Three component reactions of enamines, O,O-dialkyldithiophosphoric acids, and electrophiles

Article abstract of DOI:10.1007/s11172-020-2730-x

The product of addition of O, O-dialkyldithiophosphoric acid to enamine reacted with the third reaction component of electrophilic nature, for instance, acetyl chloride, α-bromo ether, or sulfenyl bromide. The reaction involving sulfenyl bromide gave the

Full text of DOI:10.1007/s11172-020-2730-x

110
Russian Chemical Bulletin, International Edition, Vol. 69, No. 1, pp. 110—113, January, 2020
Three component reactions of enamines,
O,O-dialkyldithiophosphoric acids, and electrophiles
M. B. Gazizov, R. A. Khairullin, Yu. S. Kirillina, S. Yu. Ivanova, K. S. Gazizova, and Kh. R. Khayarov
Kazan National Research Technological University,
8 ul. K. Marksa, 420015 Kazan, Russian Federation.
6
Fax: +7 (843) 231 9505. E-mail: mukattisg@mail.ru
The product of addition of O,O-dialkyldithiophosphoric acid to enamine reacted with the
third reaction component of electrophilic nature, for instance, acetyl chloride, α-bromo ether,
or sulfenyl bromide. The reaction involving sulfenyl bromide gave the product of reduction of
the C—Hal bond of iminium salt and bis(dialkoxythiophosphorylthio) disulfide. This experi-
mentally confirmed the occurrence of the reaction between 2-halo-substituted ald- or ketimines
with thio acids via enamine intermediates.
Key words: enamines, O,O-dialkyldithiophosphoric acids, sulfenyl bromides, bis(dialkoxy-
thiophosphoryl) disulfide, iminium salts.
Phosphorus(IV) dithio acids occupy a prominent place
substituted ald- and ketimines 1 with O,O-dialkyldithio-
phosphoric acids 2. The possibilities to find new reactions
leading to novel multifunctional derivatives were also
anticipated. We have found that O,O-dialkyldithiophos-
phoric acids 2 reacted with N-alkyl-2-bromo-2-methyl
1
—4
in the chemistry of organophosphorus compounds.
Pronounced electrophilic and nucleophilic properties of
phosphorus(IV) dithio acids are caused by their rela-
tively strong acidity and the high nucleophilicity of the
P(S)S triad. These acids readily add to multiple bonds,
1
1—13
14
(1a,b)
, -2-chloro-2-phenyl (1c) , -2,2-dichloro
4
—8
15,16
for instance, to the C=N iminium double bonds.
(1d), and -dibromo (1e) aldimines
and 2-methyl-1-
2
14
The reaction carried out in ethanol gives adducts R C H -
phenyl-2-chloro ketimine (1f) to give initially iminium
salts 3. The excess of acid 2 caused the reduction of the
C—Hal bond of the cation of salts 3 to produce iminium
6
4
3
1
7
CH(NHC H R )SP(S)(OR ) , while in hexane the re-
6
4
2
action stops at the protonation step to produce imin-
+
2
–
1
ium salts [PhCH=N HR ][ SP(S)(OR ) ], which were
salts 4 and bis(dialkoxythiophosphoryl) disulfides 5 as the
2
isolated pure.9 In the solutions, these salts reversibly
transform into the adducts, but upon long-term storage
they gave the complex product mixtures. Of halo-sub-
stituted imines, only chloral imine was involved in
the reactions with phosphorus(IV) dithio acids. These
main products.
11—16
We suggested that the reduction of
salt 3 is a halophilic elimination initiated by O,O-dialkyl-
‒
dithiophosphoric anion (RO) P(S)S that proceeds via
2
intermediate (dialkoxythiophosphoryl)sulfenyl halide
(RO) P(S)SHal 6 and bipolar ion 7a. Structure 7a can be
2
transformations gave a stable adduct CCl CH(NHPh)-
regarded as a resonance structure of enamine 7b with the
3
1
0
14—16
SP(S)(OR)2.
separated charges.
Protonation of species 7 and
Earlier, we preformed the first studies of the reactions
of 2-monohalo- and 2,2-dihalo-substituted N-alkyl-
abstraction of dithiophosphoric anion with sulfenyl halide
6 provides the final products 4 and 5 (Scheme 1).
Scheme 1
1
i
1
t
1
t
1
: X = Me, Hal = Br, Y = H, R = Pr (a), Bu (b); X = Ph, Hal = Cl, Y = H, R = Bu (c); X = Hal = Cl, Y = H, R = Bu (d); X = Hal = Br, Y = H,
1
i
1
i
2
i
R
= Pr (e); X = Me, Hal = Cl, Y = Ph, R = Pr (f); 2: R = Pr (a), Et (b)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0110—0113, January, 2020.
066-5285/20/6901-0110 © 2020 Springer Science+Business Media, Inc.
1

Bis(dialkoxythiophosphoryl) disulfide
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
111
Scheme 2
To the best of our knowledge, the reactions of O,O-di-
alkyldithiophosphoric acids 2 with enamines have not been
described. In order to confirm the occurrence of the reduc-
tion of salt 3 via enamine intermediate we studied herein
the reactions of readily available and stable enamine 8 with
a series of phosphoric acids 2.
Since sulfenyl halide 6 is involved in the formation of
disulfide 5 (see Scheme 1), we started our studies from the
successive reactions of enamine 8 with acid 2a and com-
pound 6 (Scheme 2).
Addition of sulfenyl bromide 6 to the reaction mixture
initiated the exothermic process leading to disulfide 5 and
the product of reduction 12a (see Scheme 2). Compound
12a can be considered as the analog of the hypothetical
structure 14, which, in turn, is the analog of the iminium
salt 3 initially formed from compounds 1 and 2. This result
of the three-component reaction of enamine, dithio acid,
and sulfenyl bromide proves the occurrence of the reaction
between compounds 1 and 2 via enamine intermediates
of type 7 (see Scheme 1).
These reactions give the product of addition to the
double bond 11a. We believe that the reaction is initiated
by protonation of the nitrogen atom of enamine 8 with
acid 2a to give an ammonium salt, O,O-diisopropyl S-4-
(
2-methyl-1-propenyl)morpholinium dithiophosphate (9).
With the aim to synthesize new multifunctional de-
rivatives, we expanded the scope of the electrophiles. For
instance, we examined the behavior of propionyl chloride
Next, due to a prototropic exchange, salt 9 is intercon-
verted into an iminium salt, 4-(2-methylpropylidene)-
morpholinium dithiophosphate (10a). Finally, salt 10a is
transformed into the isolated product of the reaction,
O,O-diisopropyl S-1-(morpholin-4-yl)-2-methylpropyl
dithiophosphate (11a).
(
15) and α-bromo ether 16 (Scheme 4).
Propionyl thio derivative 17 has not been previously
described. However, closely related S-acetyl O,O-dialkyl
i
dithiophosphates (RO) P(S)SCOMe, including (Pr O) -
We were unable to experimentally confirm the forma-
tion of salts 9 and 10a. Besides, the structurally related
2
2
P(S)SCOMe, are known. For the synthesis of these com-
pounds several following methods were suggested: the
4
-cyclopentylidenemorpholinium O,O-diisopropyl dithio-
phosphate 10b was prepared pure from enamine 13
Scheme 3). It should be noted that in this case product
1b was not detected.
reaction of potassium ((RO) P(S)SK) or lead ([(RO) P-
2
2
(
S)S] Pb) salts of dialkyldithiophosphoric acid with acetyl
(
1
2
1
7
chloride; the addition of sulfur to S-acetyl dialkyl thio-
1
8
phosphites (RO) PSC(O)Me; and the reaction of MeCN
2
1
9
with acid 2 in the presence of acetic acid. Thus, we
developed a new synthetic procedure to O,O-dialkyl
S-alkanoyl dithiophosphates.
Scheme 3
We also suggested a new method for synthesizing O,O-di-
ethyl S-methoxymethyl dithiophosphate (18) (see Scheme 4).
Earlier, compound 18 was synthesized by methylation of
O,O-diethyl S-hydroxymethyl dithiophosphate (EtO) P(S)-
2
2
0
SCH OH with diazomethane.
2
In summary, three component reactions of enamines,
O,O-diisopropyldithiophosphoric acid, and (diisoprop-
oxythiophosphoryl)sulfenyl bromide as the electrophilic

112
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
Gazizov et al.
Scheme 4
i
1
: R = Pt (a), Et (c)
species give bis(diisopropoxythiophosphoryl) disulfide and
the product of the reduction of the C—Br bond of iminium
salt. This result experimentally confirms the formation of
enamine intermediate in the reactions of 2-halo-substi-
tuted ald- and ketimines with dithio acids. New methods
towards P,S-containing organic compounds were ela-
borated.
(1.04 g, 6.5 mmol). Cooling was removed and the reaction mix-
ture was kept at room temperature for 16 h. The precipitate
formed was collected by filtration and dried to afford 2.45 g (85%)
1
of iminium salt 12a. H NMR (CDCl ), δ : 1.39 (d, 6 H, CHMe ,
3
H
2
3
JH,H = 6.7 Hz); 3.24 (m, 1 H, CHMe ); 3.96 (m, 4 H, OCH );
2
2
+
+ 3
4
.03 (m, 4 H, N CH ); 9.39 (d, 1 H, HCN , J
= 8.5 Hz).
2
H,H
13
C NMR (CDCl ), δ : 19.50 (CHMe ), 30.62 (CHMe ), 51.89,
3
C
2
2
+
+
5
9.14 (N (CH ) ), 66.35 (O(CH ) ), 180.1 (HCN ). Found (%):
2 2 2 2
C, 42.63; H, 6.98; N, 6.01. C H16BrNO. Calculated (%):
8
Experimental
C, 43.26; H, 7.26; N, 6.31. Concentration of the mother liquor
in vacuo afforded 4.30 g (78%) of disulfide 5, m.p. 92 °C (cf.
1H and 13C NMR spectra were recorded with Tesla BS-567A
Ref. 21: m.p. 91.5—93.0 °C). H NMR (CDCl ), δ : 1.40, 1.42
1
3
H
3
(
(
working frequency of 100 MHz) and Bruker AVANCE 400WB
working frequencies of 400.13 and 100.61 MHz, respectively)
(both d, 24 H, Me CH, J
= 6.4 Hz); 4.90 (d.hept, 4 H,
2
H,H
3
3
13
CHOP, J
= 6.4 Hz, J
= 12.0 Hz). C NMR (CDCl ),
H,H
P,H
3
1
13
3
3
spectrometers in CDCl . The H and C chemical shifts are
δ : 23.75 (d, Me, J
= 4.5 Hz); 23.57 (d, Me, J
= 5.5 Hz);
3
C
P,C
P,C
1
2
31
given in the δ scale relative to the residual proton signal ( H) and
74.76 (d, CH, J
= 6.7 Hz). P NMR (CDCl ), δ : 81.70.
P,C
3
P
1
3
the central signal of the carbon atom ( C) of the solvent and
O,O-Diisopropyl S-propionyl dithiophosphate (17). A reaction
mixture prepared from enamine 8 (1.41 g, 10 mmol), acid 2a
(2.14 g, 10 mmol), and dioxane (20 mL) was treated dropwise
with a solution of propionyl chloride 15 (0.92 g, 10 mmol) in
dioxane (10 mL) at –5 °C. Cooling was removed and the reaction
mixture was kept at room temperature for 16 h. The precipitate
formed was collected by filtration and dried to afford 1.70 g (96%)
of 4-(3-methylpropylidenemorpholinium) chloride (12b).
3
1
recalculated to Me Si. P NMR spectra were run on a Bruker
4
AVANCE 400WB (working frequency of 161.98 MHz) instru-
ment. The 31P chemical shifts are given relative to 85% H PO
3
4
(
an external standard).
O,O-Diisopropyl S-1-(morpholin-4-yl)-2-methylpropyl di-
thiophosphate (11a). To a solution of enamine 8 (1.41 g, 10 mmol)
in CCl (5 mL), a solution of acid 2a (2.14 g, 10 mmol) in CCl
4
4
1
3
(
10 mL) was added dropwise maintaining the reaction tempera-
H NMR (CDCl ), δ : 1.40 (d, 6 H, CHMe , J
= 6.6 Hz);
3
H
2
H,H
ture at 0—5 °C. Cooling was removed and the reaction mixture
3.03 (m, 1 H, CHMe ); 4.04 (m, 4 H, OCH ); 4.27 (m, 4 H,
2
2
+
+ 3
was kept at room temperature for 24 h. Removal of the volatiles
N CH ); 9.90 (d, 1 H, HCN , J
= 8.3 Hz). Found (%):
2
H,H
in vacuo afforded 3.27 g (92%) of crystalline product 11a with
C, 53.79; H, 8.87; N, 7.53. C H16ClNO. Calculated (%):
8
1
purity of 96%, m.p. 78—79 °C. H NMR (CDCl ), δ : 1.12 (d,
C, 54.08; H, 9.08; N, 7.88. Concentration of the mother liquor
3
H
6
H, CHMe2, 3JH,H = 6.6 Hz); 1.32 (d, 12 H, Me CHO,
in vacuo and vacuum distillation of the residue afforded 2.13 g
2
3
1
JH,H = 6.3 Hz); 2.16 (m, 1 H, CHMe ); 2.72 (t, 4 H, NCH ,
(77%) of product 17, b.p. 101—102 °C (0.09 Torr). H NMR
2
2
3
3
3
JH,H = 4.7 Hz); 3.70 (t, 4 H, OCH , J
= 4.7 Hz); 4.73 (sept,
(CDCl ), δ : 1.18 (t, 3 H, MeCH , J
= 7.5 Hz); 1.34, 1.39
2
H,H
3
H
2
H,H
3
3
3
2
H, CHOP, J
= 6.3 Hz); 4.97 (d, 1 H, CHN, J
= 10.2 Hz).
(both d, 12 H, CHMe , J
= 6.2 Hz); 2.65 (q, 2 H, MeCH ,
H,H
H,H
2
H,H 2
1
3
3
3
31
C NMR (CDCl ), δ : 20.98 (CHMe ), 23.73 (d, Me CHO,
JH,H = 7.5 Hz); 4.96 (sept, 2 H, CHOP, J
= 6.2). P NMR
H,H
3
C
2
2
3J
6
(
= 5.0 Hz); 32.81 (CHMe ), 49.84 (NCH ), 63.72 (SCH),
(CDCl ), δ : 76.86. Found (%): C, 39.73; H, 7.26; P, 11.32.
C H O PS . Calculated (%): C, 39.98; H, 7.08; P, 11.46.
9 19 3 2
P,C
2
2
3 P
2
31
6.33 (OCH ), 72.47 (d, POCH, JP,C = 7.5 Hz). P NMR
2
CDCl ), δ : 98.9. Found (%): C, 47.16; H, 8.23; N, 3.61; P, 8.51.
O,O-Diethyl S-methoxymethyl dithiophosphate (18). A reac-
3
P
C14H30NO PS . Calculated (%): C, 47.30; H, 8.51; N, 3.94;
tion mixture prepared from enamine 8 (4.10 g, 29 mmol), acid
3
2
P, 8.73.
-(3-Methylpropylidene)morpholinium bromide (12a). To
2b (5.39 g, 29 mmol), and CCl (40 mL) was treated dropwise
4
4
with a solution of bromo(methoxy)methane 16 (3.60 g, 30 mmol)
a solution of enamine 8 (2.79 g, 13 mmol) in CCl (10 mL),
in CCl (40 mL) at –5 °C. Cooling was removed and the mixture
4
4
a solution of acid 2a (1.84 g, 13 mmol) in CCl (10 mL) was
was kept at room temperature for 16 h. The precipitate formed
was collected by filtration and dried to afford 5.50 g (86%) of
iminium salt 12a. Concentration of the mother liquor in vacuo
and vacuum distillation of the residue afforded 5.20 g (79%) of
4
added dropwise maintaining the reaction temperature at 0—5 °C.
Cooling was removed and the mixture was stirred at room tem-
perature for 5 h. 31P NMR spectrum showed intense resonance
at δ 98.9 attributable to the phosphorus atom of compound 11a.
product 18, b.p. 75—76 °C (0.05 Toff) (cf. Ref. 20: b.p. 103 °C
P
1
The mixture was cooled to –15 °C and treated dropwise with
(0.1 Torr)). H NMR (CDCl ), δ : 1.35 (t, 6 H, MeCH ,
3
H
2
3
a solution of (diisopropoxythiophosphoryl)sulfenyl bromide (6)
JH,H = 7.1 Hz); 3.38 (s, 3 H, OMe); 4.10, 4.18 (both q, 4 H,
3
3
in CCl , prepared from disulfide 5 (2.77 g, 6.5 mmol) and bromine
CH OP, J
= 7.1 Hz); 5.06 (d, 2 H, SCH , J
= 20.4 Hz).
4
2
H,H
2
P,H

Bis(dialkoxythiophosphoryl) disulfide
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
113
1
3
C NMR (CDCl ), δ : 15.90 (Me), 56.95 (OMe), 63.75
6. I. V. Konovalova, L. A. Burnaeva, Reaktsiya Pudovika [The
Pudovik Reaction], Izd-vo KGU, Kazan´, 1991, 146 pp.
(in Russian).
7. A. N. Pudovik, M. K. Sergeeva, Zh. Obshch. Khim. [Russ. J.
Gen. Chem.], 1955, 25, 1759 (in Russian).
8. A. N. Pudovik, M. G. Zimin, Pure Appl. Chem., 1980, 52, 989.
9. M. G. Zimin, N. G. Zabirov, R. A. Cherkasov, A. N. Pudovik,
Zh. Obshch. Khim. [Russ. J. Gen. Chem.], 1978, 48, 1020
(in Russian).
10. M. G. Zimin, N. G. Zabirov, R. A. Cherkasov, A. N. Pudovik,
Zh. Obshch. Khim. [Russ. J. Gen. Chem.], 1980, 50, 1458
(in Russian).
11. M. B. Gazizov, N. G. Aksenov, O. G. Sinyashin, Tetrahedron
Lett., 2015, 56, 4993; DOI: 10.1016/j.tetlet.2015.07.010.
12. M. B. Gazizov, R. A. Khairullin, A. I. Perina, A. A. Minni-
khanova, N. G. Aksenov, O. I. Gnezdilov, A. V. Il´yasov,
Kh. R. Khayarov, Russ. J. Gen. Chem., 2016, 86, 499.
13. M. B. Gazizov, R. A. Khairullin, Yu. S. Kirillina, N. Yu.
Bashkirtseva, K. S. Gazizova, S. Yu. Ivanova, in Advances in
Chemistry Research, Ed. J. C. Taylor, Nova Sci. Publ.,
New York, 2017, Vol. 41, p. 1.
3
C
2
2
(
d, POCH , J
= 5.6 Hz), 78.48 (d, SCH , J
= 3.8 Hz).
2
P,C
2
P,C
3
1
P NMR (CDCl ), δ : 94.77. Found (%): C, 31.12; H, 6.78;
3
P
P, 13.45. C H O PS . Calculated (%): C, 31.29; H, 6.57;
6
15
3
2
P, 13.28.
-Cyclopentylidenemorpholinium O,O-diisopropyl dithiophos-
phate (10b). To a solution of 4-(cyclopent-1-en-1-yl)morpholine
13) (1.53 g, 10 mmol) in anhydrous CCl (10 mL), a solution
4
(
4
of acid 2a (2.14 g, 10 mmol) was added dropwise under argon
maintaining the reaction temperature at 0—5 °C. Cooling was
removed and the reaction mixture was stirred at room tempera-
ture for 5 h. The precipitate formed was collected by filtration
and dried to afford 3.50 g (95%) of salt 10b contaminated with
1
5
% morpholinium dithiophosphate. H NMR (CDCl ), δ : 1.25
3
H
3
(
d, 12 H, MeCHOP, J
= 6.6 Hz); 2.13 (m, 4 H, 2 CH );
H,H 2
3
.22 (m, 4 H, =C(CH ) ); 4.09 (m, 4 H, O(CH ) ); 4.14 (m, 4 H,
2 2 2 2
+
N (CH ) ); 4.69 (sept, 2 H, CHOP). Found (%): C, 48.79;
2
2
H, 7.95; N, 4.03; P, 8.21. C15H30NO PS . Calculated (%):
3
2
C, 49.02; H, 8.23; N, 3.81; P, 8.45.
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).
14. M. B. Gazizov, R. A. Khairullin, Yu. S. Kirillina, S. Yu.
Ivanova, Kh. R. Khayarov, O. D. Khairullina, Russ. Chem.
Bull., 2018, 67, 2241.
5. M. B. Gazizov, R. A. Khairullin, N. G. Aksenov, Yu. S.
Kirillina, A. Yu. Bandikova, Russ. Chem. Bull., 2016, 65, 1119.
1
References
1
6. M. B. Gazizov, R. A. Khairullin, N. G. Aksenov, Tetrahedron
Lett., 2016, 57, 272; DOI: 10.1016/j.tetlet.2015.11.095.
17. M. I. Kabachnik, T. A. Mastryukova, Russ. Chem. Bull., 1954,
3, 369; DOI: 10.1007/BF01167812.
18. V. A. Al´fonsov, D. A. Pudovik, R. Z. Musin, V. N. Naz-
mutdinova, Yu. Ya. Efremov, É. S. Batyeva, A. N. Pudovik,
Zh. Obshch. Khim. [Russ. J. Gen. Chem.], 1988, 58, 1734
(in Russian).
19. N. G. Zabirov, F. M. Shamsevaleev, R. A. Cherkasov,
Zh. Obshch. Khim. [Russ. J. Gen. Chem.], 1991, 61, 616
(in Russian).
20. H. G. Corkins, L. Storace, D. Weinberger, E. Osgood,
S. Lowery, Phosphorus Sulfur Relat. Elem., 1981, 10, 133;
DOI: 10.1080/03086648108077494.
1
. D. Purdela, R. Vîlceanu, Chimia compuşilor organici ai fos-
forului şi ai acizilor lui [Chemistry of Organophosphorus
Compounds], Editura Academiei R. S. Romania, Bucharest
1
965, 539 p. (in Romanian).
. É. E. Nifant´ev, Khimiya fosfororganicheskikh soedinenii
Chemistry of Organophosphorus Compounds], Izd-vo Moscow
2
3
4
[
State University, Moscow, 1971, 351 pp. (in Russian).
. D. E. C. Corbridge, Phosphorus: Chemistry, Biochemistry and
Technology, Elsevier Sci. Publ., Amsterdam—New York,
2
nd ed., 1980, 560 pp.
. R. A. Cherkasov, Stroenie ditiokislot fosfora i ikh reaktsion-
naya sposobnost´ v reaktsiyakh pricoedineniya [Structure of
Phosphorous Dithio Acids and their Reactivity in Addition
Reactions], in Stroenie i reaktsionnaya sposobnost´ orga-
nicheskikh soedinenii [Structure and Reactivity of Organic
Compounds], Nauka, Moscow, 1978, 202 pp. (in Russian).
. A. N. Pudovik, I. V. Gur´yanova, É. A. Ishmaeva, Reaktsii i
metody issledovaniya organicheskikh soedinenii [Reactions and
Evaluation of Organic Compounds], Eds B. A. Kazanskii, I. L.
Knunyants, M. M. Shemyakin, N. N. Mel´nikova, Khimiya,
Moscow, 1968, Vol. 19, 848 pp. (in Russian).
21. A. G. Liakumovich, V. Kh. Kadirova, N. A. Mukmenova,
S. V. Bukharova, Zh. Obshch. Khim. [Russ. J. Gen. Chem.],
1991, 61, 260 (in Russian).
5
Received June 7, 2019;
in revised form September 2, 2019;
accepted October 4, 2019