2
Journal of Chemistry
and verify the theoretical results. e energies of HOMO-
LUMO frontier orbitals will be used to estimate molecu-
lar reactivation towards nucleophilic/electrophilic reagents.
Electrostatic potential energy maps (ESP maps) will be
graphically presented to locate binding sites of these new
derivatives.
Ethyl thiazole-2-ylglycinate (2b). Yield 80%; m.p. 142–144∘C;
orange crystals; (EtOH); IR (KBr) 3346 cm−1 (]NH),
3045 cm−1 (]Olefinic), 1730 cm−1 ester (]C=O). 1HNMR
(300 MHz, DMSO-d6) ꢀ ppm: 1.4 (trip, 3H, CH3), 3.2 (quar,
2H, CH2), 5.1 (S, 2H, CH2), 7.0 (d, 1H, thiazole H, J = 8.4 Hz),
7.4 (d, 1H, thiazole H, J = 8.4 Hz), 10.2 (s, 1H, NH, D2O
exchangeable), Anal. Calculated for C H N O S (186.23):
7
10
2
2
C, 45.15; H, 5.41; N, 15.04, Found: C, 45.01; H, 5.37; N, 14.84.
2. Experimental Section
1-Phenyl-3-(thiazole-2-yl) Urea (2c). Yield 78%; m.p.
125–127∘C; yellow crystals; (EtOH/benzene); IR (KBr) 3326,
3284 cm−1 (]NH), 3063 cm−1 (]Aromatic), 1648 cm−1 (]C=O).
1HNMR (300 MHz, DMSO-d6) ꢀ ppm: 7.00 (d, 2H, J
= 7.2 HZ) 7.4 (m, 3H, ArH), 7.1 (d, 1H, thiazole H, J =
8.0 Hz), 7.8 (d, 1H, thiazole H, J = 8.0 Hz), 8.9 (s, 1H NH,
D2O exchangeable,), 10.6 (s, 1H, NH, D2O exchangeable),
13CNMR (300 MHz, DMSO-d6) ꢀ ppm: 90.3, 100.2,
105.7, 120.8, 138.5, 140.9, 159.3, 165.4, Anal. Calculated for
C H N OS (219.26): C, 54.78; H, 4.14; N, 19.16, Found: C,
2.1. Synthesis. All melting points were measured on an
electric melting point apparatus and were uncorrected. e
infrared spectra were recorded using potassium bromide
disks on a Pye Unicam SP-3-300 infrared spectrophotome-
ter; the established values of the gas phase frequencies
1
are given between brackets. HNMR spectra were run at
300 MHz, on a Varian Mercury VX-300 NMR spectrometer
and Brukeravance III 400 MHZ, using TMS as an internal
standard in deuterated dimethylsulphoxide. Chemical shifs
ꢀ are quoted in ppm. e mass spectra were recorded on
Shimadzu GCMS-QP-1000EX mass spectrometers at 70 eV.
All the spectral measurements were carried out at the NMR
Laboratory of Cairo University, Egypt, and the NMR Labo-
ratory of Faculty of Pharmacy, Ain shams University, Egypt;
the microanalytical data were measured in Central Lab of
Cairo University, Egypt; the Ministry of Defense Chemical
Laboratories, Egypt; and the Microanalytical Center of Ain
Shams University, Egypt. All the chemical reactions were
monitored by TLC. e bold values corresponded to values
calculated from DFT.
10
9
3
54.52; H, 4.17; N, 18.94.
1-Phenyl-3-(thiazole-2-yl) Thiourea (2d). Yield 76%; m.p.
178–180∘C; brownish red crystals; (butanol); IR (KBr) 3169,
3081 cm−1 (]NH), 3009 cm−1 (]aromatic). HNMR (300 MHz,
1
DMSO-d6) ꢀ ppm: 7.00 (d, 2H, J = 7.2 HZ), 7.4 (m, 3H, ArH),
7.4 (d, 1H, thiazole H, J = 7.8 Hz), 7.6 (d, 1H, thiazole H, J
= 7.8 Hz), 10.4 (s, 1H, NH, D2O exchangeable), 12.4 (s, 1H,
NH, D2O exchangeable), 13CNMR (300 MHz, DMSO-d6) ꢀ
ppm: 125.3, 126.4, 128.7, 129.4, 111.2, 137.4, 162.4, 176.6, Anal.
Calculated for C H N S (235.32): C, 51.04; H, 3.86; N, 17.86,
10
9
3
2
Found: C, 51.01; H, 4.07; N, 17.74.
2.1.1. General Procedure for the Preparation of Compounds
2a–g. A mixture of 2-aminothiazole 1 (1 g, 10 mmol) and
different electrophilic reagents, namely, 2-chloro-N-(4-
sulfamoylphenyl) acetamide, ethyl chloroacetate, phenyl
cyanate, chloroacetyl chloride, 2-chloro-N-(4-chlorophenyl)
acetamide, phenyl cyanate, phenyl thiocyanate, chloroacetyl
chloride and 2-chloro-N-(4-chlorophenyl) acetamide
(10 mmol) in dimethylformamide (20 ml), and anhydrous
potassium carbonate, was refluxed for 5–8 h. e reaction
mixture was poured in ice water (200 ml); the formed ppt
was filtered off, dried, and crystallized from ethanol afforded
compounds 2a–g. It should be noticed that quantum
chemically calculated spectroscopic parameters in gaseous
phase are given in {bold font} for comparison with the
experimentally obtained parameters.
2-Chloro-N-(thiazole-2-yl) Acetamide (2e). Yield 60%; m.p.
220–222∘C; brownish red crystals; m.p. 162–164∘C (butanol);
IR (KBr) 3187 cm−1 {3643} (]NH), 3041 cm−1 (]olefinic H),
1703 cm−1 {1825} (]C=O). HNMR (300 MHz, DMSO-d6): ꢀ
1
ppm: 4.5 (s, 2H, CH2), 7.2 (d, 1H, thiazole H, J = 8.2 Hz), 7.6
(d, 1H, thiazole H, J = 8.2 Hz), 12.4 (s, 1H, NH, D2O exchange-
able), 13CNMR (300 MHz, DMSO-d6) ꢀ ppm: 39.7, 114.5,
137.7, 157.8, 157.6, 164.4, Anal. Calculated for C H ClN OS
5
5
2
(176.62): C, 34.00; H, 2.85; N, 15.86, Found: C, 34.12; H, 3.07;
N, 15.74.
N-(4-Chlorophenyl)-2-(thiazole-2-ylamino) Acetamide (2f).
Yield 68%; m.p. 198–200∘C; red crystals; (butanol); IR
(KBr) 3292, 3184 cm−1 (]NH), 3047 cm−1 (]Aromatic), 1694 cm−1
1
(]C=O). HNMR (300 MHz, DMSO-d6) ꢀ ppm: 2.4, 2.6 (s,
2H, 2NH, D2O exchangeable), 7.1 (s, 2H, CH2), 7.2 (d, 2H,
J = 7.6 Hz), 7.6 (m, 3H, ArH), 8.0 (d, 1H, thiazole H, J =
8.2 Hz), 8.2 (d, 1H, thiazole H, J = 8.2 Hz) Anal. Calculated for
C H ClN OS (267.73): C, 34.35; H, 3.76; N, 15.70, Found: C,
N-(4-Sulfamoylphenyl)-2-(thiazol-2-ylamino) Acetamide (2a).
Yield 65%; m.p. 118–120∘C; orange crystals; (EtOH); IR
(KBr) broad band at 3378, 3325, 3273 cm−1 (]NH), 3022 cm−1
11 10
3
1
(]Aromatic), 2958 cm−1 (]Aliphatic), 1691 cm−1 (]C=O). HNMR
34.12; H, 3.67; N, 15.74.
(300 MHz, DMSO-d ) ꢀ ppm: 5.1 (s, 2H, CH ), 7.15 (d, 1H,
6
2
thiazole H, J = 8.6 Hz), 7.4 (d, 1H, thiazole H, J = 8.6 Hz), 7.2
2.1.2. General Procedure for the Preparation of Compounds
3a–e. A mixture of 2e (1.76 g, 10 mmol) and different nucle-
ophilic reagents, namely, p-toluidine, thiourea, anthranilic,
aminothiophenol, and quinoxaline-2,3-diol (10 mmol) in
dimethylformamide (20 ml) and anhydrous potassium car-
bonate was refluxed for 4-5 h. e reaction mixture was
(s, 2H, NH , D O exchangeable), 7.7 (d, 2H, Ar-H), 7.8 (d, 2H,
2
2
Ar-H), 10.8 (s, 1H, D O exchangeable NH), 7.1 and 12 (br s, 1H,
2
D O exchangeable NH-OH tautomerism). Anal. Calculated
2
for C H N O S (312.36): C, 42.30; H, 3.87; N, 17.94 Found:
11 12
4
3
2
C, 42.01; H, 4.07; N, 17.84.