Synthesis, crystal structure, and interconversions of new N-aryl-1,3,5-dithiazinanes, 1,3,5-thiadiazinanes, and 1,5-dithia-3,7- diazacyclooctanes

Article abstract of DOI:10.1007/s11172-010-0196-y

Chemoselectivity of multicomponent reaction of anilines with the CH ₂O-H₂S thiomethylating mixture in the synthesis of N-aryl-substituted 1,3,5-dithiazinanes, 1,3,5-thiadiazinanes, and 1,5-dithia-3,7-diazacyclooctanes has been studied depending on the type and mutual arrangement of substituents in the starting anilines, ratio of reagents, temperature, and reaction time. Conformation of the synthesized heterocycles in crystal has been found by X-ray diffraction. Interconversion of the heterocycles showed stability of N-aryl-1,3,5-dithiazinanes.

Full text of DOI:10.1007/s11172-010-0196-y

Russian Chemical Bulletin, International Edition, Vol. 59, No. 5, pp. 1002—1009, May, 2010
1002
Synthesis, crystal structure, and interconversions
of new Nꢀarylꢀ1,3,5ꢀdithiazinanes, 1,3,5ꢀthiadiazinanes,
and 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
V. R. Akhmetova,a Z. T. Niatshina,a G. R. Khabibullina,a I. S. Bushmarinov,b
A. O. Borisova,b Z. A. Starikova,b L. F. Korzhova,c and R. V. Kunakovaa
aInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences,
141 prosp. Oktyabrya, 450075, Ufa, Russian Federation.
Fax: +7 (347) 284 2750. Eꢀmail: ink@anrb.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: star@xray.ineos.ac.ru
cBashkirian Republican Ecological Research Center,
147 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347) 284 3503. Eꢀmail: ecocnt@diaspro.ru
Chemoselectivity of multicomponent reaction of anilines with the CH2O—H2S thiomethylꢀ
ating mixture in the synthesis of Nꢀarylꢀsubstituted 1,3,5ꢀdithiazinanes, 1,3,5ꢀthiadiazinanes,
and 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes has been studied depending on the type and mutual
arrangement of substituents in the starting anilines, ratio of reagents, temperature, and reacꢀ
tion time. Conformation of the synthesized heterocycles in crystal has been found by Xꢀray
diffraction. Interconversion of the heterocycles showed stability of Nꢀarylꢀ1,3,5ꢀdithiazinanes.
Key words: multicomponent reaction, thiomethylating mixture, substituted anilines,
hydrogen sulfide, formaldehyde, Xꢀray diffraction study.
Results and Discussion
Saturated sulfurꢀ and nitrogenꢀcontaining heterocycles
are involved into formation of transition metal complexes
and, therefore, are of interest as potential bidentate
ligands.1,2
Regioselective synthesis of 1,3,5ꢀdithiazinanes takes
place at stoichiometric ratio of the starting reagents
aniline : CH2O : H2S equal to 1 : 3 : 2.
In the last years, we have in detail studied cycloꢀ
thiomethylation of aliphatic amines with formaldehyde
and H2S in the selective synthesis of 1,3,5ꢀdithiazinanes.3—5
Heterocyclization of anilines with CH2O and H2S proꢀ
ceeded with the formation of different types of heteroꢀ
cyclic compounds:6 1,3ꢀthiazetidines, 1,3,5ꢀdithiazinanes,
1,3,5ꢀthiadiazinanes, and 1,3,5ꢀoxathiazinanes and, deꢀ
pending on the nature and position of a substituent in the
aromatic ring, predominant formation of one of the listed
heterocycles occurred.
The present work deals with the study of chemoꢀ
selectivity of the multicomponent reaction of anilines 1a—l
with the CH2O—H2S thiomethylating mixture (see Ref. 7)
in the directed synthesis of Nꢀarylꢀsubstituted 1,3,5ꢀdiꢀ
thiazinanes, 1,3,5ꢀthiadiazinanes, and 1,5ꢀdithiaꢀ3,7ꢀ
diazacyclooctanes depending on the type and mutual
arrangement of substituents in the starting anilines, ratio
of the starting reagents, solvent effect, temperature, and
the experiment duration.
Using aniline as an example, it was found that the
choice of the solvent (H2O, C6H6, Et2O, EtOAc, MeOH,
EtOH, BuOH) has no effect on the direction of the proꢀ
cess, but influences the reaction conversion and selecꢀ
tivity. The use of aqueous ethanol as the solvent in further
experiments is due to good solubility of the starting
components in this solvent mixture, efficiency of the proꢀ
cess, easy isolation of the reaction products, availability,
and lower toxicity. It was found that the highest yield is
reached in the temperature interval 40—60 °C. NꢀArylꢀ
substituted 1,3,5ꢀdithiazinanes 2a—l were selectively synꢀ
thesized under indicated conditions (the ratio 1 : 3 : 2,
40—60 °C, EtOH—H2O) (Scheme 1). Note that an inꢀ
crease in the reaction time to 10—12 h leads to an
increase in regioselectivity of the process (see Ref. 6),
apparently due to the in situ transformation of the less
stable intermediate heterocycles 3a—l and 4a—l to
Nꢀarylꢀ1,3,5ꢀdithiazinanes 2a—l.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 980—987, May, 2010.
1066ꢀ5285/10/5905ꢀ1002 © 2010 Springer Science+Business Media, Inc.

New Nꢀarylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1003
Scheme 1
Br(1)
C(7)
C(6)
C(8)
C(9)
C(5)
C(4)
N(1)
Reagents and conditions: CH2O—H2S (3 : 2), 40—60 °C,
EtOH—H2O
At the same time, metaꢀsubstituted anilines under these
conditions, along with 1,3,5ꢀdithiazinanes, give small
amounts (10—20%) of 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
3c, 3f, and 3i (Table 1).
C(3)
S(2)
C(1)
S(1)
Aniline 1a and paraꢀsubstituted anilines 1d,g,j,l are
more active in the heterocyclization with CH2O and H2S.
An increase in reactivity was also observed for the steriꢀ
cally hindered orthoꢀsubstituted anilines with an electronꢀ
withdrawing substituent (NO2, I). To sum up, the heteroꢀ
cyclization of orthoꢀ and paraꢀsubstituted anilines
1b,d,e,g,h,j—l to 1,3,5ꢀdithiazinanes occurs the more
readily, the less basic is the NH2 group. According to the
experimental data, the yields of 1,3,5ꢀdithiazinanes
increase in the following order: for paraꢀsubstituted
anilines, pꢀOMe < pꢀMe < pꢀBr < pꢀNO2; for orthoꢀ
substituted anilines, oꢀOMe < oꢀMe < oꢀI < oꢀNO2.
The structure of compound 2l was unambiguously esꢀ
tablished by Xꢀray diffraction analysis. In the crystal, the
1,3,5ꢀdithiazinane ring is in the chair conformation with
the axial pꢀbromophenyl substituent (Fig. 1). The lone
pair of electrons (further, lp) on the N(1) atom is in
C(2)
Fig. 1. Molecular structure of 2l in crystal. Atoms are repreꢀ
sented by thermal ellipsoids (p = 50%).
conjugation with the aromatic substituent and is involved
into stereoelectronic interactions lpN→σ*C—S with the
C(1)—S(1) and C(3)—S(2) bonds. The nature of this
interaction and its effect on the structure of compounds
studied in this work will be more in details considered
below.
Heterocycles 2a—l are characterized by free inversion
of the dithiazinane ring in solution at room temperature,
which was inferred from the singlet signals of the NCH2S
and SCH2S methylene protons in the 1H NMR spectra in
the region δ 4.70—5.74 and 3.38—4.38, respectively.
The 13C NMR spectra of dithiazinanes 2a,b,h—l
exhibit the corresponding signals for the methylene groups
between two sulfur atoms (δC 33.7—43.0) and between
nitrogen and sulfur atoms (δC 55.1—63.4). In the mass
spectra of products 2a, 2b, and 2k, molecular ions [M]+
are observed with m/z 197, 211, and 323, respectively, as
well as peaks of characteristic fragment ions with the
successive loss of the methylenesulfide units CH2S.
For the directed synthesis of 1,3,5ꢀthiadiazinanes, the
reaction was carried out with the ratio aniline : CH2O :
H2S = 2 : 3 : 1 at 0°C (see Ref. 9). Regioselectivity of this
process is determined by the structure of the starting
anilines 1a—l.
Table 1. Yields of condensation products of arylamines
with CH2O and H2S in proportion 1 : 3 : 2 at 40—60 °C
8
1
R
pKa
Yield (%)
2
3
a
b
c
d
e
f
g
h
i
H
oꢀMe
mꢀMe
pꢀMe
oꢀOMe
mꢀOMe
pꢀOMe
oꢀNO2
mꢀNO2
pꢀNO2
oꢀI
4.58
4.39
4.69
5.12
4.49
4.2
5.29
–0.29
2.5
65
40
48
68
34
37
60
64
45
76
56
70
—
—
10
—
—
10
—
—
20
—
—
—
It was found that for all the anilines under these conꢀ
ditions, the corresponding 1,3,5ꢀdithiazinanes 2a—l are
immediately formed (TLC monitoring) together with the
target 1,3,5ꢀthiadiazinanes, the amount of which increases
with the increase in the reaction time. The complete conꢀ
j
k
l
1.02
2.6
3.91
pꢀBr

1004
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Akhmetova et al.
S(1)
version is reached after 10 h with the formation of a mixꢀ
ture of heterocycles 2—4 (Scheme 2, Table 2), which
were separated by column chromatography on silica
gel. Note that weak bases 1h—j form no 1,3,5ꢀthiaꢀ
diazinanes, while the stronger base, pꢀbromoaniline 1l,
gives 1,3,5ꢀthiadiazinane 4l in 83% yield. Earlier,10 the
corresponding 1,3,5ꢀthiadiazinane was synthesized under
analogous conditions from ethyl pꢀaminobenzoate in 93%
yield. oꢀSubstituted anilines 1b,e,h,k are characterized by
low conversion, apparently, due to the “orthoꢀeffect”,11
with anilines 1e,k giving no thiadiazinanes at all. mꢀIsoꢀ
mers 1c,f, similarly to the preceding experiments (see
Scheme 1), form 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes 3 along
with the target 4c,f (see Scheme 2, Table 2).
C(1)
C(3)
N(2)
N(1)
C(14)
C(5)
C(6)
C(7)
C(2)
C(15)
C(4)
C(13)
C(9)
C(10)
C(11)
C(12)
C(8)
4a
Scheme 2
S(1)
C(1)
N(1)
C(10)
N(2)
C(2)
C(8)
C(12)
C(11)
C(16)
C(3)
Reagents and conditions: CH2O—H2S (3 : 1), 0 °C, EtOH—H2O
C(7)
C(13)
paraꢀSubstituted anilines are more reactive in the
series of syntheses of 1,3,5ꢀthiadiazinanes, their activity
increases with the increase in acidity: pꢀOMe < pꢀMe <
< pꢀBr < pꢀCOOEt.
C(4)
C(5)
C(6)
C(14)
C(15)
The structures of compounds 4a and 4d were conꢀ
firmed by Xꢀray diffraction. The 1,3,5ꢀthiadiazinane rings
in both molecules were in the chair conformation with
the synꢀaxial arrangement of the substituents (Fig. 2).
C(9)
C(17)
4d
1
The H and 13C NMR spectra of thiadiazinanes
Fig. 2. Molecular structures of 4a and 4d in crystal. Atoms are
represented by thermal ellipsoids (p = 50%).
4a,b,l exhibit the corresponding signals for the methylene
groups between two nitrogen atoms (δH 5.18—5.27 and δC
69.3—71.7) and between the nitrogen and the sulfur
atoms (δH 4.94—5.01 and δC 53.4—53.8).
Table 2. Yields of condensation products of arylamines with
CH2O and H2S in proportion 2 : 3 : 1 at 0 °C
1
Yield (%)
According to the data in Ref. 12, a predominant forꢀ
mation of 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes 3a,c,d,f
occurs with the ratio aniline—CH2O—H2S equal to 1 : 6 : 4
at 0 °C (EtOH—H2O) (Scheme 3). Heterocycles obtained
starting from aniline 1a and metaꢀsubstituted anilines 1c,f,i
proved more stable (Table 3), whereas orthoꢀsubstiꢀ
tuted anilines 1b,e,h,k under these conditions yield only
2
3
4
a
b
c
d
e
f
g
h
i
50
15
5
—
—
31
—
—
36
—
—
33
—
—
—
15
34
45
52
—
30
23
—
—
—
—
83
20
20
15
55
21
25
35
37
5
1
dithiazinanes 2b,e,h,k. In the H NMR spectra of eightꢀ
membered dithiadiazacyclooctanes, the methylene proꢀ
tons, in contrast to dithiazinanes and thiadiazinanes, are
found as doublets of doublets (δH 4.86—5.29), that indiꢀ
cates decelerated inversion of the cyclooctane ring in
solution.13,14 In the 13C NMR spectra, the singlet methylꢀ
ene signals are found in the region δ 55.9—56.4
j
k
l

New Nꢀarylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1005
Table 3. Yields of condensation products 2—4 of arylamines
with CH2O and H2S in proportion 1 : 6 : 4 at 0 °C
C(1)
C(4)
C(3)
N(2)
C(2)
N(1)
1
Yield (%)
C(11)
2
3
4
S(1)
S(2)
C(5)
C(10)
C(9)
C(12)
C(13)
C(6)
C(7)
a
b
c
d
e
f
g
h
i
10
31
20
55
25
20
57
28
42
41
40
66
70
—
50
5
—
48
10
—
44
8
10
28
—
—
—
—
—
—
—
—
—
—
C(16)
C(15)
C(14)
C(8)
Fig. 3. Molecular structure of 3a in crystal. Atoms are repreꢀ
sented by thermal ellipsoids (p = 50%).
j
k
l
—
10
electronic interaction and can increase to 1.860 Å if it is
present.16
To sum up, aniline and mꢀsubstituted anilines only
Based on the data given in Table 4, a conclusion
can be drawn that the conjugation between the lone pair
of electrons on the nitrogen atom and the phenyl ring is
present in all the compounds studied (the N—Carom bond
is shorter than the value of 1.430 Å characteristic of
(Alk)2Nsp3—Carom).17 At the same time, this conjugation
does not lead to a noticeable flattening the nitrogen atom
(the nitrogen atom comes out of the plane by 0.15—0.28 Å).
The lpN>σ*C—S interaction operates in all the molecules
considered as well, resulting in considerable elongation of
the C—S bond as compared to a typical for the N—CH2—S
bond value of 1.814 Å (see Ref. 16). In compounds 4a
and 4d, this elongation is more pronounced, which is
explained by involvement of each nitrogen atom into one
lp—N—C—S stereoelectronic interaction, rather than in
two as in compounds 2l and 3a. It should be noted that
the synꢀdiaxial arrangement of substituents in compounds
4a and 4d is unfavorable from the point of view of their
steric repulsion, but at the same time is optimum for the
interaction of the lone pairs on the nitrogen atoms with
the σ*C—S antibonding orbitals of the C—S bonds
(B, Scheme 4). Thus, a generalized anomeric effect in
this case is a determining one for the conformation of
have tendency to the formation of 1,5ꢀdithiaꢀ3,7ꢀdiazaꢀ
cyclooctanes under indicated conditions. Apparently,
1,3,5ꢀdithiazinanes are the stable form for oꢀ and pꢀsubꢀ
stituted isomers.
Scheme 3
Reagents and conditions: CH2O—H2S (6 : 4), 0 °C, EtOH—H2O
The structure of compound 3a was established by
Xꢀray diffraction. 1,5ꢀDithiaꢀ3,7ꢀdiazacyclooctane ring
in crystal of 3a adopts the chairꢀchair (or crown) conforꢀ
mation13 with the axial arrangement of the Nꢀaryl subꢀ
stituents (Fig. 3).
In all the compounds considered, the nitrogen atoms
could be involved in both the conjugation with the
aromatic substituents and stereoelectronic lpN→σ*C—S
interactions. The conjugation with the aromatic substiꢀ
tuent results in the flattening the nitrogen atom and shortꢀ
ening the N—Carom bond, whereas the lpN→σ*C—S interꢀ
action to operate requires antiperiplanar arrangement of
the lone pair on the nitrogen atom and polar C—S bond,
that corresponds to the value of pseudotorsional angle
lp—N—C—S close to 180° (see Ref. 15). The strength of
the stereoelectronic interaction can be estimated from
the change of the C—S bond distance, which in the
N—CH2—S system is 1.814 Å in the absence of the stereoꢀ
Table 4. Bond lengths (d), distances, and pseudotorsional angle
lp—N—C—S in molecules 2l, 3a, 4a, and 4d
Comꢀ d(N—Car) d(N—CH2—S)a
ΔNb
lp—N—C—S
/deg
pound
Å
2l
1.412(2)
1.408(2)
1.418(3)
1.419(2)
1.837(4)
1.839(2)
1.847(2)
1.846(2)
0.24
0.15
0.28
0.27
177
176
169
167
3a
4a
4d
a The average bond distance C—S in the system N—CH2—S.
b The distance from the nitrogen atom to the plane of substiꢀ
tuents.

1006
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Akhmetova et al.
1,3,5ꢀthiadiazinane heterocycle. Conformations of comꢀ
pounds 2l and 3a also satisfy the maximum possible
amount of the lpN→σ*C—S interactions.
acetic acid (5c) with aniline 1a and pꢀtoluidine 1d, we
showed that more stable Nꢀarylꢀ1,3,5ꢀdithiazinanes 2a,d
are formed (Scheme 6). No transamination takes place
upon the action of ammonia, methylꢀ and tertꢀbutylamine,
and glycine on aromatic 1,3,5ꢀdithiazinanes 2a,d
and 1,3,5ꢀthiadiazinane 3d. As it is seen, arylꢀsubstituted
1,3,5ꢀthiadiazinanes are more stable compounds and reꢀ
tain stability upon standing for several years, in contrast
to aliphatic analogs, which are decomposing with time.20,21
Scheme 4
Scheme 6
24 h
To sum up, formation of 1,3,5ꢀdithiazinanes 2a—l,
obviously, the final stable products, was observed under
any conditions, in which the reaction has been carried out.
To confirm this result, 1,3,5ꢀthiadiazinanes 4a—d,l
and 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane 3a were treated with
CH2O and H2S to obtain 1,3,5ꢀdithiazinanes 2a—d,l
(Scheme 5). It should be emphasize that for the formation
of dithiazinanes from thiadiazines, a longer time is necesꢀ
sary, since the latter, obviously, are more stable comꢀ
pounds than 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes.
Rґ = Me (5a), But (5b), CH2COOH (5c)
In conclusion, the following chemoselectivity can be
tracked in the synthesis of saturated Nꢀarylꢀsubstituted
heterocycles by the multicomponent condensation of
anilines with the CH2O—H2S thiomethylating mixture:
paraꢀsubstituted anilines tend to form 1,3,5ꢀdithiazinanes
and 1,3,5ꢀthiadiazinanes, whereas aniline and metaꢀsubꢀ
stituted anilines tend to give 1,5ꢀdithiaꢀ3,7ꢀdiazacycloꢀ
octanes. Conformations in crystal of the compounds
studied is in the first place determined by the generalized
anomeric effect in the lp—N—C—S system: the conforꢀ
mations with the maximum possible amount of the
lpN→σ*C—S interactions are present Stability of Nꢀarylꢀ
substituted 1,3,5ꢀdithiazinanes was demonstrated by
the transamination and interconversion reactions of the
heterocycles.
Scheme 5
Experimental
1H and 13C NMR spectra were recorded on a Jeol FX 90Q
spectrometer (80.00 MHz for 1H, 22.50 MHz for 13C) with
Me4Si as an internal standard and CDCl3 (for compounds 2a,k,e,
3a, 4a,b,l) and DMSOꢀd6 (for compounds 2h—j, 3c,f,i) as the
solvents. The 1H and 13C NMR spectra of compounds 2c—d, as
well as 4c—d, are identical to those described earlier.6 Sorbfil
(Sorbpolymer, Krasnodar, Russia) plates were used for TLC in
the system benzene—ethanol, 9 : 1 with visualization in I2 vapors.
Silica gel L (KSKG, 50—160 μm) was used for column chromꢀ
atography. GLCꢀMS analysis of compounds was performed on a
Finnigan 4021 instrument (a 50000×0.25ꢀmm glass capillary
column, HPꢀ5 as a stationary phase, helium as a carrier gas,
Reagents and conditions: i. CH2O—H2S (3 : 3), 20 °C, CHCl3;
ii. CH2O—H2S (2 : 2), 20 °C, CHCl3.
Attempted reverse transformation of 2a—d,l to 4a—d,l
and 3a were unsuccessful. However, a number of transꢀ
formations of 2,4,6ꢀalkylꢀsubstituted dithiazinanes to
thiadiazinanes by the reaction of the former with amines
and ammonia are known,18 as well as their transamination
reactions.19 Using the reaction of 5ꢀmethylꢀ (5a), 5ꢀtertꢀ
butyldithiazinanes (5b) and 4ꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)ꢀ
temperature was programmed from 50 to 300 °C at 5 deg min–1
the injector temperature was 280 °C, the temperature of the
,

New Nꢀarylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1007
source of ions was 250 °C, 70 eV). Elemental analysis was
performed on a Carlo Erba 1106 element analyzer; Bromine
was determined by burning in a flask with oxygen (the Scheniger
method). Compounds obtained are characterized by melting
points determined on a PHMK 80/2617 instrument.
C(11)); 143.0 (s, C(8)); 143.3 (s, C(7)). Found (%): C, 44.84;
H, 4.33; N, 11.05; S, 25.97. C9H10N2O2S2. Calculated (%):
C, 44.61; H, 4.16; N, 11.56; S, 26.47.
5ꢀ(3ꢀNitrophenyl)ꢀ1,3,5ꢀdithiazinane (2i). The yield was 45%,
m.p. 100—102 °C. 1H NMR (80 MHz), δ: 4.36 (s, 2 H, C(2)H2);
5.18 (s, 4 H, C(4)H2, C(6)H2), 7.15—7.86 (m, 4 H, Ar).
13C NMR (22.5 MHz), δ: 33.3 (t, C(2)); 53.4 (t, C(4), C(6));
111.1 (d, C(12)); 113.5 (d, C(10)); 123.5 (d, C(8)); 130.1 (d,
C(9)); 149.0 (s, C(11)); 146.3 (s, C(7)). Found (%): C, 44.56;
H, 4.10; N, 11.84; S, 26.45. C9H10N2O2S2. Calculated (%):
C, 44.61; H, 4.16; N, 11.56; S, 26.47.
5ꢀ(4ꢀNitrophenyl)ꢀ1,3,5ꢀdithiazinane (2j). The yield was 65%,
m.p. 198—200 °C. 1H NMR (80 MHz), δ: 4.38 (s, 2 H, C(2)H2);
5.74 (s, 4 H, C(4)H2, C(6)H2); 7.23 (d, 2 H, C(8)H, C(12)H,
J = 8.0 Hz); 7.96 (d, 2 H, C(9)H, C(11)H, J = 8.0 Hz).
13C NMR (22.5 MHz), δ: 33.4 (t, C(2)); 53.0 (t, C(4), C(6));
116.2 (d, C(8), C(12)); 125.2 (d, C(9), C(11)); 138.8 (s, C(10));
150.9 (s, C(7)). Found (%): C, 45.00; H, 4.28; N, 11.35;
S, 26.50. C9H10N2O2S2. Calculated (%): C, 44.61; H, 4.16;
N, 11.56; S, 26.47.
Xꢀray diffraction studies of compounds 2l, 3a, 4a, and 4d
were performed on a SMART APEX 1000 CCD (2n) and
SMART APEX II CCD diffractometers (3a, 4a, and 4d) using
MoKα irradiation, a graphite monochromator, and ωꢀscanning.
The structures were solved by the direct method and refined by
the leastꢀsquares method in anisotropic fullꢀmatrix approxiꢀ
mation on F2 . The basic crystallographic data, refinement
hkl
parameters, and CCDC are given in Table 5. All the calculations
were performed using the SHELXTL 5.10 program package.22
NꢀArylꢀ1,3,5ꢀdithiazinanes 2a—l. Aniline (0.005 mol) in
EtOH (95%, 5 mL) was added dropwise to 37% aqueous
formaline (1.1 mL, 0.015 mol) saturated with hydrogen sulfide
over 30 min. The mixture was stirred for 10 h at 40 °C. Comꢀ
pounds 2a,b,e,g,k,l were extracted with chloroform, isolated,
and washed with ethanol; 2c,f,i were isolated by fractional crysꢀ
tallization; 2d,h,j were filtered off and washed with chloroform.
5ꢀPhenylꢀ1,3,5ꢀdithiazinane (2a). The yield was 65%,
m.p. 165—167 °C (Ref. 6: 169—170 °C). 1H NMR (80 MHz), δ:
4.27 (s, 2 H, C(2)H2); 4.96 (s, 4 H, C(4)H2, C(6)H2);
7.01—7.41 (m, 5 H, Ar). 13C NMR (22.5 MHz), δ: 34.7
(t, C(2)); 56.4 (t, C(4), C(6)); 117.3 (d, C(12), C(18)); 120.4
(d, C(10)); 129.4 (d, C(11), C(9)); 144.7 (s, C(7)). MS, m/z
(Irel (%)): 197 [M]+ (55), 151 [M – CH2S]+ (13), 119 [M – SCH2S]+
(45), 105 [M – SCH2SCH2]+ (100), 91 [M – SCH2SCH2CH2]+
(58), 77 [C6H5]+ (15). Found (%): C, 54.64; H, 5.40; N, 7.45;
S, 31.98. C9H11NS2. Calculated (%): C, 54.78; H, 5.62;
N, 7.10; S, 32.50.
5ꢀ(2ꢀIodophenyl)ꢀ1,3,5ꢀdithiazinane (2k). The yield was 56%,
1
170—172 °C. H NMR (80 MHz), δ: 3.68 (br.s, 2 H, C(2)H));
4.72 (br.s, 4 H, C(4)H2, C(6)H2); 6.90—7.81 (m, 4 H, Ar).
13C NMR (22.5 MHz), δ: 34.0 (t, C(2)); 57.9 (t, C(4), C(6));
99.0 (s, C(8)); 126.8 (d, C(10)); 127.0 (d, C(12)); 128.8 (d,
C(11)); 139.8 (d, C(9)); 148.8 (s, C(7)). MS, m/z (Irel (%)): 323
[M]+ (25), 245 [M – SCH2S]+ (25), 231 [M – SCH2SCH2]+
(100), 150 [M – CH2S – I]+ (60), 127 [I]+ (72); 77 [C6H5]+
(40). Found (%): C, 33.04; H, 3.46; N, 4.45; S, 20.15. C9H10INS2.
Calculated (%): C, 33.44; H, 3.12; N, 4.33; S, 19.84.
5ꢀ(4ꢀBromophenyl)ꢀ1,3,5ꢀdithiazinane (2l). The yield was
70%, m.p. 130—132 °C. 1H NMR (80 MHz), δ: 4.23 (s, 2 H,
C(2)H2); 4.90 (s, 4 H, C(4)H2, C(6)H2); 6.90 (d, 2 H, C(8)H,
C(12)H, J = 8.3 Hz); 7.32 (d, 2 H, C(9)H, C(11)H, J = 8.0 Hz).
13C NMR (22.5 MHz), δ: 34.8 (t, C(2)); 55.1 (t, C(4), C(6));
113.3 (s, C(10)); 119.4 (C(8), C(12)); 132.4 (d, C(9), C(11));
144.1 (s, C(7)). Found (%): C, 38.44; H, 3.58; N, 4.95; S, 23.15;
Br, 29.50. C9H10BrNS2. Calculated (%): C, 39.13; H, 3.65;
N, 5.07; S, 23.22; Br, 28.93.
N,NꢀDiarylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes 3a,c,f,i. Aniline
(0.005 mol) in EtOH (95%, 5 mL) was added dropwise to 37%
aq. formaline (2.2 mL, 0.03 mol) saturated with hydrogen sulꢀ
fide over 30 min. The mixture was stirred for 10 h at 0 °C.
Compound 3a was filtered off, washed with ethanol, 3c,i were
isolated by fractional crystallization, 3f was isolated by column
chromatography (SiO2, benzene—C2H5OH, 9 : 1).
5ꢀ(2ꢀMethylphenyl)ꢀ1,3,5ꢀdithiazinane (2b). The yield was
40%, a resinꢀlike compound. 1H NMR (80 MHz), δ: 2.20 (s,
3 H, C(13)H3); 4.22 (br.s, 2 H, C(2)H2); 4.70 (br.s, 4 H, C(4)H2,
C(6)H2); 7.13—7.35 (m, 4 H, Ar). 13C NMR (22.5 MHz), δ:
17.6 (q, C(13)); 33.7 (t, C(2)); 57.0 (t, C(4), C(6)); 122.2 (d,
C(12)); 124.4 (d, C(10)); 126.0 (d, C(11)); 130.6 (d, C(9));
133.4 (s, C(8)); 146.7 (s, C(7)). MS, m/z (Irel (%)): 211 [M]+
(47), 133 [M – SCH2S]+ (38), 132 [M – SCHS]+ (100), 119
[M – CH2SCH2S]+ (41), 118 [M – CH3SCH2S]+ (90), 91
[M – NCH2SCH2SCH2]+ (31). Found (%): C, 56.50; H, 6.45;
N, 6.93; S, 31.00. C10H13NS2. Calculated (%): C, 56.83;
H, 6.20; N, 6.63; S, 30.34.
5ꢀ(3ꢀMethylphenyl)ꢀ1,3,5ꢀdithiazinane (2c). The yield was
48%, m.p. 150—152 °C (Ref. 6: 154—155 °C).
5ꢀ(4ꢀMethylphenyl)ꢀ1,3,5ꢀdithiazinane (2d). The yield
was 68%, m.p. 146—148 °C (Ref. 6: 147—148 °C).
3,7ꢀDiphenylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane (3a). The yield
was 70%, m.p. 174—175 °C. H NMR (80 MHz), δ: 4.86 (br.s,
1
5ꢀ(2ꢀMethoxyphenyl)ꢀ1,3,5ꢀdithiazinane (2e). The yield was
34%, m.p. 100—102 °C (Ref. 6: 104—105 °C).
5ꢀ(3ꢀMethoxyphenyl)ꢀ1,3,5ꢀdithiazinane (2f). The yield
was 37%, m.p. 115—117 °C (Ref. 6: 119—120 °C).
5ꢀ(4ꢀMethoxyphenyl)ꢀ1,3,5ꢀdithiazinane (2g). The yield was
60%, m.p. 112—113 °C (Ref. 6: 109—110 °C).
5ꢀ(2ꢀNitrophenyl)ꢀ1,3,5ꢀdithiazinane (2h). The yield
was 64%, m.p. 260—262 °C. 1H NMR (80 MHz), δ: 3.38 (s,
2 H, C(2)H2); 4.75 (s, 4 H, C(4)H2, C(6)H2); 6.74 (t, 1 H,
C(10)H, J = 7.4 Hz); 7.13 (d, 1 H, C(12)H, J = 7.4 Hz); 7.55
(t, 1 H, C(11)H, J = 7.4 Hz); 8.06 (d, 1 H, C(9)H, J = 7.4 Hz).
13C NMR (22.5 MHz), δ: 43.0 (t, C(2)); 63.4 (t, C(4), C(6));
115.6 (d, C(10)); 116.2 (d, C(12)); 126.1 (d, C(9)); 135.9 (d,
8 H, C(2)H2, C(4)H2, C(6)H2, C(8)H2); 6.81—7.40 (m, 10 H,
2 Ar). 13C NMR (22.5 MHz), δ: 56.4 (t, C(2), C(4), C(6),
C(8)); 115.0 (d, C(10), C(14); C(16), C(20)); 119.5 (d, C(12),
C(18)); 129.6 (d, C(11), C(13), C(17), C(19)); 144.3 (s, C(9),
C(15)). Found (%): C, 63.23; H, 5.87; N, 9.13; S, 20.92.
C16H18N2S2. Calculated (%): C, 63.54; H, 6.00; N, 9.26;
S, 21.20.
3,7ꢀBis(3ꢀmethylphenyl)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane
(3c). The yield was 50%, m.p. 183—184 °C. 1H NMR (80 MHz),
δ: 2.35 (s, 6 H, C(21)H3, C(22)H3); 5.29 (br.s, 8 H, C(2)H2,
C(4)H2, C(6)H2, C(8)2); 6.62—7.12 (m, 8 H, Ar). 13C NMR
(22.5 MHz), δ: 22.0 (s, C(21), C(22)); 55.9 (t, C(2), C(4), C(6),
C(8)); 108.1 (d, C(10), C(20)); 112.3 (d, C(14), C(16)); 120.6

1008
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
Akhmetova et al.
(d, C(12), C(18)); 137.5 (d, C(13), C(17)); 130.1 (s, C(11),
C(19)); 144.3 (s, C(9), C(15)). Found (%): C, 65.49; H, 6.23;
N, 8.61; S, 19.97. C18H22N2S2. Calculated (%): C, 65.41; H,
6.71; N, 8.48; S, 19.40.
3,5ꢀDiphenylꢀ1,3,5ꢀthiadiazinane (4a). The yield was 20%,
Rf 0.21, m.p. 102—104 °C. 1H NMR (80 MHz), δ: 5.01 (s, 4 H,
C(2)H2, C(6)H2); 5.27 (s, 2 H, C(4)H2); 7.52—7.69 (m, 10 H,
Ar). 13C NMR (22.5 MHz), δ: 53.4 (t, C(2), C(6)); 69.3 (t,
C(4)); 117.6 (d, C(18), C(14), C(12), C(8)); 120.3 (d, C(16),
C(10)); 128.8 (d, C(17), C(15), C(11), C(9)); 147.4 (s, C(7),
C(13)). Found (%): C, 71.12; H, 6.43; N, 10.16; S, 12.45.
C15H16N2S. Calculated (%): C, 70.27; H, 6.29; N, 10.93;
S, 12.51.
3,5ꢀDi(2ꢀmethylphenyl)ꢀ1,3,5ꢀthiadiazinane (4b). The yield
was 34%, a resinꢀlike compound, Rf 0.21, nD20 1.5065. 1H NMR
(80 MHz), δ: 4.95 (s, 2 H, C(4)H2); 5.20 (s, 4 H, C(2)H2,
C(6)H2); 7.11—7.79 (m, 8 H, Ar). 13C NMR (22.5 MHz), δ:
17.9 (q, C(19), C(20)); 55.4 (t, C(2), C(6)); 71.7 (t, C(4));
122.4 (d, C(12), C(18)); 123.8 (d, C(10), C(16)); 126.8 (d,
C(9), C(15)); 130.1 (d, C(11), C(17)); 132.3 (s, C(8), C(14));
147.7 (s, C(7), C(13)). Found (%): C, 72.23; H, 6.94; N, 9.43;
S, 11.64. C17H20N2S. Calculated (%): C, 71.79; H, 7.09;
N, 9.85; S, 11.27.
3,7ꢀBis(3ꢀmethoxyphenyl)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane
(3f). The yield was 48%, Rf 0.33. 1H NMR (80 MHz), δ: 3.80
(s, 6 H, C(22)H2, C(24)H2); 4.84 and 4.93 (both d, C(2)H2,
C(4)H2, C(6)H2, C(8)2, J = 7.2 Hz); 6.44—6.67 (m, 8 H, Ar).
13C NMR (22.5 MHz), δ: 54.8 (q, C(22), C(24)); 56.6 (d, C(2),
C(4), C(6), C(8)); 104.5 (d, C(10), C(16)); 105.2 (d, C(12),
C(18)); 110.1 (d, C(14), C(20)); 130.3 (d, C(13), C(19)); 146.1
(s, C(9), C(15)); 158.3 (s, C(13), C(19)). Found (%): C, 60.07;
H, 6.17; N, 7.56; S, 17.99. C18H22N2O2S2. Calculated (%):
C, 59.64; H, 6.12; N, 7.73; S, 17.69.
3,7ꢀBis(3ꢀnitrophenyl)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane (3i).
The yield was 44%, m.p. 210—212 °C. 1H NMR (80 MHz), δ:
5.12 and 5.21 (both d, 8 H, C(2)H2, C(4)H2, C(6)H2, C(8)H2,
J = 7.2 Hz); 7.15—7.52 (m, 8 H, Ar). 13C NMR (22.5 MHz), δ:
55.9 (t, C(2), C(4), C(6), C(8)); 108.1 (d, C(10), C(16)); 112.3
(d, C(12), C(18)); 120.64 (d, C(14), C(20)); 144.3 (s, C(9),
C(18)); 148.7 (s, C(11), C(17)). Found (%): C, 49.11; H, 4.26;
N. 15.00; S, 15.80. C16H16N4S2O4. Calculated (%): C, 48.97;
H, 4.11; N, 14.28; S, 16.34.
3,5ꢀDi(3ꢀmethylphenyl)ꢀ1,3,5ꢀthiadiazinane (4c). The yield
was 50%, m.p. 195—196 °C (Ref. 6: 196—197 °C).
3,5ꢀDi(4ꢀmethylphenyl)ꢀ1,3,5ꢀthiadiazinane (4d). The
yield was 45%, m.p. 101—103 °C (Ref. 23: 105 °C).
3,5ꢀDiphenylꢀ1,3,5ꢀthiadiazinanes 4a—d,f,g,l. Aniline
(0.005 mol) in EtOH (95%, 5 mL) was added dropwise to 37%
aq. formaline (0.55 mL, 0.0075 mol) saturated with hydrogen
sulfide over 30 min. The mixture was stirred for 10 h at 0 °C.
Compound 4c was isolated by fractional crystallization, 4a,b,f,l
by column chromatography (SiO2, benzene—C2H5OH, 9 : 1),
4d,g were filtered off and washed with ethanol.
3,5ꢀDi(3ꢀmethoxyphenyl)ꢀ1,3,5ꢀthiadiazinane (4f). The yield
was 30%, m.p. 155—156 °C (Ref. 6: 153—154 °C).
3,5ꢀDi(4ꢀmethoxyphenyl)ꢀ1,3,5ꢀthiadiazinane (4g). The
yield was 23%, m.p. 148—150 °C (Ref. 6: 145—146 °C).
3,5ꢀDi(4ꢀbromophenyl)ꢀ1,3,5ꢀthiadiazinane (4l). The yield
was 83%, Rf 0.24, m.p. 157—159 °C. 1H NMR (80 MHz), δ:
4.94 (s, 4 H, C(2)H2, C(6)H2); 5.18 (s, 2 H, C(4)H2); 6.90 (d,
Table 5. Principal crystallographic data and parameters of refinement for 2l, 3a, 4a, and 4d
Compound
2l
3a
4a
4d
CCDC number
Molecular formula
Molecular weight
T/K
731758
C9H10BrNS2
276.21
120
731759
C16H18N2S2
302.44
100
731761
C15H16N2S
256.36
100
731762
C17H20N2S
284.41
100
Crystal system
Space group
Triclinic
P1
Monoclinic
P21/c
Monoclinic
P21/c
Monoclinic
P21/n
Z
2
4
4
4
a/Å
b/Å
c/Å
α/deg
4.8446(6)
9.7580(13)
11.1243(15)
105.121(4)
92.685(2)
95.425(3)
504.00(11)
1.820
11.184(2)
13.331(3)
10.324(2)
90.00
103.035(4)
90.00
1499.6(5)
1.340
3.46
8.9325(6)
14.1147(9)
11.0129(7)
90.00
110.0060(10)
90.00
9.0310(15)
18.623(3)
9.1076(15)
90.00
103.437(3)
90.00
1489.9(4)
1.268
2.09
β/deg
γ/deg
V/Å3
1304.71(15)
1.305
dcalc/g cm–3
μ/cm–1
44.42
2.31
F(000)
276
640
544
608
2θmax/deg
59
54
58
56
Numbre of measured reflections
5728
14204
13966
22032
Number of independent reflections
2784
3271
3449
3586
Number of reflections with I > 2σ(I)
2360
1892
3133
2238
Number of refined parameters
118
181
163
183
R1
wR2
GOOF
0.0332
0.0850
1.002
0.0549
0.0984
1.000
0.0352
0.0945
1.012
0.0438
0.0953
1.001
Residual electron
1.205/–0.523
0.381/–0.389
0.403/–0.289
0.401/–0.377
density/e Å–3(dmax/dmin
)

New Nꢀarylꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctanes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
1009
4 H, C(8)H, C(12)H, C(14)H, H(18), J = 6.5 Hz); 7.31 (d, 4 H,
C(9)H, C(11)H, C(15)H, C(17)H, J = 6.5 Hz). 13C NMR (22.5
MHz), δ: 53.8 (t, C(2), C(6)); 69.7 (t, C(4)); 113.4 (s, C(10),
C(16)); 119.7 (d, C(8), C(12), C(14), C(18)); 132.3 (d, C(9),
C(11), C(15), C(17)); 147.9 (s, C(7), C(13)). Found (%): C,
44.08; H, 3.56; N, 6.50; S, 7.80; Br, 38.62. C15H14Br2N2S.
Calculated (%): C, 43.50; H, 3.41; N, 6.76; S, 7.74; Br, 38.59.
11. Comprehensive Org. Chem., Eds S. D. Barton and W. D.
Ollis, Pergamon Press, Oxford—New York—Toronto, 1979.
12. J. L. Nelson, C. Kenneth, E. Y. Andrew, J. Org. Chem.,
1962, 27, 2019.
13. G. CadenasꢀPliego, M. J. RosalesꢀHoz, R. Contreras,
A. FloresꢀParra, Tetrahedron: Asymmetry, 1994, 5, 633.
14. V. R. Akhmetova, G. R. Nadyrgulova, T. V. Tyumkina,
Z. A. Starikova, D. G. Golovanov, M. Yu. Antipin, R. V.
Kunakova, U. M. Dzhemilev, Izv. Akad. Nauk, Ser. Khim.,
2006, 1758 [Russ. Chem. Bull., Int. Ed., 2006, 55, 1824].
15. A. J. Kirby, The Anomeric Effect and Related Stereoelectronic
Effects at Oxygen, Springer, Berlin, 1983.
References
1. M. O. Talismanova, A. A. Sidorov, G. G. Aleksandrov,
V. N. Charushin, S. K. Kotovskaya, V. P. Ananikov, I. L.
Eremenko, I. I. Moiseev, Izv. Akad. Nauk, Ser. Khim., 2008,
45 [Russ. Chem. Bull., Int. Ed., 2008, 57, 47].
16. I. S. Bushmarinov, M. Y. Antipin, V. R. Akhmetova, G. R.
Nadyrgulova, K. A. Lyssenko, J. Phys. Chem. A, 2008, 112,
5017.
2. T. M. Buslaeva, S. P. Gromov, N. I. Sidorenko, Ros. Khim.
Zh. (Zh. Mendeleev Ros. Khim. Obshchestva), 2006, No. 4, 26
[Mendeleev Chem. J. (Engl. Transl.), 2006, No. 4, 26].
3. S. R. Khafisova, V. R. Akhmetova, L. F. Korzhova, T. V.
Tyumkina, G. R. Nadyrgulova, R. V. Kunakova, E. A.
Krangles, U. M. Dzhemilev, Izv. Akad. Nauk, Ser. Khim.,
2005, 423 [Russ. Chem. Bull., Int. Ed., 2005, 54, 432].
4. S. R. Khafisova, V. R. Akhmetova, G. R. Nadyrgulova, I. V.
Rusakov, R. V. Kunakova, U. M. Dzhemilev, Neftekhim.,
2005, 5, 374 [Petroleum Chemistry, 2006, 5, 345].
17. F. H. Allen, D. G. Watson, L. Brammer, A. G. Orpen,
R. Taylor, in International Tables for Crystallography, Chester,
England, Intern. Union of Crystallography, 2006, vol. C,
p. 790.
18. G. M. Gavrilov, B. A. Trofimov, V. I. Gostevskaya, S. V.
Amosova, Khim. Geterotsikl. Soedin., 1982, 652 [Chem.
Heterocycl. Compd. (Engl. Transl.), 1982, 18, 652].
19. A. FloresꢀParra, S. A. SanchesꢀRuiz, Heterocycles, 1999, 51,
2079.
20. T. Kawai, M. Irie, M. Sakaguchi, J. Agr. Food Chem., 1985,
33, 393.
21. Y. Zhang, H. ChiꢀTang, J. Agr. Food Chem., 1989, 37, 1016.
22. G. Sheldrick, Acta Cryst. Sect. A, 2008, 64, 112.
23. D. Collins, J. Graymore, J. Chem. Soc., 1953, 4089.
5. V. R. Akhmetova, G. R. Nadyrgulova, T. V. Tyumkina,
Z. A. Starikova, M. Yu. Antipin, R. V. Kunakova, U. M.
Dzhemilev, Zh. Org. Khim., 2007, 43, 919 [Russ. J. Org.
Chem. (Engl. Transl.), 2007, 43, 919].
6. S. R. Khafisova, V. R. Akhmetova, R. V. Kunakova, U. M.
Dzhemilev, Izv. Akad. Nauk, Ser. Khim., 2003, 1722 [Russ.
Chem. Bull., Int. Ed., 2003, 52, 1817].
7. A. Wohl, Ber., 1886, 19, 2344.
8. Spravochnik khimika [Chemist’s Handbook], 3, Khimiya,
Moscow, 1964, 1000 (in Russian).
9. E. R. Braithwaite, J. Graymore, J. Chem. Soc., 1950, 2, 208.
10. V. R. Akhmetova, G. R. Nadyrgulova, Z. T. Niatshina,
R. R. Khairullina, Z. A. Starikova, A. O. Borisova, M. Y.
Antipin, R. V. Kunakova, U. M. Dzhemilev, Heterocycles,
2009, 78, 45.
Received July 10, 2009;
in revised form October 2, 2009