PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
electron-withdrawing action of the anellated triazole ring carbo(thio)hydrazide 1a-d or 1,3-diamino-guanidine hydro-
[31]. Additionally, the mass spectra also confirmed the
molecular ions in accordance with the formation of
final compounds.
chloride 1e (5 mmol) was added to the previous residue and
heated under reflux at 140 ꢁ 150 ꢀC for 1 ꢁ 2 h. After dis-
appearance of the reactants as monitored by TLC (ethyl
acetate: petroleum ether 2:1), the mixtures were cooled and
treated with water (30 mL). The formed solids were filtered
off and crystallized from ethanol.
Antimicrobial activities
The in vitro antibacterial activities of the synthesized com-
pounds were screened against three organisms, namely
6-Ethoxy-6-oxido-3-oxo-2,5,7-trihydro-1,2,4-triazo-
lo[3,4-e][1,2,3]diazaphosphole (2a)
Streptococcus
pyogenes,
Staphylococcus
aureus
and
Escherichia coli. Moreover, all the synthesized compounds
were also screened for their in vitro antifungal activities
against three organisms, namely Aspergillus niger, Aspergillus
clavatus and Candida albicans [32,33]. Minimum inhibitory
concentration (MIC) of all synthesized compounds was
determined and given in Table S1 (Supplemental Materials).
MIC is defined as the lowest concentration of inhibitor at
which organism growth was not visually apparent.
Ciprofloxacin and Ketoconazole were used as standard drugs
for the antibacterial and antifungal activities, respectively.
All the products recorded good to excellent antimicrobial
activities toward the used microorganisms. The products
2a,b,e showed acceptable inhibitory activities toward all bac-
teria organisms and moderate effects toward all fungi organ-
isms in comparison with the standard drugs. On the other
hand, the products 2c and 2d recorded excellent antibacter-
ial and antifungal effects equal to the standard drugs. The
presence of phenyl rings attached to triazolodiazaphosphole
system in one molecular frame exhibited extremely excellent
antibacterial and antifungal activities.
Yellow solid in 68% yield; mp 201 ꢁ 202 ꢀC. IR (KBr), (v
max, cmꢁ1): 3440 (br, 2 NH), 2923, 2893 (C ꢁ Haliph), 1719
(C ¼ O), 1603, 1592 (C ¼ N), 1241 (P ¼ O), 1069
(P ꢁ O ꢁ C). 1H-NMR (600 MHz, DMSO-d6): 1.36 (t, 3H,
J ¼ 7.2 Hz, CH3), 2.64 (d, 2H, JPCH¼23.4 Hz, CH2ꢁP),
4.38 ꢁ 4.43 (m, 2H, CH2O), 5.87 (s, 1H, NH), 11.80 (s, 1H,
NH). 13C-NMR (150 MHz, DMSO-d6): 13.9 (CH3), 42.4 (d,
JPC¼139.5 Hz, CH2ꢁP), 61.9 (CH2O), 157.4 (C ꢁ 7a), 159.5
(C ¼ O). 31P-NMR (242 MHz, DMSO-d6): 17.32 ppm. MS
(m/z, I %): 204 (Mþ, 18%). Anal. Calcd for C5H9N4O3P
(204.13): C, 29.42%; H, 4.44%; N, 27.45%. Found: C,
29.26%; H, 4.29%; N, 27.28%.
6-Ethoxy-6-oxido-3-thioxo-2,5,7-trihydro-1,2,4-tria-
zolo[3,4-e][1,2,3]diazaphosphole (2 b)
Yellow solid in 72% yield; mp 210 ꢁ 211 ꢀC. IR (KBr), (v
max, cmꢁ1): 3295, 3253 (2 NH), 2957, 2863 (C ꢁ Haliph),
1589, 1525 (C ¼ N), 1258 (P ¼ O), 1197 (C ¼ S), 1066
(P ꢁ O ꢁ C). 1H-NMR (600 MHz, DMSO-d6): 1H-NMR
(600 MHz, DMSO-d6): 1.29 ꢁ 1.36 (m, 3H, CH3), 2.76 (d,
2H, JPCH¼24.6 Hz, CH2ꢁP), 4.36 ꢁ 4.45 (m, 2H, CH2O),
5.75 (s, 1H, NH), 11.33 (s, 1H, NH). 13C-NMR (150 MHz,
DMSO-d6): 13.9 (CH3), 42.5 (d, JPC¼135.0 Hz, CH2ꢁP),
63.7 (CH2O), 158.2 (C ꢁ 7a), 180.7 (C ¼ S). 31P-NMR
(242 MHz, DMSO-d6): 16.94 ppm. MS (m/z, I %): 220 (Mþ,
12%). Anal. Calcd for C5H9N4O2PS (220.19): C, 27.27%; H,
4.12%; N, 25.45%; S, 14.56%. Found: C, 27.09%; H, 4.01%;
N, 25.31%; S, 14.38%.
Experimental
The melting points were measured on a digital Stuart SMP-
3 apparatus in an open capillary tube. Infrared spectra were
measured on FT-IR spectrophotometer (Nicolet iS10) using
KBr disks. The NMR spectra were recorded on a Bruker
600 MHz instrument in DMSO using TMS as an internal
standard. Mass spectra were recorded on direct probe con-
troller inlet part to single quadropole mass analyzer in
(Thermo Scientific GCMS). Elemental microanalysis was
performed on Perkin-Elmer 2400II at the Chemical War
department, Ministry of Defense, Egypt. The purity of the
synthesized compounds was checked by thin layer chroma-
tography (TLC) and elemental microanalysis. The
6-Ethoxy-6-oxido-3-oxo-5-phenyl-2,5,7-trihydro-1,2,4-tria-
zolo[3,4-e][1,2,3]diazaphosphole (2c)
White solid in 65% yield; mp 223 ꢁ 224 ꢀC. IR (KBr), (v
max, cmꢁ1): 3120 (NH), 3055 (C ꢁ Harom), 2946, 2852
Supplemental Materials contains sample 1H, 13C and 31P (C ꢁ Haliph), 1714 (C ¼ O), 1597, 1581 (C ¼ N), 1245
1
NMR spectra of the products 2 (Figures S1–S15).
(P ¼ O), 1065 (P ꢁ O ꢁ C). H-NMR (600 MHz, DMSO-d6):
1.37 (t, 3H, J ¼ 7.2 Hz, CH3), 2.79 (d, 2H, JPCH¼21.6 Hz,
CH2ꢁP), 4.38 ꢁ 4.42 (m, 2H, CH2O), 7.20 (t, 1H, J ¼ 9.0 Hz,
Ph ꢁ H), 7.39 (d, 2H, J ¼ 8.4 Hz, Ph ꢁ H), 7.61 (td, 2H,
J ¼ 7.2 and 1.2 Hz, Ph ꢁ H), 11.93 (s, 1H, NH). 13C-NMR
(150 MHz, DMSO-d6): 13.9 (CH3), 42.1 (d, JPC¼147.0 Hz,
CH2ꢁP), 63.9 (CH2O), 118.0 (C ꢁ 2,6Phenyl), 121.6
(C ꢁ 4Phenyl), 130.0 (C ꢁ 3,5Phenyl), 140.0 (C ꢁ 1Phenyl), 157.5
(C ꢁ 7a), 161.8 (C ¼ O). 31P-NMR (242 MHz, DMSO-d6):
19.14 ppm. MS (m/z, I %): 280 (Mþ, 40%). Anal. Calcd for
C11H13N4O3P (280.22): C, 47.15%; H, 4.68%; N, 19.99%.
General procedure for synthesis of 6-ethoxy-6-oxido-3-
oxo(thioxo)(imino)-2,5,7-trihydro-1,2,4-
triazolo[3,4-e][1,2,3]diazaphospholes 2a-e
A mixture of triethyl phosphite (5 mmol, 0.82 mL) and ethyl
bromoacetate (5 mmol, 0.4 mL) was heated under reflux at
140 ꢁ 150 ꢀC for 3 h. The reaction progress was observed by
thin layer chromatography. The excess materials were
removed under vacuum to form the intermediate residue A.
An
equimolar
amount
of
the
corresponding Found: C, 47.02%; H, 4.59%; N, 19.73%.