Synthesis of 2-(alkylsulfanyl)propyltriphenylphosphonium bromides and their alkaline hydrolysis with potassium tert-butoxide

Article abstract of DOI:10.1134/S1070363214030153

A series of 2-(alkylsulfanyl)propyltriphenylphosphonium salts was obtained starting from allyltriphenylphosphonium bromide. Alkaline hydrolysis of the obtained sulfur-containing quaternary phosphonium salts by the action of potassium tert-butoxide afforded 2-(alkylsulfanyl)propyldiphenylphosphine oxides in high yields.

Full text of DOI:10.1134/S1070363214030153

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 3, pp. 501–504. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © M.R. Grigoryan, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 3, pp. 443–446.
Synthesis of 2-(Alkylsulfanyl)propyltriphenylphosphonium
Bromides and Their Alkaline Hydrolysis
with Potassium tert-Butoxide
M. R. Grigoryan
Scientific and Technological Center of Organic and Pharmaceutical Chemistry,
Institute of Organic Chemistry, National Academy of Sciences of Armenia,
pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: meri-grigoryan19@rambler.ru
Received July 29, 2013
Abstract―A series of 2-(alkylsulfanyl)propyltriphenylphosphonium salts was obtained starting from allyltri-
phenylphosphonium bromide. Alkaline hydrolysis of the obtained sulfur-containing quaternary phosphonium
salts by the action of potassium tert-butoxide afforded 2-(alkylsulfanyl)propyldiphenylphosphine oxides in
high yields.
DOI: 10.1134/S1070363214030153
Study of nucleophilic addition to quaternary phos-
phonium salts with both existing and potential vinyl
groups are of great interest [1–4]. In this connection,
allyltriphenylphosphonium bromide attracts particular
attention. Ammonia, primary and secondary amines
react readily with allyltriphenylphosphonium iodide to
form N-substituted (2-aminopropyl)triphenylphospho-
nium salts [5].
Taking into account regularities of the alkaline
hydrolysis of quaternary phosphonium salts and the
anionization of the most anion-labile radical, it may be
presumed that the resulting salts II–VI can be
convenient synthons for obtaining 2-(alkylsulfanyl)-
propyldiphenylphosphine oxides containing an asym-
metric carbon atoms and potentially practically
interesting.
The first experiments showed that the phosphonium
salts II and VI react with a two-fold amount of
potassium tert-butoxide in THF at room temperature to
give the expected phosphine oxides VII (47%) and
VIII (45%) as a result of alkaline hydrolysis. In
addition, in both cases diphenylpropenylphosphine
oxide IX was obtained with 28 and 40% yield,
respectively, as the product of competitive reaction
(1,2-cleavage) (Scheme 2).
In this work we synthesized a series of 2-(alkyl-
sulfanyl)propyltriphenylphosphonium salts by se-
quential reacting equimolar amounts of allyltriphenyl-
phosphonium bromide I with triethylamine and thiols.
As can be seen from the scheme, prototropic iso-
merization of the phosphonium salt I by the action of
amine followed by the addition of RSH to the formed
α,β-double bond gives rise to phosphonium salts II–VI
with over 80% yields. Triphenyl-2-(β-dimethylamino-
ethylsulfanyl)propylphosphonium bromide V was
obtained with the lowest yield (72%) (Scheme 1).
The yields of target phosphines VII and VIII
increased (61 and 56%, respectively) with decrease in
the reaction temperature (–5 to –7°C); in addition, the
Scheme 1.
RSH
Et3N
Ph3P+
Br−
Ph3P+
Br−
Ph3P+
Br−
SR
I
II−VI
R = Et (II), Bu (III), tert-C5H11 (IV), CH2CH2N(CH3)2 (V), CH2CH2OH (VI).
501

502
GRIGORYAN
Scheme 2.
Ph2P
O
−C6H6
SR
VII, VIII
Ph3P+
Br−
t-BuOK
SR
−RSH
Ph2P
O
II, VI
IX
R = C2H5 (II, VII), CH2CH2OH (VI, VIII).
Scheme 3.
Ph3P+
Br−
t-BuOK
−C6H6
Ph2P
O
SR
SR
III−V
X−XII
R = C4H9 (III, X), tert-C5H11 (IV, XI), CH2CH2N(CH3)2 (V, XII).
yield of phosphine oxide IX reduced to 15 and 26%,
respectively.
stirred at room temperature for 24 h. Chloroform was
removed, and the residue was washed with benzene
and anhydrous diethyl ether, then dried in a vacuum.
Alkaline hydrolysis of the phosphonium salts III–V
with potassium tert-butoxide under the same
conditions resulted only in the tertiary phosphine
oxides X–XII containing alkyl- or (β-dimethylamino)
ethylsulfanyl group (Scheme 3).
1
Yield 1.55 g (89.1%), mp 101–103°C. H NMR
spectrum, δ, ppm (J, Hz): 1.15 t (3Н, SСН2СН3, J 7.4),
1.4 d.d (3Н, СН3СН, J1 6.7, J2 1.5 ), 2.45 q (2Н,
SCH2CH3, J 7.4), 3.09–3.2 m (1Н, СН), 4.05–4.25 m
(2Н, Р+СН2), 7.65–8.0 m (15Н, Р+Ph3). 31Р NMR
spectrum: δP 26.94 ppm. Found, %: Br 17.55; P 6.78.
C23H26BrPS. Calculated, %: Br 17.97; P 6.97.
Thus our research shows that an increase in the
reaction temperature and higher mobility of anionic
substituent at the sulfur atom favor 1,2-cleavage, and
conversely, lower temperature and the presence of
alkyl substituents at the sulfur atom favor the
formation of 2-(alkylsulfanyl)propyldiphenylphosphine
oxides.
2-(Butylsulfanyl)propyltriphenylphosphonium
bromide (III) was obtained similarly from 1.5 g
(3.9 mmol) of salt I, 0.4 g (3.9 mmol) of triethylamine
and 0.35 g (3.9 mmol) of n-butanethiol in 20 mL of
1
chloroform. Yield 1.67 g (90.8%), mp 124–126°C. H
EXPERIMENTAL
NMR spectrum, δ, ppm (J, Hz): 0.88 t (3Н, СН2СН3, J
7.1), 1.35 d.d (3Н, СН3СН, J1 6.9, J2 1.7), 1.25–1.45 m
(4Н, СН2СН2СН3), 2.47 t (2Н, SCH2CH2, J 7.3), 3.1–
3.21 m (1Н, СН), 4.1–4.2 m (2Н, Р+СН2), 7.45–7.9 m
(15Н, Р+Ph3). 31Р NMR spectrum: δP 27.13 ppm.
Found, %: Br 17.24; P 6.32. C25H30BrPS. Calculated,
%: Br 16.91; P 6.55.
1H NMR and 31P spectra were recorded on a Varian
Mercury-300 spectrometer [300.077 (1H), 121.47 MHz
(31P)] at 303 K, using DMSO-d6–CCl4 mixture (1 : 3)
as a solvent. Chemical shifts are given relative to
references TMS (1H) and 85% H3PO4 (31P).
All reactions were performed in a 50 mL three-
necked flask equipped with a mechanical stirrer, reflux
condenser, dropping funnel, and gas inlet. Allyl-
triphenylphosphonium bromide I was obtained by a
known method [4].
2-(1,1-Dimethylpropylsulfanyl)propyltriphenyl-
phosphonium bromide (IV) was obtained similarly
from 1.5 g (3.9 mmol) of salt I, 0.4 g (3.9 mmol) of
triethylamine and 0.41 g (3.9 mmol) of 1,1-dimethyl-
propanethiol in 20 mL of chloroform. Yield 1.56 g
1
Triphenyl-[2-(ethylsulfanyl)propyl]phosphonium
bromide (II). A mixture of 1.5 g (3.9 mmol) of salt I,
0.4 g (3.9 mmol) of triethylamine, and 0.24 g
(3.9 mmol) of ethanethiol in 20 mL of chloroform was
(82.2%), mp 133–135°C. H NMR spectrum, δ, ppm
(J, Hz): 0.86 t (3Н, СН2СН3, J 7.1), 1.02 s and 1.03 s
[6Н, С(СН3)2], 1.36 d.d (3Н, СН3СН, J1 6.8, J2 1.6),
1.42 q (2Н, СН2СН3, J 7.4), 3.08–3.19 m (1Н, СН),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

SYNTHESIS OF 2-(ALKYLSULFANYL)PROPYLTRIPHENYLPHOSPHONIUM BROMIDES
503
4.0–4.15 m (2Н, Р+СН2), 7.6–7.9 m (15Н, Р+Ph3). 31Р
NMR spectrum: δP 26.87 ppm. Found, %: Br 16.78; Р
6.64. С26Н32BrPS. Calculated, %: Br 16.43; P 6.37.
1H NMR spectrum, δ, ppm (J, Hz): 1.12 t (3Н,
СН3СН2, J 7.4), 1.31 d (3Н, СН3СН, J 6.7), 2.42 d.d.d
(1Н, РСН2, J1 15.0, J2 11.5, J3 10.4), 2.48 q (2Н,
SCH2, J 7.4), 2.66 d.d.d (1Н, РСН2, J1 15.0, J2 10.5, J3
3.1), 3.01–3.12 m (1Н, СН), 7.41–7.82 m (10Н, РPh2).
31Р NMR spectrum: δP 31.65 ppm. Found, %: С 67.34;
Н 6.91; Р 10.26. С17Н21ОPS. Calculated, %: С 67.11;
Н 6.91; P 10.19.
2-(2-Dimethylaminoethylsulfanyl)propyltriphenyl-
phosphonium bromide (V). To a mixture of 0.53 g
(5.2 mmol) of triethylamine and 1 g (2.6 mmol) of salt
I in 10 mL of chloroform was added dropwise a
solution of 0.36 g (2.6 mmol) of N,N-dimethyl-2-sulfa-
nylethylammonium chloride in 10 mL of chloroform.
The reaction mixture was stirred at room temperature
for 20 h, and then treated with diluted aqueous sodium
carbonate solution. The organic layer was separated,
dried over MgSO4, filtered, and evaporated. The
residue was washed with benzene and anhydrous
diethyl ether, dried in a vacuum. Yield 0.91 g (72%),
Diphenylpropenylphosphine oxide IX was isolated
from the benzene extract. Yield 0.18 g (27.5%), mp
113–114°C. The substance showed no melting point
depression when mixed with an authentic sample [6].
b. Phosphine oxide VII was obtained similarly
from 1.2 g (2.7 mmol) of the salt II and 0.6 g
(5.4 mmol) of potassium tert-butoxide in 20 mL of
anhydrous THF at –5 to –7°C. Yield 0.5 g (61.1%) (1H
and 31P NMR data coincided with those of an authentic
sample). Additionally, 0.1 g (15.3%) of phosphine
oxide IX was obtained.
1
mp 165–167°C. H NMR spectrum, δ, ppm (J, Hz):
1.42 d.d (3Н, СН3, J1 6.6, J2 1.5), 2.45 br. s [6Н, N
(CH3)2], 2.61–2.81 m (4Н, SCH2CH2N), 3.06 m (1Н,
СН), 4.11–4.30 m (2Н, Р+СН2), 7.71–7.79 m (6Н,
P+Ph), 7.82–7.89 m (3Н, P+Ph), 7.92–8.02 m (6Н,
P+Рh). 31Р NMR spectrum: δP 27.83 ppm. Found, %:
Br 15.98; N 3.01; Р 6.56. С25Н31BrNPS. Calculated,
%: Br 16.39; N 2.87; P 6.35.
2-(2-Hydroxyethylsulfanyl)propyldiphenylphos-
phine oxide (VIII) was obtained similarly (method a)
from 1.5 g (3.3 mmol) of salt VI and 0.73 g (6.5 mmol)
of potassium tert-butoxide in 25 mL of anhydrous
THF. Yield 0.48 g (45.5%). 1H NMR spectrum, δ, ppm
(J, Hz): 1.3 d (3Н, СН3, J 6.8), 2.4–2.6 m (3Н, SCH2,
PCH2), 2.78 d.d.d (1Н, РСН2, J1 13.5, J2 10.2, J3 3.0),
3.05–3.2 m (1Н, СН), 3.45 t.d (2Н, ОСН2, J1 7.3, J2
7.1), 7.4–7.85 m (10Н, РPh2). 31Р NMR spectrum: δP
31.99 ppm. Found, %: С 64.02; Н 6.93; Р 9.37.
С17Н21О2PS. Calculated, %: С 63.75; Н 6.56; P 9.68.
Additionally, 0.32 g (40.1%) of phosphine oxide IX
was obtained.
2-(2-Hydroxyethylsulfanyl)propyltriphenylphos-
phoniumbromide (VI). A mixture of 0.4 g (3.9 mmol)
of triethylamine and 0.3 g (3.9 mmol) of 2-sul-
fanylethanol was added dropwise to a solution of 1.5 g
(3.9 mmol) of the salt I in 20 mL of chloroform. The
reaction mixture was refluxed for 8 h. After the solvent
removal in a vacuum the residue was washed with
benzene and anhydrous diethyl ether, and then dried in
1
a vacuum. Yield 1.59 g (88.4%), mp 170–173°C. H
NMR spectrum, δ, ppm (J, Hz): 1.4 d.d (3Н, СН3, J1
6.7, J2 1.5), 2.55 t (2Н, SCH2, J 7.3), 3.02–3.19 m (1Н,
СН), 3.4 t.d (2Н, ОСН2, J1 7.1, J2 7.1), 4.0–4.18 m
(2Н, Р+СН2), 4.65 t (1Н, OH, J 7.1), 7.65–7.8 m (6Н,
P+Ph), 7.8–8.0 m (9Н, P+Ph). 31Р NMR spectrum: δP
27.76 ppm. Found, %: Br 17.52; Р 6.41. С23Н26BrОPS.
Calculated, %: Br 17.35; P 6.72.
b. Phosphine oxide VIII was obtained similarly
from 1.5 g (3.3 mmol) of salt VI and 0.73 g (6.5 mmol)
of potassium tert-butoxide in 25 mL of anhydrous
1
31
THF. Yield 0.6 g (56.8%) H and P NMR data coin-
cided with those of an authentic sample). Additionally,
0.2 g (26.3%) of the phosphine oxide IX was obtained.
2-(Butylsulfanyl)propyldiphenylphosphine oxide
(X) was obtained similarly using method b from 1.0 g
(2.1 mmol) of salt III and 0.47 g (4.2 mmol) of
potassium tert-butoxide in 20 mL of anhydrous THF.
Diphenyl-2-(ethylsulfanyl)propylphosphine oxide
(VII). a. To a suspension of 1.2 g (2.7 mmol) of salt II
in 20 mL of anhydrous THF was added 0.6 g
(5.4 mmol) of potassium tert-butoxide under nitrogen
atmosphere. The reaction mixture was stirred at room
temperature for 5 h. Then the solution was filtered, and
the residue was twice treated with anhydrous THF.
Combined tetrahydrofuran extracts were evaporated in
a vacuum. The residue was washed with anhydrous
benzene and dried in a vacuum. Yield 0.39 g (47.2%).
1
Yield 0.54 g (77.5%). H NMR spectrum, δ, ppm (J,
Hz): 0.87 t (3Н, СН3СН2, J 7.1), 1.32 d (3Н, СН3СН,
J 6.7), 1.28–1.46 m (4Н, СН2СН2СН3), 2.35–2.48 m
(3Н, РСН2, SCH2), 2.66 d.d.d (1Н, РСН2, J1 13.4, J2
10.3, J3 3.2), 2.97–3.08 m (1Н, СН), 7.43–7.81 m
(10Н, РPh2). 31Р NMR spectrum: δP 31.83 ppm.
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GRIGORYAN
Found, %: С 68.33; Н 7.32; Р 9.78. С19Н25ОPS. Cal-
culated, %: С 68.67; Н 7.53; P 9.34.
(3Н, СН3, J 6.7), 2.15 s [6Н, N(СН3)2], 2.25 d.d.d (1Н,
РСН2, J1 15.1, J2 11.3, J3 10.2), 2.32–2.40 m (4Н,
SCH2CH2N), 2.50 d.d.d (1Н, РСН2, J1 15.1, J2 10.4, J3
2.9), 3.0–3.1 m (1Н, СН), 7.4–7.8 m (10Н, РPh2). 31Р
NMR spectrum: δP 31.64 ppm. Found, %: С 65.46; Н
7.14; Р 9.16. С19Н26ОNPS. Calculated, %: С 65.71; Н
7.49; P 8.93.
2-(1,1-Dimethypropylsulfanyl)propyldiphenyl-
phosphine oxide (XI) was obtained similarly from
1.33 g (2.7 mmol) of salt IV and 0.6 g (5.4 mmol) of
potassium tert-butoxide in 25 mL of anhydrous THF.
1
Yield 0.66 g (70.6%). H NMR, δ, ppm (J, Hz): 0.85 t
(3Н, СН3СН2, J 7.4), 1.06 s and 1.07 s [ 6Н, С(СН3)2],
1.32 d (3Н, СН3СН, J 6.8), 1.4 q (2Н, СН3СН2, J
7.4 ), 2.5 d.d.d (1Н, РСН2, J1 15.0, J2 11.5, J3 10.3),
2.65 d.d.d (1Н, РСН2, J1 15.0, J2 10.4, J3 3.0), 3.01–
3.18 m (1Н, СН), 7.41–7.8 m (10Н, РPh2). 31Р NMR
spectrum: δP 31.21 ppm. Found, %: С 69.04; Н 7.62; Р
9.13. С20Н27ОPS. Calculated, %: С 69.36; Н 7.80; P
8.96.
REFERENCES
1. Shweizer, E.E. and Wehmann, A.T., J. Chem. Soc. (C),
1971, p. 343.
2. McIntosh, J.M. and Goodbrand, H.B., Synthesis, 1974,
no. 12, p. 862.
3. Samaan, S., Tetrahedron Lett., 1974, no. 45, p. 3927.
4. Keough, P.T. and Grayson, M., J. Org. Chem., 1964,
vol. 29, no. 3, p. 631.
2-(2-Dimethylaminoethylsulfanyl)propyldiphenyl-
phosphine oxide (XII) was obtained similarly from
1.28 g (2.6 mmol) of salt V and 0.59 g (5.2 mmol) of
potassium tert-butoxide in 25 mL of anhydrous THF.
5. Nesmeyanov, N.A., Mikul’shina, V.V., Kharitonov, V.G.,
Petrovskii, P.V., and Reutov, О.А., Russ. Chem. Bull.,
1989, no. 5, p. 1076.
6. Horner, L., Ertel, I., Ruprecht, H., and Belovsky, O.,
1
Chem. Ber., 1970, vol. 103, p. 1582.
Yield 0.64 g (70.9%). H NMR, δ, ppm (J, Hz): 1.4 d
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014