2-(1,3,5-Dithiazinan-5-yl)ethanol heterocycles, structure and reactivity

Article abstract of DOI:10.3987/com-04-10151

Treatment of 2-(1,3,5-dithiazinan-5-yl)ethanol (1), 2-(1,3,5-dithiazinan-5- yl)-1-phenylethanol (2), 2-(1,3,5-dithiazinan-5-yl)-1-methylethanol (3) and 2-(1,3,5-dithiazinan-5-yl)-2-methyl-1-phenylethanol (4) with TsCl and NEt ₃ in CH₂Cl₂ afforded the corresponding 3-tosyl-1,3-oxazolidine derivatives (5-8), whereas tosylation of 1-4 in the presence of NHMe₃Cl gave the corresponding O-tosyl-2-(1,3,5- dithiazinan-5-yl)ethanol derivatives (11-14). The direct preparation of 5 and 7 from formaldehyde and N-tosylethanolamine (9) or N-tosyl-2-propanolamine was not successful. Reactions of 1 or 3 with benzylamine furnish 1,3,5-tribenzyl-1,3,5- triazinane. Heating of 1 and 2 affords the corresponding 1,3,5-tri(2- hydroxyethyl)-1,3,5-triazinanes. X-Ray diffraction studies of compounds (1-9 and 11) are reported.

Full text of DOI:10.3987/com-04-10151

HETEROCYCLES, Vol. 63, No. 10, 2004, pp. 2269 - 2285
Received, 15th June, 2004, Accepted, 25th August, 2004, Published online, 27th August, 2004
2-(1,3,5-DITHIAZINAN-5-YL)ETHANOL
HETEROCYCLES, STRUCTURE AND REACTIVITY
Juan Carlos Gálvez-Ruiz, Javier C. Jaen-Gaspar, Indira G.
Castellanos-Arzola, Rosalinda Contreras, and Angelina Flores-Parra*
Chemistry Department, Centro de Investigación y de Estudios Avanzados
del IPN. AP 14-740, CP 07000, Mexico D. F., Mexico
aflores@mail.cinvestav.mx
Abstract – Treatment of 2-(1,3,5-dithiazinan-5-yl)ethanol (1), 2-(1,3,5-dithia-
zinan-5-yl)-1-phenylethanol (2), 2-(1,3,5-dithiazinan-5-yl)-1-methylethanol (3)
and 2-(1,3,5-dithiazinan-5-yl)-2-methyl-1-phenylethanol (4) with TsCl and NEt3
in CH2Cl2 afforded the corresponding 3-tosyl-1,3-oxazolidine derivatives (5-8),
whereas tosylation of 1-4 in the presence of NHMe3Cl gave the corresponding
O-tosyl-2-(1,3,5-dithiazinan-5-yl)ethanol derivatives (11-14). The direct
preparation of 5 and 7 from formaldehyde and N-tosylethanolamine (9) or
N-tosyl-2-propanolamine was not successful. Reactions of 1 or 3 with
benzylamine furnish 1,3,5-tribenzyl-1,3,5-triazinane. Heating of 1 and 2 affords
the corresponding 1,3,5-tri(2-hydroxyethyl)-1,3,5-triazinanes. X-Ray diffraction
studies of compounds (1-9 and 11) are reported.
INTRODUCTION
We are interested in the synthesis and structure of nitrogenated 1,3-hetero-5-azinanes,1 which are widely
used as flavoring agents,2a antibiotics,2b enzymatic inhibitors,2c and organic reagents,2d and their
aluminum,3a,b indium3b and boron3b-g coordination compounds.

We have reported compounds (1-3) (Scheme 1) which were synthesized from the corresponding primary
amines and formaldehyde, compounds bearing sulfur atoms are obtained with the mentioned reagents and
in the presence of NaSH.3a Herein, we report the tosylation reactions of compounds (1-4) which afford
N-tosyl-1,3-oxazolidines and O-tosyl-2-(1,3,5-dithiazinan-5-yl)-1-ethanols and amination reactions which
gives 1,3,5-triazinanes. Also thermic rearragement of 1-4 was observed, giving the corresponding
1,3-oxazolidines and 1,3,5-tri(2-hydroxyethyl)-1,3,5-triazinanes.
R
R
N
1 R= H, R'= H
2 R= Ph, R'= H
3 R= Me, R'= H
4 R= Ph, R'= Me
R'
8
OH
7
Y
X
S
N
4
S
2
X, Y = O, NR or S
6
Scheme 1
RESULTS AND DISCUSSION
1,3,5-DITHIAZINANES (1-4)
Compounds (1-4) were prepared by reaction of formaldehyde, the corresponding β-ethanolamine and
NaHS. Their 13C NMR spectra present the characteristic chemical shifts for six membered ringcompounds
1
(δ for C4-C6 appears around 58.6 ppm and C2 at 33.7). H NMR spectra show that 1-3 are in
conformational equilibrium at room temperature, their ring inversion energy was calculated from variable
temperature NMR experiments [∆G# = 45.4, 1; 49.3, 2; and 49.5 kJmol-1, 3]. Found values were not far
from those reported for N-methyl-1,3,5-dithiazinane2f,g [∆G# = 46.0 kJmol-1]. The preferred ring
1
conformation of compound (4) was evidenced by its H NMR spectrum at room temperature which show
different resonances for axial and equatorial protons (H-4ax and H-6ax 4.66; H-4eq and H-6eq 4.53 ppm,
their geminal coupling constants values are 14 Hz). Compound (1) has the exocyclic ethanol chain in
conformational equilibrium, whereas 2-4 with alkyl or aryl substituent at the chain present a preferred
staggered conformation deduced from the 1H coupling pattern and originated by a hydrogen bond forming
a “five membered ring”. The anti or syn position of hydrogen atoms in the molecule arm is deduced from

3
3
the values of the coupling constants J(H7A,H8) = 9.9 Hz (anti) and J(H7B,H8) = 2.9 Hz (syn). An
interesting fact in the 1H NMR spectra of 2 and 3 is the deshielding effect (≈ 0.68 ppm) for H-7A protons
with respect to H-7B due to their position pointing at the sulfur atoms [for 2 H-7A δ = 3.08; H-7B δ = 2.40
and for 3 H-7A δ = 3.49; H-7B δ = 2.81 ppm] as it was confirmed by the X-Ray diffraction analyses (see
15
below). In solution, the N chemical shift and the O-H higher frequency signals indicate the strength of
the hydrogen bond.4 According to that, compound (3) has the strongest hydrogen bond (δ 15N NMR data in
CDCl3: 1 -352.9 ppm; 2 -333.5; 3 -310.6; 4 -343.9; N-methyl-1,3,5-dithiazinane2d -360.5 ppm). The
corresponding solid state structures of dithiazinanes (1-4) were obtained. (Figures 1-2)
C12
C13
C11
C14
C10
C9
C8
C7
C82
O9
H9
S3
C81
O9
S3
S1
C7
C4
C4
N5
H9
C2
N5
2.24 Å
S1
C2
C6
C6
2
1
C9
C8
C7
O9
S1
C6
2.30 Å
N5
3
S3
C4
C2
Figure 1 Molecular structures of compounds (1-3)
In all compounds the ring has a chair conformation with the N-R in axial position and the nitrogen atom
presenting a 54% of sp2 hybridation [Σ(C-N-C) angle values: 1 342.4o; 2 342.9o; 3 342.3o; 4 340.5o]. In 1-3,

the O-H hydrogen is pointing to N-5 forming hydrogen bonds, distances N5···H9: 1 2.93; 2 2.24 and 3 2.30
Å. The unit cell of 4 presents two molecules forming a dimer with two intermolecular hydrogen bonds
[O-H···N 2.33 Å and C-H8···O 2.54 Å]. The macromolecular helix arrangement produced by
intermolecular hydrogen bonds is shown in Figure 2a for compound (1) [H9···O9’ (1.97 Å), S3···H8B”’
(2.97 Å)]. In structures (1-4) short contacts between H7B and sulfur atoms (1 2.86; 2 3.01 and 3.15; 3
2.86; 4 2.80 and 3.13 Å) were observed [(ΣrVW) H···S 3.25 Å], as it is represented in Figure 2b for 4.
a)
b)
Figure 2
a) Macromolecular arrangement of 1; b) short contacts between H7B and sulfur atoms in 4
TOSYLATION REACTIONS
Tosylation products depend on the reaction conditions: for primary hydroxy groups it can be performed
with tosyl chloride and Et3N in CH2Cl2, while compounds (1-4) under these conditions did not afford the
O-tosylated derivatives. In contrast, N-tosyl-1,3-oxazolidines (5-8) are obtained in good yields (90-95%)
with a N-tosyl derivative and imines A as possible intermediates. (Scheme 2)
Structures of oxazolidines (5-8) were deduced from the NMR spectral data and by comparison with those
of 1-4. In the 13C NMR spectra of 5-8, the CH2 signals of the dithiazinanyl cycle disappeared and those of

[OCH2N] emerged at δ ≈ 81 ppm, the C-8 resonances were shifted to lower frequencies (∆δ ≈ 5.0). The
15N signals for 5-8 appeared at -265 ppm, characteristic for N-tosyl groups.4 Crystals of compounds (5-8)
were studied by X-Ray diffraction. (Figures 3-5).
R
R
R
O
N
R
Cl
Cl
8
R'
R'
R'
OH
7
OH
NaHCO3
-HCl
OH
N+
S
S
R'
4
N+
N
S
S
Ts
TsCl, Et3N
Ts
Ts
2
6
5 R= H, R'= H
6 R= Ph, R'= H
7 R= Me, R'= H
8 R= Ph, R'= Me
A
1-4
Scheme 2 Possible reaction path to 1,3-oxazolidines in tosylation reactions
C5
O1
C4
C2
N3
O6B
O6A
S6
C7
C12
C8
C9
C11
C10
C13
a)
b)
Figure 3 a) ORTEP representation of compound (5) and b) macromolecular arrangement of (5)
The oxazolidine ring in 5-8 has an envelop conformation with the oxygen atom out of the molecular plane
[O3-C4-C5-N1, 25.39o]. Intramolecular hydrogen bonds between oxygen atoms of the tosyl group and the
neighboring hydrogen atoms were found, as shown in Figure 4 for compound (6). Oxygen atoms of the
tosyl groups show intermolecular interactions, giving different macromolecular arrangements in the unit
cell, as well as the formation of polymers by intermolecular hydrogen bonds.

a)
b)
Figure 4 Compound (6) a) intramolecular hydrogen bonds and b) intermolecular hydrogen bonds
C5
C4
C6
N3
O7A
C2
O1
C9
S7
O7B
C8
C10
C11
7
C13
8
C12
C14
Figure 5 Molecular structures of compounds (7 and 8)
N-Tosylethanolamines (9 and 10) were prepared in order to probe if the N-tosyl-1,3-oxazolidines could be
directly prepared from them. (Scheme 3) Ethanolamine and 2-propanolamine were treated with tosyl
chloride in the presence of NHMe3Cl. Two compounds were obtained from the ethanolamine, they were
separated through a chromatographic column: N-tosylethanolamine (9, 50%) and the N-tosylaziridine
(50%), both were identified by NMR and MS spectra and in the case of 9 also by X-Ray diffraction
analysis.

OH
R
9 R= H
10 R= Me
NHTs
a)
b)
Scheme 3 a) Compounds (9-10) and b) intermolecular hydrogen bonds in the cell of compound (9)
2-Propanolamine gave N-tosyl-2-propanolamine (10, 90%) and the corresponding N-tosyl-2-methyl-
aziridine (10%). Syntheses of N-tosylated oxazolidines from 9 or 10 with formaldehyde failed.
Crystals of compound (9) were analyzed, four different conformers were observed in the unit cell (A-D),
Scheme 4. Conformer A is enantiomer of C and D, conformer B has the sharper dihedral angle S-N-C-C.
All of them have cis OH and N-H groups without forming intramolecular hydrogen bonds, they present
strong intermolecular hydrogen bonds as is represented in Scheme 3b.
angles
A
B
C
D
[S-N-C-C] 174.91
104.83
63.30
113.89
121.22
114.61
178.14
65.28
123.79
119.10
108.24
175.47
65.37
114.83
118.43
104.21
[O-C-C-N]
[H-N-S]
[C-N-S]
56.29
116.99
116.42
103.19
[H-N-C]
Scheme 4 View of the four conformers (A-D) of 9 in the unit cell, the N-C bond is eclipsed

O-Tosylated compounds (11-14) were obtained by treatment of 1-4 with TsCl in presence of NHMe3Cl
and Et3N.5 (Scheme 5). The 13C NMR signal for C-8 in compounds (11-14) was shifted to higher
frequencies (∆δ = 8.7, 8,2, 14.1 and 0.1 ppm, respectively). Crystalline structure of 11 was obtained; it is
represented in Schemes 5b and 5c, showing the intra- and intermolecular hydrogen bonds.
1-4
TsCl, Et3N
R
R'
OTs
S
S
N
11 R= H, R'= H
12 R= Ph, R'= H
13 R= Me, R'=H
14 R= Ph, R'= Me
a)
b)
c)
Scheme 5 a) Synthesis of compounds (11-14), b) solid state structure of compound (11), hydrogen bonds are
represented, c) a dimer is formed for 11 by collaborative intermolecular hydrogen bonds.
REACTION OF DITHIAZINANES (1) AND (3) WITH BENZYLAMINE.
Compounds (1 and 3) undergo in THF, at room temperature, a benzylamine nucleophilic attack at the
endocyclic methylene groups to give the imine B intermediate which by trimerization affords the
triazinane (15) in 95%. Heterocycle (15) was identified by comparison with the reported structure.6 The
direct preparation of triazinane from primary amines and formaldehyde is also known.2c (Scheme 6)
R
Ph
1 R = H
3 R = Me
R
Ph
Ph
N
N
OH
N
OH
1/3
+
NH2Bn
N
S
S
N
NH2
Ph
15
B
Scheme 6

THERMIC TREATMENT OF DITHIAZINANES (1) AND (2)
Compound (1) was heated without solvent at 100 oC (0.125 mmHg) and distilled at 80 oC (0.125 mmHg),
to quantitatively afford the 1,3,5-triazinane (16) (Scheme 7). Compound (16) presents only one broad
o
signal at 4.67 ppm (1H) and 73.8 ppm (13C) for the NCH2N protons.2c Heating compound (2) at 200 C
[0.5 mmHg] yields the 5-phenyl-1,3-oxazolidine (18, 90%) which is a liquid, that can be distilled (bp 190
oC, 0.5 mmHg), 13C NMR spectrum presents a signal at 82 ppm characteristic for the [NCH2O]
oxazolidine group.
At room temperature, after two days in CHCl3 or without solvent, compound (18) was transformed into
triazinane (17, 80%). Under the same heating conditions, compound (3) only sublimated. Reactions between
corresponding ethanolamines and formaldehyde did not afford triazinanes (16 and 17), but other
heterocycles.7 Therefore heating of 2-(1,3,5-dithiazinan-5-yl)ethanols (1 and 2) is a good synthetic method
for preparation of 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinanes (16 and 17). It seems clear that imine C is
an intermediate for these reactions. Compound (16) is already known as metal atoms ligand.8
R
R
R
HO
OH
∆
OH
R = H
1/3
N
N
OH
R
N
S
-3 [CH2SCH2]n
N
HO
N
S
16 R= H (bp 80oC)
17 R= Ph
C
R
1 R = H
2 R = Ph
R
rt, CDCl3
O
R = Ph
N
18 (bp 190oC)
H
Scheme 7 Thermic rearrangement of compounds (1 and 3)
CONCLUSIONS
Our study confirms the versatility in the synthesis of dithiazinanols, which can be converted into different
compounds depending on the reaction conditions and substitutents. Herein, we reported the synthesis of
N-tosyloxazolidines (5-8) via opening of 2-(1,3,5-dithiazinan-5-yl)alkylethanols. The direct synthesis

through of tosylation of the N-H oxazolidine or cyclization of N-tosyl hydroxyamine does not work. O-Ts
derivatives (11-14) can be obtained modifying the tosylation reaction conditions. We found that
dithiazinanols (1-3) are also starting materials for substituted triazines. The X-Ray analyses of dithiazinanols
(1-4), the N-tosyloxazolidines (5-8) and N-tosylhydroxyamine (9) and O-tosyldithiazinanol (11) allowed us
to confirm the structures and to study their preferred conformations derived in part from the hydrogen
bonding.
EXPERIMENTAL
1
13
15
All solvents were freshly distilled. H, C and N NMR spectra were recorded with a JEOL GXS- 270
(1H 270 MHz) or a JEOL Eclipse (1H 400 MHz). 1H and 13C δ are referenced to TMS, and 15N to CH3NO2.
15N spectra were obtained at 27.25 MHz (JEOL GXS-270) by the refocused INEPT pulse sequence with
2J(15N-1H) =2.5 Hz. Variable temperature experiments were performed with a temperature controller to
keep the temperature constant within 0.3oC. Samples were dissolved in THF-d8. Melting points were
measured on a Gallenkamp apparatus and are uncorrected. Elemental analyses were performed by Oneida
Research Services, Whitesboro, New York. The MS spectra were obtained to 20 eV in a HP 5989
spectrometer.
Crystal data were obtained with an Enraf-Nonius Kappa CCD or a Siemens-P4 diffractometer both
equipped with area-detectors. Relevant data are reported in the complementary information. Computation
for compounds (1-4, 5-8) were performed by SHELXS-97 (Sheldrick 1990) and SHELXL-97 programs
(Sheldrick 1997). Atomic form factors for neutral C, N, O and H were taken from ref. 9. Hydrogen atoms
were found on difference electron density maps. Crystallographic data (excluding structure factors) have
been deposited at the Cambridge Crystallographic Data Bank CCDC 236636 (1), 236637 (2), 236638 (3),
236639 (4), 236640 (5), 236641 (6), 236642 (7), 237220 (8), 241303 (9) and 236643 (11). Copies of the
data can be obtained free of charge on application to, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: int.
Code + 44(1223)336-033; E-mail: deposit@ccdc.cam.ac.uk].

2-(1,3,5-Dithiazinan-5-yl)ethanol (1). General procedure for compounds (1-4). To a cool (5oC) solution of
ethanolamine (10 mL, 0.166 mol) in water (50 mL), another aqueous solution (5 oC) of NaHS (27.9 g, 0.5
mol) and aqueous formaldehyde (37%, 62.3 mL, 0.83 mol) were slowly added. The reaction mixture was
o
stirred for 30 min at 5 C and 24 h at rt. Then, the white solids were washed with water and dissolved in
CHCl3 (30 mL). The chloroformic solution was dried with anhydrous Na2SO4 and concentrated under
o
1
vacuum. Crystals were obtained from CHCl3 (24.6 g, 90%). Mp 39 C. H NMR (CDCl3): δ 4.32 (s, 4H,
3
3
2H-4 and 2H-6), 3.99 (s, 2H, H-2), 3.54 (t, J 5.2 Hz, 2H, H-8), 3.08 (t, J 5.2 Hz, 2H, H-7), 2.67 (s, 1H,
OH). 13C NMR (CDCl3): δ 58.8 (C8), 58.4 (C4 and C6), 51.3 (C7), 33.8 (C2). 15N NMR (CHCl3): δ
-352.9. Anal. Calcd for C5H11NOS2: C, 36.34; H, 6.71; N, 8.47. Found: C, 36.24; H, 6.94; N, 8.44.
2-(1,3,5-Dithiazinan-5-yl)-1-phenylethanol (2). To 2-phenylethanolamine (10 g, 72.9 mmol) in water (75
mL) and THF (5 mL) were added NaHS (12.2 g, 219 mmol) and aqueous formaldehyde (37%, 27.4 mL,
365 mmol). Yellow crystals were obtained (12.3 g, 70%). Mp 56-59 oC. 1H NMR (CDCl3): δ 7.4-7.2 (br s,
5H, Ph), 4.60 (dd, 3J 13.5, 2.9 Hz, 1H, H-8), 4.31 (br s, 4H, 2H-4 and 2H-6), 4.00 (br s, 2H, H-2), 3.63 (s,
2
3
2
3
1H, OH), 3.49 (dd, J 13.5, J 2.9 Hz, 1H, H-7A), 2.81 (dd, J 13.5, J 9.9 Hz, 1H, H-7B). 13C NMR
(CDCl3): δ 141.8 (Ci), 128.2 (2Cm), 127.2 (Cp), 125.6 (2Co), 69.5 (C8), 58.8 (br s, C4 and C6), 57.1 (C7),
33.4 (C2). 15N NMR (CDCl3): δ -333.5. Anal. Calcd for C11H15NOS2: C, 54.74; H, 6.26; N, 5.80.
Found: C, 54.39; H, 6.23; N, 5.92.
2-(1,3,5-Dithiazinan-5-yl)-1-methylethanol (3). To isopropanolamine (40 mL, 0.51 mol) in water (75 mL)
were added NaHS (85.8 g, 1.53 mol) and aqueous formaldehyde (37%, 191.7 mL, 2.55 mol). Crystals were
o
1
obtained from CHCl3 (69 g, 75%). Mp 70 C. H NMR (CDCl3): δ 4.32 (s, 4H, 2H-4 and 2H-6), 3.99 (s,
3
2
3
2H, H-2), 3.54 (qdd, J 6.2, 9.9, 2.9 Hz, 1H, H-8), 3.08 (dd, J 13.5, J 2.9 Hz, 1H, H-7A), 2.67 (s, 1H,
2
3
3
13
OH), 2.4 (dd, J 13.5, J 9.9 Hz, 1H, H-7B), 1.15 (d, J 6.2 Hz, 3H, CH3-9). C NMR (CDCl3): δ 63.6
(C8), 58.7 (br s, C4 and C6), 57.2 (C7), 33.7 (C2), 20.1 (C9). 15N NMR (CHCl3): δ -310.6. Anal. Calcd for
C6H13NOS2: C, 40.19; H, 7.31; N, 7.81. Found: C, 40.07; H, 7.79; N, 7.83.
(-)-(1R,2S)-2-(1,3,5-Dithiazinan-5-yl)-2-methyl-1-phenylethanol (4). To (-)-(1R,2S)-norephedrine (0.5 g,

3.30 mmol) in CH3OH (20 mL), a solution of NaHS (0.55 g, 9.91 mmol) and aqueous formaldehyde (37%,
1.24 mL, 16.53 mmol) were added. A viscous yellow solid was crystallized from CHCl3/CH3OH (70/30)
(0.79 g, 94%). Mp 73-75 oC. 1H NMR (CDCl3): δ 7.4 (m, 5H, Ph), 5.2 (d, 3J 3.0 Hz, 1H, H-8), 4.66 (d, 2J
14.0 Hz, 2H, H-4eq and H-6eq), 4.53 (d, 2J 14.0 Hz, 2H, H-4ax and H-6ax), 4.10 (s, 2H, H-2), 3.83 (dq, 3J
3
13
6.0, 3.0 Hz, 1H, H-7), 0.93 (d, J 6.0 Hz, 3H, CH3). C NMR (CDCl3): δ 141.1 (Ci), 129.9 (Cp), 128.1
(2Cm), 125.7 (2Co), 70.9 (C8), 57.3 (C7), 56.2 (C4 and C6), 33.8 (C2), 10.0 (CH3). 15N NMR (CDCl3): δ
-343.9. Anal. Calcd for C12H17OS2N: C, 56.46; N, 5.48; H, 6.66. Found: C, 56.58; N, 5.27; H,
6.64. [α]D = -35.8o (C 0.1, CH3OH).
3-Tosyl-1,3-oxazolidine (5). General procedure for the preparation of 3-tosylated oxazolidines. To an
aqueous solution of 1,3,5-dithiazinane (1) (7.7 g, 46.6 mmol) NaHCO3 (4.2 g, 50 mmol) and TsCl (8.89 g,
46.6 mmol) in dry CHCl3 (30 mL) were added. The reaction mixture was stirred for 12 h at rt and filtered.
Then, 10 mL of H2O was added and the product extracted with CHCl3 (2x30 mL). The organic solutions
were dried with NaSO4 and concentrated under vacuum. The white solid was crystallized from CHCl3
(10.0 g, 95%). Mp. 100-101 oC. 1H NMR (CDCl3): δ 7.67 (d, 3J 8.4 Hz, 2H, Ho-Ts), 7.27 (d, 3J 8.4 Hz, 2H,
Hm-Ts), 4.77 (s, 2H, H-2), 3.58 (t, 3J 6.7 Hz, 2H, H-5), 3.36 (t, 3J 6.7 Hz, 2H, H-4), 2.36 (s, 3H, CH3-Ts).
13C NMR (CDCl3): δ 145.4 (Ci-Ts), 134 (Cp-Ts), 129.9 (Co-Ts), 127.7 (Cm-Ts), 80.67 (C2), 66.1 (C5),
46.1 (C4), 21.6 (CH3-Ts). 15N NMR (CDCl3): δ -267.2. Anal. Calcd for C10H13NO3S: C, 52.86; H, 5.72; N,
6.16. Found: C, 52.45; H, 5.68; N, 6.06.
5-Phenyl-3-tosyl-1,3-oxazolidine (6) was prepared following the general procedure from dithiazinane (2)
(1.24 g, 5.1 mmol), NaHCO3 (1.7 g, 20.4 mmol) and TsCl (7.0 g, 5.1 mmol). Compound (6) is a pale
yellow liquid (1.4 g, 90%). 1H NMR (CDCl3): δ 7.68 (d, 3J 7.0 Hz, 2H, Ho-Ts), 7.53 (m, 5H, Ph) 7.28 (d,
3J 7.0 Hz, 2H, Hm-Ts), 4.91 (d, 2J 5.8 Hz, 1H, H-2A), 4.68 (d, 2J 5.8 Hz, 1H, H-2B), 3.80 (dd, 3J 6.4, 9.5
Hz, 1H, H-5), 3.51 (dd, 2J 10.0, 3J 6.4 Hz, 1H, H-4A), 2.80 (dd, 2J 10.0, 3J 9.5 Hz, 1H, H-4B), 2.42 (s, 3H,
13
CH3-Ts). C NMR (CDCl3): δ 144.0 (Ci-Ts), 141.6 (Ci), 133.7 (Cp-Ts), 129.7 (2Cm-Ts), 128.1 (2Cm),
128.0 (2Co-Ts), 127.6 (2Co-Ts), 127.0 (Cp), 127.0(Cp), 125.5 (2Co), 80.1 (C2), 74.1 (C5), 52.2 (C4), 21.4

(C16). 15N NMR (CDCl3): δ -265.4. Anal. Calcd for C16H17NO3S: C, 63.35; H, 5.65; N, 4.62. Found:
C, 63.32; H, 6.13; N, 4.56.
5-Methyl-3-tosyl-1,3-oxazolidine (7) was prepared from dithiazinane (3) (1.74 g, 9.7 mmol), compound
o
1
3
(7) was crystallized from CHCl3 (2.1 g, 90%). Mp 82-84 C. H NMR (CDCl3): δ 7.69 (d, J 8.0 Hz, 2H,
Ho-Ts), 7.21 (d, 3J 8.0 Hz, 2H, Hm-Ts), 5.92 (q br, 3J 6.2 Hz, 1H, H-5), 3.81 (br s, 1H, H-2A), 3.50 (br s,
2
3
2
3
1H, H-2B), 2.89 (dd, J 13.2, J 3.3 Hz, 1H, H-4A), 2.71 (t, J 13.2, J Hz, 1H, H-4B), 2.32 (s, 3H,
3
13
CH3-Ts), 1.04 (d, J 6.2 Hz, 3H, CH3-6). C NMR (CDCl3): δ 144.0 (Ci-Ts), 143.4 (Ci), 133.5 (Cp-Ts),
129.7 (2Cm-Ts), 128.0 (2Co-Ts), 127.4 (Cp), 126.9 (2Co), 66.5 (C2), 50.0 (C3), 21.4 (CH3-Ts), 20.4
(CH3). 15N NMR (CDCl3): δ -265.4. Anal. Calcd for C11H17NOS2: C, 54.30; H, 7.04; N, 5.76. Found: C,
54.39; H, 7.13; N, 5.64.
(4S,5R)-4-Methyl-5-phenyl-3-tosyl-1,3-oxazolidine (8) was prepared from compound (4) (0.36 g, 1.42
mmol). The white solid was recrystallized from CHCl3/CH3OH (70/30) (0.41 g, 90%). Mp 102-104 ºC. IR
1
3
3
(KBr): υ (cm-1) 2988, 1594. H NMR (CDCl3): δ 7.82(d, J 7.2, 2H, 2Ho). 7.36 (d, J 7.0, 2H, 2Ho-Ts),
7.35 (m, 3H, 2Hm and Hp), 7.13 (d, 3J 7.0, 2H, 2Hm-Ts), 4.37 (d, 3J 5.0, 1H, H-5), 4.06 (dq, 3J 5.0 and 7.0,
1H, H-4), 3.44 (s, 2H, 2H-2), 2.44 (s, 3H, Ts-CH3), 0.83 (d, 3J 7.0, 3H, CH3). 13C NMR (CDCl3): δ 144.2
(Ci-Ts), 135.8 (Cp-Ts), 134.6 (Ci), 130.0 (Co-Ts), 128.3 (Co), 127.8 (Cp), 127.6 (Cm), 125.9 (Cm-Ts),
81.7 (C2), 79.4 (C5), 57.5 (C4), 21.5 (CH3-Ts), 16.3 (CH3). MS: m/z (%) 317.2 [M+]. Anal.
Calcd for C17H19NO3S: C, 64.36; H, 5.98; N, 4.41. Found: C, 64.08; H, 5.99; N, 4.41.
N-Tosylethanolamine (9). General procedure for tosylation. Ethanolamine (1.0 g, 16.3 mmol), NHMe3Cl
(0.15 g, 1.6 mmol) and NEt3 (4.54 mL, 32.7 mmol) were dissolved in a mixture of toluene/CH2Cl2 (1:1, 10
mL), at 0 oC. TsCl (4.68 g, 24.5 mmol) was dissolved in 10 mL of a mixture of the same solvents, added to
the reaction mixture and stirred for 1 h at 0 oC. Then, the solids were filtered and water (5 mL) was added
to the filtrate and it was extracted with CHCl3. The solution was dried with Na2SO4 and the solvent
evaporated under vacuum. A colorless liquid (3.5 g) was obtained as a mixture of compound (9, 50%) and
N-tosylaziridine (50%). Compound (9) crystallized from CHCl3. The reaction mixture was directly

analyzed by NMR and by MS spectra previous separation a the chromatographic column. Compound (9):
1H NMR (CDCl3): δ 7.70 (d, 3J 8.0, 2H, Ho-Ts), 7.33 (d, 3J 8.0, 2H, Hm-Ts), 5.39 (br s, 1H, OH), 4.04 (t,
3
13
3J 5.0 Hz, 2H, H-1), 3.66 (t, J 5.0 Hz, 2H, H-2), 2.45 (s, 3H, CH3). C NMR (CDCl3): δ 145.5 (Ci-Ts),
132.3 (Cp-Ts), 130.2 (Cm-Ts), 128.1 (Co), 68.9 (C1), 61.3 (C2), 21.8 (CH3-Ts). MS: m/z (%) 215(2) [M+],
184(77), 155(100), 91(83).
1
3
3
N-Tosylaziridine: H NMR (CDCl3): δ 7.75 (d, J 8.0, 2H, Ho-Ts), 7.28 (d, J 8.0, 2H, Hm-Ts), 3.20(t, 3J
4.9 Hz, 4H, 2H-1 and 2H-2), 2.41 (s, 3H, CH3-Ts). 13C NMR (CDCl3): δ 143.9 (Ci-Ts), 136.8 (Cp-Ts),
130.0 (Cm-Ts), 127.2 (Co), 45.4 (C1 and C2), 21.7 (CH3). MS: m/z (%) 197(11) [M+], 91(60), 42(100).
N-Tosyl-2-propanolamine (10) was prepared as compound (9) from 1-aminopropan-2-ol (1.0 g, 13 mmol),
NHMe3Cl (0.12 g, 1.3 mmol) NEt3 (3.61 mL, 26 mmol) and TsCl (3.81 g, 20 mmol). Compound (10) is a
viscous liquid (2.8 g, 90%). 1H NMR (CDCl3): δ 7.74 (d, 3J 8.2, 2H, Ho-Ts), 7.25 (d, 3J 8.2, 2H, Hm-Ts),
3
3
2
6.00 (dd, J 8.02, 3.1, 1H, NH), 3.53 (br s, 1H, OH), 3.16 (qdd, J 6.3, 7.0, 5.4, 1H, H-1), 2.96 (ddd, J
12.8, 3J 7.0, 3.1, 1H, H-2A), 2.74 (ddd, 2J 12.8, 3J 8.0, 5.4, 1H, H-2B), 2.38 (s, 3H, CH3), 1.08 (d, 3J 6.3,
13
3H, CH3). C NMR (CDCl3): δ 143.3 (Ci-Ts), 136.8 (Cp-Ts), 129.7 (Cm-Ts), 127.0 (Co-Ts), 66.4 (C2),
50.1 (C3), 21.5 (CH3), 20.4 (CH3-Ts). MS: m/z (%) 230(3) [M++1], 200(38), 184(33), 155(100),
91(90).
O-Tosyl-2-(1,3,5-dithiazinan-5-yl)ethanol (11) was prepared as compound (9) from 1 (1.0 g, 6.0 mmol),
NHMe3Cl (58 mg, 6.0 mmol), TsCl (1.72 g, 9.0 mmol). Compound (11) is a yellow solid (1.8 g, 98%). IR
(KBr): ν (cm-1) 3051 [C-H], 1261.78 [N-C]. 1H NMR (CDCl3): δ 7.47 (d, 3J 8.1 Hz, 2H, Ho-Ts ), 7.25 (d,
3J8.1 Hz, 2H, Hm-Ts), 4.27 (br s, 4H, 2H-4 and 2H-6), 4.04 (t, 3J 5.4 Hz, 2H, H-8), 4.02 (s, 2H, H-2), 3.24
3
13
(t, J 5.4 Hz, 2H, H-8), 2.46 (s, 3H, CH3-Ts). C NMR (CDCl3): δ 145.0 (Ci-Ts), 142.9 (Cp-Ts), 129.9
(2Co-Ts), 127.9 (2Cm-Ts), 33.7 (C2), 58.5 (C4 and C6), 48.0 (C7), 67.6 (C8), 21.7 (CH3-Ts). Anal. Calcd
for C5H11NOS2: C, 46.20; H, 5.44; N, 4.28. Found: C, 46.37; H, 5.46; N, 4.38.
O-Tosyl-2-(1,3,5-dithiazinan-5-yl)-1-phenylethanol (12) was prepared as compound (9) from 2 (1.0 g,
5.0 mmol), NHMe3Cl (47 mg, 0.5 mmol) NEt3 (1.39 mL, 10 mmol) and TsCl (1.42 g, 7.5 mmol).

Compound (12) is as a brown liquid (1.5 g, 84%). 1H NMR (CDCl3): δ 7.57 (d, 3J 8.0, 2H, Ho-Ts), 7.20 (m,
3
3
5H, Ph), 7.12 (d, J 8.0, 2H, Hm-Ts), 4.02 (s, 2H-2), 4.56 (dd, J 7.8, 3.9, 1H, H-8), 4.07 (br s, 4H, 2H-4
and 2H-6), 3.43( dd, 2J 14.7 Hz, 3J 3.9 Hz, 1H, H-7A), 2.83 (dd, 2J 14.7 Hz, 3J 7.8 Hz, 1H, H-7B), 2.39 (s,
3H-16). 13C NMR (CDCl3): δ 144.5 (Ci-Ts ), 141.6 (Ci), 134.3(Cp-Ts), 129.6(2Co-Ts), 128.0 (2Cm),
127.7 ( 2Cm-Ts), 127.1 (Cp), 125.7 (Co), 77.7 (C8), 59.0 (C4 and C6), 54.3 (C7), 33.5 (C2), 21.6
(CH3-Ts). Anal. Calcd for C18H21NO3S3: C, 54.96; H, 5.83; N, 4.50. Found: C, 54.87; H, 6.04; N, 4.64.
O-Tosyl-2-(1,3,5-dithiazinan-5-yl)-1-methylethanol (13) was prepared as compound (9) from 3 (1.0 g,
5.0 mmol), HNMe3Cl (47 mg, 0.5 mmol) NEt3 (1.39 mL, 0.01 mol) and TsCl (1.42 g, 7.5 mmol).
Compound (13) is a brown liquid (1.5 g, 84%). 1H NMR (CDCl3): δ 7.57 (d, 3J 8.0, 2H, Ho-Ts), 7.02 (d, 3J
2
3
8.0, 2H, Hm-Ts), 4.02 (s, 2H, H-2), 4.07 (br s, 4H, 2H-4 and 2H-6), 3.13 (dd, J 14.7, J 3.9, 1H, H-7A),
2.83 (dd, 2J 14.7, 3J 7.8, 1H, H-7B), 4.56 (qdd, 3J 6.4, 7.8, 3.9, 1H, H-8), 2.39 (s, 3H, CH3-Ts), 1.25 (d, 3J
13
6.4 Hz, 3H, CH3). C NMR (CDCl3): δ 144.5 (Ci-Ts), 134.6 (Cp-Ts), 130.0 (2Cm-Ts), 129.6 (2Co-Ts),
77.7 (C8), 59.0 (C4 and C6), 54.3 (C7), 33.5 (C2), 21.6 (CH3-Ts), 19.0 (CH3). Anal. Calc. for
C13H19NO3S3: C, 48.22; H, 6.27; N, 4.75. Found: C, 48.34; H, 6.60; N, 4.58.
O-Tosyl-2-(1,3,5-dithiazinan-5-yl)-2-methyl-1-phenylethanol (14) was prepared as compound (9) from
(4) (1.0 g, 3.9 mmol), NHMe3Cl (37 mg, 0.4 mmol) NEt3 (1.08 mL, 7.8 mmol) and TsCl (1.11 g, 5.87
mmol). Compound (14) is a colorless liquid (1.5 g, 98%). 1H NMR (CDCl3): δ 7.57 (d, 3J 8.0, 2H, Ho-Ts),
3
3
2
7.21 (m, 5H, Ph), 7.02 (d, J 8.0, 2H, Hm-Ts), 4.98 (d, J 1.0, 1H, H-8), 4.52 (d, J 13.9, 2H, H-4ax,
2
H-6ax), 4.37 (d, J 13.9, 2H, H-4eq and H-6eq), 4.02 (br s, 2H, H-2), 3.67 (m, 1H, H-7), 2.21 (s, 3H,
3
13
CH3-Ts), 0.79 (d, J 6.8, 3H, CH3). C NMR (CDCl3): δ 143.1 (Ci-Ts), 142.2 (Ci), 140.2 (Cp-Ts), 129.1
(2Cm-Ts), 128.3 (2Cm), 127.1 (Cp), 126.2 (2Co), 126.1 (2Co-Ts), 77.1 (C8), 57.6 (C7), 56.6 (C4 and C6),
34.0 (C2), 21.6 (CH3-Ts), 10.4 (CH3). Anal. Calcd for C19H23NO3S3: C, 55.72; H, 5.66; N, 3.42. Found:
C, 55.74; H, 5.60; N, 3.58.
1,3,5-Tribenzyl-1,3,5-triazinane (15). To compound (1) (0.34 g, 3 mmol), benzylamine (2.0 mL, 30
mmol) was added and the mixture was stirred 24 h at rt, then the reaction mixture was dissolved in CHCl3

(30 mL) and washed with water (3 x 20 mL) and the chloroformic solution dried with Na2SO4 and
evaporated. The 1,3,5-triazinane was obtained as a yellow liquid, it crystallized after one day at rt (1.0 g,
o
1
95%). mp 41-43 C. H NMR (CDCl3): δ 7.33 (br s, 15H, Ph), 3.56 (br s, 6H, 2H-2, 2H-4 and 2H-6),
3.80(s, 2H, CH2-Ph). 13C NMR (CDCl3): δ 138.6 (3Ci), 129.0 (6Co), 128.4 (6Cm), 127.1 (3Cp), 74.1 (C2,
C4 and C6), 57.2 (3CH2-Ph).
1,3,5-Tri(2-hydroxyethyl)-1,3,5-triazinane (16). Compound (1) (10 g, 60.7 mmol) was distilled at 100 oC,
0.12 mmHg and transformed into triazinane (16), viscous liquid (3.8 g, 85%). 1H NMR (CDCl3): δ 4.67 (br
s, 6H, CH2-O), 3.51 (t, 3J 5.2 Hz, 6H, CH2-N), 2.47 (t, 3J 5.2 Hz, 6H, 2H-2, 2H-4 and 2H-6), 3.31 (br s, 3H,
OH). 13C NMR (CDCl3): δ 73.8 (3CH2-O), 59.20 (C2, C4 and C6), 55.01 (3CH2-N). Anal. Calcd for
C9H21N3O3·1/2[H2O]: C, 47.35; H, 9.71, N, 18.41. Found: C, 47.33; H, 9.74; N, 18.45.
o
5-Phenyl-1,3-oxazolidine (18) was obtained from 3 by distillation at 190 C and 0.5 mmHg. Oxazolidine
(18) is a colorless liquid (2.8 g, 90%). 1H NMR (CDCl3): δ 7.3-7.23 (br s, 5H, Ph), 4.80 (br s, 1H, H-2A),
4.71 (br s, 1H, H-5), 4.50 (br s, 1H, H-2B), 3.46 (br s, 1H, H-4A), 2.85 (br s, 1H, H-4B). 13C NMR
(CDCl3): δ 142.6 (Ci), 128.6 (Cm), 127.4 (Cp), 125.4 (Co), 83.2 (C2), 76.9 (C5), 55.9 (C4). Anal. Calcd
for C27H33N3O3: C, 72.46; H, 7.43; N, 9.39. Found: C, 72.31; H, 7.49; N, 9.50.
1,3,5-Tri(2-phenyl-2-hydroxyethyl)-1,3,5-triazinane (17). Compound (18) in CHCl3 (or without solvent)
was transformed after 45 h at rt into a colorless liquid which is a mixture in a 80/20 ratio of compounds
1
3
17/18. H NMR (CDCl3): δ 7.4-7.2 (br s, 15H, Ph), 4.78 (d, J 8.4 Hz, 3H, H-8), 3.53 (br s, 6H, 2H-2,
2H-4 and 2H-6), 2.70 (d, 2J 10.6 Hz, 3H, H-7A), 2.55 (dd, 2J 10.6, 3J 8.4 Hz, 3H, H-7B), 2.4 (s, 3H, OH).
13C NMR (CDCl3): δ 142.5 (3Ci), 128.5 (6Cm), 127.6 (3Cp), 126.1 (6Co), 74.0 (C2, C4 and C6), 70.8
(3C8), 61.3 (3C7). Anal. Calcd for C27H33N3O3· H2O: C, 71.50; H, 7.48; N, 9.26. Found: C, 71.27; H,
7.41; N, 8.89.
ACKNOWLEDGEMENTS
Thanks to Cinvestav-México and Conacyt-México for financial support and scholarships of J.C. G.-R. and
I.G. C.-A.

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