Thiomethylation of amino alcohols using formaldehyde and hydrogen sulfide

Article abstract of DOI:10.1134/S1070428007060218

Three-component condensations of formaldehyde with hydrogen sulfide and hydroxylamine or amino alcohols at a ratio of 3:2:1 give 47-73% of N-hydroxy(or hydroxyalkyl)-1,3,5-dithiazinanes. The reactions of CH₂O with H ₂S and hydroxylamine or α-amino alcohols at a ratio of 4:3:1 involve both amino and hydroxy groups, leading to the corresponding dithiazinanes. 4-Aminobutan-1-ol reacts with CH₂O and H₂S under analogous conditions only at the amino group to form 4-(1,3,5-dithiazinan- 5-yl)butan-1-ol.

Full text of DOI:10.1134/S1070428007060218

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 6, pp. 918–925. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.R. Akhmetova, G.R. Nadyrgulova, T.V. Tyumkina, Z.A. Starikova, M.Yu. Antipin, R.V. Kunakova, U.M. Dzhemilev, 2007,
published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 6, pp. 919–926.
Thiomethylation of Amino Alcohols Using Formaldehyde and
Hydrogen Sulfide
V. R. Akhmetovaa, G. R. Nadyrgulovaa, T. V. Tyumkinaa, Z. A. Starikovab, M. Yu. Antipinb,
R. V. Kunakovaa, and U. M. Dzhemileva
a Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
b Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, Moscow, Russia
Received March 10, 2006; revised September 8, 2006
Abstract—Three-component condensations of formaldehyde with hydrogen sulfide and hydroxylamine or
amino alcohols at a ratio of 3:2:1 give 47–73% of N-hydroxy(or hydroxyalkyl)-1,3,5-dithiazinanes. The
reactions of CH2O with H2S and hydroxylamine or α-amino alcohols at a ratio of 4:3:1 involve both amino and
hydroxy groups, leading to the corresponding dithiazinanes. 4-Aminobutan-1-ol reacts with CH2O and H2S
under analogous conditions only at the amino group to form 4-(1,3,5-dithiazinan-5-yl)butan-1-ol.
DOI: 10.1134/S1070428007060218
Thiomethylation of various amines with formalde-
hyde and hydrogen sulfide is known to give 1,3,5-di-
thiazinanes [1–3]. With a view to extent the scope of
application of this method and elucidate the possibility
of using difunctional amino- and hydroxy-containing
monomers as substrates, in the present study we
examined for the first time reactions of aliphatic amino
alcohols with CH2O and H2S. As initial compounds we
selected aqueous ammonia, hydroxylamine, 2-amino-
ethanol, R-(–)-2-aminobutan-1-ol, 2-amino-3-hydroxy-
propionic acid (serine), and 4-aminobutan-1-ol. Ac-
cording to [4], hydroxylamine reacts with formalde-
hyde to give exclusively 1,3,5-trihydroxy-1,3,5-tri-
azine. We have found that three-component condensa-
tion of hydroxylamine with CH2O and H2S at a ratio
of 1:2:1 or 1:3:2 at 20°C leads to the formation of
1,3,5-dithiazinan-5-ol (I) (Scheme 1). When the
amount of the thiomethylating agent (CH2O–H2S) in-
creases (reactant ratio 1:4:3), the hydroxy group of the
substrate is also involved in the process. At a reactant
ratio of 1:2:1, the yield of compound I is ~31%; also,
5-methyl-1,3,5-dithiazinane (II) is formed as minor
product: its fraction does not exceed 1% (Table 1). In
the presence of excess CH2O and H2S (NH2OH–H2O–
H2S ratio 1:4:3), the major product is 1,3,5-dithia-
zinan-5-yloxymethanol (III, ~56%). In addition, ~3%
of 1,3,5-dithiazinane (IV) and ~2% of 1,2,4-trithiolane
(V) are formed. Further raising of the amount of
CH2O–H2S to a ratio of (5:3):1 with respect to
hydroxylamine favors preferential formation of alcohol
III which is likely to arise from compound I and
formaldehyde.
Scheme 1.
7
5
N
6
OH
Me
3S
2
S
N
4
CH2O–H2S (2:1), 20°C, 3 h
+
1
S
S
I
II
NH2OH·HCl
7
9
5
N
6
S4
O
OH
3S
2
S
N
4
CH2O–H2S (4:3), 0 to 70°C, 3 h
3
5
8
I
+
+
+
1
S
2S S1
S
III
IV
V
918

THIOMETHYLATION OF AMINO ALCOHOLS
919
Table 1. Reaction of hydroxylamine with formaldehyde and
hydrogen sulfide
The yield of dithiazine I is 46–47% at a stoichio-
metric reactant ratio (NH2OH–CH2O–H2S, 1:3:2) in
the temperature range from 20 to 70°C (Table 1). The
formation of 5-methyl-1,3,5-dithiazinane (II) may be
explained assuming that methylamine is generated
during the process; its reaction with CH2O and H2S
leads to dithiazinane II, which is consistent with the
data of [5–7]. Dithiazinanes I and III were isolated as
individual substances by column chromatography on
silica gel using toluene–ethyl acetate–acetone (4:1:1)
as eluent. The structure of compound I was proved by
X-ray analysis.
Yield, %
Ratio NH2OH– Tempera-
CH2O–H2S
ture, °C
I
II
III
IV
V
1: 2: 1
1: 3: 2
20
20
40
70
00
40
70
40
31
47
46
47
10
05
05
05
1
2
5
3
3
1
6
4
–
–
–
–
–
1
3
4
3
–
–
–
–
2
2
1
2
02
07
05
38
56
39
54
1: 4: 3
1: 5: 3
According to the X-ray diffraction data, the crystal-
line structure of I includes two independent molecules
IA and IB (Fig. 1), each having chair conformation of
the heteroring with axial orientation of the hydroxy
group but different geometric parameters (Table 2).
Molecules IA and IB in crystal are linked to give
H-dimers via O2–H2···O1 hydrogen bonds with the fol-
lowing parameters: O1···O2 2.892(2), H2···O1 2.33 Å,
∠O2H2O1 124°. The hydroxy proton (H1) in molecule
IB is not involved in intermolecular hydrogen bond,
but it gives rise to intramolecular hydrogen bond with
the S1 sulfur atom, which provides additional stabiliza-
tion of the heteroring conformation. The distance from
H1 to S1 (2.61 Å) is shorter than to S2 (2.74 Å), while
the distances H2···S3 and H2···S4 in molecule IA are
approximately equal (2.72 and 2.75 Å, respectively).
Analogous chair conformation of the dithiazinane ring
was found previously for such compounds as 2,4,6-tri-
methyl-5-nitroso-5,6-dihydro-4H-1,3,5-dithiazine [9],
2-(6-methoxy-3,5,6-trimethyltetrahydro-2H-pyran-5-
yl)-1,3,5-dithiazinane [10], and 2,4,6-trimethyl-1,3,5-
dithiazinane [11].
Table 2. Bond lengths (Å) and bond angles (deg) in mole-
cules IA and IB in crystal
Parameter
N–O bond
Molecule IA
Molecule IB
N2–O2 1.408(2)
N1–O1 1.422(2)
N–C bond
N2–C5 1.457(2)
N1–C2 1.442(2)
N2–C6 1.451(2)
N1–C3 1.446(2)
S–C bond
S3–C5 1.823(2)
S4–C6 1.824(2)
S3–C4 1.804(2)
S4–C4 1.801(2)
S1–C2 1.822(2)
S2–C3 1.822(2)
S1–C1 1.801(2)
S2–C1 1.800(2)
Intramolecular
O2···S3 3.163
O1···S1 3.107
O···S distance O2···S4 3.169
O1···S2 3.135
Intramolecular
S···H distance S4···H2O 2.75
S3···H2O 2.72
S1···H1O 2.61
S2···H1O 2.74
Dihedral angle
ONCS
O2N2C5S3 62.1(2) O1N1C2S1 60.4(2)
O2N2C6S4 61.5(2) O1N1C3S2 61.0(2)
Deviation from
ΔC4 0.884
ΔC1 0.881
ΔN1 0.634
S1···S3 3.756
the C2S2 plane ΔN2 0.650
Intermolecular
S···S distance
The H-dimers are linked to zigzag chains (Fig. 2)
via specific S2–S4′ dipole–dipole interaction, the S2···S4′
distance being 3.530 Å. Packing of molecules I in
crystal is largely determined by hydrogen bonding; as
a result, stacks along the 0a crystallographic axis are
S2···S4 3.530
S2···S3 3.800
S4···S4 3.492
S1···S2 3.924
S1···O2 3.427
Intermolecular
S···O distance
Scheme 2.
formed. The chains are extended along the 0b axis and
are linked with each other through specific S4–S4′
dipole–dipole interactions with a distance of 3.492 Å
(Fig. 3).
S
NH
70°C, 3 h
NH4OH
+ CH2O + H2S
S
VI, 9%
The condensation of aqueous ammonia with CH2O
and H2S at 70°C gave ~9% of 1,3,5-dithiazinane (VI),
while the major products were urotropin (VII, ~20%)
and 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane (VIII,
~39%) (Scheme 2). It is known that analogous reaction
N
N
S
+
+
N
N
S
N
N
VII, 20%
VIII, 39%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

AKHMETOVA et al.
920
thiazinan-5-yl)-3-hydroxypropionic acid (Xc), and
S2
C4
4-(1,3,5-dithiazinan-5-yl)butan-1-ol (XIII), respec-
tively (Schemes 3, 4). Increase in the concentration of
CH2O and H2S (amine–CH2O–H2S ratio 1:4:3) leads
to hydroxymethylation of the hydroxy group with
formation of [2-(1,3,5-dithiazinan-5-yl)ethoxy]metha-
nol (XIa), (R)-[2-(1,3,5-dithiazinan-5-yl)butoxy]meth-
anol (XIb), and 3-(hydroxymethoxy)-2-(1,3,5-dithia-
zinan-5-yl)propionic acid (XIc) (Scheme 3).
Like α-amino alcohols, 4-aminobutan-1-ol (XII) re-
acted with CH2O and H2S at a ratio of 1:3:2, yielding
~51% of 4-(1,3,5-dithiazinan-5-yl)butan-1-ol (XIII).
When the reaction was performed with increased
amount of CH2O–H2S (reactant ratio 1:4:3), the yield
of XIII was ~42%, and minor CH2O–H2S condensa-
tion products, 1,2,4-trithiolane (V, 5%) and 1,2,4,6,8-
pentathiononane (XIV, 3%) were also formed.
S3
C1
H1
S4
O1
S1
C3
H2
C6
C5
C2
N1
O2
N2
Fig. 1. Structure of two independent molecules IA and IB
according to the X-ray diffraction data (the atoms are num-
bered according to SHELXTL PLUS 5 [8]).
S4′
In all cases, no intramolecular cyclization products
were detected, though examples of condensation of
α-amino alcohols with CH2O to 1,3-oxazolidines
[16–20] and with epoxyethane to morpholine [20]
were reported. Presumably, the reason is that the amino
group in amino alcohols is more nucleophilic than the
hydroxy group; therefore, the reaction with CH2O and
H2S occurs stepwise. Initially, selective condensation
at the amino group gives dithiazinanes Xa–Xc which
then undergo hydroxymethylation with excess CH2O
to form compounds XIa–XIc. α-Amino alcohols IXb
and IXc having a substituent at the carbon atom
bearing the amino group give rise to greater yields of
compounds Xb, Xc and XIb, XIc. The examined
amino alcohols can be ranked as follows with respect
to their reactivity in the thiomethylation with CH2O
and H2S: 2-aminobutan-1-ol (IXb) > serine (IXc) >
2-aminoethanol (IXa).
C1
S1
S2″
S2
H1
O1
C3
C4
S4
S3
C2
H2
N1
C5
O2
C6
N2
Fig. 2. Intermolecular contacts in the crystalline structure of
1,3,5-dithiazinan-5-ol (I).
of gaseous ammonia or ammonium sulfide leads to the
formation of compounds VII and VIII exclusively
[12]; the formation of 1,3,5-dithiazinanes from aque-
ous ammonia was observed only in reactions with
formaldehyde alkyl acetals [13–15].
2-Aminoethanol (IXa), R-(–)-2-aminobutan-1-ol
(IXb), 2-amino-3-hydroxypropionic acid (IXc), and
4-aminobutan-1ol (XII) reacted with CH2O–H2S (3:2)
to afford 2-(1,3,5-dithiazinan-5-yl)ethanol (Xa), (R)-2-
(1,3,5-dithiazinan-5-yl)butan-1-ol (Xb), 2-(1,3,5-di-
In the condensation of R-(–)-2-aminobutan-1-ol
with CH2O and H2S we obtained optically active di-
thiazinanes Xb, [α]D18 = +5.4° (c = 0.38, CHCl3), and
Scheme 3.
R
7
9
OH
5
N
3S
4
CH2O–H2S (3:2)
a
8
6
2
1
S
R
Xa–Xc
OH
R
7
H2N
11
OH
9
O
5
N
6
3S
2
4
IXa–IXc
CH2O–H2S (4:3)
8
10
+
Xa, Xb
1
S
b
XIa–XIc
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

THIOMETHYLATION OF AMINO ALCOHOLS
921
Scheme 4.
11
9
7
5
4
OH
3S
2
N
CH2O–H2S (3:2), 20°C, 3 h
8
10
6
1
S
XIII, 51%
HO
NH2
S
S
XII
CH2O–H2S (4:3), 40°C, 3 h
XIII
+
V
+
S
S
S
XIV
42%
XIb, [α]D17 = –61.4° (c = 1.00, DMSO). Due to the
presence of an asymmetric center, protons in the meth-
ylene groups located between the nitrogen and sulfur
atoms in the dithiazinane rings of Xb and XIb are
pounds III and XIa–XIc also displayed signals in
the region δC 82–90 ppm, which belong to side-chain
methylene carbon atoms located between oxygen
atoms.
1
nonequivalent. In the H NMR spectrum of Xb, dia-
stereotopic protons in the methylene groups at the
nitrogen atom appear as an AB spin system, δ 4.38 and
4.48 ppm (3J = 13.6 Hz), while the corresponding
protons in XIb resonate at δ 4.33 and 4.47 ppm (3J =
11.5 Hz). With a view to determine the absolute con-
figuration of these enantiomers we analyzed the 1H and
13C NMR spectra of Xb, recorded in the presence of
a chiral lanthanide shift reagent, tris[3-(heptafluoro-
butyryl)-l-camphorato]europium. No additional signals
were observed, which indicated the presence of only
one R-enantiomer [21–23]. We can conclude that the
formation of 1,3,5-dithiazinane ring from R-(–)-2-
aminobutan-1-ol (IXb), CH2O, and H2S is stereoselec-
tive and that the configuration of the asymmetric
carbon atom in 2-(R)-Xb is the same as in the initial
chiral amino alcohol.
0
c
a
8
9
CH2CH3
H
CH2OH
10 11
7
Hb
S3
4
N5
Hc
S
Hb
b
1
2
6
Ha
Hd
Ha
Xb
The mass spectra of all heterocyclic products I, III,
Xa–Xc, XIa–XIc, and XIII contained strong molec-
1
ular ion peaks. In the H NMR spectra of these com-
pounds, signals at δ 3.80–4.50 and 4.25–4.90 ppm had
an intensity ratio of 1:2, which confirmed the presence
of a 1,3,5-dithiazinane ring in their molecules. The
corresponding carbon nuclei resonated in the 13C NMR
spectra at δC 30.44–33.82 and 53.96–58.78 ppm. Com-
Fig. 3. Packing of molecules of 1,3,5-dithiazinan-5-ol (I) in
crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

AKHMETOVA et al.
922
Table 3. Condensation of aqueous ammonia with formalde-
hyde and hydrogen sulfide
CDCl3 and DMSO-d6 were used as solvents. The IR
spectra were obtained on a Specord 75IR spectrometer
from samples dispersed in mineral oil. Gas chromatog-
raphy–mass spectrometry was performed on a Finni-
gan 4021 instrument (HP-5 glass capillary column,
50000×0.25 mm; carrier gas helium; oven temperature
programming from 50 to 300°C at a rate of 5 deg/min;
injector temperature 280°C; ion source temperature
250°C; electron impact, 70 eV). The elemental com-
positions were determined on a Carlo Erba Model
1106 CHNS analyzer. The specific rotations were
measured on a Perkin–Elmer-141 polarimeter. Hydro-
gen sulfide was bubbled using an ANP-10 peristaltic
pump. The melting points were determined on
an RNMK 80/2617 hot stage. The purity of the prod-
ucts was checked by TLC on Silufol UV-254 plates;
development with iodine vapor.
Yield, %
Ratio NH4OH– Tempera-
CH2O–H2S
ture, °C
V
VI
VII VIII
1:2:1
1:3:2
1:3:2
15
40
70
1
–
–
4
5
9
29
42
20
44
19
39
2-(2-Hydroxyethylamino)ethanol, being a secon-
dary amine, failed to react with CH2O and H2S, i.e.,
both amino and hydroxy groups therein are inactive
under the examined conditions.
Thus, the condensation of amino alcohols with
formaldehyde and hydrogen sulfide can occur either at
the amino group or at both nucleophilic centers (amino
and hydroxy groups in hydroxylamine and α-amino
alcohols), depending on the reactant ratio. Increase in
the distance between the amino and hydroxy groups in
going to 4-aminobutan-1-ol leads to increased reac-
tivity of the amino group, while the reactivity of the
hydroxy group becomes weaker; as a result, the prod-
uct is dithiazinane XIII which does not undergo sub-
sequent hydroxymethylation with formaldehyde. Pre-
sumably, the reactivity of the amino group increases
due to reduction of –I effect of the hydroxy group and
weakening of intramolecular hydrogen bond typical of
amino alcohols [24] (strong IR bands in the region
3350–3180 cm–1 [25]). The condensation of R-(–)-2-
aminobutan-1-ol with CH2O and H2S is enantioselec-
tive, and the configuration of the chiral center is re-
tained; depending on the reactant ratio, (R)-2-(1,3,5-di-
thiazinan-5-yl)butan-1-ol (Xb) or (R)-[2-(1,3,5-dithia-
zinan-5-yl)butoxy]methanol (XIb) is formed in 73 and
52% yield, respectively.
X-Ray analysis of 1,3,5-dithiazinan-5-ol (I).
A 0.60× 0.45×0.35-mm single crystal of I was grown
by crystallization from toluene–ethyl acetate–acetone
(4:1:1). The X-ray diffraction data were acquired on
an Enraf–Nonius CAD 4 diffractometer at 293 K
(λMoKα irradiation, 2θmax = 29.99°). Colorless crystals;
C3H7NOS2, M 137.22; monoclinic crystal system,
space group P212121. Unit cell parameters (293 K):
a = 10.672(5), b = 10.279(3), c = 10.916(4) Å; β =
103.73(2)°; V = 1163.2(8) Å3; Z = 8, dcalc = 1.567 g×
cm–3. Averaging of equivalent reflections left 3373 in-
dependent reflections with Rint = 0.0397, which were
used in the structure solution and refinement. The
structure was solved by the direct method, and the po-
sitions of atoms were determined from the difference
syntheses of electron density and were refined with
respect to F2 in anisotropic–isotropic approximation.
The final divergence factors were R1 = 0.0380 [cal-
culated by Fhkl for 2800 reflections with I > 2σ(I)] and
2
wR2 = 0.1019 (calculated by Fhkl for 3373 reflections
involved in the final refinement step); GOOF 1.021;
127 refined parameters. All calculations were perform-
ed using SHELXTL PLUS 5 software package [8].
EXPERIMENTAL
The thiomethylation products were analyzed by
GLC on a Chrom-5 chromatograph equipped with
a flame-ionization detector and a 2400×3-mm steel
column packed with 5% of SE-30 on Chromaton
N-AW-HMDS; carrier gas helium; oven temperature
programming from 50 to 270°C at a rate of 8 deg/min.
The 1H NMR spectra of compounds Xb and XIb were
recorded on a Bruker AM-300 spectrometer at
300 MHz, and of the other compounds, on a Tesla BS-
487 instrument (80 MHz); the 13C NMR spectra were
measured on a Jeol FX 90Q instrument at 22.50 MHz;
tetramethylsilane was used as internal reference, and
General procedure for thiomethylation of hy-
droxylamine hydrochloride, aqueous ammonia,
2-aminoethanol (IXa), R-(–)-2-aminobutan-1-ol
(IXb), 2-amino-3-hydroxypropionic acid (IXc), and
4-aminobutan-1-ol (XII). A three-necked flask equip-
ped with a stirrer, reflux condenser, and a gas-inlet
tube was charged with a required amount of 37%
formaldehyde solution, and hydrogen sulfide (generat-
ed from sodium sulfide and hydrochloric acid) was
bubbled through the solution at a specified temperature
over a period of 30 min to attain a CH2O–H2S ratio of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

THIOMETHYLATION OF AMINO ALCOHOLS
923
32.7 s (C3, C5). Mass spectrum: m/z 124 [M]+. The
3:2 (method a) or 4:3 (method b) [2, 3]. A solution of
1 equiv of the corresponding amine (hydroxylamine
hydrochloride dissolved in hot water, 10% aqueous
ammonia, 2-aminoethanol, R-(–)-2-aminobutan-1-ol,
or 2-amino-3-hydroxypropionic acid dissolved in hot
water, or neat 4-aminobutan-1-ol) was added dropwise,
and the mixture was stirred at a specified temperature
(0 to 70°C). The product obtained from hydroxylamine
hydrochloride was neutralized with a 10% solution of
NaOH, and the precipitate was filtered off and dried.
A mixture of compounds I–V, obtained at 0°C
(method b), was separated by column chromatography
on silica gel using toluene–ethyl acetate–acetone
(4:1:1) as eluent.
1
melting point and IR, H and 13C NMR, and mass
spectra of V were identical to those reported in [5].
In the reaction with aqueous ammonia (method a)
we isolated compounds VI–VIII. Compound VI was
purified by recrystallization from hexane, and com-
pound VIII was recrystallized from chloroform as de-
scribed in [26].
1,3,5-Dithiazinane (VI). Yield 9%, mp 96–98°C.
Mass spectrum, m/z (Irel, %): 121 (85) [M]+, 92 (3)
[M – CH2NH]+, 75 (45) [M – CH2S]+, 64 (4) [M –
CSCH]+, 57 (7) [CSCH]+, 46 (58) [CH2S]+, 43 (100)
[CH2NHCH2]+.
1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane (VII).
Yield 20%, mp 263°C [27]. Mass spectrum, m/z
(Irel, %): 140 (59) [M]+, 112 (8) [M – NCH2]+, 85 (8)
[M – NCH2NCH]+, 42 (100) [NCH2N]+.
1,3,5-Dithiazinan-5-ol (I). Yield 10%, colorless
crystals, mp 86–87°C, Rf 0.63 (toluene–ethyl acetate–
acetone, 4:1:1). IR spectrum, ν, cm–1: 750, 1050, 1200–
1
1180, 1480, 2880. H NMR spectrum (DMSO-d6), δ,
ppm: 4.12 br.s (2H, 2-H), 4.58 br.s (4H, 4-H, 6-H).
13C NMR spectrum, δC, ppm: 30.63 t (C2), 58.78 t (C4,
C6). Mass spectrum, m/z (Irel, %): 137 (47) [M]+, 120
(6) [M – OH]+, 104 (60) [M – CH]+, 92 (29) [M –
SCH]+, 64 (17) [SS]+, 59 (14) [M – SCH2S]+, 46 (100)
[CH2S]+. Found, %: C 27.05; H 5.11; N 10.11; S 46.88.
C3H7ONS2. Calculated, %: C 26.26; H 5.14; N 10.21;
S 46.73. M 137.21.
3,7-Dithia-1,5-diazabicyclo[3.3.1]nonane (VIII).
Yield 39%, mp 199–200°C [26]. Mass spectrum, m/z
(Irel, %): 162 (39) [M]+, 129 (11) [M – SH]+, 120 (17)
[M – CH2NCH2]+, 97 (14) [M – NCH2NCC]+, 89 (16)
[M – SCH2NCH]+, 73 (6) [SCH2NCH]+, 57 (14)
[CSCH]+, 46 (31) [CH2S]+, 42 (100) [CH2NCH2]+. The
1H NMR spectrum of VIII was identical to that report-
ed previously [26].
5-Methyl-1,3,5-dithiazinane (II). Mass spectrum,
m/z (Irel, %): 135 (67) [M]+, 89 (40) [M – SH2S]+, 76
(10) [M – CH2SCN]+, 57 (62) [CSCH]+, 46 (32)
[CH2S]+, 44 (100) [CS]+, 42 (86) [CS – 2]+.
2-(1,3,5-Dithiazinan-5-yl)ethanol (Xa) was ob-
tained according to method a; yield 56%, mp 47–48°C;
published data: mp 44–45°C [2], 49°C [28]. IR spec-
trum, ν cm–1: 580, 650, 1050, 1170, 2850, 3610. Mass
spectrum, m/z (Irel, %): 165 (21) [M]+, 133 (3) [M – S]+,
119 (12) [M – SCH2]+, 87 (26) [M – SCH2S]+. The
1H and 13C NMR spectra were identical to those de-
scribed in [2].
1,3,5-Dithiazinan-5-yloxymethanol (III). Yield
38%, white powder, mp 106–108°C, Rf 0.90 (toluene–
ethyl acetate–acetone, 4:1:1). IR spectrum, ν, cm–1:
740, 810, 1050, 1380, 1450, 2870, 3100–3300.
1H NMR spectrum (DMSO-d6), δ, ppm: 3.38 br.s (2H,
2-H), 4.30 br.s (4H, 4-H, 6-H), 4.79 br.s (2H, 8-H),
6.33 br.s (1H, OH). 13C NMR spectrum, δC, ppm:
30.44 t (C2), 57.22 t (C4, C6), 89.98 t (C8). Mass
spectrum, m/z (Irel, %): 167 (5) [M]+, 135 (7) [M – S]+,
121 (57) [M – SCH2]+, 110 (8) [M – CSCH]+, 91 (10)
[CHSCH2S]+, 75 (32) [HOCH2ONHCH2]+, 57 (29)
[ONCH2CH]+, 46 (76) [CH2S]+, 45 (100) [CHS]+.
Found, %: C 29.64; H 5.68; N 8.41; S 38.68.
C4H9O2NS2. Calculated, %: C 28.72; H 5.42; N 8.37;
S 38.34. M 167.25.
R-2-(1,3,5-Dithiazinan-5-yl)butan-1-ol (Xb). In
the reaction with compound IXb according to method
a we isolated a product which was passed through
a column charged with silica gel (benzene–acetone–
diethyl ether, 5:1:1) to obtain Xb as a transparent oily
substance. Yield 73%, Rf 0.50 (benzene–acetone–di-
ethyl ether, 5:1:1), [α]D18 = +5.4° (c = 0.38, CHCl3). IR
spectrum, ν, cm–1: 680, 1070, 1270, 1380, 2950, 3400.
1H NMR spectrum (CDCl3), δ, ppm: 0.80 t (3H, 9-H,
J = 7.3 Hz), 1.52 d.q (2H, 8-H, J = 16.1, 7.3 Hz),
3.00 s (1H, 7-H), 3.66 m (2H, 10-H), 4.11 s (2H, 2-H),
4H-1,3,5-Dithiazine (IV). Mass spectrum, m/z
(Irel, %): 119 (100) [M]+, 92 (59) [M – NCH]+, 86 (29)
[M – S]+, 73 (36) [M – SCH2]+, 64 (11) [SS]+, 45 (90)
[SCH]+.
2
4.38 d (2H, part A of AB quartet, 4-HA, 6-HA, J =
13.6 Hz), 4.48 d (2H, part B of AB quartet, 4-HB, 6-HB,
2J = 13.6 Hz). 13C NMR spectrum, δC, ppm: 9.99 q
(C9), 20.61 t (C8), 33.47 t (C2), 55.48 t (C4, C6),
59.75 d (C7), 62.25 t (C10). Mass spectrum, m/z
1,2,4-Trithiolane (V). Rf 0.92 (toluene–ethyl
13
acetate–acetone, 4:1:1). C NMR spectrum, δC, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

AKHMETOVA et al.
924
(Irel, %): 193 (6) [M]+, 177 (13) [M – OH]+, 149 (100)
[M – CHCH2OH]+, 121 (21) [HNCH2SCH2SCH2]+,
104 (34) [CHSCH2SCH]+, 93 (32) [SCH2SCH3]+.
Found, %: C 43.45; H 7.80; N 7.31; S 33.05.
C7H15ONS2. Calculated, %: C 43.52; H 7.77; N 7.25;
S 33.16. M 193.33.
2-(1,3,5-Dithiazinan-5-yl)-3-(hydroxymethoxy)-
propionic acid (XIc). The reaction with compound
IXc (method b) gave a mixture of products V and XIc.
Compound XIc was isolated by fractional crystalliza-
tion from CHCl3. Yield 64%, mp 270°C (decomp.). IR
spectrum, ν, cm–1: 700, 1000, 1450, 1650, 2900, 3300.
1H NMR spectrum (DMSO-d6), δ, ppm: 3.20–3.80 m
(9H, 2-H, 4-H, 6-H, 7-H, 8-H), 4.25 br.s (2H, 10-H).
13C NMR spectrum, δC, ppm: 33.82 t (C2), 53.96 t (C4,
C6), 60.27 d (C7), 64.34 t (C8), 82.23 d (C10), 166.40 s
(C12). Found, %: C 35.58; H 5.22; N 5.51; S 26.83.
C7H13O3NS2. Calculated, %: C 35.15; H 5.44; N 5.86;
S 26.78.
3-Hydroxy-2-(1,3,5-dithiazinan-5-yl)propionic
acid (Xc) was synthesized from compound IXc
(method a), mp 158–159°C; published data [28]:
mp 154–155°C. The spectral parameters of compound
Xc were given in [3].
[2-(1,3,5-Dithiazinan-5-yl)ethoxy]methanol
(XIa). The reaction with compound IXa according to
method b gave a mixture of Xa and XIa (27 and 18%,
respectively), which were separated by crystallization
4-(1,3,5-Dithiazinan-5-yl)butan-1-ol (XIII). The
reaction with amino alcohol XII according to method a
gave compound XIII in 51% yield; following meth-
od b, a mixture of compounds V (5%), XIII (42%),
and XIV (3%) was obtained. Colorless oily substance.
IR spectrum, ν, cm–1: 680, 1050, 1270, 2900, 3350.
1H NMR spectrum (CDCl3), δ, ppm: 1.30–1.52 br.s
(4H, 8-H, 9-H), 2.91 s (2H, 7-H), 3.48 s (2H, 10-H),
3.97 s (2H, 2-H), 4.30 s (2H, 4-H, 6-H). 13C NMR
spectrum, δC, ppm: 22.82 t (C8), 29.72 t (C9), 33.27 t
(C2), 47.96 t (C7), 57.43 t (C4, C6), 61.54 d (C10). Mass
spectrum, m/z (Irel, %): 193 (17) [M]+, 114 (100)
[M – N(CH2)4OH]+, 84 (11) [SCH2NC2]+, 71 (16)
[HO(CH2)3C]+, 58 (31) [CH2SC]+, 42 (58) [SCH2]+.
Found, %: C 43.75; H 7.78; N 7.47; S 33.25.
C7H15ONS2. Calculated, %: C 43.52; H 7.77; N 7.25;
S 33.16. M 193.33.
1
from chloroform. Yield 18%, mp 50–52°C. H NMR
3
spectrum (DMSO-d6), δ, ppm: 1.95 t (2H, 7-H, J =
3
7.1 Hz), 3.60 t (2H, 8-H, J = 7.1 Hz), 4.50 br.s (2H,
3
2-H), 4.90 br.s (4H, 4-H, 6-H), 5.19 d (2H, 10-H, J =
5.4 Hz), 6.99 t (1H, OH, 3J = 5.4 Hz). 13C NMR spec-
trum, δC, ppm: 31.52 t (C2), 53.53 t (C7), 57.11 t (C4,
C6), 63.37 t (C8), 88.44 t (C10). Mass spectrum, m/z
(Irel, %): 195 (13) [M]+, 193 (89) [M – 2]+, 148 (26)
[M – SCH2]+, 147 (100) [M – SHCH3]+, 134 (47) [M –
CH2OCH2OH]+, 115 (79) [(CH2)2NCH2CH2OCH2OH]+,
102 (97) [CHNCH2CH2OCH2OH]+, 73 (89)
[CCH2OCH2OH]+, 56 (79) [CSC]+. Found, %:
C 37.04; H 6.63; N 7.16; S 32.78. C6H13O2NS2.
Calculated, %: C 36.92; H 6.67; N 7.18; S 32.82.
M 195.31.
1,2,4,6,8-Pentathiacyclononane (XIV). Yield 3%.
Mass spectrum, m/z (Irel, %): 216 (7) [M]+, 170 (5)
[M – SCH2]+, 124 (38) [M – (SCH2)2]+, 78 (47)
[SCH2S]+, 45 (100) [CHS]+.
(R)-[2-(1,3,5-Dithiazinan-5-yl)butoxy]methanol
(XIb) was obtained from compound IXb (method b).
Yield 52%, colorless oily substance, [α]D17 = –61.4° (c =
1.00, DMSO). IR spectrum, ν, cm–1: 730, 1010, 1170,
1
This study was performed under financial support
by the Ministry of Education of the Russian Federation
(project no. NSh 1060.2003.03) and by the Foundation
for Support of Russian Science.
1370, 2940, 3400. H NMR spectrum (DMSO-d6), δ,
ppm: 0.92 t (3H, 9-H, J = 7.5 Hz), 1.45 d.q (2H, 8-H,
J = 22.3, 7.0 Hz), 3.06 m (1H, 7-H), 3.35 s (1H, OH),
3.92 s (2H, 12-H), 3.94 m (2H, 10-H), 4.02 s (2H,
2-H), 4.33 d (2H, part A of AB quartet, 4-HA, 6-HA,
2J = 11.5 Hz), 4.47 d (2H, part B of AB quartet, 4-HB,
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