Synthesis and characterization of novel benzaldehyde derivatives containing 1,3,4-thiadiazole

Article abstract of DOI:10.1007/s11164-013-1065-8

In the work discussed in this paper, a series of novel benzaldehyde derivatives containing 1,3,4-thiadiazole were prepared in high yield from 4-fluorobenzaldehyde and 2-amino-5-substituted-1,3,4-thiadiazole. The products were characterized by determination of melting point, elemental analysis, and UV-visible, IR, ¹H NMR, and ¹³C NMR spectroscopy. The fluorescence properties of the compounds were also studied by recording their fluorescence emission spectra.

Full text of DOI:10.1007/s11164-013-1065-8

Res Chem Intermed
DOI 10.1007/s11164-013-1065-8
Synthesis and characterization of novel benzaldehyde
derivatives containing 1,3,4-thiadiazole
•
Yu-Ting Liu Li Feng Da-Wei Yin Bao-Jun Su
•
•
Received: 5 September 2012 / Accepted: 17 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract In the work discussed in this paper, a series of novel benzaldehyde
derivatives containing 1,3,4-thiadiazole were prepared in high yield from 4-fluo-
robenzaldehyde and 2-amino-5-substituted-1,3,4-thiadiazole. The products were
characterized by determination of melting point, elemental analysis, and UV–visi-
1
ble, IR, H NMR, and 13C NMR spectroscopy. The fluorescence properties of the
compounds were also studied by recording their fluorescence emission spectra.
Keywords Benzaldehyde derivatives Á 1,3,4-Thiadiazole Á Fluorescence Á
Characterization
Introduction
In recent years there has been intense investigation of different classes of
thiadiazole compounds, many of which are known to have interesting biological
properties, for example antimicrobial [1], anti-tuberculosis [2], anti-inflammatory
[3], anti-convulsant [4], anti-hypertensive [5], local anesthetic [6], anticancer [7],
and hypoglycemic [8] activity.
1,3,4-Thiadiazole is a heterocyclic compound containing N and S heteroatoms
[9–11] and obvious conjugation and aromaticity [12].The 2,5-substituents as active
Y.-T. Liu Á D.-W. Yin
Key laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of
Education, Shaanxi University of Science and Technology, Xi’an 710021, China
L. Feng (&) Á B.-J. Su
School of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology,
Xi’an 710021, China
e-mail: fengli870708@163.com
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Y.-T. Liu et al.
N
N
CHO
DMF
+
NH2
R
triethylamine
S
F
CHO
N
N
NH
R
S
R: a=H; b=CH3; c=C2H5; d=C3H7; e=Ph-OCH2; f=NAPh-OCH2
Scheme 1 Synthesis of novel benzaldehyde derivatives containing 1,3,4-thiadiazole
groups can react with many compounds, so 2,5-disubstituted-1,3,4-thiadiazole
compounds are often important intermediates in organic synthesis and medicinal
chemistry [13, 14]. As a result of increasing research work, 1,3,4-thiadiazole
compounds have been widely used in agriculture, industry, medicine, and materials,
among others [15]. Benzaldehyde derivatives are used as intermediates in the
pharmaceutical, dye, and spice industries [16, 17].
Because biological and analytical interest in 1,3,4-thiadiazole derivatives, to
discover more biologically active compounds we prepared a series of novel
benzaldehyde derivatives containing 1,3,4-thiadiazole, in high yield, from 4-fluo-
robenzaldehyde and 2-amino-5-substituted-1,3,4-thiadiazole. The products
were characterized by determination of melting point, elemental analysis, and
1
UV–visible, IR, H NMR, and 13C NMR spectroscopy.
The results showed that the structures of the target product were consistent with
initial predictions (Scheme 1).
Results and discussion
Effect of acid-binding agent (triethylamine)
An acid-binding agent is a compound with weak nucleophilicity and strong
alkalinity used to avoid the occurrence the nucleophilic reaction with starting
materials. Amines are usually nucleophilic. Because of the large steric hindrance
of triethylamine it is not conducive to attack by electrophilic reagents. If acid,
for example hydrogen fluoride, is released during a reaction triethylamine
quickly absorbs it. In this way it accelerates the reaction in the required direction
and reduces formation of by-products. Thus, the main purpose of adding a small
amount of triethylamine was to neutralize any acid produced in the reaction and
increase yields; it did not participate in the reaction. The mechanism of the
reaction was:
123

Synthesis and characterization of novel benzaldehyde derivatives
CHO
H
N
H
N
N
N
CHO
N
N
R
··
NH2 +
S
R
F
F
S
Et3N
CHO
N
NH
R
S
Effect of K2CO3
In this work we investigated addition of anhydrous potassium carbonate to the
reactants, in accordance with the literature [18]. Anhydrous potassium carbonate
was difficult to dissolve in the solution, however, and the reaction time was long
(24 h) and the yield was low (60 %). When anhydrous potassium carbonate was not
added, reaction time was greatly reduced (10 h) and the yield was increased
substantially (more than 90 %).
Infrared analysis
In the IR spectra of the novel benzaldehyde derivatives containing 1,3,4-thiadiazole, the
characteristic absorption of N–H bonds was at 3,500–3,100 cm-1, the characteristic
absorption of aldehyde groups was at 2,850–2,720 cm-1, the characteristic absorption
of phenyl ring carbon–carbon bonds was at 1,600–1,450 cm-1, and the characteristic
absorption of p-disubstituted phenyl rings was at 860–800 cm-1
.
Fluorescence properties
The fluorescence spectra of the novel compounds (1 9 10-4 mol dm-3) were
measured in ethanol as solvent at room temperature. They were very similar to the
spectra of corresponding solids. The fluorescence of the compounds in the solid
state was much stronger than that of the corresponding compounds in solution.
However, additional fluorescence observed for 4-(2-amino-5-b-naphthoxymethyl-
ene-1,3,4-thiadiazole)benzaldehyde was not observed for the other five new
compounds. The was possibly because the reversibility of charge transfer led to
fluorescence quenching, or because of the naphthalene ring.
Thus the new fluorescent reagent 4-(2-amino-5-b-naphthoxymethylene-1,3,4-
thiadiazole)benzaldehyde might be of theoretical and practical significance for the
development of metal or other complexes as a new types of fluorescent probe.
123

Y.-T. Liu et al.
Experimental
Melting points were determined in open capillaries on a Tempo Mel Temp
apparatus and are uncorrected.
Reported yields of the compounds are after purification. IR spectra were recorded
with a Perkin–Elmer model 337 grating infrared spectrophotometer (mmax in cm-1
)
in KBr pellets. NMR spectra were recorded in DMSO-d6 at 100 and 400 MHz on
Bruker spectrospin and Varian EM-360 spectrometers with TMS as internal
standard (chemical shifts in d ppm). UV–visible spectra were recorded on a model
TU-1900 double-beam UV–visible spectrophotometer. Fluorescence spectra were
recorded on a model F-4500 fluorescence spectrometer. Elemental analysis was
performed with a Yan aco CHN Corder MT-3 instrument. The 2-amino-5-
substituted-1,3,4-thiadiazoles were prepared in accordance with literature proce-
dures [19]. Phenoxyacetic acid and naphthoxyacetic acid were synthesized in our
laboratories.
4-(2-amino-5-substituted-1, 3, 4-thiadiazole) benzaldehyde (a–f)
General procedure
DMF (5 mL), 4-fluorobenzaldehyde (6 mmol), 2-amino-5-substituted-1,3,4-thia-
diazol (5 mmol), and triethylamine (0.5 mL) were placed in a round-bottomed flask.
The reaction mixture turned yellow and was stirred for 10 h at 85 °C (TLC). After
cooling to room temperature, it was poured into ice-water (10 mL), and a pale-
yellow solid formed immediately. The product was isolated by filtration and dried in
vacuo to give a–f.
4-(2-Amino-1,3,4-thiadiazole)benzaldehyde (a) M.p. 191–192 °C, Yield 90.2 %;
UV–visible (C2H5OH, kmax, nm): 265, 2.654. IR (KBr, m/cm-1): 3,423.56 cm-1
(msN–H,s); 3,017.37 cm-1 (vC–H,s); 2,854.58 cm-1 (vC–H,s); 1,679.10 cm-1 (mC=O,s);
1,626.74 cm-1 (mC=N,s); 1,596.20 cm-1, 1,570.34 cm-1, 1,496.69 cm-1, 1,441.63 cm-1
;
1,387.06 cm-1 (mN–H,s); 1,261.93 cm-1 (mCN,s); 1,033.61 cm-1, 1,009.34 cm-1
,
494.73 cm-1 (mN–C–S,w); 812.34 cm-1; 716.56 cm-1 (mC–S–C,w); 1H NMR (DMSO-d6),
d:10.58 (s,1H,–CHO); 6.63–7.87 (m, 4H, Ph-H); 6.61 (s,1H,–CH); 3.09 (s,1H,–NH);13C
NMR (DMSO-d6), d: 120.34, 121.45, 127.31, 149.66, 163.89, 169.56, 190.13. Anal. Calcd.
for C9H7N3SO: C, 52.67; H, 3.44; N, 20.47; Found: C, 52.53, H, 3.43; N, 20.42.
4-(2-Amino-5-methyl-1,3,4-thiadiazole)benzaldehyde (b) M.p. 155–156 °C, Yield
93.5 %; UV–visible (C2H5OH, kmax, nm): 263, 1.104. IR (KBr, m/cm-1): 3,417.56 cm-1
(msN–H,s); 3,067.84 cm-1 (vC–H, s); 2,805.20 cm-1 (vC–H,s); 1,653.35 cm-1 (mC=O,s);
1,620.96 cm-1 (mC=N,s); 1,600.92 cm-1, 1,581.14 cm-1, 1,509.09 cm-1, 1,434.87
cm-1; 1,382.61 cm-1 (mN–H,s); 1,381.27 cm-1; 1,267.34 cm-1 (mC–N,s); 1,038.74
cm-1, 1,013.75 cm-1, 488.74 cm-1 (mN–C–S,w); 838.78 cm-1; 729.78 cm-1 (mC–SC,w);
1H NMR (DMSO-d6), d: 10.69 (s,1H,–CHO); 7.03–8.03 (m,4H,Ph-H); 3.10 (s,1H,–NH);
2.34 (s,3H,–CH3); 13C NMR (DMSO-d6), d: 16.28, 121.34, 123.45, 128.31, 149.96,
123

Synthesis and characterization of novel benzaldehyde derivatives
163.99, 170.56, 190.53. Anal. Calcd. for C10H9N3SO: C, 54.78; H, 4.14; N, 19.16; Found:
C, 54.68, H, 4.15; N, 19.14.
4-(2-Amino-5-ethyl-1,3,4-thiadiazole)benzaldehyde (c) M.p. 101–102 °C, Yield
92.8 %; UV–visible (C2H5OH, kmax, nm): 264, 1.854. IR (KBr, m/cm-1):
3,391.25 cm-1 (msN–H,s); 3,066.60 cm-1 (vC–H,s); 2,865.23 cm-1 (vC–H,s);
1,688.19 cm-1 (mC=O,s); 1,625.67 cm-1 (mC=N,s); 1,619.11 cm-1, 1,589.46 cm-1
,
1,509.01 cm-1, 1,450.86 cm-1; 1,377.89 cm-1 (mN–H,s); 1,470.57 cm-1, 1,380.27
cm-1; 1,173.72 cm-1 (mC–N,s); 1,032.78 cm-1,1,012.05 cm-1,496.90 cm-1 (mN–C–S,w);
817.24 cm-1; 803.44 cm-1 (mC–S–C,w). 1H NMR (DMSO-d6), d: 10.89 (s, 1H, –CHO);
6.63–8.01 (m,4H,Ph-H); 2.04 (m, 2H, –CH2); 3.11 (s, 1H, –NH); 1.49–1.27 (m, 3H,–
CH3);13C NMR (DMSO-d6), d: 17.34, 24.28, 122.34, 124.45, 129.31, 150.26, 164.69,
171.56, 190.43. Anal. Calcd. for C11H11N3SO: C, 56.63; H, 4.75; N, 18.01; Found: C,
56.54, H,4.74; N, 17.99.
4-(2-Amino-5-propyl-1,3,4-thiadiazole)benzaldehyde (d) M.p. 212–213 °C, Yield
94.6 %; UV–visible (C2H5OH, kmax, nm): 263, 2.053. IR (KBr, m/cm-1): 3,366.66
cm-1 (msN–H,s); 3,103.08 cm-1 (vC–H,s); 2,870.66 cm-1 (vC–H,s); 1,589.74 cm-1
(mC=O,s); 1,637.73 cm-1 (mC=N,s); 1,601.22 cm-1, 1,588.74 cm-1, 1,496.99 cm-1
,
1,461.83 cm-1; 1,386.71 cm-1 (mN–H,s); 1,461.83 cm-1, 1,380.72 cm-1; 1,168.80
cm-1 (mC–N,s); 1,041.79 cm-1, 1,006.54 cm-1, 486.25 cm-1 (mN–C–S,w); 841.15 cm-1
;
813.62 cm-1 (mC–S–C,w); H NMR (DMSO-d6), d: 10.78 (s,1H,–CHO); 7.00–8.06
1
(m,4H,Ph-H); 4.11 (s,2H,–CH2); 2.84 (m, 2H, –CH2); 3.16 (s, 1H,–NH); 1.01–1.06
(m,3H,–CH3); 13C NMR (DMSO-d6), d: 13.64, 24.90, 32.25, 122.54, 125.31, 131.31,
150.46, 165.34, 172.16, 190.29. Anal. Calcd. For C12H13N3SO: C, 58.28; H, 5.30; N,
16.99; Found: C, 58.21, H, 5.31; N, 16.96.
4-(2-Amino-5-phenoxymethylene-1,3,4-thiadiazole)benzaldehyde (e) M.p. 200–
201 °C, Yield 95.3 %; UV–visible (C2H5OH, kmax, nm): 256, 1.578. IR (KBr,
v/cm-1): 3,468.75 cm-1 (msN–H,s); 3,097.97 cm-1 (vC–H,s); 2,780.74 cm-1 (vC–H,s);
1,772.88 cm-1 (mC=O,s); 1,666.77 cm-1 (mC=N,s); 1,609.39 cm-1, 1,583.24 cm-1
,
1,509.39 cm-1, 1,453.75 cm-1; 1,386.26 cm-1 (mN–H,s); 1,464.24 cm-1, 1,171.56
752.03 cm-1 624.43 cm-1 580.05 cm-1
,
cm-1 (mC–N,s); 1,042.04 cm-1
,
,
,
1
530.05 cm-1 (vN–C–S,w); 841.14 cm-1; 827.37 cm-1 (mC–S–C,w); H NMR (DMSO-
d6), d: 10.60 (s,1H,–CHO); 6.98–8.00 (m, 4H, Ph-H); 6.11–7.98 m, 5H, Ph-H); 4.62 (s,
2H,–CH2); 3.10 (s,1H,–NH); 13C NMR (DMSO-d6), d: 72.84, 116.02, 120.94, 121.09,
126.47, 129.12, 130.63, 131.33, 156.73, 164.33, 169.79, 173.72, 192.48. Anal. Calcd.
for C16H13N3SO2: C, 61.72; H, 4.20; N,13.50; Found: C, 61.78, H, 4.21; N, 13.48.
4-(2-Amino-5-naphthoxymethylene-1,3,4-thiadiazole)benzaldehyde (f) M.p. 201–
202 °C, Yield 96.1 %; FS: stimulating peak 320 nm, fluorescence peak 398 nm,
luminous intensity 10,780. UV–visible (C2H5OH, kmax, nm): 261, 0.491. IR (KBr,
v/cm-1): 3,427.25 cm-1 (msN–H,s); 3,103.08 cm-1 (vC–H,s); 2,735.24 cm-1 (vC–H,s);
1,837.11 cm-1 (mC=O,s); 1,627.74 cm-1 (mC=N,s); 1,601.22 cm-1, 1,583.34 cm-1
,
1,498.99 cm-1, 1,461.83 cm-1; 1,382.23 cm-1 (mN–H,s); 1,453.21 cm-1; 1,188.80
cm-1 (mC–N,s); 1,041.79 cm-1 741.28 cm-1 611.20 cm-1 599.81 cm-1
,
,
,
,
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Y.-T. Liu et al.
1
556.72 cm-1 (vN–C–S,w); 841.15 cm-1; 813.82 cm-1 (mC–S–C,w); H NMR (DMSO-
d6), d: 10.69 (s, 1H, –CHO); 6.03–7.77 (m, 4H,Ph-H); 7.26–7.87 (m, 8H, NAPh-H);
4.34 (s, 2H, –CH2); 3.23 (s, 1H, –NH); 13C NMR (DMSO-d6), d: 56.78, 116.02, 120.94,
121.78, 126.89, 129.12, 131.45, 135.78, 137.30, 140.18, 146.41, 156.73, 164.46,
169.79, 173.72, 193.36. Anal. Calcd. for C20H15N3SO2: C, 66.46;H, 4.18; N, 11.63;
Found: C, 66.50, H, 4.17; N, 11.65.
Conclusions
In the work discussed in this paper, novel benzaldehyde derivatives containing
1,3,4-thiadiazole were prepared in high yield from 4-fluorobenzaldehyde and
2-amino-5-substituted-1,3,4-thiadiazole without anhydrous potassium carbonate.
This synthetic method has the advantages of mild reaction conditions, high reaction
speed, high yield, and simple posttreatment procedure. The products were
1
characterized by melting point determination, UV–visible, IR, H NMR, and 13C
NMR spectroscopy, and elemental analysis. In the fluorescence performance tests,
additional fluorescence found in 4-(2-amino-5-b-naphthoxymethylene-1,3,4-thiadi-
azole)benzaldehyde was not found for the other five new compounds.
Acknowledgments This work was supported by the Natural Science Foundation of Shaanxi Province,
People’s Republic of China (Project No: 2009JZ002).
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