Intramolecular C-thiocarbamoylation of aroxy(Isothiocyanato)phosphonium salts

Article abstract of DOI:10.1002/hc.20491

Isothiocyanatophosphonium salts bearing an aroxy group at the phosphorus atom have been obtained for the first time. As found, these compounds undergo an intramolecular heterocyclization to give hitherto unknown benzoxazaphosphininethiones or cyanoiminoph

Full text of DOI:10.1002/hc.20491

Heteroatom Chemistry
Volume 19, Number 7, 2008
Intramolecular C-Thiocarbamoylation of
Aroxy(Isothiocyanato)Phosphonium Salts
R. V. Smalii, A. P. Marchenko, Y. N. Koidan, A. A. Chaikovskaya,
A. M. Pinchuk, and A. A. Tolmachev
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv-94,
02094, Ukraine
Received 3 April 2008; revised 25 June 2008
group is combined with a C-nucleophilic center,
ABSTRACT: Isothiocyanatophosphonium salts
thus affording an intramolecular heterocyclization.
bearing an aroxy group at the phosphorus atom
have been obtained for the first time. As found,
these compounds undergo an intramolecular hete-
RESULTS AND DISCUSSION
rocyclization to give hitherto unknown benzoxaza-
phosphininethiones or cyanoiminophosphoranes,
according to the nature of the substituents on the aryl
As synthetic precursors of bifunctional isothio-
cyanatophosphonium salts, unsubstituted phenol
and its electron-donor-substituted derivatives were
used (Fig. 1), because compounds of this kind
have been thoroughly studied in both inter- and in-
tramolecular C-carbamoylations [4,5,8,9].
ꢀ
C
ring.
2008 Wiley Periodicals, Inc. Heteroatom Chem
19:667–670, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20491
To synthesize hitherto unknown aroxy
(isothiocyanato)phosphonium salts, we started
from aroxyphosphonium salts 2a–d obtained by the
reaction of O-phosphorylated phenols 1a–d with
dichloroethane (Scheme 1).
INTRODUCTION
Reactions of intramolecular C-(thio)carbamoylation
with various iso(thio)cyanates have been ex-
tensively used in heterocyclic synthesis [1–6].
Iso(thio)cyanatophosphonium salts have not
yet been studied in this respect in spite
of their great structural diversity and high
(thio)carbamoylation reactivity toward C-nucleo-
philic substrates. As shown by us previously,
Aroxy(chloro)phosphonium chlorides 2a–b con-
taining a diethylamino group on the aromatic
ring were treated with trimethylsilyl isothio-
cyanate to provide the corresponding aroxy
(isothiocyanato)phosphonium isothiocyanates 3a,b,
which were characterized by 31P NMR spectra with-
out isolation. They were cyclized in situ in the pres-
ence of the equivalent quantity of triethylamine at
20◦C. As was expected, the intramolecular cycliza-
tion furnished new heterocycles, benzoxazaphos-
phininethiones 4a and 4b, with respective yields of
33% and 25% (Scheme 2). Compounds 4a,b were
obtained as pale yellow high-melting solids stable to
atmospheric moisture and oxygen.
amido(isothiocyanato)phosphonium
compounds
efficiently thiocarbamoylate a number of electron-
rich heterocycles and enamines [7]. The present
study addresses the design of novel phosphonium
salts in which an electrophilic P-isothiocyanato
Correspondence to: A. A. Chaikovskaya; e-mail: chaikoff2005@
As one would expect in going to phenol
derivatives 2c,d bearing less electron-donating
ukr.net.
c
ꢀ
2008 Wiley Periodicals, Inc.
667

668 Smalii et al.
alent quantity of triethylamine, the corresponding
benzoxazaphosphininethiones or cyanoiminophos-
phoranes. The course of the reaction is governed
by the electron-donating properties of the sub-
stituents on the aryl ring: a decreased nucleophilic-
ity of the aromatic carbon atoms stabilizes the
aroxy(isothiocyanato)phosphonium salt both in the
pure state and in solution, hinders the heterocycliza-
tion, and favors cyanoiminophosphorane formation.
HO
HO
HO
OMe
N(Me)2
FIGURE 1
three substituents, intermediate aroxy(isothio-
cyanato)phosphonium salts 5a,b become much
more stable, so that these compounds can be isolated
in the pure state, provided they are not heated above
40◦C. It was, however, unexpected that the heterocy-
clization did not occur, if attempted under more se-
vere conditions; instead, carbon disulfide was elim-
inated and cyanoiminophosphoranes 6a and 6b
were formed in 74% and 35% yields, respectively
(Scheme 3).
Scheme 4 represents a plausible mechanism
for the formation of cyanoiminophosphoranes from
salts 5a,b. It is likely that the counterion (in our case,
thiocyanate anion) initially attacks the carbon atom
of the isothiocyanate group, which is typical of such
compounds [10], followed by a rearrangement and
elimination of carbon disulfide.
EXPERIMENTAL
1H (300 MHz, TMS as internal standard) and 31P
(282.2 MHz, 85% H3PO4 as external standard) NMR
spectra were recorded on a Varian VXR-300 spec-
trometer. IR spectra were obtained on an UR-20
spectrometer for samples in KBr disks. Mass spectra
were registered using an Agilent 1100 series LC/MSD
system. All reactions were carried out under dry
argon using the Schlenk-type glassware. Solvents,
including deuterated solvents used for NMR spec-
troscopy, were dried and distilled prior to use.
CONCLUSION
Aroxy(chloro)phosphonium Chlorides 2a,b
As found, aroxy(isothiocyanato)phosphonium isoth-
iocyanates furnish, in the presence of the equiv-
To a stirred solution of aroxyphosphines 1a,b
(0.01 mol) in benzene (20 mL) at 5◦C for 1a or in Et2O
+
C2Cl6
a: R = NEt2 , R′ = t-Bu
R′ P O
R2P O
2
−Cl2C=CCl2
b: R = NEt2 , R′ = Me2N
c: R = OMe , R′ = t-Bu
Cl
Cl
R
R
d: R = H ,
R′ = t-Bu
1a-d
2a-d
SCHEME 1
NEt2
R
R
O
NEt2
NEt3
NEt3*HNCS
2 Me3Si-N=C=S
2Me3SiCl
P
R2P O
2a,b
-
-
N
N
NCS
a: R = t-Bu
b: R = Me2N
C
S
S
4a,b
3a,b
SCHEME 2
t-Bu
-
NCS
t-Bu
O
+
2 Me3Si-N=C=S
Me3SiCl
NEt3
CS2
P
t-Bu2P O
2c,d
: R = OMe
a
-
-
N
C
N
C
b: R = H
S
R
R
N
5a,b
6a,b
SCHEME 3
Heteroatom Chemistry DOI 10.1002/hc

Intramolecular C-Thiocarbamoylation of Aroxy(Isothiocyanato)Phosphonium Salts 669
+
R3
P
N
C
S
-
N
C
S
S
S
S
S
+
P
S
S
+
R3P
R3
N
C
R3P
N
N
C
R3P
N
C
N
N
C
N
C
S
N
C
S
C
C
S
+
R3P
+
R3P
S
+
R3P
N
C
C
S
N
C
N
-
N
C
S
N
-
-CS2
-CS2
N
-
R3P
N
C
N
SCHEME 4
(20 mL) at −40◦C for 1b, a solution of C2Cl6 (2.37 g,
0.01 mol) in benzene (20 mL) for 1a or in Et2O (20
mL) for 1b was added. The reaction mixture was
heated to 20◦C and held at this temperature for 2
h. After decanting the solvent, Et2O (20 mL) was
poured over the oily product and it was rubbed un-
til crystallization occurred. The resulting precipitate
was filtered off on a dry filter and washed with Et2O
(2 × 10 mL).
2,2-Dimethyl-4H-1,3,2λ5-
benzoxazaphosphinine-4-thiones 4a,b
To a solution of aroxy(chloro)phosphonium chlo-
rides 2a,b (0.01 mol) in CH2Cl2 (10 mL), a solu-
tion of Me3SiNCS (3.28 g, 0.025 mol) in CH2Cl2
(10 mL) was added at 20◦C and the reaction mix-
ture was held at this temperature for 2 h. Resulting
aroxy(isothiocyanato)phosphonium isothiocyanates
3a,b were characterized by 31P NMR spectra with-
out isolation. 31P NMR (CH2Cl2), δP (ppm) for 4a: br
81.18 and for 4b: br 19.5, ca. 50% intensity relative to
the other signals. After adding triethylamine (2.52 g,
0.025 mol) to the reaction mixture, it was allowed
to stand for 1 h and then evaporated. The product
was extracted from the residue with benzene, fol-
lowed by evaporation of benzene and extraction of
the product from the residue with Et2O (5 × 20 mL).
The resulting ether solution was held over activated
charcoal, filtered, evaporated to 1/4 of its volume,
and left overnight. The crystals that deposited from
the solution were filtered off and dried until the con-
stant mass was achieved.
Compound 2a. Yield 3.19 g (84%). 31P NMR
1
(C6D6), δP(ppm): 126.70. H NMR (C6D6), δ (ppm):
0.91 (t, JHH = 6.9 Hz, 6H, CH3), 1.18 (d, JHP = 11.7
Hz, 18H, t-Bu), 2.99 (q, JHH = 6.9 Hz, 4H, CH2), 6.25
(m, 1H, Ar), 6.81 (m, 2H, Ar), 7.14 (m, 1H, Ar).
Compound 2b. Yield 3.44 g (84%). 31P NMR
(C6D6), δP(ppm): 39.00.
Aroxy(chloro)phosphonium Chlorides 2c,d
To a stirred solution of aroxyphosphines 1c,d (0.01
mol) cooled to −40◦C, a solution of C2Cl6 (2.37 g, 0.01
mol) in Et2O (10 mL) was added. The reaction mix-
ture was heated to 20◦C and held at this temperature
for 1 h. The precipitate of the product was filtered
off on a dry filter and washed with Et2O (2 × 10 mL).
7-(Diethylamino)-2,2-di-tert-butyl-2,2-dihydro-
4H-1,3,2-benzoxazaphosphinine-4-thione 4a. Yield
1.21 g (33%), mp 177–178◦C. 31P NMR (C6D6),
Compound 2c. Yield 2.88 g (85%), mp 85–86◦C.
1
δP(ppm): 64.30. H NMR (C6D6), δ (ppm): 0.78 (t,
31P NMR (C6D6), δP (ppm): 127.90.
JHH = 7.2 Hz, 6H, CH3), 1.00 (d, JHP = 15.6 Hz, 18H,
t-Bu), 2.80 (q, JHH = 7.2 Hz, 4H, CH2), 6.13 (d,
J = 2.7 Hz, J = 2.7 Hz, 1H, Ar), 6.18 (dd, JHH = 9.3
Hz, J = 2.7 Hz, 1H, Ar), 9.41 (d, JHH = 9.3 Hz,
Compound 2d. Yield 2.72 g (88%), mp 80–85◦C.
31P NMR (C6D6), δP (ppm): 128.10.
Heteroatom Chemistry DOI 10.1002/hc

670 Smalii et al.
1H, Ar). m/z 366 [M]+. Found: P 8.37; S 8.84.
C19H31N2OPS. Calcd.: P 8.45; S 8.75.
added (2.00 g, 0.02 mol). The reaction mixture was
heated at 100◦C in a hermetically sealed flask for
20 min and evaporated until the constant mass was
achieved. After extracting the residue with Et2O (4 ×
20 mL), the solution was evaporated and the residue
was recrystallized from Et2O.
7-(Diethylamino)-2,2-bis(dimethylamino)-2,2-di-
hydro-4H-1,3,2-benzoxazaphosphinine-4-thione 4b.
Yield 0.85 g (25%), mp 158–159◦C. 31P NMR (C6D6),
δP (ppm): 19.80. 1H NMR (C6D6), δ (ppm): 0.75
(t, JHH = 6.6 Hz, 6H, CH3), 2.21 (d, JHP = 10.5 Hz,
12H, Me), 2.78 (q, JHH = 6.6 Hz, 4H, CH2), 6.10 (d,
JHH = 2.7 Hz, 1H, Ar), 6.24 (dd, JHH = 9.3 Hz, J = 2.7
Hz, 1H, Ar), 9.39 (d, JHH = 9.3 Hz, 1H, Ar). m/z 340
[M]+. Found: P 9.19; S 9.38. C15H25N4OPS. Calcd.: P
9.10; S 9.42.
3-Methoxyphenyl P,P-di(tert-butyl)-N-cyanophos-
phinimidoat 6a. Yield 1.08 g (35%), mp 104–105◦C.
1
31P NMR (C6D6), δP (ppm): 65.40. H NMR (C6D6),
δ (ppm): 1.18 (d, JHP = 11.7 Hz, 18H, t-Bu), 3.31 (s,
3H, OMe), 6.53 (d, JHH = 7.8 Hz, 1H, Ar), 7.00 (d,
JHH = 7.8 Hz, 1H, Ar), 7.10 (d, JHH = 8.1 Hz, 1H, Ar),
7.32 (s, 1H, Ar). IR (KBr) ꢀν = 2200 cm−1(C≡N).
Aroxy(isothiocyanato)phosphonium
Isothiocyanates 5a,b
Phenyl P,P-di(tert-butyl)-N-cyanophosphinimidoat
6b. Yield 2.06 g (74%), mp 73–74◦C. 31P NMR
To a solution of aroxy(chloro)phosphonium chlo-
rides 2c,d (0.01 mol) in CH2Cl2 (10 mL), a solution of
Me3SiNCS (3.28 g, 0.025 mol) in CH2Cl2 10 mL was
added at 20◦C, and the reaction mixture was held
at this temperature for 5 min. After evaporating the
solvent at a bath temperature not above 30–35◦C, the
residue was washed several times with Et2O. Ether
was then decanted, and the residue was dried under
vacuum.
(C6D6), δP (ppm): 66.00. 1H NMR (C6D6),
δ
(ppm): 1.05 (d, JHP = 15.9 Hz, 18H, t-Bu), 6.82
(t, JHH = 7.5 Hz, 1H, Ar), 7.01 (t, JHH = 8.1 Hz, 2H, Ar),
7.22 (d, JHH = 8.1 Hz, 2H, Ar). IR (KBr) ꢀν = 2200
cm−1(C N).
REFERENCES
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Compound 5a. Yield 3.27 g (85%), mp 76–78◦C.
1
31P NMR (C6D6), δP (ppm): 80.80. H NMR (C6D6), δ
(ppm): 1.93 (s, 9H, t-Bu), 1.98 (s, 9H, t-Bu), 3.81 (s,
3H, OMe), 6.42 (d, 7.8 Hz, 1H, Ar), 6.52 (d, JHH = 7.8
Hz, 1H, Ar), 6.67(d, JHH = 8.0 Hz, 1H, Ar), 7.20 (s,
1H, Ar).
Compound 5b. Yield 3.01 g (85%), mp 85–89◦C.
1
31P NMR (C6D6), δP (ppm): 80.70 H NMR (C6D6), δ
(ppm): 1.94 (s, 9H, t-Bu), 1.98 (s, 9H, t-Bu), 6.85
(t, JHH = 7.8 Hz, 1H, Ar), 7.07 (t, JHH = 7.8 Hz, 2H,
Ar), 7.27 (d, JHH = 7.8 Hz, 2H, Ar).
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Cyanoiminophosphoranes 6a,b
To a solution of aroxy(isothiocyanato)phosphonium
salts 5a,b in CH2Cl2 (20 mL), triethylamine was
Heteroatom Chemistry DOI 10.1002/hc