Protonation of sulfinamides. Does it occur at oxygen or nitrogen?

Full text of DOI:10.1021/jo960205j

J . Org. Chem. 1996, 61, 7593-7596
7593
Notes
Therefore, each of three atoms can be protonated by
protonic acids affording the corresponding protonated
sulfinamide structures A, B, and C.
P r oton a tion of Su lfin a m id es. Does It
Occu r a t Oxygen or Nitr ogen ?
Bogdan Bujnicki,† J o´zef Drabowicz,†
Marian Mikołajczyk,*,† Alfred Kolbe,‡ and
Lech Stefaniak§
Center of Molecular and Macromolecular Studies, Polish
Academy of Sciences, Sienkiewicza 112, 90-363 Ło´dz´,
Poland, Institute of Physical Chemistry, Department of
Chemistry, Martin Luther University, Halle-Wittenberg, K.
Mothes 2, D-06120, Halle, Germany, and Institute of
Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/ 52, 01-224 Warsaw, Poland
The third structure C resulting from protonation at
sulfur is rather unlikely in view of the fact that structur-
ally related sulfoxides are protonated at oxygen and not
at sulfur.8 Considering the first two structures A and
B, it should be pointed out that both are equally probable
and, moreover, they can exist in equilibrium.
Received J anuary 31, 1996
In tr od u ction
The acid-catalyzed reaction of sulfinamides with alco-
hols (eq 1) developed by us1-3 has become the method of
choice for the preparation of racemic and chiral sulfinic
acid esters. The studies on the synthesis of chiral
sulfinates from easily available chiral sulfinamides have
shown that this conversion exhibits unique stereochem-
ical features.4,5 It was found, namely, that chiral sulfi-
nates are produced either with a full or predominant
inversion or predominant retention of configuration at
the sulfinyl sulfur atom depending on both the structure
of the sulfinamide used and the steric requirements of
an alkyl group in alcohol. Taking into account the fact
that opposite conversion can be accomplished in the
reaction between sulfinates and metalated amines (eq 2),6
it is evident that protonation of the sulfinamide nitrogen
atom creates a driving force for substitution of the
nitrogen-containing ligand as an ammonium leaving
group in the acid-catalyzed conversion of sulfinamides
to sulfinates.
In this context it is interesting to note that the
protonation site strongly depends on the structure of a
heteroatomic molecule. For instance, whereas carboxylic
acid amides are protonated at oxygen,9 in thioamides
protonation occurs at sulfur.10 On the other hand,
selenoamides are protonated at nitrogen.11 Acetoxyhy-
droxamic acid is protonated at the carbonyl oxygen.12
Protonation of phosphonoamidates occurs at nitrogen
rather than oxygen,13 while in aminophosphines the
phosphorus atom is a protonation site.14 Sulfenamides15
and sulfonamides16 undergo protonation at nitrogen. Very
recently, Scorrano and co-workers15 on the basis of
theoretical calculations and 14N NMR spectroscopic stud-
ies of a limited number of sulfinamides suggested that
sulfinamides are protonated at oxygen. This prompted
us to report our spectroscopic observations which indi-
cate, however, that protonation of sulfinamides occurs
preferentially at the nitrogen atom.
Resu lts a n d Discu ssion
To compare IR and NMR spectra of the free and
protonated sulfinamides, the following model amides 1
have been prepared. The protonated forms of sulfina-
mides, 1-H+X-, were generated by treatment of 1 with 1
equiv of trifluoroacetic acid or gaseous hydrogen chloride
in aprotic solvents unless otherwise stated. As further
Since protonation of a sulfinamide molecule is the first
preequilibrium step in the acid-catalyzed sulfinamide to
sulfinate conversion and does not have to occur only at
the nitrogen atom, we decided to compare spectral
properties of the free and protonated sulfinamides in the
hope of determining the preferred site of protonation in
these structures.7
Et
Theoretically, the molecule of sulfinamide contains
three basic centers located on the sulfinyl oxygen atom,
tricoordinated nitrogen atom, and sulfinyl sulfur atom.
† Center, Polish Academy of Sciences, Ło´dz´.
‡ Institute, Martin Luther University, Halle.
§ Institute, Polish Academy of Sciences, Warsaw.
(1) Mikołajczyk, M; Drabowicz, J .; Bujnicki, B. J . Chem. Soc., Chem.
Commun. 1976, 568.
(2) Mikołajczyk, M.; Bujnicki, B.; Drabowicz, J . Bull. Acad. Polon.
Sci. 1977, 25, 267.
(3) Mikołajczyk, M.; Drabowicz, J .; Bujnicki, B. Tetrahedron Lett.
1985, 26, 5699.
(4) Mikołajczyk, M. Phosphorus Sulfur 1986, 27, 31.
(5) Mikołajczyk, M. In Perspectives in the Organic Chemistry of
Sulfur; Zwanenburg, B., Klunder, A. J . H., Eds.; Elsevier: New York,
1987; p 23.
model compounds in our investigations, pyrrolidine (2),
its trifluoroacetate 3, and methoxypyrrolidinylphenyl-
sulfonium trifluoromethanesulfonate (4) were chosen.
The ammonium salt 3 should imitate the N-protonated
(6) Colonna, S.; Giovini, R.; Montanari, F. J . Chem. Soc., Chem.
Commun. 1968, 865.
S0022-3263(96)00205-8 CCC: $12.00 © 1996 American Chemical Society

7594 J . Org. Chem., Vol. 61, No. 21, 1996
Notes
form of 1a while the O-methoxy sulfonium salt 42,17
should mimic the O-protonated form of this sulfinamide.
In the first series of experiments the IR spectra of the
sulfinamide 1a measured alone and in the presence of
an equimolar amount of trifluoroacetic acid were re-
corded. The free sulfinamide 1a showed two absorptions
at 1060 and 1080 cm-1 characteristic of the sulfinyl
group, SdO. The assignment of these two bands as being
originated by the SO group was given by Mori and Ueda18
and, in detail, by Kolbe and Wenschuh.19 The last-
mentioned authors discussed these two bands in terms
of conformational isomerism arising from the rotation
around the S-aromatic ring bond. It should be pointed
out that a substantial coupling between the SO streching
vibration and the SN bonding vibration cannot take place
due to the difference in the force constants for both
vibrations. Upon addition of trifluoroacetic acid the two
SO bands were shifted to higher wavenumbers and
appeared at 1160 and 1200 cm-1, respectively. The same
direction of change was observed when gaseous hydrogen
chloride was passed through a solution of 1a in methyl-
ene chloride (see Figure 1). Thus, the IR spectrum of
the free sulfinamide 1a in methylene chloride shows two
SO bands at 1058 and 1083 cm-1. Another band seen in
the spectrum near to 1020 cm-1 is tentatively assigned
to the N-CH2 streching vibration. This band was found
to appear also in the Raman spectrum of 1a , supporting
our assignment. In the presence of hydrogen chloride
these three discussed bands were shifted to higher
wavenumbers and appeared at 1150, 1115, and 1076
cm-1, respectively. To confirm that the recorded IR
spectrum is due to the protonated sulfinamide 1a , i.e.,
1a -H+Cl-, this solution, after the spectrum was recorded
(ca. 20 s), was washed with a 5% solution of sodium
carbonate. The IR spectrum evidenced the presence of
the regenerated sulfinamide 1a only (Figure 1). The
observed substantial shift of the SdO and N-CH2
absorptions toward higher wavenumbers may be consid-
ered as strongly indicative of protonation at nitrogen
because only in this case does the strength of the SdO
and N-C bonds increase.
F igu r e 1. IR spectra of N,N-diethyl p-toluenesulfinamide
(1a ): (‚‚‚) before protonation; (‚-‚) after protonation with
gaseous HCl; (s) recovered from the protonated sample by
washing with 5% aqueous solution of Na2CO3.
acid was added, the singlet at 2.40 ppm disappeared
completely and only the singlet at 2.70 ppm was ob-
served. Such a picture indicates that the exchange
between free and protonated sulfinamide 1b does not
occur at -60 °C.
1
The H NMR spectra of the sulfinamide 1b provided
However, from the point of view of the problem under
discussion, 13C NMR spectra of the sulfinamide 1c and
evidence that it is fully protonated by fluoroantimonic
acid at low temperatures. Thus, in the spectrum re-
corded at -60 °C in methanol-d4 the resonance signal of
the N-methyl protons appeared as a singlet at 2.40 ppm.
After addition of 0.5 equiv of fluoroantimonic acid, a new
signal at 2.70 ppm was observed. When 1 equiv of the
its protonated form are more interesting, 1c-H+CF 3CO2
,
-
especially when compared with those of the reference
compounds 2, 3, and 4. The values of carbon chemical
shifts for 1c, 1c-H+CF 3CO2-, pyrrolidine (2) and its
trifluoroacetate 3 are collected below. It should be noted
that the spectra were recorded under the same condi-
tions, i.e., in ethanol-d1 at -60 °C.
(7) The results were presented at the IX International Conference
on the Organic Chemistry of Sulfur, Merseburg, Germany, 1994.
Bujnicki, B.; Drabowicz, J .; Mikołajczyk, M.; Kolbe, A. Phosphorus,
Sulfur, Silicon Relat. Elem. 1994, 95, 419.
(8) Taft, R. Progr. Phys. Org. Chem. 1983, 14, 247. Furukawa, N.;
Fujihara, H. In The Chemistry of Sulfones and Sulfoxides; Patai, S.,
Rappoport, Z., Stirling, C. J . M., Eds.; Wiley: New York, 1988; p 541.
See also ref 15.
(9) Perrin, C.; J ohnston, E. J . Am. Chem. Soc. 1981, 103, 4697.
Birchall, T.; Gillespie, R. J . Can. J . Chem. 1963, 41, 2642; 1965, 43,
1045. Olah, A.; Brydon, D. L.; Porter, R. D. J . Org. Chem. 1970, 35,
317.
(10) Bagno, A.; Comuzzi, C.; Scorrano, G. J . Chem. Soc., Perkin
Trans. 2 1993, 283.
(11) Paulmier, C.; Lerouge, P.; Outurquin, F.; Chapelle, S.; Granger,
P. Magn. Reson. Chem. 1987, 25, 955.
(12) Bagno, A.; Comuzzi, C.; Scorrano, G. J . Am. Chem. Soc. 1994,
116, 916.
(13) Rahil, J .; Haake, P. J . Am. Chem. Soc. 1981, 103, 1723.
Thatcher, G. R. J .; Kluger, R. Adv. Phys. Org. Chem. 1989, 25, 99.
(14) Nifantyev, E. E.; Gratchev, M. K.; Burmistrov, S. Y.; Antipin,
M. Y.; Struchkov, Y. T. Phosphorus, Sulfur, Silicon Relat. Elem. 1992,
70, 159.
(15) Bagno, A.; Eustace, S.; J ohansson, L.; Scorrano, G. J . Org.
Chem. 1994, 59, 232.

Notes
J . Org. Chem., Vol. 61, No. 21, 1996 7595
Ta ble 1. 15N NMR Sp ectr a l Da ta for F r ee a n d P r oton a ted Su lfin a m id es 1
free amide 1
solvent
temp (°C)
δ (ppm)
protonated amide 1
solvent
temp (°C)
δ (ppm)
∆δ (ppm)
1c
1d
1d
1d
1e
1f
C2H5OD
CH2Cl2
CH2Cl2
CDCl3
CDCl3
CH2Cl2
CDCl3
-60
-80
-80
22
22
-80
22
-288.67
-311.49
-311.49
-309.12
-295.65
-284.05
-280.10
1c-H+
1d -H+
1d -H+
1d -H+
1e-H+
1f-H+
1f-H+
CH2Cl2
CH2Cl2
CDCl3
-80
0
22
-317.90
-316.67
-317.48
6.51 v
5.18 v
8.36 v
CH2Cl2
CDCl3
-80
22
-290.50
-288.17
6.45 v
8.07 v
1f
Furthermore, the 13C NMR spectrum of 1c was re-
corded in nitromethane-d3 at room temperature and
compared with that of 4. The pertinent data are shown
below.
DMSO to CF3CO2H as solvents the 15N resonances of
MeSO2NHPh, MeSO2NHBut, and MeSO2NH2 undergo
upfield shift, the ∆δ values being 4.1, 7.6, and 7.6 ppm,
respectively. When water is used as solvent, an interest-
ing dependence of the 15N resonance signal for MeSO2-
NH2 on pH was found. At pH ) 12.3-12.4, this amide
resonates at δ ) -273.5 ppm, while in the acidic region
at pH ) 1.0-1.1, the signal appeared at δ ) -284.4 ppm,
i.e., was upfield shifted (∆δ ) 10.8 ppm). These results
led Kricheldorf16 to the conclusion that the sulfonamide
nitrogen is protonated and involved in hydrogen bond
formation.
In summary, the results of our comparative studies on
spectral properties of neutral and protonated sulfina-
mides 1 indicate that protonation occurs at nitrogen and
not at oxygen.21 However, as was mentioned earlier, the
validity of this conclusions is based on the assumption
that spectral changes of neutral and protonated sulfina-
mides as well as those of reference compounds show the
same trends. On the basis of our qualitative data, it is
not possible to exclude some amounts of the O-protonated
form being in equilibrium with the N-protonated sulfi-
namide. Moreover, depending on the measurements
conditions (protic and aprotic solvents, concentration,
acidity), the preferred site of the protonation of sulfina-
mides 1 may be different. This may be a reason for
different results obtained by us and the Italian group.
An inspection of the above spectral data reveals that
the resonance signals of the R and â carbons of the
pyrrolidine ring in 1c are upfield shifted upon protona-
tion. The same upfield shift of the R and â carbons is
observed when pyrrolidine is protonated to give the
N-protonated form 3.20 On the contrary, the resonance
signal of the pyrrolidine R carbon in the sulfonium salt
4, in which sulfur and not nitrogen is positively charged,
is downfield shifted with respect to that of 1c.
Assuming that the spectral behavior of sulfinamides,
their protonated forms and reference compounds are
similar, we observe 13C NMR spectral changes and
especially those of the pyrrolidine R and â carbons in 1c-
H+ and 4 that may indicate that the sulfinamide nitrogen
is a preferred site of protonation.
More convincing arguments in support of the above
conclusion were provided by comparison of the 15N NMR
spectra of free and protonated sulfinamides 1 recorded
in ethanol-d1, dichloromethane, and chloroform-d1 as
solvent at different temperatures (-80, -60, 0 and 22
°C). It was found that the 15N singlet resonances of 1
(see Table 1) are shifted to higher fields upon protonation,
indicating that a positive charge should be located at the
nitrogen atom.
Exp er im en ta l Section
Benzenesulfinyl and p-toluenesulfinyl chlorides were
prepared by chlorination of the appropriate disulfides
either with gaseous chlorine in methylene chloride and
acetic anhydride22 or with sulfuryl chloride and trimeth-
ylsilyl acetate.23 Adamantanesulfinyl chloride was ob-
tained by the reaction of adamantane and thionyl chlo-
ride in the presence of AlCl3.24
Sulfinamides 1a and 1d were prepared from the
appropriate sulfinyl chlorides and diethylamine or gas-
eous ammonia. The amides 1b and 1c were obtained by
treatment of benzenesulfinyl chloride with methylamine
and pyrrolidine, respectively. Adamantanesulfinamides
1e and 1f were synthesized from adamantanesulfinyl
chloride, benzylamine, and (()-R-phenylethylamine. All
the above reactions were carried out in anhydrous ether
at -10 °C. All sulfinamides 1 were purified by column
chromatography on silica gel using ether-hexane as
eluent and characterized by NMR and mass spectra.
Methoxpyrrolidinylphenylsulfonium trifluoromethane-
sulfonate (4) was prepared by methylation of the sulfi-
namide 1c with an excess of methyl trifluoromethane-
sulfonate in a nitromethane solution at room tempera-
As in the case of 13C NMR spectra, the 15N NMR signal
of the methoxy sulfonium salt 4 was recorded for com-
parison purposes. It appeared at δ ) -168.13 ppm (CD3-
NO2, rt) and was strongly downfield shifted with respect
to that of the reference sulfinamide 1c (δ ) -281.36 ppm,
CD3NO2, rt).
It is appropriate to mention that similar changes in
15N NMR spectra were observed for the structurally
closely related sulfonamides.16 Thus, on going from
(16) Kricheldorf, H. Angew. Chem. 1978, 90, 489; Angew. Chem.,
Int. Ed. Engl. 1978, 17, 442.
(17) For conclusive X-ray evidence for O-methylation of sulfinamides
by methyl triflate, see: Pickersgill, I. F.; Marchington, A. P.; Thornton-
Pett, M; Rayner, C. M. Chem. Commun. 1995, 647.
(18) Mori, K.; Ueda, Y. Chem. Pharm. Bull. 1972, 20, 829.
(19) Kolbe, A.; Wenschuh, E. J . Mol. Struct. 1975, 28, 359.
(20) The same direction of changes in the chemical shifts for the R
and â carbons was observed when morpholine and R-phenylethylamine
were protonated in ethanol-d1. The upfield shift of these carbons in
morpholine was ∆δ ) 4.35 and 3.19 ppm, respectively. The correspond-
ing values for R-phenylethylamine were 6.46 and 2.47 ppm.
(21) Protonation on nitrogen was also assumed in studies of pK
values of sulfenamides and sulfinamides: Bayfield, R. F.; Cole, E. R.
Phosphorus, Sulfur, Silicon Relat. Elem. 1989, 45, 237. Clarke, V.; Cole,
E. R. Phosphorus, Sulfur, Silicon Relat. Elem. 1989, 45, 243.
(22) Douglas, J . B.; Norton, R. V. J . Org. Chem. 1968, 33, 2104.
(23) Drabowicz, J .; Bujnicki, B.; Dudzin˜ski, B. Synth. Commun.
1994, 27, 1207.
(24) Streter, H.; Krause, M.; Last, W. D. Chem. Ber. 1969, 102, 3357.

7596 J . Org. Chem., Vol. 61, No. 21, 1996
Notes
ture.2 Its 1H, 13C, and 15N NMR spectra are in accord
with the structure; the methoxy resonance signal appears
ployed, and a flip angle ca. 40°, aquisition time 2.0 s, and
a relaxation delay of 4-8 s were applied for proton-
decoupled spectra. External nitromethane was used as
1
at 4.25 ppm in the H NMR (CDNO2, 80 MHz) spectrum
and at 62.5 ppm in the 13C NMR (CDNO2, 50.33 MHz)
spectrum.
a
15N reference (δN ) 0.0 ppm).
Infrared (IR) spectra were obtained as neat films
unless otherwise stated. 1H NMR spectra were recorded
at 80, 200, and 300 MHz with chemical shifts (δ)
downfield from TMS as internal standard. 13C NMR
spectra were recorded at 50.33 and 75.4 MHz.
15N NMR measurements were done on a 500 MHz
spectrometer. The frequency of 50.698 MHz was em-
Su p p or tin g In for m a tion Ava ila ble: Raman spectra of
PhSONEt2 (2 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O960205J