Bis-heterocycles. Part I: Tetrahydro-5,5′- bi(1,2,4-triazin-6-ones)

Article abstract of DOI:10.1515/znb-2018-0148

Selected sets of tetrahydro-5,5′-bi(1,2,4-triazines) (1-3) appended with acetyl, benzoyl, and ester moieties at C-3 position and N-1 (p-substituted)phenyl ring have been prepared and characterized by spectral (IR, NMR, MS) data and X-ray diffraction for c

Full text of DOI:10.1515/znb-2018-0148

Z. Naturforsch. 2018; aop
Hanan H. Mohammad, Mustafa M. El-Abadelah*, Salim S. Sabri, Firas F. Awwadi
and Wolfgang Voelter*
Bis-heterocycles. Part I: tetrahydro-5,5′-
bi(1,2,4-triazin-6-ones)
https://doi.org/10.1515/znb-2018-0148
novel oxidative coupling of alkanones and cycloalkanones
Received July 12, 2018; accepted August 31, 2018
with 3-(pyridine-2-yl)-1,2,4-triazinones coordinated to Pd
(II) [14, 15]. A number of reports have also recently dealt
with the synthesis of 4,5-dihydro-1,2,4-triazin-6-ones [16–
22], some of which have potentials as antifungal [19, 20],
anticonvulsant [21], and peptidomimetic [22] agents. Inter-
est in bis-heterocyclic systems stems from the fact that
many of these dimeric compounds exhibit higher activity
than their monoheterocyclic analogs. In this context, we
have reported on a direct synthesis of model tetrahydro-
5,5′-bi(1,2,4-triazin-6-ones) (1a, b; Fig. 1) [23]. We felt that
Abstract: Selected sets of tetrahydro-5,5′-bi(1,2,4-triazines)
(1–3) appended with acetyl, benzoyl, and ester moieties at
C-3 position and N-1 (p-substituted)phenyl ring have been
prepared and characterized by spectral (IR, NMR, MS)
data and X-ray diffraction for compound 3a. Their synthe-
sis was achieved in high yield via the reaction of diethyl
aminomalonate with various N-(aryl)hydrazonoyl chlo-
rides in the presence of triethylamine.
Keywords: diethyl aminomalonate; dihydro-1,2,4-triazin- this synthetic route and the various attainable dimeric
6-ones; hydrazonoyl chlorides; oxidative dimerization; triazinones, exemplified by compounds 1–3, illustrated in
X-ray crystal structure.
Scheme 1 (see below), are worthy of follow-up and deserve
further inspection.
1 Introduction
2 Results and discussion
1,2,4-Triazine entity, fused to pyrimidine-2,4-diones, is
found in a class of naturally occurring antibiotics, for
example, reumycin [1]. The chemistry of 1,2,4-triazines has
been well documented [2, 3]. Several of their derivatives
exhibited remarkable biological activity such as antago-
nist receptor at the corticotropin-releasing factor [4], anti-
HIV [5], and anticancer activity [5, 6]. Besides, synthetic
procedures for various 5,5′-bi(1,2,4-triazines), exempli-
fied in Fig. 1, have been published [7–10]; their herbicidal
activity [9] and use as bidentate nitrogen ligands in metal-
losupramolecular chemistry [10] have also been reported.
In the 1990s, we became interested in the chemistry of
triazines and had the occasion to develop a facile method
toward the synthesis of optically active 4,5-dihydro-1,2,4-
triazin-6-ones [11–13]. Recently, we have also reported on a
2.1 Synthesis
The versatile reaction of chiral α-amino esters with N-
(aryl)hydrazonoyl chlorides (precursors of nitrile imine
1,3-dipolar species) yields the respective chiral 4,5-dihy-
dro-1,2,4-triazin-6-ones [11]. Yet, our recent study has
shown that the reaction of aminomalonic ester with N-
(aryl)hydrazonoyl chlorides (Ia, b) yielded the respective
dimeric products, namely, diethyl-l6,6′-dioxo-tetrahydro-
5,5′-bi(1,2,4-triazine)-5,5′-dicarboxylates 1a, b (Fig. 1).
Herein, we produce further examples, dimers 1–3, on this
novel one-pot synthesis (involving oxidative dimerization
modes) with different R groups, together with various
para-X substituents at the N-aromatic ring (Scheme 1).
The production of the bis-heterocycles 1–3 most logi-
cally proceeds via initiated formation of the monomeric
6-oxo-4,5-dihydro-1,2,4-triazine-5-carboxylates (1A–3A);
the latter precursors are then transformed into 1–3, for
which a plausible radical-mediated pathway involving
a single-electron transfer is postulated in Scheme 2. The
instability of 1A–3A in basic media might be due to the ten-
dency of their resonance-stabilized enolate anions 1B–3B
to form radical species 1R–3R by the action of oxygen in
*Corresponding authors: Mustafa M. El-Abadelah, Chemistry
Department, Faculty of Science, The University of Jordan,
Amman 11942, Jordan, e-mail: mustelab@ju.edu.jo; and Wolfgang
Voelter, Interfakultäres Institut für Biochemie, Universität Tübingen,
Hoppe-Seyler Straße 4, Tübingen 72076, Germany,
e-mail: wolfgang.voelter@uni-tuebingen.de
Hanan H. Mohammad, Salim S. Sabri and Firas F. Awwadi:
Chemistry Department, Faculty of Science, The University of Jordan,
Amman 11942, Jordan
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ꢀꢀꢀꢁ
2ꢀ
ꢀH.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)
R3
Ar
N
N
N
N
N
Ac
O
R6
N
HN
CO2Et
NH
R6
EtO2C
O
N
Ac
N
N
N
R3
Ar
5,5'-bi(1,2,4-triazines)
X
Ar:
R3 = H, OMe, SMe, NH2 / R6 = H
R3 = H, OMe, SMe / R6 = Me
1a (X = Cl); 1b (X = Br)
Fig. 1:ꢀSynthetic 5,5′-bi(1,2,4-triazines) and 1a, b.
X
4'''
X
3'''
5'''
2'''
6'''
1'''
N
O
1
N
2
3
6
5
[H3N−CH2(CO2Et)2]+ Cl−
CO2Et
H
NH
4
NEt3, EtOH / 0 oC to r. t.
N
N
R
R
N
4'
H
3'
2'
5'
6'
EtO2C
N
1'
Cl
R
O
N
1''
I (R = Ac)
II (R = CO2Et)
III (R = PhCO)
2''
3''
6''
5''
4''
X
Entry
X
a
b
c
d
e
f
g
1−3
Cl Br H CO2Me Me CN OMe
O
1''''
4''''
)
4'''''H
C 1'''''
Compounds: 1c−g (R = Ac); 2a−f (R = CO2Et); 3a−e (R =
Scheme 1:ꢀFormation of compounds 1–3.
basic solution; the resulting carbon radicals 1R–3R are consistent with the suggested structures. Thus, the
then liable to undergo radical coupling, thereby producing mass spectra display the correct molecular ion peaks
the respective dimeric products 1–3 (Scheme 2). This mode for which the measured high-resolution mass spectra
of oxidative dimerization has recently been noted [23].
(HRMS) data are in good agreement with the calculated
The newly synthesized compounds 1–3 were char- values. Distortionless enhancement of polarization
1
acterized by IR, MS, H, and 13C NMR spectral data. transfer and 2D (correlation spectroscopy, heteronuclear
These data, detailed in the Experimental Section, are multiple quantum coherence, heteronuclear multiple
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ꢁꢀꢀꢀ
ꢂ3
H.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)ꢂ
Ar
Ar
N
N
OH
O
N
base
N
H
R
N
H
CO2Et
R
N
H
CO2Et
[1A−3A]
Ar
N
Ar
N
O
O
[O]
N
N
1−3
R
N
H
CO2Et
R
N
H
CO2Et
[1B−3B]
[1R−3R]
Scheme 2:ꢀProposed mechanism for the formation of the dimeric compounds 1–3.
Table 1:ꢀCrystal data and numbers pertinent to data collection and
structure refinement of 3a.
bond correlation) experiments showed correlations that
1
helped in the H and 13C signal assignments to the dif-
ferent carbons and their attached and/or neighboring
Empirical formula
Formula weight, g mol−1
Temperature, K
Wavelength λ, Å
Crystal system
Space group
a, Å
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C38H30Cl N6O8
769.58 2
293 (2)
1
hydrogen atoms. Notably, the H and 13C NMR spectra
of the reaction products lack the methine H-5 protons
signal as well as the HC-5 cabon signal (absent in DEPT
experiments) that are characteristic of the monomeric
dihyro-1,2,4-triazinnes. Conversely, the 13C NMR spectra
displayed a low-intensity signal at δꢀ≈ꢀ65 ppm (absent in
DEPT); this signal is assigned to the equivalent quatere-
nary hetero-ring carbons C-5/C-5′ and is diagnostic of the
dimeric products 1–3.
0.71073
Triclinic
̅
P1
9.6845 (5)
9.8357 (5)
19.9354 (11)
90.587 (4)
99.905 (4)
105.203 (4)
1802.09 (16)
2
b, Å
c, Å
α, deg
β, deg
γ, deg
Volume, Å3
Z
Density (calcd.), g cm−3
Abs. coeff. μ(MoKα), mm−1
F(000), e
1.418
0.243
2.2 Crystal and molecular structure of 3a
796
θ range for data collection, ꢃ
2.90‒25.00
deg
An X-ray crystal structure determination was performed
to confirm the structure of 3a as a representative example
of the new synthetic 3-benzoyl dimeric products 3a–e.
A summary of the crystal data and numbers pertinent
to data collection and refinement parameters is given
in Table 1. Selected bond lengths and angles are pro-
Index ranges hkl
ꢃ
ꢃ
ꢃ
−11ꢁ≤ꢁhꢁ≤ꢁ11, 11ꢁ≤ꢁkꢁ≤ꢁ10, ‒23ꢁ≤ꢁlꢁ≤ꢁ19
13525
6353/0.0261
99.8
Semiempirical from equivalents
1.00000/0.90331
Full-matrix least-squares on F2
6353/0/506
Reflections collected
Reflections unique/Rint
Completeness to θꢁ=ꢁ25.0°, %ꢃ
Absorption correction
Max./min. transmission
Refinement method
ꢃ
ꢃ
ꢃ
ꢃ
vided in Table 2. The molecular structure of 3a is shown Data/restraints/
parameters
̅
in Fig. 2. The compound crystallizes in space group P1
Final R1/wR2 [Iꢁ>ꢁ2 σ(I)]a,b
Final R1/wR2 (all data)a,b
Goodness-of-fitc on F2
ꢃ
ꢃ
ꢃ
0.0513/0.1109
0.0889/0.1319
1.017
with two different half-molecules in the asymmetric
unit; the other two halves are generated by a center of
inversion as is shown in Fig. 2 for one of the two crys-
tallographically independent molecules. Bond distances
and angles are similar in the two crystallographically
Largest diff. peak/hole, e Å−3ꢃ
0.24/−0.23
2
2
aR1ꢁ=ꢁΣꢁ||ꢁFo|–|ꢁFc||/Σꢁ|ꢁFoꢁ|. bwR2ꢁ=ꢀ[Σw(Fo ꢁ−ꢁFc2)2/Σw(Fo )2]1/2
,
wꢁ=ꢀ[σ2(Fo )ꢁ+ꢁ(AP)2ꢁ+ꢁBP]−1, where Pꢁ=ꢀ(Max(Fo , 0)ꢁ+ꢁ2Fc2)/3.
2
2
independent molecules. For example, the C5–C5A bond cGoFꢁ=ꢁSꢁ=ꢁ[Σw(Fo ꢁ−ꢁFc2)2/(nobsꢁ−ꢁnparam)]1/2
.
2
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4ꢀ ꢀH.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)
Table 2:ꢀSelected bond lengths (Å) and angles (deg) for one of the
two crystallographically independent molecules of 3a.
length is 1.574(4) Å and the corresponding bond length
in the other crystallographically independent molecule
is 1.579(19) Å, which is slightly longer than the average
C–C single bond by 0.03 Å. The 1,3,4-thiadiazine ring is
planar; the mean deviation of the atoms from average
plane are 0.036 and 0.066 Å in the two half-molecules in
the asymmetric unit. In each molecule, the two halves are
linked by two N–Hꢀ·ꢀ·ꢀ·ꢀO hydrogen bonding interactions
as is shown in Fig. 2. The hydrogen bonding parameters
are 2.16 Å, 2.716(3) Å, and 122.5° for H4ꢀ·ꢀ·ꢀ·ꢀO6, N4ꢀ·ꢀ·ꢀ·ꢀO6,
and N4–H4ꢀ·ꢀ·ꢀ·ꢀO6A, respectively. The corresponding
distances and angles in the other molecule are 2.02 Å,
2.661(3) Å, and 130.8°.
N(2)–N(1)
N(2)–C(3)
N(4)–C(3)
N(4)–C(5)
C(6)–C(5)
C(6)–N(1)
O(6)–C(6)
N(1)–C(7)
C(13)–C(3)
C(5)–C(20)
O(13)–C(13)
C5–C5Aa
1.402(2)
1.286(3)
1.344(3)
1.439(3)
1.534(3)
1.358(3)
1.221(3)
1.436(3)
1.513(3)
1.551(3)
1.214(3)
1.574(4)
C(6)–N(1)–N(2)
C(6)–N(1)–C(7)
C(3)–N(2)–N(1)
N(2)–C(3)–N(4)
N(2)–C(3)–C(13)
C(3)–N(4)–C(5)
N(4)–C(5)–C(6)
C(6)–C(5)–C(20)
N(1)–C(6)–C(5)
O(6)–C(6)–C(5)
C(20)–C(5)–C(5)a
124.9(2)
122.2(2)
115.6(2)
126.0(2)
120.4(2)
123.6(2)
110.7(2)
107.4(2)
118.0(2)
119.7(2)
108.1(2)
The supramolecular structure is mainly developed
based on chlorineꢀ·ꢀ·ꢀ·ꢀchlorine contacts and the nonclas-
sical –Hꢀ·ꢀ·ꢀ·ꢀO hydrogen bonding interaction. There are
several weak hydrogen bonding interactions; these inter-
actions will be ignored because of the abundance of C–H
groups. Chlorineꢀ·ꢀ·ꢀ·ꢀchlorine contacts connect the mole-
cular units to form a chain structure (Fig. 3), whereby the
interchlorine distances are 3.351 and 3.336 Å; these dis-
tances are 0.15 and 0.17 Å less than the sum of the van der
Waals radii. The C–Clꢀ·ꢀ·ꢀ·ꢀCl angles are 148.0° and 151.8°;
these values are within the preferred values for these
contacts [24]. Two types of chlorineꢀ·ꢀ·ꢀ·ꢀchlorine contacts
are known: the symmetrical arrangement (also known
as type I) and the perpendicular arrangement (known
as type II). The observed chlorineꢀ·ꢀ·ꢀ·ꢀchlorine contacts,
shown in Fig. 3, follow type I geometry [24].
aSymmetry transformation used to generate equivalent atoms:
−xꢁ+ꢁ1, −y, −zꢁ+ꢁ2.
3 Conclusion
Fig. 2:ꢀOrtep view of the molecular structure of 3a in the
crystal and atom numbering scheme adopted. Only one of
the two crystallographically independent molecules is shown.
Displacement ellipsoids are drawn at the 30% probability
level, and hydrogen atoms are shown as spheres with arbitrary
radii. The unlabeled atoms are generated by a center of inversion.
N–Hꢁ·ꢁ·ꢁ·ꢁO hydrogen bonding interactions are shown as dashed
lines.
A variety of substituted tetrahydro-5,5′-bi(1,2,4-triazin-
6-ones) is prepared via the reaction of aminomalonic
ester with various N-(aryl)hydrazonoyl chlorides in the
presence of triethylamine. This versatile and efficient
one-pot synthetic route uses readily available inexpensive
Fig. 3:ꢀIllustration of Clꢁ·ꢁ·ꢁ·ꢁCl contacts in 3a.
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H.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)ꢂ ꢂ5
reactants, is conveniently conducted at or below room solution of the appropriate hydrazonoyl chlorides I–III
temperature, and provides direct access to the desired (0.01 mol) in ethanol (40 mL). Triethylamine (5 g, 0.05 mol)
dimmers decorated with a wide variety of substituents in ethanol (10 mL) was added to this resulting mixture,
appended at N-1 and C-3 hetero-ring positions. The studies cooled in an ice-salt bath (Tꢀ=ꢀ0–5°C). Thereafter, stirring
on biological activity of the synthesized compounds are was continued at Tꢀ=ꢀ~0–5°C for 2 h and then at room tem-
currently underway.
perature for 12 h. The reaction mixture was then diluted
with cold H2O (100 mL). The resulting solid product was
collected by suction filtration, washed with cold water
(2ꢀ×ꢀ20 mL), dried, and recrystallized from the appropriate
solvent.
4 Experimental section
Diethyl
aminomalonate
hydrochloride,
3-chloro-
2,4-pentanedione, ethyl 3-chloroacetoacetate, 2-chloro-
acetophenone, methyl 4-aminobenzoate, aniline, and 4.2.1 Diethyl 3,3′-diacetyl-6,6′-dioxo-1,1′-diphenyl-
4-(substituted)anilines were purchased from Acros (Geel,
Belgium). Melting points (uncorrected) were determined
on a Gallenkamp electrothermal melting temperature
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-triazine)-5,
5′-dicarboxylate (1c)
apparatus (London, UK) in open capillary tubes. IR spectra Yield: 77%; m. p. 141–142°C. – IR (KBr): vmaxꢀ=ꢀ3325, 1751,
were recorded as KBr discs on a Nicolet Impact-400FT-IR 1704, 1661 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.28 (t,
1
1
13
spectrophotometer (Waltham, MA, USA). H and C NMR Jꢀ=ꢀ7.1 Hz, 6H, 2CH3CH2O), 2.47 (s, 6H, 2CH3C=O), 4.29 (q,
spectra were recorded on a 500-MHz Bruker Avance-III Jꢀ=ꢀ7.1 Hz, 4H, 2OCH2Me), 7.39 (t, Jꢀ=ꢀ7.6 Hz, 2H, 4″-H/4″′-
spectrometer (Bruker Daltonic, Bremen, Germany) with H), 7.50 (overlapped dd, Jꢀ=ꢀ7.6 Hz, 8.2 Hz, 4H, 3″-H, 5″-
TMS as internal standard. Chemical shifts are expressed in H/3″′-H, 5″′-H), 7.62 (d, Jꢀ=ꢀ8.2 Hz, 4H, 2″-H, 6″-H/2″′-H,
1
1
δ units in ppm; J values for H– H coupling constants are 6″′-H), 8.40 (br s, 2H, N(4)-H/N(4′)-H, exchangeable
given in Hertz. HRMS data were acquired using the electro- with D2O) ppm. – 13C NMR (125 MHz, CDCl3): δꢀ=ꢀ13.9 (2
spray ion trap (ESI) technique by collision-induced disso- CH3CH2O), 23.8 (2CH3C=O), 63.5 (2 OCH2Me), 65.1 (C-5/
ciation on a Bruker APEX-IV (7 T) instrument (Karlsruhe, C-5′), 125.3 (C-2″, C-6″/C-2″′, C-6″′), 127.8 (C-4″/C-4″′),
Germany).
128.8 (C-3″, C-5″/C-3″′, C-5″′), 139.0 (C-3/C-3′), 140.5 (C-1″/
C-1″′), 158.2 (C-6/C-6′), 166.9 (2 CO2Et), 191.7 (2 Me-C=O)
ppm. – HRMS ((+)-ESI): m/zꢀ=ꢀ577.20308 (calcd. 577.20414
+
4.1 N-(aryl)hydrazonoyl chlorides (I–III)
for C28H29N6O8, [Mꢀ+ꢀH] ), 599.18575 (calcd. 599.18608 for
+
C28H28N6O8Na, [Mꢀ+ꢀNa] ).
Compounds Ic–g [11, 25–27] and IIa–f [27–32] were
reported in the literature and are prepared in this study
via the Japp Klingemann reaction [33–36], which involves
coupling of the appropriate arenediazonium chloride
with the respective 3-chloro-2,4-pentanedione (or ethyl
2-chloroacetoacetate) following standard procedures
[11]. Compounds IIIa–e [11, 27, 30, 37, 38] were prepared
by coupling of the appropriate arenediazonium chloride
with phenacyl chloride following reported procedures
[11, 38].
4.2.2 Diethyl 3,3′-diacetyl-1,1′-bis[4-(methoxycarbonyl)
phenyl]-6,6′-dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-
5,5′-bi(1,2,4-triazine)-5,5′-dicarboxylate (1d)
Yield: 88%; m. p. 178–179°C. – IR (KBr): vmaxꢀ=ꢀ3313, 1730,
1
1698, 1675, 1643, 860 cm−1. – H NMR (500 MHz, CDCl3):
δꢀ=ꢀ1.27 (t, Jꢀ=ꢀ7.0 Hz, 6H, 2 CH3CH2O), 2.51 (s, 6H, 2 CH3C=O),
3.97 (s, 3H, CO2CH3), 4.29 (q, Jꢀ=ꢀ7.0 Hz, 4H, 2 OCH2Me), 7.75
(d, Jꢀ=ꢀ8.6 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H), 8.16 (d, Jꢀ=ꢀ8.6 Hz,
4H, 3″-H, 5″-H/3″′-H, 5″′-H), 8.39 (br s, 2H, N(4)-H/N(4′)-H,
exchangeable with D2O) ppm. – 13C NMR (125 MHz, CDCl3):
δꢀ=ꢀ13.9 (2 CH3CH2O), 23.8 (2 CH3C=O), 63.7 (2 OCH2Me), 65.2
(C-5/C-5′), 124.6 (C-2″, C-6″/C-2″′, C-6″′), 129.3 (C-4″/C-4″′),
130.2 (C-3″, C-5″/C-3″′, C-5″′), 139.2 (C-3/C-3′), 144.1 (C-1″/
C-1″′), 158.2 (C-6/C-6′), 166.3 (2 CO2Me), 166.7 (2 CO2Et),
4.2 General procedure for the synthesis of
diethyl-1,1′-diaryl-5,5′-bis(dihydro-6-
oxo-1,2,4-triazine)-5,5′-dicarboxylates
(1–3)
A solution of diethyl aminomalonate hydrochloride 191.5 (2 Me-C=O) ppm. – HRMS ((+)-ESI): m/zꢀ=ꢀ693.21565
(2.54 g, 0.012 mol) in ethanol (20 mL) was added to a (calcd. 693.21510 for C32H33N6O12, [Mꢀ+ꢀH] ).
+
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6ꢀ ꢀH.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)
4.2.3 Diethyl 3,3′-diacetyl-6,6′-dioxo-1,1′-di(4-
methylphenyl)-1,1′,4,4′,5,5′,6,6′-octahydro-5,
5′-bi(1,2,4-triazine)-5,5′-dicarboxylate (1e)
55.6 (4″-OCH3/4″′-OCH3), 63.4 (2 OCH2Me), 65.0 (C-5/C-5′),
114.1 (C-3″, C-5″/C-3″′, C-5″′), 126.6 (C-2″, C-6″/C-2″′, C-6″′),
133.5 (C-1″/C-1″′), 139.0 (C-3/C-3′), 158.2 (C-4″/C-4″′), 159.0
(C-6/C-6′), 167.0 (2 CO2Et), 191.7 (2 Me-C=O) ppm. – HRMS
Yield: 86%; m. p. 150–151°C. – IR (KBr): vmaxꢀ=ꢀ3325, 1746, ((+)-ESI): m/zꢀ=ꢀ637.22504 (calcd. 637.22527 for C30H33N6O10,
1702, 1662, 825 cm−1. – 1H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.23 (t, [Mꢀ+ꢀH] ), 659.20773 (calcd. 659.20721 for C30H32N6O10Na,
+
+
Jꢀ=ꢀ7.1 Hz, 6H, 2CH3CH2O), 2.38 (s, 6H, 4″-CH3/4″′-CH3), 2.42 [Mꢀ+ꢀNa] ).
(s, 6H, 2CH3C=O), 4.24 (q, Jꢀ=ꢀ7.1 Hz, 4H, 2OCH2Me), 7.26 (d,
Jꢀ=ꢀ8.3 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H), 7.43 (d, Jꢀ=ꢀ8.3 Hz,
4H, 3″-H, 5″-H/3″′-H, 5″′-H), 8.35 (br s, 2H, N(4)-H, N(4′)-H, 4.2.6 Tetraethyl 1,1′-bis(4-chlorophenyl)-6,6′-dioxo-
exchangeable with D2O) ppm. – 13C NMR (125 MHz, CDCl3):
δꢀ=ꢀ14.0 (2 CH3CH2O), 21.2 (4″-CH3/4″′-CH3), 23.8 (2CH3C=O),
63.4 (2 OCH2Me), 65.1 (C-5/C-5′), 125.1 (C-2″, C-6″/C-2″′,
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-triazine)-
3,3′,5,5′-tetracarboxylate (2a)
C-6″′), 129.5 (C-3″, C-5″/C-3″′, C-5″′), 137.9 (C-4″/C-4″′), 138.1 Yield: 82%; m. p. 213–215°C. – IR (KBr): vmaxꢀ=ꢀ3333, 1746,
(C-1″/C-1″′), 139.0 (C-3/C-3′), 158.2 (C-6/C-6′), 167.0 (2 CO2Et), 1726, 1668, 833 cm−1. – 1H NMR (500 MHz, CDCl3):
191.7 (2 Me-C=O) ppm. – HRMS ((+)-ESI): m/zꢀ=ꢀ605.23567 δꢀ=ꢀ1.30 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-C3′),
+
(calcd. 605.23544 for C30H33N6O8, [Mꢀ+ꢀH] ), 627.21647 1.38 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-C5′),
+
(calcd. 627.21738 for C30H32N6O8Na, [Mꢀ+ꢀNa] ).
4.32 (q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C5/CH3CH2CO2-C5′),
4.39 (q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C3/CH3CH2CO2-C3′), 7.43
(d, Jꢀ=ꢀ8.6 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.54 (d, Jꢀ=ꢀ8.6 Hz,
4H, 2″-H, 6″-H/2″′-H, 6″′-H), 8.56 (br s, 2H, N(4)-H/N(4′)-H,
exchangeable with D2O) ppm. – 13C NMR (125 MHz, CDCl3):
δꢀ=ꢀ13.9 (CH3CH2CO2-C3/CH3CH2CO2-C3′), 14.1 (CH3CH2CO2-
C5/CH3CH2CO2-C5′), 63.4 (CH3CH2CO2-C3/CH3CH2CO2-C3′),
4.2.4 Diethyl 3,3′-diacetyl-1,1′-bis(4-cyanophenyl)-6,6′-
dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-
triazine)-5,5′-dicarboxylate (1f)
Yield: 78%; m. p. 178–179°C. – IR (KBr): vmaxꢀ=ꢀ3319, 2227, 63.8 (CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.1 (C-5/C-5′), 126.8
1706, 1669, 839 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.26 (C-2″, C-6″/C-2″′, C-6″′), 129.0 (C-3″, C-5″/C-3″′, C-5″′), 133.5
1
(t, Jꢀ=ꢀ7.0 Hz, 6H, 2 CH3CH2O), 2.52 (s, 6H, 2 CH3C=O), 4.28 (C-4″/C-4″′), 134.7 (C-1″/C-1″′) 138.8 (C-3/C-3′), 157.9 (C-6/
(q, Jꢀ=ꢀ7.0 Hz, 4H, 2 OCH2Me), 7.78 (d, Jꢀ=ꢀ8.5 Hz, 4H, 3″-H, 5″- C-6′), 159.7 (C3-CO2Et/C3′-CO2Et), 166.6 (C5-CO2Et/C5′-
H/3″′-H, 5″′-H), 7.83 (d, Jꢀ=ꢀ8.5 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′- CO2Et) ppm. – HRMS ((+)-ES1): m/zꢀ=ꢀ705.14740, (calcd.
H), 8.35 (br s, 2H, N(4)-H/N(4′)-H, exchangeable with D2O) 705.14732 for C30H3135Cl2N6O10, [Mꢀ+ꢀH] ), 707.14492 (calcd.
+
ppm. – 13C NMR (125 MHz, CDCl3): δꢀ=ꢀ13.9 (2 CH3CH2O), 23.8 707.14533 for C30H3135Cl37Cl N6O10, [Mꢀ+ꢀ2ꢀ+ꢀH] ), 709.14081
+
(2 CH3C=O), 63.9 (2 OCH2Me), 65.2 (C-5/C-5′), 110.9 (C-4″/ (calcd. 709.14143 for C30H3137Cl2N6O10, [Mꢀ+ꢀ4ꢀ+ꢀH] ).
+
C-4″′), 118.0 (2 CN), 125.2 (C-2″, C-6″/C-2″′, C-6″′), 132.7
(C-3″, C-5″/C-3″′, C-5″′), 139.3 (C-3/C-3′), 143.8 (C-1″/C-1″′),
158.3 (C-6/C-6′), 166.5 (2 CO2Et), 191.3 (2 Me-C=O) ppm. – 4.2.7 Tetraethyl 1,1′-bis(4-bromophenyl)-6,6′-dioxo-
HRMS ((+)-ESI): m/zꢀ=ꢀ627.19490 (calcd. 627.19464 for
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-triazine)-
3,3′,5,5′-tetracarboxylate (2b)
+
C30H27N8O8, [Mꢀ+ꢀH] ).
Yield: 75%; m. p. 230–233°C. – IR (KBr): vmaxꢀ=ꢀ3332,
1
4.2.5 Diethyl 3,3′-diacetyl-1,1′-bis(4-methoxyphenyl)-
6,6′-dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-
bi(1,2,4-triazine)-5,5′-dicarboxylate (1g)
1746, 1724, 1668, 830 cm−1. – H NMR (500 MHz, CDCl3):
δꢀ=ꢀ1.30 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-C3′),
1.39 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.31
(q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.40
Yield: 74%; m. p. 119–120°C. – IR (KBr): vmaxꢀ=ꢀ3329, 1744, (q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C3/CH3CH2CO2-C3′), 7.48 (d,
1701, 1661, 835 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.28 Jꢀ=ꢀ8.6 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.58 (d, Jꢀ=ꢀ8.6 Hz,
1
(t, Jꢀ=ꢀ7.1 Hz, 6H, 2CH3CH2O), 2.46 (s, 6H, 2CH3C=O), 3.87 (s, 4H, 2″-H, 6″-H/2″′-H, 6″′-H), 8.55 (br s, 2H, N(4)-H/N(4′)-H,
6H, 4″-OCH3/4″′-OCH3), 4.28 (q, Jꢀ=ꢀ7.1 Hz, 4H, 2OCH2Me), exchangeable with D2O) ppm. – 13C NMR (125 MHz, CDCl3):
7.01 (d, Jꢀ=ꢀ8.8 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.50 (d, δꢀ=ꢀ13.9 (CH3CH2CO2-C3/CH3CH2CO2-C3′), 14.1 (CH3CH2CO2-
Jꢀ=ꢀ8.8 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H), 8.39 (br s, 2H, C5/CH3CH2CO2-C5′), 63.4 (CH3CH2CO2-C3/CH3CH2CO2-C3′),
13
N(4) H/N(4′)-H, exchangeable with D2O) ppm. – C NMR 63.8 (CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.1 (C-5/C-5′), 121.5
(125 MHz, CDCl3): δꢀ=ꢀ13.9 (2 CH3CH2O), 23.8 (2 CH3C=O), (C-4″/C-4″′), 127.1 (C-2″, C-6″/C-2″′, C-6″′), 132.0 (C-3″,
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ꢁꢀꢀꢀ
H.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)ꢂ ꢂ7
C-5″/C-3″′, C-5″′), 134.7 (C-1″/C-1″′) 139.3 (C-3/C-3′), 157.9 52.3 (C4″-CO2CH3/C4″′-CO2CH3), 63.5 (CH3CH2CO2-C3/
(C-6/C-6′), 159.6 (C3-CO2Et/C3′-CO2Et), 166.6 (C5-CO2Et/ CH3CH2CO2-C3′), 63.9 (CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.2
C5′-CO2Et) ppm. – HRMS (ES1): m/zꢀ=ꢀ793.04580 (calcd. (C-5/C-5′), 125.0 (C-2″, C-6″/C-2″′, C-6″′), 129.1 (C-4″/C-4″′),
793.04629 for C30H3179Br2N6O10, [Mꢀ+ꢀH] ), 795.04570 (calcd. 130.3 (C-3″, C-5″/C-3″′, C-5″′), 134.8 (C-3/C-3′), 144.0 (C-1″/
+
795.04455 for C30H3179Br81BrN6O10, [Mꢀ+ꢀ2ꢀ+ꢀH] ), 797.04340 C-1″′), 158.0 (C-6/C-6′), 159.7 (C3-CO2Et/C3′-CO2Et), 166.4
+
(calcd. 797.04331 for C30H3181Br2N6O10, [Mꢀ+ꢀ4ꢀ+ꢀH] ), (C4″-CO2CH3/C4″′-CO2CH3) 166.5 (C5-CO2Et/C5′-CO2Et)
+
815.02823 (calcd. 815.02824 for C30H3079Br2N6O10 Na, ppm. – HRMS ((+)-ESI): m/zꢀ=ꢀ775.21782 (calcd. 775.21817
[Mꢀ+ꢀNa] ), 817.02593 (calcd. 817.02650 for C30H30N6O1079Br- for C34H36N6O14Na, [Mꢀ+ꢀNa] ), 1527.44658 (calcd. 1527.44712
+
+
81BrNa, [Mꢀ+ꢀ2ꢀ+ꢀNa] ), 819.02583 (calcd. 819.02526 for for C68H72N12O28Na, [2Mꢀ+ꢀNa] ).
+
+
C30H3081Br2N6O10Na, [Mꢀ+ꢀ4ꢀ+ꢀNa] ).
+
4.2.10 Tetraethyl 6,6′-dioxo-1,1′-di(4-methylphenyl)-
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-
triazine)-3,3′,5,5′-tetracarboxylate (2e)
4.2.8 Tetraethyl 6,6′-dioxo-1,1′-diphenyl-1,1′,4,4′,5,5′,
6,6′-octahydro-5,5′-bi(1,2,4-triazine)-3,3′,5,5′-
tetracarboxylate (2c)
Yield: 76%; m. p. 218–220°C. – IR (KBr): vmaxꢀ=ꢀ3294,
1
1743, 1722, 1665, 861 cm−1. – H NMR (500 MHz, CDCl3):
Yield: 87%; m. p. 218–223°C. – IR (KBr): vmaxꢀ=ꢀ3328,
δꢀ=ꢀ1.31 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-
C3′), 1.36 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-
C5′), 2.40 (s, 6H, 4″-CH3/4″′-CH3) 4.33 (q, Jꢀ=ꢀ7.1 Hz, 4H,
CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.38 (q, Jꢀ=ꢀ7.1 Hz, 4H,
CH3CH2CO2-C3/CH3CH2CO2-C3′), 7.27 (d, Jꢀ=ꢀ8.2 Hz, 4H, 3″-H,
5″-H/3″′-H, 5″′-H), 7.44 (d, Jꢀ=ꢀ8.2 Hz, 4H, 2″-H, 6″-H/2″′-H,
6″′-H), 8.59 (br s, 2H, N(4)-H/N(4′)-H, exchangeable with
D2O) ppm. – 13C NMR (125 MHz, CDCl3): δꢀ=ꢀ14.0 (CH3CH2CO2-
C3/CH3CH2CO2-C3′), 14.1 (CH3CH2CO2-C5/CH3CH2CO2-C5′),
21.2 (4″-CH3/4″′-CH3), 63.2 (CH3CH2CO2-C3/CH3CH2CO2-C3′),
63.5 (CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.1 (C-5/C-5′), 125.5
(C-3″, C-5″/C-3″′, C-5″′), 129.5 (C-2″, C-6″/C-2″′, C-6″′), 134.5
(C-1″/C-1″′), 137.9 (C-4″/C-4″′), 137.9 (C-3/C-3′), 157.9 (C-6/
C-6′), 159.8 (C3-CO2Et/C3′-CO2Et), 166.8 (C5-CO2Et/C5′-
CO2Et) ppm. – HRMS ((+)-ES1): m/zꢀ=ꢀ665.25608, (calcd.
1
1743, 1719, 1666 cm−1. – H NMR (500 MHz, CDCl3):
δꢀ=ꢀ1.32 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-C3′),
1.37 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.34
(q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.39
(q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C3/CH3CH2CO2-C3′), 7.37
(t, Jꢀ=ꢀ7.3 Hz, 2H, 4″-H, 4″′-H), 7.47 (pseudo t, Jꢀ=ꢀ7.7 Hz,
4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.58 (d, Jꢀ=ꢀ7.7 Hz, 4H,
2″-H, 6″-H/2″′-H, 6″′-H), 8.60 (br s, 2H, N(4)-H/N(4′)-H,
exchangeable with D2O) ppm. – 13C NMR (125 MHz, CDCl3):
δꢀ=ꢀ14.0 (CH3CH2CO2-C3/CH3CH2CO2-C3′), 14.1 (CH3CH2CO2-
C5/CH3CH2CO2-C5′), 63.3 (CH3CH2CO2-C3/CH3CH2CO2-C3′),
63.6 (CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.1 (C-5/C-5′), 125.7
(C-2″, C-6″/C-2″′, C-6″′), 128.0 (C-4″/C-4″′), 128.9 (C-3″,
C-5″/C-3″′, C-5″′), 134.6 (C-1″/C-1″′), 140.4 (C-3/C-3′), 157.9
(C-6/C-6′), 159.8 (C3-CO2Et/C3′-CO2Et), 166.8 (C5-CO2Et/
C5′-CO2Et) ppm. – HRMS ((+)-ESI): m/zꢀ=ꢀ637.22572 (calcd.
+
665.25657 for C32H37N6O10, [Mꢀ+ꢀH] ).
+
637.22527 for C30H33N6O10, [Mꢀ+ꢀH] ).
4.2.11 Tetraethyl 1,1′-bis(4-cyanophenyl)-6,6′-dioxo-
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-triazine)-
3,3′,5,5′-tetracarboxylate (2f)
4.2.9 Tetraethyl 1,1′-bis[4-(methoxycarbonyl)phenyl]-
6,6′-dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-
bi(1,2,4-triazine)-3,3′,5,5′-tetracarboxylate (2d)
Yield: 92%; m. p. 220–222°C. – IR (KBr): vmaxꢀ=ꢀ3301,
1
2232, 1744, 1677, 851 cm−1. – H NMR (500 MHz, CDCl3):
Yield: 91%; m. p. 198–200°C. – IR (KBr): vmaxꢀ=ꢀ3310, δꢀ=ꢀ1.26 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-C3′),
1725, 1673, 1651, 860 cm−1. – H NMR (500 MHz, CDCl3): 1.38 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-C5′),
1
δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C3/CH3CH2CO2-C3′), 4.30 (q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C5/CH3CH2CO2-C5′),
1.38 (t, Jꢀ=ꢀ7.1 Hz, 6H, CH3CH2CO2-C5/CH3CH2CO2-C5′), 3.95 4.40 (q, Jꢀ=ꢀ7.1 Hz, 4H, CH3CH2CO2-C3/CH3CH2CO2-C3′),
(s, 6H, C4″-CO2CH3/C4″′-CO2CH3), 4.32 (q, Jꢀ=ꢀ7.1 Hz, 4H, 7. 74 (d, Jꢀ=ꢀ8.6 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.79 (d,
CH3CH2CO2-C5/CH3CH2CO2-C5′), 4.39 (q, Jꢀ=ꢀ7.1 Hz, 4H, Jꢀ=ꢀ8.6 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H), 8.54 (br s, 2H,
13
CH3CH2CO2-C3/CH3CH2CO2-C3′), 7.71 (d, Jꢀ=ꢀ8.6 Hz, 4H, 3″-H, N(4)-H/N(4′)-H, exchangeable with D2O) ppm. – C NMR
5″-H/3″′-H, 5″′-H), 8.13 (d, Jꢀ=ꢀ8.6 Hz, 4H, 2″-H, 6″-H/2″′-H, (125 MHz, CDCl3): δꢀ=ꢀ13.9 (CH3CH2CO2-C3/CH3CH2CO2-C3′),
6″′-H), 8.57 (br s, 2H, N(4)-H/N(4′)-H, exchangeable with 14.0 (2 CH3CH2CO2-C5/CH3CH2CO2-C5′), 63.6 (CH3CH2CO2-
D2O) ppm. – 13C NMR (125 MHz, CDCl3): δꢀ=ꢀ13.9 (CH3CH2CO2- C3/CH3CH2CO2-C3′), 64.0 (CH3CH2CO2-C5/CH3CH2CO2-C5′),
C3/CH3CH2CO2-C3′), 14.0 (2 CH3CH2CO2-C5/CH3CH2CO2-C5′), 65.2 (C-5/C-5′), 111.1 (C-4″/C-4″′), 118.3 (2 CN), 125.5 (C-2″,
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ꢀꢀꢀꢁ
8ꢀ ꢀH.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)
C-6″/C-2″′, C-6″′), 132.8 (C-3″, C-5″/C-3″′, C-5″′), 135.0 (C-1″/ 134.4 (C-1″″/C-1″″′), 139.5 (C-1″/C-1″′), 139.7 (C-3/C-3′),
C-1″′) 143.8 (C-3/C-3′), 158.0 (C-6/C-6′), 159.5 (C3-CO2Et/C3′- 157.9 (C-6/C-6′), 166.8 (2 CO2Et), 184.4 (2 Ph-C=O) ppm.
CO2Et), 166.4 (C5-CO2Et/C5′-CO2Et) ppm. – HRMS ((+)-ESI): – HRMS ((–)-ESI): m/zꢀ=ꢀ855.04226 (calcd. 855.04191 for
m/zꢀ=ꢀ687.21632 (calcd. 687.21577 for C32H31N8O10, [Mꢀ+ꢀH] ).
C38H2979Br2N6O8, [Mꢀ–ꢀH]−), 857.04104 (calcd. 857.04029
for C38H2979Br81BrN6O8, [Mꢀ+ꢀ2ꢀ–ꢀH]−), 859.04021 (calcd.
859.03932 for C38H2981Br2N6O8, [Mꢀ+ꢀ4ꢀ–ꢀH]−).
+
4.2.12 Diethyl 3,3′-dibenzoyl-1,1′-bis(4-chlorophenyl)-
6,6′-dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-
bi(1,2,4-triazine)-5,5′-dicarboxylate (3a)
4.2.14 Diethyl 3,3′-dibenzoyl-6,6′-dioxo-1,1′-diphenyl-
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-
triazine)-5,5′-dicarboxylate (3c)
Yield: 83%; m. p. 212–214°C. – IR (KBr): vmaxꢀ=ꢀ3311, 1746,
1670, 1655, 833 cm−1. – 1H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.29 (t,
6H, 2 CH3CH2O), 4.32 (q, 4H, 2 OCH2Me), 7.45 (d, Jꢀ=ꢀ8.9 Hz, Yield: 82%; m. p. 205–207°C. – IR (KBr): vmaxꢀ=ꢀ3308, 1747,
4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.46 (pseudo t, 4H, Jꢀ=ꢀ7.5, 3″″- 1670, 1656 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.26
1
H, 5″″-H/3″″′-H, 5″″′-H), 7.60 (d, Jꢀ=ꢀ8.9 Hz, 4H, 2″-H, 6″- (t, Jꢀ=ꢀ7.0 Hz, 6H, 2 CH3CH2O), 4.28 (q, Jꢀ=ꢀ7.0 Hz, 4H, 2
H/2″′-H, 6″′-H), 7.62 (dd, 2H, Jꢀ=ꢀ7.5, 2.0, H-4″″/H-4″″′), 8.24 OCH2Me), 7.34 (t, Jꢀ=ꢀ7.5 Hz, 2H, H-4″/H-4″′), 7.42 (pseudo
(d, 4H, Jꢀ=ꢀ7.5, 2″″-H, 6″″-H/2″″′-H, 6″″′-H), 8.67 (br s, 2H, t, Jꢀ=ꢀ7.8 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.46 (pseudo t,
13
N(4)-H/N(4′)-H, exchangeable with D2O) ppm. – C NMR Jꢀ=ꢀ7.7 Hz, 4H 3″″-H, 5″″-H/3″″′-H, 5″″′-H), 7.56 (t, Jꢀ=ꢀ7.5 Hz,
(125 MHz, CDCl3) δꢀ=ꢀ14.0 (2 CH3CH2O), 63.7 (2 OCH2Me), H-4″″/H-4″″′), 7.62 (d, Jꢀ=ꢀ7.7 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-
65.5 (C-5/C-5′), 126.8 (C-2″, C-6″/C-2″′, C-6″′), 128.1 (C-3″″, H), 8.23 (d, Jꢀ=ꢀ7.4 Hz, 4H, 2″″-H, 6″″-H/2″″′-H, 6″″′-H), 8.68
C-5″″/C-3″″′, C-5″″′), 128.9 (C-3″, C-5″/C-3″′, C-5″′), 131.1 (br s, 2H, N(4)-H/N(4′)-H, exchangeable with D2O) ppm.
13
(C-2″″, C-6″″/C-2″″′, C-6″″′) 133.1 (C-4″/C-4″′), 133.6 (C-4″″/ – C NMR (125 MHz, CDCl3): δꢀ=ꢀ14.2 (2 CH3CH2O), 63.7 (2
C-4″″′) 134.4 (C-1″/C-1″′), 139.0 (C-3/C-3′), 139.6 (C-1″″/C-1″″′) OCH2Me), 65.7 (C-5/C-5′), 125.3 (C-2″, C-6″/C-2″′, C-6″′),
158.0 (C-6/C-6′), 166.8 (2 CO2Et), 184.4 (2 Ph-C=O) ppm. 127.8 (C-4″/C-4″′), 128.3 (C-3″″, C-5″″/C-3″″′, C-5″″′) 129.0
– HRMS ((–)-ESI): m/zꢀ=ꢀ767.14276 (calcd. 767.14294 for (C-3″, C-5″/C-3″′, C-5″′), 131.4 (C-2″″, C-6″″/C-2″″′, C-6″″′),
C38H2935Cl2N6O8, [Mꢀ–ꢀH]−), 769.14183 (calcd. 769.14129 for 133.7 (C-4″″/C-4″″′), 134.8 (C-1″/C-1″′), 139.8 (C-3/C-3′),
C38H2935Cl37ClN6O8, [Mꢀ+ꢀ2ꢀ–ꢀH]−), 771.13528(calcd. 771.13595 140.8 (C-1″″/C-1″″′), 158.2 (C-6/C-6′), 167.2 (2 CO2Et), 184.7
for C38H2937Cl2N6O8, [Mꢀ+ꢀ4ꢀ–ꢀH]−).
(2 Ph-C=O) ppm. – HRMS (ESI): m/zꢀ=ꢀ701.23601 (calcd.
+
Yellow needle-like crystals of 3a, suitable for X-ray 701.23544 for C38H33N6O8, [Mꢀ+ꢀH] ), 699.22168 (calcd.
crystallography, were grown slowly by allowing a clear 699.22089 for C38H31N6O8, [Mꢀ–ꢀH]−).
dilute solution of 3a in ethanol to stand in an open vessel
at room temperature for 10–12 days.
4.2.15 Diethyl 3,3′-dibenzoyl-1,1′-bis[4-
(methoxycarbonyl)phenyl]-6,6′-dioxo-
4.2.13 Diethyl 3,3′-dibenzoyl-1,1′-bis(4-bromophenyl)-
6,6′-dioxo-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-
bi(1,2,4-triazine)-5,5′-dicarboxylate (3b)
1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-bi(1,2,4-triazine)-
5,5′-dicarboxylate (3d)
Yield: 87%; m. p. 192–194°C. – IR (KBr): vmaxꢀ=ꢀ3310,
Yield: 85%; m. p. 208–210°C. – IR (KBr): vmaxꢀ=ꢀ3306, 1742, 1718, 1655, 865 cm−1. – H NMR (500 MHz, CDCl3):
1
1
1743, 1669, 1665, 828 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.28 (t, 6H, 2 CH3CH2O), 3.97 (s, 6H, 2CO2-CH3), 4.32
δꢀ=ꢀ1.30 (t, Jꢀ=ꢀ7.0 Hz, 6H, 2 CH3CH2O), 4.32 (q, Jꢀ=ꢀ7.0 Hz, (q, 4H, 2 OCH2Me), 7.47 (pseudo t, Jꢀ=ꢀ7.8 Hz, 4H, 3″″-H,
4H, 2 OCH2Me), 7.46 (pseudo t, Jꢀ=ꢀ7.8 Hz, 4H, 3″″-H, 5″″-H/3″″′-H, 5″″′-H), 7.62 (t, Jꢀ=ꢀ7.5 Hz, 4H, H-4″″/H-
5″″-H/3″″′-H, 5″″′-H), 7.55 (d, Jꢀ=ꢀ8.7 Hz, 4H, 2″-H, 6″- 4″″′), 7.78 (d, Jꢀ=ꢀ8.6 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H),
H/2″′-H, 6″′-H), 7.60 (t, H-4″″/H-4″″′), 7.61 (d, Jꢀ=ꢀ8.7 Hz, 8.15 (d, Jꢀ=ꢀ8.6 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 8.25 (d,
4H, 3″-H, 5″-H/3″′-H, 5″′-H), 8.23 (d, Jꢀ=ꢀ7.5 Hz, 4H, 2″″- Jꢀ=ꢀ7.5 Hz, 4H, 2″″-H, 6″″-H/2″″′-H, 6″″′-H), 8.69 (br s,
13
H, 6″″-H/2″″′-H, 6″″′-H), 8.66 (br s, 2H, N(4)-H/N(4′)-H, 2H, N(4)-H/N(4′)-H, exchangeable with D2O) ppm. – C
exchangeable with D2O) ppm. – 13C NMR (125 MHz, NMR (125 MHz, CDCl3): δꢀ=ꢀ14.0 (2 CH3CH2O), 52.3 (2CO2-
CDCl3): δꢀ=ꢀ14.0 (2 CH3CH2O) 63.7 (2 OCH2Me), 65.4 (C-5/C- CH3), 63.8 (2 OCH2Me), 65.4 (C-5/C-5′), 124.4 (C-2″, C-6″/C-
5′), 121.1 (C-4″/C-4″′), 126.6 (C-2″, C-6″/C-2″′, C-6″′), 128.2 2″′, C-6″′), 128.2 (C-3″″, C-5″″/C-3″″′, C-5″″′), 128.8 (C-4″/
(C-3″″, C-5″″/C-3″″′, C-5″″′), 131.1 (C-2″″, C-6″″/C-2″″′, C-4″′), 130.2 (C-3″, C-5″/C-3″′, C-5″′), 131.1 (C-2″″, C-6″″/
C-6″″′), 131.9 (C-3″, C-5″/C-3″′, C-5″′), 133.6 (C-4″″/C-4″″′), C-2″″′, C-6″″′), 133.7 (C-4″″/C-4″″′), 134.3 (C-1″″/C-1″″′),
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ꢁꢀꢀꢀ
ꢂ9
H.H. Mohammad et al.: Bis-heterocycles: tetrahydro-5,5′-bi(1,2,4-triazin-6-ones)ꢂ
139.6 (C-3/C-3′), 144.2 (C-1″/C-1″′), 158.0 (C-6/C-6′), 166.4
5 Supporting information
(2 CO2Me), 166.8 (2 CO2Et), 184.4 (2 Ph-C=O) ppm. –
HRMS ((–)-ESI): m/zꢀ=ꢀ815.23097 (calcd. 815.23184 for 1H and C NMR spectra of representative compounds 1e
13
C42H35N6O12, [Mꢀ–ꢀH]−).
(Figs. S1–S5), 2e (Figs. S6–S10), and 3e (Figs. S11–S13)
are given as supplementary material available online
(DOI: 10.1515/znb-2018-0148).
4.2.16 Diethyl 3,3′-dibenzoyl-6,6′-dioxo-1,1′-di(4-
methylphenyl)-1,1′,4,4′,5,5′,6,6′-octahydro-5,5′-
bi(1,2,4-triazine)-5,5′-dicarboxylate (3e)
Acknowledgments: We wish to thank the Deanship of
Scientific Research at the University of Jordan, Amman,
Jordan, for financial support.
Yield: 92%; m. p. 210–211°C. – IR (KBr): vmaxꢀ=ꢀ3299, 1739,
1
1668, 1645, 824 cm−1. – H NMR (500 MHz, CDCl3): δꢀ=ꢀ1.26
(t, 6H, 2 CH3CH2O), 2.39 (s, 6H, Ar-CH3), 4.28 (q, 4H, 2
OCH2Me), 7.26 (d, Jꢀ=ꢀ8.9 Hz, 4H, 2″-H, 6″-H/2″′-H, 6″′-H),
7.41 (pseudo t, Jꢀ=ꢀ7.8, 4H 3″″-H, 5″″-H/3″″′-H, 5″″′-H), 7.50
(d, Jꢀ=ꢀ8.0 Hz, 4H, 3″-H, 5″-H/3″′-H, 5″′-H), 7.55 (t, Jꢀ=ꢀ7.4,
H-4″″/H-4″″′), 8.22 (d, Jꢀ=ꢀ7.4 Hz, 4H, 2″″-H, 6″″-H/2″″′-H,
6″″′-H), 8.67 (br s, 2H, N(4)-H/N(4′)-H, exchangeable
with D2O) ppm. – 13C NMR (125 MHz, CDCl3): δꢀ=ꢀ14.0 (2
CH3CH2O), 21.2 (Ar-CH3), 63.5 (2 OCH2Me), 65.4 (C-5/C-
5′), 125.0 (C-2″, C-6″/C-2″′, C-6″′), 128.1 (C-3″″, C-5″″/C-
3″″′, C-5″″′) 129.4 (C-3″, C-5″/C-3″′, C-5″′), 131.2 (C-2″″,
C-6″″/C-2″″′, C-6″″′) 133.4 (C-4″″/C-4″″′) 134.6 (C-1″/C-1″′),
138.2 (C-4″/C-4″′), 139.6 (C-1″″/C-1″″′), 140.0 (C-3/C-3′),
158.0 (C-6/C-6′), 167.1 (2 CO2Et), 184.5 (2 Ph-C=O) ppm.
– HRMS ((+)-ESI): m/zꢀ=ꢀ751.24813 (calcd. 751.24868 for
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Supplementary Material: The online version of this article offers
supplementary material (https://doi.org/10.1515/znb-2018-0148).
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Z. Naturforsch.ꢂ
ꢂ2018 | Volume x | Issue x(b)
Graphical synopsis
Hanan H. Mohammad, Mustafa M.
El-Abadelah, Salim S. Sabri, Firas F. Awwadi
and Wolfgang Voelter
Bis-heterocycles. Part I: tetrahydro-5,5′-
bi(1,2,4-triazin-6-ones)
https://doi.org/10.1515/znb-2018-0148
Z. Naturforsch. 2018; x(x)b: xxx–xxx
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