Synthesis, structures of some unsymmetrical 3,6-disubstituted-1,2,4,5- tetrazines

Article abstract of DOI:10.1002/jhet.5570450628

(Chemical Equation Presented) A series of new unsymmetrical 3-phenyl-6-benzyl-1,2,4,5-tetrazine derivatives 10a-i were synthesized and characterized by IR, NMR, MS, and element analysis. The structures of 4a, 10c, 10d and 10h were analyzed by X-ray crystallography, which had intermolecular C-H...N, C-H...Cl, C-H...Π and Π...Π H interactions.

Full text of DOI:10.1002/jhet.5570450628

Nov-Dec 2008
1745
Synthesis, Structures of some Unsymmetrical 3,6-Disubstituted-
1,2,4,5-Tetrazines
Wei-Xiao Hu* and Feng Xu
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032,
People’s Republic of China
*E-mail: huyang@mail.hz.zj.cn
Received September 13, 2007
R1
CN
N
N
N
N
(i) Sulfur/ NH2NH2·H2O
(ii)
R1
CH2
R2
NaNO2/ CH3COOH
R2
CH2 CN
a
b
c
d
e
f
g
h
i
R1
R2
H
H
H
H
CF3
H
CF3
CF3
Cl
Cl
Cl
OCH3 Cl
OCH3 Cl
H
OCH3 Cl
A series of new unsymmetrical 3-phenyl-6-benzyl-1,2,4,5-tetrazine derivatives 10a-i were synthesized
and characterized by IR, NMR, MS, and element analysis. The structures of 4a, 10c, 10d and 10h were
analyzed by X-ray crystallography, which had intermolecular C-H...N, C-H...Cl, C-H...ꢀ and ꢀ...ꢀ
interactions.
J. Heterocyclic Chem., 45, 1745 (2008).
Scheme I
INTRODUCTION
OC2H5
HCl
Compounds containing the 1,2,4,5-tetrazine skeleton
can be used as dyes [1], herbicides [2], and antibacterial
[3]. In addition, recently, some 1,2,4,5-tetrazine
derivatives have been found with good antitumor activity
by our research team [4-8]. Although some synthesis and
crystallographic studies of 1,2,4,5-tetrazine have been
NH·HCl
R1
C
R1
CN
EtOH
NH2NH2·H2O
-10°C
1a-d
NH2
HCl/ EtOH
NH4OH
CH3CN
H3C
C
NH·HCl
2
N
N
N
HN
N
published [9], only
unsymmetrical 3,6-disubstituted-1,2,4,5-tetrazines [10],
which is due to the difficulty and troublesome work in
a few of them referred to
NaNO2/ CH3COOH
R1
CH3
R1
CH3
N
N
NH
4a-d
3a-d
separation and purification of
disubstituted-1,2,4,5-tetrazines.
unsymmetrical 3,6-
a
b
c
d
R1
H
CH3
Cl
OCH3
According to Lang’s method [10a,b], the traditional
way to synthesize unsymmetrical 3,6-disubstituted-
1,2,4,5-tetrazines is as follows: ethyl (p-substituted)
iminobenzoate hydrochloride 1a-d and acetamidine
hydrochloride 2 were reacted with hydrazine hydrate to
Scheme II
N
N
HN
N
N
H+
CH2
CH2
N
isomerization
NH
NH2
form dihydro-1,2,4,5-tetrazines 3a-d,
a
series of
6
5
somewhat unstable compounds, which were then easily
oxidized by sodium nitrite and acetic acid to obtain
corresponding unsymmetrical 3-(substitutedphenyl)-6-
methyl-1,2,4,5-tetrazines 4a-d (Scheme ꢀ). However,
when using this method to prepare 3-phenyl-6-benzyl-
1,2,4,5-tetrazine, the yield was very low(<5%), the main
product we obtained was 4-amino-3-benzyl-5-phenyl-
1,2,4-trizole 6, which may have been formed by the
isomerization of 3-phenyl-6-benzyl-1,4-dihydro-1,2,4,5-
tetrazine 5 under acid conditions [11] (Scheme ꢁ) .
In this contribution we want to report about a facile
preparation of a series of new unsymmetrical 3-phenyl-6-
benzyl-1,2,4,5-tetrazine derivatives.
RESULTS AND DISCUSSION
Synthesis. The synthetic procedures of our new unsym-
metrical 3-phenyl-6-benzyl-1,2,4,5-tetrazine derivatives
10a-i are shown in scheme ꢂ. The p-substituted
benzonitrile 7a-i and p-substituted benzylcyanide 8a-i
were reacted with 85% hydrazine hydrate in the presence
of sulfur powder, to initially form 3-(p-substituted-
phenyl)-6-p-(substitutedbenzyl)-1,4-dihydro-1,2,4,5-tetra-
zine 9a-i, which were then easily oxidized by sodium
nitrite and acetic acid to obtain 3-phenyl-6-benzyl-1,2,4,5-

1746
W. –X. Hu and F. Xu
Vol 45
tetrazine derivatives 10a-i. In addition to 10a-i, this
reaction also caused other two series of products:
symmetrical 3,6-disubstituted phenyl-1,2,4,5-tetrazines
and 3,6-disubstituted benzyl-1,2,4,5-tetrazine, which were
formed by 7a-i and 8a-i, respectively. When the reaction
performed in the absence of sulfur powder, product 10a
was not detected even when the reaction time was
prolonged from 3 hours to 10 hours. When the molar ratio
of 7a-8a-sulfur was 1:1:1, the yield of 10a was 33.8 %.
By increasing the amount of sulfur power and changing
the molar ratio of 7a-8a-sulfur to 1:1:2, the yield of 10a
decreased to 28.2 %. These results showed that adding a
suitable amount of sulfur powder had a significant effect
on the yield of 10a.
Crystal structures. The selected bond lengths and
angles for compounds 4a, 10c-d and 10h are given in
Table 3. Parameters for data collection and refinement of
4a, 10c-d and 10h are summarized in Table 4. It should
be noted that, although the synthesis of 4a have been
reported [13], the crystal structure has not previously been
presented. The ORTEP view of 4a with atom numbering
scheme is shown in Figure 1. It is obvious that the
tetrazine ring N1-C6 (centroid Cg1), the phenyl ring C8-
C13 (centroid Cg2) and the C7 atom are almost coplanar,
the crystal packing (Figure 2) exhibits weak ꢀꢁꢀ
stacking interaction, proved by the short distance
Cg1…Cg2i of 3.758(3)Å. [symmetry codes: (i)1-x,1-y,1-z].
The C…C distance is within the range associated with ꢀꢁ
ꢀ interactions [3.3-3.8 Å] [12].
From these results the reaction conditions we choose
were 7a-i (25 mmol), 8a-i (25 mmol), sulfur powder (25
mmol), and 85% hydrazine hydrate (10 mL). Using this
reaction system, a series of new unsymmetrical 3-phenyl-
6-benzyl-1,2,4,5-tetrazine
derivatives
10a-i
were
synthesized. The results are summarized in Table 1. From
the Table, it can be seen that, for 10a-i, when R2 are the
same, the yields increase with the enhancement of
electron withdrawing ability of R3 group (Cl>H>OCH3).
On the contrary, when R3 are the same, the yields
decrease with the enhancement of electron withdrawing
ability of R2 group (H> Cl>CF3).
Figure 1. ORTEP view of compound 4a with atom numbering
scheme. Ellipsoids are drawn at the 50% probability level (arbitrary
spheres for H atoms).
Scheme III
R2
CN
HN
N
N
Sulfur
7a-i
8a-i
R2
CH2
R3
NH
NH2NH2·H2O
9a-i
R3
CH2 CN
Figure 2. The packing diagram of compound 4a view along the a axis.
The atom-labelling schemes of compound 10c and 10d
are shown in Figure 3. It is clear to see that 10c and 10d
have similar crystal structure. The central tetrazine rings
N1-C6 of 10c and 10d are almost coplanar with the
phenyl rings C14-C19 and C7-C12, with the dihedral
angles of 2.46(3)° and 5.90(2)°, respectively, but twisted
with respect to the benzyl-phenyl rings C8-C13 and C15-
C20, with the dihedral angles of 69.40(3)°and 76.70(2)°,
N
N
N
N
NaNO2
R2
CH2
R3
CH3COOH
10 a-i
a
b
c
d
e
f
g
h
i
R2
R3
H
H
H
H
CF3
H
CF3
OCH3 Cl
CF3
Cl
H
Cl
Cl
OCH3 Cl
OCH3 Cl
Table 1
The synthetic results of 10a-i
Entry
R2
R3
Isolated yieldꢀ
10a
10b
10c
10d
10e
10f
10g
10h
10i
H
H
H
CF3
CF3
CF3
Cl
H
OCH3
Cl
H
OCH3
Cl
H
OCH3
Cl
33.8
21.8
39.2
23.9
18.6
25.6
26.2
19.1
30.2
10c
10d
Figure 3. ORTEP view of compounds 10c and 10d with atom
numbering schemes. Ellipsoids are drawn at the 30% probability level
(arbitrary spheres for H atoms) .For 10d, only the major component of
the disordered CF3 group is shown.
Cl
Cl
ꢀall yields are based on 7a-i(or 8a-i).

Nov-Dec 2008
respectively.
New Unsymmetrical 3,6-Disubstituted-1,2,4,5-tetrazines
1747
The central bond lengths C3-C14 in
molecule 10c and C3-C7 in molecule 10d are 1.469(4) Å
and 1.462(4) Å, respectively, which are similar to that of
C3-C8 in 4a [1.461(3)Å]. The packing diagram of 10c is
shown in Figure 4, which indicates the weak C—H---N
hydrogen bonding occurs between neighboring molecules
(Table 5).
Figure 5. ORTEP view of compound 10h with atom numbering scheme.
Ellipsoids are drawn at the 30% probability level (arbitrary spheres for
H atoms).
Figure 4. The packing diagram of compound 10c view along the b
axis (the dotted line representing C-H---Cl hydrogen bonding).
The ORTEP view of 10h with atom numbering scheme
is shown in Figure 5. Compound 10h crystallizes with
two crystallographically independent molecules in the
asymmetric unit that differ in the orientation of the
methoxy group. In both molecules the chlorophenyl ring
is almost coplanar with the central tetrazine ring, but the
methoxyphenyl ring is twisted. C7-C12 and C14-C19
benzene rings make dihedral angles of 2.32(3)° and
76.74(2)°, respectively, with the central tetrazine ring N1-
C6. The C27-C37 and C34-C39 benzene make dihedral
angles of 2.32(3)° and 80.47(2)°, respectively, with the
central tetrazine ring N21-C26.
Figure 6. The packing diagram of compound 10h view along the a axis
(the dotted line representing C-H---Cl hydrogen bonding).
In conclusion, we have adopted two different methods
to prepare some unsymmetrical disubstituted-1,2,4,5-
tetrazines 4a-d and 10a-i. The structures of 4a, 10c, 10d
and 10h were analyzed by X-ray crystallography, and
these X-ray data may be helpful to find out the potential
drug-enzyme interactions between these compounds and
some tumor receptors, which we are studying on.
In the crystal structure (Figure 6), a C-H---Cl hydrogen
bonding is observed between the two independent
molecules, pair of C-H--ꢀ interactions involving the C34-
C39 ring (centroid Cg1) link the molecules into a
dimer(Table 6).
EXPERIMENTAL
Solvents and reagents were commercially available and used
without further purification. Melting points were measured on an
XRC-1 apparatus and are uncorrected. Infrared spectra were
Table 3
Selected bond lengths(Å) and bond angles(°) for 4a, 10c, 10d and 10h.
4a
N1-N2
N4-N5
N2-N1-C6
N5-C6-N1
1.319(3)
1.320(2)
118.50(2)
123.6(2)
N1-C6
N5-C6
N1-N2-C3
N4-N5-C6
1.327(3)
1.323(3)
118.17(2)
118.41(2)
N2-C3
C6-C7
N4-C3-N2
N1-C6-C7
1.335(2)
1.475(3)
123.10(2)
118.30(2)
C3-N4
C3-C8
N5-N4-C3
N2-C3-C8
1.334(2)
1.461(3)
118.29(2)
118.85(2)
10c
Cl1-C11
N4-N5
C6-C7
N2-C3-N4
N1-C6-N5
1.730(3)
1.314(3)
1.501(4)
123.5(3)
124.4(3)
N1-N2
N5-C6
C3-C14
N2-C3-C14
N1-C6-C7
1.325(3)
1.332(4)
1.469(4)
118.3(2)
118.4(3)
N1-C6
C3-N4
N2-N1-C6
N5-N4-C3
C6-C7-C8
1.328(3)
1.337(3)
117.5(2)
118.2(2)
112.1(2)
N2-C3
C7-C8
N1-N2-C3
N4-N5-C6
C10-C11-Cl1 120.2(3)
1.329(3)
1.505(4)
118.4(2)
117.9(2)
10d
N1-N2
C3-C7
C14-C15
N2-C3-C7
N1-C6-C14
1.325(4)
1.462(4)
1.503(4)
118.3(2)
118.1(3)
N1-C6
N4-N5
N2-N1-C6
N5-N4-C3
C6-C14-C15
1.333(4)
1.324(4)
118.8(3)
118.7(2)
112.5(2)
N2-C3
N5-C6
N1-N2-C3
N4-N5-C6
1.342(3)
1.335(4)
118.0(2)
118.1(2)
C3-N4
C6-C14
N4-C3-N2
N1-C6-N5
1.340(3)
1.482(4)
123.0(3)
123.4(3)

1748
W. –X. Hu and F. Xu
Vol 45
Table 3 (continued)
10h
Cl1-C10
N1-N2
N5-C6
1.701(4)
1.303(5)
1.379(5)
O1-C20
1.384(6)
O1-C17
1.552(6)
1.250(4)
1.617(6)
122.7(3)
124.6(4)
124.5(3)
N1-C6
1.259(5)
1.302(5)
1.446(5)
125.0(4)
123.3(4)
N2-C3
1.394(5)
1.454(6)
112.2(4)
123.6(3)
122.6(3)
C3-N4
N4-N5
C6-C13
C13-C14
N1-N2-C3
N1-C6-N5
C9-C10-Cl1
C3-C7
C20-O1-C17 118.8(5)
C6-N1-N2
N4-N5-C6
N2-C3-C7
N4-C3-N2
N5-C6-C13
C3-N4-N5
C8-C7-C3
111.9(4)
115.8(4)
Table 4
X-ray structure data collection and refinement parameters for 4a, 10c, 10d and 10h.
4a
10c
C15H11ClN4
THF/EtOH=1:4(V/V)
282.73
10d
C16H11F3N4
THF
316.29
Monoclinic
P21/C
10h
C16H13ClN4O
THF/EtOH=1:4(V/V)
Formula
Recrystallization solvent
C9H8N4
Acetone
172.19
Triclinic
P-1
M/(g mol-1)
Crystal system
Space group
Unit cell
a/(Å)
312.75
Triclinic
P-1
Monoclinic
P21/C
7.311(3)
8.746(4)
14.164(6)
76.400(5)
82.966(6)
85.491(6)
872.5(7)
4
6.246(2)
16.671(6)
14.173(4)
90
112.611(2)
90
4.701(2)
30.810(4)
10.899(5)
90
109.490(3)
90
9.471(3)
10.170(3)
16.911(7)
101.429(6)
97.597(6)
107.012(4)
1495.0(9)
4
b/(Å)
c/(Å)
ꢀ/(°)
ꢁ/(°)
ꢂ/(°)
V/ (Å)
Z
1361.9(8)
4
1486.8(3)
4
Index ranges
-8ꢃhꢃ7
-6ꢃhꢃ3
-11ꢃhꢃ11
-7ꢃꢀꢃ8ꢁ
-18ꢃkꢃ21
-18ꢃlꢃ16
0.275
6707
2976
182
584
0.96
0.077/0.233
0.249/-0.400
-6ꢃkꢃ10
-16ꢃlꢃ16
0.086
3626
3008
238
360
0.97
0.051/0.164
0.150/-0.184
-40ꢃkꢃ39
-12ꢃlꢃ14
0.114
9146
3418
236
648
1.00
0.073/0.261
0.410/-0.304
-12ꢃkꢃ11
-16ꢃlꢃ20
0.262
8415
5475
399
648
0.95
0.076/0.286
0.625/-0.312
Linear absorption coefficient/(mm-1)
No. Measured reflections
No. independent reflections
No. Refined parameters
F(000)
Goodness-of-fit(F2)
R1(F)/ꢄR2(F2)(I>2ꢅ(I))
Largest different peak and hole (e Å-3)
X-ray single diffraction was carried with Enraf-Nonius CAD-4
diffractometer by the Analysis center of Fu-Dan university. Data
were collected and refined by CAD-4 EXPR- ESS. Program(s)
used to solve and refine the structure were SHELXS97.
Molecular graphics were solved by ORTEX. The software used
to prepare material for publication was SHELXL 97.
Table 5
Hydrogen-bond geometry (Å, °) of 10c.
D-H…A
C13-H13…N5i
D-H
0.93
H…A
2.55
D…A
3.295(4)
D-H…A
137
Symmetric code: (i) x-1,y,z.
General Procedure for the Synthesis of 4a-e were according
to the Lang’s method [10].
Table 6
3-Phenyl-6-methyl-1,2,4,5-tetrazine (4a). Red prism, yield:
[13]). IR (KBr, cm-1): 3050
Hydrogen-bond geometry (Å, °) of 10h.
22.0%. mp: 74~76
(74.5-76
(Ar-H), 2926 (CH2), 1402, 1361 (C=N), 1088. MS (m/z, %): 172
(M+, 12), 103 (100), 76 (16).
D-H…A
C16-H16…C12i
C20-H20A…Cg1i
D-H
0.93
0.96
H…A
2.82
2.64
D…A
D-H…A
137
147
3.555(6)
3.482(8)
3-(4-Methylphenyl)-6-methyl-1,2,4,5-tetrazine (4b). Red
prism, yield: 26.5%. mp: 116~118
(115~118
[10b]). IR
(KBr, cm-1): 3056 (Ar-H), 2928 (CH2), 1404, 1381 (C=N), 1087.
MS (m/z, %): 186 (M+, 25), 117 (100), 90 (32), 63(7).
Symmetric code: (i) -x,-y+1,-z+1. Cg1 is the centroid of the C14-C19
ring
3-(4-Chlorophenyl)-6-methyl-1,2,4,5-tetrazine (4c). Red
recorded from KBr discs on a Nicolex FI-IR-170 instrument. 1H
NMR spectra were run on a Bruker AC400(400 MHz). Mass
spectra were obtained on a HP5989A spectrometer at an ionising
voltage of 70 eV by electron impact. Elemental analyses were
performed on a ThermoFinnigan Flash EA 1112 instrument.
prism, yield: 32.5%. mp: 142~144
(143~145
[10a]). IR
(KBr, cm-1): 3049 (Ar-H), 2980 (CH2), 1405, 1364 (C=N), 1093.
MS (m/z, %): 206 (M+, 15), 136 (100), 102 (25), 75(10).
3-(4-Methoxyphenyl)-6-methyl-1,2,4,5-tetrazine (4d). Red
prism, yield: 20.2%. mp: 103~105
(103~106
[10a]). IR

Nov-Dec 2008
New Unsymmetrical 3,6-Disubstituted-1,2,4,5-tetrazines
1749
(KBr, cm-1): 3056 (Ar-H), 2985 (CH2), 1401, 1360 (C=N), 1088.
MS (m/z, %): 202 (M+, 35), 133 (100), 103 (24), 89(28), 63(7).
General Procedure for the Synthesis of 10a-i. Under a N2
atmosphere, 85% hydrazine hydrate (10 mL, 170 mmol) was
added dropwise to an anhydrous ethanol solution (15 mL) of
p-substituted benzyl cyanide (25 mmol) 8a-i and p-substituted
benzonitrile (25 mmol) 7a-i at 298 K with existing sulfur
powder (0.8 g, 25 mmol). After refluxing for 3 h, the mixture
was cooled to room temperature and the resulting yellow solid
product was collected by filtration. The solid product was then
dissolved in diethyl ether (15 mL); to this solution was added 10
mL aqueous solution of sodium nitrite (1.0 g, 14 mmol) and was
then added dropwise of 8 mL aqueous solution of acetic acid
(0.9 g, 14 mmol). After standing for 4 h, the purple precipitate
was collected and washed with cold anhydrous ethanol (5 mL),
which was then chromatographed on a silica gel column using
cyclohexane–dichloromethane (V/V, 4:1) as the eluent. The first
eluting material, a pink crystal, was 3,6-di(p-substituted phenyl)-
s-tetrazine. The second one, a red crystal, was 3-(p-substituted
phenyl)-6-(p-substituted benzyl)-s-tetrazine 10a-i; the third one,
a red crystal, was 3,6-di(p-substituted benzyl)-s-tetrazine.
Crystal Structure Determination. Single-crystal X-ray
stucuture determination were made on crystal of molecule 4a,
10c-d and 10h. Data collection for the block-shaped single
crystals of 4a, 10c-d and 10h was performed on a Bruker CCD
system with graphite monochromated Mo Kꢀ radiation (ꢁ=
0.71073 Å) at 293 K. The model type of the diffractometer was
CCD area detector. The sizes of the crysrals used for data
collection were 0.25ꢂ0.20ꢂ0.15 mm3 for 4a, 0.25ꢂ0.20ꢂ0.20
mm3 for 10c, 0.30ꢂ0.25ꢂ0.20 mm3 for 10d, and 0.25ꢂ0.20 ꢂ0.15
mm3 for 10h. The structure was solved by direct methods and
refined on F2 using SHELXTL software. Anisotropic thermal
parameters were applied for all the non-hydrogen atoms. All
hydrogen atoms were positioned geometrically and refined as
(CDCl3, ppm) ꢄ8.58 (d, 2 H, J = 6.8 Hz), 7.57-7.63 (m, 3 H, Ar-
H), 7.40 (d, 2 H, J = 8.0 Hz), 6.87 (d, 2 H, J = 8.0 Hz), 4.65 (s, 2
H). MS (m/z, %): 282 (M+, 4), 151 (33), 116 (82), 103(100), 89
(14), 75 (21). Anal. Calcd. for C15H11N4Cl (282.07): C, 63.72; H,
3.92; N,19.82. Found: C, 63.68; H, 3.84; N, 19.80.
3-[4-(Trifluoromethyl)phenyl]-6-benzyl-1,2,4,5-tetreazine
(10d). Red needles, yield: 1.9 g. mp: 135~136ꢃ. IR (KBr,
cm-1): 3071 (Ar-H), 2950 (CH2), 1328 (C=N), 1123 (CF3), 1091.
1H NMR (DMSO-d6, ppm) ꢄ 8.66 (d, 2 H, J = 8.4 Hz), 8.04 (d, 2
H,J = 8.4 Hz), 7.28-7.44 (m, 5 H,Ar-H), 4.71 (s, 2 H). MS (m/z,
%): 316(M+, 5), 297 (4), 117 (62), 152 (22), 117 (100), 102 (8),
90 (35), 75 (8).Anal. Calcd. for C16H11N4F3 (316.28): C, 60.76;
H, 3.51; N, 17.71. Found: C, 60.79; H, 3.37; N, 17.69.
3-[4-(Trifluoromethyl)phenyl]-6-(4-methoxybenzyl)-1,2,4,
5-tetreazine (10e). Red needles, yield: 1.6 g. mp: 137~138ꢃ.
IR (KBr, cm-1): 3071 (Ar-H), 2958 (CH2), 2837 (CH3), 1328
(C=N), 1112 (CF3), 1090. 1H NMR (CDCl3, ppm) ꢄ8.70 (d, 2 H,
J = 8.8 Hz), 7.84 (d, 2 H, J = 8.8 Hz), 7.38 (d, 2 H, J = 8.8 Hz),
6.88 (d, 2 H, J = 8.8 Hz), 4.65 (s, 2 H), 3.78(s, 3 H). MS (m/z,
%): 346 (M+, 5), 317 (10), 171 (60), 145 (45), 97 (60), 72 (80).
C17H13N4F3O (346.31): C, 58.96; H, 3.78; N, 16.18. Found: C,
58.78; H, 3.53; N, 15.94.
3-[4-(Trifluoromethyl)phenyl]-6-(4-chlorobenzyl)-1,2,4,5-
tetreazine (10f). Red needles, yield: 2.2 g. mp: 140~142 ꢃ. IR
(KBr, cm-1): 3071 (Ar-H), 2950 (CH2), 1326 (C=N), 1113 (CF3),
1
1090, 709 (Ar-Cl). H NMR (DMSO-d6) ꢄ8.66 (d, 2 H, J = 8.8
Hz), 8.05 (d, 2 H, J = 8.8 Hz), 7.47 (d, 2 H, J = 8.8 Hz), 7.42 (d,
2 H, J = 8.8 Hz), 4.73 (s, 2 H). MS (m/z, %): 350 (M+, 5), 171
(70), 151 (37), 116 (100), 102 (8), 89 (20), 75 (15).
C16H10N4F3Cl (350.73): C, 54.79; H, 2.87; N, 15.97.Found: C,
54.87; H, 2.77; N, 15.86.
3-(4-Chlorophenyl)-6-benzyl-1,2,4,5-tetreazine (10g). Red
flat crystal, yield: 1.8 g. mp: 157~158ꢃ. IR (KBr, cm-1): 3087
(Ar-H), 2924 (CH2), 1384 (C=N), 1091, 737 (Ar-Cl). 1H NMR
(CDCl3, ppm) ꢄ8.54 (d, 2 H, J = 8.8 Hz), 7.57 (d, 2 H, J = 8.8
Hz), 7.47 (d, 2 H, J = 8.0 Hz), 7.27-7.37 (m, 3 H, Ar-H), 4.70 (s,
2 H). MS (m/z, %): 282 (M+, 12), 137 (100), 117 (98), 102 56),
90 (45), 75 (23). Anal. Calcd. for C15H11N4Cl (282.73): C, 63.72;
H, 3.92; N, 19.82. Found: C, 63.65; H, 3.84; N, 19.81.
riding, with C-H distances of 0.97(2)
Å
and with
Uiso(H)=1.2Ueq(C). Crystallographic parameters and agreement
factors are contained in Table 4. CCDC-634552, 621205,
642406 and 642405 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html
or
from
the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK [Fax: +44-1223/336-033; Email:
depoist@ccdc.cam.ac.uk] .
3-(4-Chlorophenyl)-6-(4-methoxybenzyl)-1,2,4,5-tetreazine
(10h). Red flat crystal, yield: 1.5 g. mp: 153~155ꢃ. IR (KBr,
cm-1): 3089 (Ar-H), 2930 (CH2), 2850 (CH3), 1388 (C=N), 1093,
715 (Ar-Cl). 1H NMR (CDCl3, ppm) ꢄ8.53 (d, 2 H, J = 8.8 Hz),
7.57 (d, 2 H, J = 8.8 Hz), 7.38 (d, 2 H, J = 8.4 Hz), 6.88 (d, 2 H,
J = 8.4 Hz), 4.64 (s, 2 H), 3.80 (s, 3 H). MS (m/z, %): 312 (M+,
17), 147 (98), 137 (100), 116 (8), 102 (35), 91 (5), 77 (23). Anal.
Calcd. for C16H13N4ClO (312.75): C, 61.44; H,4.19; N, 17.91.
Found: C, 61.14; H, 4.13; N, 17.55.
3-Phenyl-6-benzyl-1,2,4,5-tetreazine(10a). Red prism, yield:
2.1 g. mp: 112~113 ꢃ (110~111 ꢃ [14]). IR (KBr, cm-1): 3064
(Ar-H), 2926 (CH2), 1385 (C=N), 1089. 1H NMR (CDCl3, ppm)
ꢄ 8.57 (d, 2 H, J= 9.2 Hz), 7.58-7.66 (m, 3 H, Ar-H), 7.48 (d, 2
H, J = 8.0 Hz), 7.29-7.38 (m, 3 H, Ar-H), 4.62 (s, 2 H), 3.78 (s, 3
H). MS (m/z, %): 248 (M+, 10), 117 (90), 103 (98), 90 (36), 76
(42).
3-(4-Chlorophenyl)-6-(4-chlorobenzyl)-1,2,4,5-tetreazine
(10i). Red flat crystal, yield: 2.4 g.mp: 181~183ꢃ. IR (KBr,
cm-1): 3089 (Ar-H), 2937 (CH2), 1389 (C=N), 1094, 725 (Ar-
Cl). 1H NMR (CDCl3, ppm): ꢄ8.52 (d, 2 H, J = 8.8 Hz), 7.56 (d,
2 H, J = 8.8 Hz), 7.39 (d, 2 H, J = 8.4 Hz), 7.31 (d, 2 H, J = 8.4
Hz), 4.65(s, 2 H). MS (m/z, %): 316 (M+, 10), 151 (17), 137
(100), 116 (65), 102 (33), 89 (15),75 (15). Anal. Calcd. for
C15H10N4Cl2 (317.17): C, 56.50; H, 3.18; N,17.66. Found: C,
56.53; H, 3.22; N, 17.47.
3-Phenyl-6-(4-methoxybenzyl)-1,2,4,5-tetreazine (10b).
Red prism, yield: 1.5 g. mp: 120~123 ꢃ. IR (KBr, cm-1): 3066
1
(Ar-H), 2937 (CH2), 2837 (CH3), 1381(C=N), 1247, 1089. H
NMR (CDCl3, ppm) ꢄ8.57 (d,2 H, J = 6.8 Hz), 7.55-7.61 (m, 3
H, Ar-H), 7.37 (d, 2 H, J = 8.4 Hz), 6.87 (d, 2 H, J = 8.4Hz),
4.62 (s, 2 H), 3.78 (s, 3 H). MS (m/z, %): 278 (M+, 17), 238
(92), 147 (80), 135 (67), 121 (25), 103 (100), 91 (7), 77 (57).
Anal. Calcd. for C16H14N4O (278.31): C, 69.05; H, 5.07; N,
20.13. Found: C, 68.78; H, 5.13; N, 20.06.
Acknowledgement. We are indebted to the National Natural
Science Foundation of China (grant No. 20272053) for financial
support.
3-Phenyl-6-(4-chlorobenzyl)-1,2,4,5-tetreazine (10c). Red
prism, yield: 2.8 g. mp: 143~145ꢃ. IR (KBr, cm-1): 3054 (Ar-
H), 2937 (CH2), 1384 (C=N), 1088, 740 (Ar-Cl). 1H NMR

1750
W. –X. Hu and F. Xu
Vol 45
Sauer, J.; Jagerovic, N.; Elguero, J.; Motherwell, S. Helv. Chim.
Acta 2003, 86, 1205. [c] Gao, H. -X; Wang, R. -H.; Twamley, B.;
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[10] See for examples: [a] Lang Jr., S. A.; Johnson, B. D.;
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H. Heterocycl. Commun. 1998, 4(4), 301.
[11] Frabzen, H.; Kraft, F. J. Prakt. Chem. 1911, 84, 122.
[12] See for examples: [a] Prout, K. C.; Orley, T. M.; Tickle, I.
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Kubo, K.; Mori, A.; Ujiie, S.; Tschierske, C. J. Oleo Sci. 2005, 54,
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Crystallogr., Sect. E: Struct. Rep. Online 2005, E61, o3041. [d]
Kubo, K.; Matsumoto, T.; Katahira, K.; Mori, A. Acta Crystallogr.,
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