Synthesis, structure, and dynamic behavior in solution of arylamino-1,3,5-triazines. 1. Unsymmetrically substituted arylamino-1,3,5- triazines

Article abstract of DOI:10.1007/s11172-006-0135-0

Ten unsymmetrically substituted arylamino-1,3,5-triazines were synthesized and studied by dynamic NMR spectroscopy. The free energies of the hindered rotation ΔG^≠ are in 59-77 kJ mol^-1 range. Using difference-mode NOE NMR experiments

Full text of DOI:10.1007/s11172-006-0135-0

Russian Chemical Bulletin, International Edition, Vol. 54, No. 10, pp. 2441—2451, October, 2005
2441
Synthesis, structure, and dynamic behavior in solution
of arylaminoꢀ1,3,5ꢀtriazines
1. Unsymmetrically substituted arylaminoꢀ1,3,5ꢀtriazines
P. A. Belyakov,aꢀ A. V. Shastin,b and Yu. A. Strelenkoa
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: pbel@server.ioc.ac.ru
bInstitute of Problems of Chemical Physics, Russian Academy of Sciences,
1 prosp. Akad. Semenova, 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 515 3588. Eꢀmail: shastin@icp.ac.ru
Ten unsymmetrically substituted arylaminoꢀ1,3,5ꢀtriazines were synthesized and studied
by dynamic NMR spectroscopy. The free energies of the hindered rotation ∆G≠ are in
59—77 kJ mol–1 range. Using differenceꢀmode NOE NMR experiments, the structures of the
major and minor rotation isomers were proved. The DFT B3LYP/6ꢀ31G* calculations were
performed. The difference between the calculated rotation barriers and the experimental values
obtained by line shape analysis is less than 7.6 kJ mol–1. The height of the rotation barrier varies
in a 18 kJ mol–1 range depending on the substituents in the triazine ring.
Key words: arylaminoꢀ1,3,5ꢀtriazines, synthesis, structure in solution, hindered rotation,
activation parameters, substitution effects, dynamic NMR spectroscopy, DFT B3LYP/6ꢀ31G*
calculations.
The internal dynamics of organic compounds has a
pronounced influence on their thermodynamic, electriꢀ
cal, optical, chemical, and other properties, which is esꢀ
pecially important for biochemical processes, for underꢀ
standing of the mechanisms of action, and for the design
of new biologically active substances, first of all, medical
drugs.1
1,3,5ꢀTriazines, or symmꢀtriazines, have been known2
for more than 100 years. Their derivatives are used as
herbicides, pesticides,3,4 drugs,5 as the base for the liquidꢀ
phase or carrierꢀsupported combinatorial libraries,6 and
as condensing reagents in peptide synthesis.7 Recently, a
fully unsymmetrically substituted triazine has been found
in the algae Halimeda xishaensis, isolated, and characterꢀ
ized by a set of physicochemical methods.8 This was the
first aromatic symmꢀtriazine found in a natural object (for
discussion on this point, see Ref. 9).
The hindered rotation in substituted 1,3,5ꢀtriazines
has been discovered not long ago; therefore, data on the
stereodynamics of these compounds are few10—15 as comꢀ
pared with the data on the synthesis and other properties
of 1,3,5ꢀtriazines, which were considered in more than a
thousand publications during the last 5 years alone. Iniꢀ
tially, it was found that the NMR spectra of symmetriꢀ
cally substituted alkyl(aryl)aminoꢀ1,3,5ꢀtriazines exhibit
double sets of signals for the substituents in the triazine
ring.10 At higher temperatures, only one set of signals
remains. The discovered process cannot be attributed to
inversion of the nitrogen lone pair or to prototropic tauꢀ
tomerism. The presence of electronꢀwithdrawing substituꢀ
ents in the triazine ring and different substituents at the
exocyclic nitrogen atom are necessary conditions for obꢀ
serving two or several conformational isomers of aminoꢀ
1,3,5ꢀtriazines in the NMR spectra at room temperaꢀ
ture.16 For diaminoꢀ1,3,5ꢀtriazines, the coalescence temꢀ
perature is usually <0 °C and for triaminoꢀ1,3,5ꢀtriazines,
it is close to the freezing point of the solvent.11 For a
number of aminoꢀ1,3,5ꢀtriazines, the activation energies
have been determined and the rotation barriers have been
calculated theoretically.11—15 The researchers cited atꢀ
tribute the hindered rotation in substituted aminoꢀ1,3,5ꢀ
triazines to the electronꢀwithdrawing properties of the
triazine ring, resulting in a higher Ctr—Nam bond order
(tr is triazine, am is amine). Earlier studies into the dyꢀ
namic effects are represented by scattered examples.
The free activation energies of hindered rotation deterꢀ
mined in these studies for various compounds using the
WinnꢀJones equation17 cannot be properly compared with
one another, as these values have been obtained for difꢀ
ferent temperatures (at the coalescence points). No data
are available on the stereodynamics of substituted arylꢀ
aminoꢀ1,3,5ꢀtriazines, which are of obvious theoretical
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2366—2376, October, 2005.
1066ꢀ5285/05/5410ꢀ2441 © 2005 Springer Science+Business Media, Inc.

2442
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
Belyakov et al.
interest from the standpoint of interaction of two classical
aromatic18 systems. The activation parameters for the
rotation about the Ctr—NAr bond in the arylaminoꢀsubꢀ
stituted symmꢀtriazines have not been found in the literaꢀ
ture either. In addition, the hindered rotation in unꢀ
symmetrically substituted triazines has been scarcely studꢀ
ied and no data on the ∆H≠ or ∆S≠ values in the fully
unsymmetrically substituted symmꢀtriazines are available.
Meanwhile, 1,3,5ꢀtriazines are excellent model comꢀ
pounds for investigating hindered rotation in the heteroꢀ
cyclic series.
Study of the hindered rotation processes has also a
practical value as regards the study of biological objects.
In particular, in the case of 1,3,5ꢀtriazines, dynamic NMR
was used to estimate the efficiency of drugs employed for
decreasing the multidrug resistance of tumor cells.14
In a study of hindered rotation in unsymmetrically
substituted 2ꢀchloroꢀ4ꢀmethoxyꢀ6ꢀphenylaminoꢀ1,3,5ꢀ
triazine (1), we found that the sterically more hindered
rotation isomer is thermodynamically more stable in
solution.19 Here we continued the study of this pheꢀ
nomenon in the series of unsymmetrically and symꢀ
metrically substituted analogs of compound 1 using quanꢀ
tum chemical calculations and dynamic NMR. The purꢀ
pose of this study was to gain information on the activaꢀ
tion parameters of the hindered rotation in arylaminoꢀ
1,3,5ꢀtriazines with various substituents and to analyze
the effect of the substituent nature in the triazine ring and
the steric effect of the arylamine group on the height of
the barrier to hindered rotation. Dynamic NMR line
shape analysis (LSA) for arylaminoꢀ1,3,5ꢀtriazines has
been carried out.20 LSA is the most accurate method for
determining the rate constants for twoꢀposition exꢀ
change.21,22
Results and Discussion
Synthesis. Unsymmetrical symmꢀtriazines were preꢀ
pared by a procedure that makes it possible to avoid hydroꢀ
lysis and transalkoxylation. The point is in the use of the
lithium hydride base, which offers a number of advanꢀ
tages over aqueous solutions of alkali, carbonates, and
bicarbonates or tertiary amines, which are used most ofꢀ
ten in the modification of chlorotriazines.23—29 The reacꢀ
tion of alcohols with lithium hydride is irreversible, giving
the corresponding alkoxide and hydrogen. In addition,
the reaction rate can be controlled by changing the grain
size in the lithium hydride powder. Using this base, it is
possible to create microconcentrations of the alkoxide,
which allows one to take full advantage of the existing
difference between the reactivities of diꢀ and monoꢀ
chlorotriazines for selective replacement of one chloꢀ
rine atom.
Published data on the synthesis and use of trifluoroꢀ
ethoxyꢀsymmꢀtriazines are few.30—34 We have not found
any data on hexafluoroisopropoxyꢀsymmꢀtriazine derivaꢀ
tives; these triazine compounds were obtained for the first
time. The yields of triazines 1—10 were 85—99%; the
synthetic procedures are given in the Experimental.
Dynamic behavior. Aminoꢀsymmꢀtriazines show hinꢀ
dered rotation about the exocyclic C—N bond (Scheme 1),
which is partially double, due to the n—πꢀconjugation of
the lone pair of the amine nitrogen with the triazine ring.35
The relatively high rotation barrier in aminotriazines can
be attributed to the contribution of the dipolar canonical
structures (see Scheme 1). The substituents R1, R2, R3,
and R4 that stabilize these structures increase the barrier
to hindered rotation. Dynamic effects in aminoꢀsymmꢀ
triazines with two identical substituents in the triazine
ring have been detected previously10—15 and described as
the hindered internal rotation about the C—N bond. For
arylaminoꢀsubstituted symmꢀtriazines with three different
substituents in the triazine ring, similar effects are to be
expected; however, the relative energies of the rotation
isomers (conformers) may prove to be different, which
would give rise to a nonꢀdegenerate exchange proꢀ
cess12 (Fig. 1).
The study was carried out with alkoxyꢀ and perfluoroꢀ
alkoxyꢀsubstituted anilinochlorotriazines 2—10, symmetꢀ
ric and unsymmetric analogs of compound 1. They were
chosen from the following considerations: in monoarylꢀ
aminoꢀsubstituted alkoxytriazines, only one bond is inꢀ
volved in the hindered rotation; variation of the substituꢀ
ents in the triazine ring allows one to change its electronꢀ
withdrawing properties; the introduction of various subꢀ
stituents into the arylamine fragment provides the possiꢀ
bility of estimating the substituent contributions. The use
of perfluoroalkoxy groups pursued two goals, namely, the
change in the donorꢀacceptor properties of the substituꢀ
ents and an increase in the solubility of model compounds.
For some aminodichlorotriazine derivatives, the problem
of solubility at low temperatures proved unsolvable.11,12,15
Owing to the presence of fluorine in perfluoroalkoxyꢀ
1,3,5ꢀtriazine molecules, dynamic experiments can take
advantage of 19F NMR spectroscopy, which requires less
experimental time than 13C NMR and covers a broader
It has been shown previously19 that at low temperaꢀ
tures, the H and 13C NMR spectra of compound 1 exꢀ
1
hibit two sets of signals corresponding to two rotation
isomers, namely, conformers A and B (the arrow thickꢀ
ness reflects different electronꢀwithdrawing characterꢀ
istics of substituents in the triazine ring). For other
symmꢀtriazines with three different substituents (3—10),
signals of different conformers in a ratio other than 1 : 1
are also observed. The structure of the major and minor
conformers was determined using nuclear Overhauser efꢀ
fect experiments36 (NOE).
1
range of chemical shifts than H NMR, which is signifiꢀ
DFT B3LYP calculations. The difference between the
ground state energies of conformers A and B (see Fig. 1) is
cant for shortening the experimental time.

Hindered rotation of symmꢀtriazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
2443
Scheme 1
Comꢀ
pound
R1
R2
R3
R4
Cl
OMe
Cl
Comꢀ
pound
R1
R2
R3
R4
Cl
OMe
Cl
1
2
3
4
5
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
OMe
OMe
OCH2CF3
OCH2CF3
OEt
6
7
8
9
10
Ph
Ph
H
H
H
H
OCH(CF3)2
OCH(CF3)2
OCH2CF3
OMe
2,6ꢀMe2C6H3
oꢀPhC6H4
Ph
OMe
Cl
Cl
Cl
Me
OMe
corresponding to the rotation about the N—Ctr bond was
found in compound 1. NOE experiments have shown19
that conformer А predominates in an equilibrium mixture
(see above).
In order to elucidate the molecule geometry in the
ground and transition states and to calculate the hindered
rotation barriers, we carried out DFT B3LYP/6ꢀ31G*
quantum chemical calculations for some arylaminoꢀsymmꢀ
triazines. Several of transition states (TS) corresponding
to the hindered rotation were identified. The calculation
results are presented in Table 1.
due to the fact that one is energetically preferred over the
other. A twoꢀposition nonꢀdegenerate exchange process
E
∆G≠
∆G°
Fig. 1. Hindered rotation in fully unsymmetrically substituted arylaminoꢀsymmꢀtriazines (A and B are conformers, TS1 is the
transition state); the thickness of the arrows reflects different electronꢀwithdrawing characteristics of substituents in the triazine ring.

2444
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
Belyakov et al.
Table 1. Bond lengths (d) and sums of bond angles at the amine N atom (Σω) in the ground states
(conformer A) and in the transition state TS1 during rotation about the N—Ctr bond and barriers
to rotation about this bond (∆G≠298) found for symmꢀtriazines 1, 3, 5, 8, and 10 by DFT
B3LYP/6ꢀ31G* calculations
Comꢀ
pound
Ground state
d/Å
Transition state TS1
Σω
/deg
d/Å
Σω
∆G≠
298
/kJ mol–1
/deg
N—Ctr
N—CAr
N—Ctr
N—CAr
1
3
5
8
1.358
1.357
1.360
1.354
1.363
1.411
1.411
1.409
1.432
1.434
360.0
360.0
360.0
359.1
359.7
1.421
1.420
1.422
1.425
1.420
1.415
1.417
1.415
1.442
1.416
341.6
341.3
341.8
333.9
349.1
72.7
68.3
71.1
81.2
66.8
10
Structure of symmꢀtriazines 1, 3, 5, 8, and 10 in conꢀ
formations A and B. The conformers of symmꢀtriazine 1
are shown in Fig. 2, a and b. The relative energies of the
conformers are equal to within the accuracy of the calcuꢀ
lation method.37 It is noteworthy that in conformations A
and B of molecule 1, the triazine ring, the NH group, and
the benzene ring occur in one plane. The sum of the bond
angles at the amine nitrogen atom (N(9), see Fig. 2, a
and b) in these conformations is 360° (see Table 1). In
conformer A, the C(6)—N(9) bond length (1.358 Å) is
smaller than the C(11)—N(9) bond length (1.411 Å), i.e.,
the order of the C(6)—N(9) bond is greater than the
C(11)—N(9) bond order. Thus, the conjugation of the
lone pair with the triazine ring is more efficient than that
with the benzene ring. Similar data were obtained for
conformer B, the C(6)—N(9) and C(11)—N(9) bond
lengths being 1.359 and 1.411 Å, respectively.
According to DFT B3LYP/6ꢀ31G* calculations, the
other symmꢀtriazines have a similar structure (see Table 1).
Exceptions are compounds 8 and 10 in which the benzene
Cl(8)
a
b
H(18)
C(10)
H(17)
N(9)
Cl(8)
N(5)
H(20)
H(22)
H(19)
C(13)
C(4)
N(3)
H(21)
C(15)
C(14)
C(6)
C(4)
N(5)
C(11)
C(12)
H(19)
C(12)
C(11)
C(14)
C(15)
N(3)
C(6)
N(9)
H(17)
N(1)
C(2)
H(25)
C(16)
H(21)
C(2)
C(13)
H(20)
H(24)
C(10)
H(24)
O(7)
H(22)
N(1)
H(25)
H(23)
C(16)
O(7)
H(18)
H(23)
H(12)
C(4)
H(23)
C(15)
H(21)
C(11)
c
d
H(11)
O(14)
H(22)
C(10)
H(13)
C(5)
C(6)
H(20)
H(24)
C(3)
C(2)
H(25)
Cl(20)
C(16)
C(9)
N(3)
C(4)
C(12)
C(13)
H(19)
H(18)
C(8)
N(15)
C(14)
H(10)
N(17)
C(7)
H(9)
N(5)
C(6)
C(2)
N(7)
H(17)
N(1)
H(8)
C(18)
O(21)
N(19)
H(25)
C(22)
N(1)
H(23)
Cl(16)
H(24)
Fig. 2. Geometrical structure of the molecule of compound 1 in conformations A (a) and B (b) and in the transition states TS1 (c) and
TS2 (d) corresponding to hindered rotation about the N—Ctr and N—CAr bonds, respectively.

Hindered rotation of symmꢀtriazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
2445
Table 2. Total charges on the triazine fragment (Σztr), the Ph
and NH groups (ΣzPh and ΣzNH, respectively) in conformers A
and B of the molecule of compound 1 and in the transition state
TS1 during rotation about the N—Ctr bond and changes in the
charges relative to the state TS1 (∆Σz)
ring of the aniline substituent does not lie in the same
plane with the triazine ring. The N—CAr bonds in these
molecules are longer than those in other compounds, i.e.,
the lone pair is conjugated only with the triazine ring. In
compound 8, this appears to be due to the presence of two
orthoꢀMe groups in the benzene ring, which create steric
hindrances to the coplanar arrangement of the rings. In
symmꢀtriazine 10, a coplanar arrangement of the rings is
prevented by the Me group at the exocyclic nitrogen atom.
The sums of the bond angles at the amine nitrogen in
compounds 8 and 10 are less than 360° (see Table 1), i.e.,
the N atom has a partially pyramidal structure.
Conformer,
state
Σztr
∆Σztr ΣzPh ∆ΣzPh
ΣzNH
∆ΣzNH
A
B
TS1
–0.22 0.33 0.63
–0.22 0.33 0.63
–0.41
–0.41
0
–0.41 0.08
–0.41 0.08
0.11
0
0.22
–0.33
0
Structure of the transition state TS1 to the rotation
about the N—Ctr bond in compounds 1, 3, 5, 8, and 10.
The results of calculation of the geometry of the transiꢀ
tion state TS1, corresponding to the hindered rotation
about the N—Ctr bond in compound 1, are shown in Fig.
2, c. In this transition state, the triazine ring and the
substituents in the amino group occur in nearly perpenꢀ
dicular planes. Unlike the ground state of conformers A
and B, in the transition state, the sum of the bond angles
at exocyclic nitrogen is 341.6° (see Table 1). Since no
n—πꢀconjugation with the triazine ring is present, the
nitrogen lone pair in this transition state, as shown by
calculations, is conjugated only with the benzene ring.
The N—Ctr bond in the transition state related to the
rotation around this bond is substantially elongated comꢀ
pared with that in conformers A and B, being equal to
1.421 Å. The N—CAr bond length virtually does not
change with respect to those in the ground states (1.415 Å).
This bond is somewhat shorter than the N—Ctr bond, due
to the conjugation between the nitrogen lone pair and the
benzene ring.
The other symmꢀtriazines studied by DFT
B3LYP/6ꢀ31G* calculations have a similar structure in
the transition state TS1 (see Table 1). An exception is
compound 8 in which no n—πꢀconjugation with the benꢀ
zene ring occurs in the transition state TS1 due to the
reasons outlined above. The sum of the bond angles at the
amine nitrogen in its molecule is the smallest, while the
N—CAr bond is the longest among the group of comꢀ
pounds in question (see Table 1). Hence, the aromatic
ring of the aniline fragment in symmꢀtriazine 8 does not
show πꢀdonor properties in either the ground state or the
transition state TS1.
the negative activation entropy of the rotation (∆S≠ =
–27.3 J mol–1 К–1). The negative ∆S≠ values correspond
to molecules with more polar ground state.38 Thus, the
calculations are in line with the negative ∆S≠ value found
experimentally19 for symmꢀtriazine 1.
The transition state TS2 to the rotation around the
N—CAr bond in triazines 1, 3, 5, 8, and 10. The results of
geometry calculations of the transition state TS2, correꢀ
sponding to the rotation around the N—CAr bond in comꢀ
pound 1, are shown in Fig. 2, d. In the transition state
TS2, the benzene ring and the aminoꢀgroup substituents
occur almost in perpendicular planes. As in conformaꢀ
tions A and B, the sum of the bond angles at the exocyclic
nitrogen (Σω) in the state TS2 amounts to 360°. Thus, the
n—πꢀconjugation with the benzene ring is not realized
and, according to calculation results, the nitrogen lone
pair in this transition state is involved in conjugation only
with the triazine ring.
The N—Ctr bond in TS2 is somewhat shorter than
that in the initial conformers A and B, being equal to
1.355 Å. The N—CAr bond length is longer than that in
the ground states, namely, 1.433 Å (see Table 1).
The barriers to rotation about the N—Ctr bond
found by DFT B3LYP/6ꢀ31G* calculations are in the
67—81 kJ mol–1 range, i.e., they are somewhat higher
than the earlier15 estimates of the rotation barriers in
symmꢀtriazines.
According to calculations, the barriers to rotation
about the N—CAr bonds in the compounds under study
(12—27 kJ mol–1) are much lower than those about the
N—Ctr bond, which is in line with the estimates of the
barrier to rotation around this bond in symmꢀtriazines
reported previously15 (17 kJ mol–1).
Charge distribution in the ground and transition states
of compound 1. Comparison of the charge distribution in
conformers A and B with that in the transition state to
rotation about the N—Ctr bond in compound 1 demonꢀ
strates that the transition state is less polar than the ground
states (Table 2). Indeed, unlike conformers A and B,
the TS1 state has overall charge of the same sign on the
triazine and benzene rings, due to the back migration
of the electron density to nitrogen and partly to the
benzene ring. The foregoing can also be confirmed by
Thus, the DFT B3LYP/6ꢀ31G* calculations indicate
that the barrier to rotation about the N—Ctr bond in
anilinoꢀsymmꢀtriazines is much higher than the barrier to
rotation about the N—CAr bond.
The data obtained show that rotation about the N—CAr
bond can be regarded as free, while rotation about the
N—Ctr bond is hindered. The calculated heights of the
barriers to rotation for the compounds in question are in
67—81 kJ mol–1 range and do not differ much from the
corresponding values for formamides.39

2446
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
Belyakov et al.
Table 3. Ratios of conformers A and B and energy differences
(∆G°) for fully unsymmetrically substituted symmꢀtriazines 1, 3,
5, and 10
In Nꢀmethylaniline derivative 10, the ∆G° value is
much lower than in aniline derivative 1 (see Table 3). The
methyl group is more bulky than a hydrogen atom. Acꢀ
cording to calculations, the triazine and benzene rings in
the ground state of compound 10, unlike those in comꢀ
pounds 1, 3, and 5, do not lie in one plane and no
n—πꢀconjugation of the nitrogen lone pair with the benꢀ
zene ring is present. Nevertheless, even in this case, conꢀ
former A predominates in solution.
In a previous publication,19 we suggested that an inꢀ
tramolecular hydrogen bond may have an influence on
the distribution of the conformers. The data obtained for
Nꢀmethylaniline derivative 10 are inconsistent with this
hypothesis. A conformer ratio other than 1 : 1 exists also
in the absence of hydrogen in compound 10. The introꢀ
duction of electronꢀwithdrawing substituents into the triꢀ
azine ring results in a decrease in the conformer ratio.
Nevertheless, the energy difference between conformers
A and B observed experimentally is so small that currently
it is impossible to draw definite conclusions concerning
the reasons for higher stability of conformer A on the basis
of the available calculation results.37,43
Experimental determination of the barriers. In this
study, the activation parameters of the hindered rotation
in 1,3,5ꢀtriazines with different substituents were deterꢀ
mined experimentally by LSA. The results of studies are
given in Table 4.
The free activation energies for the hindered rotation
in symmꢀtriazines determined experimentally lie in the
range of 59—77 kJ mol–1. Note that the barriers found by
the DFT B3LYP/6ꢀ31G* calculations are somewhat
higher than those determined experimentally by dynamic
NMR. Nevertheless, the calculation results are in good
agreement with experimental data.
Comꢀ
pound
A : B
∆G°
/kJ mol–1
1
3
5
10
1 : 0.51
1 : 0.63
1 : 0.50
1 : 0.90
1.2
0.9
1.6
0.1
Determination of the conformer ratio. The ratios and
the relative energies of the conformers (∆G°) of some fully
unsymmetrically substituted symmꢀtriazines are summaꢀ
rized in Table 3. The ∆G° value for the ethoxy derivative 5
is somewhat higher than that for 1 (see Table 3). The
ethoxy group is more bulky than the methoxy group; thereꢀ
fore, the higher ratio of the conformers in compound 5
with respect to compound 1 cannot be attributed to steric
factors. The steric factors do not have a substantial influꢀ
ence on the conformer ratio in symmꢀtriazines, unlike
those in other known40 cases of hindered rotation about
the C—N bond. The increase in the ∆G° value may be due
to electronic factors, in particular, lower electronꢀwithꢀ
drawing properties of the EtO group compared to the
MeO group.
In the trifluoroethoxy derivative 3, the difference beꢀ
tween the conformer energies is smaller than this differꢀ
ence for compounds 5 and 1 (see Table 3). In this case,
the steric factors do not, most likely, exert a substantial
effect on the relative energies of the two conformers. The
OCH2CF3 group is a strong electron acceptor with the
constant σI = 0.81,41 which is much higher than these
values for ethoxy and methoxy groups (σI = 0.22—0.33).42
The decrease in the energy difference between conformꢀ
ers A and B with respect to that in compound 1 or 5 can be
attributed to more pronounced electronꢀwithdrawing
properties of the substituents in the triazine ring.
The rotation barrier in Nꢀmethylꢀ2,4,6ꢀtrinitroaniline
is only 47.2 kJ mol–1 44
i.e., the barriers to rotation in
,
triazines are much higher than in anilines. This is attribꢀ
utable to the fact that the triazine ring is a stronger elecꢀ
Table 4. Activation parameters of the hindered rotation about the N—Ctr bond in symmꢀtriꢀ
azines 1—10
Comꢀ
pound
∆H≠
∆S≠
∆G≠
*
∆T/К
Monitored
nucleus
298
/kJ mol–1
/J mol–1 K–1
/kJ mol–1
1
2
3
4
5
57.4 1.9
75.2 1.1
65.8 0.9
67.1 0.4
55.3 1.8
62.6 3.2
68.9 1.3
75.5 2.5
65.1 2.1
88.1 5.8
–27.3 6.5
54.3 3.9
–0.2 3.0
19.3 1.4
–27.6 5.4
–18.1 10.3
18.6 4.7
–3.8 7.6
9.6 7.7
65.6
59.0
65.8
61.4
63.5
68.0
63.4
76.6
62.3
62.2
269—304
260—285
280—305
270—290
270—290
295—320
255—290
320—344
265—285
273—287
13C
13C
19F
19F
13C
19F
1H
6
7
8
9
19F
1H
10
87.0 20.7
13C
* Determination error is 0.8 kJ mol–1
.

Hindered rotation of symmꢀtriazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
2447
tron acceptor than the benzene ring. The height of the
barrier to hindered rotation about the C—N bond is most
sensitive to the πꢀelectronꢀwithdrawing properties, beꢀ
cause these properties determine the order of the bond
around which the rotation takes place. Due to the presꢀ
ence of substituents (Cl, alkoxy group, and other), the
triazine ring has stronger electronꢀwithdrawing properties
than the trinitrobenzene fragment. Previously,45,46 a comꢀ
parative study of the rotation barriers in dimethylaminoꢀ
substituted nitropyridines and pyrimidines has been carꢀ
rier out. On the basis of the obtained results, the researchꢀ
ers concluded that the effect of one or several nitrogen
atoms on the electronꢀwithdrawing properties of the
heterocyclic ring is comparable with the effect of introꢀ
duction of a nitro group in the appropriate position of a
carbon ring. In view of the rotation barriers in Nꢀmethylꢀ
2,4,6ꢀtrinitroaniline, nitroꢀsubstituted pyrimidines, pyꢀ
ridines, and 1,3,5ꢀtriazines, the triazine ring is the stronꢀ
gest acceptor of the electron lone pair of the exocyclic
nitrogen atom.
of the lone electron pair of the exocyclic nitrogen with the
benzene ring. Hence, the n—πꢀconjugation with the triꢀ
azine ring becomes predominant and the N—Ctr bond
order increases, giving rise to a higher barrier to rotation
about this bond. Without n—πꢀconjugation with the
arylamine group, this group can be represented as a bulky
alkylamine group, as indicated by the similarity of the
activation parameters of the hindered rotation, which are
76.6 and 78 kJ mol–1 for compound 8 and dichloroꢀ
octylaminoꢀsymmꢀtriazine,12 respectively. Thus, the value
of 11 kJ mol–1 determined experimentally can serve as a
quantitative measure of the energy of n—πꢀconjugation of
the lone electron pair of the exocyclic nitrogen with the
aromatic group. This value is in good agreement with the
calculation results.
Note that in those cases where the substituents in the
aniline fragment do not violate the planar structure of the
triazine—aniline substituent system (cf. ∆G≠ for comꢀ
298
pounds 2, 9, and 10; see Table 4), the barrier height does
not change much. A quantitative estimation of the effect
of substituents in the arylamino fragment on the height of
the rotation barrier will be given elsewhere.
Note that hindered rotation in some of the symmꢀtriꢀ
azines studied is characterized by great absolute magniꢀ
tudes of ∆S≠. On the basis of calculations, these ∆S≠ valꢀ
ues can be explained by assuming that the ground state is
more polar than the transition state in the case of negative
activation entropies. Conversely, high positive values of
the activation enthalpy are attributed to less polar ground
state compared to the transition state.38 It has been shown
above that in compound 1, the high negative activation
entropy is in good agreement with the calculated results.
The ∆S≠ value in Nꢀmethylꢀ2,4,6ꢀtrinitroaniline is also
The effect of substituents in the triazine ring on the
height of the hindered rotation barriers. The electronꢀwithꢀ
drawing properties of the groups R3 and R4 influence the
height of the rotation barrier in arylaminoꢀsymmꢀtriꢀ
azines.11 Comparison of the changes in the ∆G≠ values
298
for the pairs of compounds 2 and 1, 3 and 4, and 6 and 7
(see Table 4) provides the following conclusion: the reꢀ
placement of the chlorine atom in the triazine ring by the
MeO group entails a decrease in the barrier to hindered
rotation. This is in line with the previous data11 on variaꢀ
tion of the rotation barriers in bisꢀ and tris(N,Nꢀdialkylꢀ
amino)ꢀsymmꢀtriazines. A decrease in the barrier may be
due to the decrease in the electronegative effect of the
triazine ring upon the replacement of the chlorine atom
by the less electronegative methoxy group.11 This is acꢀ
companied by a decrease in the electron density on the
N—Ctr bond, inducing a decrease in the barrier to rotaꢀ
tion about this bond.
The NMR spectra of fully unsymmetrically substiꢀ
tuted 1,3,5ꢀtriazines exhibit a nonꢀdegenerate twoꢀposiꢀ
tion exchange process, representing the hindered rotation
about the N—Ctr bond. Using quantum chemical calcuꢀ
lations, the geometries and the relative energies of the
ground and transition states were calculated. It was found
that conformer А predominates in an equilibrium mixture
for symmꢀtriazines 3—10 (see above). However, the enꢀ
ergy difference between the conformers observed experiꢀ
mentally is so minor that no categorical conclusions conꢀ
cerning the reasons for higher stability of conformer A can
be currently drawn based on the calculation results. Preꢀ
sumably, the energy difference between the conformers is
related to different electronꢀwithdrawing properties of the
groups in the triazine ring. The activation parameters for
rather high and amounts to 39 J mol–1 K–1
.
The effect of the structure of the aromatic substituent
on the barrier height. According to experimental data, the
rotation around the N—CAr bond remains free on the
NMR time scale. It can be hampered due to n—πꢀconjuꢀ
gation of the lone pair of the exocyclic nitrogen atom with
the aryl substituent. According to calculation results, the
barrier to rotation around this bond in compound 1 is
13.4 kJ mol–1. By comparing the heights of the rotation
barrier for compounds 3 and 8, one can estimate quantiꢀ
tatively the energy of interaction between the exocyclic
nitrogen lone pair and the aryl group. The presence of
orthoꢀmethyl groups in the aniline ring of compound 8 is
an essential steric hindrance to a coplanar arrangement of
the triazine and benzene rings. According to calculations,
this should result in a pronounced increase in the N—CAr
bond length accompanied by some decrease in the N—Ctr
bond length (see Table 1). The ∆G≠
value for comꢀ
298
pound 8 is 11 kJ mol–1 higher than that for compound 3
and is comparable with this value for dichloroalkylaminoꢀ
symmꢀtriazines.12 Based on the calculations, this proꢀ
nounced increase in the rotation barrier can be ascribed
to the fact that two bulky groups in the orthoꢀpositions of
the aromatic ring preclude the effective n—πꢀconjugation

2448
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
Belyakov et al.
calculations were carried out using the DYNNMR program,10
which iterates the intensities, the resonance frequencies of the
exchanging signals, and the lifetimes in particular states. The
crossꢀrelaxation times were measured in each temperature point.
The geometry optimization and the calculation of the enꢀ
ergy of symmꢀtriazines was carried out using the B3LYP hybrid
potential49—51 in the standard 6ꢀ31G* basis set.52 This method
ensures a sufficient accuracy of calculations compared with other
methods.43 The character of the stationary points found was
checked by calculating the eigen values of the matrix of the
second derivatives of energy (the absence of imaginary frequenꢀ
cies for the ground states and the presence of one imaginary
frequency for the transition states). The atom charges were calꢀ
culated by the Mulliken method. The thermodynamic functions
were determined within the harmonic oscillator—rigid rotator
model. All calculations were performed using the Gaussian 98
software.53 For visualization of molecular structures and vibraꢀ
tions, the MOLDEN graphical package was used.54
the hindered rotation in ten symmꢀtriazines were meaꢀ
sured experimentally. The barrier heights are in good
agreement with the calculation results.
This communication opens a series of publications
devoted to the synthesis, structure, and dynamic behavior
in solution of arylaminoꢀ1,3,5ꢀtriazines. This paper gives
an account of studies dealing with unsymmetrically subꢀ
stituted arylaminoꢀ1,3,5ꢀtriazines. The theoretical secꢀ
tion is an attempt to estimate the scope of the DFT
B3LYP/6ꢀ31G* quantum chemical calculations for the
studies of hindered rotation in symmꢀtriazines. The use of
other methods and basis sets for taking into account the
electron correlation is the subject of further theoretical
studies. The subsequent publications are planned to conꢀ
sider the behavior of arylaminoꢀ1,3,5ꢀtriazines containꢀ
ing substituents in the aniline fragment, paraꢀsubstituted
arylaminoꢀ1,3,5ꢀtriazines, and to study the entropy—enꢀ
thalpy compensation.
2ꢀChloroꢀ4ꢀmethoxyꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine (1).
2,4ꢀDichloroꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine (5 g, 20.75 mmol),
synthesized by known procedures,23—26 was dissolved in methaꢀ
nol (50 mL) and cooled to 0 °C on an ice bath. A lithium hydride
coarse powder (grain size 1—2 mm) (190 mg, 23.75 mmol) was
added with stirring, the mixture was stirred for 2.5 h (the prodꢀ
uct may precipitate during the reaction), and the bath was reꢀ
moved. The reaction mixture was left for ~14 h, diluted with
water, and filtered. The precipitate was dried on the filter to as
constant weight. Yield 4.70 g (95.8%), m.p. 140—141 °C (methaꢀ
nol). Found (%): C, 50.78; H, 3.88; Cl, 14.52; N, 24.12.
C10H9ClN4O. Calculated (%): C, 50.75; H, 3.83; Cl, 14.98;
Experimental
1
The H, 13C—{1H}, and 19F—{1H} NMR spectra were reꢀ
corded by standard procedures on Bruker AMꢀ300, Bruker
WMꢀ250, and Bruker ACꢀ200 spectrometers. Dynamic NMR
experimental series were carried out using the GlobalꢀDNMR
software we developed.47 For each compound, seven to twelve
points were recorded in the range from 20—30 °C below the
coalescence point to 10—15 °C above coalescence point. For
NMR experiments, solutions of compounds in a methylene
dichloride—chloroform—carbon tetrachloride (60 : 27 : 13) sysꢀ
tem were used; this solvent mixture allowed working in a broad
temperature range. The NOE experiments for compounds 1, 3,
5, and 10 were carried out at –23 °C. The conformer ratio in
fully unsymmetrically substituted triazines was determined unꢀ
der standard conditions based on the NMR integral intensities
1
N, 23.67. H NMR (DMSOꢀd6), δ: 3.95 (s, 3 H, OMe); 7.12
(m, 1 H, H arom.); 7.35, 7.68 (both m, 2 H each, H arom.);
10.58 (br.s, 1 H, NH). MS, m/z (Irel (%)): 236 [M]+ (86); 235
[M – H]+ (100); 201 [M – Cl]+ (18); 159 [M – C6H5]+ (10);
159 [M – C6H5NH]+ (23); 118 [C6H5NHCN]+ (42); 91
[C6H5N]+ (25); 77 [C6H5]+ (60).
2,4ꢀDimethoxyꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine (2). 2,4ꢀDiꢀ
chloroꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine (2.41 g, 10 mmol) was disꢀ
solved in methanol (50 mL), lithium hydride fine powder
(240 mg, 30 mmol) was added with cooling and stirring and the
mixture was left for ~14 h. Methanol was evaporated on a rotary
evaporator, the residue was washed with water and dried on
a filter to a constant weight. Yield 1.98 g (85.5%), m.p.
134—135 °C (methanol) (cf. Ref. 27: m.p. 133—134 °C (methaꢀ
nol—water)).
2ꢀChloroꢀ6ꢀphenylaminoꢀ4ꢀ(2,2,2ꢀtrifluoroethoxy)ꢀ1,3,5ꢀtriꢀ
azine (3). 2,4ꢀDichloroꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine23—26
(2.41 g, 10.0 mmol) was dissolved in anhydrous THF (10 mL),
2,2,2ꢀtrifluoroethanol (2.5 mL, 34.3 mmol) was added, the mixꢀ
ture was cooled to 0 °C on an ice bath, a lithium hydride coarse
powder (grain size 1—2 mm) (100 mg, 12.5 mmol) was added
with stirring, the mixture was stirred for an additional 2.5 h, and
the bath was removed. The reaction mixture was left for ~14 h,
diluted with water, and filtered. The precipitate was dried on
the filter to a constant weight. Yield 2.9 g (95.2%), m.p.
125—126 °C (heptane). Found (%): C, 43.41; H, 2.86; N, 18.34.
C11H8ClF3N4O. Calculated (%): C, 43.37; H, 2.63; N, 18.39.
1H NMR (DMSOꢀd6), δ: 5.02 (q, 2 H, OCH2); 7.15 (m, 1 H,
H arom.); 7.37, 7.65 (both m, 2 H each, H arom.); 10.84 (br.s,
1 H, NH). MS, m/z (Irel (%)): 304 [M]+ (91); 303 [M – H]+
(100); 285 [M – F]+ (5); 269 [M – Cl]+ (15); 205
R = Imaj/Imin
,
where R is the conformer ratio, Imaj and Imin are the integral
intensities of the signals from the major and minor conformers,
respectively.
The melting points were measured on a Boetius hot stage
with a heating rate of 4 °C min–1 at the melting point. Mass
spectra were recorded on a Varian CHꢀ6 instrument with direct
sample injection into the ion source at an ionizing electron
energy of 70 eV, an accelerating voltage of 1.75 kV, and an
emission current of 100 mA. The molecular ion peaks and fragꢀ
ment ions from chlorineꢀcontaining compounds 1, 3, 5, and
8—10 refer to 35Cl.
The results of the NMR experiments were processed
using standard Bruker software (DISNMR on ASPECTꢀ3000
operating under Adakos, XWINNMR on IBMꢀcompatible
PC operating under Linux) and the programs we developed
for recording and automated processing the DNMR spectra
(GlobalꢀDNMR).47
All procedures for conversion of the spectra into various
data formats were carried out using the CODER7 program.48
For LSA, the signals of the alkoxy and fluoroalkoxy subꢀ
1
stituents in the H, 13C, and 19F NMR spectra were used. The

Hindered rotation of symmꢀtriazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
2449
[M – OCHCF3]+ (10); 185 [(M – NCNHC6H5) – H]+ (12);
144 [269 – CNOCH2CF3]+ (35); 118 [NCNHC6H5]+ (45); 91
[C6H5N]+ (15); 77 [C6H5]+ (35); 69 [CF3]+ (10).
fluoropropꢀ2ꢀoxide (from 2.5 mL of 1,1,1,3,3,3ꢀhexafluoroꢀ
propanꢀ2ꢀol and 195 mg of finely dispersed lithium hydride
powder, 24.4 mmol each) in anhydrous THF (15 mL), the mixꢀ
ture was left for ~14 h, the solvent was evaporated, and the
residue was washed with water and dried on the filter to a conꢀ
stant weight. Yield 3.5 g (95%), m.p. 82—83 °C (methanol).
Found (%): C, 42.54; H, 2.83; N, 15.13. C13H10F6N4O2. Calcuꢀ
lated (%): C, 42.40; H, 2.74; N, 15.21. 1H NMR (DMSOꢀd6), δ:
3.99 (s, 3 H, OMe); 6.94 (m, 1 H, OCH); 7.12 (m, 1 H, H arom.);
7.37 (m, 2 H, H arom.); 7.68 (br.m, 2 H, H arom.); 10.44 (br.s,
1 H, NH). MS, m/z (Irel (%)): 368 [M]+ (89); 367 [M – H]+
(100); 349 [M – F]+ (10); 201 [M – OCH(CF3)2]+ (16); 159
[C8H5N3O]+ (50); 118 [NCNHC6H5]+ (45); 91 [C6H5N]+ (15);
77 [C6H5]+ (25); 69 [CF3]+ (32).
2ꢀChloroꢀ6ꢀ(2,6ꢀdimethylphenylamino)ꢀ4ꢀ(2,2,2ꢀtrifluoroꢀ
ethoxy)ꢀ1,3,5ꢀtriazine (8). 2,4ꢀDichloroꢀ6ꢀ(2,6ꢀdimethylphenylꢀ
amino)ꢀ1,3,5ꢀtriazine (2.69 g, 10 mmol) synthesized by a
known procedure28 was dissolved in anhydrous THF (10 mL),
2,2,2ꢀtrifluoroethanol (5 mL, 68.6 mmol) was added, the mixꢀ
ture was cooled to 0 °C on an ice bath, and a lithium hydride
coarse powder (grain size 1—2 mm) (100 mg, 12.5 mmol) was
added with stirring. The mixture was stirred for 2.5 h, and the
bath was removed. The reaction mixture was left for ~14 h,
diluted with water, and filtered. The precipitate was dried on
the filter to a constant weight. Yield 3.3 g (99.2%), m.p.
160—161 °C (heptane). Found (%): C, 46.71; H, 3.64; N, 16.97.
C13H12ClF3N4O. Calculated (%): C, 46.93; H, 3.64; N, 16.84.
1H NMR (DMSOꢀd6), δ: 2.13 (s, 6 H, 2 Me); 4.40, 5.04 (q, 2 H,
OCH2, ratio 56 : 44); 7.13 (m, 3 H, H arom.); 10.05, 10.15 (br.s,
1 H, NH, ratio 44 : 56). MS, m/z (Irel (%)): 332 [M]+ (50); 317
[M – CH3]+ (48); 297 [M – Cl]+ (15); 249 [M – CH2CF3]+
(61); 212 [M – C8H9NH]+ (25); 186 [M – C8H9NHCN]+ (5);
145 [C8H9NCN]+ (100); 118 [C8H9NCN – HCN]+ (30); 91
[C6H5N]+ (40); 77 [C6H5]+ (50).
2ꢀMethoxyꢀ6ꢀphenylaminoꢀ4ꢀ(2,2,2ꢀtrifluoroethoxy)ꢀ1,3,5ꢀ
triazine (4). 2ꢀChloroꢀ4ꢀmethoxyꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine
(2.37 g, 10 mmol) was added with stirring at room temperature
to a solution of lithium 2,2,2ꢀtrifluoroethoxide (from 2.5 mL of
2,2,2ꢀtrifluoroethanol and 274 mg of finely powdered lithium
hydride, 34.3 mmol each) in anhydrous THF (15 mL). The
mixture was left for ~14 h, the solvents were evaporated, and the
residue was washed with water and dried on the filter to a conꢀ
stant weight. Yield 2.9 g (96.7%), m.p. 126—127 °C (heptane).
Found (%): C, 47.62; H, 3.76. C12H11F3N4O2. Calculated (%):
C, 48.00; H, 3.69. 1H NMR (DMSOꢀd6), δ: 3.95 (s, 3 H, OMe);
4.98 (q, 2 H, OCH2); 7.07 (m, 1 H, H arom.); 7.33, 7.68 (both m,
2 H each, H arom.); 10.16 (br.s, 1 H, NH). MS, m/z (Irel (%)):
300 [M]+ (85); 299 [M – H]+ (100); 281 [M – F]+ (7); 269
[M – OCH3]+ (7); 201 [M – OCHCF3]+ (5); 159 [C8H5N3O]+
(15); 118 [NCNHC6H5]+ (15); 91 [C6H5N]+ (5); 77 [C6H5]+
(10); 69 [CF3]+ (5).
2ꢀChloroꢀ4ꢀethoxyꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine
(5).
2,4ꢀDichloroꢀ6ꢀphenylaminoꢀ1,3,5ꢀtriazine23—26 (2.41 g,
10.0 mmol) was dissolved in ethanol (30 mL), the solution was
cooled to 0 °C on an ice bath, a lithium hydride coarse powder
(grain size 1—2 mm) (100 mg, 12.5 mmol) was added with
stirring, the mixture was stirred for 2.5 h (during the reaction,
the product may precipitate), and the bath was removed. The
reaction mixture was left for ~14 h, diluted with water, and
filtered. The precipitate was dried on the filter to a conꢀ
stant weight. Yield 2.31 g (92.2%), m.p. 103—104 °C (hepꢀ
tane). Found (%): C, 52.93; H, 4.43; Cl, 14.15; N, 22.26.
C11H11ClN4O. Calculated (%): C, 52.71; H, 4.42; Cl, 14.14;
1
N, 22.35. H NMR (DMSOꢀd6), δ: 1.34 (t, 3 H, Me); 4.40 (q,
2 H, OCH2); 7.12 (m, 1 H, H arom.); 7.37, 7.68 (both m,
2 H each, H arom.); 10.55 (br.s, 1 H, NH). MS, m/z (Irel (%)):
250 [M]+ (83); 249 [M – H]+ (30); 221 [M – C2H5]+ (72); 205
[M – OC2H5]+ (28); 186 [221 – Cl]+ (25); 144 [186 – CNO]+
(35); 118 [C6H5NHCN]+ (77); 91 [C6H5N]+ (30); 77
[C6H5]+ (100).
2ꢀChloroꢀ6ꢀ(biphenylꢀ2ꢀylamino)ꢀ4ꢀmethoxyꢀ1,3,5ꢀtriazine
(9). 6ꢀ(Biphenylꢀ2ꢀylamino)ꢀ2,4ꢀdichloroꢀ1,3,5ꢀtriazine (3.17 g,
10.0 mmol), synthesized by a known procedure26 from cyanuric
chloride and 2ꢀaminobiphenyl, was dissolved in ethanol (50 mL),
the solution was cooled to 0 °C on an ice bath, and a lithium
hydride coarse powder (grain size 1—2 mm) (100 mg, 12.5 mmol)
was added with stirring, the mixture was stirred for 2.5 h (the
product may precipitate during the reaction), and the bath was
removed. The reaction mixture was left for ~14 h, diluted with
water, and filtered. The precipitate was dried on the filter to a
constant weight. Yield 3.0 g (96.0%), m.p. 99—100 °C (hepꢀ
tane). Found (%): C, 61.90; H, 4.13; Cl, 10.77; N, 18.19.
C16H13ClN4O. Calculated (%): C, 61.45; H, 4.19; Cl, 11.31;
2ꢀChloroꢀ4ꢀ(1,1,1,3,3,3ꢀhexafluoropropꢀ2ꢀoxy)ꢀ6ꢀphenylꢀ
aminoꢀ1,3,5ꢀtriazine (6). 2,4ꢀDichloroꢀ6ꢀphenylaminoꢀ1,3,5ꢀ
triazine23—26 (2.41 g, 10.0 mmol) was dissolved in anhydrous
THF (10 mL), 1,1,1,3,3,3ꢀhexafluoropropanꢀ2ꢀol (5 mL,
47.5 mmol) was added, the mixture was cooled to 0 °C on an ice
bath, a lithium hydride coarse powder (grain size 1—2 mm)
(100 mg, 12.5 mmol) was added with stirring, the mixture was
stirred for 2.5 h, and the bath was removed. The reaction mixꢀ
ture was left for ~14 h, diluted with water, and extracted with
ether (100 mL). The extract was dried with calcined sodium
sulfate, and ether was evaporated to give 3.5 g (94.0%) of the
target product as a thick oil contaminated by a minor amount
(<5%) of 2,4ꢀdi(1,1,1,3,3,3ꢀhexafluoropropꢀ2ꢀoxy)ꢀ6ꢀphenylꢀ
aminoꢀ1,3,5ꢀtriazine, which could not be separated by chromaꢀ
tography due to little difference between the Rf values of these
compounds. 1H NMR (DMSOꢀd6), δ: 6.94 (m, 1 H, OCH);
7.18 (m, 1 H, H arom.); 7.40, 7.61 (both m, 2 H each, H arom.);
11.09 (br.s, 1 H, NH).
1
N, 17.91. H NMR (DMSOꢀd6), δ: 3.50 (s, 3 H, OMe); 7.38
(m, 9 H, H arom.); 9.95 (br.s, 1 H, NH). MS, m/z (Irel (%)): 312
[M]+ (100); 311 [M – H]+ (36); 277 [M – Cl]+ (32); 235
[M – C6H5]+ (49); 220 [235 – CH3]+ (49); 193 [C12H9NCN]+
(21); 178 [235 – CH3OCN]+ (80); 167 [C12H9N]+ (49); 152
[178 – CN]+ (25); 77 [C6H5]+ (12).
2ꢀChloroꢀ4ꢀmethoxyꢀ6ꢀ[(Nꢀmethyl)phenylamino]ꢀ1,3,5ꢀtriꢀ
azine (10). 2,4ꢀDichloroꢀ6ꢀ[(Nꢀmethyl)phenylamino]ꢀ1,3,5ꢀ
triazine (2.59 g, 10.0 mmol), synthesized by a known proceꢀ
dure,29 was dissolved in methanol (50 mL), cooled to 0 °C on an
ice bath, and a lithium hydride coarse powder (grain size
1—2 mm) (190 mg, 23.75 mmol) was added with stirring, the
mixture was stirred for 2.5 h (the product may precipitate during
the reaction), and the bath was removed. The reaction mixture
2ꢀMethoxyꢀ4ꢀ(1,1,1,3,3,3ꢀhexafluoropropꢀ2ꢀoxy)ꢀ6ꢀpheꢀ
nylaminoꢀ1,3,5ꢀtriazine (7). 2ꢀChloroꢀ4ꢀmethoxyꢀ6ꢀphenylꢀ
aminoꢀ1,3,5ꢀtriazine (2.37 g, 10 mmol) was added with stirring
at room temperature to a solution of lithium 1,1,1,3,3,3ꢀhexaꢀ

2450
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
Belyakov et al.
was left for ~14 h, diluted with water, and filtered. The precipiꢀ
tate was dried on the filter to a constant weight. Yield 2.30 g
(92%), m.p. 103—104 °C (heptane). Found (%): C, 52.72;
H, 4.39; Cl, 14.51; N, 22.35. C11H11ClN4O. Calculated (%):
16. A. V. Popov, A. V. Shastin, E. L. Luzina, A. N. Pushin, and
T. N. Gavrishova, Izv. Akad. Nauk. Ser. Khim., 1999, 1568
[Russ. Chem. Bull., 1999, 48, 1548 (Engl. Transl.)].
17. N. M. Emanuel´ and D. G. Knorre, Kurs khimicheskoi
kinetiki [Course of Chemical Kinetics], Vysshaya shkola, Mosꢀ
cow, 1969, 65 (in Russian).
18. M. V. Gorelik and L. S. Efros, Osnovy khimii i tekhnologii
aromaticheskikh soedinenii [Foundations of the Chemistry and
Technology of Aromatic Compounds], Khimiya, Moscow,
1992, 32 (in Russian).
1
C, 52.70; H, 4.42; Cl, 14.14; N, 22.35. H NMR (DMSOꢀd6),
297 К, δ: 3.50 (s, 3 H, NMe); 3.70 (br.s, 3 H, OMe); 7.32, 7.45
1
(m, 5 H, H arom.). H NMR (CDCl3), 297 К, δ: 3.52 (s, 3 H,
NMe); 3.76, 4.00 (br. s, 3 H, OMe); 7.32, 7.45 (m, 5 H,
1
H arom.). H NMR (CDCl3), 230 К, δ: 3.52 (s, 3 H, NMe);
3.76, 4.05 (s, 3 H, OMe); 7.32, 7.45 (m, 5 H, H arom.). 13C NMR
(CDCl3), δ: 171.23, 170.72 (C(2) and C(4) triazine); 166.35
(C(6) triazine); 143.00, 129.80, 127.74, 126.70 (C6H5); 56.05,
55.90 (OMe (conformers)); 39.58, 39.40 (NMe (conformers)).
MS, m/z (Irel (%)): 250 [M]+ (48); 249 [M – H]+ (100); 235
[M – CH3]+ (3); 173 [M – C6H5]+ (9); 158 [235 – C6H5]+ (5);
131 [CH2NCNC6H5]+ (20); 106 [CH3NC6H5]+ (28); 77
[C6H5]+ (22).
19. P. A. Belyakov, A. V. Shastin, and Yu. A. Strelenko, Izv.
Akad. Nauk. Ser. Khim., 2001, 2361 [Russ. Chem. Bull., Int.
Ed., 2001, 50, 2473 (Engl. Transl.)].
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The authors are grateful to V. P. Ananikov for assisꢀ
tance in the calculations using the Gaussian software and
interpretation of the results.
23. K. R. Desai and M. M. Pathak, J. Indian Chem. Soc., 1985,
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Received October 21, 2004;
in revised form September 7, 2005