Unexpected differences in the α-halogenation and related reactivity of sulfones with perhaloalkanes in KOH-t-BuOH

Article abstract of DOI:10.1021/jo025781w

Most alkyl phenyl sulfones are readily α-chlorinated with CCl₄ and α-brominated with CBrCl₃ in KOH-t-BuOH via radical-anion radical pair (RARP) reactions. While isopropyl mesityl sulfone (4) is easily α-chlorinated with CCl₄, it was completely recovered when treated with the more reactive CBrCl₃. Subsequent investigations showed the latter result to be due to the poor acidity of 4 together with the rapid depletion of CBrCl₃ and KOH by their reaction with each other, and led to a variety of other important results. 4-Hydroxyphenyl isopropyl sulfone (6) is unreactive with either CCl₄ or CBrCl₃ in KOH-t-BuOH, its phenoxide anion strongly reducing the electronegativity of the sulfonyl group, thereby inhibiting α-anion formation. This effect is reversed by the electron-withdrawing influence of two α-phenyls, so that benzhydryl 4-hydroxyphenyl sulfone (8) is readily α-halogenated in KOH-t-BuOH with CCl₄ or CBrCl₃. On further contact with KOH-t-BuOH the α-halogenated sulfones from 8 are decomposed into benzophenone and phenol. While the α-halogenated derivatives of 4-methoxyphenyl benzhydryl sulfone (9) are stable to base, they are decomposed even under mildly acidic conditions into 4-methoxyphenyl 4-methoxybenzenethiolsulfonate (9c), phenol, and benzophenone. Mono-α-halogenation of benzyl phenyl sulfone (10) enhances the rate of the subsequent halogenation, so that α,α-dihalogenation is attained while much substrate is still present and the mono-α-halogenated product is not detected. The ease of reductive debromination of α-bromo sulfones with Cl₃C^- was correlated with the stability of the formed α-anions, explaining the success with α-bromobenzylic sulfones but failure with α-bromoalkyl sulfones. In the presence of air and the absence of competing halogenation, formation of the α-anions of alkyl aryl sulfones is quickly accompanied by oxidative cleavage by atmospheric O₂, leading to the formation of arenesulfonyl alcohols, arenesulfonyl halides, and haloarenes.

Full text of DOI:10.1021/jo025781w

Un exp ected Differ en ces in th e r-Ha logen a tion a n d Rela ted
Rea ctivity of Su lfon es w ith P er h a loa lk a n es in KOH-t-Bu OH
Cal Y. Meyers,*,†,§ Roch Chan-Yu-King,§,‡ Duy H. Hua,§,¶ Vera M. Kolb,§,
Walter S. Matthews,§,| Thomas E. Parady,§,& Toyokazu Horii,§,# Paul B. Sandrock,†,§
Yuqing Hou,†,§ and Songwen Xie†,§
Meyers Institute for Interdisciplinary Research in Organic and Medicinal Chemistry, and Department of
Chemistry and Biochemistry-4409, Southern Illinois University, Carbondale, Illinois 62901
cal@chem.siu.edu
Received March 31, 2002
Most alkyl phenyl sulfones are readily R-chlorinated with CCl4 and R-brominated with CBrCl3 in
KOH-t-BuOH via radical-anion radical pair (RARP) reactions. While isopropyl mesityl sulfone
(4) is easily R-chlorinated with CCl4, it was completely recovered when treated with the more reactive
CBrCl3. Subsequent investigations showed the latter result to be due to the poor acidity of 4 together
with the rapid depletion of CBrCl3 and KOH by their reaction with each other, and led to a variety
of other important results. 4-Hydroxyphenyl isopropyl sulfone (6) is unreactive with either CCl4 or
CBrCl3 in KOH-t-BuOH, its phenoxide anion strongly reducing the electronegativity of the sulfonyl
group, thereby inhibiting R-anion formation. This effect is reversed by the electron-withdrawing
influence of two R-phenyls, so that benzhydryl 4-hydroxyphenyl sulfone (8) is readily R-halogenated
in KOH-t-BuOH with CCl4 or CBrCl3. On further contact with KOH-t-BuOH the R-halogenated
sulfones from 8 are decomposed into benzophenone and phenol. While the R-halogenated derivatives
of 4-methoxyphenyl benzhydryl sulfone (9) are stable to base, they are decomposed even under
mildly acidic conditions into 4-methoxyphenyl 4-methoxybenzenethiolsulfonate (9c), phenol, and
benzophenone. Mono-R-halogenation of benzyl phenyl sulfone (10) enhances the rate of the
subsequent halogenation, so that R,R-dihalogenation is attained while much substrate is still present
and the mono-R-halogenated product is not detected. The ease of reductive debromination of R-bromo
sulfones with Cl3C- was correlated with the stability of the formed R-anions, explaining the success
with R-bromobenzylic sulfones but failure with R-bromoalkyl sulfones. In the presence of air and
the absence of competing halogenation, formation of the R-anions of alkyl aryl sulfones is quickly
accompanied by oxidative cleavage by atmospheric O2, leading to the formation of arenesulfonyl
alcohols, arenesulfonyl halides, and haloarenes.
In tr od u ction
to account for these halogenations,3 as illustrated in
Scheme 1 for the chlorinations with CCl4. The suggestion
of a RARP transition state instead of an intermediate
Some years ago we published a series of reports noting
the facile R-chlorination of sulfones and ketones in
powdered KOH-t-BuOH with CCl4 and R-bromination/
chlorination with CBrCl3, some subsequent reactions, and
the reactions of alcohols with these reagents.1 The
potential utility of these reactions has received consider-
able attention.2 Single-electron transfers proceeding from
the R-sulfonyl carbanion or enolate anion via a radical-
anion radical pair (RARP) transition state were suggested
(1) (a) Meyers, C. Y.; Malte, A. M.; Matthews, W. S. J . Am. Chem.
Soc. 1969, 91, 7510-7512. (b) Meyers, C. Y.; Malte, A. M.; Matthews,
W. S. Quart. Rept. Sulfur Chem. 1970, 5, 229. (c) Meyers, C. Y.; Ho, L.
L. Tetrahedron Lett. 1972, 2319-2322. (d) Meyers, C. Y.; Sataty, I.
Tetrahedron Lett. 1972, 4323-4326. (e) Meyers, C. Y.; Ho, L. L.;
McCollum, G. J .; Branca, J . C. Tetrahedron Lett. 1973, 1843-1846.
(f) Meyers, C. Y.; Matthews, W. S.; McCollum, G. J .; Branca, J . C.
Tetrahedron Lett. 1974, 1105-1108. (g) Meyers, C. Y. Prepr. Am. Chem.
Soc., Div. Pet. Chem. 1974, 19 (2), 199-203. (h) Meyers, C. Y.; Kolb,
V. M. J . Org. Chem. 1978, 43, 1985-1990. Meyers, C. Y.; Kolb, V. M.
J . Org. Chem. 1979, 44, 3739.
(2) (a) Meyers, C. Y.; Matthews, W. S.; Malte, A. M. U.S. Patent
3,830,862, August 20, 1974. (b) Meyers, C. Y.; Ho, L. L. U.S. Patent
3,876,689, April 8, 1975. (c) Meyers, C. Y.; Malte, A. M. U.S. Patent
3,896,164, J uly 22, 1975. (d) Meyers, C. Y.; Matthews, W. S.; Malte,
A. M. U.S. Patent 3,949,001, April 6, 1976. (e) Meyers, C. Y.; Matthews,
W. S. U.S. Patent 3,953,494, April 27, 1976. (f). Meyers, C. Y.; Ho, L.
L. J apanese Patent 973405, Sept. 28, 1979. (g) Meyers, C. Y.; Read, R.
B. U.S. Patent 5,022,983, J une 11, 1991.
* To whom correspondence should be addressed. E-mail: meyers@
chem.siu.edu. FAX: 618-453-6408.
† Meyers Institute for Interdisciplinary Research in Organic and
Medicinal Chemistry.
§ Department of Chemistry and Biochemistry.
‡ Present address: Science Division, University of Science and Arts
of Oklahoma, Chickasha, OK 73018.
¶
Present address: Department of Chemistry, Kansas State Uni-
versity, Manhattan, KS 66506.
Present address: Department of Chemistry, University of Wis-
consin-Parkside, Kenosha, WI 53141-2000.
(3) (a) Meyers, C. Y.; Matthews, W. S.; Ho, L. L.; Kolb, V. M.; Parady,
T. E. In Catalysis in Organic Syntheses; Smith, G. V., Ed.; Academic
Press: New York, 1977; pp 197-278. (b) Meyers, C. Y. In Topics in
Organic Sulfur Chemistry; Tisler, M., Ed.; University Press: Ljubljana,
Yugoslavia, 1978; pp 207-60.
| Present address: Intel Corp., Santa Clara, CA 90502.
&
Present address: Roquette America, Keokuk, IA 52632.
#
Present address: Radiation Center, Osaka Prefecture, J apan.
10.1021/jo025781w CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/13/2002
500
J . Org. Chem. 2003, 68, 500-511

R-Halogenation and Related Reactivity of Sulfones
TABLE 1. r-Ha logen a tion of R1R2CHSO2Ar in
KOH-t-Bu OH w ith CCl4 (a ) a n d w ith CBr Cl3 (b)a
SCHEME 1
was based on the observation that R-chlorination was
attained with retention of R-carbon configuration.4
Illustrative examples of these halogenations are shown
in Table 1. While isopropyl phenyl sulfone (1) as well as
isopropyl mesityl ketone (5) were readily R-halogenated
with CCl4 or CBrCl3, we were surprised, therefore, to find
that isopropyl mesityl sulfone (4), although readily
R-chlorinated with CCl4, was quantitatively recovered
when treated with the more reactive CBrCl3, even after
prolonged reaction time. As shown in Scheme 2, however,
when treated with n-BuLi in THF followed by CBrCl3, 4
was readily converted into R-bromoisopropyl mesityl
sulfone (4b) along with some R-chloroisopropyl mesityl
sulfone (4a ); when the n-BuLi treatment was followed
by the addition of Br2, 4b was formed in good yield, easily
isolated chromatographically, and found to be a stable
compound.5,6 Thus, the following questions arose: How
does 4 differ from related sulfones and even from the
corresponding mesityl ketone? Why cannot 4 be haloge-
nated by CBrCl3 in KOH-t-BuOH when it is readily
halogenated by CCl4 in this medium? In studies seeking
the answers, a variety of related reaction phenomena was
uncovered.
a
The brominations of the sulfones with CBrCl3 were sometimes
b
accompanied by minor amounts of chlorination. In contrast, the
corresponding mesityl ketone (5) reacted with CBrCl3 to form 5b
(100% yield), as well as with CCl4 to form 5a (100% yield). c Under
the conditions of its formation, 8b was rapidly fragmented into
Resu lts a n d Discu ssion
d
other products; see discussion. Reaction with CCl4 not carried
Solvin g t h e Isop r op yl Mesit yl Su lfon e E n igm a .
The failure of 4b to be detected as a product from the
treatment of 4 with CBrCl3 or CBr4 in KOH-t-BuOH was
originally associated with the possibility that it was
indeed formed, but was reductively debrominated back
to 4-R-anion by reaction with the Cl3C- generated in
these halogenations (see Scheme 1). Such a possibility
seemed reasonable in light of the abundance of Br- we
found after many reaction attempts and from the reduc-
tive debromination of R-bromobenzhydryl phenyl sulfone
(7b) and R,R-dibromobenzyl phenyl sulfone (10b)7 with
out. e Also from 10, C2Cl6, aq NaOH/P-T-C. f Also from 10, CBrCl3,
aq NaOH/P-T-C.
SCHEME 2
(4) (a) Meyers, C. Y.; Sam, T. W. International Conference on
Conformational Analysis, University of New Hampshire, Durham,
J une 29-J uly 2, 1981; Abstracts. (b) Sam, T. W.; Hua, D. H.;
Badanyan, Sh.; Kolb, V. M.; Rihter, B.; Meyers, C. Y. International
Conference on Conformational Analysis, University of New Hampshire,
Durham, J une 29-J uly 2, 1981; Abstracts.
(5) Meyers, C. Y.; Hou, Y.; Sandrock, P.; Robinson, P. D.; Hua, D.
H.; Chan-Yu-King, R. Abstracts of Papers, National Meeting of the
American Chemical Society, Boston, MA, Aug 23-28, 1998; American
Chemical Society: Washington, DC, 1998; ORGN 637.
(6) Chan-Yu-King, R.; Hou, Y.; Sandrock, P.; Meyers, C. Y.;
Robinson, P. D. Acta Crystallogr. 2001, Sect. E, 57, 449-450.
(7) Lauritzen, S. E.; Romming, C.; Skattebøl, L. Acta Chem. Scand.
1981, B35, 263-268.
Cl3C-. However, this suggestion was ruled out: 4b was
quantitatively recovered when treated with Cl3C- (CHCl3-
KOH-t-BuOH) at 25 °C. These results are summarized
in Scheme 3. The failure of 4 to react with CBrCl3 was
J . Org. Chem, Vol. 68, No. 2, 2003 501

Meyers et al.
SCHEME 3
The rate of these halogenations is related to the acidity
of the substrate and the reactivity of the generated
carbanion with the perhaloalkane.3 Regarding the first,
we reasoned that if the formation of 4-R-carbanion is
slow, while CBrCl3 and KOH, but not CCl4 and KOH,
are consumed rapidly by reaction with each other, this
combination of factors might explain the contrasting
activity between CCl4 and CBrCl3 with 4 in KOH-t-
BuOH. Two D/H exchange experiments provided direct
evidence of the poor acidity of 4. When a solution of 4 in
excess t-BuOD was stirred with KOH for 16 min, ca. 10%
R-D/H exchange was observed; in an hour, only 28% D/H
exchange was observed. But when a solution of CBrCl3
in t-BuOD was added to a mixture of 4 and powdered
KOH and the entity stirred for an hour, 4 was almost
completely recovered, n o R D-H exchange was observed,
the KOH was virtually consumed, and an abundance of
Br- and Cl- was produced (Scheme 5). The rapid deple-
tion of CBrCl3 and KOH by their reaction with each other
was also borne out. When the KOH was added to a
solution of 1, CBrCl3, and t-BuOH, 76% R-halogenation
was observed in 1.25 h. However, when the same
amounts of these reagents were used but a mixture of
the CBrCl3, KOH, and t-BuOH was stirred for an hour
before 1 was added, then for an additional hour, only 5%
R-halogenation occurred, although substantial amounts
of Cl- and Br- were generated. Therefore, substantial
amounts of KOH and CBrCl3 were consumed by their
reaction with each other prior to the addition of 1, thereby
precluding any significant amount of halogenation. These
facts lead to the conclusion that the CBrCl3 and KOH
are consumed faster than 4 is deprotonated and can react
with residual CBrCl3. From its estimated pKa, mesityl
sulfone 4 is between 1 and 2 pKa units less acidic than
its counterpart phenyl sulfone 1, and about 5 pKa units
less acidic than the mesityl ketone 5, both of which
undergo R-halogenation with CBrCl3-KOH-t-BuOH.
SCHEME 4
in stark contrast to its ease of chlorination to provide 4a
with the less reactive CCl4 at 25 °C. Furthermore, during
several hours of contact with CCl4 in KOH-t-BuOH, 4a
underwent dichlorination of one of its o-methyls, forming
2-chloro-2-propyl 4-(5-dichloromethyl-1,3-xylyl) sulfone
(4c); subsequent dehydrochlorination followed by Michael
addition and R-chlorination provided 1-tert-butoxy-2-
chloro-2-propyl 4-(5-dichloromethyl-1,3-xylyl) sulfone (4d )
(Scheme 4).
In light of the reactivity of 4a with CCl4 but unreac-
tivity with CBrCl3, it seemed paradoxical that KOH-t-
BuOH was virtually unreactive with CCl4 but very
reactive with CBrCl3. At 25 °C in this medium, the
reaction of CBrCl3 with KOH rapidly decomposed both,
easily recognized by the generation of large amounts of
Cl- and Br- as well as of isobutylene oxide.1a,8,9 Similarly,
reaction of CBrCl3 with aqueous NaOH under phase-
transfer catalysis also provided Cl- and Br- (eq 1).
The failure of isopropyl 4-hydroxyphenyl sulfone (6) to
undergo R-halogenation in KOH-t-BuOH with either
CCl4 or CBrCl3 is associated with its rapidly formed
phenoxide anion, which greatly reduces the electronega-
tivity of the sulfonyl group and, thereby, the R-CH acidity
(Scheme 6),3 precluding formation of 6-R-anion. Since
(8) (a) Meyers, C. Y.; Tykal, J . A. Midwest Regional Meeting of the
American Chemical Society, Manhattan, KS, Oct 1968; American
Chemical Society: Washington, DC, 1968; p 32. (b) Walling, C.;
Kjellgren, J . J . Org. Chem. 1969, 34, 1487-1488.
(9) See, for example: (a) Walling, C.; Kjellgren, J . J . Org. Chem.
1969, 34, 1488-1489. (b) Pearson, D. E.; Buehler, C. A. Chem. Rev.
1974, 74, 45-86, especially pp 79-83 and references therein. (c)
Mottley, C.; Mason, R. P. Arch. Biochem. Biophys. 1988, 267, 681-
689.
502 J . Org. Chem., Vol. 68, No. 2, 2003

R-Halogenation and Related Reactivity of Sulfones
TABLE 2. Rela tive r-CH Acitities of Som e Ar om a tic
Su lfon es a n d Keton es
SCHEME 5
a
b
Reference 10. Estimated.
SCHEME 7
SCHEME 6
this is not the case with the corresponding 4-methoxy
sulfone, 2, it was halogenated with CBrCl3 and also CCl4,
although much slower than was 1.
KOH alone. The effect on R-haloisopropyl sulfones was
indirectly illustrated from the extended treatment of 4
with CCl4 in KOH-t-BuOH (Scheme 4). Direct treatment
of R-chloroisopropyl phenyl sulfone, 1a , with excess KOH
in t-BuOH at 25 °C for an hour resulted in its dehydro-
halogenation into phenyl 2-propenyl sulfone (1c) and
subsequent formation of the Michael addition products,
1-hydroxy-2-propyl phenyl sulfone (1d ) and 1-tert-butoxy-
2-propyl phenyl sulfone (1e), in an overall yield of about
47%. In contrast, over 95% of R-chlorobenzhydryl sulfone
7a was recovered after similar treatment (Scheme 7).
The effect of the 4-hydroxyphenyl substituent in pre-
venting R-halogenation of isopropyl sulfone 6 is overcome
in the corresponding benzhydryl 4-hydroxyphenyl sulfone
(8). Despite the rapid formation of its 4-phenoxide anion,
Ben zh yd r yl Ar yl Su lfon es. The greater effectiveness
of the benzhydryl group than the isopropyl group in
promoting anion formation was exhibited by the haloge-
nations of the benzhydryl aryl sulfones. Conversion of
benzhydryl phenyl sulfone (7) to its R-chloro sulfone 7a
in theoretical yield required only a 30-min treatment with
CCl4-KOH-t-BuOH at 3 °C. Even more impressive, the
R-bromo sulfone 7b was obtained in over 90% yield upon
treatment of 7 with CBrCl3 at 0 ° C for only 10 min. For
the same reason, R-halobenzhydryl sulfones are reduc-
tively dehalogenated far more readily than haloisopropyl
sulfones, as already illustrated with 7b vs 4b in Scheme
3. Another significant difference between these two types
of R-halo sulfones resides in their reactivity with excess
J . Org. Chem, Vol. 68, No. 2, 2003 503

Meyers et al.
SCHEME 8
SCHEME 9
However, refluxed in dioxane alone for 24 h, 9b was ca.
100% recovered. A mechanism for the acid-catalyzed
decomposition of 9b is suggested in Scheme 9.
its effect is offset by the strong R-anion-stabilizing effect
of the benzhydryl substituent, so that a theoretical yield
of R-chlorobenzhydryl 4-hydroxyphenyl sulfone (8a ) was
isolated when 8 was treated with CCl4-KOH-t-BuOH
at 25 °C for a short time. When heated in this basic
medium, 8a underwent decomposition mainly into ben-
zophenone and phenol. Its counterpart R-bromobenzhy-
dryl 4-hydroxyphenyl sulfone (8b), decomposes much
more rapidly. After treatment of 8 with CBrCl3 in KOH-
t-BuOH at 25 °C for only 2 h, benzophenone and phenol
were the major products, along with only a very small
amount of initially formed 8b (Scheme 8).
As would be expected, benzhydryl 4-methoxyphenyl
sulfone (9) undergoes R-halogenation substantially faster
than 8. Within 30 min at 25 °C, 9 was converted to
R-bromobenzhydryl 4-methoxyphenyl sulfone (9b) in 98%
yield by treatment with CBrCl3-KOH-t-BuOH. The
complete absence of decomposition products, in contrast
to that observed in the preparation of 8b, supports the
suggested decomposition mechanism involving the phe-
noxide anion of 8a and 8b illustrated in Scheme 8.
Decomposition of 9b does occur under acidic conditions.
Refluxed in aqueous acetic acid, 9b was converted into
benzophenone and 4-methoxyphenyl 4-methoxybenzene-
thiolsulfonate (9c) as major products, along with ani-
sole.11,12 Refluxing 9b in acetic acid-48% HBr produced
a 98% yield of benzophenone and 50% yield of phenol.
Ben zyl P h en yl Su lfon es. The two R-hydrogens of
benzyl phenyl sulfone (10) make it unique among the
other sulfones in these halogenation reactions. Mono-R-
halogenation enhances the acidity of the residual R-H so
that R,R-dihalogenation is attained while much 10 is still
present and the monohalogenated product is not detected,
viz. R,R-dichlorobenzyl phenyl sulfone (10a ) was easily
prepared in high yields from 10 treated with CCl4 in
KOH-t-BuOH or with C2Cl6-aq NaOH under phase-
transfer catalysis. It was reported by Skattebøl et al.7
that a 12-h treatment of 10 at 25 °C with a large excess
of CBrCl3 in 50% aq NaOH-CH2Cl2 under P-T-C condi-
tions (TEBA) produced R,R-dibromobenzyl phenyl sulfone
(10b) and the corresponding R-bromo-R-chloro sulfone.
Since we previously found that 10b was the only product
when 10 was treated with CBrCl3-KOH-t-BuOH for a
very short time, we believed that reversibility of the
brominations, and subsequent chlorination, was respon-
sible for the formation of the R-chloro-R-bromo sulfone.
Repeating the reaction under the Skattebøl conditions,
we found that 10b indeed was initially formed but was
slowly converted into the R-bromo-R-chloro sulfone, which
itself was transformed in ca. 20 h into the R,R-dichloro
sulfone, 10a . The reductive debrominations effected with
the generated Cl3Cl:- are fast and are followed by the
much slower chlorinations, while subsequent reductive
dechlorination is even slower and was not observed. Our
observation (Scheme 3) that 10b is readily reductively
debrominated to R-bromobenzyl phenyl sulfone (10c) by
treatment with Cl3C:- reasonably accounts for the ob-
served sequence, shown in Scheme 10. However, in
KOH-t-BuOH, but in the absence of CBrCl3 or CCl4, 10a
reductively monochlorinated 1 equiv of 10, forming 2
equiv of R-chlorobenzyl phenyl sulfone (10d ), which was
stable to further treatment (Scheme 11).
(10) (a) Bordwell, F. G.; Branca, J . C.; Hughes, D. L.; Olmstead, W.
N. J . Org, Chem. 1990, 45, 3305-3313. (b) Bordwell, F. G. Acc. Chem.
Res. 1988, 21, 456-463. (c) Taft, R. W.; Bordwell, F. G. Acc. Chem.
Res. 1988, 21, 463-469. (d) Bordwell, F. G.; Bares, J . E.; Bartmess, J .
E.; McCollum, G. J .; Van Der Puy, M.; Vanier, N. R.; Matthews, W. S.
J . Org, Chem. 1977, 42, 321-325. (e) Bordwell, F. G.; Matthews, W.
S. J . Am. Chem. Soc. 1974, 96, 1216-1217. (f) Bordwell, F. G.; J arvis,
B. B. J . Org. Chem. 1968, 33, 1182-1185.
(11) Vinkler, E.; Klivenyl, F. Acta Chim. Acad. Sci. Hung. 1955, 5,
159-166.
(12) It is well-known that sulfinic acids undergo disproportionation,
the corresponding thiolsulfonate being a major product. See: Oae, S.
Organic Chemistry of Sulfur; Plenum Press: New York, 1977; pp 613-
616 and references therein.
Effect of Atm osp h er ic Oxygen on th e Ha logen a -
tion Rea ction s. Most of the halogenations with CCl4,
504 J . Org. Chem., Vol. 68, No. 2, 2003

R-Halogenation and Related Reactivity of Sulfones
SCHEME 10
SCHEME 12
SCHEME 11
on when the Br2 was introduced. For example, when a
solution of sulfone 1 and n-BuLi was stirred at -63 °C
for an hour attached to such an argon-filled balloon before
1 equiv of Br2 was added and the reaction was worked
up after a few minutes, the major product was 2,3-
dimethyl-3-benzenesulfonyl-2-butanol (1f) (49%), along
with the expected R-bromo product 1b (41%) and benzene-
sulfonyl bromide (10%). The same reaction carried out
with twice the amount of Br2 provided virtually identical
results, suggesting that the unexpected major product,
1f, was produced before the addition of Br2.
This possibility was evaluated by eliminating the Br2
and simply purging a flask containing 1 with argon from
a rubber balloon that had been filled an hour earlier. THF
was then added, followed by n-BuLi, and the mixture was
stirred at -63 °C for an hour before being worked up.
Compound 1f was isolated in 95% yield, along with
lithium benzenesulfinate and lithium benzenesulfonate.
A number of related reactions were studied which
provided corresponding results. Ultimately, the procedure
was followed in which the initial argon purge was only
for 1 min, the stopcock was then closed and the THF and
n-BuLi were syringed into the closed flask and the
mixture was stirred for an hour; 1 was 100% recovered.
The products resulted from R-lithiated 1 being rapidly
oxidized by the air diffusing through the rubber-balloon
argon reservoir, precluding bromination by the subse-
quently added Br2. The mechanistic reaction sequence
suggested in Scheme 12 is similar to that reported for
related air oxidations of R-nitro anions.13,14 The same
reactions of 1 were followed by the corresponding R-lithi-
ated mesityl sulfone 4 maintained under argon from a
rubber-balloon reservoir; 4b and 2,3-dimethyl-3-mesity-
lenesulfonyl-2-butanol (4e) were obtained as major prod-
ucts, along with mesitylenesulfonyl bromide and a com-
pound incompletely characterized as bromomesitylene as
minor products.
CBrCl3, CBr4, etc. in powdered KOH-t-BuOH described
here were carried out under inert gas in sealed reaction
flasks attached directly via Tygon tubing to the gas
cylinder. No side reactions were observed. Some of the
brominations in which the substrates were initially
treated with n-BuLi and the Br2 was added later were
carried out under argon generally from an argon-filled
rubber balloon. In the latter cases, other products were
often formed, sometimes in significant yield, depending
J . Org. Chem, Vol. 68, No. 2, 2003 505

Meyers et al.
95 °C. 1H NMR (CCl4): δ 2.00 (s, 6 H), 7.48-7.75 (m, 3 H),
7.88-8.12 (m, 2 H). Anal. Calcd for C9H11BrO2S: C, 41.08; H.
4.21; Br, 30.36; S, 12.18. Found: C, 41.31; H, 4.10; Br, 29.91;
S, 11.93. The structure was unequivocally characterized by
X-ray crystal analysis.16
(b) Rea ction of 1 w ith CBr Cl3. F or m a tion of 1a a n d
1b. A mixture of 1 (0.92 g, 5.0 mmol), CBrCl3 (10 mL, 101
mmol), t-BuOH (10 mL) and KOH (4.0 g, 61 mmol), treated
as described in subsection (a) above, provided an oil that slowly
solidified (mp 72-80 °C) shown by 1H NMR to be composed of
24% recovered 1 and 76% of a mixture of 1b and 1a in a mole
ratio of 80:20. Elemental analysis showed it contained 20.38%
Br and 2.34% Cl, which is a mole ratio of 79.5:20.5 of 1b:1a ,
essentially the same as that indicated by NMR. Varying the
equivalent amounts of KOH substantially affected the relative
amounts of 1a and 1b obtained as well as that of 1c, often
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are corrected, 1H and
13C NMR spectra were taken at 300 and 75 MHz, respectively,
in CDCl3, IR spectra were taken on Nujol mulls, and elemental
analysis were performed by the Microanalysis Laboratory,
University of Illinois - Urbana-Champaign, unless stated
otherwise. All the reactions, except the oxidations, were
generally carried out under argon or nitrogen. When KOH was
used, it was powdered [from commercial pellets (85% KOH:
15% H2O by weight; 9:5 mol ratio)1,2]. The unhalogenated
sulfones were prepared by refluxing an aromatic thiol, the
chloro or bromo compound, and K2CO3 in acetone to provide
the sulfide, which was then oxidized with 30% H2O2-acetic
acid. Unless stated otherwise, R-halogenation of the sulfones
and ketones was carried out by treating them with a perha-
loalkane in KOH-t-BuOH, the mixture was then diluted with
water and extracted with ether, and the extracts were washed
with water, dried, and evaporated in vacuo.
Isop r op yl P h en yl Su lfon e (1). As reported,15 1 was an
oil. 1H NMR δ 1.23 (d, J ) 6.8 Hz, 6 H), 3.28 (hep, J ) 6.8 Hz,
1 H), 7.48-8.10 (m, 5 H).
2-Ch lor o-2-p r op yl P h en yl Su lfon e (1a ). Rea ction of 1
w ith CCl4. A mixture of 1 (0.93 g, 5.05 mmol), CCl4 (10 mL),
t-BuOH (10 mL), and KOH (4.0 g, 61 mmol), refluxed for 30
min, provided white crystals (aq EtOH) of 1a in quantitative
yield, mp 89-90 °C. 1H NMR (CCl4): δ 1.84 (s, 6 H), 7.39-
found as
a secondary product readily detected from its
characteristic 1H NMR resonances (noted above). Similar
reactions of 1 with CCl2Br2 or CBr2F2 instead of CBrCl3 also
provided varying yields of 1b.
(c) Rea ction of 1 w ith n -Bu Li follow ed by Br 2, At-
ta ch ed to a n Ar gon -filled Ba lloon . F or m a tion of 1b, 2,3-
Dim et h yl-3-b en zen esu lfon yl-2-b u t a n ol (1f), a n d Ben -
zen esu lfon yl Br om id e. A flask containing 1 (0.47 g, 2.6
mmol), connected to a vacuum line and an argon-filled balloon,
was gently heated. Dried THF was added, and the solution
was cooled to -63 °C and stirred while n-BuLi-hexane (1.65
mL, 1.55 M n-BuLi, 2.6 mmol) was added, then stirred for 1 h
longer. A solution of Br2 (0.13 mL, 2.6 mmol) in hexane (4.45
mL), maintained at -63 °C, was then added, and the mixture
was stirred for 2 min, then worked up, leaving a dark oil (0.46
g), which, via column chromatography, afforded crystalline 1b
(41%, mp 90-92 °C), 1f (49%), and benzenesulfonyl bromide
(10%). Purification of 1f by prep TLC (acetone:hexane 10:90)
gave colorless crystals with mp 105.5-107 °C. 1H NMR: δ 1.30
(s, 6 H), 1.50 (s, 6 H), 3.85 (br s, 1 H), 7.45-7.75 (m, 3 H),
7.75-8.00 (m, 2 H). Anal. Calcd for C12H18O3S: C 59.48; H,
7.49; S, 13.23. Found: C, 59.33; H, 7.50; S, 12.95. The same
reaction with 2 equiv of Br2 instead of 1 gave essentially
identical results.
7.73 (m, 3 H), 7.85-8.10 (m, 2 H). Anal. Calcd for C9H11
ClO2S: C, 49.43; H, 5.07; Cl, 16.21; S, 14.66. Found: C, 48.95;
H, 5.32, Cl, 16.38; S, 14.55.
Tr ea tm en t of 1a w ith Excess KOH-t-Bu OH. F or m a -
tion of P h en yl 2-P r op en yl Su lfon e (1c), 1-Hyd r oxy-2-
p r op yl P h en yl Su lfon e (1d ), a n d 1-ter t-Bu toxy-2-p r op yl
P h en yl Su lfon e (1e). A mixture of 1a (0.354 g, 1.62 mmol)
in t-BuOH (6 mL) and KOH (3.04 g, 54.3 mmol) was stirred
at 25 °C for 1 h, water was added, the mixture was extracted
with ether, and the dried extracts were evaporated leaving
-
1
0.346 g of colorless oil, which solidified on standing. H NMR
indicated recovered 1a along with 1c, 1d , and 1e in a ratio of
18:2:9:5, i.e., ca. 47% of 1a was converted into various
products: δ, 1c, 1.96 (m, 3 H), 5.73 (q, J ) 1.5 Hz, 1 H, dCH
trans to SO2), 6.29 (q, J ) 1.2 Hz, 1 H, dCH cis to SO2); 1d ,
1.26 (d, J ) 6.9 Hz, 3 H), 2.88 (dd, J ) 5.4, 7.8 Hz, 1 H), 3.30
(m, 1 H), 3.93 (dd, J ) 5.4, 7.2 Hz, 1 H); 1e, 1.07 (s, 9 H), 1.36
(d, J ) 7.2 Hz, 3 H), 3.30 (m, 1 H), 3.44 (dd, J ) 9.3, 7.2 Hz,
1 H), 3.76 (dd, J ) 9.3, 4.8 Hz, 1 H). The aqueous layer was
acidified with 2 N HNO3, aq AgNO3 was added, and the
resulting white precipitate was isolated, washed with water
and acetone, and dried; 0.108 g of AgCl, 0.75 mmol, i.e., 46.3%
of the chlorine contained in the original substrate 1a , con-
firmed its conversion into the corresponding equivalents of the
products noted. The dehydrochlorination required a very large
equivalent excess of KOH relative to the R-chloro sulfone.
2-Br om o-2-p r op yl P h en yl Su lfon e (1b). (a ) Rea ction of
1 w ith CBr 4. A mixture of 1 (1.86 g, 10.1 mmol), CBr4 (33 g,
100 mmol), t-BuOH (10 mL), and KOH (4.0 g, 61 mmol) stirred
briefly in a cold water, then at 25 °C for ca. 1 h, provided 1b,
which crystallized on being triturated with pentane. Steam
distillation removed residual CBr4 and recrystallization (li-
groin) provided white crystals (0.87 g, 33% yield) with mp 94-
Rea ction of 1 w ith n -Bu Li. Th e Effect of Air on th e
F or m a tion of 2,3-Dim eth yl-3-ben zen esu lfon yl-2-bu ta n ol
(1f), Lith iu m Ben zen esu lfin a te, a n d Lith iu m Ben zen e-
su lfon a te. A procedure similar to the above was repeated, but
without the addition of Br2. A flask containing 1 (0.096 g, 0.5
mmol) was connected to the vacuum line and a rubber balloon
that had been filled with argon 1 h earlier. THF (1.10 mL)
was added, the solution was stirred at -63 °C, n-BuLi-hexane
(0.36 mL, 1.55 M n-BuLi, 0.5 mmol) was added, and stirring
was continued for 1 h, giving rise to a flocculent precipitate.
Ether was added and the white precipitate was collected by
filtration, washed with ether, and oven dried (0.052 g) and
identified as a mixture of PhSO3Li (major) and PhSO2Li. IR
(Nujol): 1190 cm-1 (s, SO3-), 1040 cm-1 (s, SO2-). The
combined filtrate and ether washings were dried and concen-
trated in vacuo leaving 1f, 0.063 g (95% yield, based on the
theoretical formation of 1 mol of 1f from 2 mol of 1; see Scheme
1
12), an oil, which slowly solidified. Its H NMR spectrum was
the same as that of 1f shown above. No starting sulfone (1)
was detected.
The above procedure was followed, except that the balloon
was filled with argon 2 h prior to use and the mixture was
stirred at -63 °C for only 15 min before being worked up; the
yield of 1f was only 52%, and 38% of 1 was recovered.
Repeating this procedure but maintaining the mixture under
argon from a balloon that had just been filled, only a 15% yield
of 1f was realized, and 84% of 1 was recovered. Finally, when
the initial argon purge was for only 1 min, the stopcock then
closed, the THF and n-BuLi-hexane added, and the solution
stirred for 1 h, recovery of 1 was 100%.
(13) This reaction is analagous to the autoxidation of 2-nitropropane
in alkaline solution reported by Russell (Russell, G. A. J . Am. Chem.
Soc. 1954, 76, 1595-1600) and his suggested mechanism:
(14) Walling, C. Free Radicals in Solution; Wiley & Sons: New York,
1957; Chapter 9.
(15) Bohme, H.; Gran, H. J . Ann. Chim. 1952, 577, 68.
(16) Robinson, P. D.; Parady, T. E.; Hou, Y.; Meyers, C. Y. Acta
Crystallogr. 2001, Sect. E, 57, o584-o586.
506 J . Org. Chem., Vol. 68, No. 2, 2003

R-Halogenation and Related Reactivity of Sulfones
Sou r ce of th e Ben zen esu lfon yl Br om id e in th e Rea c-
tion of 1 w ith n -Bu Li follow ed by Br 2. Rea ction of
Lith iu m Ben zen esu lfin a te w ith Br 2. The mixtures of
lithium benzenesulfinate and lithium benzenesulfonate formed
in the above reactions were isolated, combined, suspended in
THF, and stirred for 1 h at -63 °C and a solution of Br2 in
hexane was added. The mixture was filtered and the filtrate
dried and concentrated as a pale yellow oil. IR (Nujol): 1366
cm-1 (SO2 asym), 1170 cm-1 (SO2 sym). 1H NMR: δ 7.42-7.80
(m, 3 H), 7.88-8.10 (m, 2 H). IR and 1H NMR results are
consistent with those of benzenesulfonyl bromide, whose
preparation from a benzenesulfinate salt treated with Br2 is
well documented.17 Lithium benzenesulfonate similarly treated
with Br2 failed to provide benzenesulfonyl bromide.
(ethanol). 1H NMR: δ 1.50 (d, J ) 6.5 Hz, 6 H), 3.88 (hep, J )
6.5 Hz, 1 H). Anal. Calcd for C9H7Cl5O2S: C, 30.30; H, 1.98;
Cl, 49.73; S, 8.99. Found: C, 30.40; H, 2.05; Cl, 49.61; S, 8.86.
Sulfone 3 was almost quantitatively recovered when treated
with KOH-t-BuOH at 25 °C for 1 h.
2-Ch lor o-2-p r op yl P en ta ch lor op h en yl Su lfon e (3a ). A
mixture of 3 (1.78 g, 5 mmol), CCl4 (6 mL), t-BuOH (10 mL),
and KOH (4.0 g, 70 mmol), stirred for 1 h at 25 °C, provided
1
1.54 g of yellow crystals, shown by H NMR to be composed of
3a (76% yield) and recovered 3 (3.2%). Trituration with ethanol
washed away 3, leaving 3a with mp 195-196 °C (ethanol). 1H
NMR: δ 2.11 (s). Anal. Calcd for C9H6Cl6O2S: C, 27.65; H,
1.55; Cl, 54.41; S, 8.20. Found: C, 27.68; H, 1.55; Cl, 54.26; S,
8.09.
Isop r op yl 4-Meth oxyp h en yl Su lfon e (2). Colorless oil,
bp 125-126 °C/0.08 mm. H NMR: δ 1.28 (d, J ) 7 Hz, 6 H),
2-Br om o-2-p r op yl P en t a ch lor op h en yl Su lfon e (3b ).
The addition of KOH (0.80 g, 14 mmol) to a stirred mixture of
3 (0.71 g, 2 mmol), CBrCl3 (5 mL), and t-BuOH (5 mL) led to
a vigorous exotherm. The mixture was immediately cooled in
an ice bath and stirred at 25 °C for 20 min, to provide 0.80 g
of yellow crystals shown by 1H NMR to be composed of 3b (80%
yield), 3a (4.2% yield), and recovered 3 (10%). Recrystallization
(benzene) afforded hair-like white needles of 3b with mp 211-
1
3.17 (hep, J ) 7 Hz, 1 H), 3.89 (s, 3 H), 7.05 (d, J ) 9.5 Hz, 2
H), 7.85 (d, J ) 9.5 Hz, 2 H). Anal. Calcd for C10H14O3S: C,
56.05; H 6.59; S, 14.96. Found: C, 55.86; H, 6.87; S, 15.20.
2-Ch lor o-2-p r op yl 4-Meth oxyp h en yl Su lfon e (2a ). Re-
a ction of 2 w ith CCl4. A mixture of 2 (0.492 g, 2.30 mmol),
t-BuOH (2 mL), CCl4 (5 mL), and KOH (0.82 g, 12 mmol; 5.5
mol equiv relative to 2) provided 0.503 g of a yellow oil, shown
1
213 °C, not suitable for X-ray analysis. H NMR: δ 2.24 (s).
1
by H NMR to be composed of 0.423 g of 2 (86% recovery) and
Anal. Calcd for C9H6BrCl5O2S: C, 24.83; H, 1.39; Br, 18.35;
Cl, 40.72; S, 7.36. Found: C, 24.84; H, 1.43; Br, 18.43; Cl,
40.90; S, 7.36.
0.080 g of 2a (14% yield). When 12 mol equiv of KOH was used,
recovery of 2 was 20% and the yield of 2a was 79%; with 18
equiv of KOH, the yield of 2a was 91%; mp 88.5-89.5 °C
2-Ch lor o-2-p r op yl Mesityl Su lfon e (4a ). Rea ction of
1
(ethanol-petroleum ether). H NMR: δ 1.84 (s, 6 H), 3.90 (s,
Isop r op yl Mesit yl Su lfon e (4) w it h CCl4. (a ) F or 1 h .
3 H), 7.07, (d, J ) 9.5 Hz, 2 H), 7.92 (d, J ) 9.5 Hz, 2 H).
Anal. Calcd for C10H13ClO3S: C, 48.29; H, 5.27; Cl, 14.25; S,
12.89. Found: C, 48.32; H, 5.28; Cl, 14.53; S, 12.96.
Sulfone 4 was prepared as reported19 with mp 74.5-76 °C (lit.19
mp 80 °C).
1H NMR: δ 1.33, (d, J ) 7 Hz, 6 H), 2.27 (s, 3 H),
2.68 (s, 6 H), 3.28 (hep, J ) 7 Hz, 1 H), 6.98 (s, 2 H). A mixture
of 4 (0.226 g, 1 mmol), CCl4 (1 mL, 10.4 mmol), t-BuOH (1
mL), and KOH (1.2 g, 18 mmol) stirred at 25 °C for 1 h
provided a viscous yellow oil shown by NMR to be composed
of 0.096 g (37% yield) of 4a and 0.142 g (63%) of recovered 4.
White crystalline 4a was obtained via column chromatography
(silica gel; benzene-chloroform) with mp 87-89 °C (petroleum
ether). 1H NMR: δ 1.90 (s, 6 H), 2.30 (s, 3 H), 2.74 (s, 6 H),
6.98 (s, 2 H). Anal. Calcd for C12H17ClO2S: C, 55.27; H 6.57;
Cl, 13.59; S, 12.29. Found: C, 55.40; H, 6.65; Cl, 13.63; S,
12.06. The crystals were unequivocally characterized by X-ray
analysis.20
2-Br om o-2-p r op yl 4-m eth oxyp h en yl Su lfon e (2b). (a )
Rea ction of 2 w ith CBr 4. A mixture of 2 (2.14 g, 10 mmol),
t-BuOH (20 mL), CBr4 (33.2 g, 100 mmol), and KOH (12.0 g,
180 mmol), stirred for 1 h at 10 °C, provided an oil which,
after the residual CBr4 was removed by vacuum distillation,
was shown by NMR to be composed of 2 (84% recovery) and
2b (16% yield). Compound 2b was isolated by column chro-
matography (silica gel; benzene-CHCl3) as white crystals with
1
mp 72-73 °C (ethanol-petroleum ether). H NMR: δ 2.05 (s,
6 H), 3.90 (s, 3 H), 7.07 (d, J ) 9.5 Hz, 2 H), 7.92 (d, J ) 9.5
Hz, 2 H). Anal. Calcd for C10H13BrO3S: C, 40.97; H, 4.47; Br,
27.25; S, 10.94. Found: C, 41.04; H, 4.50; Br, 27.03; S, 10.76.
(b) Rea ction of 2 w ith CBr Cl3. F or m a tion of 2a a n d
2b. A mixture of 2 (1.07 g, 5 mmol), CBrCl3 (5 mL), t-BuOH
(5 mL), and KOH (4.0 g, 60 mmol) stirred for 30 min at 25 °C
afforded 1.26 g of yellow oil shown by NMR to be composed of
recovered 2 (27%), 2b (43% yield), 2a (14% yield), and
4-methoxyphenyl 2-propenyl sulfone (16%). The 1H NMR
resonances of the latter’s propenyl group, δ 1.95 (m, 3 H,
R-CH3), 5.68 (m 1 H, dCH trans to SO2), 6.23 (m, 1 H, )CH
cis to SO2), were almost identical with those which identified
the corresponding phenyl compound 1c.
The aqueous residue from the workup was acidified with 2
N HNO3, a 5% AgNO3 solution was added, and the mixture
was washed with ether. The AgCl precipitate was collected
and dried: 0.524 g, 3.65 mmol, which represents about four
times the amount of Cl- expected from this reaction in which
63% of 4 was recovered and only 37% of 4a was obtained. The
ether washings were washed with brine, dried, and concen-
trated to a yellow oil, 0.52 g, whose respective IR and 1H
spectra were identical with those of formic acid, which we have
previously found to form from the reaction of KOH with the
Cl2C: formed in similar R-chlorinations with CCl4.1,2
(b) F or 7.5 h . F or m a tion of 4a , 2-Ch lor o-2-p r op yl 4-(5-
Dich lor om eth yl-1,3-xylyl) Su lfon e (4c), a n d P ossibly
1-ter t-Bu toxy-2-ch lor o-2-p r op yl 4-(5-Dich lor om eth yl-1,3-
xylyl) Su lfon e (4d ). A mixture of 4 (1.13 g, 5 mmol), CCl4 (5
mL, 51.8 mmol), t-BuOH (5 mL), and KOH (5.85 g, 90 mmol)
stirred at 25 °C for 4 h provided a viscous oil, which was
treated again with the same amounts of CCl4, t-BuOH, and
KOH for an additional 3.5 h, to give a yellow oil, 1.18 g.
Column chromatography (silica gel) led to the isolation of 4a
(1.56 mmol, 31.2% yield) as white crystals with mp 89.5-90.5
°C (petroleum ether) (see above); 4c (0.22 mol, 4.4% yield) as
white crystals with mp 123-124 °C ((petroleum ether) [1H
NMR: δ 1.93 (s, 6 H), 2.44 (s, 3 H), 2.77 (s, 3 H), 7.18 (s, 1 H),
7.96 (s, 1 H), 8.15 (s, 1 H). Anal. Calcd for C12H15Cl3SO2: C,
43.72; H, 4.59; Cl, 32.26; S, 9.73. Found: C, 43.99; H, 4.57;
Rela tive Ra tes of Rea ction of 1 vs 2 w ith CBr Cl3. In
separate vessels, 5 mmol of 1 and 5 mmol of 2 were treated
with CBrCl3 (5 mL), t-BuOH (5 mL), and KOH (30 mmol). Each
mixture was stirred for 10 min at 0 °C. Recovery of 1 was 78%,
the yield of 1b was18%, and that of 1a was 4%, while 93% of
2 was recovered, the yield of 2b was 5.5%, and that of 2a was
1.5%.
Isop r op yl P en ta ch lor op h en yl Su lfon e (3). Isopropyl
pentachlorophenyl sulfide was prepared from pentachloroben-
zenethiol [mp 242-243 °C (lit.18 mp 241.5-242 °C)] and
2-bromopropane [mp 66-67 °C (ethanol)]. 1H NMR: δ 1.26
(d, J ) 6.5 Hz, 6 H), 3.58 (hep, J ) 6.5 Hz, 1 H). Anal. Calcd
for C9H7Cl5S: C, 33.31; H, 2.17; Cl, 54.63; S, 9.88. Found: C,
33.24; H, 2.09; Cl, 54.49; S, 9.76. The sulfide was quantitatively
converted into 3 as white crystals with mp 135.5-136 °C
(17) Suter, C. M. The Organic Chemistry of Sulfur, reprinted ed.;
Intra-Science Research Foundation: Santa Monica, CA, 1969; p 513
and references therein.
(19) Shostakovskii, S. M.; Bobrov, A. V. Zh. Org. Khim. 1969, 5,
908-913.; J . Org. Chem. USSR (Engl. Transl.) 1969, 5, 896-900.
(20) Meyers, C. Y.; Hua, D. H.; Hou, Y.; Robinson, P. D. Acta
Crystallogr. 2001, Sect. E, 57, o587-o589.
(18) Lucas, C. R.; Peach, M. E. Can. J . Chem. 1970, 48, 1869-1875.
J . Org. Chem, Vol. 68, No. 2, 2003 507

Meyers et al.
1
Cl, 32.48; S, 9.94]; a compound suggested by 1H NMR to be
4d (1.56 mmol, 2.4% yield) [1H NMR: δ 1.16 (s, 9 H), 1.90 (s,
3 H), 2.44 (s, 3 H), 2.77 (s, 3 H), 7.18 (s, 1 H), 7.96 (s, 1 H),
8.15 (s, 1 H)]; and 4 (2.89 mmol, 57.8% recovery) with mp
73.5-74.5 °C.
86 °C (lit.21 mp 85-86 °C). H NMR: δ 2.35 (s, 3 H), 2.75 (s,
6 H), 6.98 (s, 2 H).
Fraction 3 (eluent, as above): 4b, 0.22 g (48% yield). The
mp and NMR spectra were virtually identical with those for 4
noted in subsection (a) above.
Tr ea tm en t of CCl4 w ith KOH-t-Bu OH. A mixture of
KOH (1.20 g, 18.0 mmol), CCl4 (1 mL, 10.3 mmol), and t-BuOH
(1 mL) was stirred for 1 h at 25 °C, acidified with 1 N HNO3,
and washed with ether, a 5% solution of AgNO3 was added,
and the precipitated AgCl was isolated and dried: 0.0450 g,
0.30 mmol, amounting to only 0.75% decomposition of CCl4
from its direct reaction with excess KOH.
F a ilu r e of r-Br om in a tion of Isop r op yl Mesityl Su lfon e
(4). (a ) With CBr 4-KOH-t-Bu OH. The identical procedure
described for the bromination of 1 to 1b with CBr4 was
followed. A mixture of 4 (0.452 g, 2 mmol), CBr4 (6.64 g, 20
mmol), t-BuOH (10 mL), and KOH (0.800 g, 10.7 mmol) was
stirred for 1 h at 25 °C. Crystalline 4, 0.430 g (95%), was
recovered. There was no indication of the formation of R-bro-
moisopropyl mesityl sulfone (4b).
(b) With CBr Cl3-KOH-t-Bu OH.5 The same procedure
described for the conversion of 1 to 1a and 1b with CBrCl3
was followed. A mixture of 4 (0.226 g, 1 mmol), CBrCl3 (1 mL),
t-BuOH (1 mL), and KOH (0.400 g, 6.1 mmol) was stirred for
1 h at 25 °C. Again, crystalline 4 (0.210 g (93%) was recovered;
neither 4b nor 4a was detected. The aqueous residue from the
workup was acidified with 2 N HNO3 and treated with 5% aq
AgNO3, which provided 0.48 mmol of AgBr and 1.4 mmol of
AgCl. In light of the fact that virtually all of 4 was recovered,
the amount of halide ion observed here is exceptionally high.
Extending this treatment for 24 h likewise afforded only near-
quantitative recovery of 4.
Fraction 4 (eluent: benzene-CH2Cl2 10:90; then EtOAc-
CH2Cl2 10:90): 2,3-dimethyl-3-mesitylenesulfonyl-2-butanol
(4e, 0.12 g). Purification via thick layer chromatography (silica
gel plate, eluent: acetone-hexane 10:40) (0.083 g, 37% yield)
gave white crystals (pentane) with mp 105.5-107 °C. 1H
NMR: δ 1.34 (s, 6 H), 1.48 (s, 6 H), 2.30 (s, 3 H), 2.71 (s, 6 H),
4.23 (s, 1 H), 6.99 (s, 2 H). Anal. Calcd for C15H24O3S: C, 63.35;
H, 8.51; S, 11.27. Found: C, 63.25; H, 8.68; S, 11.00.
F or m a tion of 4a a n d 4b fr om Rea ction of 4 w ith
n -Bu Li F ollow ed b y CBr Cl3. To solution of 4 (0.225 g, 1
mmol) in THF (5 mL) maintained at -70 to -60 °C was added
n-BuLi in hexane (2.2 M, 0.6 mL, 1.3 mmol) and the mixture
was stirred for 15 min. The cold bath was removed, CBrCl3
(0.16 mL, 1.6 mmol) was injected, and the mixture was stirred
at 25 °C for 2 h, then worked up: 0.21 g of yellow oil shown
1
by H NMR to be composed of 4b, 4a , and 4 in a molar ratio
of 1.54:1.09:1.0, i.e., 42% bromination, 30% chlorination, and
28% recovery of 4.
Tr ea tm en t of 1 w ith CBr Cl3-KOH-t-Bu OH w h ich w a s
P r eviou sly Stir r ed for 1 h . A mixture of KOH, t-BuOH (1
mL), and CBrCl3 (1.40 g, 7.1 mmol) was stirred at 25 °C under
argon for 1 h. Sulfone 1 (0.203 g, 1.09 mmol) was then added
and the mixture was stirred for another 1 h. A light yellow oil
1
(0.203 g) was obtained, shown by H NMR to be composed of
1, 1b, and 1a in a mole ratio of 87:4:1, i.e., only 5.4% of 1
underwent halogenation.
Failu r e of Redu ctive Debr om in ation of 4b with CHCl3-
KOH-t-Bu OH. KOH (1.14 g) was added to a stirred solution
of 4b (0.129 g 0.42 mmol) in t-BuOH (1 mL) and CHCl3 (1 mL),
and the mixture was cooled in an ice bath, then stirred at 25
°C and monitored by TLC after 30, 45, and 90 min and 2.5 h,
all of which showed the presence mainly of 4b. The mixture,
then worked up and column chromatographed (silica gel;
hexanes-ethyl acetate 5:1), provided only 4b, 0.120 g (93%
recovery).
Rea ction of CBr Cl3 w ith KOH-t-Bu OH a n d w ith
t-Bu -O-Li-t-Bu OH. A mixture of KOH (4.0 g, 60 mmol),
CBrCl3 (10 mL, 101.5 mmol), and t-BuOH (10 mL) was stirred
vigorously at 25 °C for 1 h. A very small sample of the
suspended material was withdrawn and dissolved in water;
litmus paper indicated neutral pH. The main mixture was
acidified with 1 N HNO3 and washed with ether, and a 5% aq
solution of AgNO3 was added to the aq solution. The precipi-
tated silver halide, washed with water and dried, weighed 1.92
g (3.1 mmol of AgBr and 9.3 mmol of AgCl, assuming a molar
ratio of 1 AgBr:3 AgCl). That is, much of the KOH was used
up rapidly in reacting with the CBrCl3 leading to the formation
of KBr, KCl, HC(O)OK, etc.1,2
In a similar procedure, a solution of t-BuOH (3 mL) into
which n-BuLi in hexane (3.5 mL, 2.2 M, 7.8 mmol) was injected
was flushed with argon and cooled in a ice-water bath, and
CBrCl3 (1 mL, 10.15 mmol) was added. The mixture was
stirred at 25 °C for 1 h, then acidified with HNO3, and excess
aq AgNO3 was added. The precipitated silver halides were
washed and dried: 0.183 g, virtually the same as found in the
reaction with KOH, on a per-mole basis.
Tr ea tm en t of 4 w ith KOH-t-Bu OD. A suspension of 4
(0.45 g, 2 mmol) and KOH (0.8 g, 12 mmol) in t-BuOD (2 mL)
was cooled in an ice-water bath for 2 min then stirred at 25
°C. Small samples were taken at successive intervals and put
into small vials containing ether; dilute aq HCl was then
added. Since not all of 4 was dissolved after 36 min, another
2 mL of t-BuOD was then injected into the stirred mixture,
followed by the addition of ether and, 24 min later, aq HCl,
2-Br om o-2-p r op yl Mesityl Su lfon e (4b). Br om in a tion
of 4 w ith n -Bu Li F ollow ed by Br om in e. (a ) Rea ction
Ma in ta in ed u n d er Ar gon by a Tu be Dir ectly Atta ch ed
to th e Ar gon Cylin d er . In a sealed flask, a solution of 4
(0.476 g, 2.1 mmol), THF (5 mL), and n-BuLi-hexane (1.2 mL,
2.6 mmol of n-BuLi), maintained between -70 and -60 °C and
under argon via a Tygon tube directly attached to the argon
cylinder, was stirred for 1 h. A bromine-hexanes solution (2.8
mL, 1.126 M, 3.15 mmol of Br2) was added, and the mixture
was stirred for 30 min at -65 °C, diluted with ether, and
worked up, giving a yellow oil shown by 1H NMR to be mainly
4b. Chromatographic purification (silica gel, 20:1 hexanes-
ethyl acetate) provided 0.438 g (69% yield) of 4b as a yellow
solid: recrystallization (hexanes) provided colorless square
plates with mp 87-88 °C. 1H NMR: δ 2.07 (s, 6H), 2.33 (s,
3H), 2.78 (s, 6H), 7.11 (s, 2H). 13C NMR: δ 21.01, 24.46, 28.60,
77.88, 127.14, 132.76, 142.99, 144.07. Anal. Calcd for C12H17
-
BrO2S: C, 47.22; H, 5.61; S, 10.50; Br, 26.18. Found: C, 47.04;
H, 5.59; S, 10.58; Br, 26.25. The structure of 4b was unequivo-
cally characterized by X-ray crystal analysis.5,6
(b) Rea ction Ma in ta in ed u n d er Ar gon fr om a n Ar gon -
F illed Ba lloon . F or m a tion of 4b, 2,3-Dim eth yl-3-m esity-
len esu lfon yl-2-b u t a n ol (4e), Mesit ylen esu lfon yl Br o-
m id e, a n d Br om om esitylen e. A flask containing 4 (0.37 g.
1.6 mmol) and connected to a rubber balloon previously filled
with argon was purged with argon from the balloon for several
minutes before THF (3.25 mL) followed by n-BuLi-hexane
(1.55 M, 1.1 mL, 1.7 mmol) were added. The mixture was
stirred for 1 h at -63 °C while being maintained under argon
from the balloon, Br2 (0.17 mL, 3.3 mmol) in hexane (3.25 mL)
was then added, and stirring was continued for 1.5 h at
-55 °C. Ether and water were then added and the mixture
worked up as usual, leaving 0.42 g of yellow oil, which was
column chromatographed (silica gel).
Fraction 1 (eluent: benzene-petroleum ether 20:80): bro-
momesitylene (0.031 g, 6% yield) (1H NMR δ 2.20 (s, 3 H), 2.33
(s, 6 H), 6.87 (s, 2 H), and minor extraneous singlets at δ 1.85
and 1.21.
Fraction 2 (eluent: benzene-petroleum ether 40:60): mesi-
tylenesulfonyl bromide (0.020 g, 5% yield) with mp (crude) 76-
(21) Huthmacher, K.; Effenberger, F. Chem. Ber. 1976, 109, 2315-
2326.
508 J . Org. Chem., Vol. 68, No. 2, 2003

R-Halogenation and Related Reactivity of Sulfones
i.e., 1 h total reaction time. The respective ether layers from
the removed samples were separated, dried, and evaporated
leaving colorless crystals composed of 4 and 4-R-D. The amount
bath for 2 h, diluted with water, neutralized with aq NaHCO3,
and extracted with ether. Concentration of the dried extracts
left 7.44 g (92% yield) of 6, which was distilled (bp 202-210
1
1
of R-deuteration was determined by H NMR: 2 min, 2.4%; 6
°C/0.75 mm) as a colorless oil. H NMR: δ 1.29 (d, J ) 7 Hz,
min, 7.7%; 11 min, 11%; 16 min, 25%; 26 min, 29.2%; and 36
min, 29%.
6 H), 3.24 (hep, J ) 7 Hz, 1 H), 7.04 (d, J ) 9 Hz, 2 H), 7.50
(br s, 1 H), 7.72 (d, J ) 9 Hz, 2 H). Anal. Calcd for C9H12O3S:
C, 53.98; H, 6.04; S, 16.01. Found: C, 53.96; H, 6.32; S, 16.10.
F a ilu r e of r-Ha logen a tion of 6 w ith Eith er CCl4 or
CBr Cl3. A mixture of KOH (4.0 g, 70 mmol), 6 (1.0 g, 5 mmol),
t-BuOH (10 mL), and CCl4 (10 mL) was stirred at 25 °C for 18
h, acidified with 1 N HNO3 (100 mL), and worked up, providing
only 6 (0.95 g, 95% recovery). Repeating this procedure but
under reflux (82 °C) for 1 h, only 6 (0.96 g, 96%) was again
recovered, and when reflux was continued for 18 h, 93% of 6
was recovered and no products were detected.
Bromination was attempted with a mixture of KOH (1.60
g, 28 mmol), 6 (0.40 g, 2 mmol), t-BuOH (7 mL), and CBrCl3
(7 mL), treated as above at 25 °C for 48 h. Workup provided
only 6 (0.38 g, 94% recovery). When the mixture was stirred
under reflux for 3 h, again only 6 (0.37 g, 96% recovery) was
found. There was no indication that 6 underwent halogenation
or any other transformation by treatment with CCl4 or CBrCl3
in KOH-t-BuOH.
Tr ea tm en t of 4 w ith CBr Cl3-KOH-t-Bu OD. The above
procedure was followed, except that CBrCl3 (0.8 g, 14.2 mmol)
was present, dissolved in the t-BuOD (2 mL). This solution
was added to a mixture of 4 (0.45 g, 2 mmol) and KOH (0.8 g.
12.1 mmol), and the mixture was cooled in an ice bath for 2
min then stirred at 25 °C. At intervals of 5, 10, 16, 26, and 36
min, small samples were removed and diluted with ether and
dilute HCl. After 1 h, the main reaction mixture was similarly
treated. The respective ether layers were separated, dried, and
1
evaporated in vacuo leaving a crystalline mass, shown by H
NMR to be only undeuterated 4, i.e., no 4b was found and no
deuterium was incorporated into 4 in any of the samples,
including that from the mixture stirred for 1 h. Total recovery
of undeuterated 4 was over 90%.
2-Ch lor o-2-p r op yl Mesityl Keton e (5a ). Rea ction of
Isop r op yl Mesityl Keton e (5). (a ) With CCl4. Isopropyl
mesityl ketone (5)22 (0.95 g, 5.0 mmol) was added to a stirred
mixture of CCl4 (7.5 mL), KOH (2 g), and t-BuOH (3 mL),
producing an exotherm. The mixture was cooled to 25 °C,
stirred for 5 h, and worked up: 1.12 g (quantitative yield) of
r-Ch lor oben zh yd r yl P h en yl Su lfon e (7a ). Benzhydryl
phenyl sulfone (7) was prepared via the sulfide as reported;24
white needles, mp 186-187 °C (ethanol; lit. mp 187-188 °C).
A mixture of 7 (1.00 g, 3.4 mmol), CCl4 (10 mL), t-BuOH (10
mL), and KOH (4.0 g) was stirred at 3 °C for 30 min,
quantitatively yielding crystalline 7a (1.15 g, 3.4 mmol) as
1
5a , distilled as a colorless oil, bp 113-115 °C/3 mm. H NMR
(CCl4): δ 1.75 (s, 6 H), 2.16 and 2.23 (2 s, 9 H), 6.68 (s, 2 H).
Anal. Calcd for C13H17ClO: C, 69.50; H, 7.62; Cl, 15.78.
Found: C, 70.22; H, 7.70; Cl, 16.10.
1
colorless needles (ethanol) with mp 141-141.5 °C. H NMR:
δ 7.10-7.80 (m). 13C NMR: δ 91.61, 127.85, 127.95, 129.37,
129.91, 131.31, 133.95, 134.70, 136.48. Carrying out the
reaction at 25 °C for 4 h provided identical results.
(b) With SO2Cl2. A solution of 5 (0.85 g, 4.5 mmol) and SO2-
Cl2 (1.68 g, 12.5 mmol) in absolute ether (10 mL) was refluxed
for 5 h, then maintained at 25 °C for 13 h and concentrated to
1
A mixture of 7a (0.636 g, 1.86 mmol), KOH (3.05 g, 54.5
mmol), and t-BuOH (6 mL) stirred at 25 °C for 1 h afforded
0.606 g (95.3% recovery) of 7a and a trace of 7 (1H NMR: δ
5.29). The aqueous layer from the workup was acidified with
2 N HNO3 and 5% AgNO3 was added. Only 0.006 g of AgCl
was formed, representing 2.2% of the chlorine contained in
the original substrate 7a , which is consistent with the minute
conversion of 7a to 7 by the KOH treatment.
r-Br om oben zh yd r yl P h en yl Su lfon e (7b). KOH (1.0 g,
15 mmol) was added to a stirred solution of 7 (0.77 g, 2.50
mmol) in CBrCl3 (2.5 mL, 25 mmol) and t-BuOH (2.5 mL),
producing a large exotherm. The thick mixture was stirred in
an ice bath for 10 min, then at 25 °C for another 10 min, ether
and water were added, and the solids (mp 185-188 °C dec)
were removed. The ether layer was evaporated leaving a solid,
which was combined with the removed solid material: 0.88 g,
shown by NMR to be 7b (91% yield) as white crystals (from
ether) with mp 186.5-187.5 °C dec. 1H NMR: δ 7.03-7.82 (m).
Anal. Calcd for C19H15BrO2S: C, 58.92; H, 3.90; Br, 20.63; S,
8.28. Found: C, 59.04; H, 3.91; Br, 20.66; S, 8.19. The R-chloro
sulfone 7a was not coformed in this reaction.
an oil, identified by H NMR to be composed mainly of 5a (ca.
90% yield).
2-Br om o-2-p r op yl Mesityl Keton e (5b). Rea ction of
Isop r op yl Mesityl Keton e (5) w ith CBr Cl3. Ketone 5 (0.30
g, 1.58 mmol) was added to a stirred mixture of KOH (1.20 g),
t-BuOH (5 mL), and CBrCl3 (5 mL). When the exotherm
subsided, stirring was continued at 25 °C for 1 h, providing
0.42 g of an oil that did not solidify on standing (lit.23 mp 27
°C), identified by NMR as essentially pure 5b (quantitative
1
yield). H NMR (CCl4): δ 1.86 (s. 6 H), 2.16 (s, 6 H), 2.22 (s, 3
H), 6.63 (s, 2 H). No R-chlorination occurred; some of the
sulfones, similarly treated, underwent minor R-chlorination.
R-Bromo sulfone 5b was also prepared by the reaction of
mesitylene with R-bromoisobutyryl bromide (general method
of Fisher et al.23) as a colorless oil with bp 83-90 °C/0.8 mm
(79% yield). 1H NMR (CDCl3): δ 1.97 (s, 6 H), 2.26 (s, 6 H),
2.28 (s, 3 H), 6.86 (s, 2 H). 13C NMR: δ 20.59, 20.89, 31.75,
63.65, 128.29, 132.48, 137.49, 138.16, 208.93. These NMR
spectra of 5b were obtained in CDCl3; that above was taken
in CCl4.
4-Hyd r oxyp h en yl Isop r op yl Su lfon e (6). A mixture of
4-hydroxybenzenethiol (10.71 g, 85 mmol), 2-bromopropane
(17.22 g, 140 mmol), and K2CO3 (12.42 g, 90 mmol) in acetone
(100 mL) was stirred for 12 h. The mixture was filtered, the
filtrate was concentrated leaving an oil, ether was added, and
the solution was washed with 2 N NaOH; the washings were
acidified with 6 N HCl and extracted with ether and the
extracts were concentrated to an oil (13.42 g, 93% yield) of
4-hydroxyphenyl isopropyl sulfide, purified by distillation, with
Ben zh yd r yl 4-Hyd r oxyp h en yl Su lfon e (8). A mixture of
4-hydroxybenzenethiol (6.3 g, 50 mmol), benzhydryl chloride
(10.13 g, 50 mmol), and K2CO3 (7.0 g, 50 mmol) in acetone
(100 mL) was stirred under reflux for 17 h. The solid inorganic
salts were removed by filtration and the filtrate was concen-
trated leaving a blue viscous oil. The isolated inorganic salts
were dissolved in water, the solution was extracted with ether
and the extracts were combined with the blue oil, washed with
5% NaOH, and concentrated to provide a viscous blue oil (3.67
g), suggested by 1H NMR to be composed of recovered ben-
zhydryl chloride, diphenylmethane, and 1,4-cyclohexadiene-
3-one-6-thione. The NaOH washings were acidified with 6 N
HCl and extracted with ether and the dried extracts concen-
trated, leaving benzhydryl 4-hydroxyphenyl sulfide (11.0 g,
75% yield) as white crystals (CHCl3-pentane) with mp 126.5-
1
bp 154 °C/12 mm. H NMR: δ 1.23 (d, J ) 6.5 Hz, 6 H), 3.23
(hep, J ) 6.5 Hz, 1 H), 6.25 (br s, 1 H), 6.88 (d, J ) 8.5 Hz, 2
H), 7.45 (d, J ) 8.5 Hz, 2 H). Anal. Calcd for C9H12OS: C,
64.25; H, 7.19; S, 19.05. Found: C, 64.69; H, 7.22; S, 19.46. A
solution of the sulfide (6.77 g, 40 mmol) and 30% H2O2 (25
mL, 300 mmol) in 50 mL of acetic acid was heated on a steam
1
127.5 °C. H NMR: δ 2.82 (s, 1 H), 5.54 (s, 1 H), 6.69 (d, J )
(22) Klages, A.; Stamm, C. Chem. Ber. 1904, 37, 924.
(23) Fisher, C. H.; Oakwood, T. S.; Fuson, R. C. J . Am. Chem. Soc.
1930, 52, 5036-5040.
(24) Bordwell, F. G.; Pitt, B. M. J . Am. Chem. Soc. 1955, 77, 572.
J . Org. Chem, Vol. 68, No. 2, 2003 509

Meyers et al.
9 Hz, 2 H), 7.1-7.6 (m, 12 H). Anal. Calcd for C19H16OS: C,
78.05; H, 5.52; S, 10.96. Found: C, 77.73; H, 5.46; S, 11.10.
Br, 19.11; S, 7.60. There was no indication of decomposition
of 9b during its preparation or purification.
Acid -Ca ta lyzed Hyd r olytic F r a gm en ta tion of 9b. F or -
m a tion of Ben zop h en on e, 4-Meth oxyp h en yl 4-Meth oxy-
ben zen eth iolsu lfon a te (9c), a n d P h en ol a s Ma jor P r od -
u cts. A solution of 9b (0.417 g, 1.0 mmol) in acetic acid and
water (3 mL) was stirred under reflux for 24 h, diluted with
water (50 mL), and extracted with ether. Evaporation of the
dried extracts left a mass of yellow crystals (0.285 g) that was
column chromatographed (silica gel; benzene-petroleum ether)
to provide benzophenone (0.162 g, 0.89 mmol, 89% yield),
anisole (0.0108 g, 0.10 mmol, 10% yield), unidentified material
(0.057 g), and a white crystalline compound suggested by its
1H NMR spectrum and mp 83-84 °C (methanol) to be 9c (0.062
g, 0.20 mmol (40% yield; lit.11 mp 86-88 °C)). 1H NMR: δ 3.81
(s, 3 H), 3.85 (s, 3 H), 6.79 (d, J ) 9 Hz, 2 H), 6.82 (d, J ) 9
Hz), 7.34 (d, J ) 9 Hz, 2 H), 7.53 (d, J ) 9 Hz, 2 H).
The sulfide was converted to crystalline sulfone 8 (5.64 g,
ca. 90% yield) with mp 211-212 °C dec (ethanol-pentane).
1H NMR: δ 3.21 (s, 1 H), 5.68 (s, 1 H), 6.84 (d, J ) 9 Hz, 2 H),
7.16-7.83 (m, 12 H). Anal. Calcd for C19H16O3S: C, 70.35; H,
4.97; S, 9.88. Found: C, 70.16; H, 5.08; S, 9.97. Unlike 8, the
corresponding 4-methoxyphenyl sulfone (9) (below) melts
sharply without decomposition.
r-Ch lor oben zh yd r yl 4-Hyd r oxyp h en yl Su lfon e (8a ).
Rea ction of 8 w ith CCl4. To a solution of 8 (1.62 g, 5 mmol)
in CCl4 (30 mL) and t-BuOH (30 mL) at 5 °C was added KOH
(8.0 g, 140 mmol), the mixture was stirred at 25 °C for 3 h
and 1 N HNO3 (100 mL) was then added. Workup provided
8a (1.77 g, 99% yield) as white crystals (benzene) with mp
1
149-149.5 °C dec. H NMR: δ 3.10 (s, b, 1 H), 6.79 (d, J ) 9
Hz, 2 H), 7.1-7.9 (m, 12 H). Anal. Calcd for C19H15ClO3S: C,
63.60; H, 4.21; Cl, 9.88; S, 8.93. Found: C, 63.79; H, 4.24; Cl,
9.88; S, 9.00.
Identical treatment of a solutuon of 9b (1.50 g, 3.6 mmol)
in acetic acid (17 mL), but to which 48% HBr (22 mL) was
added, provided a yellow oil (0.994 g) composed of benzophe-
none (0.640 g, 98% yield), phenol (0.169 g, 50% yield), and
unidentified material (0.183 g).
Hyd r olytic F r a gm en ta tion of 8a w ith KOH-t-Bu OH.
F or m a tion of Ben zop h en on e a n d P h en ol. A mixture of
8a (0.359 g, 1.00 mmol), KOH (1.20 g, 18.2 mmol), and t-BuOH
(6 mL) was stirred under reflux for 1 h, cooled, acidified with
1 N HNO3 (100 mL), and extracted with ether. The extracts
were concentrated and the residue column chromatograhed
(silica gel; CHCl3-petroleum ether), providing benzophenone
(0.180 g, 99% yield), phenol (0.028 g, 30% yield), and unidenti-
fied material (0.10 g). Addition of a 5% solution of AgNO3 to
the aqueous residue from the ether extractions precipitated
AgCl, 0.137 g, representing 95% fragmentation of 8a .
A solution of 9b (0.417 g, 1 mmol) in dioxane (20 mL)
containing 1 mL of water was refluxed for 24 h and extracted
with ether. The aqueous residue was acidified with 1 N HNO3
(10 mL) and a 5% solution of AgNO3 added, affording precipi-
tated AgBr (0.0175 g, 0.093 mmol), i.e., 9% Br- was generated
from the 9b. The ether extracts were worked up leaving 0.410
g of a semisolid mass that was composed of benzophenone
(0.0091 g, 5% yield) and 9b [0.375 g (90% recovery)]. When
9b was treated exactly as above but in dry dioxane, no
benzophenone was formed and recovery of 9b was 97%.
r,r-Dich lor oben zyl P h en yl Su lfon e (10a ). Rea ction of
Ben zyl P h en yl Su lfon e (10). (a ) With C2Cl6 in Aqu eou s
Na OH Un d er P h a se-Tr a n sfer Ca ta lysis. Sulfone 10 was
prepared as reported,7 mp 147-148 °C. A mixture of 10 (0.10
g, 0.4 mmol), C2Cl6 (0.31 g, 1.3 mmol), Aliquat 336 (0.01 g,
0.025 mmol), 2 mL of CH2Cl2, and 50% aq NaOH (0.65 mL, 12
mmol) was stirred for 12 h. Water and CH2Cl2 were then added
and the organic layer was separated, dried, and concentrated
as white crystals of 10a (0.12 g, 93% yield) with mp 151-152
°C (lit.25 mp 151-152 °C). 1H NMR: δ 7.23-7.63 (m, 6 H),
7.75 (dd, J ) 8 and 2 Hz, 4 H). 13C NMR: δ 99.61 (CCl2),
127.75, 128.24, 129.47, 130.91, 131.57, 131.97.132.38, 134.79.
(b) With CCl4-KOH-t-Bu OH. A stirred solution of 10
with excess CCl4 in KOH-t-BuOH at 25 °C likewise provided
10a (95% yield).1a,3a
Rea ction of 8 w ith CBr Cl3 in KOH-t-Bu OH. In Situ
F or m a tion -Hyd r olytic F r a gm en ta tion of r-Br om oben -
zh yd r yl 4-Hyd r oxyp h en yl Su lfon e (8b) in to Ben zop h e-
n on e a s th e Ma jor P r od u ct. A mixture of 8 (1.35 g, 4.17
mmol), KOH (6.70 g, 102 mmol), CBrCl3 (25 mL), and t-BuOH
(25 mL) was stirred at 10 °C for 5 min, then at 25 °C for 2 h,
diluted with 1 N HNO3 (120 mL), and extracted with ether.
The combined extracts were washed with aq NaOH and
concentrated, leaving 0.791 g of dark yellow crystals shown
by 1H NMR to be composed of benzophenone (2.97 mmol, 71%
yield) and fuchsone (0.125 mmol, 3% yield). The aq NaOH
washings were combined, acidified with 1 N HNO3, and
extracted with ether. Concentration of the extracts left dark-
colored crystals which were column chromatographed (silica
gel; CHCl3-petroleum ether) to provide 0.42 g of a mixture
consisting (by TLC) of five compounds, including phenol,
possibly 4-hydroxybenzenesulfinic acid, and a small amount
of 8b.
Rea ction of 10 w ith 1 Equ iv of 10a in KOH-t-Bu OH.
Qu a n tita tive F or m a tion of 2 Equ iv of r-Ch lor oben zyl
P h en yl Su lfon e (10d ). A mixture of 10a (0.10 g, 0.3 mmol),
10 (0.077 g, 0.3 mmol), and KOH (3.0 g) in t-BuOH (10 mL)
was stirred at 25 °C for 17 h, then diluted with water and
extracted with ether. The combined extracts were dried and
evaporated leaving a pale yellow solid (0.16 g, 80% yield),
shown by NMR to be exclusively 10d with mp 180-181 °C
(lit.26 mp 185-186 °C), with no indication of any recovered 10
or 10a . The overall yield of 10d was estimated to be well over
Ben zh yd r yl 4-Meth oxyp h en yl Su lfon e (9). A mixture of
4-methoxybenzenethiol (5.70 g, 40 mmol), benzhydryl chloride
(8.25 g, 40 mmol), and K2CO3 (8.0 g, 60 mmol) in acetone (50
mL) refluxed for 12 h provided benzhydryl 4-methoxyphenyl
1
sulfide (11.3 g, 91% yield) with mp 87.5-88.5 °C (CHCl3). H
NMR: δ 3.69 (s, 3 H), 5.34 (s, 1 H), 6.68 (d, J ) 9 Hz, 2 H),
7.05-7.55 (m, 12 H). Anal. Calcd for C20H18OS: C, 78.39; H,
5.92; S, 10.46. Found: C, 78.50; H, 6.09; S, 10.41. The sulfide
(8.20 g, 27 mmol), heated with 30% H2O2 (30 mL 260 mmol)
in acetic acid on a steam for 2 h, was converted into benzhydryl
4-methoxyphenyl sulfone (9) as white crystals (8.36 g, 92%
1
90%, its poor solubility in ether accounting for some loss. H
NMR (very dilute CDCl3): δ 5.65 (s, 1 H), 7.28-7.68 (m, 8 H),
7.75 (dd, J ) 8 Hz, 2 Hz, 2 H). A mixture of 10d -KOH-t-
BuOH was stirred at 25 °C for 17 h, diluted with water, and
extracted with ether; 10d was ∼100% recovered.
1
yield) with mp 163.5-164.5 °C (CHCl3-petroleum ether). H
NMR: δ 3.76 (s, 3 H), 5.30 (s, 1 H), 6.82 (d, J ) 9 Hz, 2 H),
7.05-783 (m, 12 H). Anal. Calcd for C20H18O3S: C, 70.98; H,
5.36; S, 9.47. Found: C, 71.16; H, 5.56; S, 9.33.
r,r-Dibr om oben zyl P h en yl Su lfon e (10b). Rea ction of
10 w ith CBr Cl3 in Aqu eou s Na OH Un d er P h a se-Tr a n sfer
Ca ta lysis. (a ) F or 1 h At 25 °C. A mixture of 10 (1.50 g, 6.5
mmol), CBrCl3 (20 mL, 200 mmol), CH2Cl2 (10 mL), 50% aq
NaOH (10 mL, 190 mmol), and Aliquat 336 (0.172 g, 0.42
mmol) was stirred at 25 °C for 1 h, and CH2Cl2 (10 mL) was
r-Br om oben zh yd r yl 4-Meth oxyp h en yl Su lfon e (9b).
Rea ction of 9 w ith CBr Cl3. A mixture of 9 (1.69 g, 5 mmol),
KOH (4.00 g, 61 mmol), t-BuOH (30 mL), and CBrCl3 (30 mL)
stirred at 25 °C for 30 min provided crystals of 9b (2.04 g,
98% yield)with mp 169.5-170.5 °C (CHCl3). 1H NMR [CDCl3-
(CD3)2CdO]: δ 3.78 (s, 3 H), 6.72 (d, J ) 9 Hz, 2 H), 7.10-748
(m, 8 H), 7.50-783 (m, 4 H). Anal. Calcd for C20H17BrO3S: C,
57.56; H, 4.11; Br, 19.15; S, 7.68. Found: C, 57.41; H, 4.12;
(25) Shirota, Y.; Nagai, T.; Tokura, N. Bull. Chem. Soc. J pn. 1966,
39, 405.
(26) Tuleen, D. L.; Marcum, C. J . Org. Chem. 1967, 32, 204-206.
510 J . Org. Chem., Vol. 68, No. 2, 2003

R-Halogenation and Related Reactivity of Sulfones
added. The organic layer was separated and evaporated in
vacuo leaving yellow crystals shown by 1H NMR to be
composed of 10b (2.36 g, 85% yield) and 10 (0.20 g, 13%
recovery). Column chromatography (silica gel; methylene
chloride/low-boiling petroleum ether) afforded the separation
of 10b as white needles with mp 125.5-126 °C. 1H NMR
(CDCl3): δ 7.10-7.65 (m, 8 H), 7.75 (dd, J ) 8 and 2 Hz, 2 H).
13C NMR: δ 79.17 (CBr2), 127.87, 128.22, 130.85, 131.34,
132.39, 133.78, 134.80. Anal. Calcd for C13H10Br2O2S: C, 40.03;
H, 2.58; Br, 40.97; S, 8.22. Found: C 40.14; H, 2.31; Br, 40.72;
S, 8.19.
(b) F or In cr ea sin g P er iod s of Tim e. F or m a tion of 10b,
r-Br om o-r-Ch lor oben zyl P h en yl Su lfon e, a n d 10a . A
mixture similar that in subsection a above was stirred at 25
°C, and aliquots (6 mL) were removed at the end of 1, 2, 4, 7,
and 12 h and worked up as above. Analysis via 13C NMR
indicated that 10b was initially formed exclusively, and was
slowly converted into the R-chloro-R-bromo sulfone during the
12-h period. When the reaction was repeated but stirring was
continued for 24 h, the composition of the mass of white
crystals that formed was identified by 13C NMR as 10b (20%;
δ 79.25, CBr2), the R-Cl-R-Br sulfone (55%; δ 90.07, CBrCl),
and 10a (20%; δ 99.69, CCl2).
Redu ctive Debr om in ation of r,r-Dibr om oben zyl P h en -
yl Su lfon e (10b) to r-Br om oben zyl P h en yl Su lfon e (10c)
w ith CHCl3. (a ) In Aqu eou s Na OH/CH2Cl2 u n d er P h a se-
Tr a n sfer Ca ta lysis. A mixture of 10b (0.350 g, 0.90 mmol),
Aliquat 336 (0.022 g, 0.054 mmol), 2.0 mL of CH2Cl2, and 1.4
mL of a 50% aq solution of NaOH (27 mmol) was stirred at 25
°C for 10 min; CHCl3 (0.72 mL, 8.9 mmol) was then added
and stirring was continued for 1 min. Water and CH2Cl2 were
added and the organic layer was separated and worked up as
usual, providing 10c (0.253 g, 91% yield) as white crystals
(CHCl3) with mp 190-192 °C (lit.10f mp 193-194 °C). 1H NMR
(very dil CDCl3): δ 5.71 (s, 1 H), 7.61-7.25 (m, 8 H), 7.75 (dd,
J ) 8 Hz, 2 Hz, 2H).
(b) In KOH-t-Bu OH. A mixture of 10b and KOH in
t-BuOH was stirred at 25 °C for a few minutes, CHCl3 was
then added, and the mixture was stirred for an additional 1-2
min. Water was added, the mixture was acidified with dil
HNO3 and extracted with ether, and the extracts were dried
and evaporated, leaving 10c in over 90% yield: mp as above.
F a ilu r e of Red u ctive Debr om in a tion of r,r-Dibr o-
m oben zyl P h en yl Su lfon e (10b) w ith CH 2Cl2 in Aqu eou s
Na OH Un d er P h a se-Tr a n sfer Ca ta lysis. A mixture of 10b
(0.131 g, 0.30 mmol), Aliquat 336 (0.008 g, 0.02 mmol) in CH2-
Cl2 (3.30 mL, 52 mmol), and 0.51 mL of a 50% aq solution of
NaOH (9.6 mmol) was stirred at 25 °C for 12 h, then diluted
with CH2Cl2 and water. The usual workup provided a mass of
crystals that was washed with cold pentane to remove residual
Aliquat 336 and give white crystals (0.124 g, 95% recovery) of
10b, confirmed by mp, 1H NMR, IR, and Rf ,which were
identical, respectively, to those of the starting material.
Ack n ow led gm en t. Special gratitude is expressed
to Professor Frederick G. Bordwell for his consultation
and input in this investigation. V.M.K. expresses her
thanks for a Fulbright Fellowship, and D.H.H. and
W.S.M. thank Southern Illinois University for graduate
fellowships, during the course of these studies. P.B.S.
and S.X. express gratitude for the Graduate Research
Assistantships provided them by the Meyers Institute
for Interdisciplinary Research in Organic and Medicinal
Chemistry at Southern Illinois University. C.Y.M. ex-
presses appreciation for the special research funding
associated with his Distinguished Professorship.
J O025781W
J . Org. Chem, Vol. 68, No. 2, 2003 511