Reaction of Thiocarboxylic Acids with N-tert-Butyl-2-halo-2-methylpropanimines

Article abstract of DOI:10.1134/S0012500818060022

Reaction of N-tert-butyl-2-chloro-2-methylpropanimine with thiocarboxylic acids has proceeded by two routes, one involving nucleophilic substitution of the chlorine atom in the primary iminium salt by acylthio group, and another via reduction of its catio

Full text of DOI:10.1134/S0012500818060022

ISSN 0012-5008, Doklady Chemistry, 2018, Vol. 480, Part 2, pp. 111–113. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © R.A. Khairullin, M.B. Gazizov, Yu.S. Kirillina, S.Yu. Ivanova, N.Yu. Bashkirtseva, R.F. Karimova, 2018, published in Doklady Akademii Nauk, 2018,
Vol. 480, No. 4, pp. 430–432.
CHEMISTRY
Reaction of Thiocarboxylic Acids
with N-tert-Butyl-2-halo-2-methylpropanimines
R. A. Khairullina, M. B. Gazizova,*, Yu. S. Kirillinaa, S. Yu. Ivanovaa,
N. Yu. Bashkirtsevaa, and R. F. Karimovaa
Presented by Academician A.I. Konovalov December 27, 2017
Received February 12, 2018
Abstract—Reaction of N-tert-butyl-2-chloro-2-methylpropanimine with thiocarboxylic acids has proceeded
by two routes, one involving nucleophilic substitution of the chlorine atom in the primary iminium salt by
acylthio group, and another via reduction of its cation at the C–Cl bond. Thiocarboxylic acids have reacted
with 2-bromoaldimines only via reduction of primary salt cation at the C–Br bond. Acylthio-substituted
iminium salts, aldehydes, and their acetals have been prepared.
DOI: 10.1134/S0012500818060022
Reactions of dithiophosphoric acids with N-alkyl- substitution of chlorine atom in salt III by thioacyl
2-haloaldimines I have been described in the literature group increased with acid strength and chloroimine I
[1, 2], but there are no data on the reactions of com- excess. This seems to be due to the additional shift of
pounds I with thiocarboxylic acids II, which can result equilibrium toward the formation of intermediate
in formation of new types of organic compounds with salt III, i.e., more complete binding of acid I that par-
useful properties.
ticipate in the reduction of the C–Cl bond.
Both acids II reacted with bromoimine Ib only
through one route: the cation of intermediate salts VII
underwent reduction at the C–Br bond to give the
bromide salt of reduced iminium VIII and disulfide VI
(Scheme 2).
With the aim to confirm the structure of iminium
salts IV and synthesize new types of S-containing organic
compounds, we prepared aldehydes IX by hydrolysis and
converted them into acetals X (Scheme 3).
Thus, the reaction between N-tert-butyl-2-chloro-
2-methylpropanimine and thiocarboxylic acids, stud-
ied for the first time, proceeds via two routes: nucleo-
philic substitution of chlorine atom in the intermedi-
ate iminium salt by acylthio group and reduction of its
cation at the C–Cl bond. The contribution of each
route depended on the acid nature and reagent ratio.
Enhancement of acidic properties and an excess of 2-
chloroaldimine favored nucleophilic substitution
because it led to a decrease in the content of the acid
involved in the reduction of the C–Cl bond. N-tert-
Butyl-2-bromo-2-methylpropanimine reacted with
the thiocarboxylic acids only via one route by the
reduction of the cation of the intermediate salt at the
C–Br bond to form the bromide salt of reduced imin-
ium and the disulfide. In the course of the work, we
prepared new types of iminium salts and aldehydes
and their acetals.
The aim of this work is to reveal the routes of reac-
tion between compounds I and II, determine their
contribution to the overall process, and synthesize
new types of aldehydes and their derivatives.
We established for the first time (Scheme 1) that
the reaction between N-tert-butyl-2-chloroaldimine
Ia and acids II proceeds by two routes: the nucleop-
hilic substitution (SN) of chlorine atom in intermedi-
ate iminium salt III by thioacyl group (a) and the
reduction (Red, b) of its cation at the C–Cl bond.
The contribution of each route depended on the
structure of acid II and reagent ratio. At the 1 : 1 ratio
of initial reagents for acids IIa and IIb, the contribu-
tions of routes (a) and (b) were 4 : 1 and 3 : 2, respec-
tively. These ratios were determined from the inte-
grated intensities of resonance signals in the 1H NMR
spectra of mixtures of compounds IV and V isolated
from the reaction mixtures after removal of disulfide VI.
At a twofold excess of chloroimine I, the ratio of con-
tributions of routes (a) and (b) for acid IIb increased
from 3 : 2 to 4 : 1; i.e., the contribution of nucleophilic
aKazan State Technological University, Kazan,
420015 Russia
*e-mail: mukattisg@mail.ru
111

112
KHAIRULLIN et al.
Me2C(Cl)CH=N+HBu-t RC(O)S
Me2C(Cl)CH=NBu-t + RC(O)SH
II
III
Ia
a, SN
Me2C[S(O)CR]CH=N+HBu-t Cl
IV
Red, b
Me2CHCH=N+HBu-t Cl + RC(O)S=SC(O)R
V
VI
II, III, IV, VI: R=Ph (a), Me (b)
Scheme 1.
Me2C(Br)CH=N+HBu-t RC(O)S
Me2C(Br)CH=NBu-t + RC(O)SH
Ib
II
VII
RC(O)SH
Me2CHCH=N+HBu-t Br + RC(O)S=SC(O)R
VIII VI
II, VII, VI: R=Ph (a), Me (b)
Scheme 2.
3
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Tesla
BS 567 A (100 MHz) and a Bruker AVANCE 400WB
(400.13 and 100.61 MHz, respectively) spectrometers
in CDCl3. Chemical shifts were determined relative to
tetramethylsilane using the signals of residual protons
and carbon nuclei of the deuterated solvent as refer-
ences.
Reaction of thiobenzoic acid IIa with imine Ia.
A solution of 6.9 g (0.05 mol) of acid IIa in 15 mL of
CH2Cl2 was added dropwise at 5–10°C to a solution of
8.1 g (0.05 mol) of chloroimine Ia in 25 mL of CH2Cl2.
Three days later, the solvent was removed, the residue
was treated with methyl-tert-butyl ether, and the resul-
tant crystals were separated by filtration and dried to
give 9.08 g of a mixture of salts IVa and V in 4 : 1 ratio.
(sextet, 1H, Me2CH, JHH = 6.8 Hz), 8.35 (br s, 1H,
CH=N+), 15.72 (br s, 1H, N+H). Dibenzoyl disulfide
VIa (1.55 g) was isolated from the mother liquor, mp
128–129°C (ethanol, mp 128°C, [3]).
Reaction of thioacetic acid (IIb) with imine Ia.
Ratio 1 : 1. A solution of 4.6 g (0.06 mol) of acid IIb in
10 mL of CH2Cl2 was added dropwise to a solution
of 9.70 g (0.06 mol) of chloroimine Ia in 35 mL of
CH2Cl2 at 5–10°C. Four days later, the solvent was
removed and the residue was treated with ether. The
resultant oil became crystalline when stored for 2 days
in a refrigerator. The crystals were separated by filtra-
tion and dried in a vacuum to give 6.68 g of a mixture
of salts IVb and V in 3 : 2 ratio.
Diacetyl disulfide VIb (1.5 g), bp 49–50°C
(0.1 mmHg) and 72–74°C (2 mmHg, [3]) was isolated
from the mother liquor.
Ratio 1 : 2. Similarly, 24.3 g (0.15 mol) of chloroi-
mine IIa and 5.7 g (0.075 mol) of acid IIb in 50 mL of
CH2Cl2 were reacted to give 11.2 g of a mixture of salts
IVb and V in 4 : 1 ratio. Disulfide VIb (1.3 g) was
obtained from the mother liquor.
1H NMR (CDCl3, δ, ppm): salt IVa: 1.60 (s,
9H, CMe3), 1.98 (s, 6H, CMe2), 7.47 (dd, 2H, m-
3
3
CHАr, JHH = 7.6 Hz), 7.64 (dd, 1H, p-CHАr JHH
=
3
7.6 Hz), 7.87 (dd, 2H, o-CHАr JHH = 7.6 Hz), 8.25 (br s,
1H, CH=N+), 15.31 (br s, 1H, N+H); salt V: 1.24 (d,
6H, MeCH2, 3JHH = 6.8 Hz), 1.52 (s, 9H, CMe3), 3.75
Reaction of thiobenzoic acid (IIa) with imine Ib.
Acid IIa (2.76 g, 0.02 mol) was added dropwise to a
solution of 2.06 g (0.01 mol) of imine Ib in 15 mL of
CCl4 at 0–5°C. The reaction mixture was stirred at
ambient temperature for 3 h and allowed to stand over-
night. The resultant crystals were separated by filtra-
tion, washed with CCl4, and dried to give 1.72 g (83%)
of salt VIII, mp 103–104°C.
Me2C CHO
Me2C CH(OEt)2
SC(O)R
SC(O)R
IX
X
IX, X: R=Ph (a), Me (b)
1H NMR (CDCl3, δ, ppm): 1.31 (d, 6H,
Me2CH, 3JHH = 6.8 Hz), 1.61 (s, 9H, CMe3), 3.80 (d
Scheme 3.
DOKLADY CHEMISTRY
Vol. 480
Part 2
2018

REACTION OF THIOCARBOXYLIC ACIDS
113
septets, 1H, Me2CH, 3JHH = 6.8 Hz, 3JHH = 9.0 Hz),
8.41 (dd, 1H, CH=N, 3JHH = 9.0 Hz, 3JHH = 6.8 Hz),
14.81 (br s, 1H, N+H).
For C8H18NBr anal. calcd. (%): C, 46.17; H, 8.72;
N, 6.73.
1,1-Dimethyl-2,2-diethoxyethyl thiobenzoate Xa.
Two drops of sulfuric acid was added to a solution of
5.2 g (0.025 mol) of aldehyde IXa and 7.4 g (0.05 mol)
of triethyl orthoformate in 15mL of benzene. A slight
heating was observed. Twenty four hours later, the sol-
vent and the excess ortho ester were removed and the
residue was distilled in a vacuum to give 6.2 g (88%) of
Found (%): C, 45.91; H, 8.93; N, 6.58.
1
acetal Xa, bp 98–99°C (0.04 mmHg). H NMR
(CDCl3, δ, ppm, J, Hz): 1.19 (t, 6H, CH2Me, 3JHH
=
Dibenzoyl disulfide VIa (2.08 g, 76%), mp 130–
131°C (ethanol), was isolated from the mother liquor.
1H NMR (CDCl3, δ, ppm): 7.52 (dd, 4H, m-CHАr,
7.0), 1.50 (s, 6H, CMe2), 3.56 and 3.77 (both dq, 4H,
OCH2, 3JHH = 7.0, 2JHH = 9.0), 4.91 (s, 1H, CH), 7.35
3JHH = 3JHH = 8.0 Hz), 7.65 (dd, 2H, p-CHАr, 3JHH
=
3
(t, 2H, m-CHAr, JHH = 7.5), 7.46 (t, 1H, p-CHAr,
3JHH = 8.0 Hz), 8.07 (d, 4H, o-CHАr, 3JHH = 8.0 Hz).
3
3JHH = 7.5), 7.87 (d, 2H, o-CHAr, JHH = 7.5). 13C
NMR (CDCl3, δ, ppm): 15.40 (s, CH2Me), 22.55 (s,
CMe2), 55.20 (s, S–C), 66.10 (s, OCH2), 105.46 (s,
CH), 126.95 (s, m-CHAr), 128.34 (s, p-CHAr), 132.81
(s, o-CHAr), 138.06 (s, CAr-CO), 192.34 (s, C=O).
For C15H22O3S anal. calcd. (%): C, 63.80; H, 7.85;
S, 11.35.
Reaction of thioacetic acid (IIb) with imine Ib. Sim-
ilarly to the previous experiment, the reaction of 4.09 g
(0.0199 mol) of imine Ib, 1.51 g (0.0199 mol) of
acid IIb in 20 mL of CCl4 resulted in 1.89 g (91%) of
salt VIII, mp 103–104°C. Disulfide VIb (1.17 g,
78.5%), bp 50–51°C (0.1 mmHg), was obtained from
the mother liquor. 1H NMR (CDCl3, δ, ppm): 2.44 (s,
6H, Me).
Found (%): C, 63.58; H, 7.68; S, 11.43.
1,1-Dimethyl-2,2-diethoxyethyl thioacetate Xb.
Similarly to the previous preparation, 5.8 g (0.04 mol)
of aldehyde IXb and 8.9 g (0.06 mol) are of triethyl
orthoformate were reacted in 15 mL of benzene to give
7.1 g (81%) of acetal Xb, bp 61–62°C (0.08 mmHg).
1H NMR (CDCl3, δ, ppm): 1.12 (t, 6H, CH2Me,
For C4H6O2S2 anal. calcd. (%): C, 31.98; H, 4.02;
S, 42.69.
Found (%): C, 31.78; H, 3.91; S, 42.50.
1,1-Dimethyl-2-oxoethyl thiobenzoate IXa. A solu-
tion of 4.15 g (0.03 mol) of acid IIa in 10 mL of CH2Cl2
was added dropwise to a solution of 7.3 g (0.045 mol)
of chloroimine Ia in 30 mL of CH2Cl2 at 5–10°C.
Forty eight hours later, the solvent and the excess
chloroimine were removed in a vacuum. The residue
was dissolved in 40 mL of CH2Cl2 and 10 mL of water
was added at 10–15°C. After 40 min, the organic layer
was separated and dried with magnesium sulfate. The
solvent was removed and the residue was distilled in a
vacuum to give 4.4 g (71%) of aldehyde IXa, bp 86–
3JHH = 7.0 Hz), 1.33 (s, 6H, CМе2), 2.13 (s, 3H,
MeCO), 3.49 (q, 4H, CH2Me, 3JHH = 7.0 Hz), 4.61 (s,
1H, CH).
For C10H20O3S anal. calcd. (%): C, 54.51; H, 9.15;
S, 14.55.
Found (%): C, 54.70; H, 9.09; S, 14.41.
ACKNOWLEDGMENTS
1
87°C (0.03 mmHg). H NMR (CDCl3, δ, ppm): 1.47
3
3
This work was supported by the Ministry of Educa-
tion and Science of the Russian Federation in the
framework of the basic part of State Research Con-
tract (project no. 4.5348.2017/8.9).
(s, 6H, CMe2), 7.38 (dd, 2H, m-CHАr, JHH = JHH
=
7.6 Hz), 7.52 (dd, 1H, p-CHАr, 3JHH = 3JHH = 7.6 Hz),
7.85 (dd, 2H, o-CHАr, JHH = 7.6 Hz), 9.44 (s, 1H,
3
CHO).
For C11H12O2S2 anal. calcd. (%): C, 63.34; H, 5.81;
S, 15.40.
REFERENCES
1. Gazizov, M.B., Khairullin, R.A., Aksenov, N.G., and
Musin, R.Z., Tetrahedron Lett., 2015, vol. 56, no. 10,
pp. 1175–1178. doi 10.1016/j.tetlet.2015.01.104
2. Gazizov, M.B., Khairullin, R.A., Perina, A.I., Min-
nikhanova, A.A., Aksenov, N.G., Gnezdilov, O.I.,
Il’yasov, A.V., and Khayarov, Kh.R., Russ. J. Gen.
Chem., 2016, vol. 86, no. 3, pp. 499–507. doi
10.1134/S1070363216030014
Found (%): C, 63.27; H, 5.68; S, 15.22.
1,1-Dimethyl-2-oxoethyl thioacetate IXb. Similarly
to the previous preparation, 16.1 g (0.1 mol) of chloro-
imine Ia was reacted with 3.8 g (0.05 mol) of acid IIb
using 60 mL of CH2Cl2 and 10 mL of water to give 5.1 g
1
(70%) of aldehyde IXb, bp 80–81°C (10 mmHg). H
NMR (CDCl3, δ, ppm): 1.31 (s, 6H, CМе2), 2.21 (s,
3H, CH3CO), 9.28 (s, 1H, CHO).
3. Kazuhiko, K., Hiroaki, N., and Shinichi, M., Bull.
Chem. Soc. Jpn., 1977, vol. 50, no. 10, pp. 2751–2753.
doi 10.1246/bcsj.50.2751
For C6H10O2S2 anal. calcd. (%): C, 49.29; H, 6.89;
S, 21.93.
Found (%): C, 49.03; H, 7.01; S, 21.79.
Translated by I. Kudryavtsev
DOKLADY CHEMISTRY Vol. 480 Part 2 2018