S-Methyl diethylthiophosphinate in mono- and di(dechloromethylthioylation) of substituted benzylidene chlorides

Article abstract of DOI:10.1007/s11172-019-2642-9

The main route of a new reaction of (dichloromethyl)arenes with S-methyl diethylthiophosphinate is the attack of the thiol sulfur atom (P–SMe) on the methylene carbon atom. A new method for synthesizing dimethyl dithioacetals of arenecarbaldehydes without

Full text of DOI:10.1007/s11172-019-2642-9

Russian Chemical Bulletin, International Edition, Vol. 68, No. 10, pp. 1889—1892, October, 2019
1889
S-Methyl diethylthiophosphinate in mono- and di(dechloromethylthioylation)
of substituted benzylidene chlorides
M. B. Gazizov, G. D. Valieva, S. Yu. Ivanova, R. A. Khairullin, Yu. S. Kirillina,
O. D. Khairullina, and Sh. N. Ibragimov
Kazan National Research Technological University,
68 ul. K. Marx, 420015 Kazan, Russian Federation.
Fax: +7 (843) 231 9505. E-mail: mukattisg@mail.ru
The main route of a new reaction of (dichloromethyl)arenes with S-methyl diethylthio-
phosphinate is the attack of the thiol sulfur atom (P—SMe) on the methylene carbon atom.
A new method for synthesizing dimethyl dithioacetals of arenecarbaldehydes without using
highly toxic methanethiol was developed. The suggested approach involves di(dechloro-
methylthioylation) of the dichloromethyl group of (dichloromethyl)arenes with S-methyl
diethylthiophosphinate at a reagent ratio of 1 : 2.
Key words: S-methyl diethylthiophosphinate, substituted benzylidene chlorides, mono- and
di(dechloromethylthioylation), thiol sulfur atom, dimethyl dithioacetals of arenecarbaldehydes,
methanethiol.
Earlier, the reactions of the ambident (P=O,P—O)-
nucleophiles, namely, the full methyl esters of phos-
phorus(IV) acids, with (dichloromethyl)arenes to give
aromatic aldehydes and the anhydrides of the correspond-
ing PIV acids have been described.1,2 However, no data
on the reactions of these gem-dichlorides with ambident
(P=O,P—S)-nucleophiles, including S-methyl diethyl-
thiophosphinate, were published.
The aim of the present work is the prediction and
experimental confirmation of the main route of a new
reaction of S-methyl diethylthiophosphinate (1a) with
(dichloromethyl)arenes 2 and elaboration of the synthetic
method towards dimethyl dithioacetals of arenecarbalde-
hydes avoiding the use of highly toxic gaseous methane-
thiol with strong unpleasant odor.
We found a new reaction taking place between S-methyl
diethylthiophosphinate (1a) and (dichloromethyl)arenes
2a,b. Theoretically, this reaction can proceed following
two routes. We believe that dechloromethylthioylation to
give compounds 3a,b (Scheme 1, route a) can be accom-
plished by two following pathways: without charge separa-
tion as a concerted electron transfer involving four-
membered transition state A and with charge separation
via intermediate sulfonium cation B. Subsequent substitu-
tion of the chlorine atom of compounds 3a,b with the
methylthio group should result in dithioacetals 5a,b and
Scheme 1
2, 3, 5—8: Ar = 4-MeOC6H4 (a), 3,5-But2-4-HOC6H2 (b)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1889—1892, October, 2019.
1066-5285/19/6810-1889 © 2019 Springer Science+Business Media, Inc.

1890
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 10, October, 2019
Gazizov et al.
diethylphosphinoyl chloride (4). An alternative route
(Scheme 1, route b) is an attack of the phosphoryl oxygen
atom on the methine carbon atom of gem-dichloride 2. In
this case, the initially formed quasi-phosphonium salt 6
losses methyl chloride to give the dechlorodiethylthio-
phosphinyloxylation product 7. This compound, in anal-
ogy with its oxygen-containing counterpart ArCH(Cl)-
OP(O)Et2, should be unstable and decompose to arene-
carbaldehyde 8 and diethylphosphinoyl chloride 9.
When the reaction between compounds 1a and 2 was
carried out at a molar ratio 1a : 2 = 2.5 : 1 or the reaction
mixture obtained at a molar ratio 1a : 2 = 1 : 1 was treated
with an additional 1 equiv. of phosphinate 1a and then
heated for 1.5—3 h, compounds 2 undergo di(dechloro-
methyl)thioylation to give dithioacetals 5a,b. Compounds
5a,b were isolated pure by vacuum distillation (Scheme 2).
Scheme 2
In order to choose the most probable route of this
reaction, we analyzed the electronic structure of S-alkyl
esters of phosphorus(IV) acids R1R2P(O)SR 1a—e. Table 1
summarizes the vertical ionization potential (IP) of the high-
est occupied molecular orbitals of compounds 1a—e.3,4
Table 1 indicates that the IP values of the nS molecular
orbitals of compounds 1a—e are much lower (9.03—9.30 eV)
than the IP values of the p,0 molecular orbitals (9.81—
10.54 eV), consequently, the electron donating ability of the
Me—S group is much higher than that of the P=O group.
These data allowed us to conclude that the most probable
pathway of this reaction is the route a (see Scheme 1).
Compound 1a was selected for further studies since it
contains, in contrast to compounds 1c,d, only two electron
donating centers, the S—Me and P=O groups. The reac-
tions of (dichloromethyl)arenes 2a,b and S-methyl diethyl-
thiophosphinate (1a) were carried out at a ratio 1a : 2 =
= 1 : 1 at 80—100 C. The experiments completely con-
firmed that this reaction proceeds by the route a. According
2, 3, 5: Ar = 4-MeOC6H4 (a), 3,5-But2-4-HOC6H2 (b)
Conventionally, compound 5 is synthesized from meth-
anethiol and its different mercaptides.5—7 Only one ex-
ample8 of the synthesis of compound 5 by electroreduction
of alkyl dithiocarboxylates is known. Note that alkyl di-
thiocarboxylates used in the synthesis were prepared9
using toxic CS2 and oranomagnesium compounds.
Intermediate -chlorothioesters 3a,b were not isolated
pure; their structures were confirmed by several transfor-
mations: by the reactions with an additional 1 equiv. of
compound 1a (see Scheme 2) and trialkyl phosphites 10
(Scheme 3), and by thermal decomposition to arenethio-
carbaldehydes, which are stable only in trimeric forms
11a,b (see Scheme 3). The reactions of compounds 3a,b
with trialkyl phosphites 10 were performed as three com-
ponent reactions between compounds 1a, 2, and 10.
This reactions result in new P,S-containing organic com-
pounds 12a,b.
1
to H and 31P NMR spectroscopy, the mixture obtained
by the reaction of 4-methoxybenzylidene dichloride (2a)
and ester 1a under the above conditions contains mainly
compounds 4 (P 75.0) and 3a (H 6.04 (s, ClCHSMe),
2.32 (s, SMe)). These data are indicative of the initial
attack of the thiol sulfur atom of compound 1a on the
methine carbon atom of gem-dichloride 2.
Apparently, no attack of the phosphoryl oxygen atom
of ester 1a on the methine carbon atom of dichloride 2
1
occurs since the H and 31P NMR spectra of the reac-
tion mixtures contain no signals at H 10.0 (ArCHO,
compound 8) and P 108.8 (Et2P(S)Cl, compound 9).
Scheme 3
Table 1. Vertical ionization potentials of the nS, p,0, and
n0 molecular orbitals of S-alkyl esters of phosphorus(IV)
acids 1a—e
Compound
nS
p,0
eV
n0
MeSP(O)Et2 (1a)
9.17*
9.03
9.12
9.26
9.30
9.87*
9.81
10.48
10.54
10.12
—
EtSP(O)Et2 (1b)
—
MeSP(O)(OEt)2 (1c)
EtSP(O)(OEt)2 (1d)
EtSP(O)(OMe)Me (1e)
11.23
10.95
10.70
11: Ar = 4-MeOC6H4 (a), 3,5-But2-4-HO-C6H2 (b)
12: Ar = 3,5-But2-4-HO-C6H2, R = Me (a), Et (b)
* Calculated from additivity of IP of the nS and p,0 orbit-
als of compounds 1b and 1c,d.

Mono- and di(dechloromethylthioylation)
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 10, October, 2019
1891
(s, 6 H, SCH3); 3.75 (s, 3 H, OCH3); 4.70 (s, 1 H, CH); 6.76,
-, -, and -Forms of trimers of arenethiocarb-
aldehydes were described earlier.10 - and -Forms are
different stereoisomers of individual trimers and -form
is a eutectic mixture of - and -forms. Melting point
of -form is much lower than that of -form. High
3
7.24 (both d, 2 H each, C6H4, JH,H = 8.6 Hz). Found (%):
C, 55.88; H, 6.73; S, 29.47. C10H14OS2. Calculated (%): C, 56.03;
H, 6.58; S, 29.92.
B. A mixture of dichloride 2a (3.82 g, 20 mmol) and S-methyl
diethylthiophosphinate (1a) (3.04 g, 20 mmol) was heated at
100 C for 4 h. 1H NMR spectrum of the reaction mixture showed
the resonances of compound 3a at H 6.04 (s, ClCH—S) and
H 2.32 (s, CHSMe). To the reaction mixture, compound 1a
(4.57 g, 30 mmol) was added and the mixture was heated at 100 C
for 3 h. The mixture was worked up as described in method A to
afford 2.23 g (52%) of compound 5a.
3,5-Di-tert-butyl-4-hydroxybenzaldehyde dimethyl dithio-
acetal (5b) was synthesized as described for compound 5a fol-
lowing method A from dichloride 2b (1.00 g, 3.5 mmol) and
thiophospinate 1a (1.58 g, 10.5 mmol). Yield 0.53 g (43%),
colorless crystals, m.p. 69—70 C. 1H NMR (acetone-d6), :
1.59 (s, 18 H, C(CH3)3); 2.24 (s, 6 H, SCH3); 4.89 (s, 1 H, CH);
5.56 (s, 1 H, OH); 7.32 (s, 2 H, C6H2). Found (%): C, 64.89;
H, 9.15; S, 20.13. C17H28OS2. Calculated (%): C, 65.33; H, 9.03;
S, 20.52.
1
melting points and H NMR spectral data of the syn-
thesized trimers 11a,b (one singlet signal for three axial
CH protons10) indicate that they exist in the β-form.
According to Campaigne and co-workers,10 the trithiane
ring of β-form of arenethiocarbaldehyde trimers adopts
the chair conformation with the axially positioned
three methine hydrogen atoms and the equatorially
positioned aryl groups. Thus, β-form of trimers of aren-
ecarbaldehydes 11a,b is (e,e,e)-cis,cis-2,4,6-triaryl-
1,3,5-trithiane.
Dimethyl [(3,5-di-tert-butyl-4-hydroxyphenyl)(methylthio)-
methyl]phosphonate (12a). A mixture of 3,5-di-tert-butyl-4-
hydroxybenzylidene dichloride (2b) (1.45 g, 5 mmol) and
S-methyl diethylthiophosphinate (1a) (1.14 g, 7.5 mmol) was
heated at 80 C for 1 h. The mixture was cooled to room tem-
perature and treated dropwise with trimethyl phosphite 10a
(1.55 g, 12.5 mmol) under stirring. The warming up of the reac-
tion mixture and evaluation of methyl chloride were observed.
After 16 h, the reaction mixture was diluted with diethyl ether
(10 mL) and washed with water (210 mL). The organic layer
was separated, dried with anhydrous NaSO4, and the drying agent
was filtered off. The solvent was removed in vacuo and the residue
was treated with anhydrous hexane (10 mL) to afford 0.86 g
(46% for two steps) of compound 12a, colorless crystals, m.p.
130—131 C (heptane). 1H NMR (acetone-d6), : 1.49 (s, 18 H,
(CH3)3); 2.16 (d, 3 H, SCH3, 4JP,H = 1.0 Hz); 3.57, 3.80 (both d,
In summary, in the present work we described a new
reaction between S-methyl diethylthiophosphinate and
(dichloromethyl)arenes. The analysis of the electronic
structure of S-alkyl esters of phosphorus(IV) acids predicted
and the experimental studies confirmed that this reaction
proceeds as either mono- or di(dechloromethylthioylation)
of the dichloromethyl group to give -chlorothioester and
dithioacetal of arenecarbaldehyde, respectively. The de-
veloped approach towards dimethyl dithioacetals of arene-
carbaldehydes excludes the use of highly toxic gaseous
methanethiol with an unpleasant odor.
3
2
3 H each, OCH2, JP,H = 10.5 Hz); 4.16 (d, 1 H, CH, JP,H
=
= 19.3 Hz); 6.19 (s, 1 H, OH); 7.40 (d, 2 H, C6H2, 4JH,H = 1.8 Hz).
31P NMR (acetone-d6), : 25.4. IR, /cm–1: 622, 634, 752
(C—S—C); 1179 (P—O—C); 1224 (P=O); 3138 (br., OH).
Found (%): C, 57.47; H, 8.63; P, 8.05, 8.19; S, 8.16, 8.31.
Experimental
1H NMR spectra were run on Tesla BS-567A and Bruker
MSL-400 instruments (the working frequencies of 100 and
400 MHz). The 1H NMR chemical shifts are given in the  scale
relative to the residual proton signals of the deuterated solvents
(DMSO-d6, acetone-d6, CDCl3). 31P NMR spectra were re-
corded on a Bruker MSL-400 spectrometer (the working fre-
quency of 162 MHz) using 85% H3PO4 as an external standard.
IR spectra were recorded on a Perkin-Elmer Spectrum 65 FT-IR
spectrometer within the range of 400—4000 cm–1; the samples
were prepared as the Nujol mulls. The reaction course was
monitored by 1H and 31P NMR spectroscopy.
4-Methoxybenzaldehyde dimethyl dithioacetal (5a). A. A mix-
ture of 4-methoxybenzylidene dichloride (2a) (3.82 g, 20 mmol)
and S-methyl diethylthiophosphinate (1a) (7.61 g, 50 mmol) was
heated at 100 C for 4 h. The reaction mixture was treated with
diethyl ether (20 mL), washed with water (220 mL), and dried
with anhydrous sodium sulfate. Removal of the solvent in vacuo
and subsequent vacuum distillation of the residue afforded
2.10 g (49%) of compound 5a, b.p. 169—170 C (12 Torr) (cf.
Ref. 8: b.p. 129—132 C (0.2 Torr)). 1H NMR (CDCl3), : 2.03
C
18H31O4PS. Calculated (%): C, 57.73; H, 8.34; P, 8.27; S, 8.56.
Diethyl [(3,5-di-tert-butyl-4-hydoxyphenyl)(methylthio)-
methyl]phosphonate (12b) was synthesized as described for
compound 12a from dichloride 2b (1.45 g, 5.0 mmol), thio-
phosphinate 1a (1.14 g, 7.5 mmol), and triethyl phosphite 10b
(2.08 g, 12.5 mmol). Yield 1.29 g (64%), colorless crystals, m.p.
101—104 C. 1H NMR (acetone-d6), : 1.15, 1.31 (both t,
3 H each, CH3, 3JH,H = 7.0 Hz); 1.50 (s, 18 H, C(CH3)3); 2.18
4
(d, 3 H, SCH3, JP,H = 1.0 Hz); 3.88—4.36 (m, 5 H, CH and
2 OCH2); 6.21 (s, 1 H, OH); 7.38 (d, 2 H, C6H2, 4JH,H = 1.8 Hz).
31P NMR (acetone-d6), : 23.1. Found (%): C, 59.37; H, 8.76;
P, 7.46, 7.52; S, 7.85, 8.01. C20H35O4PS. Calculated (%):
C, 59.62; H, 8.69; P, 7.71; S, 7.96.
(e,e,e)-cis,cis-2,4,6-Tris(4-methoxyphenyl)-1,3,5-trithiane
(11a). A mixture 4-methoxybenzylidene dichloride (2a) (3.82 g,
20 mmol) and S-methyl diethylthiophosphinate (1a) (3.04 g,
20 mmol) was heated at 100 C for 2 h and at 140 C for 4 h. The
reaction mixture was treated with anhydrous CCl4 (10 mL),
the crystalline product was collected by filtration, and washed

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 10, October, 2019
Gazizov et al.
successively with anhydrous CCl4 (25 mL) and acetone to
obtain 2.28 g (75%) of compound 11a, m.p. 181—182 C (ethyl
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This work was financially supported by the Ministry of
Science and Higher Education of the Russian Federation
in the framework of the basic part of the state task in the
field of scientific activity (Project No. 4.5348.2017/8.9).
Received May 13, 2019;
in revised form June 20, 2019;
accepted July 1, 2019