Novell synthesis of α-amino carboxamides and their related compounds via α-oxo sulfones starting from 2,2-disulfonyloxiranes

Article abstract of DOI:10.1246/bcsj.77.1897

2-(Methylsulfonyl)-2-(p-tolylsulfonyl)oxiranes 1 are easily prepared by the condensation of methylthiomethyl p-tolyl sulfone (MT-sulfone) with aldehydes and the subsequent oxidation with MCPBA. They smoothly reacted with 2 molar amounts of primary or seco

Full text of DOI:10.1246/bcsj.77.1897

ꢀ 2004 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 77, 1897–1903 (2004) 1897
Novel Synthesis of ꢀ-Amino Carboxamides and Their Related
Compounds via ꢀ-Oxo Sulfones Starting from 2,2-Disulfonyloxiranes
ꢀ
Shoji Matsumoto, Michiko Ishii,1 Kazuto Kimura,1 and Katsuyuki Ogura
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University,
1-33 Yayoicho, Inage-ku, Chiba 263-8522
1Graduate School of Science and Technology, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522
Received April 12, 2004; E-mail: katsuyuki@faculty.chiba-u.jp
2-(Methylsulfonyl)-2-(p-tolylsulfonyl)oxiranes 1 are easily prepared by the condensation of methylthiomethyl p-
tolyl sulfone (MT-sulfone) with aldehydes and the subsequent oxidation with MCPBA. They smoothly reacted with 2
molar amounts of primary or secondary amines to give ꢀ-amino carboxamides in high yield. This reaction can be suit-
ably extended to the reaction with one molar amount of 1,n-diaminoalkanes (n ¼ 2, 3, or 4) to form the corresponding
2,5-diazacyclohexanone, 2,6-diazacycloheptanone, or 2,7-diazacyclooctanone, respectively. The reaction of 1 with some
related compounds having two nucleophilic sites are also described.
Epoxides are versatile intermediates in organic synthesis.1
Thus, various synthetic routes via the epoxides have been de-
veloped for preparing biologically active natural products and
medical supplies.2,4a The epoxides undergo many kinds of re-
action, such as ring-opening with a nucleophile,3 acid-promot-
ed rearrangement,4 and introduction of a substituent on their
ring that is achieved by deprotonation and the subsequent reac-
tion with an electrophile.5 The easy ring-opening reaction with
various nucleophiles to produce glycols, 2-aminoethanols, and
2-sulfanylethanols seems to result from high strain of the ring.
When an electron-withdrawing group (EWG) is situated on the
ring, the attack of a nucleophile is generally followed by elim-
ination of the EWG to produce a carbonyl compound II, as de-
picted in Eq. 1. Thus, the epoxides having cyano, nitro, sulfon-
yl, or sulfinyl group are reported to give the corresponding car-
bonyl derivatives.6
If another group (Y) of the epoxide I in Eq. 1 has good leav-
ing ability, the resultant carbonyl derivative II would be re-
garded as an active form of a carboxylic acid. This is the case
when the epoxide having two cyano groups (I; EWG =
Y = CN) reacts with a nucleophile.7 Some researchers report-
ed that 2,2-dicyanooxiranes react with halide ion to give ꢀ-hal-
oacyl cyanides that are converted to ꢀ-halo carboxamides7f,g
or ꢀ-halo hydroxamic acids7e,h by successive treatment with
amines or hydroxylamine derivatives. An optically active ke-
tene dithioacetal S,S0-dioxide (I; EWG + Y = –SO–(CH2)3–
SO–) was reported to react with an amine.8 In this reaction,
the corresponding intermediate II would undergo further reac-
tion with the amine to give an ꢀ-amino carboxamide.
Against such background, our investigation on the reaction
of 2,2-bis(alkyl- or arylsulfonyl)oxiranes with a nucleophile
was initiated in expectation of developing a novel method
for preparing ꢀ-oxo sulfones III (Eq. 2).
Some ꢀ-oxo sulfones bearing electron-donating group(s)
such as OR or NRR0 as well as ꢀ-oxo sulfones bearing two ar-
yl groups at both ends have been reported.9 These ꢀ-oxo sul-
fones could be synthesized by oxidation of the corresponding
ꢀ-oxo sulfides or ozonolysis of ꢀ-diazo sulfones. However,
no aliphatic ꢀ-acyl sulfone has appeared in the literature. Since
the corresponding aliphatic ꢀ-acyl sulfoxides were reported to
exhibit significant reactivity toward various nucleophiles,10 it
is likely that the ꢀ-oxo sulfones are too reactive to be isolated.
Here, we wish to report an efficient preparation of acyclic and
cyclic ꢀ-amino carboxamides and their related compounds by
the use of the reactivity of the ꢀ-oxo sulfones that are formed
by the reaction of 2-(methylsulfonyl)-2-(p-tolylsulfonyl)oxi-
ranes 1 with nucleophiles (Scheme 1).
Results and Discussion
Previously, we reported that 2-(methylsulfonyl)-3-phenyl-2-
(p-tolylsulfonyl)oxirane (1; R = Ph) was produced by oxida-
tion of the corresponding ketene dithioacetal S,S-dioxide, de-
rived from methylthiomethyl p-tolyl sulfone (MT-sulfone;
2)11 and benzaldehyde, with an excess amount of m-chloroper-
benzoic acid (MCPBA).12 In addition, some epoxides having
two sulfonyl groups were reported by other researchers, but
their reactivity was not examined well.13,14 According to the
procedure described in our previous paper, various 2-(methyl-
sulfonyl)-2-(p-tolylsulfonyl)oxiranes 1 were prepared by the
EWG
O
R
R
O
Y
O
ð1Þ
ð2Þ
R
EWG
Y
O
Nuc
Nuc
SO Me
2
R
O
Nuc
I
II
HNR'R''
Y
HNR'R''
O
R
R
NR'R''
Ts
R''R'N
SO R'''
O
2
R
O
R
SO R''
2
1
R''R'N
O
(Ts = p-TolSO2)
SO R''
2
R
SO R'
Nuc
SO R'
2
2
Nuc
III
SO R'
Nuc
2
Scheme 1.
Published on the web October 9, 2004; DOI 10.1246/bcsj.77.1897

1898 Bull. Chem. Soc. Jpn., 77, No. 10 (2004)
Reaction of 2,2-Disulfonyloxiranes with Amines
Table 1. Preparation of 2,2-Disulfonyloxiranes (1)
1) TMSCl, n-BuLi
O
SO Me
2
O
Et
Bn
+
Bn-NH
2
Et
SMe
SMe
N
CDCl
3
Ts
2) R-CHO
H
1 (R=Et) (1 mol. amt.)
R
NH
+
Ts
Ts
2
Bn
THF
5
3
-78 °C
1 (R=Et)
MCPBA (3 mol. amt.)
O
SO Me
2
(K CO )
2
3
O
Et
R
CHCl
SO R'
3
2
Ts
rt
1
NH
Bn
(R'=Me or p-Tol)
4
Entry
R
Yield of 3/%
Yield of 1/%
Scheme 2.
1
2
3
4
5
6
7
8
Ph
p-Br–C6H4
94
93
84
89
p-MeOCO–C6H4
m-MeO–C6H4
p-Me–C6H4
1-Naphthyl
Et
89
72
64
59
96
100
quant.
93
complex mixture
2-aminobutanamide (5 in Scheme 2) was observed, even
though most of the starting epoxide remained unchanged. This
suggests that the expected ꢀ-oxo sulfone 4 reacts with benzyl-
amine much faster than the starting epoxide. Hence, we decid-
ed to employ more than 2 molar amounts of an amine in the
reaction with 1.
complex mixture
81
87
i-Pr
To a solution of 1 (R = Ph) in chloroform was added 2.7
molar amounts of morpholine, and the resulting mixture was
stirred for 24 h at room temperature. By evaporation and col-
umn chromatography on silica gel, 4-(2-morpholino-2-phenyl-
acetyl)morpholine was obtained in 77% yield (Table 2, entry
1). Since 4-(p-tolylsunfinyl)morpholine15 and 4-(methylsulfi-
nyl)morpholine were also detected among the reaction mixture
components (30% and 10%, respectively), morpholine was
shown to work not only as a nucleophile, but also as a trapping
reagent of the by-products, such as p-toluenesulfinic acid and
methanesulfinic acid.16 This is the reason why an excess
amount of morpholine improves the yield of 5 (entry 2). Inter-
estingly, the present reaction is applicable to various primary
and secondary amines, as shown in Table 2 (entries 3 and
4). Aniline also reacted with 1 to give the corresponding 5 (en-
try 5), though it has lower nucleophilicity.17 The reaction with
1 (R = i-Pr) required a long period of time to complete the re-
action, probably because of the steric hindrance of the isoprop-
yl group against the attack of the amine (entries 10 and 11).
olefination of 2 with aliphatic and aromatic aldehydes, fol-
lowed by oxidation with 3 molar amounts of MCPBA. The
results are summarized in Table 1. It should be noted that
the oxidation of 3 to give 1 was accelerated by coexisting
K2CO3 (0.5 mol. amt.). The oxiranes were obtained as a single
stereoisomer by recrystallization. The 2,2-disulfonyloxiranes
having an electron-rich aromatic residue as R (for example,
p-tolyl and 1-naphthyl groups in entries 5 and 6, respectively)
were too reactive to be isolated in a pure form by column chro-
matography.
With various 2,2-disulfonyloxiranes in hand, we tested the
reaction of the epoxide using benzylamine as a nucleophile
in an NMR tube. About one equimolar amount of benzylamine
was added to a solution of 1 (R = Et) in CDCl3 and the reac-
tion progress was monitored by 1H NMR. The reaction started
at an ambient temperature, but we could not detect any signal
corresponding to the ꢀ-oxo sulfone 4 that would be formed as
an intermediate. Instead, a smooth formation of N,N0-dibenzyl-
Table 2. Reaction of 1 with Amines
O
R'
+ HN
R''
SO Me
2
R
R'
O
N
R
CHCl
rt
15 h
Ts
N
R''
3
R''
R'
5
1
Mol. amt.
of amine
Entry
R
R0
R00
Yield of 5/%
1a)
2
3
4
5
6
7
8
Ph
–(CH2)2–O–(CH2)2–
2.7
4.2
4.1
4.0
4.1
4.1
4.1
4.1
4.0
4.0
4.0
77 (quant.)b,c)
97
99
84
48c)
95
98
quant.
85
66 (95)b)
82 (96)b)
Bn
Bn
Ph
Bn
H
Me
H
p-Br–C6H4
p-MeOCO–C6H4
m-MeO–C6H4
H
9
10
11d)
Et
i-Pr
a) Reacted for 24 h. b) Value in parenthesis was shown the yield based on the consumption of 1. c)
Tolyl- and methylsulfinylamides were observed. d) Reacted for 72 h.

S. Matsumoto et al.
Bull. Chem. Soc. Jpn., 77, No. 10 (2004) 1899
Table 4. Formation of Various Cyclic Compounds from 1
O
O
SO Me
2
SO Me
2
O
R
R
O
2
R
Ts
SO R
2
SO Me
Ts
2
H-Nuc
H-Nuc'
7
R
O
NH
+
N
Nuc'
R
R''
CHCl
rt
R'
R''
4
R'
R''
3
Ts
HN
Nuc
R'
1
NH
R''
1
HOS(O)R
R'
Mol. amt. Additive
fast
Time h
Yield %
Entry
R
Product
2
of 7
(Mol. amt.)
HOS(O)R
O
1
2
(R , R =Me or p-Tol)
O
NaOHa)
(1.1)
R
R''
N
R
1
2
Ph
Et
1.2
3
81
88
NH
N
R'
O
R'
R''
5
NaOHa)
(1.1)
1.2
3.5
8
Scheme 3.
O
DBU
(2.2)
3
4
Ph
Et
1.1
1.1
0.5
0.5
59
66
R
S
Table 3. Reaction of 1 with Diamines
S
DBU
(2.2)
9
O
SO Me
2
O
R
O
H N
2
+
NH
n
Et
R
R
NH
2
DBU
(2.2)
S
CHCl
Ts
n
3
5
Et
1.1
0.5
25
HN
1
rt
S
6
10
O
Mol. amt.
of diamine
NEt3
(3.5)
Entry
R
n
Time/h
Yield of 6/%
6
7
Ph
Et
1.5
1.5
0.5
0.5
88
97
S
S
1
2
3
4
5
6
7
Ph
1
2
3
3
1
2
3
3.6
2.5
2.0
1.2
3.9
2.5
2.5
24
14
15
25
50
21
4
90
96
trace
31
92
92
72
NEt3
(3.0)
11
O
Et
Et
NH
NEt3
(1.1)
8
Et
1.1
2
57
S
12
As mentioned above, the attack of amine to the intermediary
ꢀ-oxo sulfone 4 is much faster than its attack to the starting
oxirane 1 (Scheme 3). This phenomenon would be favorably
utilized for synthesizing cyclic ꢀ-amino carboxamides, i.e.,
ꢀ-azalactams 6, from 1 and 1,!-diaminoalkanes: in this reac-
tion, the intermediary ꢀ-oxo sulfone has one amino group,
which can react intramolecularly with the carbonyl part to
give 6.
a) Reacted in THF.
butane to a 0.03 M solution of 1 (R = Et). Thus, the present
reaction system was shown to be suitable for the ꢀ-azalactam
formation.
Furthermore, we succeeded in the formation of various cy-
clic compounds from 1 and the reagents 7 having two different
nucleophilic sites, as summarized in Table 4. To achieve the
nucleophilic attack by OH or SH group, the addition of a base
was effective to promote the reaction.
In summary, we examined the reactivity of 2,2-disulfonyl-
oxiranes 1 toward various amines. A double nucleophilic addi-
tion occurred smoothly to give the ꢀ-amino carboxamide in
good yield. Especially, cyclic ꢀ-azalactams and their related
compounds were effectively formed from various reagents
having two nucleophilic sites.
In fact, the expected 2,5-diazacyclohexanone (3-azapenta-
nelactam) (6; R = Ph, n ¼ 1) was afforded in 90% yield when
3.6 molar amounts of ethylenediamine was added to a 0.03 M
(1 M = 1 mol dmꢁ3) solution of 1 (R = Ph) in chloroform and
the resulting solution was stirred at room temperature. Analo-
gously, 3-azahexanelactam (6; R = Ph, n ¼ 2) was obtained in
96% yield in the reaction of propylenediamine and 1
(R = Ph). Other results are summarized in Table 3. Although
the formation of an eight-membered ring from an acyclic sys-
tem is usually a process of great difficulty,18 we tried to pre-
pare an eight-membered 3-azaheptanelactam (6; n ¼ 3). In
the reaction of 1 (R = Ph) under conditions similar to those
of the above reactions using an excess amount (2 mol. amt.)
of 1,4-diaminobutane, the expected 6 was formed in trace
amounts, but we obtained a large amount of insoluble oligo-
mer-like solid. This was the expected result. To our delight,
6 (R = Ph; n ¼ 3) was produced as a major product (31%
yield) when 1.2 molar amount of 1,4-diaminobutane was drop-
wise added to the solution of 1 (R = Ph) (entry 4). Notably,
the eight-membered 3-azaheptanelactam (6; R = Et, n ¼ 3)
was formed in 72% yield by dropwise addition of 1,4-diamino-
Experimental
General. Melting points were determined with a Yanaco MP-
1
J3 and values were uncorrected. H NMR measurement was per-
formed on a Varian GEMINI 300 (300 MHz) spectrometer. Chem-
ical shifts (ꢁ) of 1H NMR were expressed in parts per million
downfield from tetramethylsilane as an internal standard
(ꢁ ¼ 0). Multiplicities are indicated as br (broadened), s (singlet),
bs (broadened singlet), d (doublet), t (triplet), q (quartet), quint
(quintet), sept (septet), and m (multiplet). Coupling constants (J)
are reported (Hz). Infrared (IR) spectra were recorded on JASCO
A-202 or JASCO FT/IR-350 spectrometers. Elemental analyses
(EA) and high-resolution mass spectroscopy (HRMS) were carried
out by the Chemical Analysis Center of Chiba University. Analyt-

1900 Bull. Chem. Soc. Jpn., 77, No. 10 (2004)
Reaction of 2,2-Disulfonyloxiranes with Amines
ical thin-layer chromatography (TLC) was performed on glass
plates pre-coated with silica gel (Merck Kieselgel 60 F254, layer
thickness 0.25 mm). Visualization was accomplished by UV light
(254 nm) and anisaldehyde or iodine. Column chromatography
was performed on a Merck Silica Gel 60 (70–230 mesh). Prepara-
tive GPC was performed on JAIGEL-1H and 2H with a LC-908
(Japan Analytical Industry, Co. Ltd.). Commercially available ma-
terials were purchased from Aldrich Chemical Co., Tokyo Kasei
Chemical Industry Co., Wako Pure Chemical Co., Kanto Chemi-
cal Co., and Nacalai Tesque Inc. and no further purification was
employed except for otherwise noted. Tetrahydrofuran (THF)
was distilled from sodium diphenylketyl immediately prior to
use. Chloroform was distilled after being treated with K2CO3.
The reaction was performed under nitrogen atmosphere unless
otherwise noted.
the resulting mixture was stirred for 10 h. After addition of 10%
aqueous solution of NaHSO3 (5 mL) and 30% aqueous solution
of K2CO3 (10 mL), the mixture was extracted with chloroform
(20 mL ꢃ 3). The combined extract was dried with Na2SO4 and
evaporated to give a colorless oil. This was subjected to column
chromatography on SiO2 (hexane:ethyl acetate = 3:1) to give
trans-2-(4-bromophenyl)-3-(methylsulfonyl)-3-(p-tolylsulfonyl)-
oxirane (1; R = p-Br–C6H4) (0.762 g, 1.78 mmol; 89% yield) as
colorless plate crystals. The product was furthermore purified by
recrystallization from mixture of hexane and ethyl acetate: mp
121.0–122.0 ꢂC (dec.); 1H NMR (CDCl3) ꢁ 2.49 (s, 3H), 2.90
(s, 3H), 5.24 (s, 1H), 7.35 (d, 2H, J ¼ 8:5 Hz), 7.41 (d, 2H, J ¼
8:4 Hz), 7.55 (d, 2H, J ¼ 8:7 Hz), 7.93 (d, 2H, J ¼ 8:4 Hz); IR
(KBr) 3008, 1593, 1489, 1309, 1188, 1149, 1117, 812, 675,
596, 536, 511 cmꢁ1. Anal. Found: C, 44.55; H, 3.41%. Calcd
for C16H15BrO5S2: C, 44.55; H, 3.51%.
Preparation of Epoxides. To a solution of methylthiomethyl
p-tolyl sulfone (5.01 g, 23.7 mmol) in THF (100 mL) ꢂwas added
trimethylsilyl chloride (6.45 mL, 51.1 mmol) at ꢁ78 C. To the
resulting solution was dropwise added butyllithium (1.6 M in hex-
ane, 43.5 mL, 69.6 mmol) and this mixture was stirred for 75 min
at that temperature. Then, freshly distilled propanal (1.85 mL,
25.8 mmol) was added and the reaction mixture was stirred for
1.5 h. After the addition of saturated aqueous solution of NH4Cl
(5 mL) and water (50 mL), the mixture was extracted with diiso-
propyl ether (50 mL ꢃ 3). The combined extracts were washed
with brine, dried with MgSO4 and evaporated to give a colorless
oil. These were subjected to column chromatography on SiO2
(hexane:ethyl acetate = 4:1) to give (E)-1-methylthio-1-(p-tolyl-
sulfonyl)-1-butene (5.64 g, 22.0 mmol; 96% yield) as a colorless
oil. To a solution of the thus-obtained (E)-1-methylthio-1-(p-tolyl-
sulfonyl)-1-butene (3.00 g, 11.7 mmol) in chloroform (200 mL)
was added m-chloroperbenzoic acid (70 wt %, 10.1 g, 40.9 mmol)
trans-2-(4-Methoxycarbonylphenyl)-3-(methylsulfonyl)-3-
(p-tolylsulfonyl)oxirane (1; R = p-MeOCO–C6H4). The titled
compound was prepared in 89% overall yield (two steps) accord-
ing to a procedure similar to that mentioned above: white powder;
1
mp 178.5–178.9 ꢂC (dec.); H NMR (CDCl3) ꢁ 2.49 (s, 3H), 2.90
(s, 3H), 3.93 (s, 3H), 5.32 (s, 1H), 7.42 (d, 2H, J ¼ 8:1 Hz), 7.55
(d, 2H, J ¼ 8:1 Hz), 7.94 (d, 2H, J ¼ 8:4 Hz), 8.08 (d, 2H, J ¼
8:5 Hz); IR (KBr) 3005, 2925, 1720, 1435, 1344, 1288, 1161,
1111, 756, 675, 598, 538 cmꢁ1. Anal. Found: C, 52.60; H,
4.38%. Calcd for C18H18O7S2: C, 52.67; H, 4.42%.
trans-2-(3-Methoxylphenyl)-3-(methylsulfonyl)-3-(p-tolyl-
sulfonyl)oxirane (1; R = m-MeO–C6H4). The titled compound
was prepared in 67% overall yield (two steps) according to a pro-
cedureꢂsimilar to that mentioned above: white powder; mp 102.1–
1
103.0 C; H NMR (CDCl3) ꢁ 2.48 (s, 3H), 2.85 (s, 3H), 3.80 (s,
3H), 5.29 (s, 1H), 6.94 (dd, 1H, J ¼ 2:3, 8.2 Hz), 7.01 (diffused s,
1H), 7.06 (dm, 1H, J ¼ 7:6 Hz), 7.32 (t, 1H, J ¼ 8:0 Hz), 7.40 (d,
2H, J ¼ 8:5 Hz), 7.94 (dm, 2H, J ¼ 8:5 Hz); IR (KBr) 3003,
2837, 1597, 1495, 1338, 1255, 1151, 1122, 1039, 661, 602, 532
cmꢁ1. Anal. Found: C, 53.26; H, 4.64%. Calcd for C17H18O6S2:
C, 53.39; H, 4.74%.
trans-2-Isopropyl-3-(methylsulfonyl)-2-(p-tolylsulfonyl)oxi-
rane (1; R = i-Pr). The titled compound was prepared in 78%
overall yield (two steps) according to a procedure similar to that
mentioned above: colorless cubic crystals; mp 153.1–153.9 ꢂC;
1H NMR (CDCl3) ꢁ 1.02 (d, 3H, J ¼ 6:9 Hz), 1.16 (d, 3H, J ¼
6:6 Hz), 2.40–2.53 (m, 1H), 2.47 (s, 3H), 3.29 (s, 3H), 3.70 (d,
1H, J ¼ 9:8 Hz), 7.38 (d, 2H, J ¼ 8:5 Hz), 7.85 (d, 2H, J ¼ 8:4
Hz); IR (KBr) 3016, 2979, 2931, 1469, 1340, 1147, 985, 764,
660, 542, 505 cmꢁ1. Anal. Found: C, 48.91; H, 5.77%. Calcd
for C13H18O5S2: C, 49.04; H, 5.70%.
ꢂ
at 0 C. The resulting mixture was gradually warmed up to room
temperature and then stirred for 39 h. After addition of 10% aque-
ous solution of NaHSO3 (10 mL) and 30% aqueous solution of
K2CO3 (30 mL), the mixture was extracted with chloroform
(100 mL ꢃ 3). The combined extract was dried with Na2SO4
and evaporated to give a colorless oil. This was subjected to col-
umn chromatography on SiO2 (hexane:ethyl acetate = 2:1) fol-
lowed by recrystallization from a mixture of hexane and ethyl ace-
tate to give trans-2-ethyl-3-(methylsulfonyl)-3-(p-tolylsulfonyl)-
oxirane (1; R = Et) (2.88 g, 9.48 mmol; 81% yield) as colorless
crystals: mp 138.0–139.0 ꢂC; 1H NMR (CDCl3) ꢁ 1.16 (t, 3H, J ¼
7:5 Hz), 1.99–2.21 (m, 2H), 2.47 (s, 3H), 3.28 (s, 3H), 4.01 (dd,
1H, J ¼ 7:8, 5.0 Hz), 7.38 (d, 2H, J ¼ 8:3 Hz), 7.86 (d, 2H, J ¼
8:5 Hz); IR (KBr) 1596, 1338, 1138, 1115, 1086, 998, 812, 766,
660, 559, 575, 541, 500, 471 cmꢁ1. Anal. Found: C, 47.19; H,
5.25%. Calcd for C12H16O5S2: C, 47.35; H, 5.30%.
trans-2-(Methylsulfonyl)-3-phenyl-2-(p-tolylsulfonyl)oxirane
(1; R = Ph).12 The titled compound was prepared in 79% over-
all yield (two steps) according to a procedure similar to that men-
tioned above: colorless crystals; 1H NMR (CDCl3) ꢁ 2.49 (s, 3H),
2.84 (s, 3H), 5.31 (s, 1H), 7.39–7.50 (m, 7H), 7.94 (d, 2H, J ¼ 8:4
Hz).
trans-2-(4-Bromophenyl)-3-(methylsulfonyl)-3-(p-tolylsulfo-
nyl)oxirane (1; R = p-Br–C6H4). To a solution of (E)-1-(4-bro-
mophenyl)-2-methylthio-2-(p-tolylsulfonyl)ethene (0.763 g, 2.00
mmol), prepared according to a procedure similar to that men-
tioned above, in chloroform (20 mL) was added m-chloroperben-
zoic acid (70 wt %, 1.594 g, 6.46 mmol) at 0 ꢂC. The resulting
mixture was gradually warmed up to room temperature and then
stirred for 7 h. After addition of K2CO3 (0.140 g, 1.00 mmol),
Reaction with Amines. To a solution of trans-2-(methylsul-
fonyl)-3-phenyl-2-(p-tolylsulfonyl)oxirane (1; R = Ph) (0.177 g,
0.50 mmol) in chloroform (17 mL) was added morpholine (190
mL, 2.1 mmol) at room temperature. After the solution was stirred
for 15 h, the resulting mixture was evaporated to give a colorless
oil. This was subjected to column chromatography on SiO2 (ethyl
acetate) to give 4-(2-morpholino-2-phenylacetyl)morpholine (5;
R = Ph, R0 = R00 = –(CH2)2–O–(CH2)2–) (0.142 g, 0.49 mmol;
1
97% yield) as a colorless oil: H NMR (CDCl3) ꢁ 2.45–2.59 (m,
4H), 3.11–3.78 (m, 12H), 4.22 (s, 1H), 7.28–7.42 (m, 5H); IR
(neat) 2960, 2854, 1650, 1452, 1278, 1227, 1116, 1069, 1011,
879, 752 cmꢁ1. HRMS (FAB): m=z 291.1717 ([M þ H]þ). Calcd
for C16H23N2O3: m=z 291.1709.
N-Benzyl-2-(benzylamino)-2-phenylacetamide (5; R = Ph,
R0 = Bn, R00 = H). A colorless oil: 1H NMR (CDCl3) ꢁ 2.78

S. Matsumoto et al.
Bull. Chem. Soc. Jpn., 77, No. 10 (2004) 1901
(bs, 1H), 3.74 (d, 1H, J ¼ 13:2 Hz), 3.79 (d, 1H, J ¼ 13:2 Hz),
4.34 (s, 1H), 4.43 (d, 2H, J ¼ 6:0 Hz), 7.18–7.40 (m, 15H),
7.55 (t(br), 1H, J ¼ 6:0 Hz); IR (neat) 3309, 3061, 3029, 1658,
1519, 1496, 1454, 1028, 734, 698 cmꢁ1. HRMS (FAB): m=z
331.1815 ([M þ H]þ). Calcd for C22H23N2O: m=z 331.1810.
N-Benzyl-N-methyl-2-[benzyl(methyl)amino]-2-phenylacet-
Calcd for C18H23N2O: m=z 283.1810. Anal. Found: C, 72.55; H,
7.47; N, 9.28%. Calcd for C18H22N2O + 0.15CHCl3: C, 72.60;
H, 7.43; N, 9.33%.
N-Benzyl-2-(benzylamino)isovaleramide (5; R = i-Pr, R0 =
Bn, R00 = H). A colorless oil: 1H NMR (CDCl3) ꢁ 0.90 (d,
3H, J ¼ 6:9 Hz), 0.97 (d, 3H, J ¼ 7:0 Hz), 1.61 (bs, 1H), 2.16
(dsept, 1H, J ¼ 4:5, 6.9 Hz), 3.03 (d, 1H, J ¼ 4:5 Hz), 3.64 (d,
1H, J ¼ 13:1 Hz), 3.74 (d, 1H, J ¼ 13:1 Hz), 4.47 (d, 2H, J ¼
5:9 Hz), 7.19–7.37 (m, 10H), 7.55 (bs, 1H); IR (neat) 3311,
3030, 2960, 1647, 1522, 1454, 1232, 1078, 1028, 735, 698
cmꢁ1. Anal. Found: C, 76.71; H, 8.04; N, 9.40%. Calcd for
C19H24N2O: C, 76.99; H, 8.16; N, 9.45%.
amide (5; R = Ph, R0 = Bn, R00 = Me).
A colorless oil:
1H NMR (CDCl3) ꢁ 2.37 (s, 1.8H), 2.72 (s, 1.8H), 3.69 (d,
0.6H, J ¼ 13:5 Hz), 3.88 (d, 0.6H, J ¼ 13:5 Hz), 4.56 (d, 0.6H,
J ¼ 14:6 Hz), 4.65 (s, 0.6H), 4.72 (d, 0.6H, J ¼ 14:4 Hz), 7.21–
7.47 (m, 9H); amide rotamer: ꢁ 2.30 (s, 1.2H), 3.00 (s, 1.2H),
3.49 (d, 0.4H, J ¼ 13:6 Hz), 3.81 (d, 0.4H, J ¼ 13:6 Hz), 4.19
(d, 0.4H, J ¼ 16:8 Hz), 4.58 (d, 0.4H, J ¼ 16:9 Hz), 4.66 (s,
0.4H), 6.99 (diffused d, 0.8H, J ¼ 7:7 Hz), 7.21–7.47 (m, 5.2H);
IR (neat) 3028, 2931, 1653, 1493, 1452, 1400, 1254, 1209,
1107, 1028, 737, 698 cmꢁ1. Anal. Found: C, 80.30; H, 7.41; N,
7.76%. Calcd for C24H26N2O: C, 80.41; H, 7.31; N, 7.81%.
N-Phenyl-2-anilino-2-phenylaceticamide (5; R = Ph, R0ꢂ =
Ph, R00 = H). A colorless spherical solid: mp 143.0–144.0 C;
1H NMR (CDCl3) ꢁ 4.48 (bs, 1H), 4.83 (d, 1H, J ¼ 2:1 Hz),
6.72 (diffused d, 2H, J ¼ 7:7 Hz), 6.86 (t, 1H, J ¼ 7:3 Hz),
7.11 (t, 1H, J ¼ 7:4 Hz), 7.23 (diffused t, 2H, J ¼ 7:4 Hz), 7.30
(diffused t, 2H, J ¼ 7:6 Hz), 7.36–7.44 (m, 3H), 7.50 (diffused
d, 2H, J ¼ 8:1 Hz), 7.53 (diffused d, 2H, J ¼ 7:6 Hz), 8.74 (bs,
1H); IR (KBr) 3406, 3315, 3053, 3022, 1672, 1603, 1520, 1502,
1441, 1313, 1265, 750, 690 cmꢁ1. Anal. Found: C, 79.39; H,
6.02; N, 9.30%. Calcd for C20H18N2O: C, 79.44; H, 6.00; N,
9.26%.
Reaction with Diamines. To a solution of trans-2-(methylsul-
fonyl)-3-phenyl-2-(p-tolylsulfonyl)oxirane (1; R = Ph) (0.103 g,
0.292 mmol) in chloroform (10 mL) was dropwise added ethyl-
enediamine (70 mL, 1.0 mmol) at room temperature. After being
stirred for 24 h, saturated aqueous solution of NaHCO3 and brine
were added and the resulting mixture was extracted with chloro-
form (30 mL ꢃ 3). The combined extracts were dried with K2CO3
and evaporated to give 6-phenyl-2,5-diazacyclohexanone (6;
R = Ph, n ¼ 1) (0.0463 g, 0.262 mmol; 90% yield) as colorless
ꢂ
1
crystals: mp 144.0–145.0 C; H NMR (CDCl3) ꢁ 1.74 (bs, 1H),
3.08 (ddd, 1H, J ¼ 4:3, 8.5, 12.6 Hz), 3.17 (dt, 1H, J ¼ 12:6,
4.5 Hz), 3.39 (dq-like, 1H, J ¼ 11:5, 3.9 Hz), 3.55 (dddd, 1H,
J ¼ 1:2, 4.7, 8.7, 11.8 Hz), 4.60 (s, 1H), 6.21 (bs, 1H), 7.28–
7.45 (m, 5H); IR (neat) 3854, 3752, 3677, 3651, 3202, 1677,
1491, 1338, 1261, 1092, 800, 705 cmꢁ1. Anal. Found: C, 67.96;
H, 6.76; N, 15.88%. Calcd for C10H12N2O: C, 68.16; H, 6.86;
N, 15.90%.
N-Benzyl-2-(benzylamino)-2-(4-bromophenyl)acetamide (5;
R = p-Br–C6H4, R0 = Bn, R00 = H). A colorless powder: mp
125.3–126.4 ꢂC; 1H NMR (CDCl3) ꢁ 2.00 (bs, 1H), 3.75 (s,
2H), 4.25 (s, 1H), 4.44 (d, 2H, J ¼ 5:9 Hz), 7.19–7.36 (m,
12H), 7.41 (t(br), 1H, J ¼ 5:9 Hz), 7.47 (dm, 2H, J ¼ 8:5 Hz);
IR (KBr) 3286, 3086, 3028, 1651, 1558, 1489, 1454, 1263,
1026, 827, 725, 700 cmꢁ1. Anal. Found: C, 64.50; H, 5.18; N,
6.75%. Calcd for C22H21BrN2O: C, 64.55; H, 5.17; N, 6.84%.
N-Benzyl-2-(benzylamino)-2-(4-methoxycarbonylphenyl)-
7-Phenyl-2,6-diazacycloheptanone (6; R = Ph, n ¼ 2). Col-
orelss crystals: mp 153.0–154.0 ꢂC; 1H NMR (CDCl3) ꢁ 1.69–1.83
(m, 3H), 3.05 (ddd, 1H, J ¼ 4:7, 8.8, 13.6 Hz), 3.33 (dt, 1H,
J ¼ 13:6, 4.7 Hz), 3.40 (m, 2H), 4.59 (s, 1H), 6.02 (bs, 1H),
7.28–7.38 (m, 5H); IR (KBr) 3288, 2922, 1663, 1459, 1411,
1254, 1123, 814, 746, 698 cmꢁ1. Anal. Found: C, 69.35; H,
7.41; N, 14.64%. Calcd for C11H14N2O: C, 69.45; H, 7.42; N,
14.72%.
acetamide (5; R = p-MeOCO–C6H4, R0 = Bn, R00 = H).
A
8-Phenyl-2,7-diazacyclooctanone (6; R = Ph, n ¼ 3). Pale
yellow solid (purified with preparative GPC): mp 111.5–113.0
ꢂC; 1H NMR (CDCl3) ꢁ 1.68–1.95 (m, 5H), 3.04–3.18 (m, 2H),
3.22–3.38 (m, 1H), 4.60 (s, 1H), 4.79–4.86 (m, 1H), 5.80 (bs,
1H), 7.29–7.48 (m, 5H); IR (KBr) 1655, 1560, 1543, 1508,
1459, 1420, 1303, 1262, 1118, 790, 701 cmꢁ1. HRMS (FAB):
m=z 205.1345 ([M þ H]þ). Calcd for C12H17N2O: m=z 205.1341.
6-Ethyl-2,5-diazacyclohexanone (6; R = Et, n ¼ 1). A yel-
colorless cotton-like solid: mp 110.2–111.2 ꢂC; 1H NMR (CDCl3)
ꢁ 2.06 (bs, 1H), 3.76 (s, 2H), 3.91 (s, 3H), 4.35 (s, 1H), 4.45 (d,
2H, J ¼ 5:9 Hz), 7.21 (dm, 4H, J ¼ 7:4 Hz), 7.27–7.35 (m,
6H), 7.45 (dm, 2H, J ¼ 8:4 Hz), 7.49 (bs, 1H), 8.01 (dm, 2H, J ¼
8:4 Hz); IR (KBr) 3735, 3030, 2927, 2848, 1709, 1655, 1529,
1454, 1286, 1117, 742, 698 cmꢁ1. Anal. Found: C, 73.99; H,
6.15; N, 7.18%. Calcd for C24H24N2O3: C, 74.21; H, 6.23; N,
7.21%.
1
low oil: H NMR (CDCl3) ꢁ 1.03 (t, 3H, J ¼ 7:4 Hz), 1.73 (ddq,
N-Benzyl-2-(benzylamino)-2-(3-methoxyphenyl)acetamide
(5; R = m-MeO–C6H4, R0 = Bn, R00 = H). A colorless oil:
1H NMR (CDCl3) ꢁ 1.98 (bs, 1H), 3.76 (s, 5H), 4.26 (s, 1H),
4.45 (d, 2H, J ¼ 6:0 Hz), 6.84 (ddd, 1H, J ¼ 0:8, 2.6, 8.2 Hz),
6.91 (t-like, 1H, J ¼ 2:5 Hz), 6.96 (d(br), 1H, J ¼ 7:7 Hz),
7.21–7.33 (m, 11H), 7.44 (t(br), 1H, J ¼ 5:1 Hz); IR (neat)
3315, 3028, 2935, 2835, 1657, 1599, 1517, 1491, 1456, 1261,
1155, 1045, 752, 698 cmꢁ1. Anal. Found: C, 76.57; H, 6.70; N,
7.69%. Calcd for C23H24N2O2: C, 76.64; H, 6.71; N, 7.77%.
N-Benzyl-2-(benzylamino)butyramide (5; R = Et, R0 = Bn,
1H, J ¼ 8:2, 15.7, 7.4 Hz), 1.92 (bs, 1H), 1.99 (ddq, 1H, J ¼ 3:7,
15.2, 7.7 Hz), 2.98 (ddd, 1H, J ¼ 4:3, 9.8, 12.9 Hz), 3.156 (dt, 1H,
J ¼ 12:8, 3.8 Hz), 3.26–3.46 (m, 3H), 6.63 (bs, 1H); IR (neat)
3282, 2961, 2927, 2873, 1685, 1492, 1459, 1335, 1073, 802
cmꢁ1. HRMS (FAB): m=z 128.0940 ([M]þ). Calcd for C6H12N2O:
m=z 128.0950.
7-Ethyl-2,6-diazacycloheptanone (6; R = Et, n ¼ 2). Color-
ꢂ
1
elss crystals: mp 95.7–97.0 C; H NMR (CDCl3) ꢁ 1.00 (t, 3H,
J ¼ 7:4 Hz), 1.53 (dquint, 1H, J ¼ 13:7, 7.4 Hz), 1.60–1.75 (m,
3H), 1.90 (dquint, 1H, J ¼ 13:7, 7.4 Hz), 2.92 (ddd, 1H,
J ¼ 3:6, 11.1, 13.7 Hz), 3.16 (dd, 1H, J ¼ 6:3, 7.1 Hz), 3.24–
3.45 (m, 3H), 5.96 (bs, 1H); IR (neat) 3219, 2933, 1655, 1459,
1430, 1337, 1146, 808, 569 cmꢁ1. HRMS (FAB): m=z 143.1176
([M þ H]þ). Calcd for C7H15N2O: m=z 143.1184.
1
R00 = H). A colorless oil: H NMR (CDCl3) ꢁ 0.95 (t, 3H, J ¼
7:5 Hz), 1.61–1.86 (m, 2H), 1.72 (bs, 1H), 3.15 (dd, 1H, J ¼ 5:1,
7.3 Hz), 3.68 (d, 1H, J ¼ 13:1 Hz), 3.74 (d, 1H, J ¼ 13:1 Hz),
4.46 (d, 2H, J ¼ 5:9 Hz), 7.20–7.33 (m, 10H), 7.58 (bs, 1H); IR
(neat) 3297, 3029, 2965, 2930, 1651, 1523, 1454, 1228, 1122,
1030, 733, 698 cmꢁ1. HRMS (FAB): m=z 283.1805 ([M þ H]þ).
8-Ethyl-2,7-diazacyclooctanone (6; R = Et, n ¼ 3). Pale
yellow crystals (purified with preparative GPC): mp 93.2–94.5

1902 Bull. Chem. Soc. Jpn., 77, No. 10 (2004)
Reaction of 2,2-Disulfonyloxiranes with Amines
1
ꢂC; H NMR (CDCl3) ꢁ 0.95 (t, 3H, J ¼ 7:4 Hz), 1.55–1.91 (m,
3-Phenyl-1,4-benzodithiin-2(3H)-one (11; R = Ph). To a
solution of trans-2-(methylsulfonyl)-3-phenyl-2-(p-tolylsulfonyl)-
oxirane (1; R = Ph) (0.203 g, 0.575 mmol) in chloroform (20 mL)
were dropwise added 1,2-benzenedithiol (98 mL, 0.851 mmol) and
triethylamine (235 mL, 2.01 mmol) at room temperature. After the
solution was stirred for 30 min, the resulting mixture was washed
with water (50 mL ꢃ 3) and 0.5 M HCl (50 mL). The organic lay-
er was dried with MgSO4 and evaporated to give a pale yellow
solid. This solid was subjected to column chromatography on
SiO2 (chloroform) to give 3-phenyl-1,4-benzodithiin-2(3H)-one
(11; R = Ph) (0.131 g, 0.507 mmol, 88% yield) as a colorelss sol-
id: mp 123.3–124.1 ꢂC; 1H NMR (CDCl3) ꢁ 4.59 (s, 1H), 7.18 (dd,
1H, J ¼ 1:8, 7.3 Hz), 7.22–7.33 (m, 7H), 7.53 (diffused dd, 1H,
J ¼ 1:8, 7.1 Hz); IR (KBr) 1683, 1451, 1053, 1011, 804, 747,
737, 698, 602, 440 cmꢁ1. Anal. Found: C, 65.07; H, 4.02%. Calcd
for C14H10OSÞ2: C, 65.08; H, 3.90%.
6H), 1.84 (dquint, 1H, J ¼ 13:5, 7.6 Hz), 2.90–3.05 (m, 2H),
3.40–3.52 (m, 1H), 3.47 (dd, 1H, J ¼ 5:9, 7.6 Hz), 3.66–3.76
(m, 1H), 5.81 (bs, 1H); IR (KBr) 3266, 3066, 2925, 1654, 1498,
1461, 1434, 1299, 1139, 905 cmꢁ1
. HRMS (FAB): m=z
157.1338 ([M þ H]þ). Calcd for C8H17N2O: m=z 157.1341.
Reaction with Aminophenol. To a solution of o-aminophenol
(0.130 g, 1.19 mmol) in THF (30 mL) was added NaOH (0.103 g,
1.08 mmol) at room temperature, and the resulting mixture was
stirred for 15 min. After trans-2-(methylsulfonyl)-3-phenyl-2-(p-
tolylsulfonyl)oxirane (1; R = Ph) (0.350 g, 0.99 mmol) was add-
ed, the mixture was stirred for 3 h, and then acidified to pH ꢄ 3
with 1 M HCl. Water (20 mL) was added and the extraction
was performed with chloroform (50 mL ꢃ 3). The combined ex-
tracts were dried with K2CO3 and evaporated to give a colorless
oil. This was subjected to column chromatography on SiO2 (hex-
ane–chloroform) to give 2-phenyl-2H-1,4-benzoxazin-3(4H)-one
(8; R = Ph) (0.182 g,ꢂ0.808 mmol; 81%ꢂyield) as colorless crys-
3-Ethyl-1,4-benzodithiin-2(3H)-one (11; R = Et). A color-
1
less oil; H NMR (CDCl3) ꢁ 1.04 (t, 3H, J ¼ 7:5 Hz), 1.57 (sept-
tals: mp 171.5–172.5 C (lit.19 169–170 C); H NMR (CDCl3) ꢁ
like, 1H, J ¼ 7:7 Hz), 1.90 (sept-like, 1H, J ¼ 7:3 Hz), 3.35 (dd,
1H, J ¼ 6:5, 8.1 Hz), 7.24–7.31 (m, 3H), 7.53 (diffused dd, 1H,
J ¼ 1:6, 6.6 Hz); IR (neat) 2967, 2932, 1681, 1454, 1428, 1113,
1053, 991, 749, 437 cmꢁ1. Anal. Found: C, 57.18; H, 4.85%.
Calcd for C10H10OS2: C, 57.11; H, 4.79%.
1
5.71 (s, 1H), 6.78–6.81 (m, 1H), 6.92–7.06 (m, 3H), 7.34–7.39 (m,
3H), 7.44–7.48 (m, 2H), 8.51 (bs, 1H); IR (KBr) 2964, 1685
(CONH), 1500, 1398, 1261, 11213, 1039, 802, 746, 700 cmꢁ1
Anal. Found: C, 74.69; H, 4.86; N, 6.13%. Calcd for C14H11NO2:
C, 74.65; H, 4.92; N, 6.22%.
2-Ethyl-2H-1,4-benzoxazin-3(4H)-one (8; R = Et). Color-
less solid: mp 104.0–105.0 C; 1H NMR (CDCl3) ꢁ 1.10 (t, 3H,
;
2-Ethyl-2H-1,4-benzothiazin-3(4H)-one (12). Orange solid;
mp: 100.0–101.0 ꢂC (lit.19 103–104 ꢂC); 1H NMR (CDCl3) ꢁ
1.07 (t, 3H, J ¼ 7:4 Hz), 1.64 (ddq, 1H, J ¼ 8:8, 14.4, 7.1 Hz),
1.95 (ddq, 1H, J ¼ 5:9, 14.4, 7.3 Hz), 3.32 (dd, 1H, J ¼ 5:9,
8.8 Hz), 6.88 (dd, 1H, J ¼ 1:2, 8.0 Hz), 7.01 (dt, 1H, J ¼ 1:4,
7.7 Hz), 7.17 (dt, 1H, J ¼ 1:5, 7.8 Hz), 7.32 (dd, 1H, J ¼ 1:5,
7.8 Hz), 8.97 (bs, 1H); IR (KBr) 3193, 3052, 2975, 1679 (CONH),
ꢂ
J ¼ 7:4 Hz), 1.83–2.02 (m, 2H), 4.52 (dd, 1H, J ¼ 4:7, 8.0 Hz),
6.79 (dd, 1H, J ¼ 2:1, 6.0 Hz), 6.92–7.11 (m, 3H), 8.30 (bs,
1H); IR (KBr) 3651, 3198, 2369, 2345, 1685 (CONH), 1610,
1503, 1408, 743 cmꢁ1. Anal. Found: C, 67.57; H, 6.20; N,
7.85%. Calcd for C10H11NO2: C, 67.78; H, 6.26; N, 7.90%.
Reaction with Thiols. To a solution of trans-2-(methylsulfo-
nyl)-3-phenyl-2-(p-tolylsulfonyl)oxirane (1; R = Ph) (0.352 g,
1.00 mmol) in chloroform (30 mL) was added 1,2-ethanedithiol
(92 mL, 1.10 mmol) at room temperature. Then, DBU (330 mL,
2.21 mmol) was added at that temperature. After the solution
was stirred for 30 min, the resulting mixture was washed with sat-
urated aqueous solution of NaHCO3 (30 mL ꢃ 3). The washings
were extracted with chloroform (30 mL ꢃ 3). The combined or-
ganic layer was dried with MgSO4 and evaporated to give a color-
less oil. These were subjected to column chromatography on SiO2
(chloroform), followed by preparative GPC to give 3-phenyl-1,4-
dithian-2-one (9; R = Ph) (0.125 g, 0.594 mmol; 59% yield) as
colorless crystals: mp 111.0–112.0 ꢂC; 1H NMR (CDCl3) ꢁ
3.14–3.37 (m, 3H), 3.39–3.49 (m, 1H), 4.83 (s, 1H), 7.29–7.44
(m, 5H); IR (KBr) 1671, 1455, 1430, 1270, 1031, 1020, 796,
728, 696, 599 cmꢁ1. Anal. Found: C, 56.04; H, 5.04%. Calcd
for C10H10OS2 + 0.25H2O: C, 55.91; H, 4.93%.
1583, 1479, 1369, 755, 696, 549 cmꢁ1
.
References
1
a) R. E. Parker and N. S. Isaacs, Chem. Rev., 59, 737
(1959). b) R. J. Gritter, ‘‘The Chemistry of Functional Groups,’’
ed by S. Patai, Interscience, London (1967), Vol. 3, Chap. 9,
pp. 373–443. c) J. G. Smith, Synthesis, 1984, 629. d) I. Erden,
‘‘Comprehensive Heterocyclic Chemistry II,’’ ed by A. R.
Katritzky, C. W. Ree, and E. F. V. Scriren, Pergamon, Oxford
(1996), Vol. 1A, pp. 97–171. e) S. Florio ed, Tetrahedron, 59,
9683 (2003).
2
a) K. B. Sharpless, C. H. Behrens, T. Katsuki, A. W. M.
Lee, V. S. Martin, M. Takatani, V. Muneo, M. Steven, F. J.
Walker, and S. S. Woodard, Pure Appl. Chem., 55, 589 (1983).
b) A. S. Rao, S. K. Paknikar, and J. G. Kirtane, Tetrahedron,
39, 2323 (1983). c) R. M. Hanson, Chem. Rev., 91, 437 (1991).
d) C. Bonini and G. Righi, Synthesis, 1994, 225. e) T.-H. Chuang
and K. B. Sharpless, Helv. Chim. Acta, 83, 1734 (2000).
3-Ethyl-1,4-dithian-2-one (9; R = Et).
A yellow oil:
1H NMR (CDCl3) ꢁ 1.07 (t, 3H, J ¼ 7:5 Hz), 1.61 (septet like,
1H, J ¼ 7:2 Hz), 2.06 (ddq, 1H, J ¼ 6:2, 7.3, 14.4 Hz), 2.99–
3.12 (m, 1H), 3.29–3.48 (m, 3H), 3.60 (t, 1H, J ¼ 6:6 Hz); IR
(neat) 2966, 2928, 1668, 1455, 1432, 1113, 1016, 999, 776
cmꢁ1. Anal. Found: C, 44.35; H, 6.12%. Calcd for C6H10OS2:
C, 44.41; H, 6.21%.
3
a) G. H. Posner, Org. React., 22, 253 (1975). b) A.
Alexakis, G. Cahiez, and J. F. Normant, Tetrahedron, 36, 1961
(1980). c) H. Yamashita, Bull. Chem. Soc. Jpn., 61, 1213
(1988). d) H. Kotsuki, K. Hayashida, T. Shimanouchi, and H.
Nishizawa, J. Org. Chem., 61, 984 (1996). e) T. Iida, N.
Yamamoto, S. Matsunaga, H.-G. Woo, and M. Shibasaki, Angew.
Chem., Int. Ed., 37, 2223 (1998). f) S. K. Taylor, Tetrahedron, 56,
1149 (2000). g) J. M. Ready and E. N. Jacobsen, J. Am. Chem.
Soc., 123, 2687 (2001). h) M. Sasaki, K. Tanino, and M.
Miyashita, J. Org. Chem., 66, 5388 (2001). i) J. S. Yadav, B. V.
S. Reddy, and G. Baishya, Chem. Lett., 2002, 906. j) M. Bandini,
P. G. Cozzi, P. Melchiorre, and A. Umani-Ronchi, J. Org. Chem.,
67, 5386 (2002).
3-Ethyl-1,4-dithiepan-2-one (10). Colorless solid: mp 67.0–
67.5 ꢂC (lit.20 65–65.5 ꢂC); 1H NMR (CDCl3, 300 MHz) ꢁ 1.05 (t,
3H, J ¼ 7:4 Hz), 1.62 (sept-like, 1H, J ¼ 7:3 Hz), 1.96 (sept-like,
1H, J ¼ 7:0 Hz), 2.03–2.17 (m, 1H), 2.53–2.63 (m, 1H), 2.86–
3.08 (m, 3H), 3.23 (ddd, 1H, J ¼ 1:5, 11.5, 15.4 Hz), 3.60 (t,
1H, J ¼ 7:1 Hz); IR (KBr) 2970, 2930, 1644, 1457, 1421, 1243,
1113, 1020, 907, 786 cmꢁ1
.

S. Matsumoto et al.
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