NMR studies of the dynamic behavior of 2-anilino-6-chloro-4-methoxy-1,3,5-triazine in solution

Article abstract of DOI:10.1023/A:1015076722511

2-Anilino-6-chloro-4-methoxy-1,3,5-triazine was synthesized and studied by dynamic NMR. The activation parameters of hindered internal rotation in unsymmetrically substituted arylamino-sym-triazine were determined for the first time. It was found that a sterically more hindered rotational isomer is thermodynamically more stable in this compound (slow-exchange NOE data).

Full text of DOI:10.1023/A:1015076722511

Russian Chemical Bulletin, International Edition, Vol. 50, No. 12, pp. 2473—2474, December, 2001
2473
NMR studies of the dynamic behavior of
2-anilino-6-chloro-4-methoxy-1,3,5-triazine in solution
P. A. Belyakov,a« 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.
Fax: +7 (095) 135 5328. E-mail: paul043@mail.ru
bInstitute of Problems of Chemical Physics, Russian Academy of Sciences,
18 Institutskii prosp., 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (096) 515 3588. E-mail: shastin@icp.ac.ru
2-Anilino-6-chloro-4-methoxy-1,3,5-triazine was synthesized and studied by dynamic
NMR. The activation parameters of hindered internal rotation in unsymmetrically substi-
tuted arylamino-sym-triazine were determined for the first time. It was found that a sterically
more hindered rotational isomer is thermodynamically more stable in this compound (slow-
exchange NOE data).
Key words: 2-anilino-6-chloro-4-methoxy-1,3,5-triazine, hindered internal rotation,
activation parameters, dynamic NMR spectroscopy.
It is known that rotation about the C—N bond in
aminotriazines is hindered because the order of this
bond is higher than unity.1 This phenomenon for
sym-triazines was described only in a few papers,1—5 but
the thermodynamic characteristics of unsymmetrically
substituted triazines are lacking. While measuring2—4
the energy parameters of hindered internal rotation from
the coalescence temperature of exchanging signals, one
cannot determine ∆H# and ∆S#.
equation and was modified for the case of chemical
exchange.9 According to this method, spectra are re-
corded at different temperatures, which makes the op-
eration longer, but allows one to determine activation
parameters for a temperature range rather than a free
activation energy in a single temperature point. The
results thus obtained are more reliable, and the energy
characteristics of different compounds can be compared
under standard conditions.
A study of intramolecular rotation is of considerable
interest since this phenomenon largely influences sev-
eral essential properties of molecules and substances
(thermodynamic, electrical, and optical), their reactivi-
ties (including biological activity), reaction mechanisms,
etc.6 However, experimental data on the barriers are
scarce, while calculations usually provide rough esti-
mates.4 The goal of this study was to collect and analyze
such data.
Scheme 1
No NOE
NOE
Me
Me
O
H
O
δ–
δ+
H
4
4
N
N
k1
k2
3
3
5
5
N
N
N
N
H
2
2
1
1
6
6
N
H
δ+
N
δ–
Results and Discussion
Cl
Cl
A
B
In the present work, the synthesis of 2-anilino-6-
chloro-4-methoxy-1,3,5-triazine (1) containing three
different substituents in the ring is described. Unlike
aminotriazines with two identical substituents in the
heterocycle,1—5 the ratio between rotational isomers for
compound 1 differed from 1 : 1 (k1 ≠ k2) (Scheme 1). A
simplified estimation7 (from the coalescence tempera-
ture) of a barrier to hindered internal rotation is not
correct as, strictly speaking, the coalescence tempera-
ture in such processes cannot be determined.8 We per-
formed complete analysis of the line shape in the dy-
namic NMR spectra. The analysis is based on the Bloch
The activation parameters of hindered internal
rotation in triazine 1 were found to be ∆H#
=
–1
–1
–1
57.4±1.9 kJ mol , ∆S# = –27.3±6.5 J mol K , and
–1
∆G#
= 65.6±2.0 kJ mol .
298
The nuclear Overhauser effects10 (NOE) obtained
for slow exchange show that the sterically more hin-
dered conformer A is dominant in solution (see
Scheme 1).
In compound 1, the steric factors insignificantly
influence the relative stabilities of rotational isomers, as
distinct from other known examples11 of hindered inter-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2361—2362, December, 2001.
1066-5285/01/5012-2473 $25.00 © 2001 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 50, No. 12, December, 2001
Belyakov et al.
compound 1 was 4.70 g (96%), m.p. 140—141 °C (MeOH).
Found (%): C, 50.78; H, 3.88; Cl, 14.52; N, 24.12.
C10H9ClN4O. Calculated (%): C, 50.75; H, 3.83; Cl, 14.98;
N, 23.67. MS, m/z (Irel (%)): 236 [M]+ (86), 235 [M – H]+
(100), 201 [M – Cl]+ (18), 159 [M – Ph]+ (10), 159
[M – PhNH]+ (23), 118 [PhNHCN]+ (42), 91 [PhN]+ (25),
nal rotation about the C—N bond, while a higher stabil-
ity of conformer A is due to electronic factors. Most
probably, this is associated with an effective electrostatic
interaction of the positively charged H atom of the
amino group with the N(1) atom of the triazine ring (see
Scheme 1), which bears more negative charge than N(3)
owing to a stronger electron-acceptor effect of the Cl
atom. The causes of this phenomenon will be elucidated
in further investigations involving other triazines.
1
77 [Ph]+ (60). H NMR, δ: 4.02 (br.s, 3 H, OMe); 7.16 (m,
1 H, p-Ph); 7.37 (m, 2 H, m-Ph); 7.56 (br.m, 3 H, o-Ph and
NH). 13C-{1H} NMR, δ: 56.2 (br.s, 1 C, OMe); 122.1 (br.s,
2 C, o-Ph); 125.4 (br.s, 1 C, p-Ph); 129.5 (s, 2 C, m-Ph);
137.5 (s, 1 C, i-Ph); 166.0 (s, 1 C, C(6) triazine); 171.1, 172.0
(both br.s, 2 C, C(2), C(4) triazine).
Experimental
References
1
H and 13C-{1H} NMR spectra were recorded on Bruker
AC-200 (200.13 and 50.43 MHz, respectively) and Bruker
AM-300 (300.13 and 75.43 MHz, respectively) spectrometers
in a mixture of CD2Cl2, CDCl3, and CCl4 (60 : 27 : 13).
Nuclear Overhauser effects were measured at –23 °C.
1. A. V. Shastin, T. I. Godovikova, S. P. Golova, M. V.
Povorin, D. E. Dmitriev, M. O. Dekaprilevich, Yu. A.
Strelenko, Yu. T. Struchkov, L. I. Khmel´nitskii, and B. L.
Korsunskii, Khim. Geterotsikl. Soedin., 1995, 5, 679 [Chem.
Heterocycl. Compd., 1995, 5 (Engl. Transl.)].
The NMR data were processed using a standard Bruker
software (DISNMR on ASPECT-3000 with the Adakos OS).
Spectra were transcoded into different data formats with the
CODER7 program.12 The 13C-{1H} signals from the methoxy
groups were used to perform a complete analysis of the line
shape with consideration of a temperature dependence of the
resonance frequencies of exchanging signals. The temperature
in the spectrometer was calibrated with reference to an exter-
nal standard.13 Seven spectra recorded in a temperature range
from –4 to 31 °C were used for calculations. Two sets of
narrow signals from both conformers in the spectrum at –23 °C
indicated that the conditions of slow exchange were reached.
At 54 °C, the spectrum contained an averaged set of narrow
signals from both conformers, which is characteristic of rapid
exchange. The resonance frequencies of exchanging signals
were iterated with the DYNNMR program.1 Relaxation times
were measured at each temperature point.
Melting points were determined on a Boetius hot stage (the
heating rate at the melting point was 4 °C min–1). Mass
spectrum was recorded on a Varian CH-6 instrument (direct
inlet of a sample into the ion source, ionizing voltage 70 eV,
accelerating voltage 1.75 kV, emission current 100 mA). The
molecular ion peak in the mass spectrum of compound 1
relates to the 35Cl isotope.
2. A. R. Katritzky, I. Chiviriga, P. J. Steel, and D. C. Oniciu,
J. Chem. Soc., Perkin Trans. 2, 1996, 443.
3. S. A. Brewer, H. T. Burnell, I. Holden, B. G. Jones, and
C. R. Willis, J. Chem. Soc., Perkin Trans. 2, 1999, 1231.
4. V. M. Rumjanek, J. B. N. da Costa, A. Echevarria, and
M. F. Cavalcante, Structural Chemistry, 2000, 11, 303.
5. H. E. Birkett, R. K. Harris, P. Hodgkinson, K. Carr,
M. H. Charlton, J. C. Cherryman, A. M. Chippendale, and
R. P. Glover, Magn. Reson. Chem., 2000, 38, 504.
6. I. A. Godunov and V. M. Tatevskii, Zh. Fiz. Khim., 1995,
69, 141 [Russ. J. Phys. Chem., 1995, 69 (Engl. Transl.)].
7. H. S. Gutowsky and C. H. Holm, J. Chem. Phys., 1956,
25, 1228.
8. N. M. Sergeev, Spektroskopiya YaMR (dlya khimikov-
organikov) [NMR Spectroscopy for Organic Chemists], MGU,
Moscow, 1981, 115.
9. R. A. Sack, Mol. Phys., 1958, 1, 163.
10. J. H. Noggle and R. E. Shirmer, The Nuclear Overhauser
Effect. Chemical Applications, Academic Press, New York,
1971, 266 pp.
11. T. Ozawa, Y. Isoda, H. Watanabe, T. Yuzuri, H. Suezawa,
K. Sakakibara, and M. Hirota, Magn. Reson. Chem., 1997,
35, 323.
12. A. O. Krasavin, CODER7, http://nmr.ioc.ac.ru/coder7.zip.
13. A. L. Van Geet, Anal. Chem., 1970, 42, 679.
14. N. V. Kozlova, D. F. Kutepov, D. N. Khokhlov, and A. I.
Krymova, Zh. Obshch. Khim., 1963, 33, 3304 [J. Gen.
Chem. USSR, 1963, 33 (Engl. Transl.)].
2-Anilino-6-chloro-4-methoxy-1,3,5-triazine (1). Coarsely
ground (grain size 1—2 mm) LiH (190 mg, 23.75 mmol) was
added with stirring at 0 °C to a solution of 2-anilino-4,6-di-
chloro-1,3,5-triazine14 (5 g, 20.75 mmol) in 50 mL of MeOH.
The reaction mixture was stirred at 0 °C for 2.5 h (a precipitate
of a product is occasionally formed in the course of the
reaction) and then allowed to warm for ∼14 h. The resulting
mixture was diluted with water, and the precipitate that formed
was filtered off and dried to a constant weight. The yield of
Received May 29, 2001;
in revised form September 10, 2001