N-alkylation of amidothiophosphoryl compounds under phase-transfer catalysis conditions. Synthesis and properties of 1,3,2-thiazaphosphacyclanes

Article abstract of DOI:10.1007/s11172-009-0032-4

N (ω-Haloalkyl)amidothiophosphates, N (ω-Haloalkyl) amidothiophosphonates, and N- (ω-Haloalkyl)amidothiophosphinates (Hal = Cl or Br) were obtained in high yields by alkylation of phosphorus(V) acid thioamides with 6h,ω-dihaloalkanes under phase-transfer

Full text of DOI:10.1007/s11172-009-0032-4

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 216—222, January, 2009
216
NꢀAlkylation of amidothiophosphoryl compounds
under phaseꢀtransfer catalysis conditions.
Synthesis and properties of 1,3,2ꢀthiazaphosphacyclanes*
O. I. Artyushin, E. V. Sharova, P. V. Petrovskii, and I. L. Odinets
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Eꢀmail: shipov@ineos.ac.ru
Nꢀ(ωꢀHaloalkyl)amidothiophosphates, Nꢀ(ωꢀhaloalkyl)amidothiophosphonates, and
Nꢀ(ωꢀhaloalkyl)amidothiophosphinates (Hal = Cl or Br) were obtained in high yields by
alkylation of phosphorus(V) acid thioamides with α,ωꢀdihaloalkanes under phaseꢀtransfer
catalysis (PTC) conditions or through the use of NaH as a base. Thermal rearrangement of
Nꢀ(3ꢀiodopropyl)ꢀ or Nꢀ(4ꢀiodobutyl)amidothiophosphate and Nꢀ(3ꢀiodopropyl)ꢀ or Nꢀ(4ꢀiodoꢀ
butyl)amidothiophosphonate obtained in situ by the Finkelstein reaction provides a convenient
route to 2ꢀoxoꢀ1,3,2ꢀthiazaphosphinanes and 2ꢀoxoꢀ1,3,2ꢀthiazaphosphepanes. Reactions
of Nꢀ(ωꢀhaloalkyl)amidothiophosphinates with NaClO4 in MeCN afforded the first example of
stable 1,3,2ꢀthiazaphosphacyclanium salts containing P—C bonds.
Key words: amidothiophosphates, amidothiophosphonates, amidothiophosphinates,
alkylation, phaseꢀtransfer catalysis, intramolecular cycloalkylation, 2ꢀoxoꢀ1,3,2ꢀthiazaphosꢀ
phinanes, 2ꢀoxoꢀ1,3,2ꢀthiazaphosphepanes, ring—chain halotropic isomerism.
The most convenient and versatile route to Nꢀ(ωꢀhaloꢀ
Fiveꢀ and sixꢀmembered 1,3,2ꢀthiazaphosphacyclanes
alkyl)ꢀsubstituted amidothiophosphoryl compounds
involves alkylation of the N atom in appropriate amides.
However, in contrast to amidophosphates,11 alkylation of
amidothiophosphates is known to occur at both the nitroꢀ
gen12 and sulfur atoms,13 depending on the reaction
conditions. Earlier,12,14 such reactions were carried out
in anhydrous solvents under an inert atmosphere in the
presence of ButOK, BunLi, NaH, or NaNH2 for deproꢀ
tonation of the amide N atom.
We discovered that thioamides of phosphorus(V) acids
containing a sufficiently acid NH proton (e.g., when a
phenyl group is attached to the amide N atom) can be
easily and selectively alkylated at the N atom with
were first synthesized in 1963 from phosphorus acid
(including thioic acids) dichlorides and amino thiols.1,2
However, because amino thiols are difficult to prepare
and are very unstable,3 thiazaphospholanes and especially
phosphinanes still remain not easily accessible comꢀ
pounds: the former are currently represented by several
decades and the latter, by several compounds only.1,4—8
At the same time, along with theoretical interest, such
cyclic systems with three adjacent dissimilar heteroatoms
can be of practical value in medicine and agriculture as
potential biologically active compounds.1,2
Earlier,9,10 we developed a general approach to 2ꢀoxoꢀ
1,2ꢀthiaꢀ and 2ꢀoxoꢀ1,2ꢀazaphosphacyclanes and
1,2ꢀthiaꢀ and 1,2ꢀazaphosphacyclanium salts. The
approach involves intramolecular alkylation of thiophosꢀ
phoryl or imidophosphoryl compounds, respectively, with
their own ωꢀhaloalkyl substituent. Nꢀ(ωꢀHaloalkyl)amides
of phosphorus acids are assumed to be appropriate starting
substrates for the synthesis of various 1,3,2ꢀthiazaꢀphosphaꢀ
cyclanes. An additional argument for this assumption
has been found in the synthesis of 2ꢀoxoꢀ1,3,2ꢀthiazaꢀ
phosphinanes by thermal cyclization (120—140 °C) of
Nꢀ(3ꢀchloropropyl)amidothiophosphates.6
Scheme 1
i. DMSO, MeCN/solid KOH
R
1 = R2 = Ph (1a), EtO (1b), PrnO (1c); R1 = Me, R2 = EtO (1d);
* Dedicated to Academician A. I. Konovalov on his 75th birthꢀ
day.
Hal = Cl, Br; n = 2—4
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 214—220, January, 2009.
1066ꢀ5285/09/5801ꢀ0216 © 2009 Springer Science+Business Media, Inc.

Synthesis of 1,3,2ꢀthiazaphosphacyclanes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
217
Table 1. Yields and elemental analysis data for the compounds R1R2P(S)NR3R4 2a—l and 3a,b
Comꢀ
pound
R1
R2
R3
R4
Yield (%)а
Found
Calculated
Molecular
formula
(%)
P
C
H
N
S
Hal
2a
2b
2c
2d
2e
2f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bun
Me
Ph
(CH2)2Cl
(CH2)3Cl
(CH2)4Cl
(CH2)3Cl
(CH2)4Br
(CH2)3Cl
(CH2)4Cl
(CH2)3Cl
(CH2)4Br
(CH2)4Br
(CH2)5Cl
(CH2)4I
52
(45)
82
64.23 4.93
64.60 5.15
—
7.59
8.33
7.80
8.03
7.45
7.74
9.99
9.63
8.17
8.14
—
9.12
9.53
9.08
9.19
—
C20H19ClNPS
C21H21ClNPS
C22H23CLNPS
3.09
3.63
—
—
—
—
—
(70)b
90
Ph
Ph
65.92 5.64
66.06 5.81
48.09 6.36
48.52 6.58
44.46 6.19
44.22 6.10
50.90 7.19
51.50 7.20
—
(85)c
72
(65)
70
(62)
75
(66)
78
(67)
75
(62)
78
(65)
74
(62)
82
EtO
EtO
PrO
PrO
Me
Me
Me
Me
Ph
EtO
EtO
PrO
PrO
EtO
EtO
EtO
BuO
Ph
—
—
—
—
—
—
—
—
—
—
C13H21ClNO2PS
C14H23BrNO2PS
C15H25ClNO2PS
C16H27ClNO2PS
C12H19ClNOPS
C13H21BrNOPS
C11H25BrNOPS
C11H25ClNOPS
C22H23INPS
9.15 9.77
8.85 9.17
2g
2h
2i
8.93 9.92
8.81 9.74
49.24 6.43
49.40 6.56
44.74 6.20
44.58 6.04
—
9.94 11.51
10.62 0.99
8.90
8.84
9.68 10.00
9.38 9.71
10.79
10.84
6.13
6.30
12.84 13.39
13.16 13.62
—
—
—
—
—
2j
2k
2l
—
—
—
—
—
–
(70)
100
(95)d
53.40 4.52
53.77 4.73
—
—
25.60
25.82
—
3a
3b
Me
Me
EtO
BuO
Bun CH2CH=CH2 72
(63)
Me CH2CH=CH2 71
(64)
С10H22NOPS
49.01 9.15
48.85 9.11
13.82
14.00
—
—
C9H20NOPS
a According to 31P NMR data for the reaction mixtures; the yields of the isolated products are given in parentheses.
b M.p. 117—118 °C (heptane).
c M.p. 76—77 °C (for the product purified by column chromatography).
d Compound 2l was obtained from 2c by the Finkelstein reaction.
α,ωꢀdihaloalkanes under PTC conditions (MeCN +
DMSO/solid KOH) to give Nꢀ(ωꢀhaloalkyl)amidothioꢀ
phosphates, Nꢀ(ωꢀhaloalkyl)amidothiophosphonates, or
Nꢀ(ωꢀhaloalkyl)amidothiophosphinates 2 in high yields,
the particular products being dependent on the starting
reagents (Scheme 1).
tal analysis data, and spectroscopic characteristics of
compounds 2a—i are presented in Tables 1 and 2.
Scheme 2
The use of DMSO as a cosolvent is crucial for successꢀ
ful synthesis: in the absence of DMSO, the reactions do
not occur at all, while in DMSO alone, many byꢀproducts
are formed. We found experimentally that the optimum
MeCN : DMSO ratio is 5 : 1 and that the roomꢀtemperaꢀ
ture reaction time should be no longer than 1 h to prevent
intense hydrolysis. At elevated temperatures, the reaction
produces more byꢀproducts, while a decrease in the
temperature substantially inhibits the targeted alkylation.
The use of symmetrical α,ωꢀdihaloalkanes is preferred
because alkylation with 1ꢀbromoꢀ3ꢀchloropropane or
1ꢀbromoꢀ4ꢀchlorobutane gives both ωꢀchloroalkyl and
ωꢀbromoalkyl derivatives (~5—7%). The yields, elemenꢀ
R1 = Et, R2 = Bun (1e); R1 = Bun, R2 = Me (1f);
Hal = Cl, Br; n = 4, 5

218
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Artyushin et al.
1
Table 2. Selected parameters of the 31P and H NMR spectra (CDCl3) of the compounds R1R2P(S)N(R3)(CH2)nHal (2a—m)
Comꢀ
pound
R1
R2
R3
n
Hal
δ
δΗ (J/Hz)
P
CH2Hal, t
NCH2
NCH2CH2CH2, m
CH3P
2a
2b
2c*
2d
2e
2f*
2g
2h
2i
Ph
Ph
Ph
EtO
EtO
PrO
PrO
Me
Me
M
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
nBu
Me
Ph
Ph
2
3
4
3
4
3
4
3
4
4
5
4
3
Cl
Cl
Cl
Cl
Br
Cl
Cl
Cl
Br
Br
Cl
I
66.9
67.4
67.5
72.4
72.3
73.3
72.6
85.9
85.4
87.8
88.4
67.8
67.3
3.57(8.6)
3.42(6.7)
3.18(6.0)
3.53(6.4)
3.36(6.8)
3.27(6.8)
3.49(6.4)
3.56(7.2)
3.37(6.8)
3.44(6.8)
3.52(6.0)
2.49(6.8)
2.98(6.7)
3.65—3.70
3.45—3.55
3.20—3.30
3.72—3.80
3.60—3.67
3.79—3.87
3.61—3.70
3.70—4.00
3.55—3.88
3.00—3. 25
3.07—3.26
3.25—3.35
3.37—3.43
—
—
—
—
—
—
—
—
1.90—2.00
1.48—1.53
1.85—1.93
1.60—1.85
1.75—1.85
1.55—1.90
1.90—2.00
1.49—1.88
1.24—1.67
1.31—1.82
1.27—1.47
1.95—2.05
EtO
EtO
PrO
PrO
EtO
EtO
EtO
BuO
Ph
1.69(14.8)
1.61(14.8)
1.75(14.8)
1.73(13.5)
—
2j
2k
2l*
2m
Me
Ph
Ph
Ph
I
—
* The 31P and 1H NMR spectra were recorded in C6D6.
Replacement of the phenyl substituent at the N atom
by an electronꢀdonating alkyl group increases the elecꢀ
tron density on it and, correspondingly, makes the NH
proton less acid. That is why highꢀyielding alkylation
of compounds 1e,f with α,ωꢀdihaloalkanes under the
aforementioned PTC conditions with DMSO alone as a
solvent is impossible. To obtain products 2j,k, it is more
expedient to deprotonate compounds 1e,f with NaH
in DMF and then alkylate the resulting anion with
α,ωꢀdihaloalkanes (Scheme 2).
an intermediate lithium or sodium salt of the amide
dehydrobrominates, as a strong base, 1,3ꢀdibromopropane
or 1ꢀbromoꢀ2ꢀchloroethane more rapidly than the alkylaꢀ
tion occurs (Scheme 3).
Thus, the aforementioned phaseꢀtransfer catalysis
conditions provide a convenient alternative route to
Nꢀ(ωꢀhaloalkyl)ꢀNꢀphenyl derivatives of amidothiophosꢀ
phoryl compounds, while their Nꢀalkyl analogs become
accessible through the use of NaH as a deprotonating
agent.
Note that this method failed in the synthesis of
Nꢀ(2ꢀchloroethyl) and Nꢀ(3ꢀhalopropyl) derivatives
(n = 2, 3). For instance, the starting amidothiophosꢀ
phonate was recovered intact from its reaction mixture
with 1ꢀbromoꢀ2ꢀchloroethane, while alkylation with
1ꢀbromoꢀ3ꢀchloropropane or 1,3ꢀdibromopropane gave
NꢀalkylꢀNꢀallylꢀPꢀmethylamidothiophosphonates 3a,b in
high yields. It should be emphasized that the correspondꢀ
ing unsaturated products were not detected in the synꢀ
thesis of homologs 2j,k (n = 4, 5) under similar condiꢀ
tions (see Experimental). NꢀAlkylꢀNꢀ(3ꢀbromopropyl)ꢀ
Pꢀmethylamidothiophosphonates (R2 = Me and Bun)
were not obtained with BunLi as a base. In other words,
The products obtained are crystalline solids (2b,c) or
viscous oils (2a,d—k, 3a,b). They are stable below 100 °C
and undergo no transformations in boiling MeCN over
40—50 h. Insofar as the intramolecular alkylation rate
for ωꢀhaloalkylthiophosphoryl compounds is known to
increase in the order Cl < Br < I (see Ref. 6), a substantial
decrease in the cyclization temperature could be expected
for Nꢀ(iodoalkyl)amidothiophosphoryl compounds. Indeed,
when the Cl or Br atom in compounds 2d,f,h—k is
replaced by an I atom in the Finkelstein reaction with
NaI in boiling MeCN, iodides 4a—f undergo intraꢀ
molecular Sꢀalkylation followed by dealkylation of the
alkoxy group at the P atom, which results in the formation
Scheme 3
i. MH/DMF (M = Li, Na); Hal(CH ) Br, Hal = Cl, n = 2; Hal = Br, n = 3; ii. NaH/DMF; Hal(CH2)3Br, Hal = Cl, Br
2 n

Synthesis of 1,3,2ꢀthiazaphosphacyclanes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
219
Scheme 4
Comꢀ
pound 5
a
b
c
R1
R3
n
Comꢀ
pound 5
d
e
f
R1
R3
n
R1 = Et, PrnO, Me; R2 = EtO, PrnO, BunO;
3 = Me, Bun, Ph; R4 = Et, Prn, Bun;
EtO
Prn
Me
Ph
Ph
Ph
3
3
3
Me
Me
Me
Ph
Bun
Me
4
4
5
R
Hal = Cl, Br; n = 3—5
of 2ꢀoxoꢀ1,3,2ꢀthiazaphosphacyclanes 5a—f already
during the exchange reaction (Scheme 4).
higher that alkylation of amidothiophosphoryl compounds
under PTC conditions is impossible. At the same time,
the S atom becomes more nucleophilic, which facilitates
cyclization of Nꢀ(ωꢀhaloalkyl)amidothiophosphonates.
Indeed, the complete conversion of Nꢀphenyl derivative
2i into sevenꢀmembered heterocycle 5d was achieved via
reflux in MeCN for 45 h, while structurally similar
compound 2j containing the nꢀbutyl group at the N atom
was converted into product 5e under the same conditions
only in 15 h.
The presence of an alkyl group at the N atom also
improves the complexing properties of 2ꢀoxoꢀ1,3,2ꢀthiaꢀ
zaphosphacyclanes 5. A complex of 5e with NaI is very
stable and can be isolated by column chromatography in
the individual state. Earlier,9 the same has been noted for
structurally similar 2ꢀethylꢀ2ꢀoxoꢀ1,2λ5ꢀthiaphospholane
and 2ꢀethylꢀ2ꢀoxoꢀ1,2λ5ꢀthiaphosphinane.
Heterocyclic compounds 5 are mostly viscous oils.
Their yields, elemental analysis data, and spectroscopic
characteristics are given in Tables 3 and 4. However, not
all 2ꢀoxoꢀ1,3,2ꢀthiazaphosphacyclanes 5a—f were isolated
in the individual state because they are liable to hydrolyꢀ
sis.4—6 For instance, the yield of compound 5f (δP 51.5)
with an eightꢀmembered heterocycle is ~40% (31P NMR
data); however, it decomposes completely during attempted
purification by column chromatography. Obviously, the
decomposition involves hydrolysis with ring opening and
formation of the corresponding phosphorus acids, which
are virtually immobile on silica gel. For the same reason,
compounds 5a—e are isolated in yields differing noticeꢀ
ably (sometimes twice as much) from those calculated
from the spectra of the reaction mixtures.
As noted above, the basicity of the N atom bound to
an alkyl substituent (instead of the phenyl one) is so much
In contrast to Nꢀ(ωꢀiodoalkyl)amidothiophosphates
and Nꢀ(ωꢀiodoalkyl)amidothiophosphonates, which
Table 3. Yields and elemental analysis data for 2ꢀoxoꢀ1,3,2ꢀthiazaphosphacyclanes 5a—e and 1,3,2ꢀthiazaꢀ
phosphacyclanium salts 6b—d
Comꢀ
pound
M.p./°С
Yield (%)*
Found
Calculated
Molecular
formula
(%)
C
H
P
S
5a
5b
5c
5d
5e
6b
6c
6d
Oil
Oil
90(50)
95(55)
95(60)
85(45)
83(42)
45
51.26
51.35
53.07
53.12
53.08
52.85
54.18
54.76
41.45
41.77
54.53
55.11
56.03
56.16
—
6.19
6.27
6.74
6.69
6.13
6.21
6.63
6.68
7.37
7.79
4.32
4.39
4.77
4.78
3.21
3.02
12.10
12.04
11.09
11.41
13.32
13.63
11.90
12.84
—
12.42
12.46
11.84
11.82
14.11
14.11
13.37
13.29
11.81
11.97
6.96
C11H16NO2PS
C12H18NO2PS
C10H14NOPS
Oil
104—105
Oil
C11H16NOPS
C9H20NOPS·1/4NaI
C20H19ClNO4PS
C21H21ClNO4PS
C22H23ClNO4PS
209—210
184—186
172—173
3.17
3.21
3.07
3.14
—
7.11
6.73
6.89
—
36
42
* According to 31P NMR data for the reaction mixtures; the yields of the isolated products are given in parentheses.

220
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Artyushin et al.
Table 4. Spectroscopic data for 2ꢀoxoꢀ1,3,2ꢀthiazaphosphacyclanes 5a—e and 1,3,2ꢀthiazaphosphacyclanium salts 6a—d
Comꢀ R1
pound
R2
n
X
δ
δ
H (J/Hz)
IR
P
vP = 0/cm–1
SCH2,
m
NCH2,
m
SCH2CH2, NCH2CH2, CH3P,
m
m
—
d
5a
EtO
Ph
3
—
22.8
3.66—3.77,
3.87—3.95
3.53—3.62
3.51—3.63,
3.87—4.09
3.45—3.55,
4.00—4.12
2.57—2.68
3.32—3.44
3.65—3.75,
3.95—4.05
4.40—4.47
3.95—4.00
4.06—4.12
2.93—3.04,
3.09—3.17
2.62—2.71
2.90—3.01,
3.15—3.27
2.98—3.07
2.0—2.1
1.78—1.65
1.02—1.10
2.02—2.14
—
1270
1270
5b
5c
PrnO Ph
3
3
—
—
21.3
42.6
—
—
—
Me
Me
Me
Ph
1.80
(14.4)
1.63
(14.8)
1.67
(14.8)
—
1205
1225
1205
1220
1205
1215
—
5d
5e
6a
Ph
4
4
3
—
—
I–
49.6
51.5
57.6
2.00—2.18
2.00—2.10
1.98—2.05
1.70—1.86
1.56—1.86
2.40—2.48
Bun
Ph
2.82—3.00,
3.17—3.26
3.35—3.50
–
6b
6c
6d
Ph
Ph
Ph
2
3
4
ClO4– 72.9
ClO4– 57.5
3.93—3.98
3.55—4.00
3.43—3.67
—
2.38—2.40
—
—
—
—
—
—
—
—
—
ClO4
—
1.14—1.18
1.23—1.24
undergo in situ transformations into phosphinanes 5a—c
and phosphepanes 5d—e via intramolecular Sꢀalkylation
followed by dealkylation of the alkoxy group at the P atom,
Nꢀ(ωꢀiodoalkyl)amidothiophosphinates are less prone
to this cyclization. For instance, stable Nꢀ(4ꢀiodobutyl)ꢀ
Nꢀphenyldiphenylphosphinamidothioate (2l) remains
unchanged during prolonged reflux in MeCN and is
recovered in the individual state. The corresponding
2ꢀiodoethyl derivative is unstable and decomposes when
synthesized from compound 2a by the Finkelstein reaction.
In contrast, Nꢀ(3ꢀiodopropyl)ꢀNꢀphenyldiphenylphosꢀ
phinamidothioate (2m) readily undergoes intramolecular
cyclization into 2,2ꢀdiphenylꢀ1,3,2ꢀthiazaphosphinanium
iodide 6a (Scheme 5). Note that only 2,2ꢀdichloroꢀ1,3,2ꢀ
thiazaphospholanium salts with the poorly nucleophilic
For instance, the content of more polar cyclic form 6a
increases in polar solvents but decreases at elevated temꢀ
peratures (see Table 5); this fully agrees with the pattern
observed for thiaphosphacyclanium salts.15 The following
features of salt 6a are worth noting: very slow establishꢀ
ment of equilibrium (this takes several hours at 60 °C,
several days at 20 °C, and several weeks at –20 °C) and
the aforesaid impossibility of separating isomers 2m
and 6a. This makes it difficult to perform any quantitative
experiments and calculate the thermodynamic parameters
of the process.
Replacement of the iodide anion in compound 6a
by a weakly nucleophilic perchlorate anion shifts the
equilibrium to the stable cyclic salt 6c, which crystallizes
from the reaction mixture. At the same time, when the
–
–
anions AlCl4 and SbCl4 have been obtained hitherto
from 2ꢀchloroꢀ1,3,2ꢀthiazaphospholanes and appropriate
Lewis acids (see Refs 7, 8).
Table 5. Content of form 6a (C6a) in the equilibrium 6a
2m
in different solvents at different temperatures
Iodide 2m and its cyclic isomer 6a can be easily distinꢀ
guished by spectroscopic techniques. Their characterisꢀ
tics are given in Tables 2 (2m) and 4 (6a). Unfortunately,
we failed to isolate individual isomers 2m and 6a from
their mixture by standard methods. Like other equilibria,
Solvent
C6a (%)
20 °С 30 °С 40 °С 50 °С 60 °С 70 °С 80 °С
СН2Сl2 9.4
CHCl3 14.0 13.9 13.7 11.4
MeCN 17.2 16.7 16.6 15.0 14.8 13.4 13.1
9.1
8.7
—
—
—
—
—
—
—
the equilibrium 2m
6a depends on many factors (solꢀ
vent polarity, temperature, nature of the counterion, etc.).
Scheme 5
6a

Synthesis of 1,3,2ꢀthiazaphosphacyclanes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
221
perchlorate anion in salt 6c is replaced by I– under the
action of KI in MeCN (in which KClO4 is insoluble), the
Therefore, the hydrolysis results in cleavage of both
the P—S and P—N bonds, the ring opening being comꢀ
pleted within 15—20 min. No intermediate products are
detected even at low conversion degrees.
resulting mixture of isomers 6a
2m is the same as in
the synthesis of salt 6a from chloride 2b. It takes several
weeks for equilibrium to be established (Scheme 6).
Experimental
Scheme 6
The course of the reactions was monitored by 31P NMR
spectroscopy on Bruker CXPꢀ200 and Bruker WPꢀ200 instruꢀ
ments (81 MHz) with 85% H3PO4 as the external standard. The
4
1
31P, 13C, and H NMR spectra of individual compounds were
recorded on a Bruker AMXꢀ400 instrument (161.98 (31P),
100.1 (13C), and 400.13 MHz (1H)). The signals of the residual
protons of deuterated solvents served as the internal standards
(1H, 13C) and 85% H3PO4 served as the external standard (31P).
IR spectra were recorded on a URꢀ20 instrument in thin films
(NaCl) and in KBr pellets.
All compounds were purified by column chromatography
(unless otherwise specified) on silica gel (130—270 mesh,
Aldrich). The proportion of the column diameter to the column
length was 1 : 20. An acetone—hexane mixture was used as an
eluent with an increasing content of the former component from
1 : 100 to 1 : 10 (to 1 : 1 for compounds 5a—e). Solvents were
purified according to standard procedures.17 The starting
amidothiophosphoryl compounds (1a—d) were prepared as
described earlier.18
Clearly, we observed a new example of uncommon
ring—chain halotropic tautomerism in organophosphorus
chemistry.
Using the poorly nucleophilic perchlorate anion, we
easily obtained previously inaccessible 1,3,2ꢀthiazaphosꢀ
phacyclanium salts 6b—d directly from linear isomers
containing a terminal Cl atom (Scheme 7).
Scheme 7
Ethyl NꢀbutylꢀPꢀmethylphosphonamidothioate (1e) was
obtained from ethyl methylphosphonothiochloridate and
butylamine according to a known procedure.18 The yield was
88%, b.p. 90—92 °C (0.5 Torr), nD20 1.4909. 31P NMR (CDCl3),
δ: 82.0. 1H NMR (CDCl3), δ: 1.72 (d, 3 H, CH3P, 2JP,H = 14.8 Hz);
2.80 (br.s, 1 H, NH); 3.70—4.00 (m, 2 H, NCH2). Found (%):
C, 43.01; H, 9.27; P, 15.33; S, 16.85. C7H18NOPS. Calculated (%):
C, 43.06; H, 9.29; P, 15.86; S, 16.41.
Note that the cyclization rate in the synthesis of comꢀ
pounds 6b—d varies with the ring size. Thus, the formaꢀ
tion of the most thermodynamically stable fiveꢀmembered
ring (6b) is completed in 2 h. The cyclization into a sixꢀ
membered ring (6c) takes 35 h, while that resulting in a
sevenꢀmembered ring (6d) is completed only in 70 h at
80 °C. The yields, elemental analysis data, and specꢀ
troscopic characteristics of products 6b—d are given in
Tables 3 and 4. The spectroscopic characteristics of comꢀ
pounds 6a and 5a—c are closely related to those of strucꢀ
turally similar cyclic compounds.6,16
Hydrolysis of thiazaphospholanium perchlorate 6b
and thiazaphosphinanium perchlorate 6c gives diphenylꢀ
phosphinic acid as a sole phosphorusꢀcontaining product,
regardless of the ring size and the hydrolysis medium
(basic or acid) (Scheme 8).
Butyl N,Pꢀdimethylphosphonamidothioate (1f) was obtained
from butyl methylphosphonothiochloridate and methylꢀ
amine according to a known procedure.18 The yield was 85%,
b.p. 95—96 °C (0.5 Torr), nD 1.4942. 31P NMR (CDCl3), δ:
20
83.9. 1H NMR (CDCl33), δ: 1.67 (d, 3 H, CH3P, 2JP,H = 15.2 Hz);
2.60 (d, 3 H, NCH3, JP,H = 13.2 Hz); 2.70 (br.s, 1 H, NH).
Found (%): C, 39.39; H, 8.74; P, 16.94; S, 17.65. C6H16NOPS.
Calculated (%): C, 39.76; H, 8.90; P, 17.09; S, 17.69.
Nꢀ(ωꢀHaloalkyl)ꢀNꢀphenylamidothiophosphoryl compounds
(2a—i) (general procedure). Powdered KOH (0.01 mol) was
added to a stirred solution of Nꢀphenyl thioamide 1 (0.005 mol)
in a mixture of MeCN (5 mL) and DMSO (1 mL). Then an
appropriate α,ωꢀdihaloalkane (0.01 mol) was slowly added for
15—20 min. The reaction mixture was stirred at 20 °C for 1 h.
The acetonitrile was removed in vacuo and the residue was
diluted with benzene (20 mL) and water (15 mL). The resulting
immiscible layers were separated. Organic material from the
aqueous layer was extracted with benzene (10 mL). The comꢀ
bined benzene extracts were washed with water (10 mL), dried
over Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography.
Scheme 8
OꢀAlkyl NꢀalkylꢀNꢀ(ωꢀhaloalkyl)ꢀPꢀmethylphosphonamidoꢀ
thioates 2j,k (general procedure). Sodium hydride (0.01 mol) as
a 60% suspension (0.4 g) in mineral oil was added under argon
at 0 °C to a solution of an appropriate Nꢀalkylamidothioꢀ
phosphonate 1e,f (0.005 mol) in DMF (20 mL) freshly distilled
n = 2, 3

222
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Artyushin et al.
over CaH2. After hydrogen evolution ceased, the mixture
was stirred at 20 °C for 10 min. Then 1,4ꢀdibromobutane
or 1,5ꢀdichloropentane (0.01 mol) was added dropwise for
10—15 min. The reaction mixture was stirred at 20 °C for 4 h
and diluted with water (20 mL) and ether (20 mL). The resulting
immiscible layers were separated. Organic material from the
aqueous layer was extracted with ether (10 mL). The combined
ether extracts were washed with water (10 mL), dried over
Na2SO4, and concentrated in vacuo. The residue was purified by
column chromatography.
Ethyl NꢀallylꢀNꢀbutylꢀPꢀmethylphosphonamidothioate (3a)
was obtained as described for compounds 2j,k with 1,3ꢀdibromoꢀ
propane as an alkylating reagent. 31P NMR (CDCl3), δ: 87.8.
1H NMR (CDCl3), δ: 1.74 (d, 3 H, CH3P, 2J = 14.8 Hz);
3.67—3.80 (m, 2 H, NCH2—CH=CH2); 5.60—5.75 (m, 1 H,
NCH2—CH=CH2); 5.10—5.20 (m, 2 H, NCH2—CH=CH2).
Elemental analysis data are given in Table 1.
Butyl NꢀallylꢀN,Pꢀdimethylphosphonamidothioate (3b) was
obtained analogously. 31P NMR (CDCl3), δ: 87.9. 1H NMR
(CDCl3), δ: 1.75 (d, 3 H, CH3P, 2JP,H = 14.8 Hz); 2.64 (d, 3 H,
NCH3, 3JP,H = 11.2 Hz); 3.72—3.85 (m, 2 H, NCH2—CH=CH2);
5.65—5.75 (m, 1 H, NCH2—CH=CH2); 5.11—5.25 (m, 2 H,
NCH2—CH=CH2). Elemental analysis data are given in Table 1.
2ꢀOxoꢀ1,3,2ꢀthiazaphosphacyclanes 5a—e (general proceꢀ
dure). A solution of dry NaI (0.006 mol) in MeCN (10 mL) was
added to a solution of Nꢀ(ωꢀhaloalkyl)amidothiophosphoryl
compound 2d,f,h—k (0.005 mol) in MeCN (10 mL). The resultꢀ
ing mixture was refluxed for 15—45 h. The completion of the
rearrangement was checked by 31P NMR spectroscopy. On coolꢀ
ing to ambient temperature, the precipitate of NaCl or NaBr
was filtered off, the solvent was removed in vacuo, and the resiꢀ
due was purified by column chromatography.
31P NMR (CDCl3), δ: 29.7. 1H NMR (CDCl3), δ: 7.1 (br.s, 1 H,
OH); 7.32—7.36, 7.43—7.50, and 7.69—7.74 (all m, 10 H each,
C6H5P).
Similar results were obtained in acid hydrolysis using
20% HCl.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ32478).
References
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2ꢀMethylꢀ2ꢀoxoꢀ3ꢀphenylꢀ1,3,2ꢀthiazaphosphepane (5d).
1
13C NMR (CDCl3), δ: 18.8 (d, PCH3, JP,C = 100.0 Hz); 27.9
2
(s, SCH2CH2); 30.0 (d, SCH2, JP,C = 3.7 Hz); 31.1 (s,
2
NCH2CH2); 51.0 (d, NCH2, JP,C = 5.0 Hz).
11. B. A. Arbuzov, P. I. Alimov, M. A. Zvereva, Izv. Akad. Nauk
SSSR, Otd. Khim. Nauk, 1954, 6, 1042 [Bull. Acad. Sci.
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Petrovskii, K. A. Lyssenko, M. Yu. Antipin, T. A. Mastryukova,
M. I. Kabachnik, Zh. Obshch. Khim., 1998, 68, 1421 [Russ.
J. Gen. Chem. (Engl. Transl.), 1998, 68].
16. I. M. Aladzheva, O. V. Bykhovskaya, D. I. Lobanov, K. A.
Lyssenko, M. Yu. Antipin, T. A. Mastryukova, M. I. Kabachnik,
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3ꢀButylꢀ2ꢀmethylꢀ2ꢀoxoꢀ1,3,2ꢀthiazaphosphepane (5e).
1
13C NMR (CDCl3), δ: 19.3 (d, PCH3, JP,C = 100.0 Hz); 26.9
2
(s, SCH2CH2); 28.0 (d, SCH2, JP,C = 3.1 Hz); 31.5 (s,
2
NCH2CH2); 45.1 (d, NCH2, JP,C = 2.7 Hz); NHBun: 13.6
(s, NCH2CH2CH2CH3); 19.7 (s, NCH2CH2CH2CH3);
31.0 (s, NCH2CH2CH2CH3); 44.5 (d, NCH2CH2CH2CH3,
2JP,C = 5.0 Hz).
1,3,2ꢀThiazaphosphacyclanium perchlorates 6b—d (general
procedure). A solution of compound 2a—c (0.001 mol) in MeCN
(5 mL) was added to a solution of NaClO4 (0.002 mol) in
MeCN (5 mL). The reaction mixture was heated at 100 °C
in a sealed tube. The course of the reaction was monitored by
31P NMR spectroscopy. The precipitate of NaCl that formed
was filtered off and the solvent was removed in vacuo. The resiꢀ
due was diluted with CH2Cl2, the excess of NaClO4 was filtered
off, and the solvent was removed in vacuo. The crystalline prodꢀ
uct was washed with benzene and ether and dried in vacuo to a
constant weight.
Hydrolysis of 1,3,2ꢀthiazaphosphacyclanium salts 6b,c.
A solution of compound 6b or 6c (0.01 mol) in methanol
(10 mL) was added to a stirred solution of NaOH (0.01 mol) in
water (5 mL). After 15 min, the mixture was acidified with HCl
(pH ~1.0) and volatile products were removed in vacuo. The
residue was recrystallized three times from THF, washed with
ethanol, and dried in vacuo. The yield of diphenylphosphinic acid
was 0.003 mol (30%), m.p. 195 °C (cf. Ref. 19: m.p. 193—195 °C).
19. V. V. Kormachev, M. S. Fedoseev, Preparativnaya khimiya
fosfora [The Preparative Chemistry of Phosphorus], Izd. UrO
RAN, Perm, 1992, 466 (in Russian).
Received March 5, 2008;
in revised form July 15, 2008