JOURNAL
OF MAGNETIC
RESONANCE
98, 109- 114 ( 1992)
Solvent Effects on Nitrogen NMR Shieldingsof 1,2,4-Triazine
M. WITANOWSIU AND W. SICIPJSKA
Institute
of Organic
Chemistry,
Polish
Academy
of Sciences,
01-224
Warsaw,
Poland
AND
G. A. WEBB*
Department
of Chemistry,
University
of Surrey,
Guildford,
Surrey,
United
Kindgom
Received September 4, 199 1
Nitrogen NMR shieldings of 1,2,4-triazine are shown, as an example, to be capable of
providing deep insight into solvent-induced, site-oriented electric charge redistributions
and solvent-solute hydrogen bonding effectsin an unsymmetrical molecule. A sharp contrast
is observed in the solvent effects on the nitrogen atoms in positions 1 and 2 with respect
to that at position 4. The former pair of atoms exhibits a remarkable affinity to hydrogenbond donor solvents. Their electron densities appear to be significantly dependent upon
the solvent polarity. In contrast N4 appears to be relatively uninfluenced by solvent effects.
0 1992 Academic Press, Inc.
We have previously demonstrated that solvent effects on nitrogen NMR shieldings
of azine systems with equivalent nitrogen atoms, pyridine, isomeric diazines, and
1,3,5-triazine, are large and provide useful information on hydrogen bonding and
solvent polarity effects ( 1) . These contributions to the variations of nitrogen shieldings,
induced by solvents, can be analyzed in terms of
XYZ = XYZrJ + s(a* + da) + ax + b/3.
[II
Equation [ 1] has been introduced to account for bulk solvent-solute interactions (2).
The quantity XYZ corresponds to nitrogen shielding for a solute molecule in a particular solvent; XYZ, is the nitrogen shielding in cyclohexane solution chosen as a
reference state; r* is the polarizability-polarity
term for the solvent; (Yrepresents its
hydrogen-bond donor strength; /3 corresponds to its hydrogen-bond acceptor strength;
6 is a correction for polychlorinated solvents (6 = 0.5) and aromatic solvents (6 =
1.O) ; and S, a, b, and d are the corresponding responses of the appropriate solute
molecular property to the relevant solvent property.
The values of a obtained for simple, symmetrical azine systems appear to reflect
solvent-to-solute hydrogen-bond strength ( 1) . The main aim of the present work is
to determine whether an analogous approach can be employed in the more difficult
* To whom correspondence should be addressed.
109
0022-2364192 $5.00
Copyright 0 1992 by Academic Press, Inc.
All rights of reproduction in any form reserved.
110
WITANOWSKI,
SICINSKA,
AND WEBB
problem of evaluating the relative affinities to hydrogen bonding of nonequivalent
nitrogen atoms within a single molecule. A good example for such an investigation is
provided by 1,2,4-triazine (I), which contains three nonequivalent nitrogen atoms:
(4)
N
\
(’
I
N#‘J (2)
(1)
A further aim is to determine whether the weak response of the nitrogen shielding of
1,3,5-triazine to changes in solvent is due to the number of nitrogen atoms present or
to the symmetry of the structure ( I ) . An additional interest is in whether the aggregation
of nitrogen atoms in positions 1 and 2 produce very large nitrogen shielding variations
in solvent effects in all cases such as found in 1,2diazine ( 1) . The latter represents
the largest variation, about 50 ppm, observed for nitrogen shieldings as a function of
solvent for diamagnetic systems ( 2 ) .
RESULTS AND DISCUSSION
The observed solvent effects on (I) are reported in Table 1. These were produced
by high-precision 14N NMR measurements and are corrected for solvent bulk magnetic
TABLE 1
Solvent Effects on the Nitrogen NMR Shielding of 1,2,CTriazine (I)
Nitrogen NMR shielding (in ppm) referred to
neat MeNOZb
Solvent
Nl
N2
N4
CFSCH20H
-18.48
-21.24
-33.87
-36.65
-39.24
-41.64
-42.12
-42.23
-43.42
-45.40
-47.59
-48.37
-51.16
-21.63
-22.65
-11.29
+8.80
+4.89
+2.47
+2.41
+2.33
-0.76
-1.26
-2.67
-3.82
-6.84
+85.51
+84.63
+80.03
+79.5 1
+80.34
+80.60
+80.24
+80.43
+80.94
+80.98
+80.22
+79.95
+79.95
H20
MeOH
EtOH
DMSO
CH2C12
CHCl,
Acetone
Dioxane
Benzene
Et20
CCL
Cyclohexane
a Solute concentration 0.25 M, at a temperature of 35°C; the shieldings
are corrected for bulk susceptibility effects.
* The precision of the shieldings reported is such that only the last digit
is uncertain. The data given are with respect to neat nitromethane such that
an increase in nitrogen shielding corresponds to a positive increment.
SOLVENT
EFFECTS ON NITROGEN
111
SHIELDING
TABLE 2
Solvent Parameters Employed”
Parameters employed in Eq. [l]
Solvent
a
P
7r*
6
Cyclohexane
Benzene
cc14
CHCl,
CHQ
Et,0
Dioxane
Acetone
DMSO
EtOH
MeOH
CF$HrOH
Hz0
0
0
0
0.34
0.22
0
0
0.07
0
0.86
0.98
(1.51)
(1.13)
0
0.1
0
0
0
0.47
0.37
0.48
0.76
0.77
0.62
(W
(0.18)
0
0.59
0.29
0.76
0.80
0.27
0.55
0.72
1.oo
0.54
0.60
(1.22)’
(1.09)
0
1.0
0.5
0.5
0.5
0
0
0
0
0
Dielectricb constant
(4
1.87
2.25
2.21
4.55
8.54
3.89
2.19
19.75
45.80
24.20
30.71
c&
w
76.70
LIThe parameters are essentially those recommended in Ref. (I).
b The dielectric constants are reported for a temperature of 35°C as calculated from the data given in
Ref. (5).
c These values are too uncertain to be employed in the calculations.
susceptibility effects as described under Experimental: The adjacent nitrogen atoms
N, ,NZ show a large shielding sensitivity to a change of solvent; this is in sharp contrast
to that exhibited by N4. For the range of solvents studied, the Ni ,NZ shielding variation
is about 30 ppm; this compares with variations of about 40 ppm for pyridine and 50
ppm for 1,Zdiazine ( I ) . In contrast the N4 shielding variation is about 6 ppm, which
is even lessthan that observed for 1,3,5-triazine, about 10 ppm ( 1). The large difference
observed in the sensitivity of the nitrogen shieldings of (I) to a change in solvent
shows that nitrogen NMR is a satisfactory means of investigating the differences in
solvation effects at various points of an unsymmetrical. molecule.
By use of Eq. [l] and the solvent parameters given in Table 2 we can arrive at the
set of parameters in Table 3, which represent the responses of the nitrogen shieldings
TABLE 3
Calculated Responses of the Nitrogen Shieldings of 1,2,4-Triazine (I)
to Solvent Properties According to Eiq. [l]
Nitrogen
atom
N,
N2
N4
b
(ppm/unit
scaleof P)
s (ppm/unit
scaleof 7r*)
d
XYZ, (mm)
a (ppm/unit
scaleof a)
(percentage Correlation
scaleof 6)
coefficient
--51.06 t 0.70
-6.47 f 0.56
+80.25 k 0.77
+8.66 k 0.87
+9.53 f 0.70
+1.09 * 0.70
+3.35 k 1.62
f3.88 + 1.22
-3.76 i 1.18
+9.42 k 1.26
+8.71 f 0.98
+2.90 + 1.09
~0.03 it 0.16
-0.05 + 0.13
-0.77 ? 0.44
0.9911
0.9946
0.9017
Standard
deviation
(m-d
0.88
0.72
0.98
112
WITANOWSKI,
SICINSKA,
AND WEBB
of (I) to solvent properties such as polarizability-polarity
and hydrogen-bond donor
and acceptor strengths. The responses of the shieldings of N1 and N2 to solvent polarity,
the term s, are about 9 ppm/unit scale. This is much larger than that in most azines;
only 1,2diazine has a greater response ( 1). The corresponding case of N4 is similar
to that of 1,3,54riazine ( 1). The most likely interpretation of this observation is that
the electron density at N, ,NZ increases significantly as the solvent polarity increases,
while that at N4 does not undergo any significant change.
These observations are corroborated by INDO / S-SOS solvation calculations of the
nitrogen shielding as a function of the dielectric constant ( f ) of the medium (Fig. 1).
The calculations underestimate the extent of the nitrogen shielding sensitivity to solvent
polarizability-polarity
changes, as indicated by E, but they do show the correct sign.
A sharp distinction is predicted between N4 which is quite insensitive to solvent polarity
effects and the other two nitrogen atoms, N1 ,NZ, whose shieldings are expected to be
quite sensitive to solvent polarity effects. This prediction is borne out by the values
of the corresponding s terms given in Table 3. This proposal is also consistent with
the evaluated responses to solvent-to-solute hydrogen bonding, term a in Eq. [ 11,
which is also about 9 ppm/unit scale for N, ,N2, while that for N4 is almost insignificant.
As shown in Fig. 2, the calculated values of the term a for the three nitrogen atoms
of (I) show a reasonable relationship to the ab initio calculated (3) values of the
relevant gas-phase protonation energies. The basis set used in the ab initio calculations
was 6-3 lG*, the results indicate that, if protonation occurs at either N, or NZ, the
2.50
T”“““‘l”“““‘I”“““‘l”“““‘I”““‘I
.oo
6.00
dielectric
11 .oo
constant
of
16.00
-,he
21 .oo
medium
FIG. 1. INDO/S-SOS solvation calculated nitrogen NMR shielding increments with respect to a dielectric
constant of the medium c = 1, for compound (I); increments plotted against the dielectric constant of the
medium.
SOLVENT
10.00
EFFECTS
ON
NITROGEN
113
SHIELDING
y
N-2
A
N-l
A
N-4
A
o.“:04:T
224.00
gas-phase
protonation
energy
(kcal/mol)
FIG. 2. A plot of the nitrogen shielding responses of (1) to solvent-to-solute hydrogen bonding, a, against
ab initio calculated values of the gas-phase protonation energies ( 3).
proton in question interacts strongly with the other nitrogen of this pair (3). A corresponding situation is found in the present work where the values of a (Table 3) are
very similar for both N, and N2.
The term b in Eq. [ 11, which represents the nitrogen shielding responses of I to
the hydrogen-bond acceptor strengths of the solvents, is smaller for N, ,NZ than are
the a and s terms. For Nq, the value of b is the largest of the fitting parameters (Table
3). It seems likely that the presence of three electron-attracting atoms within a given
ring produces a net positive charge in the remaining part which enables the solute molecule to interact with the basic centers of the solvent molecules. For the azine systems
previously studied only 1,3,5-triazine showed a similar effect (1); pyridine-N-oxide
has also been demonstrated to exhibit a comparable interaction with solvents (4).
The nitrogen shielding results obtained for I show that such results act as sensitive
probes of solvent-induced electric charge redistributions at specific sites in unsymmetrical heteroaromatic ring systems. In addition, the relative affinities of various
nitrogenous basic centers to solvent-to-solute hydrogen bonding can also be evaluated.
EXPERIMENTAL
The sample (I) used was prepared by a published procedure (6). All NMR sample
preparations were performed in an atmosphere of dry argon. Where applicable the solvents were dried. Very pure and dry solvents were prepared as reported previously ( I ) .
All NMR measurements were taken at 35.0 -t 0.2 “C, maintained by a VT unit, on
a Bruker AM500 instrument. Concentric tubes, 10/4 mm, were used; a 0.3 Msolution
114
WITANOWSKI,
SICINSKA,
AND WEBB
of nitromethane in acetone-d, was placed in the inner tube to provide both a deuterium
lock and a secondary standard.
The primary standard was neat nitromethane which resonates at a frequency of
36.141524 MHz at a field corresponding to the resonance of a bare nitrogen nucleus
at 36.136826 MHz ( 7). The nitrogen shielding of the 0.3 A4 solution of nitromethane
has been measured by means of concentric spherical containers in order to remove
bulk susceptibility effects on nitrogen shielding, and is found to be 0.77 ppm (8) with
respect to that of neat nitromethane. The shieldings given in Table 1 are with respect
to that of neat nitromethane after including bulk susceptibility corrections and 0.77
ppm for the standard used as given by
aN(ref. I) = crN(ref. II) + 0.77 - ) (x,, iI - xsampIe),
121
where ref. I is neat liquid nitromethane, ref. II is a 0.3 M solution of nitromethane in
acetone-& and X is the volume magnetic susceptibility in SI units ( 7). The measurements were taken with the sample and reference tubes parallel to the direction of the
applied magnetic field. The following parameters were commonly used in the 14N
measurements; 90” pulse corresponding to 40 ps; spectral width about 8 kHz with
quadrature detection; acquisition time about 0.13 s; zero relaxation delay; and about
2000 accumulated scans per spectrum.
The INDO/ S-SOS solvation shielding calculations were performed on the University
of Surrey Primenet System using a standard geometry (9) and procedures given elsewhere (10, II).
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