Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides and Related Novel Biscarbonyldisulfides

Article abstract of DOI:10.1055/s-2001-14566

Under solvent-free conditions, various unsymmetrical benzoyldisulfides and symmetrical novel biscarbonyldisulfides were easily prepared in good yields at room temperature by the mixing of thiosulfonates with thiocarboxylic S-acids in the absence or presen

Full text of DOI:10.1055/s-2001-14566

PAPER
1035
Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides and Related Novel
Biscarbonyldisulfides
S
olvent-free Synth
i
esis of
y
U
nsymmetr
o
kisulfides o Fujiki,* Shizuka Akieda, Hironobu Yasuda, Yohei Sasaki
Department of Agricultural Chemistry, Meiji University, Kawasaki 214–8571, Japan
Fax +81(44)9347831; E-mail: fujiki@isc.meiji.ac.jp
Received 7 December 2000; revised 12 March 2001
Scheme 1 shows the general reaction for the preparation
Abstract: Under solvent-free conditions, various unsymmetrical
benzoyldisulfides and symmetrical novel biscarbonyldisulfides
were easily prepared in good yields at room temperature by the mix-
ing of thiosulfonates with thiocarboxylic S-acids in the absence or
presence of an amine.
of monobenzoyl disulfides 3–6 by the sulfenylation of
thiobenzoic S-acids 1 with thiosulfonates 2 in the absence
or presence of an amine as an activator. Novel biscarbon-
yldisulfides 8 and 9 were also prepared from thiocarbox-
ylic acids having two SH groups such as adipoyl dithiol 7a
and terephthaloyl dithiol 7b in the solid state (Scheme 2).
Key words: benzoyldisulfides, thiocarboxylic S-acid, carbonyldis-
ulfides, thiosulfonates, sulfenylation
O
O
S
R2
R1
Acyldisulfides are of pharmaceutical or physiological in-
terest because of their biological activities. Some of these
disulfides proved to have significant activities in control-
ling the growth of bacteria or fungi.1 Recently, monoacyl
disulfides have come into use as a mediator of the peptide
bond formation between the unprotected peptide seg-
ments.2 However, only a few reports on the monoacyl dis-
ulfides are known compared with those of the symmetric
diacyl disulfides.3 These reports include the reaction of
acetyl sulfenyl chloride with thiols4a,b or with activated ar-
omatic compounds4c to give monoacetyl disulfides, and
the reaction of thiocarboxylic S-acids with sulfenyl chlo-
rides,5,1b thiosulfonates6,1b or alkyl thiosulfates.7 Recently,
it was shown that sulfines from aliphatic dithioesters un-
dergo rearrangement to monoacyl disulfides.8 Among
these reagents, thiosulfonates are the most stable and
powerful sulfenylating agent unlike the sulfenyl halides or
acylsulfenyl halides. However, the synthetic examples of
monoacyl disulfides by use of the thiosulfonates as a
sulfenylating agent are few in the usual solution state, es-
pecially only two benzoyl disulfides have been reported,6
and it was noted that the purification of some unsymmet-
rical carbonyldisulfides was difficult.1b
R
S
O
O
S
S
R2
R1
SH
2a : R=Me
2b: R=Cl
3: R=OMe
4: R=H
1
5: R=Cl
6: R=NO2
Scheme 1
O
O
O
O
2
S
S
S
R3
S
R2
HS
R3
SH
R2
8: R3 = (CH2)4
9: R3 =p--C6H4
7
Scheme 2
When 1 and 2 were mixed in the molar ratio of 1:1.2, the
reaction proceeded and the spot on the TLC plate corre-
sponding to 1, and its odor disappeared (= reaction time).
Nucleophilic S-S bond scission of the p-toluenethiosul-
fonate 2a with thiobenzoic S-acids 1 bearing an electron-
donating group such as a methoxy group at their p-posi-
tion (R1), rapidly occurred (3a–3f, Table 1). In contrast,
the p-nitro and p-chlorothiobenzoic S-acids needed a long
reaction time (over 1.5 h) even in the presence of an
amine, as an activator of the thiol and as a trapping agent
of the liberated sulfinic acid. Thiobenzoic S-acid itself
also needed the aid of the amine to complete the reaction
within a few minutes (4a–4i, Table 1). The amine, p-ami-
noacetanilide, was much preferred, over other stronger
basic amines such as p-toluidine and p-chloroaniline, for
prevention of the formation of amides1,12 with the thiocar-
boxylic S-acid. The reactivity depended not only on the
electronegativity of R1 in 1 but also on the p-substituted
group R at the sulfonyl phenyl in the thiosulfonates 2. The
electron-donating groups R such as a Me group increased
the reaction time, whereas the electron-withdrawing
Previously, we succeeded in developing the new prepara-
tion of aryl thiocyanates9 and unsymmetrical
aryldisulfides10, the latter have a tendency to dispropor-
tionate in solvent, by the reaction of thiosulfonates with
nucleophiles under solvent-free conditions, with recogni-
tion that in some cases, the reaction may proceed more ef-
ficiently and even more selectively in the solvent-free or
solid state.11 Now we report the solvent-free synthesis of
unsymmetrical benzoyldisulfides and related novel bis-
carbonyldisulfides at room temperature.
Synthesis 2001, No. 7, 01 06 2001. Article Identifier:
1437-210X,E;2001,0,07,1035,1042,ftx,enF06800SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1036
K Fujiki et al.
PAPER
Table 1 Benzoyl Disulfides 3 and 4 from Thiobenzoic S-Acid and
p–Toluenethiosulfonate Prepareda
Table 2 Benzoyl Disulfides 5 and 6 from Thiobenzoic S-Acid and
p-Chlorobenzenethiosulfonate Prepareda
Compd
3a
3b
3c
R1
R2
Yield (%)b
Compd
R1
R2
Reaction
time (h)
Yieldb (%)
OMec
OMec
OMec
OMec
OMec
OMec
Hd
Me
70
68
71
73
70
81
67
77
76
71
72
71
74
69
75
5a
Cl
Me
1
65
63
99
68
59
88
45
46
73
66
50
63
60
29
62
41
Bn
5b
5c
Cl
Bn
1
Cy
Cl
Cy
2
3d
3e
Ph
5d
5e
Cl
Ph
4
p-Tolyl
p-FluoroPh
Me
Cl
p-Tolyl
p-FluoroPh
Me
1
3f
5f
Cl
1.5
1c
5
4a
4b
4c
6ac
6a’
6b
6cc
6c’
6dc
6ec
6e’
6fc
6f’
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
Hd
i-Pr
Me
Hd
Bn
Bn
2
4d
4e
Hd
Cy
Cy
2c
4
Hd
Ph
Cy
4f
Hd
p-Tolyl
p-FluoroPh
p-BromoPh
2-Naphthyl
Ph
3c
2c
8
4g
4h
4i
Hd
p-Tolyl
p-Tolyl
p-FluoroPh
p-FluoroPh
Hd
Hd
5c
6
a Reaction time: 1 min at r.t.
b Isolated yield is based on the amount of thiobenzoic S-acid 1 used.
c Reaction conditions: The molar ratio of 1 to p-toluenethiosulfonate
2a = 0.3:0.36 mmol.
a Reaction conditions: The molar ratio of thiobenzoic S-acid 1 to p-
chlorobenzenethiosulfonate 2b = 0.3:0.36 mmol.
d Reaction conditions: 1:2a:amine (p-aminoacetanilide) = 0.3:0.36:0.9
mmol.
b Isolated yield is based on the amount of 1 used.
c Further 0.9 mmol of p-aminoacetanilide was added.
groups decreased it. When p-chlorobenzenethiosulfonate
2b was used instead of p-toluenethiosulfonate 2a, the re- for the corresponding disulfides were low and the purifi-
action time dramatically decreased (several hours to 1–2 cation was difficult. That is, under the solvent or solvent-
h) even in the absence of the amine (p-chlorothiobenzoic free system, the reactivity complemented each other.
S-acid series 5a–5f, Table 2). Furthermore, 2b was very
effective in decreasing the reaction time even for the p-ni-
trothiobenzoic S-acid series (1 day to several hours),
The reaction of thioacetic S-acid with thiosulfonates in a
similar way reached no end-point along with the forma-
tion of diacetyl disulfide in both the presence and absence
where the presence of the amine somewhat enhanced the
of solvent.
reaction (6a–6f’, Table 2).
In conclusion, the stable unsymmetrical benzoyldisulfides
and novel biscarbonyldisulfides were successfully pre-
pared under solvent-free conditions using thiosulfonates,
especially p-chlorobenzene thiosulfonate, as the strong
For terephthaloyl dithiol 7b, only reactive 2b was effec-
tive to form dithioperoxyterephthalate 9 within a few min-
utes, although adipoyl dithiol 7a rapidly reacted with 2a
to give dithioperoxyadipate 8 (Scheme 2, Table 3).
sulfenylating agent toward a (C=O)SH group. The
The benzoyl disulfides shown in Tables 1 and 2 demon- present method has some advantages, such as avoiding the
strate the scope of the sulfenylation, namely each of the use of the unstable and unavailable reagents, facile proce-
thiobenzoic S-acids bearing an electron-donating or with- dure without the byproducts and good yields.
drawing groups can react with various types of thiosul-
fonates in good yields at room temperature.
Mps (uncorrected) were determined using a Yanagimoto micro
melting point apparatus Mp-S3. 1H and 13C NMR spectra: JNM-AL
The similar sulfenylation with thiosulfonates was exam-
30 (JOEL), chemical shift ( ) are relative to TMS. IR spectra: Hita-
ined in the solvent system. The results are of interest. The
chi-Nicolet FT-IR 5020. Mass spectra: JMS SX-102(JOEL). Ele-
mental analyses were performed at the Elemental Analysis Center,
University of Tsukuba. Chromatography: SEP-PAK cartridge SIL-
ICA PLUS (Waters). The starting materials 1, 7 and 2 were pre-
thiobenzoic S-acids having an electron-attracting group at
their p-position rapidly reacted with 2a, but in contrast,
for those having an electron-donating group, dispropor-
tionation competed with desired sulfenylation. The yields
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides
1037
Table 3 Biscarbonyldisulfides 8 and 9 Prepared from Thiosul-
Compounds 3 (R1 = OMe)
fonates and Adipoyl or Terephthaloyl Dithiols
Prepared by Method 1 with 2a. An oily product was obtained after
chromatography (Method 2).
Compd
R3
R2
Reaction
time (min)
Yielda (%)
3a (R2 = Me)
Colorless.
b
b
b
b
b
b
8a
8b
8c
8d
8e
8f
(CH2)4
(CH2)4
(CH2)4
(CH2)4
(CH2)4
(CH2)4
Me
1
1
1
1
1
1
1
2
2
3
2
5
88
82
87
67
82
78
81
82
66
67
79
62
Mp 64.0–65.0°C.
IR (KBr): = 1662.85 (C=O) cm–1.
Bn
1H NMR (300 MHz, CDCl3): = 7.97 (d, 2H, J = 9.0 Hz, Bz-2,6),
6.95 (d, 2H, J = 9.0 Hz, Bz-3,5), 3.88 (s, 3H, OCH3), 2.46 (s, 3H,
CH3).
13C NMR (75 MHz, CDCl3): =188.30 (C=O), 164.31 (Bz-4),
129.99 (Bz-2,6), 128.47 (Bz-1), 114.08 (Bz-3,5), 55.58 (OCH3),
22.76 (CH3).
Cy
Ph
p-Tolyl
p-FluoroPh
Me
MS (FAB): m/z (%) = 215 (4.30) [M + H]+, 151 (7.96), 135 (100)
c
c
c
c
c
c
9a
9b
9c
9d
9e
9f
p-C6H4
p-C6H4
p-C6H4
p-C6H4
p-C6H4
p-C6H4
[MeOPhCO]+, 121 (3.23), 107 (2.57).
Bn
Anal. Calcd for C9H10O2S2: C, 50.44; H, 4.70. Found: C, 50.74; H,
4.78.
Cy
3b (R2 = benzyl)
Colorless.
Ph
p-Tolyl
p-FluoroPh
Mp 56.0–57.0°C.
IR (KBr): = 1691.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.95 (d, 2H, J = 9.0 Hz, Bz-2,6),
7.36 7.26(m, 5H, Bn), 6.94 (d, 2H, J = 9.0 Hz, Bz-3,5), 3.99 (s, 2H,
Bn-CH2), 3.87 (s, 3H, OCH3).
13C NMR (75 MHz, CDCl3): = 188.21 (C=O), 164.33 (Bz-4),
136.28 (Bn-1), 130.05 (Bn-3,5), 129.52 (Bz-2,6), 128.55 (Bn-2,6),
128.48 (Bz-1), 127.70 (Bn-4), 114.10 (Bz-3,5), 55.59 (OCH3),
42.85 (Bn-CH2).
a Isolated yield is based on the amount of adipoyl dithiol used (8a–8f),
and of p-chlorobenzenethiosulfonates 2b used (9a–9f).
b Reaction conditions: The molar ratio of adipoyl dithiol to p-tolu-
enethiosulfonate 2a = 0.3:0.66 mmol.
c Reaction conditions: The molar ratio of terephthaloyl dithiol to
2b = 0.24:0.4 mmol.
MS (FAB): m/z (%) = 291 (11.53) [M + H]+, 151 (24.76), 135 (100)
pared according to the literature procedure13 and by the reaction of
sulfinic acid with disulfides,10 respectively.
[MeOPhCO]+, 121 (7.41), 107 (6.21), 91 (29.64).
Anal. Calcd for C15H14O2S2: C, 62.04; H, 4.86. Found: C, 61.62; H,
5.02.
Monoacyl Disulfides and Biscarbonyldisulfides; Typical
Procedures
3c (R2 = cyclohexyl)
Colorless oil.
IR (thin film): = 1691.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.00 (d, 2H, J = 9.0 Hz, Bz-2,6),
6.94 (d, 2H, J = 9.0 Hz, Bz-3,5), 3.87 (s, 3H, OCH3), 2.84 (nonet,
1H, J = 3.6 Hz, Cy-1), 2.05 (2H), 1.77 (2H), 1.59 (1H), 1.46–1.15
(m, 5H, Cy).
13C NMR (75 MHz, CDCl3): =188.96 (C=O), 164.22 (Bz-4),
130.00 (Bz-2,6),128.55 (Bz-1), 114.02 (Bz-35), 55.57 (OCH3),
49.60 (Cy-1), 32.60 (Cy-2,6), 25.99 (Cy-3,5), 25.51 (Cy-4).
Method 1: p-Chlorobenzoyl p-Fluorophenyl Disulfide (5f)
A mixture of p-chlorothiobenzoic S-acid (51.8 mg, 0.3 mmol) and
(S)-p-fluorophenyl p-chlorobenzenethiosulfonate (109.0 mg, 0.36
mmol) was allowed to stand at 25°C and occasionally stirred. After
disappearance of the thioacid spot a TLC plate, the reaction mixture
was extracted with hexane (6 5 mL) followed by filtration and
concentration at reduced pressure. The residue was recrystallized
from EtOH–H2O.
Method 2: Benzoyl Cyclohexyl Disulfide (4d)
A mixture of thiobenzoic S-acid (41.5 mg, 0.3 mmol), (S)-cyclohex-
yl p-toluenethiosulfonate (97.4 mg, 0.36 mmol) and p-aminoaceta-
nilide (135.2 mg, 0.9 mmol) was allowed to stand at 25°C and
occasionally stirred. The work-up was carried out as described in
Method 1. The residue was subjected to chromatography (CCl4)
with a Sep-Pak cartridge.
MS (FAB): m/z (%) =283 (27.99) [M + H]+, 151 (23.00), 135 (100)
[MeOPhCO]+, 121 (9.84), 107 (6.08), 83 (10.91).
Anal. Calcd for C14H18O2S2: C, 59.54; H, 6.42. Found: C, 59.63; H,
6.40).
3d (R2 = phenyl)
Colorless.
Method 3: Bis(p-fluorophenyl)dithioperoxyterephthalate (9f)
After stirring a mixture of the finely powdered thioterephthalic
(S)-acid (237.9 mg, 1.2 mmol) and (S)-p-fluorophenyl p-chloroben-
zenethiosulfonate (605.3 mg, 2.0 mmol), the reaction mixture was
extracted with hexane (50 + 15 mL), followed by filtration and con-
centration at reduced pressure. The concentrate was dissolved in
CHCl3 (2 mL), and MeOH (4 mL) was added. Colorless crystals
were formed as a precipitate.
Mp 51.0–52.0°C.
IR (KBr): = 1693.72 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.99 (d, 2H, J = 9.0 Hz, Bz-2,6),
7.56 (dd, 2H, J = 2.0, 8.5 Hz, Ph-2,6), 7.33–7.25 (m, 3H, Ph-3,4,5),
6.95 (d, 2H, J = 9.0 Hz, Bz-3,5), 3.88 (s, 3H, OCH3).
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York

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K Fujiki et al.
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13C NMR (75 MHz, CDCl3): =187.26 (C=O), 164.46 (Bz-4),
136.11 (Ph-1), 130.24 (Bz-2,6), 130.16 (Ph-2,6), 129.08,(Ph-3,5),
128.13 (Bz-1), 128.07 (Ph-4), 114.16 (Bz-3,5), 55.62 (OCH3).
1H NMR (300 MHz, CDCl3): = 8.02 (d, 2H, J = 8.0 Hz, Bz-2,6),
7.62 (t, 1H, J = 8.0 Hz, Bz-4), 7.49 (t, 2H, J = 8.0 Hz, Bz-3,5), 3.14
(sept, 1H, J = 7.0 Hz), 1.32 (d, 6H, J = 7.0 Hz, 2 CH3).
MS (FAB): m/z (%) = 277 (13.03) [M + H]+, 151 (24.53), 135 (100)
13C NMR (75 MHz, CDCl3): = 190.56 (C=O), 135.84 (Bz-1),
133.96 (Bz-4), 128.85 (Bz-3,5), 127.74 (Bz-2,6), 41.54 (i-Pr CH),
22.48 (CH3).
[MeOPhCO]+, 121 (4.77), 107 (5.15).
Anal. Calcd for C14H12O2S2: C, 60.84; H, 4.38. Found: C, 60.70; H,
4.52.
MS (EI): m/z (%) = 212 (5.93) [M]+, 105 (100) [PhCO]+, 77 (30.28).
Anal. Calcd for C10H12OS2: C, 56.57; H, 5.70. Found: C, 56.21; H,
5.67.
3e (R2 = p-tolyl)
Colorless.
Mp 59.0–60.0°C.
4c (R2 = benzyl)
Colorless.
IR (KBr): = 1699.50 (C=O) cm–1.
Mp 52.0–53.0°C.
IR (KBr): = 1682.14 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.97 (d, 2H, J = 9.0 Hz, Bz-2,6),
7.49 (d, 2H, J = 8.1 Hz, tolyl-2,6), 7.10 (d, 2H, J = 8.1 Hz, tolyl-3,5),
6.94 (d, 2H, J = 9.0 Hz, Bz-3,5), 3.87 (s, 3H, OCH3), 2.31 (s, 3H,
CH3).
13C NMR (75 MHz, CDCl3): = 187.59 (C=O), 164.37 (Bz-4),
138.67 (tolyl-4), 132.69 (tolyl-1), 131.24 (tolyl-3,5), 130.18 (tolyl-
2,6), 129.87 (Bz-2,6), 128.23 (Bz-1), 114.11 (Bz-3,5), 55.59
(OCH3), 21.17 (CH3).
1H NMR (300 MHz, CDCl3): = 7.96 (d, 2H, J = 7.5 Hz, Bz-2,6),
7.61 (t, 1H, J = 7.5 Hz, Bz-4), 7.48 (t, 2H, J = 7.5 Hz, Bz-3,5), 7.36–
7.25 (m, 5H, Bn), 4.00 (s, 2H, Bn-CH2).
13C NMR (75 MHz, CDCl3): = 189.98 (C=O), 136.14 (Bn-1),
135.76 (Bz-1), 134.03 (Bz-4), 129.51 (Bn-3,5), 128.88 (Bz-3,5),
128.58 (Bn-2,6), 127.73 (Bz-2,6), 127.73 (Bn-4), 42.72 (Bn-CH2).
MS (FAB): m/z (%) = 291 (20.91) [M + H]+, 151 (21.21), 135 (100)
MS (EI): m/z(%)= 260 (2.89) [M]+, 246 (2.73), 105 (100) [PhCO]+,
91 (45.14), 77 (66.76).
[MeOPhCO]+, 121 (3.19), 107 (4,71).
Anal. Calcd for C15H14O2S2: C, 62.04; H, 4.86; S, 22.08. Found: C,
62.04; H, 4.95; S, 21.80.
Anal. Calcd for C14H12OS2: C, 64.58; H, 4.65. Found: C, 64.39; H,
4.71.
3f (R2 = p- fluorophenyl)
Colorless.
4d (R2 = cyclohexyl)
Colorless oil.
Mp 83.0–84.0°C.
IR (KBr): = 1693.72 (C=O) cm–1.
IR (thin film): = 1691.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.01 (d, 2H, J = 7.5 Hz, Bz-2,6),
7.61 (t, 1H, J = 7.5 Hz, Bz-4), 7.48 (t, 2H, J = 7.5 Hz, Bz-3,5), 2.87
(nonet, 1H, J = 3.5 Hz, Cy-1), 2.05 (2H), 1.79 (2H), 1.60 (1H),
1.44–1.18 (m, 5H, Cy).
13C NMR (75 MHz, CDCl3): = 190.77 (C=O), 135.87 (Bz-1),
133.91 (Bz-4), 128.83 (Bz-3,5), 127.13 (Bz-2,6), 49.66 (Cy-1),
32.68 (Cy-2,6), 26.00 (Cy-3,5), 25.50 (Cy-4).
1H NMR (300 MHz, CDCl3): = 7.96 (d, 2H, J = 8.6 Hz, Bz-2,6),
7.60 [dd, 2H, J = 9.0 Hz, Ph-2,6, JmH-F = 5.3 Hz], 7.00 (d, 2H, J = 8.6
Hz, Bz-3,5), 6.96 [t, 2H, J = 9.0 Hz, Ph-3.5, JoH-F = 9.0 Hz], 3.87 (s,
H, OCH3).
13C NMR (75 MHz, CDCl3): = 187.29 (C=O), 164.50 (Bz-4),
162.99 (J4C-F = 247.3 Hz), 133.62 (JmC-F = 8.0 Hz), 131.45
(JpC-F = 3.2 Hz), 130.22 (Bz-2,6), 128.03 (Bz-1), 116.25 (JoC-F = 22.3
Hz), 114.18 (Bz-3,5), 55.62 (OCH3).
MS (EI): m/z (%) = 252 (1.99) [M]+, 105 (100) [PhCO]+, 83 (2.72),
77 (23.66).
MS (FAB): m/z (%) = 295 (15.53) [M + H]+, 151 (31.01), 135 (100)
Anal. Calcd for C13H16OS2: C, 61.87; H, 6.39. Found: C, 62,09; H,
6.48.
[MeOPhCO]+, 121 (3.55), 107 (7.17).
Anal. Calcd for C14H11FO2S2: C, 57.13; H, 3.77. Found: C, 57.06;
H, 3.73.
4e (R2 = phenyl)
Colorless.
Mp 29.5–30.0°C (Lit.4a,6 52–53°C).
IR (KBr): = 1693.72 (C=O) cm–1.
Compounds 4 (R1 = H)
Prepared by Method 2 with 2a.
4a (R2 = Me)
Colorless oil.
IR (thin film): = 1687.93 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.01 (d, 2H, J = 7.5 Hz, Bz-2,6),
7.62 (t, 1H, J = 7.5 Hz, Bz-4), 7.58 (d, 2H, J = 7.5 Hz, Ph-2,6), 7.49
(t, 2H, J = 7.5 Hz, Bz-3,5), 7.32–7.27 (m, 3H, Ph-3,4,5).
13C NMR (75 MHz, CDCl3): = 189.09 (C=O), 135.79 (Bz-1),
135.43 (Ph-1), 134.22 (Bz-4), 130.42 (Ph-2,6), 129.13 (Ph-3,5),
128.94 (Bz-3,5), 128.25 (Ph-4), 127.89 (Bz-2,6).
1H NMR (300 MHz, CDCl3): = 7.98 (d, 2H, J = 7.5 Hz, Bz-2,6),
7.62 (t, 1H, J = 7.5 Hz, Bz-4), 7.48 (t, 2H, J = 7.5 Hz, Bz-3,5), 2.48
(s, 3H, CH3).
13C NMR (75 MHz, CDCl3): = 190.09 (C=O), 135.76 (Bz-1),
134.05 (Bz-4), 128.89 (Bz-3,5), 127.69 (Bz-2,6), 22.61 (CH3).
MS(EI): m/z (%)= 246 (5.32) [M]+, 218 (1.60), 141 (5.81), 105
(100) [PhCO]+, 77 (76.47).
MS (EI): m/z (%) = 184 (0.71) [M]+, 105 (100) [PhCO]+, 77 (50.41).
Anal. Calcd for C13H10OS2: C, 63.38; H, 4.09. Found: C, 63.55; H,
4.31.
Anal. Calcd for C8H8OS2: C, 52.15; H, 4.38. Found: C, 52.27; H,
4.50.
4f (R2 = p-tolyl)
Colorless.
Mp 37.5–38.0°C (Lit.5 37–39°C).
4b (R2 = i-Pr)
Colorless oil.
1
IR (thin film): = 1691.79 (C=O) cm–1.
IR (KBr): = 1691.79 (C=O) cm .
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides
Compounds 5 (R1 = Cl)
1039
1H NMR (300 MHz, CDCl3): = 7.98 (d, 2H, J = 7.5 Hz, Bz-
2,6),7.60 (t, 1H, J = 7.5 Hz, Bz-4), 7.51 (d, 2H, J = 8.0 Hz, tolyl-
2,6), 7.47 (t, 2H, J = 7.5 Hz, Bz-3,5), 7.11 (d, 2H, J = 8.0 Hz, tolyl-
3,5), 2.31 (s, 3H, CH3).
13C NMR (75 MHz, CDCl3): = 189.38 (C=O), 138.86 (tolyl-4),
135.56 (Bz-1), 134.10 (Bz-4), 132.39 (tolyl-1), 131.48 (tolyl-3,5),
129.92 (tolyl-2,6), 128.84 (Bz-3,5), 127.8 4 (Bz-2,6), 21.17 (CH3).
Prepared by Method 1 with 2b. The oily products were subjected to
chromatography (method 2).
5a (R2 = Me)
Colorless oil.
IR (thin film): = 1686.00 (C=O) cm–1.
MS (EI): m/z (%)= 260 (3.55) [M]+, 246 (8.23), 123 (15.50), 105
1H NMR (300 MHz, CDCl3): = 7.92 (d, 2H, J = 9.0 Hz, Bz-2,6),
7.46 (d, 2H, J = 9.0 Hz, Bz-3,5), 2.48 (s, 3H, CH3).
(100) [PhCO]+, 77 (36.43).
Anal. Calcd for C14H12OS2: C, 64.58; H, 4.65. Found: C, 64.52; H,
4.77.
13C NMR (75 MHz, CDCl3): =189.14 (C=O), 140.58 (Bz-4),
134.04 (Bz-1), 129.25 (Bz-2,6), 129.02 (Bz-3,5), (22.60, CH3).
MS (EI): m/z (%) = 218 (0.45) [M]+, 139 (100) [ClPhCO]+, 111
(28.77).
4g (R2 = p- fluorophenyl)
Colorless oil.
IR (thin film): = 1691.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.98 (d, 2H, J = 7.5 Hz, Bz-2,6),
7.63 (t, 1H, J = 7.5, Bz-4), 7.61 (d, 2H, J = 8.5 Hz, Ph-2,6), 7.48 (t,
2H, J = 7.5 Hz, Bz-3,5),7.00 (dd, 2H, J = 8.5 Hz, Ph-3,5, JoH-F = 9.0
Hz).
Anal. Calcd for C8H7ClOS2: C, 43.93; H, 3.23. Found: C, 44.03; H,
3.39.
5b (R2 = benzyl)
Colorless.
Mp 65.0–66.0°C.
IR (KBr): = 1695.64 (C=O) cm–1.
13C NMR (75 MHz, CDCl3): = 189.11 (C=O), 164.08 (JC-F
=
247.5 Hz), 135.36 (Bz-1), 134.28 (Bz-4), 133.90 (JmC-F = 8.3 Hz),
131.14 (JPC-F = 2.8 Hz), 128.96 (Bz-3,5), 127.86 (Bz-2,6), 116.31
(JoC-F = 21.9 Hz).
1H NMR (300 MHz, CDCl3): = 7.88 (d, 2H, J = 9.0 Hz, Bz-2,6),
7.45 (d, 2H, J = 9.0 Hz, Bz-3,5), 7.33–7.27 (m, 5H, Bn), 4.00 (s, 2H,
Bn-CH2).
13C NMR (75 MHz, CDCl3): = 189.01 (C=O), 140.58 (Bn-1),
136.00 (Bz-4), 134.07 (Bz-1), 129.52 (Bz-2,6), 129.23 (Bz-3,5),
129.05 (Bn-3,5), 128.60 (Bn-2,6), 127.83 (Bn-4), 42.73 (Bn CH2).
MS (EI): m/z (%) = 264 (1.98) [M]+, 159 (3.91), 127 (25.28), 105
(100) [PhCO]+, 77 (56.68).
Anal. Calcd for C13H9FOS2: C, 59.07; H, 3.43. Found: C, 58.85; H,
3.52.
MS (EI): m/z (%) = 294 (0.69) [M]+, 139 (100) [ClPhCO]+, 111
4h (R2 = p-bromophenyl)
(20.52), 91 (25.94).
Colorless.
Anal. Calcd for C14H11ClOS2: C, 57.04; H, 3.76. Found: C, 56.85;
H, 3.85.
Mp 45.5–47.0°C.
IR (KBr): = 1693.72 cm–1.
5c (R2 = cyclohexyl)
Colorless oil.
IR (thin film): = 1689.86 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.95 (d, 2H, J = 8.5 Hz, Bz-2,6),
7.46 (d, 2H, J = 8.5 Hz, Bz-3,5), 2.87 (nonet, 1H, J = 3.6 Hz, Cy-1),
2.05 (2H), 1.80 (2H), 1.61 (1H), 1.46–1.29 (m, 5H, Cy).
13C NMR (75 MHz, CDCl3): = 189.84 (C=O), 140.45 (Bz-
4),134.18 (Bz-1),129.17 (Bz-2,6), 129.06 (Bz-3,5), 49.75 (Cy-1),
32.64 (Cy-2,6), 25.99 (Cy-3,5), 25.48 (Cy-4).
1H NMR (300 MHz, CDCl3): = 7.79 (d, 2H, J = 8.0 Hz, Bz-2,6),
7.63 (t, 1H, J = 8.0 Hz, Bz-4), 7.49 (t, 2H, J = 8.0 Hz, Bz-3,5), 7.45
(d, 2H, J = 8.5, Ph-3,5), 7.42 (d, 2H, J = 8.5 Hz, Ph-2,6).
13C NMR (75 MHz, CDCl3): = 188.70 (C=O), 135.24 (Bz-1),
135.01 (Ph-1), 134.39 (Bz-4), 132.22 (Ph-3,5), 132.06 (Ph-2,6),
129.01 (Bz-3,5), 127.92 (Bz-2,6), 122.59 (Ph-4).
MS (EI): m/z (%) = 324 (0.66) [M]+, 219 (0.37), 187 (7.21), 105
(100) [PhCO]+, 77 (29.02).
Anal. Calcd for C13H9BrOS2: C, 48.01; H, 2.79. Found: C, 48.15; H,
2.87.
MS (EI): m/z (%) = 286 (1.58) [M]+, 139 (100) [ClPhCO]+, 111
(14.43), 83 (2.84).
4i (R2 = 2-naphthyl)
Colorless.
Anal. Calcd for C13H15ClOS2: C, 54.44; H, 5.27. Found: C, 54.50;
H, 5.37.
Mp 69.0–70.0°C (Lit.4a 69°C).
IR (KBr): = 1695.64 (C=O) cm–1.
5d (R2 = phenyl)
Colorless.
1H NMR (300 MHz, CDCl3): = 8.09 (s, 1H, naph-1), 8.02 (d, 2H,
J = 7.5 Hz, Bz-2,6), 7.78 (d, 3H, J = 7.5 Hz, naph-4,5,8), 7.62(t, 2H,
J = 7.5 Hz, naph-6,7), 7.49 (t, 3H, J = 7.5 Hz, Bz-3,4,5), 7.47 (d, 1H,
J = 7.5 Hz, naph-3).
13C NMR (75 MHz, CDCl3): = 189.12 (C=O), 135.47 (Bz-1),
135.46 (naph-9), 134.24 (Bz-4), 133.34 (naph-10), 132.91 (naph-2),
129.95 (naph-1), 129.05 (Bz-3,5), 128.96 (naph-4), 127.91 (naph-
5,8), 127.74 (Bz-2,6), 126.76 (naph-6,7), 126.72 (naph-3).
Mp 79.0–80.0°C.
IR (KBr): = 1686.00 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.94 (d, 2H, J = 8.4 Hz, Bz-2,6),
7.57 (dd, 2H, J = 2.0, 7.5 Hz, Ph-2,6), 7.46 (d, 2H, J = 8.4 Hz, Bz-
3,5), 7.31–7.28 (m, 3H, Ph-3,4,5).
13C NMR (75 MHz, CDCl3): = 188.19 (C=O), 140.77 (Bz-4),
135.53 (Ph-1), 133.75 (Bz-1), 130.69 (Bz-2,6), 129.30 (Ph-2,6),
129.20 (Bz-3,5), 129.20 (Ph-3,5), 128.47 (Ph-4).
MS (EI): m/z (%) = 296 (7.69) [M]+, 219 (0.37), 187 (7.21), 105
MS (EI): m/z (%) = 280 (2.08) [M]+, 248, 139 (100) [ClPhCO]+, 111
(19.98), 109 (11.75).
(100) [PhCO]+, 77 (29.02).
Anal. Calcd for C17H12OS2: C, 68.89; H, 4.08. Found: C, 68.56; H,
4.20.
Anal. Calcd for C13H9ClOS2: C, 55.61; H, 3.23. Found: C, 55.27; H,
3.31.
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York

1040
K Fujiki et al.
PAPER
5e (R2 = p-tolyl)
Colorless.
Anal. Calcd for C14H11NO3S2: C, 55.07; H, 3.63; N, 4.59. Found: C,
55.27, H, 3.69; N, 4.53.
Mp 61.5–63.5°C.
IR (KBr): = 1682.14 (C=O) cm–1.
6c (6c’) (R2 = cyclohexyl)
Cream yellow.
1H NMR (300 MHz, CDCl3): = 7.92 (d, 2H, J = 8.4 Hz, Bz-2,6),
7.51 (d, 2H, J = 8.1 Hz, tolyl-2,6), 7.45 (d, 2H, J = 8.4 Hz, Bz-3,5),
7.12 (d, 2H, J = 8.1 Hz, tolyl-3,5), 2.32 (s, 3H, CH3).
13C NMR (75 MHz, CDCl3): = 188.50 (C=O), 140.64 (Bz-4),
139.14 (tolyl-4), 133.87 (Bz-1), 132.12 (tolyl-1), 131.75 (tolyl-3,5),
129.98 (Bz-2,6), 129.25 (tolyl-2,6), 129.16 (Bz-3,5), 21.20 (CH3).
Mp 72.0–73.0°C.
IR (KBr): = 1682.14 (C=O), 1522.03 (NO2), 1350.34 (NO2) cm–1.
1H NMR (300 MHz, CDCl3): = 8.34 (d, 2H, J = 9.0 Hz, Bz-3,5),
8.17 (d, 2H, J = 9.0 Hz, Bz-2,6), 2.91 (nonet, 1H, J = 3.6 Hz, Cy-1),
2.05 (2H), 1.82 (2H), 1.61 (1H), 1.47–1.21 (m, 5H, Cy).
13C NMR (75 MHz, CDCl3,): = 190.06 (C=O), 150.81 (Bz-4),
140.55 (Bz-1), 128.73 (Bz-2,6), 124.07 (Bz-3,5), 49.98 (Cy-1),
32.70 (Cy-2,6), 25.98 (Cy-3,5), 25.43 (Cy-4).
MS (EI): m/z (%) = 294 (2.85) [M]+, 155 (2.58), 139 (100)
[ClPhCO]+, 123 (15.68), 111 (19.90), 91 (10.67).
Anal. Calcd for C14H11ClOS2: C, 57.04; H, 3.76. Found: C, 57.18;
H, 3.89.
MS (EI): m/z (%) = 297 (4.47) [M]+, 150 (100) [NO2PhCO]+, 120
(5.03), 104 (15.05), 92 (5.98), 83 (6.63).
5f (R2 = p-fluorophenyl)
Colorless.
Anal. Calcd for C13H15NO3S2: C, 52.51; H, 5.08; N, 4.71. Found: C,
52.43; H, 5.11; N, 4.52.
Mp 64.0–65.5°C.
IR (KBr): = 1687.93 (C=O) cm–1.
6d (R2 = phenyl)
Colorless.
1H NMR (300 MHz, CDCl3): = 7.94 (d, 2H, J = 8.7 Hz, Bz-2,6),
7.62 [dd, 2H, J = 8.7 Hz, Ph-2,6, JmH-F = 5.3 Hz], 7.46 (d, 2H, J = 8.7
Hz, Bz-3,5), 7.01 [dd, 2H, J = 8.7 Hz, Ph-3,5, JoH-F = 8.7 Hz].
Mp 74.0–76.0°C.
IR (KBr): = 1684.07 (C=O), 1522.03 (NO2), 1344.56 (NO2) cm–1.
1H NMR (300 MHz, CDCl3): = 8.33 (d, 2H, J = 8.7 Hz, Bz-3,5),
8.14 (d, 2H, J = 8.7 Hz, Bz-2,6), 7.61 (dd, 2H, J = 2.4, 7.5 Hz, Ph-
2,6), 7.35–7.31 (m, 3H, Ph-3,4,5).
13C NMR (75 MHz, CDCl3): = 188.45 (C=O), 150.92 (Bz-4),
140.12 (Bz-1), 134.97 (Ph-1), 131.33 (Ph-2,6), 129.34 (Ph-3,5),
128.95 (Ph-4), 128.86 (Bz-2,6), 124.14 (Bz-3,5).
13C NMR (75 MHz, CDCl3): = 188.21 (C=O), 163.23 (JC-F
=
247.7 Hz), 140.85 (Bz-4), 134.20 (JmC-F = 8.0 Hz), 133.7 (Bz-1),
130.90 (JpC-F = 3.8 Hz), 129.33 (Bz-2,6), 129.18 (Bz-3,5), 116.39
(JoC-F = 22.3 Hz).
MS (EI): m/z (%) = 298 (0.76) [M]+, 159 (16.22), 139 (100 )
[ClPhCO]+, 127 (16.22), 111 (24.70), 95 (4.09).
MS (EI): m/z (%) = 291 (5.11) [M]+, 150 (100) [NO2PhCO]+, 141
(6.27), 120 (5.71), 109 (17.51), 104 (20.19).
Anal. Calcd for C13H8ClFOS2: C, 52.26; H, 2.70. Found: C, 52,23;
H, 2,72.
Anal. Calcd for C13H9NO3S2: C, 53.59; H, 3.11; N, 4.81; S, 22.01.
Found: C, 53.61; H, 3.18; N, 4.64; S, 22.01.
Compounds 6 (R1 = NO2)
Prepared by Method 1 or Method 2 with 2b
6e (6e’) (R2 = p-tolyl)
Colorless.
6a (6a’) (R2 = Me)
Pale yellow.
Mp 98.5–100.5°C.
Mp 65.0°C.
IR (KBr): = 1689.86 (C=O), 1529.75 (NO2), 1348.41 (NO2) cm–1.
IR (KBr): = 1674.43 (C=O), 1522.03 (NO2), 1348.41 (NO2) cm–1.
1H NMR (300 MHz, CDCl3): = 8.34 (d, 2H, J = 9.0 Hz, Bz-3,5),
8.14 (d, 2H, J = 9.0 Hz, Bz-2,6), 2.52 (s, 3H, CH3).
1H NMR (300 MHz, CDCl3): = 8.32 (d, 2H, J = 9.0 Hz, Bz-3,5),
8.13 (d, 2H, J = 9.0 Hz, Bz-2,6), 7.54 (d, 2H, J = 8.1 Hz, tolyl-2,6),
7.14 (d, 2H, J = 8.1 Hz, tolyl-3,5), 2.34 (s, 3H, CH3).
13C NMR (75 MHz, CDCl3): = 189.30 (C=O), 150.85 (Bz-4),
140.34 (Bz-1), 128.69 (Bz-2,6), 124.13 (Bz-3,5), 22.48 (CH3).
MS (EI): m/z (%) = 229 (2.39) [M]+, 150 (100) [NO2PhCO]+, 120
13C NMR(75 MHz, CDCl3): = 188.73 (C=O), 150.84 (Bz-4),
140.24 (Bz-1), 139.69 (tolyl-4), 132.33 (toly-3,5), 131.51 (tolyl-1),
130.11 (tolyl-2,6), 128.81 (Bz-2,6), 124.10 ( Bz-3,5), 21.24 (CH3).
MS (EI): m/z (%) = 305 (7.40) [M]+, 273 (2.55), 246 (8.67), 150
(100) [NO2PhCO]+, 123 (18.20), 120 (6.29), 104 (18.46), 91
(10.67).
(5.00), 104 (25.27).
Anal. Calcd for C8H7NO3S2: S, 27.97. Found: S, 28.03.
6b (R2 = benzyl)
Colorless.
Anal. Calcd for C14H11NO3S2: C, 55.07; H, 3.63; N, 4.59. Found: C,
54.75; H, 3.38; N, 4.46.
Mp 111.0–112.5°C.
IR (KBr): = 1693.72 (C=O), 1525.89 (NO2), 1350.34 (NO2) cm–1.
6f (6f’) (R2 = p-fluorophenyl)
Colorless.
1H NMR (300 MHz, CDCl3): = 8.32 (d, 2H, J = 8.7 Hz, Bz-3,5),
8.09 (d, 2H, J = 8.7 Hz, Bz-2,6), 7.34–7.29 (m, 5H, Bn), 4.03 (s, 2H,
Bn-CH2).
13C NMR (75 MHz, CDCl3): = 189.18 (C=O), 150.82 (Bz-4),
140.34 (Bz-1), 135.66 (Bn-1), 129.54 (Bz-2,6), 128.69 (Bn-3,5),
128.66 (Bn-2,6), 127.98 (Bn-4), 124.10 (Bz-3,5), 42.63 (Bn CH2).
Mp 86.5–87.5°C.
IR (KBr): = 1697.57 (C=O), 1545.18 (NO2), 1350.34 (NO2) cm–1.
1H NMR (300 MHz, CDCl3): = 8.33 (d, 2H, J = 8.8 Hz, Bz-3,5),
8.12 (d, 2H, J = 8.8 Hz, Bz-2,6), 7.66 (dd, 2H, J = 8.7 Hz, Ph-2,6,
JmH-F = 5.1 Hz), 7.03 (dd, 2H, J = 8.7 Hz, Ph-3,5, Jo=H-F = 8.7 Hz).
13C NMR (75 MHz, CDCl3): = 188.45 (C=O), 163.46 (d, Ph-4,
MS (EI): m/z (%) = 305 (4.17) [M]+, 150 (100) [NO2PhCO]+, 123
(4.34), 120 (5.80), 104 (18.52), 91 (42.67).
JC-F = 248.5 Hz), 150.95 (Bz-4), 140.06 (Bz-1), 134.84 (d, Jm
=
C-F
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent-free Synthesis of Unsymmetrical Benzoyldisulfides
IR (KBr): = 1732.30 (C=O) cm–1.
1041
8.0 Hz), 130.29 (d, JpC-F = 3.8 Hz), 128.84 (Bz-2,6), 124.17 (Bz-
3,5), 116.55 (d, JoC-F = 22.3 Hz).
MS (EI): m/z (%) = 309 (3.95) [M]+, 159 (5.05), 150 (100)
[NO2PhCO]+, 127 (21.25), 120 (6.71), 104 (21.96), 95 (3.72), 92
(9.10), 83 (13.28), 76 (14.26).
1H NMR (300 MHz, CDCl3): = 7.48 (dd, 4H, J = 2.4, 7.8 Hz, Ph-
2,6), 7.30–7.28 (m, 6H, Ph-3,4,5), 2.71 (t, 4H, J = 6.6 Hz), 1.73
(quint, 4H, J = 3.3 Hz).
13C NMR (75 MHz, CDCl3): = 196.70 (C=O), 135.67 (Ph-1),
130.28 (Ph-2,6), 129.19 (Ph-3,5), 128.33 (Ph-4), 41.60 (1-CH2),
24.50 (2-CH2).
Anal. Calcd for C13H8FNO3S2: C, 50.48; H, 2.61; N, 4.53. Found:
C, 50.43; H, 2.69; N, 4.32.
MS (FAB): m/z (%) = 395 (0.60) [M + H]+, 253 (36.18), 207
Compounds 8 (R3 = Tetramethylene)
Prepared by Method 3 with 2a
(30.32), 141 (19.15), 111 (100) [CO(CH2)4CO]+.
Anal. Calcd for C18H18O2S4: C, 54.79; H, 4.60. Found: C, 54.53; H,
4.69.
8a (R2 = Me)
Colorless.
8e (R2 = p-tolyl)
Colorless.
Mp 24.0–25.0°C.
IR (KBr): = 1718.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 2.70 (t, 4H, J = 6.9 Hz), 2.41 (s,
6H, CH3), 1.76 (quint, 4H, J = 3.6 Hz).
13C NMR (75 MHz, CDCl3): = 197.37 (C=O), 41.91 (1-CH2),
24.59 (2-CH2), 22.74 (CH3).
Mp 54.0–55.0°C.
IR (KBr): = 1710.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.41 (d, 4H, J = 8.1 Hz, tolyl-2,6),
7.11 (d, 4H, J = 8.1 Hz, tolyl-3,5), 2.68 (t, 4H, J = 6.9 Hz), 2.32 (s,
6H, CH3), 1.72 (quint, 4H, J = 3.6 Hz).
13C NMR (75 MHz, CDCl3): = 196.96 (C=O), 138.94 (tolyl-4),
132.30 (tolyl-1), 131.30 (toly-3,5), 129.97 (tolyl-2,6), 41.60 (1-
CH2), 24.51 (2-CH2), 21.17 (CH3).
MS (FAB): m/z (%) = 271 (5.15) [M + H]+, 191 (71.95), 145
(29.83), 111 (100) [(CH2)4(CO)2]+.
Anal. Calcd for C8H14O2S4: C, 35.53; H, 5.22. Found: C, 35.63; H,
5.00.
MS (FAB): m/z (%) = 421 (1.22) [M – 1]+, 267 (44.25), 221 (23.85),
155 (18.87), 123 (29.65), 111 (100) [CO(CH2)4CO]+.
8b (R2 = benzyl)
Colorless.
Anal. Calcd for C20H22O2S4: C, 56.84; H, 5.25. Found: C, 56.62; H,
5.26.
8f (R2 = p-fluorophenyl)
Mp 39.0–40.0°C.
IR (KBr): = 1720.72 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.33–7.27 (m, 10H, Bn), 3.92 (s,
4H, Bn-CH2), 2.56 (t, 4H, J = 7.2 Hz), 1.61 (quint, 4H, J = 3.6 Hz).
13C NMR (75 MHz, CDCl3): = 197.49 (C=O), 136.05 (Bn-1),
129.48 (Bn-3,5), 128.58 (Bn-2,6), 127.80 (Bn-4), 42.88 (Bn-CH2),
41.58 (1-CH2), 24.45 (2-CH2 )
Colorless.
Mp 57.0–58.0°C.
IR (KBr): = 1713.01 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 7.53 (dd, 4H, J = 8.7 Hz, Ph-2,6,
JmH-F = 5.1 Hz), 7.00 (dd, 4H, J = 8.7 Hz, Ph-3,5, JoH-F = 8.1 Hz),
2.68 (t, 4H, J = 6.9 Hz, 1-CH2), 1.73 (quint, 4H, J = 3.6 Hz, 2-CH2).
MS (FAB): m/z (%) = 423 (0.42) [M + H]+, 267 (33.01), 221
(14.09), 155 (1.99), 123 (6.53), 111 (54.84), 91 (100) [PhCH2]+.
13C NMR (75 MHz, CDCl3): = 196.44 (C=O), 163.11 (d, Ph-4,
J
C-F = 247.9 Hz), 133.85 (d, JmC-F = 8.6), 131.03 (d, JpC-F = 3.7 Hz),
Anal. Calcd for C20H22O2S4: C, 56.84; H, 5.25. Found: C, 56.74; H,
5.24.
116.38 (d, JoC-F = 22.2 Hz), 41.71 (1-CH2), 24.49 (2-CH2).
MS (FAB): m/z (%) = 429 (0.28) [M – 1]+, 271 (24.77), 225 (22.27),
159 (20.25), 127 (24.93), 111 (100) [CO(CH2)4CO]+, 95 (3.49), 83
(17.87).
8c (R2 = cyclohexyl)
Colorless.
Mp 48.0–49.0°C.
IR (KBr): = 1724.58 (C=O) cm–1.
Anal. Calcd for C18H16F2O2S4: C, 50.21; H, 3.75. Found: C, 50.00;
H, 3.76.
1H NMR (300 MHz, CDCl3): =2.74 (nonet, 2H, J = 3.9 Hz, Cy-
1), 2.71 (t, 4H, J = 6.9 Hz), 1.98 (4H, Cy), 1.76 (quint, 4H + 4H,
Cy), 1.60 (2H, Cy), 1.40–1.16 (m, 10H, Cy).
Compounds 9 (R3 = p-Phenylene)
Prepared by Method 3 with 2b.
13C NMR (75 MHz, CDCl3): = 198.24 (C=O), 49.71 (Cy-1),
41.79 ((1-CH2), 32.58 (Cy-2,6), 25.96 (Cy-3,5), 25.45 (Cy-4), 24.68
(2-CH2).
MS (FAB): m/z (%) = 407 (1.64) [M + H]+, 259 (71.49), 213 (9.22),
177 (15.31), 159 (5.94), 131 (7.78), 111 (100) [CO(CH2)4CO]+, 83
(28.23) [C6H11]+.
9a (R2 = Me)
Pale yellow.
Mp 152.0–153.0°C.
IR (KBr): = 1684.07 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.07 (s, p-phenylene-4H), 2.50 (s,
6H, CH3).
13C NMR (75 MHz, CDCl3): = 189.73 (C=O), 139.69 (p- phe-
nylene-1,4), 128.08 (p-phenylene-2,3,5,6), 22.52 (CH3).
Anal. Calcd for C18H30O 2S4: C, 53.16; H, 7.44. Found: C, 53.19; H,
7.33.
8d (R2 = phenyl)
Colorless.
MS (EI): m/z (%) = 290 (0.39) [M]+, 211 (100), 179 (10.89), 132
(48.30), 104 (55.00),76 (23.65).
Mp 66.0–67.5°C.
Anal. Calcd for C10H10O2S4: C, 41.35; H, 3.47. Found: C, 40.89; H,
3.49.
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K Fujiki et al.
PAPER
9b (R2 = benzyl)
Colorless.
MS (EI): m/z (%) = 442 (1.03) [M]+, 287 (20.48), 255 (100), 184
(4.91), 165 (11.68), 155 (5.59), 132 (27.09), 123 (28.20), 104
(42.29). 91 (17.11), 76 (14.08).
Mp 156–157.5°C.
Anal. Calcd for C22H18O2S4: S, 28.97. Found: S, 28.80.
IR (KBr): = 1689.86 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.02 (s, p-phenylene-4H), 7.35–
7.26 (m, 10H, Bn), 4.02 (s, 4H, Bn-CH2),
9f (R2 = p-fluorophenyl)
Colorless.
13C NMR (75 MHz, CDCl3): = 189.62 (C=O), 139.68 (p-phe-
nylene-1,4), 135.84 (Bn-1), 129.53 (Bn-3,5), 128.64 (Bn-2,6),
128.08 (p-phenylene-2,3,5,6), 127.91 (Bn-4), 42.67 (Bn-CH2).
MS (EI): m/z (%) = 442 (0.24) [M]+, 287 (30.49), 255 (61.05), 132
(16.02), 104 (22.68), 91 (100).
Mp 115.5–117°C.
IR (KBr): = 1687.93 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.05 (s, p-phenylene-4H), 7.64
(dd, 4H, J = 8.7 Hz, Ph-2,6, JmH-F = 5.1 Hz), 7.02 (t, 4H, J = 8.7 Hz,
Ph-3,5, JoH-F = 9.0 Hz).
13C NMR (75 MHz, CDCl3): = 188.84 (C=O), 163.34 (d, Ph-4,
JC-F = 248.6 Hz), 139.48 (p-phenylene-1,4), 134.57 (d, JmC-F = 8.0
Hz), 130.53 (d, JpC-F = 3.1 Hz), 128.27 (p-phenylene-2,3,5,6),
116.48 (d, JoC-F = 22.2 Hz).
MS (EI): m/z (%) = 450 (0.18) [M]+, 291 (9.17), 259 (100), 159
(13.89), 136 (3.75), 132 (28.19), 127 (51.11), 104 (43.64), 95
(4.18), 83 (25.13), 76 (16.59).
Anal. Calcd for C22H18O2S4: C, 59.70; H, 4.10; S, 28.97. Found: C,
59.28; H, 4.04, S, 28.63.
9c (R2 = cyclohexyl)
Colorless.
Mp 93.5–95.5°C.
IR (KBr): = 1691.79 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.09 (s, p-phenylene-4H), 2.90
(nonet, 2H, J = 3.6 Hz, Cy-1), 2.06 (4H), 1.79 (4H), 1.58 (2H),
1.48–1.21 (m, 10H, Cy).
Anal. Calcd for C20H12F2O2S4: C, 53.32; H, 2.68. Found: C, 53.37;
H, 2.88.
13C NMR (75 MHz, CDCl3): = 190.51 (C=O), 139.75 (p-phe-
nylene-1,4), 128.08 (p-phenylene-2,3,5,6), 49.85 (Cy-1), 32.67
(Cy-2,6), 25.79 (Cy-3,5), 25.46 (Cy-4).
MS (EI): m/z (%) = 426 (1.39) [M]+, 279 (100), 247 (53.21), 165
(19.36), 132 (42.14), 104 (34.31), 83 (22.50),76 (9.58).
References
(1) (a) Buckmann, J. D.; Johnson, B. S.; Field, L. Can. J.
Microbiol. 1966, 12, 1263. (b) Field, L.; Hanley, W. S. J.
Med. Chem. 1971, 14, 202; and references cited therein.
(2) Chuan-Fa, L.; Chang, R.; Tam, J. P. Tetrahedron Lett. 1996,
37, 933.
Anal. Calcd for C20H26O2S4: S, 30.06. Found: S, 29.55.
(3) (a) Flank, R. L.; Blegen, J. R. Org. Synth. Coll., Vol. 3;
Wiley: Chichester, 1955, 116–118. (b) Tanaka, S.; Masue,
K.; Okano, M. Bull. Chem. Soc. Jpn. 1978, 51, 659.
(c) Kodamari, M.; Fukuda, M.; Yoshitomi, S. Synthesis
1981, 637. (d) Kato, S. Phosphorus, Sulfur Silicon Relat.
Elem. 1997, 120 & 121, 213. (e) Robert, J.; Anouti, M.;
Abarbi, M.; Paris, J. J. Chem. Soc., Perkin Trans. 2 1997,
1759. (f) Niyomura, O.; Kitoh, Y.; Nagayama, K.; Kato, S.
Sulfur Letters 1999, 22, 195.
(4) (a) Böhme, H.; Clement, M. Liebigs Ann. Chem. 1952, 576,
61. (b) Böhme, H.; Zinner, G. Liebig Ann. Chem. 1954, 585,
142. (c) Fujisawa, T.; Kobayashi, N. J. Org. Chem. 1971, 36,
3546.
(5) (a) Field, L.; Hanley, W. S.; McVeigh, I. J. Org. Chem.
1971, 36, 2735. (b) Neumann, W. P.; Schwindt, J. Chem.
Ber. 1975, 108, 1339.
(6) Field, L.; Buckmann, J. D. J. Org. Chem. 1967, 32, 3467.
(7) Milligan, B.; Saville, B.; Swan, J. M. J. Chem. Soc. 1961,
4850.
(8) Metzner, P.; Thinhan, P. J. Chem. Soc., Chem. Commun.
1988, 390.
(9) Fujiki, K.; Yoshida, E. Synth. Commun. 1999, 29, 3289.
(10) Manuscript in preparation.
(11) (a) Toda, F. Synlett 1993, 303. (b) Toda, F. Acc. Chem. Res.
1995, 480. (c) Dittmwe, D. Chem. Ind. 1997, 779.
(d) Tanaka, K.; Toda, F. Chem. Rev. 2000, 1025.
(12) Hirabayashi, Y.; Mizuta, M.; Kojima, M.; Horio, Y. Bull.
Chem. Soc. Jpn. 1971, 44, 791; and references cited therein.
(13) Kobayashi, Y.; Itabashi, K. Synthesis 1985, 671.
9d (R2 = phenyl)
Pale yellow.
Mp 97.0–99.0°C.
IR (KBr): = 1687.93 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.07 (s, p-phenylene-4H), 7.61
(dd, 4H, J = 2.4, 7.9 Hz, Ph-2,6), 7.34 7.30 (m, 6H, Ph-3,4,5).
13C NMR (75 MHz, CDCl3): = 188.83 (C=O), 139.51 (p-phe-
nylene-1,4), 135.22 (Ph-1), 131.03 (Ph-2,6), 129.26 (Ph-3,5),
128.71 (Ph-4), 128.27 (p-phenylene-2,3,5,6).
MS (EI): m/z (%) = 414 (0.20) [M]+, 350 (3.94), 273 (4.51), 241
(100), 165 (4.80), 141 (13.92), 132 (18.11), 109 (25.19), 104
(35.87), 76 (14.04).
Anal. Calcd for C20H14O2S4: C, 57.94; H, 3.40. Found: C, 57.50; H,
3.45.
9e (R2 = p-tolyl)
Yellow.
Mp 131.0–133.0°C.
IR (KBr): = 1686.00 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): = 8.04 (s, p-phenylene-4H), 7.52 (d,
4H, J = 8.1 Hz, tolyl-2,6), 7.13 (d, 4H, J = 8.1 Hz, tolyl-3,5), 2.32 (s,
6H, CH3).
13C NMR (75 MHz, CDCl3,): = 189.12 (C=O), 139.59 (p-phe-
nylene-1,4), 139.41 (tolyl-4), 132.07 (tolyl-1), 131.83 (tolyl-3,5),
130.05 (tolyl-2,6), 128.27 (p-phenylene-2,3,5,6), 21.21 (CH3).
Synthesis 2001, No. 7, 1035–1042 ISSN 0039-7881 © Thieme Stuttgart · New York