Alkylation of cyclic Mannich bases, derivatives of thiourea and simple amino acids

Article abstract of DOI:10.1134/S1070363212020132

Aminomethylation of thiourea with aqueous formaldehyde and simple amino acids (glycine, β-alanine, γ-aminobutyric acid) have resulted in the formation of (4-thioxo-1,3,5-triazinan-1-yl)-substituted acetic, propionic, and butyric acids, respectively. By alkylation of these compounds corresponding S-methyl and S-ethyl iodides were obtained, and by the action of tert-butylamine, the corresponding salts. The same salts were obtained by the reaction of amine exchange between 5-tert-butyl-1,3,5-triazinan-2-thione and these amino acids in water. As a result of neutralization of S-methyl iodides with tert-butylamine in 2-propanol or aqueous 2-propanol zwitterionic [4-(methyl-sulfanyl)-3,6-dihydro-1,3,5-triazin-1(2H)-yl] derivatives of these acids were isolated. From aqueous solutions of S-methyl iodides and tert-butylamine ion associates of the corresponding zwitter-ions and tert-butylammonium iodide have crystallized. The same associates have formed at treating S-methyl iodides with tert-butylamine or diethylamine in the absence of a solvent. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212020132

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 236–246. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © Song Minyan, S.M. Ramsh, V.S. Fundamensky, S.Yu. Solov’eva, V.I. Zakharov, 2012, published in Zhurnal Obshchei Khimii, 2012,
Vol. 82, No. 2, pp. 240–250.
Alkylation of Cyclic Mannich Bases, Derivatives
of Thiourea and Simple Amino Acids
Song Minyan, S. M. Ramsh, V. S. Fundamensky, S. Yu. Solov’eva, and V. I. Zakharov
St. Petersburg State Technological Institute, Moscovskii pr. 26; St. Petersburg, 190013 Russia
e-mail: gsramsh@mail.wplus.net
Received April 12, 2011
Abstract—Aminomethylation of thiourea with aqueous formaldehyde and simple amino acids (glycine, β-
alanine, γ-aminobutyric acid) have resulted in the formation of (4-thioxo-1,3,5-triazinan-1-yl)-substituted
acetic, propionic, and butyric acids, respectively. By alkylation of these compounds corresponding S-methyl
and S-ethyl iodides were obtained, and by the action of tert-butylamine, the corresponding salts. The same salts
were obtained by the reaction of amine exchange between 5-tert-butyl-1,3,5-triazinan-2-thione and these amino
acids in water. As a result of neutralization of S-methyl iodides with tert-butylamine in 2-propanol or aqueous
2-propanol zwitterionic [4-(methyl-sulfanyl)-3,6-dihydro-1,3,5-triazin-1(2H)-yl] derivatives of these acids were
isolated. From aqueous solutions of S-methyl iodides and tert-butylamine ion associates of the corresponding
zwitter-ions and tert-butylammonium iodide have crystallized. The same associates have formed at treating S-
methyl iodides with tert-butylamine or diethylamine in the absence of a solvent.
DOI: 10.1134/S1070363212020132
It was shown in [1] that 3-tert-butyl-6-(methylsul-
fanyl)-1,2,3,4-tetrahydro-1,3,5-triazine hydroiodide enters
in the amine exchange reaction with glycine and β-
alanine. In the case of glycine the final product of the
exchange, [4-(methylsulfanyl)-5,6-dihydro-1,3,5-triaz-
3-inium-1(2H)-yl] acetate, was isolated from the
reaction mixture of transamination in the individual
form. In this paper we describe the independent
synthesis of this compound and its homologs by
aminomethylation of thiourea with aqueous formal-
dehyde and simple amino acids and the subsequent
methylation of thus obtained cyclic Mannich bases
with methyl iodide followed by the neutralization of
the resulting isothiuronium salts with tert-butylamine.
none of these sources does not contain their charac-
teristics.
Indeed, as in the case of aminomethylation using
simple aliphatic amines [7], thiourea (I) in aqueous
formaldehyde easily enters into a similar reaction with
the simplest amino acids like glycine, β-alanine, and γ-
aminobutyric acid forming well-crystallized Mannich
bases IIa–IIc. Probably, this reaction may be used to
protect amino groups in peptide synthesis, just as it is
suggested to do with the use of urea and formaldehyde
[8].
In acetone or 2-propanol Mannich bases IIa–IIc
readily in nearly quantitative yield are alkylated with
simple alkyl halides forming a well-crystallized
isothiuronium salts IIIa–IIIc, IVa–IVc. In 2-propanol
or 2-propanol–water the action of an equivalent
amount of tert-butylamine on the S-methyl iodides
IIIa–IIIc converts the latter into zwitterionic structures
Va–Vc, the first of which (Va) was obtained by us
earlier as a result of “recrystallization” of its ion-
associate with tert-butilammonium iodide (VIa), and
by transamination of tert-butylamine analog of com-
pound IIIa with glycine in 2-propanol or ethanol [1].
So, after neutralization with tert-butylamine of slightly
heated solution of compound IIIa in aqueous 2-pro-
The scientific literature contains no data on the
aminomethylation of thiourea (I) with amino acids as
the amino component. There are a number of patents
[2–6] describing use of cyclic Mannich bases IIa–IIc,
the derivatives of thiourea and amino acids, as
stabilizers of silver halide emulsion layers of the
material for color photography, silver halide solvents
for a photographic developer compositions and toners,
the components of thermographic and photothermo-
graphic materials. The patent [2], which refers to several
other patents and the work [7], describes a general
method for the preparation of these compounds, but
236

ALKYLATION OF CYCLIC MANNICH BASES
237
panol and subsequent cooling of the neutralized solu-
tion it crystallizes as a dihydrated zwitter-ion Va·2H2O.
cyclic methylene groups, obviously due to ionic
interactions in the associate. Similar difference occurs
in the spectra of the solutions of zwitter-ion Vb and its
ionic associate with tert-butylammonium iodide VIb
as well as zwitter-ion Vc and its ionic associate with
tert-butylammonium iodide VIc. In the spectra of ionic
associate VIb the signals of these groups are shifted by
0.08–0.09 ppm compared with the zwitter-ion Vb,
while for the ionic associate VIc the shift is 0.04 ppm
compared with zwitter-ion Vc, in both cases upfield.
The zwitter-ion Vc can be isolated also by treating
the corresponding ionic associate VIc with 2-propanol,
that is, actually by washing out the tert-butylammo-
nium iodide from the zwitter-ion Vc with this solvent.
From aqueous solutions of isothiuronium salts
IIIa–IIIc mixed in equimolar ratio with tert-butyl-
amine after complete evaporation of water the ion
associates crystallized of the respective zwitter-ions
Va–Vc and tert-butylammonium iodide, a kind of
“quadrupole” VIa–VIc, which had been obtained
earlier in the reaction of amine exchange (transamina-
tion) from the 3-tert-butyl-6-(methylsulfanyl)-1,2,3,4-
tetrahydro-1,3,5-triazine hydroiodide and the corres-
ponding amino acid in water [1].
Treating the cyclic thioureas IIa–IIc with tert-
butylamine in ethanol results in the salts VIIa–VIIc.
The salts VIIa, VIIb can be obtained in another way,
in the reaction of the corresponding amino acid with
the cyclic thiourea VIII in water that indicates the
occurrence under these conditions of the reaction of
amine exchange (transamination). A similar reaction
between compound VIII iodomethylate and amino
acids in water has been described earlier [1]. The
driving force of amine exchange in these cases, in
addition to protonation of tert-butylamine is, ap-
parently, the fact that compound VIII and its iodo-
methylate bearing bulky substituents are less stable
than compounds II and V, respectively, stabilized
either by intramolecular hydrogen bonding and salt
formation or by Coulomb interaction and ionic
association, respectively.
We attempted to perform aminolysis of the iso-
thiuronium derivatives IIIb, IIIc under mild condi-
tions by keeping them at room temperature in the
medium of the aliphatic amine: for 5 min in the case of
derivatives IIIb, IIIc and tert-butylamine and for 2 h
in the case of the derivative IIIb and diethylamine. In
all three cases corresponding ion associates VIb–VId
were identified. In the first two cases we confirmed the
formation of associates VIb, VIc by coincidence of
spectral characteristics of the samples isolated from the
reaction mixture of aminolysis with those of the
samples of compounds VIb, VIc obtained earlier in [1]
and (or) in this study by the above way. In the third
case the formation of ionic associate VId is suggested
by analogy and needs to be confirmed by X-ray dif-
fraction data, but we have not succeeded yet to grow a
single crystal required for the XRD study.
The action of γ-aminobutyric acid on cyclic
thiourea VIII in water also results in transamination,
but in contrast to similar reactions with glycine and β-
alanine, where the products of amine exchange IIa, IIb
could be isolated only in the form of tert-butyl-
ammonium salts VIIa, VIIb, in this case, the product
of amine exchange IIc precipitates directly from the
reaction solution as large crystals, without binding
with the tert-butylamine.
At the attempted aminolysis of the glycine
derivative IIIa by tert-butylamine, in the solid residue
of the reaction mixture, alongside ionic associate VIa
also another compound was detected by 1H NMR spec-
troscopy. We failed to separate these two substances.
Judging from the integral intensity of the signals in the
NMR spectrum, it is presumable that this substance,
formed in a twice less amount than associate VIa, is a
cyclic urea, similar to cyclic thiourea IIa.
Salt VIIc at the attempted recrystallization from
96% ethanol hydrolyzed to the cyclic thiourea IIc. It
was shown in [1] that iodomethylates VI behave
similarly turning into zwitter-ions V at the recrystal-
lization from aqueous 2-propanol.
In 85% aqueous ethanol cyclic thiourea VIII does
not undergo the amine exchange with amino acids, and
can be identified unchanged in the dry residue of the
reaction mixture (according to NMR spectrum of its
solution in DMSO-d6).
These results indicate that basicity of the aliphatic
amine used is insufficient for the dehydroiodination of
the isothiuronium salts IIIa–IIIc.
1
It was found in [1] that in the H NMR spectra of
DMSO solutions of zwitter-ion Va and its ionic as-
sociate with tert-butilammonium iodide VIa there was
a difference in positions of the signals of methyl and
The structure of IIa is a six-membered heterocycle
that forms an envelope, whose five atoms, including
the sulfur atom, lie in one plane and the N1 atom is out
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238
SONG MINYAN et al.
1.202 Å and O2–C1 1.325 Å (1.22 Å for C=O and 1.43 Å
for C–O [9]). Some shortening of the O2–C1 bond is
due to the hydrogen bonding C1–O2H···S1=C4 (Fig. 1).
Table 1. Bond lengths (d) and bond angles (ω) in compound
IIa
Bond
S1–C4
d, Å
Angle
C4N2C3
ω, deg
The six-membered heterocycle conformation in the
structure IIIa·H2O, is an envelope, like in the case of
compound IIa, with the N1 atom significantly deviated
out of the plane of the rest ring atoms. Just as in the
structure IIa, the N1–C2 bond is almost perpendicular
to the flat fragment of the ring. Neighboring molecules
are connected in pairs by hydrogen bonds (the O2···O1
distance is 2.645 Å) through the carboxy groups in the
dimeric fragments. In addition, the oxygen O1 of the
carboxy group is involved in hydrogen bonding with
the oxygen of the hydration water O3. The O3 atom is
involved in an intermolecular hydrogen bond with the
H atom at the nitrogen N3 (the hydrogen atom at the O2
atom of the carboxy group and one of the hydrogens at
the oxygen of hydration water O3 are not localized).
Thus, the hydration water molecules combine the
dimeric fragments by hydrogen bonds into the endless
bands, which, in turn, are combined by van der Waals
contacts in the three-dimensional framework. Iodide
ion is linked by a hydrogen bond with N2 atom of the
heterocycle. In contrast to structure IIa, in the structure
IIIa·H2O in the hydrogen bonds only two nitrogen
atoms of the heterocycle are involved (Fig. 2).
The bonds N2–C4 1.32 Å and N3–C4 1.29 Å (Table 2)
are almost double bonds, and their asymmetry is due to
the involvement of the nitrogen atoms N2 and N3 in
various hydrogen bonds, N2H···I and N3H···O3 (Table 3).
What has been said about non-zwitter-ionic structure
of the glycine fragment of compound IIa is even more
true for the glycine fragment of compound IIIa,
because the positive charge of its isothiuronium
fragment even more stabilizes the non-protonated form
and destabilizes the form protonated at the N1 atom
(second protonation of the ring). The bond lengths in
the carboxy fragment O1=C1 1.21 Å and O2–C1 1.32 Å
do not differ from those in the compound IIa. The
O2–C1 bond is also shortened due to the hydrogen
bond C1–O2H···O1=C1 (Table 3).
1.713(4)
123.1(3)
N2–C4
N2–C3
O1–C1
O2–C1
N1–C5
N1–C2
N1–C3
N3–C4
N3–C5
C1–C2
1.330(5)
1.472(5)
1.202(5)
1.325(4)
1.459(5)
1.457(5)
1.453(5)
1.324(5)
1.462(5)
1.508(5)
C5N1C3
C2N1C3
C2N1C5
C5N3C4
N2C4S1
N3C4S1
N3C4N2
O1C1C2
O2C1C2
O2C1O1
N3C5N1
N1C2C1
N1C3N2
108.0(3)
112.9(3)
112.2(3)
121.4(3)
120.4(3)
121.3(3)
118.3(3)
125.0(3)
110.7(3)
124.3(3)
110.6(3)
112.5(3)
110.4(3)
of the plane, so that the N1–C2 bond is almost
perpendicular to the plane. The plane of the carboxy
group is almost perpendicular to the plane of the
heterocyclic fragment. The oxygen atoms of the
carboxy group (hydrogen atom at O2 of the carboxy
group is not localized), the sulfur atom and all nitrogen
atoms of the heterocycle are involved into the
intermolecular hydrogen bonding.
The length of S1=C4 bond is 1.713 Å (Table 1),
intermediate between those for double (1.61 Å) and
single bonds (1.81 Å) [9]. The same, but to a lesser
extent, is characteristic of the bonds N2–C4 (1.330 Å)
and N3–C4 (1.324 Å) (the C=N and C–N bond lengths
are 1.27 and 1.47 Å, respectively [9]). This indicates a
significant contribution of the thiol canonical form
with separate charges into the structure of the
compound IIa, in other words, a significant shift
occurs of electron density from the nitrogen atoms N2
and N3 to the sulfur atom. This, in turn, leads to a
significant decrease in the basicity of the nitrogen N1
(due to the destabilization of the form protonated at the
atom N1 and the stabilization of the non-protonated
form) and explains the existence of the glycine
fragment of compound IIa in a neutral, rather than
zwitter-ionic form, as show the bond lengths O1=C1
The XRD study of compounds Va, VIa [1], and
IIIa showed that these glycine derivatives crystallize
as mono- or dihydrates. The presence of hydration
water in the samples is also seen in the appearance of
the respective vibration bands in the IR spectra. For β-
alanine and γ-aminobutyric homologues of these
compounds, as well as for iodoethylates IVa–IVc,
which were not studied by XRD, the conclusion about
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ALKYLATION OF CYCLIC MANNICH BASES
239
Fig. 1. Structure of the molecule and the hydrogen bonds in the crystal of IIa by X-ray diffraction data.
Fig. 2. Structure of the molecule and the hydrogen bonds in the crystal of IIIa·H2O by X-ray diffraction data.
the presence or absence of hydration water in samples
was made on the basis of elemental analysis, and by
comparison of shortwave regions of their IR spectra
with the corresponding regions of the IR spectra of the
hydrates Va·2H2O, VIa·H2O, and IIIa·H2O.
According to elemental analysis, the samples of
compounds IIIb, IIIc and IVa–IVc do not contain
water. The non-hydration nature of the iodomethylates
IIIb, IIIc and iodoethylates IVa–IVc is consistent
with the fact that their IR spectra do not include the
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240
SONG MINYAN et al.
Table 2. Bond lengths (d) and bond angle (ω) in compound
IIIa·H2O
Table 3. Parameters of hydrogen bonds in the crystal of
IIIa·H2O
Bond
S1–C4
d, Å
Angle
C6S1C4
ω, deg
Bond (D–H···A)
O2···O1
d (D···A), Å
1.77(1)
102.5(6)
2.645
S1–C6
N2–C4
N2–C3
O1–C1
O2–C1
N1–C5
N1–C2
N1–C3
N3–C4
N3–C5
C1–C2
1.79(1)
1.32(1)
1.49(1)
1.21(1)
1.32(2)
1.44(2)
1.47(2)
1.44(2)
1.29(2)
1.49(2)
1.49(2)
C4N2C3
C5N1C3
C2N1C3
C2N1C5
C5N3C4
N2C4S1
N3C4S1
N3C4N2
O1C1C2
O2C1C2
O2C1O1
N3C5N1
N1C2C1
N1C3N2
119.0(9)
109(1)
O3···O1
N3···O3
2.853
2.803
3.516
3.522
112.8(9)
112.8(8)
120(1)
N2···I
O3···Iа
a Not shown in Fig. 2.
120.7(8)
116.3(8)
122(1)
absorption bands characteristic of stretching vibrations
of hydration water, whereas in the IR spectrum of the
hydrated iodomethylate IIIa·H2O (XRD data) it is
detected by an intense ν(O–H) band at 3510 cm–1.
125(1)
The results of elemental analysis of the zwitter-ions
Vb, Vc indicate their dihydrate structure. The presence
in the IR spectra of these compounds of broad low
intensity bands at 3425 and 3432 cm–1, respectively,
does not contradict this conclusion, since in the IR
spectrum of the zwitter-ion Va·2H2O, whose dihydrate
structure is unambiguously determined by XRD study
112(1)
122(1)
111.8(9)
111.4(9)
111.1(8)
S
HN CH2
CH2O, NH2(CH2)nCOOH
(CH2)nCOOH
HN CH2
S
C
N
H2N
NH2
HN CH2
IIa_IIc
I
I_
HN CH2
t-BuNH2
RI
(CH2)n
(CH2)nCOOH
+
+
S
S
C
N
C
N
i-PrOH, i-PrOH_H2O
HN CH2
HN CH2
H3C
R
C
_
O
O
Va_Vc
IIIa_IIIc, IVa_IVc
t-BuNH2
H2O
I_
HN CH2
(CH2)n
+
S
C
N
CH3
HN CH2
H3C
C
_
O
O
H3N+
C
C
CH3
CH3
IIc
O
VIa_VIc
CH3
HN CH2
HN CH2
NH2(CH2)nCOOH
t-BuNH2
IIa_IIc
S
C
N
CH3
CH3
C
(CH2)n
S
C
N
(n = 1, 2)
CH3
CH3
CH3
HN CH2
HN CH2
C
_
H3N+
VIII
O
VIIa_VIIc
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ALKYLATION OF CYCLIC MANNICH BASES
I_
241
HN CH2
HNRR1
+
H2N+RR1
(CH2)n
IIIb, IIIc
S
C
N
HN CH2
H3C
C
_
O
VIb_VId
O
n = 1 (a), 2 (b), 3 (c); III, R = CH3; IV, R = C2H5; VIb, n = 2, R = H, R1 = t-Bu; VIc, n = 3, R = H, R1 = t-Bu; VId, n = 2,
R = R1 = Et.
[1], the absorption of hydration water appears as a
8.657(2), c 9.562(2) Å, α 91.68(2), β 105.11(2), γ
105.89(3)°, V 612.40(26), Z 2. A set of 2121 reflec-
tions (F > 4σ), collected in the angular range 2θ 0°–
60°, was obtained from a colorless crystal of the size
0.22×0.24×0.37 mm, R 0.64.
broad intense band ν(O–H) at 3380 cm–1.
The IR spectrum of the associate VIa with
determined by X-ray data hydrate structure [1]
includes a strong band at 3466 cm–1, which can be
attributed to the stretching vibrations of O–H bonds of
the hydration water. In the IR spectra of compounds
VIb, VIc such a characteristic band is not observed,
but there are broad bands of moderate intensity in the
range 3430–3440 cm–1. It is impossible to attribute
them definitely to vibrations of the O–H or N–H
bonds. Elemental analysis indicates anhydrous (non-
hydrated) form of compound VIb and hydrated form
of VIc.
Images of crystal structures were obtained using the
Mercury 2.2 [11] and Chem3D Ultra 10.0 software.
(4-Thioxo-1,3,5-triazinan-1-yl)acetic acid (IIa).
To a mixture of 7.61 g (100 mmol) of thiourea and
15.0 ml of 37% aqueous formaldehyde (186.7 mmol)
was added at vigorous stirring 7.51 g (100 mmol) of
glycine, and stirring was continued for another 15 min
until it dissolved. A day latter, the precipitate was
filtered off and recrystallized from a mixture of 2-
propanol–water (1:1). Yield 13.40 g (76.5%), mp 176–
178°C. IR spectrum (thin film), ν, cm–1: 1550 (C–N,
δNH), 1721 (C=O), 2484, 2618 (NH), 2889, 2934
(CH2), 3063, 3205 (NH), 3379 (OH). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 3.31 s (2H,
CH2COO), 4.04 s (4H, C2H2, C6H2), 7.98 s (2H, N3H,
N5H), 12.40 s ( 1H, COOH). Found, %: C 34.86, H
5.14; N 24.46. C5H9N3O2S. Calculated, %: C 34.28; H
5.18; N 23.98.
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker AM-
400 (400 MHz) and Bruker AM-200 (200 MHz)
instruments, solvents DMSO-d6 and D2O. IR spectra
were recorded on a Shimadzu FTIR-8400S spectro-
photometer from KBr tablets. Elemental analysis was
performed on a Leco CHNS (O) 942 analyzer. TLC
was performed on Silufol UV-254 plates, eluent
chloroform–ethanol, 1:10. Acetone (commercial) was
dried and purified by the method of [10]. 2-propanol of
chemically pure grade was used without purification.
3-(4-Thioxo-1,3,5-triazinan-1-yl)propanoic acid
(IIb) was prepared similarly. Yield 16.30 g (86.1%),
mp 116–118°C. IR spectrum (thin film), ν, cm–1: 1554
(C–N, δNH), 1692 (C=O), 2556, 2614 (NH), 2888,
The XRD analysis was performed on a single-
crystal automatic diffractometer IPDS 2T STOE (MoKα-
radiation). The structure was solved and refined using
the SIR software package.
1
2932 (CH2), 3214, 3278 (NH), 3363 (OH). H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 2.37 t (2H,
NCH2CH2COO, J 6.9 Hz), 2.76 t (2H, NCH2CH2COO,
J 6.9 Hz), 3.98 s (4H, C2H2, C6H2), 7.94 s (2H, N3H,
N5H). Found, %: C 38.46, H 6.39; N 21.72. C6H11·
N3O2S. Calculated, %: C 38.08; H 5.86; N 22.21.
The structure IIa crystallizes in the monoclinic
system, space group P21/c, cell dimensions: a
7.138(2), b 9.118(2), c 12.268(3) Å, β 102.26(2)°, V
780.25(34), Z 4. A set of 1080 reflections (F > 4σ),
collected in the angular range 2θ 0–60, was obtained
from a colorless crystal of the size 0.27×0.32×0.41 mm,
R 0.42.
4-(4-Thioxo-1,3,5-triazinan-1-yl)butanoic acid (IIс).
a. The preparation was the same as for compound IIa.
Yield 14.80 g (72.8%), mp 148–152°C. IR spectrum
(thin film), ν, cm–1: 1540 (C–N), 1560 (δNH), 1698
(C=O), 2503, 2587, 2633 (NH), 2884, 2946, 3075
(CH2), 3174, 3288 (NH), 3380 (OH). 1H NMR
The structure IIIa·H2O crystallizes in the triclinic
space group P1¯, cell dimensions: a 8.014(2), b
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242
SONG MINYAN et al.
spectrum (400 MHz, DMSO-d6), δ, ppm: 1.66 m (2H,
NCH2CH2CH2COO), 2.22 t (2H, NCH2CH2CH2COO,
J 6.9 Hz), 2.53 t (2H, NCH2CH2CH2COO, J 6.9 Hz),
3.97 s (4H, C2H2, C6H2), 7.91 s (2H, N3H, N5H ),
11.87 s (1H, COOH). Found, %: C 41.87, H 6.35; N
21.32. C7H13N3O2S. Calculated, %: C 41.36; H 6.45; N
20.67.
washed with a small amount of 2-propanol. Yield 3.2 g
(60.6%), mp 160–162°C (2-propanol). IR spectrum
(thin film), ν, cm–1: 1565, 1602 (C–N, δ+NH), 1706
(C=O, δ+NH), 2929, 2978 (CH2, CH3), 3048, 3148,
1
3173, 3254 (NH), 3403 (OH), 3510 (H2O). H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 2.57 s (3H,
CH3), 3.45 s (2H, CH2COO), 4.41 s (4H, C2H2, C4H2),
9.90 br.s (NH, OH). Found, %: C 22.07, H 4.14, N
13.08. C6H12IN3O2S·H2O. Calculated, %: C 21.50; H
4.21; N 12.54.
b. Hydrolysis of salts VIIc. 1.319 g (4.77 mmol) of
compound VIIc was boiled a few min in 5 ml of 96%
ethanol, the solution was cooled, and the precipitate
was filtered off. Yield 0.732 g. Crystallization was
repeated once more, mp 157–158°C. IR spectrum (thin
film), ν, cm–1: 1539 (C–N), 1561 (δNH), 1702 (C=O),
2505, 2583, 2626 (NH), 2886, 2945, 3072 (CH2),
3178, 3290 (NH), 3381 (OH). 1H NMR spectrum (400
MHz, DMSO-d6), δ, ppm: 1.67 m (2H, NCH2CH2·
CH2COO), 2.24 t (2H, NCH2CH2CH2COO, J 7.4 Hz),
2.54 t (2H, NCH2CH2CH2COO, J 6.9 Hz), 3.98 s (4H,
C2H2, C6H2), 7.95 s (2H, N3H, N5H .) Found, %: C
40.77, H 6.00; N 20.09. C7H13N3O2S. Calculated, %: C
41.36; H 6.45; N 20.67.
3-(2-Carboxyethyl)-6-(methylsulfanyl)-2,3,4,5-
tetrahydro-1,3,5-triazin-1-ium iodide (IIIb). a. To a
mixture of 1.890 g (9.99 mmol) of compound IIb and
30 ml of acetone under vigorous stirring at room
temperature was added 2.1 ml (4.786 g, 33.72 mmol)
of methyl iodide. The starting material completely
dissolved, but after 30 min on the flask wall started to
form a precipitate. After 1 day the precipitated product
was filtered off and washed with a small amount of
acetone. Yield 2.202 g (63.1%), mp 142–144°C. IR
spectrum (thin film), ν, cm–1: 1545, 1597 (C–N, δ+NH),
1728 (C=O, δ+NH), 2872, 2923, 2969, 2990 (CH2, CH3),
c. From 1,733 g (10 mmol) of compound VIII in
30 ml of water and 1.031 g (10 mmol) of γ-amino
butyric acid in 10 ml of water at 45°C similarly to the
preparation of compounds VIIa and VIIb by the
method b (see below). 15 min after mixing the reagents
dissolved. The reaction mixture was left at room
temperature. In 2 days large crystals precipitated,
which were washed with water and dried first in air
and then in a vacuum desiccator over CaCl2. Yield
1.323 g (65.1%), mp 163–167°C. IR spectrum (thin
film), ν, cm–1: 1540 (C–N), 1560 (δNH), 1702 (C=O),
2518, 2583, 2628 (NH), 2884, 2946, 3072 (CH2),
3171, 3289 (NH), 3375 (OH). 1H NMR spectrum (400
MHz, DMSO-d6), δ, ppm: 1.66 m (2H, NCH2CH2·
CH2COO), 2.23 m (2H, NCH2CH2CH2COO), 2.53 m
(2H, NCH2CH2CH2COO), 3.98 s (4H, C2H2, C6H2),
7.92 s (2H, N3H, N5H), 11.79 br.s (1H, COOH).
Found, %: C 40.70, H 6.09; N 20.20. C7H13N3O2S.
Calculated, %: C 41.36; H 6.45; N 20.67.
1
3045, 3110, 3149 (NH), 3351 (OH). H NMR spec-
trum (400 MHz, DMSO-d6), δ, ppm: 2.47 t (2H,
NCH2CH2COO, J 6.9 Hz), 2.57 s (3H, CH3), 2.85 m
(2H, NCH2CH2COO, J 6.9 Hz), 4.35 s (4H, C2H2,
C4H2), 9.80 br.s (NH, OH). Found, %: C 25.97, H
4.10; N 13.28. C7H14IN3O2S. Calculated, %: C 25.39;
H 4.26; N 12.69.
b. To a mixture of 1.890 g (9.99 mmol) of
compound IIb and 30 ml of 2-propanol under vigorous
stirring was added at room temperature 2.1 ml (4.786 g,
33.72 mmol) of methyl iodide. Within 15 min the
initial material completely disappeared, and after 10 min
the product began to precipitate. After 2 h the pre-
cipitate formed was filtered off and washed with a
small amount of 2-propanol. Yield 2.35 g (67.3%), mp
140–144°C.
3-(3-Carboxypropyl)-6-(methylsulfanyl)-2,3,4,5-
tetrahydro-1,3,5-triazin-1-ium iodide (IIIc). a. The
preparation was the same as for compound IIIb from
2.030 g (9.99 mmol) of compound IIc and 2.1 ml
(4.786 g, 33.72 mmol) of methyl iodide in 30 ml of
acetone. Yield 2.226 g (64.5%), mp 98–100°C. IR
spectrum (thin film), ν, cm–1: 1546, 1596 (C–N, δ+NH),
1697 (C=O, δ+NH), 2924, 3051 (CH2, CH3), 3115, 3151,
3235 (NH), 3446 (OH). 1H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 1.73 m (2H, NCH2CH2CH2COO),
2.26 t (2H, NCH2CH2CH2COO, J 6.9 Hz), 2.57 s (3H,
3-(2-Carboxyethyl)-6-(methylsulfanyl)-2,3,4,5-tetra-
hydro-1,3,5-triazin-1-ium iodide (IIIa), hydrate. To
a mixture of 1.750 g (9.99 mmol) of compound IIa and
30 ml of 2-propanol under vigorous stirring was added
at room temperature 2.1 ml (4.786 g, 33.72 mmol) of
methyl iodide. The precipitate of the starting material
completely dissolved, but after 30 min on the flask
wall started to form precipitate of the product. A day
latter, the resulting precipitate was filtered off and
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ALKYLATION OF CYCLIC MANNICH BASES
243
CH3), 2.62 t (2H, NCH2CH2CH2COO, J 6.9 Hz ), 4.34
s (4H, C2H2, C4H2), 9.78 br.s (NH, OH). Found, %: C
28.35, H 4.55; N 12.71. C8H16IN3O2S. Calculated, %:
C 27.83; H 4.67; N 12.17.
temperature was added 2.4 ml (4.639 g, 29.8 mmol) of
ethyl iodide. After 5 h the starting material completely
dissolved. The reaction solution was left to stand at
room temperature. After 2 days at the bottom of the
flask formed a transparent film, which over 2 days has
turned into a solid white precipitate. Yield 1,987 g
(55.4%), mp 98–100°C. IR spectrum (thin film), ν, cm–1:
1544, 1601 (C–N, δ+NH), 1731 (C=O, δ+NH), 2865, 2924,
b. The preparation was the same as for compound
IIIb from 2.030 g (9.99 mmol) of compound IIc and
2.1 ml (4.786 g, 33.72 mmol) of methyl iodide in
30 ml of 2-propanol. Yield 2.44 g (70.8%), mp 101–
103°C.
1
2954 (CH2, CH3), 3106, 3162 (NH) , 3447 (OH). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 1.29 t
(3H, CH3CH2, J 7.2 Hz), 1.72 m (2H, NCH2CH2·
CH2COO), 2.26 t (2H, NCH2CH2CH2COO, J 6.9 Hz),
2.60 t (2H, NCH2CH2CH2COO, J 6.9 Hz), 3.14 q (2H,
CH3CH2, J 7.2 Hz), 4.35 s (4H, C2H2, C4H2), 9.84 br.s
(2H, N1H, N5H), 11.91 br.s [1H, C(O)OH]. Found, %:
C 30.63, H 4.73; N 12.18. C9H18IN3O2S. Calculated,
%: C 30.09; H 5.05; N 11.70.
3-(Carboxymethyl)-6-(ethylsulfanyl)-2,3,4,5-
tetrahydro-1,3,5-triazin-1-ium iodide (IVа). To a
solution of 1.750 g (9.99 mmol) of compound IIa in
30 mL of ethanol at 45°C under vigorous stirring was
added 2.4 ml (4.639 g, 29.8 mmol) of ethyl iodide. The
reaction mixture was stirred for 1 h to cool to room
temperature. 0.035 g of precipitated glycine was
filtered off (data of NMR spectroscopy in D2O) and
the filtrate was placed in a Petri dish to evaporate the
solvent. The large yellow crystals formed within a day
were washed with 2-propanol, filtered off and dried in
a vacuo over CaCl2. Yield 1.101 g (33.3%), mp 110–
114°C. IR spectrum (thin film), ν, cm–1: 1562, 1597
(C–N, δ+NH), 1703, 1719 (C=O, δ+NH), 2728, 2882,
2960, 2983 (CH2, CH3), 3100 3141, 3201 (NH), 3389
[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-3-
ium-1(2H)-yl] acetate (Vа) dihydrate. A mixture of
0.317 g (0.946 mmol) of compound IIIa·H2O
recrystallized from ethanol, and 0.105 ml (0.073 g,
0.999 mmol) of tert-butylamine in 5 ml of 2-propanol–
water (9:1) was refluxed at 40–45°C for ~10 min to
complete dissolution of compound IIIa. The preci-
pitate formed after cooling the reaction mixture was
filtered off, washed with a small amount of 2-propanol,
and dried in a vacuum desiccator. Yield 0.068 g
(31.9%), mp 158–160°C (125°C [1]). IR spectrum
(thin film), ν, cm–1: 1589 (C–N, δ+NH, CO2–), 1646
(δ+NH), 2890, 2931 (CH2, CH3), 3193 (NH), 3380
1
(OH). H NMR spectrum (400 MHz, DMSO-d6), δ,
ppm: 1.30 t (3H, CH3CH2, J 7.4 Hz), 3.15 q (2H,
CH3CH2, J 7.9 Hz), 3.45 s (2H, CH2COO), 4.43 s (4H,
C2H2, C4H2). Found, %: C 25.02, H 4.26; N 12.36.
C7H14IN3O2S. Calculated, %: C 25.39; H 4.26; N
12.69.
1
(H2O). H NMR spectrum (400 MHz, DMSO-d6), δ,
ppm: 2.24 (3H, SCH3), 3.27 s (2H, CH2COO), 4.13 s
(4H, C2H2, C6H2). Found, %: C 32.58, H 6.54; N
18.68. C6H11N3O2S·2H2O. Calculated, %: C 31.99; H
6.71; N 18.65.
3-(2-Carboxyethyl)-6-(ethylsulfanyl)-2,3,4,5-
tetrahydro-1,3,5-triazin-1-ium iodide (IVb). The
preparation was the same as for compound IIIb by the
method a from 1.890 g (9.99 mmol) of compound IIb
and 2.4 ml (4.639 g, 29.8 mmol) of ethyl iodide. Yield
1.33 g (38.6%), mp 102–105°C. IR spectrum (thin
film), ν, cm–1: 1550, 1594 (C–N, δ+NH), 1724 (C=O,
δ+NH), 2856, 2896, 2946 (CH2, CH3), 3019, 3252 (NH) ,
3420 (OH). 1H NMR spectrum (400 MHz, DMSO-d6),
δ, ppm: 1.29 t (3H, CH3CH2, J 6.9 Hz), 2.47 t (2H,
NCH2CH2COO, J 6.4 Hz), 2.82 t (2H, NCH2CH2COO,
J 6.4 Hz), 3.11 q (2H, CH3CH2, J 6.9 Hz), 4.33 s (4H,
C2H2, C4H2), 9.70 br.s (2H, N1H, N5H). Found, %: C
28.40, H 4.88; N 12.78. C8H16IN3O2S. Calculated, %:
C 27.83; H 4.67; N 12.17.
3-[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-
3-ium-1(2H)-yl] propanoate (Vb) dihydrate. Pre-
pared similarly from 0.331 g (1.00 mmol) of com-
pound IIIb and 0.105 ml (0.0731 g, 1.00 mmol) of
tert-butylamine. Yield 0.113 g (55.6%), mp 136°C. IR
spectrum (thin film), ν, cm–1: 1567, 1595 (C–N, δ+NH
,
CO2–), 1710 (δ+NH), 2915, 2973, 3031, 3083 (CH2, CH3),
3137, 3425 (NH) 1H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 2.37 s (3H, CH3), 2.41 t (2H,
NCH2CH2COO, J 7.4 Hz), 2.81 t (2H, NCH2CH2·
COO, J 7.4 Hz) , 4.19 s (4H, C2H2, C6H2). Found, %:
C 34.60, H 6.82; N 16.96. C7H13N3O2S·2H2O. Cal-
culated, %: C 35.13; H 7.16; N 17.56.
3-(2-Carboxypropyl)-6-(ethylsulfanyl)-2,3,4,5-
tetrahydro-1,3,5-triazin-1-ium iodide (IVc). To a
mixture of 2.030 g (9.99 mmol) of compound IIс and
30 ml of acetone under vigorous stirring at room
4-[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-
3-ium-1(2H)-yl] butyrate (Vc) dihydrate. a. The
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244
SONG MINYAN et al.
preparation was the same from 0.345 g (1.00 mmol) of
compound IIIc in 5 ml of 2-propanol. Yield 0.1058 g
(48.7%), mp 140–142°C (2-propanol). IR spectrum
(thin film), ν, cm–1: 1569 (C–N, δ+NH), 1612 (CO2–),
1721 (δ+NH), 2856, 2912, 2937 (CH2, CH3), 3069, 3164,
3252, 3432 (NH). 1H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 1.70 m (2H, NCH2CH2CH2COO),
2.25 t (2H, NCH2CH2CH2COO, J 6.9 Hz), 2.37 s (3H,
CH3), 2.58 t ( 2H, NCH2CH2CH2COO, J 5.9 Hz), 4.18
s (4H, C2H2, C6H2). Found, %: C 37.34, H 7.01; N
16.16. C8H15N3O2S·2H2O. Calculated, %: C 37.93; H
7.56; N 16.59.
b. A mixture of 0.331 g (0.999 mmol) of compound
IIIb and 10 ml of tert-butylamine was stirred with a
magnetic stirrer at room temperature to form a
gelatinous slurry. After 5 min the suspension was
transferred to a Petri dish for evaporation of the amine.
After 3 days the solid residue was crushed and dried in
a vacuum. Yield 0.318 g (79.4%), mp 121–124°C
(127–130°C [1]). IR spectrum (thin film), ν, cm–1:
1536, 1562, 1583 (C–N, δ+NH), 1608 (CO2–), 2878,
2926, 2967 (CH2, CH3), 3160 sh, 3425 (NH). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 1.26 s [9H, C
(CH3)3], 2.23
s
(3H, SCH3), 2.34
t
(2H,
NCH2CH2COO, J 6.9 Hz), 2.77 t (2H, NCH2CH2COO,
J 6.9 Hz), 7.4 s (4H, C2H2, C6H2). Found, %: C 31.96,
H 6.47; N 13.94. C7H13N3O2S·C4H12IN. Calculated, %:
C 32.68, H 6.523; N 13.86.
b. To 0.389 g (0.930 mmol) of compound VIc was
added 30.0 ml of 2-propanol, insoluble precipitate was
filtered off and dried in vacuo over CaCl2. Yield 0.111 g
(55.0%), mp 142–144°C.
4-[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-
3-ium-1(2H)-yl] butanoate associate with tert.-
butylammonium iodide (1:1) (VIc) hydrate. a. The
preparation was the same as for compound VIa from
0.363 g (1.052 mmol) of compound IIIc and 0.15 ml
(0.104 g, 1,427 mmol) of tert-butylamine in 5 ml of
water. Yield 0.298 g (67.7%), mp 134–138°C. IR
spectrum (thin layer), ν, cm–1: 1563, 1571 (C–N, δ+NH),
1607, 1718 (CO2–), 2934, 2976 (CH2, CH3), 3066,
[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-3-
ium-1(2H)-yl] acetate associate with tert-butyl-
ammonium iodide (1:1) (VIa) hydrate. A mixture of
0.335 g (1.000 mmol) of compound IIIa·H2O in 7 ml
of water and 0.15 ml (0.104 g, 1,427 mmol) of tert-
butylamine was stirred for 2 h at room temperature and
then poured into a Petri dish for evaporation of the
solvent. After 5 days solid shiny single crystals
formed, which were dried in vacuo over CaCl2. Yield
0.304 g (74.4%), mp 125–128°C (127–129°C [1]). IR
spectrum (thin film), ν, cm–1: 1593 (C–N, δ+NH, CO2–),
2884, 2926, 2978 (CH2, CH3), 3049 (NH), 3432 (H2O).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
1.25 s [9H, C(CH3) 3], 2.35 s (3H, SCH3), 3.20 s (2H,
CH2COO), 4.22 s (4H, C2H2, C6H2). Found, %: C
29.62, H 5.90; N 13.80. C6H11N3O2S·C4H12IN·H2O.
Calculated, %: C 29.42, H 6.17; N 13.72.
1
3173, 3431 (NH). H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 1.25 s [9H, C(CH3)3], 1.67 m (2H,
NCH2CH2CH2COO), 2.22 t (2H, NCH2CH2CH2COO,
J 6.9 Hz), 2.25 s (3H, CH3), 2.54 t (2H, NCH2CH2·
1
CH2COO, J 6.9 Hz), 4.08 s (4H, C2H2, C6H2). H
NMR spectrum (400 MHz, D2O), δ, ppm: 1.36 s [9H,
C(CH3)3], 1.80 m (2H, NCH2CH2CH2COO), 2.22 t
(2H, NCH2CH2CH2COO, J 7.4 Hz), 2.56 s (3H, CH3),
2.72 t (2H, NCH2CH2CH2COO, J 7.4 Hz), 4.44 s (4H,
C2H2, C6H2). Found, %: C 32.50, H 6.22; N 12.69.
C8H15N3O2S·C4H12IN·H2O. Calculated, %: C 33.03, H
6.70; N 12.84.
3-[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-
3-ium-1(2H)-yl] propanoate associate with tert-
butylammonium iodide (1:1) (VIb). a. The prepara-
tion was the same from 0.348 g (1.051 mmol) of
compound IIIb and 0.15 ml (0.104 g, 1.427 mmol) of
tert-butylamine in 3 ml of water. Yield 0.311 g
(73.2%), mp 130–133°C (127–130°C [1]). IR spectrum
(thin film), ν, cm–1: 1536, 1566 (C–N, δ+NH), 1606
(CO2–), 2923, 2967 (CH2, CH3), 3160 sh, 3439 (NH).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
1.25 s [9H, C(CH3)3], 2.28 s (3H, SCH3), 2.33 t (2H,
NCH2CH2COO, J 7.4 Hz), 2.76 t (2H, NCH2CH2COO,
J 7.4 Hz), 4.11 s (4H, C2H2, C6H2). Found, %: C 32.84,
H 5.94; N 13.76. C7H13N3O2S·C4H12IN. Calculated, %:
C 32.68, H 6.23; N 13.86.
b. To 0.345 g (0.999 mmol) of compound IIIc was
added while stirring 10 ml of tert-butylamine. After a
few seconds the initial compound dissolved, and an
amorphous precipitate began to form in the entire
volume of the reaction mixture. The reaction mixture
was left overnight. In the flask formed a finely
dispersed suspension, which was transferred to a Petri
dish for evaporation of the amine excess. After
2 months the whole mass solidified. Yield 0.183 g
(42.0%), mp 102–104°C. IR spectrum (thin film), ν,
cm–1: 1562 (C–N, δ+NH), 1609, 1712 (CO2–), 2878, 2913,
2978 (CH2, CH3), 3002, 3056, 3153, 3257, 3418 (NH).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
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ALKYLATION OF CYCLIC MANNICH BASES
245
1.25 s [9H, C(CH3)3], 1.67 m (2H, NCH2CH2·
CH2COO), 2.21 t (2H, NCH2CH2CH2COO, J 6.9 Hz),
2.30 s (3H, CH3), 2.54 t (2H, NCH2CH2CH2COO,
J 6.9 Hz), 4.12 s ( 4H, C2H2, C6H2). Found, %: C
32.04, H 5.95; N 12.63. C8H15N3O2S·C4H12IN·H2O.
Calculated, %: C 33.03; H 6.70; N 12.84.
After 2 days the resulting crystals were dried in a
vacuum over CaCl2 and recrystallized from ethanol.
Yield 0.982 g (39.5%), mp 180–183°C. IR spectrum
(thin film), ν, cm–1: 1529 (C–N), 1562 (δ+NH), 1630
(CO2–), 2532, 2622, 2730, 2835, 2872, 2934, 2982
1
(CH2, CH3), 3030, 3242, 3416 (NH). H NMR spec-
trum (400 MHz, DMSO-d6), δ, ppm: 1.22 s [9H,
C(CH3)3], 3.01 s (2H, CH2COO), 4.06 s (4H, C2H2,
C6H2), 7.89 (2H, NH). Found, %: C 43.81, H 7.76; N
22.97; S 12.35. C9H20N4O2S. Calculated, %: C 43.53,
H 8.12; N 22.56; S 12.91.
3-[4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-
3-ium-1(2H)-yl] propanoate associate with
diethylammonium iodide (1:1) (VId). A mixture of
0.331 g (0.999 mmol) of compound IIIb and 10 ml of
diethylamine was stirred with a magnetic stirrer at
room temperature for 30 min, the dissolution was not
observed. After 2 h the upper liquid layer (diethyl-
amine) was decanted, and a syrupy suspension at
bottom was transferred to a Petri dish for the amine
evaporation. After 3 days the solid residue was crushed
and dried in a vacuum. Yield 0.287 g (71.7%), mp
108–110°C. IR spectrum (thin film), ν, cm–1: 1562
(C–N, δ+NH), 1611 (CO2–), 2813, 2859, 2910, 2959,
2-Methylpropane-2-ammonium(4-thioxo-1,3,5-
triazinane-1-yl) propanoate (VIIb). a. The prepara-
tion was the same as for compound VIIa from 0.360 g
(1.9 mmol) of compound IIb and 0.139 g (0.20 ml,
1.9 mmol) of tert-butylamine in 20 ml of ethanol.
Yield 0.456 g (91.5%), mp 157–160°C. IR spectrum
(thin film), ν, cm–1: 1543 (C–N, δ+NH), 1629 (CO2–),
2543, 2616, 2732, 2845, 2885, 2931, 2975 (CH2, CH3),
3079, 3196, 3415 (NH). 1H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 1.19 s [9H, C(CH3)3],
2.14 br.s (2H, NCH2CH2COO), 2.70 br.s (2H,
NCH2CH2COO), 3.97 s (4H, C2H2, C6H2), 7.95 (2H,
NH). Found, %: C 45.28, H 7.92; N 21.93.
C10H22N4O2S. Calculated, %: C 45.78, H 8.45; N 21.35.
1
2988 (CH2, CH3), 3048, 3218, 3418 sh ( NH). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 1.19 t
(6H, CH2CH3, J 7.4 Hz), 2.35 t (2H, NCH2CH2COO,
J 6.9 Hz), 2.38 s (3H, SCH3), 2.77 t (2H, NCH2CH2·
COO, J 6.9 Hz), 2.91 q (4H, CH2CH3, J 7.4 Hz), 4.19 s
(4H, C2H2, C6H2). Found, %: C 32.12, H 6.15; N
13.70. C11H25IN4O2S. Calculated, %: C 32.68, H 6.23;
N 13.86.
b. The preparation was the same as for compound
VIIa from 1.733 g (10 mmol) of compound VIII and
0.891 g (10 mmol) of β-alanine. Yield 1.129 g
(43.0%), mp 159–162°C. IR spectrum (thin film), ν,
cm–1: 1528 (C–N), 1630 (CO2–), 2543, 2627, 2738,
2844, 2890, 2930, 2978 (CH2, CH3), 3007, 3199, 3340
2-Methylpropane-2-ammonium(4-thioxo-1,3,5-
triazinane-1-yl) acetate (VIIa). a. To 0.333 g (1.9 mmol)
of compound IIa in 50 ml of ethanol at 45–50°C at
vigorous stirring was added 0.139 g (0.20 ml,
1.9 mmol) of tert-butylamine. After 1 day the
precipitate was filtered off, washed with ethanol, and
dried in a vacuum desiccator over CaCl2. Yield 0.334 g
(70.8%), mp 185–186°C. IR spectrum (thin film), ν,
cm–1: 1528 (C–N), 1571 (δ+NH), 1630 (CO2–), 2533,
2622, 2834, 2874, 2934, 2982 (CH2, CH3), 3030 3243,
3418 (NH). 1H NMR spectrum (400 MHz, DMSO-d6),
δ, ppm: 1.22 s [9H, C(CH3)3], 2.98 s (2H, CH2COO),
4.05 s (4H, C2H2, C6H2), 7.92 (2H, NH). Found, %: C
44.02, H 8.41; N 23.04. C9H20N4O2S. Calculated, %: C
43.53, H 8.12; N 22.56.
1
(NH). H NMR spectrum (400 MHz, DMSO-d6), δ,
ppm: 1.20 with [9H, C(CH3)3], 2.15 br.s (2H,
NCH2CH2COO), 2.70 br.s (2H, NCH2CH2COO), 3.97
s (4H, C2H2, C6H2), 7.94 (2H, NH). Found, %: C
46.22, H 7.91; N 21.74; S 11.63. C10H22N4O2S.
Calculated, %: C 45.78, H 8.45; N 21.35; S 12.22.
2-Methylpropane-2-ammonium(4-thioxo-1,3,5-
triazinane-1-yl) butanoate (VIIc). The preparation
was the same as for compound VIIa from 0.386 g
(1.9 mmol) of compound IIb and 0.139 g (0.20 ml,
1.9 mmol) of tert-butylamine in 10 ml of ethanol at
65°C. Yield 0.495 g (94.3%), mp 138–140°C. IR
spectrum (thin film), ν, cm–1: 1551 (C–N, δ+NH), 1637
(CO2–), 2534, 2614, 2846, 2925, 2975 (CH2, CH3),
3044, 3186, 3389 (NH). 1H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 1.16 s [9H, C(CH3)3], 1.62 m (2H,
NCH2CH2CH2COO), 2.03 t (2H, NCH2CH2CH2COO,
J 6.9 Hz), 2.51 t (2H, NCH2CH2CH2COO, J 6.9 Hz),
b. To a suspension of 1.733 g (10 mmol) of
compound VIII in 30 ml of water was added with
stirring a solution of 0.751 g (10 mmol) of glycine in
10 ml of water. The reaction mixture was heated to 60°C
and kept at this temperature for 1.5 h, after which the
solution was left to stand for 1 day at room
temperature, and then was poured into a Petri dish.
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SONG MINYAN et al.
3.97 s (4H, C2H2, C6H2), 7.94 (2H, NH). Found, %: C
48.44, H 9.00; N 20.83. C11H24N4O2S. Calculated, %:
C 47.80, H 8.75; N 20.27.
5. Haijima, A., Yoshikawa, S., and Kojima, T., Japan
Patent no. 09005951, 1997; C. A., 1997, vol. 126,
no. 14, 192860.
6. Gehin, G.M., Bredoux, F.J., Gautier, P.J.P., and
Hatif, P.R., France Patent no. 2500179, 1982; C. A.,
1983, vol. 98, no. 14, 117062.
5-tert-Butyl-1,3,5-triazinan-2-thione VIII was
obtained by the method of [7].
7. Lazarev, D.B., Ramsh, S.M., and Ivanenko, A.G., Zh.
Obshch. Khim., 2000, vol. 70, no. 3, p. 475.
REFERENCES
1. Song Minyan, Ramsh, S.M., Fundamenskii, V.S.,
Solov’eva, S.Yu., and Zakharov, V.I., Zh. Obshch.
Khim., 2010, vol. 80, no. 3, p. 489.
2. Lynch, D.C., Ulrich, S.M., and Skoug, P.G., USA
Patent no. 6703191, 2004, C. A., 2004, vol. 140, no. 15,
243521.
3. Bergthaller, P., Borst, H.-U., and Siegel, J., German
Patent no. 19920354, 2000; C. A., 2000, vol. 133,
no. 25, 357189.
4. Yoshikawa, S., Kojima, T., and Haijima, A., Japan
Patent no. 09005962, 1997; C. A., 1997, vol. 126, no. 15,
205415.
8. Greene, T.W. and Wuts, P.G.M., Protective Groups in
Organic Synthesis, New York: John Wiley and Sons,
1999. 799 p.
9. Rabinovich, V.A. and Khavin, Z.Ya., Kratkii khimi-
cheskii spravochnik (Brief Chemical Handbook), Lenin-
grad: Khimiya, 1977.
10. Bekker, G., Organikum, Moscow: Mir, 1979, vol. 2.
11. Macrae, C.F., Bruno, I.J., Chisholm, J.A., Edgington, P.A.,
McCabe, P., Pidcock, E., Rodrigues-Monge, L., Taylor, R.,
van de Streek, J., and Wood, P.A., J. Appl. Cryst., 2008,
vol. 41, no. 2, p. 466.
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