Reactions of Benzylidene Chlorides with S-Methyl Diethylphosphinothioate

Article abstract of DOI:10.1134/S1070363219120107

S-Methyl diethylphosphinothioate reacted with benzylidene chlorides to give the corresponding aryl(chloro)methyl methyl sulfide and diethylphosphinoyl chloride. The product structure suggests initial attack of the methylsulfanyl group on the CH carbon ato

Full text of DOI:10.1134/S1070363219120107

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 12, pp. 2386–2389. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Obshchei Khimii, 2019, Vol. 89, No. 12, pp. 1869–1873.
Reactions of Benzylidene Chlorides
with S-Methyl Diethylphosphinothioate
M. B. Gazizova,*, G. D. Valievaa, S. Yu. Ivanovaa, R. F. Karimovaa,
R. A. Khairullina, and K. S. Gazizovaa
a Kazan National Research Technological University, Kazan, Tatarstan, Russia
*e-mail: mukattisg@mail.ru
Received May 15, 2019; revised May 15, 2019; accepted May 20, 2019
Abstract—S-Methyl diethylphosphinothioate reacted with benzylidene chlorides to give the corresponding
aryl(chloro)methyl methyl sulfide and diethylphosphinoyl chloride. The product structure suggests initial attack
of the methylsulfanyl group on the CH carbon atom of dichloromethylarene. Arenecarbothialdehyde dithioacetals
and trimers and O,O-dialkyl[aryl(methylsulfanyl)methyl]phosphonates were synthesized.
Keywords: S-methyl diethylphosphinothioate, benzylidene chlorides, α-chloro sulfide, arenecarbothialdehyde
trimers, O,O-dialkyl[aryl(methylsulfanyl)methyl]phosphonates
DOI: 10.1134/S1070363219120107
We previously showed that four-coordinate phospho-
rus acid methyl esters, in particular most nucleophilic
methyl diethylphosphinate (1), react with benzylidene
chlorides 2 to give the corresponding aromatic aldehydes
and phosphorus acid chloride. The reaction of the latter
with initial ester 1 leads to the formation of acyclic an-
hydride [1, 2]. The phosphoryl and ester oxygen atoms in
P(V) acid esters are electron-donor centers. However, on
the basis of the results of these reactions it is impossible
to determine which oxygen atom is subject to primary
attack of CH carbon atom of benzylidene chloride.
in 2 by diethylphosphinothioyl group (Scheme 1, path
a). As well as oxygen analog Et2P(O)OCH(Cl)Ar [4, 5],
compound 8 is unstable, and it decomposes during the
reaction (100°C) to form diethylphosphinic chloride (6)
and arenecarbothialdehyde [3]. Neither arenecarbalde-
hyde 11 nor diethylphosphinothioic chloride (10) was
detected among the products. This indicates that path b
implying initial attack of the ester oxygen atom of 3 on
the CH carbon atom of 2 is not operative (Scheme 1).
In continuation of these studies, we examined the
reaction of S-methyl diethylphosphinothioate (4) with
dichloromethylarenes 2 (Scheme 2). The attack of the
P–S sulfur atom should lead to the formation of α-chloro
sulfide 12 and chloride 6 (path a), whereas arenecarbalde-
hyde 11 and diethylphosphinothioic chloride (10) should
be formed in the case of initial attack of the phosphoryl
oxygen atom (P=O; path b).
It might be expected that replacement of one oxygen
atom in a phosphinic acid ester molecule by another
heteroatom, e.g., sulfur, would provide an opportunity to
identify the site of primary attack of benzylidene chloride.
This should determine the reaction path and product struc-
ture. Therefore, we selected O-methyl diethylphosphino-
thioate (3) and S-methyl diethylphosphinothioate (4) as
ambident nucleophiles.
The reactions of dichloromethylarenes 2 with S-
methyl diethylphosphinothioate (4) were carried out
with equimolar amounts of the reactants at 80–100°C.
We have recently shown [3] that O-methyl ester 3
reacts with benzylidene chlorides to produce the cor-
responding arenecarbothialdehyde (as trimer 5) and
diethylphosphinoyl chloride (6). This result implies ini-
tial attack of the thionic sulfur atom of 3 on the Cl2CH
carbon atom of 2; elimination of methyl chloride from
intermediate phosphonium adduct 7 gives compound 8
which is the product of substitution of one chlorine atom
1
According to the H and 31P NMR data, the reaction
mixture obtained from 4-methoxybenzylidene chloride
(2a) and ester 4 contained compounds 6 (δP 75.0 ppm)
and 12 [δ 6.04 ppm (CH), 2.32 ppm (SMe)]. These find-
ings confirm the initial attack of the sulfur atom (path a).
The absence of aldehyde 11 and chloride 10 in the reaction
mixture indicates that path b is not operative. It should
2386

REACTIONS OF BENZYLIDENE CHLORIDES WITH S-METHYL DIETHYLPHOSPHINOTHIOATE
2387
Scheme 1.
+ ArCHCl2
Et2P(S)OMe
3
2
+
ɚ
P=S
Et2P(Ɉ)SCHAr
Et2PSCHAr
(ArCHS) (Ɉ)PCl
3 + Et2
ꢀMeCl
Me O
Cl
Cl
Cl
5
6
8
7
b
P(S)Cl
10
ArCH(ɈMe)Cl + Et2
10
ArCHO +
P–O
ꢀMeCl
9
11
Scheme 2.
+ ArCHCl
Et2P(O)SMe
2
4
2
O
O
ɚ
Et2PCl + ArCHCl
Et2P
SMe
P–S
SMe
12
Cl
CH(Cl)Ar
6
S
S
+
Et2POCHAr
PCl
ArCHO + Et2
Et2POCHAr
b
–MeCl
P=O
Cl
Cl
Me
S
ClH
13
14
10
11
t-Bu
(a),
HO
t-Bu
H
Ar = 4-MeOC6
(b).
4
be noted that the reaction carried out under more severe
conditions (140°C) afforded trimer 5 as one of the main
products (Scheme 3). Compound 5 is formed as a result
of decomposition of α-chloro sulfide 12, which was con-
firmed by special experiment. The structure of 12 was
also confirmed by chemical transformations. When the
reaction mixture containing sulfide 12 was treated with
trialkyl phosphites, an exothermic reaction occurred, and
O,O-dialkyl[aryl(methylsulfanyl)methyl]phosphonates
14a and 14b were isolated (Scheme 3). Dithioacetals
15 were isolated in the reactions of 2 and 4 at a ratio of
1 : 2.5 on heating for 1.5–3 h or when 1 equiv of 4 was
added to the reaction mixture of 2 and 4 at an initial ratio
of 1 : 1, followed by heating (Scheme 3).
It should be noted that the proposed procedure for the
synthesis of aromatic aldehyde dimethyl dithioacetals
avoids the use of mathanethiol which is a highly toxic
gas with a very unpleasant odor.
It is known that cyclic arenecarbothialdehyde trimers
exist as α- and β-stereoisomers [6] having different melt-
ing points. The β-isomer melts at a considerably higher
temperature than the α-isomer. In addition, a eutectic
mixture of these isomers can be isolated (γ-form). Taking
into account high melting points and 1H NMR spectra data
(a singlet from three axial CH protons), trimers 5a and 5b
were identified as β-isomers. In keeping with published
1H NMR data for arenecarbothialdehyde trimers [6], the
trithiane ring of the β-isomer has a chair conformation
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

2388
GAZIZOV et al.
Scheme 3.
(ArCHS)3
ꢀ
MeCl
5
(RO)3P
ArCHP(O)(OR)2
ꢀ
ArCH(SMe)Cl
RCl
12
SMe
ꢀꢁɚ, 14b
4
+ 6
ArCH(SMe)2
15ɚ, 15b
t-Bu
(a), HO
H
Ar = 4-MeOC6
(b), R = Me (14a), Et (14b).
4
t-Bu
1-[Di(methylsulfanyl)methyl]-4-methoxybenzene-
(4-methoxybenzaldehyde dimethyl dithioacetal,
15a). a. A mixture of 3.82 g (20 mmol) of 4-methoxy-
benzylidene chloride (2a) and 7.61 g (50 mmol) of S-
methyl diethylphosphinothioate (4) was heated for 4 h
at 100°C. The mixture was cooled, treated with 20 mL
of diethyl ether, washed with water (2 × 20 mL), and
dried over anhydrous sodium sulfate. The solvent was
removed under reduced pressure, and the residue was
distilled in a vacuum. Yield 2.10 g (49%), bp 169–170°C
(12 mmHg); published data [7]: yield 34%, bp 129–132°C
(0.2 mmHg). 1H NMR spectrum (CCl4–CDCl3), δ, ppm:
7.24 d and 6.76 d (4H, C6H4, 3JHH = 8.6 Hz), 4.70 s (1H,
CH), 3.75 s (3H, OCH3), 2.03 s (6H, SCH3). Found, %:
C 55.88; H 6.73; S 29.47. C10H14OS2. Calculated, %: C
56.03; H 6.58; S 29.92.
where the three CH hydrogen atoms while the aryl sub-
stituents are equatorial, i.e., the β-isomer can be regarded
as (eq,eq,eq)-cis,cis-2,4,6-triaryl-1,3,5-trithiane 5.
Scheme 4.
H
H
Ar
S
H
Ar
S
S
Ar
In summary, we have studied the reaction of S-methyl
diethylphosphinothioate with benzylidene chlorides and
shown that it involves initial attack of the methylsulfanyl
sulfur atom on the Cl2CH carbon atom of dichloroo-
methylarene with the formation of α-chloro sulfide and
diethylphosphinoyl chloride. The resulting α-chloro
sulfide decomposes at 140°C to give arenecarbothialde-
hyde trimer. Arenecarbothialdehyde acetals have been
synthesized without using highly toxic methanethiol.
b. A mixture of 2a (3.82 g, 20 mmol) and 4 (3.04 g,
1
20 mmol) was heated at 100°C for 4 h. The H NMR
spectrum of the reaction mixture contained intense
signals at δ 6.04 (s, ClCHS) and 2.32 ppm (s, CHSMe)
due to compound 12. An additional portion of 4 (4.57 g,
30 mmol) was added, and the mixture was heated at
100°C for 3 h more and treated as described above in a.
Yield 2.23 g (52%).
EXPERIMENTAL
The 1H NMR spectra were recorded on Tesla BS-567A
and Bruker MSL-400 spectrometers at 100 and 400 MHz,
respectively, relative to the residual proton signals of the
deuterated solvent (DMSO-d6, acetone-d6, CDCl3). The
31P NMR spectra were recorded on a Bruker MSL-400
instrument operating at 162 MHz relative to 85% H3PO4
as external standard. The IR spectra were measured in
the range 400–4000 cm–1 on a Perkin Elmer Spectrum
65 IR spectrometer with Fourier transform from samples
dispersed in mineral oil. The progress of reactions was
monitored by 1H and 31P NMR.
2,6-Di-tert-butyl-4-[di(methylsulfanyl)methyl]-1-
benzenol (3,5-di-tert-butyl-4-hydroxybenzaldehyde di-
methyl dithioacetal, 15b) was synthesized in a similar
way from 1.00 g (3.5 mmol) of 2b and 1.58 g (10.5 mmol)
of 4. Yield 0.53 g (43%), colorless crystals, mp 69–70°C.
1H NMR spectrum (CCl4–acetone-d6), δ, ppm: 7.32 s
(2H, Harom), 5.56 s (1H, OH), 4.89 s (1H, CH), 2.24 s
(6H, SCH3), 1.59 s (18H, t-Bu). Found, %: C 64.89; H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

REACTIONS OF BENZYLIDENE CHLORIDES WITH S-METHYL DIETHYLPHOSPHINOTHIOATE
2389
9.15; S 20.13. C17H28OS2. Calculated, %: C 65.33; H
9.03; S 20.52.
The filtrate was evaporated under reduced pres-
sure, and vacuum distillation of the residue gave 1.21 g
(43%) of diethylphosphinoyl chloride (6), bp 99–101°C
(11 mmHg); published data [8]: bp 102–104°C
(15 mmHg). 31PNMR spectrum: δP 75.0 ppm. Found, %:
C 62.94; H 5.37; S 20.86. C24H24O3S3. Calculated, %: C
63.13; H 5.30; S 21.07.
cis,cis-4,4′,4″-(1,3,5-Trithiane-2,4,6-triyl)tris(2,6-
di-tert-butyl-1-benzenol) (5b) was synthesized in a
similar way from 2.89 g (10 mmol) of 2b and 1.52 g
(10 mmol) of 4. Yield 1.30 g (52%), light yellow powder,
mp 278–279°C (decomp.). IR spectrum, ν, cm–1: 3641
(OH), 722, 700, 620 (S–C–S). Found, %: C 71.66, 71.59;
H 9.21, 9.12; S 12.99, 13.13. C45H66O3S3. Calculated, %:
C 71.95; H 8.85; S 12.80.
O,O-Dimethyl [(3,5-di-tert-butyl-4-hydroxyphenyl)-
(methylsulfanyl)methyl]phosphonate (14a).Amixture
of 1.45 g (5 mmol) of 2b and 1.14 g (7.5 mmol) of 4 was
stirred for 1 h at 80°C and allowed to cool down to room
temperature. Trimethyl phosphite, 1.55 g (12.5 mmol),
was added dropwise with stirring, the mixture spontane-
ously warmed up, and evolution of methyl chloride was
observed. The mixture was left overnight and dissolved
in 10 mL of diethyl ether, and the solution was washed
with water (2 × 10 mL) and dried over anhydrous sodium
sulfate. The drying agent was filtered off, the solvent was
removed under reduced pressure, and the residue was
treated with 10 mL of anhydrous hexane. Yield 0.86 g
(46% over 2 stages), colorless powder, mp 130–131°C
(from heptane). IR spectrum, ν, cm–1: 3138 br (OH),
1224 (P=O), 1179 (P–O–C), 752, 634, 622 (C–S–C). 1H
Diethylphosphinoyl chloride (6), 0.42 g (30%), was
isolated from the filtrate; bp 98–100°C (10 mmHg).
FUNDING
This study was performed under financial support by the
Ministry of Science and Higher Education of the Russian Fede-
ration in the framework of the base part of state assignment in
the sphere of research activity (project no. 4.5348.2017/BCh).
NMR spectrum (acetone-d6), δ, ppm: 7.40 d (2H, Harom
,
4JHH = 1.8 Hz), 6.19 s (1H, OH), 4.16 (1H, CH, 2JPH
=
19.3 Hz), 3.80 d and 3.57 d (6H, OCH3, 3JPH = 10.5 Hz),
4
2.16 d (3H, SCH3, JPH = 1.0 Hz), 1.49 s (18H, t-Bu).
CONFLICT OF INTERESTS
31P NMR spectrum: δP 25.4 ppm. Found, %: C 57.47; H
8.63; P8.19, 8.05; S 8.16, 8.31. C18H31O4PS. Calculated,
%: C 57.73; H 8.34; P 8.27; S 8.56.
No conflict of interest was declared by the authors.
REFERENCES
O,O-Diethyl [(3,5-di-tert-butyl-4-hydroxyphenyl)-
(methylsulfanyl)methyl]phosphonate (14b) was synthe-
sized in a similar way from 1.45 g (5 mmol) of 2b, 1.14 g
(7.5 mmol) of 4, and 2.08 g (12.5 mmol) of triethyl
phosphite. Yield 1.29 g (64%), colorless powder, mp
101–104°C. 1H NMR spectrum (acetone-d6), δ, ppm: 7.38
d (2H, Harom, 4JHH = 1.8 Hz), 6.21 s (1H, OH), 4.36–3.88
1. Gazizov, M.B., Kachalova, T.N., Karimova, R.F.,
Khairullin, R.A., and Sinyashin, O.G., Russ. J. Gen.
Chem., 1997, vol. 67, no. 12, p. 1942.
2. Gazizov, M.B., Kachalova, T.N., Karimova, R.F., and
Sinyashin, O.G., Dokl. Akad. Nauk, 1998, vol. 359,
no. 5, p. 644.
3. Gazizov, M.B., Valieva, G.D., Ivanova, S.Yu., Karimo-
va, R.F., Ismagilov, R.K., and Khairullin, R.A., Russ. J.
Gen. Chem., 2018, vol. 88, no. 8, p. 1754.
https://doi.org/10.1134/S1070363218080327
4. Gazizov, M.B., Ivanova, S.Yu., Bagauva, L.R.,
Khairullin, R.A., and Musin, R.Z., Tetrahedron
Lett., 2016, vol. 57, no. 2, p. 210.
https://doi.org/10.1016/j.tetlet. 2015.12.005
5. Gazizov, M.B., Ivanova, S.Yu., Bagauva, L.R., Kari-
mova, A.A., Ibragimov, Sh.N., and Musin, R.Z., Russ. J.
Gen. Chem., 2015, vol. 85, no. 9, p. 2209.
https://doi.org/10.1134/S1070363215090297
6. Campaigne, F., Chamberlain, N.F., and Edwards, B.N.,
J. Org. Chem., 1962, vol. 27, p. 135.
https://doi.org/10.1021/jo01048a033
7. Drosten, G., Mischke, P., and Voß, J., Chem. Ber.,
1987, vol. 120, p. 1757.
m (5H, CH, OCH2), 2.18 d (3H, SCH3, 4JPH = 1.0 Hz),
3
1.50 s (18H, t-Bu), 1.31 t and 1.15 t (6H, CH3, JHH
=
7.0 Hz). 31P NMR spectrum: δP 23.1 ppm. Found, %: C
59.37; H 8.76; P 7.52, 7.46; S 8.01, 7.85. C20H35O4PS.
Calculated, %: C 59.62; H 8.69; P 7.71; S 7.96.
cis,cis-2,4,6-Tri(4-methoxyphenyl)-1,3,5-trithiane
(5a). A mixture of 3.82 g (20 mmol) of 2a and 3.04 g
(20 mmol) of 4 was heated for 2 h at 100°C and then
for 4 h at 140°C. The mixture was cooled and treated
with 10 mL of anhydrous carbon tetrachloride, and the
crystalline solid was filtered off, washed with anhydrous
carbon tetrachloride (2 × 5 mL) and acetone, and dried.
Yield 2.28 g (75%), mp 181–182°C (from EtOAc–AcOH,
1 : 4); published data [6]: mp 183°C. 1H NMR spectrum
https://doi.org/10.1002/cber.19871201023
8. Kosolapoff, G.M. and Watson, R.M., J. Am. Chem.
Soc., 1951, vol. 73, p. 5466.
(DMSO-d6), δ, ppm: 7.39 d and 6.96 d (12H, Harom
3JHH = 8.5 Hz), 5.70 s (3H, CH), 3.74 s (9H, OCH3).
,
https://doi.org/10.1021/ja01155a532
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019