K. Marciniec et al. / Journal of Molecular Structure 1015 (2012) 46–50
49
Table 5
ence (12.7 ppm) is observed for isomer 2a. With regard to the lit-
erature data [28,29] on nitrogen NMR spectroscopy, the results
are significant, and the calculations correlate satisfactorily with
the experimental data.
Comparison between experimental (dexp) and calculated (dcalcd) 15N chemical shifts of
the N,N-dimethylsulfamoylquinolines 2a–g.
Compd
Nitrogen
d
exp
d
calcd
Diffa
d
calcd
Diffa
(
HF//HF)
(B3LYP//MP2)
In general, there are no significant differences between both
methods as respective calculated values are close. Better correla-
tions between the experimental chemical shifts and the theoretical
shielding constants of the endocylic nitrogen nuclei were achieved
when the geometry was optimized by the MP2/6-31G(d,p) method
and the chemical shielding constants were computed using the
B3LYP/6-311++G(d,p) method. On the other hand, the best results
for the nitrogen of the sulfonamide group were achieved when
the geometry was optimized by the HF/6-31G(d,p) method and
the chemical shielding constants were computed using the HF/6-
311++G(d,p) method.
2
2
2
2
2
2
2
a
b
c
d
e
f
N
N
N
N
N
N
N
N
N
N
N
N
N
N
arom
sulfon
arom
sulfon
arom
sulfon
arom
sulfon
arom
sulfon
arom
sulfon
arom
sulfon
À75.3
À78.3
3.0
5.3
13.0
0.9
À88.0
À287.8
À75.9
12.7
À303.3
À68.0
À308.6
À81.0
À15.5
7.9
À299.3
À55.3
À300.2
À52.4
À281.8
À56.7
À17.5
1.4
À2.9
À301.9
À70.5
À305.2
À75.2
3.3
À286.5
À74.5
À15.4
4.7
2.3
5.8
5.2
1.5
4.6
7.7
7.9
4.0
À301.0
À71.8
À303.3
À77.6
À284.9
À73.9
À16.1
2.1
À299.8
À67.6
À305.0
À69.1
À287.0
À69.2
À12.8
1.6
À299.8
À72.6
À304.4
À80.3
À285.5
À77.7
À14.3
5.1
À10.8
g
À305.0
À312.9
À294.2
4
. Conclusion
a
Diff = dexp–dcalcd
The synthesis and assigments of the 15N NMR spectra for seven
positional isomers of N,N-dimethylsulfamoylquinoline 2a–g were
reported. Effect of the position of the sulfamoyl moiety on the
chemical shift of the endocyclic nitrogen atom is much more visi-
effect of the substituent. The polar sulfamoyl group as well as
the lone pair on the endocyclic nitrogen create an electric field.
Consequently, an intramolecular effect that causes distortion of
the electron density is observed in isomers 2a and 2g, and the
N chemical shifts are affected.
The positions of the nitrogen signals of the N,N-dimethylsulfa-
1
5
ble (D Narom = 20.0 ppm) than the influence of different isomeric
1
5
quinolinyl groups on the chemical shift of the sulfonamide nitro-
1
5
gen atom (
D Nsulfon = 5.7 ppm). The individual resonances deter-
mined experimentally were compared with the calculated
chemical shifts. Several levels of the theory were considered: the
HF-, MP2-, and B3LYP-optimized geometries [6-31G(d,p) basis
set] and the HF, BLYP, and B3LYP spectral calculations [6-
moyl substituents in compounds 2a–g (À305.0 to À299.3 ppm)
are comparable to the respective data [27]. The quinoline moiety
has an insignificant effect on the 15N NMR chemical shifts of the
N,N-dimethylsulfonamide group, except in the case of compounds
3
11++G(d,p) basis set]. The best results were achieved when the
geometry was optimized by the HF/6-31G(d,p) and MP2/6-
1G(d,p) methods and the chemical shielding constants were com-
2
a and 2g (see Table 2) probably because of the steric effect of the
sulfamoyl group as well as the electronic field of the substituent, as
mentioned above.
3
puted using the HF/6-311++G(d,p) and B3LYP/6-311++G(d,p)
methods (r value of 0.9995). The predictive accuracy seems to be
sufficient for various routine practical applications of theoretical
calculated chemical shifts.
The absolute nitrogen magnetic sheldings
r and the calculated
chemical shifts dcalcd, as obtained at nine different computational
levels, are given in Table 3 and Table 4, respectively. The choice
of the optimized geometries seems to be of minor importance,
which agrees with the experimental data [25]. The best correlation
of the results with the experimental data was obtained for the
geometry optimized by the HF and MP2 methods and the chemical
shielding constants were computed using the HF and B3LYP,
respectively.
A linear correlation between the theoretical and experimental
nitrogen shifts for the HF/HF and B3LYP/MP2 are very satisfactory.
Least squares fit all data showing a strong relationship with an r
value of 0.9995 for the HF/HF and B3LYP/MP2 methods and an
overall standard error of estimate is 3.895 and 3.869, respectively.
Acknowledgements
The calculations were performed with the Gaussian 09 software
[
24] installed at the Academic Computer Centre CYFRONET AGH in
´
Kraków (Poland), Grant No. MNiSW/SGI3700/-SUM/036/2011.
References
[
1] A. Birch, R. Davies, L. Maclean, K.J. Robinson, J. Chem. Soc. Perkin Trans. I (1994)
87.
3
The following correlations dcalcd = a + b
r
were obtained: a = À4.7,
[2] C.P. Dorn, P.E. Finke, B. Oates, R.J. Budhu, S.G. Mills, M. MacCoss, L. Malkowitz,
M.L. Springer, B.L. Daugherty, S.L. Gould, J.A. DeMartino, S.J. Siciliano, A. Carella,
G. Carver, K. Holmes, R. Danzeisen, D. Hazuda, J. Kessler, J. Lineberger, M.
Miller, W.A. Schleif, E.A. Emini, Bioorg. Med. Chem. Lett. 11 (2001) 259.
[3] H.I. Skulnik, P.D. Johnson, P.A. Aristoff, J.K. Morris, K.D. Lovasz, W.J. Howe, K.D.
Watenpaugh, M.N. Janakiraman, D.J. Anderson, R.J. Reischer, T.M. Schwartz, L.S.
Banitt, P.K. Tomich, J.C. Lynn, J. Med. Chem. 40 (1997) 1149.
b = 0.999 for the HF//HF method and a = À10.7, b = 0.916 for the
B3LYP//MP2 method. A calculated values for both methods are
close.
A closer inspection of Table 5 shows that for nitrogens of sulfon-
amide group, the lowest level HF geometries yielded better corre-
lations than the computationally most affordable highest level
MP2 geometries. A good quantitative agreement within 0.9–
[
4] A. Scozzafava, T. Owa, A. Mastrolorenzo, C.T. Supuran, Curr. Med. Chem. 10
(2003) 925.
[5] J. Borras, A. Scozzafava, L. Menabuoni, F. Mincione, F. Briganti, G. Mincione, C.T.
Supuran, Bioorg. Med. Chem. 7 (1999) 2397.
7
.9 ppm for the HF/HF method was observed for the sulfonamide
[
[
6] S.G. Mills, M. Maccoss, M. S. Springer, US patent 5, 962,462 (October, 5, 1999).
7] A.E. Weber, R.J. Mathvink, L. Perkins, J.E. Hutchins, M.R. Candelore, L. Tota, C.D.
Strader, M.J. Wyrvratt, M.H. Fischer, Bioorg. Med. Chem. Lett. 8 (1998) 1101.
8] P. Caldirola, U. Bremberg, A. Jensen, G. Johansson, A. Mott, L. Sutin, J. Tejbrant,
Patent WO 02, 92, 585 (21 November, 2002).
group nitrogen.
The highest correlations between the experimental chemical
shifts and the theoretical shielding constants of the endocylic
nitrogen nuclei were achieved when the geometry was optimized
by the MP2 method and the chemical shielding constants were
computed using the B3LYP method. The correlation between theo-
retical and experimental aromatic nitrogen chemical shifts for the
B3LYP/MP2 method is clearly seen in Table 5. A good quantitative
agreement within 1.4–7.9 ppm for the isomers 2b–g is observed,
which appears to be very satisfactory. In particular, a large differ-
[
[
9] A. Ma s´ lankiewicz, K. Marciniec, M. Pawłowski, P. Zajdel, Heterocycles 71
(2007) 1975.
[
10] A. Ma s´ lankiewicz, M.J. Ma s´ lankiewicz, K. Marciniec, Magn. Reson. Chem. 46
2008) 182.
11] J.L. Eveloch, D.F. Bocian, J.L. Sudmeier, Biochemical 20 (1981) 4951.
(
[
[12] S. Lindskog, Adv. Inorg. Biochem. 4 (1982) 115.
13] K. Kanamori, J.D. Roberts, Biochemical 22 (1983) 2658.
14] P.W. Finn, M. Bandara, C. Butcher, A. Finn, R. Hollinshead, N. Khan, N. Law, S.
Murthy, R. Romero, C. Watkins, V. Andrianov, R.M. Bokaldere, K. Dikovska, V.
[
[