Studies on the reaction of diimines with thiourea: Synthesis and solvent-induced cis/trans-isomerization of 1,3,5-triazinane-2-thiones

Article abstract of DOI:10.1055/s-0029-1216884

The reaction of N,Nc-bis(arylmethylidene)arylmethane diimines with thiourea under reflux in methanol was studied. The reaction gave a diastereomeric mixture of 4,6-disubstituted 1,3,5-triazinane-2-thiones in good yields. Two diastereoisomers of 4,6-diphenyl-1,3,5-triazinane-2-thione were detected in a solution of CDCl3 by NMR analysis. According to the NMR studies, the cisdiastereoisomer undergoes a solvent-induced cis/trans-isomerization process, producing the trans-diastereoisomer in DMSO. The stereochemistry of the trans-diastereoisomer was determined by Xray crystallographic analysis.

Full text of DOI:10.1055/s-0029-1216884

PAPER
3089
Studies on the Reaction of Diimines with Thiourea: Synthesis and
Solvent-Induced cis/trans-Isomerization of 1,3,5-Triazinane-2-thiones
S
tudies on the Re
a
action of
D
b
iimines with
a
Thioure
a
k Kaboudin,*a Tahereh Ghasemi,a Tsutomu Yokomatsub
a
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45195-1159, Iran
Fax +98(241)4249023; E-mail: kaboudin@iasbs.ac.ir
b
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horonouchi, Hachioji, Tokyo 192-0392, Japan
Received 29 April 2009; revised 5 May 2009
For the facile preparation of triazinane derivatives, a
readily available nitrogen source is required. Diimines
serve as a good precursor for the synthesis of numerous
organic compounds, especially aza-cyclic compounds.13
Abstract: The reaction of N,N¢-bis(arylmethylidene)arylmethane
diimines with thiourea under reflux in methanol was studied. The
reaction gave a diastereomeric mixture of 4,6-disubstituted 1,3,5-
triazinane-2-thiones in good yields. Two diastereoisomers of 4,6-
diphenyl-1,3,5-triazinane-2-thione were detected in a solution of This easily accessible precursor can be produced by the
CDCl3 by NMR analysis. According to the NMR studies, the cis-
diastereoisomer undergoes a solvent-induced cis/trans-isomeriza-
reaction of aromatic aldehydes with ammonia solution.
Reaction of diimines with thioamides and alkylthiourea
tion process, producing the trans-diastereoisomer in DMSO. The
has been reported in the literature.14 Recently, we have re-
stereochemistry of the trans-diastereoisomer was determined by X-
ported on the reaction of diimines with diethyl phosphite
ray crystallographic analysis.
for the preparation of bis(1-diethoxyphosphoryl-
Key words: diimines, thiourea, 1,3,5-triazinanes, configurational
alkyl)amines.15 As a part of our efforts to introduce novel
isomerism
methods for the synthesis and study of heterocyclic com-
pounds,16 we investigated the reaction of diimines with
thiourea. Herein, we report that the reaction proceeds to
The remarkable ability of heterocyclic nuclei to serve both
give 4,6-disubstituted 1,3,5-triazinane-2-thiones in good
as biomimetics and active pharmacophores has contribut-
yields, along with evidence for solvent-induced isomer-
ed to their unique value as traditional key elements of nu-
ization of the resulting diastereoisomers.
merous drugs.1 Among the heterocyclic compounds,
We first carried out the reaction of diimine 1a, as a model
triazine derivatives are gaining in interest in medicinal
compound,17 with thiourea under reflux for five hours in
and industrial chemistry and they are also being devel-
methanol (Scheme 1). During this time, a white solid pre-
oped as a precursor for the synthesis of nitrogen-contain-
organic compounds.2
The
triazine
and
cipitated out. The molecular formula of the solid was as-
signed as C15H15N3S by HR-ESI-MS (observed m/z =
270.1085 [M + H]+). Based on the molecular weight, the
yield for this reaction was 65%. This molecular formula is
consistent with a molecule of 4,6-diphenyl-1,3,5-triazi-
nane-2-thione (2a). Due to the presence of two stereogen-
ic carbons bonded to the nitrogen atom, the triazinane can
theoretically exist in two diastereomeric forms (cis-2a and
trans-2a) as shown in Scheme 1. A 50:50 diastereomeric
ratio of cis and trans 2a was determined by careful analy-
sis of their NMR spectra.
ing
hexahydrotriazine (triazinane) nucleus constitute well-
known compounds that have been used as an anticonvul-
sant,3 anticoccidial,4 antiplasmodial,5 antimalarial,6 and
herbicidal agients.7 In addition, some of these compounds
can serve as hydrogen sulfide scavengers,8 chiral
discriminators9 and low-toxicity drug deliverers.10 Fur-
thermore, heterocyclic compounds containing a thiourea
or urea structural unit have a special place among pharma-
ceutically important natural and synthetic materials,
showing powerful ectoparasiticidal action, potent antidia-
betic properties, and anti HIV activity.11,12 On the basis of
above reports, we were interested in studying the incorpo-
ration of a thiourea unit into the triazinane nucleus.
1
The H NMR spectrum in CDCl3 exhibited two doublets
with equal intensity at d = 5.21 (J = 8.7 Hz) and 5.54 ppm
(J = 12.0 Hz); two triplets were also observed with equal
Ph
Ph
S
Ph
H
N
S
Ph
NH2
Ph
Ph
Ph
HN
N
N
N
H2N
NH2
N
N
N
N
H
H
H
H
Ph
N
N
NH2
N
+
– [PhCH=NH]
H
H
MeOH, reflux
5 h
N
H
H
H
Ph
S
H
Ph
Ph
S
Ph
trans-2a
H
S
1a
3a
cis-2a
4a
Scheme 1
SYNTHESIS 2009, No. 18, pp 3089–3093
x
x.
x
x
.
2
0
0
9
Advanced online publication: 01.07.2009
DOI: 10.1055/s-0029-1216884; Art ID: Z08409SS
© Georg Thieme Verlag Stuttgart · New York

3090
B. Kaboudin et al.
PAPER
H
intensity at d = 2.00 (J = 12.0 Hz) and 2.55 ppm (J = 8.5
Hz). When the sample was treated with 1–2 drops of D2O
and shaken for a few seconds, the doublet signals at d =
5.21 and 5.54 ppm changed into singlets and the peaks at
d = 2.00 and 2.55 ppm disappeared. On the basis of these
experiments, the signals at d = 5.21 and 5.54 ppm were as-
signed to the benzylic protons corresponding to cis-2a and
trans-2a, respectively, and the assignments were eventu-
ally confirmed by crystallographic studies (vide infra).
H
N
Ph
H
N
Ph
NH2
Ph
H
N
Ph
H
Ph
H
Ph
H
CHCl3
CHCl3
N
N
N
N
N
S
S
S
trans-2a
cis-2a
3a
DMSO
trans-2a
It should be noted that when the diastereomeric mixture
was dissolved in DMSO-d6 and the solution was analyzed
by 1H NMR, the peak at d = 5.21 ppm immediately disap-
peared and intensity of the peak at d = 5.54 ppm increased.
The results suggested that one of the diastereomers (cis-2a
or trans-2a) isomerized to the other in DMSO-d6. The dia-
stereomerically pure 4,6-diphenyl-1,3,5-triazinane-2-
thione could be obtained as a crystal suitable for X-ray
analysis by exposing the diastereomeric mixture to non-
deuterated DMSO in a large scale at room temperature.
The 13C NMR spectrum of the crystal dissolved in
DMSO-d6 confirmed the presence of only one diastereo-
isomer in the sample, whereas the structure and stereo-
chemistry were unambiguously determined to be trans-2a
by X-ray crystallographic analysis (Figure 1). An ORTEP
drawing of trans-2a is shown in Figure 1. At this stage, it
was clear that cis-2a isomerized to trans-2a in DMSO. It
should be pointed out that trans-2a was transformed into
an equilibrium mixture (1:1) of cis-2a and trans-2a in
CHCl3 (Scheme 2).
Scheme 2
on equilibria is particularly important when the structures
in equilibrium have different dipole moments, and is often
rationalized in terms of solute–solvent electrostatic inter-
molecular interaction.19 Intermolecular hydrogen bonding
between the NH group and DMSO is assumed for the sol-
vent-induced cis/trans isomerization process. Increasing
the temperature reduces the hydrogen-bond strength,
however, the 1H NMR spectrum of trans-2a in DMSO-d6
at high temperatures showed only slight changes to the
spectrum. The transformation process may be explained
by the higher polarity of the trans-isomer 2a, which favors
the polar DMSO solvent (Scheme 2).20
This process was successfully applied to other aldehydes
as summarized in Table 1 and Scheme 3. As shown in
Scheme 3 and Table 1, the reaction of various aldehydes
with ammonia followed by reaction with thiourea, afford-
ed 1,3,5-triazinane-2-thiones (2a–n) in good yields. Aro-
matic aldehydes reacted with ammonia followed by
reaction with thiourea under reflux conditions in methanol
to give the products 2a–k in good yield. The reaction of
polynucleic aromatic aldehydes with ammonia followed
by reaction with thiourea under the same conditions gave
the desired products 2l and 2m in good yields. 2-Furfural
as a heterocyclic aldehyde also gave the desired product
2n in 40% yield. Using the same conditions for aliphatic
aldehydes gave unknown mixed products.
H
N
S
R
R
H
R
H
H2N
NH2
NH4OH
N
N
RCHO
3
N
N
MeOH, reflux
5–12 h
R
R
S
1
2
Scheme 3
In conclusion, the reaction of diimines 1 with thiourea,
under reflux conditions in methanol, was investigated.
The reactions proceeded readily to give the mixture of two
diastereoisomers (cis and trans-2) of 4,6-diaryl-1,3,5-tri-
azinane-2-thione in CDCl3. According to the NMR stud-
ies, one of the diastereoisomers undergoes a solvent-
induced cis/trans-isomerization process, producing the
trans-2 form in DMSO. The structure and stereochemistry
of the trans-2a diastereoisomer was determined by X-ray
crystallographic analysis. An intermediate 3a was sug-
Figure 1 ORTEP drawing of trans-2a
Heterocyclohexanes, such as triazinanes, prefer to adopt
the chair conformation unless specific intramolecular in-
teractions stabilize the more strained twist or boat con-
formers.18 Substituents in the ring normally prefer to
adopt equatorial over axial positions. The solvent effect
Synthesis 2009, No. 18, 3089–3093 © Thieme Stuttgart · New York

PAPER
Studies on the Reaction of Diimines with Thiourea
3091
5–12 h at reflux. When the reaction mixture was cooled to room
temperature, a white solid precipitated. The precipitates were fil-
tered and recrystallized from EtOAc to give product 2 in 38–72%
yield. All products gave satisfactory spectral data in accordance
with the assigned structures.
Table 1 Reaction of Aromatic Aldehydes with Ammonia Followed
by Reaction with Thiourea
Entry
R
Time (h) Yield (%)a Mp (°C)
of 2
65
66
69
70
72
38
51
52
36
55
59
59
62
40
of 2
4,6-Diphenyl[1,3,5]triazinane-2-thione (2a)2c
a
b
c
d
e
f
Ph
5
7
155–156
170–172
177–179
177–178
162–163
169–170
184–186
167–168
192–193
198–200
197–199
186–187
188–190
151–152
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.01 (t, J = 11.75 Hz, 1 H, NH), 2.55 (t, J = 8.75 Hz, 1 H, NH), 5.21
(d, J = 8.75 Hz, 2 H), 5.54 (d, J = 12 Hz, 2 H), 6.91 (s, 2 H, NH),
7.21 (s, 2 H, NH), 7.30–7.50 (m, 20 H).
4-MeC6H4
4-(i-Pr)C6H4
4-MeOC6H4
4-MeSC6H4
2-ClC6H4
2-FC6H4
8
7
13C NMR (CDCl3, 62.9 MHz): d (mixture of two diastereoisomers) =
65.7, 69.6, 126.4, 126.6, 128.9, 129.0, 129.2, 129.7, 137.1, 138.3,
176.7, 178.4.
HRMS: m/z [M + H+] calcd for C15H15N3S: 270.1065; found:
270.1085.
7
12
12
10
12
10
9
g
h
i
4,6-Di(4-methylphenyl)[1,3,5]triazinane-2-thione (2b)
2-MeC6H4
3-FC6H4
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
1.92 (t, J = 12.0 Hz, 1 H, NH), 2.20–2.60 (m, 13 H), 5.14 (d,
J = 7.75 Hz, 2 H), 5.48 (d, J = 12 Hz, 2 H), 6.90–7.60 (m, 20 H).
j
2,4-Cl2C6H3
2,6-Cl2C6H3
1-naphthyl
2-naphthyl
2-furyl
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
21.2, 64.9, 127.2, 129.2, 137.6, 137.8, 176.1.
HRMS: m/z [M + H+] calcd for C17H19N3S: 298.1378; found:
298.1386.
k
l
10
10
12
m
n
4,6-Di(4-isopropylphenyl)[1,3,5]triazinane-2-thione (2c)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
1.15–1.35 (m, 24 H), 2.03 (t, J = 11.5 Hz, 1 H, NH), 2.50–2.65 (br,
1 H, NH), 2.85–3.05 (m, 4 H), 5.18 (d, J = 7.25 Hz, 2 H), 5.50 (d,
J = 12 Hz, 2 H), 7.20–7.40 (m, 20 H).
a Yields refer to the isolated pure products after column chromatogra-
phy.
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
gested for the conversion process. Further investigations
on this reaction are now in progress.
21.2, 64.9, 127.2, 129.2, 137.6, 137.8, 176.1.
HRMS: m/z [M + H+] calcd for C21H27N3S: 354.2004; found:
354.2001.
All chemicals were commercial products, which were either dis-
tilled or recrystallized before use. Melting points are uncorrected.
NMR spectra were taken with a 250 MHz instrument with the
chemical shifts are reported as d ppm relative to TMS and couplings
(J) expressed in hertz. Mass spectra were measured on LCMASS
micromass LCT and Micromass Autospec instruments.
4,6-Di(4-methoxyphenyl)[1,3,5]triazinane-2-thione (2d)2c
1H NMR (DMSO-d6, 250 MHz): d (single diastereoisomer, trans) =
3.73 (s, 6 H), 3.78 (t, J = 8.5 Hz, 1 H, NH), 4.91 (d, J = 8.5 Hz,
2 H), 6.92 (d, J = 8.5 Hz, 4 H), 7.27 (d, J = 8.5 Hz, 4 H), 8.64 (s,
2 H, NH).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
55.6, 64.7, 114.1, 128.5, 132.7, 159.4, 176.0.
X-ray crystal data of 2a were collected on a Bruker Apex2 diffrac-
tometer. The structure was solved by a direct method using
SHELXS-9721 and refined with a full matrix least-squares method.
Molecular formula = C21H19O4P; MW = 366.33; orthorhombic;
space group = Pna2(1); Unit cell dimensions a = 15.461(3) Å,
b = 19.710(4) Å, c = 5.7408(11) Å; V = 1749.4(6) Å3; T = 90 K;
Z = 4; D (calcd) = 1.391 Mg/m3; (Mo-Ka) = 0.71073 Å; absolute
structure parameter = 0.12(10), R = 0.0415 over independent re-
flections (4015). Crystallographic data (excluding structure factors)
for the X-ray crystal structure analysis reported in this paper have
been deposited with the Cambridge Crystallographic Data Center
(CCDC) as supplementary publication No. CCDC 714161, copies
of these data can be obtained, free of charge, upon application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
+44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
HRMS: m/z [M + H+] calcd for C17H19N3O2S: 330.1276; found:
330.1280.
4,6-Di(4-thiomethylphenyl)[1,3,5]triazinane-2-thione (2e)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
1.50–1.60 (br, 1 H, NH), 1.94 (t, J = 12.0 Hz, 1 H, NH), 2.45 (s,
6 H), 2.49 (s, 6 H), 5.14 (d, J = 6.0 Hz, 2 H), 5.49 (d, J = 12 Hz,
2 H), 6.80 (s, 2 H, NH), 7.08 (s, 2 H, NH), 7.20–7.40 (m, 16 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
15.2, 68.6, 125.9, 128.2, 136.2, 138.4, 176.1.
HRMS: m/z [M + H+] calcd for C17H19N3S3: 362.0819; found:
362.0840.
4,6-Di(2-chlorophenyl)[1,3,5]triazinane-2-thione (2f)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.30 (t, J = 12 Hz, 1 H, NH), 2.72 (t, J = 8.25 Hz, 1 H, NH), 5.61 (d,
J = 8.25 Hz, 2 H), 5.96 (d, J = 12 Hz, 2 H), 7.17 (s, 2 H, NH), 7.20–
7.60 (18 H, m).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
63.41, 127.1, 128.0, 130.4, 130.5, 133.2, 135.0, 177.6.
4,6-Disubstituted 1,3,5-Triazinane-2-thiones (2); General Pro-
cedure
The aldehyde (3 mmol) was added to NH4OH (30%, 15 mL) and the
solution was stirred for 5 h at reflux. During this time, a white pre-
cipitate formed. The precipitate was removed by filtration and
dried. The solid was dissolved in MeOH (5 mL), thiourea (1 mmol)
was added to the mixture and the resulting solution was stirred for
Synthesis 2009, No. 18, 3089–3093 © Thieme Stuttgart · New York

3092
B. Kaboudin et al.
PAPER
HRMS: m/z [M + H+] calcd for C15H13N3SCl2: 338.0285; found:
HRMS: m/z [M + H+] calcd for C23H19N3S: 370.1378; found:
338.0283.
370.1397.
4,6-Di(2-fluorophenyl)[1,3,5]triazinane-2-thione (2g)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.88 (t, J = 11.5 Hz, 1 H, NH), 3.10–3.40 (br, 1 H, NH), 5.98 (s,
2 H), 6.23 (d, J = 11.5 Hz, 2 H), 7.20–8.30 (m, 20 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
59.5 (d, JC–F = 3.8 Hz), 116.0 (d, JC–F = 21.4 Hz), 124.7, 127.2 (d,
JC–F = 12.6 Hz), 129.0 (d, JC–F = 3.1 Hz), 130.8 (d, JC–F = 8.2 Hz),
159.9 (d, JC–F = 247.2 Hz), 177.0.
4,6-Di(b-naphthyl)[1,3,5]triazinane-2-thione (2m)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.10–2.40 (br, 1 H, NH), 2.60–2.80 (br, 1 H, NH), 5.30–5.45 (br,
2 H), 5.70–5.85 (br, 2 H), 6.90–7.05 (br, 2 H, NH), 7.15–8.30 (m,
30 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
69.3, 125.8, 126.6, 127.9, 128.0, 128.4, 132.9, 133.3, 137.0, 178.0.
HRMS: m/z [M + H+] calcd for C23H19N3S: 370.1378; found:
370.1400.
HRMS: m/z [M + H+] calcd for C15H13N3SF2: 306.0877; found:
306.0890.
4,6-Di(2-furyl)[1,3,5]triazinane-2-thione (2n)
4,6-Di(2-methylphenyl)[1,3,5]triazinane-2-thione (2h)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
1.78 (t, J = 12.25 Hz, 1 H, NH), 2.15 (s, 6 H), 2.28 (t, J = 8.5 Hz,
1 H, NH), 2.44 (s, 6 H), 5.32 (d, J = 8.5 Hz, 2 H), 5.76 (d, J = 12.25
Hz, 2 H), 6.99 (s, 2 H, NH), 7.10–7.55 (m, 18 H).
13C NMR (CDCl3, 62.9 MHz): d (mixture of two diastereoisomers) =
18.31, 18.77, 63.4, 66.45, 124.4, 125.8, 126.1, 126.7, 128.9, 129.4,
131.0, 131.1, 135.3, 135.9, 136.3, 136.4, 177.7, 179.3.
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.59 (t, J = 12.25 Hz, 1 H, NH), 2.85–3.00 (br, 1 H, NH), 5.39 (d,
J = 8.0 Hz, 2 H), 6.23 (d, J = 12.25 Hz, 2 H), 6.38–6.55 (m, 8 H),
7.19 (s, 2 H, NH), 7.30–7.55 (m, 6 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
60.0, 108.7, 110.6, 143.3, 153.0, 176.2.
HRMS: m/z [M + Na+] calcd for C11H11N3O2S: 272.0470; found:
272.0442.
HRMS: m/z [M + H+] calcd for C17H19N3S: 298.1378; found:
298.1375.
Acknowledgment
4,6-Di(3-fluorophenyl)[1,3,5]triazinane-2-thione (2i)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.88 (t, J = 11.5 Hz, 1 H, NH), 3.10–3.40 (br, 1 H, NH), 5.98 (s,
2 H), 6.23 (d, J = 11.5 Hz, 2 H), 7.20–8.30 (m, 20 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
64.4, 113.9 (d, JC–F = 22.6 Hz), 115.3 (d, JC–F = 20.8 Hz), 123.1 (d,
JC–F = 1.9 Hz), 130.7 (d, JC–F = 8.2 Hz), 142.5 (d, JC–F = 6.9 Hz),
162.2 (d, JC–F = 244.7 Hz), 175.8.
The Institute for Advanced Studies in Basic Sciences (IASBS) is
thanked for supporting this work. The authors thank Mr. Haruhiko
Fukaya, Tokyo University of Pharmacy and Life Sciences for help
in carrying out the X-ray crystallographic analysis.
References
(1) Roth, H. J.; Kleemann, A. Pharmaceutical Chemistry, Drug
Synthesis, Vol. 1; Wiley: New York, 1990.
HRMS: m/z [M + H+] calcd for C15H13N3SF2: 306.0877; found:
306.0890.
(2) (a) Giumanini, A. G.; Verardo, G.; Gorassini, F.; Strazzolini,
P.; Benetollo, F.; Bombieri, G. J. Chem. Soc., Perkin Trans.
1 1994, 1643. (b) Groendaal, B.; Vugts, D. J.; Schmitz, R.
F.; de Kanter, F. J. J.; Ruijter, E.; Groen, M. B.; Orru, R. V.
A. J. Org. Chem. 2008, 73, 719. (c) Soliman, A. A.-W.
J. Chem. Eng. Data 1984, 29, 99.
4,6-Di(2,4-dichlorophenyl)[1,3,5]triazinane-2-thione (2j)
1H NMR (CDCl3, 250 MHz): d (single diastereoisomer, trans) =
4.29 (t, J = 12.25 Hz, 1 H, NH), 6.34 (d, J = 12.25 Hz, 2 H), 6.84 (s,
2 H, NH), 7.20–7.48 (m, 6 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
(3) Perry, A. A.; Virgel, E. G.; Brian, P. L. US Patent 3689651,
1972.
66.3, 129.0–136.0 (Ar), 178.0.
(4) Fukami, H.; Hashimoto, M.; Niwata, S.; Imose, J.;
Kawaguchi, H.; Takahashi, T. US Patent 5424310, 1995.
(5) Klenke, B.; Barrett, M. P.; Brun, R.; Gilbert, I. H.
J. Antimicrob. Chemother. 2003, 52, 290.
(6) Kinyanjui, S. M.; Mberu, E. K.; Winstanley, P. A.; Jacobus,
D. P.; Watkins, W. M. Am. J. Trop. Med. Hyg. 1999, 60, 943.
(7) Soong, Ch.-L.; Ogawa, J.; Sakuradani, E.; Shimizu, S.
J. Biol. Chem. 2002, 227, 7051.
HRMS: m/z [M + H+] calcd for C15H11N3SCl4: 405.9506; found:
405.9523.
4,6-Di(2,6-dichlorophenyl)[1,3,5]triazinane-2-thione (2k)
1H NMR (CDCl3, 250 MHz): d = (single diastereoisomer, trans) =
4.29 (t, J = 12.25 Hz, 1 H, NH), 6.37 (d, J = 12.25 Hz, 2 H), 6.65–
6.90 (br, 2 H, NH), 7.20–7.48 (m, 6 H).
13C NMR (DMSO-d6, 62.9 MHz): d (single diastereoisomer, trans) =
66.3, 129.0–136.0 (Ar), 178.0.
(8) Bakke, J. M.; Buhaug, J. B. Ind. Eng. Chem. Res. 2004, 43,
1962.
(9) Sugimoto, H.; Yamane, Y.; Inoue, S. Tetrahedron:
Asymmetry 2000, 11, 2067.
(10) (a) Murray, A. P.; Miller, M. J. J. Org. Chem. 2003, 68, 191.
(b) Ghosh, M.; Miller, M. J. J. Org. Chem. 1994, 59, 1020.
(11) Zhang, Z.; Xian, D.; Li, J.; Zhang, G. Acta Crystallogr., Sect.
C 2008, 64, o191.
(12) (a) Enders, E.; Ebbighausen, V.; Gau, W.; Wunsche, C.;
Stendel, W. US Patent 4 173 645, 1979. (b) Lenzen, S.;
Ahmad, R. German Patent DE 10 012 401, 2001.
(c) Acharya, A. N.; Ostresh, J. M.; Houghten, R. A. J. Comb.
Chem. 2001, 3, 612.
HRMS: m/z [M + H+] calcd for C15H11N3SCl4: 405.9506; found:
405.9562.
4,6-Di(a-naphthyl)[1,3,5]triazinane-2-thione (2l)
1H NMR (CDCl3, 250 MHz): d (mixture of two diastereoisomers) =
2.45 (t, J = 11.75 Hz, 1 H, NH), 2.78 (t, J = 8.5 Hz, 1 H, NH), 5.92
(d, J = 8.5 Hz, 2 H), 6.47 (d, J = 11.75 Hz, 2 H), 7.0–7.1 (br, 2 H,
NH), 7.15–8.30 (m, 30 H).
13C NMR (CDCl3, 62.9 MHz): d (mixture of two diastereoisomers) =
67.6, 70.4, 128.8, 129.1, 129.3, 129.8, 130.1, 130.2, 130.7, 130.9,
131.0, 131.2, 133.5, 133.6, 133.7, 134.0, 135.3, 135.8, 138.4, 138.6,
139.6, 139.9, 182.4, 183.9.
Synthesis 2009, No. 18, 3089–3093 © Thieme Stuttgart · New York

PAPER
Studies on the Reaction of Diimines with Thiourea
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(13) (a) Saigo, K.; Kubota, N.; Takebayashi, S.; Hasegawa, M.
Bull. Chem. Soc. Jpn. 1986, 59, 931. (b) Corey, E. J.;
Kuhnle, F. N. M. Tetrahedron Lett. 1997, 38, 8631.
(c) Larter, M. L.; Phillips, M.; Ortega, F.; Aguirre, G.;
Somanathan, R.; Walsh, P. J. Tetrahedron Lett. 1998, 39,
4785. (d) Lozinskaya, N. A.; Tsybezova, V. V.; Proskurnina,
M. V.; Zefirov, N. S. Russ. Chem. Bull. 2003, 52, 674.
(e) Nishiyama, K.; Saito, M.; Oba, M. Bull. Chem. Soc. Jpn.
1988, 61, 609. (f) Uchida, H.; Shimizu, T.; Reddy, P. Y.;
Nakamura, S.; Toru, T. Synthesis 2003, 1236. (g) Uchida,
H.; Tanikoshi, H.; Nakamura, S.; Reddy, P. Y.; Toru, T.
Synlett 2003, 1117. (h) Corey, E. J.; Grogan, M. J. Org. Lett.
1999, 1, 157. (i) Isobe, T.; Fukuda, K.; Araki, Y.; Ishikawa,
T. Chem. Commun. 2001, 243. (j) Anastassiadou, M.;
Baziard-Mouysset, G.; Payard, M. Synthesis 2000, 1814.
(k) Corey, E. J.; Huang, H. C. Tetrahedron Lett. 1989, 30,
5235. (l) Corey, E. J.; Imwinkelried, R.; Pikul, S. B. J. Am.
Chem. Soc. 1989, 111, 5493. (m) Corey, E. J.; Kim, S. S.
J. Am. Chem. Soc. 1990, 112, 4976.
(15) (a) Kaboudin, B.; Moradi, K. Synthesis 2006, 2339.
(b) Kaboudin, B.; Jafari, E. Synthesis 2006, 3063.
(c) Kaboudin, B.; Jafari, E. Synthesis 2007, 1823.
(16) (a) Balakrishna, M. S.; Kaboudin, B. Tetrahedron Lett.
2001, 42, 1127. (b) Kaboudin, B.; Navaee, K. Heterocycles
2001, 55, 1443. (c) Kaboudin, B.; Navaee, K. Heterocycles
2003, 60, 2287. (d) Kaboudin, B.; Saadati, F. J. Heterocycl.
Chem. 2005, 42, 699. (e) Kaboudin, B.; Saadati, F.
Heterocycles 2005, 65, 353. (f) Kaboudin, B.; Saadati, F.
Tetrahedron Lett. 2007, 48, 2829.
(17) Kaboudin, B.; Moradi, K. Tetrahedron Lett. 2005, 46, 2989.
(18) Shainyan, B. A.; Meshcheryakov, V. I.; Albanov, A. I.;
Sigalov, M. V. Tetrahedron Lett. 2005, 46, 6199.
(19) (a) Conde, J. P.; Ramos, J. J. M. J. Chem. Educ. 1986, 63,
823. (b) Ramos, J. J. M.; Dumont, L.; Stien, M. L.; Russe, J.
J. Am. Chem. Soc. 1980, 102, 4150. (c) Eliel, E. L.; Wilen,
S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; Wiley: New York, 1994. (d)de Oliveira, P. R.;
Rittner, R. J. Mol. Struct. 2005, 743, 69.
(14) (a) Takajo, T.; Kambe, S. Synthesis 1985, 92. (b) Pingda,
R.; Tingwei, D. Chin. J. Org. Chem. 1994, 14, 153.
(20) Liao, Ch.-Y.; Chan, K.-T.; Chang, Y.-C.; Chen, Ch.-Y.; Tu,
Ch.-Y. Organometallics 2007, 26, 5826.
(21) Sheldrick, G. M. SHELXS-97; University of Göttingen:
Germany, 1997.
Synthesis 2009, No. 18, 3089–3093 © Thieme Stuttgart · New York