1530
J . Org. Chem. 1996, 61, 1530-1532
Sch em e 1
A Gen er a l a n d Efficien t Meth od for
th e P r ep a r a tion of Or ga n ic Su lfon ic
Acid s by In ser tion of Su lfu r Tr ioxid e
in to th e Meta l-Ca r bon Bon d of
Or ga n olith iu m s
temperature, gave a complex mixture of products, includ-
ing the product of addition of butyllithium to pyridine.15
Treatment of sulfur trioxide-trimethylamine complex
(STTAC) with n-butyllithium in diethyl ether also re-
sulted in a complex mixture. However, when THF was
used as the solvent the reaction of commercial STTAC
with n-butyllithium gave a mixture containing the de-
sired butanesulfonate and just one other major compo-
nent, possibly lithium butanesulfinate.16,17 Many at-
tempts to vary the conditions failed to inhibit the
formation of the byproduct when commercial STTAC was
used directly.
Keith Smith* and Duanjie Hou
Department of Chemistry, University of Wales Swansea,†
Singleton Park, Swansea SA2 8PP, UK
Received November 22, 1995
Although direct sulfonation of aromatic compounds is
the most general method of preparing aromatic sulfonic
acids, alternative methods are sometimes required, es-
pecially in the case of complex compounds. The most
common method for generation of aliphatic sulfonate
salts is reaction of aliphatic bromides with sodium
sulfite,1,2 but this reaction is not suitable for vinyl and
aryl bromides. Much work has been done on the inser-
tion reaction of sulfur dioxide with organometallic com-
pounds to form sulfinic acids.3-5 On the other hand, the
only reports of similar reactions of sulfur trioxide have
been of insertions into the bonds between carbon and
other elements of main Group IV6-9 or mercury.10 The
lack of reports concerning reactions of reactive organo-
metallic reagents with sulfur trioxide and our continuing
interest in organolithium chemistry11-13 prompted us to
investigate the reactions of organolithium reagents with
sulfur trioxide in order to see if organic sulfonic acids
could be produced.
1
The H NMR spectrum of commercial STTAC showed
that it contained two major components with signals at
δ 3.06 and 2.77. We therefore undertook its purification
by recrystallization from cold water.18,19 A saturated
solution of the commercial material was concentrated to
one-fourth of its volume in the cold. White crystals were
recovered in 50% yield and dried under vacuum. The
crystalline material consisted almost entirely of a single
1
component (δ 3.06) according to its H NMR spectrum.
The reaction of this with butyllithium was therefore
studied in more detail. The following procedure was
found to be useful.
To a suspension of crystalline STTAC (835 mg, 6 mmol)
in dry THF (30 mL) was added a solution of n-butyl-
lithium (2.5 M in hexane, 2.4 mL, 6 mmol) dropwise at
-78 °C with a syringe over 15 min. The reaction mixture
was stirred for another 2 h at -78 °C and then allowed
to warm to room temperature over 20 h. After removal
of the solvent on a rotary evaporator, hydrochloric acid
(6 M, 4 mL, 24 mmol) was added. The mixture was
extracted with ethyl acetate (4 × 25 mL), and the
combined organic extract was dried (MgSO4) and then
evaporated to give a viscous oil. Diethyl ether (20 mL)
was added and some white solid precipitated. This was
washed with further ether (2 × 15 mL). The ether
solution was concentrated to give 1-butanesulfonic acid
(5) (665 mg, 79%, but 96% pure, so yield 76%).
Since sulfur trioxide complexes14 are much milder and
easier to handle, we chose them as starting materials
instead of free SO3. We now report that trimethyl-
amine-sulfur trioxide reacts with organolithiums to give
lithium sulfonates. Subsequent treatment with acid
affords the corresponding sulfonic acids (Scheme 1).
Our initial investigations involved the reactions of
n-butyllithium with commercial SO3 complexes of pyri-
dine and trimethylamine. The reaction of sulfur triox-
ide-pyridine with n-butyllithium, in diethyl ether or
tetrahydrofuran (THF) and at -78 °C rising to room
A similar procedure was applied to the synthesis of a
range of sulfonic acids from the corresponding organo-
lithium reagents (Table 1). Compounds 5-9 were ob-
tained using commercial solutions of the organolithiums,
and compound 10 was obtained using a commercial
solution of allylmagnesium bromide. The reagent used
for preparation of 11 was obtained by treatment of
4-bromotoluene with 1 equiv of n-butyllithium.20 The
reagents used for the syntheses of 12 and 13 were
obtained by double lithiation of N-pivaloylaniline11a,21,22
and 2-methyl-3-(pivaloylamino)quinazolin-4(3H)-one,23,24
respectively.
† Formerly known as The University College of Swansea.
(1) Houlton, H. G.; Tartar, H. V. J . Am. Chem. Soc. 1938, 60,
544.
(2) Wagner, F. C.; Reid, E. E. J . Am. Chem. Soc. 1931, 53, 3407.
(3) Pinnick, H. W.; Reynolds, M. A. J . Org. Chem. 1979, 44, 160.
(4) Truce, W. E.; Murphy, A. M. Chem. Rev. 1951, 48, 69.
(5) Marvel, C. S.; J ohnson, R. S. J . Org. Chem. 1948, 13, 822.
(6) (a) Eaborn, C.; Hashimoto, T. Chem. Ind. 1961, 1081. (b) Bott,
R. W.; Eaborn, C.; Hashimoto, T. J . Chem. Soc. 1963, 3906. (c) Bott,
R. W.; Eaborn, C.; Hashimoto, T. J . Organomet. Chem. 1965, 3,
442.
(7) Schmibaur, H,; Sechser, L.; Schmidt, M. J . Organomet. Chem.,
1968, 15, 77.
(8) Dubac, J .; Mazerolles, P. J . Organomet. Chem. 1969, 20, P5.
(9) Kitching, W.; Fong, C. W. Organomet. Chem. Rev. Sect. A 1970,
5(3), 281.
(10) Salib, K. A. R.; Senior, J . B. J . Chem. Soc., Chem. Commun.
1970, 1259.
(15) Lithium 2-butyl-1,2-dihydropyridine-1-sulfonate appeared to be
present in the mixture.
(11) (a) Smith, K.; Pritchard, G. Angew. Chem., Int. Ed. Engl. 1990,
29, 282. (b) Smith, K.; Lindsay, C. M.; Pritchard G. J . J . Am. Chem.
Soc. 1989, 111, 665. (c) Smith, K.; Lindsay, C. M.; Morris, I. K.;
Matthews, I.; Pritchard, G. J . Sulfur Lett. 1994, 17, 197.
(12) Smith, K.; Hou, D. J . Chem. Soc., Perkin Trans. 1 1995,
185.
(13) Smith, K.; Anderson, D.; Matthews, I. J . Org. Chem. 1996, 61,
662. (b) Smith, K.; Lindsay, C. M.; Morris I. K. Chem. Ind. (London)
1988, 9, 302. (c) Smith, K.; Anderson, D.; Matthews, I. Sulfur Lett.
1995, 18, 79.
(16) We have not characterized the impurity in commercial STTAC,
but it may be trimethylamine oxide-sulfur dioxide, which could react
with butyllithium to form butanesulfinic acid (see ref 17).
(17) Burg, A. B. J . Am. Chem. Soc. 1943, 65, 1629.
(18) Lecher, H. Z.; Hardy, W. B. J . Am. Chem. Soc. 1948, 70,
3789
(19) Moede, J . A.; Curran, C. J . Am. Chem. Soc. 1949, 71, 852.
(20) Chetcuti, M. J .; Chisholm, M. H.; Folting, K.; Haitko, D. A.;
Huffman, J . C.; J anos, J . J . Am. Chem. Soc. 1983, 105, 1163.
(21) Fu¨hrer W.; Gschwend, H. W. J . Org. Chem. 1979, 44, 1133.
(14) Gilbert, E. E. Chem. Rev. 1962, 62, 549.
0022-3263/96/1961-1530$12.00/0 © 1996 American Chemical Society