Methyl sulfinates as electrophiles in friedel-crafts reactions. Synthesis of aryl sulfoxides

Article abstract of DOI:10.1021/jo2006335

The Friedel-Crafts reaction of methyl alkyl- and arylsulfinates with aromatic systems, activated by one or more electron-donating substituents (OH, OMe, NHR, NR₂), provides alkyl aryl and diaryl sulfoxides under mild conditions and in moderate to good yields. The very high regioselectivity usually observed in these sulfinylation reactions is rationalized on the basis of a Wheland intermediate having a trigonal bypyramidal structure in which steric and electronic interactions are significant factors strongly destabilizing the attack to the ortho positions.

Full text of DOI:10.1021/jo2006335

ARTICLE
pubs.acs.org/joc
Methyl Sulfinates as Electrophiles in FriedelꢀCrafts Reactions.
Synthesis of Aryl Sulfoxides
Francisco Yuste,*,† Angꢀelica Hernꢀandez Linares,† Virginia M. Mastranzo,† Benjamín Ortiz,†
Rubꢀen Sꢀanchez-Obregꢀon,† Alberto Fraile,‡ and Josꢀe Luis García Ruano*,‡
†Instituto de Química, Universidad Nacional Autꢀonoma de Mꢀexico, Circuito Exterior, Cd. Universitaria, Coyoacꢀan 04510,
Mꢀexico D. F.
‡Departamento de Química Orgꢀanica (C-1), Universidad Autꢀonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
S Supporting Information
b
ABSTRACT: The FriedelꢀCrafts reaction of methyl alkyl- and
arylsulfinates with aromatic systems, activated by one or more
electron-donating substituents (OH, OMe, NHR, NR2), pro-
vides alkyl aryl and diaryl sulfoxides under mild conditions and
in moderate to good yields. The very high regioselectivity
usually observed in these sulfinylation reactions is rationalized
on the basis of a Wheland intermediate having a trigonal
bypyramidal structure in which steric and electronic interactions are significant factors strongly destabilizing the attack to the
ortho positions.
’ INTRODUCTION
sulfinyl chlorides (they are easily hydrolyzed), determining its
easy decomposition in air and imposing the need of their use
freshly prepared. In this sense, the use as electrophiles of alkyl
sulfinates, much more stable and therefore easier to store and
handle, could be a good alternative if they were reactive enough
under FriedelꢀCrafts conditions. However, a pioneer report
from Olah and Nishimura9 indicated that most of the sulfinates
(i-propyl, t-butyl, benzyl, p-methoxybenzyl, m-methoxybenzyl,
and p-methylbenzyl arenesulfinates) gave alkylation instead of
sulfinylation of benzene and toluene in nitromethane solution
using aluminum chloride as a catalyst, which could explain that
there is not any other further reference centered in the study of
sulfinates as sulfinylating electrophiles in FriedelꢀCrafts reac-
tions. However, in ref 9, the low reactivity of the p-nitrobenzyl
and ethyl arenesulfinates (they only reacted in the presence of
neat aluminum chloride) and the unreactivity of methyl benze-
nesulfinate are also reported. The low stability of the p-nitro-
benzyl and ethyl carbenium ions, and the even lower stability of
The great importance of the sulfoxides in organic synthesis
justifies the large efforts made in the search for efficient methods
for their preparation.1 The oxidation of thioethers2 and the
reaction of organometallic compounds with sulfinic acid deriva-
tives are among the most used methods for the preparation of
sulfoxides (mainly in enantiomerically pure form),3 but other
methods involving the reaction of sulfinyl carbanions with
electrophiles and rearrangements of sulfenic acid esters have also
been reported.1
The FriedelꢀCrafts sulfinylation of aromatic compounds to
form diaryl or alkyl aryl sulfoxides is relatively unexplored given
that the synthesis of phenyl p-tolyl sulfoxide from benzene and
p-toluenesulfinyl chloride was reported in 1926.4 More than 30
years later, Douglas et al.5 reported a 26% yield of methyl phenyl
sulfoxide by reaction of benzene with methanesulfinyl chloride in
the presence of anhydrous aluminum chloride, and Replogle and
Maynard6 described lowyields of the corresponding sulfoxides for
the direct electrophilic sulfinylation of the azulene ring with
alkane or arenesulfinyl chlorides. Olah and Nishimura7 have
reported the high selectivity of the aluminum chloride catalyzed
arenesulfinylation of benzene and polymethylbenzenes with sub-
stituted benzenesulfinyl chlorides in nitromethane solution,
whereas Chasar and Pratt8 prepared a number of 2- and 4-hydro-
xydiaryl sulfoxides by the direct arenesulfinylation of substituted
phenols in the presence of anhydrous aluminum chloride.
All of the above methods are related by the use of alkyl or
arylsulfinyl chlorides to induce the electrophilic aromatic sub-
stitution under Lewis acid catalysis. A problem associated with
these procedures (probably responsible for their low use for
obtaining sulfoxides) is the usually moderated stability of the
þ
the CH3 (resulting from methyl sulfinates), can explain this
behavior. This result suggested to us that methyl sulfinates would
be the only appropriate sulfinylating agents under Friedelꢀ
Crafts conditions. The failure to generate sulfoxides in the
reactions studied in ref 9 suggests that the aromatic systems
used as substrates (benzene and toluene) were too unreactive to
be sulfinylated by methyl sulfinates.
We have recently reported the advantages of using methyl
sulfinates instead of sulfonyl chlorides for obtaining sulfonamides.10
The notable differences in reactivity with oxygenated nucleophiles
Received: March 25, 2011
Published: April 20, 2011
r
2011 American Chemical Society
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Scheme 1. Synthesis of Sulfoxides from Methyl Arenesulfi-
nates via FriedelꢀCrafts Reactions
Scheme 2. Synthesis of Methyl Sulfinates from Thiols
methyl group decreases the activating character of the o-OMe
group as a consequence of partial steric inhibition of the resonance.
Phenol is also activated enough to react with methyl benze-
nesulfinate. However, it yields a mixture of ortho and para
derivatives with para substitution being favored by a factor of 4
(entry 5). The smaller size of the OH group as compared to the
methoxy moiety, and mainly its ability to form hydrogen bonds
with the electrophile, thus partially compensating for their
stereoelectronic repulsion, must be responsible for the formation
of the ortho product (absent in reaction from anisole, entry 1). As
expected, the para:ortho selectivity decreases when the reaction
was performed at 80 °C (entry 5), but the yield remains almost
unaltered. The incorporation of a methyl group into the phenol
ring causes significant changes in the regioselectivity. As ex-
pected, p-cresol gave 7a exclusively (entry 6). m-Cresol (entry 7)
afforded a 90:10 mixture of compounds 8a and 9a, where the
incorporation of the electrophile at C-6 (ortho with respect to the
OH group) predominates over the attack at C-4 (para to the OH
group). This inversion of the regioselectivity, with respect to that
observed for phenol (entry 5), is presumably due to the steric
hindrance exerted by the methyl group at C-2 and C-4. A
comparison of entries 3 (exclusive attack to C-4) and 7
(predominant attack at C-6) confirms that the OMe group only
orients para, whereas the OH allows the incorporation of the
sulfinyl group at the ortho and para positions. The behavior of
o-cresol (entry 8) is the expected one, with a regioselectivity
similar to that of phenol (compare entries 5 and 8). The
incorporation of the methyl group ortho to the hydroxyl group
does not have a significant effect on the reactivity.
The introduction of a methoxy group into phenol also
produces interesting changes in the regioselectivity. The behav-
ior of the monomethyl derivative of the hydroquinone (entry 9)
is the expected one (only sulfoxide 12a, resulting from attack
of the sulfinate at C-2, is formed). 3-Methoxyphenol yields a
mixture of 13a and 14a (entry 10) with the attack at C-6 (ortho
with respect to the OH group), predominating over attack at
C-4 (para to the hydroxyl group). This behavior is under-
standable taking into account the previously commented diffi-
culties of the sulfinate for approaching to the ortho positions
of the OMe group. Reaction of guaiacol is completely regio-
selective, affording only the sulfoxide 15a, derived from attack at
C-4 (entry 11), despite that it is deactivated by the OMe group at
C-2. These facts can be explained by the existence of an
intramolecular hydrogen bond between the phenolic OH and
the ortho-OMe group, which confers a higher deactivating
character to the positively charged OMe group (thus decreasing
the reactivity) and reduces the intermolecular association of the
OH with the electrophile.
determines a much higher stability of the sulfinates, whereas both
are similarly reactive with nitrogen-based nucleophiles. On this
basis, we reasoned that methyl sulfinates might also exhibit a good
reactivity with carbon-based nucleophiles like those involved
in the FriedelꢀCrafts reactions, thus providing a new entry for
synthesizing diaryl and alkyl aryl sulfoxides from stable and easily
available substrates. The low reactivity of toluene and benzene
with methyl sulfinates under conditions used in ref 9 indicated
that any study concerning the use of these substrates in Friedelꢀ
Crafts reactions should consider more activated aromatic systems,
such as phenols or anilines. In this paper, we describe the results
obtained in these reactions (Scheme 1) with the aim of revealing
their main features (reactivity, regioselectivity, and possible me-
chanism) as well as the scope of methyl sulfinates as sulfinylating
reagents.
’ RESULTS AND DISCUSSION
The methyl sulfinates used in this study (1) were easily
synthesized by a two-step process from the commercially avail-
able thiols by simple oxidation to the disulfides with air under
sonication,11 which were directly transformed into the methyl
sulfinates by the method of Brownbridge et al.12 (Scheme 2).
We first studied the reactions of methyl benzenesulfinate 1a
(1 equiv) with anisole (2 equiv) in the presence of AlCl3 (1 equiv).
After 15 h at rt, we observed the exclusive formation of the
4-(phenylsulfinyl)anisole 2a in 53% isolated yield (entry 1,
Table 1). This result demonstrated that methyl sulfinates could
be successfully used as electrophiles in the sulfinylation of an
activated aromatic system. The complete regioselectivity of this
reaction suggested significant differences with respect to con-
ventional FriedelꢀCrafts reactions of methoxylated aromatic
substrates. FriedelꢀCrafts sulfinylation reactions are much more
sensitive to the steric and/or electronic repulsions between
reagent and the OMe group, determining that it exclusively
orientates the electrophile to its para position. The fact that
4-methylanisole does not react after 48 h under similar condi-
tions (entry 2) agrees with the exclusive para orientating
character of the OMe group in these reactions, which would
also explain the complete regioselective transformation of
3-methylanisole and 2-methylanisole into the sulfoxides 3a
(entry 3) and 4a (entry 4), respectively, resulting in the attack
of the sulfinate to the para position of the OMe group.
Unexpectedly, reactivity of 3-methylanisole is lower than that
of the anisole (compare reaction times and yields of entries 1 and
3), but it could be explained by assuming that steric repulsion
exerted by the Me group on its ortho positions must be more
marked than the activation produced by its electronic effects.
However, the fact that 2-methylanisole exhibits an even lower
reactivity (4a is obtained in 20% yield after six days, entry 4) is
not easily understandable, and it could be suggesting that the
The results obtained in the sulfinylation of naphthols and their
O-methyl derivatives (entries 12ꢀ15) deserve special comment.
β-Oxygenated naphtalene is sulfinylated only in the R-position,
which is specially activated by the other ring (entries 12 and 13).
The higher reactivity of the β-naphthol with respect to its
O-methyl derivative (shorter reaction times and better yields)
is easily explained on the basis of the negative effect exerted by
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Table 1. Reactions of Aromatic Methyl Ethers, Phenols, and Napthols with Methyl Benzenesulfinate
a T = 80 °C.
the OMe group on the attack at its ortho positions (see before).
It also explains the exclusive formation of the 4-sulfinyl deriv-
ative 18a from 1-methoxynaphthalene (entry 14), as well as its
higher reactivity with respect to that of 2-methoxynaphthalene
(compare reaction times and yields in entries 12 and 14).
However, the reaction time required for 1-methoxynaphthalene
is higher than that observed for anisole (compare entries 1 and
14), which suggests that attack at C-4 of 1-methoxynaphthalene
is less facile than expected for electronic reasons. The sulfinyla-
tion of 1-naphthol occurs exclusively at C-2 to give 19a (entry
15). This behavior was not expected taking into account the
reaction of phenol (entry 5) which affords a mixture of regio-
isomers where the p-sulfinyl derivative is predominant. It also
indicates some factor making difficult the attack to C-4 of
1-naphthol, indicating that the ortho orientating character of
the OH group is much higher for 1-naphthol than for phenol.
In Table 2 are collected some results obtained in the sulfinyla-
tion of other activated phenols with methyl sulfinates at room
temperature. All of them give a single product in very high yields.
We have also examined the reactivity of several substituted
methyl arenesulfinates (Ar = Ph, p-Tol, and p-Cl-C6H4) with
several of these phenol derivatives, and only one product was
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Table 2. Reactions of Different Phenols with Methyl Sulfinates
observed in every case (compare entries 1, 4, and 5 in Table 2).
We have also studied the reaction of methyl isobutylsulfinate
with 2,5-dimethylphenol (entry 2). The lower yield obtained
under conditions similar to those used with arenesulfinates is not
unexpected due to the inductive effect of the alkyl group and
Scheme 3. Reactions of Aniline with Methyl Sulfinates
agrees with their expected lower reactivity.
We then studied the sulfinylation of the anilines and deriva-
tives. Despite that the aromatic rings of these compounds will be
more activated than those of the phenols, suggesting they will be
able to react with methyl sulfinates under similar conditions, the
reactions of aniline with methyl phenyl sulfinate and various p-
substituted derivatives thereof gave sulfinamides exclusively and
efficiently (Scheme 3). This means that the nucleophilic power of
the nitrogen is much higher than that of the aromatic carbons.
Interestingly, the time required for completing the attack of
nitrogen to sulfur is 15ꢀ36 h, similar to those of the phenols in
Table 2 to afford aryl sulfoxides. The lower nucleophilicity of the
phenolic oxygen suggests it would require longer times to form
the sulfinates, which supports that these are not intermediates in
the formation of the sulfoxides (see later), which must be there-
fore formed by direct FriedelꢀCrafts reactions of the phenols.
Next, we studied the behavior of N-alkyl and N,N-dialkylani-
lines (Table 3). The reaction with the N,N-disubstituted anilines
gave compounds 25ꢀ27 exclusively (entries 1ꢀ3, Table 3)
with sulfinylation occurring only para to the nitrogen atom. This
can also be explained by assuming a large stereoelectronic
hindrance of the NR2 at the ortho positions, resulting in the
exclusive attack at the para position. This is not unexpected given
that it had been also observed with anisoles (Table 1) and that
the size of the NR2 group is considerably larger than that of the
OMe group. The only notable fact is the lower yield usually
observed as the size of the N-substituents is increased (i-Pr < Et <
Me), which could be a consequence of the loss of conjugation
(steric inhibition of the resonance of the lone electron pair at
nitrogen with the ring) produced to minimize the steric interac-
tion of the R group with the ortho hydrogens. Reaction of N,
N-dimethylaniline with alkyl sulfinates like methyl isobutylsulfinate
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Table 3. Reactions of N-Alkyl and N,N-Dialkylanilines with Methyl Arenesulfinates
exhibits a similar behavior only yielding compound 26d in good
yield (entry 4, Table 3).
R group (aliphatic or aromatic), and the methoxy moiety
(Figure 1). To minimize the steric interactions of these equator-
ial substituents with the aromatic ring acting as a nucleophile, the
lone electron pair is arranged toward the ring (it is also favored by
its electrostatic attraction with the positively charged ring), which
determines that H(1) bisects the two larger equatorial substitu-
ents. The Wheland intermediate A evolves into B transferring the
hydrogen (probably to the OMe group thus increasing its ability
as a leaving group) and regenerating the aromatic system.
Elimination of methanol from B (this process will presumably
require a pseudorotation placing the OMe group at the apical
position) would yield the final sulfoxide. This general mechanism
will be followed by amines and ethers when the attacked position
lacks substituents at the ortho sites. If one or both of these
positions is occupied by a substituent (in this paper, Me, OMe,
NR2), reactions are much more difficult because of the steric
and/or electronic repulsions between the ortho substituent and
the equatorial substituent on the sulfur (A or A0 in Figure 1). This
would explain the exclusive para orientating character of the
OMe and NR2 groups. The attack at C-1 and C-4 (R positions)
The sulfinylation of mono-N-alkylanilines are also occurs
exclusively in the para position yielding compounds 28ꢀ30
(entries 5ꢀ7). As in the case of the N,N-disubstituted congeners,
the yields decrease as the size of the alkyl group increases. It is
worth noting the difference in the orientating power of the
NHMe (only p-sulfinyl derivatives are obtained) and the OH
groups (yielding ortho/para mixtures), which could be due to the
lower ability of the NH group to form hydrogen bonds and to the
larger size of the NHMe group.
To explain the observed regiochemistry of these processes, we
propose that reactions of methyl sulfinates with aromatic rings
containing OMe and NR2 groups are FriedelꢀCrafts type
sulfinylation processes, catalyzed by AlCl3, where the tetrahedral
sulfur is attacked by the ring carbons with higher aromatic
density. The sulfur in the Wheland intermediate A has a trigonal
bipyramid structure with the aromatic carbon and the oxygen
joined to sulfinyl sulfur occupying the apical positions. The
equatorial positions are occupied by the lone electron pair, the
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Figure 1. Mechanistic proposal for explaining the FriedelꢀCrafts sulfinylation reactions with methyl sulfinates.
Scheme 4. Comparison of the Results Obtained in Sulfinylation of Phenols and Rearrangement of Aryl Benzenesulfinates
of the naphthalene rings must be relatively destabilized by the
steric interaction of the equatorial sulfur substituents and C-8
and C-5, respectively (A00 in Figure 1), determining that it was
less favored than expected from electronic reasons.
those shown in entries 7 and 8 of Table 1 (Scheme 4). It suggests
that 31 and 32 do not act as the intermediates in reactions from
m-cresol and o-cresol. However, it could be argued that the
conditions are not exactly the same, because Jung used 2 equiv of
AlCl3 in CH2Cl2, whereas only 1 equiv of the catalyst in
(CH2Cl)2 was used for the results shown in Table 1. Thus, we
performed the reaction of 32 under the same conditions used in
entry 8 in Table 1 (Scheme 4), and we recovered the starting
benzenesulfinates, which unequivocally demonstrates that they
cannot be intermediates in the conditions we have used for the
sulfinylation of phenols.14
The second explanation for understanding the different
behavior of phenols and anisoles consists of assuming that the
attack of the methyl sulfinates at the ortho position of phenols is
favored by the formation of hydrogen bonds between the OH
and the sulfinate oxygen atoms. This would minimize the
stereoelectronic repulsion between the oxygenated functions
shown in Figure 1, making the formation of the ortho sulfinyl
derivatives easier (A1, Figure 2). The exclusive formation of the
p-tolylsulfinyl derivatives starting from guaiacol (entry 11,
Phenols show a behavior different from anisoles. The OH
group mainly orientates to the para position, but it is able to form
the ortho sulfinyl derivatives, which was not possible for the OMe
compounds. There are two possible explanations for this differ-
ence. The first one involves assuming a different mechanism for
both substrates. Since the ThiaꢀFries rearrangement of the aryl
benzenesulfinates to ortho and para sulfinyl phenols catalyzed by
Lewis acids has been reported,13 we could assume that reactions
of phenols with methyl sulfinates yield aryl sulfinates in a first
step, which will be further transformed into the corresponding
sulfoxides. To check this proposal, the results obtained when
some aryl sulfinates are exposed to reaction conditions similar or
identical to those used in Table 1 are indicated in Scheme 4. Jung
et al.13 reported the reactions of 31 and 32 with AlCl3 (2 equiv)
in CH2Cl2 at room temperature in 1 h. The results indicate that
the reactivity, yield, and mainly regioselectivity are different from
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was washed with brine (3 ꢁ 5 mL), dried (Na2SO4), and concentrated.
The residue was purified as indicated for each case below.
4-Methoxy-2-methyl-1-(phenylsulfinyl)benzene (3a). The
product was purified by flash chromatography (hexaneꢀEtOAc, 6:4),
1
brown oil. IR (KBr): 1599, 1479, 1442, 1287, 1242, 1041 cmꢀ1. H
NMR (300 MHz, CDCl3): δ 2.38 (s, 3H), 3.81 (s, 3H), 6.70 (d, J = 2.4
Hz, 1H), 6.88 (dd, J = 2.7, 8.7 Hz, 1H), 7.40ꢀ7.49 (m, 3H), 7.53ꢀ7.60
(m, 2H), 7.75 (d, J = 8.7, 1H). 13C NMR (75 MHz, CDCl3): δ 18.7,
55.3, 112.4, 116.5, 125.4, 127.5, 129.1, 130.7, 134.3, 138.3, 145.1, 161.8.
EIMS: m/z 246 (100%, Mþ), 229 (52), 227 (42), 198 (38), 168 (51),
137 (63), 108 (33). HRMS-FAB: m/z [Mþ] calcd for C14H14O2S,
246.0715; found, 246.0718.
4-Methoxy-3-methyl-1-(phenylsulfinyl)benzene (4a). The
product was purified by flash chromatography (hexaneꢀEtOAc, 6:4),
yellow oil. IR (film): 1592, 1492, 1443, 1254, 1088, 1043 cmꢀ1. 1H NMR
(300 MHz, CDCl3): δ 2.20 (s, 3H), 3.84 (s, 3H), 6.86(d, J = 8.4 Hz, 1H),
7.37 (d, J = 1.5 Hz, 1H), 7.41ꢀ7.51 (m, 4H), 7.59ꢀ7.63 (m, 2H). 13C
NMR (75 MHz, CDCl3): δ 16.3, 55.5, 110.1, 124.6, 125.0, 127.4, 129.1,
130.6, 136.0, 136.5, 145.9, 160.3. EIMS: m/z 246 (45%, Mþ), 198 (100),
183 (26), 169 (62), 153 (35), 137 (80), 77 (12). HRMS-FAB: m/z
[M þ 1]þ calcd for C14H15O2S, 247.0793; found, 247.0799.
Figure 2. Mechanistic proposal for explaining the FriedelꢀCrafts
sulfinylation of phenols and naphthols.
Table 1), where the intramolecular association of the OMe group
with the OH group reduces the likelihood of forming an
intermolecular hydrogen bond with the sulfinate oxygens, agrees
with this explanation. On the other hand, the exclusive 2-sulfi-
nylation of 1-naphthol (entry 15, Table 1) is understandable if we
take into account that A3, the intermediate resulting in the attack
at the para position, must be less stable than A2 due to the 1,3-syn
diaxial interactions of the OMe group with the second ring
(Figure 2). Moreover, the fact that 1-naphthol is more acidic than
phenol suggests stronger hydrogen bonds in the first case, which
would also favor the attack at the ortho position of 1-naphthol.
In conclusion, we report in this paper that methyl sulfinates
can be used as electrophiles in FriedelꢀCrafts reactions with
aromatic systems activated by OH, OR, NHR, and NR2 groups
under AlCl3 catalysis, providing a new entry for the synthesis of
aryl sulfoxides under mild conditions which avoid the use of the
unstable and hazardous sulfinyl chlorides. The orientating char-
acter of the substituents is different from that shown in other
SEAr reactions, with the steric interactions seriously restricting
the approach of the methyl sulfinates to their ortho positions,
unless substituents and electrophiles can be associated by a
hydrogen bond. This is a consequence of the trigonal bipyrami-
dal structure around the sulfur adopted by the Wheland inter-
mediate of these reactions.
5-Methyl-2-(phenylsulfinyl)phenol (8a). The product was pur-
ified by flash chromatography (hexaneꢀEtOAc, 8:2), mp 160ꢀ162 °C.
IR (KBr): 2988 (br), 1602, 1562, 1302, 1233, 987 cmꢀ1. 1H NMR (300
MHz, CDCl3 þ DMSO-d6): δ 2.34 (s, 3H), 6.67 (d, J = 2.1 Hz, 1H), 6.82
(dd, J = 2.4, 8.4 Hz, 1H), 7.40ꢀ7.46 (m, 3H), 7.52ꢀ7.60 (m, 3H), 9.30
(s, 1H). 13C NMR (75 MHz, CDCl3 þ DMSO-d6): δ 18.4, 114.3, 117.8,
125.2, 127.7, 128.9, 130.4, 132.1, 138.5, 144.9, 160.1. EIMS: m/z 232
(15%, Mþ), 183 (23), 109 (100), 77 (14). HRMS-FAB: m/z [Mþ] calcd
for C13H12O2S, 232.0558; found, 232.0556.
3-Methyl-4-(phenylsulfinyl)phenol (9a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 7:3), mp 163ꢀ
165 °C. IR (KBr): 3063 (br), 1595, 1414, 1009 cmꢀ1. 1H NMR (300
MHz, CDCl3): δ 2.29 (s, 3H), 6.70 (s, 1H), 6.72 (d, J = 7.5 Hz, 1H), 7.12
(d, J = 7.5 Hz, 1H), 7.46ꢀ7.50 (m, 3H), 7.65ꢀ7.70 (m, 2H), 10.02
(s, 1H). 13C NMR (75 MHz, CDCl3): δ 21.5, 120.0, 120.9, 124.7, 125.9,
129.4, 130.0, 131.3, 144.0, 144.2, 159.3. EIMS: m/z 232 (95%, Mþ), 184
(100), 110 (33), 77 (28). HRMS-FAB: m/z [Mþ] calcd for C13H12O2S,
232.0558; found, 232.0556.
2-Methyl-4-(phenylsulfinyl)phenol (10a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 5:5), mp 160ꢀ
162 °C. IR (deposited film): 3146 (br), 1589, 1497, 1408, 1280, 1084,
1012 cmꢀ1. 1H NMR (300 MHz, CDCl3 þ DMSO-d6): δ 2.19 (s, 3H),
6.90 (d, J = 8.1 Hz, 1H), 7.29 (dd, J = 2.1, 8.1 Hz, 1H), 7.33 (d, J = 1.8 Hz,
1H), 7.40ꢀ7.49 (m, 3H), 7.56ꢀ7.62 (m, 2H) (the OH proton was not
observed). 13C NMR (75 MHz, CDCl3 þ DMSO-d6): δ 16.0, 115.4,
124.5, 124.9, 126.3, 128.1, 128.9, 130.3, 134.1, 145.5, 158.6. EIMS: m/z
232 (45%, Mþ), 216 (15), 184 (100), 155 (47), 139 (18), 123 (31), 110
(57), 94 (28), 77 (22). HRMS-FAB: m/z [M þ 1]þ calcd for
C13H13O2S, 233.0636; found, 233.0635.
’ EXPERIMENTAL SECTION
General Methods. All reactions were carried out in anhydrous 1,
2-dichloroethane under argon and monitored by TLC on silica gel. Flash
chromatography was performed on silica gel 60 (230ꢀ400 mesh ASTM).
Melting points were determined in open capillary tubes and are uncor-
rected. The IR spectra were recorded with an FT-IR spectrophotometer.
The 1H and 13C NMR spectra were acquired at 200 (or 300) and 50.3 (or
75.5) MHz, respectively. Mass spectra were obtained with a double sector
mass spectrometer. Compounds 2a,15 5a,8,16 6a,16 7a,8 16a,17 17a,17,18
24a,19,20 24b,20 24c,20 25a,21 25b,21 and 25c22 have been previously
described in the literature.
General Procedure for the Synthesis of Sulfoxides and
Sulfinamides. To a stirred suspension of aluminum chloride (0.5
mmol) in 0.3 mL of 1,2-dichloroethane was added a solution of methyl
sulfinate 1 (0.5 mmol) in 0.3 mL of 1,2-dichloroethane. The mixture was
stirred at room temperature for 1 h. Then a solution of the corresponding
starting material (1 mmol) in 0.3 mL of 1,2-dichloroethane was added,
and the resulting mixture was stirred for the time indicated in Tables 1ꢀ3
and in the text. After the addition of CH2Cl2 (10 mL), the organic phase
2-Methyl-6-(phenylsulfinyl)phenol (11a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 8:2), mp 80ꢀ
1
82 °C. IR (film): 3160 (br), 1582, 1464, 1430, 1255, 1079 cmꢀ1. H
NMR (300 MHz, CDCl3): δ 2.18 (s, 3H), 6.82 (t, J = 7.5 Hz, 1H), 7.10
(d, J = 7.2 Hz, 1H), 7.21 (d, J = 7.5 Hz, 1H), 7.43ꢀ7.60 (m, 3H),
7.63ꢀ7.73 (m, 2H), 10.36 (br s, 1H). 13C NMR (75 MHz, CDCl3):
δ 15.3, 119.3, 122.1, 123.7, 124.7, 128.9, 129.5, 131.3, 134.2, 143.6, 157.6.
EIMS: m/z 232 (100%, Mþ), 216 (14), 200 (10), 184 (34), 110 (24), 77
(15). HRMS-FAB: m/z [M þ 1]þ calcd for C13H13O2S, 233.0636;
found, 233.0634.
4-Methoxy-2-(phenylsulfinyl)phenol (12a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 7:3), brownish
solid, mp 143ꢀ145 °C. IR (KBr): 3166 (br), 1503, 1420, 1254, 1194,
1048, 1019 cmꢀ1. 1H NMR (300 MHz, CDCl3): δ 3.75 (s, 3H), 6.76
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ARTICLE
(d, J = 2.7 Hz, 1H), 6.82 (d, J = 9.0 Hz, 1H), 6.91 (dd, J = 2.7, 9.0 Hz,
1H), 7.46ꢀ7.56 (m, 3H), 7.67ꢀ7.75 (m, 2H), 9.70 (s, 1H). 13C NMR
(75 MHz, CDCl3): δ 55.9, 110.3, 119.3, 120.3, 123.3, 124.9, 129.5,
131.5, 143.5, 152.8 (2C). EIMS: m/z 248 (100%, Mþ), 231 (51), 216
(16), 200 (34). HRMS-FAB: m/z [Mþ] calcd for C13H12O3S, 248.0507;
found, 248.0510.
158.0. EIMS: m/z 246 (100%, Mþ), 229 (66), 198 (23), 168 (51), 137
(33), 110 (28), 77 (26). HRMS-FAB: m/z [M þ 1]þ calcd for
C14H15O2S, 247.0793; found, 247.0797.
2,5-Dimethyl-4-(p-tolylsulfinyl)phenol (20b). The product
was purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
165ꢀ167 °C. IR (KBr): 3116, 1402, 1267, 1023 cmꢀ1. 1H NMR (200
MHz, CDCl3): δ 2.14 (s, 3H), 2.23 (s, 3H), 2.37 (s, 3H), 6.55 (s, 1H),
7.24ꢀ7.42 (AA0BB0system, 4H), 7.41 (s, 1H), 7.82 (s, 1H). 13C NMR
(50 MHz, CDCl3): δ 15.6, 18.1, 21.4, 117.4, 123.9, 125.5, 128.4, 129.9,
131.7, 136.0, 140.8, 141.3, 157.7. EI MS: m/z 260 (100%, Mþ), 243
(69), 241 (54), 212 (34), 168 (98), 124 (40), 108 (36), 91 (25). HRMS-
FAB: m/z [M þ 1]þ calcd for C15H17O2S, 261.0949; found, 261.0956.
4-(4-Chlorophenylsulfinyl)-2,5-dimethylphenol (20c). The
product was purified by flash chromatography (hexaneꢀEtOAc, 6:4),
5-Methoxy-2-(phenylsulfinyl)phenol (13a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 7:3), mp
141ꢀ142 °C. IR (KBr): 3062, 1594, 1421, 1277, 1210, 1004 cmꢀ1
.
1H NMR (300 MHz, CDCl3 þ DMSO-d6): δ 3.76 (s, 3H), 6.41 (d, J =
2.4 Hz, 1H), 6.50 (dd, J = 2.4, 8.7 Hz, 1H), 7.37 (d, J = 8.7 Hz, 1H),
7.41ꢀ7.49 (m, 3H), 7.65ꢀ7.70 (m, 2H), 10.09 (s, 1H). 13C NMR (75
MHz, CDCl3 þ DMSO-d6): δ 54.8, 102.3, 106.0, 118.1, 124.2, 126.2,
128.5, 130.2, 144.6, 158.0, 162.9. EIMS: m/z 248 (53%, Mþ), 232 (6),
200 (100), 171 (47). HRMS-FAB: m/z [M þ 1]þ calcd for C13H13O3S,
249.0585; found, 249.0593.
1
mp 170ꢀ173 °C. IR (KBr): 3081, 1609, 1391, 1258, 986 cmꢀ1. H
NMR (200 MHz, CDCl3 þ DMSO-d6): δ 2.18 (s, 3H), 2.31 (s, 3H),
6.64 (s, 1H), 7.37ꢀ7.51 (m, 5H) (the OH proton was not observed).
13C NMR (50 MHz, CDCl3 þ DMSO-d6): δ 15.6, 18.1, 117.1, 124.2,
126.6, 128.3, 129.2, 131.4, 135.8, 136.5, 143.8, 158.4. EIMS: m/z 280
(7%, Mþ), 214 (24), 200 (28), 183 (36), 165 (31), 91 (100). HRMS-
FAB: m/z [M þ 1]þ calcd for C14H14ClO2S, 281.0403; found,
281.0403.
3-Methoxy-4-(phenylsulfinyl)phenol (14a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 7:3), mp
121ꢀ126 °C. IR (KBr): 3106, 1582, 1429, 1206, 1006 cmꢀ1
.
1H
NMR (300 MHz, CDCl3): δ 3.62 (s, 3H), 6.39 (d, J = 1.8 Hz, 1H),
6.55 (dd, J = 1.8, 8.7 Hz, 1H), 7.39ꢀ7.46 (m, 4H), 7.59ꢀ7.65 (m, 2H),
8.63 (br, 1H). 13C NMR (75 MHz, CDCl3): δ 55.6, 99.7, 109.0, 121.1,
125.2, 127.4, 129.0, 130.8, 144.2, 158.2, 162.3. EIMS: m/z 248 (21%,
Mþ), 232 (13), 231 (46), 200 (100), 171 (23). HRMS-FAB: m/z [M þ
1]þ calcd for C13H13O3S, 249.0585; found, 249.0582.
4-(Isobutylsulfinyl)-2,5-dimethylphenol (20d). The product
was purified by flash chromatography (hexaneꢀEtOAc, 8:2), yellow oil.
IR (KBr): 3132, 2959, 1268, 998 cmꢀ1. 1H NMR (200 MHz, CDCl3): δ
1.06 (d, J = 6.6 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 2.23 (s, 3H), 2.25 (s,
3H), 2.20ꢀ2.30 (m, 1H), 2.47 (dd, J = 9.2, 13.0 Hz, 1H), 2.83 (dd, J =
4.8, 13.0 Hz, 1H), 6.64 (s, 1H), 7.58 (s, 1H). 13C NMR (50 MHz,
CDCl3): δ 15.6, 17.8, 21.6, 22.8, 24.3, 65.9, 116.9, 124.2, 126.4, 131.1,
134.1, 157.5. EIMS: m/z 226 (30%, Mþ), 170 (100), 122 (65), 107 (32).
HRMS-FAB: m/z [M þ 1]þ calcd for C12H19O2S, 227.1106; found,
227.1098.
2-Methoxy-4-(phenylsulfinyl)phenol (15a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 35:65), brownish
oil. IR (KBr): 3182 (br), 1584, 1504, 1444, 1417, 1272, 1085,
1
1030 cmꢀ1. H NMR (300 MHz, CDCl3): δ 3.87 (s, 3H), 6.96 (d,
J = 8.1 Hz, 1H), 7.13 (dd, J = 2.1, 8.1 Hz, 1H), 7.18 (d, J = 2.1 Hz, 1H),
7.42ꢀ7.49 (m, 3H), 7.58ꢀ7.63 (m, 2H). 13C NMR (75 MHz, CDCl3):
δ 56.1, 106.9, 114.8, 119.7, 124.6, 129.2, 130.8, 136.1, 145.7, 147.6,
148.7. EIMS: m/z 248 (54%, Mþ), 200 (100), 185 (23), 171 (64), 139
(63), 110 (41). HRMS-FAB: m/z [Mþ] calcd for C13H12O3S, 248.0507;
found, 248.0505.
2-Isopropyl-5-methyl-4-(phenylsulfinyl)phenol (21a). The
product was purified by flash chromatography (hexaneꢀEtOAc, 6:4),
1
mp 144ꢀ145 °C. IR (KBr): 3112, 2961, 1408, 1256, 1012 cmꢀ1. H
NMR (300 MHz, CDCl3): δ 1.13 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.9 Hz,
3H), 2.20 (s, 3H), 3.18 (sp, J = 6.9 Hz, 1H), 6.60 (s, 1H), 7.40ꢀ7.46 (m,
3H), 7.50ꢀ7.56 (m, 3H), 7.91 (br s, 1H). 13C NMR (75 MHz, CDCl3):
δ 18.0, 22.2, 22.3, 27.0, 117.9, 124.7, 125.6, 129.1, 130.7, 131.4, 134.4,
135.8, 144.2, 157.2. EIMS: m/z 274 (100%, Mþ), 257 (42), 226 (10),
215 (56), 196 (53), 165 (42), 110 (78). HRMS-FAB: m/z [M þ 1]þ
calcd for C16H19O2S, 275.1106; found, 275.1107.
1-Methoxy-4-(phenylsulfinyl)naphthalene (18a). It was ob-
tained following the general procedure slightly modified as follows: 1.0
mmol of methyl sulfinate and 0.5 mmol of 1-methoxynaphthalene were
used. The product was purified by flash chromatography (hexaneꢀ
EtOAc, 2:1), brownish oil. IR (film): 1620, 1572, 1508, 1460, 1380,
1
1322, 1271, 1245, 1089, 1044 cmꢀ1. H NMR (300 MHz, CDCl3):
δ 4.02 (s, 3H), 6.92 (d, J = 8.2 Hz, 1H), 7.34ꢀ7.41 (m, 3H), 7.45ꢀ7.54
(m, 2H), 7.62ꢀ7.66 (m, 2H), 8.07 (d, J = 8.2 Hz, 1H), 8.19ꢀ8.24
(m, 1H), 8.27ꢀ8.33 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 55.8,
103.3, 122.5, 123.0, 125.1, 125.9, 126.0, 126.5, 127.8, 129.1, 130.5, 131.1,
145.4, 158.5. MS (FABþ): m/z 283 (100%, MþHþ). HRMS-FAB: m/z
[M þ 1]þ calcd for C17H15O2S, 283.0793; found, 283.0784.
4-(Phenylsulfinyl)benzene-1,3-diol (22a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
125ꢀ127 °C. IR (deposited film): 3250, 3043, 1591, 1442, 1234,
1170 cmꢀ1. 1H NMR (300 MHz, CDCl3 þ DMSO-d6): δ 6.38 (d, J =
2.4 Hz, 1H), 6.44 (dd, J = 2.4, 8.4 Hz, 1H), 7.43 (m, 3H), 7.65 (m, 2H),
9.45 (br s, 1H), 9.86 (br s, 1H). 13C NMR (75 MHz, CDCl3 þ DMSO-
d6): δ 104.2, 107.8, 116.1, 124.3, 126.7, 128.6, 130.1, 144.7, 158.4, 161.5.
EIMS: m/z 234 (67%, Mþ), 218 (9), 186 (100), 157 (32). HRMS-FAB:
m/z [M þ 1]þ calcd for C12H11O3S, 235.0429; found, 235.0428.
4-(p-Tolylsulfinyl)benzene-1,3-diol (22b). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 75ꢀ78 °C.
2-(Phenylsulfinyl)naphthalen-1-ol (19a). It was obtained fol-
lowing the general procedure. The 1-naphthol was added undissolved in
1,2-dichloroethane. The product was purified by flash chromatography
(hexaneꢀdiethyl ether, 5:1), brown solid, mp 81ꢀ83 °C. IR (film):
1
3057 (br), 1627, 1574, 1444, 1397, 1300, 1080 cmꢀ1. H NMR (300
MHz, CDCl3): δ 7.13 (d, J = 8.6 Hz, 1H), 7.35 (d, J = 8.6 Hz, 1H),
7.44ꢀ7.58 (m, 5H), 7.73ꢀ7.77 (m, 3H), 8.29 (app d, J = 7.7 Hz, 1H),
11.5 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 114.5, 119.6, 121.2, 122.4,
125.0, 126.0, 126.3, 127.5, 128.5, 129.5, 131.6, 135.4, 143.9, 157.1. MS
(FABþ): m/z 269 (100%, M þ Hþ), 268 (46%, Mþ), 251 (38). HRMS-
FAB: m/z [M þ 1]þ calcd for C16H13O2S, 269.0636; found, 269.0641.
2,5-Dimethyl-4-(phenylsulfinyl)phenol (20a). The product
was purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
154ꢀ156 °C. IR (KBr): 3092, 1399, 1265, 1004 cmꢀ1. 1H NMR (300
MHz, CDCl3): δ 2.18 (s, 3H), 2.30 (s, 3H), 6.65 (s, 1H), 7.40ꢀ7.47 (m,
4H), 7.52ꢀ7.57 (m, 2H), 9.20 (s, 1H). 13C NMR (75 MHz, CDCl3): δ
15.4, 17.8, 116.7, 123.6, 124.8, 127.8, 128.7, 130.1, 131.3, 135.3, 145.0,
1
IR (KBr): 3159 (br), 1593, 1458, 1247, 1176 cmꢀ1. H NMR (300
MHz, CDCl3 þ DMSO-d6): δ 2.37 (s, 3H), 6.38 (d, J = 2.4 Hz, 1H),
6.42 (dd, J = 2.4, 8.4 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.25ꢀ7.52
(AA0BB0system, 4H), 9.10 (s, 1H), 10.13 (s, 1H). 13C NMR (75 MHz,
CDCl3 þ DMSO-d6): δ 21.2, 105.6, 108.1, 114.4, 124.8, 127.4, 129.9,
141.4 (2C), 160.4, 161.9. EIMS: m/z 248 (59%, Mþ), 232 (28), 200
(100), 91 (18). HRMS-FAB: m/z [M þ 1]þ calcd for C13H13O3S,
249.0585; found, 249.0583.
4-(4-Chlorophenylsulfinyl)benzene-1,3-diol (22c). The pro-
duct was purified by flash chromatography (hexaneꢀEtOAc, 6:4),
1
colorless oil. IR (film): 3163 (br), 1593, 1471, 1176 cmꢀ1. H NMR
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(200 MHz, CDCl3 þ DMSO-d6): δ 6.39 (d, J = 2.4 Hz, 1H), 6.45
(dd, J = 2.4, 8.4 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.42ꢀ7.57
(AA0BB0system, 4H), 9.18 (br s, 1H), 9.86 (s, 1H). 13C NMR (50
MHz, CDCl3 þ DMSO-d6): δ 105.4, 108.4, 114.7, 126.1, 127.4, 129.4,
137.0, 143.0, 159.9, 162.2. EIMS: m/z 268 (45%, Mþ), 252 (58), 220
(100), 157 (50), 112 (34). HRMS-FAB: m/z [M þ 1]þ calcd for
C12H10ClO3S, 269.0030; found, 269.0030.
HRMS-FAB: m/z [M þ 1]þ calcd for C17H22NOS, 288.1422; found,
288.1427.
N,N-Diethyl-4-(isobutylsulfinyl)aniline (26d). The product
was purified by flash chromatography (hexaneꢀEtOAc, 8:2), colorless
oil. IR (film): 3214, 2996, 1594, 1510, 1093, 1032 cmꢀ1. 1H NMR (300
MHz, CDCl3): δ 1.05 (d, J = 6.6 Hz, 3H), 1.10 (d, J = 6.6 Hz, 3H), 1.18
(t, J = 7.2 Hz, 6H), 2.05ꢀ2.20 (m, 1H), 2.45 (dd, J = 8.4, 12.9 Hz, 1H),
2.88 (dd, J = 5.4, 12.9 Hz, 1H), 3.39 (q, J = 7.2 Hz, 4H), 6.72 (half of an
A2X2 system, 2H), 7.47 (half of an A2X2 system, 2H). 13C NMR (75
MHz, CDCl3): δ 12.3, 21.8, 22.7, 24.2, 44.4, 66.9, 111.3, 126.4, 127.8,
149.9. EIMS: m/z 253 (8%, Mþ), 222 (16), 196 (100), 181 (44), 152
(12). HRMS-FAB: m/z [M þ 1]þ calcd for C14H24NOS, 254.1579;
found, 254.1573.
N,N-Diisopropyl-4-(phenylsulfinyl)aniline (27a). The pro-
duct was purified by flash chromatography (hexaneꢀEtOAc, 8:2), mp
109ꢀ112 °C. IR (KBr): 2967, 1589, 1508, 1293, 1034 cmꢀ1. 1H NMR
(300 MHz, CDCl3): δ 1.25 (d, J = 6.9 Hz, 6H), 1.26 (d, J = 6.9 Hz, 6H),
3.87 (sp, J = 6.9 Hz, 1H), 6.77ꢀ6.83 (half of an A2X2 system, 2H),
7.36ꢀ7.48 (m, 5H), 7.59ꢀ7.64 (half of an A2X2 system, 2H). 13C NMR
(75 MHz, CDCl3): δ 20.8, 21.1, 47.4, 115.4, 124.6, 127.4, 128.9, 130.1,
130.4, 146.0, 150.7. EIMS: m/z 301 (52%, Mþ), 286 (100), 244 (75),
119 (28). HRMS-FAB: m/z [M þ 1]þ calcd for C18H24NOS, 302.1579;
found, 302.1570.
2-Methyl-4-(phenylsulfinyl)benzene-1,3-diol (23a). The
product was purified by flash chromatography (hexaneꢀEtOAc, 7:3),
mp 128ꢀ129 °C. IR (deposited film): 3150, 2923, 1593, 1304,
1179 cmꢀ1. 1H NMR (300 MHz, CDCl3): δ 2.03 (s, 3H), 6.48 (d, J =
8.5 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 7.45 (m, 3H), 7.60 (m, 2H), 8.87
(br s, 1H), 10.12 (br s, 1H). 13C NMR (75 MHz, CDCl3): δ 7.5, 107.2,
113.2, 114.4, 124.2, 124.5, 129.1, 130.7, 144.1, 158.5, 159.9. EIMS: m/z
248 (84%, Mþ), 232 (26), 200 (100), 171 (43). HRMS-FAB: m/z
[M þ 1]þ calcd for C13H13O3S, 249.0585; found, 249.0587.
2-Methyl-4-(p-tolylsulfinyl)benzene-1,3-diol (23b). The
product was purified by flash chromatography (hexaneꢀEtOAc, 7:3),
1
mp 160ꢀ163 °C (dec). IR (KBr): 3321, 1604, 1430, 1081 cmꢀ1. H
NMR (300 MHz, CDCl3 þ DMSO-d6): δ 2.03 (s, 3H), 2.37 (s, 3H),
6.46 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 7.26ꢀ7.49
(AA0BB0system, 4H), 8.87 (s, 1H), 10.26 (s, 1H). 13C NMR (75
MHz, CDCl3 þ DMSO-d6): δ 7.5, 21.1, 107.1, 113.3, 114.4, 124.0,
124.6, 129.8, 141.2 (2C), 158.6, 159.7. EIMS: m/z 262 (70%, Mþ), 246
(15), 214 (100), 91 (12). HRMS-FAB: m/z [M þ 1]þ calcd for
C14H15O3S, 263.0742; found, 263.0747.
N,N-Diisopropyl-4-(p-tolylsulfinyl)aniline (27b). The pro-
duct was purified by flash chromatography (hexaneꢀEtOAc, 7:3), mp
1
95ꢀ97 °C. IR (KBr): 2972, 1589, 1505, 1292, 1039 cmꢀ1. H NMR
(200 MHz, CDCl3): δ 1.25 (d, J = 6.8 Hz, 6H), 1.26 (d, J = 7.0 Hz, 6H),
2.37 (s, 3H), 3.87 (sp, J = 6.8 Hz, 2H), 6.79 (half of an A2X2 system, 2H),
7.25ꢀ7.51 (AA0BB0 system, 4H), 7.38 (half of an A2X2 system, 2H). 13C
NMR (75 MHz, CDCl3): δ 20.7, 21.0, 21.3, 47.3, 115.3, 124.6, 127.2,
129.6, 130.5, 140.5, 142.7, 150.6. EIMS: m/z 315 (38%, Mþ), 300 (100),
258 (61), 119 (23). HRMS-FAB: m/z [M þ 1]þ calcd for C19H26NOS,
316.1735; found, 316.1728.
4-(4-Chlorophenylsulfinyl)-2-methylbenzene-1,3-diol (23c).
The product was purified by flash chromatography (hexaneꢀEtOAc, 8:2),
1
yellow oil. IR (film): 3191, 1600, 1472, 1308, 1080 cmꢀ1. H NMR
(200 MHz, CDCl3): δ 2.05 (s, 3H), 5.99 (br s, 1H), 6.43 (d, J = 8.4 Hz,
1H), 7.02 (d, J = 8.4 Hz, 1H), 7.44ꢀ7.54 (AA0BB0system, 4H), 10.08
(s, 1H). 13C NMR (50 MHz, CDCl3): δ 7.4, 107.2, 114.0, 114.4, 124.5,
126.0, 129.6, 137.4, 142.2 (2C), 158.7. EIMS: m/z 282 (58%, Mþ), 266
(29), 234 (100), 171 (47), 83 (21). HRMS-FAB: m/z [M þ 1]þ calcd for
C13H12ClO3S, 283.0196; found, 283.0196.
N-Methyl-4-(phenylsulfinyl)aniline (28a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 121ꢀ
122 °C. IR (KBr): 3339, 1600, 1526, 1087, 1020 cmꢀ1 1H NMR
.
2-Methyl-N-phenylpropane-1-sulfinamide (24d). It was ob-
tained following the general procedure with 36 h of reaction time. The
product was purified by flash chromatography (hexaneꢀEtOAc, 8:2),
mp 52ꢀ54 °C. IR (KBr): 3417, 3158, 2961, 1600, 1495, 1041 cmꢀ1. 1H
NMR (200 MHz, CDCl3): δ 1.03 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.8 Hz,
3H), 2.15 (m, 1H), 2.83 (dd, J = 8.0, 12.8 Hz, 1H), 2.94 (dd, J = 6.4, 13.0
Hz, 1H), 6.96ꢀ7.08 (m, 3H), 7.19ꢀ7.29 (m, 2H). 13C NMR (50 MHz,
CDCl3): δ 21.8, 22.3, 24.6, 64.7, 118.3, 123.0, 129.4, 141.3. EIMS: m/z
197 (42%, Mþ), 141 (60), 140 (68), 93 (100), 92 (67), 57 (52). HRMS-
FAB: m/z [M þ 1]þ calcd for C10H16NOS, 198.0953; found, 198.0945.
N,N-Diethyl-4-(phenylsulfinyl)aniline (26a). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 161ꢀ
1H NMR (300 MHz, CDCl3): δ 1.14 (t, J = 7.1 Hz, 6H), 3.36 (q, J = 7.1
Hz, 4H), 6.60ꢀ6.66 (half of an A2X2 system, 2H), 7.38ꢀ7.47 (m, 5H),
7.58ꢀ7.63 (half of an A2X2 system, 2H). 13C NMR (75 MHz, CDCl3):
δ 12.4, 44.4, 111.3, 124.6, 128.2, 128.9, 129.6, 130.1, 146.1, 150.1. EIMS:
m/z 273 (71%, Mþ), 258 (35), 225 (59), 210 (74), 196 (100), 181 (50),
133 (28). HRMS-FAB: m/z [M þ 1]þ calcd for C16H20NOS, 274.1266;
found, 274.1258.
(300 MHz, CDCl3): δ 2.83 (s, 3H), 4.09 (br s, 1H), 6.57 (half of an A2X2
system, 2H), 7.38ꢀ7.48 (m, 5H), 7.59 (half of an A2X2 system, 2H).
13C NMR (75 MHz, CDCl3): δ 30.2, 112.3, 124.6, 127.9, 128.9, 130.2,
131.9, 146.2, 151.9. EIMS: m/z 231 (35%, Mþ), 215 (9), 183 (100), 154
(89), 122 (37). HRMS-FAB: m/z [Mþ] calcd for C13H13NOS,
231.0718; found, 231.0719.
N-Methyl-4-(p-tolylsulfinyl)aniline (28b). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
148ꢀ150 °C (dec). IR (KBr): 3324, 1607, 1088, 1010 cmꢀ1
.
1H
NMR (200 MHz, CDCl3): δ 2.36 (s, 3H), 2.82 (s, 3H), 4.18 (br s,
1H), 6.57 (half of an A2X2 system, 2H), 7.24ꢀ7.47 (AA0BB0 system,
4H), 7.41 (half of an A2X2 system, 2H). 13C NMR (50 MHz, CDCl3): δ
21.3, 30.2, 112.2, 124.6, 127.8, 129.6, 131.9, 140.6, 142.9, 151.8. EIMS:
m/z 245 (25%, Mþ), 197 (100), 154 (52), 122 (27).
164 °C. IR (deposited film): 3058, 2972, 1591, 1509, 1272, 1097 cmꢀ1
.
4-(4-Chlorophenylsulfinyl)-N-methylaniline (28c). The pro-
duct was purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
145ꢀ147 °C (dec). IR (KBr): 3312, 1607, 1086, 1015 cmꢀ1. 1H NMR
(200 MHz, CDCl3): δ 2.84 (s, 3H), 4.22 (br s, 1H), 6.57 (half of an A2X2
system, 2H), 7.38ꢀ7.42 (AA0BB0system, 4H), 7.52 (half of an A2X2
system, 2H). 13C NMR (50 MHz, CDCl3): δ 30.1, 112.2, 125.9, 128.0,
129.2, 131.2, 136.4, 144.7, 152.1. EIMS: m/z 265 (30%, Mþ), 217 (100),
154 (95), 122 (31). HRMS-FAB: m/z [Mþ] calcd for C13H13ClNOS,
266.0406; found, 266.0403.
N,N-Diethyl-4-(p-tolylsulfinyl)aniline (26b). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 80ꢀ83 °C.
1
IR (KBr): 2968, 1589, 1509, 1089, 1039 cmꢀ1. H NMR (200 MHz,
CDCl3): δ 1.14 (t, J = 7.0 Hz, 6H), 2.37 (s, 3H), 3.35 (q, J = 7.0 Hz, 4H),
6.62 (half of an A2X2 system, 2H), 7.24ꢀ7.50 (AA0BB0system, 4H), 7.41
(half of an A2X2 system, 2H). 13C NMR (50 MHz, CDCl3): δ 12.3, 21.3,
44.4, 111.2, 124.6, 128.0, 129.6 (2C), 140.4, 142.9, 149.9. EIMS: m/z
287 (72%, Mþ), 272 (30), 239 (68), 224 (100), 196 (91), 181 (33).
N-Ethyl-4-(phenylsulfinyl)aniline (29a). The product was pur-
ified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 80ꢀ82 °C. IR
(KBr): 3304, 1598, 1524, 1086, 1025 cmꢀ1 1H NMR (300 MHz,
.
CDCl3): δ 1.23 (t, J = 7.1 Hz, 3H), 3.14 (q, J = 7.1 Hz, 2H), 6.56 (half of
an A2X2 system, 2H), 7.36ꢀ7.47 (m, 5H), 7.59 (half of an A2X2 system,
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dx.doi.org/10.1021/jo2006335 |J. Org. Chem. 2011, 76, 4635–4644

The Journal of Organic Chemistry
ARTICLE
2H). 13C NMR (75 MHz, CDCl3): δ 14.5, 37.9, 112.4, 124.6, 128.0,
128.9, 130.2, 131.6, 146.0, 151.0. EIMS: m/z 245 (54%, Mþ), 229 (8),
197 (88), 182 (54), 168 (100), 153 (28), 136 (29). HRMS-FAB: m/z
[M þ 1]þ calcd for C14H16NOS, 246.0953; found, 246.0947.
(4) Sch€oberl, A.; Wagner, A. In Houben-Weyl, 4th ed.; M€uller, E., Ed.;
Thieme: Stuttgart, 1955; Vol. IX, p 217.
(5) Douglas, J. B.; Farah, B. S. J. Org. Chem. 1958, 23, 805.
(6) Replogle, L. L.; Maynard, J. R. J. Org. Chem. 1967, 32, 1909.
(7) Olah, G. A.; Nishimura, J. J. Org. Chem. 1974, 39, 1203.
(8) Chasar, D. W.; Pratt, T. M. Phosphorus Sulfur 1978, 5, 35.
(9) Olah, G. A.; Nishimura, J. J. Am. Chem. Soc. 1974, 96, 2214.
(10) García Ruano, J. L.; Parra, A.; Yuste, F.; Mastranzo, V. M.
Synthesis 2008, 311.
N-Isopropyl-4-(phenylsulfinyl)aniline (30a). The product
was purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp
76ꢀ78 °C. IR (deposited film): 3314, 1597, 1522, 1089, 1029 cmꢀ1
.
1H NMR (300 MHz, CDCl3): δ 1.19 (d, J = 6.3 Hz, 6H), 3.61 (sp, J = 6.3
Hz, 1H), 3.95 (br s, 1H), 6.53 (half of an A2X2 system, 2H), 7.36ꢀ7.47
(m, 5H), 7.59 (half of an A2X2 system, 2H). 13C NMR (75 MHz,
CDCl3): δ 22.7, 43.9, 112.8, 124.6, 128.1, 128.9, 130.1, 131.3, 146.1,
150.2. EIMS: m/z 259 (60%, Mþ), 211 (90), 196 (81), 182 (100), 167
(18), 140 (41), 119 (23). HRMS-FAB: m/z [M þ 1]þ calcd for
C15H18NOS, 260.1109; found, 260.1103.
(11) García Ruano, J. L.; Parra, A.; Aleman, J. Green Chem. 2008,
10, 706.
(12) Brownbridge, P.; Jowett, I. C. Synthesis 1987, 252.
(13) Jung, M. E.; Lazarova, T. I. Tetrahedron Lett. 1996, 37, 7.
(14) In this regard, one of the referees suggested we studied the
behavior of the O-methyl derivative of 6a under conditions similar to
those used in entry 1 of Table 1. This suggestion is based on the
possibility that the p-substituted product 2a, exclusively formed in the
reaction of anisole, was formed by rearrangement of the kinetically
formed o-product, thermodynamically much less stable than 2a [in such
a case, the lack of reaction of p-methylanisole (entry 2, Table 1) could be
explained from the low thermodynamic stability of the o-product]. We
synthesized the O-methyl derivative of 6a (reaction with MeI in basic
media), but it remained unaltered for 48 h under the indicated reaction
conditions. It proves that 2-fenylsulfinyl anisole is not the intermediate
in the formation of 2a.
N-Isopropyl-4-(p-tolylsulfinyl)aniline (30b). The product was
purified by flash chromatography (hexaneꢀEtOAc, 6:4), mp 78ꢀ80 °C.
IR (KBr): 3277, 1593, 1084, 1021 cmꢀ1. 1H NMR (200 MHz, CDCl3):
δ 1.19 (d, J = 6.2 Hz, 6H), 2.37 (s, 3H), 3.62 (sp, J = 6.2 Hz, 1H), 3.94 (br s,
1H), 6.54 (half of an A2X2 system, 2H), 7.24ꢀ7.48 (AA0BB0 system,
4H), 7.38 (half of an A2X2 system, 2H). 13C NMR (50 MHz, CDCl3): δ
21.3, 22.7, 43.9, 112.8, 124.6, 128.0, 129.6, 131.5, 140.6, 142.8, 150.0.
EIMS: m/z 273 (50%, Mþ), 225 (88), 210 (100), 182 (72), 140 (28),
119 (18), 97 (45), 83 (60). HRMS-FAB: m/z [M þ 1]þ calcd for
C16H20NOS, 274.1266; found, 274.1263.
(15) Furukawa, N.; Ogawa, S.; Matsumura, K.; Fujihara, H. J. Org.
Chem. 1991, 56, 6341.
(16) Amstutz, E. D.; Hunsberger, I. M.; Chessick, J. J. J. Am. Chem.
Soc. 1951, 73, 1220.
(17) Bell, K. H.; McCaffery, L. F. Aust. J. Chem. 1994, 47, 1925.
(18) Serreqi, A. N.; Kazlauskas, R. J. Can. J. Chem. 1995, 73, 1357.
(19) Pennington, R. L.; Sha, X.; King, S. B. Bioorg. Med. Chem. Lett.
2005, 15, 2331.
’ ASSOCIATED CONTENT
S
Supporting Information. Proton and carbon NMR spec-
b
tra for all new compounds prepared. This material is available
free of charge via the Internet at http://pubs.acs.org.
(20) Uchino, M.; Suzuki, K.; Sekiya, M. Chem. Pharm. Bull. 1979, 27,
1199.
(21) Oae, S.; Yamada, O.; Maeda, T. Bull. Chem. Soc. Jpn. 1974,
47, 166.
(22) (a) Melzig, L.; Rauhut, C. B.; Knochel, P. Synthesis 2009, 1041.
(b) Rauhut, C. B.; Melzig, L.; Knochel, P. Org. Lett. 2008, 10, 3891.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: yustef@unam.mx; joseluis.garcia.ruano@uam.es.
’ ACKNOWLEDGMENT
Financial support of this work by the Ministerio de Ciencia y
Tecnología (CTQ2009-12168), UAM-Comunidad de Madrid,
and Comunidad de Madrid (AVANCAT, S-2009-PPQ-1634) is
gratefully acknowledged. We thank M. I. Chꢀavez, E. García-Ríos,
E. Huerta, R. Pati~no, M. A. Pen~a, J. Pꢀerez, B. Quiroz, H. Ríos,
L. Velasco, and M. N. Zavala for their technical assistance. A.H.L.
thanks DGAPA (UNAM) for a postdoctoral fellowship. We also
thank Dr. J. M. Muchowski for the critical reviewing of the
manuscript.
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