Smiles-type free radical rearrangement of aromatic sulfonates and sulfonamides: Syntheses of arylethanols and arylethylamines

Article abstract of DOI:10.1039/b303728b

Smiles-type free radical rearrangements of arenesulfonates and arenesulfonamides are exploited for synthetic purposes. 4-Substituted benzenesulfonates cause Smiles-type rearrangement only when substituted by an electron withdrawing group. Therefore, ipso-sttack by an alkyl radical on arenesulfonates takes place in an electrophilic manner. Arenesulfonamides rearrange only when the amide nitrogen is substituted by an alkoxycarbonyl group, due to the electron withdrawing nature of this group. Sulfonates and the N-ethoxycarbonylsulfonamide derivatives of naphthalene, quinoline, and thiophene cause more rearrangement and show synthetic utility. Aromatic amino acid analogues were synthesized by Smiles-type rearrangement with moderate yields. The radical Smiles-type rearrangement of sulfonate and sulfonamide derivatives can be a useful synthetic route when we understand the electronic character of these reactions.

Full text of DOI:10.1039/b303728b

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Smiles-type free radical rearrangement of aromatic sulfonates and
sulfonamides: syntheses of arylethanols and arylethylamines
Masaru Tada,* Hiroyasu Shijima and Masaharu Nakamura
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku,
Tokyo 169-8555, Japan. E-mail: mtada@waseda.jp
Received 4th April 2003, Accepted 19th May 2003
First published as an Advance Article on the web 11th June 2003
Smiles-type free radical rearrangements of arenesulfonates and arenesulfonamides are exploited for synthetic
purposes. 4-Substituted benzenesulfonates cause Smiles-type rearrangement only when substituted by an electron
withdrawing group. Therefore, ipso-attack by an alkyl radical on arenesulfonates takes place in an electrophilic
manner. Arenesulfonamides rearrange only when the amide nitrogen is substituted by an alkoxycarbonyl group,
due to the electron withdrawing nature of this group. Sulfonates and the N-ethoxycarbonylsulfonamide derivatives
of naphthalene, quinoline, and thiophene cause more rearrangement and show synthetic utility. Aromatic amino
acid analogues were synthesized by Smiles-type rearrangement with moderate yields. The radical Smiles-type
rearrangement of sulfonate and sulfonamide derivatives can be a useful synthetic route when we understand the
electronic character of these reactions.
the free forms of sulfonamide (SO2NH-) are not suitable
substrates for the Smiles-type rearrangement.
Introduction
The ionic Smiles rearrangement1 has a broad utility in the
organic syntheses of aromatic compounds. However, Smiles-
type free radical rearrangement has rarely been observed in
previous synthetic studies. Aromatic sulfonates and sulfon-
amides are readily available substrates that are expected to
yield phenols or aromatic amines. Motherwell and Pannell,2
Ryokawa and Togo,3 and Caddick et al.4 reported the syntheses
of biphenyl derivatives by radical Smiles-type rearrange-
ments of aryl radicals, and they discussed the effect of the ipso-
substitution on the ring and the conformational effect of the
amide moiety on the Smiles-type rearrangement (Scheme 1).
Results and discussion
Para-substituted benzenesulfonyloxyethyl bromides, 1a–1c are
expected to yield the corresponding 2-phenylethanols, 2a–2c by
a Smiles-type rearrangement. Similarly, sulfonamide 1d and its
derivatives, 1e and 1f are expected to yield 2-phenylethylamine
derivatives, 2d–2f via the radical rearrangement (Scheme 2).
Scheme 1
Scheme 2
Although a vinyl radical can be a substrate for Smiles-type
rearrangement in some cases,5 rearrangement starting from
an alkyl radical has been reported only for some sulfonates6
and sulfonamides7 and only a few synthetic discussions have
covered the structure–reactivity relationship.
In free radical ipso-substitution, the position substituted by
the sulfone or the sulfoxide group is more reactive than non-
substituted or thio-substituted aromatics6,8 and we have studied
the free radical rearrangement of aromatic sulfonates and
sulfonamides. In this paper, we report the Smiles-type radical
rearrangement of arenesulfonates and arenesulfonamides,
where the expected products are 2-arylethanols and 2-aryl-
ethylamine derivatives including aromatic α-amino acid
analogues. The rearrangement is triggered by free radical
attack at the ipso-position of the sulfonates or sulfonamides
The sulfonates or the sulfonamides in benzene were treated
with tributyltin hydride and the reaction conditions were
kept identical throughout all the reactions described in this
paper. The tributyltin hydride was added slowly over a period
of 10 hours using a syringe pump under reflux, and then the
reaction mixture was refluxed for a further 12 hours.
The para-substituted benzenesulfonyloxyethyl radical from
the bromides (1) gave Smiles-type rearrangement products (2)
as well as ortho-substitution products (3) and reduction
products (4) in varying yields (Table 1). Para-substituted
2-phenylethanols, 2b and 2c were formed by ipso-substitution
followed by the loss of sulfur dioxide and hydrogen abstraction
from the tin hydride. Free radical substitution at the ortho-
position gave the cyclisation products 3, and the direct reduc-
tion of the radical intermediate with tributyltin hydride gave
reduction products 4. As shown in Table 1, the radical reactions
yielded 4-chlorophenylethanol (2b) (8%) and 4-cyanophenyl-
in
a nucleophilic manner. N-Ethoxycarbonylsulfonamide
derivatives yield 20–76% of the rearranged products although
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
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Table 1 Free radical reaction of benzenesulfonyl derivatives
Table 3 Free radical reaction of thiophenesulfonyl derivatives
Yield (%)
Yield (%)
Bromide
R
Y
2
3
4
2 : 4
Bromide
Y
11
12
13
11 : 13
1a
1b
1c
1d
1e
1f
CH3
Cl
CN
Cl
Cl
Cl
O
O
O
0.0
8.0
31
0.0
0.0
16
22
13
8.0
15
30
20
43
37
38
49
21
44
0.0
10a
10b
10c
O
74
Trace
51
9.0
0.0
0.0
13
42
13
5.7
∼0
0.22
0.82
0.0
0.0
0.34
NMe
NCO2Et
3.9
NH
NMe
NCO2Et
Hz); 8.08 (J = 1.2 and 8.4 Hz), and both of these appear as
a double-doublet. The alternative structure resulting from
ortho-substitution leaves two hydrogens on the same ring, which
would result in no meta-hydrogen being available for long-range
coupling to induce the double-doublet.
Table 2 Free radical reaction of naphthalene- and quinoline-sulfonyl
derivatives
The rearrangement becomes a major reaction process in
the cases of 1-naphthyl or 8-quinolyl derivatives (5a–5d). How-
ever, the 2-naphthyl derivative 9 gave a complex mixture of
products, which contained only 4% of the rearrangement
product, 2-(2-naphthyl)-ethanol (Scheme 4).
Yield (%)
Bromide
X
Y
6
7
8
6 : 8
5a
5b
5c
5d
CH
N
CH
N
O
O
53
63
51
76
2.0
0.0
0.0
0.0
12
14
13
10
4.4
4.5
3.9
7.6
NCO2Et
NCO2Et
The 2-thiophenesulfonyl derivatives (10a and 10c) gave
reasonable yields of the rearranged products 11a and 11c
(Scheme 5 and Table 3), whereas the 3-thiophenesulfonyl deriv-
ative (14) gave the rearranged product, 2-(3-thienyl)-ethanol, in
poor yield (5%), along with a complex mixture .
Scheme 3
ethanol (2c) (31%). The carbamate derivative 2f (16%) was
formed in poor yield, but there were no rearrangement products
from bromides 1a, 1d and 1e. These substitution effects indicate
that the radical Smiles-type rearrangement takes place through
an ipso-substitution characterized by nucleophilic attack of the
radical centre (Scheme 3). The radical intermediate giving 3 is
considered to aromatise in one of two reported processes. One
is the reaction with the tin hydride to produce molecular hydro-
gen and the substrate radical,9 and the other is the reaction with
AIBN to produce the (AIBN)-H radical.10 Therefore, Smiles-
type rearrangement is not a practical synthetic process for
phenylethyl alcohols and phenylethylamines, even under the
high dilution conditions described here.
Scheme 5
N-(2-bromoethyl)-4-chlorophenylsulfonamides gave the
Smiles-type rearrangement product only when the amide
nitrogen was substituted by an ethoxycarbonyl group (1f ).
Throughout the phenyl, naphthyl, and thiophenyl sulfonamide
derivatives, the free N–H forms gave either no yield or poor
yield of the rearranged products. This property was also
reported for the ortho-(benzenesulfonamidyl)-phenyl radical3
and was accounted for by the distance between the radical
centre and the ipso-position. Lower population of the syn-
conformer in the present study is predicted from an analogy
with the reported case of benzoanilide (Scheme 6a).11 The
corresponding N-methyl derivatives 1e and 10b do not improve
the rearrangement process, and this behaviour cannot be
explained by the conformational population effect of the
intermediate radical. The substitution of sulfonamide with the
ethoxycarbonyl group (1f, 5c, 5d and 10c) gave better yields of
the rearranged product. Simple molecular model inspection
and MOPAC (PM3) calculations12 suggest that the syn-form is
less stable (Scheme 6b) due to the Coulomb repulsion between
the sulfonyl oxygen and the ethoxycarbonyl group, though the
rearrangement requires the syn-conformation. Experimental
results, however, show that substitution of the amide nitrogen
Bromides with larger aromatic systems, such as the 1-naph-
thyl or 8-quinolyl moieties, gave better results, as shown in
Scheme 4 and Table 2. Only the sulfonate 5a gave the cyclisation
product 7a resulting from peri-substitution, and its structure
1
was assigned from H-NMR. The protons on the ring bearing
the sulfonate group resonate downfield, δ 8.36 (J = 1.4 and 7.4
Scheme 4
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
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Table
4
Free radical reaction of N-ethoxycarbonyl-sulfonamide
of the reactions except in the case of 15a–c, since the reaction
derivatives
centre is located far from the aromatic moiety. This means that
the formation of the reduction products, 4, 8 and 13 can be an
internal clock for other radical processes, and the ratio
[rearrangement product] : [reduction product] is an intrinsic
index of the ease of Smiles-type radical rearrangement. Ben-
zene derivatives (1a–1f ) give smaller values of 2 : 4, and
rearrangement is a minor process in this system. The rather
higher ratios of 6 : 8, 11a : 13a, and 11c : 13c indicate that pos-
ition-1 on naphthalene, position-8 on quinoline and position-2
on thiophene are susceptible to radical ipso-substitution.
The present experimental results show us the scope and the
limitations of Smiles-type free radical rearrangement as a syn-
thetic utility, and also that radical ipso-substitution is con-
trolled by a polar effect . Thus the 5-exo cyclisation leading to
the rearrangement and the 6-exo cyclisation leading to the
ortho-substitution take place competitively in the present sys-
tems. We have seen that the benzene derivative is not suitable for
this type of transformation (ArSO2XCH2CH2Br to ArCH2-
CH2XH) but that naphthalene and heteroaromatic systems
such as thiophene and quinoline are suitable. These features
must be a consequence of a low-lying LUMO to accept nucleo-
philic free radicals and the easy break of aromaticity by the
formation of intermediates. Larger π-systems or hetero-
aromatics are favourable for the free radical Smiles-type
rearrangement and they may be promising synthetic substrates
if we keep the factors described in this paper in mind and
seek an alternative non-harmful method of free radical
generation.
Product yield (%)
Bromide
16
17
16 : 17
15a
15b
15c
25
31
41
0.80
0.44
3.10
18
21a
6.6a
a Most of the starting material remained intact.
Scheme 6
by an ethoxycarbonyl group leads to Smiles-type rearrange-
ment as the main radical process. This must be due to the
electron withdrawing effect of the ethoxycarbonyl group,
and this concept is in accord with the comparable reactivity
of the sulfonate derivatives and the corresponding N-ethoxy-
carbonylamide derivatives. Thus, corresponding sulfonate
derivatives and N-ethoxycarbonylsulfonamide derivatives show
comparable yields of Smiles-type rearrangement products; 1b
(8.0%) and 1f (16%), 5a (53%) and 5c (51%), 5b (63%) and 5d
(76%), 10a (74%) and 10c (51%).
Amides 5c, 5d, and 10c containing the N-ethoxycarbonyl
group give reasonable yields of the rearrangement products
(51–76%), and we attempted the radical rearrangement of
esters 15a–15c, which contain β-ethoxycarbonyl-substituted
radical centres, because the expected rearrangement products,
16a–16c, are analogues of aromatic α-amino acids such as tyro-
sine, tryptophane, and histidine. However, reactions under the
same conditions as for 1d resulted in rather poor yields of the
rearrangement products (16) (Scheme 7 and Table 4) and no
ortho-cyclisation took place. One of the reasons of the results
must be the steric hindrance of the ester group near the radical
centre for both ipso- and ortho-substitution, and another reason
may be the reduction of the nucleophilicity of the radical centre
by the ester substitution.
Experimental
1
All the H-NMR spectra were measured by a JEOL AL-400
spectrometer (400 MHz) in deuteriochloroform. Chemical
shifts and coupling constants are recorded in δ-values and Hz
respectively. 13C-NMR spectra were measured by a Bruker
AVANCE-600 spectrometer (150 MHz). IR spectra were
measured by a HORIBA FT-700 spectrometer in chloroform of
0.1 mm thickness. High resolution mass spectra were measured
by a JEOL SX-162A spectrometer by FAB ionization unless
otherwise mentioned using 3-nitrobenzyl alcohol as matrix.
Preparative TLC was performed on Merck Kieselgel 60PF254
plate (20 × 20 × 0.2 cm).
Preparation of the starting materials
a) 2-Bromoethylarenesulfonates. One of the arenesulfonates
(6.0 × 10Ϫ3 mol) and 2-bromoethanol (649 mg, 5.2 × 10Ϫ3 mol)
were dissolved in 10 ml of dry dichloromethane under nitrogen
atmosphere. Triethylamine (1.4 ml, 1.0 × 10Ϫ2 mol) was added
dropwise to the mixture under ice-cooling and stirred overnight
under cooling. Diethyl ether (30 ml) was added and the mixture
washed twice with 40 ml 2 M hydrochloric acid and 40 ml
saturated sodium chloride solution. Evaporation of the sol-
vents after drying over magnesium sulfate gave the crude
products, which were separated by silica gel column chromato-
graphy (4.0(ꢀ) × 10 cm) eluted with hexane–ethyl acetate (4 : 1)
for 1a (28%), dichloromethane–hexane (1 : 5) for 1e (83%),
dichloromethane–hexane (1 : 3) for 1f (60%) and 5a (78%),
dichloromethane for 5b (36%), and ethyl acetate–hexane (1 : 5)
for 10a (45%).
1a, bp 155 ЊC/1.8 Torr.13 1H-NMR 2.46(3H, s), 3.47(2H, t,
J = 6.6), 4.29(2H, t, J = 6.), 7.35(2H, d, J = 8.8), 7.82(2H, d,
J = 8.8).
1b, mp 32–33 ЊC (lit. 33 ЊC).14 1H-NMR 3.50(2H, t, J = 6.4),
4.33(2H, t, J = 6.4), 7.56(2H, d, J = 8.8), 7.88(2H, d, J = 8.8).
Scheme 7
1
The trends seen in the reactions of the sulfonates and
sulfonamides indicate a nucleophilic ipso-attack of the alkyl
radical on the aromatic system. The formation rate of
the reduction products must essentially be the same for all
1c, mp 53–54 ЊC. H-NMR 3.52(2H, t, J = 6.2), 4.40(2H, t,
J = 6.2), 7.89(2H, d, J = 8.8), 8.07(2H, d, J = 8.8); IR 3030, 3014,
2234, 1362, 1199 cmϪ1; MS (EI/70 eV) m/z 210(17), 166(36),
102(100), 75(42).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
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Anal. C, 37.23; H, 2.41; N, 4.70. C9H8BrNO3S requires C,
37.26; H, 2.78; N, 4.83%.
5a, oil. H-NMR 3.43(2H, t, J = 6.8), 4.27(2H, t, J = 6.8),
d) N-(2-Bromoethyl)-N-ethoxycarbonyl-arenesulfonamides.
Sodium hydride mineral dispersion (198 mg, 4.8 × 10Ϫ3 mol)
and 3 ml of THF were placed in a nitrogen flushed flask and
treated with N-(2-bromoethyl)-arenesulfonamide (4.0 × 10Ϫ3
mol) in 5 ml of dry THF under ice-cooling. The mixture was
stirred until hydrogen evolution ceased and then treated with
ethyl chloroformate (520 mg, 4.5 × 10Ϫ3 mol) in 3 ml dry THF.
After stirring for 5 min, the reaction was quenched by adding
5 ml 1 M tartaric acid solution and extracted three times with
10 ml dichloromethane. Evaporation of the solvent after drying
over magnesium sulfate gave the crude product, which was
purified by silica gel column chromatography (2.6(ꢀ) × 21 cm)
eluted with dichloromethane (1f ), dichloromethane–hexane (2
: 3) (5c), and dichloromethane–hexane (3 : 1) (5d). Compound
10c was purified by Kugelrohr distillation without chromato-
graphy.
1
7.58(1H, dd, J = 8.4 and 7.6), 7.64(1H, dd, J = 8.0 and 7.6),
7.73(1H, dd, J = 8.8 and 7.6), 7.97(1H, d, J = 8.0), 8.16(1H, d,
J = 8.4), 8.30(1H, d, J = 7.6), 8.63(1H, d, J = 8.8); 13C-NMR
27.12, 68.96, 123.92, 124.92, 127.31, 128.29, 128.74, 128.79,
130.45, 130.82, 134.10; IR 3030, 1558, 1509, 1060, 981, 963
cmϪ1
.
HRMS m/z
=
313.9584. C12H11BrO3S requires m/z =
313.9612.
1
5b, mp 89–90 ЊC. H-NMR 3.56(2H, t, J = 6.8), 4.75(2H, t,
J = 6.8), 7.59(1H, dd, J = 4.0 and 8.4), 7.68(1H, dd, J = 8.2 and
7.4), 8.14(1H, dd, J = 8.2 and 1.4), 8.29(1H, dd, J = 8.4 and
1.8), 8.54(1H, dd, J = 7.4 and 1.4), 9.15(1H, dd, J = 4.0 and 1.8);
13C-NMR 27.79, 70.21, 122.32, 125.13, 128.83, 132.88, 133.72,
134.76, 136.43, 143.65, 151.66; IR 3034, 1615, 1598, 1565, 1058,
1
1f, oil. H-NMR 1.23(3H, t, J = 7.0), 3.59(2H, t, J = 7.2),
989, 962 cmϪ1
.
4.16–4.21(4H, m), 7.52(2H, d, J = 8.8), 7.92(2H, d, J = 8.8):
13C-NMR 14.10, 28.66, 47.74, 64.07, 129.05, 129.90, 137.49,
140.46, 151.63; IR 3034, 1734, 1586, 1478, 1445, 1093, 1014,
Anal C, 41.70; H, 2.84; N, 4.27. C11H10BrNO3S requires C,
41.79; H, 3.19; N, 4.43%.
10a, oil, bp 110–120 ЊC/1.0 Torr (Kugelrohr). 1H-NMR
3.51(2H, t, J = 6.6), 4.38(2H, t, J = 6.6), 7.17(1H, dd, J = 5.0 and
4.0), 7.74(1H, dd, J = 5.0 and 1.2), 7.77(1H, dd, J = 4.0 and 1.2);
13C-NMR 27.07, 69.49, 127.58, 134.04, 134.56, 135.07; IR 3030,
954 cmϪ1
.
Anal. C, 35.70; H, 3.46; N, 3.69. C11H13BrClNO4S requires C,
35.65; H, 3.54; N, 3.78%.
1
5c, mp 74–74 ЊC. H-NMR 1.00(3H, t, J = 7.2), 3.69(2H,
1559, 1508, 1455, 1095, 1021, 988, 965 cmϪ1
.
t, J = 7.8), 4.11(2H, q, J = 7.2), 4.40(2H, t, J = 7.8), 7.60(1H, dd,
J = 8.4 and 7.2), 7.62(1H, dd, J = 8.0 and 7.2), 7.71(1H, dd,
J = 8.4 and 7.2), 7.97(1H, d, J = 8.0), 8.14(1H, d, J = 8.4),
8.23(1H, d, J = 8.4), 8.43(1H, d, J = 7.2); 13C-NMR 13.78,
28.28, 47.58, 63.74, 123.40, 123.87, 126.89, 128.01, 128.71,
129.24, 132.40, 133.94, 134.00, 135.32, 151.64; IR 3034, 3013,
Anal C, 26.60; H, 2.42. C6H7BrO3S2 requires C, 26.58; H,
2.62%.
b) N-(2-Bromoethyl)-arenesulfonamides. One of the
arenesulfonyl chlorides (9.9 × 10Ϫ3 mol) and 2-bromoethyl-
ammonium bromide (2.23 g, 1.1 × 10Ϫ2 mol) were dissolved in
15 ml dry dichloromethane under a nitrogen atmosphere. The
mixture was treated dropwise with 3.2 ml triethylamine under
ice-cooling and then stirred for 5 min under cooling. The reac-
tion mixture was washed twice with 25 ml 2 M hydrochloric
acid and 25 ml saturated sodium chloride solution. Evaporation
of the organic solvent after drying over magnesium sulfate gave
the crude product, which was purified by silica gel column
chromatography (4(ꢀ) × 17 cm) eluted with dichloromethane–
hexane (4 : 1) to give 1d (96%).
1734, 1595, 1569, 1035, 1033, 1010, 974, 952 cmϪ1
.
Anal. C, 46.64; H, 4.18; N, 3.36. C15H16BrNO4S requires C,
46.59; H, 4.06; N, 3.52%.
5d, mp 125–127 ЊC. 1H-NMR 0.98(3H, t, J = 7.0), 3.77(2H, t,
J = 8.0), 3.99(2H, q, J = 7.0), 4.59(2H, t, J = 8.0), 7.55(1H, dd,
J = 4.2 and 8.4), 7.69(1H, dd, J = 8.0 and 7.8), 8.11(1H, dd,
J = 8.0 and 1.4), 8.26(1H, dd, J = 8.4 and 1.4), 8.60(1H, dd,
J = 7.8 and 1.4), 9.04(1H, dd, J = 1.4 and 4.2); 13C-NMR 13.80,
29.42, 49.00, 63.40, 122.22, 125.19, 128.64, 133.73, 134.31,
136.17, 136.46, 143.43, 151.39, 152.11; IR 3033, 3013, 1734,
1616, 1597, 1565, 1144 cmϪ1
.
1
1d, mp 88–89 ЊC. H-NMR 3.34–3.41(4H, m), 5.03(1H, s,
Anal. C, 43.33; H, 3.68; N, 7.08. C14H15BrN2O4S requires C,
43.42; H, 3.90; N, 7.23%.
NH), 7.49(2H, d, J = 8.8), 7.80(2H, d, J = 8.8); 13C-NMR 31.59,
44.57, 128.39, 129.50, 138.35, 139.45; IR 3388, 3029, 1588,
10c, bp 140–150 ЊC/0.35 Torr (Kugelrohr). 1H-NMR
1.30(3H, t, J = 7.2), 3.58(2H, t, J = 7.6), 4.18(2H, t, J = 7.6),
4.26(2H, q, J = 7.2), 7.12(1H, dd, J = 4.0 and 5.2), 7.70(1H, dd,
J = 1.6 and 5.2), 7.82(1H, dd, J = 4.0 and 1.6); 13C-NMR 14.17,
28.53, 48.11, 64.13, 127.03, 133.76, 134.99, 143.47, 151.80; IR
1478, 1412, 1095, 1015, 912 cmϪ1
.
HRMS m/z = 297.9268. C8H9BrClNO2S requires m/z =
297.9304.
Anal. C,32.23; H, 2.91; N, 4.69. C8H9BrClNO2S requires C,
32.18; H, 3.04; N, 4.96%.
3035, 3012, 1739, 1507, 1466, 1092, 1016 cmϪ1
.
HRMS m/z = 343.9436. (C9H1281BrNO4S2 ϩ H) requires m/z
= 343.9449.
c) N-(2-Bromoethyl)-N-methyl-arenesulfonamides.
The
N-methyl-arenesulfonamides were prepared using the same
method for arenesulfonamides but using 2-bromoethyl-methyl-
ammmonium bromide instead of 2-bromoethylammonium
bromide. Silica gel chromatography was performed using di-
chloromethane to give 1e (83%) and using dichloromethane–
hexane (2 : 1) to give 10b (73%).
e) N-(2-Bromo-1-ethoxycarbonyl)ethyl-N-ethoxycarbonyl-
arenesulfonamides. The three amides (15a, 15b, and 15c) were
prepared by the same method and the procedure for 15a is
described as an example. Into a pre-dried two-necked flask were
placed N-(2-bromo-1-ethoxycarbonyl)ethyl-4-chlorobenzene-
sulfonamide (2.2 g, 6.0 × 10Ϫ3 mol) and 9 ml dry THF, and
the mixture was treated under cooling with sodium hydride
(310 mg, 7.2 × 10Ϫ3 mol) dispersed in 3 ml THF. After hydrogen
evolution ceased, 1.20 ml (1.2 × 10Ϫ2 mol) ethyl chloroformate
was slowly added and the mixture was stirred for 100 h. After
neutralization with tartaric acid solution, the mixture was con-
densed to remove most of the THF, 30 ml water was added and
the mixture was extracted with chloroform (30 ml × 3). The
condensate of the extract was subjected to chromatography on
silica gel (10(ꢀ) × 45 cm) eluted with chloroform to give amide
15a (960 mg, 36.2%).
1
1e, mp 85–86 ЊC. H-NMR 2.86(3H, s), 3.40–3.50(4H, m),
7.52(2H, d, J = 8.4), 7.75(2H, d, J = 8.4); 13C-NMR 28.77,
36.03, 51.82, 128.62, 129.47, 136.17, 139.37; IR 3033, 1587,
1348, 1228, 1209, 1165, 1093, 994, 950 cmϪ1
.
Anal. C, 34.65; H, 3.42; N, 4.40. C9H11BrClNO2S requires C,
34.58; H, 3.55; N, 4.48%.
1
10b, mp 68–69 ЊC. H-NMR 2.90(3H, s), 3.40–3.52(4H, m),
7.14(1H, dd, J = 5.2 and 4.0), 7.59(1H, dd, J = 4.0 and 1.2),
7.62(1H, dd, J = 5.2 and 1.2); 13C-NMR 29.01, 36.43, 52.17,
127.52, 131.93, 132.14, 137.55; IR 3032, 1559, 1507, 1091, 993,
949 cmϪ1
.
1
Anal. C, 29.57; H, 3.38; N, 4.85. C7H10BrNO2S2 requires C,
29.58; H, 3.55; N, 4.93%.
15a, oil. H-NMR 1.06(3H, t, J = 7.2), 1.26(3H, t, J = 6.8),
3.95(1H, dd, J = 10.4 and 11.2), 4.10–4.17(3H, m), 4.26(2H, q,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
2502

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J = 6.8), 5.39–5.43(1H, m), 7.52(2H, d, J = 8.7), 8.05(2H, d,
J = 8.7); 13C-NMR 13.87, 14.00, 29.45, 60.71, 62.52, 64.16,
128.59, 130.73, 137.09, 140.33, 150.84, 166.88; IR 1741, 1397,
2c, oil.16 1H-NMR 2.93(2H, t, J = 6.4), 3.90(2H, t, J = 6.4),
7.36(2H, d, J = 8.0), 7.61(2H, d, J = 8.0).
1
3c, solid. H-NMR 3.28(2H, t, J = 6.0), 4.96(2H, t, J = 6.0),
1375, 1351, 1280, 1171, 1093, 1015, 854, 829 cmϪ1
.
7.63(1H, s), 7.74(1H, d, J = 8.4), 7.97(1H, d, J = 8.4); 13C-NMR
HRMS m/z = 441.9730. (C14H17ClNO6S ϩ H) requires m/z =
27.79, 69.81, 116.58, 116.73, 126.03, 131.34, 132.82, 135.48,
441.9727.
139.25; IR 3016, 2240, 1374, 1362, 1190, 1011, 957 cmϪ1
.
1
15b, oil. H-NMR 1.09(3H, t, J = 7.3), 1.23(3H, t, J = 7.3),
HRMS (EI/70eV) m/z = 209.0181. C9H7NO3S requires m/z =
3.98(1H, dd, J = 10.0 and 11.2), 4.08–4.19(3H, m), 4.24(2H, q,
J = 7.3), 5.50(1H, dd, J = 4.8 and 10.0), 7.50–7.80(2H, m), 7.91–
8.02(3H, m), 8.07(1H, dd, J = 1.8 and 8.6), 8.67(1H, d, J = 1.6);
13C-NMR 13.88, 14.07, 29.58, 60.77, 62.50, 64.06, 123.78,
127.50, 127.84, 128.41, 129.34, 129.38, 131.48, 131.57, 135.24,
135.60, 151.15, 167.13; IR 1740, 1394, 1376, 1289, 1161, 1074,
209.0147.
4c, solid. 1H-NMR 1.35(3H, t, J = 7.2), 4.21(2H, q, J = 7.2),
7.87(2H, d, J = 8.0), 8.04(2H, d, J = 8.0); 13C-NMR 14.86,
67.98, 116.94, 117.40, 128.37, 132.92, 140.55; IR 3030, 2238,
1375, 1363, 1189, 1177, 1002, 924 cmϪ1
HRMS (EI/70eV) m/z = 211.0340. C9H9NO3S requires m/z =
.
1020, 858 cmϪ1
.
211.0303.
HRMS m/z = 458.0275. (C18H20BrNO5S ϩ H) requires m/z =
6a, oil.17 1H-NMR 3.33(2H, t, J = 6.8), 3.96(2H, t, J = 6.8),
7.36(1H, d, J = 6.4), 7.41(1H, dd, J = 6.4 and 8.4), 7.46–
7.53(2H, m), 7.74(1H, d, J = 8.4), 7.85(1H, d, J = 7.6), 8.04(1H,
d, J = 8.4).
458.0273.
1
15c, oil. H-NMR 1.24(3H, t, J = 7.3), 1.25(3H, t, J = 7.1),
3.94(1H, dd, J = 10.2 and 11.2), 4.10(1H, dd, J = 4.6 and 11.2),
4.10–4.17(4H, m), 5.39(1H, dd, J = 4.6 and 10.2), 7.12(1H, dd,
J = 3.9 and 4.9), 7.71(1H, dd, J = 1.5 and 4.9), 7.90(1H, dd,
J = 1.5 and 3.9); 13C-NMR 13.93, 29.48, 61.20, 62.37, 64.22,
65.89, 126.78, 134.14, 135.68, 138.48, 151.07, 166.80; IR 1740,
1
7a. H-NMR 3.93(2H, t. J = 6.4), 4.74(2H, t, J = 6.4), 7.50–
7.59(3H, m), 7.89(1H, dd, J = 2.4 and 7.2), 8.08(1H, dd, J = 1.4
and 8.4), 8.36(1H, dd, J = 1.4 and 7.4); 13C-NMR 35.42, 72.67,
124.44, 126.79, 129.11, 129.32, 131.06, 134.78; IR 3029, 1599,
1401, 1376, 1353, 1287, 1235, 1169, 1093, 1020, 859 cmϪ1
.
1350, 1176, 1014, 908, 827 cmϪ1
.
HRMS m/z = 413.9699. (C12H16BrNO6S2 ϩ H) requires m/z =
413.9681.
HRMS m/z = 235.0425. (C12H10O3S ϩ H) requires m/z =
235.0429.
8a.18 1H-NMR 1.25(3H, t, J = 7.2), 4.09(2H, q, J = 7.2),
7.57(1H, dd, J = 8.4 and 7.6), 7.63(1H, dd, J = 8.0 and 7.2),
7.71(1H, dd, J = 8.8 and 7.2), 7.96(1H, d, J = 8.0), 8.13(1H, d,
J = 8.4), 8.29(1H, d, J = 7.6), 8.63(1H, d, J = 8.8).
Radical reaction of 2-bromoethyl-arenesulfonates
All the radical reactions were carried out under the same reac-
tion conditions described below. One of the 2-bromoethyl-
arenesulfonates (3.0 × 10Ϫ4 mol) was placed in a two-necked
flask equipped with a condenser and a rubber septum. The
vessel was then flushed with argon and dry benzene was added,
which was deaerated by bubbling argon for 30 min in an ultra-
sonic bath. Under reflux, tributyltin hydride (174 mg, 6.0 × 10Ϫ4
mol) and AIBN (24.7mg, 1.5 × 10Ϫ4mol) in 0.6 ml dry benzene
were added slowly over 9–10 h using a syringe pump, and the
mixture was heated for a further 12 h.
1
6b, oil. H-NMR 3.48(2H, t, J = 5.6), 4.01(2H, t, J = 5.6),
4.22(1H, s, OH), 7.44(1H, dd, J = 4.2 and 8.2), 7.49(1H, t,
J = 7.6), 7.58(1H, d, J = 7.6), 7.73(1H, d, J = 7.6), 8.21(1H, dd,
J = 8.2 and 1.8), 8.88(1H, dd, J = 4.2 and 1.8); 13C-NMR 36.76,
63.84, 120.84, 126.56, 128.55, 130.43, 136.90, 139.35, 146.84,
148.93; IR 3240, 1597, 1580, 1503, 1235, 949 cmϪ1
.
HRMS m/z = 147.0911. (C11H11NO ϩ H) requires m/z =
147.0919.
8b.19 1H-NMR 1.35(3H, t, J = 7.2), 4.44(2H, q, J = 7.2),
7.57(1H, dd, J = 8.4 and 4.4), 7.66(1H, dd, J = 8.0 and 7.2),
8.12(1H, dd, J = 8.0 and 1.2), 8.27(1H, dd, J = 8.4 and 1.8),
8.51(1H, dd, J = 7.2 and 1.2), 9.16(1H, dd, J = 4.4 and 1.8).
11a.20 1H-NMR 3.01(2H, t, J = 6.0), 3.79(2H, t, J = 6.0),
6.08(1H, dd, J = 3.6 and 1.2), 6.89(1H, dd, J = 3.6 and 5.2),
7.10(1H, dd, J = 5.2 and 1.2).
The reactions of sulfonates, 1a–1c, 5a, 5b, and 10a were
worked up as follows: the reaction mixture was condensed
under reduced pressure, dissolved in 10 ml ethyl acetate, treated
with 5 ml saturated aqueous potassium fluoride and 1.0 g of
powdered potassium fluoride, and stirred for 5 h at room tem-
perature. The organic layer of the reaction mixture was evapor-
ated after drying over magnesium sulfate to give the product
mixture. The mixture was passed through a short column of
silica gel using dichloromethane–hexane to remove polar by-
products. The condensed eluate was subjected to preparative
TLC developed with dichloromethane–hexane to give products
2–4, 6–8, and 11–13.
12a, solid. 1H-NMR 3.10(2H, t, J = 5.8), 4.93(2H, t, J = 5.8),
6.93(1H, d, J = 5.2), 7.57(1H, d, J = 5.2); 13C-NMR 26.12,
71.16, 126.25, 128.51, 129.65, 130.14; IR 3031, 3015, 1358, 1184
cmϪ1
.
HRMS m/z = 190.9842. (C6H6O3S ϩH) requires m/z =
190.9837.
3a, solid. 1H-NMR(90 MHz) 2.39(3H, s), 3.15(2H, t, J = 5.7),
4.87(2H, t, J = 5.7), 7.07(1H, s), 7.12(1H, d, J = 7.9), 7.72(1H, d,
J = 7.9); 13C-NMR 21.50, 28.03, 69.95, 124.96, 128.41, 129.45,
132.78, 134.12, 143.42; IR 3033, 1351, 1187, 1079, 1016, 889
13a, oil. H-NMR 1.35(3H, t, J = 7.2), 4.21(2H, q, J = 7.2),
1
7.14(1H, dd, J = 5.0 and 4.0), 7.69(1H, dd, J = 5.0 and 1.2),
7.72(1H, dd, J = 4.0 and 1.2); 13C-NMR 14.73, 67.82, 127.38,
133.31, 133.97, 136.11; IR 3032, 3016, 1509, 1373, 1180, 1093
cmϪ1
.
cmϪ1
.
HRMS m/z = 199.0404. (C9H10O3S ϩ H) requires m/z =
HRMS m/z = 193.0013. (C6H8O3S2 ϩ H) requires m/z =
192.9993.
199.0429.
4a, mp 33 ЊC.15 1H-NMR 1.30(3H, t, J = 7.0), 2.46(3H, s),
4.11(2H, q, J = 7.0), 7.33(2H, d, J = 8.5), 7.80(2H, d, J = 8.5).
2b, oil.13 1H-NMR 2.27(2H, t, J = 6.4), 3.78(2H, t, J = 6.4),
7.10(2H, d, J = 8.2), 7.21(2H, d, J = 8.2).
Radical reaction of N-(2-bromoethyl)-arenesulfonamides and
N-(2-bromoethyl)-N-methyl-arenesulfonamides
1
3b, white powder. H-NMR 3.20(2H, t, J = 6.1), 4.91(2H, t,
The reaction of 4-chlorobenzenesulfonamide 1d and N-methyl-
arenesulfonamides, 1e and 10b were worked up in the following
manner: the condensed residue from the reaction mixture was
dissolved in 5 ml dichloromethane and washed five times with
5 ml 1 M hydrochloric acid. The combined aqueous layer
was treated with 10% sodium hydroxide solution until the pH
was alkaline and extracted five times with 15 ml ethyl acetate.
Condensation of the ethyl acetate extract after drying over
magnesium sulfate gave the crude basic products. The neutral
J = 6.1), 7.30(1H, s), 7.42(1H, d, J = 8.0), 7.79(1H, d, J = 8.0);
13C-NMR 28.97, 69.99, 126.57, 128.51, 129.11, 134.06, 136.07,
138.90; IR 3035, 1593, 1565, 1474, 1373, 1358, 1186, 1010, 952
cmϪ1
.
HRMS m/z = 218.9894. (C8H7ClO3S ϩ H) requires m/z =
218.9883.
4b, white solid.14 1H-NMR 1.33(3H, t, J = 7.0), 4.15(2H, q,
J = 7.0), 7.54(2H, d, J = 8.8), 7.86(2H, d, J = 8.8).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
2503

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products (3d, 4d, 3e, 4e, 11b, and 13b) from the first dichloro-
methane extract were separated by preparative TLC using ethyl
acetate–hexane (1 : 2). We attempted to purify the basic prod-
ucts from the ethyl acetate extract by GPC (gel permeation
chromatography) using JAIGEL-1H (Japan Analytical Indus-
try) but the products were a complex mixture in most cases.
6c, solid.1H-NMR 1.24(3H, t, J = 7.2), 3.30(2H, t, J = 6.8),
3.55(2H, t, J = 6.8), 4.13(2H, q, J = 7.2), 4.72(1H, s, NH),
7.33(1H, d, J = 7.0), 7.41(1H, dd, J = 7.0 and 8.0), 7.49(1H, dd,
J = 8.0 and 7.2), 7.54(1H, dd, J = 8.0 and 7.2), 7.75(1H, d,
J = 8.0), 7.86(1H. d, J = 8.0), 8.10(1H, d, J = 8.0); 13C-NMR
14.65, 33.40, 41.57, 60.75, 123.62, 125.48, 125.68, 126.16,
126.77, 127.31, 128.79, 131.92, 133.92, 134.89, 156,67; IR 3455,
1
3d, solid. H-NMR 2.91(2H, t, J = 6.3), 3.74(2H, dt, J = 6.3
and 7.6), 4.45(1H, t, J = 7.6, NH), 7.19(1H, s), 7.30(1H, d, J =
8.4), 7.69(1H, d, J = 8.4); 13C-NMR 28.24, 41.81, 125.79,
128.10, 129.41, 136.57, 137.17, 138.17; IR 3342, 1592, 1562,
3027, 3013, 1715, 1517 cmϪ1
.
HRMS m/z = 244.1355. (C15H17NO2 ϩ H) requires m/z =
244.1337.
1471, 1401, 1338, 1327, 1169 cmϪ1
.
8c, oil. H-NMR 0.97(3H, t, J = 7.2), 1.45(3H, t, J = 7.2),
1
HRMS m/z = 218.0043. (C8H8ClNO2S ϩ H) requires m/z =
3.97(2H, q, J = 7.2), 4.12(2H, q, J = 7.2), 7.57(1H, dd, J = 8.0
and 7.6), 7.58(1H, dd, J = 8.0 and 7.2), 7.65(1H, dd, J = 8.0 and
7.2), 7.94(1H, d, J = 8.0), 8.09(1H, d, J = 8.4), 8.34(1H, d,
J = 8.0), 8.40(1H, d, J = 7.6); 13C-NMR 13.76, 15.52, 42.37,
63.16, 123.76, 123.96, 126.79, 128.17, 128.46, 129.18, 132.08,
218.0044.
1
4d,21 solid. H-NMR 3.13(3H, t, J = 7.2), 2.99–3.07(2H, m),
4.33(1H, br s, NH), 7.50(2H, d, J = 8.4), 7.81(2H, d, J = 8.4).
3e, oil. 1H-NMR 2.81(3H, s), 2.94(2H, t, J = 6.4), 3.80(2H, t,
J = 6.4), 7.18(1H, s), 7.30(1H, d, J = 8.4), 7.71(1H, d, J = 8.4);
13C-NMR 22.91, 35.14, 47.92, 126.53, 127.93, 129.16, 134.24,
136.56, 137.98; IR 3022, 3014, 1592, 1470, 1336, 1167, 1098,
134.02, 134.87, 134.97, 152.13; IR 3020, 1728, 1351, 1260 cmϪ1
.
HRMS m/z = 308.0966. (C15H17NO4S ϩ H) requires m/z =
308.0956.
977, 950 cmϪ1
.
6d, oil. H-NMR 1.19(3H, t, J = 7.0), 3.46(2H, t, J = 6.4),
1
HRMS m/z = 232.0194. (C9H10ClNO2S ϩ H) requires m/z =
3.61(2H, t, J = 6.4), 4.06(2H, q, J = 7.0), 7.41(1H, dd, J = 4.0
and 8.2), 7.48(1H, dd, J = 6.8 and 8.2), 7.59(1H, dd, J = 6.8 and
1.4), 7.71(1H, dd, J = 8.2 and 1.4), 8.15(1H, dd, J = 8.2 and 1.6),
8.93(1H, dd, J = 4.0 and 1.6); 13C-NMR 14.64, 31.80, 42.22,
60.83, 121.00, 126.43, 126.77, 128.46, 130.01, 136.54, 138.04,
232.0199.
4e, oil. 1H-NMR 1.14(3H, t, J = 7.2), 2.75(3H, s), 3.11(2H, q,
J = 7.2), 7.49(2H, d, J = 8.8), 7.73(2H, d, J = 8.8); 13C-NMR
12.86, 33.74, 44.67, 128.41, 129.01, 136.00, 138.53; IR 3027,
1587, 1476, 830 cmϪ1
.
146.89, 149.43, 156.68; IR 3451, 3026, 3010, 1700, 1517 cmϪ1
.
HRMS m/z = 234.0375. (C9H12ClNO2S ϩ H) requires m/z =
HRMS m/z = 245.1274. (C14H16N2O2 ϩ H) requires m/z =
234.0356.
245.1290.
11b.21 1H-NMR 2.40(1H, s), 2.58(3H, s), 3.07(2H, t, J = 7.6),
3.21(2H, t, J = 7.6), 6.88(1H, d, J = 3.2), 6.94(1H, dd, J = 3.2
and 5.2), 7.17(1H, d, J = 5.2).
8d, solid. 1H-NMR 0.99(3H, t, J = 7.0), 1.49(3H, t, J = 7.0),
3.98(2H, q, J = 7.0), 4.29(2H, q, J = 7.0), 7.52(1H, dd, J = 4.0
and 8.4), 7.67(1H, dd, J = 7.6 and 8.0), 8.08(1H, dd, J = 1.4 and
8.0), 8.24(1H, dd, J = 1.8 and 8.4), 8.60(1H, dd, J = 7.6 and 1.4),
9.01(1H, dd, J = 4.0 and 1.8); 13C-NMR 13.79, 15.94, 43.97,
62.82, 122.11, 125.21, 128.63, 133.63, 134.02, 136.39, 136.88,
13b, oil. 1H-NMR 1.17(3H, t, J = 7.2), 2.78(3H, s), 3.13(2H,
q, J = 7.2), 7.12(1H, dd, J = 5.2 and 4.4), 7.55(1H, dd, J = 4.4
and 1.2); 13C-NMR 12.87, 33.94, 44.92, 127.25, 131.39, 131.47,
137.39; IR 3020, 1347, 1261, 1153, 916 cmϪ1
.
143.70, 151.36, 152.59; IR 3034, 3015, 1726, 1350 cmϪ1
.
HRMS m/z = 206.0285. (C7H11NO2S2 ϩ H) reqires m/z =
206.0309.
HRMS m/z = 309.0880. (C14H16N2O4S ϩ H) requires m/z =
309.0909.
1
11c, oil. H-NMR 1.33(3H, t, J = 7.2), 3.03(2H, t, J = 8.4),
3.45(2H, t, J = 8.4), 4.11(2H, q, J = 7.2), 4.80(1H, br s, NH),
6.83(1H, dd, J = 4.4 and 1.2), 6.94(1H, dd, J = 4.4 and 6.8),
7.16(1H, dd, J = 6.8 and 1.2); 13C-NMR 14.60, 30.34, 42.23,
60.78, 123.90, 125.33, 126.99, 141.20, 156.49; IR 3451, 3027,
Radical reaction of N-(2-bromoethyl)-N-ethoxycarbonyl-
arenesulfonamides
The reactions of N-ethoxycarbonyl-sulfonamides (1d, 5c, 5d,
and 10c) were carried out in the same manner as mentioned
above and worked up as follows: the condensed reaction mix-
ture was passed through a short column of silica gel to remove
polar by-products using dichloromethane–ether and the residue
from the eluate was subjected to preparative TLC with di-
chloromethane to give products 2f, 3f, 4f, 6c, 8c, 6d, 8d, 11c,
and 13c.
3013, 1717, 1517 cmϪ1
.
HRMS m/z = 200.0733. (C9H13NO2S ϩ H) requires m/z =
200.0745.
1
13c, oil. H-NMR 1.28(3H, t, J = 7.2), 1.33(3H, t, J = 7.2),
3.91(2H, q, J = 7.2), 4.23(2H, q, J = 7.2), 7.09(1H, dd, J = 3.8
and 5.0), 7.65(1H, dd, J = 5.0 and 1.4), 7.78(1H, dd, 3.8 and
1.4); 13C-NMR 12.87, 33.94, 44.92, 127.25, 131.39, 131.47,
1
2f, solid. H-NMR 1.23(3H, t, J = 7.0), 2.78(2H, t, J = 6.8),
137.39; IR 3020, 1347, 1261, 1153, 916 cmϪ1
.
3.41(2H, t, J = 6.8), 4.10(2H, q, J = 7.0), 4.65(1H, br s, NH),
7.12(2H, d, J = 8.2), 7.27(2H, d, J = 8.2); 13C-NMR 14.61,
35.54, 41.94, 60.79, 128.70, 130.11, 132.30, 137.25, 156.52; IR
HRMS m/z = 206.0285. (C7H11NO2S2ϩH) requires m/z =
206.0309.
3455, 3026, 3014, 1717, 1517 cmϪ1
.
Radical reaction of N-(2-bromo-1-ethoxycarbonyl)ethyl-
N-ethoxycarbonyl-arenesulfonamides
HRMS m/z = 228.0800. (C11H14ClNO2 ϩ H) requires m/z =
228.0791.
1
3f, solid. H-NMR 1.37(3H, t, J = 7.2), 3.13(2H, t, J = 6.2),
The reactions of sulfonamides 15a–15c were carried out and
worked up in the same manner as the N-ethoxycarbonyl-
sulfonamides mentioned above.
4.27(2H, t, J = 6.2), 4.35(2H, q, J = 7.2), 7.30(1H, d, J = 1.6),
7.41(1H, dd, J = 8.4 and 1.6), 7.84(1H, d, J = 8.4); 13C-NMR
14.18, 27.74, 45.43, 64.29, 126.06, 128.09, 129.09, 136.63,
1
16a, oil. H-NMR 1.16(3H, t, J = 7.1), 1.17(3H, t, J = 7.1),
137.59, 138.99, 152.07; IR 3033, 3020, 1728, 1591, 1564 cmϪ1
.
2.93–3.10(2H, m), 4.03(2H, q, J = 7.1), 4.05–4.20(2H, m),
4.53(1H, dd, J = 6.4 and 13.2), 5.08(1H, NH), 7.00(2H, d,
J = 8.8), 7.18(2H, d, J = 8.8); 13C-NMR 14.18, 14.57, 37.78,
54.56, 61.21, 61.57, 128.55, 130.58, 132.87, 134.33, 155.70,
171.25; IR 3024, 1733, 1717, 1509, 1494, 1375, 1340, 1201,
HRMS m/z = 290.0235. (C11H12ClNO4S ϩ H) requires m/z =
290.0254.
1
4f, oil. H-NMR 1.21(3H, t, J = 7.2), 1.35(3H, t, J = 7.2),
3.92(2H, q, J = 7.2), 4.15(2H, q, J = 7.2), 7.49(2H, d, J = 8.8),
7.90(2H, d, J = 8.8): 13C-NMR 13.96, 15.50, 42.64, 63.41,
128.96, 129.84, 138.19, 139.99, 151.99; IR 3035, 1731, 1585
1093, 1064 cmϪ1
.
HRMS m/z = 300.1028. (C14H18NO4 ϩ H) requires m/z =
cmϪ1
.
300.1003.
1
HRMS m/z = 292.0399. (C11H14ClNO4S ϩ H) requires m/z =
17a, oil. H-NMR 1.15(3H, t, J = 6.8), 1.21(3H, t, J = 7.2),
292.0410.
1.69(3H, d, J = 7.6), 4.09–4.23(4H, m), 5.19(1H, q, J = 7.6),
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
2504

View Article Online
7.50(2H, d, J = 8.6), 7.98(2H, J = 8.6); 13C-NMR 13.91, 14.09,
17.04, 55.39, 61.79, 63.71, 128.74, 130.09, 137.56, 140.14,
151.05, 169.65; IR 3019, 1737, 1479, 1375, 1349, 1279, 1173,
References
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2 W. B. Motherwell and A. M. K. Pannell, J. Chem. Soc., Chem.
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4 S. Caddick, C. L. Shering and S. N. Wadman, Tetrahedron, 2000, 56,
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7 D. C. Harrowven, M. I. T. Nunn, N. A. Newman and D. R.
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10 (a) W. R. Bowman, H. Heaney and B. M. Jordan, Tetrahedron, 1991,
47, 10119; (b) C. Moody and C. L. Norton, J. Chem. Soc., Perkin
Trans. 1, 1997, 2639.
11 (a) A. Itai, Y. Toriumi, N. Tomioka, H. Kagechika, I. Azumaya and
K. Shudo, Tetrahedron Lett., 1989, 30, 6177; (b) I. Azumaya,
H. Kagechika, K. Yamaguchi and K. Shudo, Tetrahedron, 1995, 51,
5277.
12 Calculated using MOPAC(PM3) program in Chem 3D Ultra,
Cambridge Soft, Cambridge, MA, 2000.
13 W. F. Edgell and L. Parts, J. Am. Chem. Soc., 1955, 77, 4899.
14 K. Szabo and E. Oswald, Magy. Kem. Foly., 1954, 60, 99
(Chem. Abs., 1957, 51, 14593).
15 R. S. Tipson, M. A. Clapp and L. H. Cretcher, J. Org. Chem., 1947,
12, 133.
16 T. W. Greenlee and W. A. Bonner, J. Am. Chem. Soc., 1959, 81,
4303.
17 S. W. Pelletier and D. M. Locke, J. Am. Chem. Soc., 1957, 79,
4531; C. J. Pauchert and J. Behuke, The Aldrich Library of 13C and
1H FT-NMR, Aldrich Chemical, Milwaukee, 1992, vol. 2, spectral #
380.
1093, 1016, 855, 824 cmϪ1
.
HRMS m/z = 364.0531. (C14H18ClNO6S ϩ H) requires m/z =
364.0543.
1
16b, oil. H-NMR 1.21(6H, t, J = 7.3), 3.24–3.29(2H, m),
4.10(2H, q, J = 7.3), 4.17(2H, q, J = 7.3), 4.70(1H, dd, J = 4.4
and 14.0), 5.14(1H, d, J = 4.4, NH), 7.27(1H, dd, J = 4.0 and
8.4), 7.43–7.49(3H, m); 13C-NMR 14.17, 14.58, 38.56, 54.73,
61.15, 61.53, 121.89, 125.64, 126.05, 127.24, 127.46, 127.55,
128.01, 132.37, 133.29, 155.79, 171.55; IR 3431, 3027, 1717,
1509, 1376, 1340, 1234, 1198, 1064, 1033, 864 cmϪ1
.
HRMS m/z = 380.1130. (C18H21NO2 ϩ H) requires m/z =
380.1168.
17b, 1H-NMR 1.08(3H, t, J = 6.8), 1.17(3H, t, J = 6.8),
1.73(3H, d, J = 6.8), 4.03–4.12(2H, m), 4.13–4.21(2H, m),
5.28(1H, q, J = 6.8), 7.59–7.70(2H, m), 7.90–8.02(4H, m),
8.62(1H, d, J = 1.2); 13C-NMR 13.89, 14.08, 17.04, 55.31, 61.70,
63.56, 123.14, 127.48, 127.83, 128.61, 129.20, 129.33, 131.66,
135.13, 136.02, 151.21, 169.79; IR 3019, 1739, 1736, 1375, 1346,
1170, 860 cmϪ1
.
HRMS m/z = 316.1514. (C18H21NO6S ϩ H) requires m/z =
316.1549.
16c, oil.1H-NMR 1.25(3H, t, J = 7.2), 1.28(3H, t, J = 6.8),
3.37(2H, d, J = 4.8), 4.13(2H, q, J = 7.2), 4.20(2H, q, J = 7.2),
4.59–4.66(1H, m), 5.28(1H, d, J = 8.0), 6.81(1H, dd, J = 1.2 and
3.6), 6.93(1H, dd, J = 3.6 and 4.8), 7.17(1H, dd, J = 1.2 and 4.8);
13C-NMR 14.56, 14.99, 32.85, 54.89, 61.58, 62.07, 125.12,
127.07, 127.25, 137.54, 156.11, 171.23; IR 3432, 3028, 1734,
1507, 1376, 1339, 1236, 1196, 1064, 701 cmϪ1
.
HRMS m/z = 272.0950. (C12H17NO4S ϩ H) requires m/z =
272.0957.
1
17c, oil. H-NMR 1.09(3H, t, J = 7.2), 1.15(3H, t, J = 6.8),
1.60(3H, d, J = 7.2), 4.06(2H, q, J = 7.2), 4.08–4.18(2H, m),
5.08(1H, q, J = 7.2), 7.04(1H, dd, J = 1.2 and 3.4), 7.63(1H, dd,
J = 3.4 and 5.1), 7.77(1H, dd, J = 1.2 and 5.1); 13C-NMR 13.92,
13.95, 16.89, 55.91, 61.59, 63.70, 126.77, 133.54, 134,92, 138.95,
151.18, 169.49; IR 3027, 1740, 1735, 1376, 1261, 1172, 1093,
18 A. A. Spryskov, Zh. Obshch. Khim., 1946, 16, 1060 (Chem. Abs.,
1947, 41, 2720) (Engl. Transl. S. 2126).
19 G. E. McCashland, J. Org. Chem., 1946, 11, 277.
20 F. F. Blicke and J. H. Burckhalter, J. Am. Chem. Soc., 1942, 64,
47; C. J. Pauchert, and J. Behuke, The Aldrich Library of 13C and 1H
FT-NMR, Aldrich Chemical, Milwaukee, 1992, vol. 3, spectral #
50.
1019, 859 cmϪ1
.
HRMS m/z = 336.0573. (C12H17NO6S2 ϩ H) requires m/z =
336.0576.
21 J. Grigorowski, Zh. Obshch., Khim., 1958, 27, 531 (Engl. Transl.
Acknowledgements
S. 601).
This study was supported by the Annual Project Program
(2001A-097 and 2002B-019) of Waseda University.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 9 9 – 2 5 0 5
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