Intramolecular cyclization of ω-haloalkylsubstituted thiophosphorylacetonitriles: Synthesis and stereochemistry of 3-cyano-2-oxo-1,2-thiaphosphacyclanes

Article abstract of DOI:10.1002/hc.1101

Intramolecular S-alkylation in a series of ω-haloalkyl-substituted thiophosphorylacetonitriles 5-7 presents an effective synthetic route to the hitherto unknown 3-cyano-2-oxo-1,2-thiaphospholanes 14 and thiaphosphinanes 15. The compounds were obtained as a mixture of cis- and trans-isomers that were resolved to individual stereoisomers in most cases. For some of them, X-ray diffraction analysis has been performed. It was shown that ³¹P NMR spectroscopy can be used to assign the stereochemistry of 3-cyano-2-oxo-1,2-thiaphosphacyclanes.

Full text of DOI:10.1002/hc.1101

Heteroatom Chemistry
Volume 13, Number 1, 2002
Intramolecular Cyclization
of ω-Haloalkylsubstituted
Thiophosphorylacetonitriles: Synthesis
and Stereochemistry of 3-Cyano-2-
oxo-1,2-thiaphosphacyclanes
Irene L. Odinets, Natalya M. Vinogradova, Konstantin A. Lyssenko,
Michail Yu. Antipin, Pavel V. Petrovskii, and Tatyana A. Mastryukova
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813
Moscow, GSP-1, Vavilova str.28
Received 31 January 2001; revised 19 April 2001
phosphacyclanes with a single phosphorus het-
ABSTRACT: Intramolecular S-alkylation in a series
eroatom [1], and polyheteraphosphacyclanes and
of ꢀ-haloalkyl-substituted thiophosphorylacetonitriles
unsaturated derivatives [2–6] have been investi-
5–7 presents an effective synthetic route to the hith-
gated most extensively. As regards saturated 1,2-
erto unknown 3-cyano-2-oxo-1,2-thiaphospholanes
heteraphosphacyclanes with oxygen, nitrogen, or
14 and thiaphosphinanes 15. The compounds were
sulfur as heteroatoms, 1,2-oxaphosphacyclanes have
obtained as a mixture of cis- and trans-isomers that
been studied sufficiently thoroughly, and some of
were resolved to individual stereoisomers in most
them have found practical application in the indus-
cases. For some of them, X-ray diffraction analysis
try, specifically as nonflammable hydraulic liquids
has been performed. It was shown that 31P NMR spec-
and plasticizers [7,8], additives to oils, lubricants [9],
troscopy can be used to assign the stereochemistry of
flame retardants [10,11], thermostabilizing additives
ꢀ
C
3-cyano-2-oxo-1,2-thiaphosphacyclanes.
2002 John
to fibers [12–14], and surfactants [15]. Moreover, de-
spite the fact that 1,2-thiaphosphacyclanes should
be of no less practical interest, at the beginning of
the present investigation, only a few of the simplest,
nonfunctionalized representatives of such types of
compounds have been described. It was shown re-
cently in our laboratory [16–19] that thiophospho-
ryl compounds 1, with the phosphorus atom bear-
ing the ω-haloalkyl moiety, rather easily undergo
intramolecular S-alkylation reactions yielding five-
and six-membered 1,2-thiaphosphacyclanium salts
2. In the case of the presence of at least one
alkoxy group at the phosphorus atom, a sub-
sequent dealkylation takes place leading to for-
mation of the 2-oxo-1,2-thiaphosphacyclanes 3
(Scheme 1).
Wiley & Sons, Inc. Heteroatom Chem 13:1–21, 2002; DOI
10.1002/hc.1101
INTRODUCTION
By now, many phosphorus-containing heterocycles
have been described in the literature, among them
Correspondence to: Irene L. Odinets; e-mail: odinets@ineos.
ac.ru.
Contract Grant Sponsor: Russian Foundation of Basic
Research.
Contract Grant Number: 99-03-033014.
Contract Grant number: 00-15-9738.
Contract Grant Number: 00-03-328079.
2002 John Wiley & Sons, Inc.
c
ꢀ
1

2
Odinets et al.
S
3
1
2
_
Hlg
R
R
=R =Ph
+
2P
3
i: Cl(CH2)3Br
i: R Hlg
Ph
Hlg=Br, I
_
1
2
1
2
1 2
R R P(S)CH CN
R R P(S)CH2CN
R R P(S)CCN
ii: Hlg'(CH2)nBr
(CH2)n-2
4a-f
(CH2)3Cl
2
(CH2)nHlg'
6a-c; 7a-f; 8a,b
1
2
R R P(S)(CH2)nHlg
5a-f
1
_
Hlg
S
S
+
2P
EtO
O
n=3,4
R
=R =OEt
R1
R2
R1
R2
R3
Me
Me
Et
Me
Me
Me
Pr
n
2
2
2
2
3
3
3
3
3
3
3
4
4
Hlg'
Cl
Cl
Cl
Cl
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl(Br)
Cl
1
2
(EtO)
P
Hlg= I
4a,5a
4b,5b
4c,5c
4d,5d
4e,5e
4f,5f
OEt
OPr
Me
Me
Ph
OEt
OPr
OPri
OBui
OEt
Ph
6a OEt OEt
(CH2)
(CH2)
n-2
n-2
6b Ph
6c Ph
6d Ph
OEt
OEt
Ph
3
7a OEt OEt
7b OPr OPr
7c OEt OEt
SCHEME 1
Ph
i: 50% aq. NaOH/CH2Cl2/TEBA
ii: s.KOH/CH3CN/TEBA
Hlg = Br,I
7d Me
7e Me
7f Ph
7g Ph
OPri
Me
OBui Me
The subsequent functionalization of such
compounds, with the introduction of substituents to
the ring, represents, however, a rather complicated
task. Nevertheless, such an S-alkylation must obvi-
ously be a general method of 1,2-thiaphosphacyclane
structure formation. Therefore, one should strive to
obtain the functional compounds of the said type
starting from the functionalized thiophosphoryl
compounds having an ω-haloalkyl group.
Earlier [20,21], we confirmed this assumption
by the synthesis of a few (3-halopropyl)-substituted
thiophosphonylacetonitriles and thiophosphinylace-
tonitriles. In this case, the intramolecular cycliza-
tions proceeding under elevated temperatures,
yielded the 2-ethoxy- and 2-methyl-3-cyano-2-oxo-
1,2-thiaphosphinanes. To elucidate the limits of the
application of the aforementioned synthetic scheme
and to estimate the influence of the initial compound
structures on the result and stereochemistry of the
process, we have synthesized a variety of ω-haloalkyl-
substituted compounds 5–8 and investigated their
intramolecular transformations.
OEt
Ph
Me
Me
Me
Me
8a OEt OEt
8b Ph
Ph
SCHEME 2
isolation of the intermediate alkylation products.
The optimal catalyst for both biphasic systems is tri-
ethylbenzylammonium chloride (TEBA).
Use of the α, ω-dibromoalkanes for an alky-
lation of monoalkylsubstituted thiophosphorylace-
tonitriles, under the aforementioned conditions,
could afford alkylation compounds having a termi-
nal bromine atom. In this case, however, a side
reaction proceeds to give symmetrical bis(thi-
ophosphoryl) alkanedinitriles. For example, the re-
action of diethylthiophosphorylpropionitrile with
1,3-dibromopropane to give 7a is accompanied to
a great extent by the formation of the heptanecar-
bodinitrile 9, even with substantial dilution of the
reaction mixture and with use of an excess of the
alkylating agent (Scheme 3). When the said reac-
tion was carried out under the standard dilution
conditions suggested previously [23] for unsymmet-
ric α, ω-bromochloroalkanes, 9 was found to be the
main reaction product (yield 77%).
RESULTS AND DISCUSSION
Synthesis of ω-Halo-2-
thiophosphorylalkanonitriles
Compound 9 was obtained as a mixture with
the statistical ratio of meso and racemic d,l-isomers
and was almost insoluble in hexane. This allowed
us to separate it readily from 7a. Stereoisomers 9
were, in turn, separated by column chromatogra-
phy. The structure of the meso-form 9 (RC, SC) was
confirmed by single crystal X-ray diffraction anal-
ysis (Figure 1). The bond lengths and angles in 9
are characterized by the typical values for analogous
Compounds 5–8, having a terminal chlorine atom,
were obtained as the result of an alkylation of
thiophosphorylacetonitriles 4 under phase-transfer
catalysis conditions based on the conditions of
these reactions investigated by us earlier [22,23]
(Scheme 2). Namely, it was established that C-
monoalkylation of compounds
4 with mono-
haloalkanes and 1,3-bromochloropropane can be
carried out in a 50% aq. NaOH/CH2Cl2 medium with
high a degree of selectivity. The secondary alky-
lation of C-alkylated thiophosphorylacetonitriles
with monohaloalkanes and unsymmetrical α, ω-
dihaloalkanes, in turn, proceeded easily in the het-
erophase medium s. KOH/CH3CN. It should be noted
that the synthesis of disubstituted thiophosphory-
lacetonitriles 6–8 is most readily affected without
Me
(EtO)2P(S)C(CH2)3CP(S)(OEt)2
CN CN
9 (meso, d,l)
Me
Me
MeI
i:
(EtO)2P(S)CH2CN
(EtO)2P(S)CCN
+
ii:Br(CH2)3Br
4a
(CH2)3Br
7a
SCHEME 3

Intramolecular Cyclization of ꢀ-Haloalkylsubstituted Thiophosphorylacetonitriles
3
˚
FIGURE 1 Molecular structure of meso-9. The disordering of OEt groups is omitted for clarity. Selected bond lengths (A):
P(1)-O(2) 1.561(3), P(1)-O(1) 1.571(3), P(1)-C(1) 1.849(3), P(1)-S(1) 1.917(2), P(2)-O(4) 1.562(3), P(2)-O(3) 1.565(3), P(2)-
C(5) 1.838(3), P(2)-S(2) 1.915(2); Selected angles (deg.): O(2)-P(1)-O(1) 103.8(2), O(2)-P(1)-C(1) 101.0(2), O(1)-P(1)-C(1)
100.4(2), O(2)-P(1)-S(1) 116.7(2), O(1)-P(1)-S(1) 117.1(1), C(1)-P(1)-S(1) 115.3(1), O(4)-P(2)-O(3) 104.6(2), O(4)-P(2)-C(5)
101.9(1), O(3)-P(2)-C(5) 100.2(1), O(4)-P(2)-S(2) 116.8(1), O(3)-P(2)-S(2) 116.8(1), C(5)-P(2)-S(2) 114.3(1).
compounds [24]. In both of the S P(OEt)2 frag-
ments, the P S group is characterized by the an-
tiperiplanar orientation with respect to the CN
group. The slight shortening of P S bonds, to
1.915(2)A in 9, is probably caused by the electron-
withdrawing effect of the cyano group [24].
Yields, elemental analysis data, physicochemi-
cal constants, and spectroscopy data of the com-
pounds 5–8 are summarized in Tables 1 and 2. It
should be mentioned that, in order to accelerate
the intramolecular S-alkylation, compounds with a
terminal chlorine atom were transformed, in some
cases, to the corresponding iodo-derivatives by the
exchange reaction with NaI/CH3CN.
cyanosubstituted analogs 10a and 11a are stable and
may be isolated. The corresponding cyclic forms 12
and 13 were formed slowly in acetonitrile solutions
of 10a and 11a, the equilibrium between linear and
cyclic forms (ring-chain halotropic tautomerism) be-
ing established in about six months (Scheme 4). Af-
ter the equilibrium had been reached, the amounts
of cyclic forms were found to be 14% (12) and 9%
(13), according to the 31P NMR data.
However, due to the subsequent irreversible
dealkylation in the intermediate thiaphosphacycla-
nium salts, the cyclization of the initial compounds
5–7 proceeds rather readily, even for the compounds
having a terminal chlorine atom, when there is
at least one alkoxy group bonded to the phospho-
rus atom. Thus, 5–7 are only partly transformed
to the five- and six-membered 3-cyano-2-oxo-1,2-
thiaphosphacyclanes 14 and 15, even under dis-
tillation in vacuo (Scheme 5, method I). Hence,
although the introduction of the cyano group de-
creases the thione sulfur atom nucleophilicity, it pro-
motes, at the same time, the dealkylation process
in the intermediate thiaphosphacyclanium salt. It
should be noted that the substituted thiophospho-
rylacetonitrile 8a, bearing the 4-chlorobutyl moiety
˚
Intramolecular S-Alkylation of
ω-Halo-2-thiophosphorylalkanonitriles
Investigation of the intramolecular S-alkylation in
a series of ω-halo-2-thiophosphorylalkanonitriles 5–
8 (performed by the example of the compounds
bearing the diphenylthiophosphinyl group 5f, 7g)
has demonstrated that the presence of the electron-
withdrawing α-cyano group results in a regular
decrease in the thione sulfur atom nucleophilic-
ity, and, consequently, in an increase in ω-halo-2-
thiophosphorylalkanonitriles stability.
Thus, unlike (3-iodobutyl)diphenylphosphine
sulfide, which readily undergoes spontaneous in-
tramolecular S-alkylation yielding diphenyl 1,2λ5-
thiaphosphinanium iodide [16], during the prepa-
ration from (3-chlorobutyl)diphenylphosphine sul-
fide by the exchange reaction with sodium iodide, its
S
+
Ph2P(S)C(R)CN
(CH2)3Cl
Ph2P(S)C(R)CN
(CH2)3I
NaI/CH3CN
Ph
I -
2P
∆
R
CN
10a,11a
5f, 7g
12,13
R = H (10a,12); R = Me (11a,13)
SCHEME 4

4
Odinets et al.
TABLE 1 Physical and Elemental Analyses Data for Compounds 5–9, 14 and 15
Found (%)
Calculated (%)
Yielda
(%)
m.p./ ◦C or
Compound
b.p./ ◦C (mm Hg)
Formula
C
H
N
P
5ab
83 (46)
70 (41)
82 (60)
65 (40)
87 (61)
75 (55)
93 (70)
80 (69)
71 (60)
Oil
C9H17ClNO2PS
40.11
40.08
43.67
43.37
43.88
43.60
44.31
44.86
51.94
51.74
62.68
62.17
40.55
40.07
51.88
51.74
53.18
53.25
—
47.10
47.22
46.16
46.23
47.19
46.89
47.10
46.89
53.22
53.24
62.30
62.15
—
6.28
6.35
7.13
7.11
6.84
6.75
7.20
7.15
5.87
5.64
4.98
5.10
5.87
6.31
5.42
5.64
5.93
6.02
—
7.93
7.43
7.39
7.38
7.69
7.51
7.69
7.51
6.03
6.06
5.50
5.50
—
5.35
5.19
—
11.58
11.48
10.12
10.40
12.23
12.20
11.23
11.57
10.16
10.28
9.26
9.29
—
—
—
—
—
—
—
—
5bb
5c
Oil
C11H21ClNO2PS
C9H17ClNOPS
C10H19ClNOPS
C13H17ClNOPS
C17H17ClNPS
C9H17ClNO2PS
C13H17ClNOPS
C14H19ClNOPS
—
—
170–175 (1)
5.45
5.52
5.35
5.23
5.06
4.64
4.29
4.20
5.38
5.19
4.83
4.64
4.68
4.44
—
5db
5eb
5fb
Oil
Oil
88–89
Oil
6ab
6bb
6cb
Oil
Oil
7ac
7b
65 (57)d
75 (63)
165–175 (1)
155–160 (1)
C
12H23ClNO2PS
—
7cc
7d
85 (50)
80 (64)
90 (68)
100 (83)
83 (65)
150–165 (1)
170–175 (1)
Oil
C12H23ClNO2PS
C10H19ClNOPS
C11H21ClNOPS
C14H19ClNOPS
C18H19ClNPS
4.96
4.49
—
9.85
9.95
11.31
10.99
11.31
10.99
9.55
9.81
8.80
8.90
—
7eb
7fb
—
Oil
4.36
4.44
4.30
4.03
—
3.68
3.87
6.05
6.17
7gb
65–66
8ae
8b
92 (73)
71 (59)
150–195 (0.1)
87–89 (Petrol. ether)
—
C19H21ClNPS
62.96
63.06
44.93
44.93
5.77
5.85
6.91
7.05
—
9
Oil (meso:D,L = 30:70)
94–95 (meso:D,L = 70:30)
93 (hexane, meso)
166–167 (A:B = 94:6)
108–109 (B)
C17H32N2O4P2S2
—
14b
14c
15a
15b
15c
15d
15e
15f
—
61 (30)
95 (54)
Quant. (57)
75 (51)
—
C11H12NOPS
C12H14NOPS
C7H12NO2PS
—
55.58
55.70
57.31
57.37
40.60
40.96
—
5.08
5.06
5.69
5.58
5.93
5.89
—
5.81
5.91
5.62
5.58
6.70
6.83
—
—
—
101–102 (A)
71–72 (B)
65–70 (A:B = 50:50)
15.12
15.09
—
116–118 (B)
55 (21)
32 (17)
30 (18)
53 (25)
44 (21)
79 (34)
29 (10)
73–74 (A:B = 50:50)f
136–137 (A)
132–134 (B)
111–112 (A)
C6H10NOPS
C11H12NOPS
C9H16NO2PS
41.73
41.14
55.56
55.70
46.36
46.35
56.44
56.37
—
44.35
44.44
43.62
43.83
5.72
5.71
5.06
5.06
7.08
6.87
5.82
5.58
—
6.62
6.35
6.36
6.50
7.78
8.00
5.70
5.91
5.99
6.01
5.44
5.58
—
7.31
7.41
6.43
6.39
—
—
80–81 (B)
13.05
13.30
11.77
12.35
—
16.09
16.40
—
19 (6)
Quant. (24)
15 (6)
134–136 (A:B = 84:16)
C12H14NOPS
15g
15h
Oil (A:B = 64:36)g
—
64 (22)
151–152 (B)
C7H12NOPS
—
15i
75 (45)
94–95 (A:B = 70:30)
C8H14NO2PS
107–108 (A:B = 5:95)
aAccording to 31P NMR data (shown in parenthesis is the product yield after purification); for compounds 14 and, 15 the yield is based on the both diastereomers;
shown first is the yield for chloroderivatives cyclization, the second is that for iododerivatives cyclization; for purification conditions, see Experimental section.
bPurified by column chromatography (silica gel 40-100 µm, hexane—acetone 100:4).
cPurified by distillation and column chromatography.
d86% Purity according to 1H NMR data.
eA 85:15 mixture of compounds having terminal chlorine and bromine atoms according to 1H NMR data.
f 87% purity according to 1H NMR data.
g86% purity according to 1H NMR data.

TABLE 2 Selected 31P, 1H, and 13C NMR and IR Data for Compounds 5–8
NMR Spectra (δ ppm, J/Hz)a,b
1H
13C
IR
νCN
(cm−1
(NC)CH-P ddd
δ31
P
(
2 J PH /3 J HHA
/
C 6H-C(CN)-P
CH2C1
3 JH H
C(1)
1 J PC
C(2)
2 JPC
C(3)
3 JPC
C(5)
2 JPC
C(6)
2 JPC
Compound
)
(ppm)
3 J HHB
)
(
3 JPH
)
(
)
(
)
(
)
(
)
C(4)
(
)
(
)
5a
2245
2245
2235
85.60
3.03
(21.2/10.3/3.9)
3.05
(21.2/9.6/4.0)
2.95
(18.4/10.4/3.9)
2.93
(9.1/8.0/4.0)
2.50
(19.2/11.2/4.2)
2.29
(13.0/12.0/4.4)
3.21
(20.0/11.2/4.4)
3.01-3.10 m
—
3.54 t (5.9)
3.55 t (6.0)
3.56 t (5.6)
3.57 t (6.0)
36.00 d
(113.7)
36.36 d
(113.8)
37.08 d
(65.9)
37.22 d
(66.8)
—
24.23
24.62
23.78
23.18
—
29.51 d
(13.1)
29.80 d
(13.1)
29.72 d
(12.0)
29.67 d
(11.9)
—
34.08
115.28 d
(7.8)
115.57 d
(8.0)
115.84 d
(7.3)
116.0 d
(5.3)
—
—
5b
85.50
89.54
88.87
90.20
90.10
84.70
84.66
—
—
—
43.23
43.01
43.01
—
5cc
5dc
2235
2240
—
—
—
2.94-2.99
br.t
—
5ec,d
—
3.52 t (6.4)
3.53 t (6.0)
38.24 (73.5)
38.40 (73.1)
24.26
24.18
30.14 d
(12.6)
43.24
116.11 d
(6.2)
—
—
29.94 d
(12.3)
29.81 d
(11.5)
—
5f
2240
2240
45.03
90.68
3.58
(14.0/11.6/4.0)
—
—
3.54 t (6.5)
34.72 (49.4)
28.12
36.50
43.00
116.40 d
(5.4)
118.11 d
(6.9)
6a
1.55 d
(18.0)
3.70 (HA),
3.63 (HB),
40.14 d
(114.9)
38.95 d
(11.5)
19.18 d
(2.6)
(2 J H = 10.8)
H
B
A
6bc
6cc
2240
92.91
92.02
93.04
92.09
—
—
—
1.64 d
(16.0)
3.54 (HA),
3.50 (HB),
40.22 d
(74.2)
36.03
—
—
—
—
38.73 d
(13.5)
118.51 d
(5.1)
17.94
18.84
(2 J H = 11.2)
H
B
A
1.27 d
(18.4)
3.77 (HA),
3.69 (HB),
39.64 d
(74.5)
35.29 d
(2.3)
39.08 d
(9.6)
118.54 d
(5.4)
(2 J H = 10.8)
H
B
A
2235
1.38–1.47 m
1.59–1.68 m
(CH2(Et))
3.47 (HA),
3.26 (HB),
44.81 d
(74.4)
34.71
39.71 d
(4.2)
117.72 d
(5.0)
25.97 d
(3.0)
(2 J H = 10.4)
H
B
A
3.73 (HA, HB),
45.28 d
(74.0)
34.6 d
(2.8)
38.84 d
(8.5)
117.68 d
(4.6)
25.72
(2 J H = 11.2)
H
B
A

TABLE 2 (continued) Selected 31P, 1H, and 13C NMR and IR Data for Compounds 5–8
NMR Spectra (δ ppm, J/Hz)a,b
1H
13C
IR
νCN
(cm−1
(NC)CH-P ddd
δ31
P
(
2 J PH /3 J HHA/
C 6H-C(CN)-P
3 J PH
CH2C1
3 J H H
C(1)
1 JPC
C(2)
2 JPC
C(3)
3 JPC
C(4)
C(5)
2 JPC
C(6)
2 JPC
Compound
)
(ppm)
3 J HHB
)
(
)
(
)
(
)
(
)
(
)
(
)
(
)
7ae
2230
2240
2240
91.90
—
1.52 d
(17.6)
1.46 d
(17.6)
3.49–3.54 m
3.49–3.55 m
40.35 d
(115.2)
40.90 d
(115.2)
45.48 d
(112.4)
32.03
31.50
30.40
27.45 d
(10.0)
27.65 d
(10.0)
28.17 d
(6.1)
32.20
43.82
44.24
118.54 d
(6.9)
118.54 d
(6.8)
18.90
19.21
7b
91.77
92.2
—
—
7cf
1.86–2.10 m
(CH2CH2CH3)
3.55 t
(6.4)
118.5
18.28 d
(7.7)
7dc
7ec
7fc
2235
2235
2240
98.06
97.55
99.91
99.33
93.61
92.99
55.14
92.34
—
1.53 d
(15.6)
1.52 d
(17.6)
1.29 d
(15.5)
1.18 d
(17.4)
—
3.05–3.13 m
—
—
—
—
—
—
—
—
—
—
—
—
3.09–3.14 m
41.03 d
(69.4)
40.75 d
(69.9)
40.78 d
(75.4)
40.33 d
(75.3)
38.12 d
(49.4)
41.22 d
(115.2)
30.41
28.11 d
(9.0)
28.02 d
(10.5)
27.68 d
(8.4)
27.19 d
(11.0)
27.84 d
(9.1)
21.64 d
(10.1)
44.13
44.01
43.71
43.50
43.63
44.36
119.90 d
(3.9)
113.81 d
(4.4)
18.67
17.85
18.85
18.11
31.42 d
(2.0)
30.86
—
—
119.39
—
30.30
31.3
119.35
121.90
7g
2245
2235
1.61 d
(16.2)
1.46 d
(17.2)
3.50 t
(7.8)
3.49 t
(6.4)
18.91
(3.9)
18.67
8ag
31.72
119.21 d
(6.6)
8bh
11a
2240
56.10
55.09
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
1.58 d
(16.4)
3.10 t
(8.0)
aSolvent CDCl3; 1H NMR (5a–e; 6a–c; 7a–d,f,g; 11a); NMR 13C (5a–c,e; 6a–c; 7a–d).
bSolvent C6D6; 1H NMR (5f, 7e); NMR 13C (5d,f , 7e,f,g).
cTwo diastereomers A:B = 1:1 (5c,d), 60:40 (5e), 57:43 (6b), 64:36 (6c), 1:1 (7d), 65:35 (7e), 64:36 (7f).
dIn CH3CN the diastereomers signals are interchanged (δP(A) 84.71, δP (B) 84.82).
eThe compound having bromine terminal atom.
f The proton P–C–CH2 (Pr) and CH2CH2CH2Cl signals are overlapped.
gSolvent CD3CN for 1H, 31P, 13C NMR, spectrum is shown for the corresponding chlorine derivative.
hSolvent CH2Cl2.

Intramolecular Cyclization of ꢀ-Haloalkylsubstituted Thiophosphorylacetonitriles
7
3
R
S
cally (up to 5–7%) with the insertion of the alkyl rad-
ical into the α-position to the phosphorus (compare
15b and 15e). Even 7a, bearing a terminal bromine
atom, transforms under distillation to the cyclic
product with a yield of 7% only. Compounds 6, when
distilled, afforded the 3-alkyl-3-cyano-2-oxo-1,2-
thiaphospholanes 14 far more readily and in consid-
erably higher yields than observed for six-membered
compounds, 15, even in spite of the presence of an
alkyl radical in the α-position to the phosphorus in
the initial compounds 6a,c. This fact corresponds
to the general rule that five-membered rings are
formed more readily than six-membered ones [25–
27]. It should be mentioned that addition of catalytic
amounts of TEBA to the initial compounds 5–7 in-
creases the yields of the target compound 14 and 15.
As one could expect, the intramolecular cycliza-
tion of the ω-iodoalkyl-substituted thiophosphinates
and thiophosphonates 10 and 11 obtained from
the corresponding chloroderivatives 5–7 in situ
(with use of 2 equiv. NaI/CH3CN and with 2 hours
reflux, method II) proceeds under milder condi-
tions. Intramolecular S-alkylation proceeds slowly
even at room temperature. Thus, cyclic deriva-
tive 15c is formed in 62% yield from the iodo
derivative 5d (R1 = Me, R2 = Bu-i, R3 = H, n= 3)
during one year at 20◦C. Upon refluxing 5–7 in
acetonitrile for 2–20 hours, 2-alkyl(phenyl)-3-cyano-
2-oxo-1,2-thiaphosphacyclanes 14 and 15 are
S
+
P
1
1
o
1
Cl-
R
R
~200
C
R
(CH2)
(CH2)
n-
P(S)CCN
n-
2
P
2
RO
RO
1 mm Hg
- RCl
O
R
3
(CH2) Cl
3
n
R
CN
CN
5a-e; 6a,c; 7b,c,f
14a,c; 15a-g
R1
R3
n
2
2
3
3
3
3
3
3
3
14a
OEt Me
14c
15a
15b
15c
15d
15e
15f
Ph
OEt
OPr
Me
Ph
Et
H
H
H
H
OPr Me
Ph
OEt
Me
Pr
15g
SCHEME 5
(the cyclization of which could afford only a seven-
membered ring), does not cyclize under the afore-
mentioned conditions. This can apparently be ex-
plained by the lesser thermodynamic stability of the
said ring compared to the corresponding five- and
six-membered analog.
The yield of 3-cyano-2-oxo-1,2-thiaphospha-
cyclanes 15 under distillation in vacuo depends
mainly on the easiness of dealkylation for the RO
group (Table 3). In other words, it decreases with
an increase of the volume of the radical (compare
15a and 15b) and also when passing from a pri-
mary radical to a secondary one (compare 15c, ob-
tained from 5c and 5d). Furthermore, the yields of
the six-membered heterocycles are decreased drasti-
TABLE 3 Dependence of Yields and Diastereomer Ratio of 3-Cyano-2-oxo-1,2-thiaphosphacyclanes 14 and 15 on the Initial
Substrate Structure and Cyclization Method
Yield 14 and 15, % ( 31P NMR), Diastereomer Ratio
Method I
Distillation in vacuo
Method II
NaI/MeCN, Reflux
Substrate
Thiaphosphacyclane
b
6a
14a
19
A > B (60:40)
quanta
40c
b
b
6b
6c
5a
5b
5c
5d
5e
7a
7b
14b
14c
15a
15b
15c
15c
15d
15i
61
quant.
quant.d
32
83
53
A < B (40:60)
95
75
55
7
30
44c
7
A > B (70:30)
A ≈ B
A < B (30:70)
b
A ≈ B
A ≈ B
A > B (60:40)
A > B (60:40)
A < B (40:60)
A < B (40:60)
A ≈ B
A > B (55:45)
79
b
75e
29
A < B (40:60)
A < B (40:60)
15e
5.6
A > B (60:40)
17c
7c
7e
7f
15g
15h
15f
15
A > B (60:40)
30
64
quant.
A < B (30:70)
A ≈ B
b
b
19
A > B (55:45)
A < B (40:60)
aCyclic sodium salt 16.
bThe experiment was not carried out.
cTriethylbenzylammonium chloride addition (cat.) upon distillation.
dCyclic sodium salt 17.
eCyclization of the compound having terminal bromine atom upon refluxion in the acetonitrile solution.

8
Odinets et al.
3
3
The presence of two asymmetric centers—
phosphorus and carbon C(3) atoms—in the 3-cyano-
2-oxo-1,2-thiaphosphacyclanes determines their
formation as a mixture of two diastereomers (A and
B), each being a racemic mixture of the enantiomers.
In the 31P NMR spectrum (Table 4), two singlets
correspond to these diastereomers A and B (with
those denoted by diastereomer A showing a low-
field chemical shift). The ratio of the diastereomers
formed during the cyclization depends on the initial
compound structure (mainly by the presence of
the alkyl substituent in the α-position), the method
of cyclization and the ring size. The influence of
these factors on the diastereomeric composition of
3-cyano-2-oxo-1,2-thiaphosphacyclanes 14 and 15
obtained is shown in Table 3.
For 2-alkoxy-3-cyano-2-oxo-1,2-thiaphosphina-
nes, 15a,b, without an alkyl substituent in the 3-
position, the diastereomeric ratio is 1:1, while for
their 3-alkylsubstituted analog, 15e–i, the propor-
tion of diastereomer A is generally higher when the
cyclization is carried out by distillation in vacuo (Hlg
= Cl), and diastereomer B is formed in a greater
amount under milder conditions (when cyclizing 5-
iodo(bromo)-2-thiophosphorylpentanonitriles). The
same regularities may be observed for 3-cyano-2-
oxo-1,2-thiaphospholanes, 14. The preferential for-
mation of one or another diastereomer obviously de-
pends on steric and electronic factors determining
the structure of the intermediate phosphonium salt
and conditions of the cyclization as well.
R
R
S
1
R
NaI/CH3CN
∆
(CH2)
1(
P
3
n-
2
1(
R
RO)P(S)CCN
R
RO)P(S)CCN
∆
O
R
(CH2) I
n
10,11
CN
(CH2) Cl
5b-e; 6c,d; 7b,c,e,f
n
14b,c; 15b-h
3
3
10: R = H; 11: R = Alk,
n = 2, 3
R1
Ph
R3
n
2
3
14b
15h
Me
Me Me
SCHEME 6
formed in yields up to quantitative (Scheme 6,
Table 3).
It should be noted that cyclization of the
thiophosphonates 5a and 6a occurred under such
conditions (with an excess of NaI), followed by
dealkylation of the second alkoxy group at the phos-
phorus atom in the desired 1,2-thiaphosphocyclanes
14a and 15a. As a result, the sodium salts of the cor-
responding cyclic acids 16 and 17 were obtained in
practically quantitative yields. In the case of 8a, this
cyclization method resulted in a polymer product of
nonidentified structure schemes.
To obtain 3-cyano-2-ethoxy-3-methyl-2-oxo-1,2-
thiaphosphinane, 15i, which is formed under ther-
mal cyclization of the initial chloride in low yield
(7%) and apparently could not be obtained from
the corresponding iodo derivative (see Scheme 7),
we have used S-alkylation of the corresponding
ω-bromo-2-thiophosphorylalkanonitrile proceeding
under reflux in the acetonitrile solution schemes.
The compounds 14 and 15 were isolated from
the reaction mixtures as diastereomer mixtures (e.g.,
by precipitation using ether). These mixtures were
resolved into the individual diastereomers in most
cases by column chromatography and fractional
crystallization. Satisfactory elemental analysis data
were obtained both for the diastereomeric mixtures
isolated and for the individual isomers (Table 1). The
main spectral parameters of the heterocycles synthe-
sized (1H, 13C, 31P NMR and IR) are listed in Tables
4–6.
3
3
(EtO)2P(S)C(R )CN
(EtO)2P(S)C(R )CN
∆
- EtI
NaI/CH3CN, ∆
- NaCl
(CH2) Cl
n
5a,6a
(CH2) I
n
S
S
NaO
EtO
NaI
- EtI
(CH2)
P
(CH2)
n-
2
P
n-
2
O
O
R
3
3
R
CN
CN
14a,15a
3
In the IR spectra, the absorption bands charac-
teristic of P O and CN groups are observed in the
expected areas, and the difference for diastereomers
A and B does not exceed 10 cm−1 (Table 5).
16: n = 2, R = Me
3
17: n = 3, R = H
SCHEME 7
In the 31P NMR spectra (Table 4), 1,2-thia-
phospholanes 14 show signals in CH2Cl2 in the
δ = 61–73 ppm region. For compounds 15 the
range of the chemical shift values in CH2Cl2 is
35–44 ppm for 2-alkoxyderivatives 15a,b,e,g, 41–52
ppm for 2-methylsubstituted compounds 15c,h, and
32–44 ppm for 2-phenylsubstituted analogs 15d,f.
Note that, as for the initial linear compounds 5–
7, the introduction of an alkyl substituent into the
Me
(EtO)2P(S)CCN
(CH2)3Br
S
EtO
CH3CN
- EtBr
P
O
Me
CN
15i
7
a
SCHEME 8

Intramolecular Cyclization of ꢀ-Haloalkylsubstituted Thiophosphorylacetonitriles
9
TABLE 4 Chemical Shift Values (δ ppm) in 31P NMR Spectra for 3-Cyano-2-oxo-1,2-thiaphosphacyclanes 14 and 15 (A and
B diastereomers) in Different Solvents
CH3CN
CH2Cl2
CDCl3
C6H6
Solvent
Compound
δ ( A)
δ ( B)
ꢀδ
δ ( A)
δ ( B)
ꢀδ
δ ( A)
δ ( B)
ꢀδ
δ ( A)
δ ( B)
ꢀδ
14a
14b
14c
15a
15b
15c
15d
15e
15f
—
—
—
69.62
68.12
65.56
61.79
35.58
35.55
41.91
34.29
41.00
40.05
40.93
47.45
—
1.50
6.23
—
—
—
—
—
—
—
—
—
—
62.87
34.05
—
37.42
—
—
—
—
45.50
—
—
—
7.75
0.87
—
1.94
—
—
—
—
5.93
—
74.20
73.83
36.49
37.06
44.98
35.44
44.04
—
68.61
66.14
36.19
36.58
44.61
34.56
41.43
—
5.59 71.79
7.69 72.21
0.30 35.89
0.48 36.00
0.37 42.64
0.88 35.05
2.61 43.56
10.42 72.71
0.31 36.65
0.45 36.54
0.73 41.99
0.76 35.15
2.56 43.88
3.93 44.51
2.35 43.69
65.11
36.21
36.16
39.38
34.57
41.38
40.54
41.43
—
7.60 70.62
0.44 34.92
0.38
—
2.61 39.36
0.58
2.50
3.97
2.26
—
—
—
—
—
51.43
—
—
—
43.98
43.28
15g
15h
15i
—
52.48
43.70
—
47.64
41.04
4.84 51.67
2.66
4.22
—
—
43.93
—
41.51
2.42
six membered heterocycles results in a considerable
downfield shift (ꢀδ 7–9 ppm).
membered compounds 14, the signals of the C(4)
atom are placed at δ = 43.31–50.11. It should be
noted that, in six-membered ring compounds, the
above C(4) signals are shifted upfield about 2–5 ppm
compared to the P–C(CN) signal in the initial linear
ω-haloalkyl-substituted thiophosphorylacetonitriles
5 and 7. On the contrary, in the five-membered rings
14, the signals of the C(4) atom are shifted about 3–
10 ppm downfield with respect to the P–C(CN) signal
in the initial 6. Furthermore, the decrease of 1 JPC (4–
17 Hz) is noted in the cyclic compounds compared to
the initial compounds 5–7. This fact is explained log-
ically by the change in the surroundings of the phos-
phorus atom attached to the aforementioned carbon
atom (from R1(RO)P(S)- to R1(O)PSR-). It should be
The difference between the chemical shifts of
the 1,2-thiaphosphacyclanes A and B diastereomers
(ꢀδ) in the 31P NMR spectra depends on the ring size,
the presence of an alkyl substituent in the 3-position,
and the solvent (Table 4). All other factors being the
same, ꢀδ is generally higher for the compounds with
a methyl or phenyl group bonded to the phosphorus
atom. Furthermore, for the initial compounds 5–7
having two asymmetric centers, the change of the
solvent often results in the change of the mutual sig-
nal positions of diastereomers A and B in 31P NMR
spectra, while for 14 and 15, the mutual position of
stereomers A and B remains unchangeable indepen-
dently of the solvent in use, which is easy to follow
in comparing their integral intensities.
1
mentioned that JPC is generally less in case of the
A-isomer both for five- and six-membered rings. In
1,2-thiaphosphinanes, the signal of the cyclic C(1)
atom attached to sulfur appears as a doublet with
2 JPC 3.7–5.9 Hz at δ = 24.85–29.78 for 15a–d and at
δ = 33.45–37.98 for their alkyl-substituted analogues
15e–i. For 1,2-thiaphospholanes 14b,c, the doublet
of the C(1) atom is placed in the same region as for
In its 1H NMR spectra, 3-cyano-2-oxo-1,2-
thiaphosphacyclanes show the characteristic SCH2
signal at the δ = 2.80–3.60 region, which in some
cases appears as an overall complex multiplet for
both protons, and, for 14b,c, and 15c-e,h, two
separate multiplets are observed corresponding to
the protons in the trans- and cis-positions to the
phosphoryl group oxygen atom. For 3-cyano-2-
oxo-1,2-thiaphosphinanes, 15a–d, the signal of the
methine proton at the α-position to the phosphorus
atom appears, as a rule, as a doublet of doublets of
doublets, as it does for the initial compounds, 5, but
in lower field compared with the latter ones (Table 5).
In the 13C NMR spectra of 14 and 15 (Table 6)
the signals of the carbon atoms C(4) [28] bonded
to the cyano-group are placed at δ = 31.49–34.09
for 3-cyano-2-oxo-1,2-thiaphosphinanes 15a–d and
are shifted downfield (36.87–43.99) for their 3-alkyl-
substituted analogs 15e–i. In the case of the five-
2
their 6-membered analogues, but with the JPC cou-
pling constant increasing to 7.6–8.5 Hz. This con-
stant is maximal for the cyclic salt 16 (9.2 Hz). Thus,
alkyl substituent insertion into the α-position to the
phosphorus atom results in a downfield shift of C(4),
C(1), and C(6) signals. The signal of the CN-group
carbon atom is located in the characteristic region of
δ = 115–120, appearing usually as a doublet for the
A-isomer and as a singlet for the B-isomer. It should
be noted that the signal of this group for the initial
compounds 5–7 usually is situated in the same δ re-
gion as the doublet with 2 JPC coupling constant equal
to 4.4–8.0 Hz.

TABLE 5 Selected 1H NMR and IR spectra parameters for 3-cyano-2-oxo-1,2-thiaphosphacyclanes 14 and 15
1H NMR Spectrum (δ, ppm, J Hz, CDCl 3)
IR Spectrum
C4 (R3)
ν/cm−1
νCN
,
KBr
νPO
R 3 = H
Compound
n
Diastereomer
δH (R 1)
C 1H2
C 2H2
C 3H2
(
3 J HH
/
3 J HH
/
2 J PH
)
R 3 = Alk
14b
2
A
2240
2235
1210
1210
7.54–7.58 m
7.64–7.68 m
7.97–8.02 m
(C6H5)
3.31 (HC)
3.36 (HD)
—
2.37 (HA)
2.91 (HB)
1.23 d
(3 J PH 16.4)
(3 J PH 10.8,
(3 J PH 20.0,
C
A
3 J PH 8.0,
3 J PH 23.6,
D
B
2 J H
11.2)
2 J H H 14.0)
HD
C
C
14b
2
B
7.54–7.59 m
7.64–7.69 m
8.05–8.11 m
(C6H5)
3.49–3.60 m
—
2.58D(HA)
—
1.66 d
(3 J PH 13.6)
2.72 (HB)
(3 J PH 11.6,
A
3 J PH 12.8,
B
2 J H H 12.8)
C
D
14c
14c
2
2
A
B
2230
2230
1200
7.50–7.56 m
7.62–7.65 m
7.93–8.10 m
(C6H5)
7.48–7.53 m
7.58–7.62 m
8.03–8.09 m
(C6H5)
3.24–3.60 m
(HA)
3.61–3.68 m
(HB)
—
—
2.24–2.35 m
(HC)
2.73–2.85 m
(HD)
2.64–2.69 m
(HC)
2.72–2.78 m
(HD)
1.21–1.48 m
(CH2(Et))
1215a
—
—
1210
3.46–3.54 m
1.91–2.10 m
(CH2(Et))
1230a
15a
3
3
3
3
3
A
B
A
B
A
2240
2240
2240
2245
2245
1245
1240
1245
1245
1190
4.05–4.09 mb
2.92–3.06 mc
1.75–1.95,
2.12–2.23 two m 2.43–2.60 two m
2.24–2.33,
3.25 ddd
(3.6/5.2/22.4)
3.16 ddd
(3.8/10.0/18.0)
3.27 ddd
(3.6/4.8/22.8)
3.16 ddd
(4.0/8.0/18.0)
3.25 dt
(3.9/16.7)
—
—
—
—
—
(OCH2)
b
c
15a
1.86–1.90, 2.26–2.32,
2.15–2.10 two m 2.50–2.54 two m
1.98–2.09, 2.12–2.28
15bd
15bd
15c
4.02–4.28b
2.82–2.92c
(OCH2)
2.32–2.48 three me
b
c
—
—
1.98 d (CH3P)
(3 J PH 13.4)
2.87–2.92,
3.36–3.58 two m
2.12–2.19 m
2.25–2.39,
2.52–2.56 two m

15c
3
B
—
—
1.96 d (CH3P)
2.88–2.92,
3.36–3.59 two m
2.91–3.03,
3.40–3.50 two m
2.61–2.78,
3.14–3.54 two m
2.21–2.32 m
2.27–2.42,
2.54–2.58 two m
2.47–2.55,
3.02 ddd
(4.8/6.1/11.6)
3.24 ddd
(4.8/8.0/12.4)
3.20–3.25 m
—
(3 J PH 13.2)
7.50–7.88 m
(C6H5)
15dd
15dd
3
3
Af
Bf
2245
1210
1.85–2.01,
2.28–2.38 two m
1.90–2.01 m
—
—
2.59–2.73 two m
—
—
7.53–7.58 m
7.63–7.67 m
7.88–7.94 m
(C6H5)
2.12–2.48 me
15e
15fd
15fd
3
3
3
B
A
B
2240
2240
—
1240
1210
—
4.08–4.16 m
2.85–2.88
2.90–2.91 two m
2.80–3.05 mc
1.98–2.33 m
—
—
—
1.66 d
(3 J PH 14.8)
1.52 d
(OCH2)
7.50–8.05 m
(C6H5)
2.20–2.30, 2.30–2.49 two me
1.96–2.08, 2.10–2.30 two me
(3 J PH 17.2)
1.38 d
c
7.50–7.65 m
(C6H5)
4.07–4.25 m
(OCH2)
(3 J PH 14.8)
1.40–1.60 m
(CH2(Pr))
1.71 d
15gd,g
15h
3
3
A
A
—
—
2.71–3.00 m
2.65–2.74,
1.78–2.29 m
—
—
2235
1245
1.84 (CH3P)
1.95–2.10, 2.74–2.84 two me
(2 J PH 13.2)
3.21–3.30 two m
(3 J PH 16.4)
1.64 d
15id
15id
16h
3
3
2
A
B
—
—
—
—
—
b
c
e
(3 J PH 16.4)
1.62 d
2235
1245
4.19–4.32 mb
(OCH2)
—
2.84–2.90 mc
2.03–2.26 me
(3 J PH 14.8)
1.33 d
2235,
2255
1230,
1240
1.98–2.03
2.92–2.97 two m
—
2.00 m (HA)
(3 J HH 6.6,
3 J HH 6.8
(3 J PH 13.2)
3 J PH 14.8,
A
2 J H
13.2),
HB
2.2A7 m (HB)
(3 J HH = 5.6),
(3 J PH 23.2),
aTwo conformers.
bThe signals of OCH2 protones of A and B diastereomers are overlapped.
cThe signals of C1H2 protones of A and B diastereomers are overlapped.
dA and B diastereomers mixture in 63:37 (15b), 29:71 (15d), 64:36 (15g), 5:95 (15i) ratio.
eThe signals of C2H2 and C3H2 protones of A and B diastereomers are overlapped.
f Solvent CD3CN.
gThe signals of minor diastereomer B are overlapped by signal of major isomer A.
hSolvent DMSO-d6.

12 Odinets et al.
TABLE 6 Selected 13C NMR Data for 3-Cyano-2-oxo-1,2-thiaphosphacyclanes 14, 15 and 16
13C NMR Spectrum (δ, ppm, J/Hz, CDCl3)
Compound
14b
n
2
2
3
3
3
3
3
3
3
Diastereomer
C(1)2J PC
C(2) 3 JPC
C(3)2 J PC
C(4)1J PC
C(5)2J PC
C(6)2 J PC
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
37.56 (8.5)
37.73 (7.7)
35.69 (8.5)
35.96 (7.6)
29.69 (5.8)
29.08 (5.8)
29.78 (5.7)
29.17 (5.9)
24.85 (5.0)
26.34 (5.0)
26.90 (5.0)
25.44 (5.0)
36.70 (3.9)
37.98 (4.9)
33.45 (3.7)
34.56 (4.0)
35.07 (4.0)
34.20 (5.4)
33.93
—
—
30.82 (1.1)
31.42 (0.7)
31.05
31.18
31.20 (3.6)
29.45
30.22 (3.6)
30.15 (3.0)
26.58
43.31 (60.4)
44.09 (62.8)
49.65 (59.5)
50.11 (62.4)
32.17 (96.8)
31.73 (100.8)
32.95 (96.9)
32.53 (100.9)
34.09 (62.3)
31.49 (64.3)
33.74 (64.9)
32.31 (67.0)
39.30 (60.0)
39.51 (103.8)
36.87 (64.5)
37.99 (68.9)
41.67 (97.4)
43.99 (102.0)
36.88 (62.0)
39.51 (103.7)
38.09
118.13 (4.7)
118.86
117.06 (5.6)
117.63
114.92 (11.2)
115.22 (4.5)
114.95 (11.7)
115.24 (4.5)
115.47
116.56
117.24
117.19
119.14 (7.0)
118.85
116.80
120.19
117.92 (8.2)
117.57
119.42 (6.3)
118.85
18.92
17.04 (1.1)
25.13
14c
24.73
15a
25.64 (4.5)
23.14 (6.1)
25.71 (4.6)
23.48 (8.2)
23.44 (4.9)
23.44 (4.9)
26.47 (3.9)
23.18 (5.1)
23.55 (5.9)
25.08 (5.0)
21.51 (4.1)
25.56 (4.0)
22.84 (4.9)
24.65 (5.2)
22.50
—
—
—
—
—
—
—
—
15b
15c
27.12
15da
15e
27.27 (2.5)
26.98 (2.5)
29.99 (2.9)
30.99 (3.5)
26.37 (2.4)
26.86 (2.4)
33.67 (3.8)
32.61
18.75 (3.0)
19.61 (6.0)
19.91
20.54 (2.0)
29.88 (1.6)
30.35 (2.8)
19.99 (5.1)
19.56 (6.0)
18.68 (2.1)
15f
15g
15h
15i
3
3
2
27.50
31.05 (3.4)
27.05 (3.8)
37.93 (4.8)
36.55 (9.2)
25.07 (5.0)
16bb
—
123.18 (3.8)
aSolvent CD3CN.
bSolvent DMSO-d6.
The bond lengths and bond angles in five-
and six-membered rings exhibit the expected values
(Table 7). The P–S bond lengths in 1,2-thiaphosphi-
The structures of the series of the individual di-
astereomers 14 and 15 have been confirmed by the X-
ray diffraction analysis. Important bond lengths and
bond angles are shown in Table 7. According to the
X-ray data, five-membered rings in 14 adopt the twist
(deviation of the C(2), C(4) atoms) and the envelope
conformation (deviation of the C(2) atom) (Figures 2
and 3), while all the six-membered rings, both re-
ported herein and described by us previously [20,21],
are characterized by chair conformations (Figures
4–6), with the axial position for the CN group in
all molecules 14 and 15. The phosphorus atoms are
characterized by a slightly distorted tetrahedral con-
figuration with the endocyclic C(4)P(1)S(1) angles in
the ranges of 95.84(4) ÷ 97.87(3)◦ in five-membered
rings 14 and 103.43(7) ÷ 105.79(5)◦ in six-membered
rings 15. The torsion angles C(5)C(4)P(1)O(1) are in
the interval −35.0 to 55.2◦ for molecules having the
equatorial position of the P O group (synclinal con-
formation, cis-isomer), and from 147.6 to 170.6◦ for
the axial P O group (antiperiplanar conformation,
trans-isomer).
˚
nanes 15 (2.044(2) ÷ 2.065(2)A) are slightly shorten-
ed in comparison with the typical single P–S bond
˚
(2.08 ÷ 2.10A) [24] and are close to those observed
earlier in the series of 1,2λ5-thiaphosphinanium
˚
salts (2.05A) [18,19]. Such similarity of thiaphos-
phinanium salts and cyanosubstituted cycles 14 and
15 means that the phosphorus atom in the latter
compounds is characterized by a significant frac-
tional positive charge, mainly due to the electron-
withdrawing effect of both the CN group and the
phosphoryl oxygen. The same conclusion can be
made on the base of comparison of the P–S bond
lengths in the nonfunctionalized 2-oxo-2-phenyl-1,2-
thiaphosphinane [29] and 15d(A) (Figure 5), where
˚
the P–S bond length is shortened by 0.02A, while the
˚
P(1)–C(1) bond is elongated by 0.04A due to the pres-
ence of the CN group (Table 7). Thus, one can con-
clude that, for the P–S bond, the presence of electron-
withdrawing substituents leads not to an elongation

˚
TABLE 7 Important Bond Lengths (A) and Bond Angles (deg.) for Some Representatives of 14 and 15
14c(A)
2.0778 (9)
1.478 (2)
1.793 (2)
1.857 (2)
1.837 (2)
97.29 (8)
14c(B)
15a(B)a
2.044 (2)
1.456 (3)
1.573 (3)
1.817 (4)
1.807 (6)
105.5 (1)
15c(A)a
2.062 (2)
1.488 (2)
1.785 (3)
1.838 (4)
1.835 (3)
103.9 (1)
15c(B)
2.065 (2)
1.484 (2)
1.788 (2)
1.833 (2)
1.845 (3)
103.43 (7)
15d(A)
15i(B)a
15h(B)b
2.054 (1)
1.470 (4)
1.785 (4)
1.852 (2)
1.837 (3)
104.62 (9)
Ga,c
P(1)–S(1)
P(1)–O(1)
P(1)–R1
2.0751 (4)d
2.0832 (4)
1.4805 (8)
1.4817 (8)
1.800 (1)
1.801 (1)
1.869 (1)
1.873 (1)
1.840 (1)
1.834 (1)
95.84 (4)
97.87 (3)
117.73 (5)
110.84 (5)
94.93 (4)
95.20 (4)
165.4
2.059 (1)d
2.061 (1)
1.479 (2)
1.477 (2)
1.797 (2)
1.801 (2)
1.839 (2)
1.832 (2)
1.838 (3)
1.827 (3)
103.45 (8)
103.56 (8)
113.8 (1)
113.6 (1)
99.1 (1)
97.96 (9)
167.9
2.0558 (7)
1.469 (1)
1.572 (1)
1.836 (1)
1.832 (2)
105.79 (5)
2.082 (1)
1.474 (2)
1.801 (2)
1.790 (3)
1.828 (3)
103.4 (1)
P(1)–C(4)
S(1)–C(1)
C(4)P(1)S(1)
O(1)P(1)R1
112.2 (1)
95.7 (1)
−35.0
118
116.7 (2)
105.5 (1)
170.6
114.6 (1)
97.9 (2)
170.6
114.1 (1)
100.13 (7)
50.0
116.56 (8)
99.54 (8)
55.2
113.6 (4)
100.2 (1)
50.5
113.0 (1)
96.8 (1)
n/a
C(1)S(1)P(1)
C(5)C(4)P(1)O(1)
LpSS(1)P(1)Xe
Conformationf
147.6
170.00
173
175
−148
175
176
177.1
175
176
176
−124
Twist C(2),C(4)
(0.52, −0.11E)
Twist C(2),C(4)
(0.69, −0.13E)
Envelope C(2)
(0.64E)
chair
chair
chair
chair
chair
chair
chair
aThe numbering of atoms in 15a(B), 15c(A), 15i(B), and G is the same as for all other six-membered cycles in Figures 2–6.
bFor 15h(B) the bond lengths and angles are presented only for the molecule with the occupancy 0.80.
cG presents 2-oxo-2-phenyl-1,2-thiaphosphinane [29].
dFor molecules 14c(B) and 15d(A) bond lengths and angles are indicated for two independent molecules.
e The torsion angle between the hypothetical sulfur electron lone pair (Lps) and the phosphorus axial subsistent (X is O(1) in diasteromer A and R1 in B). The positions of Lps were calculated
in the assumption of the tetrahedral arrangement of LpS’s and C(1), P(1) atoms.
f For five-membered cycles the value in brackets corresponds to the deviation of the atom from the mean plane of remaining atoms of the cycle.

14 Odinets et al.
FIGURE 4 Molecular structure of 15c(B).
FIGURE 2 Molecular structure of 14c(A).
FIGURE 5 Molecular structure of 15d(A). Only one of two
independent molecules is shown.
FIGURE 3 Molecular structure of 14c(B). Only one of two
independent molecules is shown. The differences in their con-
formations are described in Table 7.
but to a shortening of the bond that is usual for the
polar or ionic bonds.
Besides the inductive effects of the substituents,
variation of the P–S bond can also be affected by the
interaction between the lone pair (Lps) of the sul-
fur atom and the antibonding σ-orbital of the axial
P–X bond (n-σ∗ interaction), which differs for P O,
OAlk, and Alk groups [30]. The increase of a n-σ∗ in-
teraction must be reflected in the shortening of the
P–S endocyclic bond and elongation of the axial ex-
ocyclic one.
Analysis of the important bond lengths and bond
angles in the six-membered rings indicates clearly
FIGURE 6 Molecular structure of 15h(B). The disordering is
omitted for clarity.

Intramolecular Cyclization of ꢀ-Haloalkylsubstituted Thiophosphorylacetonitriles 15
some influence of the n-σ∗ interaction in the case of
B
A
the OEt axial group in 15a(B), where not only the P–
˚
S bond attains the minimum value (2.044(2)A), but
also the S(1)-C(1) bond is the shortest one in the se-
˚
ries of compounds studied (1.807(6)A). In spite of
δ
P
O
P
pronounced shortening of the P–S bond in 15a(B),
introduction of the Me group in the 3-position of the
ring (compound 15i(B)) causes an increase of the
O
P
S
R
S
CN
2
trans
cis
1
R
1
R
CN
2
R
˚
P–S bond length by 0.01A, annulling, in fact, the in-
1
2
R =Ph; R =Alk
R* R*
p
c
R* S*
p
c
c
fluence of the n-σ∗ interaction. It’s noteworthy that
the formal strength of the n-σ∗ interaction, in ac-
cordance with the values of the pseudotorsion an-
gle LpsS(1)P(1)X and the length of the P(1)–O(2)(Et)
bond in 15a(B) and 15i(B), were found to be the
same.
O
S
P
O
S
CN
2
R
trans
cis
P
1
R
1
CN
R
2
R
1
2
R =Me, OAlk; R =H, Alk
R* R*
p
R* S*
p c
1
2
R =Ph; R =Alk
Opposite to the axial alkoxy group at the phos-
phorus atom, the influence of the n-σ∗ interaction
on the P–S bond is insignificant in the case of an
axial P O bond. For example, as it may be seen
from Table 7, the P(1)–O(1) and P(1)–S(1) bonds in
15c(A) and 15c(B) are similar. The same situation
is observed in the case of the 3-cyano-3-ethyl sub-
stituted 5-membered rings where the P(1)–S(1) and
P(1)–O(1) bonds in 14c(B), with the axial position of
the P O group are close to the corresponding values
in 14c(A) with the equatorial P O bond.
R* S*
1
2
p
c
R =Ph; R =H
R* R*
p c
SCHEME 9
oxo-1,2-thiaphosphinanes, 15, the situation changes
to the opposite one: diastereomer A with a down-
field shift in its 31P NMR spectrum corresponds to
the trans-disposition of the cyano group and phos-
phoryl oxygen atom with the opposite configura-
tion of the chiral centers (2R∗,2S∗), while the sig-
nal of the cis-isomer B with the identical configu-
ration of the asymmetric centers is shifted upfield.
The only exception is the 3-cyano-2-oxo-2-phenyl-
1,2-thiaphosphinane 15f, wherein the alteration of
substituent precedence leads to the identical config-
uration of the chiral centers in the trans-A isomer
and to the opposite one in the cis-B isomer. Scheme 9
illustrates stereoisomer 14 and 15 structures in com-
parison with δ 31P.
For the 1,2λ5-thiaphosphacyclanium salts, the
elongation of the P–S bond when passing from
the five-membered rings to the six-membered ones
˚
(2.0751(4) ÷ 2.0832(4)A) was not observed [18].
Therefore, taking into account the aforementioned
influence of the alkyl substituent in the 3-position on
the P–S bond length in 15a(B) and 15i(B), one can
˚
suppose that the difference (0.019A) between the P–
S bond lengths in 14c(B) and 15d(A) is also caused
mainly, not by the ring size change, but by introduc-
tion of the 3-ethyl substituent decreasing the frac-
tional positive charge on the phosphorus atom.
Summarizing, the P–S bond length in 1,2-
thiaphosphacyclanes is more affected by the induc-
tive effects of the substituents at the phosphorus
atom and in the 3-position of the ring than by the
n-σ∗ interaction.
Thus, 31P NMR spectroscopy allows one to
assign unambiguously the type of geometric isomer
and the configuration of the asymmetric centers in
3-cyano-2-oxo-1,2-thiaphosphinanes 14 and 15. To
determine the stereochemical structures of phos-
phacyclanes and 1,2-oxaphosphacyclanes having a
tetracoordinated phosphorus atom 1H NMR spectra
are commonly used [1,31]. This method of deter-
mination is based on the deshielding effect of the
Comparison of the 31P NMR spectra and X-ray
diffraction data allows one to conclude that for the
3-cyano-2-oxo-1,2-thiaphospholanes 14, the isomer
A (having a downfield chemical shift) is charac-
terized by the synclinal conformation of the cyano
group and phosphoryl oxygen atom (cis-isomer)
with the identical configuration of the chiral cen-
ters (2R∗,3R∗), while diastereomer B is character-
ized by an antiperiplanar disposition of the said
groups (trans-isomer) with the opposite configu-
ration of the chiral centers (2R∗,3S∗). For the 2-
P
O bond on all kinds of protons in the cis position
to the P O group. Undoubtedly, this anisotropic
effect allows the assignement of the cis and trans
arrangements of the P O group and CH-CN cyclic
proton for the compounds 15a–d or methyl [P–
C(CH3)CN-] or methylene [P–C(CH2-R)CN-] group
in 3-alkylsubstituted compounds, 14a–c and 15e–i:
δH trans-isomer > δH cis-isomer [32]. Nevertheless,
31P NMR spectroscopy is more preferable to de-
termine the geometric structure of 14 and 15 as

16 Odinets et al.
having no need for chemically pure samples and al-
lowing one to monitor the crude reaction mixtures.
We believe that regularities described previously
for the disposition of signals of cis and trans 2-
oxo-1,2-thiaphosphacyclanes in 31P NMR spectra
have to be similar in passing to other 3-substituted
1,2-thiaphophacyclanes, provided that the 3-
substituent will represent an electron-withdrawing
group.
Supplementary Material
Crystallographic data, namely atomic coordinates,
anisotropic parameters, a full list of the bond
lengths, bond and torsion angles, and F0/Fc val-
ues (excluding structure factors), reported in this
article are given in the supplementary materials
and have been deposited as supplementary nos.
CCDC-154959 (9), CCDC-154958 (14c(A)), CCDC-
154955 (14c(B)), CCDC-154956 (15c(B)), CCDC-
154957 (15d(A)), and CCDC-154954 (15h(B)) at the
Cambridge Crystallographic Data Centre. Copies of
the data may be obtained free of charge on appli-
cation to the CCDC,12 Union Road, Cambridge CB2
1EZ UK (Fax: [internat.] +44-1223/336-033; E-mail:
deposit @ccdc.cam.ac.uk).
CONCLUSION
Thus, using as an example the ω-haloalkylsubstituted
thiophosphorylalkanonitriles, the intramolecular S-
alkylation has proven to be the general principle of
the 1,2-thiaphosphacyclane ring construction which
opens wide opportunities to synthesize different
hitherto elusive 1,2-thiaphosphacyclanes, including
functionalized ones.
5-Chloro-2-thiophosphorylpentanonitriles (5):
General Procedure
To a stirred solution of thiophosphorylacetonitrile
4 (10 mmol) and TEBA (200 mg) in CH2Cl2 (based
on 15 mL of solvent for the solid 4f and 5 mL for
the liquid 4a–e) NaOH (1.6 g, 40 mmol) was added
as a 50% aqueous solution. To the reaction mixture,
1,3-bromochloropropane was added dropwise over
10 minutes. The reaction mixture was stirred for 3
hours at 20◦C and diluted with water (15 mL); the or-
ganic layer was separated, and the aqueous layer was
extracted with CH2Cl2. The organic layer was dried
(Na2SO4) and concentrated in vacuo, and the residue
was subjected to column chromatography (silica gel
40–100 ꢁm; hexane–acetone elution) or distillation
in vacuo (for 5c).
EXPERIMENTAL
General
NMR spectra were recorded on Bruker WP-200SY
and AMX-400 spectrometers in CH2Cl2, CDCl3, C6D6,
CD3CN solutions using a deutero solvent as an inter-
nal standard (1H, 13C) and 85% H3PO4 as an exter-
nal standard. IR spectra were recorded on a UR-20
spectrophotometer in a thin layer, in KBr pellets, or
in vaseline oil. The starting thiophosphorylalkanon-
itriles 4 were obtained by the reaction of phosphory-
lacetonitriles with the Lawesson reagent according
to the literature [33].
ω-Chloro-2-thiophosphorylalkanonitriles 6–8:
General Procedure
X-Ray Crystal Structure Determination
Step a: To a stirred solution of thiophosphorylace-
tonitrile 4 (12 mmol) and TEBA (200 mg) in CH2Cl2
(20 mL), NaOH as a 50% aqueous solution (48 mmol)
was added followed by the dropwise addition of the
alkyl halide R3Hlg (14.4 mmol). The reaction mix-
ture was stirred for 3 hours at 20◦C and diluted
with water (15 mL); the organic layer was separated,
and the aqueous layer was extracted with CH2Cl2.
The combined organic fractions were dried (Na2SO4)
and concentrated in vacuo. The oil thus obtained,
representing the intermediate thiophosphorylalka-
nonitrile of 87–96% purity (according to H NMR
spectrum), was used in the subsequent step without
further purification.
Step b: To a stirred solution of the afore-
mentioned oil and TEBA (200 mg) in CH3CN (15
mL) Br(CH2)nCl (n = 2 − 4) (15 mmol) was added,
followed by powdered KOH (15 mmol) portionwise
The crystallographic data for 9, 14c(A and B),
15c(B), 15d(A) and 15h(B) are presented in Table 8.
All structures were solved by the direct method and
refined by full-matrix least squares against F2 in the
anisotropic (H-atoms isotropic) approximation us-
ing the SHELXTL-97 package. Analysis of the elec-
tron density synthesis in 9 and 15h(B) has revealed
disordering of molecules in crystals. In the stucture
of 9, OEt groups were disordered by two positions,
while in 15h(B) the disordering was caused by the
superposition of two molecules with the occupancies
0.8 and 0.2, respectively. The disorder in 15h(B) with
the same ratio of occupancies was observed for two
independent single crystals. All hydrogen atoms in
9 and 14–15 were located from the electron density
difference synthesis and were included in the refine-
ment in isotropic approximation.
1

TABLE 8 Crystal Data, Data Collection, and Structure Refinement Parameters for 9 and Some Representatives of 14 and 15
Compound
9
14c(A)
14c(B)
15c(B)
15d(A)
15h(B)
Formula
Molecular weight
C17H32N2O4P2S2
454.51
C12H14NOPS
251.27
C12H14NOPS
251.27
C6H10NOPS
175.18
C11H12NOPS
237.25
C7H12NOPS
189.21
Crystal system, Space group
Monoclinic, P 21/c
Monoclinic, C 2/c
Triclinic, P1
10.6650 (4)
10.9258 (4)
11.5450 (5)
72.467 (1)
71.922 (1)
86.670 (1)
1218.52 (8)
4
Monoclinic, P 21/c
Triclinic, P1
10.312 (5)
10.996 (5)
11.523 (5)
65.13 (3)
89.34 (4)
79.30 (4)
1161 (1)
4
1.357
3.88
Siemens P3/C
298 (2)
Orthorhombic, Pbca
˚
a, A
11.478 (4)
17.654 (4)
12.634 (4)
19.072 (4)
12.890 (3)
10.796 (2)
9.113 (6)
6.073 (5)
15.077 (9)
12.4500 (9)
11.3047 (8)
13.1782 (10)
˚
b, A
˚
c, A
α (◦)
β (◦)
95.78 (3)
98.99 (3)
98.62 (5)
γ (◦)
3
˚
V, A
2547 (1)
4
1.185
2621.4 (9)
8
1.273
3.48
Siemens P3/C
153 (2)
825 (1)
4
1.410
1854.7 (2)
8
1.355
Z
d (calc.), g cm−3
µ (Mo Kα), cm−1
Diffractometer
1.370
3.75
Smart 1000 CCD
110 (2)
3.56
Siemens P3/C
298 (2)
5.19
Siemens P3/C
298 (2)
4.67
Smart 1000 CCD
100 (2)
Temperature, (K)
2θmax(◦)
50
50
60
64
50
60
No. collected refl., no. unique refl.
(Rint)
R1 (on F for refl. with I > 2σ(I )
4684, 4454
(0.0318)
0.0714
2068, 1996
(0.0275)
0.037
12751, 6760
(0.0128)
3135, 2977
(0.0403)
0.0429
4371,4123
(0.0582)
0.0425
13466, 2666
(0.0333)
0.0496
0.0321
(for 3537 refl.)
(for 1363 refl.)
(for 6173 refl.)
(for 1756 refl.)
(for 3754 refl.)
(for 2184 refl.)
2
wR 2 (on F for all refl.)
0.1849
0.0920
0.0962
0.0950
0.1124
0.1252
(for 4454 refl.)
1.048
(for 1996 refl.)
0.931
(for 6760 refl.)
1.031
(for 2977 refl.)
0.850
(for 4123 refl.)
1.003
(for 2666 refl.)
1.147
Goodness of fit on F 2

18 Odinets et al.
1.57 (d, 2 JPH 17.6 Hz, C(CN)CH3, 6H), 1.62–1.90 (m,
C(CN)CH2, 4H), 2.0–2.13 (m, CH2CH2CH2, 2H), 4.14–
4.31 (m, OCH2, 8H).
addition. The reaction mixture was stirred for 2
hours at 20◦C, a further 15 mmol of the correspond-
ing dihaloalkane was added, and stirring was con-
tinued for 1 hour. The reaction mixture was concen-
trated in vacuo, taken up in benzene (15 mL), and
diluted with water (10 mL). The organic layer was
separated, and the aqueous one was extracted with
benzene. The combined organic fractions were dried
(Na2SO4) and concentrated in vacuo. The residue
was purified by distillation or column chromato-
graphy.
The reaction of methylated 4a with Br(CH2)3Br
was carried out in the same manner, except that
25 mL of acetonitrile was used in the step of the reac-
tion with Br(CH2)3Br; the residue obtained after the
workup of the reaction mixture comprised (accord-
ing to 31P NMR spectroscopy) the target 7a (65%); 9
(20%), and the C-methylation product 4a (15%). The
residue was distilled in vacuo, the fraction with b.p.
150– 165◦C (1 mm Hg) being collected and compris-
ing the target 7a (86%); 15i (8%) and the C- methyla-
tion product 4a (6%). The fraction was used to pro-
duce 2-oxo-1,2-thiaphosphinane 15i without further
purification.
Interaction of the Methylated 4a with
Br(CH2 )3 Br
The methylation of 4a (14 mmol) was performed
according to the aforementioned step a to give the
intermediate product in quantitative yield with
1
2-Diphenylthiophosphinyl-5-iodopentanonitrile
10a
96% purity (according to H NMR spectroscopy).
For the physicochemical and spectral parameters
of the methylated 4a see Ref. [22]. The substance
was used for the subsequent stage without further
purification.
The reaction of the latter compound with
Br(CH2)3Br (18.8 mmol) was carried out according
to step b, using the standard workup of the reac-
tion mixture. After concentration, hexane was added
to the residue, and this was allowed to stand for
3 days at room temperature. The solid 9 (2.08 g,
64%; meso:d,l = 1:1) that precipitated was filtered
off.
On attempted isolation of the isomers by column
chromatography (100:1 to 100:13 hexane-acetone
elution), two main fractions were obtained, the first
(100:11 hexane-acetone) representing an oil (meso:
d,l = 3:7) and the second (100:12 hexane-acetone)
being a solid with m.p. 94–95◦C (meso:d,l = 7:3).
After recrystallization of the second fraction from
hexane, the meso form was obtained in the pure
state, (m.p. 93◦C).
The mixture of 5-chloro-2-diphenylthiophosphinyl-
pentanonitrile 5f (0.15 g, 0.45 mmol) and sodium io-
dide (81.36 mg, 0.54 mmol) in absolute acetonitrile
was heated under reflux for 6 hours. After having
been allowed to cool, the reaction mixture was con-
centrated, the residue was taken up in benzene, and
sodium chloride was filtered off. The filtrate was con-
centrated to give the target compound 10a (0.18 g,
94% purity according to 1H NMR spectroscopy). 31
P
NMR (CDCl3) δ 45.69. 1H NMR (CDCl3) δ 1.85–1.87,
1.94–1.96 (two m, 1H + 1H, CHCH2), 2.11–2.17 (m,
CH2CH2I, 2H), 3.11–3.17 (m, 3 JHH 3 JHH 8.0, 2 JH
H
B
C
D
A
14 Hz,CH2I, 2H, AB-system), 3.54–3.63 (m, CH, 1H),
7.52–7.88 (m, C6H5, 10H).
In the same manner from 5-chloro-2-diphenyl-
thiophosphinyl-2-methylpentanonitrile 7g (0.15 g,
0.43 mmol) and sodium iodide (77.5 mg, 0.52 mmol),
11a (0.17 g) was obtained (the reaction mix-
ture comprised about 20% 7g according to 31P
NMR spectroscopy). 31P NMR (CDCl3) δ 55.09.1H
Anal. found (%): C, 44.93; H, 6.91; N, 6.05;
Calcd. for C17H32N2O4P2S2 (%): C, 44.93; H, 7.05;
N, 6.17.
3
NMR (CDCl3) δ 1.58 (d, JPH 16.4 Hz, CH3C(CN),
3H), 1.82–1.90, 1.98–2.04, 2.09–2.14 (three m,
3
CH2CH2CH2I, 1H + 1H + 2H), 3.10 (t, JHH 8.0
Compound 9 (meso): 31P NMR (CDCl3) δ 92.3. 1H
Hz, 2H, CH2I), 7.52–7.58, 8.19–8.27 (two m, C6H5,
NMR (CDCl3) δ 1.35 (t, 3 JHH 7.2 Hz, CH3CH2O, 12H),
10H).
2
1.55 (d, JPH 17.6 Hz, C(CN)CH3, 6H), 1.62–1.90
(m, C(CN)CH2, 4H), 2.0–2.13 (m, CH2CH2CH2, 2H),
4.14–4.31 (m, OCH2, 8H). 13C NMR (CDCl3) δ 15.94
and 16.05 (CH3CH2O), 19.54 (C(CN)CH3), 20.44
31P NMR Study of the Intramolecular 10a and
11a S-Alkylation
3
(t, CH2CH2CH2, JPC 9.0 Hz), 34.0 (CH2CH2CH2),
1
41.18 (d, JPC 114.6 Hz, P–C), 64.41–64.30 (two
A solution of 15 mg of the compound 10a, 11a
in absolute acetonitrile was placed in a 5 mm
NMR ampule, which was sealed and stored at
20◦C with the 31P NMR spectra being recorded
weekly.
2
2
d, JPC 7.5 and 7.8 Hz, OCH2), 119.24 (d, JPC
7.1 Hz, CN).
1
Compound 9 (d,l): 31P NMR (CDCl3) δ 92.1. H
NMR (CDCl3) δ 1.36 (t, 3 JHH 7.2 Hz, CH3CH2O, 12H),

TABLE 9 Methods of purification and isolation of cis- and trans-diastereomers 14 and 15
b.p. (1 mm Hg) (I)
Yield (%)a
According to the
Cyclization
or the reflux
Methods of Purification and Isolation
Reaction Mixture
Compound
14ab
Method
duration (h) (II)
of Diastereomers
NMR 31
40
P
After Purification
I
II
I
150–170
18
Column chromatography (C6H14:Me2CO = 10:4), A:B
(60:40)
—
30
54
14b
Column chromatography (petrol. ether:Me2 CO = 10:4),
B= isomer, (petrol. ether:Me2CO = 2:1), A:B (94:6)
Column chromatography (C7H16:Me2CO = 10:4), B-isomer,
(C7H16:Me2CO = 2:1), A:B (75:15)
61
14c
170–195
95
crystallization of A and B isomer mixture (Et2O), A-isomer
Column chromatography (petrol. ether:Me2CO = 10:4), B-
isomer, (petrol. ether:Me2CO = 2:1), A:B (75:15),
precipitation Et2O - A-isomer
14c
15a
II
I
2
Quantitative
75
57
51
140–200
Precipitation Et2O-A:B (43:57), crystallization from C6H6-B-
isomer; mother liquor crystallization (Et2O), A and B
isomer mixture (1:1)
15b
15b
15c
I
II
I
190–210
32
Column chromatography (petrol. ether:Me2CO = 10:4),
55
32
30
21b
17
crystallization from C6H6, B-isomer)
Column chromatography (C6H14:Me2CO = 10:4), A:B
(63:37), crystallization from C6H14, A:B (47:53)
Crystallization from C6H6 A-isomer, mother liquor
crystallization (C7H16), B-isomer
210–220
18
15c
15d
15d
15e
II
I
II
II
15
202–210
22
Reaction mixture crystallization from C7H16 - A:B (74:26)
Column chromatography (C6H14:Me2CO = 10:4) - A-isomer
Column chromatography (C6H14:Me2CO = 10:4) - A-isomer
Column chromatography (petrol. ether:Me2CO = 10:1) - A:B
(40:60), crystallization (C6H6: Et2)-B-isomer
53
44
79
29
25
21
34
10
40
15f
I
193–210
Column chromatography (C6H14:Me2CO = 10:4) - A:B
(36:54); crystallization (C6H6: C2H14) - A:B (84:16)
Column chromatography (petrol. ether:Me2CO = 10:4) - A-isomer
Column chromatography (C6H14:Me2CO = 10:4) - A:B
(36:54); crystallization (C6H6: Et2O) - A:B (84:16)
Column chromatography (petrol. ether:Me2CO = 10:1) - A:B
(45:55), repeated column chromatography (petrol. ether:
Me2CO = 10:1) - A:B (73:27), 2:1 - A-isomer
Precipitation by Et2O - A:B (32:68), crystallization from
Et2O - B-isomer
19
6
15f
15g
II
I
16
180–190
Quantitative
15
24
6h
15h
II
25
64
22
15i
II
100
75
45
aBased on both diastereomers.
bThe compound decomposes during chromatographical purification yielding monobasic phosphonic acid EtO(HO)P(O)C(Me)(CN)CH2CH2SH (yield 5% after purification). 31P NMR (δ ppm,
3
3
DMSO-d6) 17.2. 1H NMR (δ ppm, J (Hz), DMSO-d6): 1.23 t (3H, CH3CH2, JHH 7.2), 1.43 d (3H, CH3C(CN), JPH 14.4), 1.86–1.95, 2.06–2.15 two m (1H+1H, CH2CH2SH), 2.59–2.69 m
(2H, CH2CH2SH), 4.02–4.11 m (2H, OCH2).

20 Odinets et al.
hours. The solid that precipitated by then ham-
pered the ability of the reaction mixture to boil uni-
formly. Thus, it was filtered, and heating was con-
tinued for 10 hours. After the standard work-up
(see method II) the organic fraction (0.3 g) con-
3-Cyano-2-oxo-1,2-thiaphosphacyclanes and
3-Alkyl-3-cyano-2-oxo-1,2-thiaphosphacyclanes
14, and 15.
Method I: The Intramolecular Cyclization of ω-
Chloro-2-thiophosphorylalkanonitriles (General Pro-
cedure). ω-Chloro-2-thiophosphorylalkanonitriles
5–7 produced according to the aforementioned
procedure as crude products without further pu-
rification [34] were distilled in vacuo. After low
boiling alkyl halide (R3Hlg) had been removed, the
fraction was collected, boiling, in the ∼160–210◦C
(1 mm Hg) range. The mixture of 3-cyano-2-oxo-
1,2-thiaphosphacyclanes 14 and 15 diastereomers
obtained was further purified and resolved by
column chromatography, fractional crystallization,
or by the combination of the previously mentioned
methods (Table 9).
tained no phosphorus compounds (according to 31
P
NMR). The solid obtained (2.5 g) representing a mix-
ture of the sodium salt 16 and inorganic sodium
salts was washed with CH3CN (25 mL) and CH2Cl2
(2×25 mL), and the extract was dried in vacuo. 31P
NMR δ 47.89 (DMSO-d6), 51.36 (Py). IR and 13C and
1H NMR spectroscopy data of the compound 16,
confirming the heterocycle formation, are shown in
Tables 5 and 6. All attempts to isolate the correspond-
ing acid by acidification, followed by extraction of
the organic phase, resulted in the destruction of the
ring compound.
In the same manner, the sodium salt of 3-
cyano-1,2-thiaphosphinanic acid 17 (2.2 g) was ob-
tained from 5-chloro-2-diethylthiophosphorylpenta-
nonitrile 5a (2.0 g, 7.42 mmol) and sodium iodide
(2.36 g, 15.7 mmol). 31P NMR δ 25.43 (CH3CN), 25.75
(CH2Cl2).
Method II: The Intramolecular Cyclization of
ω-Iodo-2-thiophosphorylalkanonitriles (General Pro-
cedure). The mixture of ω-chloro-2-thiophosphory-
lalkanonitrile 5–7 (3.0 mmol) and sodium iodide (6.0
mmol) in absolute acetonitrile (20 mL) was heated
under reflux for 2–40 hours (the course of the cycliza-
tion being monitored by the 31P NMR spectroscopy).
After cooling, the reaction mixture was filtered. The
filtrate was concentrated in vacuo, and the residue
was taken up in CH2Cl2 (15 mL) and filtered again.
After concentration, the residue was purified as de-
scribed in Table 9.
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