Reactions of dithiocarbamic acids derived from alkaloids, morpholine, and piperidine with acrylic acid and its derivatices

Article abstract of DOI:10.1007/s11167-005-0022-8

β-(Thiocarbamoylthio)propionic acids derived from alkaloids, morpholine, and piperidine and their esters, amides, and nitriles were prepared by reactions of the corresponding dithiocarbamic acids with acrylic acid and its derivatives. Some of the compounds were tested for insecticidal activity.

Full text of DOI:10.1007/s11167-005-0022-8

Russian Journal of Applied Chemistry, Vol. 77, No. 8, 2004, pp. 1321 1324. Translated from Zhurnal Prikladnoi Khimii, Vol. 77, No. 8, 2004,
pp. 1336 1339.
Original Russian Text Copyright
2004 by Zhivotova, Gazaliev, Ibraev, Fazylov, Kasenov.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Reactions of Dithiocarbamic Acids Derived
from Alkaloids, Morpholine, and Piperidine
with Acrylic Acid and Its Derivatices
T. S. Zhivotova, A. M. Gazaliev, M. K. Ibraev, S. D. Fazylov, and R. Z. Kasenov
Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan,
Limited Liability Company, Karaganda, Kazakhstan
Received April 20, 2004
Abstract
-(Thiocarbamoylthio)propionic acids derived from alkaloids, morpholine, and piperidine and
their esters, amides, and nitriles were prepared by reactions of the corresponding dithiocarbamic acids with
acrylic acid and its derivatives. Some of the compounds were tested for insecticidal activity.
Dithiocarbamic acids are important synthetic pre-
cursors of various antimicrobial [1], fungicidal [2],
pesticidal [3], bactericidal [4], and other biologically
active agents.
as unsaturated acids, their esters and anhydrides,
unsaturated ketones, and related compounds.
Proceeding with a search for new biologically
active dithiocarbamate derivative of alkaloids and
their synthetic structural analogs [5], we performed
reactions of dithiocarbamic acids prepared in situ
from amines I IV and CS2 (with or without the base
catalyst, triethylamine) with acrylic acid and its de-
rivatives:
Dithiocarbamic acid esters containing various func-
tional groups in the mercaptan residue can be prepared
by reactions of dithiocarbamic acids with unsaturated
electrophilic compounds in which the double bond is
activated with electron-withdrawing substituents, such
O
S
CH2=CH C
CH2=CH C
O
OH
OH
N C S CH2CH2C
V VIII
O
S
O
OR, Et3N
N C S CH2CH2C
OR
IX XII
NH + CS2
O
S
CH2=CH C
O
I IV
NH2, Et3N
N C S CH2CH2C
NH2
XIII XVI
S
CH2=CH CN
N C S CH2CH2 CN
VII XX
N
N
,
N ,
N
N
,
O
N
N
O
I, V, IX, XIII, XVII
II, VI, X, XIV, XVIII
III, VII, XI, XV, XIX
IV, VIII, XII, XVI, XX
R = CH3 (a), i-C3H7 (b), and C4H9 (c).
1070-4272/04/7708-1321 2004 MAIK Nauka/Interperiodica

1322
ZHIVOTOVA et al.
Table 1. Yields, physicochemical constants, and elemental analyses of V VIII
Found, %
Calculated, %
H
Com- Yield,
mp,
C
Rf*
Formula
pound
%
C
H
N
C
N
V
VI
VII
VIII
89
86
92
93
252 253
Oil
120 121
106-107
0.58
0.53
0.76
0.69
52.61
54.24
40.79
46.38
6.46
5.86
5.52
6.43
8.32
9.02
6.00
6.05
C15H22N2O3S2
C14H18N2O2S2
C8H13NO3S2
C9H15NO2S2
52.63
54.19
40.85
46.35
6.43
5.81
5.53
6.44
8.19
9.03
5.96
6.01
*
Eluent 2-propanol ammonia water, 7 : 2 : 1.
Table 2. Yields, physicochemical constants, and elemental analyses of IX XII
Found, %
Calculated, %
H
Com- Yield,
nD20
(mp, C)
Rf*
Formula
pound
%
C
H
N
C
N
IXa
IXb
IXc
Xa
Xb
Xc
XIa
XIb
XIc
XIIa
XIIb
XIIc
70
65
73
77
66
61
70
68
63
57
71
74
(94 95)
1.5359
(59 60)
1.5468
1.5518
1.5423
1.5585
1.5510
1.5138
1.5265
1.5172
1.5157
0.65
0.58
0.71
0.69
0.62
0.61
0.75
0.66
0.49
0.36
0.60
0.55
53.96
55.59
43.41
48.55
56.22
57.97
47.70
52.38
57.30
59.03
51.54
54.14
6.70
6.21
6.00
7.03
7.32
6.87
6.83
7.62
7.56
7.13
6.96
7.68
7.90
8.68
5.59
5.71
7.27
7.93
5.01
6.01
7.01
7.68
4.66
4.90
C16H24N2O3S2
C15H20N2O2S2
C9H15NO3S2
53.93
55.55
43.37
48.58
56.25
57.95
47.65
52.36
57.29
59.02
51.49
54.17
6.74
6.17
6.02
6.88
7.29
6.82
6.86
7.64
7.54
7.10
6.93
7.64
7.87
8.64
5.62
5.67
7.29
7.95
5.05
5.09
7.04
7.65
4.62
4.86
C10H17NO2S2
C18H28N2O3S2
C17H24N2O2S2
C11H19NO3S2
C12H21NO2S2
C19H30N2O3S2
C18H26N2O2S2
C13H21NO3S2
C13H22NO2S2
*
Eluent benzene acetone, 1 : 1.
In view of the high physiological activity of dithio-
carbamates and alkaloids, it seemed interesting to
combine, in a single molecule, alkaloid and dithio-
carbamate fragments and to study the biological prop-
erties of such compounds.
under more severe conditions, in the presence of tri-
ethylamine, apparently via formation of an ammonium
salt. The length of the carbon chain and the degree of
substitution of the -C atom in the alcoholic residue
exert no significant effect on the yield of -[alkalo-
ido(amino)thiocarbonylthio]propionic acid esters IX
XII. The yield of esters IX XII derived from methyl
(a), isopropyl (b) and butyl (c) acrylates ranges from
57 to 77% (Table 2).
Acrylic acid contains a double bond conjugated
with the carboxy group. The withdrawing effect of the
carbonyl oxygen on the electrons of the double bond
facilitates its attack by nucleophilic agents. Therefore,
dithiocarbamic acids react with acrylic acid under
mild conditions to form the corresponding -[alkalo-
ido(amino)thiocarbonylthio]propionic acids V VIII
in high yields, 86 93% (Table 1).
The reaction with acrylamide also occurs in the
presence of triethylamine; the yields of -[alka-
loido(amino)thiocarbonylthio]propionic acid amides
XIII XVI range from 74 to 91% (Table 3). In the
absence of triethylamine, the reaction takes some-
what more time and requires heating; the yield of
amides XIII XVI appreciably decreases. This may
be caused by thermal instability of dithiocarbamates
and by consumption of the amine or alkaloid as
a base for the salt formation. The product of direct
The alkyl groups in alkyl acrylate exhibit a positive
inductive effect and noticeably decrease the conjuga-
tion between the carbonyl oxygen atom and C=C
bond of the acrylate; as a result, the rate of reaction
of dithiocarbamic acids with alkyl acrylates somewhat
decreases. Compounds I IV react with alkyl acrylates
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 8 2004

REACTIONS OF DITHIOCARBAMIC ACIDS DERIVED FROM ALKALOIDS WITH ACRYLIC ACID 1323
Table 3. Yields, physicochemical constants, and elemental analyses of XIII XVI
Found, %
H
Calculated, %
H
Com- Yield,
mp,
C
Rf*
Formula
pound
%
C
N
C
N
XIII
XIV
XV
87
74
91
78
148 150
115 116
140 141
106 107
0.50
0.43
0.51
0.54
52.81
54.34
40.06
46.51
6.70
6.19
6.02
6.87
12.38 C15H23N3O2S2
13.55 C14H19N3OS2
12.01 C8H14N2O2S2
12.11 C9H16N2OS2
52.79
54.37
41.03
46.55
6.74
6.15
5.98
6.90
12.32
13.59
11.97
12.07
XVI
*
Eluent benzene acetone, 1 : 1.
Table 4. Yields, physicochemical constants, and elemental analyses of XVII XX
Found, %
Calculated, %
H
Com- Yield,
mp,
C
Rf*
Formula
pound
%
C
H
N
C
N
XVII
XVIII
XIX
85
79
87
90
41 42
Oil
88 89
78 79
0.79
0.78
0.81
0.75
55.77
57.70
44.40
50.50
6.46
5.88
5.52
6.58
13.02 C15H21N3OS2
14.48 C14H17N3S2
13.01 C8H12N2OS2
13.12 C9H14N2S2
55.73
57.73
44.44
50.47
6.50
5.84
5.56
6.54
13.00
14.43
12.96
13.08
XX
*
Eluent benzene acetone, 1 : 1.
addition of the amine to acrylamide is formed as a by-
product.
activity was compared to that of a reference agent,
Sumi-alpha (Sumito Chemical Co., Ltd, Japan).
The reactivity of acrylonitrile toward I IV is sim-
ilar to the reactivity of acrylic acid, which is due
to the high electron-withdrawing power of the nitrile
group, facilitating nucleophilic attack of the C=C
bond by the carbamate anion. The reactions of in situ
prepared diethyldithiocarbamic acids with acrylonitrile
are performed with a small excess of CS2; -[alkalo-
ido(amino)thiocarbonylthio]propionitriles XVII XX
are obtained in high yields, 78 91% (Table 4).
We found that salts of V and VIII, sodium -[cyti-
sinothiocarbonylthio]propionate and potassium -[cy-
tisinothiocarbonylthio]propionate, exhibit pronounced
insecticidal activity with respect to all of the ex-
amined pests, exceeding that of Sumi-alpha by a factor
of 1.5 2.
The results were confirmed by the results of bio-
logical tests; compounds V and VIII were recom-
mended for further comprehensive studies with the
aim to assess the possibility of their use in agriculture
as pesticides.
The nucleophilic addition of the dithiocarbamates
to acrylic acid and its derivatives occurs against the
Markownikoff rule [scheme (1)].
EXPERIMENTAL
-[Alkaloido(amino)thiocarbonylthio]propionic
acids V VIII are crystalline substances insoluble in
organic solvents, but readily soluble in alkalis with
the formation of the corresponding salts. Esters IX
XII, amides XIII XVI, and nitriles XVII XX were
isolated as crystalline substances or light yellow oils,
soluble in the majority of organic solvents.
The compositions and structures of the compounds
were confirmed by elemental analysis and IR spec-
troscopy.
The IR spectra were recorded on a UR-20 spec-
trometer (KBr pellets, mulls in mineral oil, or solu-
tions in CHCl3 and CCl4).
Some of compounds V XX and alkali metal salts
of V VIII were tested for insecticidal activity with
respect to Lepidosaphes ulmi (Diaspididae family),
Capitophorus ribis (Aphididae family), and Abrahas
grossulariata (Geometridae family). The insecticidal
-(Cytisinothiocarbonylthio)propionic acid V.
A solution of 1.90 g (0.01 mol) of cytisine in ethanol
was added to a solution of 0.76 g (0.01 mol) of
CS2 and 0.72 g (0.01 mol) of acrylic acid in ethanol.
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1324
ZHIVOTOVA et al.
The mixture was stirred for 5 6 h. After the removal
of the solvent, a white precipitate formed. Recrystal-
lization from alcohol gave 3.04 g (89.0%) of V,
mp 252 253 C. IR spectrum, , cm : 700 600
(C S), 1500 1470 (N C=S), 1320 1210 (COOH).
Compounds XIV XVI were prepared similarly.
-(Cytisinothiocarbonylthio)propionitrile XVII.
A solution of 1.9 g (0.01 mol) of cytisine in ethanol
was slowly added dropwise to a solution of 0.53 g
(0.01 mol) of acrylonitrile and 1.14 g (0.015 mol) of
CS2 in ethanol. The mixture was stirred at 40 50 C
for 2 3 h. After the removal of the solvent, a light
yellow oil crystallizing on storage was obtained. Its
recrystallization from alcohol gave 2.75 g (85.0%) of
1
Found, %: C 52.61, H 6.46, N 8.32.
C15H22N2O3S2.
Calculated, %: C 52.63, H 6.43, N 8.19.
1
XVII, mp 41 42 C. IR spectrum, , cm : 700 610
Compounds VI VIII were prepared similarly.
(C S), 1510 1460 (N C=S), 2260 2240 (C N).
Methyl -(cytisinothiocarbonylthio)propionate
IXa. A solution of 1.90 g (0.01 mol) of cytisine and
1.01 g (0.01 mol) of triethylamine in ethanol was
slowly added dropwise with stirring to a solution of
0.86 g (0.01 mol) of methyl acrylate and 0.76 g
(0.01 mol) of CS2 in ethanol. The mixture was heated
for 1 h at 60 70 C. After the removal of the solvent,
a white precipitate formed. Its recrystallization from
alcohol gave 2.5 g (70.0%) of IXa, mp 94 95 C.
Found, %: C 55.77, H 6.46, N 13.02.
C15H21N3OS2.
Calculated, %: C 55.73, H 6.50, N 13.00.
Compounds XVIII XX were prepared similarly.
CONCLUSIONS
1
(1) -[Alkaloido(amino)thiocarbonylthio]propionic
acids and their esters, amides, and nitriles were pre-
pared by reactions of dithiocarbamic acids derived
from alkaloids, morpholine, and piperidine with acryl-
ic acid and its derivatives.
IR spectrum, , cm : 700 610 (C S), 1500 1470
(N C=S), 1410 1300 (COO ).
Found, %: C 53.96, H 6.70, N 7.90.
C16H24N2O3S2.
Calculated, %: C 53.93, H 6.74, N 7.87.
(2) Alkali metal -(aminothiocarbonylthio)propio-
nates derived from cytisine and piperidine exhibit
a pronounced insecticidal activity.
Compounds Xa XIIa, IXb XIIb, and IXc XIIc
were prepared similarly.
REFERENCES
-(Cytisinothiocarbonylthio)propionamide XIII.
A solution of 1.9 g (0.01 mol) of cytisine and 1.01 g
(0.01 mol) of triethylamine in ethanol was slowly
added dropwise with stirring to a solution of 0.71 g
(0.01 mol) of acrylamide and 0.76 g (0.01 mol) of
CS2 in absolute ethanol. The mixture was heated for
4 5 h. After the removal of the solvent, a white pre-
cipitate formed. Its recrystallization from alcohol gave
2.9 g (87.0%) of XIII, mp 148 150 C. IR spectrum,
1. Desai, N.C., Indian J. Chem., 1993, vol. 32, no. 3,
pp. 343 346.
2. Gazaliev, A.M., Zhurinov, M.Zh., and Fazylov, S.D.,
Novye bioaktivnye proizvodnye alkaloidov (New Bio-
logically Active Alkaloid Derivatives), Almaty: Gylym,
1992.
3. Mel’nikov, N.N., Volkov, A.I., and Korotkova, O.A.,
Pestitsidy i okruzhayushchaya sreda (Pesticides and the
Environment), Moscow: Khimiya, 1977.
1
, cm : 710 610 (C S), 1520 1480 (N C=S),
1140 1070 (CONH2).
4. Dolin, P.J., Raviglione, M.C., and Kochi, A., Bull.
World Health Organ., 1994, vol. 72, pp. 213 220.
Found, %: C 52.81, H 6.70, N 12.38.
C15H23N3O2S2.
5. Fazylov, S.D., Gazaliev, A.M., Kudaibergenova, S.,
Calculated, %: C 52.79, H 6.74, N 12.32.
et al., Zh. Obshch. Khim., 2002, vol. 72, no. 2, p. 349.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 8 2004