Solvent-dependent reactions for the synthesis of β-keto-benzo-δ- sultone scaffolds via DBU-catalyzed o-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences

Article abstract of DOI:10.1021/jo201506d

We have developed a solvent-dependent method for the synthesis of novel benzo-δ-sultone scaffolds. A variety of benzylbenzo[e][1,2]oxathiin-4(3H)- one-2,2-dioxides were obtained in high yields in DMF using a one-pot, DBU-catalyzed condensation of 2-hydroxybenzaldehydes with a number of (E)-2-phenylethenesulfonyl chlorides. On the other hand, the initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonate derivatives underwent DBU-catalyzed reactions to a series of 3-[methoxy-(phenyl)methyl]benzo[e][1,2]oxathiine-2,2- dioxides in moderate to good yields in MeOH. These reactions presumably proceed via DBU-catalyzed O-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences, respectively (Figure presented).

Full text of DOI:10.1021/jo201506d

Article
pubs.acs.org/joc
Solvent-Dependent Reactions for the Synthesis of β-Keto-Benzo-δ-
Sultone Scaffolds via DBU-Catalyzed O-Sulfonylation/Intramolecular
Baylis−Hillman/1,3-H Shift or Dehydration Tandem Sequences
Mehdi Ghandi,* Abolfazl Hasani Bozcheloei, Seyed Hadi Nazari, and Masoud Sadeghzadeh
School of Chemistry, College of Science, University of Tehran, P.O. Box 14155 6455, Tehran, Iran
S
* Supporting Information
ABSTRACT: We have developed a solvent-dependent method
for the synthesis of novel benzo-δ-sultone scaffolds. A variety of
benzylbenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxides were ob-
tained in high yields in DMF using a one-pot, DBU-catalyzed
condensation of 2-hydroxybenzaldehydes with a number of (E)-2-
phenylethenesulfonyl chlorides. On the other hand, the initially
prepared 2-formylphenyl-(E)-2-phenylethenesulfonate derivatives
underwent DBU-catalyzed reactions to a series of 3-[methoxy-
(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-dioxides in moderate
to good yields in MeOH. These reactions presumably proceed
via DBU-catalyzed O-sulfonylation/intramolecular Baylis−Hillman/
1,3-H shift or dehydration tandem sequences, respectively.
γ-sultones were found to show dual behavior with soft or hard
nucleophiles.20
INTRODUCTION
■
A base-catalyzed reaction of carbon electrophiles with the
activated alkenes (alkynes) or electron-deficient Michael-accepting
components, known as Baylis−Hillman (BH) reaction, is an
efficient process going cleanly under very mild conditions,
affording a highly functionalized adduct.1 Considerable progress
has been achieved in developing effective catalysts such as DBU,2
DABCO,3 DMAP,4 PR3,5 Et3N,6 quinuclidine,7 and imidazole.8
The BH reaction was discovered in 1972.9 Recent attention has
been focused on the intramolecular versions of the BH reaction.10
Such reactions in principle can provide carbocyclic or heterocyclic
compounds in different ring sizes with functionality.11
Recently reported discovery of a new family of non-nucleoside
anti-HCMV and anti-VZV agents based upon the β-keto-γ-sultone
template21 prompted us to explore the synthesis of β-keto-δ-
sultone template as the structurally related analogue. To achieve
this goal, we initially prepared the bifunctional 2-formylphenyl-
(E)-2-phenylethenesulfonates (3a) (Scheme 1a). We then
Scheme 1. (1a) Proposed Procedure for the Synthesis of
β-Keto-δ-sultone, (1b) Direct Transformation of 3a into 4a
The internal esters of hydroxy sulfonic acids or sulfur
analogues of lactones, which are called sultones, constitute a
class of heterocyclic compounds whose chemistry continues to
be of interest.12 The biological activities of sultones consist of
skin sensitization13 and antiviral activities.14 Sultones are
considered as sulfoalkylating agents due to their easy reaction
with a variety of nucleophiles for the synthesis of alkylsulfonic
acids.15 Traditionally, sultone synthesis has relied on classical
cyclization protocols such as elimination reaction of the
corresponding hydroxy sulfonic acid derivatives,16 treatment
of diazotized amino sulfonic acids and esters with powdered
copper,17 and intramolecular Diels−Alder reaction of vinyl-
sulfonic acid esters.18 A number of transition-metal-catalyzed
processes and indirect methods to sultones have also recently
been reported.19 Sultones are known as valuable heterocyclic inter-
mediates that offer novel possibilities for stereoselective trans-
formations. For example, δ-sultones obtained via rhodium-
catalyzed reaction of sulfonate ester derivatives have undergone
reductive and oxidative reactions that make possible excision of the
−SO3− moiety.19a On the other hand, the β-iodo-α,β-unsaturated
examined the possibility of doing intramolecular BH reaction on
3a to obtain the corresponding BH adduct as the precursor for the
preparation of the desired β-keto-δ-sultone (4a). The preliminary
results of our investigation showed that 4a has remarkably been
generated after subjecting 3a to the BH conditions (Scheme 1b).
Details of the serendipitous formation of β-keto-benzo-δ-sultones
via an one-pot reaction is described in this presentation.
Received: July 31, 2011
Published: November 5, 2011
© 2011 American Chemical Society
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2-formylphenyl-(E)-2- phenylethenesulfonate 3a in the initial
reaction is confirmed.
This new method was applied to a range of substrates
with different substitution patterns of the aromatic rings
(Scheme 3, Table 2). The structures of 4a−n were deduced by
RESULTS AND DISCUSSION
■
Vinyl sulfonate 3a, prepared via condensation of aldehyde 1a
with (E)-2-phenylethenesulfonyl chloride (2a)22 (vide infra),
served for our early exploration of intramolecular BH chemistry
(Scheme 2, Table 1). Compared to other solvents that afford
Scheme 3. Product 4a−o Obtained via DBU-Catalyzed
Reaction of 1a−e with 2a−d
Scheme 2. Product 4a Obtained via DBU-Catalyzed BH
Reaction of 3a
Table 1. Effect of Solvent on the Formation of 4a
Table 2. Results Obtained for the Formation of 4a−o
a
entry
solvent (mL)
time (h)
yield (%)
a
entry
R1
R2
time (min)
product
yield (%)
1
2
H2O (10)
120
120
120
120
120
120
120
6
10
20
35
15
11
11
42
45
65
89
89
1
2
H
H
360
660
1080
300
210
210
220
100
140
20
4a
4b
4c
4d
4e
4f
89
90
88
88
85
85
87
84
85
84
83
87
89
88
PhCH3 (10)
MeCN (10)
CH2Cl2 (10)
1,4-dioxane (10)
Et2O (10)
6-OMe
5-OMe
4-Br
H
3
3
H
4
4
H
5
5
H
4-Me
4-Me
4-Me
4-Br
4-Br
4-Br
4-Cl
4-Cl
4-Cl
H
6
6
6-OMe
4-Br
7
DMF (10)
7
4g
4h
4i
8
DMF (3)
b
8
H
9
DMF (3)
6
b
9
6-OMe
4-Br
10
11
DMF (3)
48
c
10
11
12
13
14
15
4j
DMF (3)
6
a
b
c
H
150
180
40
4k
4l
Isolated yields. 100 mol % of DBU was used. 200 mol % of DBU
6-OMe
4-Br
was used.
4m
4n
4o
4-Cl
300
300
the cyclic adduct 4a in 10−35% yields within 120 h (entries 1−
6, Table 1), 4a was obtained in 40% yield in DMF, upon
addition of DBU (50 mol %) (entry 7, Table 1). Changing the
amount of solvent from 10 to 3 mL drastically reduced the
reaction time to 6 h (entry 8, Table 1). Increasing the DBU
amount from 50 to 100 mol % was found to increase the yield
of 4a to 65% (entry 9, Table 1). It was discovered that reaction
proceeds to completion within 48 h, affording 4a in 89% yield
(entry 10, Table 1). An excess of DBU was found to have no
effect on the increasing yield of 4a, although reaction time was
decreased to 6 h (entry 11, Table 1). It has recently been
reported that the BH reaction is second order in aldeyde.23
Therefore, the effect of decreasing amount of solvent on rate
enhancement is rationalized. Although the BH reactions have
been found to be efficient by stoichiometric amount of base,23
rate enhancement upon addition of 200 mol % of DBU may be
interpreted perhaps by shifting away from the activated alkene
toward the corresponding sulfonate anion as the initial
equilibrium is established (see Scheme 4). That the reaction
proceeds efficiently in DMF may be due to unique solvation of
the polar transition state in this solvent.
Utilization of DABCO, imidazole, 1,2,4-triazole, triethyl-
amine, DMAP, and a tertiary phosphine such as Ph3P, which
are commonly employed in the traditional BH coupling, was
ineffective at promoting cyclization of sulfonate 3a. Therefore,
DBU was used as the efficient base in the next steps.
Our later studies revealed that 4a could be prepared if
aldehyde 1a and (E)-phenylethenesulfonyl chloride (2a) were
reacted with DBU (300 mol %) in a one-pot reaction in
DMF at room temperature. Therefore, the implication of
4-NO2
H
a
Isolated yield.
1
elemental analysis, MS, IR, H NMR, and 13C NMR spectro-
1
scopy. For example, part of the H NMR spectrum of, for
example, 4a exhibited two doublet of doublets at δ 3.56 (1H,
J = 14.7, 5.6 Hz) and 3.62 (1H, J = 14.7, 7.0 Hz) due to Ph−
CH2 and one doublet of doublets at δ 4.54 (1H, J = 6.8, 5.8
1
Hz) for CHCO groups, respectively. The H-decoupled 13C
NMR spectrum of 4a showed 13 distinct signals, including a
characteristic signal at δ 185.3 due to CO group, in agreement
with the proposed structure.
The proposed mechanism for the DBU-catalyzed intra-
molecular BH reaction is illustrated in Scheme 4. The in situ
generated 3a from condensation of 1a with 2a undergoes the
nucleophilic addition of the DBU at the β position to form the
sulfonate anion I. Subsequent addition of DBU-associated
sulfonate anion I to the aldehyde group affords the
intermediate II. The generated alcohol III in the next step is
transformed into ketone 4a perhaps by a DBU-catalyzed 1,3-H
shift. The rate-determining step (RDS) of the Baylis−Hillman
reaction involves an aldol-type reaction between the zwitter-
ionic enolate and an aldehyde (Scheme 4).24 The stabilization
of the intermediate β-ammonium enolate through conjugation
seems to be a more likely explanation for the origin of the
increased reactivity of DBU (Figure 1).25 The higher basicity of
DBU as a sterically hindred base with lower pKa26 in com-
parison to DABCO,26 imidazole,27 1,2,4-triazole,28 triethyl-
amine,27 DMAP,29 and Ph3P27 may not also be overlooked.
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Surprisingly, when reaction of 3a was carried out in MeOH,
3-[methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-diox-
ides (5a) was identified as the sole product (Scheme 5). To our
Scheme 4. Suggested Mechanism for the Formation of 4a
Scheme 5. DBU-Catalyzed Reaction of 3a to 5a in MeOH
delight, reaction of 3a either with MeOH/K2CO3 or MeOH/
NaOMe solutions also afforded product 5a. To further explore
the scope of this reaction, vinyl sulfonates 3b−l were prepared
and subjected to DBU-catalyzed BH reaction in MeOH
(Scheme 6, Table 3). As seen, a range of electron-donating
Scheme 6. Results Obtained for the Formation of 5a−l
Figure 1. Stabilization of the β-ammonium enolate through
conjugation.
Therefore, in this specific case, the basicity of DBU is more
important than its steric hindrance.
Table 3. Results Obtained for the Formation of 3a−l and
5a−l
The results indicated in Table 2 support the suggested
mechanism. The increasing equilibrium concentration of
enolate I, as well as the cyclization rate of I to II, is expected
to increase by electron-withdrawing substituents present at
either phenyl rings. Notably, either unsubstituted aldehydes or
phenylethenesulfonyl chlorides and those bearing electron-
withdrawing halides on the aromatic rings readily afford the
corresponding benzo-δ-sultone (entries 1, 4, 8, 11, and 14). In
the case of 4j and 4m, in which both components bearing
electron-withdrawing halides, reactions are surprisingly fast
(entries 10 and 13). The aldehyde 4c bearing a strong electron-
donating substituent at the para-position proceeds more
sluggishly (entry 3). In addition, benzo-δ-sultones have been
formed from reaction of meta-electron-donating substituted
aldehydes with unsubstituted or para-electron-donating sub-
stituted (E)-2-phenylethenesulfonyl chlorides in moderate
times (entries 2, 5, and 6). Finally, no reaction progress was
observed with 2-hydroxy-5-nitrobenzaldehyde (1f) (entry 15).
To explore further insight into this reaction, we initially
prepared the 2-formyl-4-nitrophenyl (E)-2-phenylethenesulfo-
nate (3l) (vide infra). When subjected to BH conditions, 3l
failed to show any progress toward the formation of the desired
product. Instead, a salt-like product with no movement on the
TLC plate was found to have been formed. Consumption of
the starting aldehyde 3l along with the formation of a salt
product are telltales that 3l has been engaged in an unwanted
reaction. Although there are several reports in literature on the
base-catalyzed BH reaction of nitrophenylaldehydes with
different Michael acceptors,30 the inability of 1f to show similar
BH reactivity remains to be resolved. Further investigation on
this subject is currently underway in our laboratory.
vinyl
yield
(%)
time
yield
a
entry
R1
R2
sulfonate
(h) product (%)
1
2
H
H
3a
3b
3c
3d
3e
3f
96
95
96
97
96
95
95
94
95
96
95
95
24
36
28
58
72
12
30
24
22
48
72
72
5a
5b
5c
5d
5e
5f
53
48
55
40
36
65
56
54
60
54
44
15
6-OMe
4-Br
H
H
3
H
4
4-Me
4-Me
4-Br
4-Br
4-Br
4-Cl
4-Cl
4-Cl
H
5
4-Br
H
6
7
6-OMe
4-Br
H
3g
3h
3i
5g
5h
5i
8
9
10
11
12
6-OMe
4-Br
4-NO2
3j
5j
3k
3l
5k
5l
a
Isolated yield.
or electron-withdrawing substituents in either phenyl rings are
tolerated. The structures of 5a−l were deduced by elemental
analysis, MS, IR, H NMR, and 13C NMR spectroscopy. For
1
1
example, part of the H NMR spectrum of, for example, 5a
exhibited two singlets at δ 5.39 (1H), and 3.49 (3H) due to
PhCH and MeO groups, respectively. The H-decoupled 13C
1
NMR spectrum of 5a showed 14 distinct signals, in agreement
with the proposed structure.
The suggested mechanism for the formation of 5a is shown
in Scheme 7a. The in situ generated MeO− via acid−base
reaction with DBU promotes the intramolecular BH reaction,
affording intermediates I and II. The latter is easily transformed
into 5a through dehydration rather than the traditional reaction
to BH adduct. The pseudoaromatic character, if any, of 5a may
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acetone (30 mL). The mixture was stirred for 4 h at rt. The solvent
was evaporated under reduce pressure and the residue poured into the
water (30 mL). The mixture was extracted with CH2Cl2 (30 mL) and
the organic phase dried over Na2SO4. The solvent was then evaporated
under reduced pressure, and the crude product was recrystallized from
C2H5OH to afford 3a.
be the driving force for this process. This mechanism was
proposed on the basis of the previously reported work by
Ciganek, who showed that NaOMe in THF could mediate the
coupling of methyl acrylate with aromatic aldehydes.31 The
reactions produced α-methoxymethylcinnamic acids (after
hydrolysis) with moderate yields via Baylis−Hillman-type reac-
tions (Scheme 7b).
2-Formylphenyl-(E)-2-phenylethenesulfonate (3a): White solid
(1380 mg, 96%); mp 59−62 °C; IR (KBr) νmax 3059, 2885, 1690
1
(CO); 1604, 1361 (−SO2), 1147 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 10.37 (1H, s, CHO), 7.96 (1H, d, J = 7.6 Hz, Ar),
7.66 (1H, t, J = 7.62 Hz, Ar), 7.63 (1H, d, J = 15.5 Hz, CCHAr),
7.53−7.44 (7H, m, Ar), 7.00 (1H, d, J = 15.5 Hz, SO2CHC) ppm;
13C NMR (125 MHz, CDCl3) δ 188.3 (CO), 151.1, 147.8, 135.9,
132.6, 130.0, 129.8, 129.7, 129.6, 129.2, 128.1, 124.2, 120.3 (C−Ar)
ppm; m/z (EI, 70 eV) 287 (10, M+ − 1), 167 (88), 120 (25), 103
(100), 77 (36%). Anal. Calcd for C15H12O4S: C, 62.32; H, 4.12.
Found: C, 62.49; H, 4.20%.
Scheme 7. (a) Suggested Mechanism for the Formation of 5a
in MeOH, (b) Previously Suggested Mechanism of MeO−-
Mediated Coupling of Methyl Acrylate with an Aldehyde
2-Formyl-6-methoxyphenyl-(E)-2-phenylethenesulfonate (3b): White
solid (1510 mg, 95%); mp 96−98 °C; IR (KBr) νmax 3065, 2898, 1690
1
(CO), 1614, 1576, 1362 (−SO2), 1144 (−SO2) cm−1; H NMR
(500 MHz, CDCl3) δ 10.41 (1H, s, CHO), 7.55 (1H, d, J = 15.6 Hz,
CCHAr), 7.56−7.45 (6H, m, Ar), 7.37 (1H, t, J = 7.9 Hz, Ar), 7.21
(1H, d, J = 8.2 Hz, Ar), 7.07 (1H, d, J = 15.6 Hz, SO2CHC), 3.82
(3H, s, MeO) ppm; 13C NMR (125 MHz, CDCl3) δ 188.7 (CO),
152.0, 146.0, 140.8, 132.2, 131.8, 129.9, 129.7, 128.1, 128.4, 121.6,
120.4, 118.6 (C−Ar), 56.9 (OCH3) ppm; m/z (EI, 70 eV) 301 (1, M+ − 1),
167 (83), 151 (53), 103 (100), 77 (42%). Anal. Calcd for C16H14O5S: C,
60.29; H, 4.38. Found: C, 60.37; H, 4.43%.
2-Formyl-4-bromophenyl-(E)-2-phenylethenesulfonate (3c): White
solid (1755 mg, 96%); mp 69−70 °C; IR (KBr) νmax 3064, 2877,
1
1693 (CO), 1607, 1380 (−SO2), 1165 (−SO2) cm−1; H NMR
(500 MHz, CDCl3) δ 10.37 (1H, s, CHO), 8.07 (1H, s, Ar), 7.75 (1H,
d, J = 8.7 Hz, Ar), 7.63 (1H, d, J = 15.5 Hz, CCHAr), 7.54−7.46
(5H, m, Ar), 7.33 (1H, d, J = 8.7 Hz, Ar), 6.94 (1H, d, J = 15.5 Hz,
SO2CHC) ppm; 13C NMR (125 MHz, CDCl3) δ 186.9 (CO),
149.9, 148.4, 138.6, 132.8, 132.5, 131.6, 131.0, 129.8, 129.3, 126.0,
121.8, 119.8 (C−Ar) ppm; m/z (EI, 70 eV) 367 (1, M+ + 1), 200 (8),
167 (90), 103 (100), 77 (29%). Anal. Calcd for C15H11BrO4S: C,
49.01; H, 3.00. Found: C, 49.06; H, 3.02%.
(E)-2-Formylphenyl-2-p-tolylethenesulfonate (3d): White solid
(1465 mg, 97%); mp 58−60 °C; %; IR (KBr) νmax 3058, 1690
(CO), 1601, 1346 (−SO2), 1148 (−SO2), 854, 776 cm−1; 1H NMR
(500 MHz, CDCl3) δ 10.38 (1H, s, CHO), 7.94 (1H, dd, J = 7.5, 1.4 Hz,
Ar), 7.66 (1H, dd, J = 7.8, 1.6 Hz, Ar), 7.58 (1H, d, J = 15.4 Hz, C
CHAr), 7.46 (2H, t, J = 8.2 Hz, Ar), 7.41 (2H, d, J = 8.0 Hz, Ar), 7.27
(2H, d, J = 7.9 Hz, Ar), 6.90 (1H, d, J = 15.4 Hz, SO2CHC), 2.43
(3H, s, CH3) ppm; 13C NMR (125 MHz, CDCl3) δ 188.3 (CO),
151.2, 147.9, 143.5, 135.8, 130.5, 130.0, 129.8, 129.3, 129.1, 128.0, 124.2,
118.9 (C−Ar), 22.1 (CH3) ppm; m/z (EI, 70 eV) 301 (22, M+ − 1), 285
(17), 181 (75), 118 (100), 91 (29%). Anal. Calcd for C16H14O4S: C,
63.48; H, 4.51. Found: C, 63.56; H, 4.67%.
Notably, the vinyl sulfonate 3l containing a nitro group meta
to the aldehyde position has proceeded sluggishly to the
corresponding adduct 5l during 72 h (Table 3, entry 12). The
formation of 5l from 3l in MeOH although with low efficiency
is interesting since 3l failed to show any reactivity in DMF
(vide supra).
In conclusion, a number of solvent-dependent BH reactions
were carried out in this work for the synthesis of novel benzo-δ-
sultone scaffolds. Whereas the one-pot, DBU-catalyzed
condensation of 2-hydroxybenzaldehydes with a number of
(E)-2-phenylethenesulfonyl chlorides exhibit 3-benzylbenzo[e]-
[1,2]oxathiin-4(3H)-one, 2,2-dioxides in high yields in DMF,
reactions of the initially prepared 2-formylphenyl-(E)-2-phenyl-
ethenesulfonate derivatives with DBU afford 3-[methoxy-
(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-dioxides in moder-
ate to good yields in MeOH. These new structures broaden the
benzo-δ-scaffolds that are accessible through intramolecular BH
reactions, and many of them may represent interesting pharma-
cophores. To the best of our knowledge, no method of using an
intramolecular BH reaction in the synthesis of β-keto-benzo-δ-
sultone scaffolds via tandem sequences is found in literature.
(E)-4-Bromo-2-formylphenyl-2-p-tolylethenesulfonate (3e): Yel-
low solid (1825 mg, 96%); mp 97−99 °C; IR (KBr) νmax 3070,
1683 (CO), 1599, 1340 (−SO2), 1149 (−SO2), 834, 787 cm−1; 1H
NMR (500 MHz, CDCl3) δ 10.29 (1H, s, CHO), 8.07 (1H, d, J = 2.5
Hz, Ar), 7.75 (1H, dd, J = 8.7, 2.5 Hz, Ar), 7.60 (1H, d, J = 15.4 Hz,
CCHAr), 7.42 (2H, d, J = 8.0 Hz, Ar), 7.33 (1H, d, J = 8.8 Hz, Ar),
7.28 (2H, d, J = 8.1 Hz, Ar), 6.87 (1H, d, J = 15.4 Hz, SO2CHC),
2.44 (3H, s, CH3) ppm; 13C NMR (125 MHz, CDCl3) δ 186.9 (C
O), 150.1, 148.5, 143.8, 138.5, 132.4, 131.1, 130.5, 129.4, 128.9, 126.0,
121.8, 118.4 (C−Ar), 22.1 (CH3) ppm; m/z (EI, 70 eV) 380 (1, M+),
376 (6), 281 (26), 181 (100), 117 (99%). Anal. Calcd for
C16H13BrO4S: C, 50.38; H, 3.40. Found: C, 50.41; H, 3.44%.
(E)-2-Formylphenyl-2-(4-bromophenyl)ethenesulfonate (3f): White
solid (1740 mg, 95%); mp 101−104 °C; IR (KBr) νmax 3054, 2894,
EXPERIMENTAL SECTION
■
General Information. 1H NMR, 13C NMR, NOESY, HMBC,
MS, and elemental analysis were measured with conventional spectro-
meters. All solvents were purified and dried by following standard
procedures unless otherwise stated.
1
1690 (CO), 1676, 1601, 1341 (−SO2), 1161 (−SO2) cm−1; H
NMR (500 MHz, CDCl3) δ 10.35 (1H, s, CHO), 7.97 (1H, t, J = 7.7
Hz, Ar), 7.68 (1H, t, J = 7.8 Hz, Ar), 7.61 (2H, d, J = 8.4 Hz, Ar), 7.55
(1H, d, J = 15.5 Hz, CCHAr), 7.48 (1H, t, J = 7.5 Hz, Ar), 7.45
(1H, d, J = 8.2 Hz, Ar), 7.39 (2H, d, J = 8.4 Hz, Ar), 6.98 (1H, d, J =
Synthesis of 2-Formylphenyl-(E)-2-phenylethenesulfonate
Derivatives 3. General procedure: K2CO3 (0.69 g, 5 mmol) was
added to a solution of 2-hydroxybenzaldehyde (1a) (0.61 g, 5 mmol)
and (E)-2-phenylethenesulfonyl chloride (2a) (1.01 g, 5 mmol) in
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15.5 Hz, SO2CHC) ppm; 13C NMR (125 MHz, CDCl3) δ 188.3
(CO), 150.9, 146.3, 135.9, 133.1, 130.7, 130.5, 130.1, 129.7, 128.2,
127.3, 124.3, 121.1 (C−Ar) ppm; m/z (EI, 70 eV) 369 (2, M+ + 2),
367 (3, M+), 247 (54), 183 (94), 120 (60), 102 (100%). Anal. Calcd
for C15H11BrO4S: C, 48.98; H, 3.03. Found: C, 49.06; H, 3.02%.
(E)-2-Formyl-6-methoxyphenyl-2-(4-bromophenyl)-
ethenesulfonate (3g): White solid (1885 mg, 95%); mp 124−126 °C;
IR (KBr) νmax 3077, 1693 (CO), 1481, 1351 (−SO2), 1142 (−SO2),
1063, 857 cm−1; 1H NMR (500 MHz, CDCl3) δ 10.39 (1H, s, CHO),
7.61 (2H, d, J = 8.3 Hz, Ar), 7.55 (1H, d, J = 7.8 Hz, Ar), 7.48 (1H, d,
J = 15.5 Hz, CCHAr), 7.22 (1H, d, J = 8.2 Hz, Ar), 7.41−7.37 (3H,
m, Ar), 7.07 (1H, d, J = 15.5 Hz, SO2CHC), 3.86 (3H, s, OCH3)
ppm; 13C NMR (125 MHz, CDCl3) δ 188.6 (CO), 152.6, 144.5,
140.6, 133.1, 131.7, 131.1, 130.3, 128.5, 126.8, 122.4, 120.6, 118.7
(C−Ar), 60.0 (OCH3) ppm; m/z (EI, 70 eV) 398 (5, M+ + 2), 396
(6, M+), 247 (71), 181 (72), 151 (100), 102 (85%) . Anal. Calcd for
C16H13BrO5S: C, 49.33; H, 3.27. Found: C, 49.38; H, 3.30%.
(125 MHz, CDCl3) δ 186.1 (CO), 154.7, 149.2, 146.9, 133.2, 131.3,
130.3, 130.1, 129.9, 129.5, 125.4, 125.6, 119.5 (C−Ar) ppm; m/z (EI,
70 eV) 334 (10, M+ + 1), 316 (53), 273 (100), 183 (27), 151 (49%).
Anal. Calcd for C15H11NO6S: C, 54.00; H, 3.29; N, 4.14. Found: C,
54.05; H, 3.33; N, 4.20%.
Synthesis of 3-Benzylbenzo[e][1,2]oxathiin-4(3H)-one-2,2-
dioxide Derivatives 4. General procedure: To a stirring solution
of DBU (0.453 g, 300 mol %) in DMF (3 mL) were added
2-hydroxybenzaldehyde (1a) (0.122 g, 1 mmol) and (E)-2-phenyl-
ethenesulfonyl chloride (2a) (0.202 g, 1 mmol) at room temperature.
The progress of the reaction was followed by TLC. After completion,
CH2Cl2 (20 mL) and H2O (20 mL) were added and the mixture was
neutralized with diluted HCl. The organic phase was separated, and
aqueous phase was extracted with CH2Cl2 (3 × 10 mL). The
combined organic phase was dried over Na2SO4, and the solvent was
removed under reduced pressure. The residue was purified by column
chromatography (SiO2, eluent: 1:2, n-hexane/CH2Cl2) to afford the
ketone 4a.
(E)-4-Bromo-2-formylphenyl-2-(4-bromophenyl)ethenesulfonate
(3h): White solid (2095 mg, 94%); mp 133−135 °C; IR (KBr) νmax
3063, 1691 (CO), 1467, 1371 (−SO2), 1156 (−SO2), 845, 742
cm−1; 1H NMR (500 MHz, CDCl3) δ 10.27 (1H, s, CHO), 8.07 (1H,
d, J = 2.1 Hz, Ar), 7.77 (1H, dd, J = 8.7, 2.1 Hz, Ar), 7.62 (2H, d, J =
8.2 Hz, Ar), 7.58 (1H, d, J = 15.5 Hz, CCHAr), 7.40 (2H, d, J = 8.2
Hz, Ar), 7.33 (1H, d, J = 8.7 Hz, Ar), 6.95 (1H, d, J = 15.5 Hz,
SO2CHC) ppm; 13C NMR (125 MHz, CDCl3) δ 186.8 (CO),
149.7, 146.9, 138.6, 138.2, 132.8, 131.0, 130.6, 130.5, 127.5, 126.0,
122.0, 120.6 (C−Ar) ppm; m/z (EI, 70 eV) 447 (1, M+ + 2), 445 (1,
M+), 247 (90), 183 (84), 102 (100), 63 (28%). Anal. Calcd for
C15H10Br2O4S: C, 40.35; H, 2.18. Found: C, 40.38; H, 2.26%.
(E)-2-Formylphenyl-2-(4-chlorophenyl)ethenesulfonate (3i): Yel-
low solid (1525 mg, 95%); mp 113−116 °C; IR (KBr) νmax 3058,
3-Benzylbenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide (4a): White
solid (256 mg, 89%); mp 106−108 °C; IR (KBr) νmax 1694 (CO),
1
1374 (−SO2); 1146 (−SO2) cm−1; H NMR (500 MHz, CDCl3) δ
8.10 (1H, dd, J = 7.9, 1.6 Hz), 7.73 (1H, ddd, J = 8.3, 7.6, 1.6 Hz, Ar),
7.42 (1H, t, J = 7.6 Hz, Ar), 7.36−7.28 (6H, m, Ar), 4.54 (1H, dd, J =
6.8, 5.8 Hz, CHCO), 3.62 (1H, dd, J = 14.7, 7.0 Hz, Ph−CHH),
3.56 (1H, dd, J = 14.7, 5.6 Hz, Ph−CHH) ppm; 13C NMR (125 MHz,
CDCl3) δ 185.3 (CO), 153.9, 137.7, 135.6, 129.8, 129.7, 129.2,
128.0, 126.9, 120.9, 119.7 (C−Ar), 72.0 (CH), 31.8 (CH2) ppm; m/z
(EI, 70 eV) 288 (2, M+), 224 (100), 207 (11), 147 (53), 91 (38%).
Anal. Calcd for C15H12O4S: C, 62.48; H, 4.00 Found: C, 62.49; H,
4.20%.
3-Benzyl-8-methoxybenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
1
2887, 1691 (CO), 1595, 1350 (−SO2), 1176 (−SO2) cm−1; H
(4b): White solid (286 mg, 90%); mp 112−114 °C; IR (KBr) νmax
1
1681 (CO), 1368 (−SO2); 1150 (−SO2) cm−1; H NMR (500
NMR (500 MHz, CDCl3) δ 10.35 (1H, s, CHO), 7.97 (1H, d, J = 6.7
Hz, Ar), 7.96 (1H, t, J = 6.6 Hz, Ar), 7.57 (1H, d, J = 15.5 Hz, C
CHAr), 7.48−7.44 (6H, m, Ar), 6.96 (1H, d, J = 15.5 Hz, SO2CH
C) ppm; 13C NMR (125 MHz, CDCl3) δ 188.3 (CO), 150.9, 146.3,
138.8, 135.9, 130.4, 130.3, 130.2, 130.1, 129.8, 128.2, 124.3, 120.9 (C−
Ar) ppm; m/z (EI, 70 eV) 324 (1, M+ + 2), 322 (3, M+), 201 (74),
137 (100), 120 (41), 102 (54%). Anal. Calcd for C15H11ClO4S: C,
55.76; H, 3.38. Found: C, 55.82; H, 3.44%.
MHz, CDCl3) δ 8.02 (1H, d, J = 8.8 Hz, Ar), 7.36−7.29 (5H, m, Ar),
6.92 (1H, dd, J = 8.8, 2.0 Hz, Ar), 6.72 (1H, d, J = 2.0 Hz, Ar), 4.49
(1H, t, J = 6.2 Hz, CHCO), 3.92 (3H, s, OCH3), 3.61 (1H, dd, J =
14.7, 6.7 Hz, Ph−CHH), 3.51 (1H, dd, J 14.7, 5.8 Hz, Ph−CHH)
ppm; 13C NMR (125 MHz, CDCl3) δ 183.9 (CO), 167.2, 155.7,
135.8, 131.4, 129.7, 129.2, 127.9, 114.1, 103.9 (C−Ar), 71.5 (CH),
56.7 (OCH3), 31.9 (CH2) ppm; m/z (EI, 70 eV) 318 (0.5, M+), 254
(100), 177 (53), 150 (35), 91 (25%). Anal. Calcd for C16H14O5S: C,
60.40; H, 4.31. Found: C, 60.37; H, 4.43%.
(E)-2-Formyl-6-methoxyphenyl-2-(4-chlorophenyl)-
ethenesulfonate (3j): White solid (1690 mg, 96%); mp 118−120 °C;
IR (KBr) νmax 3071, 1695 (CO), 1372 (−SO2), 1147 (−SO2), 1060,
3-Benzyl-7-methoxybenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
1
854 cm−1; H NMR (500 MHz, CDCl3) δ 10.39 (1H, s, CHO), 7.55
(4c): White solid (280 mg, 88%); mp 91−93 °C; IR (KBr) νmax 1681
1
(CO), 1368 (−SO2); 1150 (−SO2) cm−1; H NMR (500 MHz,
(1H, dd, J = 7.8, 1.4 Hz, Ar), 7.49 (1H, d, J = 15.4 Hz, CCHAr),
7.38 (1H, t, J = 8.1 Hz, Ar), 7.46−7.43 (4H, m, Ar), 7.22 (1H, dd, J =
8.2, 1.4 Hz, Ar), 7.05 (1H, d, J = 15.5 Hz, SO2CHC), 3.86 (3H, s,
OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ 188.6 (CO), 152.6,
144.4, 140.6, 138.4, 131.7, 130.7, 130.2, 130.1, 128.5, 122.3, 120.6,
118.7 (C−Ar), 56.9 (OCH3) ppm; m/z (EI, 70 eV) 354 (1, M+ + 2),
352 (3, M+), 201 (66), 151 (62), 137 (74), 102 (49), 49 (100%). Anal.
Calcd for C16H13ClO5S: C, 54.39; H, 3.52. Found: C, 54.47; H, 3.71%.
(E)-4-Bromo-2-formylphenyl-2-(4-chlorophenyl)ethenesulfonate
(3k). Yellow solid (1905 mg, 95%); mp 118−120 °C; IR (KBr) νmax
3092, 1691 (CO), 1446, 1371 (−SO2), 1156 (−SO2), 832, 742
cm−1; 1H NMR (500 MHz, CDCl3) δ 10.27 (1H, s, CHO), 8.07 (1H,
d, J = 2.5 Hz, Ar), 7.71 (1H, dd, J = 8.7, 2.5 Hz, Ar), 7.59 (1H, d, J =
15.5 Hz, CCHAr), 7.49−7.44 (4H, m, Ar), 7.33 (1H, d, J = 8.7 Hz,
Ar), 6.94 (1H, d, J = 15.5 Hz, SO2CHC) ppm; 13C NMR (125
MHz, CDCl3) δ 186.9 (CO), 149.8, 146.8, 139.1, 138.6, 132.8,
131.0, 130.5, 130.2, 130.1, 126.0, 122.0, 120.5 (C−Ar) ppm; m/z (EI,
70 eV) 401 (2, M+), 201 (100), 137 (89), 102 (48), 63 (21%). Anal.
Calcd for C15H10BrClO4S: C, 44.81; H, 2.36. Found: C, 44.85; H,
2.51%.
CDCl3) δ 8.02 (1H, d, J = 8.8 Hz, Ar), 7.36−7.29 (5H, m, Ar), 6.91
(1H, dd, J = 8.8, 2.0 Hz, Ar), 6.72 (1H, d, J = 2.0 Hz, Ar), 4.48 (1H, t,
J = 6.3 Hz, CHCO), 3.92 (3H, s, OCH3), 3.61 (1H, dd, J = 14.7, 6.7
Hz, Ph−CHH), 3.51 (1H, dd, J = 14.7, 5.8 Hz, Ph−CHH) ppm; 13C
NMR (125 MHz, CDCl3) δ 183.9 (CO), 167.2, 155.7, 135.9, 131.4,
129.7, 129.2, 127.9, 114.1, 104.0 (C−Ar), 71.5 (CH), 56.7 (OCH3),
32.0 (CH2) ppm; m/z (EI, 70 eV) 318 (1, M+), 254 (100), 177 (53),
150 (40), 91 (21%). Anal. Calcd for C16H14O5S: C, 60.34; H, 4.32.
Found: C, 60.37; H, 4.43%.
3-Benzyl-6-bromobenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
(4d): Yellow solid (322 mg, 88%); mp 118−120 °C; IR (KBr) νmax
1
1692 (CO), 1386 (−SO2); 1165 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 8.19 (1H, d, J = 2.4 Hz, Ar), 7.81 (1H, dd, J = 8.7, 2.5
Hz, Ar), 7.36−7.29 (5H, m, Ar), 7.18 (1H, d, J = 8.7 Hz, Ar), 4.54
(1H, t, J = 6.3 Hz, CHCO), 3.59 (1H, dd, J = 14.7, 6.9 Hz, Ph−
CHH), 3.54 (1H, dd, J = 14.8, 5.8 Hz, Ph−CHH) ppm; 13C NMR
(125 MHz, CDCl3) δ 183.3 (CO), 152.7, 140.3, 135.2, 132.2, 129.7,
129.3, 128.1, 122.2, 121.6, 120.1 (C−Ar), 71.9 (CH), 31.9 (CH2)
ppm; m/z (EI, 70 eV) 368 (2, M+ + 2), 366 (2, M+), 304 (92), 302
(83), 200 (63), 91 (100%). Anal. Calcd for C15H11BrO4S: C, 49.20; H,
2.81. Found: C, 49.06; H, 3.02%.
2-Formyl-4-nitrophenyl-(E)-2-phenylethenesulfonate (3l): Cream
solid (1580 mg, 95%); mp 104−107 °C; IR (KBr) νmax 3062, 2896,
1
1693 (CO), 1609, 1344 (−SO2), 1162 (−SO2) cm−1; H NMR
3-(4-Methylbenzyl)benzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
(500 MHz, CDCl3) δ 10.37 (1H, s, CHO), 8.79 (1H, s, Ar), 8.50 (1H,
d, J = 7.9 Hz, Ar), 7.71 (1H, d, J = 15.4 Hz, CCHAr), 7.67−7.48
(6H, m, Ar), 7.02 (1H, d, J = 15.4 Hz, SO2CHC) ppm; 13C NMR
(4e): White solid (257 mg, 85%); mp 149−151 °C; IR (KBr) νmax
1
1705 (CO), 1371 (−SO2); 1165 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 8.1 (1H, dd, J = 7.9, 1.6 Hz, Ar), 7.73 (1H, dt, J = 8.4,
9979
dx.doi.org/10.1021/jo201506d | J. Org. Chem. 2011, 76, 9975−9982

The Journal of Organic Chemistry
Article
1.6 Hz, Ar), 7.42 (1H, dt, J = 7.9, 0.6 Hz, Ar), 7.29 (1H, d, J = 8.3 Hz,
Ar), 7.19 (2H, d, J = 8.0 Hz, Ar), 7.15 (2H, d, J = 8.0 Hz, Ar), 4.52
(1H, dd, J = 6.8, 6.0 Hz, CHCO), 3.58−3.51 (2H, m, CH2), 2.35
(3H, s, CH3), ppm; 13C NMR (125 MHz, CDCl3) δ 185.4 (CO),
153.9, 137.7, 137.6, 132.4, 129.9, 129.7, 129.6, 126.8, 120.9, 119.7 (C−
Ar), 72.2 (CH), 31.6 (CH2), 21.5 (CH3) ppm; m/z (EI, 70 eV) 302
(15, M+), 237 (100), 147 (52), 118 (67), 105 (58%) . Anal. Calcd for
C16H14O4S: C, 63.20; H, 4.63. Found: C, 63.56; H, 4.67%.
3-(4-Chlorobenzyl)benzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
(4k): White solid (267 mg, 83%); mp 149−151 °C; IR (KBr) νmax
1
1697 (CO), 1377 (−SO2); 1169 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 8.09 (1H, dd, J = 7.9, 1.5 Hz, Ar), 7.74 (1H, dt, J =
8.6, 1.6 Hz, Ar), 7.43 (1H, t, J = 7.3 Hz, Ar), 7.32−7.25 (5H, m, Ar),
4.52 (1H, dd, J = 6.5, 5.9 Hz, CHCO), 3.60 (1H, dd, J = 14.8, 6.8
Hz, Ph−CHH), 3.50 (1H, dd, J = 14.8, 5.7 Hz, Ph−CHH) ppm; 13C
NMR (125 MHz, CDCl3) δ 185.2 (CO), 153.9, 137.8, 134.1, 134.0,
131.1, 129.8, 129.4, 127.0, 120.8, 119.8 (C−Ar), 71.8 (CH), 31.0
(CH2) ppm; m/z (EI, 70 eV) 324 (2, M+ + 2), 322 (7, M+), 257
(100), 147 (87), 120 (87), 92 (68%). Anal. Calcd for C15H11ClO4S: C,
55.71; H, 3.31. Found: C, 55.82; H, 3.44%.
8-Methoxy-3-(4-methylbenzyl)benzo[e][1,2]oxathiin-4(3H)-one-
2,2-dioxide (4f): White solid (286 mg, 86%); mp 128−130 °C; IR
(KBr) νmax 1703 (CO), 1368 (−SO2); 1153 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 7.64 (1H, dd, J = 7.6, 1.4 Hz, Ar), 7.32
(1H, t, J = 8.0 Hz, Ar), 7.28 (1H, d, J = 6.5 Hz, Ar), 7.19 (2H, d, J =
8.0 Hz, Ar), 7.15 (2H, d, J = 7.9 Hz, Ar), 4.50 (1H, t, J = 6.5, CHC
O), 3.99 (3H, s, OCH3), 3.52 (2H, d, J = 6.5 Hz, CH2), 2.35 (3H, s,
CH3) ppm; 13C NMR (125 MHz, CDCl3) δ 185.6 (CO), 149.8,
143.2, 137.6, 132.5, 129.9, 129.5, 126.6, 121.8, 120.2, 119.7 (C−Ar),
72.1 (CH), 57.1 (OCH3), 31.6 (CH2), 21.5 (CH3) ppm; m/z (EI, 70
eV) 332 (8, M+), 268 (81), 150 (92), 122 (71), 105 (100%). Anal.
Calcd for C17H16O5S: C, 61.50; H, 4.66. Found: C, 61.43; H, 4.85%.
6-Bromo-3-(4-methylbenzyl)benzo[e][1,2]oxathiin-4(3H)-one-
2,2-dioxide (4g): White solid (370 mg, 87%); mp 129−131 °C; IR
(KBr) νmax 1684 (CO), 1387 (−SO2); 1173 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 8.19 (1H, d, J = 2.4 Hz, Ar), 7.82 (1H, dd,
J = 8.7, 2.4 Hz, Ar), 7.19−7.14 (5H, m, Ar), 4.51 (1H, t, J = 6.4,
CHCO), 3.52 (2H, d, J = 6.4 Hz, CH2), 2.35 (3H, s, CH3) ppm;
13C NMR (125 MHz, CDCl3) δ 184.3 (CO), 152.8, 140.2, 137.8,
3-(4-Chlorobenzyl)-8-methoxybenzo[e][1,2]oxathiin-4(3H)-one-
2,2-dioxide (4l): White solid (306 mg, 87%); mp 154−156 °C; IR
(KBr) νmax 1686 (CO), 1377 (−SO2); 1152 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 7.63 (1H, dd, J = 7.7, 1.5 Hz, Ar), 7.34
(2H, d, J = 8.0 Hz, Ar), 7.32−7.28 (2H, m, Ar), 7.26 (2H, d, J = 8.4
Hz, Ar), 4.49 (1H, dd, J = 6.7, 5.8 Hz, CHCO), 3.58 (1H, dd, J =
14.8, 7.0 Hz, Ph−CHH), 3.51 (1H, dd, J = 14.8, 5.7 Hz, Ph−CHH)
ppm; 13C NMR (125 MHz, CDCl3) δ 185.5 (CO), 149.8, 143.7,
134.1, 133.9, 131.1, 129.4, 126.7, 121.8, 120.2, 119.9 (C−Ar), 71.7
(CH), 57.1 (OCH3), 31.1 (CH2) ppm; m/z (EI, 70 eV) 354 (2, M+ +
2), 352 (7, M+), 288 (42), 150 (89), 91 (44), 69 (100%). Anal. Calcd
for C16H13ClO5S: C, 54.55; H, 3.54. Found: C, 54.47; H, 3.71%.
6-Bromo-3-(4-chlorobenzyl)benzo[e][1,2]oxathiin-4(3H)-one-2,2-
dioxide (4m): Yellow solid (356 mg, 89%); mp 166−168 °C; IR
(KBr) νmax 1694 (CO), 1375 (−SO2); 1158 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 8.19 (1H, d, J = 2.4 Hz, Ar), 7.83 (1H, dd,
J = 8.7, 2.4 Hz, Ar), 7.32 (2H, d, J = 8.4 Hz, Ar), 7.25 (2H, d, J = 8.4
Hz, Ar), 7.18 (1H, d, J = 8.7 Hz, Ar), 4.50 (1H, t, J = 6.3 Hz, CHC
O), 3.58 (1H, dd, J = 14.9, 8.8 Hz, Ph−CHH), 3.50 (1H, dd, J = 14.9,
5.0 Hz, Ph−CHH), ppm; 13C NMR (125 MHz, CDCl3) δ 184.1 (C
O), 152.8, 140.5, 133.7, 132.2, 131.1, 129.4, 122.2, 121.6, 120.2 (C−
Ar), 71.7 (CH), 31.0 (CH2) ppm; m/z (EI, 70 eV) 402 (11, M+ + 2),
400 (8, M+), 338 (100), 200 (63), 138 (32), 125 (58%). Anal. Calcd
for C15H10BrClO4S: C, 44.80; H, 2.18. Found: C, 44.85; H, 2.51%.
3-Benzyl-6-chlorobenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
(4n): White solid (283 mg, 88%); mp 128−130 °C; IR (KBr) νmax
133.0, 132.0, 130.0, 129.5, 122.2, 121.6, 120.0 (C−Ar), 72.0 (CH),
31.7 (CH2), 21.5 (CH3) ppm; m/z (EI, 70 eV) 382 (8, M+ + 2), 380
(8, M+), 317 (37), 118 (100), 105 (73), 77 (23%). Anal. Calcd for
C16H13BrO4S: C, 50.40; H, 3.21. Found: C, 50.41; H, 3.44%.
3-(4-Bromobenzyl)benzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxide
(4h): White solid (307 mg, 84%); mp 147−149 °C; IR (KBr) νmax
1
1697 (CO), 1376 (−SO2); 1170 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 8.10 (1H, dd, J = 7.9, 1.7 Hz, Ar), 7.75 (1H, ddd, J =
8.2, 7.5, 1.7 Hz, Ar), 7.47 (2H, d, J = 8.4 Hz, Ar), 7.43 (1H, dt, J = 8.3,
1.0 Hz, Ar), 7.30 (1H, dt, J = 4.7, 0.6 Hz, Ar), 7.21 (2H, d, J = 10.7 Hz,
Ar), 4.50 (1H, dd, J = 6.8, 5.7 Hz, CHCO), 3.59 (1H, dd, J = 14.8,
6.8 Hz, Ph−CHH), 3.49 (1H, dd, J = 14.8, 5.7 Hz, Ph−CHH) ppm;
13C NMR (125 MHz, CDCl3) δ 185.1 (CO), 153.9, 137.8, 134.6,
1
1694 (CO), 1386 (−SO2); 1165 (−SO2) cm−1; H NMR (500
MHz, CDCl3) δ 8.04 (1H, s, Ar), 7.66 (1H, d, J = 8.2 Hz, Ar), 7.34−
7.23 (6H, m, Ar), 4.54 (1H, br, CHCO), 3.57 (2H, br, CH2) ppm;
13C NMR (125 MHz, CDCl3) δ 184.4 (CO), 152.2, 137.4, 135.2,
132.3, 131.5, 129.8, 127.0, 122.1, 120.9, 119.8 (C−Ar), 71.7 (CH),
31.1 (CH2) ppm; m/z (EI, 70 eV) 368 (6, M+ + 2), 366 (6, M+), 303
(83), 147 (100), 120 (96), 92 (82%). Anal. Calcd for C15H11BrO4S: C,
48.95; H, 2.72. Found: C, 49.06; H, 3.02%.
132.8, 129.7, 129.3, 129.1, 128.1, 121.9, 121.4 (C−Ar), 71.8 (CH),
31.9 (CH2) ppm; m/z (EI, 70 eV) 324 (1, M+ + 2), 322 (3, M+), 258
(100), 181 (62), 154 (79), 91 (92%). Anal. Calcd for C15H11ClO4S: C,
55.51; H, 3.22. Found: C, 55.82; H, 3.44%.
3-(4-Bromobenzyl)-8-methoxybenzo[e][1,2]oxathiin-4(3H)-one-
2,2-dioxide (4i): Yellow solid (340 mg, 85%); mp 163−165 °C; IR
(KBr) νmax 1700 (CO), 1386 (−SO2); 1151 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 7.63 (1H, dd, J = 7.7, 1.7 Hz, Ar), 7.46
(2H, d, J = 8.4 Hz, Ar), 7.33 (1H, t, J = 7.9 Hz, Ar), 7.30 (1H, dd, J =
8.1, 1.6 Hz, Ar), 7.20 (2H, d, J = 8.4 Hz, Ar), 4.48 (1H, dd, J = 6.9, 5.8
Hz, CHCO), 3.97 (3H, s, OCH3), 3.56 (1H, dd, J = 14.8, 7.0 Hz,
Ph−CHH), 3.49 (1H, dd, J = 14.8, 5.7 Hz, Ph−CHH) ppm; 13C
NMR (125 MHz, CDCl3) δ 185.4 (CO), 149.8, 143.7, 134.7, 132.3,
131.5, 126.7, 122.0, 121.8, 120.2, 119.9 (C−Ar), 71.7 (CH), 57.1
(OCH3), 31.2 (CH2), ppm; m/z (EI, 70 eV) 398 (7, M+ + 2), 396 (7,
M+), 334 (33), 169 (34), 150 (100), 122 (67%). Anal. Calcd for
C16H13BrO5S: C, 48.40; H, 3.26. Found: C, 48.38; H, 3.30%.
6-Bromo-3-(4-bromobenzyl)benzo[e][1,2]oxathiin-4(3H)-one-
2,2-dioxide (4j): White solid (375 mg, 84%); mp 174−175 °C; IR
(KBr) νmax 1695 (CO), 1374 (−SO2); 1157 (−SO2) cm−1; 1H
NMR (500 MHz, CDCl3) δ 8.19 (1H, d, J = 2.3 Hz, Ar), 7.83 (1H, dd,
J = 8.7, 2.4 Hz, Ar), 7.47 (2H, d, J = 8.2 Hz, Ar), 7.19 (3H, d, J = 8.4
Hz, Ar), 4.50 (1H, t, J = 6.2 Hz, CHCO), 3.57 (1H, dd, J = 14.9, 6.8
Hz, Ph−CHH), 3.49 (1H, dd, J = 14.8, 5.6 Hz, Ph−CHH) ppm; 13C
NMR (125 MHz, CDCl3) δ 184.1 (CO), 152.8, 140.3, 134.2, 132.4,
132.2, 131.4, 122.3, 122.2, 121.6, 120.2 (C−Ar), 71.6 (CH), 31.1
(CH2) ppm; m/z (EI, 70 eV) 446 (6, M+ + 2), 444 (4, M+), 200 (86),
171 (67), 77 (59), 63 (100%). Anal. Calcd for C15H10Br2O4S: C,
40.51; H, 2.08. Found: C, 40.38; H, 2.26%.
Synthesis of 3-[Methoxy(phenyl)methyl]benzo[e][1,2]-
oxathiine-2,2-dioxide Derivatives 5. General procedure: To a
stirring solution of DBU (0.076 g, 50 mol %) in MeOH (10 mL) was
added 2-formylphenyl-(E)-2-phenylethenesulfonate (3a) (0.288 g,
1 mmol) at room temperature. The progress of the reaction was
followed by TLC. After completion, the solvent was removed under
reduced pressure and H2O (30 mL) and CH2Cl2 (30 mL) were added.
The two phases were separated, and the organic phase was washed
with a solution of Na2CO3 (5%, 3 × 15 mL). The organic phase was
then dried over Na2SO4, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography (SiO2,
eluent: 1:2, n-hexane/CH2Cl2) to afford 3-[methoxy(phenyl)methyl]-
benzo[e][1,2]oxathiine-2,2-dioxide (5a).
3-[Methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-dioxide
(5a): White solid (160 mg, 53%); mp 114−116 °C; IR (KBr) νmax
1
1365 (−SO2), 1171 (−SO2), 1096, 905, 762 cm−1; H NMR (500
MHz, CDCl3) δ 7.51−7.43 (6H, m, Ar), 7.35 (1H, d, J = 6.7 Hz, Ar),
7.29 (1H, d, J = 4.9 Hz, Ar), 7.27 (1H, s, Ar), 6.82 (1H, s, CCH),
5.39 (1H, s, ArCH), 3.49 (3H, s, OCH3) ppm; 13C NMR (125 MHz,
CDCl3) δ 151.4, 138.5, 136.8, 132.1, 131.9, 129.9, 129.5, 129.3, 128.1,
126.3, 120.5, 119.1 (C−Ar), 80.2 (C−OMe), 58.2 (OCH3), ppm; m/z
(EI, 70 eV) 302 (3, M+), 238 (24), 207 (100), 178 (16), 77 (5%).
Anal. Calcd for C16H14O4S: C, 63.60; H, 4.44. Found: C, 63.56; H,
4.67%.
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Article
8-Methoxy-3-[methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-
152 (18%). Anal. Calcd for C17H15BrO5S: C, 49.68; H, 3.57. Found:
C, 49.65; H, 3.68%.
2,2-dioxide (5b): White solid (159 mg, 48%); mp 126−128 °C; IR
1
(KBr) νmax 1480, 1362 (−SO2), 1163 (−SO2), 1100 cm−1; H NMR
6-Bromo-3-[(4-bromophenyl)methoxymethyl]benzo[e][1,2]-
oxathiine-2,2-dioxide (5h): White solid (248 mg, 54%); mp 145−147 °C;
IR (KBr) νmax 2927, 1370 (−SO2), 1165 (−SO2), 1073, 819 cm−1; 1H
NMR (500 MHz, CDCl3) δ 7.61 (2H, d, J = 8.3 Hz, Ar), 7.56 (1H, dd,
J = 8.7, 2.2 Hz, Ar), 7.53 (1H, d, J = 2.1 Hz, Ar), 7.36 (2H, d, J = 8.6,
Hz, Ar), 6.80 (1H, s, CCH), 5.33 (1H, s, ArCH), 3.47 (3H, s,
OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ 150.3, 139.3, 135.7,
134.9, 132.6, 132.4, 130.5, 129.7, 123.8, 122.0, 120.8, 119.2 (C−Ar),
79.5 (C−OMe), 58.2 (OCH3) ppm; m/z (EI, 70 eV) 460 (5, M+ + 2),
458 (3, M+), 396 (16), 365 (100), 285 (32), 199(44), 176 (64%).
Anal. Calcd for C16H12Br2O4S: C, 41.72; H, 2.58. Found: C, 41.76; H,
2.63%.
(500 MHz, CDCl3) δ 7.51−7.41 (5H, m, Ar), 7.20 (1H, t, J = 8.0 Hz,
Ar), 7.04 (1H, d, J = 7.5 Hz, Ar), 6.91 (1H, dd, J = 7.6, 0.8 Ar), 6.76
(1H, d, J = 1.2 Hz, CCH), 5.39 (1H, s, ArCH), 3.94 (3H, s, OCH3),
3.48 (3H, s, OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ 149.4,
140.8, 138.8, 136.8, 132.1, 129.5, 129.3, 128.1, 126.2, 121.4, 121.2,
115.2 (C−Ar), 80.2 (C−OMe), 58.1 (OCH3), 56.9 (OCH3) ppm; m/
z (EI, 70 eV) 332 (31, M+), 268 (7), 237 (100), 194 (14), 77 (12%).
Anal. Calcd for C17H16O5S: C, 61.63; H, 4.84. Found: C, 61.43; H,
4.85%.
6-Bromo-3-[methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-
dioxide (5c): White solid (209 mg, 55%); mp 135−137 °C; IR (KBr)
1
νmax 1473, 1366 (−SO2), 1169 (−SO2), 1091, 822, 697 cm−1; H
3-[(4-Chlorophenyl)methoxymethyl]benzo[e][1,2]oxathiine-2,2-
dioxide (5i): White solid (202 mg, 60%); mp 118−120 °C; IR (KBr)
NMR (500 MHz, CDCl3) δ 7.55 (1H, dd, J = 8.7, 2.3 Hz, Ar), 7.42−
7.50 (6H, m, Ar), 7.17 (1H, d, J = 8.7 Hz, Ar), 6.72 (1H, d, J = 1.1 Hz,
CCH), 5.38 (1H, d, J = 1.3 Hz, ArCH), 3.48 (3H, s, OCH3) ppm;
13C NMR (125 MHz, CDCl3) δ 150.3, 140.0, 136.4, 134.8, 132.3,
1
νmax 2946, 1370 (−SO2), 1168 (−SO2), 1087, 814, 755 cm−1; H
NMR (500 MHz, CDCl3) δ 7.48−7.43 (5H, m, Ar), 7.38 (1H, dd, J =
7.7, 1.5 Hz, Ar), 7.31−7.26 (2H, m, Ar), 6.90 (1H, s, CCH), 5.36
(1H, s, ArCH), 3.48 (3H, s, OCH3) ppm; 13C NMR (125 MHz,
CDCl3) δ 151.4, 138.0, 135.6, 132.3, 131.9, 130.0, 129.6, 129.4, 129.3,
126.5, 120.4, 119.1 (C−Ar), 79.6 (C−OMe), 58.2 (OCH3) ppm; m/z
(EI, 70 eV) 338 (1, M+ + 2), 336 (3, M+), 305 (7), 272 (20), 257 (18),
241(100), 205 (18%). Anal. Calcd for C16H13ClO4S: C, 56.99; H, 3.73.
Found: C, 57.06; H, 3.89%.
130.5, 129.7, 129.4, 128.1, 122.1, 120.8, 119.1 (C−Ar), 80.2 (C−
OMe), 58.2 (OCH3) ppm; m/z (EI, 70 eV) 382 (3, M+ + 2), 380 (3,
M+), 316 (19), 287 (100), 205 (19), 121 (28%). Anal. Calcd for
C16H13BrO4S: C, 50.29; H, 3.38. Found: C, 50.41; H, 3.44%.
3-[Methoxy(p-tolyl)methyl]benzo[e][1,2]oxathiine-2,2-dioxide
(5d): White solid (127 mg, 40%); mp 114−116 °C; IR (KBr) νmax
3-[(4-Chlorophenyl)methoxymethyl]-8-methoxybenzo[e][1,2]-
oxathiine-2,2-dioxide (5j): White solid (198 mg, 54%); mp 149−151 °C;
IR (KBr) νmax 2928, 1365 (−SO2), 1157 (−SO2), 1084, 873, 722
1
2926, 1368 (−SO2), 1168 (−SO2), 1115, 909, 815, 758 cm−1; H
NMR (500 MHz, CDCl3) δ 7.44 (1H, dt, J = 7.8, 1.5 Hz, Ar), 7.39
(2H, d, J = 8.0 Hz, Ar), 7.35 (1H, d, J = 7.5 Hz, Ar), 7.29−7.26 (4H,
m, Ar), 6.84 (1H, s, CCH), 5.36 (1H, s, ArCH), 3.47 (3H, s,
OCH3), 2.43 (3H, s, CH3) ppm; 13C NMR (125 MHz, CDCl3)
δ 151.4, 139.4, 138.7, 133.7, 132.1, 131.7, 130.0, 129.9, 128.1, 126.3,
120.5, 119.0 (C−Ar), 80.1 (C−OMe), 58.0 (OCH3), 21.7 (CH3)
ppm; m/z (EI, 70 eV) 316 (14, M+), 285 (21), 252 (75), 221 (100),
178 (55), 135 (54), 91 (21%). Anal. Calcd for C17H16O4S: C, 64.47;
H, 5.02. Found: C, 64.54; H, 5.10%.
1
cm−1; H NMR (500 MHz, CDCl3) δ 7.44 (4H, br, Ar), 7.22 (1H, t,
J = 8.0 Hz, Ar), 7.06 (1H, d, J = 7.8 Hz, Ar), 6.94 (1H, d, J = 7.7 Hz,
Ar), 6.83 (1H, s, CCH), 5.36 (1H, s, ArCH), 3.95 (3H, s,
ArOCH3), 3.47 (3H, s, OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ
149.4, 138.3, 135.6, 135.3, 132.0, 129.8, 129.6, 129.4, 126.4, 121.3,
121,2, 115.3 (C−Ar), 79.5 (C−OMe), 58.2 (OCH3), 56.9 (ArOCH3)
ppm; m/z (EI, 70 eV) 368 (5, M+ + 2), 366 (15, M+), 271 (100), 265
(13), 241 (38), 165(15), 155 (19%). Anal. Calcd for C17H15ClO5S: C,
55.58; H, 4.09. Found: C, 55.66; H, 4.12%.
6-Bromo-3-[(4-chlorophenyl)(methoxy)methyl]benzo[e][1,2]-
oxathiine-2,2-dioxide (5k): White solid (182 mg, 44%); mp 173−175
°C; IR (KBr) νmax 1473, 1368 (−SO2), 1168 (−SO2), 1090, 823 cm−1;
1H NMR (500 MHz, CDCl3) δ 7.56−7.43 (6H, m, Ar), 7.16 (1H, d,
J = 8.5 Hz, Ar), 6.80 (1H, s, CCH), 5.34 (1H, s, ArCH), 3.47 (3H,
s, OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ 150.3, 139.4, 135.6,
135.2, 134.9, 132.4, 130.5, 129.7, 129.4, 122.0, 120.8, 119.2 (C−Ar),
79.5 (C−OMe), 58.2 (OCH3) ppm; m/z (EI, 70 eV) 416 (6, M+ + 2),
414 (5, M+), 352 (25), 321 (100), 205 (13), 155 (24%). Anal. Calcd
for C16H12BrClO4S: C, 46.21; H, 2.79. Found: C, 46.23; H, 2.91%.
3-[Methoxy(phenyl)methyl]-6-nitrobenzo[e][1,2]oxathiine-2,2-di-
oxide (5l): Yellow oil (53 mg, 15%); IR (KBr) νmax 3069, 1342
(−SO2), 1157 (−SO2), 986, 826, 740 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.64 (1H, d, J = 15.5 Hz, Ar), 7.55−7.36 (6H, m, Ar), 7.75
(1H, d, J = 15.5 Hz, Ar), 3.90 (1H, s, CCH), 3.88 (3H, s, OCH3), 3.30
(1H, s, ArCH) ppm; 13C NMR (125 MHz, CDCl3) δ 145.8, 139.0, 132.3,
132.1, 130.2, 129.6, 129.4, 129.2, 129.0, 127.0, 120.6, 119.4 (C−Ar), 78.8
(C−OMe), 56.6 (OCH3) ppm; m/z (EI, 70 eV) 348 (2, M+), 181 (33),
167 (61), 103 (100), 77 (41%). Anal. Calcd for C16H13NO6S: C, 55.28;
H, 3.68; N, 3.95. Found: C, 55.33; H, 3.77; N, 4.03%.
6-Bromo-3-(methoxy-p-tolylmethyl)-benzo[e][1,2]oxathiine-2,2-
dioxide (5e): White solid (142 mg, 36%); mp 116−118 °C; IR (KBr)
1
νmax 2924, 1368 (−SO2), 1166 (−SO2), 1089, 819, 698 cm−1; H
NMR (500 MHz, CDCl3) δ 7.55 (1H, dd, J = 8.7, 2.3 Hz, Ar), 7.50
(1H, d, J = 2.3 Hz, Ar), 7.36 (2H, d, J = 8.0 Hz, Ar), 7.16 (1H, d, J =
8.7 Hz, Ar), 6.73 (1H, s, CCH), 5.34 (1H, s, ArCH), 3.46 (3H, s,
OCH3), 2.42 (3H, s, CH3) ppm; 13C NMR (125 MHz, CDCl3) δ
150.3, 139.6, 138.7, 133.3, 132.3, 131.5, 130.3, 130.1, 128.1, 122.2,
120.8, 119.0 (C−Ar), 80.0 (C−OMe), 58.0 (OCH3), 21.7 (CH3)
ppm; m/z (EI, 70 eV) 396 (4, M+ + 2), 394 (4, M+), 330 (24), 299
(100), 205 (22), 135(41), 91 (32%). Anal. Calcd for C17H15BrO4S: C,
51.55; H, 3.69. Found: C, 51.66; H, 3.83%.
3-[(4-Bromophenyl)methoxymethyl]benzo[e][1,2]oxathiine-2,2-
dioxide (5f): White solid (247 mg, 65%); mp 119−121 °C; IR (KBr)
1
νmax 2925, 1369 (−SO2), 1171 (−SO2), 1071, 815, 758 cm−1; H
NMR (500 MHz, CDCl3) δ 7.61 (2H, d, J = 8.4, Hz, Ar), 7.47 (1H, dt,
J = 8.5, 1.5 Hz, Ar), 7.40−7.37 (3H, m, Ar), 7.32−7.27 (2H, m, Ar),
6.87 (1H, s, CCH), 5.34 (1H, s, ArCH), 3.47 (3H, s, OCH3) ppm;
13C NMR (125 MHz, CDCl3) δ 151.4, 137.9, 136.1, 132.5, 132.3,
131.9, 129.9, 129.7, 126.4, 123.6, 120.4, 119.1 (C−Ar), 79.5 (C−
OMe), 58.2 (OCH3) ppm; m/z (EI, 70 eV) 382 (3, M+ + 2), 380 (4,
M+), 316 (15), 285 (100), 205 (79), 161(35), 89 (30%). Anal. Calcd
for C16H13BrO4S: C, 50.49; H, 3.25. Found: C, 50.41; H, 3.44%.
3-[(4-Bromophenyl)methoxymethyl]-8-methoxybenzo[e][1,2]-
oxathiine-2,2-dioxide (5g): White solid (230 mg, 56%); mp 167−169 °C;
IR (KBr) νmax 2927, 1364 (−SO2), 1156 (−SO2), 1069, 873, 722
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra of all compounds, plus NOESY
and HMBC of 4h and 5g. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
cm−1; H NMR (500 MHz, CDCl3) δ 7.60 (2H, d, J = 8.4 Hz, Ar),
7.38 (2H, d, J = 8.4 Hz, Ar), 7.22 (1H, t, J = 8.0 Hz, Ar), 7.06 (1H, dd,
J = 7.8, 1.1 Hz, Ar), 6.94 (1H, dd, J = 7.8, 1.1 Hz, Ar), 6.82 (1H, s,
CCH), 5.34 (1H, s, ArCH), 3.95 (3H, s, ArOCH3), 3.47 (3H, s,
OCH3) ppm; 13C NMR (125 MHz, CDCl3) δ 149.4, 138.2, 136.1,
132.6, 132.5, 132.0, 129.7, 126.4, 123.5, 121,3, 121.2, 115.3 (C−Ar),
79.6 (C−OMe), 58.2 (OCH3), 56.9 (ArOCH3) ppm; m/z (EI, 70 eV)
412 (9, M+ + 2), 410 (9, M+), 315 (100), 236 (15), 199 (14), 165(18),
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ghandi@khayam.ut.ac.ir.
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Article
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1967, 89, 2087−2097. (c) Mustafa, A.; Hilmy, M. K. J. Chem. Soc.
1952, 1339−1342.
ACKNOWLEDGMENTS
■
The authors acknowledge the University of Tehran for financial
support of this research.
(17) (a) Schetty, G. Helv. Chim. Acta 1949, 32, 24−30. (b) Schetty,
G. Helv. Chim. Acta 1947, 30, 1650.
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