Reactions of O,O-dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-methylpropanimine and its salts

Article abstract of DOI:10.1016/j.tetlet.2015.07.010

Abstract The reactions of O,O-dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-methylpropanimine and its salts resulted in reduction of the carbon-bromine bond in the iminium salt giving bis(dialkoxythiophosphoryl)disulfide and N-tert-butyl-2-methylpropaniminium bromide. This represents the first example of C-Br bond reduction by O,O-dialkyldithiophosphoric acids.

Full text of DOI:10.1016/j.tetlet.2015.07.010

Accepted Manuscript
Reactions of O,O-dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-
methylpropanimine and its salts
Mukattis B. Gazizov, Rafail A. Khairullin, Nikita G. Aksenov, Oleg G.
Sinyashin
PII:
S0040-4039(15)01140-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.07.010
TETL 46499
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
13 March 2015
18 June 2015
3 July 2015
Please cite this article as: Gazizov, M.B., Khairullin, R.A., Aksenov, N.G., Sinyashin, O.G., Reactions of O,O-
dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-methylpropanimine and its salts, Tetrahedron Letters
(
2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.07.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
Reactions of О,О-dialkyldithiophosphoric acids
with N-tert-butyl-2-bromo-2-methylpropanimine
and its salts
Leave this area blank for abstract info.
Mukattis B. Gazizov*, Rafail A. Khairullin, Nikita G. Aksenov, Oleg G. Sinyashin

1
Tetrahedron Letters
journal homepage: www.els evier.com
Reactions of О,О-dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-
methylpropanimine and its salts
Mukattis B. Gazizov*, Rafail A. Khairullin, Nikita G. Aksenov, Oleg G. Sinyashin
Kazan National Research Technological University, Karl Marx Street 68. 420015, Kazan, Russian Federation
Tel: (843)2319505, (843)2720970
E-mail: mukattisg@mail.ru
Fax: (843)2319505
ARTICLE INFO
ABSTRACT
Article history:
Received
The reactions of O,O-dialkyldithiophosphoric acids with N-tert-butyl-2-bromo-2-
methylpropanimine and its salts resulted in reduction of the carbon-bromine bond in the iminium
salt giving bis(dialkoxythiophosphoryl)disulfide and N-tert-butyl-2-methylpropaniminium
bromide. This represents the first example of C-Br bond reduction by O,O-
dialkyldithiophosphoric acids.
Received in revised form
Accepted
Available online
Keywords:
2
009 Elsevier Ltd. All rights reserved.
N-tert-butyl-2-bromo-2-methylpropanimine
O,O-dialkyldithiophosphoric acids
bis(dialkoxythiophosphoryl)disulfide
N-tert-butyl-2-methylpropaniminium bromide of a
carbon-bromine bond reduction
Introduction
Mercaptothiophosphoryl compounds, particularly O,O-
dialkyldithiophosphoric acids 1, were initially thought to form
1
a
adducts 2 by addition to N-arylarenecarbimines (Figure 1a).
However, further examination of this reaction using
physiochemical methods demonstrated that the reaction stopped
after imine protonation, resulting in the formation of iminium
1
b,c
salts 3 (Figure 1b).
When the strongly electron accepting
trichloromethyl group was placed on the imine carbon as in the
case of chloral imines, protonation of the imine group did not
occur, and instead underwent addition to the double bond to give
1
c
4
add to the imine group of 2,2-dichloropropanimine to form the
(Figure 1c). Dialkylphosphorous acids 5 are also known to
1
d
stable adduct 6 (Figure 1d).
The C–Cl bonds in the
Figure 1. Formation of adducts 2, 4, 6 and iminium salts 3
trichloromethyl and dichloromethylene groups of adducts 4 and 6
appear to be poorly-reactive and do not participate in further
substitution reactions. Conversely, the chlorine atom in adduct 8
resulting from the reaction of N-alkyl-2-chloroaldimines 7 and
dialkylphosphorous acids showed improved reactivity in
comparison to compounds 4 and 6, giving new products after
We have previously demonstrated that N-alkyl-2-chloro-2-
methylpropanimines 7 react with О,О-dialkyldithiophosphoric
acids 1 in two stages. Firstly, the nitrogen atom in the imine
undergoes protonation to give the intermediate dithiophosphate
salt 13 which undergoes further transformation into the iminium
2
3
prolonged reaction at room temperature. Formation of an
intermediate aziridinium salt 9 is involved in the isomerization of
the 2-chloroalkyl group at the P atom in 8 to give 10 with a 1-
chloride salt 14. The chlorine atom in salt 13 was found to be
highly reactive and could be substituted by the
(dialkoxythiophosphorylthio)-group (Figure 2c).
2
b,c
chloroalkyl group (Figure 2a).
aziridine 11 and phosphorylated chloroalkylammonium salts 12
The phosphorus-containing
2c
were obtained from 9 and 10 (Figure 2b).

2
Tetrahedron
cation: N-tert-butyl-2-bromo-2-methylpropaniminium bromide
2
1
2. It was found that bis(diisopropoxythiophosphoryl)disulfide
8a and N-tert-butyl-2-methylpropaniminium bromide 21 were
formed when acid 1a was reacted with iminium salt 22 in a ratio
:1 (Scheme 2).
2
Figure 2. Formation of adducts 8, and iminium salts 13 as well as the
products of their transformations 9, 10, 11, 12, 14.
Scheme 2. Reaction of O,O-diisopropyldithiophosphoric acid 1a and N-tert-
butyl-2-bromo-2-methylpropaniminium bromide 22.
The reducing properties of О,О-dialkyldithiophosphoric acids
have been described in the literature, reducing azobenzenes to
4
1
benzidine and aniline, sulfoxides and N-tosylsulfimines 15 to
The reactivity of N-alkyl-2-halo-2-methylpropanimines 7
and 19 with О,О-dialkyldithiophosphoric acids 1, appeared to
depend on the nature of the halogen, giving 2-
4a
4
d
4e
dialkylsulfides,
pyridine N-oxide to pyridine,
and
4f
diphenoquinone 16 to 4,4’-bis(2,6-di-tert-butylphenol) 17. The
acids 1 are turned into bis(dialkoxythiophosphoryl)disulfides 18
4
(dialkoxythiophosphorylthio)iminium
bis(dialkoxythiophosphoryl)disulfide
unsubstituted iminium bromide 21 respectively.
chlorides
18 and
14
or
bromine-
(
Figure 3).
3
1
Therefore, Р NMR dynamic spectroscopy was used to
determine the reason for this correlation (Tables 1 and 2). In the
case of chlorimine 7, the content of the intermediate salt 13 was
1
00% immediately after the components were mixed (Table 1).
1
The Н NMR spectrum contained no resonance signals between δ
.2-3.5 ppm, corresponding to the SH proton in acid 1. Thus, the
acid-salt equilibrium is almost completely shifted towards the
3
intermediate and the system contains no free acid 1 (Table 1).
3
1
Table 1. Р NMR dynamic spectroscopy data for the reaction
between compounds 1a and 7.
Figure 3. Reductive properties of O,O-dialkyldithiophosphoric acids 1.
Time after
mixing
δР of the
intermediate
salt 13 (ppm)
Intermediate
salt 13
content (%)
δР of the
product
14 (ppm)
Temperature
°С)
Product 14
content (%)
These examples demonstrate the reduction of organic
compounds containing unsaturated bonds. However, a literature
survey revealed no publications regarding the reduction of С-Hal
bonds (С-Hal → C-H) by these acids.
(
(
min)
-
-
60
50
3
107.5
107.1
105.1
101.5
100.5
99.2
97.6
95.9
98.8
98.8
98.7
-
100.00
100.00
99.94
99.92
97.73
91.99
75.94
54.88
20.33
10.75
4.34
-
-
0.00
0.00
0.06
0.08
2.27
8.01
24.06
45.12
79.67
89.25
95.66
100.00
23
54
73
88
-30
84.5
84.6
84.6
84.6
84.9
85.0
85.2
85.3
85.4
85.4
-
-
20
10
0
Results and Discussion
109
130
143
182
222
310
420
1
0
0
0
2
2
We began with the reaction of N-tert-butyl-2-bromo-2-
methylpropanimine 19 with О,О-dialkyldithiophosphoric acids
25
25
1
a-b. The major products of the reaction between compounds 1
2
5
0.00
and 19 at ratios of 1:1 and 1:2 were found to be
bis(dialkoxythiophosphoryl)disulfide 18 and N-tert-butyl-2-
methylpropaniminium bromide 21. When the ratio of reactants
was 1:1, half of the initial imine 19 remained unchanged, while it
was fully consumed when the ratio was 1:2 (Scheme 1).
In the case of bromimine 19, after 3 minutes the content of
the intermediate salt 20 was only 12.8%, as opposed to
р
chlorimine salt (13, 100%). The second signal at δ 81.0 ppm
1
indicated the phosphorus atoms of the initial acid, as did the Н
NMR spectrum which contained a signal δSH at 3.5 ppm. The salt
content was found at a maximum (71%) after 37 minutes (-85
°С). This dropped to 3.3% after a further 86 minutes (0 °С) due
to consumption during the formation of disulfide 18. Although
acid 1 was consumed during the reaction with salt 20, the signal
intensity at δ
disulfide 18 contains two phosphorus atoms with δ
р
81.0-82.1 ppm increases because the forming
81.0 ppm.
р
Scheme 1. Reaction of O,O-dialkyldithiophosphoric acids 1a-b and N-tert-
butyl-2-bromo-2-methylpropanimine 19
Thus, depending on the nature of the halogen atom, there are
different positions for the acid-salt equilibrium. In the case of
chlorimine 7 the equilibrium is almost fully shifted to the right
and the system contains no free acid. Intermediate salt 13
undergoes nucleophilic substitution of a chlorine atom by a
The reaction between 1a-b and 19 began at temperatures as
3
1
low as -90 °С. According to Р NMR data, the compound
formed was the intermediate salt: N-alkyl-2-bromo-2-
(
dialkoxythiophosphorylthio)-group forming product 14. When
methylpropaniminium
(
transformed into disulfide 18a-b and salt 21 which represented
the reduced salt of the initial imine. In order to prove that an
interaction existed between acid 1 and the N-tert-butyl-2-bromo-
О,О-dialkyldithiophosphate
Scheme 1). At temperatures higher than -80 °С this was
20a-b
bromimine 19 is used, the equilibrium is shifted to the left and
the reaction system contains significant amounts of the free acid
which participates in the reduction of the intermediate salt 20 and
formation of disulfide 18. It should be noted that although the
reaction mixture contains considerable amounts of salt 20 during
the first two hours, the substitution product cannot be detected.
2-methylpropaniminium cation after the formation of the
intermediate salt 20, we synthesized a stable salt containing this

3
Presumably, the reason is that the rate of the reduction process is
considerably higher than the rate of nucleophilic substitution of
bromine by the (diisopropoxythiophosphorylthio)-group.
G.; Zabirov, N. G.; Cherkasov, R. A.; Pudovik, A. N.; Zhurn. Obshch.
Khim. 1980, 50, 1458−1463; (d) Khairullin, R. A.; Gazizov, M. B.;
Aksenov, N. G.; Gazizova, K. C.; Bandikova, A. Ju.; Kirillina, Ju. S.
Herald of Kazan Technol. Univ. 2014, 5, 16−21
2
.
(a) Gazizov, M. B.; Khairullin, R. A.; Alekhina, A. I.; Litvinov, I. A.;
Krivolapov, D. B.; Latipov, Sh. K.; Balandina, A. A.; Musin, R. Z.;
Sinyashin, O. G. Mendeleev Commun. 2008, 18, 262−264; (b) Gazizov,
M. B.; Khairullin, R. A.; Minnikhanova, A. A.; Alekhina, A. I.;
Bashkirtsev, A. A.; Sinyashin, O. G. Dokl. Chem. 2010, 433, 1−5; (c)
Gazizov, M. B.; Khairullin, R. A.; Minnikhanova, A. A.; Alekhina, A. I.;
Bashkirtsev, A. A.; Sinyashin, O. G. Russ. J. Gen. Chem. 2010, 80,
3
1
Table 2. Р NMR dynamic spectroscopy data for the
reaction between compounds 1a and 19.
Total acid 1a
Time
after
mixing
δр of the
intermediate
salt 20
δР of acid
1 and
and disulfide
18 content (on
the basis of
initial acid
content) (%)
Intermediate
salt 20
content (%)
Temperature
°С)
(
disulfide
18
(
min)
(ppm)
2
425−2429
Gazizov, M. B.; Khairullin, R. A.; Aksenov, N. G. Tetrahedron Lett.
015, 56, 1175–1178
-
90
90
90
85
80
70
70
60
50
40
30
15
0
3
107.7
107.7
107.7
107.7
107.8
107.8
107.8
107.9
108.1
108.4
108.5
108.6
108.7
12.8
58.8
70.0
71.0
68.5
52.0
51.0
36.5
24.4
13.3
11.0
7.9
81.0
81.0
81.0
81.0
81.1
81.2
81.2
81.4
81.5
81.6
81.7
81.9
82.1
87.2
38.8
27.0
25.5
28.0
46.0
47.1
62.0
75.0
86.7
89.0
92.1
96.7
3
4
.
.
-
11
31
37
44
56
63
69
79
97
2
-
-
-
-
-
-
-
-
-
-
(a) Cherkasov, R. A. In Structure and Reactivity of Organic Compounds,
Science: Moscow, 1978, pp 107-145; (b) Cherkasov, R. A.; Kutyrev, G.
A.; Pudovik, A. N. Tetrahedron 1985, 31, 2567−2624; (c) Oae, S.;
Nakanishi, A.; Tsujimoto. N. Tetrahedron 1992, 38, 535−539; (d) Oae,
S.; Nakanishi, A.; Tsujimoto, N. Tetrahedron 1972, 28, 2981−2990; (e)
Nakanishi, A.; Oae. S. Chem. and Ind. 1971, 960−961; (f) Liakumovich,
A. G.; Kadirova, V. Kh.; Mukmenova, N. A.; Buharov, S. V. Zhur.
Obshch. Khim. 1991, 61, 260-261
104
109
123
5
.
Reaction of N-tert-butyl-2-bromo-2-methylpropanimine 19 and O,O-
diisopropyldithiophosphoric acid 1a. Ratio 1:1. A solution of imine 19
3.3
(
1.06 g, 5.13 mmol) in CCl
acid 1a (1.1 g, 5.13 mmol) in CCl
stirred for 3 h at 25 °С and allowed to stand for 24 h at 25 °С. The
precipitate was filtered and washed with CCl N-tert-Butyl-2-
methylpropaniminium bromide 21 was obtained as a white solid in 80%
4
(5 mL) was added dropwise to a solution of
It should be emphasized that the С-Br bond reduction does
not occur in the initial imine; it solely occurs in the iminium
cation and does not depend on the nature of the counter ion
4
(5 mL) at 0-5 °С. The mixture was
4
.
(
dithiophosphate or bromide anions). We propose that the
1
yield (0.42 g): m.p. 103-104 °С. H NMR (400 MHz, CDCl
3
, 20 °С) δ
transformation of imine 19 into iminium salt 21 enhances the
electrophilic properties of the halogen. A sulfur atom coordinates
with the partially positively charged bromine atom; a six-
membered cyclic electron transfer results in bromine substitution
by hydrogen to give O,O-dialkylthiophosphorylsulfenyl bromide
1
.28 (d, JHH =6.8 Hz, 6H, CMe ), 1.57 (s, 9H, CMe ), 3.75 (d, heptet,
2
3
3
3
3
+
HH =8.6 Hz, JHH =6.8 Hz, CH), 8.28 (d, JHH =8.6 Hz, 1H, CH=N H),
J
+ 13
14.34 (br s, 1H, N H) ppm. C NMR (100.61 MHz, CDCl , 20 °С) δ
3
19.29 (s, Me
179.88 (s, CH=N) ppm. Anal. Calcd for C
.73. Found: C, 51.71; H, 8.63; N, 6.85. The solvent (CCl
from the solution and the volatiles collected in a liquid N
2
CH), 27.95 (s, CMe
3
), 32.00 (s, Me
18BrN: C, 51.94; H, 8.72; N,
) was distilled
cooled trap
2 3
CH), 61.87 (s, CMe ),
8
H
6
4
2
3
and
N-tert-butyl-2-methylpropaniminium
O,O-
2
dialkyldithiophosphate 24. The sulfenyl bromide 23 then
undergoes nucleophilic substitution by the dithiophosphate anion
resulting in the formation of disulfide 18 and is accompanied by
the release of a bromide anion to form salt 21.
under vacuum (0.08 mm). Bis(diisopropoxythiophosphoryl)disulfide 18a
was isolated from the residue in 73% yield (0.8 g): m.p. 91 °С, lit. 91.5-
4
f
1
3
93 °С. H NMR (400 MHz, CDCl
3
, 20 °С) δ 1.40 and 1.42 (d, JHH =
6.4 Hz, 24H, Me CH), 4.90 (d, heptet, JHH =6.4 Hz, JPH =12.0 Hz, 4H,
3
3
2
3
CHOP) ppm. P NMR (162 MHz, CCl
1
1
4
, 20 °С) δ 81.57 ppm. The H
NMR spectrum of the trap condensate showed resonance signals of initial
3 2
imine 19: δ 1.03 (s, 9H, CMe ), 1.73 (s, 6H, CMe ), 7.51 (s, 1H, CH=N)
ppm.
Reaction of N-tert-butyl-2-bromo-2-methylpropanimine 19 and O,O-
diisopropyldithiophosphoric acid 1a. Ratio 1:2. By analogy with the
6
7
.
.
reaction using a 1:1 ratio, imine 19 (1.03 g, 5 mmol) in CCl
acid 1a (2.14 g, 10 mmol) in CCl (15 mL) gave N-tert-butyl-2-
4
(5 mL) and
4
methylpropaniminium bromide 21 in 78 % yield (0.81 g). Disulfide 18a
was isolated from mother liquid in 85% yield (1.8 g).
Reaction of N-tert-butyl-2-bromo-2-methylpropanimine 19 and O,O-
diethyldithiophosphoric acid 1b. Ratio 1:2. By analogy with the reaction
Scheme 3. Proposed mechanism for the interaction of O,O-
dialkyldithiophosphoric acids 1 with intermediate iminium salt 20
of acid 1a using a 1:2 ratio, imine 19 (0.99 g, 4.8 mmol) in CCl
and acid 1b (1.8 g, 9.6 mmol) in CCl (15 mL) gave iminium bromide 21
in 80 % yield (0.80 g) and disulfide 18b in 83% yield (1.47 g): m.p. 27-
4
(5 mL)
In
conclusion,
the
reactions
between
O,O-
4
dialkyldithiophosphoric acids and N-tert-butyl-2-bromo-2-
methylpropanimine and its iminium salts are described. This
resulted in the formation of bis(dialkoxythiophosphoryl)disulfide
and N-tert-butyl-2-methylpropaniminium bromide which is the
product of carbon-bromine bond reduction (C-Br → C-H) in the
intermediate iminium salt. This represents the first example of
the reduction of the C-Br bond by O,O-dialkyldithiophosphoric
acids.
4
f
28 °С (hexane), lit. 27-29 °С.
8. Reaction of N-tert-butyl-2-bromo-2-methylpropaniminium bromide 22
and O,O-diisopropyldithiophosphoric acid 1a. Ratio 1:1. Acid 1a (2.3 g,
0.7 mmol) was added dropwise to a suspension of iminium bromide 22
1
(
3.1 g, 10.8 mmol) in CH Cl (25 mL) at 0-2 °С. After 10 h the mixture
2
2
became homogeneous and it was allowed to stand at 20 °С for 48 h.
After removing CH Cl in vacuo, hexane (20 mL) was added to the solid
residue, and stirred. A solid mixture of iminium salts 21 and 22 was
2
2
1
filtered off (2.9 g) and washed with hexane (20 mL). (22) H NMR (400
MHz, CDCI , 20 °С) δ 1.73 (s, 9H, CMe ), 2.33 (s, 6H, CMe ), 8.48 (d,
3
3
2
Acknowledgments
3
+
+
3
J
HH =16.4 Hz, 1H, CH=N H), 14.39 (br s,1H, N H); (21) δ 1.31 (d, JHH
6.8 Hz 6H, CMe ), 1.59 (s, 9H, CMe ), 3.75 m (1H, Me CH), 8.22 (dd,
HH = 8.4 Hz, JPH = 16.4 Hz, 1H, CH=N H), 13.59 (br s, 1H, N H).
=
J
,
2
3
2
3
3
+
+
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)
Disulfide 18a was isolated from hexane mother liquid in 75 % yield (1.7
g).
Reaction of N-tert-butyl-2-bromo-2-methylpropaniminium bromide 22
and O,O-diisopropyldithiophosphoric acid 1a. Ratio 1:2. Acid 1a (2.65
9
.
2 2
g, 12.4 mmol) in CH Cl (5 mL) was added dropwise to a suspension of
References and notes
iminium bromide 22 (1.8 g, 6.2 mmol) in CH Cl (12 mL) at 5 °С. The
2
2
homogeneous mixture was allowed to stand at 20 °С for 96 h. After
removal of CH Cl in vacuo and working up the solid residue with
hexane, N-tert-butyl-2-methylpropaniminium bromide 21 precipitated.
1
.
(a) Pudovik, A. N.; Sergeeva, M. K. Zhur. Obshch. Khim. 1955, 25,
759−1766; (b) Zimin, M. G.; Zabirov, N. G.; Cherkasov, R. A.;
Pudovik, A. N. Zhur. Obshch. Khim, 1978, 48, 1020−1025; (c) Zimin, M.
2
2
1
This solid was filtered and washed twice with hexane (30 mL) to give

4
Tetrahedron
g).
iminium
bromide
21
in
81%
yield
(1.04
Bis(diisopropoxythiophosphoryl)disulfide 18a was isolated from the
hexane mother liquid in 73% yield (1.9 g).