Reactions of N-tert-butyl-2,2-dichloro(dibromo)propanimines and O,O-dialkyldithiophosphoric acids

Article abstract of DOI:10.1016/j.tetlet.2015.11.095

The reactions of O,O-dialkyldithiophosphoric acids and N-tert-butyl-2,2-dichloro(dibromo)propanimines initially gave primary iminium salts. These salts subsequently reacted with another two acid molecules resulting firstly in reduction of the C-Hal bond and then nucleophilic substitution of the halogen by the (dialkoxythiophosphorylthio) group. The reactions studied resulted in formation of the reduction-substitution product of the primary iminium salt and bis(dialkoxythiophosphoryl)disulfide.

Full text of DOI:10.1016/j.tetlet.2015.11.095

Tetrahedron Letters 57 (2016) 272–274
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reactions of N-tert-butyl-2,2-dichloro(dibromo)propanimines
and O,O-dialkyldithiophosphoric acids
⇑
Mukattis B. Gazizov , Rafail A. Khairullin, Nikita G. Aksenov
Kazan National Research Technological University, Karl Marx Street 68, 420015 Kazan, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2015
Revised 20 November 2015
Accepted 28 November 2015
Available online 7 December 2015
The reactions of O,O-dialkyldithiophosphoric acids and N-tert-butyl-2,2-dichloro(dibromo)propanimines
initially gave primary iminium salts. These salts subsequently reacted with another two acid molecules
resulting firstly in reduction of the CAHal bond and then nucleophilic substitution of the halogen by the
(dialkoxythiophosphorylthio) group. The reactions studied resulted in formation of the reduction–substi-
tution product of the primary iminium salt and bis(dialkoxythiophosphoryl)disulfide.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
O,O-Dialkyldithiophosphoric acid
N-tert-Butyl-2,2-dichloro(dibromo)
propanimines
Reduction of the CAHal bond
Nucleophilic substitution of halogen
Introduction
It should be emphasized that the transformation of imine 2 into
iminium salt 3 enhances the electrophilic properties of the halo-
We have previously demonstrated that the reaction of
O,O-dialkyldithiophosphoric acids 1 with N-alkyl-2-halo-2-methyl-
propanimines 2 under mild reaction conditions (À90 to À60 °C)
resulted in the formation of primary iminium salts: N-alkyl-
gen. Therefore, CABr bond reduction occurs not in the initial imine
molecule, but in the iminium salt cation 3. We have proposed that
the introduction of an additional electron-accepting group, such as
a halogen, would influence the reactivity of the iminium cation.
Herein, we report our study of the reaction of acids 1 with
N-tert-butyl-2,2-dihalopropanimines 7, which has not been previ-
ously described in literature. The additional electron-accepting
halogen atom in dihaloimines 7 was proposed to, firstly decrease
the basic properties of the imine nitrogen atom and shift the
acid–salt equilibrium to the left, which assumes the presence of
the free acid 1 in the reaction mixture and its participation in
reduction of the primary salt 8. Secondly, this would also increase
its electrophilic properties.
2-halo-2-methylpropaniminium O,O-dialkyldithiophosphates
3
(Scheme 1). Further transformations of these salts were found to
depend on the nature of the halogen. In the case of Cl-substituted
salt 3a, the chlorine atom undergoes nucleophilic substitution by
the (dialkoxythiophosphorylthio)-group resulting in formation of
N-alkyl-2-(dialkoxythiophosphorylthio)-2-methylpropaniminium
chloride 4 (Scheme 1, path A),1 whereas Br-substituted salt 3b
reacts with another acid molecule 1 to give the products of CABr
bond reduction: N-alkyl-2-methylpropaniminium bromide 5, and
bis(dialkoxythiophosphoryl)disulfide 6 (Scheme 1, path B).
Dynamic NMR 31P spectroscopy has revealed the reason for
these differences. In the case of chloroimine, the acid 1–chloroi-
minium salt 3 equilibrium is almost fully shifted to the right and
the system contains no free acid. When bromoimine 2b is used,
the equilibrium is shifted to the left and the system contains signif-
icant amounts of the free acid which participates in reduction of
the CABr bond in the intermediate iminium salt 3b.1
Results and discussion
The main products from the reaction between compounds 1
and 7 were disulfide 6, N-tert-butyl-2-halopropaniminium halide
9
and N-tert-butyl-2-(diisopropoxythiophophorylthio)propani-
minium halide 12 (Scheme 2).
The reaction of compounds 1 and 7 first formed primary imi-
nium salt 8 proposed by analogy with,1 which participates in the
reduction process by reaction with a second acid molecule 1. A
proposed mechanism is represented in Scheme 3. The reduction
⇑
Corresponding author. Tel.: +7 (843)2319505, +7 (843)2720970; fax: +7 (843)
2319505.
product
9 undergoes anionic exchange with acid 1 to give
dithiophosphate salt 10 with the release of HHal 11. Salt 10 then
E-mail address: mukattisg@mail.ru (M.B. Gazizov).
http://dx.doi.org/10.1016/j.tetlet.2015.11.095
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

M. B. Gazizov et al. / Tetrahedron Letters 57 (2016) 272–274
273
R1O
R1O
Me
Me
Me
R1O
R1O
Scheme 3 shows a proposed reduction mechanism. The thio-
phosphoryl sulfur atom coordinates with the halogen atom, while
the hydrogen in the SAH bond coordinates with a carbon atom. A
six-membered cyclic electron transfer results in halogen substitu-
tion by hydrogen to give O,O-dialkylthiophosphorylsulfenyl halide
14 and N-tert-butyl-2-halopropaniminium O,O-dialkyldithiophos-
phate 13. The sulfenyl halide 14 then undergoes nucleophilic sub-
stitution by the dithiophosphate anion resulting in the formation
of disulfide 6 which is accompanied by the release of a halide anion
to form salt 9.
S
S
S
Hal
Hal
P
P
NR2
NHR2
Me
2: Hal = Cl (a), Br (b)
SH
1
3: Hal = Cl (a), Br (b)
R1O
S
Me
NHR2
Cl
P
R1O
S
A
B
Me
4
R1O
OR1
P
OR1
Me
Me
S
S
S
H
Br
In conclusion, the primary salt of acid
N-tert-butyl-2,2-dichloro(dibromo)propaniminium
1
and imine 7,
O,O-dialkyl-
P
NHR2
R1O
S
i
dithiophosphate 8, reacts with a second molecule of acid 1 forming
disulfide 6 and N-tert-butyl-2-halopropaniminium halide 9, which
is an iminium salt reduced at the CAHal bond.4,8 Reaction with
another equivalent of acid 1 leads to product 12 formed by
substitution of the halogen atom in salt 10 by the (dialkoxythio-
phosphorylthio)-group.6
5
6:
R
1 = Pr (a), Et (b)
Scheme 1. Reactions of N-alkyl-2-halo-2-methylpropanimines
dialkyldithiophosphoric acids 1.
2 with O,O-
Hal
Me
S
S
RO
RO
Hal
Me
S
S
RO
RO
Hal
RO
RO
Hal
NtBu
red
2
x
P
P
P
NHtBu
Acknowledgments
SH
SH
1: R = iPr (a), 7: Hal = Cl (a)
1a,b
8: Hal = Cl, R = iPr (a), Et (b),
This Work was supported by the Russian Foundation for Basic
Research (Grant no. 13.03-97098/2013) and the Ministry of
Education and Science of Russian Federation (within the basic part
of task # 2014/56).
Hal = Br, R = iPr (c)
7:
7:
1: R = Et (b),
Hal = Cl (a)
Hal = Br (b)
1: R = iPr (a),
Hal
Me
S
S
S
S
RO
RO
OR
OR
Hal
H
red
P
P
NHtBu
9: Hal = Cl (a), Br (b)
6: R = iPr (a), Et (b) 85-86%
References and notes
S
RO
RO
Hal
Me
H
S
RO
RO
1. (a) Gazizov, Mukattis B.; Khairullin, Rafael A.; Aksenov, Nikita G. Tetrahedron
Lett. 2015, 56, 1175–1178; (b) Khairullin, R. A.; Gazizov, M. B.; Aksenov, N. G.;
Gazizova, K. S.; Kirillina, Ju. S.; Bandikova, A. Ju. Herald Kazan Technol. Univ. 2015,
18, 7.
Hal
NHtBu
H
Hal
Substitution
P
HHal
P
NHtBu
SH
S
Me
1a,b
9:
10
11
Hal = Cl (a), Br (b)
2. (a) De Kimpe, N.; Laurent, D. B.; Schamp, N. Org. Prep. Proced. Int. 1980, 12, 49–
180; (b) Liakumovich, A. G.; Kadirova, V. Kh.; Mukmenova, N. A.; Buharov, S. V.
Zh. Obshch. Khim. 1991, 61, 260–261.
S
RO
Me
NHtBu
Hal
HHal
P
RO
S
3. Reaction of O,O-diisopropyldithiophosphoric acid
1
and N-tert-butyl-2,2-
Me
dichloropropanimine 7a. Ratio 1:1. A solution of imine 7a (6.13 g, 33 mmol) in
CH2Cl2 (10 mL) was added dropwise to a solution of acid 1a (7.2 g, 33 mmol) in
CH2Cl2 (25 mL). The mixture was allowed to stand for 24 h at room temperature.
In the 31P NMR spectrum two resonance signals at dP 81.85 and 83.14 were
observed for the phosphorus atoms in disulfide 6a and N-tert-butyl-2-
(isopropoxythiophosphorylthio)propaniminium chloride 12a. After removal of
the solvent in vacuo and work up of the residue with hexane, a solid precipitated
which was filtered and washed twice with ether (20 mL) to give crude N-tert-
R = iPr, Hal = Cl (a), R = Et, Hal = Cl (b),
12:
R = iPr, Hal = Br (c)
66-77%
Scheme 2. Reactions of N-tert-butyl-2,2-dihalopropanimines
dialkyldithiophosphoric acids 1.
7
with O,O-
butyl-2-chloropropaniminium chloride 9a in 23% yield (1.4 g). 1H NMR
3
(400 MHz, CDCl3, 20 °C):
d
1.54 (s, 9H, CMe3), 1.79 (d, JHH = 6.8 Hz, 3H,
MeCH), 5.71 (d, 3JHH = 6.8 Hz, 3JHH = 8.8 Hz, 1H, MeCH), 8.45 (d, 3JHH = 8.8 Hz, 1H,
CH@N+), 14.1 (br s, 1H, N+H). Anal. Calcd for C7H15Cl2N: C, 45.67; H, 8.21; Cl,
38.5; N, 7.61. Found: C, 45.47; H, 8.13; Cl, 38.38; N, 7.43. Unreacted initial imine
7a in 34% yield (2.1 g) bp 50 °C (50 mm),2a and bis(diisopropoxythiophosphoryl)
disulfide 6a in 36% (2.5 g), mp 91 °C, lit. 91.5–93.0 °C2b were isolated from the
hexane mother liquid. 1H NMR of 6a (400 MHz, CDCl3, 20 °C): d 1.40 and 1.42 (d,
S
H
Me
S
S
S
S
Hal
Me
RO
RO
RO
RO
RO
Hal
Hal
Hal
P
P
C
P
NHtBu
NtBu
RO
S
Hal
8
S
S
RO
RO
S
S
Hal
RO
H
3
3
3JHH = 6.4 Hz, 24H, Me2CH), 4.90 (d, heptet, JHH = 6.4 Hz, JPH = 12.0 Hz, 4H,
CHOP). 31P NMR (162 MHz, CDCl3, 20 °C): d 81.7 ppm. 13C NMR (100.61 MHz,
CDCl3, 20 °C): d 23.75 (d, 3JPC = 5.5 Hz, Me), 23.57 (d, 3JPC = 5.5 Hz, Me), 74.76 (d,
3JPC = 6.7 Hz, CH). 1H NMR of imine 7a (400 MHz, CDCl3, 20 °C): d 1.23 (s, 9H,
CMe3), 2.66 (s, 3H, CMe), 7.81 (s, 1H, CH@N).
P
P
NHtBu
Me
RO
13
14
Hal
Me
S
S
RO
OR
OR
Hal
H
P
P
NHtBu
4. Ratio 2:1. In analogy with the 1:1 ratio reaction, acid 1a (6.4 g, 30 mmol) in
CH2Cl2 (30 mL) and dichloroimine 7a (1.82 g, 10 mmol) in CH2Cl2 (10 mL) gave
N-tert-butyl-2-(diisopropoxythiophosphorylthio)propaniminium chloride 12a
in 77% yield (2.8 g) as a thick oil. 1H NMR (100 MHz, CDCl3, 20 °C): d 1.27 (d,
3JHH = 6.4 Hz, 12H, Me2CH), 1.58 (s, 9H, CMe3), 1.71 (d, 3JHH = 6.4 Hz, 3H, MeCH),
RO
S
S
9
6
Scheme 3. Proposed mechanism for the reduction of primary iminium salt 8 to the
iminium halide salt 9.
3
3
3
4.78 (d, heptet, JHH = 6.4 Hz, JHH = 12.8 Hz, 2H, CHOP), 5.07 (heptet, JHH = 6.4
Hz, 3JHH = 7.2 Hz, 3JPH = 12.4 Hz, 1H, MeCH), 8.2 (d, 3JHH = 7.2 Hz, 1H, CH=N), 16.2
(bs, 1H, NH). 31P NMR (162 MHz, CCl4, 20 °C): d 83.15 ppm. Anal. Calcd for
C
13H29ClNO2PS2: C, 43.14; H, 8.08; N, 3.87; P, 8.56. Found: C, 43.40; H, 8.21; N,
undergoes intermolecular substitution of the halogen atom by the
(dialkoxythiophosphorylthio)-group to give 12 which is the pro-
duct of reduction–substitution of primary iminium salt 8. When
the reaction was carried out using a 1:1 ratio, partial recovery of
imine 7 was observed as acid 1 was consumed to form disulfide
6 and compound 12.3,7 Only two compounds were synthesized
using a 3:1 ratio of 1 and 7; disulfide 6 and the reduction–substi-
tution product 12.5,9 Salt 8 was reacted with acid 1a resulting in
the formation of product 12a.
4.01; P, 8.38. Bis(diisopropoxythiophosphoryl)disulfide 6a in 85% yield (1.8 g)
was isolated from the hexane mother liquid, mp 91 °C (hexane), lit. 91.5–
93 °C.2b
5. Reaction of O,O-diethyldithiophosphoric acid 1b and N-tert-butyl-2,2-
dichloropropanimine 7a. A solution of imine 7a (1.0 g, 5.5 mmol) in CH2Cl2
(5 mL) was added dropwise to a solution of acid 1b (3.06 g, 16.4 mmol) in
CH2Cl2 (15 mL) at À10 °C. The mixture was allowed to stand for 48 h at room
temperature. In the 31P NMR spectrum of the reaction mixture two resonance
signals at dP 84.25 and 86.05 were observed for the phosphorus atoms in
compounds 6b2 and 12b. After removal of the solvent in vacuo, the residue was
washed three times with hexane (15 mL) to give crude N-tert-butyl-2-

274
M. B. Gazizov et al. / Tetrahedron Letters 57 (2016) 272–274
(diethoxythiophosphorylthio)propaniminium chloride 12b in 77% yield (1.4 g)
CCl4 and volatile products were removed in vacuo from the mother liquid and
3
as a thick oil. 1H NMR (400 MHz, CDCl3, 20 °C): d 1.20 and 1.18 (t, JHH = 7.2 Hz,
collected in a trap cooled by liquid nitrogen. The residue was recrystallized
from hexane to give disulfide 6a in 86% yield (2.85 g), mp 91 °C, lit. 91.5–
93 °C.2b Unreacted dibromimine 7b in 43% yield (1.8 g) was isolated from trap
condensate, bp 58–60 °C (10 mm).2a
3
6H, MeCH2), 1.40 (s, 9H, CMe3), 1.53 (d, JHH = 7.2 Hz, 3H, CHMe), 4.84 and 4.81
3
3
(d, quintet, JHH
=
3JPH = 7.2 Hz, JHH = 7.8 Hz, 1H, CHMe), 4.05 and 4.06 (quintet,
3JHH 3JPH = 7.2 Hz), 8.25 (dd, 3JHH = 7.8 Hz, 3JHH = 13.6 Hz, 1H, CH@N), 15.19 (br
=
s, 1H, N+H). 31P NMR (CCl4, 20 °C): 86.05 ppm. Anal. Calcd for C11H25ClNO2PS2: C,
39.57; H, 7.55; N 4.19; P 9.58. Found: C, 39.81; H, 7.78; N, 4.28; P, 9.49.
6. Reaction O,O-diisopropyldithiophosphoric acid 1a and N-tert-butyl-2-
chloropropaniminium chloride 9a. A solution of acid 1a (1.26 g, 5.9 mmol) in
CH2Cl2 (5 mL) was added dropwise to a solution of iminium chloride 9a (1 g,
5.9 mmol) in CH2Cl2 (10 mL) at 0 °C. After mixing the reagents the formed HCl
was removed in vacuo. The mixture was allowed to stand for 24 h at room
temperature. After solvent removal in vacuo crude N-tert-butyl-2-
(isopropoxythiophosphorylthio)propaniminium chloride 12a in 75% yield
(1.45 g) was obtained as a thick oil. The 1H and 31P NMR spectra of compound
12 obtained by the different methods were identical.
8. Ratio 2:1. A solution of imine 7b (2.7 g, 10 mmol) in CCl4 (10 mL) was added
dropwise to a solution of acid 1a (4.3 g, 20 mmol) in CCl4 (10 mL) at 0 °C. The
mixture was allowed to stand for 24 h at room temperature. The precipitate was
filtered, washed with benzene and dried to give N-tert-butyl-2-
bromopropaniminium bromide 9b in 85% yield (2.3 g), mp 133–134 °C. After
solvent removal from the mother solution in vacuo the residue was
recrystallized from hexane to give disulfide 6a in 86% yield (3.7 g), mp 91 °C,
lit. 91.5–93 °C.2b
9. Ratio 3:1. A solution of dibromimine 7b (2.7 g, 10 mmol) in CH2Cl2 (15 mL) was
added dropwise to a solution of acid 1a (6.4 g, 30 mmol) in CH2Cl2 (25 mL). The
mixture was allowed to stand for 48 h at room temperature. In the 31P NMR
spectrum of the reaction mixture two resonance signals at dP 81.35 and 83.2
ppm were observed for the phosphorus atoms in compounds 6a and 12c. After
solvent removal in vacuo the residue was washed three times with hexane
(15 mL) to give disulfide 6a in 63% yield (2.7 g) and N-tert-butyl-2-
(diisopropoxythiophosphorylthio)-propaniminium bromide 12c in 66% yield
7. Reaction of O,O-diisopropyldithiophosphoric acid 1a and N-tert-butyl-2,2-
dibromopropanimine 7b: Ratio 1:1. A solution of imine 7b (4.2 g, 15.3 mmol)
in CCI4 (15 mL) was added dropwise to a solution of acid 1a (3.3 g, 15.3 mmol)
in CCl4 (20 mL) at À5–0 °C. The mixture was allowed to stand for 3 h at 20 °C.
The 31P NMR spectrum of the reaction mixture showed only one resonance
signal at dP 81.6 ppm for the phosphorus atom in disulfide 6. The precipitate
was filtered, and washed with benzene (15 mL) to give N-tert-butyl-2-
bromopropaniminium bromide 9b in 86% yield (1.8 g), mp 133–134 °C. 1H
3
(2.68 g) as a thick oil. 1H NMR (400 MHz, CDCl3, 20 °C): 1.26 (d, JHH = 6.4 Hz,
3
12H, Me2CH), 1.51 (s, 9H, CMe3), 1.66 (d, JHH = 5.6 Hz, 1H, CHMe), 4.72 (d,
3
3
3
heptet, JHH = 6.7 Hz, JHH = 12.8 Hz, 2H, CHOP), 4.95 (heptet, JHH = 5.6 Hz,
3JHH = 7.8 Hz, 3JPH = 12.6 Hz, 1H, PSCH), 8.37 (dd, 3JHH = 7.8 Hz, 3JHH = 16.8 Hz, 1H,
CH@N+H), 14.27 (br s, 1H, N+H). 31P NMR (162 MHz, CCl4, 20 °C): d 83.2 ppm.
Anal. Calcd for C13H29BrNO2PS2: C, 38.42; H, 7.19; N, 3.45; P, 7.62. Found: C,
38.59; H, 7.41; N, 3.63; P, 7.48.
3
NMR (400 MHz, CDCl3, 20 °C: 1.62 (s, 9H, CMe3), 2.02 (d, JHH = 6.8 Hz, 3H, Me),
3
3
3
5.93 (d, k, JHH = 6.8 Hz, JHH = 9.1 Hz, 1H, CHBr), 8.42 (dd, JHH = 9.1 Hz,
3JHH = 16.9 Hz, 1H, CH@N), 14.91 (br s, 1H, N+H). Anal. Calcd for C7H15Br2: C,
30.84; H, 5.54; Br, 58.49; N, 5.13. Found: C, 30.61; H, 5.67; N, 4.98; Br, 58.37.