthesis of new of 1,3,4-thiadiazole derivatives containing of morpholine ring are investigated. In this study, the derivatives of naphthol, amine and phenol are reacted with 4-morpholine carbonyl chloride. Then, prepared solutions are added to diazo

Full text of DOI:10.14233/ajchem.2013.13227

Asian Journal of Chemistry; Vol. 25, No. 1 (2013), 487-489
http://dx.doi.org/10.14233/ajchem.2013.13227
Synthesis of New 1,3,4-Thiadiazole Derivatives Containing of Morpholine Ring
1,*
1
2
H. HAMIDIAN , M. AFROOZ and S. FOZOONI
1Department of Chemistry, Payame Noor University, P.O. Box 19395-3697, Tehran, Iran
2Mining and Engineering Department of Zarand, Shahid Bahonar University, Kerman, Iran
*Corresponding author: Fax: +98 341 3342465; Tel: +98 341 3342465; E-mail: h_hamidian@pnu.ac.ir
(Received: 12 December 2011; Accepted: 1 August 2012)
AJC-11906
The synthesis of new of 1,3,4-thiadiazole derivatives containing of morpholine ring are investigated. In this study, the derivatives of
naphthol, amine and phenol are reacted with 4-morpholine carbonyl chloride. Then, prepared solutions are added to diazotized 2-amino-
5-mercapto-1,3,4-thiadiazole to give 2-amino-5-mercapto-1,3,4-thiadiazole products. These dyes were characterized by elemental analysis
and spectral analyses (IR, 1H NMR, 13C NMR and mass spectra).
Key Words: 1,3,4-Thiadiazole, Azo dyes, Sulfur, Synthesis, Morpholine.
magnetic resonance spectra were recorded on the BRUKER
400 spectrometer using tetramethylsilane (TMS) as an internal
standard. Mass spectra were obtained by SHIMADZU QP
1100EX. Elemental analyses were performed by Heracus CHN-
O-Rapid analyzer. UV spectra were recorded using a GBC
scientific equipment (CINTRA 5) UV visible spectrometer.
2-Amino-5-mercapto-1,3,5-thiadiazole (0.01 mol) was
added to 2.5 % sodium carbonate solution (35 mL) until it
was dissolved by boiling. The solution was then cooled and
sodium nitrite (0.01 mol) was added, with stirring, until it was
dissolved. The solution was cooled by placing it in an ice bath
and then concentrated hydrochloric acid (3 mL) and water
(5 mL) were added. By acidifying the solution, a powdery
yellow precipitate of the diazonium salt was separated.
Appropriate aromatic compounds (2) (0.01 mol) was
added to morpholine carbonyl chloride (0.01 mol) and was
refluxed for 20 min on the water bath. The residue was mixed
with water (15 mL) to give yellow solution. The solution was
added to suspension of 1,3,4-thiadiazole diazonum salt and a
powdery precipitate was separated after 1 h. The crud product
was recrystallized from appropriate solvent.
INTRODUCTION
Recently, synthesis of thiadiazoles has attracted widespread
attention due to their diverse applications as antibacterial,
antimycobacterial, antimycotic, antifungal and antimicrobial
effects1-4.
Heterocyclic azo dyes are extensively used for textile or
non-textile applications including their application in repro-
graphy, functional dye and non-linear optical systems, photo-
dynamic therapy and lasers.Azo dyes containing heterocyclic
rings lead to brighter and often deeper shades than their
benzene analogues and they are still very important for appli-
cations such as disperse dyes for polyester fibers5-7.
Dyes derived from 2-amino-5-mercapto-1,3,4-thiadiazole
are of technical interest for the production of brilliant red shades.
Comparatively less research work has been done regarding
this class compared to the other categories of dyes derived
from five-membered sulphur-containing heterocycles. In
addition, the level of recent patent activity has been low,
although papers focusing exclusively on dyes derived from
1,3,4-thiadiazole have appeared.
As no report seems to be available in the literature on the use
of 2-amino-1,3,4-thiadiazole and morpholine in the synthesis of
new 1,3,4-thiadiazole derivatives by coupling with naphthol,
amine and phenol. Herein, we wish to report synthesis of some
new 2-amino-5-mercapto-1,3,4-thiadiazole products.
N4-{4-[2-(5-Sulfanyl-1,3,4-thiadiazol-2-yl)-1-diazenyl]
phenyl}-4-morpholine carboxamide (4a): Recrystallization
in 2-propanol.Yellow powder. m.p. 135-136 ºC. IR (KBr, νmax
,
cm-1): 3266, 1635. 1H NMR (400 MHz, DMSO-d6): 3.49 (t, J
= 4.8, 4H, 2CH2); 3.60 (t, J = 4.6, 4H, 2CH2); 6.92 (s, 1H,
NH); 7.22 (d, J = 8.0, 2H, ArH); 7.44 (d, J = 7.6, 2H, ArH);
8.54 (s, 1H, NH). 13CNMR (400 MHz, DMSO-d6): 44.65,
66.48, 118.46, 120.13, 128.75, 129.21, 140.85, 155.68 ppm.
C13H14N6O2S2 calcd: C 44.57, H 4.00, N 24.00; found: C 44.66,
EXPERIMENTAL
Melting points were determined on a Gallenkamp melting
point apparatus and are uncorrected. IR spectra were recorded
with the MATTSON 1000 FT-IR Spectrophotometer. Nuclear

488 Hamidian et al.
Asian J. Chem.
RESULTS AND DISCUSSION
H 3.81, N 23.80. MS m/z: 203 (70 %), 114 (86 %), 86 (46 %),
76 (31 %), 70 (100 %).
N4-{3-Nitro-4-[2-(5-sulfanyl-1,3,4-thiadiazol-2-yl)-1-
diazenyl] phenyl}-4-morpholine carboxamide (4b): Recrys-
tallization in DMF and water (4:1).Yellow powder. m.p: 163-
164 ºC. IR (KBr, νmax, cm-1): 3280, 1663, 1530, 1349. 1H NMR
(400 MHz, DMSO-d6): 2.88 (t, J = 4.8, 4H, 2CH2); 3.35 (t, J =
4.6, 4H, 2CH2); 7.69-8.13 (m, 5H, ArH and 2NH). 13C NMR
(400 MHz, DMSO-d6): ppm. 45.78, 67.91, 115.21, 124.64,
128.12, 134,97, 138.37, 141.83, 146.47, 152.33, 159.71.
C13H13N7O4S2 calcd.: C 39.49, H 3.29, N 24.81; found: C 39.57,
H 3.11, N 24.96. MS m/z: 149 (60 %), 121 (100 %), 112 (49
%), 90 (68 %), 75 (98 %).
Morpholine carbonyl chloride (1) reacted with appropriate
aromatic compounds (2) and are produced morpholine deriva-
tives (3a-3f) (Fig. 1).
O
O
O
N
Ar
O
N
+
Cl
Ar
(2)
(1)
Aniline, 3-Nitroaniline,
(3a-3f)
Ar=
1-Naphthole, Resorcinol, 1-Amino-
2-hydroxy-4-naphthalene sulfonic acid, 4-Amino-5-hydroxy
naphthalene-2,7-disulfonic acid
Fig. 1. Reaction of Morpholine carbonyl chloride with appropriate aromatic
compounds
3-Hydroxy-4-[2-(5-sulfanyl-1,3,4-thiadiazol-2-yl)-1-
diazenyl]phenyl}-4-morpholine carboxylate (4c): Recrys-
tallization in 2-propanol. Orange powder. m.p.: 89-90 ºC. IR
1
2-Amino-5-mercapto-1,3,4-thiadiazole (4) was diazotized
satisfactorily at 0 ºC by adding to nitrosyl hydrochloric acid
(Fig. 2).
(KBr, νmax, cm-1): 3267, 3101, 1696. H NMR (400 MHz,
DMSO-d6): 3.39 (t, J = 4.8, 4H, 2CH2); 3.62 (t, J = 4.7, 4H,
2CH2); 6.47-7.83 (m, 5H, ArH, 2NH); 9.29 (s, 1H, OH).
13CNMR (400 MHz, DMSO-d6): 43.33, 63.63, 103.77, 109.52,
112.82, 129.99, 137.7, 152.44, 158.62, 159.99, 169.64. ppm.
C13H13N5O4S2 calcd.: C 42.51, H 3.54, N 19.07; found: C 42.33,
H 3.61, N 19.24. MS m/z: 149 (11 %), 114 (26 %), 84 (20 %),
58 (42 %), 42 (100 %).
N
N
N
N
NaNO2/HCl
HS
NH2
+
N2
-
HS
S
Cl
S
(4)
(5)
4-[2-(5-Sulfanyl-1,3,4-thiadiazol-2-yl)-1-diazenyl]-1-
naphthyl-4-morpholine carboxylate (4d): Recrystallization
in 2-propanol. Red powder. m.p: 52-53 ºC. IR (KBr, νmax, cm-1):
3055, 2358, 1697. 1H NMR (400 MHz, DMSO-d6): 3.36 (t, J
= 4.8, 4H, 2CH2); 3.66 (t, J = 4.6, 4H, 2CH2); 7.06-7.94 (m,
7H, Ar, NH); 9.74 (s, 1H, NH). 13C NMR (400 MHz, DMSO-
d6): 43.20, 63.69, 118.83, 119.06, 122.35, 124.07, 126.03,
127.87, 128.17, 129.73, 133.78, 135.06, 149.25, 155.77,
162.78 ppm. C17H15N5O3S2 calcd: C 50.87, H 3.74, N 17.46;
found: C 50.58, H 3.59, N 17.33. MS m/z: 256 (30 %), 144
(100 %), 114 (76 %), 70 (19 %).
Fig. 2. Diazotation of 2-amino-5-mercapto-1,3,4-thiadiazole
In order to determine the end point of diazotization, it
was found useful to check for the presence of unreacted diazo
component on TLC by sampling the diazotization mixture.
Thus, when unreacted diazo component no longer persisted
on TLC, the diazotization was ended. Coupling compounds
(3a-3f) was added to diazonum salt of 2-amino-5-mercapto-
1,3,5-thiadiazole (5) to give 2-amino-5-mercapto-1,3,4-
thiadiazole products (Fig. 3).
3-Hydroxy-4-[(morpholinocarbonyl)amino]-2-[(5-
sulfanyl-1-diazenyl]-1-naphthalene sulfonic acid (4e):
Recrystallization in ethanol. Brown powder. m.p: 57-59 ºC.
IR (KBr, νmax, cm-1): 3417, 3292, 2457, 1622. 1H NMR (400
MHz, DMSO-d6): 3.47 (t, J = 4.7, 4H, 2CH2); 3.76 (t, J = 4.5,
4H, 2CH2); 6.91-7.79 (m, 7H, Ar, OH, SO3H, NH ); 8.54 (s,
1H, NH). 13C NMR (400 MHz, DMSO-d6): 43.05, 63.62,
109.11, 119.08, 122.35, 124.07, 126.43, 127.03, 128.17,
129.73, 131.18, 133.78, 149.25, 155.77, 162.78 pm.
C17H16N6O6S3 calcd: C 41.13, H 3.23, N 16.94; found: C 40.98,
H 3.12, N 17.04. MS m/z: 463 (6 %), 158 (12 %), 105 (14 %),
86 (63 %), 56 (100 %).
N N
O
Ar
O
N
N
+
-
+
N2
HS
Cl
S
O
N N
S
N
Ar
O
N
HS
(6a-6f)
Fig. 3. Reaction of diazonum salt of 2-amino-5-mercapto-1,3,5-thiadiazole
with morpholine derivatives
All the recrystallized products exhibited well-defined
melting points characteristics of pure compounds. It would be
unwise to attempt to explain in detail their relative values,
because of the complex dependence of the melting points on
a number of factor like polarity, size, geometry, interaction,
etc. the purity of the dyes were checked by TLC using ethyl
acetate-benzene (1:4) as the solvent system. When adsorbed
onto silica chromatography plates, the dyes produced a single
colour spot.
4-Hydroxy-5- [(morpholinocarbonyl)amino]-3-[2-(5-
sulfanyl-1,3,4-thiadiazole-2-yl)-1-diazenyl]-2,7-naphthalene
disulfonic acid (4f): Recrystallization in ethanol. Purple
powder. m.p.: 117-119 ºC. IR (KBr, νmax, cm-1): 3417, 3310,
2356, 1619. 1H NMR (400 MHz, DMSO-d6): 3.43 (t, J = 4.8,
4H, 2CH2); 3.77 (t, J = 4.6, 4H, 2CH2), 7.24-7.83 (m, 5H, Ar,
OH, NH); 9.54 (broad, 3H, NH, 2SO3H). 13CNMR (400 MHz,
DMSO-d6): 46.53, 65.92, 107.13, 111.23, 112.78, 115.26,
121.68, 124.55, 129.33, 134.61, 137.34, 141.29, 148.79,
159.11, 164.83 ppm. C17H16N6O9S4 calcd.: C 35.42, H 2.78, N
14.58; found: C 35.51, H 2.61, N 14.40. MS m/z: 330 (7 %),
114 (24 %), 86 (54 %), 56 (100 %).
Generally, variation in colour of these dyes results from
the alternation in coupling components. Since the synthesized
dyes obtained varied in colour from yellow to brown, a

Vol. 25, No. 1 (2013)
Synthesis of New 1,3,4-Thiadiazole Derivatives Containing of Morpholine Ring 489
TABLE-1
YIELDS AND λmax OF PREPARED 1,3,4-THIADIAZOLE DERIVATIVES
Entry
1
Ar
Product
Yieldb (%)
72
λmaxa (nm)
NH2
N
N
O
N
N
N
HS
HS
6a
6b
6c
423
N
S
N
O
H
NH2
N
N
O
N
N
2
3
384
447
78
74
S
N
H
O
O2N
N
O2N
HO
OH
N
N
N
O
O
N
N
HS
HS
N
N
S
O
O
O
O
HO
N
N
OH
S
4
6d
542
66
O
NH2
HO
H
N
N
HO
N
N
5
N
6e
495
64
O
N
HS
S
O3SH
HSO3
O
N
NH
O
NH2 OH
HSO3
6
6f
623
58
OH
SO3H
HO3S
N
N
N
N
S
SO3H
SH
aλmax was determined in DMSO; bIsolated product
convenient method of measuring the colour of the compound
was to study the absorption spectra of their solutions. The
visible absorption maxima for the synthesized dyes were
measured in Me2SO at the concentration of 10-5 M and are
listed in Table-1. The absorption maxima of the synthesized
dyes ranged from 384 to 623 nm (Table-1).
ACKNOWLEDGEMENTS
The authors appreciated the cooperation of Department
of Chemistry, Payame Noor University of Kerman for suppor-
ting this investigation.
REFERENCES
In this work, 2-amino-5-mercapto-1,3,4-thiadiazole
derivatives in DMSO were tautomerized. (Fig 4).
1. V. Kumar and P. Singh, Asian. J. Chem., 22, 6829 (2010).
2. A. Foroumadi, S. Pournourmohammadi, F. Soltani, M.Asgharian- Rezaee,
S. Dabiri, A. Kharazmi and A. Shafiee, Bioorg. Med. Chem. Lett., 15,
1983 (2005).
O
N
N
3. O. Pintilie, L. Profire, V. Sunel, M. Popa and A. Pui, Molecules, 12,
103 (2007).
HS
N
S
N
N
H
N
S
4. A.A. Elagamey, F.M.A. El-Taweel and R.A.N. Abu-El-Enein, Phos-
phorus, Sulfur, Silicon Rel. Elem., 181, 2155 (2006).
5. P.C. Tsai and I.J. Wang, Dyes Pigments, 74, 578 (2007).
6. S. Gupta,A. Sivasubramanian, L.M. Rodrigues,A.P. Esteves, R. Hrdina
and A.M.F. Oliveira-Campos, Dyes Pigments, 75, 82 (2007).
7. S. Fozooni, A.M. Tikdari, H. Hamidian and H. Khabazzadeh, Arkivoc,
115 (2008).
O
O
N
N
N
N
H
N
H
N
S
O
Fig. 4. Tautomerism of new 1,3,4-thiadiazole compounds