MAGNETIC RESONANCE IN CHEMISTRY, VOL.

27, 233-236 (1989)

NMR Studies on the Structure of

13C
Aminosulfonic Acids in Dimethyl Sulfoxide and

Robert L. Benoit,* Danielle Boulet and Monique Frkhette

Departement de Chimie, Universite de Montrtal C.P. 6128, Succ. A. Montreal, Quebec H3C 3J7, Canada

The I3C NMR spectra of three aminosulfonic acids (HA) Ip-aminobenzenesulfonic acid (sulfanilic acid), amino-
methanesulfonic acid and 2-aminoethanesulfonic acid (taurine)] and their anions (A-) and cations (H,A+) were
obtained using aqueous H,SO, , fuming H,SO, and Me,SO solutions of trifluoromethanesulfonicacid. The chemi-
cal shifts of HA, A- and H2A+ and the protonation and deprotonation shifts of HA are compared with corre-
sponding data for related amines and sulfonic acids in Me,SO and water. Our results indicate that the three
aminosulfonic acids are essentially zwitterionic in Me,SO.
KEY WORDS "C NMR Aminosulfonic acids Sulfanilic acid Taurine Tautomerism Zwitterions Dimethyl sulfoxide

INTRODUCTION HCF,SO, (0.7-2.9 M) or aqueous HClO, (0.6-3.5 M).

Aminosulfonic (AS) acids are interesting compounds, in
particular because of their structural relationship to
amino acids. Whereas in aqueous solution AS acids are
believed to be zwitterionic,' in a non-aqueous solvent
such as dimethyl sulfoxide (Me,SO) the tautomeric
equilibrium is likely to be shifted towards the nonionic
form, as it is with related bifunctional corn pound^.^.^ As
a part of an investigation into the influence of the
solvent on the structure of AS acids we have compared
the I3C NMR spectra of three AS acids and their
anions and cations with the spectra of related sulfonic
acids and sulfonates, substituted ammonium ions and
amines in Me,SO and water. This comparative study
enables us to conclude that the three AS acids studied,
p-aminobenzenesulfonic, aminomethanesulfonic and 2-
aminoethanesulfonic acids, are predominantly zwitter-
ionic in Me,SO. This confirms our earlier claim to this
effect that was based on thermodynamic data.,
EXPERIMENTAL
13C NMR spectra were recorded at 20.2 MHz on a
Bruker WP-80 spectrometer operating in the FT mode.
Dioxane in D,O was used as external reference, the
conversion factor to the TMS scale being aTMS = ddioxane
+ 67.40 ppm. The 13C NMR spectra of aqueous and
Me,SO solutions of the aminosulfonic acids (HA) and
their LiA salts, containing increasing concentrations of
strong acids, were recorded. For the spectra of A - and
HA the NMR samples were obtained by mixing LiA
solutions (0.05-0.30 M) with Me,SO solutions of
* Author to whom correspondence should be addressed
Since pure NH,CH,SO,Li was unavailable, the NMR
samples were prepared from solutions of
NH,CH,SO,H in Me,SO or water to which
NH,CH,CH,SO,Li (0.9-0.24 M) was added. The
spectra of H,A+ were obtained by dissolving the acids,
HA, in Me,SO solutions of HCF,SO, (0-11.3 M) in
aqueous H2S04 (G17.8 M) and in 7% fuming H,SO,
(oleum), the HA concentration being 0.054.15 M.
The source and purification of the acids, HA, and the
preparation of the lithium salts have been described pre-
v i o ~ s l y . ~HCF,SO, (Aldrich), HClO, (Biopharm),
H2S04 (Baker) and 7% fuming H2S04 (Fisher) were
used without further purification. Me,SO (Anachemia)
was of reagent grade.
RESULTS
The I3C NMR shifts for the anions A-,
NH,CH,CH,SO, - and NH,C,H,SO,-, were
obtained from the 13C spectra of the lithium salts, LiA,
dissolved in Me,SO and water. For NH,CH2S0,- the
anion was prepared in situ by adding an excess of basic
NH,CH,CH,SO,Li to a solution of the acid
,
NH ,CH SO,H.
The 13C shift for the soluble acid NH,CH,SO,H was
obtained with a solution of the acid, but for the acids
NH,CH,CH,SO,H and NH,C,H,SO,H the shifts
were deduced from "C data recorded with solutions of
the lithium salts to which was added an increasing con-
centration of HCF,SO, (for Me,SO solutions) or
HClO, (for aqueous solutions). The plots of the 13C
shifts against the molar ratio, r, of added acid to lithium
salt consisted of two straight lines, intersecting at r = 1.
The horizontal line corresponding to r 2 1, indicating
no additional protonation of HA and no medium effect,
gave the 13C shifts for the acid HA. This procedure was
used in part because adding H + to solutions of LiA

0749-1 581/89/030233-04 $05.00 Received 22 June 1988

0 1989 by John Wiley & Sons, Ltd. Accepted (revised) 17 October 1988
234 R. L. BENOIT, D. BOULET AND M. FRECHETTE

Table 1. 13C NMR chemical shifts (ppm) of aminomethane- NH,CH,CH,SO,H we could only obtain 13C spectra
and 2-aminoethane-sulfonic acids and their anions and in 17.8 M H,SO, and 7% fuming H2S0,. Since both
cations in water and Me,SO spectra were nearly identical, it was assumed that the
13C shifts were those of the fully protonated species
Species Solvent c-1 c-2
H,A+. For NH,C,H,SO,H the 13C NMR spectra
NH,CH,SO,- H2O 60.40 were recorded in aqueous 13.3-17.8 M H2S0, and 7%
,
N H + CH ,SO,- HZ0 54.89 fuming H,SO,, and in acidic Me,SO with HCF,SO,
NH,+CH,SO,H" Oleum" 56.4
concentrations between 0.19 and 2.59 M, and above
NH,CH,SO,- Me,SO 61.64
54.70
7.64 M. Hence only partial sigmoid I3C 'titration curves'
NH ,+CH,SO,- Me,SO
NH,+CH,SO,H" TFMS" 55.90
could be obtained which, nevertheless, showed complete
NH,CH,CH $0,- HZ0 54.09 37.62 formation of H,A+ in the very acidic media. An esti-
NH,+CH,CH,SO,- H,O 48.46 36.60 mate of an N o value of -8.0 (14.9 M H,SO,, 83.2%
NH,+CH,CH,SO,H" Oleum" 49.0 37.0 H2S04)could also be obtained for the half-protonation
NH,CH,CH,SO,- Me,SO 55.71 39.50 of NH2C6H,S03H, i.e. -6.7 on the Noascale," in rea-
NH,+CH,CH,SO,- Me,SO 48.80 37.28 sonable agreement with a value of -7.0 deduced from
NH,+CH,CH,SO,H" TFMS" 48.37 36.77 UV data." In Me2S0 the HCF3S0, concentration
a See text. corresponding to half-protonation was near 5.5 M. The
13C shifts for H2A+, HA, A- and related compounds
are given in Tables 1 and 2.

gave supersaturated HA solutions whose HA concen- DISCUSSION

trations were high enough for recording the I3C spectra.
Plotting the I3C shifts against r also helped in the
correct carbon assignments for NH,C,H,SO,- and The discussion is based on comparisons of the I3C
NH,C,H,SO,H, and showed that data attributed to shifts of the AS acids, HA, and their anions A- and
the acid' were actually those of the anion. Full assign- cations H,A+ in both Me,SO and H,O with the shifts
ments of the carbons were made by comparing our data of related amines, sulfonic acids and their salts. We have
with those for benzene,6 benzenesulfonic also considered the protonation and deprotonation
a~id,~ and
. ~ their salts. For NH,CH,CH,SO,H the shifts of HA given in Tables 3 and 4 with those of
most deshielded carbon was taken to be C-1, on the RNH, , RS0,- and RNH3+, RS0,H. These differential
basis of data for CH,CH,SO,H and CH3CH,NH, and shifts may be simpler to interpret since they appear to
their take in account some solvent effects on the absolute
The 13C NMR spectra for the cations H,A+ proved shifts. For example, while the C-1 values of p -
difficult to obtain since addition of H,SO, or aminobenzenesulfonic acid and of its anion differ by 4-5
HCF,SO, (TFMS) initially lowered the solubility ppm in water and Me,SO, the deprotonation shifts of
of HA before the onset of formation of H2A+ again the acid differ by only 1 ppm in the two solvents. On
raised the solubility. For NH,CH,SO,H and the strength of our comparisons, we can decide which is

Table 2. I3C NMR chemical shifts (ppm) of p-aminobenzenesulfonic acid,

its anion and cation and of related compounds' in water and
Me,SO
c-l c-2 c-3 c-4
Species Solvent C-6 C-Y c-B C-31

NH2C6H5 D,O/H,Ob 120.51 130.59 1 17.51 147.35

N H ,+C,H D,O/H,Ob 130.13 131.23 123.95 131.33
NH2C6H5 Me,SOc 116.89 130.02 1 15.06 149.80
NH,+C,H, Me,SO" 129.73 131.05 124.40 132.29
NH,C,H,SO,- H2 0 133.15 127.85 116.13 150.54
,+
N H C,H,SO,- H ,O 144.29 128.28 124.74 133.45
NH3+C,H,S0,Hd Oleumd 137.80 130.87 126.06 134.75
N H ,C,H,SO,- Me,SO 137.35 127.79 113.38 149.93
NH3+C6H,S0,- Me,SO 149.6 128.20 123.97 132.80
NH,+C,H,SO,Hd TFMSd 138.4 130.0 125.3 133.9
C,H,SO,- H ,Oe 143.11 129.86 126.20 132.45
C,H,SO,H Oleum' 133.67 130.76 128.47 137.41
C,H,SO,- Me,SOe 149.37 128.85 126.63 129.68
C,H,SO,H TFMS' 134.14 130.11 127.20 136.12
"All compounds are numbered with -SO,H in the 1-position and -NH, in the
4-position, even for NH,C,H5 (see, however, footnotes b and c).
Ref. 7, -NH, is in the a-position.
Ref. 8, -NH, is in the a-position.
See text.
Unpublished results.
 13C NMR. STRUCTURE OF AMINOSULFONIC ACIDS IN DMSO AND WATER 235

Table 3. I3C NMR protonation and deprotonation shifts (ppm) Table 4. "C NMR protonation and deprotonation shifts (ppm)
of aminomethane- and 2-aminoethane-sulfonic acids of p-aminobenzenesulfonic acid and related com-
and related compounds' in water and Me,SO poundsPin water and Me,SO
Species Solvent AC-1 AC-2 AC-a AC-8 Species Solvent AC-1 AC-2 AC-3 AC-4
NH,CH,CH, Me,SOb NH,C6H,C0,H D,O/H,Ob
t +1.3 +6.0 t -11.1 +0.3 -8.2 +16.7
N H3+CH ,CH , Me,SOb NH,+C,H,CO,H D,O/H,Ob
NH,CH,CH,CH, Me,SOb NH2C6H5 D,O/H,Ob
t +3.1 +6.1 t -9.6 -0.6 -6.4 +16.0
NH,+CH,CH,CH, Me,SOb NH,+C,H, D,O/H,Ob
NH,CH,SO,- H,O NH2C6H5 Me,SO"
t +5.5 t -12.8 -1.0 -9.3 +17.5
NH,+CH,SO,- H2 0 NH ,+C,H5 Me,SO"
1 +1.5 NH,C,H,SO,- H,O
NH,+CH,SO,H Oleum t -11.1 -0.4 -8.6 +17.1
NH,CH,SO,- Me,SO NH,+C,H,SO,- H,O
t +6.9 1 -6.5 +2.6 +1.4 +1.3
NH,+CH,SO,- Me,SO NH,+C,H,SO,H Oleum
1 +1.2 N H ,C,H,SO,- Me,SO
NH,+CH,SO,H TFMS T -12.3 -0.4 -10.6 +17.1
NH,CH,CH,SO,- H2 0 NH,+C,H,SO,- Me,SO
t +5.6 +1.0 1 -11.2 +1.8 +1.3 +1.1
NH,+CH,CH,SO,- H2 0 NH,+C,H,SO,H TFMS
1 +0.5 +0.4 C,H,SO,- H ,Od
NH,+CH,CH,SO,H Oleum 1 -9.4 +0.9 +2.3 +5.0
NH,CH,CH,SO,- Me,SO C,H5S0,H Oleumd
t +6.9 +2.2 C,H,SO,- Me,SOd
NH,+CH,CH,SO,- Me,SO 1 -15.2 +1.3 +0.6 +6.4
1 -0.4 -0.5 C,H5S0,H TFMSd
NH,+CH,CH,SO,H TFMS N H ,C,H,CO, - D,O/H ,O
CH,SO,- H,OC 1 -6.6 +0.9 +0.2 +1.4
1 +0.3 NH,C,H,CO,H D,O/H,Ob
CH,SO,H H,SO,, conc.'
CH,CH,SO,- D,Od "All compounds are numbered with -SO,H in the 1 -position and
-NH, in the 4-position, even for NH,C,H,.
1 +1.2 -1.8
Ref. 7.
CH,CH,SO,H H,SO,, conc.d 'Ref. 8.
CH,CH,CH,SO,- D,Od Unpublished results.
1 +0.2 -1.4
CH,CH,CH,SO,H H,SO,, conc.d
'Acids are numbered with -SO,H in the 1-position and the
amines, using Greek letters, with -NH, in the a-position. tion and protonation shifts of HA and sulfonic acids is
Ref. 8. more informative. First, the C-1 deprotonation shifts of
NH,CH,SO,H and NH,CH,CH,SO,H are both + 6.9
'Unpublished results.
Ref. 9.
ppm (in Me,SO); these are very different in sign and
value from those of CH,S03H, CH3CH,S0,H and
CH,CH,CH,SO,H (-0.3, -1.2 and -0.2 ppm,
the dominant structure of the AS acids, i.e. NH,RSO,H respectively), but very near the deprotonation shifts of
or NH3+RS0,-. Since the alkane- and arene-sulfonic C-B of NH,+CH,CH, and NH3+CH,CH,CH, (+6.0
acids have very different I3C NMR spectra, we consider and +6.1 ppm, respectively). The C-1 protonation shifts
the acids separately. of NH,CH,SO,H and NH,CH,CH,SO,H are small
(+ 1.2 and -0.4 ppm, respectively) in Me,SO ( + 1.5
and +0.5 ppm in water); they are near those for the
Aliphatic aminosulfonic acids protonation of CH,SO,-, CH,CH,SO,- and
CH,CH,CH,SO,- and are very different from the -6
The data in Table 1 show that the 13C shifts of both ppm protonation shifts of C-b of the aliphatic amines.
aminomethane- and 2-aminoethane sulfonic acids differ Both of these results give a clear indication that the
by less than 1 ppm in water and Me,SO. This could be proton of the HA acids is lost from -NH3+ and proto-
taken as an indication that the acids HA have the same nation is on -SO,- (in both Me,SO and water), thus
structure in both solvents, although the larger I3C shifts favoring a zwitterionic structure, NH, +(CH,),SO, -, for
for the anions A- suggest that there may be complicat- the aminosulfonic acids in both solvents.
ing solvent effects. The C-1 shift of both AS acids HA It is worth noting that on deprotonation the 13C res-
cannot be used to differentiate between the -SO,- and onance of NH,CH,SO,H shifts downfield (6.9 ppm in
-SO,H structures since the corresponding values for Me,SO and 5.5 ppm in H,O), as in glycine,
methane- or ethane-sulfonic acids and sulfonates are NH,CH,CO,H (3.5 ppm in However,
both too close and at the same time too far from the whereas for glycine the protonation shift is upfield (1.5
values of HA. However, comparison of the deprotona- ppm in water), for NH,CH,S03H it is downfield ( - 1.3
236 R. L. BENOIT, D. BOULET AND M. FRECHETTE
ppm), but this may be due in part to medium effects
since the NH, +CH2S03H spectra were recorded in
oleum and HCF,SO, .
p-Aminobenzenesulfonicacid
It is apparent from the data in Table 2 that whereas the
C-2, C-3 and C-4 shifts of both p-aminobenzenesulfonic
acid and those of C-2 and C-4 of its anion change little
on changing from water to Me,SO, the C-1 shifts move
4-5 ppm downfield. This reflects the solvation change,
i.e. the loss of solvent hydrogen bonding to the polar
group -SO,-. The C-2, C-3 and C-4 shifts of the acid
are also near the corresponding C-y, C-fl and C-ct of
NH3+C6H,,whereas C-1 is close to c-1of C6H5so3-.
This strongly suggests the NH3+C H SO,- structure
for p-aminobenzenesulfonic acid 'in both solvents.
Further, the deprotonation shifts of p-
aminobenzenesulfonic acid, particularly those of C-1
(- 12.3 ppm in Me,SO) and C-4 (+ 17.1 ppm), are on
the one hand very close to those of NH,+C,H, for c-6
(- 12.8 ppm in Me,SO) and C-ct (+ 17.5 ppm), and on
the other hand very different from those of C,H,SO,H
for C-1 (+ 15.2 ppm) and C-4 (- 6.4 ppm). The proto-
nation shifts of p-aminobenzenesulfonic acid show that
those of C-1 move (upfield) by -11.2 ppm in Me,SO
(- 6.5 ppm in water), in reasonable agreement with the
values for C-1 of C,H,SO,T (-15.2 ppm in Me,SO
and -9.4 ppm in water) and in opposition to a down-
+
field move (ca 11 ppm) for C-6 of NH,C,H,. On the
basis of all these comparisons we can safely conclude
that the zwitterion NH, +C6H4S03- is the dominant
form of p-aminobenzenesulfonic acid in both solvents.
It is possible to go one step further and calculate
from the previous NMR data an estimate of the small
fraction of the molecular tautomer NH,C,H4S03H in
Me,SO. The method is based on the principle of addi-
tivity of substituent effects and has been used to obtain
the distribution of tautomers for both p - and m-
aminobenzoic acids in water.7 We proceed as follows.
First, the intrinsic chemical shifts of molecular HA and
REFERENCES
1. H. P. Hopkins, Jr, C. H. Wu and L. G. Hepler, J. Phys. Chem.
69,2244 (1965).
2. J. C. Hallb, C. Pichon and F. Terrier, J . Biol. Chem. 259, 4142
(1984).
3. J. C. Halle and M. P. Sirnonnin, J. Biol. Chem. 256, 8569
(1981).
4. R. L. Benoit, D. Boulet and M. Frbchette, Can. J. Chem. 66, to
appear in December issue of C.J.C.! (1988).
5. The Sadtler Standard Specfra, Vol. 23, No. 4449c. Sadtler
Research Laboratories, Philadelphia.
6. E. Breitrnaier and W. Voelter, 13CN M R Specfroscopy, 2nd Ed.
pp. 72 and 185-1 87. Verlag Chernie, Weinheirn (1978).
7. D. A. Laufer, R. 1. Gelb and L. M. Schwartz, J. Org. Chem. 49,
691 (1984).
zwitterionic HA* are estimated by selecting a model
system, for example NH,C,H,/NH, +C6H5for which
the protonation shift in Me,SO is A(C-1) = 12.8 ppm +
(Table 4). We add to the C-1 shift of NH2C6H4S03-
(137.5 ppm) the above -NH, (12.8 ppm) protonation
shift to obtain the C-1 shift of NH3+C6H4S03-,
= 150.3 ppm. Similarly, we subtract from the C-1
shift of NH3+C6H,S03H (138.4 ppm) the -NH3+
(12.8 ppm) deprotonation shift to obtain the C-1 shift of
HA, 6,, = 125.6 ppm. Under the condition of rapid
exchange between HA and HA * we then calculate X,, ,
the molar fraction of HA, from XHA = (6 - a,+,)/
- a+
,), where 6 is the observed C-1 shift (149.6 ppm).
We find XHA = 0.028. Using the C-4 shifts instead of
C-1 we obtain X,, = 0.020, in reasonable agreement.
However, as shown by Laufer et LIZ~,. the difficulty of the
method resides in the choice of the correct model com-
pound: values of XHAfor p-aminobenzoic acid in water
vary between 0.97 (benzoic acid as model), 0.98 (p-
hydroxybenzoic acid), 1.OO (p-aminobenzenesulfonic
acid) and 1.08 (aniline), so that aniline obviously failed
as a model in this instance. If one now takes
C,H,S03-/C6H,S03H as a model and an -S03H
deprotonation shift of 15.2 ppm and proceeds as before,
but this time characterizing protonation and deproton-
ation at the SO, - position of p-aminobenzenesulfonic
acid, a surprising value of X,, = 0.19 is found on using
C-1 data. However, it is likely that an unknown and
possibly large medium effect (changing from Me,SO to
HCF,S03) is included in the estimate of the proto-
nation shift of -SO3-, and may give erroneous values
of ,,a in particular. It would seem that more data are
required on the protonation of a series of model substi-
tuted anilines before a final answer can be given as to
the small fraction of molecular p-aminobenzenesulfonic
acid in Me,SO.
Acknowledgements
The authors acknowledge support from the Natural Scjences and
Engineering Research Council and from the Ministtre de 1'Education.
8. J. Llinares, J. Elguero, R. Faure and E. J. Vincent, Org. Magn.
Reson. 14,20 (1 980).
9. Y. Kosugi and T. Takeuchi, Org. Magn. Reson. 12, 435
(1979).
10. T. G. Bonner and J. Philips, J. Chem. SOC.B 650 (1966).
11. P. K. Maarsen, R. Bregrnan and H. Cerfontain, Tetrahedron 30,
1211 (1974).
12. W. J. Horsley and H. Sternlicht, J. Am. Chem. SOC.90, 3738
(1968).
13. W. Horsley, H. Sternlicht and J. S. Cohen, J . Am. Chem. SOC.
92,680 (1970).