Sequential Interaction of Enamine with O, O-Dialkyldithiophosphoric Acid and Electrophilic Reagent

Article abstract of DOI:10.1134/S1070363220010120

The adduct of O, O-dialkyldithiophosphoric acid and enamine reacts exothermically with an electrophilic reagent. In the case of sulfenyl bromide, the iminium salt reduced at the C-Br bond and bis(dialkoxythiophosphorylthio)-disulfide have been formed, experimentally evidencing the reaction of 2-halogenated ald- and ketimines with dithioic acid via the intermediate formation of enamine.

Full text of DOI:10.1134/S1070363220010120

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 1, pp. 84–88. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Obshchei Khimii, 2020, Vol. 90, No. 1, pp. 111–116.
Sequential Interaction of Enamine
with O,O-Dialkyldithiophosphoric Acid and Electrophilic Reagent
a
a,
a
a
a
R. A. Khairullin , M. B. Gazizov *, Yu. S. Kirillina , S. Yu. Ivanova , and L. P. Shamsutdinova
a
Kazan National Research Technological University, Kazan, 420015 Russia
*e-mail: mukattisg@mail.ru
Received June 10, 2019; revised June 10, 2019; accepted June 13, 2019
Abstract—The adduct of O,O-dialkyldithiophosphoric acid and enamine reacts exothermically with an electrophilic
reagent. Inthecaseofsulfenylbromide, theiminiumsaltreducedattheC–Brbondandbis(dialkoxythiophosphorylthio)-
disulfide have been formed, experimentally evidencing the reaction of 2-halogenated ald- and ketimines with
dithioic acid via the intermediate formation of enamine.
Keywords: enamines, O,O-dialkyldithiophosphoric acid, sulfenyl bromide, bis(dialkoxythiophosphorylthio)-
disulfide
DOI: 10.1134/S1070363220010120
We have earlier shown for the first time that the in-
teraction of N-alkyl-2-bromo-2-methyl- (1a, 1b) [1–3],
diate formation of О,О-dialkylthiophosphorylsulfenyl
halide (RO) P(S)SHlg 6 and bipolar ion 7a, the latter
2
2
-phenyl-2-chlor- (1c) [4], 2,2-dichlor- (1d), or -dibromal-
being one of the resonance structures of enamine 7b with
separated charges [4–6]. Protonation of structure 7 and
trapping the dithiophosphate anion with sulfenyl halide
6 affords the final products 4 and 5 (Scheme 1).
dimide (1e) [5–6] and 2-chloro-2-methyl-1-phenylket-
imine 1f [4] with О,О-dialkyldithiophosphoric acids 2
yields initially the iminium salt: ald- or ketiminium di-
thiophosphate 3. The presence of excess of acid 2 has led
to the reduction of the cation of salt 3 at the C–Hlg bond,
the major products being the reduced iminium salt 4 and
bis(dialkoxythiophosphorylthio) disulfide 5 (Scheme 1)
The reaction of О,О-dialkyldithiophosphoric acids 2
with enamines has not been described in the literature.
We studied it in order to experimentally confirm the
reduction of salt 3 via the intermediate enamine forma-
tion. Since the enamines bearing primary and secondary
amine groups are unstable, we utilized the enamines with
tertiary amine group. The enamines containing a nitrogen-
[1–6]. The suggested scheme of salt 3 reduction involves
the halophilic elimination under the action of О,О-
dialkyldithiophosphate anion (RO) P(S)S and interme-
‒
2
Scheme 1.
+
1
2
P(S)Sꢀ
1
2
MeC(X)(Y)CZ=NR + (R O) P(S)SH
MeC(X)(Y)CZ=N H
3
R (R O)
2
2
1
2
3
MeC(X)CZ=N HR1
+
1
2
[
MeC(X)=CZꢀNHR ] + (R O) P(S)SY
2
ꢀ
ɚ
7b
6
2
(
R O) P(S)SH
2
+
1
2
ꢀ
2
MeCH(X)CZ=N HR (R O) P(S)S + (R O) P(S)SY
2
2
+
1
2
2
MeCH(X)CZ=N HR Y + (R O) P(S)SSP(S)(OR )
2
2
4
5
1
1
X = Me, Y = Br, Z = H, R = i-Pr (1a), t-Bu (1b); X = Ph, Y = Br, Z = H, R = t-Bu (1c); X = Y = Cl, Z = H,
1
1
1
2
R = t-Bu (1d); X = Y = Br, Z = H, R = t-Bu (1e); X = Me, Y = Cl, Z = Ph, R = i-Pr (1f); R = i-Pr (ꢁɚ), Et (2b).
8
4

SEQUENTIAL INTERACTION OF ENAMINE
85
Scheme 2.
8: О,О-diisopropyl[1-(perhydro-1,4-oxazin-4-yl)-2-
methylpropylthio]dithiophosphate 12a.
Me C=CH
N
O
N
O
The formation of salts 10 and 11a could not be ob-
served experimentally. However, 4-(cyclopentene-1,1-di-
yl)perhydro-1,4-oxazinium diisopropoxydithiophosphate
2
8
9
11b analogous to salt 11a was isolated (Scheme 4). The
formation of product 12b was not observed under the
reaction conditions.
containing heterocycle such as morpholine [4-(2-methyl-
-propen-1-yl)perhydro-1,4-oxazine 8 and 4-(cyclo-
penten-1-yl-1)perhydro-1,4-oxazine 9] (Scheme 2)
1
The addition of sulfenyl bromide 6 to the mixture led
to exothermic reaction with the formation of disulfide 5
and reduction product 13 of the hypothetic analog 14 of
the iminium salt 3 initially formed from compounds 1
and 2 (Scheme 5).
were readily available.
Since the formation of disulfide 5 involved sulfenyl
halide 6, we investigated the sequential interaction of
enamines 8 and 9 with acid 2 and compound 6 (Scheme 3).
Such experimental outcome of sequential three-com-
ponent interaction of enamine, dithioacid, and sulfenyl
bromide was an evidence of the reaction of N-alkyl-
2-haloald(ket)imines 1 with О,О-dialkyldithiophosphoric
acids 2 via the intermediate formation of enamine 7.
The interaction with enamine 8 with acid 2 gave the
product of addition at the double bond 12. We suggested
that acid 2 first protonated enamine 8 at the nitrogen atom,
affording the ammonium salt: 4-(2-methyl-1-propenyl)-
perhydro-1,4-oxazinium diisopropoxydithiophos-
phate 10 which was converted into the iminium salt:
To elaborate novel methods of synthesis of poly-
functional organic compounds, we extended the range
of the electrophilic agents: propionyl chloride 15 and
α-bromoether 16 were introduced in the reaction instead
of sulfenyl bromide 6 (Scheme 6).
4,4-(2-methylpropane-1,1-diyl)perhydro-1,4-oxazinium
dithiophosphate 11a, via prototropy salt 11a was trans-
formed into the product of acid 2 addition to enamine
Scheme 3.
H
N
+
i-PrO) PSSꢀ
Me C=CH
N
O + (i-PrO) PSSH
Me
2
C=CH
O
(
2
2
2
8
2a
10
+
N
+ 6
..
N
Me CH CH
O (i-PrO) PSSꢀ
Me CH CH
O
2
2
2
S
P(OPr-i)2
11a
S
(
i-PrO) P(S)ꢀSꢀBr
2
12a
+
N
ꢀ
Me CH CH
O Br ꢁ+ [(i-PrO)
2
P(S)S]
2
2
13a
5a
Scheme 4.
ꢂ
N
ꢀ
O (i-PrO) P(S)S
N
O
2
SP(S)(OPr-i)2
11b
12b
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 1 2020

86
KHAIRULLIN et al.
Scheme 5.
NMR spectra were recorded using AVANCE 400WB
161.98 MHz) instrument, the chemical shifts were re-
ported relative to 85% H PO as external reference.
(
+
ꢀ
Me C(Hlg) CH
N
O
(RO) P(S)S
3
4
2
2
О,О-Diisopropyl[1-(perhydro-1,4-oxazin-4-yl)-2-
methylpropylthio] dithiophosphate (12a).Asolution of
1
4
2
.14 g (0.01 mol) of acid 2a in 10 mL of CCl was added
4
The obtained propionylthio derivative 17 has not
been described in the literature. However, О,О-dialkyl-S-
dropwise to a solution of 1.41 g (0.01 mol) of enamine 8 in
mL of CCl , maintaining the reaction mixture tempera-
5
4
acetyl dithiophosphates (RO) P(S)SCOMe 19 including
2
ture at 0–5°С. The temperature was increased to ambient,
and the mixture was kept during 1 day. The solvent was
evaporated under reduced pressure to afford 3.27 g (92%)
of crystalline product with purity 96%, mp 78–79°С. Н
NMR spectrum, δ, ppm: 1.12 d (6H, CHMe , J
(
1
i-PrO) P(S)SCOMe 19a have been known. Compounds
2
9 have been obtained via several methods: reaction of
potassium (RO) P(S)SK or lead [(RO) P(S)S] Pb salt
2
2
2
1
of dialkyldithiophosphoric acid with acetyl chloride
7]; addition of sulfur to dialkyl-S-acetylphosphites
3
=
2
HH
[
(
3
6
.6 Hz), 1.32 d (12H, Me CHO, J = 6.3 Hz), 2.16 m
2
HH
3
RO) PSCOMe [8]; and interaction of acetonitrile MeCN
2
(1H, CHMe ), 2.72 t (4H, NCH , J = 4.7 Hz), 3.70 t
2 2 HH
with acid 2 in the presence of acetic acid [9]. Hence,
we elaborated a novel method of synthesis of О,О-
dialkylalkanoylthio dithiophosphates.
3
(
4H, OCH ), 3 J = 4.7 Hz), 4.73 septet (2H, CHOP,
2 HH
3
JHH = 6.3 Hz), 4.97 d (1H, CHN, 3JHH = 10.2 Hz).
1
3
С NMR spectrum, δ , ppm: 20.98 (CHMe ), 23.73 d
C
2
Moreover, we suggested a novel method of preparation
of О,О-diethyl(methoxymethylthio) dithiophosphate 18
3
(Me CHO, J = 5.0 Hz), 32.81 (CHMe ), 49.84 (NCH ),
2 PC 2 2
2
6
7
4
3.72 (SCH), 66.33 (OCH ), 72.47 d (POCH, J
=
PC
2
(
Scheme 6) which has been earlier obtained via methyla-
tion of О,О-diethyl(hydroxymethylthio)dithiophosphate
EtO) P(S)SCH OH 19 using diazomethane [10].
31
.5 Hz). P NMR spectrum: δ 98.9 ppm. Found, %: C
P
7.16; H 8.23; N 3.61. C H NO PS . Calculated, %: C
1
4
30
3
2
(
2
2
47.30; H 8.51; N 3.94.
It should be noted that sequential interaction of
Sequential reactions of enamine 8 with acid 2 and
electrophiles 6, 15, or 16. a. Interaction with O,O-di-
isopropylthiophosphorylsulfenyl bromide 6. A solution
enamine with О,О-diisopropoxydithiophosphoric acid
and О,О-diisopropoxythiophosphorylsulfenyl bromide
as the electrophile gave bis(diisopropoxythiophosphoryl-
thio) disulfide and the iminium salt reduced at the C–Br
bond, experimentally evidencing the formation of the
enamine intermediate in the reactions of 2-haloald(ket)-
imines with dithioacids. Novel methods of the P,S-con-
taining organic compounds were elaborated.
of 1.84 g (0.013 mol) of acid 2a in 10 mL CCl was
4
added dropwise to a solution of 2.79 g (0.013 mol) of
enamine 8 in 10 mL of CCl maintaining the reaction
4
mixture temperature at 0–5°С. The mixture temperature
was then raised to ambient, and the mixture was stirred
31
during 5 h. The Р NMR spectrum contained a strong
resonance signal at δ 98.9 ppm assigned to phosphorus
atom in compound 12a. Asolution of sulfenyl bromide 6
P
EXPERIMENTAL
1
13
Н and С NMR spectra were recorded using Tesla
in CCl prepared from 2.77 g (0.0065 mol) of disulfide 5
4
BS-567A (100 MHz) and AVANCE 400WB (400.13
and 1.04 g (0.0065 mol) of bromine was added dropwise
at –15°С. The mixture was heated to ambient and kept
overnight. The precipitate was filtered off and dried to
and 100.61 MHz) instruments in CDCl . The chemical
3
shifts relative to TMS were determined using residual
3
1
1
protons and carbon signals of the deuterated solvent. Р
give 2.45 g (85%) of iminium salt 13a. Н NMR spectrum,
Scheme 6.
C H COCl
2
5
15
8
+ 2
Me CHCH N
O
2
(
i-PrO) P(S)SCOEt + 13b
2
R = i-Pr
17
SP(OR)2
MeOCH Br
2
16
S
(
EtO) P(S)SCH OMe + 13a
2
2
R = Et
18
1
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 1 2020

SEQUENTIAL INTERACTION OF ENAMINE
87
3
3
δ, ppm: 1.39 d (6H, CHMe , J = 6.7 Hz), 3.24 m (1Н,
4.10 q and 4.18 q (4H, CH OP, J = 7.1 Hz), 5.06 d
2 HH
2
HH
+
3
13
CHMe ), 3.96 m (4H, OCH ), 4.03 m (4H, N CH), 9.39 d
1H, CHN , J = 8.5 Hz). 13С NMR spectrum, δC,
ppm: 19.50 (CHMe ), 30.62 (CHMe ), 51.89 and 59.14
N (CH ) ], 66.35 [O(CH ) ], 180.1 (CHN ). Found, %:
(2H, SCH , J = 20.4 Hz). С NMR spectrum, δ ,
2
2
2 PH С
+
3
2
(
ppm: 15.90 (CH ), 56.95 (OCH ), 63.75 d (POCH , J =
3 3 2 PС
5.6 Hz), 78.48 d (SCH , J = 3.8 Hz). P NMR spec-
trum: δ 94.77 ppm. Found, %: C 31.12; H 6.78; P 13.45.
HH
2
31
2
2
2 PС
+
+
[
2
2
2 2
P
C 42.63; H 6.98; N 6.01. C H BrNO. Calculated, %: C
C H O PS . Calculated, %: C 31.29; H 6.57; P 13.28.
8
16
6
15
3
2
4
3.26; H 7.26; N 6.31.
Interaction of 4-(cyclopenten-1-yl-1)perhydro-1,4-
4
.3 g (78%) of disulfide 5 was isolated from the
oxazine 9 with acid 2a. A solution of 2.14 g (0.01 mol)
of acid 2a was added dropwise to a solution of 1.53 g
(0.01 mol) of enamine 9 in 10 mL of anhydrous CCl4
under argon maintaining the mixture temperature at
0–5°С. The mixture was heated to ambient and stirred
during 5 h. The crystalline precipitate was filtered off and
dried to give 3.5 g (95%) of 4-(cyclopentene-1,1-diyl)-
perhydro-1,4-oxazinium diisopropoxydithiophosphate
mother liquor via the solvent evaporation, mp 92°C (mp
1.5–93°C [11]). Н NMR spectrum, δ , ppm: 1.40 d and
.42 d (24Н, Me CH, J = 6.4 Hz), 4.90 d. sept (4H,
CHOP, J = 6.4, 3JPH = 12.0 Hz). С NMR spectrum,
δ , ppm: 23.75 d (CH , J = 4.5 Hz), 23.57 d (CH ,
3JPC = 5.5 Hz), 74.76 d (СН, 2JPC = 6.7 Hz). P NMR
spectrum: δ 81.70 ppm.
1
9
1
H
3
2
HH
3
13
HH
3
C
3
PC
3
31
P
1
1b containing admixture (5%) of morpholinium di-
b. Interaction with propanoyl chloride 15.Asolution of
.92 g (0.01 mol) of acyl chloride 15 in 10 mLof dioxane
was added dropwise at –5°С to a mixture prepared from
.41 g (0.01 mol) of enamine 8and 2.14 g (0.01 mol) of acid
1
thiophosphate. Н NMR spectrum, δ, ppm: 1.25 d (12H,
MeCHOP, J = 6.6 Hz), 2.13 m (4H, CH ), 3.22 m
0
3
HH
2
[
4H, =C(CH ) ], 4.09 m [4H, O(CH ) ], 4.14 m [4H,
2 2 2 2
1
2
+
N (CH ) ], 4.69 septet (2H, CHOP). Found, %: C 48.79;
H 7.95; N 4.03. C H NO PS . Calculated, %: C 49.02;
H 8.23; N 3.81.
2
2
a in 20 mL of dioxane. The reaction mixture was heated
1
5
30
3
2
to ambient and kept overnight. The precipitate was filtered
off and dried to give 1.70 g (96%) of iminium salt 13b.
1
3
Н NMR spectrum, δ, ppm: 1.40 d (6H, CHMe , J
=
2
HH
FUNDING
6
(
%
.6 Hz), 3.03 m (1Н, CHMe ), 4.04 m (4H, OCH ), 4.27 m
2 2
+
+ 3
4H, N CH), 9.90 d (1H, CHN , J = 8.3 Hz). Found,
This study was financially supported by the Ministry of
Education and Science of Russian Federation in the scope of
the basic part of the State Task in the field of research activity
HH
: C 53.79; H 8.87; N 7.53. C H ClNO. Calculated, %:
8 16
C 54.08; H 9.08; N 7.88.
(project no. 4.5348.2017/8.9).
Distilling off the solvent from the mother liquor gave
2
.13 g (77%) of О,О-diisopropyl-S-propanoylthio
CONFLICT OF INTEREST
1
dithiophosphate 17, bp 101–102°С (0.09 mmHg). Н
NMR spectrum, δ, ppm: 1.18 t (3H, CH CH , J
7
2
CHOP, J = 6.2 Hz). PNMR spectrum: δ 76.86 ppm.
Found, %: C 39.73; H 7.26; P 11.32. C H O PS . Cal-
culated, %: C 39.98; H 7.08; P 11.46.
No conflict of interest was declared by the authors.
3
=
3
2
HH
3
.5 Hz), 1.34 d and 1.39 d (12H, CHMe , J = 6.2 Hz),
2 HH
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.65 q (2H, CH CH , J = 7.5 Hz), 4.96 septet (2H,
3
2
HH
3
31
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1
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 1 2020