Synthesis of 4-amino-6-chloro-1,3,5-triazin-2(1H)-ones

Article abstract of DOI:10.1007/s11172-012-0015-8

Conditions for selective substitution for one chlorine atom in 2-(R,R-amino)-4,6-dichloro-1,3,5-triazines with a hydroxide ion were elaborated. Spectral and calculation methods showed that the products formed are in the lactam form, i.e., have the structure of 4-chloro-6-(R,R- amino)-1,3,5-triazin-2(1H)-ones.

Full text of DOI:10.1007/s11172-012-0015-8

Russian Chemical Bulletin, International Edition, Vol. 61, No. 1, pp. 99—112, January, 2012
99
Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀones
V. V. Bakharev,a A. A. Gidaspov,a V. E. Parfenov,a I. V. Ul´yankina,a A. V. Zavodskaya,a E. V. Selezneva,a
K. Yu. Suponitskii,b and A. B. Sheremetevc
aSamara State Technical University,
244 ul. Molodogvardeiskaya, 443100 Samara, Russian Federation.
Eꢀmail: knil@sstu.smr.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6471
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: sab@ioc.ac.ru
Conditions for selective substitution for one chlorine atom in 2ꢀ(R,R´ꢀamino)ꢀ4,6ꢀdichloroꢀ
1,3,5ꢀtriazines with a hydroxide ion were elaborated. Spectral and calculation methods showed
that the products formed are in the lactam form, i.e., have the structure of 4ꢀchloroꢀ6ꢀ(R,R´ꢀ
amino)ꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀones.
Key words: 1,3,5ꢀtriazines, 1,3,5ꢀtriazinones, lactimꢀlactam tautomerism, nucleophilic
substitution, hydrolysis, quantum chemical calculations.
1,3,5ꢀTriazine derivatives are widely used as herbiꢀ
cides,1—3 polymeric materials,4—7 pharmaceuticals,8—10
explosives,11—15 dyes,16,17 etc. A number of published reꢀ
views18—25 summarize various aspects of chemistry and
application of this very important class of heterocycles.
Among them, chloroꢀ1,3,5ꢀtriazine derivatives are studꢀ
ied the most, since they are widely used as intermediates
in the synthesis of more complex molecules.22—24
However, among a vast amount of publications on
1,3,5ꢀtriazines we found no works purposefully devoted
to the studies of preparation and structure of 2ꢀaminoꢀ
4ꢀchloroꢀ1,3,5ꢀtriazinones. Only several publications
describe selected examples of this type of comꢀ
pounds,10,17,26—30 whereas information on their structure
is virtually absent. It should be noted that aminochloroꢀ
1,3,5ꢀtriazinones are one of possible metabolites in deꢀ
composition of the triazine herbicides,2 that makes studꢀ
ies on their chemistry and structure very relevant.
The presence of a hydroxyl functional group on the
1,3,5ꢀtriazine ring suggests a possibility of the lactimꢀlacꢀ
tam tautomerism. For example, in the solid state such
derivatives are known to normally exist as 1,3,5ꢀtriazinoꢀ
nes, i.e., in the lactam form (cyanuric acid, ammeline,
ammelide, etc.).18—24 At the same time, the calculations31
in the gas phase for ammeline (4,6ꢀdiaminoꢀ1,3,5ꢀtriazinꢀ
2(1H)ꢀone) showed that the lactim form (i.e. 4,6ꢀdiaminoꢀ
2ꢀhydroxyꢀ1,3,5ꢀtriazine) is energetically more favorable.
By now, 2ꢀhydroxyꢀ4,6ꢀbis(trinitromethyl)ꢀ1,3,5ꢀtriazine
bound to the complex with a 1,4ꢀdioxane molecule is the
only experimentally confirmed (Xꢀray diffraction data)
hydroxyꢀ1,3,5ꢀtriazine.25,32
2ꢀHydroxy derivatives of 4ꢀ(R1R2ꢀamino)ꢀ6ꢀchloroꢀ
1,3,5ꢀtriazines can exist in several tautomeric forms
(Scheme 1) differing in placement of the hydrogen atom,
viz., a lactim (A), three lactam (B—D), and three zwitterꢀ
ionic structures (E—G).
The present work describes synthesis of a number of
secondary and tertiary (chloroꢀ1,3,5ꢀtriazine)amines conꢀ
taining a hydroxy(oxo) group as the third substituent on
the triazine ring, their structure was studied by spectroꢀ
scopic methods, as well as calculations performed enable
evaluation of the most probable placement of the proton in
the chain of tautomeric transformations given in Scheme 1.
Results and Discussion
Substitution for the chlorine atoms in 2,4,6ꢀtrichloroꢀ
1,3,5ꢀtriazine (1, cyanuric chloride) upon the action of
amines proceeds stepwise. In this case, an important role
in how many chlorine atoms undergo the nucleophilic
attack is played by the reaction temperature, amine basicꢀ
ity, steric factors, and the type of solvent used.18—20,33—37
The first chlorine atom is usually replaced at temperaꢀ
tures below 0 C, the second at 10—50 C, the third at
90—100 C.19,20 However, in the case when strongly basic
amines are used, substitution for two chlorine atoms in
cyanuric chloride 1 can take place already at 0 C.33—37
Acetone, dioxane, DMSO, as well as their aqueous soluꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 97—109, January, 2012.
1066ꢀ5285/12/6101ꢀ99 © 2012 Springer Science+Business Media, Inc.

100
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
Scheme 1
tions, are usually used as solvents; benzene, diethyl ether,
and some other solvents are used seldom. Excess amine
or various bases (tertiary amines, sodium (potassium)
carbonate or bicarbonate) are used as acceptors of hydroꢀ
gen chloride formed in the reaction.18—20,33—37
In the present work, 2ꢀaminoꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriꢀ
azines 2a—k were synthesized from cyanuric chloride 1 in
diethyl ether (Scheme 2). Use of 2—2.2 mol of amine per
1 mol of cyanuric chloride 1 and conducting the reaction
at temperatures below –10 C enabled us not only to seꢀ
lectively substitute for one chlorine atom, but also to inꢀ
crease the yields of dichloro derivatives 2a—k by 10—20%
as compared to those obtain earlier. The products isolated
were of such a good quality (according to the TLC data
and melting points, Table 1), that they did not require
additional purification and could be used in subsequent
reactions.
Hydrolysis of cyanuric chloride, monoꢀ and disubstiꢀ
tuted chloroꢀ1,3,5ꢀtriazines is very important reaction. In
some cases it is useful (for example, in deactivation of
triazine herbicides), and in a number of cases it is undesirꢀ
able, since leads to the side products, for example, in the
synthesis of 1,3,5ꢀtriazine derivatives in aqueous solvents
or even in the presence of atmospheric moisture. Hydrolyꢀ
sis of cyanuric chloride was studied the most thoroughly
in the works,44—46 the authors even succeeded in obtainꢀ
ing sodium salts of 4,6ꢀdichloroꢀ2ꢀhydroxyꢀ1,3,5ꢀtriazine
and 4ꢀchloroꢀ2ꢀhydroxyꢀ1,3,5ꢀtriazinꢀ6ꢀone, however,
failed in isolation of the hydroxy(oxo) derivatives themꢀ
selves. It should be noted that hydrolysis of chloroꢀ1,3,5ꢀ
triazines is facilitated by both bases and acids. It is known
that the reaction of cyanuric chloride and monosubstitutꢀ
ed dichloroꢀ1,3,5ꢀtriazines with water in the presence of
acids proceeds nonselectively and results in the formation
of cyanuric acid or monosubstituted 1,3,5ꢀtriazinediones,
respectively.19,20,46 There is the only example of selective
hydrolysis of one chlorine atom in 2ꢀanilinoꢀ4,6ꢀdichloꢀ
roꢀ1,3,5ꢀtriazine in the presence of acetic acid.47
At the same time, diamino(dialkoxy)ꢀsubstituted chloꢀ
roꢀ1,3,5ꢀtriazines are more resistant to hydrolysis. Thus,
2,4ꢀdiaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazine can be recrystallized
from boiling water without noticeable decomposition.19
Hydrolysis in the presence of bases is effected stepwise,
however this stepwise character is less pronounced than in
substitution with amines. In this case, depending on the
base used, its amount, and temperature, hydrolysis proꢀ
ceeds in different ways. It is known19 that action of 10%
aqueous sodium hydroxide on cyanuric chloride 1 results
Scheme 2

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
101
Table 1. Yields and physicochemical characteristics of compounds 2a—k, 4a—k, and 13a—i
Comꢀ
pound
NR1R2
Yield
(%)
M.p.*/C
Rf
Molecular
formula
Found
Calculated
Molecular
weight
(%)
(eluent)**
C
H
N
2a
2b
NH2
79 240 (with decomp.)
(235—236)38
0.22 (DCE)
0.55 (DCE)
C3H2Cl2N4
C5H6Cl2N4
21.79
21.84
1.18
1.22
34.03
33.96
164.98
193.04
NMe2
85
90
80
121—122
31.20
31.11
3.20
3.13
29.05
29.02
(123—124)28
2с
2d
NHPr
NHPri
67—69
(70—71)39
0.61 (DCE)
0.53 (DCE)
C6H8Cl2N4
C6H8Cl2N4
34.72
34.80
3.95
3.89
27.12
27.06
38—40
(37—40)39
34.85
34.80
3.96
3.89
27.00
27.06
207.06
2e
2f
81
87
Colorless oil
(oil)36
0.52 (DCE)
0.47 (DCE)
0.51 (DCE)
0.64 (DCE)
C9H12Cl2N4
C9H6Cl2N4
C10H8Cl2N4
C7H8Cl2N4
43.68
43.74
4.96
4.89
22.74
22.67
247.13
241.08
255.11
219.07
PhNH
132—134
(134—135)40
44.91
44.84
2.58
2.51
23.15
23.24
2g
2h
4ꢀMeC6H4NH 94
77
127—129
(129—131)40
47.02
47.08
3.24
3.16
21.98
21.96
93—95
38.43
38.38
3.77
3.68
25.59
25.57
2i
2j
87
88
72—74
(72—74)41
0.59 (DCE)
0.46 (DCE)
0.52 (DCE)
C8H10Cl2N4
C7H8Cl2N4O
41.16
41.22
4.34
4.32
23.96
24.04
233.10
235.07
152—153
(154—156)42
35.72
35.77
3.49
3.43
23.81
23.83
2k
4a
4b
AdNH
NH2
65
82
66
135—137
(136—137)43
C13H16Cl2N4
52.21
52.19
5.47
5.39
18.80
18.73
299.21
146.54
174.59
>350
0.21
C3H3ClN4O
C5H7ClN4O
24.50
24.59
2.13
2.06
38.14
38.23
(DCE—MeOH (2 : 1))
NMe2
196—198
0.50
34.48
34.40
4.10
4.04
32.01
32.09
(with decomp.) (DCE—MeOH (2 : 1))
(198)28
4c
4d
NHPr
NHPri
87
61
181—182
0.37
C6H9ClN4O
C6H9ClN4O
38.16
38.21
4.94
4.81
29.62
29.70
188.62
188.62
(DCE—MeOH (4 : 1))
169—170
0.44
38.29
38.21
4.78
4.81
29.77
29.70
(DCE—MeOH (4 : 1))
4e
77
93
270—273
0.38
C9H13ClN4O
47.22
47.27
5.63
5.73
24.52
24.50
228.68
(with decomp.) (DCE—MeOH (4 : 1))
4f
PhNH
292—293 0.53
(with decomp.) (DCE—MeOH (2 : 1))
C9H7ClN4O
C10H9ClN4O
48.65
48.55
3.11
3.17
25.24
25.17
222.64
236.66
4g
4ꢀMeC6H4NH 90
56
>350
0.54
50.72
50.75
3.83
3.75
23.76
23.67
(DCE—MeOH (2 : 1))
4h
245—246
0.62
C7H9ClN4O
41.88
41.91
4.45
4.52
28.01
27.93
200.63
(with decomp.) (DCE—MeOH (2 : 1))
(to be continued)

102
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
Table 1 (continued)
Comꢀ
pound
NR1R2
Yield
(%)
M.p.*/C
Rf
Molecular
formula
Found
Calculated
Molecular
weight
(%)
(eluent)**
C
H
N
4i
4j
65
68
170—172
0.57
C8H11ClN4O
C7H9ClN4O2
44.66
44.76
5.23
5.17
26.03
214.66
216.63
(with decomp.) (DCE—MeOH (2 : 1))
26.10
265—267
0.26
38.73
38.81
4.14
4.19
25.89
25.86
(with decomp.) (DCE—MeOH (4 : 1))
4k
AdNH
86
92
>350
0.37
C13H17ClN4O
55.56
55.62
34.96
34.88
6.06
6.10
5.40
5.37
20.05
19.96
27.02
27.11
280.76
206.63
(DCE—MeOH (4 : 1))
0.63
(DCE—MeOH (2 : 1))
13a
NMe2
(R3 = Me)
307—309
C6H10N4O2•HCl
13b
13с
13d
13e
13f
NMe2
85
83
90
82
84
305—307
312—314
281—283
302—304
300—303
0.61
C7H12N4O2•HCl
C8H14N4O2•HCl
C7H12N4O2•HCl
C8H14N4O2•HCl
C9H16N4O2•HCl
38.21
38.10
5.99
5.94
25.40
25.39
220.66
234.69
220.66
234.69
248.71
(R3 = Et)
(DCE—MeOH (2 : 1))
NMe2
(R3 = Pr)
0.65
41.03
40.94
6.37
6.44
23.92
23.87
(DCE—MeOH (2 : 1))
NHPr
(R3 = Me)
0.43
38.16
38.10
5.84
5.94
25.53
25.39
(DCE—MeOH (2 : 1))
NHPr
(R3 = Et)
0.39
40.83
40.94
6.39
6.44
23.80
23.87
(DCE—MeOH (2 : 1))
NHPr
(R3 = Pr)
0.43
43.54
43.46
6.95
6.89
22.46
22.53
(DCE—MeOH (2 : 1))
13g
13h
13i
85
80
82
310—312
314—316
301—304
0.58
C8H12N4O3•HCl
C9H14N4O3•HCl
38.55
38.64
5.19
5.27
22.58
22.53
248.67
262.70
276.72
(DCE—MeOH (2 : 1))
(R3 = Me)
(R3 = Et)
0.53
41.21
41.15
5.69
5.76
21.48
21.33
(DCE—MeOH (2 : 1))
0.59
C10H16N4O3•HCl 43.31
43.40
6.26
6.19
20.34
20.25
(DCE—MeOH (2 : 1))
(R3
= Pr)
* Literature data are given in parentheses.
** DCE stands for dichloroethane.
in substitution for only two chlorine atoms to give 2ꢀchloroꢀ
1,3,5ꢀtriazinꢀ4,6ꢀdione, whereas the third chlorine atom
is substituted for only at 120 C. Hydrolysis of compound 1
in water in the presence of excess sodium bicarbonate
gives, judging from the amount of consumed base, sodium
salt of 4,6ꢀdichloroꢀ2ꢀhydroxyꢀ1,3,5ꢀtriazine, however,
only cyanuric acid is formed upon acidification of the
aqueous solution.19 Kinetics of hydrolysis of the chlorine
atom in 2ꢀ(R1R2ꢀamino)ꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazines
were also studied;46,48—51 To reach homogeneity of the
medium (i.e., to increase the solubility of the starting
dichloro derivatives), we added solvents well miscible with
water (dioxane, acetone, DMSO). According to the data
in the work,50 use of alcohols as the cosolvents leads to the
substitution for the chlorine atom with the alkoxy group
and complete suppression of its substitution by a hydroxy
group. In addition, the hydrolysis product exhibits acidic
properties (pKa for 4ꢀchloroꢀ6ꢀethylaminoꢀ1,3,5ꢀtriazinꢀ
2(3H)ꢀone is 6.70, for 4ꢀchloroꢀ6ꢀdiethylaminoꢀ1,3,5ꢀtriꢀ
azinꢀ2(3H)ꢀone it is 6.68),50 that requires two equivalents
of an alkali. The reaction is slow in the absence of cosolꢀ
vents. Thus, in the reaction of sodium hydroxide (1.1 mol)
with 2ꢀaminoꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazine (1 mol) in waꢀ
ter at 20—25 C, ~30% of the starting dichloro derivative
remain still unreacted after 15 h.27
To sum up, for the selective substitution for one chlorine
atom in 2ꢀ(R1R2ꢀamino)ꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazines 2a—k
to occur, it is necessary to apply conditions providing a comꢀ
plete conversion of the starting compounds 2a—k, but which
do not lead to substitution for the third chlorine atom.

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
103
Taking into account the data on the selective substituꢀ
tion for one chlorine atom in molecules 2a—k given above,
we have chosen the water—acetonitrile system. Substituꢀ
tion for the chlorine in 2a—k (see Scheme 2) was effected by
the action of 10% aqueous sodium hydroxide at 20—25 C
with the molar ratio sodium hydroxide : 2a—k equal to
(2—2.4) : 1. When the base is added gradually, the reacꢀ
tion course is more even. Introduction of 20 vol.% of acetoꢀ
nitrile from the total amount of the sodium hydroxide
solution provided a required homogeneity of the reaction
mixture for all the dichloroꢀ1,3,5ꢀtriazines 2a—k. Comꢀ
pletion of the reaction was detected by TLC.
4a—k is the closest to that in compounds 7, 9b, and 10b—c,
which is apparently due to a similar electron effect of the
third substituent. Note that the absence of a proton on the
nitrogen atoms of the 1,3,5ꢀtriazinone ring adjacent to the
carbonyl group (i.e., for the fragment —CO—NR—) leads
to the shift of absorption bands of the carbonyl group to
1710—1740 cm–1, that is also observed in the spectra of
5ꢀarylꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazinꢀ2(5H)ꢀones 8a—c.55
The presence in compounds 10a and 10c of the lactam
fragment —CO—NH— was unambiguously confirmed by
the Xꢀray diffraction data.58
In the IR spectrum of 4,6ꢀdi(pyridiniumꢀ1ꢀyl)ꢀ1,3,5ꢀ
triazinꢀ2ꢀolate chloride 12 (see Ref. 59), no absorption
band is found in the region 1650—1750 cm–1, that most
likely allows us to rule out consideration of zwitterionic
structures of the type E, F, G for compounds 4a—k (see
Scheme 1).
Absorption of the N—H bonds in compounds 4a—k
are found in the regions 3300—3420 and 3190—3060 cm–1
as broad bands of medium intensity, which are due to the
presence of the exocyclic NH group and the ring NH fragꢀ
ment (see Table 2). For compounds 4b,h—j, which have
no NH fragment in the amino substituent, absorption is
observed in the region 3090—3150 cm–1, that can be asꢀ
signed to the absorption of the cyclic NH. These data are
in good agreement with the range (3100—3200 cm–1) givꢀ
en in the work54 for the structures containing a lactam
fragment —CO—NH—.
In the 1H NMR spectra of compounds 4a—k, the signal
for the acidic proton is found in the region  10.8—11.8 as
a broad singlet. Such a position of the proton signal correꢀ
sponds to the fragment N—H and agrees with the shifts
observed in the spectra of compounds 7, 9a—b, and 10b.
In the complex of 2ꢀhydroxyꢀ4,6ꢀbis(trinitromethyl)ꢀ
1,3,5ꢀtriazine with dioxane, the signal for the proton of
the hydroxyl group appears in the region  12 as a broad
singlet (CDCl3).32
The 13C NMR spectrum of compound 4b completely
agrees with that published earlier.28 In the 13C NMR specꢀ
trum of compound 11, only two signals for the quaternary
carbon atoms are found at  158.2 and 158.7, which the
authors of the work29 interpret as an overlap of the signals
for two carbon atoms of the 1,3,5ꢀtriazine ring. The
13C NMR spectra of compounds 4a—k exhibit a highꢀ
field shift of the signals for all the ring carbon atoms: thus,
for the carbon atom bonded to the chlorine atom, by
18—20 ppm with respect to the signal for the carbon atom
in cyanuric chloride ( 172.5);28 for the signal of the carꢀ
bon atom bonded to the amino group, by 10—15 ppm with
respect to the signal for the carbon atom in 2,4,6ꢀtrisꢀ
(dimethylamino)ꢀ1,3,5ꢀtriazine ( 165.9).28 The signal for
the carbon atom of the carbonyl group in compounds 4a—k
is close to the signal for the carbon atom in cyanuric acid
( 149.8).28 Similar pattern in the 13C NMR spectra is
observed for the series of disubstituted 1,3,5ꢀtriazinones
The time (t, the complete conversion) required for hyꢀ
drolysis of 2ꢀ(R1R2ꢀamino)ꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazines
2a—k with various substituents NHR1R2 is given below.
NHR1R2
NH2
NMe2
NHPr
NHPri
t/h
28
10
22
22
NHR1R2
NHC6H4Meꢀp
N(CH2)4
N(CH2)5
N(CH2CH2)2O 20
NHAd 24
t/h
24
20
20
NHC6H10ꢀcyclo 22
NHPh 24
It is seen that the time necessary for the reaction to
reach completion virtually does not depend on the strucꢀ
ture of amine fragment in the triazine ring and only in the
case of dimethylamine substituent the reaction is someꢀ
what faster than in other cases. To isolate the target
4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinꢀ2(3H)ꢀones 4a—k, the
homogeneous reaction mixture containing salt 3a—k was
acidified with dilute hydrochloric acid to pH 3—4. Triꢀ
azinꢀ2(1H)ꢀones 4a—k are obtained in good yields (see
Table 1) and are contaminated with neither the starting
compounds, nor the products of further hydrolysis.
To sum up, we found conditions for selective hydrolyꢀ
sis of one chlorine atom in molecules of 2ꢀ(R1R2ꢀamino)ꢀ
4,6ꢀdichloroꢀ1,3,5ꢀtriazines 2a—k containing structuralꢀ
ly different amino substituents.
For clarification of specific structural characteristics
of obtained 1,3,5ꢀtriazinones 4a—k having three different
substituents, we performed detailed spectral analysis takꢀ
ing into account the literature data on 1,3,5ꢀtriazines with
substituents of similar type. The major issue which reꢀ
quires clarification is position of the proton, whose migraꢀ
tion is responsible for the possibility of the lactimꢀlactam
tautomerism (see Scheme 1).
In the IR spectra of compounds 4a—k (Tables 2 and 3),
a strong absorption band is present in the region
1686—1707 cm–1 characteristic of the amideꢀtype C=O
group, that corresponds more to tautomer B, C, or D,
rather than A.
According to the literature data (see Table 3), in 1,3,5ꢀ
triazinones 5a—f, 6a—c, 7, and 9a,b an absorption band
of the carbonyl group is in the region 1665—1695 cm–1
.
Position of the C=O band in the synthesized compounds

104
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
Table 2. Spectral characteristics of 6ꢀaminoꢀ4ꢀchloroꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀones 4a—k and 4ꢀalkoxyꢀ6ꢀaminoꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀone
hydrochlorides 13a—i
Comꢀ
pound
IR,
/cm–1
1H NMR
(DMSOꢀd6), 
13C NMR (DMSOꢀd6), 
C(4) C(6) Other
C(2)
4a
4b
4c
4d
4e
4f
3192, 3038, 2777, 1707 (C=O),
1674, 1551, 1477, 1396, 1342,
1300, 1188, 1134, 997, 862,
793, 712, 638
8.90 (br.s, 2 H, NH2);
11.77 (br.s, 1 H, NH)
148.06 154.04 149.89
150.84 153.55 150.84
148.34 153.39 151.02
148.17 152.22 150.80
148.96 153.06 152.02
154.07 154.07 154.07
—
3095, 3012, 2984, 2957, 2887,
2820, 1701 (C=O), 1624, 1524,
1499, 1468, 1445, 1418, 1389,
1306, 1213, 993, 847, 787, 735
3.10, 3.12 (both s, 6 H, NMe,
 = 6 Hz);
11.34 (br.s, 1 H, NH)
38.90, 39.10
(NMe2)
3068, 2964, 2943, 2926, 2750,
2714, 1701 (C=O), 1637, 1512,
1466, 1377, 1352, 1294, 1265,
1001, 852, 785
0.88 (t, 3 H, Me, J = 7 Hz); 1.51
(m, 2 H, CH2); 3.27 t, 2 H,
(NCH2, J = 6.7 Hz); 9.00 (br.s,
1 H, NH); 11.41 (br.s, 1 H, NH)
10.98 (Me);
21.73 (CH2);
42.76 (NCH2)
3176, 3068, 2974, 2931, 2735,
1707 (C=O), 1630, 1514, 1460,
1446, 1371, 1338, 1311, 1265,
1003, 849, 785
1.16 (d, 6 H, Me, J = 6.5 Hz);
4.02 (m, 1 H, CH); 9.13 (br.s,
1 H, NH); 11.47 (br.s, 1 H,
NH)
22.03 (Me);
43.91 (NCH)
3169, 3066, 2931, 2858, 2731,
1703 (C=O), 1632, 1578, 1512,
1456, 1362, 1306, 1275, 1259,
1030, 1001, 835, 785
1.26 m, 1.52 d, 1.67 s, 1.80 d
(10 H, cycloꢀC6H10); 3.71 (m,
1 H, CH); 8.52 (br.s, 1 H,
NH); 11.13 (br.s, 1 H, NH)
23.76, 24.74,
31.71, 49.45,
49.55
(cycloꢀC6H11
)
3051, 2982, 2930, 2903, 2729,
2631, 1701 (C=O), 1618, 1585,
1518, 1499, 1464, 1439, 1369,
1259, 997, 854, 781, 752, 729,
667
7.15 t, 7.37 t, 7.54 d (5 H,
Ph); 9.60 (br.s, 1 H, NH);
10.95 (br.s, 1 H, NH)
121.78, 124.81,
129.02, 136.76
(Ph)
4g
4h
4i
3338, 3091, 3003, 1701 (C=O),
1612, 1578, 1487, 1385, 1315,
1286, 1246, 999, 928, 816, 779,
752, 735, 625
2.28 (s, 3H, Me); 7.18, 7.39
(both d, 4 H, pꢀC6H4, J = 8 Hz);
9.12 (br.s, 1 H, NH); 11.03
(br.s, 1 H, NH)
153.87 153.87 153.87
150.03 150.03 150.03
150.64 151.61 150.64
20.58 (Me),
122.30, 129.54,
133.71, 134.53
(pꢀC6H4)
3117, 2982, 2930, 2891, 2795,
1691 (C=O), 1624, 1608, 1522,
1491, 1458, 1419, 1362, 1279,
1186, 1140, 993, 787
1.92 (d, 4 H, CH2, J = 6.3 Hz);
3.50 (s, 4 H, CH2NCH2);
11.48 (br.s, 1 H, NH)
24.57 (CH2),
48.62 (NCH2)
3118, 3043, 2943, 2858, 2806,
1686 (C=O), 1610, 1529, 1491,
1450, 1416, 1292, 1271, 1209,
1111, 1009, 978, 852, 785
1.54, 1.59 (both d, 6 H, CH2,
J = 4 Hz); 3.64 (t, 4 H,
CH2NCH2, J = 4 Hz);
11.30 (br.s, 1 H, NH)
22.76 (CH2),
24.65 (CH2),
46.44 (NCH2)
4j
3151, 3115, 3032, 2968, 2933,
2858, 2804, 1686 (C=O),
1605, 1541, 1493, 1419, 1369,
1296, 1256, 1157, 1109, 1018,
980, 928, 839, 783
3.63 (d, 8 H, NCH2CH2O,
J = 6.8 Hz); 11.05 (br.s,
1 H, NH)
152.15 153.98 153.51
154.05
44.89, 44.95
(NCH2);
65.46, 65.57
(OCH2)
4k
3421, 3276, 3077, 3025, 2908,
2850, 2780, 1720 (C=O),
1618, 1591, 1513, 1457, 1405,
1363, 1309, 1295, 1249, 1232,
1159, 1132, 1097, 1004, 977,
842, 815, 794
1.57 s, 1.60 s, 1.62 s, 1.98 s,
2.02 s (15 H, Ad);
7.83 (br.s, 1 H, NH);
10.81 (br.s, 1 H, NH)
154.59 154.59 154.59
29.13, 36.06,
41.08, 53.12
(Ad)
13a
3344, 2956, 2879, 2840, 2763,
2692, 2622, 1747, 1660, 1606,
1537, 1486, 1402, 1322, 1224,
1089, 927, 883, 838, 765
3.17, 3.21 (both s, 6 H, NMe,
 = 16 Hz); 3.97 (s, 3 H,
OMe); 10.72 (br.s, 0.6 H, NH)
150.73 162.52 157.72
38.15, 38.34
(NMe2);
57.02 (OMe)
(to be continued))

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
105
Table 2 (continued)
Comꢀ
pound
IR,
/cm–1
1H NMR
(DMSOꢀd6), 
13C NMR (DMSOꢀd6), 
C(2)
C(4)
C(6)
Other
13b
3548, 3392, 3261, 2908, 2875,
2765, 2726, 2707, 2676, 2628,
1749, 1660, 1608, 1540, 1492,
1415, 1396, 1373, 1319, 1220,
1091, 1000, 891, 864, 827, 763
1.30 (t, 3 H, Me, J = 8.0 Hz);
3.16, 3.20 (both s, 6 H, NMe,
 = 16 Hz); 4.46 (q, 2 H,
OCH2, J = 8.0 Hz)
150.19 161.67 157.31
14.36 (Me);
38.44, 38.94
(NMe2);
66.86 (OCH2)
13с
3157, 3031, 2979, 2879, 2817,
2780, 1726, 1673, 1585, 1525,
1427, 1398, 1375, 1288, 1238,
1062, 1051, 885, 837, 761
0.91 (t, 3 H, Me, J = 7.8 Hz);
1.68 (sextet, 2 H, CH2,
J = 7.8 Hz); 3.09, 3.14 (both s, 6 H,
NMe,  = 20 Hz); 4.32 (t, 2 H,
OCH2, J = 7.8 Hz); 10.50 (br.s,
1 H, NH)
153.82 162.50 156.18
10.60 (Me);
21.78 (CH2);
37.78 (NMe2);
70.81 (OCH2)
13d
13e
3267, 2966, 2877, 2804, 2686,
2622, 1753, 1650, 1589, 1558,
1527, 1432, 1328, 1307, 1195,
1155, 1083, 1037, 927, 837, 771
0.88 (t, 3 H, Me, J = 8.0 Hz);
1.53 (m, 2 H, CH2); 3.38
(m, 2 H, CH2); 4.00 (s, 3 H,
OMe); 9.54 (br.s, 0.5 H, NH);
11.05 (br.s, 0.2 H, NH)
148.39 163.97 158.27
11.47, 11.59
(Me); 22.11,
22.31 (CH2);
43.15, 43.27,
43.45 (NCH2);
57.45 (OMe)
3149, 3066, 2962, 2931, 2871,
2797, 2771, 2774, 2682 1739,
1660, 1585, 1533, 1438, 1371,
1319, 1180, 1151, 1101, 958,
865, 759
0.88 (t, 3 H, Me, J = 7.8 Hz);
1.30 (t, 3 H, Me, J = 7.6 Hz);
1.53 (m, 2 H, CH2); 3.39
(m, 2 H, CH2); 4.48 (q, 2 H,
OCH2, J = 7.6 Hz); 9.53 (br.s,
0.8 H, NH); 11.15 (br.s, 0.3 H,
NH)
148.18 163.18 158.26
11.47, 11.56,
11.67 (Me);
14.35, 14.47
(CH2); 22.11,
22.35 (CH2);
42.98, 43.27
(NCH2); 67.31
(OCH2)
13f
3131, 3066, 2964, 2937, 2873,
2798, 2761, 2624, 1741, 1658,
1585, 1537, 1438, 1332, 1317,
1089, 941, 760
0.89, 0.92 (m, 6 H, Me); 1.50
(m, 2 H, CH2); 1.71 (m, 2 H,
CH2); 3.35 (t, 2 H, CH2,
J = 7.6 Hz); 4.36 (t, 2 H, OCH2,
J = 7.6 Hz); 9.42 (br.s, 1 H,
NH); 10.92 (br.s, 0.8 H, NH)
148.46 163.48 158.27
10.51 (Me);
11.61, 11.66
(Me); 21.79
(CH2); 22.12,
22.34 (CH2);
42.75, 43.27,
43.42 (NCH2);
72.27 (OCH2)
13g
13h
13i
3099, 3006, 2929, 2860, 2814,
2746, 1741, 1606, 1542, 1488,
1442, 1419, 1326, 1307, 1274,
1110, 1066, 1008, 931, 916,
875, 767
3.64, 3.81 (m, 8 H,
NCH2CH2O); 3.96 (s, 3 H,
OMe); 10.72 (br.s, 0.7 H, NH)
151.62 163.08 157.99
151.26 162.36 157.73
151.05 162.47 157.52
45.40, 46.06
(NCH2);
56.92 (OMe);
65.99 (OCH2)
3162, 3054, 2993, 2941, 2798,
1741, 1668, 1585, 1468, 1442,
1403, 1378, 1344, 1270, 1180,
1114, 1056, 1010, 883, 827, 765
1.28 (t, 3 H, Me, J = 7.8 Hz);
3.67, 3.82 (m, 8 H,
NCH2CH2O); 4.66 (q, 2 H,
OCH2, J = 7.8 Hz); 10.70
(br.s, 0.3 H, NH)
14.40 (Me);
45.41, 46.12
(NCH2); 65.98,
66.13 (OCH2);
66.62 (OCH2)
3342, 3023, 2975, 2860, 2809,
2684, 1754, 1625, 1602, 1542,
1490, 1444, 1390, 1378, 1317,
1272, 1112, 1064, 1012, 896,
858, 771
0.90 (t, 3 H, Me, J = 7.6 Hz);
1.67 (q, 2 H, CH2,
J = 7.6 Hz); 3.65, 3.81
(m, 8 H, NCH2CH2O); 4.36
(t, 2 H, OCH2, J = 7.6 Hz);
10.54 (Me);
21.81 (CH2);
45.49, 46.15
(NCH2); 65.75,
65.99 (OCH2);
71.79 (OCH2)
Note. Position of the proton in the molecule of 11 was not determined, judging by the name of the compound in the Results and
Discussion and Experimental sections.29

106
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
Table 3. Spectral characteristics of substituted 1,3,5ꢀtriazinones
Compound

C=O (KBr)/cm–1
 (NH of 1,3,5ꢀtriazine ring)
(DMSOꢀd6)
4a—k
1686—1707
10.81—11.77
—
5a (NR1R2 = NMe2)
5b (NR1R2 = N(CH2)5)
5c (NR1R2 = N(CH2CH2)2O)
5d (NR1R2 = NBu)
1675 (see Ref. 52)
1680 (see Ref. 52)
1670 (see Ref. 52)
—
—
—
11.80 (see Ref. 53)
—
5e (NR1R2 = NCH2Ph)
5f (NR1R2 = NHPh)
6a (NR1R2 = N(CH2CH2)2O)
6b (NR1R2 = N(CH2)5)
6c (NR1R2 = N(Me)Ph)
7
1670 (see Ref. 53)
1665 (see Ref. 53)
1690 (see Ref. 54)
1680 (see Ref. 54)
1660 (see Ref. 54)
1698 (see Ref. 54)
1710 (see Ref. 55)
1730 (see Ref. 55)
1720, 1740 (see Ref. 55)
—
10.05—10.25 (see Ref. 53)
10.21 (see Ref. 54)
9.78 (see Ref. 54)
10.20 (see Ref. 54)
11.47 (see Ref. 54)
—
8a (R = Ph)
8b (R = 2,6ꢀ(MeC6H3)2)
8c (R = 4ꢀBrꢀ2,6ꢀ(MeC6H2)2)
9a (R = Ph)
9b (R = ꢀDꢀribofuranosyl)
10a (R = R´ = N(CH2CH2)2O)
10b (R = R´ = N(CH2)5)
10c (R = OMe, R´ = N(CH2CH2)2O)
11
—
—
11.60 (see Ref. 56)
11.24 (see Ref. 57)
10.52 (see Ref. 58)
11.45 (see Ref. 58)
12.30 (see Ref. 58)
11.13, 11.54 (see Ref. 29)
1693 (see Ref. 57)
—
1670 (see Ref. 58)
1690 (see Ref. 58)
—
and monosubstituted 1,3,5ꢀtriazinediones.23,28,60—62 The
highꢀ field shift of the signals for the carbon atoms is, in
our opinion, caused by redistribution of electron density
between 1,3,5ꢀtriazine ring and substituents. It is known19
that the nitrogen atoms in the 1,3,5ꢀtriazine heteroaroꢀ
matic ring carry partial negative charge due to their elecꢀ
tronꢀwithdrawing character, while the carbon atoms carry
partial positive charge. Such a distribution of electron denꢀ
sity is responsible for the position of signals for the carbon
atoms in the 13C NMR spectrum ( 163—175),23 as well
as for the tendency of 1,3,5ꢀtriazine derivatives to nucleoꢀ
philic substitution reactions. In the 13C NMR spectrum of
the complex of 2ꢀhydroxyꢀ4,6ꢀbis(trinitromethyl)ꢀ1,3,5ꢀ
triazine with dioxane, the signal for the carbon atom bondꢀ
ed to the hydroxyl group is found at  171 (CDCl3).32 In
the 13C NMR spectrum of tertꢀbutylaminium salt of
2ꢀhydroxyꢀ4,6ꢀbis(trinitromethyl)ꢀ1,3,5ꢀtriazine, the sigꢀ
nal for the carbon atom bonded to the negatively charged
oxygen is found at  165 (acetoneꢀd6).63 Disruption of
heteroaromatic character in compounds 4a—k results in
the fact that the ring nitrogen atom bearing a proton beꢀ
comes an electronꢀdonating substituent with respect to
the rest of the conjugated system, which includes the carꢀ
bonyl group and two C=N bonds of the ring. Displaceꢀ
ment of the lone pair on the nitrogen atom toward the
conjugated system leads to an increase in electron density
on the carbon atoms of the 1,3,5ꢀtriazine ring and, as
a consequence, to the highꢀfield shift of the signals for the

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
107
carbon atoms in the 1,3,5ꢀtriazine ring ( 148—154). To
sum up, position of signals in the 13C NMR spectra of
compounds 4a—k evidences also in favor of structures B,
C, D and allows us to rule out structures A, E, F, G.
In order to determine the structure of 1,3,5ꢀtriazinoꢀ
nes 4a—k, we attempted to grow single crystals suitable
for Xꢀray diffraction studies. Compounds 4a—k have
proved insoluble in nonpolar and weakly polar solvents,
therefore, we used DMF, DMSO, acetone, acetonitrile,
methanol, ethanol, and their mixtures to grow the crysꢀ
tals. However, no acceptable single crystal was obtained.
Moreover, use of alcohols or their mixtures with other
solvents results in the reaction, leading to substitution for
the chlorine in compounds 4 by an alkoxy group (Scheme 3).
Thus, when compounds 4b,c,j were dissolved in methaꢀ
nol, ethanol, or nꢀpropanol at room temperature in the
absence of bases, substitution for the chlorine is comꢀ
pleted already within 24—96 h (see Experimental), in
which case the corresponding 4ꢀalkoxyꢀ6ꢀaminoꢀ1,3,5ꢀ
triazinꢀ2(1H)ꢀone hydrochlorides 13a—i are obtained in
high yields.
that the guanidine fragment in the starting molecule plays
the role of a base, whereas formation of the saltꢀlike prodꢀ
uct is a driving force for the process.
Since the spectral characteristics do not allow us to
unambiguously chose between possible tautomers (see
Scheme 1), we performed quantum chemical calculations.
The calculations were performed in terms of the densiꢀ
ty functional theory using the GAUSSIAN program64 and
the M052X functional with the augꢀccꢀpvdz basis for tauꢀ
tomers A, B, C, D of the molecule 4b with correction for
the zeroꢀpoint vibrations (ZPE). This approximation has
been successfully used earlier65,66 for analysis of geomeꢀ
try, energy, and intermolecular interactions. The choice
between neutral (B, C, D) and zwitterionic (E, F, G) forms
was made based on the distribution of bond distances in
the triazine ring and the C—O bond distance. The values
of atomic charges in this case are less indicative, since the
signs "+" and "–" commonly shown in schemes, first, are
very arbitrary, and a charge assigned to an atom is in
reality spread between this atom and its neighbors. Second,
the neutral and the zwitterionic forms are only two boundꢀ
ary cases (two canonical structures, see in Scheme 1),
whereas a true electron structure of the molecule (mol) is
their hybrid (mol = an + bi, where  is the wave funcꢀ
tion, and the structure is assigned for either neutral (n), or
zwitterionic (i) form depending on coefficients a and b).
This is clearly illustrated by Table 4, in which the charge
distributions (estimated in terms of the natural analysis of
populations, included into the GAUSSIAN program) are
given together with geometric characteristics.
Scheme 3
As it is seen from the data given in Table 4, zwitterionic
forms are less stable than their neutral counterparts B, C,
D, obtained by optimization. This follows, first, from the
C—O bond distance, which corresponds to that of a douꢀ
ble bond, and, second, from the ring geometry, correꢀ
sponding to the lactam structure.
Calculation of relative energies (Table 5) show that in
the isolated state, i.e., in the gas phase, the first tautomer
out of A, B, C, and D is the most stable, that agrees
with the data in the work.31 Tautomer D has proved the
most energetically unfavorable, being inferior to the isoꢀ
13: NR1R2 = NMe2, R3 = Me (a), Et (b), Pr (c);
NR1R2 = NHPr, R3 = Me (d), Et (e), Pr (f)
NR1R2 = N(CH2CH2)O, R3 = Me (g), Et (h), Pr (i)
The readiness of substitution for the chlorine atom in
compounds 4b,c is apparently accounted for by the fact
Table 4. Bond distances and charge distributions in tautomers A—D of molecule 4b in the isolated state (calculation in the M052X/augꢀ
ccꢀpvdz approximation)
Tautoꢀ
mer
Bond distance*/Å
Charge/e
C(1)—O(1) C(1)—N(1) N(1)—C(2) C(2)—N(2) N(2)—C(3) C(3)—N(3) N(3)—C(1) –qO(1) –qN(1) –qN(2) –qN(3)
A
B
C
D
1.334
1.210
1.212
1.206
1.222
1.341
1.373
1.433
1.438
1.370
1.323
1.299
1.337
1.259
1.308
1.310
1.339
1.281
1.369
1.323
1.358
1.328
1.390
1.387
1.343
1.349
1.356
1.323
1.297
1.361
1.315
1.419
1.355
1.390
1.400
0.69 0.67 0.63 0.64
0.64 0.63 0.67 0.70
0.65 0.69 0.63 0.69
0.60 0.57 0.69 0.67
0.71 0.68 0.67 0.68
B**
* Numeration of atoms is shown in Figure 1.
** Parameters of the tautomer B complex with DMSO are also given for comparison (see below).

108
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
O(1)
C(1)
O(1)
C(1)
N(1)
N(1)
N(3)
N(3)
C(5)
N(4)
C(2)
C(2)
C(3)
C(3)
C(5)
N(4)
C(4)
N(2)
N(2)
Cl(1)
Cl(1)
C(4)
A
B
O(1)
O(1)
C(1)
C(1)
N(3)
N(3)
N(1)
N(1)
C(2)
C(3)
N(4)
N(4)
C(2)
C(3)
C(5)
C(5)
N(2)
N(2)
Cl(1)
Cl(1)
C(4)
C(4)
C
D
Fig. 1. General view of the optimized tautomers A—D of molecule 4b with numeration of atoms.
mers placed under similar conditions by no less than
12—17 kcal mol–1
Usually reactions are carried out with compounds
which are in the solid or liquid phases or in solution, i.e. in the
condensed state, where there is a considerable influence of
the surrounding, which can be arbitrary separated into two
components: specific and nonspecific solvation. It is obvious
that the calculation data for the isolated molecules are not
informative enough about stabilization of different isomers
and can be considered only as a "zero approximation".
Taking this into account, we performed calculations
for the isomers in solvents in terms of the model of selfꢀ
consistent reaction field (SCRF, the model of the polarꢀ
ized continuum). Effect of specific solvation is not conꢀ
sidered in the framework of this model. In order to make
allowance, at least partially, for this effect, we have also
analyzed Hꢀbonded pairs including molecules of a comꢀ
pound and a solvent. Calculations were performed for both
isolated pairs and pairs in the solvent field (simultaneous
consideration of both polarization and specific solvation).
This allows us to analyze both contributions into stabilizaꢀ
tion of each isomer. Calculation in terms of the SCRF
model, simulating a solvent field, was performed in both
a relatively weak field, mimicking influence of such solꢀ
.
Table 5. Relative energies* (Erel) of tautomers A—D of
molecule 4b in the isolated state and in the 1,4ꢀdioxane
and DMSO fields (calculation in the M052X/augꢀccꢀ
pvdz approximation)
Tautoꢀ
mer
Erel/kcal mol–1
Isolated
state
1,4ꢀDioxane
DMSO
A
0
0
2.6
0
2.1
19.5
B
C
D
5.3
3.0
18.0
2.0
1.5
13.8
* The energies should be compared within a column.

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
109
Table 6. Relative energies (Erel) of the Hꢀbonded pairs of tautomer—solvent in the isolated state, in the 1,4ꢀdioxane
and DMSO fields (calculations in the M052X/augꢀccꢀpvdz approximation)
Pair
Erel/kcal mol–1
Pair
Erel/kcal mol–1
Isolated
state
1,4ꢀDioxane DMSO
Isolated
state
1,4ꢀDioxane DMSO
A...MeNO2
B...MeNO2
C...MeNO2
D...MeNO2
0
0
0
1.4
13.7
2.6
0
2.8
9.6
A...DMSO
B...DMSO
C...DMSO
D...DMSO
0
0
0
1.6
1.8
18.2
3.3
3.7
19.8
2.2
3.3
—
1.0
2.8
—
vent as 1,4ꢀdioxane ( = 2.2), and a strong field, correꢀ
sponding to the action of DMSO ( = 46.8). The data in
Table 4 clearly demonstrate (for tautomer B as an examꢀ
ple) that even for the highly polar solvent, optimization of
geometry leads exactly to the neutral form (i.e., the tauꢀ
tomer B, rather than E, that follows from the bond disꢀ
tance value for C=O, corresponding to that of a double
bond). In this case, the solvent field shifts the equilibrium
somewhat to the side of zwitterionic form (the C—O bond
is elongated by 0.012 Å), and this was expected. However,
this effect is very weak (see Table 4). Similar results were
also obtained for tautomers C and D (are not included in
Table 4). Therefore, the zwitterionic forms E, F, and G are
excluded from our further consideration.
It is important that the relative stability of neutral
tautomers A—D sharply changes in solvents, which is apꢀ
proximated in terms of the SCRF model. The most favorꢀ
able in the isolated state tautomer A becomes third in
stability in the DMSO field (see Table 5). Tautomer A is
more favorable in the weak 1,4ꢀdioxane field, though, the
difference in relative energies decreases more than twoꢀ
fold as compared to the isolated state.
formed for these pairs in both the isolated state and the
1,4ꢀdioxane and DMSO fields, are given in Table 6.
As it follows from Table 6, for the pair with nitroꢀ
methane and in the isolated state, and in DMSO, as and
in the case of the individual tautomers of compound 4b,
tautomer A is the most stable, in which case the gain in
energy, as compared to tautomers B and C, is less than
2 kcal mol–1 for the pair with MeNO2 and ~3.5 kcal mol–1
for the pair with the strong Hꢀbond (in DMSO). Formation
of Hꢀbonds leads to the change in the relative stability of
tautomers B and C (see Tables 5 and 6). Tautomer D
remains the least stable form of compound 4b in the case
under consideration (i.e., as a pair with the solvent), as well.
This gives the reason to exclude it out of consideration.
Further, we have analyzed the nature of interactions of
different forms of compound 4b with MeNO2 and DMSO
in terms of the R. Bader topological theory "Atoms in
molecules"67,68 with subsequent application of the correꢀ
lation between potential energy density in the critical point
and the contact energy69,70 to evaluate the bonding energy.
The optimized structures of pairs (we were limited to the
topological analysis of the isolated pairs tautomer—solvent,
i.e., without using the SCRF procedure) and the graph of
their binding, plotted based on the search results for the
critical points of the bond (3, –1), are given in Figure 2.
Calculation results for the Hꢀbonded complexes of tauꢀ
tomers A—D with DMSO (strong Hꢀbonding) and nitroꢀ
methane (medium Hꢀbonding) molecules, which were perꢀ
C(6)
O(2)
C(7)
C(6)
H(6)
C(7)
H(6)
O(1)
S(1)
S(1)
C(7)
O(1)
S(1)
O(2)
H(1)
O(1)
C(1)
N(1)
O(2)
C(1)
C(6)
H(6)
C(1)
N(3)
H(1)
N(3)
C(3)
H(1)
N(3)
N(4)
N(1)
C(2)
H(5)
C(5)
N(1)
C(2)
C(2)
N(2)
C(3)
C(5)
C(3)
N(4) N(2)
C(5)
N(4)
N(2)
Cl(1)
Cl(1)
Cl(1)
C(4)
C(4)
C(4)
A
B
C
Fig. 2. The structure of the Hꢀbonded pairs of tautomers A—C of molecule 4b with the DMSO molecule (the pair with nitromethane
molecule differs only in the absence of the S...O interaction and is not shown in Figure).

110
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
Energies of intermolecular binding for the pair tauꢀ
lar solvents, the equilibrium could have been (compounds
4a—k do not dissolve in such solvents!) shifted to the side
of tautomer A.
tomer—DMSO, evaluated as the sums of all the inꢀpair
interactions, are –26.8, –18.3, and –20.0 kcal mol–1 for
tautomers A, B, and C, respectively. For the pairs of tauꢀ
tomer—nitromethane, a relative difference in the binding
energies is significantly lower, though, the sequence reꢀ
mains: –10.8, –10.1, and –10.3 kcal mol–1, respectively.
It is logically to suppose that tautomer A Hꢀbonded
into the pair with the solvent should be energetically yet
more favorable as compared to tautomers B and C than
the individual tautomer A. However, the calculations perꢀ
formed (see Table 6) indicate that the converse is true.
A relative gain in energy for the pair A—solvent is less than
that for the individual tautomer (see Table 5, the first
column). This, at first glance, contradiction can be exꢀ
plained if we take into account that, besides formation of
Hꢀbonds and shortened interactions in the pair tauꢀ
tomer—solvent, a DMSO or nitromethane molecule poꢀ
larizes the molecule of 4b. The polarization effect (nonꢀ
specific solvation), as shown above (see Table 6), leads to
the decrease in stability of tautomer A, but increases that
of tautomer B, whose interaction with the solvent moleꢀ
cule is the weakest.
If interaction of molecules in pair is strong enough,
which is the case of DMSO, then the gain in energy due to
the strong O—H...O bond is not swamped by the polarizaꢀ
tion effect, and tautomer A has proved the most favorable.
If the proton is accepted by a weaker group, for example,
a nitro group of nitromethane, the difference in the binding
energy of tautomers with the solvent molecule decreases,
and the influence of the strong solvent field becomes suffiꢀ
cient for stabilization of tautomer B. The results obtained
explain, in particular, the formation of the lactim form in
the Hꢀbonded complex of 2ꢀhydroxyꢀ4,6ꢀbis(trinitroꢀ
methyl)ꢀ1,3,5ꢀtriazine with 1,4ꢀdioxane,56 whose lactim
structure (i.e., built similar to the type of tautomer A)
of the triazine ring was confirmed by Xꢀray diffracꢀ
tion studies. Dioxane forms relatively strong Hꢀbond,
thereby stabilizing the lactim tautomer. In this case, the
dioxane field, from which solution the crystals were obꢀ
tained, is weak and, as a result, stabilization of the lactam
structures due to the solvent field turned out to be smaller
than stabilization of the lactim form due to the formation
of Hꢀbonding.
Experimental
Melting points were determined on a Gallenkamp melting
point apparatus and were not corrected. 1H and 13C NMR
spectra were recorded on a Bruker Avance II spectrometer
1
(1H, 400.13; 13C, 100.61 MHz). Chemical shifts in the H and
13C NMR spectra are given in the  scale, using Me4Si, as an
internal standard. IR spectra were recorded on an Avatar 360
ESP spectrometer (KBr pellets). Elemental analysis was perꢀ
formed on a Eurovector EA 3000 instrument. Reaction course
and purity of products were monitored by TLC on Silufol UVꢀ254
plates.
2ꢀAminoꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazines 2a—k (general proceꢀ
dure). An amine (0.02 mol) (ammonia as a 25% aqueous soluꢀ
tion, dimethylamine as a 33% aq. solution, other amines as a 10%
solution in diethyl ether) was added dropwise to a vigorously
stirred suspension of cyanuric chloride 1 (3.69 g, 0.02 mol) in
diethyl ether (60 mL) at –(15—10) C over 1 h. After addition of
the amine, the reaction mixture was stirred for 30—45 min under
the same conditions (TLC monitoring for cyanuric chloride,
eluent DCE). Diethyl ether was evaporated to dryness, and the
residue was treated with water (50 mL) using magnetic stirring.
Insoluble white crystalline precipitate of 2a—d,f—k was filtered
off and dried. Compound 2e was obtained by extraction with
DCE (40 mL) of the residue after evaporation of diethyl ether.
After the insoluble residue was separated, the DCE solution was
dried with sodium sulfate and filtered, DCE was evaporated
in vacuo, the residue was evacuated.
4ꢀAminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀones 4a—k (general
procedure). 2ꢀAminoꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazine 2a—k
(0.002 mol) was added to a magnetically stirred mixture of 1.0 M
aq. sodium hydroxide (4 mL) and acetonitrile (10 mL) at ~20 C.
The reaction mixture was stirred for 20 min under the same
conditions, then 1.0 M aq. sodium hydroxide (4 mL) and
2ꢀaminoꢀ4,6ꢀdichloroꢀ1,3,5ꢀtriazine 2a—k (0.002 mol) were adꢀ
ditionally added. After stirring for 20 min, this operation was
repeated 3 more times. The completion of the reaction was monꢀ
itored by TLC for the starting 2a—k (eluent DCE). After it was
over, the reaction mixture was filtered from a small amount of
a precipitate, and the filtrate was acidified with a dilute hydroꢀ
chloric acid to pH 2—3. Precipitates of compounds 4a—k were
filtered off, washed with water (2×30 mL), and dried. The yields
and physicochemical properties of the products are given in
Tables 1 and 2.
In conclusion, the calculations performed show that in
the condensed state compound 4b, depending on proporꢀ
tion of specific and nonspecific solvation effects, will exist
as tautomer A or B, which are the most stable. Formation
of tautomer C is improbable, whereas of tautomer D, virꢀ
tually impossible.
On the whole, summarizing spectral and calculation
data, we can say that in the solid state compounds 4a—k
exist as 6ꢀaminoꢀ4ꢀchloroꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀones. In
strongly polar solvents (of DMSO type), an equilibrium
exists between tautomers A and B, whereas in weakly poꢀ
4ꢀAlkoxyꢀ6ꢀaminoꢀ1,3,5ꢀtriazinꢀ2(1H)ꢀone hydrochlorides
13a—i (general procedure). 6ꢀAminoꢀ4ꢀchloroꢀ1,3,5ꢀtriazinꢀ
2(1H)ꢀone 4b,c,j (0.005 mol) was added to the corresponding
alcohol (20 mL) at 20—25 C with stirring. The reaction mixture
was stirred under the same conditions (in methanol for 24 h,
in ethanol for 72 h, in nꢀpropanol for 96 h), monitoring the
reaction progress by TLC for the starting 4b,c,j (eluent methaꢀ
nol—DCE (4 : 1)). After completion of the reaction, the alcohol
was evaporated to dryness, the residue was treated with water
(20 mL) with magnetic stirring. An insoluble residue was filtered
off, the filtrate was concentrated to dryness. The crystalline
product obtained was suspended in diethyl ether, insoluble prodꢀ

Synthesis of 4ꢀaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
111
ucts 13a—i were filtered off, dried at 100—110 C. The yields
and properties of the products are summarized in Tables 1 and 2.
26. T. Ueda, S. Toyoshima, I. Nakata, Pharm. Bull., 1953, 1, 252.
27. S.ꢀH. Kim, D. G. Bartholomew, L. B. Allen, R. K. Robins,
G. R. Revankar, P. Dea, J. Med. Chem., 1978, 21, 883.
28. A. Talebian, A. Ghiorghis, C. F. Hammer, E. A. Murril,
F. Pallas, J. Heterocycl. Chem., 1992, 29, 979.
29. R. A. Coxall, S. G. Harris, D. K. Henderson, S. Parsons,
P. A. Tasker, R. E. P. Winpenny, J. Chem. Soc., Dalton Trans.,
2000, 2349ꢀ2356.
30. US Pat. 4246408; http://worldwide.espacenet.com/searchꢀ
Results?DB=worldwide.espacenet.com&loca.
31. Y. Wang, C. U. Pittman, S. Saebo, J. Org. Chem., 1993,
58, 3085.
32. A. V. Shastin, T. I. Godovikova, S. P. Golova, V. S. Kuz´min,
L. I. Khmel´nitskii, B. L. Korsunskii, Mendeleev Commun.,
1995, 5, 17.
33. G. Just, I. Pokorny, W. Pritzkow, J. Prakt. Chem., 1995,
337, 133.
References
1. H. M. LeBaron, J. E. McFarland and O. C. Burnside, in
The Triazine Herbicides, Eds M. L. Homer, E. M. Janis,
C. B. Orvin, Elsevier, San Diego, 2008, p. 1.
2. H. Behrendt, J. Altschuh, S. Sixt, J. Gasteiger, R. Höllering
and T. Kostka, Chemosphere, 1999, 38, 1811.
3. K. Koizumi, N. Kuboyama, K. Tomono, A. Tanaka, A. Ohki,
H. Kohno, K. Wakabayashi, P. Böger, Pestic. Sci., 1999,
55, 642.
4. US Pat. 4102872; http://worldwide.espacenet.com/searchꢀ
Results?DB=worldwide.espacenet.com&loca.
5. R. Fink, C. Frenz, M. Thelakkat, H.ꢀW. Schmidt, Macroꢀ
molecules, 1997, 30, 8177.
6. J. Z. Jan, B. H. Huang, J. J. Lin, Polymer, 2003, 44, 1003.
7. A. D. Sagar, R. D. Shingte, P. P. Wadgaonkar, M. M. Saꢀ
lunkhe, Eur. Polym. J., 2001, 37, 1493.
34. H. S. Mosher, F. C. Whitmore, J. Am. Chem. Soc., 1945,
67, 662.
35. W. M. Pearlman, C. K. Banks, J. Am. Chem. Soc., 1948,
70, 3726.
8. N. Baindur, N. Chadha, B. M. Brandt, D. Asgari, R. J.
Patch, C. SchalkꢀHiHi, T. E. Carver, I. P. Petrounia, C. A.
Baumann, H. Ott, C. Manthey, B. A. Springer, M. R. Player,
J. Med. Chem., 2004, 48, 1717.
9. E. Boven, M. M. Nauta, H. M. M. Schlüper, C. A. M.
Erkelens, H. M. Pinedo, Cancer Chemoth. Pharm., 1986,
18, 124.
36. J. T. Thurston, J. R. Dudley, D. W. Kaiser, I. Hechenꢀ
bleikner, F. C. Schaefer, D. HolmꢀHansen, J. Am. Chem.
Soc., 1951, 73, 2981.
37. V. P. Wystrach, D. W. Kaiser, F. C. Schaefer, J. Am. Chem.
Soc., 1955, 77, 5915.
38. J. N. Ashley, S. S. Berg, R. D. MacDonald, J. Chem. Soc.
(Res.), 1960, 4525.
10. E. A. H. Friedheim, J. Am. Chem. Soc., 1944, 66, 1775.
11. M. H. V. Huynh, M. A. Hiskey, D. E. Chavez, D. L. Naud,
R. D. Gilardi, J. Am. Chem. Soc., 2005, 127, 12537.
12. J. C. Oxley, J. L. Smith, J. S. Moran, J. Energ. Mater., 2009,
27, 63.
13. M. H. V. Huynh, M. A. Hiskey, C. J. Pollard, D. P. Monꢀ
toya, E. L. Hartline, R. Gilardi, J. Energ. Mater., 2004,
22, 217.
39. H. Koopman, J. Daams, Recl. Trav. Chim. PaysꢀBas, 1958,
77, 235.
40. N. Nohara, S. Sekiguchi, K. Matsui, J. Heterocycl. Chem.,
1970, 7, 519.
41. A. Kumar, K. Srivastava, S. Raja Kumar, M. I. Siddiqi, S. K.
Puri, J. K. Sexana, P. M. S. Chauhan, Eur. J. Medel. Chem.,
2011, 46, 676.
42. N. Sunduru, M. Sharma, K. Srivastava, S. Rajakumar, S. K.
Puri, J. K. Saxena, P. M. S. Chauhan, Biorg. Med. Chem.,
2009, 17, 6451.
43. M. Hedayatullah, C. Lion, A. B. Slimane, L. D. Conceiçao,
I. Nachawati, Heterocycles, 1999, 51, 1891.
44. K. Matsui, I. Sakamoto, J. Synth. Org. Chem. Jpn, 1960,
18, 175.
45. H. E. FierzꢀDavid, M. Matter, J. Soc. Dyers Colour., 1937,
53, 424.
46. S. Horrobin, J. Chem. Soc. (Res.), 1963, 4130.
47. N. V. Kozlova, D. F. Kutepov, D. N. Khokhlov, A. I. Kryꢀ
mova, Zh. Obshch. Khim., 1963, 33, 3303 [J. Gen. Chem.
USSR (Engl. Transl.), 1963, 33, 3232].
14. A. K. Sikder, N. Sikder, J. Hazard. Mater., 2004, 112, 1.
15. A. A. Korkin, R. J. Bartlett, J. Am. Chem. Soc., 1996,
118, 12244.
16. R. Budziarek, J. Chem. Soc. C., 1971, 74.
17. M. Veirong, Kh. Minfen, N. P. Samoilova, M. V. Gorelik,
Zh. Org. Khim., 1996, 32, 1593 [Russ. J. Org. Chem.
(Engl. Transl.), 1996, 32, 1544].
18. E. M. Smolin, L. Rapoport, SꢀTriazines and Derivatives,
Wiley, New York—London, 1959.
19. K. Matsui, J. Synth. Org. Chem Jpn, 1959, 17, 528.
20. V. I. Mur, Usp. Khim., 1964, 33, 182 [Russ. Chem. Rev.
(Engl. Transl.), 1964, 33, 92].
21. K. Matsui, J. Synth. Org. Chem Jpn, 1972, 30, 19.
22. J. M. E. Quirke, in Comprehensive Heterocyclic Chemistry,
Eds A. R. Katritzky, C. W. Rees, Pergamon, Oxford, 1984,
p. 457.
23. D. Bartholomew, in Comprehensive Heterocyclic Chemistry II,
Eds A. R. Katritzky, C. W. Rees, E. F. V. Scriven, Pergaꢀ
mon, Oxford, 1996, p. 575.
24. G. Giacomelli, A. Porcheddu, in Comprehensive Heterocyclic
Chemistry III, Eds A. R. Katritzky, C. A. Ramsden, E. F. V.
Scriven, R. J. K. Taylor, Elsevier, Oxford, 2008, p. 197.
25. A. V. Shastin, T. I. Godovikova, B. L. Korsunskii, Usp. Khim.,
2003, 72, 311 [Russ. Chem. Rev. (Engl. Transl.), 2003,
72, 279].
48. A. F. Cockerill, G. L. O. Davies, D. M. Rackham, J. Chem.
Soc., Perkin Trans. 2, 1974, 723.
49. M. Hunter, A. Renfrew, J. A. Taylor, J. M. J. Whitmore,
A. Williams, J. Chem. Soc., Perkin Trans. 2, 1994, 2389.
50. T. N. Motorova (Bykhovskaya), O. N. Vlasov, I. A. Mel´niꢀ
kova, N. N. Mel´nikov, Zh. Obshch. Khim., 1975, 45, 1847
[J. Gen. Chem. USSR (Engl. Transl.), 1975, 45, 1810].
51. R. Budziarek, P. Hampson, J. Chem. Soc. C., 1971, 1167.
52. H. Hartmann, J. Liebscher, P. Czerney, Tetrahedron, 1985,
41, 5371.
53. S. Kohra, K. Ueda, Y. Tominaga, Heterocycles, 1996, 43, 839.
54. Y. Kihara, S. Kabashima, T. Yamasaki, T. Ohkawara,
M. Furukawa, J. Heterocycl. Chem., 1990, 27, 1213.

112
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Bakharev et al.
55. R. Bunnenberg, J. C. Jochims, H. Härle, Chem. Ber., 1982,
115, 3587.
56. N. B. Hanna, M. Masojídková, P. Fiedler, A. Pískala, Colꢀ
lect. Czech. Chem. Commun., 1998, 63, 222.
57. T. A. Riley, W. J. Hennen, N. K. Dalley, B. E. Wilson, R. K.
Robins, J. Heterocycl. Chem., 1986, 23, 1709.
58. S. N. Mikhailichenko, A. A. Chesnyuk, V. E. Zavodnik, S. I.
Firgang, L. D. Konyushkin, V. N. Zaplishnyi, Khim. Geteroꢀ
tsikl. Soedin., 2002, 326 [Chem. Heterocycl. Compd.
(Engl. Transl.), 2002, 38, 292].
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J.
Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala,
K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain,
O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford,
J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Alꢀ
Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe,
P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzaꢀ
lez, J. A. Pople, GAUSSIAN 03, Revision E.01, Gaussian,
Inc., Wallingford (CT), 2004.
59. J. K. Chakrabarti, D. E. Tupper, Tetrahedron, 1975, 31, 1879.
60. B. Akteries, J. C. Jochims, Chem. Ber., 1986, 119, 1133.
61. A. R. Katritzky, B. V. Rogovoy, V. Y. Vvedensky, N. Hebert,
B. Forood, J. Org. Chem., 2001, 66, 6797.
65. K. Yu. Suponitsky, Y. Liao, A. E. Masunov, J. Phys. Chem.
A, 2009, 113, 10994.
62. V. Kikelj, K. Julienne, P. Janvier, J.ꢀC. Meslin, D. Deniaud,
Synthesis, 2008, 3453.
66. K. Yu. Suponitsky, A. E. Masunov, M. Yu. Antipin, Menꢀ
deleev Commun., 2009, 19, 311.
63. A. V. Shastin, T. I. Godovikova, B. L. Korsunskii, Khim.
Geterotsikl. Soedin., 1999, 79 [Chem. Heterocycl. Compd.
(Engl. Transl.), 1999, 35, 75].
67. R. F. W. Bader, Atoms in Molecules. A Quantum Theory, Clarꢀ
endon Press, Oxford, 1990, 438 pp.
68. T. A. Keith, AIMAll (Version 09.04.23), 2009, http://
aim.tkgristmill.com.
69. E. Espinosa, E. Molins, C. Lecomte, Chem. Phys. Lett., 1998,
285, 170.
70. E. Espinosa, I. Alkorta, I. Rozas, J. Elguero, E. Molins,
Chem. Phys. Lett., 2001, 336, 457.
64. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, T. V. Jr.,
K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajiꢀ
ma, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E.
Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo,
Received July 19, 2011;
in revised form November 8, 2011