Thermolyses of α-phosphorylmethyl tetrazolyl sulfoxides in the presence of 2,3-dimethyl-1,3-butadiene and their reactions with several amines

Article abstract of DOI:10.1016/j.tet.2008.01.082

We have synthesized α-(phosphoryl)methyl tetrazolyl sulfoxides and examined the reactivities in the thermolyses and in the presence of several amines, such as aniline, benzylamine, piperidine, pyrrolidine, and morpholine. 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 addition, novel phosphinecarbothioamides were obtained in the reaction of the derivatives with amines.

Full text of DOI:10.1016/j.tet.2008.01.082

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3589e3595
www.elsevier.com/locate/tet
Thermolyses of a-phosphorylmethyl tetrazolyl sulfoxides
in the presence of 2,3-dimethyl-1,3-butadiene
and their reactions with several amines
*
Hiroyuki Morita , Shintaro Tashiro, Masahiro Takeda, Ken Fujimori, 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 19 December 2007; received in revised form 16 January 2008; accepted 16 January 2008
Available online 30 January 2008
Abstract
We have synthesized a-(phosphoryl)methyl tetrazolyl sulfoxides and examined the reactivities in the thermolyses and in the presence of
several amines, such as aniline, benzylamine, piperidine, pyrrolidine, and morpholine. 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 addition, novel phosphinecar-
bothioamides were obtained in the reaction of the derivatives with amines.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: a-Phosphoryl sulfoxide; Tetrazole; Phosphinecarbothioamide; Hetero DielseAlder reaction
1. Introduction
tetrazolyl sulfoxides with several amines as a short communi-
cation.2 In order to obtain the scope and limitations of the
reactions, we further prepared several tetrazolyl substituted
a-phosphorylmethyl sulfoxides and studied their thermolyses
in the presence of 2,3-dimethyl-1,3-butadiene and also their
reactions with several amines. Herein, we report the results
of thermolyses and the reactions in the presence of amines.
Previously, we reported thioaldehyde and/or sulfine forma-
tion in the thermal reaction of heteroaryl substituted b-keto-
sulfoxides in the presence or absence of bases.1 Namely,
thermolyses of benzothiazolyl phenacyl sulfoxides in the
presence of 2,3-dimethyl-1,3-butadiene afforded thiopyran de-
rivatives, which is considered to be formed by the hetero
DielseAlder reaction of diene with the corresponding thioal-
dehyde formed initially.1a On the other hand, in the reaction
of tetrazolyl phenacyl sulfoxides under the same conditions,
the corresponding cycloadducts with sulfines were formed in
excellent yields.1b These results revealed that different mech-
anistic pathways were operating depending on the heteroaryl
moieties, resulted in the formation of two different types of
products, i.e., thioaldehydes or sulfines.
2. Results and discussion
2.1. Preparation of 5-(1-phenyl)-1H-tetrazolyl
a-(dimethylphosphoryl)-, a-(diphenylphosphoryl)-,
and a-(diethoxyphosphoryl)methyl tetrazolyl sulfoxides
a-(Dimethylphosphoryl)methyl 5-(1-phenyl)-1H-tetrazolyl
sulfide (1) was prepared by the reaction of chloromethyl(dime-
thyl)phosphine oxide with 1-phenyl-5-mercapto-1H-tetrazole
in the presence of triethylamine. The corresponding sulfoxide,
i.e., a-(dimethylphosphoryl)methyl 5-(1-phenyl)-1H-tetrazolyl
sulfoxide (2) was obtained by the oxidation of 1 with m-CPBA
as shown in Scheme 1.
Recently, we have reported the phosphinecarbothioamide
formation in the reactions of a-(dimethylphosphoryl)methyl
* 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.2008.01.082

3590
H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
O
O
yields, which is considered to be formed by the hetero Dielse
O
S
O
Ph
N
i
ii
Me
P
Me
CH2 Cl
Tet
S CH2
P
Me
Me
Tet
CH2
P
Me
Me
Alder reaction of the diene with the corresponding sulfines
formed initially.1b Therefore, the thermolysis of 2 in the pres-
ence of the same diene was studied in 1,4-dioxane at several
temperatures. The results are summarized in Table 1. 4,5-
Dimethyl-2-(dimethylphosphoryl)-3,6-dihydro-2H-thiopyran S-
oxide (10) was expectedly observed to be formed in high yields
(entry 1). In the presence of triethylamine, the reaction pro-
ceeded more smoothly even at low temperature (entry 2). The
thermolyses of 5 and 8 in the presence of the same diene were
studied. The results are summarized in Table 2. In the case of
entry 1, the thermolysis of 5 at 140 ꢀC for 1 h afforded 4,5-
dimethyl-2-(diphenylphosphoryl)-3,6-dihydro-2H-thiopyran S-
oxide (11) and tetrazole 9 in almost quantitative yields. After
2 h at the same temperature, 11 and 9 were obtained in 28 and
32% yields, respectively (entry 2). In this case, 3,4-dimethyl-6-
(diphenylphosphoryl)-2H-thiopyran (12) was formed in 27%
yield. Compound 12 was considered to be formed by the de-
hydration of 11, probably due to the strong acidic nature of
hydrogens both at a- and b-position of phosphoryl group.
The controlled reaction of 11 in 1,4-dioxane at 140 ꢀC re-
vealed to produce 12 exclusively by the elimination of H2O
as depicted in Scheme 4. When the thermolysis of 5 was car-
ried out in the presence of triethylamine at the same tempera-
ture for 1 h, 12 and 9 were obtained in 73 and 37% yields,
respectively (entry 3). The formation of 12 from 11 also seems
to proceed in a relatively short time. The thermolysis of 8 was
carried out at 160 ꢀC. The obtained products were the corre-
sponding cycloadducts 4,5-dimethyl-2-(diethoxyphosphoryl)-
3,6-dihydro-2H-thiopyran S-oxide (13) and the successive
dehydrated product, i.e., 3,4-dimethyl-6-(diethoxyphosphoryl)-
2H-thiopyran (14) (entry 4).
Tet=
N
N
N
1
2
Scheme 1. Preparation of 2. (i) TeteSH, Et3N, CHCl3, 70 ꢀC, 6 h, 85%; (ii)
m-CPBA, CHCl3, rt, 3 h, 57%.
a-(Diphenylphosphoryl)methyl 5-(1-phenyl)-1H-tetrazolyl
sulfoxide (5) was prepared by following the procedure shown
in Scheme 2. Diphenylphosphorylmethyl tosylate (3) was ob-
tained bythe reaction of tosylchloridewith the corresponding al-
cohol prepared via three steps starting from triphenylphosphine
by the MichaeliseArbuzov type reaction.3 Sulfide 4 was pre-
pared by the reaction of 3 with 1-phenyl-5-mercapto-1H-tetra-
zole in the presence of K2CO3 as a base. The corresponding
sulfoxide 5 was obtained by the oxidation of 4 with m-CPBA.
O
O
ii
iii
i
Ph3P CH2OMe
Cl
PPh3
iv
Ph P CH2OMe
Ph
Ph P CH2OH
Ph
O
S
O
P
O
P
Ph
O
vi
v
Ph
OTs
Tet
S
CH2 P Ph
Ph
Tet
CH2
Ph
CH2
Ph
4 100%
5 64%
3
Scheme 2. Preparation of 5. (i) Chloromethoxymethane, CHCl3, rt, 5.5 h; (ii)
30% aqueous NaOH, 0e100 ꢀC, 10 h, 75%; (iii) 47% HBr, 120 ꢀC, 12 h, 83%;
(iv) TsCl, Et3N, CH2Cl2, rt, 8 h, 98%; (v) TeteSH, K2CO3, DMF, 90 ꢀC, 4 h,
100%; (vi) m-CPBA, CHCl3, rt, 1 h, 64%.
O
O
O
i
ii
EtO P
EtO
H
CH2OH
iv
EtO P
EtO
EtO P CH2 OTs
EtO
6
O
O
P OEt
OEt
O
P OEt
OEt
iii
Tet
S
CH2
Tet
S CH2
2.3. Reactions of a-(phosphoryl)methyl sulfoxides 2, 5, and 8
with several amines
7 76%
8 89%
Scheme 3. Preparation of 8. (i) Paraformaldehyde, Et3N, 120 ꢀC, 5 h, 42%; (ii)
TsCl, Et3N, rt, 6 h, 60%; (iii) TeteSH, K2CO3, DMF, 80 ꢀC, overnight, 76%;
(iv) m-CPBA, CHCl3, rt, 1 h, 89%.
It is reported that sulfines reacted with amines to afford the
corresponding sulfinamide derivatives;5 we studied the reac-
tions of 2 with several amines. The results are summarized
in Table 3. In all cases, the expected corresponding sulfina-
mides were not obtained, but unexpected formation of novel
phosphinecarbothioamide derivatives were observed.2
a-(Diethoxyphosphoryl)methyl 5-(1-phenyl)-1H-tetrazolyl
sulfoxide (8) was prepared by following the procedure shown
in Scheme 3.
Diethoxyphosphorylmethyl tosylate (6) was obtained in 60%
yield by the reaction of tosylchloride with the corresponding al-
cohol prepared by hydroxymethylation with paraformaldehyde
starting from phosphonic acid diethyl ether.4 Sulfide 7 was
prepared by the reaction of tosylate 6 with 1-phenyl-5-mer-
capto-1H-tetrazole in the presence of K2CO3. The correspond-
ing sulfoxide 8 was obtained similarly as compound 5.
Table 1
Thermolysis of 2 in the presence of 2,3-dimethyl-1,3-butadiene
O
Me
Me
O
P
O
S
O
2,3-dimethyl-1,3-butadiene
(10 equiv.)
S
+
H
Tet
Tet
CH2
P
Me
1,4-dioxane, Δ
Me
2
9
10
2.2. Thermolyses of 2, 5, and 8 in the presence
of 1,3-dimethyl-2,3-butadiene
Entry
Conditions
Yieldsa (%)
9
10
As mentioned in Section l, the thermolyses of tetrazolyl
phenacyl sulfoxides in the presence of 2,3-dimethyl-1,3-buta-
diene afforded the thiopyran oxide derivatives in excellent
1
2
a
100 ꢀC, 20 h
97
99
85
72
70 ꢀC, 3 h, Et3N (1.5 equiv)
Isolated yields.

H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
3591
Table 2
Thermolyses of 5 and 8 in the presence of 2,3-dimethyl-1,3-butadiene
O
R
R
O
R
R
O
P
P
O
S
O
S
S
2,3-dimethyl-1,3-butadiene (10 equiv.)
Tet
H
+
Tet
CH2
P
R
R
+
1,4-dioxane, Δa
5 (R = Ph)
8 (R = OEt)
11 (R = Ph)
13 (R = OEt)
12 (R = Ph)
14 (R = OEt)
9
Entry
Sulfoxide
Conditions
Yieldsb (%)
9
11/13
12/14
1
2
3
4
a
5
5
5
8
140 ꢀC, 1 h
99
97
28
0
Trace
27
73
140 ꢀC, 2 h
32c
37c
12c
140 ꢀC, 1 h, Et3N (1.5 equiv)
160 ꢀC, 2 h
21
58
In sealed tubes.
Isolated yields.
Low yield of 9 is due to the thermal decomposition of 9 itself at the higher temperature.
b
c
O
O
O
O
S
Ph
Ph
Ph
Ph
H
H
Ph
Ph
Ph
Ph
O
HO
O
P
P
P
P
S
S
S
+
H2O
11
12
Scheme 4. The probable elimination mechanism for 11 to 12.
Table 4
Reaction of 5 and 8 with several amines
Further, we have prepared the tetrazolyl sulfoxides bearing
several similar phosphoryl groups, such as a-(diphenylphos-
phoryl)- and a-(diethoxyphosphoryl)methyl groups, and stud-
ied the reaction in the presence of several amines. The results
are summarized in Table 4.
The reactions of 5 with 2.2 equiv of amines in 1,4-dioxane
at 90 ꢀC were found to afford the corresponding phosphine-
carbothioamide derivatives 16aee (entries 1e5). In the case
of 8 under similar conditions at 100 ꢀC the corresponding
O
S
O
S
C
O
R1
N
amine (2.2 equiv.)
1,4-dioxane, conditions
Tet
CH2
P
R
R
Tet
H
+
R
P
R
R2
16a-e R = Ph
17a-e R = OEt
5 R = Ph
8 R = OEt
9
Entry
Sulfoxide
Amide
Temp
(ꢀC)
Time
(h)
Yielda (%)
9
16/17
1
2
5
5
a, PheNH2
90
90
12.0
1.75
42
42 (16a)
Table 3
Reaction of 2 with several amines
b,
98
69
98
99
42
98
78
75
49 (16b)
30 (16c)
44 (16d)
87 (16e)
50 (17a)
50 (17b)
47 (17c)
53 (17d)
Ph
NH2
NH
NH
NH
O
S
O
S
C
O
R1
R2
amine (2.2 equiv.)
1,4-dioxane, 70 °C
3
4
5
6
7
8
9
5
5
5
8
8
8
8
c,
d,
e,
90
90
1.5
2.0
1.0
0.8
0.8
0.5
0.5
Tet
CH2
P
Me
+
H
Tet
Me
P
N
Me
Me
O
2
9
15a-e
90
Entry
Amine (2.2 equiv)
Time (h)
Yieldsa (%)
9
15
a, PheNH2
100
100
100
100
1
2
a, PheNH2
1.5
2.5
83
99
50 (15a)
50 (15b)
Ph
b,
c,
d,
NH2
NH
NH
b,
NH2
NH
NH
Ph
3
4
0.75
1.0
99
75
52 (15c)
53 (15d)
c,
d,
O
O
5
e,
0.75
82
52 (15e)
10
8
e,
100
0.5
80
57 (17e)
NH
NH
a
a
Isolated yields.
Isolated yields.

3592
H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
OH
O
S
O
O
O
Me P
O
Me P
S
C
S
C
R1
R2
O
P
Me
R1R2NH
R1R2NH
H2O
(base)
Tet S CH2 P Me
H
Me
N
1
2
Me
18
H
Me
Me
NR R
Tet
9
H
2
19
15
Scheme 5.
phosphinecarbothioamide derivatives 17aee were obtained in
almost similar yields (entries 6e10).
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 of high-
est quality and further purified by distillation or recrystalliza-
tion. The solvents were further purified by general method.
In conclusion, the reactions of 2, 5 and 8 with amines were
found to afford novel phosphinecarbothioamides 15e17 in
moderate isolated yields. The relatively low yields of 15e17
are probably due to their unstable nature, because the TLC
monitoring showed that the reaction proceeded cleanly to
afford 9 and 15e17.
The probable mechanism for the formation of phosphinecar-
bothioamides 15e17 is shown in Scheme 5 (the scheme was
drawn using 2 as the representative of 2, 5, and 8). First, the ther-
molytic reaction of starting sulfoxides 2, 5, and 8 afforded the
corresponding sulfines 18. Successively, the nucleophilic at-
tacking of amines at the oxythiocarbonyl carbon occurred to
afford the sulfenic acid intermediate 19. Finally, the elimination
of H2O from the intermediate leads to the product 15.
In contrast to our results, it is reported that in the reactions
of common sulfines with nucleophiles, attacking of nucleo-
philes takes place on the partially positive-charged sulfur
(thiophilic attack) predominantly. In the case of primary and
secondary amines, the products were the corresponding sulfine
amides.6aed However, in the reaction of tetrazolyl a-phosphor-
ylmethyl sulfoxides, the sulfines formed initially have a strong
electron withdrawing phosphoryl group at a-position probably
controlling the reaction pathway of the attack on the carbon
(carbophilic attack) to produce phosphinecarbothioamide
derivatives. Similar results in the case of chlorosulfines were
reported.7aed
4.2. a-(Dimethylphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfide (1)
To a stirred solution of 1-phenyl-5-mercapto-1H-tetrazole
(2.0 g, 11.2 mmol) in CHCl3 were added triethylamine
(2.34 mL, 16.8 mmol) and chloromethyl(dimethyl)phosphine
oxide (2.13 g, 16.8 mmol) at rt. This reaction mixture was
stirred for 24 h at 70 ꢀC. After cooling and addition of H2O,
the reaction mixture was extracted with CHCl3. The organic
layer was washed with H2O and dried over anhydrous
MgSO4, and then evaporated to give 2.5 g of 1 as colorless
oil in 85% yield. This oily product was used for the prepara-
tion of 2 without further purification. Spectral data: oil product
(without further purification); 1H NMR (CDCl3) d 1.67 (d, J¼
12.8 Hz, 6H), 3.80 (d, J¼8.0 Hz, 2H), 7.58e7.60 (m, 5H); 13
C
¼
1
1
NMR (CDCl3) d 16.1 (d, JCeP¼71.0 Hz), 31.8 (d, JCeP
70.7 Hz), 123.7, 130.0, 130.5, 133.2, 153.3; IR (KBr):
. HRMS (EI) calcd for
3700e3100, 1504, 1171 cmꢁ1
C10H13N4OPS: 268.0548; found: m/z 268.0550.
3. Conclusion
4.3. General procedure for the preparation of
a-(diphenylphosphoryl)- and a-(diethoxyphosphoryl)-
methyl sulfide 4 and 7
Several tetrazolyl substituted phosphorylmethyl sulfoxides
2, 5 and 8 were prepared and their thermolysis and their reac-
tions with amines were examined. In the thermolysis in the
presence of 2,3-dimethyl-1,3-butadiene, the hetero Dielse
Alder reaction adducts 10, 11, and 13 were formed. Compounds
11 and 13 were found to lead to 2H-thiopyrane derivatives 12
and 14. In the reaction of tetrazolyl sulfoxides 2, 5, and 8, the
formation of phosphinecarbothioamides 15e17 was considered
to be via sulfine, which was formed initially by the elimination
of tetrazole due to the high leaving ability.
To a stirred solution of 3 or 6 (1.0 mmol) and 1-phenyl-5-
mercapto-1H-tetrazole (1.2 mmol) in DMF (5.0 mL) was
added K2CO3 (3.0 mmol) at rt. The reaction mixture was stirred
at 90 or 80 ꢀC. After consumption of the starting materials,
DMF was evaporated off under reduced pressure. The residue
was dissolved in CHCl3 and then the precipitate was filtered
off. The organic layer was washed with H2O and dried over
anhydrous MgSO4. After removal of the solvent, the residue
was purified by flash column chromatography on silica gel.
4. Experimental
4.3.1. a-(Diphenylphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfide (4)
4.1. General
Yield 100%; mp 111e113 ꢀC (CH2Cl2eAcOEtehexane);
1H NMR (CDCl3) d 4.34 (d, J¼7.6 Hz, 2H), 7.40e7.58 (m,
11H), 7.78e7.84 (m, 4H); 13C NMR (CDCl3) d 31.8 (d,
All the melting points were uncorrected using micromelting
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
2
1JCeP¼66.1 Hz), 123.7, 128.8 (d, JCeP¼12.3 Hz), 129.8,
1
3
130.3, 130.3 (d, JCeP¼103.2 Hz), 131.1 (d, JCeP¼9.1 Hz),

H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
3593
4
132.6 (d, JCeP¼3.37 Hz), 133.1, 153.3; IR (KBr): 1498,
4.59 (dt, J¼0.8, 14.4 Hz, 1H), 7.60e7.65 (m, 3H), 7.71e
1200, 756, 696 cmꢁ1. HRMS (EI) calcd for C20H17N4OPS:
392.0861; found: m/z 392.0879.
7.76 (m, 2H); 13C NMR (CDCl3) d 16.1 (d, JCeP¼6.6 Hz),
3
1
2
49.7 (d, JCeP¼136.1 Hz), 63.3 (d, JCeP¼6.6 Hz), 63.5 (d,
2JCeP¼6.6 Hz), 124.9, 129.9, 131.3, 132.7, 156.9; IR (KBr):
4.3.2. a-(Diethoxyphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfide (7)
2985, 2910, 1498, 1255, 1043, 1018, 976, 766, 692 cmꢁ1
.
HRMS (EI) calcd for C12H17N4O4PS: 344.0708; found: m/z
344.0706.
Yield 73%; colorless oil; 1H NMR (CDCl3) d 1.31 (t,
J¼6.8 Hz, 6H), 3.76 (d, J¼6.8 Hz, 2H), 4.13e4.20 (m, 4H),
3
7.56e7.69 (m, 5H); 13C NMR (CDCl3) d 16.3 (d, JCeP
¼
4.5. General procedure for the thermal reaction of sulfoxides
2, 5, and 8 in the presence of 2,3-dimethyl-1,3-butadiene
1
2
6.2 Hz), 26.3 (d, JCeP¼148.1 Hz), 63.2 (d, JCeP¼6.6 Hz),
123.8, 129.9, 130.4, 133.4, 153.2; IR (KBr): 1500, 1392,
.
1254, 1049, 1022, 972 cmꢁ1
HRMS (EI) calcd for
Sulfoxide 2, 5, or 8 (0.1 mmol) and 2,3-dimethyl-1,3-buta-
diene (1.0 mmol) were dissolved in 1,4-dioxane (2.0 mL). The
solution 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.
C12H17O3N4PS: 328.0759; found: m/z 328.0722.
4.4. General procedure for the preparation of
a-(dimethylphosphoryl)-, a-(diphenylphosphoryl)-,
and a-(diethoxyphosphoryl)methyl sulfoxide 2, 5, and 8
To a stirred solution of sulfide (1.0 mmol) in CHCl3
(20 mL) was added m-CPBA (1.2 mmol) in CHCl3 (20 mL)
at rt. After stirring for 1 or 3 h at rt, the reaction mixture
was washed with aqueous saturated solution of NaHCO3 three
times. The aqueous layer was extracted with CHCl3. The com-
bined organic layer was washed with water and dried over an-
hydrous MgSO4. After removal of the solvent, the residue was
purified by flash column chromatography on silica gel.
4.5.1. 4,5-Dimethyl-2-(dimethylphosphoryl)-3,6-dihydro-
2H-thiopyran S-oxide (10)
1H NMR (CDCl3) d 1.72e1.78 (m, 12H), 2.44e2.54 (m,
1H), 2.82 (d, J¼18.8 Hz, 1H), 3.23e3.29 (m, 1H), 3.49 (d,
J¼15.6 Hz, 1H), 3.69 (dd, J¼15.2, 15.2 Hz, 1H); 13C NMR
1
1
(CDCl3) d 13.9 (d, JCeP¼68.5 Hz), 18.5 (d, JCeP
¼
¼
70.3 Hz), 19.0, 19.9, 29.9 (d, 3JCeP¼1.71 Hz), 56.1 (d, 2JCeP
1
6.63 Hz), 59.0 (d, JCeP¼63.7 Hz), 118.5, 128.0. HRMS (EI)
calcd for C9H17O2PS: 220.0687; found: m/z 220.0676.
4.4.1. a-(Dimethylphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfoxide (2)
Spectral data: yield 57%; mp 125e127 ꢀC (CH2Cl2ehex-
4.5.2. 4,5-Dimethyl-2-(diphenylphosphoryl)-3,6-dihydro-
2H-thiopyran S-oxide (11)
1
ane); H NMR (CDCl3) d 1.72 (d, J¼13.2 Hz, 3H), 1.80 (d,
J¼13.2 Hz, 3H), 4.19e4.31 (m, 2H), 7.59e7.65 (m, 3H),
Mp 162e164 ꢀC (CH2Cl2eAcOEtehexane); 1H NMR
(CDCl3) d 1.66 (s, 3H), 1.74 (s, 3H), 2.32e2.41 (m, 1H), 2.74e
2.83 (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
1
7.72e7.74 (m, 2H); 13C NMR (CDCl3) d 18.6 (d, JCeP
¼
1
1
70.8 Hz), 18.8 (d, JCeP¼70.7 Hz), 53.3 (d, JCeP¼56.0 Hz),
124.9, 130.1, 131.4, 132.7, 156.9; IR (KBr): 1080 cmꢁ1
.
3
Anal. Calcd for C10H13N4O2PS: C, 42.25; H, 4.61; N, 19.71.
Found: C, 41.77; H, 4.54; N, 19.61.
NMR (CDCl3) d 19.4, 20.1, 27.5 (d, JCeP¼1.6 Hz), 53.4
2
1
(d, JCeP¼3.3 Hz), 58.1 (d, JCeP¼64.5 Hz), 118.5, 127.3 (d,
3JCeP¼6.6 Hz), 128.7 (d, JCeP¼6.6 Hz), 128.8 (d, JCeP
¼
¼
3
3
1
1
4.4.2. a-(Diphenylphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfoxide (5)
6.6 Hz), 130.3 (d, JCeP¼100.8 Hz), 130.9 (d, JCeP
2
2
101.6 Hz), 131.2 (d, JCeP¼9.1 Hz), 131.5 (d, JCeP¼9.1 Hz),
4
4
Yield 64%; mp 137e139 ꢀC (CH2Cl2eAcOEtehexane);
1H NMR (CDCl3) d 4.48 (dd, J¼14.0, 14.0 Hz, 1H), 5.23
(dd, J¼8.8, 8.9 Hz, 1H), 7.45e7.68 (m, 11H), 7.71e7.73
(m, 2H), 7.78e7.84 (m, 2H); 13C NMR (CDCl3) d 54.2 (d,
132.3 (d, JCeP¼3.3 Hz), 132.5 (d, JCeP¼3.3 Hz); IR (KBr):
1198, 1049 cmꢁ1. Anal. Calcd for C19H21O2PS: C, 66.26; H,
6.15. Found: C, 66.57; H, 6.44.
3
1JCeP¼60.3 Hz), 124.9, 129.0 (d, JCeP¼7.4 Hz), 129.1
4.5.3. 3,4-Dimethyl-6-(diphenylphosphoryl)-2H-
thiopyran (12)
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) calcd
for C19H19OPS: 326.0894; found: m/z 326.0875.
3
1
(d, JCeP¼8.2 Hz), 129.5 (d, JCeP¼107.3 Hz), 130.0, 130.5
1
2
(d, JCeP¼116.5 Hz), 130.7 (d, JCeP¼10.7 Hz), 131.0 (d,
2JCeP¼9.9 Hz), 131.2, 132.7, 132.96 (d, JCeP¼3.3 Hz),
4
4
3
132.99 (d, JCeP¼3.3 Hz), 157.2 (d, JCeP¼4.92 Hz); IR
(KBr): 1497, 1438, 1197, 1121, 1069, 761, 745, 691 cmꢁ1
.
Anal. Calcd for C20H17N4O2PS: C, 58.82; H, 4.20; N, 13.72.
Found: C, 58.85; H, 4.26; N, 13.73.
4.5.4. 4,5-Dimethyl-2-(diethoxyphosphoryl)-3,6-dihydro-
2H-thiopyran S-oxide (13)
4.4.3. a-(Diethoxyphosphoryl)methyl 5-(1-phenyl)-1H-
tetrazolyl sulfoxide (8)
Colorless oil; 1H NMR (CDCl3) d 1.35 (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
1
Yield 89%; colorless oil; H NMR (CDCl3) d 1.27e1.34
(m, 6H), 3.95 (dt, J¼0.8, 14.4 Hz, 1H), 4.06e4.20 (m, 4H),

3594
H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
1
(m, 4H); IR (KBr): 3600e3100, 1246, 1022, 970, 773 cmꢁ1
HRMS (EI) calcd for C11H21O4PS: 280.0898; found: m/z
280.0912.
.
4.70 (t, J¼4.2 Hz, 2H); 13C NMR (CDCl3) d 19.3 (d, JCeP
¼
3
3
78.2 Hz), 50.4 (d, JCeP¼2.4 Hz), 51.9 (d, JCeP¼3.3 Hz),
1
66.5, 67.4, 199.0 (d, JCeP¼81.4 Hz); IR (KBr): 1480, 1267,
1236, 1162, 1152, 1038 cmꢁ1; Anal. Calcd for C7H14NO2PS:
C, 40.57; H, 6.81; N, 6.76. Found: C, 40.73; H, 6.71; N, 6.60.
4.5.5. 3,4-Dimethyl-6-(diethoxyphosphoryl)-2H-
thiopyran (14)
Unstably brown oil compound; 1H NMR (CDCl3) d 1.28 (t,
J¼6.79 Hz, 6H), 1.76 (s, 3H), 1.84 (s, 3H), 3.13 (s, 2H), 4.00e
4.12 (m, 4H), 6.89 (d, J¼18.4 Hz, 1H); IR (KBr): 1246, 1022,
970, 773 cmꢁ1. HRMS (EI) calcd for C11H19O3PS: 262.0793;
found: m/z 262.0815.
4.6.5. Dimethylphosphorylthioformic acid pyrrolidide (15e)
Mp 153e155 ꢀC (yellow crystal from CH2Cl2eAcOEte
hexane); 1H NMR (CDCl3) d 1.91 (d, J¼13.6 Hz, 6H),
1.94e2.00 (m, 2H), 2.06e2.13 (m, 2H), 3.86e3.90 (m, 2H),
1
4.29e4.33 (m, 2H); 13C NMR (CDCl3) d 18.4 (d, JCeP
¼
76.5 Hz), 22.8, 28.9, 52.7, 55.4; IR (KBr): 1474, 1441,
1292, 1178, 1153, 1023, 933, 875 cmꢁ1. HRMS (EI) calcd
for C7H14NOPS: 191.0534; found: m/z 191.0518.
4.6. General procedure for the reaction of sulfoxides 2, 5,
and 8 with amines
The solution of sulfoxide 2, 5, or 8 (0.1 mmol) and amine
(0.22 mmol) in 1,4-dioxane (3.0 mL) was stirred for appropri-
ate reaction time at the applied temperatures under nitrogen.
The separation and purification of the products were made
by preparative thin layer chromatography on silica gel eluting
with AcOEtehexaneeCHCl3 complex.
4.6.6. Diphenylphosphorylthioformic acid anilide (16a)
Mp 161e162 ꢀC (yellow crystal from CH2Cl2eAcOEte
1
hexane); 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);
2
13C NMR (CDCl3) d 121.6, 127.4, 128.4 (d, JCeP
¼
¼
13.3 Hz), 129.0 (d, 1JCeP¼108.1 Hz), 129.1, 132.7 (d, 4JCeP
3
2
4.6.1. Dimethylphosphorylthioformic acid anilide (15a)
Mp 139e147 ꢀC (dec) (yellow crystal from CH2Cl2e
AcOEtehexane); 1H NMR (CDCl3) d 1.81 (d, J¼28.4 Hz,
6H), 7.32 (t, J¼7.6 Hz, 1H), 7.44 (t, J¼7.6 Hz, 2H), 8.75 (d,
3.3 Hz), 132.9 (d, JCeP¼9.9 Hz), 138.4 (d, JCeP¼11.5 Hz),
1
194.0 (d, JCeP¼89.2 Hz); IR (KBr): 2800e3300, 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.
J¼7.6 Hz, 2H), 10.75 (br, 1H); 13C NMR (CDCl3) d15.7 (d,
3
1JCeP¼74 Hz), 121.5, 127.5, 129.1, 138.2 (d, JCeP
¼
4.6.7. Diphenylphosphorylthioformic acid benzylamide
(16b)
Mp 164e166 ꢀC (pale yellow crystal from CH2Cl2e
AcOEtehexane); 1H 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
1
11.5 Hz), 197.0 (d, JCeP¼85.5 Hz); IR (KBr): 3700e2800,
1180 cmꢁ1. Anal. Calcd for C9H12NOPS: C, 50.70; H, 5.67;
N, 6.57. Found: C, 50.71; H, 5.73; N, 6.57.
4.6.2. Dimethylphosphorylthioformic acid benzylamide
(15b)
1
3
(d, JCeP¼5.8 Hz), 128.29, 128.30, 128.4 (d, JCeP¼5.8 Hz),
1
3
Mp 100e101 ꢀC (yellow crystal from CH2Cl2eAcOEte
129.0, 129.2 (d, JCeP¼108.1 Hz), 132.6, 132.7 (d, JCeP¼
1
hexane); H NMR (CDCl3) d 1.77 (d, J¼15 Hz, 6H), 4.88
9.9 Hz), 135.1, 197.1 (1JCeP¼86.7 Hz); IR (KBr): 2900e
3350, 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.
(d, J¼1.6 Hz, 2H), 7.32e7.36 (m, 5H); 13C NMR (CDCl3)
1
3
d 15.9 (d, JCeP¼74.1 Hz), 49.4 (d, JCeP¼5.8 Hz), 128.2,
128.4, 128.9, 135.2, 199.9 (1JCeP¼83.9 Hz); IR (KBr):
3700e2900, 1170 cmꢁ1. Anal. Calcd for C10H14NOPS: C,
52.85; H, 6.21; N, 6.16. Found: C, 52.78; H, 6.24; N, 6.09.
4.6.8. Diphenylphosphorylthioformic acid piperidide (16c)
Mp 153e154 ꢀC (yellow crystal from CH2Cl2eAcOEte
1
hexane); H NMR (CDCl3) d 1.40e1.43 (m, 2H), 1.67e1.71
4.6.3. Dimethylphosphorylthioformic acid piperidide (15c)
Mp 62e63 ꢀC (yellow crystal from CH2Cl2eAcOEte
hexane); 1H NMR (CDCl3) d 1.76 (br s, 6H), 1.91 (d,
J¼13.2 Hz, 6H), 4.20 (br s, 2H), 4.60 (br s, 2H); 13C NMR
(m, 4H), 4.21 (t, J¼5.6 Hz, 2H), 4.36 (t, J¼5.6 Hz, 2H),
7.45e7.57 (m, 6H), 7.81e7.86 (m, 4H); 13C NMR (CDCl3)
3
3
d 24.1, 25.6, 26.7, 51.8 (d, JCeP¼2.9 Hz), 53.7 (d, JCeP
¼
2
1
4.2 Hz), 128.2 (d, JCeP¼12.3 Hz), 131.88 (d, JCeP d,¼
1
3
(CDCl3) d 19.3 (d, JCeP¼78.1 Hz), 24.2, 25.6, 27.6, 51.8
109.8 Hz), 131.95 (d, JCeP¼9.0 Hz), 131.97, 194.5 (d,
3
3
(d, JCeP¼2.5 Hz), 52.5 (d, JCeP¼4.1 Hz), 197.3 (1JCeP
¼
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.
82.3 Hz); IR (KBr): 2944, 1483, 1442, 1247, 1179, 1110,
869 cmꢁ1. Anal. Calcd for C8H16NOPS: C, 46.81; H, 7.86;
N, 6.82. Found: C, 46.72; H, 7.63; N, 6.79. HRMS (EI) calcd
for C8H16NOPS: 205.0690; found: m/z 205.0684.
4.6.9. Diphenylphosphorylthioformic acid morpholide (16d)
Mp 165e167 ꢀC (yellow crystal from CH2Cl2eAcOEte
hexane), lit. mp 150e151 ꢀC;5 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), 4.48 (t, J¼4.8 Hz, 2H), 7.26e7.51 (m, 4H), 7.55e7.59
(m, 2H), 7.81e7.86 (m, 4H); 13C NMR (CDCl3) d 50.4 (d,
4.6.4. Dimethylphosphorylthioformic acid morpholide (15d)
Mp 87e88 ꢀC (pale yellow crystal from CH2Cl2eAcOEte
hexane); 1H NMR (CDCl3) d 1.95 (d, J¼13.6 Hz, 6H), 3.80 (t,
J¼5.2 Hz, 2H), 3.84 (t, J¼5.2 Hz, 2H), 4.30 (t, J¼4.8 Hz, 2H),

H. Morita et al. / Tetrahedron 64 (2008) 3589e3595
3595
3
3
2
3JCeP¼2.9 Hz), 52.9 (d, JCeP¼3.9 Hz), 66.5, 66.9, 128.3
54.6 (d, JCeP¼4.1 Hz), 64.2 (d, JCeP¼8.2 Hz), 190.3 (d,
1JCeP¼188.3 Hz); IR (KBr): 3700e3200, 3100e2800, 1438,
1240, 1086 cmꢁ1. HRMS (EI) calcd for C10H20NO3PS:
265.0902; found: m/z 265.0882.
2
1
(d, JCeP¼12.4 Hz), 131.3 (d, JCeP¼110.1 Hz), 132.0 (d,
4
1
3JCeP¼9.0 Hz), 132.2 (d, JCeP¼3.3 Hz), 196.3 (d, JCeP
¼
88.8 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.
4.6.14. Diethoxyphosphorylthioformic acid morpholide
(17d)
1
4.6.10. Diphenylphosphorylthioformic acid pyrrolidide
(16e)
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
Mp 153e155 ꢀC (yellow crystal from CH2Cl2eAcOEte
3
3
(CDCl3) d 16.2 (d, JCeP¼6.6 Hz), 49.3 (d, JCeP¼6.5 Hz),
1
hexane); H NMR (CDCl3) d 1.91e2.03 (m, 4H), 3.84e3.91
3
2
53.8 (d, JCeP¼3.3 Hz), 64.5 (d, JCeP¼7.4 Hz), 66.4, 66.9,
1
(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,
191.9 (d, JCeP¼187.6 Hz); IR (KBr): 3700e2800, 1478,
1437, 1253, 1120, 1065, 1030 cmꢁ1. HRMS (EI) calcd for
3
3
26.6, 52.7 (d, JCeP¼2.5 Hz), 55.4 (d, JCeP¼3.3 Hz), 128.2
C9H18NO4PS: 267.0694; found: m/z 267.0705.
2
1
(d, JCeP¼12.3 Hz), 131.1 (d, JCeP¼109.0 Hz), 132.1 (d,
3
1
4JCeP¼2.4 Hz), 132.2 (d, JCeP¼9.0 Hz), 192.1 (d, JCeP
¼
4.6.15. Diethoxyphosphorylthioformic acid pyrrolidide
(17e)
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.
1
Yellow oil; H NMR (CDCl3) d 1.37 (dt, J¼0.8, 7.2 Hz,
6H), 1.97e2.12 (m, 4H), 3.81e3.85 (m, 2H), 4.07e4.11
(m, 2H), 4.23e4.37 (m, 2H); 13C NMR (CDCl3) d 16.2 (d,
3JCeP¼6.6 Hz), 23.4, 26.5, 53.2 (d, JCeP¼1.6 Hz), 54.3 (d,
3
4.6.11. Diethoxyphosphorylthioformic acid anilide (17a)
1
3JCeP¼6.6 Hz), 64.3 (d, JCeP¼7.4 Hz), 191.9 (d, JCeP
¼
2
1
Yellow oil; H 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
187.6 Hz); IR (KBr): 3700e2700, 1450, 1250, 1168, 1062,
. HRMS (EI) calcd for C9H18NO3PS:
1030, 980 cmꢁ1
251.0745; found: m/z 251.0744.
3
2
NMR (CDCl3) d 16.1 (d, JCeP¼6.6 Hz), 65.3 (d, JCeP
¼
3
7.4 Hz), 122.0, 127.4, 129.0, 138.0 (d, JCeP¼14.9 Hz),
1
190.6 (d, JCeP¼181.7 Hz); IR (KBr): 3400e2900, 1360,
References and notes
1230 cmꢁ1. HRMS (EI) calcd for C11H16NO3PS: 273.0589;
found: m/z 273.0618.
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.
4.6.12. Diethoxyphosphorylthioformic acid benzylamide
(17b)
2. Takeda, M.; Yoshimura, T.; Fujii, T.; Ono, S.; Shimasaki, C.; Morita, H.
Tetrahedron Lett. 1999, 40, 2327.
Mp 75e77 ꢀC (pale yellow crystal from CH2Cl2eAcOEte
1
hexane); H NMR (CDCl3) d 1.37 (t, J¼7.2 Hz, 6H), 4.17e
3. (a) Wittig, G.; Schlosser, M. Chem. Ber. 1961, 94, 1373; (b) Trippett, S.
J. Chem. Soc. 1961, 2813.
4.33 (m, 4H), 4.85 (dd, J¼2.0, 5.6 Hz, 2H), 7.31e7.39 (m,
5H), 9.19 (br, 1H); 13C NMR (CDCl3) d 16.2 (d, JCeP
¼
4. Pollinion, D. P.; Andrew, S. S. Tetrahedron Lett. 1986, 27, 1477.
5. Khokhlov, P. S.; Murabuldaev, A. M.; Osipov, V. N.; Ignatenko, A. V.;
Zavarzin, I. V. Russ. Chem. Bull. 2003, 52, 2298.
6. (a) Schultz, A. G.; Schlessinger, R. H. Chem. Commun. 1970, 747; (b)
Rewinkel, J. B. M.; Porskamp, P. A. T. W.; Zwanenburg, B. Recl. Trav.
Chim. Pays-Bas 1988, 107, 563; (c) Zwanenburg, B.; Keilbasinski, P.
Tetrahedron 1979, 35, 169; (d) Porskamp, P. A. T. W.; Lammerink,
B. H. M.; Zwanenburg, B. J. Org. Chem. 1984, 49, 263.
3
3
2
6.6 Hz), 49.3 (d, JCeP¼8.2 Hz), 65.1 (d, JCeP¼7.4 Hz),
1
128.3, 128.4, 129.0, 135.0, 193.2 (d, JCeP¼180.2 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.
7. (a) Zwanenburg, B.; Thijs, L.; Strating, J. Recl. Trav. Chim. Pays-Bas 1970,
89, 687; (b) Loontjes, J. A.; Van der Leij, M.; Zwanenburg, B. Recl. Trav.
Chim. Pays-Bas 1980, 99, 39; (c) Holm, A.; Carlsen, L. Tetrahedron Lett.
1973, 34, 3203; (d) Carlsen, L.; Holm, A.; Snyder, J. P.; Koch, E.;
Stilkerieg, B. Tetrahedron 1977, 33, 2231.
4.6.13. Diethoxyphosphorylthioformic acid piperidide (17c)
1
Yellow oil; H NMR (CDCl3) d 1.38 (t, J¼7.2 Hz, 6H),
1.75 (br, 6H), 4.16e4.37 (m, 8H); 13C NMR (CDCl3) d 16.2
3
3
(d, JCeP¼6.5 Hz), 24.2, 25.4, 26.9, 50.6 (d, JCeP¼6.6 Hz),