Chemical transformations of N-morpholinylacetic acid hydrazide and steric structure of its derivatives

Article abstract of DOI:10.1134/S1070363213030183

The reaction of N-morpholinylacetic acid hydrazide with various isothiocyanates and potassium thiocyanate resulted in the corresponding potentially biologically active thiosemicarbazide derivatives. Potassium N′-(2-morpholin-4-ylacetyl)hydrazinocarbothioate was synthesized and involved into heterocyclization in acidic environment to yield cyclic 5-(morpholinomethyl)-1,3,4-thiadiazole-2-thione. The structure of the synthesized compounds was established by IR, ¹H NMR spectroscopy, mass spectrometry, and XRD analysis.

Full text of DOI:10.1134/S1070363213030183

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 3, pp. 520–525. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © O.A. Nurkenov, S.D. Fazylov, Zh.B. Satpaeva, I.V. Kulakov, K.M. Turdybekov, D.M. Turdybekov, S.A. Talipov, B.T. Ibragimov,
2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83, No. 3, pp. 467–472.
Chemical Transformations of N-Morpholinylacetic Acid
Hydrazide and Steric Structure of Its Derivatives
O. A. Nurkenova, S. D. Fazylova, Zh. B. Satpaevaa, I. V. Kulakova, K. M. Turdybekovb,
D. M. Turdybekovc, S. A. Talipovd, and B. T. Ibragimovd
a Institute of Organic Synthesis and Coal Chemistry of Kazakhstan, ul. Alikhanova 1; Karaganda, 100008 Kazakhstan
e-mail: nurkenov_oral@mail.ru
b International Research and Production Holding “Phytochemistry,”
ul. Gazalieva 4, Karaganda, 100008 Kazakhstan
c Multi-Profile Humanitarian-Technical University, pr. Bukhar Zhyrau 12, Karaganda, 100000 Kazakhstan,
d Sadykov Institute of Bioorganic Chemistry, Academy of Science of Uzbekistan, Tashkent, Uzbekistan
Received February 13, 2012
Abstract―The reaction of N-morpholinylacetic acid hydrazide with various isothiocyanates and potassium
thiocyanate resulted in the corresponding potentially biologically active thiosemicarbazide derivatives. Potassium
N'-(2-morpholin-4-ylacetyl)hydrazinocarbothioate was synthesized and involved into heterocyclization in
acidic environment to yield cyclic 5-(morpholinomethyl)-1,3,4-thiadiazole-2-thione. The structure of the
synthesized compounds was established by IR, 1H NMR spectroscopy, mass spectrometry, and XRD analysis.
DOI: 10.1134/S1070363213030183
Thiosemicarbazide derivatives are known [1–3] as
compounds possessing a wide range of biological
action, including anticonvulsant, hypoglycemic,
antiphlogistic, and antibacterial. In this regard, we
were interested to carry out the synthesis of new
thiosemicarbazide derivatives II–IV based on the N-
morpholinylacetic acid hydrazide (I). The isothio-
cyanate method allows introducing a thioamide group
into the structure of the initial hydrazide to form the
corresponding thiosemicarbazide. This not only
expands the possibility of the modification of these
com-pounds, but may lead to new types of bioactivity.
We studied the condensation reaction of allyl-,
benzoyl-, and 4-bromobenzoyl isothiocyanates with N-
morpholinylacetic acid hydrazide I in the alcohol
medium at the equimolar ratio of the reactants. The
synthesis of new thiosemicarbazides II–IV was per-
formed in two stages, the first of which involves the
synthesis of the corresponding isothiocyanate by
heating allyl bromide and benzoyl chloride with
potassium thiocyanate in acetone medium and further
its reaction in situ (without isolation) with N-mor-
pholinylacetic acid hydrazide along the following
scheme:
O
O
S
O
+
S=C=NR
O
NCH2C
NCH2C
NHNH2
NHNHCNHR
II_IV
I
R = CH2=CHCH2 (II), C6H5C(O) (III), 4-Br-C6H4C(O) (IV).
The yield of thiosemicarbazides II–IV was 59–
74%. The synthesized thiosemicarbazide derivatives
II–IV are white crystals, soluble in polar organic
solvents. The composition, structure, homogeneity of
the compounds II–IV were confirmed by elemental
analysis, IR, and 1H NMR spectroscopy.
The IR spectra of compounds II–IV contain an
absorption band in the region of 1140–1240 cm–1
characteristic of the NH–CS group of the thiosemi-
carbazide fragment. The absorption band of the amide
group C(O)NH appears in the region of 1690–
1675 cm–1 and of NH group, at 3390–3360 cm–1. In the
520

CHEMICAL TRANSFORMATIONS OF N-MORPHOLINYLACETIC ACID HYDRAZIDE
521
1H NMR spectrum of the N-morpholinylacetic acid N-
allylthiosemicarbazide II the signals of methylene
protons of morpholine fragment give rise to two
triplets centered at 2.45 and 3.59 ppm. The signal of
methylene protons of NCH2 fragment appears at
3.01 ppm as a narrow singlet. Methylene protons of the
allyl fragment give a broad triplet at 4.09 ppm.
Methine proton of the vinyl fragment is observed as a
complex multiplet at 5.82 ppm. Methylene protons of
the same vinyl residue give two doublets at 5.04 and
10.3 Hz, J2 = 17.3 Hz. The signals of the amide and
tioamide N–H protons are three singlets in a weak
field, at 9.65, 9.20, and 7.98 ppm. The ratio of integral
intensities corresponds to the structure II.
In order to expand the number of new biologically
active substances with thiosemicarbazide fragment we
carried out also the synthesis of monosubstituted
thiosemicarbazide derivative V by the reaction of the
N-morpholinylacetic acid hydrazide with potassium
thiocyanate along the scheme:
5.13 ppm with spin-spin coupling constants J1
=
O
O
HCl
95oC
S
O
+
N
O
KSC
NCH2C
NCH
2C
NHNHCNH2
NHNH2
I
V
The reaction was carried out in an acidic envi-
ronment (diluted aqueous HCl) at 95°C within 4 h. The
reaction product V was obtained in 57% yield.
of azaheterocycles [4, 5]. Using a variety of reagents
and changing reaction conditions, the cyclization can
be directed to the formation of 1,3,4-oxadiazoles,
1,3,4-thiadiazoles, and 1,2,4-triazoles. Among these
heterocyclic aza derivatives, a group of 1,3,4-
thiadiazoles is interesting in both the chemical and
pharmacological respects, being essentially a cyclic
analog of thiosemicarbazones. In the literature there
are only few data on these cyclic organic compounds
[6–8]. In this regard, we studied the possibility of
condensation of N-morpholinylacetic acid hydrazide I
to obtain 1,3,4-thiadiazole derivative by the reaction of
I with carbon disulfide in alkaline medium.
IR spectrum of compound V contains absorption
bands of stretching vibrations of NH2 groups at 3305–
3240 cm–1 and an absorption band at 3210 cm–1
characteristic of NH groups. In the regions of 1660 and
1270 cm–1 there are absorption bands of carbonyl
(C=O) and tiocarbonyl (C=S) groups, respectively.
It is known that derivatives of hydrazides and thio-
semicarbazide are important synthons in the synthesis
NH NH
O
KOH
EtOH
O
CS2
+
O
NCH2 C
NCH2 C
O
C
S
NHNH2
SK
I
VI
The potassium salt VI formed in the first stage
further underwent cyclization in 5-(morpholinome-
thyl)-1,3,4-thiadiazole-2(3H)-thione VII at low tem-
perature under the action of concentrated sulfuric acid:
5-(Morpholinomethyl)-1,3,4-thiadiazole-2(3H)-
thione VII belongs to heterocyclic compounds and,
moreover, is capable of tautomeric thione-thiol
NH NH
O
NCH2C
C
S
O
SK
VI
N
NH
C
H2SO4
0oC
O
NCH2C
S
S
Fig. 1. Spatial arrangement of molecule II.
VII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 3 2013

522
NURKENOV et al.
Table 2. Bond angles (ω, deg) in structure II
Table 1. Bond lengths (d, Å) in structure II
Angle
ω
Angle
O8C8C7
N9C8C7
C8N9N10
ω
Bond
d
Bond
C8–N9
d
C7N1C6
C7N1C2
C6N1C2
N1C2C3
O4C3C2
C3O4C5
O4C5C6
N1C6C5
N1C7C8
O8C8N9
111.9(2)
111.2(3)
109.6(2)
122.4(3)
114.3(2)
122.0(2)
S1–C11
N1–C7
N1–C6
N1–C2
C2–C3
C3–O4
O4–C5
C5–C6
C7–C8
C8–O8
1.702(3)
1.450(4)
1.453(4)
1.470(3)
1.499(6)
1.416(5)
1.420(4)
1.504(5)
1.518(3)
1.209(3)
1.344(4)
1.383(3)
1.343(4)
1.320(4)
1.446(4)
1.546(6)
1.267(6)
0.68(7)
0.89(7)
N9–N10
N10–C11
C11–N12
N12–C13
C13–C14
C14–C15
O1W–H1W
O1W–H2W
109.5(3)
111.3(3)
110.3(3)
111.2(3)
110.3(3)
114.2(2)
123.2(2)
C11N10N9
N12C11N10
N12C11S1
N10C11S1
C11N12C13
N12C13C14
C15C14C13
121.6(2)
118.8(2)
124.1(2)
117.1(2)
124.0(2)
111.7(3)
125.7(5)
transformations. This type of compounds in the
crystalline state are usually thiones, which is
confirmed by IR spectra. A band in the region of
2700–2450 cm–1 characteristic of stretching vibrations
of SH-group is not observed, but there are distinct
bands of the group NH (3300–3100 cm–1) and C=S
(1350 cm–1) .
A general view of the molecule of 5-(mor-
pholinomethyl)-1,3,4-thiadiazolo-2(3H)-thione VII is
shown in Fig. 2. In the independent part of the unit cell
of VII there are two molecules, VIIa and VIIb. It
follows from the data obtained that the bond lengths
and bond angles in both molecules are close to normal
(Tables 4 and 5) [9]. The morpholine rings in VIIa and
VIIb are present in an almost perfect chair
In order to establish the steric structure of
compounds II, VII, and to confirm the cation structure
of compound VII an X-ray diffraction study of these
compounds was performed. The study of compound II
revealed that the N-morpholinylacetic acid N-allyl-thio-
semicarbazide II at recrystallization formed the cor-
responding monohydrate crystal. Its general view is
shown in Fig. 1. It follows from the XRD data that the bond
lengths and bond angles in compounds II are close to
2
4,5
conformation (ΔCS = 0.3° and ΔC2 = 1.6° for VIIa,
2
5,6
ΔCS = 1.7° and ΔC2 = 0.3° for VIIb). Thiadiazole
rings in both molecules are planar (the atoms S1, C2,
N3, N4 and C5 in VIIa and S1', C2', N3', N4', and C5' in
VIIb are coplanar with an accuracy of ±0.004 and
±0.003 Å, respectively), the intracyclic torsion angles
are shown in Table 6. The C6 atom is oriented
equatorially with respect to the morpholine ring.
normal (Tables 1 and 2) [9]. The morpholine ring is
In the crystal the molecules are linked into infinite
bands along the crystallographic axis 21 (0,y,0) by the
hydrogen bonds O1–H (x, y, z)···O2 (–x, 0.5 + y, 1/2 – z)
(the distances O1···O2 2.77 Å, H···O2 1.99 Å, angle
OH···O 158.7°), O3–H (1 – x, 0.5 + y, 0.5 – z)···
O1 (x, y, z) (the distances O1···O2 2.76 Å, H···O1 1.94 Å,
angle OH···O 173.8°), O4–H(x, y, z) ···O5 (–1 + x, y, z)
(the distances O4···O5 2.75 Å, H···O5 2.03 Å, angle
OH···O 170.7°) and O4–H (x, y, z)···O5 (–0.5 + x, 0.5 –
y, 1 – z) (the distances O4···O5 2.74 Å, H···O5 1.91 Å,
angle OH···O 177.5°).
3
present in an almost ideal chair conformation (ΔCS
=
4,5
0.9° and ΔC2 = 0.6°) (the intracyclic torsion angles
are given in Table 3), and C7 atom is oriented equa-
torially with respect to the ring. In the crystal, the
molecules of II are associated with the hydration water
molecules by hydrogen bonds N12–H (x, y, z)···
O1W (x, y, z) (the distances N12···O1W 2.86 Å,
H12···O1W 2.09 Å, angle NH···O 149.5°), O1W–H (x, y, z)···
O8 (x, y, z) (the distances O1W····O8 2.78 Å, H1W···O8
1.90 Å, the angle OH···O 167.3°).
Table 3. Torsion angles (τ, deg) in structure II
Thus, proceeding from the N-morpholinylacetic acid
hydrazide I using one-step isothiocyanate method we
synthesized related thiosemicarbazides II–V and per-
formed heterocyclization of compound I into the cor-
responding 5-(morpholinomethyl)-1,3,4-thiadiazole-2-
thione VII.
Angle
τ
Angle
τ
C6N1C2C3
–56.9(4)
C3O4C5C6
58.0(4)
N1C2C3O4
C2C3O4C5
58.7(4)
O4C5C6N1
C2N1C6C5
–57.3(4)
56.3(3)
–59.2(4)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 3 2013

CHEMICAL TRANSFORMATIONS OF N-MORPHOLINYLACETIC ACID HYDRAZIDE
Table 4. Bond lengths (d, Å) in structure VII Table 5. Bond angles (ω, deg) in structure VII
523
Angle
C5S1C2
N3C2S2
N3C2S1
S2C2S1
ω
Angle
C5'S1'C2'
N3'C2'S2'
N3'C2'S1'
S2'C2'S1'
ω
Bond
S1–C5
S1–C2
d
Bond
S1'–C5'
S1'–C2'
d
89.3(1)
89.7(2)
1.740(3)
1.744(3)
1.740(3)
1.745(4)
126.2(2)
107.0(2)
126.8(2)
119.5(3)
109.5(3)
122.8(3)
114.7(2)
122.4(2)
112.4(3)
111.6(3)
109.7(2)
108.9(3)
110.6(3)
111.2(3)
110.6(3)
110.2(3)
109.8(3)
126.8(3)
106.3(3)
126.9(2)
119.7(3)
110.0(3)
122.5(3)
114.4(3)
123.1(2)
112.3(3)
109.2(3)
108.5(3)
111.3(3)
110.9(3)
111.0(3)
110.3(3)
110.2(3)
109.4(3)
S2–C2
1.659(3)
1.331(4)
1.364(4)
1.283(4)
1.493(4)
1.459(4)
1.458(4)
1.468(4)
1.506(5)
1.426(5)
1.432(5)
1.507(5)
S2'–C2'
1.658(4)
1.344(5)
1.352(5)
1.283(5)
1.494(5)
1.456(4)
1.454(4)
1.474(4)
1.512(5)
1.441(5)
1.422(4)
1.507(4)
C2–N3
N3–N4
N4–C5
C5–C6
C6–N7
N7–C12
N7–C8
C8–C9
C9–O10
O10–C11
C11–C12
C2'–N3'
N3'–N4'
N4'–C5'
C5'–C6'
C6'–N7'
N7'–C8'
N7'–C12'
C8'–C9'
C9'–O10'
O10'–C11'
C11'–C12'
C2N3N4
C5N4N3
N4C5C6
N4C5S1
C6C5S1
N7C6C5
C12N7C6
C12N7C8
C6N7C8
N7C8C9
O10C9C8
C9O10C11
O10C11C12
N7C12C11
C2'N3'N4'
C5'N4'N3'
N4'C5'C6'
N4'C5'S1'
C6'C5'S1'
N7'C6'C5'
C8'N7'C6'
C8'N7'C12'
C6'N7'C12'
N7'C8'C9'
O10'C9'C8'
C11'O10'C9'
O10'C11'C12'
N7'C12'C11'
EXPERIMENTAL
IR spectra were recorded on a NICOLET Fourier
transform spectrometer AVATAR-320 from tablets
with KBr. 1H NMR spectra were recorded on a Bruker
DRX500 spectrometer at a frequency 500 MHz from
DMSO-d6 solution with internal reference TMS. Mass
spectra were recorded on a FINNIGAN MAT.INCOS
50 instrument with direct input, ionization energy
70 eV. Melting points were measured on a Boetius
heating block. The TLC analysis was performed on
Sorbfil plates, development by iodine vapor.
calculated positions and included in the refinement
within the rider model, except for the hydrogen atoms
of hydration water in compound II, which were
identified from the difference electron density syn-
Table 6. Intracyclic torsion angles (τ, deg) in structure VII
Angle
τ
Angle
τ
Thiadiazole cycles
C5S1C2N3
S1C2N3N4
C2N3N4C5
N3N4C5S1
C2S1C5N4
0.9(2)
–1.3(4)
1.1(5)
C5'S1'C2'N3'
0.5(3)
–0.9(4)
0.8(5)
XRD analysis of compounds II and VII. The cell
parameters and the intensities of the 2938 and 4063
independent reflections for crystals II and VII,
respectively, were measured on a Xcalibur diffracto-
meter (CuKα radiation, graphite monochromator, θ/2θ-
scanning, 2θ ≤ 151° and 169° for II and VII,
respectively). Crystals of II are monoclinic: a =
11.2684(6), b = 9.5490(5), c = 14.0296(9) Å, β =
108.606(6)°, V = 1430.7(9) Å3, Z = 4 (C10H18N4O2S· H2O),
space group P21/n, dcalc = 1.283 g cm–3. The crystals
of VII are triclinic: a = 8.837(6), b = 9.818(5), c =
12.126(13) Å, α = 83.78(6), β = 80.74(7), γ = 80.40(5)°,
V = 1020 (2) Å3, Z = 4 (C7H11N3OS2), space group P1,
dcalc = 1.413 g cm–3. The structure was solved by the
direct method. The positions of nonhydrogen atoms
were refined in the anisotropic full-matrix approxima-
tion. Hydrogen atoms were placed in geometrically
S1'C2'N3'N4'
C2'N3'N4'C5'
N3'N4'C5'S1'
C2'S1'C5'N4'
–0.2(4)
–0.4(3)
–0.3(4)
–0.1(3)
Morpholine cycles
C12N7C8C9
N7C8C9O10
C8C9O10C11
C9O10C11C12
O10C11C12N7
C8N7C12C11
55.7(4)
–56.0(4)
57.9(4)
C12'N7'C8'C9'
N7'C8'C9'O10'
C8'C9'O10'C11'
57.1(4)
–56.4(4)
57.0(4)
–59.6(4)
59.6(4)
C9'O10'C11'C12' –59.7(4)
O10'C11'C12'N7'
C8'N7'C12'C11'
61.4(4)
–57.5(4)
–59.3(3)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 3 2013

524
NURKENOV et al.
1
propanol). H NMR spectrum, δ, ppm (J, Hz): 2.55 t
[4H, N(CH2)2, J = 4.3], 3.32 br.s (2H, NCH2), 3.63 t
[4H, O(CH2)2, J = 4.6], 7.66 m (5H, Ar), 10.7 ush.s.
(1H, NHNC=O); 11.8 s (1H, NHNC = O); 12.7 br.s
[1H, C(O)NNC=S]. Mass spectrum, m/z, (Irel, %): 322
[M]+ (2), 105 (76), 100 (100), 77 (66.8) 56 (32.5), 51
(33.9), 42 ( 28.4).
Fig. 2. Spatial arrangement of molecule VII.
4-Bromo-N-[2-(2-morpholinoacetyl)hydrazinocar-
bonothioyl]benzamide (IV) was synthesized similarly
to compound III from 2.41 g (0.011 mol) 4-bromo-
benzoyl chloride, 1.07 g (0.011 mol) of potassium
thesis and refined in the isotropic approximation. In
the calculations 2306 and 3447 reflections were used
for II and VII, respectively, with I ≥ 2σ(I). The final
divergence factors R1 = 0.0638, WR2 = 0.1999 for II
and R1 = 0.0731, WR2 = 0.2122 for VII. The structure
was solved and refined using the SHELXS-97 and
SHELXL-97 software [10]. The CIF-files of the
atomic coordinates are deposited at the Cambridge
Crystallographic Center Database, (CCCD 853 555)
and (CCCD 861 096) for II and VII, respectively.
thiocyanate, and 1.59
g (0.01 mol) of mor-
pholinylacetic acid hydrazide I. 9.2 g (52.3%) of white
crystalline substance was isolated, mp 229–230°C (2-
1
propanol). H NMR spectrum, δ, ppm (J, Hz): 2.55 t
[4H, N(CH2)2, J = 4.2], 3.30 br.s (2H, NCH2), 3.63 t
[4H, O(CH2)2, J = 4.5], 7.74 d, 7.89 d (4H, ArBr, J =
8.55), 10.65 br.s. (1H, NHNC=O); 11.85 s (1H,
NHNC=O); 12.60 br.s [1H, C(O)NHNC=S]. Mass
spectrum, m/z, (Irel,%): 402 [M]+ (4), 400 [M]+ (4), 100
(100), 56 (19), 42 (14.7).
N-Morpholinylacetic acid N-allylthiosemicar-
bazide (II). 1.59 g (0.01 mol) of N-morpholinylacetic
acid hydrazide was dissolved in ethanol, and then 0.9 g
(0.011 mol) of allyl isothiocyanate was added
dropwise. The mixture was stirred for 60 min at 50–
60°C. The completion of the reaction was controlled
by TLC. The solution was cooled, the crystalline
precipitate was filtered off and washed with a small
amount of cold ethanol. After recrystallization from
benzene we isolated 1.91 g (74%) of compound II, mp
137–138°C. A crystal of compound II for XRD studies
was obtained by natural evaporation of a saturated
alcoholic solution of the compound. Mass spectrum,
m/z, (Irel, %): 258 [M]+ (0.2), 115 (26.7), 100 (100), 56
(39.5) 41 (34.3).
N-Morpholinylacetic acid N-thiosemicarbazide
(V). A mixture of 1.59 g (0.01 mol) of N-mor-
pholinylacetic acid hydrazide, 1.4 g (0.015 mol) of
potassium thiocyanate, and 1.5 ml of conc.
hydrochloric acid in 40 ml of water was heated with
stirring for 4 h at 95°C. The reaction mixture was left
to stand for 24 h at room temperature. The solution
was then alkalinized to pH = 6–7, the precipitate
formed was filtered off and washed with water. After
recrystallization from isopropyl alcohol we isolated
1.24 g (57%) of morpholinylacetic acid N-thio-
1
semicarbazide V, mp 203–204°C. H NMR spectrum,
δ, ppm (J, Hz): 2.44 br.s [4H, N(CH2)2], 3.0 (2H,
NCH2), 3.58 t [4H, O(CH2)2, J = 4.5], 7.37 s, 7.85 s
[2H, H2NC(S)], 9.13 s [1H, C(O)NHNH], 9.68 s [1H,
C(O)NHNH]. Mass spectrum, m/z (Irel, %): 218 [M]+
(12.9), 100 (100), 70 (27.8) 60 (40.45), 56 (50), 43
(42.8), 42 ( 52.1), 41 (24.6).
N-[2-(2-Morpholinoacetyl)hydrazinocarbonothioyl]-
benzamide (III). To a solution of 1.55 g (0.011 mol)
of benzoyl chloride in 15 ml of acetone while stirring
with a magnetic stirrer was added 1.07 g (0.011 mol)
of potassium thiocyanate. The mixture was stirred for
2 h at room temperature and for half an hour under
reflux. The solution was filtered from the precipitated
KCl through a double paper filter, washed several
times with acetone, and then 1.59 g (0.01 mol) of
morpholinylacetic acid hydrazide I in 10 ml of water-
free isopropyl alcohol was added dropwise to the
solution. Further stirring was continued at 60°C for
3 h, and the solvent was distilled off. The residue
crystallizes upon cooling. 1.91 g (59.5%) of white
crystalline substance was isolated, mp 186–187°C (2-
Potassium N'-(2-morpholin-4-ylacetyl)hydrazino-
carbothionate (VI). A mixture of 1.59 g (0.01 mol) of
morpholinylacetic acid hydrazide I and 0.84 g
(0.015 mol) of potassium hydroxide were dissolved in
15 ml of water-free ethanol and 1.52 g (0.02 mol) of
carbon disulfide was added dropwise with cooling. The
reaction mixture was stirred for 2–3 h. The precipitated
powder product was filtered off and washed several
times with anhydrous diethyl ether. 2.27 g (83%) was
obtained, mp 212–214°С.
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CHEMICAL TRANSFORMATIONS OF N-MORPHOLINYLACETIC ACID HYDRAZIDE
525
2. Bagrov, F.V., Efimov, V.A., Petrukhina, V.A., and
5-(Morpholinylmethyl)-1,3,4-thiadiazole-2-thione
(VII). 1.36 g (5 mmol) of potassium hydrazinodithio-
morpholinylacetate VI was dissolved by portions in
3 ml of conc. sulfuric acid cooled to 0°C. The resulting
solution was poured into 50 ml of ice-water and
neutralized. The reaction product was extracted with
ethyl acetate. After drying over calcined potassium
carbonate and distilling the solvent off we isolated
0.97 g (45%) of product VII, mp 136–137°C (ethanol).
Crystals of compound VII for X-ray diffraction study
were obtained by natural evaporation of a saturated
alcoholic solution of the compound. 1H NMR
spectrum, δ, ppm (J, Hz): 2.46 t [4H, N(CH2)2, J =
4.44], 3.32 s (2H, NCH2), 3.57 t [4H, O(CH2)2, J =
4.58], 14.37 s (1H, NH). Mass spectrum, m/z (Irel, %):
217 [M]+ (50.3), 132 (20.1), 100 (100), 86 (65.5) 56
(28.8), 55 (24.6), 42 ( 22.3), 41 (15.7).
Kol’tsov N.I., Zh. Org. Khim., 1997, vol. 33, no. 1, p. 83.
3. Kolla, V.E. and Berdinskii, I.S., Farmakologiya i
khimiya proizvodnykh gidrazina (Pharmacology and
Chemistry of Hydrazine Derivatives), Yoshkar-Ola:
Mariiskoe Kn. Izd., 1976.
4. El’derfil’d, R., Geterotsiklicheskie soedineniya (Hetero-
cyclic Compounds), Moscow: Mir, 1965, vol. 7, p. 448.
5. Nesinov, E.P. and Grekov, A.P., Usp. Khim., 1964,
vol. 33, no. 10, p. 35.
6. Ovsepyan, T.R., Dilanyan, E.R., Engoyan, A.P., and
Melik-Ogandzhanyan, R.G., Khim. Geterotsicl. Soed.,
2004, no. 9, p. 1377.
7. Mamolo, M.G., Vio, L., and Banfi, E., Farmaco, 1996,
vol. 51, no. 1, p. 71.
8. Orlinskii, M.M., Zh. Org. Khim., 1996, vol. 32, no. 1,
p. 144.
9. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc., Perkin
Trans. 2, 1987, p. S1.
REFERENCES
10. Sheldrick, G.M., SHELX-97. Programs for Crystal
Structure Analysis, Release 97-2, University of
Göttingen, Germany, 1997.
1. Ovsepyan, T.R. and Dilanyan, E.R., Arm. Khim. Zh.,
1984, vol. 37, no. 4, p. 249.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 3 2013