The reaction of benzothiazolyl substituted α-phosphorylmethyl sulfoxides with several amines

Article abstract of DOI:10.1016/j.tet.2008.02.028

We have examined the reactivities of α-phosphorylmethyl benzothiazolyl sulfoxides in the thermolyses and in the presence of several amines, such as aniline, benzylamine, piperidine, morpholine, and pyrrolidine. Thermolyses of the derivatives in the presen

Full text of DOI:10.1016/j.tet.2008.02.028

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4496e4505
www.elsevier.com/locate/tet
The reaction of benzothiazolyl substituted a-phosphorylmethyl
sulfoxides with several amines
*
Hiroyuki Morita , Shintaro Tashiro, Masahiro Takeda, Nobuhiko Yamada,
Md. Chanmiya Sheikh, Hiroyuki Kawaguchi
Department of Material Systems Engineering and Life Science, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
Received 28 December 2007; received in revised form 1 February 2008; accepted 3 February 2008
Available online 14 February 2008
Abstract
We have examined the reactivities of a-phosphorylmethyl benzothiazolyl sulfoxides in the thermolyses and in the presence of several amines,
such as aniline, benzylamine, piperidine, morpholine, and pyrrolidine. Thermolyses of the derivatives in the presence of 2,3-dimethyl-1,3-
butadiene afforded 2-phosphoryl substituted 4,5-dimethyl-3,6-dihydro-2H-thiopyran S-oxide. In the reaction with amines, the complex product
mixture, which contains a-phosphorylmethyl benzothiazolyl sulfides (2 and 5), a-phosphorylmethyl disulfides (15 and 16), and 2-amino
substituted benzothiazole 14 was found to be formed besides the target phosphinecarbothioamides. Several mechanistic studies were performed
to elucidate the formation mechanism, particularly for deoxygenated products from the starting sulfoxides, i.e., 2 and 5 from 3 and 6, respec-
tively.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: a-Phosphorylmethyl sulfoxide; Benzothiazole; Phosphinecarbothioamide; Hetero DielseAlder reaction
1. Introduction
sulfoxides bearing benzothiazole group and studied their reac-
tions with several amines. Herein, we report the results of the
thermolysis in the presence of the diene and their reactions
with amines with mechanistic studies.
Previously, wereportedthatthethermolyticreactionofhetero-
aryl-substituted b-ketosulfoxides in the presence or absence of
bases afforded the corresponding thioaldehyde or sulfines,1 de-
pending on the substituted heteroaryl groups. In the thermolyses
of the sulfoxides bearing benzothiazolyl group, thioaldehydes are
considered to be formed via the rearranged sulfenate ester inter-
mediate.1a In contrast, 5-(1-phenyl)-1,2,3,4-tetrazolyl derivatives
revealed to afford sulfines via the elimination of tetrazole by the
E2 type elimination mechanisms.1b
Recently, we have extended the reaction of heteroaryl-
substituted a-phosphorylmethyl sulfoxides under similar condi-
tions, and reported novel phosphinecarbothioamide formations
in the reaction of tetrazolyl a-phosphorylmethyl sulfoxides
with several amines.2,3
2. Results and discussion
2.1. Thermolyses of a-phosphorylmethyl sulfoxides 3 and 6 in
the presence of 1,3-dimethyl-2,3-butadiene
Benzothiazolyl substituted a-(diphenylphosphoryl)- and
a-(diethoxyphosphoryl)methyl sulfoxides (3 and 6) were pre-
pared following the procedure, which was reported previously.3
The thermolysis of 3 in the presence of 2,3-dimethyl-1,3-butadi-
ene was studied in 1,4-dioxane at several temperatures. The
results are summarized in Table 1. The cycloadduct 8 or 10
was expectedly observed to be formed in moderate to high
yields, via the hetero DielseAlder reaction of diene with sulfine
formed initially as similarly in the case of a-phosphorylmethyl
tetrazolyl sulfoxides.3 In these cases compound 9 or 11 were
also formed by elimination of H2O from 8 or 10.3
In order to obtain the scope and limitations of the reactions,
we further prepared several substituted a-phosphorylmethyl
* Corresponding author. Tel.: þ81 76 445 6851; fax: þ81 76 445 6703.
E-mail address: morita@eng.u-toyama.ac.jp (H. Morita).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.028

H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
4497
Table 1
Thermolyses of 3 and 6 in the presence of 2,3-dimethyl-1,3-butadiene
O
O
R
R
R
R
O
P
P
O
S
O
S
S
(10 equiv.)
Btz
CH2
P
R
R
Btz
H
+
+
a
1,4-dioxane,
3 R = Ph
6 R = OEt
8 R = Ph
10 R = OEt
9 R = Ph
11 R = OEt
7
Entry
Sulfoxide
Conditions
Yieldsb (%)
7
8/10
9/11
1
2
3
4
a
3
3
3
6
140 ꢀC, 5 h
36
53
39
0
61c
0
22e
96e
68e
57f
140 ꢀC, 2 h, Et3N (1.5 equiv)
160 ꢀC, 1 h
0
29d
160 ꢀC, 8 h
In sealed tube.
b
c
d
e
f
Isolated yields.
Product is 8.
Product is 10.
Product is 9.
Product is 11.
When the reaction of 3 was carried out at 140 ꢀC for 5 h,
5-(1-phenyl)-1H-tetrazolyl sulfoxide with several amines. In
all cases, the expected corresponding sulfinamides were not ob-
tained, but unexpected formation of phosphinecarbothioamide
derivatives was seen as shown in Scheme 1 (the scheme is
depicted using pyrrolidine as a base for the clarity).2
The mechanism was considered as shown in Scheme 2.
In order to examine the effect of heteroaryl groups, we
further extended the study of the reaction of 3 or 6 with
amines under similar conditions. Contrary to the results in
a-(dimethylphosphoryl)methyl 5-(1-phenyl)-1H-tetrazolyl
sulfoxide (cf. Scheme 1),3 the reactions afforded the complex
product mixtures and their distributions were revealed to
change greatly depending on the several amines used as sum-
marized in Table 2. The great difference compared with the
results in the case of a-phosphorylmethyl 5-(1-phenyl)-1H-
tetrazolyl sulfoxides is as follows: (1) the formation of the
unexpected deoxygenated compounds 2 and 5, which were
formally formed by the reduction of 3 and 6, respectively,
the obtained products were 2-(diphenyl)phosphoryl-3,6-dihy-
dro-4,5-dimethyl-2H-thiopyran S-oxide (8), 6-(diphenyl)phos-
phoryl-3,4-dimethyl-2H-thiopyran (9), and benzothiazole (7),
in 36, 61, and 22% yields, respectively (entry 1). At higher
temperature, 160 ꢀC for 1 h, 8 disappeared and 9 was formed
in 68% (entry 3). When the thermolysis was carried out in the
presence of triethylamine at 140 ꢀC, 9 was obtained quantita-
tively with 53% yield of 7 (entry 2).
In the thermolysis of 6 for 8 h at 160 ꢀC, 10 and 11 were
obtained in 29 and 57% yields, respectively (entry 4).
2.2. Reactions of benzothiazolyl sulfoxides 6 and 11 bearing
a-(diphenylphosphoryl)- and a-(diethoxyphosphoryl)methyl
groups with several amines
Since it is reported that the sulfines react with amines to
afford the sulfinamide derivatives,4 we studied the reaction of
Ph
Ph
N
O
S
O
S
C
O
P
Ph
N
N
N
CH2 P Ph
Ph
HN
N
N
+
H
Ph
N
+
1,4-dioxane, 90 °C, 1 h
N
N
98%
87%
Scheme 1. The reaction of a-(diphenylphosphoryl)methyl tetrazolyl sulfoxide with pyrrolidine.
O
OH
Ph
N
S
C
O
S
O
O
O
S
C
S
C
O
P
R
R1
R2
R1R2NH
R1R2NH
(base)
Ph
N
N
CH
H
P R
R
R P
R
H
R P
R
H
R
N
NR1R2
N
R = Ph
R = OEt
N
N
H
N
N
Scheme 2. Plausible mechanism for the formation of phosphinecarbothioamides.

4498
H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
Table 2
Reaction of 3 and 6 with several amines
O
O
O
S
C
O
P
R
R1
R2
amine (2.2 equiv.)
+
+
Btz
S CH2
P
R
R
Btz H
Btz
S CH2
P
R
R
N
R
1,4-dioxane, conditions
2 R = Ph
3 R = Ph
12a-e R = Ph
7
13a-e R = OEt
6 R = OEt
5 R = OEt
O
R1
+
+
N
CH2
S
R
P
R
Btz
R2
2
15 R = Ph
16 R = OEt
14a-e
Entry
Sulfoxide
Amine
Conditions
Yieldsa (%)
2/5
11b
42b
7
12/13
14
15/16
a,
Ph NH2
1
2
3
3
90 ꢀC, 64 h
90 ꢀC, 3.5 h
40
0
12 (12a)
20 (12b)
15 (14a)
51 (14b)
Traced
Traced
b, Ph
c,
NH2
3
4
5
3
3
3
90 ꢀC, 1 h
20b
28b
24b
0
0
12 (12c)
19 (12d)
6 (12e)
67 (14c)
72 (14d)
81 (14e)
Traced
32d
NH
NH
d,
O
90 ꢀC, 0.75 h
90 ꢀC, 0.5 h
Tracec
Traced
e,
NH
a,
Ph NH2
6
7
6
6
100 ꢀC, 6 h
100 ꢀC, 3 h
Trace
18c
0
0
Trace (13a)
13 (13b)
76 (14a)
39 (14b)
51e
26e
Ph
NH2
NH
b,
c,
8
9
6
6
6
100 ꢀC, 0.25 h
100 ꢀC, 1 h
27c
20c
26c
0
0
0
24 (13c)
24 (13d)
26 (13e)
35 (14c)
53 (14d)
27 (14e)
15e
15e
29e
d,
O
NH
NH
e,
10
100 ꢀC, 0.25 h
a
Isolated yields.
Product is 2.
b
c
d
e
Product is 5.
Product is 15.
Product is 16.
(2) the yield of 7 is almost 0%, (3) the formations of 2-amino
substituted benzothiazole 14 were observed, (4) low yields of
12 and 13, and (5) the formation of disulfides 15 and 16 were
observed.
In the reactions of 3 the deoxygenated product 2 was
formed in 11e42% yields together with the formation of phos-
phoryl substituted disulfide 15. In addition, the yields for the
corresponding phosphinecarbothioamide derivatives 12aee
were reduced greatly, and particularly, benzothiazole (7) was
not formed at all except entries 1 and 5.
The reactions of 6 with the same amines proceeded slowly
compared with 3. Therefore, the reactions of 6 were carried
out at 100 ꢀC. Similar results were obtained, however, the
yields of the corresponding a-phosphorylmethyl derivatives
16 became higher compared with the case of 3. This result
seems to suggest that 16 is more stable than 15 under same
conditions. The effect of the phosphoryl substituents and
used amines on the yields and distribution of the products sug-
gests that the amine used played crucial role, probably in the
hydrogen abstraction and/or nucleophilic step in the reaction
course, as mentioned later.
2.3. Mechanistic studies on the reaction of benzothiazolyl
a-(phosphoryl)methyl sulfoxide with amines
As shown in Scheme 1, the reaction of a-(diphenylphos-
phoryl)methyl 5-(1-phenyl)-1H-tetrazolyl sulfoxide proceeded
cleanly to give the corresponding phosphinecarbothioamide
derivatives 12 and tetrazole in moderate and good yields, re-
spectively. In the reaction of 3 and 6 under the same condi-
tions, similar reaction pathway will be also conceivable.
However, in the reaction pathway the formation of deoxygen-
ated products 2 and 5, the formation of 2-amino substituted
benzothiazole 14 and the disulfides 15 and 16, and the absence
or very low yield of benzothiazole (7) could not be rational-
ized. Particularly, the formation of 14 in relatively high yield
seems to suggest that the different mechanistic pathways,
namely, direct displacement reaction of 3 or 6 with amines
to form 14 are involved, as shown later in Scheme 8.
In order to elucidate the possible mechanism, we carried out
the following model or controlled reactions. First, the formation
of the reduction products 2 and 5 is unexpected and not conceiv-
able easily, because no apparent redox conditions seem to exist

H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
4499
O
S
S
CH2
Ph
P
Ph
O
O
S
O
N
S
N
amine base
2
CH2
Ph
Ph
CH2SH +
P
Ph
P
Ph
O
CH2
Ph
S OH
17
3
P
Ph
18
Scheme 3. Possible route to 2 by nucleophilic reactions of 3 with 17.
O
O
O
O
BnSH/DBU
1,4-dioxane
Btz S CH2
+
+
R
P R
R
Btz
S
Bn
R P
R
S OH
CH2
Btz
S
CH2
P
R
a
18
3 R = Ph
6 R = OEt
21 78%
21 71%
2 R = Ph 11%
5 R = OEt 11%
b
20
adisulfide 15 was obtained in 17% yielded instead of sulfenic acid 18
bdisulfide 16 was obtained in 30% yielded instead of sulfenic acid 20
Scheme 4. The reaction of 3 or 6 with benzylthiol in the presence of DBU.
in the reaction system. Probably, one of the possible routes to the
deoxygenated product 2 will be via the nucleophilic displace-
ment reaction of 3 with diphenylphosphorylmethyl thiol (17),
in the presence of bases, producing the corresponding sulfenic
acid 18, as depicted in Scheme 3. Diethoxyphosphoryl
substituted derivative 5 proceeded also in the same way, to
produce the deoxygenated product 5 and sulfenic acid 20.
Therefore, the controlled reactions of the same compound 3
or 6 with benzylthiol in the presence of DBU were carried out.
In both cases, the displacement product benzothiazolyl benzyl
sulfide 21 was expectedly formed in high yields together with
the disulfides 15 or 16 and others as shown in Scheme 4.
These experiments indicate clearly that the nucleophilic
displacement reaction (additioneelimination mechanism) at
C-2 position of benzothiazole ring with phosphorylmethyl
thiols 17 or 19 is involved.
The formation of the thiol 17-trapped product 23 was ob-
served expectedly, however, the yield was very low, together
with the major formation of morpholine Michael adduct 22
and other complex products derived from the further reaction
with thiol 17 formed initially.
In order to make sure the formation of thiol 17 (or the cor-
responding thiolate anion) by the reaction of disulfide 15 with
the amines used, 15 was prepared authentically and the reac-
tion with morpholine was carried out in the presence of N-phe-
nylmaleimide. The similar product distribution was obtained
as in the case of the reaction of 3 under similar conditions
as shown in Scheme 6. This result clearly indicated that thiol
17 (or the corresponding thiolate) is formed by the nucleo-
philic attacking with morpholine toward 15. Usually, the com-
mon disulfide is hard to cleave with amines, however, similar
nucleophilic cleavage of the SeS bond by amines was reported
in the case of the disulfides bearing electron withdrawing sub-
stituents, such as di-o-dinitrophenyl disulfide.5
Further, in order to obtain the clue for the formation of the
thiol 17 in the reaction sequence, we carried out the reaction of
3 with morpholine in the presence of N-phenylmaleimide as
the Michael addition acceptor under the same conditions as
shown in Scheme 5.
Further, in order to study more clearly the behavior of the
disulfide in the course of reaction, 15 was subjected to the con-
trolled reaction under several conditions. First, the reaction of
O
O
O
S
O
O
i
ii
Btz
CH2
P
Ph
N
CH2
S
Ph
P
+
N
O
N
+ etc...
Ph
Ph
Ph
Ph
O
O
3
22
23
Scheme 5. The reaction of 3 with morpholine in the presence of N-phenylmaleimide. (i) Morpholine, 1,4-dioxane, 90 ꢀC, 15 min; (ii) N-phenylmaleimide, 7.5 h.
O
O
O
O
i
ii
CH2
S
Ph
P
N
Ph
P
CH2
S
+
O
+ etc...
N
N
Ph
Ph
Ph
Ph
O
O
2
22
15
23
Scheme 6. The reaction of 15 with morpholine in the presence of N-phenylmaleimide. (i) Morpholine, 1,4-dioxane, 90 ꢀC, 30 min; (ii) N-phenylmaleimide,
1,4-dioxane, 90 ꢀC, 3 h.

4500
H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
15 with benzothiazole in 1,4-dioxane at 90 ꢀC was carried out,
however, the formation of the deoxygenated product 2 was not
observed even after prolonged reaction time. Therefore, the di-
rect displacement reaction of 15 with benzothiazole seems not
to be involved. Second, the reactions of disulfide 15 with mor-
pholine were carried out under several conditions. The results
seem to indicate that 12d was formed directly through disul-
fide 15, as shown in Scheme 7. The formations of the corre-
sponding derivatives were reported in the reaction of
phenacyl disulfides with morpholine under similar conditions.6
presence of amine base. The addition reaction of the sulfines
thus formed with amines led to phosphinecarbothioamide 12
or 13. Then, the nucleophilic attacking with the eliminated
thiol 17 and 19 toward 3 or 6 took place to afford the deoxy-
genated product 2 or 5 in the presence of amine base, respec-
tively. Meanwhile, the formation of disulfide 15 or 16 occurred
consecutively by the cascade reaction of thiolsulfinate 24.
Consequently, this route 1 seems to explain the formation of
all the products in the reaction of 3 or 6 with amines.
The route 2 to the product 12 or 13 by the reaction of 15 or
16 with amines, respectively, seems also to be involved, as
shown in Scheme 9 (the mechanistic pathway is depicted in
the case of the reaction 15 with morpholine for clarity).
First, sulfenamide 25 was formed by the nucleophilic cleav-
age of disulfide 15 with amines as mentioned previously. Suc-
cessively, sulfonium salt 260 was formed by sulfenylation of
disulfide 15 with sulfenamide. The formation of the similar
sulfonium salt intermediate 26 was also reported.7 Finally,
phosphinecarbothioamide 12d was formed via the sequence
of the reaction of 27 to 28 as depicted in Scheme 9. In this
route, the deoxygenated product 2 is also formed by the reac-
tion of 3 with the thiol 17. As a result, this reaction seems to
provide the redox system involving reduction of disulfide 15 to
thiol 17 and oxidation of disulfide 15 to 12d. However,
whether route 1 or 2 is mainly involving or not is still
controversial.
O
O
S
C
HN
O
CH2
S
Ph
P
Ph
P
N
O
+
15
1,4-dioxane, 90 °C
7 h, Under N2
Ph
Ph
2
15
12d 40%
18%
Scheme 7. Reaction of 15 with morpholine.
From all the model and controlled experiments, we propose
two mechanistic pathways. Namely, the possible mechanism
for the formation of anomalous product 12d or 13d is as fol-
lows: route 1: via the reaction of thiolsulfinate 24 formed ini-
tially with amines, and route 2: via the reaction of disulfide 15
or 16 formed initially with amines.
Route 1 is depicted in Scheme 8. First, the displacement
reaction of 3 or 6 with amines proceeded to afford 14 and
sufenic acid 18 or 21, which was immediately converted to
thiolsulfinate 24 by self-condensation. Successively, the elim-
ination reaction of 24 proceeded to afford the sulfines in the
Finally, in order to make clear the formation of thiol 17 or
19 in the course of the reaction, a-(diphenylphosphoryl)-
methyl 2-(5-chlorobenzothiazolyl)sulfoxide (30) was prepared
Route 1
O
S
O
O
R1
N
S
R1R2NH +
P
R
R
Btz
+
CH2
N
CH2 S OH
R
P
R
R2
3 or 6
sulfenic acid (18 or 20)
14a-e
R = Ph, OEt
O
O
O
S
O
O
CH2
P
R
R
S
CH2
S
R
P
R
CH2
R
P
R
2
R
P
R
CH2
S
OH
H2O
2
thiolsulfinate ( 24)
18 or 20
15 or 16
O
O
O
O
O
S
C
O
R1R2NH
CH2SH
P
R
+
R
P
R
CH2
S
S
R
R
P
R
CH
R
P
R
H
H
sulfine
24
17 or 19
O
OH
O
R1
R2
S
C
S
C
O
S
C
O
R1R2NH
R1R2NH
R
P
R
N
R
P
R
H
R
P
R
H
NR1R2
sulfine
12a-e or 13a-e
O
O
O
O
N
R
P
R
CH2SH
+
S
CH2
18 or 20
+
P
R
R
Btz
S
CH2
P
R
R
S
17 or 19
3 or 6
2 or 5
Scheme 8. Routes 1 (possible route to 12aee or 13aee, 15 or 16, and 2 or 5, respectively).

H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
4501
Route 2
O
O
O
O
O
HN
O
Ph P CH2
S
S
S
CH2
P
Ph
Ph
15
Ph
P
CH2
S
S
P
Ph
Ph
Ph P CH2
Ph
S
N
O
CH2
Ph
O
Ph
O
Ph
P
Ph
CH2
15
25
N
O
Ph P CH2SH
Ph
17
26'
H
C
O
P
Ph
O
O
P
Ph
H
C
Ph
CH2
S
S
P
Ph
Ph
O
HN
O
HN
O
Ph
CH2
O
S
S
P
Ph
Ph
17
O
H
S
Ph
P
Ph
CH2
O
17
17
Ph
P
Ph
CH2S
Ph
P
Ph
CH2S
27
26
O
O
S
HN
O
N
O
O
Ph
P
C
N
O
Ph
P
CH2
S
S
C
H
P
Ph
Ph
17
Ph
Ph
28
12d
net reaction
O
O
O
O
P
R
S
CH2
S
S
R
+
+
2 R
P
R
P
R
3
CH2SH
R
P
R
CH2
HN
O
+
+
R
C
N
O
2
(R
S
15, 16
S
R)
(R SH)
3
17, 19
morpholine
12d, 13d
Scheme 9. Route 2 (possible route to 12d).
and the cross-over reaction between 6 and 30 with morpholine
under similar conditions were carried out. The results are sum-
marized in Scheme 10. The formation of the cross-over prod-
uct 2 and the distribution of other products clearly suggest that
the involvement of the route via the reaction of 6 with thiol 17
derived from 30.
nature of C-2 carbon. The greater electrophilicity at C-2 carbon
of 30 by the electronic effect at 5-chloro substituent accelerated
the displacement reaction than that toward 6, which resulted in
the 60% recovery of 6. It is interesting to note that disulfides 15
and 16 seems to be rather stable and obtained in 22 and 16%
yield, respectively, despite the formation of 12d in 31% yield.
These results may indicate that the route 1 (Scheme 8)
proceeded more predominantly than route 2 (Scheme 9).
The observation of the difference of the reactivities between
6 and 17 will be explained by the difference of the electronic
O
S
O
O
S
N
S
CH2
P
Ph
Ph
S
CH2
P
Ph
Ph
N
Cl
Cl
O
i
30
29 4%
Btz
S
CH2
P
Ph
Ph
+
+
O
S
O
P
O
P
2 16%
Btz
CH2
OEt
Btz
S
CH2
OEt
OEt
OEt
5 2%
6
a
other products
O
P
S
O
P
O
S
N
Ph
P
Ph
C
N
O
O
N
O
CH2
S
Ph
Ph
S
CH2
EtO
Cl
Ph
EtO
16 16%
2
2
12d 31%
31 81%
15 22%
O
O
S
C
O
P
Btz
EtO
N
N
O
CH2
S
S
CH2
P
OEt
P
EtO
13d trace
OEt
Ph
23d 7%
32 9%
a
6 was recovered 60%
Scheme 10. Cross-over reaction of 30 and 6 with morpholine. (i) Morpholine 5.0 equiv, 1,4-dioxane, rt, 2 days.

4502
H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
1
3. Conclusion
5H); 13C NMR (CDCl3) d 31.0 (d, JCeP¼67.7 Hz), 121.0,
2
121.4, 124.5, 126.0, 128.6 (d, JCeP¼12.3 Hz), 130.9 (d,
3
4
Several heteroaryl phosphoryl substituted methyl sulfox-
ides 3 and 6 were prepared, and their thermolysis and their
reaction with amines were examined. In the thermolysis, in
the presence of 2,3-dimethyl-1,3-butadiene, the hetero
DielseAlder reaction adducts were formed and converted to
3,6-dihydro-thiopyrane derivatives 8e11 as similarly in the
case of the heteroaryl b-ketosulfoxides.1b In the reaction of
tetrazolyl sulfoxide, the formation of phosphinecarbothio-
amides 12 and 13 was considered to be via sulfine, which
was formed initially by the base catalyzed elimination of tet-
razole due to the high leaving ability. In the reaction of benzo-
thiazolyl sulfoxides 3 and 6 with amines, the formation of
phosphinecarbothioamide derivatives was poor with complex
product distribution when compared with tetrazolyl substituted
phosphoryl sulfoxides, and the formation of deoxygenated
products 2 and 5 was observed. In view of the results of the
intensive mechanistic studies, it is suggested that the reaction
proceed via thiol 17 or 19, which was formed in the course of
the reaction.
1JCeP¼103.2 Hz), 131.2 (d, JCeP¼9.9 Hz), 132.3 (d, JCeP
¼
3
2.3 Hz), 135.6, 152.3, 164.8 (d, JCeP¼5.6 Hz); IR (KBr):
3054, 2959, 2908, 1190 cmꢁ1. Anal. Calcd for C20H16NOPS2:
C, 62.97; H, 4.23; N, 3.67. Found: C, 63.02; H, 4.25; N, 3.67.
4.2.2. a-(Diphenylphosphoryl)methyl 2-(5-chlorobenzo-
thiazolyl)sulfide (29)
Yield 93%; mp 160e161 ꢀC (white crystal from CH2Cl2/
1
AcOEt/hexane); H NMR (CDCl3) d 4.34 (d, J¼8.4 Hz, 2H),
7.25e7.28 (m, 1H), 7.42e7.53 (m, 6H), 7.59 (d, J¼8.4 Hz,
1H), 7.80e7.87 (m, 5H); 13C NMR (CDCl3) d 31.0 (d, 1JCeP
¼
67.8 Hz), 121.2, 121.6, 124.8, 128.6 (d, 2JCeP¼12.3 Hz), 130.8
(d, 1JCeP¼103.2 Hz), 131.1 (d, 3JCeP¼9.1 Hz), 132.1, 132.3 (d,
4JCeP¼2.5 Hz), 133.7, 153.0, 167.1 (d, JCeP¼5.7 Hz); IR
3
(KBr): 1431, 1198, 999 cmꢁ1. Anal. Calcd for C20H15NOPS2Cl:
C, 57.76; H, 3.64; N, 3.37. Found: C, 57.73; H, 3.63; N, 3.13.
4.3. a-(Diethoxyphosphoryl)methyl 2-benzothiazolyl
sulfide (5)
4. Experimental section
To a stirred solution of tosylate 4 (1.0 equiv) and 2-mercap-
tobenzothiazole (1.2 equiv) in DMF was added K2CO3
(3.0 equiv) at rt. This reaction mixture was stirred for about
8 h at 80 ꢀC. After the starting materials were consumed,
DMF was evaporated off, residue was dissolved in CHCl3,
and then the precipitate was filtered off. The organic layer
was washed with H2O and dried over anhydrous MgSO4.
Then, the removal of solvent afforded to crude sulfide 5, which
was purified by flash chromatography. Yield 83%; colorless
oil; 1H NMR (CDCl3) d 1.30 (t, J¼7.1 Hz, 6H), 3.81 (d,
J¼7.1 Hz, 2H), 4.15e4.22 (m, 4H), 7.29e7.33 (m, 1H),
7.40e7.44 (m, 1H), 7.75e7.77 (m, 1H), 7.85e7.87 (m, 1H);
4.1. General
All the melting points were uncorrected using micro melt-
ing point apparatus. 1H NMR (400 MHz) and 13C NMR
(100 MHz) spectra were recorded in CDCl3 using TMS as
an internal standard. The elemental analyses were performed
at Micro analytical Laboratory of the Department of Material
Systems Engineering and Life Science, University of Toyama.
All the reactions were monitored with TLC and the products
were separated by column chromatography using silica gel
60 and also by preparative layer chromatography using silica
gel 60 PF254 with UV detection. All the reagents were the
highest quality and further purified by distillation or recrystal-
lization. The solvents were further purified by general method.
13C NMR (CDCl3) d 16.3 (d, 3JCeP¼6.0 Hz), 25.9 (d, 1JCeP
¼
148.7 Hz), 63.0 (d, 2JCeP¼6.4 Hz), 121.1, 121.5, 124.5, 126.1,
135.5, 152.6, 164.9; IR (NaCl disc): 2360, 1252, 1049, 1022,
; HRMS (EI) m/z calcd for C12H16NO3PS2:
970 cmꢁ1
317.0309. Found: 317.0316.
4.2. General procedure for the preparation of sulfides
2 and 29
4.4. General procedure for the preparation of sulfoxides 3, 6,
and 30
To a stirred solution of diphenylphosphinomethyl tosylate 1
(1.0 equiv) and 2-mercaptobenzothiazole (1.2 equiv) in THF
was added K2CO3 (3.0 equiv) at rt and stirred for about 2 h.
After the starting materials were consumed, THF was evapo-
rated off, residue was dissolved in CHCl3, and then the precip-
itate was filtered off. The organic layer was washed with H2O
and dried over anhydrous MgSO4. Then, the removal of sol-
vent afforded crude sulfides 2 and 29, which were purified
by flash chromatography.
To a stirred solution of sulfide (1 mmol) in CHCl3 (20 mL)
was added m-CPBA (1.2 mmol) in CHCl3 (20 mL) at rt. After
stirring for 1 h, the reaction mixture was washed with satu-
rated solution of NaHCO3 three times. The aqueous layer
was extracted with CHCl3.The combined organic layer was
washed with water and dried over anhydrous MgSO4. After re-
moval of the solvent, the residue was purified by flash column
chromatography on silica gel.
4.2.1. a-(Diphenylphosphoryl)methyl 2-benzothiazolyl
sulfide (2)
4.4.1. a-(Diphenylphosphoryl)methyl 2-benzothiazolyl
sulfoxide (3)
1
1
Yield 81%; mp: 125e126 ꢀC (CH2Cl2/AcOEt/hexane); H
Yield 81%; mp 170e171 ꢀC (CH2Cl2/AcOEt/hexane); H
NMR (CDCl3) d 4.36 (d, J¼7.6 Hz, 2H), 7.27e7.31 (m,
NMR (CDCl3) d 4.23 (dd, J¼14.4, 14.4 Hz, 1H), 4.35 (dd,
1H), 7.39e7.52 (m, 7H), 7.68e7.71 (m, 1H), 7.81e7.86 (m,
J¼14.4, 14.4 Hz, 1H), 7.45e7.60 (m, 8H), 7.81e7.88 (m,

H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
4503
3
3
1
4H), 7.96 (d, J¼8.4 Hz, 1H), 8.03 (d, J¼8.0 Hz, 1H); 13C NMR
(CDCl3) d 58.2 (d, 1JCeP¼60.2 Hz), 122.2, 124.2, 126.4, 127.0,
128.8 (d, 2JCeP¼12.1 Hz), 128.9 (d, 2JCeP¼13.2 Hz), 130.8 (d,
(d, JCeP¼6.6 Hz), 128.8 (d, JCeP¼6.6 Hz), 130.3 (d, JCeP
¼
1
2
100.8 Hz), 130.9 (d, JCeP¼101.6 Hz), 131.2 (d, JCeP
¼
2
4
9.1 Hz), 131.5 (d, JCeP¼9.1 Hz), 132.3 (d, JCeP¼3.3 Hz),
132.5(d, 4JCeP¼3.3 Hz);IR (KBr):1198, 1049 cmꢁ1. Anal. Calcd
for C19H21O2PS: C, 66.26; H, 6.15. Found: C, 66.57; H, 6.44.
1JCeP¼100.8 Hz), 131.0 (d, 1JCeP¼105.8 Hz), 131.2 (d, 3JCeP
¼
3
4
9.8 Hz), 131.4 (d, JCeP¼10.7 Hz), 132.6 (d, JCeP¼2.5 Hz),
4
3
132.7 (d, JCeP¼2.4 Hz), 136.4, 153.4, 169.7 (d, JCeP
¼
10.3 Hz); IR (KBr): 1055 cmꢁ1. Anal. Calcd for C20H16NO2PS2:
C, 60.44; H, 4.06; N, 3.52. Found: C, 60.48; H, 4.11; N, 3.50.
4.5.2. 6-(Diphenyl)phosphoryl-3,4-dimethyl-2H-
thiopyran (9)
Unstably brown crude compound; 1H NMR (CDCl3) d 1.85
(s, 3H), 1.90 (s, 3H), 3.19 (s, 2H), 6.98 (d, J¼16.2 Hz, 1H),
7.45e7.58 (m, 6H), 7.79e7.83 (m, 4H); HRMS (EI) m/z calcd
for C19H19OPS: 326.0894. Found: 326.0875.
4.4.2. a-(Diethoxyphosphoryl)methyl 2-benzothiazolyl
sulfoxide (6)
Yield 68%; colorless oil; 1H NMR (CDCl3) d 1.34 (t,
J¼7.1 Hz, 3H), 1.37 (t, J¼7.1 Hz, 3H), 3.65 (dd, J¼12.9,
12.9 Hz, 1H), 3.86 (dd, J¼14.8, 14.8 Hz, 1H), 4.18e4.29
(m, 4H), 7.49e7.53 (m, 1H), 7.56e7.61 (m, 1H), 8.00e8.03
(m, 1H), 8.07e8.10 (m, 1H); 13C NMR (CDCl3) d 16.2
4.5.3. 2-(Diethoxy)phosphoryl-5,6-dihydro-3,4-dimethyl-
2H-thiopyran S-oxide (10)
Colorless oil; 1H NMR (CDCl3)d1.35 (t, J¼7.07 Hz, 3H), 1.36
(t, J¼7.03 Hz, 3H), 1.75 (s, 3H), 1.78 (s, 3H), 1.95e2.05 (m, 1H),
2.60e2.71 (m, 1H), 3.38 (d, J¼16.1 Hz, 1H), 3.66 (d, J¼16.1 Hz,
1H), 3.87 (dt, J¼6.79, 6.79 Hz, 1H), 4.11e4.26 (m, 4H); IR
(KBr): 3600e3100, 1246, 1022, 970, 773 cmꢁ1; HRMS (EI)
m/z calcd for C11H21O4PS: 280.0898. Found: 280.0912.
3
3
(d, JCeP¼6.0 Hz), 16.3 (d, JCeP¼4.5 Hz), 53.4 (d,
1JCeP¼139.8 Hz), 63.20 (d, JCeP¼6.2 Hz), 63.22 (d,
2
2JCeP¼6.2 Hz), 122.3, 124.1, 126.5, 127.1, 136.2, 153.5,
3
176.8 (d, JCeP¼13.4 Hz); IR (NaCl disc): 1473, 1255,
1045, 1020, 974, 822, 798, 764 cmꢁ1; HRMS (EI) m/z calcd
for C12H16NO4PS2: 333.0258. Found: 333.0260.
4.5.4. 6-(Diethoxy)phosphoryl-3,4-dimethyl-2H-
thiopyran (11)
4.4.3. a-(Diphenylphosphoryl)methyl 2-(5-chlorobenzo-
thiazolyl)sulfoxide (30)
Unstably compound; 1H NMR (CDCl3) d 1.28 (t,
J¼6.79 Hz, 6H), 1.76 (s, 3H), 1.84 (s, 3H), 3.13 (s, 2H),
4.00e4.12 (m, 4H), 6.89 (d, J¼18.4 Hz, 1H); IR (NaCl
disc): 1246, 1022, 970, 773 cmꢁ1; HRMS (EI) m/z calcd for
C11H19O3PS: 262.0793. Found: 262.0815.
1
Yield 89%; mp 172e174 ꢀC (CH2Cl2/AcOEt/hexane); H
NMR (CDCl3) d 4.22 (dd, J¼14.4, 14.4 Hz, 1H), 4.34 (dd,
J¼14.4, 14.4 Hz, 1H), 7.45e7.61 (m, 7H), 7.80e7.89 (m, 5H),
1
8.00 (d, J¼2.0 Hz, 1H); 13C NMR (CDCl3) d 58.0 (d, JCeP
¼
2
60.3 Hz), 122.9, 123.9, 127.0, 128.8 (d, JCeP¼12.4 Hz), 128.9
4.6. General procedure for the reaction of sulfoxides 3 and 6
with amines
2
1
(d, JCeP¼13.2 Hz), 130.9 (d, JCeP¼104.9 Hz), 130.8 (d,
1JCeP¼104.9 Hz), 131.1 (d, JCeP¼10.7 Hz), 131.4 (d, 3JCeP
¼
3
4
4
10.6 Hz), 132.6 (d, JCeP¼3.3 Hz), 132.7 (d, JCeP¼3.3 Hz),
133.1, 134.7, 154.1, 179.0 (d, 3JCeP¼10.7 Hz); IR (KBr): 1435,
The solution of sulfoxide 3 or 6 (1.0 equiv) and amine
(2.2 equiv) in 1,4-dioxane (3.0 mL) was stirred for appropriate
reaction time at the applied temperatures under nitrogen. The
separation and purification of the products were made by pre-
parative thin layer chromatography on silica gel eluting with
AcOEt/hexane/CHCl3 mixture.
1196, 1057, 903, 746, 694 cmꢁ1
.
Anal. Calcd for
C20H15NO2PS2Cl: C, 55.62; H, 3.50; N, 3.24. Found: C, 55.56;
H, 3.61; N, 3.11.
4.5. General procedure for the thermal reaction of sulfoxides
3 and 6 in the presence of 2,3-dimethyl-1,3-butadiene
4.6.1. Diphenylphosphorylthioformic acid anilide (12a)
Mp 161e162 ꢀC (yellow crystal from CH2Cl2/AcOEt/hex-
1
Sulfoxide 3 or 6 (1.0 equiv) and 2,3-dimethyl-1,3-butadiene
(10 equiv) were dissolved in 1,4-dioxane (2.0 mL). The solu-
tion was placed and sealed in a Pyrex tube under nitrogen.
The reaction was carried out for appropriate reaction time at
the applied temperature. The separation and purification of
the products were made by preparative thin layer chromatog-
raphy on silica gel with AcOEt/hexane/CHCl3 mixture.
ane); H NMR (CDCl3) d 7.30 (t, J¼6.7 Hz, 1H), 7.43 (t,
J¼8.0 Hz, 2H), 7.47e7.52 (m, 4H), 7.60 (t, J¼7.4 Hz, 2H),
7.99e8.04 (m, 4H), 8.09 (d, J¼8.4 Hz, 2H), 11.18 (br, 1H);
13C NMR (CDCl3) d 121.6, 127.4, 128.4 (d, JCeP¼13.3 Hz),
2
1
4
129.0 (d, JCeP¼108.1 Hz), 129.1, 132.7 (d, JCeP¼3.3 Hz),
132.9 (d, 3JCeP¼9.9 Hz), 138.4 (d, 2JCeP¼11.5 Hz), 194.0 (d,
1JCeP¼89.2 Hz); IR (KBr): 3300e2800, 1172, 1116 cmꢁ1
.
Anal. Calcd for C19H16NOPS: C, 67.64; H, 4.78; N, 4.15.
Found: C, 67.81; H, 5.09; N, 4.28.
4.5.1. 2-(Diphenyl)phosphoryl-3,6-dihydro-4,5-dimethyl-
2H-thiopyran S-oxide (8)
Mp 162e164 ꢀC (CH2Cl2/AcOEt/hexane); 1H NMR (CDCl3)
d 1.66 (s, 3H), 1.74 (s, 3H), 2.32e2.41 (m, 1H), 2.74e2.83 (m,
1H), 3.49 (dd, J¼15.8, 15.6 Hz, 2H), 3.77 (q, J¼6.8 Hz, 1H),
7.50e7.60 (m, 6H), 7.81e7.91 (m, 4H); 13C NMR (CDCl3)
4.6.2. Diphenylphosphorylthioformic acid benzyl-
amide (12b)
Mp 164e166 ꢀC (pale yellow crystal from CH2Cl2/AcOEt/
1
hexane); H NMR (CDCl3) d 4.91e4.93 (m, 2H), 7.26e7.38
(m, 5H), 7.46e7.51 (m, 4H), 7.57e7.60 (m, 2H), 7.96e8.01
(m, 4H), 9.82 (br, 1H); 13C NMR (CDCl3) d 49.5 (d,
3
2
d 19.4, 20.1, 27.5 (d, JCeP¼1.6 Hz), 53.4 (d, JCeP¼3.3 Hz),
58.1 (d, 1JCeP¼64.5 Hz), 118.5, 127.3 (d, 3JCeP¼6.6 Hz), 128.7

4504
H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
3
3JCeP¼5.8 Hz), 128.29, 128.30, 128.4 (d, JCeP¼5.8 Hz),
(m, 5H), 9.19 (br, 1H); 13C NMR (CDCl3) d 16.2 (d,
1
2
3
2
129.0, 129.2 (d, JCeP¼108.1 Hz), 132.6, 132.7 (d, JCeP
¼
3JCeP¼6.6 Hz), 49.3 (d, JCeP¼8.2 Hz), 65.1 (d, JCeP
¼
1
1
9.9 Hz), 135.1, 197.1 (d, JCeP¼86.7 Hz); IR (KBr): 3500e
2900, 1168, 1123 cmꢁ1. Anal. Calcd for C20H18NOPS:
C, 68.36; H, 5.16; N, 3.99. Found: C, 68.35; H, 5.18; N,
3.89.
7.4 Hz), 128.3, 128.4, 129.0, 135.0, 193.2 (d, JCeP
¼
180.2 Hz); IR (KBr): 3340e2850, 1520, 1500, 1394, 1250,
1050 cmꢁ1. Anal. Calcd for C12H18NO3PS: C, 50.16; H,
6.31; N, 4.87. Found: C, 50.31; H, 6.18; N, 4.85.
4.6.3. Diphenylphosphorylthioformic acid piperidide (12c)
Mp 153e154 ꢀC (yellow crystal from CH2Cl2/AcOEt/hex-
4.6.8. Diethoxyphosphorylthioformic acid piperidide (13c)
1
Yellow oil; H NMR (CDCl3) d 1.38 (t, J¼7.2 Hz, 6H),
1.75 (br s, 6H), 4.16e4.37 (m, 8H); 13C NMR (CDCl3)
1
ane); H NMR (CDCl3) d 1.40e1.43 (m, 2H), 1.67e1.71 (m,
3
3
4H), 4.21 (t, J¼5.6 Hz, 2H), 4.36 (t, J¼5.6 Hz, 2H), 7.45e
d 16.2 (d, JCeP¼6.5 Hz), 24.2, 25.4, 26.9, 50.6 (d, JCeP¼
7.57 (m, 6H), 7.81e7.86 (m, 4H); 13C NMR (CDCl3) d 24.1,
6.6 Hz), 54.6 (d, JCeP¼4.1 Hz), 64.2 (d, JCeP¼8.2 Hz),
3
2
3
3
1
25.6, 26.7, 51.8 (d, JCeP¼2.9 Hz), 53.7 (d, JCeP
¼
190.3 (d, JCeP¼188.3 Hz); IR (NaCl disc): 3700e3200,
2
1
4.2 Hz), 128.2 (d, JCeP¼12.3 Hz), 131.88 (d, JCeP
¼
3100e2800, 1438, 1240, 1086 cmꢁ1; HRMS (EI) m/z calcd
for C11H20NO3PS: 265.0902. Found: 265.0882.
3
109.8 Hz), 131.95 (d, JCeP¼9.0 Hz), 131.97, 194.5 (d,
1JCeP¼91.8 Hz); IR (KBr): 1186, 1117 cmꢁ1. Anal. Calcd for
C18H20NOPS: C, 65.63; H, 6.12; N, 4.25. Found: C, 65.47; H,
6.14; N, 4.03.
4.6.9. Diethoxyphosphorylthioformic acid morpholide (13d)
1
Yellow oil; H NMR (CDCl3) d 1.39 (dt, J¼0.8, 7.2 Hz,
6H), 3.78e3.82 (m, 4H), 4.23e4.35 (m, 8H); 13C NMR
3
3
4.6.4. Diphenylphosphorylthioformic acid morpholide (12d)
Mp 165e167 ꢀC (yellow crystal from CH2Cl2/AcOEt/hex-
ane), lit. mp 150e151 ꢀC;8 1H NMR (CDCl3) d 3.55 (t,
J¼4.8 Hz, 2H), 3.79 (t, J¼4.8 Hz, 2H), 4.30 (t, J¼4.8 Hz, 2H),
(CDCl3) d 16.2 (d, JCeP¼6.6 Hz), 49.3 (d, JCeP¼6.5 Hz),
3
2
53.8 (d, JCeP¼3.3 Hz), 64.5 (d, JCeP¼7.4 Hz), 66.4, 66.9,
1
191.9 (d, JCeP¼187.6 Hz); IR (NaCl disc): 3700e2800,
1478, 1437, 1253, 1120, 1065, 1030 cmꢁ1; HRMS (EI) m/z
calcd for C9H18NO4PS: 267.0694. Found: 267.0705.
4.48 (t, J¼4.8 Hz, 2H), 7.26e7.51 (m, 4H), 7.55e7.59 (m, 2H),
3
7.81e7.86 (m, 4H); 13C NMR (CDCl3) d 50.4 (d, JCeP
¼
3
2.9 Hz), 52.9 (d, JCeP¼3.9 Hz), 66.5, 66.9, 128.3 (d,
4.6.10. Diethoxyphosphorylthioformic acid pyrrolidide
(13e)
1
3
2JCeP¼12.4 Hz), 131.3 (d, JCeP¼110.1 Hz), 132.0 (d, JCeP
¼
9.0 Hz), 132.2 (d, 4JCeP¼3.3 Hz), 196.3 (d, 1JCeP¼88.8 Hz); IR
(KBr): 1183, 1173, 1109 cmꢁ1. Anal. Calcd for C17H18NO2PS:
C, 61.62; H, 5.47; N, 4.23. Found: C, 61.57; H, 5.49; N, 4.05.
Yellow oil; H NMR (CDCl3) d 1.37 (dt, J¼0.8, 7.2 Hz,
1
6H), 1.97e2.12 (m, 4H), 3.81e3.85 (m, 2H), 4.07e4.11 (m,
2H), 4.23e4.37 (m, 4H); 13C NMR (CDCl3) d 16.2 (d,
3
3JCeP¼6.6 Hz), 23.4, 26.5, 53.2 (d, JCeP¼1.6 Hz), 54.3 (d,
2
1
4.6.5. Diphenylphosphorylthioformic acid pyrrolidide (12e)
Mp 153e155 ꢀC (yellow crystal from CH2Cl2/AcOEt/hex-
3JCeP¼6.6 Hz), 64.3 (d, JCeP¼7.4 Hz), 191.9 (d, JCeP
¼
187.6 Hz); IR (NaCl disc): 3700e2700, 1450, 1250, 1168,
;
1
ane); H NMR (CDCl3) d 1.91e2.03 (m, 4H), 3.84e3.91(m,
2H), 4.12e4.15 (m, 2H), 7.45e7.49 (m, 4H), 7.53e7.57 (m,
2H), 7.83e7.89 (m, 4H); 13C NMR (CDCl3) d 22.9, 26.6,
1062, 1030, 980 cmꢁ1
C9H18NO3PS: 251.0745. Found: 251.0744.
HRMS (EI) m/z calcd for
3
3
52.7 (d, JCeP¼2.5 Hz), 55.4 (d, JCeP¼3.3 Hz), 128.2 (d,
4.7. General procedure for the preparation of disulfides
15 and 16
2JCeP¼12.3 Hz), 131.1(d, 1JCeP¼109.0 Hz), 132.1 (d, 4JCeP
¼
¼
3
1
2.4 Hz), 132.2 (d, JCeP¼9.0 Hz), 192.1 (d, JCeP
88.5 Hz); IR (KBr): 1193, 1182, 1115, 1101 cmꢁ1. Anal.
Calcd for C17H18NOPS: C, 64.75; H, 5.75; N, 4.44. Found:
C, 64.85; H, 5.78; N, 4.32.
To a stirred solution of Na2S (1.0 equiv) in EtOH (15 mL)
was added S8 (1.05 equiv). The solution was refluxed for
30 min under stirring. Tosylate 1 or 4 (1.0 equiv) solution in
EtOH (15 mL) was added dropwise into the Na2S2 solution.
The solution was refluxed for 7e12 h. After removal of
EtOH, the residue was treated with CHCl3 and the precipitate
was filtered off. The organic layer was separated and dried
over anhydrous MgSO4. After the removal of solvent, the
residue was separated and purified by preparative thin layer
chromatography on silica gel to give disulfide 15 or 16.
4.6.6. Diethoxyphosphorylthioformic acid anilide (13a)
Yellow oil; 1H NMR (CDCl3) d 1.40 (dt, J¼0.8, 7.2 Hz, 6H),
4.22e4.34 (m, 4H), 7.29e7.32 (m, 1H), 7.44 (t, J¼8.0 Hz, 2H),
7.98(d, J¼8.1 Hz, 2H), 10.57 (br, 1H); 13C NMR (CDCl3) d 16.1
(d, 3JCeP¼6.6 Hz), 65.3 (d, 2JCeP¼7.4 Hz), 122.0, 127.4, 129.0,
3
1
138.0 (d, JCeP¼14.9 Hz), 190.6 (d, JCeP¼181.7 Hz); IR
(NaCl disc): 3400e2900, 1360, 1230 cmꢁ1; HRMS (EI) m/z
calcd for C11H16NO3PS: 273.0589. Found: 273.0618.
4.7.1. Bis-(diphenyl)phosphorylmethyl disulfide (15)
1
Yield 80%; mp 174e176 ꢀC (CH2Cl2/AcOEt/hexane); H
4.6.7. Diethoxyphosphorylthioformic acid benzyl-
amide (13b)
NMR (CDCl3) d 3.77 (d, J¼7.2 Hz, 4H), 7.43e7.54 (m,
12H), 7.74e7.79 (m, 8H); 13C NMR (CDCl3) d 40.2 (d,
2
3
Mp 75e77 ꢀC (pale yellow crystal from CH2Cl2/AcOEt/
1JCeP¼65.3 Hz), 128.7 (d, JCeP¼11.6 Hz), 131.2 (d, JCeP
¼
1
hexane); H NMR (CDCl3) d 1.37 (t, J¼7.2 Hz, 6H), 4.17e
9.0 Hz), 131.6 (d, 1JCeP¼101.6 Hz), 132.1 (d, 4JCeP¼3.3 Hz);
4.33 (m, 4H), 4.85 (dd, J¼2.0, 5.6 Hz, 2H), 7.31e7.39
IR (KBr): 3432 (br), 1437, 1190, 1120 cmꢁ1. Anal. Calcd for

H. Morita et al. / Tetrahedron 64 (2008) 4496e4505
4505
C26H24O2P2S2: C, 63.14; H, 4.89. Found: C, 63.06; H, 4.95;
HRMS (EI) m/z calcd for C26H24O2P2S2: 494.0693. Found:
494.0694.
132.2 (d, 1JCeP¼100.1 Hz), 132.3 (d, 4JCeP,¼2.41 Hz), 173.3,
175.8; IR (KBr): 1712, 1385, 1188, 750, 696 cmꢁ1. Anal. Calcd
for C23H20NO3PS: C, 65.55; H, 4.78; N, 3.32. Found: C, 65.10;
H, 4.92; N, 3.18.
4.7.2. Bis-(diethoxy)phosphorylmethyl disulfide (16)
Yield 89%; colorless oil; 1H NMR (CDCl3) d 1.34 (t,
J¼7.1 Hz, 12H), 3.22 (d, J¼13.0 Hz, 4H), 4.13e4.23 (m, 8H);
4.10. General procedure for the reaction of disulfide 15 with
morpholine
13C NMR (CDCl3) d 16.4 (d, 3JCeP¼5.7 Hz), 34.1 (d, 1JCeP
¼
2
The solution of disulfide 15 (1.0 equiv) and amine (5.0 equiv)
in 1,4-dioxane (3.0 mL)was stirred forappropriate reaction time
at 90 ꢀC under nitrogen at 7 h. The separation and purification of
the products were made by preparative thin layer chromatogra-
phy on silica gel eluting with AcOEt/hexane/CHCl3 mixture.
145.4 Hz), 62.7 (d, JCeP¼6.6 Hz); IR (NaCl disc): 3600e
3300, 2982, 2909, 2360, 2341, 1249, 1049, 1023, 968, 822,
; HRMS (EI) m/z calcd for C10H24O6P2S2:
804 cmꢁ1
366.0490. Found: 366.0453.
4.8. General procedure for the reaction of sulfoxides 3 and 6
with benzylthiol in the presence of DBU
4.11. General procedure for the cross-over reaction of
sulfoxides 6 and 30 with morpholine
The solution of sulfoxide 3 or 6 (1.0 equiv) and DBU
(2.0 equiv) in 3.0 mL of 1,4-dioxane was stirred for 5 min at
rt. To the solution was added benzylthiol (2.0 equiv) and reac-
tion proceeded in a short time. The separation and purification
of the products were made by preparative thin layer chromatog-
raphy on silica gel eluting with AcOEt/hexane/CHCl3 mixture.
The solution of sulfoxides 6 and 30 (1.0 equiv) and amine
(5.0 equiv) in 1,4-dioxane (5.0 mL) was stirred for 2 days at rt
under nitrogen. The separation and purification of the products
were made by preparative thin layer chromatography on silica
gel eluting with AcOEt/hexane/CHCl3 mixture.
4.11.1. 2-N-Morpholino-(5-chlorobenzothiazole) (31)
4.9. General procedure for the thiol trapping reaction
Mp 108e110 ꢀC (CH2Cl2/hexane), lit. mp 115 ꢀC;10 1H
NMR (CDCl3) d 3.62 (t, J¼4.80 Hz, 4H), 3.83 (t, J¼4.80 Hz,
4H), 7.06 (dd, J¼2.10, 0.50 Hz, 1H), 7.50 (d, J¼8.39 Hz, 1H),
7.54 (d, J¼2.00 Hz, 1H); 13C NMR (CDCl3) d 48.4, 66.2,
119.3, 121.3, 121.7, 128.8, 131.9, 153.6, 170.0; IR (KBr):
1533, 1446, 1377, 1342, 1284, 1227, 1114, 883 cmꢁ1. Anal.
Calcd for C11H11N2OSCl: C, 51.86; H, 4.35; N, 11.00. Found:
C, 51.84; H, 4.35; N, 10.88; HRMS (EI) m/z calcd for
C11H11ClN2OS: 254.0281. Found: 254.0264.
The solution of sulfoxide 3 or disulfide 15 (1.0 equiv) and
morpholine (4.0 equiv) in 1,4-dioxane (3.0 mL) was stirred
for appropriate reaction time at 90 ꢀC under nitrogen. Then,
N-phenylmaleimide (1.0 equiv) was added to the reaction mix-
ture. After 7.5 h, reaction mixture was reduced in vacuo. The
separation and purification of the products were made by pre-
parative thin layer chromatography on silica gel eluting with
AcOEt/hexane/CHCl3 mixture.
4.11.2. (Diphenylphosphinoylmethyldisulfanylmethyl)-
phosphonic acid diethyl ester (32)
Oily product; 1H NMR (CDCl3) d 1.31 (t, J¼7.07 Hz, 6H),
3.14 (d, J¼12.8 Hz, 2H), 3.83 (d, J¼7.51 Hz, 2H), 4.09e4.16
(m, 4H), 7.48e7.58 (m, 6H), 7.76e7.81 (m, 4H); HRMS (EI)
m/z calcd for C18H24O4P2S2: 430.0591. Found: 430.0596.
4.9.1. 3-(Morpholin-4-yl)-1-phenylpyrrolidine-2,5-
dione (22)
Mp 155e157 ꢀC (colorless crystal from CH2Cl2/hexane), lit.
mp 175 ꢀC;9 1H NMR (CDCl3) d 2.61e2.66 (m, 2H), 2.83 (dd,
J¼24.6, 18.8 Hz, 1H), 2.90e2.95 (m, 2H), 3.03 (dd, J¼18.6,
18.8 Hz, 1H), 3.76 (t, J¼4.40 Hz, 4H), 3.90 (dd, J¼8.99,
8.79 Hz, 1H), 7.25e7.28 (m, 2H), 7.38e7.42 (m, 1H), 7.45e
7.50 (m, 2H); 13C NMR (CDCl3) d 31.8, 49.6, 62.6, 66.8,
126.4, 128.8, 129.2, 131.4, 173.9, 174.7; IR (KBr): 1711, 1498,
1387, 1198, 1171, 1115 cmꢁ1. Anal. Calcd for C14H16N2O3: C,
64.60; H, 6.20; N, 10.76. Found: C, 64.42; H, 6.26; N, 10.60.
References and notes
1. (a) Morita, H.; Takeda, M.; Kamiyama, H.; Fujii, T.; Yoshimura, T.;
Shimasaki, C. J. Org. Chem. 1997, 62, 9018; (b) Morita, H.; Takeda,
M.; Kamiyama, H.; Yoshimura, T.; Fujii, T.; Ono, S.; Shimasaki, C.
J. Org. Chem. 1999, 64, 6730.
4.9.2. 3-(Diphenyl-phosphinoylmethylsulfanyl)-1-phenyl-
pyrrolidine-2,5-dione (23)
2. Takeda, M.; Yoshimura, T.; Fujii, T.; Ono, S.; Shimasaki, C.; Morita, H.
Tetrahedron Lett. 1999, 40, 2327.
Mp 178e182 ꢀC (CH2Cl2/AcOEt/hexane); 1H NMR
(CDCl3) d 2.58 (dd, J¼18.8, 18.8 Hz, 1H), 3.27 (dd, J¼20.6,
25.9 Hz, 1H), 3.43 (dd, J¼15.0, 15.6 Hz, 1H), 4.13 (dd,
J¼15.2, 15.2 Hz, 1H), 4.49 (ddd, J¼9.59, 4.00, 1.20 Hz, 1H),
3. Morita, H.; Tashiro, S.; Takeda, M.; Fujimori, K.; Yamada, N.; Sheikh,
Md. C.; Kawaguchi, H. Tetrahedron 2008, 64, 3589.
4. Davis, F. A.; Johnston, R. P., II. J. Org. Chem. 1972, 37, 859.
5. Schwab, M.; Sundermeyer, W. Chem. Ber. 1986, 119, 2458.
6. Lo Vullo, A.; Purrello, G. Gazz. Chim. Ital. 1976, 106, 205.
7. Giuseppe, C. Pure Appl. Chem. 1987, 59, 989.
7.26e7.28 (m, 2H), 7.38e7.42 (m, 1H), 7.45e7.59 (m, 8H),
1
7.75e7.83 (m, 4H); 13C NMR (CDCl3) d 29.0 (d, JCeP
¼
8. Khokhlov, P. S.; Murabuldaev, A. M.; Osipov, V. N.; Ignatenko, A. V.;
Zavarzin, I. V. Russ. Chem. Bull. 2003, 52, 2298.
3
69.4 Hz), 35.4, 38.5, 126.4, 128.7 (d, JCeP¼3.5 Hz), 128.80,
9. Mercedes, M. S.; Ulf, P. Helv. Chim. Acta 1991, 74, 430.
10. D’amico, J. J.; Cambert, R. H.; Webster, S. T.; Twine, C. E. J. Org. Chem.
1965, 30, 3625.
3
1
128.84 (d, JCeP¼3.3 Hz), 129.2, 130.8 (d, JCeP¼105.7 Hz),
2
2
130.9 (d, JCeP¼9.9 Hz), 131.3 (d, JCeP¼9.1 Hz), 131.4,