The ^(15)N chemical shifts of a series of para-substituted nitrobenzenes have been measured. Comparison with the para-^(13)C chemical shifts in monosubstituted benzenes and with ^(19)F chemical shifts in para-substituted fluorobenzenes, indicates that similar factors determine the chemical shifts of these three nuclei. With p-nitroaniline, the ^(15)N chemical shift appears to have an extra paramagnetic contribution, since this is the only compound studied that does not fit the correlation with ^(13)C and ^(19)F chemical shifts

Clark, David T.

Roberts, John D.

Caltech Authors - Main

745 
Nitrogen- 15 Magnetic Resonance Spectroscopy. VII. 
Chemical Shifts of para-Substituted Nitrobenzenes' 
David T. Clark and John D. Roberts 
Contribution No. 3308 from the Gates and Crellin Laboratories of Chemistry, 
California Institute of Technology, Pasadena, California. 
Received September 30, 1965 
Abstract: The 15N chemical shifts of a series of para-substituted nitrobenzenes have been measured. Comparison 
with the para-13C chemical shifts in monosubstituted benzenes and with 19F chemical shifts in para-substituted 
fluorobenzenes, indicates that similar factors determine the chemical shifts of these three nuclei. With p-nitro- 
aniline, the l5N chemical shift appears to have an extra paramagnetic contribution, since this is the only com- 
pound studied that does not fit the correlation with 13C and l9F chemical shifts. 
n the Pople2 theory of chemical shifts, the screening I constant of a nucleus A is divided into four contri- 
butions 
where adAA and upAA are the diamagnetic and paramag- 
netic contributions from the electrons of atom A, UAB 
is the contribution from the electrons of atom B, and 
U A , ~ ~ ~ ~  is the contribution due to ring currents. Investi- 
gations in this and other laboratories have shown that 
in the case of c a r b ~ n , ~ ? ~  nitrogen,6-8 and f l u ~ r i n e , ~ , ~ ~  
the main contributions to the shielding constant of the 
nucleus A comes from the paramagnetic term U ~ A A .  
If the comparison of shielding parameters is confined 
to a suitable series of closely related compounds, e.g., 
substituted benzene derivatives, then contributions 
from the substituent anisotropy ( C U A ~ )  and ring 
current ( u A , ~ ~ , , ~ )  terms may be expected to remain essen- 
tially constant. If the mean electronic excitation ener- 
gies, AE, involved in the closure approximation for the 
uPaA's are also constant, then the contribution to the 
shielding constants from and upAA may be related 
in a simple way to the local electron density at the 
nucleus. Such correlations have been reported for 13C 
chemical shifts1 1 , 1 4  in monosubstituted benzenes and 
19F chemical shifts10~12 in para-substituted fluoroben- 
zenes. 
By contrast there has been no detailed investigation of 
I5N chemical shifts in an analogous series of compounds 
despite the obvious theoretical interest of such an in- 
vestigation. With this in mind we have examined 
'jN chemical shifts of a series of para-substituted 15N 
nitrobenzenes in the hope of demonstrating similar 
correlations to those found previously for the and 
19F chemical shifts. 
(1) Supported in part by the Public Health Service Research Grant 
11072-02 from the Division of General Medical Sciences and the 
National Science Foundation. 
(2) J. A. Pople, J .  Chem. Phys. ,  37, 53 (1962). 
(3) M. Karplus and J. A. Pople, ibid., 38, 2803 (1963). 
(4) J. A. Pople, Mol. Phys.,  7, 301 (1963). 
(5) B. E. Holder and M. P. Klein, J .  Chem. Phys. ,  23, 1956 (1955). 
(6) B. M. Schmidt, L. C. Brown, and D. Williams, J .  Mol. Specfry . ,  
(7) J. B. Lambert, G.  Binsch, and J. D. Roberts, Proc. Natl. Acad. 
(8) D. H. Evans and R. E. Richards, Mol. Phys. ,  8, 19 (1964). 
(9) M. Karplus and T. P. Das, J.  Chem. Phys., 34, 1683 (1961). 
(IO) F. P. Prosser and L. Goodman, ibid., 38, 374 (1963). 
(11) H. Spiesecke and W. G. Schneider, ibid., 35, 731 (1961). 
(12) T. K. Wu and B. P. Dailey, ibid., 41, 2796 (1964). 
A#B 
2, 539 (1958); ibid., 3, 30 (1959). 
Sci. US., 51, 735 (1964). 
The series of nitro compounds were chosen for study 
for two reasons : firstly, convenience of preparation, 
and secondly, because the main contribution to the 
paramagnetic term (upas) is expected to arise from 
the u 6 T* transitions of the nitrogen atoms.13 The 
energy of the latter transitions should remain roughly 
constant throughout the series. Also the variation in 
the ring current (u.+ing) and anisotropy terms ( C u A B )  
are expected to remain constant throughout the series. 
(The main contribution to Cu.iB arises from the n + 
T* transition of the oxygen lone pairs, and the energy of 
this transition is little affected by substituents in the 
para position, e.g., nitrobenzene no + T* 330 mp,14 
p-nitrophenol no -+ T* 334 mp.I5) 
Results and Discussion 
Table I gives the 'jN chemical-shift differences of a 
series of para-substituted nitrobenzenes relative to 15N 
nitrobenzene as 15 mole solutions in dimethyl 
sulfoxide. Bulk susceptibility corrections were not 
applied, since these are likely to be well within the ex- 
perimental error (*0.16 p.p.m.), for the relatively 
dilute solutions employed. 
that of IH at constant field) precludes any accurate 
measurement of chemical shifts over a wide range of 
concentrations. 
The first point to note from Table I is the relatively 
small range of chemical shifts, namely 8.23 p.p.m. 
This may be compared with the corresponding '9F 
and chemical shifts in para-substituted fluoro- 
benzenes of 24.35 p.p.m.16" and chemical shifts in 
para-substituted toluenes of 1 p.p.m.16b for the same 
substituents. The intermediate range of the 15N 
chemical shifts is as expected if the paramagnetic terms 
upAA dominate the shielding constants for these nuclei, 
and is indicative that the mean electronic excitation 
energies are at least approximately constant in the 
series.17 
chemical shifts of the para-carbon atom in monosub- 
stituted benzenes with the 19F chemical shifts of para- 
A # B  
A#  B 
The low sensitivity ( 
Previous investigations have correlated the 
(13) See ref. 3, p. 2805. 
(14) K. L. Wolf and W. Herold, Z .  Physik. Chem.,  B13, 201 (1931). 
(15) K. Semba, Bull. Chem. SOC. Japan, 33, 1640 (1960). 
(16) (a) R. W. Taft, E. Price, I. R. Fox, I. C. Lewis, K. K. Anderson, 
and G. T. Davis, J .  Am. Chem. Soc., 85, 3146 (1963); (b) P. C. 
Lauterber, Ann. N .  Y .  Acad. Sci. ,  70, 841 (1958). 
(17) A. Saika and C. P. Slichter. J .  Chem. Phys., 22, 26 (1954). 
Clark, Roberts 1 Chemical Shifts of para-Substituted Nitrobenzenes 
746 
1 
0 NH2 
13c I 
/ 
r 0 OM0 
19F 
-4.0 
-. -6.0 
Figure 1. Plot of para-13C chemical shifts in monosubstituted 
benzenes vs. 1jN chemical shift of nitro group in para-substituted 
nitrobenzenes. Data for 13C are from ref. 11. 
substituted fluorobenzenes.12 In the former case, the 
chemical shifts are determined by the n-electron dis- 
tributions at the carbon atoms,” and the implied cor- 
relation of 19F chemical shifts with n-electron density 
at the attached carbon atom then arises out of the near 
equivalence of the terms involving the C-F B bond 
order and the r-electron density on fluorine. l o  
Table I. 
para-Substituted Nitrobenzenes 
15N Chemical Shifts of the Nitro Group in 
Substituent 
Chemical 
shift, 
p.p.m.“ 
NH2 
OMe 
F 
NHCOCH3 
c1 
Br 
H 
C N  
NOz 
4 .38  
4 .38  
3.57 
3 .07  
2.09 
1 .32  
0.00 
- 2 . 5 8  
-3 .85  
Experimental error is approximately 1 0 . 1 6  p.p.m. A posi- 
tive value of the chemical shift indicates a shift upfield from nitro- 
benzene. 
The chemical shifts are shown plotted against the 
pa r~z - ’~C chemical shifts in monosubstituted benzenes 
and 19F chemical shifts in para-substituted fluoroben- 
zenes in Figures 1 and 2 .  There is a good over-all 
correlation in the two graphs except possibly for the 
15N chemical shift in p-nitroaniline. This would seem 
to confirm that similar factors are operative in deter- 
mining the chemical shift of 15N, 19F, and 13C nuclei. 
By analogy with the theory developed for the cor- 
responding fluorine chemical shifts, l8 the 15N nitro 
chemical shift differences in para-substituted nitro- 
benzenes, should depend on the following factors: 
(1) the n-electron density of the nitrogen atom; (2) 
the 7r-electron density at the adjacent carbon and oxygen 
atoms; (3) the N-C B bond order; (4) the N-0 B 
bond order. The presence of the two oxygen atoms in 
(18) R. W. Taft, F. hosser, L. Goodman, and G. T. Davis, J .  
Chem. Phys. ,  38, 380 (1963). 
A :  -5.0 
, 
Figure 2. Plot of l9F chemical shifts in para-substituted fluoro- 
benzenes vs. 15N chemical shift of nitro group in para-substituted 
nitrobenzenes: A, 19F chemical shifts in dimethyl sulfoxide; 0,  
l9F chemical shifts in cyclohexane. 
the nitro group means that the expression for the 
shielding parameter of the nitrogen atom will be con- 
siderably more complex than that for fluorine. How- 
ever, whatever the contributing factors are, they are 
not all expected to operate in the same direction.lO 
For example, a relatively strong mesomeric substituent, 
such as methoxyl, should increase the electron density 
at the nitrogen atom (l), and also at the carbon and 
oxygen atoms (2 ) ,  thus resulting in an upfield shift 
relative to nitrobenzene. The same substituent is 
expected to increase the N-C n bond order (3), while the 
N-0 7r bond order should decrease (4), the first term 
causing a downfield shift, the latter an upfield shift. 
Despite the possible subtle interplay of these factors, 
there is a good correlation with the corresponding 19F 
and 13C chemical shifts, only p-nitroaniline is possibly 
anomalous. The amino group is known from spec- 
troscopic data to have a much larger (+M) effect than 
the other substituents, l9 and this and dipole moment 
dataz0 indicate that there is considerable interaction 
between the amino and nitro groups. Since the 
increase in C-N n bond order is expected to be larger 
than the decrease in N-0 7r bond order, the extra 
paramagnetic shift implies that the former term more 
than compensates for the increased electron densities 
at the carbon, nitrogen, and oxygen atoms in p-nitro- 
aniline. An alternative explanation would be that for 
p-nitroaniline, the charge-transfer states are much lower 
in energy than for the other nitrobenzenes.21 The 
mean electronic excitation energy A E  for the (T + B* 
transition might thus be expected to be smaller in this 
case, leading to an increased paramagnetic ( U ~ A A )  
contribution to the shielding constant 
Experimental Section 
The nitrogen-15 spectra were obtained with a Varian Model 
V-4300B spectrometer, operated at 6.08 Mc.p.s. and 14,100 gauss, 
(19) J. N. Murrell, “The Theory of the Electronic Spectra of Organic 
(20) A. L. McClellan, “Tables of Experimental Dipcle Moments,” 
(21) Cf. ref. 20, Chapter 10. 
MoIecules,” Methuen and Co. Ltd., London, 1963, p. 226. 
W. H. Freeman and Co., San Francisco, Calif., 1963, p. 192. 
Journal of the American Chemical Society / 88:4 / February 20, 1966 
747 
p-FI~oronitrobenzene-1~N was prepared from fluorobenzene and 
38% nitric-16N acid in the presence of sulfuric acid at 70’. The 
product was isolated in the same way as for the nitrobenzene-l5N 
preparation. 
p-Nitro-16N-anisole was prepared by the reaction of p-bromonitro- 
‘SN-benzene with sodium methoxide in dimethyl sulfoxide solution 
at room temperature. The reaction mixture was poured onto 
crushed ice, and the pale yellow crystals of nitr~-~~N-anisole were 
removed by filtration. 
p-DinitroJ5N-benzene (labeled with 15N in one nitrogen) was pre- 
pared by diazotized p-nitr~-~SN-aniline according to the procedure 
given by Hodgson, et ai. 2 8  
p-Nitro-15N-benzonitrile was prepared from pnitro- 15N-aniline by 
the Sandmeyer reaction in a manner analogous to that previously 
described by Bogert and Hand.27 
The yield was almost quantitative. 
as described previ0usly.’~2~ Most of the following compounds 
were prepared on a 0.5-g. scale. 
pNitroJ5N-acetanilide was prepared by the nitration of acetan- 
ilide with 38% nitric l5N acid (Merck Sharp and Dohme 97% 
l5N), according to the procedures given by VogeL23 
pNitro-l5N-aniline was obtained by the acid hydrolysis of p 
nitro- 16N-acetanilide. 2 3  
Nitrobenzene-l6N was prepared by the nitration of benzene with 
38% nitric-15N acid according to the method given by VogeL2* 
p-Bromonitroben~ene-~5N was prepared by the nitration of 
bromobenzene with 38% n i t r i ~ - ~ ~ N  acid according to the method 
given by Voge1.25 
p-Chloronitroben~ene-~~N was prepared by the nitration of 
chlorobenzene with 38 % nitric-16N acid using similar conditions 
to those in the p-bromonitrobenzene-15N preparation. 
(22) G. Binsch, J. B. Lambert, B. W. Roberts, and J. D. Roberts, 
(23) A. I. Vogel, “A Textbook of Practical Organic Chemistry,” 
(24) Cy. ref. 23, p. 525. 
J .  Am. Chem. Soc., 86, 5564 (1964). 
3rd Ed., Longmans, Green and Co., London, p. 581. 
(25) Cf. ref. 23. D. 527. 
(26) H. H. Hodison, F. Heyworth, and E. R. Ward, J. Chem. SOC., 
(27) M. T. Bogert and W. F. Hand, J .  Am. Chem. Soc., 24, 1035 
1512 (1948). 
(1902). 
Neighboring Carboxyl Group Participation in the Hydrolysis of 
Monoesters of Phthalic Acid. The Dependence of Mechanisms 
on Leaving Group Tendencies 
John W. Thanassi’ and Thomas C. Bruice2 
Contribution f rom the Departments of Biological Sciences and Chemistry, 
University of California at Santa Barbara, Santa Barbara, California. 
Received October 9, 1965 
Abstract: The hydrolyses of the following monohydrogen phthalate esters have been investigated in the region of 
the carboxyl group pK,’ : I, methyl; II,2’-monochloroethyl; 111, propargyl; IV, 2’,2‘,2’-trifluoroethyl; and V, 
phenyl. In addition, the hydrolysis of (VI) 0-phthaloyl-N-acetylserinamide was also investigated. The pKs’ 
values of the alcohols employed in the preparation of the esters fall in the order I > I1 > I11 = VI > IV > V. 
Esters I and I1 hydrolyzed with neighboring COOH group participation while esters IV and V hydrolyze with 
COO- participation. Thus, the mechanism changes with increase in leaving tendencies. The crossover between 
mechanisms occurs for esters of alcohols with pK,’ values of ca. 13.5 so that esters I11 and IV are equally prone to 
COOH and COO- neighboring group catalyzed hydrolysis. These results are considered in the light of the possible 
participation of carboxyl groups in the mechanism of esterases. Extrapolation from this study suggests that such 
participation could be effective but defies detection through conventional examination of pH-rate profiles. 
n order to understand the mechanism of enzyme I action, it is important that the functional groups on 
the protein necessary for activity be identified and that 
their mode of action in the catalytic process be eluci- 
dated. The study of intramolecular catalysis in model 
systems has been a most useful tool in this d i r e ~ t i o n . ~  
This paper deals with neighboring carboxyl group par- 
ticipation in the hydrolysis of half-esters of phthalic 
acid. 
It has been demonstrated that carboxyl anion par- 
ticipates in the hydrolyses of acetyl salicylic acid,4 
substituted phenyl acid succinates and glutarates,j and 
mono-p-bromphenyl esters of substituted glutaric and 
succinic acids.6 On the other hand, ethyl hydrogen 
(1) Postdoctoral Fellow, University of California at Santa Barbara. 
(2) To whom inquiries should be addressed. 
(3) T. C. Bruice, Brookhaven Symp. B i d ,  15,52 (1962). 
(4) E. R. Garret, J.  Am. Chem. Soc., 79, 3401 (1947). 
( 5 )  (a) H. Morawetz and E. W. Westhead, J .  Polymer Sci., 16, 273 
(1955); (b) E. Gaetjens and H. Morawetz, J .  Am. Chem. Soc., 82, 5328 
(1960). 
phthalate’ and methyl hydrogen 3,6-dimethylphthal- 
ates hydrolyze with participation by the neighboring 
protonated carboxyl group. It would appear, then, that 
those monoesters of dicarboxylic acids having good leav- 
ing groups hydrolyze with assistance by neighboring 
carboxyl anion (COO-) and those having poor leaving 
groups hydrolyze with the aid of the neighboring car- 
boxyl group (COOH). 
Carboxyl groups have been implicated in the mech- 
anism of action of several enzymes. Thus, Bernhard 
and Gutfreunds have found that in the ficin-catalyzed 
hydrolysis of benzoyl arginine ethyl ester, a carboxyl 
anion apparently participates in the hydrolysis of the 
acyl enzyme. This has been interpreted to occur by 
means of a rate-limiting attack of the carboxyl anion 
(a) T. C. Bruice and U. K. Pandit, ibid., SO, 5384 (1958); (b) 
Bruice and W. C. Bradbury, ibid., 87, 4846 (1965). 
A. Agren, U. Hedston, and B. Jonnson, Acta Chem. Scand., 15, 
1532 (1961). 
(8) L. Eberson, ibid., 18, 2015 (1964). 
(9) S. A. Bernhard and H. Gutfreund, Biochem. J., 63, 61 (1956). 
Thanassi, Bruice Hydrolysis of Monoesters of Phthalic Acid 


Nitrogen-15 Magnetic Resonance Spectroscopy. VII. Chemical Shifts of para-Substituted Nitrobenzenes

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Nitrogen-15 Magnetic Resonance Spectroscopy. VII. Chemical Shifts of para-Substituted Nitrobenzenes

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