Rapidly, highly yielded and green synthesis of dihydrotetrazolo[1,5-a]pyrimidine derivatives in aqueous media using recoverable Pd (II) thiazole catalyst accelerated by ultrasonic: Computational studies

Article abstract of DOI:10.1002/aoc.6320

Here, we synthesized new thiazole complexes from Cu (II), Fe (III), and Pd (II) ions. Such complexes were characterized to present their chemical formulae, firstly. The octahedral geometry was suggested for the investigated complexes except Pd (II) complex (ARPTPd), which has a square-planer arrangement. ARPTPd was planned to be used as a catalyst for synthesis of dihydrotetrazolo[1,5-a]pyrimidine derivatives at mild conditions. The catalytic activity of ARPTPd complex in four-components reaction approach was deliberately monitored till it reaches the most favorable conditions. The advantages of suggested catalyst were basically summarized by using green solvent (H₂O), lower reaction time, and high products yields. Also, the superiority of ARPTPd complex and ultrasonic irradiation towards synthesis of dihydrotetrazolo[1,5-a]pyrimidine derivatives was revealed compared with other Lewis acids, basic, and ionic liquid catalysts. Furthermore, the mildness of conversion and compatibility with different functional groups makes it attractive. In addition, in consecration, computational aspects were often taken according to their effect on the declaration or discrimination of variable functional characteristics. Crystal packing systems of complexes were configured to extract important surface properties. DFT study was also applied to explain the causes behind the superiorly of ARPTPd complex. Also, the optimization process for intermediates was executed to support the suggested mechanism. Finally, this simple, economical, and green catalytic procedure may be applied to the industry in future.

Full text of DOI:10.1002/aoc.6320

Received: 27 March 2021
DOI: 10.1002/aoc.6320
Revised: 6 May 2021
Accepted: 18 May 2021
R E S E A R C H A R T I C L E
Rapidly, highly yielded and green synthesis of
dihydrotetrazolo[1,5-a]pyrimidine derivatives in aqueous
media using recoverable Pd (II) thiazole catalyst
accelerated by ultrasonic: Computational studies
Mahmoud Abd El Aleem Ali Ali El-Remaily1
| Ahmed M. M. Soliman1
| Nashwa M. El-Metwaly3,4 | Amerah Alsoliemy3
| Ahmed M. Abu-Dief1,5
|
Mohamed E. Khalifa2
|
Tarek El-Dabea1
1Department of Chemistry, Faculty of
Science, Sohag University, Sohag, Egypt
2Department of Chemistry, College of
Science, Taif, Saudi Arabia
3Department of Chemistry, Faculty of
Applied Science, Umm Al-Qura
University, Makkah, Saudi Arabia
4Department of Chemistry, Faculty of
Science, Mansoura University, Mansoura,
Egypt
Here, we synthesized new thiazole complexes from Cu (II), Fe (III), and Pd
(II) ions. Such complexes were characterized to present their chemical
formulae, firstly. The octahedral geometry was suggested for the investigated
complexes except Pd (II) complex (ARPTPd), which has a square-planer
arrangement. ARPTPd was planned to be used as a catalyst for synthesis of
dihydrotetrazolo[1,5-a]pyrimidine derivatives at mild conditions. The catalytic
activity of ARPTPd complex in four-components reaction approach was
deliberately monitored till it reaches the most favorable conditions. The
advantages of suggested catalyst were basically summarized by using green
solvent (H2O), lower reaction time, and high products yields. Also, the
superiority of ARPTPd complex and ultrasonic irradiation towards synthesis of
dihydrotetrazolo[1,5-a]pyrimidine derivatives was revealed compared with
other Lewis acids, basic, and ionic liquid catalysts. Furthermore, the mildness
of conversion and compatibility with different functional groups makes it
attractive. In addition, in consecration, computational aspects were often
taken according to their effect on the declaration or discrimination of variable
functional characteristics. Crystal packing systems of complexes were
configured to extract important surface properties. DFT study was also applied
to explain the causes behind the superiorly of ARPTPd complex. Also, the
optimization process for intermediates was executed to support the suggested
mechanism. Finally, this simple, economical, and green catalytic procedure
may be applied to the industry in future.
5Department of Chemistry, College of
Science, Taibah University, Madinah,
Saudi Arabia
Correspondence
Mahmoud Abd El Aleem Ali Ali El-
Remaily, Department of Chemistry,
Faculty of Science, Sohag University,
82524 Sohag, Egypt.
Email: mahmoud_ali@science.sohag.edu.
eg; msremaily@yahoo.com
Nashwa M. El-Metwaly, Department of
Chemistry, Faculty of Science, Mansoura
University, Mansoura, Egypt.
Email: nmmohamed@uqu.edu.sa
Ahmed M. Abu-Dief, Department of
Chemistry, College of Science, Taibah
University, P.O. Box 344, Madinah, Saudi
Arabia.
Email: amamohammed@taibahu.edu.sa;
ahmed_benzoic@yahoo.com
K E Y W O R D S
DFT, recoverable catalyst, tetrazolopyrimidine derivatives, thiazole complexes, ultrasonic
irradiation
Funding information
Taif University Researchers Supporting
Project, Grant/Award Number: TURSP-
2020/43
Appl Organomet Chem. 2021;e6320.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6320

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EL-REMAILY ET AL.
1 | INTRODUCTION
2 | EXPERIMENTAL
Under mild conditions that otherwise require strict pres-
sure and temperature conditions, the ultrasonic state
increases the rate of organic transformation.[1] Ultrasonic
irradiation is often used to promote different synthetic
reactions through the creation, rising, and implosive col-
lapse of bubbles in a liquid.[2] High pressures, extreme
local heating, and a very short service life are created by
the collapse of the bubbles initiated by cavitation. Cavita-
tion functions as a way of focusing the diffuse energy of
sound.[3] Ultrasonic irradiation is capable of triggering
several reactions by supplying activation energy in the
microenvironment, compared with traditional heating
that supplies thermal energy in the macrosystem.[4] In
addition, the other benefits of ultrasonic irradiation are
high product yield, fast reaction times, minimization of
by-products,[5] non-toxic and environmentally friendly
solvents,[6] and energy saving.
All materials and solvents were utilized as received from
Sigma Aldrich or Alfa Aesar. Each device was character-
ized, and the measurement details were also reported in
the supporting information. In addition, other essential
conditions will be displayed in discussion part,
separately.
2.1 | Instrumentation and methods
All physical measurements and requirements of each
system used in this study were reported in the supporting
information. Some specifications were individually car-
ried out in discussion portion.
2.2 | Synthesis of ARPT ligand
Variable features were remarked regarding biological
activity for heterocycles azo-category. As reported previ-
ously, few conventional and progressive one-pot synthe-
sis strategy for heterocyclic tetrazolo [1,5-a]pyrimidine
derivatives was investigated.[7–12] Due to their structural
similarity to heterocyclic DNA and RNA bases, azolo-
annulated pyrimidines and 1,2,4-triazines have attracted
continuing interest. Consequently, these compounds can
serve as biologically efficient antimetabolites. Azolo
[1,5-a]pyrimidines are known as structural analogs of
DNA and RNA purine bases.[13] As an anti-HBV (hepati-
tis B virus),[14] antitumor,[15] and anticancer agents,[16]
substituted tetrazolo pyrimidine are used as well as
antimicrobial and antioxidant agents.[17,18] In connection
with our interest in the design and production of
MCRs,[19] the catalytic activity of the new Pd
(II) complex towards dihydrotetrazolo[1,5-a]pyrimidine-
6-carboxylic ester 5a–o derivative synthesis using ultra-
sonic irradiation under mild reaction conditions should
be mentioned herein.
Consequently, Cu (II), Pd (II), and Fe (III) complexes
were synthesized and structurally elucidated by all avail-
able techniques. After that, the catalytic protocol was
conducted through four-component coupling reactions.
Cyanoguanidine, sodium azide, aromatic aldehydes, and
ß-ketoesters were the components used for synthesis by
ultrasonic irradiation in green solvent, to produce aimed
bio-active heterocyclic compounds. The target products
have been deposited in excellent yields through facile
reaction. The catalytic behavior has been supported
through crystal packing properties as well as DFT-
quantum parameters.
The ligand is prepared according to the procedures men-
tion in a previous study[20] as follows: in a round-bottom
flask (100 ml), 10 mmol of arylidenemalononitrile,
10 mmol of 2,4-thiazolidinedione, 30 mmol of EtOH,
and 20 mmol of piperidine were mixed. Then the
mixture was refluxed under stirring for 2 h, and
arylidenemalononitrile was isolated and processed. The
solid product was washed by hot EtOH and filtered off,
and then the purity was checked by TLC.
2-Amino-6-oxo-3-(piperidinylamidino)-4-phenyl-6,7-
dihydro-pyrano[2,3-d]-5,7-thiazol was the product (abbre-
viation; ARPT); color: pale yellow molecular formula
C18H20N4O2S(356), mp: 235ꢀC. Anal. Calcd (%): C,
60.69, H, 5.62, N, 15.77; found (%): C, 60.67, H, 5.62, N,
15.73. Solubility: ethanol.
IR (KBr pellet, cmꢁ1, Figure S1): 3398 ν(N─H), 3308–
3193 ν(NH2), 1589 ν(C═O). NMR δ in DMSO-d6: 9.87,
7.40–7.30, 6.99, 4.64, 4.46, 3.34–3.32, and 1.55–1.46 ppm
for (s, 1H, NH), (m, 5H, ArH), (s, 2H, NH2), (d, 1H, CH),
(d, 1H, NH), (t, 4H, 2CH2), and (m, 6H, 3CH2), respec-
tively. 13C NMR δ in DMSO-d6: 24.18, 25.85, 45.68, 51.93
(alp-C), 56.19, 71.48, 118.64, 127.84, 128.12, 129.84,
142.71 (N─C─O, thiazol), 152.49 (N─C─O, pyran),
162.17 (N─C═NH), and 171.07 (C═O) (Figures 1, S2,
and S3).
2.3 | Synthesis of metal complexes
Equi-molar reactants from ARPT ligand (5 mmol) and
each metal salt (5 mmol), Cu (II), Fe (III) ions (in 20 ml

EL-REMAILY ET AL.
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FIGURE 1 Calculated optical band gap for the tested complexes
EtOH) and Pd (II) salt (in 20 ml hot AcOH), were mixed.
The mixed solutions were stirred under reflux for 2–3 h,
and then the precipitates were separated and washed by
hot EtOH or Aceton (Scheme 1).
3029–3060 ν(NH2), 1588 ν(C═O), 445(M─N) and
552 (M─O).
[ARPTCu] (Pale green); [Cu (OAc)2(ARPT)(H2O)2].
H2O: Molecular formula C22H32N4 O9SCu (591.5),
decom.t: 244ꢀC. Anal. Calcd (%): C, 44.55, H, 5.52, N,
9.46, found (%): C, 44.63, H, 5.41, N, 9.46, solubility:
DMF, Ʌm: 10.49 (Ωꢁ1 cm2 molꢁ1), IR (KBr pellet, cmꢁ1):
3405 ν(N─H), 3314–3199 ν(NH2), 1587 ν(C═O),
450 (M─N) and 571 (M─O).
[ARPTFe] (Brown); [Fe (NO3)3(ARPT)(H2O)].1.5H2O:
Molecular formula C18H25N7O13.5 SFe (643.34), decom.t:
270ꢀC. Anal. Calcd (%): C, 33.19, H, 3.87, N, 15.05, found
(%): C, 33.18, H, 3.84, N, 15.05, solubility: DMF, Ʌm:
15.38 (Ωꢁ1 cm2 molꢁ1), IR (KBr pellet, cmꢁ1): 3409
ν(N─H), 3318–3200 ν(NH2), 1584 ν(C═O), 458 (M─N)
and 533 (M─O)
2.4 | Stoichiometry and formation
constants of complexes in solution
Stoichiometric ratio and stability of complexes in solution
were estimated according to Job's method (mole ratio and
continuous variation).[20,21] The absorbance was noted for
all prepared solutions after mixing (M and L) and let to
equilibrate. Then schemed versus ([L]/[L] + [M]) or
([L]/[M]) (Figures S4 and S5). The formation constants
(Kf) of complexes were often achieved through the spec-
trophotometric procedure by the following relation[22]
;
Kf = A Am/(1ꢁA/A)2, where [A] is the absorbance values
along each side of absorption peaks which randomly
assigned, [Am] is the highest absorbance for absorbance
peak, and [C] is the molar concentration of the metal. In
addition, ΔG* values (free energy changes) were estimated
from the following equation [ΔG = ꢁRT Ln Kf] (at 25ꢀC),
where, Kf, R, and T are the constant of formation, con-
stant of gas, and the temperature in Kelvin, respectively.
[ARPTPd] (Orange); [Pd (OAc)2(ARPT)].3H2O;
molecular formula C22H32N4O9SPd (634.4), decom.t:
290ꢀC. Anal. Calcd (%): C, 41.69, H, 5.02, N, 8.85, found
(%): C, 41.61, H, 5.04, N, 8.82, solubility: DMF, Ʌm: 8.78
(Ωꢁ1 cm2 molꢁ1), IR (KBr pellet, cmꢁ1): 3426 ν(N─H),

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EL-REMAILY ET AL.
SCHEME 1 Synthetic
strategy for preparation of the
ligand and its complexes
2.5 | Procedure for thermo-kinetic
features
1 (1 mmol) and sodium azide 2 (1.1 mmol) was dissolved
in 20 ml distilled water in presence of 10 mol % Pd
(II) complex (ARPTPd). Then, the mixture was sonicated
at 20 kHz frequency and 40 W power at 60ꢀC, for 10 min
to give 5-aminotetrazole in approximately 100% yield. After
that, an aromatic aldehydes 3 (1 mmol) and methyl or ethyl
acetoacetate 4 (1 mmol) were added to reaction pot.[31,32]
Next, the mixture was sonicated at 20 kHz frequency
and 40 W power at 60ꢀC, for desired appropriate time.
The reaction end was detected by thin layer chroma-
tography (TLC). Then, the reaction mixture was allowed
to cool to room temperature and filtered off the catalyst
(ARPTPd). The organic materials were extracted by using
ethyl acetate (3 ꢂ 10 ml). So tetrazolopyrimidine deriva-
tives 5a–o combined organic phase, were washed with
water, dried over anhydrous Na2SO4, and concentrated
under reduced pressure. The resulting solids were
isolated and recrystallized from ethanol to give pure
products. These products were characterized by melting
points and spectroscopy (FT-IR and NMR).
Thermo-kinetic parameters were calculated regarding
TGA curves for the tested complexes. Pre-exponential
factor (A) and activation energy (E*), in addition to ΔS,
ΔH, and ΔG, were the parameters examined. The
degradation steps mostly have specific borders with a
defined fraction that breaks down (α) within the step for
each temperature point.
Variable researchers[23–30] developed equations for
such purpose and clarified their advantages. Among
those, Coat-Redfern[23] and Horowitz-Metzger[30] equa-
tions have been selected to estimate such parameters.
2.6 | Catalytic application
2.6.1 | Procedure for synthesis of
dihydrotetrazolo[1,5-a]pyrimidine derivatives
5a–o
Spectral data for the synthesized compounds
In a flask with round bottom, 5-aminotetrazole was pre-
pared in situ as follows: briefly, a mixture of cyanoguanidine
Compound 5a: mp = 202–204ꢀC. IR (KBr) cmꢁ1 = 3184,
3090, 2940, 1712, 1593, 1521; 1H NMR (400 MHz, DMSO-

EL-REMAILY ET AL.
5 of 18
d6) δ = 11.46 (s, 1H, NH), 8.25 (s, 2H, ArH), 7.91 (s, 1H,
ArH), 7.61 (s, 1H, ArH), 7.25 (s, 1H, ArH), 6.92 (s,
1H, CH), 4.01 (q, J = 6.9 Hz, 2H, OCH2CH3), 2.43 (s, 3H,
CH3), 1.08 (t, J = 6.9 Hz, 3H, OCH2CH3). Anal. Calcd for
C14H15N5O2: C, 58.94; H, 5.30; N, 24.55. Found: C,
58.91; H, 5.32; N, 24.54.
Compound 5h: mp = 188–190ꢀC, IR (KBr) cmꢁ1 = 3162,
3102, 2920, 1692, 1623, 1504; 1H NMR (400 MHz, DMSO-
d6) δ = 11.44 (s, 1H, NH), 8.16 (d, J = 7.9 Hz, 2H, ArH),
7.85 (d, J = 7.9 Hz, 2H, ArH), 7.04 (s, 1H, CH), 6.87
(s, 1H, CH), 3.60 (s, 3H, CH3), 2.40 (s, 3H, CH3). Anal.
Calcd for C13H13N5O2: C, 57.56; H, 4.83; N, 25.82.
Found: C, 57.58; H, 4.86; N, 25.80.
Compound 5b: mp = 236–238ꢀC. IR (KBr) cmꢁ1 = 3244,
1
3180, 3104, 2966, 1707, 1653, 1554; H NMR (400 MHz,
Compound 5i: mp = 220–222ꢀC, IR (KBr) cmꢁ1 = 3256,
3043, 2941, 1704, 1640, 1554; 1H NMR (400 MHz, DMSO-
d6) δ = 11.33 (s, 1H, NH), 7.56 (d, J = 7.9 Hz, 2H, ArH),
7.28 (d, J = 7.9 Hz, 2H, ArH), 6.71 (s, 1H, CH), 3.55 (s,
3H, CH3), 2.45 (s, 3H, CH3). Anal. Calcd for
C13H12BrN5O2: C, 44.59; H, 3.45; N, 20.00. Found: C,
44.61; H, 3.46; N, 19.98.
DMSO-d6) δ = 11.39 (s, 1H, NH), 7.55 (d, J = 7.7 Hz, 2H,
ArH), 7.26 (d, J = 7.7 Hz, 2H, ArH), 6.69 (s, 1H, CH),
3.99 (q, J = 6.9 Hz, 2H, OCH2CH3), 2.44 (s, 3H, CH3),
1.03 (t, J = 6.9 Hz, 3H, OCH2CH3). Anal. Calcd for
C14H14BrN5O2: C, 46.17; H, 3.87; N, 19.23. Found: C,
46.20; H, 3.85; N, 19.21.
Compound 5c: mp = 185–187ꢀC. IR (KBr) cmꢁ1 = 3241,
Compound 5j: mp = 183–185ꢀC, IR (KBr) cmꢁ1 = 3272,
3187, 3058, 2956, 1672, 1579; 1H NMR (400 MHz, DMSO-
d6) δ = 11.29 (s, 1H, NH), 7.27–7.42 (m, 4H, ArH), 6.70
(s, 1H, CH), 3.56 (s, 3H, CH3), 2.45 (s, 3H, CH3). Anal.
Calcd for C13H12ClN5O2: C, 51.07; H, 3.96; N, 22.91.
Found: C, 51.10; H, 3.98; N, 22.89.
1
3162, 3049, 2929, 1700, 1650, 1552; H NMR (400 MHz,
DMSO-d6) δ = 11.41 (s, 1H, NH), 7.45 (s, 1H, ArH), 7.41
(d, J = 4.7 Hz, 2H, ArH), 7.25 (t, J = 4.7 Hz, 1H, ArH),
6.70 (s, 1H, CH), 3.97 (q, J = 6.9 Hz, 2H, OCH2CH3), 2.46
(s, 3H, CH3), 1.01 (t, J = 6.9 Hz, 3H, OCH2CH3). Anal.
Calcd for C14H14ClN5O2: C, 52.59; H, 4.41; N, 21.90.
Found: C, 52.60; H, 4.39; N, 21.87.
Compound 5k: mp = 253–255ꢀC, IR (KBr) cmꢁ1 = 3167,
3043, 2951, 1711, 1690, 1552; 1H NMR (400 MHz, DMSO-
d6) δ = 11.42 (s, 1H, NH), 7.69 (s, 1H, ArH), 7.45 (s, 2H,
ArH), 7.01 (s, 1H, CH), 3.54 (s, 3H, CH3), 2.47 (s, 3H,
CH3). Anal. Calcd for C13H11Cl2N5O2: C, 45.90; H,
3.26; N, 20.59. Found: C, 45.88; H, 3.27; N, 20.5ꢁ61.
Compound 5d: mp = 256–258ꢀC. IR (KBr) cmꢁ1 = 3233,
1
3169, 3060, 2954, 1706, 1655, 1574; H NMR (400 MHz,
DMSO-d6) δ = 11.40 (s, 1H, NH), 7.667 (s, 1H, ArH),
7.46–7.50 (m, 2H, ArH), 7.01 (s, 1H, CH), 3.96
(q, J = 6.9 Hz, 2H, OCH2CH3), 2.44 (s, 3H, CH3), 1.00
(t, J = 6.9 Hz, 3H, OCH2CH3). Anal. Calcd for
C14H13Cl2N5O2: C, 47.47; H, 3.70; N, 19.77. Found: C,
47.44; H, 3.68; N, 19.74.
Compound 5l: mp = 225–227ꢀC, IR (KBr) cm = 3243,
1
3168, 3044, 2952, 1712, 1687, 1556; H NMR (400 MHz,
DMSO-d6) δ = 11.42 (s, 1H, NH), 7.72–8.18 (m, 4H,
ArH), 6.92 (s, 1H, CH), 3.54 (s, 3H, CH3), 2.46 (s, 3H,
CH3). Anal. Calcd for C13H12N6O4: C, 49.37; H, 3.82; N,
26.57. Found: C, 49.33; H, 3.80; N, 26.54.
Compound 5e: mp = 208–210ꢀC, IR (KBr) cmꢁ1 = 3182,
1
3090, 2924, 1720, 1654, 1578, 1534; H NMR (400 MHz,
DMSO-d6) δ = 11.41 (s, 1H, NH), 8.24 (s, 2H, ArH), 7.78
(s, 1H, ArH), 7.67 (s, 1H, ArH), 6.94 (s, 1H, CH), 3.98
(q, J = 6.9 Hz, 2H, OCH2CH3), 2.48 (s, 3H, CH3), 0.99
(t, J = 6.9 Hz, 3H, OCH2CH3). Anal. Calcd for
C14H14N6O4: C, 50.91; H, 4.27; N, 25.44. Found: C,
50.89; H, 4.380; N, 25.41.
Compound
5m:
mp = 231–233ꢀC,
IR
(KBr)
cmꢁ1 = 3187, 3053, 2937, 1699, 1554; 1H NMR (400 MHz,
DMSO-d6) δ = 11.40 (s, 1H, NH). 8.21 (d, J = 7.9 Hz, 2H,
ArH), 7.66 (d, J = 7.9 Hz, 2H, ArH), 6.88 (s, 1H, CH),
3.53 (s, 3H, CH3), 2.46 (s, 3H, CH3). Anal. Calcd for
C13H12N6O4: C, 49.37; H, 3.82; N, 26.57. Found: C,
49.40; H, 3.85; N, 26.55.
Compound 5f: mp = 211–213ꢀC, IR (KBr) cmꢁ1 = 3238,
3174, 3051, 2982, 1703, 1657, 1570, 1523; 1H NMR
(400 MHz, DMSO-d6) δ = 11.31 (s, 1H, NH), 6.91–6.96
(m, 2H, ArH), 6.75–6.79 (m, 1H, ArH), 6.71 (s, 1H, CH),
3.99 (q, J = 6.9 Hz, 2H, OCH2CH3), 3.79 (s, 6H, 2 OCH3),
2.43 (s, 3H, CH3), 1.02 (t, J = 6.9 Hz, 3H, OCH2CH3).
Anal. Calcd for C16H19N5O4: C, 55.64; H, 5.55; N, 20.28.
Found: C, 55.62; H, 5.57; N, 20.25.
Compound 5n: mp = 219–221ꢀC, IR (KBr) cmꢁ1 = 3177,
3043, 2954, 1701, 1661, 1559; 1H NMR (400 MHz, DMSO-
d6) δ = 11.31 (s, 1H, NH), 6.75–6.99 (m, 3H, ArH), 6.22
(s, 1H, CH), 3.75 (s, 3H, CH3O), 3.71 (s, 3H, CH3O), 3.55
(s, 3H, CH3), 2.44 (s, 3H, CH3). Anal. Calcd for
C15H17N5O4: C, 54.38; H, 5.17; N, 21.14. Found: C,
54.41; H, 5.18; N, 21.12.
Compound 5g: mp = 185–187ꢀC, IR (KBr) cmꢁ1 = 3277,
3044, 2979, 1705, 1600, 1541; 1H NMR (400 MHz, DMSO-
d6) δ = 11.22 (s, 1H, NH), 7.00–7.23 (m, 4H, ArH), 6.68
(s, 1H, CH), 4.01 (q, J = 6.9 Hz, 2H, OCH2CH3), 2.44 (s,
3H, CH3), 1.10 (t, J = 6.9 Hz, 3H, OCH2CH3), 1.03 (m,
6H, [CH3]2N). Anal. Calcd for C16H20N6O2: C 58.52; H
6.14; N 25.59. Found, %: C 58.55; H 6.18; N 25.55.
Compound 5o: mp = 233–235ꢀC, IR (KBr) cmꢁ1 = 3371,
1
3035, 2944, 1691, 1568; H NMR (400 MHz, DMSO-d6)
δ = 11.22 s (1H, NH), 6.82–7.11 (m, 4H, ArH), 6.58
(s, 1H, CH), 3.63 (s, 3H, CH3), 2.82 (s, 6H, N [CH3]2),
2.43 (s, 3H, CH3). Anal. Calcd for C15H18N6O2:
C, 57.31; H, 5.77; N, 26.74. Found, %: C, 57.35; H, 5.79;
N, 26.71.

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EL-REMAILY ET AL.
2.6.2 | Catalyst recovery and reuse
(NH) and (NH2) groups. A sharp band at 1589 cmꢁ1
,
which was assigned to ν(C═O) in the ARPT ligand, was
slightly shifted to ꢃ1587, 1584, and 1588 cmꢁ1 in the
metal chelates, which reflects its absence from
coordination.[39]
Heterogeneous catalyst could be separated and reused
easily many times, and the efficiency can be tested. The
filtered catalyst was washed by ethanol and double dis-
tilled with water. After drying at 90ꢀC for 3 h, the catalyst
was recycled for another reaction-run under the same
conditions.
Additionally, the bands at the lower wavenumber
region are assigned to ν(M─O) and ν(M─N) vibrations
(Figure S1, i. e.). Other significant bands appeared at
1495 and 1384 cmꢁ1 in ARPTCu spectrum and at 1430
and 1375 cmꢁ1 in the ARPTPd spectrum, which coincide
with υas (OAc) and υs (OAc) vibrational, respectively.[40]
Furthermore, bands at 1452 and 1378 cmꢁ1 appeared in
the ARTPFe spectrum and assigned to υas (NO3) and υs
(NO3), respectively. The separation between two bands
(Δ = υas-υs) is high enough to judge on monodentate
nature of the conjugated anions (OAcꢁ and NO3ꢁ).
1H NMR spectrum of PTP ligand (in DMSO-d6,
Figure 1) showed three singlet signals at δ (ppm); 9.87 (s,
1H, NH), 4.64 (s, 1H, CH), and 4.46 (s, 1H, NH). Also,
doublet signal at δ (ppm); 6.99 (d, 2H, NH2), triplet signal
at δ (ppm); 3.34–3.32 (t, 4H, 2CH2) ppm, multiplet sig-
nals at δ (ppm); 7.40–7.30 (m, 5H, ArH) and 1.55–1.46(m,
6H, 3CH2) range, appeared. 13C NMR spectrum of PTP
ligand (Figure 2) presented a sharp signal at 171.07 ppm
due to C═O. Also, sharp signals at 162.17, 56.19–152.49,
and 24.18–40.83 ppm due to N─C═NH, 8CH─Ar, and
4CH2─Aliph, respectively. 1H NMR spectral data in
ARTP ligand exhibit the following remarks: signals at δ
(ppm); 9.87 (s, 1H, NH), 7.40–7.30 (m, 5H, ArH), 6.99 (d,
2H, NH2), 4.64 (d, 1H, CH), 4.46 (d, 1H, NH), 3.34–3.32
(t, 4H, 2CH2), and 1.55–1.46 (m, 6H, 3CH2) range.[20] 13C
NMR spectrum of the ligand displayed band at
190.96 ppm for C═O, band is appreciated at 162.42 ppm
for N─C═NH, about 56.03–152.5 ppm for 4CH─Ar
seemed and 24.19–51.22 ppm for 4CH2─Aliph[41]
(Figure S2 and S3).
2.7 | Geometry optimization
Materials Studio package[33] was used to simulate and
optimize the studied compounds. This software was
developed by Accelrys, to configure the structural forms
and obtain essential quantum data. This was executed by
DMOL3 program under DFT/B3LYP method through
double numerical plus polarization basis set (DNP),
which recommended for transition metal ion com-
plexes.[34] The program already proceeded without any
constrain under Becke3–Lee–Yang–Parr (B3LYP) of
exchange-correlation functional within GGA and RPBE
functionals.[35] The frequency values (positive) are the
major determiner for suitability of structural forms
obtained. Time-dependent DFT (TD-DFT) was applied
through polarizable continuum model. Moreover, inte-
gral equation formalism variant (IEF-PCM) was used
through B3LYP level to evaluate characteristics of ground
or excited state.[36]
3 | RESULTS AND DISCUSSION
3.1 | General properties
The tested complexes were instituted to require ligand:
metal ratio to be 1 ARPT: 1 Metal. According to physical
and analytical data of ARPT ligand and its complexes,
there was a good agreement between CHN micro-
analyses and the chemical formulae suggested. The con-
ductivity measurements performed in DMF and proved
that the complexes are non-electrolytic due to low molar
conductivity values, as represented above.[37,38]
3.3 | Electronic spectroscopy
Electronic transitions within the ligand and its complexes
happened under influence of UV–Vis light as intraligand,
charge transfer (CT), and ligand field splitting. This scan-
ning was executed in DMF (at RT) over 200–800 nm
range (Figure S6). Functional transitions were extracted
and assigned (Table S1) to examine changes in the bands
due to complexation. Ligand spectrum exhibited absorp-
tion band belongs to n ! π* transition. Regarding
ARPTCu complex spectrum, different bands belong to
π ! π*, n ! π*, and CT appeared beside the band at
3.2 | IR and 1H NMR spectroscopy
The sharp bands at 3398 and 3193–3308 cmꢁ1 were
assigned to ν(NH) and ν(NH2) in ARPT ligand. But these
bands were moved sequentially (at ꢃ3405, 3409, and
3426 cmꢁ1) and (at ꢃ3199–3314, 3200–3318, and 3029–
3060 cmꢁ1 ranges) in ARPTCu, ARPTFe, and ARPTPd
complexes. This appearance indicates the coordination of
2
410 nm, which assigned to 2Eg ! T2g transition in octa-
hedral form. Regarding ARPTFe complex spectrum,
bands of intraligand transitions and CT appeared in

EL-REMAILY ET AL.
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FIGURE 2 Recyclability of ARPTPd in
the model reaction
addition to a band at 532 nm which assigned to
where α and A are the absorption coefficient and
energy independent constant.The value of m differenti-
ates direct or indirect transition at m = 0.5 or 2, respec-
tively. So, calculating α values from Equation 1 to be
used in Equation 2 and then calculates (αhυ)2 values.
Draw graphical relation between (αhυ)2 and hυ
(Figure 1) and extrapolating a straight line to interact
with x-axis at (αhυ)2 = 0, the Eg value could being
obtained.[34]
4
6A1g ! T2g transition within high spin octahedral form.
Regarding ARPTPd complex spectrum, bands of n ! π*,
π ! π*, and CT transitions, appeared in addition to a
1
band at 450 nm, which assigned to 1A1g ! A2g transition
in square-planer form.[20,42,43]
According to UV–Vis spectra, energy separation
between the ground and excited states (optical band dif-
ference, Eg) can be measured. An important indicator of
distinct properties such as conductivity, optical proper-
ties, and catalytic activity is the distance between the
valence band and the conduction band. The minimum
quantum (hυ) essential to expel electron from its ground
state to another exited level and leaving a positive hole
although the attraction force in between is known by the
optical band gap energy (Eg). The lower the gap value,
the closeness valence band and conduction band, which
facilitates excitation and leading to optical or conductiv-
ity property.[44] This gap is known theoretically as the
separation between HOMO and LUMO levels, which
points to activation energy value and semiconductors-like
property.[44] As known, the optical band gap energy value
of Si as a standard semiconductor is 1.14 eV, which is suf-
ficiently lower to a significant level of conducting feature.
The calculated values for ARPTPd, ARPTFe, and
ARPTCu complexes are 2.538, 2.5.79, and 2.638 eV,
respectively (Figure 4). The lower value of the ARPTPd
complex predicts its distinguish optical property as well
as the lower activation energy needed for any application
as a catalytic role in any heterogamous catalysis. Optical
band gap value can be obtained by a facilitated method
as follows:
3.4 | TGA and kinetic aspects
TGA was executed for ARPT complexes up to 25–800ꢀC
range, to examine their thermal stability and put a suit-
able degradation scheme along the decomposition stages
appeared. The curves obtained for the complexes
appeared relatively identical that reflects the same degra-
dation pathways (Scheme S1). All complexes reveal lower
thermal stability due to the presence of crystal water is
expelled below 120ꢀC. Four degradation steps were
recorded till 700ꢀC in all TGA curves, and the residual
parts coincide with stable metal oxide. The suggested
mass-decompose was tabulated (Table 1), and the high
conformity between the calculated and found percent-
ages reflects the exact determination for step borders
without overlapping between follower steps.[20,45,46]
Moreover, to illustrate the characteristics of degrada-
tion phases, kinetic, and thermodynamic parameters
were determined for degradation phases.[47]
1- After removing crystal water molecules in the first
step, higher activation energy values recorded particu-
larly with ARPTPd and ARPTFe complexes mean the
greater the stability of them.
2- The negative ΔS sign refers to ordered activated com-
plex, and the degradation process has non-
spontaneous nature.
α ¼ 1=dlnA
where d is the cell width.
ð1Þ
À
Á
m
αhυ ¼ A hυ-Eg
ð2Þ

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EL-REMAILY ET AL.

EL-REMAILY ET AL.
9 of 18
3- The positive sign of ΔH implies endothermic condi-
tions of degradation stages.
4- The positive sign of ΔG indicates nonspontaneous
decomposition behavior, and TΔS values increased
from step to another and led to increase ΔG values.
In studied experiments, the condensation reaction
was monitored under influence of significant factors as,
catalyst dose, ultrasonic irradiation, solvent used, differ-
ent Lewis acid and basic or ionic liquid catalysts on the
catalytic activity. The condensation reaction performed
without the catalyst and ultrasonic irradiation consumed
a long reaction time. When used ultrasonic irradiation
only without catalyst, the product got more yield at a
longer reaction time. Although both suggested catalyst
(ARPTPd) and ultrasonic irradiation, the yield of
products and reaction time was improved (Scheme 2). A
series of aromatic aldehydes 3 that undergo electrophilic
substitution reactions are successfully synthesized in
excellent yields as displayed in Scheme 2.
3.5 | Studies in solution
3.5.1 | Stoichiometry and formation constant
of complexes
Molar ratio and continuous variation routes were
applied to evaluate stoichiometry of tested complexes
through their formation in solution by reaction of ARPT
ligand and each metal ion [Fe (III), Pd (II), and Cu (II)].
As displayed (Figures S4 and S5), the highest absorbance
in the curve was detected at mole fraction (X = 0.5)
according to 1 metal: 1 ligand ratio. Using a continuous
variation process, spectrophotometric measurements
were used to calculate formation constants (Kf) of
complexes. High Kf values appeared with all tested
complexes, which reveal stability in the following order
of ARPTFe > ARPTCu > ARPTPd. Due to negative Gibbs
free energy, the reaction between metals and ARPT
ligand was desirable and spontaneous.[48]
3.6.2 | Effect of catalyst loading
The effect of catalyst amounts on product yields was
studied, and the data were presented (Table 2). In
particular, loading of catalyst from 3 to 10 mol %
improved the product yield from 13% to 98%. Increasing
the product yield with increasing ARPTPd amount may
refer to an increase in the number of available active sites
and an increase in collision chance between catalyst
surface and reactants molecules. Notably, the further
increase in catalyst amount from 10 to 11 mol %, and the
yields and reaction times did not change significantly.
3.5.2 | Influence of pH variations
Therefore, 10 mol
amount used.
% of catalyst was the optimal
The curves obtained for three complexes under variable
pH values (Figure S7) appeared identical, and the steady
range was broad enough along pH = 4–10 range. This
wide range facilitates their applications at different
basicity levels without affections.[20,49]
3.6.3 | Effect of solvents
Based on attempts to reach the best conditions, we must
choose the effective solvent among several classical sol-
vents, till reach the best one (Table 3). The role of solvent
was investigated with reaction 5a (i. e.). The outcomes
(Table 3) suggested better effect of polar protic solvents
(MeOH, EtOH, AcOH, and H2O), which exceed the apro-
tic solvents (DCM, DMF, THF, CH3CN, and CHCl3). This
may be due to extent of solubility for reactants in polar
solvents without coordination probability with the
complex. Also, it is evident that water solvent is the best
choice for targeted condensation reaction, which is a
preferable green synthesis approach.
3.6 | Catalytic role of ARPTPd complex
by ultrasonic irradiation
3.6.1 | Synthesis of dihydrotetrazolo[1,5-a]
pyrimidine derivatives 5a–o
The catalytic activity of palladium (II) complex
(ARPTPd) seems to be a promising eco-friendly catalyst
in facile one-pot synthesis for hybrid molecules
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylic esters 5a–
o using ultrasonic irradiation. This was done through
coupling reaction between four components as
cyanoguanidine 1 (1 mmol), sodium azide 2 (1.1 mmol),
aromatic aldehydes 3 (1 mmol), and methyl or ethyl
acetoacetate 4a,b (1 mmol), in water using ultrasonic
irradiation under mild conditions.
3.6.4 | Effect of various Lewis acid, basic or
ionic liquid catalysts
Recently, Pd (II) complexes had a lot of attention as mild
Lewis acid, basic or ionic liquid catalysts for many

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EL-REMAILY ET AL.
SCHEME 2 Dihydrotetrazolo[1,5-a]
pyrimidine derivatives 5a–o time of
reaction (min) and yield (%)
organic transformation reactions. The reaction of
cyanoguanidine 1, sodium azide 2, aromatic aldehydes 3,
and ethyl acetoacetate 4, at the same conditions but
without catalyst and ultrasonic irradiation, a trace of the
product was the only obtained (Table 4, entry 1). When
we have used ultrasonic irradiation, only the product was
got more yield at a longer reaction time (Table 4, entry
2). We have tested variable Lewis acids, basic catalysts, or
ionic liquid to differentiate their effectiveness. By using
Brønsted or Lewis acids catalysts such as AlCl3, Pd
(OAc)2, FeCl3.6H2O, ZnBr2, CuCl2, CuO, and PTSA, the
product yield in each case is very low (Table 4, entries
3–9). Using the basic catalyst and ionic liquid such as
Et3N, piperidine, TBABrc, or [EMIM]Cld, the product
yield was slightly improved than the previous case
(Table 4, entries 10–13). It is worthy to note that ARPTPd
catalyst was a much better one in comparing to all others
catalysts studied and yield product by 98% yield (Table 4,
entry 16).
3.6.5 | Recycling of catalyst
The effectiveness of this heterocyclic strategy was
measured by the magnitude of recovery for the solid
catalyst to be used in following cycles, as an economic
feature. Consequently, the planned model reaction
(cyanoguanidine 1, sodium azide 2, aromatic aldehydes

EL-REMAILY ET AL.
11 of 18
TABLE 2 Amount of catalyst used
for synthesis of dihydrotetrazolo[1,5-a]
pyrimidine derivatives 5aa
Entry
Cat. mol%
Yield %b
Entry
Cat. mol%
Yield %b
1
2
3
4
3
5
6
7
13
32
56
73
5
6
7
8
8
84
92
98
98
9
10
11
aReaction conditions: 1 (1 mmol), 2 (1.1 mmol), benzaldehyde 3 (1 mmol), and ethyl acetoacetate 4a
(1 mmol) in water by ultrasonic irradiation condition, 10 min.
bIsolated yields based on 5a.
TABLE 3 Effect of solvent on synthesis of dihydrotetrazolo
[1,5-a]pyrimidine derivatives 5aa
TABLE 4 Different catalysts used for reaction 5a
Entry
Cat (mol%)
Conditionsa
Yield (%)b
Solvent
DCM
Time (min)
Yield (%)b
1
No catalyst,
No US
Water, 1 day
Trace
60
60
60
60
60
30
30
10
10
47
56
56
61
67
77
81
92
98
2
No catalyst
AlCl3 (10)
Water, 1 h
47
39
59
62
63
55
78
66
71
77
62
69
88
91
98
90
DMF
3
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
Water, 10 min
THF
4
FeCl3.6H2O (10)
ZnBr2(10)
CH3CN
CHCl3
MeOH
ACOH
EtOH
H2O
5
6
CuCl2(10)
7
CuO(10)
8
Pd (OAc)2(10)
PTSA (10)
9
aReaction conditions: 1 (1 mmol), 2 (1.1 mmol), benzaldehyde 3 (1 mmol),
ethyl acetoacetate 4a (1 mmol), and ARPTPd catalyst (10% mol) in water by
ultrasonic irradiation condition, 10 min.
10
11
12
13
14
15
16
17
Et3N (10)
Pipyridine (10)
TBABrc (10)
[EMIM]Cld (10)
ARPTCu (10)
ARPTFe (10)
ARPTPd (10)
bIsolated yields based on 5a.
3, ethyl acetoacetate 4a, and H2O as a solvent, by
ultrasonic irradiation, 10 min) that carried out in
presence of ARPTPd was studied six times for synthesis
of compound 5a, approximately by the same efficiency
(Figure 2). But when we tried other next runs (6–9) under
the same conditions, gave low catalytic activity.[49]
ARPTPd (10)
No US
aReaction conditions: 1 (1 mmol), 2 (1.1 mmol), benzaldehyde 3 (1 mmol),
and ethyl acetoacetate 4a (1 mmol) in water by ultrasonic irradiation
condition, 10 min.
bIsolated yields based on 5a.
cTetrabutylammonium bromide.
3.6.6 | Expected mechanism for catalytic
behavior in synthesis process
dEthyl-3-methylimidazolium chloride.
We proposed a plausible mechanism for the synthesis of
dihydrotetrazolo[1,5-a]pyrimidine derivatives 5a–o as
outlined in Scheme 3. It is conceivable that
5-aminotetrazole 6 was produced in the presence of
ARPTPd catalyst by ultrasonic irradiation by condensa-
tion of cyanamide (in situ created from its stable chemi-
cal equivalent 1) with sodium Azide 2. Michael acceptor
α,β-unsaturated 7 was formed by Knoevenagel condensa-
tion from another parallel reaction of benzaldehyde
3 and ethyl acetoacetate 4.[50] Then, intermediate 8 was
intramolecular nucleophilic addition of NH2 group of
enamine tautomer of 8 to the second keto CO group, to
give compound 9, which changed to target product 5a
after releasing H2O molecule.
3.7 | Theoretical aspects
3.7.1 | Hirshfeld crystal packing
formed from
a
nucleophilic Michael addition for
Using Crystal Explorer software 3.1,[51] the virtual crystal
model can be demonstrated for the studied complexes
5-aminotetrazole 6 to 7. Finally, it was followed by

12 of 18
EL-REMAILY ET AL.
SCHEME 3 Suggested mechanism for
synthesis of dihydrotetrazolo[1,5-a]
pyrimidine derivatives and the catalytic role
of ARPTPd by ultrasonic irradiation
condition
after orientation steps through the VESTA package.[52]
This study gives a good view about contact strength
inside crystal packing, morphology, and elemental contri-
bution in crystal contacts. All these properties conduct to
evaluate the catalytic behavior of tested complexes.
Three-dimensional models for the complexes were built
by normalized contact distance (dnorm) and fragment pat-
ches (Figure 3). Normalized contact distance model
(dnorm), divided crystal surface to zones according to con-
tact strength with other neighboring crystals. Such zones
were chromatically displayed by red, white, and blue
colors that correspond to strong, moderate, and weak
contact, respectively. The contact strength between
neighboring surfaces was adapted based on van der
Waals radii as short, moderate, or long contact-length,
which categorize the contact from strong to weak. H-
bonding is the interaction type between crystal surfaces.
As seen (Figure 3), the red spot was appeared around the
central atom particularly the secondary ligand coordinat-
ing (OAcꢁ, NO3ꢁ2, and H2O), which indicates their close-
ness to contact, whereas the fragment patches colors are
referred to the degree of proximity with other neighbor-
ing molecules. Reddish-brown spot is the closest contact
zone with neighboring crystal.[52] On the other hand, 2D
fingerprint plots were extracted to identify the contribu-
tion of elements in contact strength between particles
(Figure S6). Accordingly, the contribution of oxygen atom
in the packing systems of complexes was obviously
appeared by 7.4%, 9.2%, and 16.0% with ARPTCu,
ARPTPd, and ARPTFe crystals, respectively. The effective
presence of oxygen atoms in the crystal surface may
initiate trapping the compounds on the surface easily,
which is considered the first step in any catalytic
behavior inside the reaction medium.[53] ARPTPd and
ARPTFe crystals have this property.
Some crystal parameters (Table 5) as volume, surface
area, globularity, and asphericity were calculated, and
the data suggest distinguish surface properties of ARPTPd
and ARPTFe complexes. As known, morphology, surface
area, and particulate shape have a significant impact in
the catalytic role commonly. Also, the unit cell of each
complex was built using the VESTA package and
appeared by face-centered cubic (ARPTCu) or body-
centered cubic shape. The unit cell obtained presented
the central metal atom far from each other, which
prevents their interaction.
3.7.2 | Global reactivity and MEP maps
DMOL3 program was used to ordinate the structural
forms of ARPT ligand and its complexes till obtain the
best geometry. The DFT method was used under
Becke3–Lee–Yang–Parr (B3LYP) exchange-correlation
functionals and according to DNP basis set, the structural
forms were optimized (Figure S7). Ligand configuration
represents suitable distribution for N(19)H2 and N(18)H
groups, which helps for their coordination towards the

EL-REMAILY ET AL.
13 of 18
FIGURE 3 Crystal models of d norm (a), fragment patches (b), and unit cell of ARPTCu, ARPTFe, and ARPTPd complexes
TABLE 5 Hirshfeld crystal packing properties for ARPT
Furthermore, the frontier maps (Figures 4) exhibited
well distribution for the two opposing orbitals (HOMO
and LUMO) on the whole molecule except piperidine
and benzene zones. This perfect distribution that
covered coordinating functional groups explains flexibility
in electron pair donation during coordination.[56] Electro-
static potential maps (MEP) were also established over
cubic contour (Figure 5) to differentiate nucleophilic and
electrophilic attack zones beside the neutral one. This
differentiation was done chromatically by red, blue, and
green colors, respectively. Suitable nucleophilicity was
noticed with N(19)H2 and N(18)H groups, which sufficient
for their interaction with positive centers as metal ions.[57]
Fukui indices were also calculated utilizing perfect
conditions of DFT-semi-core pseudopods values (dspp)
with polarization functional (DNP) and double numerical
basis sets.[36] Under a double numerical polarization
(DNP) basis set, Fukui indices for all complexes were
computed using the DMol3 module. Established equa-
tions were used to calculate the global reactivity indices
as softness, electrophilicity, hardness and electronegativ-
ity (Table S6).[58] The magnitude of nucleophilic (f þk ),
complexes
Properties
Volume (Å3)
Area (Å2)
ARPTFe
1960.28
1211.09
0.749
ARPTPd
2158.27
1242.41
0.707
ARPTCu
1872.63
1187.18
0.753
Globularity
Asphericity
0.046
0.022
0.010
metal ions via neutral bidentate mode of bonding.[54]
Also, the structural forms of complexes exhibited
significant elongation for C(17)─N(18) and C(4)─N
(19) bonds, due to coordination of nitrogen atoms,
whereas the other bond lengths did not suffer any strain.
Moreover, important quantum parameters were calcu-
lated to evaluate and rank stability of formed complexes
according to different energy content kinds (Table S2).
The energy content of complexes reflects their high sta-
bility in comparing with free ARPT ligand, whereas the
lower stability recorded for ARPTPd complex, due to its
four-coordination number, which reveals less stability
than six-coordination that appeared with the other com-
plexes. This less stability is preferable in cyclic reactions
as catalytic process. Also, the energy gap between ELUMO
and EHOMO levels appeared low with ARPTPd complex,
which points to the ease of electronic transitions between
frontier orbitals at low activation energy.[55]
0
radical (ƒk ), and electrophilic (f ꢁk ) attack was estimated
(Tables S3–S5). On N(18) and N(19) sites, a high nucleo-
philic (f þk ) attack may occur, whereas this feature was
significantly reduced after complexation due to their
coordination (Table S4). ARPTPd complex exhibited the
higher electrophilicity (Tables S4 and S5), which
indicates its superiority in nucleophilic attack. Also, the

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EL-REMAILY ET AL.
FIGURE 4 Frontiers orbitals for ARPT ligand and its complexes

EL-REMAILY ET AL.
15 of 18
FIGURE 5 MEP maps for ARPT ligand and its complexes
overall global softness (δ) and global electrophilicity (ω)
were estimated (Table S6). The softness of ARPTPd
complex appeared high to significant level, which is
preferred in many applications. Electrophilicity indices,
on the other hand, were found to be important in
ARPTFe and ARPTpd complexes, which indicate the lack
of electron density over the two molecules.[58] This fea-
ture points to its ability for acquiring electrons or extra-
coordinate bonds. This feature is very significant for the
suggested catalyst to be success. The intermediate com-
pounds appeared having a different coordination number
than the original catalyst which mainly exceeded.
reach to five or six coordination in intermediate states
without the necessity of substituting any secondary
ligand.
2- Crystal properties of ARPTPd complex exhibited
broad surface area of the complex which is favorable
in catalysis, in general. Also, oxygen atoms have an
effective contribution in contact interaction with
other surfaces, oxygen could initiate trapping the
compounds over the surface, which is considered
the first step in any catalytic behavior inside the
reaction medium.
3- Also, the energy gap (ΔE) recorded with Pd
(II) complex, appeared low which points to ease of
transition between two frontier orbitals under
lower activation energy. Moreover, the intermediate
compounds as 6, 7, and 9 that suggested during the
synthesis process for dihydrotetrazolo[1,5-a]pyrimidine
(Scheme 3) in presence of ARPTPd catalyst were
optimized to evaluate their stability level. This optimi-
zation was carried out by using Gaussian09[59] under
DFT/B3LYP method and valence double-zeta polarized
basis set (6-31G*). Because orbitals of the same form
must be equivalent, even if they are chemically
un-equivalent in the molecule, the double zeta
3.7.3 | Supporting information for catalytic
behavior
Finally, we could summarize the promising properties of
the ARPTPd complex towards catalytic uses as follows:
1- First of all, the square-planer geometry of the complex
is considered the effective supporter for its distinguish
catalytic behavior. This is due to the presence of two
vacant sites over the z-axis capable of interaction till

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EL-REMAILY ET AL.
SCHEME 4 Summary of catalytic reaction stepwise to produce dihydrotetrazolo[1,5-a]pyrimidine
functions are needed. Compared with LANL2DZ basis
set, the DFT method produces results that were
significantly closer to experimental evidence. The
formation energy of intermediates (6, 7, and 9), as well
as the final product, was E (a. u.), ꢁ313.3612,
ꢁ612.7316, ꢁ219.2425, and ꢁ961.304, respectively.
This indicates the relative stability of 6 and 7,
compound 9 is highly unstable, whereas the final
product is highly stable. The stability of compounds
6 and 7 predicts the proceeding of synthesis process
directly. The instability of compound 9 explains the ease
of isolation for the complex from compound 9 to obtain
the product as well as the catalyst again (Scheme 4).
irradiation, and solvent were adjusted. The priority of its
catalytic role was asserted in comparison with other
recommended catalysts. The green synthesis process that
was accomplished in a small time with high yield is the
conclusion of ARPTPd and ultrasonic irradiation role.
Also, computational studies were done to confirm or dis-
criminate variable practical features. Crystal surface prop-
erties were obtained by using Crystal Maker, among the
significant proximity of oxygen atoms to the surface which
is effective in catalysis. DFT study was performed to
optimize structural forms and offers essential quantum
parameters. Also, the catalytic behavior of the ARPTPd
catalyst was suggested and supported by DTF outcomes.
ACKNOWLEDGEMENTS
Dr. Mohamed acknowledge Taif University Researchers
Supporting Project number (TURSP-2020/43), Taif Uni-
versity, Taif, Saudi Arabia.
4 | CONCLUSION
A series of Cu (II), Fe (III), and Pd (II)-thiazole complexes
were synthesized and characterized by analytical and
spectral tools. In four- to six-coordination geometry, the
ligand acted as a neutral bidentate. ARPTPd was
successfully used as a catalyst in the synthesis of bioactive
compounds as dihydrotetrazolo[1,5-a]pyrimidine deriva-
tives from cyanoguanidine 1, sodium azide 2, aromatic
aldehydes 3, and ethyl acetoacetate 4 using ultrasonic irra-
diation under mild conditions. The optimum conditions
for the synthesis process as the catalyst amount, ultrasonic
CONFLICT OF INTEREST
The authors declare no conflict of interest.
AUTHOR CONTRIBUTIONS
Mahmoud Abd El Aleem Ali Ali El-Remaily: Supervi-
sion. Ahmed M. M. Soliman: Supervision. Mohamed
Khalifa: Methodology. Nashwa El-Metwaly: Supervi-
sion. Amerah Alsoliemy: Methodology. Tarek El-
Dabea: Investigation. Ahmed Abu-Dief:Supervision.

EL-REMAILY ET AL.
17 of 18
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ORCID
Mahmoud Abd El Aleem Ali Ali El-Remaily https://
orcid.org/0000-0002-3591-0077
Ahmed M. M. Soliman https://orcid.org/0000-0003-
2541-638X
Mohamed E. Khalifa https://orcid.org/0000-0003-4914-
4796
[18] A. Haleel, D. Mahendiran, V. Veena, N. Sakthivel, A. K.
Rahiman, Mater. Sci. Eng. C. 2016, 68, 366.
Nashwa M. El-Metwaly https://orcid.org/0000-0002-
0619-6206
Tarek El-Dabea https://orcid.org/0000-0002-5359-6931
Ahmed M. Abu-Dief https://orcid.org/0000-0003-3771-
9011
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SUPPORTING INFORMATION
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How to cite this article: M. A. E. A. A. A. El-
Remaily, A. M. M. Soliman, M. E. Khalifa, N.
M. El-Metwaly, A. Alsoliemy, T. El-Dabea, A.
M. Abu-Dief, Appl Organomet Chem 2021, e6320.
https://doi.org/10.1002/aoc.6320