Transformations of 1,2,4-triazines in reactions with nucleophiles: V. SNH and ipso-substitution in the synthesis and transformations of 5-cyano-1,2,4-triazines

Article abstract of DOI:10.1023/A:1019631610505

The scope of functionalization of 1,2,4-triazines can be considerably extended via successive nucleophilic substitution of hydrogen (S _N^H) and ipso-substitution. A convenient procedure has been developed for direct cyanation of 1,2,4-triazine 4-oxides with acetone cyanohydrin in the presence of triethylamine. The cyano group in the resulting 5-cyano-1,2,4-triazines is readily replaced by reactions with various aliphatic alcohols and amines.

Full text of DOI:10.1023/A:1019631610505

Russian Journal of Organic Chemistry, Vol. 38, No. 5, 2002, pp. 744 750. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 5, 2002,
pp. 780 786.
Original Russian Text Copyright
2002 by D. Kozhevnikov, V. Kozhevnikov, Kovalev, Rusinov, Chupakhin, Aleksandrov.
Transformations of 1,2,4-Triazines in Reactions
with Nucleophiles: V.* SNH and ipso-Substitution in the Synthesis
and Transformations of 5-Cyano-1,2,4-triazines**
D. N. Kozhevnikov, V. N. Kozhevnikov, I. S. Kovalev, V. L. Rusinov,
O. N. Chupakhin, and G. G. Aleksandrov
Ural State Technical University, ul. Mira 19, Yekaterinburg, 620002 Russia
Received September 10, 2000
Abstract The scope of functionalization of 1,2,4-triazines can be considerably extended via successive
nucleophilic substitution of hydrogen (SHN) and ipso-substitution. A convenient procedure has been developed
for direct cyanation of 1,2,4-triazine 4-oxides with acetone cyanohydrin in the presence of triethylamine.
The cyano group in the resulting 5-cyano-1,2,4-triazines is readily replaced by reactions with various aliphatic
alcohols and amines.
The cyano group in 5-cyano-1,2,4-triazines is
readily replaced by the corresponding groups in reac-
tions with CH acids, organomagnesium compounds,
alcohols, and water; therefore, these reactions can be
used for functionalization of 1,2,4-triazines [2 4].
However, their wide application is limited because of
difficulties in the preparation of initial cyano-1,2,4-
triazines. The known procedures for cyanation of
1,2,4-triazines include a number of intermediate
stages: introduction of a halogen atom and subsequent
halogen replacement by cyano group [2] or hydroxy-
iminomethyl group and dehydration of the latter [4].
Only one example of direct cyanation in the 1,2,4-tri-
azine series was reported: the formation of 5-cyano-
6-methyl-3-phenyl-1,2,4-triazine by the action of dry
hydrogen cyanide on 6-methyl-3-phenyl-1,2,4-triazine
[5]. We briefly reported in [6] on a method which
allowed us to smoothly accomplish nucleophilic sub-
stitution of hydrogen by cyano group in 6-phenyl-
1,2,4-triazine 4-oxides with generation of CN ion
in situ.
By treatment of substituted 1,2,4-triazine 4-oxides
Ia Ig with acetone cyanohydrin in the presence of
triethylamine we obtained in high yields (in most
cases, nearly quantitative) the corresponding 5-cyano-
1,2,4-triazines IIa IIg (Scheme 1). The reaction
occurs exclusively at position 5 of the 1,2,4-triazine
ring even when the substrate has no substituent at C3
and is accompanied by loss of the N-oxide moiety.
The structure of 5-cyano-1,2,4-triazines II was
proved by NMR spectroscopy and mass spectrometry
(Table 2). The physical parameters of 5-cyano-3,6-di-
phenyl-1,2,4-triazine (IIc) coincided with those
reported in [2]. The IR spectrum of IId contained no
absorption band typical of C N stretching vibrations
1
1
(2200 2260 cm ), but a strong band at 1400 cm
was present. An analogous pattern was observed in [3]
for compound IIc. Therefore, we performed X-ray
analysis of 5-cyano-3,6-diphenyl-1,2,4-triazine (IIc).
The central triazine ring plane in molecule IIc form
The present communication describes the results
of our studies which extend the scope of the reactions
of 1,2,4-triazine 4-oxides with cyanide ion and its
synthetic equivalents; also, the reactivity and other
properties of 5-cyano-1,2,4-triazines are reported.
____________
*
For communication IV, see [1].
**
This study was financially supported by the Russian Founda-
Molecular structure of 5-cyano-3,6-diphenyl-1,2,4-triazine
tion for Basic Research (project no. 99-03-32923).
(IIc) according to the X-ray diffraction data.
1070-4280/02/3805-0744$27.00 2002 MAIK Nauka/Interperiodica

TRANSFORMATIONS OF 1,2,4-TRIAZINES IN REACTIONS WITH NUCLEOPHILES: V.
745
Scheme 1.
I XI, R = H, R = Ph (a); R = Me, R = Ph (b); R = R = Ph (c); R = 4-ClC6H4, R = Ph (d); R = 4-O2NC6H4, R = Ph (e); R = Ph,
R = 4-ClC6H4 (f); R = R = 4-ClC6H4 (g); III, Alk = Me; IV, Alk = Et; V, Alk = i-Pr; VI, Alk = Bu; VII, Alk = HOCH2CH2.
dihedral angles of 11.1 and 48.2 , respectively, with
the benzene rings in positions 3 and 6. The C N
bond is shorter (1.129 ) than the standard one
(1.157 ), presumably due to conjugation with the
-deficient 1,2,4-triazine ring (Tables 3, 4; see figure).
This fact is likely to be responsible for the observed
IR spectral patterns of 5-cyano-1,2,4-triazines II.
The reaction leading to 5-cyano-1,2,4-triazines II
is an SHN process [7] which can be described by
a two-step mechanism. In the first stage cyanide ion
generated in situ from acetone cyanohydrin adds at
C5 of the 1,2,4-triazine ring to form H-adduct A,
as in the reactions of 1,2,4-triazine 4-oxides with
aromatic C-nucleophiles [8]. The second stage is auto-
aromatization through elimination of water molecule.
Obviously, the dehydration process follows E1cb-like
mechanism. Electron-acceptor cyano group at C5
increases acidity of the 5-H proton, and basic medium
facilitates its abstraction. The subsequent elimination
of hydroxide ion from anion B gives aromatic prod-
ucts II (Scheme 2).
in the reaction of I with potassium cyanide is forma-
tion of 5-cyano-1,2,4-triazines II, but the subsequent
fast replacement of the cyano group by the alcohol
residue yields 5-alkoxy derivatives III and IV. Thus,
treatment of preliminarily prepared 5-cyano-1,2,4-tri-
azines II with methanol or ethanol in the presence
of a catalytic amount of KOH afforded the same
5-alkoxy-1,2,4-triazines III and IV (Scheme 1).
This finding led us to develop a procedure for
synthesizing 5-alkoxy-1,2,4-triazines, which may be
illustrated using 5-cyano-3,6-diphenyl-1,2,4-triazine
(IIc) as an example. Heating of compound IIc in
boiling 2-propanol or butanol containing a catalytic
amount of the corresponding sodium alkoxide resulted
in replacement of the cyano group and formation of
5-isopropoxy- and 5-butoxy-3,6-diphenyl-1,2,4-tri-
azines Vc and VIc. The spectral parameters of alkoxy-
1,2,4-triazines IIIc, IIIf, IVa IVc, IVf, Vc, and VIc
(Table 2) are consistent with their structure. The data
for 5-methoxy-6-phenyl-1,2,4-triazine (IIIa) and
5-ethoxy-3,6-diphenyl-1,2,4-triazine (IVc) coincided
with those given in [9, 2].
We also made an attempt to use potassium cyanide
in methanol or ethanol as cyanating agent. However,
the reactions with 1,2,4-triazine 4-oxides Ia Id and If
Analogous reactions occur with polyatomic al-
cohols. By heating of 5-cyano-3,6-diphenyl-1,2,4-tri-
led to formation of the corresponding 5-methoxy- or azine (IIc) in a 1:1 mixture of DMF with ethylene
5-ethoxy-1,2,4-triazines IIIc, IIIf, IVa IVc, and IVf
in high yields (Scheme 1). Obviously, the first stage
glycol we obtained 5-(2-hydroxyethoxy)-3,6-diphenyl-
1,2,4-triazine (VIIc) (Scheme 1; Tables 1, 2). Under
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 5 2002

746
KOZHEVNIKOV et al.
Table 1. Yields, melting points, and elemental analyses of compounds II XXI
Found, %
Calculated, %
H
Comp.
no.
Yield,
%
mp,
C
Formula
C
H
N
C
N
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIIc
IIIf
IVa
IVb
IVc
IVf
Vc
VIc
VIIc
Xc
75
80
95
97
100
95
100
85
95
77
80
76
90
79
93
95
81
80
85
92
93
90
91
52
60
95
91
94
86
88
163 [2]
178
65.88
67.45
74.30
65.74
63.30
65.46
58.80
73.06
64.48
65.72
66.85
73.47
65.33
74.15
67.32
69.45
72.05
72.48
73.64
71.99
75.40
76.02
71.61
78.19
68.38
70.01
70.45
71.29
3.39
4.22
3.98
3.01
3.12
3.33
2.38
5.09
4.18
5.67
6.20
5.61
4.61
5.99
5.48
5.07
4.61
4.96
5.80
6.00
5.87
6.44
5.82
5.28
5.59
5.50
6.00
6.11
30.69
28.46
21.56
19.23
22.95
19.01
17.01
15.89
14.02
20.79
19.60
15.24
13.41
14.39
12.18
14.09
16.92
22.39
20.11
22.23
18.68
17.54
17.69
16.66
16.93
19.09
18.02
17.42
C10H6N4
C11H8N4
C16H10N4
65.93
67.34
74.41
65.65
63.37
65.65
58.74
72.99
64.54
65.66
66.96
73.63
65.49
74.21
67.16
69.61
72.28
72.56
73.89
71.90
75.47
75.92
71.68
78.08
68.25
69.85
70.57
71.23
3.32
4.11
3.90
3.10
2.99
3.20
2.46
4.98
4.06
5.51
6.09
5.45
4.53
5.88
5.34
5.15
4.45
4.87
5.84
6.03
6.00
6.37
5.70
5.36
5.43
5.52
5.92
6.29
30.75
28.55
21.69
19.14
23.09
19.14
17.12
15.96
14.11
20.88
19.52
15.15
13.48
14.42
12.37
14.33
16.86
22.57
20.27
22.06
18.53
17.71
17.60
16.56
16.76
19.16
18.29
17.49
C16H9ClN4
C16H9N5O2
C16H9ClN4
C16H8Cl2N4
C16H13N3O
C16H12ClN3O
C11H11N3O
C12H13N3O
C17H15N3O
C17H14ClN3O
C18H17N3O
C19H18ClN3O
C17H15N3O2
C15N11N3O
C15H12N4
C17H16N4
C19H19N5
C19H18N4
C20H20N4
C19H18N4O
C22H18N4
C19H18N4O2
C17H16N4O
C18H18N4O
C19H20N4O
174
164
182
117 [9]
143
82
74
103 [2]
155
101
130
129
273 [10]
218 [11]
155
XIc
XIIc
XIIIc
XIVc
XVc
XVIc
XVIIc
XVIIIc
XIXc
XXc
XXIc
154
140
139
163
145
118
141
170
60
the same conditions, the reaction of IIc with glycerol
gave an inseparable mixture of two isomers, 5-(2,3-di-
hydroxy-1-propoxy)- and 5-(1,3-dihydroxy-2-prop-
oxy)-3,6-diphenyl-1,2,4-triazines VIIIc and IXc
multiplet, nonequivalent protons of the -methylene
group appear as one-proton doublets of doublets (2J =
3
2
3
11, J = 6 Hz and J = 11, J = 4 Hz, respectively),
the -OH group gives a doublet with 3J = 5.5 Hz), and
signal from the -hydroxy proton is a triplet with
3J = 5.5 Hz. This spectral pattern suggests that sub-
stitution of the cyano group occurs as a result of
nucleophilic attack by the primary hydroxy group of
1
(Scheme 3), which was analyzed by H NMR spec-
troscopy. The -methylene group in the glycerol frag-
ment of VIIIc gives rise to a two-proton doublet of
doublets (3J = 5.5 Hz), the CH signal is a one-proton
Scheme 3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 5 2002

TRANSFORMATIONS OF 1,2,4-TRIAZINES IN REACTIONS WITH NUCLEOPHILES: V.
747
Table. 2 1H NMR spectra of compounds II IX and XI XXI in DMSO-d6
Chemical shifts , ppm (J, Hz)
X, OR R, R
Chemical shifts , ppm (J, Hz)
X, OR R, R
Comp.
no.
Comp.
no.
3
IIa
IIb
IIc
7.6 m (2H), 8.0 m (3H), VIIIc
10.09 s (3-H)
2.93 s (3H), 7.6 m (2H),
8.0 m (3H)
11, J = 6), 4.75 d.d
(1H, J2 = 11, 3J =
3
4), 4.80 d (1H, J =
5.5, OH), 5.09 d
(1H, J = 5.5, OH)
3
7.6 7.7 m (6H), 8.0 8.1 m
(2H), 8.5 m (2H)
7.50 m (3H), 7.65 m (2H),
8.09 m (4H)
7.7 m (3H), 8.2 m (2H), XIc
8.45 m (2H), 8.80 m (2H)
IXc
3.80 m (4H), 4.9 t 7.6 m (6H), 8.1 m (2H),
(2H, J = 5.5, OH); 8.5 m (2H)
5.65 m (1H)
3
IId
IIe
7.4 br.s (2H, NH2)
7.6 m (6H), 7.75 m (2H),
8.42 m (2H)
IIf
7.68 m (3H), 7.80 m (2H), XIIc
8.09 m (2H), 8.50 m (2H)
2.94 s (6H)
7.5 7.7 m (8H), 8.41 m
(2H)
IIg
IIIc
IIIf
IVa
IVb
IVc
IVf
Vc
7.56 m (2H), 7.63 m (2H), XIIIc 2.69 m (2H), 3.40 m 7.55 m (6H), 7.78 m (2H),
8.09 m (2H), 8.53 m (2H)
7.6 m (6H), 8.1 m (2H), XIVc
8.5 m (2H)
(2H)
8.41 m (2H)
4.17 s (3H)
4.15 s (3H)
1.81 m (4H), 3.20 m 7.5 m (8H), 8.45 m (2H)
(4H)
7.6 m (5H), 8.1 m (2H), XVc
8.5 m (2H)
1.52 m (6H), 3.44 m 7.60 m (6H), 7.77 m (2H),
(4H)
8.42 m (2H)
1.40 t (3H, 3J = 7), 7.4 8.1 m (5H), 9.18 s XVIc
3.46 m (4H), 3.61 m 7.60 m (6H), 7.78 m (2H),
3
4.56 q (2H, J = 7)
(3-H)
(4H)
8.42 m (2H)
1.38 t (3H, 3J = 7), 2.66 s (3H), 7.4 8.1 m XVIIc 4.69 d (2H, 3J = 6), 7.55 m (6H), 7.75 m (2H),
3
4.52 q (2H, J = 7)
(5H)
7.2 7.5
m
(5H), 8.38 m (2H)
1.46 t (3H, 3J = 7), 7.4 8.6 m (10H)
8.07 br.t (1H, 3J =
3
4.68 q (2H, J = 7)
6, NH)
1.45 t (3H, 3J = 7), 7.6 m (5H), 8.1 m (2H), XVIIIc 1.20 t (3H, 3J = 7), 7.55 m (6H), 7.72 m (2H),
3
3
4.62 q (2H, J = 7)
1.31 d (6H, 3J = 6), 7.6 m (6H), 8.1 m (2H),
5.70 m (1H) 8.5 m (2H)
8.5 m (2H)
4.16 q (2H, J = 7), 8.38 m (2H)
3
4.20 d (2H, J = 6),
7.78 br.t (1H, 3J =
3
VIc
0.96 t (3H, J = 7.5), 7.6 m (6H), 8.1 m (2H),
1.80 m (2H), 1.83 m 8.5 m (2H)
(2H), 4.62 t (2H,
6, NH)
XIXc
XXc
3.61 m (4H), 7.22 br.t 7.55 m (6H), 7.78 m (2H),
3
(1H, J = 5, OH)
8.40 m (2H)
3J = 6.5)
2.86 s (3H), 3.61 m 7.4 7.7 m (8H), 8.40 m
(4H), 4.72 br.t (1H, (2H)
VIIc
3.88 m (2H), 4.69 t 7.6 m (6H), 8.15 m (2H),
(2H, 3J = 5.5), 5.0 8.5 m (2H)
br.t (1H, 3J = 6, OH)
3J = 5, OH)
XXIc
2.24 s (6H), 2.75 t 7.6 m (6H), 8.1 m (2H),
VIIIc 3.55 d.d (2H, 3J = 7.6 m (6H), 8.1 m (2H),
(2H, 3J
=
5.5), 8.5 m (2H)
5.5), 4.00 m (1H), 8.5 m (2H)
4.71 t (2H, 3J = 5.5)
4.59 d.d (1H, J2
=
glycerol molecule. The symmetric glycerol moiety in
isomer IXc shows in the H NMR spectrum a four-
proton multiplet from two CH2 groups, one-proton
multiplet from the CH group, and two-proton triplet
(3J = 5.5 Hz) from the hydroxy groups. These data
unambiguously indicate formation of the ether bond
in IXc through the secondary -hydroxy group of
glycerol (Table 2). As follows from the signal intens-
ities, the isomer ratio VIIIc:IXc is 10:1. Taking into
account that glycerol molecule contains two primary
and one secondary hydroxy groups, the rate of sub-
stitution of the 5-cyano group in IIc by the secondary
hydroxy group is lower by a factor of 5 than the rate
of replacement by primary hydroxy group.
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 5 2002

748
KOZHEVNIKOV et al.
Scheme 4.
XII, X = NMe2; XIII, X = 1-piperazinyl; XIV, X = 1-pyrrolidinyl; XV, X = piperidino; XVI, X = morpholino;
XVII, X = PhCH2NH; XVIII, X = EtOCOCH2NH.
Scheme 5.
XIX, R = H; XX, R = Me.
Reaction of 5-cyano-1,2,4-triazine IIc with water
(2-aminoethanol or 2-methylaminoethanol) yield
5-(2-hydroxyethylamino)- and 5-[2-hydroxyethyl-
(methyl)amino]-3,6-diphenyl-1,2,4-triazines XIXc and
XXc (Scheme 5). 2-Dimethylaminoethanol having
a tertiary amino group reacts with compound IIc to
give 5-(2-dimethylaminoethoxy)-3,6-diphenyl-1,2,4-
triazine (XXIc) (Scheme 5). Aromatic amines failed
to react with 5-cyano-3,6-diphenyl-1,2,4-triazine (IIc)
under the same conditions.
Thus, nucleophilic substitution of hydrogen (SHN)
by cyano group in the 1,2,4-triazine series, followed
by replacement of the cyano group, provides a con-
venient method for preparation of a wide range of
functionalized 1,2,4-triazines.
as O-nucleophile in basic or acidic medium leads to
formation of 3,6-diphenyl-1,2,4-triazin-5(2H)-one
(Xc) in 95% yield (Scheme 1). No products of
hydrolysis of the cyano group in IIc to amide or
carboxy were detected. The structure of product Xc
1
was established on the basis of the H NMR data [10]
(Table 2). Unlike aliphatic alcohols, phenols do not
replace the 5-cyano group in 1,2,4-triazines, while
the reactions with phenoxides resulted in tarring.
No reaction with alkanethiols and benzenethiol was
observed.
On the other hand, ammonia and aliphatic or cyclic
amines readily replace the cyano group in IIc under
mild conditions. By passing gaseous ammonia through
a solution of IIc in DMF at room temperature we
obtained 65% of 5-amino-3,6-diphenyl-1,2,4-triazine
(XIc) whose properties were consistent with the pro-
posed structure and published data [11] (Tables 1, 2).
Treatment of 5-cyano-1,2,4-triazine IIc with dimethyl-
amine, piperazine, pyrrolidine, piperidine, morpholine,
and benzylamine gave the corresponding N-substituted
5-amino-1,2,4-triazines XIIc XVIIc via replacement
of the cyano group (Scheme 4). Amino acid esters
also act as N-nucleophiles toward 5-cyano-1,2,4-tri-
azines: The reaction of 5-cyano-3,6-diphenyl-1,2,4-tri-
azine (IIc) with excess glycine ethyl ester resulted
in formation of 5-ethoxycarbonylmethylamino-3,6-di-
phenyl-1,2,4-triazine (XVIIIc) in a good yield.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
WM-250 spectrometer at 250 MHz relative to TMS
as internal reference. The progress of reactions was
monitored, and the purity of products was checked,
by TLC on Silufol UV-254 plates using ethyl acetate
as eluent; spots were visualized with UV light.
X-Ray analysis of a single crystal of compound IIc
was performed on an Enraf Nonius CAD-4 automatic
diffractometer ( MoK , graphite monochromator,
-scanning, 2
54 ). Monoclinic crystals with the
max
following unit cell parameters: a = 13.595(4), b =
6.655(2), c = 14.563(7)
;
= 104.86(3) ; Z = 4,
1
Amino alcohols are capable of reacting with
5-cyano-1,2,4-triazine IIc through both nitrogen and
oxygen atoms. We have found that reactions with
alcohols having a primary or secondary amino group
V = 1273.6(9) 3; d = 1.347 g/cm3; = 0.084 cm ;
space group P21/n. The structure was solved by the
direct method and was refined by the least-squares
procedure in anisotropic approximation (isotropic for
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 5 2002

TRANSFORMATIONS OF 1,2,4-TRIAZINES IN REACTIONS WITH NUCLEOPHILES: V.
749
hydrogen atoms) using SHELX-86 and SHELX-93
programs. The final divergence factors were R = 0.051
and wR2 = 0.126 for 2181 reflections with F2 > 3 (I);
GOF = 1.081.
Table 3. Coordinates of non-hydrogen atoms and their
temperature factors on the molecule of 5-cyano-3,6-di-
phenyl-1,2,4-triazine (IIc)
2
Atom
x
y
z
Uiso/Ueq,
Initial substituted 1,2,4-triazine 4-oxides Ia Ig
were synthesized by the procedure described in [12].
N1
N2
N3
N4
C3
C5
C6
C7
C8
C9
0.5736(1) 0.7800(2) 0.5163(1) 0.0477(4)
0.5891(1) 0.7817(2) 0.6103(1) 0.0480(4)
0.9070(1) 0.8141(3) 0.4701(1) 0.0645(5)
0.7669(1) 0.8227(2) 0.6317(1) 0.0380(3)
0.6840(1) 0.8082(2) 0.6648(1) 0.0369(4)
0.7499(1) 0.8180(2) 0.5384(1) 0.0373(4)
0.6522(1) 0.8010(2) 0.4780(1) 0.0401(4)
0.6312(1) 0.7969(2) 0.3732(1) 0.0430(4)
0.6730(1) 0.9390(3) 0.3252(1) 0.0543(4)
0.6538(2) 0.9325(3) 0.2276(1) 0.0641(5)
5-Cyano-1,2,4-triazines IIa IIg (general proce-
dure). Acetone cyanohydrin, 1 ml (11 mmol), and
triethylamine, 0.3 ml (2 mmol), were added to a sus-
pension of 5 mmol of 1,2,4-triazine 4-oxide Ia Ig in
50 ml of methylene chloride. The mixture was heated
for 20 min under reflux and evaporated, and the
residue was recrystallized from chloroform.
5-Methoxy- and 5-ethoxy-1,2,4-triazines IIIa,
IIIf, IVa IVc, and IVf. 5-Cyano-1,2,4-triazine II,
2 mmol, was added to a solution of 10 mg of KOH
in 5 ml of methanol or ethanol, and the mixture was
refluxed for 10 min. It was then diluted with water,
and the precipitate was filtered off and recrystallized
from methanol or ethanol.
3,6-Diphenyl-(2-propoxy)-1,2,4-triazine (Vc) and
5-butoxy-3,6-diphenyl-1,2,4-triazine (VIc) (general
procedure). Metallic sodium, 50 mg, was dissolved
in 4 ml of 2-propanol or 1-butanol, and 774 mg
(3 mmol) of 5-cyano-3,6-diphenyl-1,2,4-triazine (IIc)
was added. The mixture was heated for 10 min under
reflux and cooled, and the precipitate was filtered off.
C10 0.5933(1) 0.7826(3) 0.1776(1) 0.0647(5)
C11 0.5520(2) 0.6419(3) 0.2247(1) 0.0666(5)
C12 0.5696(1) 0.6474(3) 0.3218(1) 0.0544(4)
C13 0.6982(1) 0.8156(2) 0.7687(1) 0.0386(4)
C14 0.6152(1) 0.8337(2) 0.8072(1) 0.0461(4)
C15 0.6294(1) 0.8402(2) 0.9044(1) 0.0516(4)
C16 0.7263(1) 0.8294(2) 0.9637(1) 0.0483(4)
C17 0.8090(1) 0.8112(2) 0.9266(1) 0.0460(4)
C18 0.7956(1) 0.8047(2) 0.8291(1) 0.0415(4)
C19 0.8388(1) 0.8194(2) 0.5009(1) 0.0439(4)
5-(2-Hydroxyethoxy)-3,6-diphenyl-1,2,4-triazine
(VIIc). A solution of 774 mg (3 mmol) of 5-cyano-
3,6-diphenyl-1,2,4-triazine (IIc) in a mixture of 1 ml
of ethylene glycol and 2 ml of anhydrous DMF was
stirred for 3 h at 80 C. The mixture was diluted with
water, and the precipitate was filtered off and recrys-
tallized from 30% ethanol.
5-(2,3-Dihydroxy-1-propoxy)-3,6-diphenyl-1,2,4-
triazine (VIIIc) and 5-(1,3-dihydroxy-2-propoxy)-
3,6-diphenyl-1,2,4-triazine (IXc). A solution of
774 mg (3 mmol) of 5-cyano-3,6-diphenyl-1,2,4-tri-
azine (IIc) in a mixture of 1 ml of glycerol and 2 ml
of anhydrous DMF was stirred for 3 h at 80 C. The
mixture was diluted with water, and the precipitate
was filtered off and recrystallized from 30% ethanol.
An inseparable mixture of isomers VIIIc and IXc
was obtained. Overall yield 820 mg (85%).
Table 4. Bond lengths d in the molecule of 5-cyano-3,6-
diphenyl-1,2,4-triazine (IIc)
Bond
d,
Bond
d,
N1 N2
N2 C3
1.331(2)
1.341(2)
1.319(2)
1.476(2)
1.449(2)
1.382(2)
1.379(2)
1.364(3)
1.388(2)
1.379(2)
1.372(2)
N1 C6
1.333(2)
1.129(2)
1.338(2)
1.397(2)
1.479(2)
1.389(2)
1.376(3)
1.372(2)
1.391(2)
1.380(3)
1.386(2)
N3 C19
N4 C3
N4 C5
C3 C13
C5 C19
C7 C8
C5 C6
C6 C7
C7 C12
C9 C10
C11 C12
C13 C18
C15 C16
C17 C18
C8 C9
C10 C11
C13 C14
C14 C15
C16 C17
3,6-Diphenyl-1,2,4-triazin-5(2H)-one (Xc).
a. 5-Cyano-3,6-diphenyl-1,2,4-triazine (IIc), 258 mg
(1 mmol), was heated for 30 min under reflux in
aqueous DMF in the presence of triethylamine. The
mixture was acidified with acetic acid and diluted
with water, and the precipitate was filtered off.
0.5 ml of concentrated hydrochloric acid was refluxed
for 10 min. It was then cooled, and the precipitate
was filtered off.
5-Amino-3,6-diphenyl-1,2,4-triazine (XIc). Com-
pound IIc, 258 mg (1 mmol), was dissolved in 3 ml
of DMF, and dry gaseous ammonia was passed
through the solution. After 30 min, the solution was
b. A mixture of 258 mg (1 mmol) of 5-cyano-3,6-
diphenyl-1,2,4-triazine (IIc), 2 ml of acetic acid, and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 5 2002

750
KOZHEVNIKOV et al.
diluted with water, and the precipitate was recrystal-
lized from 2-propanol.
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diphenyl-1,2,4-triazine, 258 mg (1 mmol), was dis-
solved in excess amine. The mixture was kept for 24 h
at 20 C and diluted with water, and the precipitate
was filtered off and recrystallized from 2-propanol.
5-Benzylamino-3,6-diphenyl-1,2,4-triazine
(XVIIc). A mixture of 258 mg (1 mmol) of 5-cyano-
3,6-diphenyl-1,2,4-triazine (IIc) and 1 ml of benzyl-
amine was heated to the boiling point and was left
to stand for 2 h at room temperature. The solution was
evaporated under reduced pressure, and the residue
was treated with 4 ml of cold ethanol and recrystal-
lized from ethanol.
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5-(Ethoxycarbonylmethylamino)-3,6-diphenyl-
1,2,4-triazine (XVIIIc). A solution of 258 mg
(1 mmol) of 5-cyano-3,6-diphenyl-1,2,4-triazine (IIc)
in 1.5 ml of a 30% solution of glycine ethyl ester
in DMF was refluxed for 15 min. The mixture was
diluted with 10 ml of water, the liquid phase was
separated by decanting, and the residue was recrystal-
lized from cyclohexane.
9. Daunis, J. and Jacquier, R., Tetrahedron, 1974,
no. 17, pp. 3171 3175.
5-(2-Hydroxyethylamino)-3,6-diphenyl-1,2,4-tri-
azine (XIXc), 5-[2-hydroxyethyl(methyl)amino]-3,6-
diphenyl-1,2,4-triazine (XXc), and 5-(2-dimethyl-
aminoethoxy)-3,6-diphenyl-1,2,4-triazine (XXIc)
(general procedure). A solution of 258 mg (1 mmol)
of 5-cyano-3,6-diphenyl-1,2,4-triazine (IIc) in excess
aminoethanol was kept for 24 h at 20 C. It was then
diluted with water, and the precipitate was filtered off.
10. Neunhoeffer, H. and Bohnisch, V., Justus Liebigs
Ann. Chem., 1976, no. 1, p. 153.
11. Fusco, R. and Rossi, S., Tetrahedron, 1958, no. 3,
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12. Kozhevnikov, D.N., Kozhevnikov, V.N., Rusi-
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Klyuev, N.A., Russ. J. Org. Chem., 1998, vol. 34,
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