Cyclothiomethylation of aryl hydrazines with formaldehyde and hydrogen sulfide

Article abstract of DOI:10.1007/s11172-006-0493-7

Cyclothiomethylation of phenyl hydrazine with CH₂O and H ₂S in a ratio of 1: 3: 2 in an acidic medium (HCl) afforded previously unknown 3-phenyl-1,3,4-thiadiazolidine (35% yield) and N-phenyl(perhydro-1,3,5-dithiazin-5-yl)amine (35%

Full text of DOI:10.1007/s11172-006-0493-7

Russian Chemical Bulletin, International Edition, Vol. 55, No. 10, pp. 1824—1834, October, 2006
1824
Cyclothiomethylation of aryl hydrazines
with formaldehyde and hydrogen sulfide
a
a
b
V. R. Akhmetova,a G. R. Nadyrgulova, T. V. Tyumkina, Z. A. Starikova,
ꢀ
D. G. Golovanov,b M. Yu. Antipin,b R. V. Kunakova,c and U. M. Dzhemileva
aInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences,
141 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347 2) 31 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 (495) 135 9271. Eꢀmail: star@xray.ineos.ac.ru
cUfa State Academy of Economics and Service,
145 ul. Chernyshevskogo, 450077 Ufa, Russian Federation.
Fax: +7 (347 2) 52 0806. Eꢀmail: nis_utis@bashnet.ru
Cyclothiomethylation of phenyl hydrazine with CH2O and H2S in a ratio of 1 : 3 : 2 in an
acidic medium (HCl) afforded previously unknown 3ꢀphenylꢀ1,3,4ꢀthiadiazolidine (35% yield)
and Nꢀphenyl(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)amine (35% yield). The analogous reaction in
an alkaline medium (BuONa) produced Nꢀphenyl(perhydroꢀ1,3ꢀthiazetidinꢀ3ꢀyl)amine
(22% yield). The reaction of 1,2ꢀdiphenyl hydrazine with CH2O and H2S in an alkaline
medium gave 1,2,4,5ꢀtetraphenylhexahydroꢀ1,2,4,5ꢀtetrazine and previously unknown
3,4ꢀdiphenylꢀ1,3,4ꢀthiadiazolidine and 5,6ꢀdiphenyltetrahydroꢀ1,3,5,6ꢀdithiadiazepine in 39
and 22% yields, respectively. Cyclothiomethylation of benzyl hydrazine afforded previously
unknown bis[(6ꢀbenzylꢀ4,2,6ꢀthiadiazolidinꢀ2ꢀyl)methyl] sulfide (60% yield) and Nꢀbenꢀ
zyl(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)amine (19% yield). The reaction of tosyl hydrazine
produced 3ꢀ[(pꢀtolyl)sulfonyl]ꢀ1,3,4ꢀthiadiazolidine, Nꢀ(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)ꢀ
pꢀtolylsulfonamide, and 3,7ꢀbis(pꢀtolylsulfonylamino)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane in 21,
38, and 41% yields, respectively.
Key words: cyclothiomethylation, aryl hydrazines, formaldehyde, hydrogen sulfide, 1,3,5ꢀdiꢀ
thiazines, 1,3,4ꢀthiadiazolidines, Xꢀray diffraction study.
Earlier,1 we have performed cyclothiomethylation of
Results and Discussion
hydrazine with formaldehyde and hydrogen sulfide and
prepared annelated 1,3,4ꢀthiadiazolidines and 1,3,5ꢀthiaꢀ
diazines. According to the available data,2—4 1,3,4ꢀthiaꢀ
diazole derivatives have found wide use as antibacterial
and antiviral agents and as inhibitors of oxidation of cyaꢀ
nine dyes and metal complexing agents.5 NꢀPhenylꢀsubꢀ
stituted nitrogenꢀcontaining heterocycles, in which the
N atoms are conjugated with chromophoric groups, are of
particular interest as photosensitive and photocontrolled
molecular devices.6
The present study is a continuation of investigations on
cyclothiomethylation of amines with CH2O and H2S.7—9
Another aim was to develop efficient methods for the
synthesis of arylꢀsubstituted thiadiazoles. The latter comꢀ
pounds are of practical interest. We examined thioꢀ
methylation of phenyl, 1,2ꢀdiphenyl, benzyl, and tosyl
hydrazines with the H2S—CH2O system under neutral,
acidic, and alkaline conditions.
Recently,10 we have found that the thiomethylaꢀ
tion pathway of hydrazine with CH2O and H2S
strongly depends on the starting component ratio, the
heterocyclization temperature, and pH of the reaction
mixture.
In the present study, we examined cyclothioꢀ
methylation of phenyl hydrazine hydrochloride (1•HCl)
with CH2O and H2S in a ratio of 1 : 3 : 2 at pH 0.45—0.50
(method A). It was found that the reaction performed
at 0 °C selectively produces 3ꢀphenylꢀ1,3,4ꢀthiadiazolꢀ
idine (2), whereas Nꢀphenyl(perhydroꢀ1,3,5ꢀdithiazinꢀ
5ꢀyl)amine (3) and 6ꢀphenylperhydro[1,3,4]thiadiaziꢀ
no[5,4ꢀd][1,3,5]dithiazine (4) are generated along
with compound 2 at higher temperature (20—70 °C)
(Scheme 1). At 70 °C, the amount of minor product 4
derived under these conditions from compound 3 is at
most 8%.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1758—1767, October, 2006.
1066ꢀ5285/06/5510ꢀ1824 © 2006 Springer Science+Business Media, Inc.

Cyclothiomethylation of aryl hydrazines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1825
Scheme 1
Reagents and conditions: A. 1•HCl : CH2O : H2S = 1 : 3 : 2, 0—70 °C, pH 0.45—0.50.
B. 1 : BuONa : CH2O : H2S = 1 : 3 : 3 : 2, 0—70 °C, pH 11.5—11.7.
C. 1 : CH2O : H2S = 1 : 3 : 2, 0—70 °C, pH 3.15—3.20.
Under alkaline (pH 11.5—11.7) or neutral (in the abꢀ
sence of acidicꢀalkaline additives, pH 3.15—3.20) condiꢀ
tions (methods B and C, respectively), compounds 2 and 3
were obtained as well. The reaction in an alkaline medium
at 70 °C afforded Nꢀphenyl(perhydroꢀ1,3ꢀthiazetidinꢀ3ꢀ
yl)amine (5) and 1,4ꢀdiphenylhexahydroꢀ1,2,4,5ꢀtetrꢀ
azine (6) as the major products in 22 and 50% yields,
respectively (Table 1). The reaction of phenyl hydrazine
with CH2O and H2S in a neutral medium at 0—20 °C
produced predominantly formaldehyde phenylhydrazone
(7) in 76% yield.
These results can be attributed to the change in the
electron density in the phenyl hydrazine molecule (1)
depending on pH of the reaction mixture.11
Unlike the reaction of compound 1, cyclothioꢀ
methylation of 2,4ꢀdinitrophenyl hydrazine (8) does not
afford sulfurꢀcontaining heterocycles. Apparently, this
behavior of compound 8 in the reaction is associated with
its low basicity12 compared to phenyl hydrazine (1) due to
which hydrazone 9 was obtained as the major product. In
these experiments, 2,4ꢀdinitrophenyl hydrazine (8) is
not involved in cyclothiomethylation regardless of pH,
and CH2O and H2S give cyclic sulfides 10 and 11 13
(Scheme 2).
Table 1. Influence of the thiomethylation conditions of phenyl
hydrazine (1) on the yield and composition of the reaction
products
Scheme 2
Method
(pH)
T
/°C
1 : СH2O : H2S
Yields of products (%)
2
3
4
5
6
7
А
0
0
20
40
70
0
20
40
70
0
20
40
70
1 : 2 : 1
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
1 : 3 : 2
31 —
35 —
26 30 —
22 26 —
20 35
20 — — 18 23 —
11 13 — 15 19 —
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
(0.45—0.50)
8
B
(11.5—11.7)
14
—
17
12
26
14
7
—
6
5
9
— 15 10 —
— 22 50 —
—
—
—
—
C
—
—
—
—
— 76
— 74
— 49
— 72
By analogy with phenyl hydrazine, we carried out
cyclothiomethylation of 1,2ꢀdiphenyl hydrazine (12)
with an expectation to prepare 3,4ꢀdiphenylꢀ1,3,4ꢀ
thiadiazolidine. However, under the conditions used
(3.15—3.20)
8

1826
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Akhmetova et al.
Scheme 3
Table 2. Influence of the thiomethylation conditions of 1,2ꢀdiꢀ
phenyl hydrazine (12) on the yield and composition of the reacꢀ
tion products
stabilization of the monoplanar transition state. For exꢀ
ample, the inversion barrier of the nitrogen atoms inꢀ
creases in the series of N,N´ꢀdialkylꢀsubstituted oxaꢀ
diazolidines (Alk = Me, Pri, or Bui) and is 44.5, 81.5,
and >88 kJ mol–1, respectively.19 The inversion barrier
pH
T/°C
Yields of products (%)
for 3,4ꢀdiisopropylꢀ1,3,4ꢀthiadiazolidine (77.2 kJ mol–1
,
13
14
15
16
T = 66 °C)16 is close to that for the oxa analog. However,
this compound is unstable and is transformed into a white
powdered polymer at 20 °C, due to which conformational
studies are difficult to perform. Unlike 3,4ꢀdiisopropylꢀ
1,3,4ꢀthiadiazolidine, phenylꢀsubstituted thiadiazolidines
2 and 14 are more stable.
3.15—3.20
0
20
40
70
0
20
40
70
17
77
46
59
21
14
16
31
5
13
2
4
9
39
11
—
—
—
—
—
—
10
22
—
—
—
—
—
—
6
11.5—11.7
For compound 14, we estimated ∆G≠ by dynamic
6
—
1
1H NMR spectroscopy. At –20 °C, the H NMR specꢀ
trum of this compound shows splitting of the singlet for
the methylene protons of the ring into two doublets
(∆δAB = 55.8 Hz, 2J = 10.0 Hz), which indicates that
inversion processes become slower on the NMR time
scale (Fig. 1). The experimental inversion barrier of the
nitrogen atoms is ~51.5 kJ mol–1 (T = –20 °C),20 which is
(method C), the reaction gave (Z )ꢀazobenzene (13) as
the major product in ~77% yield. The latter reaction also
produced 3,4ꢀdiphenylꢀ1,3,4ꢀthiadiazolidine (14), but the
yield of the latter was at most 13% (Scheme 3, Table 2).
The yield of compound 14 can be increased to 39% by
performing cyclothiomethylation of diphenyl hydrazine
12 in the presence of BuONa at 20 °C. 5,6ꢀDiphenylꢀ
tetrahydroꢀ1,3,5,6ꢀdithiadiazepine (15) and 1,2,4,5ꢀtetraꢀ
phenylhexahydroꢀ1,2,4,5ꢀtetrazine (16)14 were produced
simultaneously in 22 and 6% yields, respectively. Under
acidic conditions, diphenyl hydrazine 12 undergoes the
benzidine rearrangement.15
Earlier,16 it has been reported that configurational staꢀ
bility of the nitrogen atoms in 1,3,4ꢀoxa(thia)diazolidines
increases due to an increase in the volume of the substituꢀ
ents at the nitrogen atoms. According to the published
data,17,18 the inversion barrier of the adjacent nitrogen
atoms in oxa(thia)diazolidines is higher due to steric deꢀ
2
1
7.6
7.0
6.4
5.8
5.2
4.6
δ
Fig. 1. 1H NMR spectrum of compound 14 at –20 (1) and
25 °C (2).

Cyclothiomethylation of aryl hydrazines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1827
evidence that configurational stability of the nitrogen
atoms is insufficient for resolution of thiadiazolidine 14
into enantiomers under ambient conditions.
m/z 195 ([M – CH2S]+), 136 ([C6H5NCH2SH]+), 104
([C6H5NHN]+), 91 ([C6H5N]+), 77 ([C6H5]+), 51
([CN—NC]+), and 46 ([CH2S]+).
Heterocycles 2, 3, 5, and 6 were isolated in individual
state by column chromatography. The IR spectra of comꢀ
pounds 2—5 show stretching vibrations of the methylene
groups at 2900 cm–1. Intense absorption at 1600 cm–1 is
characteristic of vibrations of the aromatic ring. The abꢀ
sorption band at 1020—1150 cm–1 belongs to C—N
stretching vibrations. The C—S stretching vibrations are
The formation of 5,6ꢀdiphenyltetrahydroꢀ1,3,5,6ꢀ
dithiadiazepine (15) is evidenced by the fact that the
13C NMR spectrum has signals at δC 36.3 and 55.1 asꢀ
signed to C atoms located between two S atoms and to
magnetically equivalent C atoms located between the
S and N atoms. The 1H NMR spectrum of dithiadiazepine
15 shows a singlet for the methylene protons located beꢀ
tween the S atoms (δH 4.00), an AB system of the proꢀ
tons of the NCH2S fragments (δH 4.91 and 5.03,
2J = 14.8 Hz), and a multiplet for the phenyl protons
(δH 6.93—7.40); the intensity ratio is 2 : 2 : 2 : 10. In the
mass spectrum of product 15, the molecular ion peak
is absent, but the spectrum has characteristic fragꢀ
ment ion peaks at m/z 136 ([PhNHCH=S]+) and 164
([PhNNH(NCH2)CH=S]+). The molecular weight deꢀ
termined cryoscopically23 is 288 10, which corresponds
to compound 15. Based on the aboveꢀgiven physicochemiꢀ
cal characteristics of product 15, we assigned the strucꢀ
ture of 5,6ꢀdiphenyltetrahydroꢀ1,3,5,6ꢀdithiadiazepine to
this compound.
observed at 580—750 cm–1
.
The 13C NMR spectra of isomeric compounds 2 and 5
differ in the number of signals. The 13C NMR spectrum of
compound 2 shows two resonances at δC 53.8 and 55.2
due to the presence of magnetically nonequivalent C atoms
of the methylene groups, which is indicative of the presꢀ
ence of the thiadiazolidine ring. By contrast, the 13C NMR
spectrum of compound 5 contains the only signal in this
region at δC 57.3, which is evidence for the formation of
Nꢀphenyl(perhydroꢀ1,3ꢀthiazetidinꢀ3ꢀyl)amine (5).
1
In the H NMR spectra of compounds 2 and 5, the
signals are averaged due to high conformational flexibility
of the heterocycles. The resonance of the magnetically
equivalent methylene protons in thiazetidine 5 appears as
a singlet at δH 4.63, and the shifts of the protons at the
C(2) and C(5) atoms in compound 2 differ by 0.82 ppm.
The mass spectra of products 2 and 5 have the same
molecular ions [M]+ at m/z 166 and the characteristic
fragment ions generated by loss of CH2S (m/z 120) and
CH2SCH2 (m/z 105) from [M]+; however, the intensities
of the signals are different.
Recrystallization of a mixture of heterocycles 14—16
from DMSO afforded 1,2,4,5ꢀtetraphenylhexahydroꢀ
1,2,4,5ꢀtetrazine (16) in a yield of at most 6%. Xꢀray
diffraction study demonstrated that the tetrazine ring
H(11)
H(5A)
H(12)
H(6A)
C(6A)
C(11)
H(10)
C(12)
C(5A)
H(4A)
The formation of the dithiazine ring in compound 3 is
1
confirmed by two characteristic singlets in the H NMR
C(13)
H(13)
C(7A)
H(7A)
C(10)
spectra at δH 4.79 and 5.20 with an integrated intensity
ratio of 1 : 2. The aromatic protons of dithiazine 3 are
observed at low field (δH 7.37—8.13).
C(4A)
C(9)
C(8)
C(2A)
C(3A)
H(3A)
The 13C NMR spectrum of compound 6 has the only
intense signal for the C atoms of the methylene groups
(δC 63.3), which is indicative of spatial symmetry and the
absence of the sulfur atom in molecule 6. The geminal
protons at the C(3) and C(6) atoms in the 1H NMR
spectrum are diastereotopic (∆δH = 0.55), which also inꢀ
dicates that the molecule is symmetric.
H(9)
H(3)
H(1BA)
C(1A)
N(2)
N(1)
N(1A)
H(1A)
N(2A)
C(1)
H(1AA)
H(1B)
C(8A)
H(9A)
C(9A)
The structures of compounds 7 and 9 were conꢀ
firmed by comparison with the data published in the litꢀ
erature.21,22
C(2)
C(3)
C(4)
H(13A)
C(13A)
H(7)
Compounds 14 and 15 were isolated in individual state
by column chromatography. In the 1H NMR spectrum of
compound 14, the methylene protons of the thiadiꢀ
azolidine ring appear as a broadened singlet at δH 4.65
(∆ν1/2 = 24 Hz) and a multiplet at δ 6.88—8.10. In the
13C NMR spectrum of compound 14, the signal at δC 53.0
belongs to the C(2) and C(5) atoms of the thiadiazolidine
ring. The mass spectrum of product 14 has a molecular
ion [M]+ at m/z 242 and characteristic ion peaks at
C(10A)
H(10A)
C(7)
H(4)
C(5)
C(6)
H(6)
C(12A)
H(12A)
C(11A)
H(11A)
H(5)
Fig. 2. Structure of 1,2,4,5ꢀtetraphenylhexahydroꢀ1,2,4,5ꢀ
tetrazine (the atomic numbering scheme is given for crystalloꢀ
graphically independent molecule 16A).

1828
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Akhmetova et al.
C(10´)
C(4´)
C(11´)
C(12´)
C(9´)
C(5´)
C(6´)
C(7´)
C(3´)
N(1´)
C(13´)
C(8´)
N(2´)
C(2SA)
C(2´)
C(1´)
C(1S)
S(1´A)
S(1)
H(1´B)
C(1´A)
H(1´A)
O(1)
H(1´D)
N(1´A)
S(1A)
C(1SA)
H(1´C)
S(1´)
O(1A)
N(2´A)
C(8´A)
C(2´A)
C(2S)
C(7´A)
C(6´A)
C(3´A)
C(4´A)
C(13B)
C(5´A)
C(12B)
C(9´A)
C(10B)
C(11B)
Fig. 3. Hydrogen bonds in the structure of 1,2,4,5ꢀtetraphenylhexahydroꢀ1,2,4,5ꢀtetrazine (crystallographically independent molꢀ
ecule 16B).
adopts a chair conformation with four benzene rings at
the nitrogen atoms in axial positions and the rings at the
adjacent nitrogen atoms in trans positions. The crystal
structure contains two centrosymmetric independent molꢀ
ecules, 16A (Fig. 2) and 16B (Fig. 3), having similar
structures. Molecule 16B forms intermolecular bonds with
the solvent (DMSO) molecules.
substituents are in axial positions with respect to the mean
plane of the ring. The bond lengths in the ring have typiꢀ
cal values (N—N, 1.414(2) Å; C—N, 1.454(2) Å). The
N—CPh bond length is 1.411(2) Å.
The sulfur atom in the DMSO molecule is disordered
over two positions (S(1) and S(1´)) with occupancies of
0.7 and 0.3, respectively. The DMSO molecule is inꢀ
volved in the weak intermolecular C(1´)—H(1´A)...O(1)
and C(1´A)—H(1´C)...O(1A) hydrogen bonds only with
The deviation of the C(1) and C(1A) atoms from the
plane formed by the nitrogen atoms is 0.590 Å. All phenyl
Scheme 4

Cyclothiomethylation of aryl hydrazines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1829
is confirmed by the ease of addition of formaldehyde
thioꢀ and hemiacetals to the hydrazine group giving rise
to heterocycles 18 and 19, respectively.
Heterocycles 18, 19, and 21—23 were isolated in indiꢀ
vidual state by column chromatography. The structures of
these compounds were confirmed by spectroscopic methꢀ
ods (1H and 13C NMR and IR spectroscopy and positiveꢀ
ion mass spectrometry). In addition, the structures of
compounds 18 and 23 were established by Xꢀray difꢀ
fraction.
b
0
c
The 13C NMR spectrum of sulfide 18 shows four sigꢀ
nals (δC 55—60) assigned to the C atoms of the methylene
groups, which are located between the N and S atoms
and between the N atom and the Ph ring (NCH2Ph).
The signals for the aromatic C atoms are observed at
δ 127—137. It should be noted that the 13C NMR specꢀ
trum of compound 21 shows only two highꢀfield signals
(δ 57.7 and 58.1) corresponding to the nonequivalent
C atoms of the methylene groups of the thiadiazolidine
ring. The mass spectrum of compound 18 is little inforꢀ
mative due to instability of this compound. In the crysꢀ
tal structure, the bis[(6ꢀbenzylꢀ4,2,6ꢀthiadiazolidinꢀ2ꢀ
yl)methyl] sulfide molecule (18) exists as a centrosymꢀ
metric dimer, in which two monomeric fragments are
related by a twofold pseudoaxis passing through the
S(1) atom (Fig. 5).
The mass spectrum of compound 19 has a lowꢀintenꢀ
sity molecular ion peak at m/z 226; the higherꢀintensity
peak at m/z 91 corresponds to the [CHSCH2S] fragment.
The 13C NMR spectra of dithiazines 19 and 22 show,
in addition to the characteristic signals of the dithiazine
ring (at δC 31.7, 58.2 and 31.9, 60.1, respectively), sigꢀ
nals belonging to the C atoms of the aromatic ring
(δC 127—138).
a
Fig. 4. Molecular packing of compound 16. Intermolecular
C—H...S hydrogen bonds are indicated by dashed lines.
independent molecule 16B (Fig. 4). The H...O distance is
2.52(2) Å, and the C—H—O angle is 167°.
To extend the scope of cyclothiomethylation, we perꢀ
formed not only the reactions of phenyl hydrazines with
CH2O and H2S but also the reactions of benzyl hydrazine
(17) and tosyl hydrazine (20). In a neutral medium (the
reagent ratio was 1 : 3 : 2, ~20 °C), the 1,3,4ꢀthiaꢀ
diazolidine and 1,3,5ꢀdithiazine derivatives were obtained
(Scheme 4).
It was found that benzyl hydrazine (17) reacts with
CH2O and H2S to form bis[(6ꢀbenzylꢀ4,2,6ꢀthiadiazolꢀ
idinꢀ2ꢀyl)methyl] sulfide (18) and Nꢀbenzyl(perhydroꢀ
1,3,5ꢀdithiazinꢀ5ꢀyl)amine (19) in 60 and 19% yields,
respectively (see Scheme 4), whereas tosyl hydrazine (20)
gives 3ꢀ[(pꢀtolyl)sulfonyl]ꢀ1,3,4ꢀthiadiazolidine (21),
Nꢀ(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)ꢀpꢀtolylsulfonamide
(22), and 3,7ꢀbis(pꢀtolylsulfonylamino)ꢀ1,5ꢀdithiaꢀ3,7ꢀ
diazacyclooctane (23) in 21, 38, and 41% yields, respecꢀ
tively.
All our attempts to perform the selective synthesis of
1,3,4ꢀthiadiazolidines starting from tosyl hydrazine (20)
failed. Under the reaction conditions used, we obtained a
mixture of the aboveꢀmentioned nitrogenꢀ and sulfurꢀ
containing heterocycles 21—23 in all experiments.
According to the experimental data, benzyl and tosyl
hydrazines are more reactive in reactions with CH2O and
H2S in a neutral medium compared to monoꢀ and
1,2ꢀdiphenylꢀsubstituted hydrazines. In benzyl hydrazine,
there is no р—π conjugation between the aromatic ring
and the lone electron pairs on the nitrogen atoms, which
S(3)
C(20)
C(13)
C(19)
C(12)
C(14)
C(15)
C(18)
C(17)
N(4)
N(3)
N(1)
C(16)
C(6)
C(11)
S(1)
C(1)
C(7)
C(8)
N(2)
C(4)
C(5)
C(2)
S(2)
C(9)
C(10)
C(3)
Fig. 5. Molecular structure of bis[(6ꢀbenzylꢀ4,2,6ꢀthiadiazolidinꢀ
2ꢀyl)methyl] sulfide (18).

1830
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Akhmetova et al.
C(7)
C(11)
C(8)
C(6)
O(2)
C(5)
C(14)
C(13)
C(18)
O(4)
C(9)
C(10)
H(1N)
S(1)
S(4)
C(15)
C(12)
H(4N)
N(1)
N(2)
O(1)
N(4)
C(1)
C(16)
C(17) S(2)
C(2)
N(3)
C(4)
O(3)
S(3)
C(3)
Fig. 6. Molecular structure of 3,7ꢀbis(pꢀtolylsulfonylamino)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane (23) in crystals.
The 13C NMR spectrum of compound 23 has a highꢀ
field signal at δC 21.2 corresponding to the carbon atom of
the Me group and one signal at δC 62.2, which is indicaꢀ
tive of the equivalence of four C atoms of the methylene
groups and, consequently, of the symmetric structure of
3,7ꢀbis(pꢀtolylsulfonylamino)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacycloꢀ
octane (23). This is confirmed by 1H NMR spectroscopic
data. The methylene groups of the eightꢀmembered hetꢀ
erocycle are equivalent, and their signals appear as an
AB system (doublets at δH 4.04 and 4.16, 3JAB = 14.5 Hz).
According to Xꢀray diffraction data, the eightꢀmemꢀ
bered heterocycle, viz., 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane,
in the crystal structure of compound 23 adopts a
chair—chair conformation (a crown with the heteroatoms
occupying the apical positions). The aromatic substituꢀ
ents are in axial positions at the nitrogen atom in the
cis configuration (Fig. 6).
Similar conformations of the ring are also observed in
3,7ꢀdi[(R)ꢀ(+)ꢀ1´ꢀmethylbenzyl]ꢀ3,7ꢀdiazaꢀ1,5ꢀdithiaꢀ
cyclooctane24 and 1,5,3,7ꢀdiazadiphosphacyclooctaꢀ
nes.25,26 The nitrogen atoms in the latter compounds have
a planarꢀtrigonal coordination due to conjugation between
the lone electron pairs and the π systems of the benzene
rings. This conjugation fixes the conformations of the
aromatic fragments at the nitrogen atoms.
more actively react with CH2O and H2S in a neutral meꢀ
dium (without acidic or alkaline additives). All the hydrꢀ
azines under study are characterized by the formation of
1,3,4ꢀthiadiazolidines. Monosubstituted hydrazines give
also perhydroꢀ1,3,5ꢀdithiazines. In addition, the reacꢀ
tion of phenyl hydrazine produces 1,3ꢀthiazetidine and
1,2,4,5ꢀtetrazine derivatives. The reaction of tosyl hydrꢀ
azine affords also 1,5ꢀdithiaꢀ3,7ꢀdiazacyclooctane.
To summarize, the thiomethylation pathway of arylꢀ
substituted hydrazines is determined by the nature and
the structures of the starting substrates as well as by the
reaction conditions (pH and the temperature).
Experimental
Thiomethylation products 2—9 were analyzed by GLC on a
Chromꢀ5 chromatograph (flameꢀionization detector, SEꢀ30
(5%) stationary phase on Chromaton NꢀAWꢀHMDS,
2400×3 mm steel packed column, temperature programming
from 50 to 270 °C at a rate of 8 °C min–1, helium as the carrier
gas). Products 13—16 were analyzed by HPLC on an LKB chroꢀ
matograph (photometric detector, the wavelength was 238 nm).
The separation was carried out at room temperature on a metalꢀ
lic column (125×4 mm) packed with the Separon SGX C18
sorbent (grain size was 5 µm). The MeCN—H2O mixture
(60 : 40, v/v) was used as the mobile phase; the eluent flow rate
was 0.2 mL min–1. The 1H NMR spectra of compounds 2,
14—16, 18, and 23 were recorded on a Bruker spectrometer
(300 MHz). The 1H NMR spectra of the other compounds were
measured on a Tesla BSꢀ487 spectrometer (80 MHz). The
13C NMR spectra were recorded on a Jeol FX 90Q spectrometer
(22.50 MHz) in CDCl3 with Me4Si as the internal standard. The
IR spectra were measured on a Specord 75 IR spectrophotomꢀ
eter in Nujol mulls. The GLCꢀmass spectrometry was carried
out on a Finnigan 4021 instrument (50000×0.25 mm glass capilꢀ
In the crystal structure of compound 23, there is one
solvent (CHCl3) molecule per asymmetric unit.
Studies of cyclothiomethylation of phenyl and 1,2ꢀdiꢀ
phenyl hydrazines having p—π conjugation demonstrated
that heterocyclization with CH2O and H2S more effiꢀ
ciently occurs in an alkaline medium, this reaction with
phenyl hydrazine more efficiently proceeds under neutral
or acidic conditions, whereas benzyl and tosyl hydrazines

Cyclothiomethylation of aryl hydrazines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1831
lary column, HPꢀ5 stationary phase, helium as the carrier gas,
temperature programming from 50 to 300 °C at a rate of 5 °C
min–1, the vaporizer temperature was 280 °C, the ion source
temperature was 250 °C, 70 eV). Elemental analysis was perꢀ
formed on a Karlo Erba 1106 analyzer. Hydrogen sulfide was
bubbled with the use of an ANPꢀ10 peristaltic pump. The
pH values of solutions were determined on a pH meter (рHꢀ340).
Column chromatography was performed with the use of silica
gel; spots were visualized with iodine vapor. The TLC analysis
was carried out on Silufol Wꢀ254 silica gel.
Thiomethylation of phenyl hydrazine (1). Method A. A 37%
formaldehyde solution (2.21 mL, 0.03 mol) was saturated with
hydrogen sulfide (0.02 mol) at 20 °C for 30 min. Then phenyl
hydrazine hydrochloride (1.08 g, 0.01 mol) dissolved in EtOH
was added dropwise. The reaction mixture was stirred at a speciꢀ
fied temperature (0, 20, 40, or 70 °C) for 3 h and then neutralꢀ
ized with a KOH solution. The product was extracted with chloꢀ
roform (2×30 mL), and the extract was dried with CaCl2 and
concentrated, after which a mixture of products 2—4 was obꢀ
tained. The reaction product prepared at 40 °C was separated by
column chromatography (C6H14—C6H6, 1 : 3, as the eluent).
The reaction with the use of an analogous mixture of the reꢀ
agents at 0 °C afforded individual compound 2. The product was
extracted with chloroform (2×30 mL), and the extract was dried
with CaCl2 and concentrated.
at a specified temperature (0, 20, 40, or 70 °C) for 3 h, and then
neutralized with a HCl solution. The organic phase was concenꢀ
trated, and a mixture of compounds 2, 3, 5, and 6 was isolated.
The reaction product prepared at 0 °C was separated by column
chromatography (CHCl3—petroleum ether, 1 : 1, as the eluent).
NꢀPhenyl(perhydroꢀ1,3ꢀthiazetidinꢀ3ꢀyl)amine (5). The yield
was 0.3 g (18%), m.p. 128—129 °C, Rf 0.43 (CHCl3—petroleum
ether, 1 : 1). Found (%): C, 57.85; H, 6.13; N, 16.75; S, 19.52.
C8H10N2S. Calculated (%): C, 57.83; H, 6.02; N, 16.87; S, 19.28.
1
IR, ν/cm–1: 750, 1250, 1600, 2910, 3240. H NMR, δ: 4.63 (s,
4 H, C(2)H2, C(4)H2); 6.88—7.10 (m, 5 H, H arom.). 13C NMR,
δ: 57.3 (t, C(2), C(4)); 114.3 (d, C(7), C(11)); 120.4 (d, C(9));
129.2 (d, C(8), C(10)); 147.1 (t, C(6)). MS, m/z (Irel (%)):
166 [M]+ (2); 120 [M – CH2S]+ (10); 105 [M – CH2SCH3]+
(40); 92 [M – C6H5NH]+ (16); 77 [C6H5]+ (100); 61
[CH2SCH3]+ (36); 51 [CN—NC]+.
1,4ꢀDiphenylhexahydroꢀ1,2,4,5ꢀtetrazine (6). The yield was
0.55 g (23%), m.p. 164—166 °C (cf. lit. data21: m.p. 175 °C),
Rf 0.68 (CHCl3—petroleum ether, 1 : 1). IR, ν/cm–1: 600, 660,
900, 1120, 1280, 1380, 1460, 1600, 2910. 1H NMR, δ: 4.25 and
2
4.82 (both d, 2 H each, C(3)H2, C(6)H2, J = 14.2 Hz); 6.01
(br.s, 2 H, N(1)H, N(4)H); 6.80—7.35 (m, 10 H, H arom.).
13C NMR, δ: 63.3 (t, C(3), C(6)); 114.2 (d, C(8), C(12), C(14),
C(18)); 120.3 (d, C(10), C(16)); 129.3 (d, C(9), C(11), C(15),
C(17)); 145.6 (t, C(7), C(13)).
3ꢀPhenylꢀ1,3,4ꢀthiadiazolidine (2). The yield was 0.36 g
(22%), paleꢀbrown oil, Rf 0.27 (C6H14—C6H6, 1 : 3). Found (%):
C, 58.15; H, 6.11; N, 16.93; S, 18.81. C8H10N2S. Calculated (%):
C, 57.83; H, 6.02; N, 16.87; S, 19.28. IR, ν/cm–1: 750, 1020,
1300, 1600, 2920, 3050. 1H NMR (25 °C), δ: 3.98 (d, 2 H,
C(2)H2, 2J = 17.0 Hz); 4.70—4.90 (m, 2 H, C(5)H2); 4.57 (br.s,
1 H, N(3)H); 7.00—7.25 (m, 5 H, H arom.). 13C NMR, δ: 53.8
(t, C(2)); 55.2 (t, C(5)); 115.0 (d, C(7), C(11)); 121.2 (d, C(9));
128.9 (d, C(8), C(10)); 148.4 (t, C(6)). MS, m/z (Irel (%)):
166 [M]+ (23); 120 [M – CH2S]+ (100); 105 [M – NHCH2S]+
(28); 91 [M – NHCH2SCH2]+ (37); 77 [C6H5]+ (49).
NꢀPhenyl(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)amine (3). The yield
was 0.55 g (26%), a darkꢀbrown resinous substance, Rf 0.54
(C6H14—C6H6, 1 : 3). Found (%): C, 51.23; H, 5.47; N, 13.27;
S, 30.03. C9H12N2S2. Calculated (%): C, 50.94; H, 5.66;
N, 13.21; S, 30.19. IR, ν/cm–1: 750, 1380, 1600, 2900,
3300—3400 br. 1H NMR, δ: 4.79 (s, 2 H, C(2)H2); 5.20 (s, 4 H,
C(4)H2, C(6)H2); 7.37—8.13 (m, 5 H, H arom.). 13C NMR, δ:
32.2 (t, C(2)); 58.6 (t, C(4), C(6)); 114.5 (d, C(9), C(13));
120.3 (d, C(10), C(12)); 129.1 (d, C(11)); 145.9 (s, C(8)). MS,
m/z (Irel (%)): 212 [M]+ (91); 166 [M – CH2S]+ (7); 134
[M – SCH2S]+ (48); 120 [M – CH2SCH2S]+ (100).
Method C. A mixture of compounds 2, 3, and 7 was prepared
using an analogous mixture of the starting reagents at specified
temperatures without the use of BuONa/BuOH. The product
was extracted with chloroform (2×30 mL). The extract was dried
with CaCl2 and concentrated.
Formaldehyde phenylhydrazone (7). M.p. 26—27 °C (cf. lit.
data21: m.p. 28—29 °C). MS, m/z (Irel (%)): 120 [M]+ (67); 92
[M – NCH2]+ (100); 77 [M – NHNCH2]+ (8).
Thiomethylation of 2,4ꢀdinitrophenyl hydrazine (8). A 37%
formaldehyde solution (2.2 mL, 0.03 mol) was saturated with
hydrogen sulfide at 20 °C for 30 min. Then a solution of
dinitrophenyl hydrazine 8 (1.98 g, 0.01 mol) in chloroform was
added dropwise. The mixture was stirred at a specified temperaꢀ
ture (0, 20, 40, or 70 °C) for 3 h. The product was extracted with
chloroform (2×30 mL), dried with CaCl2, and concentrated.
Product 9 was obtained in a yield from 39 to 84% depending on
the reaction temperature. In addition, products 10 and 11 were
obtained.
Formaldehyde 2,4ꢀdinitrophenylhydrazone (9). M.p.
165—166 °C (cf. lit. data27: m.p. 166—167 °C). 13C NMR, δ:
115.6 (t, C(5)); 115.9 (d, C(9)); 121.7 (d, C(6)); 122.0 (d, C(8));
128.8 (t, C(7)); 136.5 (t, C(1)); 144.2 (t, C(4)). MS,
m/z (Irel (%)): 210 [M]+.
1,2,4ꢀTrithiolane (10).13 13C NMR, δ: 32.7 (s, C(3), C(5)).
MS, m/z (Irel (%)): 124 [M]+.
1,2,4,6ꢀTetrathiepane (11).13 MS, m/z (Irel (%)): 170 [M]+.
Thiomethylation of 1,2ꢀdiphenyl hydrazine (12). A 37%
formaldehyde solution (1.5 mL, 0.02 mol) was saturated with
hydrogen sulfide at 20 °C for 30 min. Then a solution of dipheꢀ
nyl hydrazine 12 (1.84 g, 0.01 mol) in chloroform was added
dropwise, and the mixture was stirred at a specified temperature
(0, 20, 40, or 70 °C) for 3 h. A mixture of products 13 and 14 was
obtained.
6ꢀPhenylperhydro[1,3,4]thiadiazino[5,4ꢀd][1,3,5]dithiazine
(4). The yield was 8%. MS, m/z (Irel (%)): 270 [M]+ (9); 224
[M
[M – SCH2SCHCH2]+ (80); 133 [M – SCH2SCHCH2S]+
(100); 119 [M
SCH2SCHCH2SCH2]+ (53); 105
[M
– –
CH2S]+ (9); 179 [M SCH2SCH]+ (56); 165
–
–
CH2SCH2SCHCH2SCH2]+ (86); 91 [M
–
NCH2SCH2SCHCH2SCH2]+ (23); 77 [C6H5]+ (75); 59
[CH2SCH]+ (31).
Method B. A 37% formaldehyde solution (11.1 mL, 0.15 mol)
was saturated with hydrogen sulfide (0.1 mol) for 30 min. Then a
mixture of phenyl hydrazine (4.93 mL, 0.15 mol) and a solution
of sodium butoxide in butanol, which was prepared according to
a standard procedure from BuOH (27×2 mL) and sodium (6.9 g,
0.3 mol), was added dropwise. The resulting mixture was stirred
Analogously to the aboveꢀdescribed procedure, a mixture of
products 13—16 was obtained upon predissolution of diphenyl
hydrazine 12 (1.84 g, 0.01 mol) in a solution of sodium butoxide

1832
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Akhmetova et al.
in butanol, which was prepared from BuOH (1.8×2 mL) and
sodium (0.46 g, 0.02 mol), at 20 °C. Compound 16 was isolated
by recrystallization from DMSO. Products 13—15 were sepaꢀ
rated by silica gel column chromatography (CCl4—petroleum
ether, 9 : 1, as the eluent).
(t, C(3)); 56.6 (t, C(5)); 57.7 (t, C(1)); 59.8 (t, C(7)); 127.5 (d,
C(11), C(11´)); 128.4 (d, C(10), C(12), C(10´), C(12´)); 129.2
(d, C(9), C(13), C(9´), C(13´)); 138.0 (t, C(8), C(8´)).
NꢀBenzyl(perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)amine (19). The
yield was 0.43 g (19%), a yellow resinous substance, Rf 0.28
(CCl4—Et2O, 5 : 1). Found (%): C, 53.07; H, 6.30; N, 12.38;
S, 28.63. C10H14N2S2. Calculated (%): C, 53.10; H, 6.19;
N, 12.39; S, 28.32. IR, ν/cm–1: 700, 1030, 1450, 1600, 2940.
1H NMR, δ: 4.25 (s, 2 H, C(2)H2); 4.63 (s, 2 H, C(8)H2); 4.72
(s, 4 H, C(4)H2, C(6)H2); 7.87—8.05 (br.s, 5 H, H arom.).
13C NMR, δ: 31.7 (t, C(2)); 58.2 (t, C(4), C(6)); 59.0 (t, C(8));
127.3 (d, C(12)); 128.4 (d, C(11), C(13)); 129.0 (d, C(10),
C(14)); 138.15 (s, C(9)). MS, m/z (Irel (%)): 226 [M]+ (30);
192 [M – H2S]+ (5); 147 [M – C6H5 – 2]+ (10); 131
[C6H5CH2NNC]+ (58); 118 [C6H5CHNN]+ (23); 91
[CHSCH2S]+ (100); 77 [C6H5]+ (58); [SCH]+ (80).
(Z )ꢀAzobenzene (13). Orangeꢀred crystals, m.p. 68 °C (cf. lit.
data28: m.p. 68 °C). MS, m/z (Irel (%)): 182 [M]+.
3,4ꢀDiphenylꢀ1,3,4ꢀthiadiazolidine (14). The yield was 0.94 g
(39%), brightꢀorange oil, Rf 0.26 (CCl4—petroleum ether, 9 : 1).
Found (%): C, 69.70; H, 5.69; N, 11.56; S, 13.17. C14H14N2S.
Calculated (%): C, 69.42; H, 5.79; N, 11.57; S, 13.22. IR,
ν/cm–1: 740, 1160, 1600, 2900, 3300. 1H NMR (25 °C), δ: 4.65
(br.s, 4 H, C(2)H2, C(5)H2, ∆ν
= 24 Hz); 6.88—8.10 (m,
1/2
1
10 H, H arom.). H NMR (–20 °C), δ: 4.23 (d, 2 H, C(2)HA,
2
2
C(5)HA, J = 10.0 Hz); 4.85 (d, 2 H, C(2)HB, C(5)HB, J =
10.0 Hz); 6.88—8.10 (m, 10 H, H arom.). 13C NMR, δ: 53.0 (t,
C(2), C(5)); 115.1 (d, C(7), C(11), C(7´), C(11´)); 122.0 (d,
C(9), C(9´)); 129.5 (d, C(8), C(10), C(8´), C(10´)); 148.2 (t,
C(6), C(6´)). MS, m/z (Irel (%)): 242 [M]+ (62); 195 [M –
CH2S]+ (100); 136 [C6H5NCH2SH]+ (12); 104 [C6H5NHN]+
(38); 91 [C6H5N]+ (16); 77 [C6H5]+ (77); 51 [CN—NC]+ (53);
46 [CH2S]+ (13).
Thiomethylation of tosyl hydrazine (20). A mixture of prodꢀ
ucts 21—23 was prepared according to the aboveꢀdescribed proꢀ
cedure (method C) from tosyl hydrazine (2.02 g, 0.01 mol) (20)
and CH2O (2.21 mL, 0.03 mol) at 0 °C. The mixture was sepaꢀ
rated by column chromatography. Compounds 21 and 22 were
eluted with a 5 : 1 CCl4—Et2O mixture; product 23, with CHCl3.
3ꢀ[(pꢀTolyl)sulfonyl]ꢀ1,3,4ꢀthiadiazolidine (21). The yield
was 0.51 g (21%), m.p. 134—135 °C, Rf 0.29 (CCl4—Et2O,
5 : 1). Found (%): C, 44.35; H, 5.00; N, 11.42; S, 26.43.
C9H12N2S2O2. Calculated (%): C, 44.24; H, 4.95; N, 11.47;
S, 26.25. IR, ν/cm–1: 720, 1150, 1300, 1600, 2900, 3200.
1H NMR, δ: 1.73 (s, 3 H, C(13)H3); 3.59 (d, 2 H, Hax(2),
Hax(5), 3J = 14.4 Hz); 4.50 (d, 2 H, Heq(2), Heq(5), 3J = 14.4 Hz);
5,6ꢀDiphenyltetrahydroꢀ1,3,5,6ꢀdithiadiazepine (15). The
yield was 0.29 g (10%), orange crystals, m.p. 123—125 °C, Rf 0.19
(CCl4—petroleum ether, 9 : 1). Found (%): C, 62.44; H, 5.61;
N, 9.33; S, 21.90. C15H16N2S2. Calculated (%): C, 62.50;
H, 5.56; N, 9.72; S, 22.22. IR, ν/cm–1: 740, 1200, 1450, 1590,
2900. 1H NMR, δ: 4.00 (s, 2 H, C(2)H2); 4.91 (d, 2 H, C(4)Ha,
2
2
C(7)Ha, J = 14.9 Hz); 5.03 (d, 2 H, C(4)Hb, C(7)Hb, J =
14.9 Hz); 6.93—7.00 (m, 6 H, H arom.); 7.30—7.40 (m, 4 H,
H arom.). 13C NMR, δ: 36.3 (t, C(2)); 55.1 (t, C(4), C(7));
113.6 (d, C(9), C(13), C(9´), C(13´)); 120.4 (d, C(11), C(11´));
129.7 (d, C(10), C(12), C(10´), C(12´)); 145.3 (t, C(8), C(8´)).
MS, m/z (Irel (%)): 164 [PhNNH(NCH2)CH=S]+, 136
[PhNHCH=S]+. MCr = 288 10.
3
7.24 (br.s, 1 H, N(3)H); 7.47 (d, 4 H, H arom., J = 8.1 Hz);
7.98 (t, 4 H, H arom., 3J = 8.1 Hz). 13C NMR, δ: 21.4 (q, C(13));
57.7 (t, C(2)); 58.1 (t, C(5)); 127.8 (d, C(7), C(11)); 129.0
(d, C(8), C(12)); 134.9 (d, C(7)); 144.3 (s, C(10)). MS,
m/z (Irel (%)): 244 [M]+ (70); 213 [M – S – 2]+ (9); 182
[M – SO2 + 2]+ (12); 154 [M – C6H5CH2]+ (6); 123
[CH3C6H5S]+ (100); 89 [HNCH2SCH2N]+ (6).
1,2,4,5ꢀTetraphenylhexahydroꢀ1,2,4,5ꢀtetrazine (16). The
yield was 0.27 g (6%), colorless crystals, m.p. 203—205 °C.
1H NMR, δ: 5.42 (br.s, 4 H, C(3)H2, C(6)H2); 6.82 (t, 4 H,
Nꢀ(Perhydroꢀ1,3,5ꢀdithiazinꢀ5ꢀyl)ꢀpꢀtolylsulfonamide (22).
The yield was 1.1 g (38%), m.p. 145—146 °C, Rf 0.86
(CCl4—Et2O, 5 : 1). Found (%): C, 41.55; H, 4.85; N, 9.80;
S, 33.58. C10H14N2S3O2. Calculated (%): C, 41.36; H, 4.86;
N, 9.65; S, 33.12. IR, ν/cm–1: 750, 1140, 1320, 1600, 2900,
3210. 1H NMR, δ: 2.59 (s, 3 H, C(15)H3); 3.59 (d, 1 H, Hеq(2),
2J = 13.7 Hz); 3.99 (d, 2 H, Hеq(4), Hеq(6), 2J = 13.6 Hz); 4.50
(d, 1 H, Hax(2), 2J = 13.7 Hz); 4.71 (d, 2 H, Hax(4), Hax(6), 3J =
3
C(10)H, C(10a)H, C(10b)H, C(10c)H), J = 7.3 Hz); 7.00 (d,
8 H, C(8)H, C(8a)H, C(8b)H, C(8c)H, C(12)H, C(12a)H,
C(12b)H, C(12c)H, 3J = 7.3 Hz); 7.20 (t, 8 H, C(9)H, C(9a)H,
3
C(9b)H, C(9c)H, C(11)H, C(11a)H, C(11b)H, C(11c)H, J =
7.3 Hz). 13C NMR, δ: 60.4 (t, C(3), C(6)); 115.1 (d, C(8),
C(8a), C(8b), C(8c), C(12), C(12a), C(12b), C(12c)); 120.2 (d,
C(10), C(10a), C(10b), C(10c)); 129.3 (d, C(9), C(9a), C(9b),
C(9c), C(11), C(11a), C(11b), C(11c)); 147.8 (t, C(7), C(7a),
C(7b), C(7c)).
3
13.6 Hz); 7.24 (br.s, 1 H, N(7)H); 7.47 (d, 2 H, H arom., J =
8.1 Hz); 7.98 (t, 2 H, H arom., 3J = 8.1 Hz). 13C NMR, δ: 20.2
(d, C(15)); 31.9 (t, C(2)); 60.1 (t, C(4), C(6)); 128.3 (d, C(11),
C(13)); 129.9 (d, C(10), C(14)); 131.2 (d, C(9)); 144.6
(s, C(12)). MS, m/z (Irel (%)): 290 [M]+ (6); 258 [M – S]+ (6);
155 [CH3C6H4SO2]+ (10); 135 [CH3C6H4SO]+ (100); 124
[CH3C6H4SH]+ (25); 91 [CH3C6H4]+ (96); 44 [CS]+ (67).
3,7ꢀBis(pꢀtolylsulfonylamino)ꢀ1,5ꢀdithiaꢀ3,7ꢀdiazacycloꢀ
octane (23). The yield was 1.66 g (41%), colorless crystals, m.p.
175—177 °C, Rf 0.09 (CCl4—Et2O, 5 : 1). Found (%): C, 44.24;
H, 4.83; N, 11.48; S, 26.26. C18H24N4O4S4. Calculated (%):
C, 44.26; H, 4.92; N, 11.48; S, 26.23. IR, ν/cm–1: 660, 1160,
1450, 1600, 2900, 3200. 1H NMR, δ: 2.42 (s, 6 H, C(17)H3,
C(17´)H3); 4.04 (d, 4 H, C(2)HA, C(4)HA, C(6)HA, C(8)HA,
3JAB = 14.5 Hz); 4.16 (d, 4 H, C(2)HB, C(4)HB, C(6)HB,
Thiomethylation of benzyl hydrazine (17). Analogously to the
aboveꢀdescribed procedure (method C), a mixture of products
18 and 19 was prepared from benzyl hydrazine (1.19 mL,
0.01 mol) at 20 °C; the starting reagents were taken in the ratio
17 : CH2O : H2S = 1 : 3 : 2. The mixture was separated by
column chromatography (CCl4—Et2O, 5 : 1, as the eluent).
Bis[(6ꢀbenzylꢀ4,2,6ꢀthiadiazolidinꢀ2ꢀyl)methyl] sulfide (18).
The yield was 2.51 g (60%), colorless crystals, m.p. 100—106 °C,
Rf 0.78 (CCl4—Et2O, 5 : 1). Found (%): C, 57.38; H, 6.26;
N, 13.50; S, 23.00. C20H26N4S3. Calculated (%): C, 57.41;
H, 6.22; N, 13.40; S, 22.97. IR, ν/cm–1: 700, 1030, 1450, 1600,
2940. 1H NMR, δ: 3.80 (br.s, 8 H, C(1)H2, C(3)H2, C(1´)H2,
C(3´)H2); 4.15—4.54 (m, 8 H, C(5)H2, C(7)H2, C(5´)H2,
C(7´)H2); 7.00—7.25 (m, 10 H, H arom.). 13C NMR, δ: 55.7
3
C(8)HB, JAB = 14.5 Hz); 7.30 and 7.77 (both d, 4 H each,
H arom., 3J = 8.2 Hz); 8.50 (br.s, 2 H, N(9)H, N(9´)H).

Cyclothiomethylation of aryl hydrazines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1833
13C NMR, δ: 21.2 (q, C(17), C(17´)); 62.2 (t, C(2), C(4), C(6),
C(8)); 127.3 (d, C(12), C(16), C(12´), C(16´)); 129.4 (d, C(13),
C(15), C(13´), C(15´)); 136.6 (s, C(14), C(14´)); 143.6 (s,
C(11), C(11´)).
Xꢀray diffraction study of compound 16, which was prepared
by recrystallization from DMSO, was carried out on an Enrafꢀ
Nonius CAD4 diffractometer (MoꢀKα radiation, graphite monoꢀ
All calculations were carried out with the use of the
SHELXTL PLUS 5 program package.29
We thank L. M. Khalilov for help in performing Xꢀray
diffraction studies and discussion of the 1H and 13C NMR
spectra.
This study was financially supported by the Council
on Grants of the President of the Russian Federation
(Program for State Support of Leading Scientific Schools
of the Russian Federation, Grant NShꢀ1060.2003.03) and
the Russian Science Support Foundation.
chromator, θ/2θ scanning technique, 2θ
= 54°) at 293 K.
max
Merging of 5713 observed reflections gave 5376 independent
reflections (Rint = 0.0603), which were used in the structure
solution and refinement. Colorless crystals of 16 (C26H24N4•
•C2H6OS) are triclinic: a = 9.172(2) Å, b = 11.932(2) Å, c =
13.087(3) Å, α = 66.65(3)°, β = 72.05(3)°, γ = 79.46(3)°, V =
1247.8(4) Å3, dcalc = 1.253 g cm–3, space group P–1, Z = 2. The
structure was solved by direct methods and refined by the fullꢀ
References
matrix leastꢀsquares method against F 2 with anisotropic disꢀ
1. S. R. Khafizova, V. R. Akhmetova, T. V. Tyumkina, L. M.
Khalilov, R. V. Kunakova, and U. M. Dzhemilev, Izv. Akad.
Nauk, Ser. Khim., 2004, 1652 [Russ. Chem. Bull., Int. Ed.,
2004, 53, 1717].
2. M. R. Stillings, A. P. Welbourn, and D. J. Walter, Med.
Chem., 1986, 29, 2280.
3. M. Kidwai, N. Negi, and S. R. Chaudhary, Acta Pharma,
1995, 45, 511.
4. US Pat. 4,246,126 (1981); Chem. Abstrs, 1981, 94, 142505h.
5. Heterocyclic Compounds, Ed. R. C. Elderfield, Wiley, New
York, 1961.
hkl
placement parameters. The hydrogen atoms were located in difꢀ
ference electron density maps and refined using a riding model.
The final R factors were as follows: wR2 = 0.1564 (calculated
based on F 2hkl for all 5376 reflections), R1 = 0.0504 (calculated
based on Fhkl for 4102 reflections with I > 2σ(I )), GOF 0.973,
328 parameters were refined.
Xꢀray diffraction study of compound 18, which was prepared
by recrystallization from a 5 : 1 CCl4—Et2O mixture, was
carried out on a Bruker SMART 1000 CCD Area Detector
diffractometer (MoꢀKα radiation, graphite monochromator,
θ/2θ scanning technique, 2θ
crystals, C20H26N4S3 (M = 218.62), are orthorhombic: a =
= 54°) at 120 K. Colorless
6. S. P. Gromov, S. N. Dmitrieva, A. I. Vedernikov, and M. V.
Churakova, Izv. Akad. Nauk, Ser. Khim., 2004, 1362 [Russ.
Chem. Bull., Int. Ed., 2004, 53, 1417].
7. R. V. Kunakova, S. R. Khafizova, Yu. S. Dal´nova, R. S.
Aleev, L. M. Khalilov, and U. M. Dzhemilev, Neftekhimiya,
2002, 42, 382 [Russ. Petroleum Chem., 2002, 42, 347 (Engl.
Transl.)].
8. S. R. Khafizova, V. R. Akhmetova, R. V. Kunakova, and
U. M. Dzhemilev, Izv. Akad. Nauk, Ser. Khim., 2003, 1722
[Russ. Chem. Bull., Int. Ed., 2003, 52, 1817].
max
9.4221(15) Å, b = 10.5469(17) Å, c = 20.836(3) Å, V =
2070.6(6) Å3, space group P212121, Z = 8, dcalc = 1.343 g cm–3
.
Merging of 15240 observed reflections gave 3843 independent
reflections (Rint = 0.0699), which were used in the structure
solution and refinement. The structure was solved by direct
methods and refined by the fullꢀmatrix leastꢀsquares method
against F 2 with anisotropic displacement parameters. The
hkl
hydrogen atoms were placed in geometrically calculated posiꢀ
tions and refined using a riding model. The final R factors were
9. S. R. Khafizova, V. R. Akhmetova, L. F. Korzhova, T. V.
Khakimova, G. R. Nadyrgulova, R. V. Kunakova, E. A.
Kruglov, and U. M. Dzhemilev, Izv. Akad. Nauk, Ser. Khim.,
2005, 423 [Russ. Chem. Bull., Int. Ed., 2005, 54, 432].
10. V. R. Akhmetova, G. R. Nadyrgulova, S. R. Khafizova,
R. R. Khairullina, E. A. Paramonov, R. V. Kunakova, and
U. M. Dzhemilev, Zh. Org. Khim., 2006, 42, 151 [Russ. J. Org.
Chem., 2006, 42 (Engl. Transl.)].
11. A. P. Grekov and V. Ya. Veselov, Fizicheskaya khimiya
gidrazina [Physical Chemistry of Hydrazine], Naukova
Dumka, Kiev, 1979, 264 pp. (in Russian).
12. Comprehensive Organic Chemistry, Eds S. D. Barton and W. D.
Ollis, Pergamon Press, Oxford—New York—Toronto—
Sydney—Paris—Frankfurt, 1979.
13. R. S. Aleev, Yu. S. Dal´nova, Yu. I. Popova, R. M.
Masagutov, and S. R. Rafikov, Dokl. Akad. Nauk SSSR,
1988, 303, 873 [Dokl. Chem., 1988 (Engl. Transl.)].
14. B. Rassow, J. Prakt. Chem., 1901, 64, 136.
15. WeygandꢀHilgetag, OrganischꢀChemische Experimentierkunst,
Leipzig, 1964.
16. R. G. Kostyanovskii, P. Rademakher, Yu. I. El´natanov,
G. K. Kadorkina, G. A. Nikiforov, I. I. Chervin, S. V.
Usachev, and V. R. Kostyanovskii, Izv. Akad. Nauk, Ser.
Khim., 1997, 1346 [Russ. Chem. Bull., 1997, 46, 1291 (Engl.
Transl.)].
as follows: wR2 = 0.0968 (calculated based on F 2 for all
hkl
3843 reflections used in the final step), R1 = 0.0456 (calculated
based on Fhkl for 3117 reflections with I > 2σ(I )), GOF 1.010,
244 parameters were refined.
Xꢀray diffraction study of compound 23, which was prepared
by recrystallization from CHCl3, was carried out on a Syntex P21
diffractometer (MoꢀKα radiation, graphite monochromator,
θ/2θ scanning technique, 2θmax = 54°) at 163 K. Colorless crysꢀ
tals, C19H25Cl3N4O4S4 (M = 608.02), are monoclinic: a =
10.528(4) Å, b = 18.293(6) Å, c = 14.916(6) Å, β = 109.45°, V =
2708.6(17) Å3, space group P21n, Z = 4, dcalc = 1.491 g cm–3
.
A total of 6289 reflections were collected. Merging of equivalent
reflections gave 5907 independent reflections (Rint = 0.0182),
which were used in the structure solution and refinement. The
structure was solved by direct methods and refined by the fullꢀ
matrix leastꢀsquares method against F 2 with anisotropic disꢀ
hkl
placement parameters. The hydrogen atoms of the NH groups
were located in difference electron density maps. The other
hydrogen atoms were placed in geometrically calculated posiꢀ
tions. All H atoms were refined using a riding model. The final
R factors were as follows: R1 = 0.0430 (calculated based on Fhkl
with the use of 3786 reflections with I > 2σ(I )), wR2 = 0.1036
(calculated based on F 2hkl for all 5907 reflections), GOF 0.998,
307 parameters were refined.

1834
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Akhmetova et al.
17. J. E. Anderson and J. M. Lehn, J. Am. Chem. Soc.,
1967, 89, 81.
18. G. V. Shustov, A. Yu. Shibaev, Yu. V. Puzanov, and R. G.
Kostyanovskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1988,
1869 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1988, 37, 1671
(Engl. Transl.)].
19. V. J. Baker, A. R. Katritzky, and J.ꢀP. Majoral, J. Chem.
Soc., Perkin Trans. 2, 1975, 1191.
20. H. Günter, NMR Spectroscopy, An Introduction, Wiley,
Chichester, 1980.
21. B. V. Ioffe and V. S. Stopskii, Dokl. Akad. Nauk SSSR, 1967,
175, 1064 [Dokl. Chem., 1967 (Engl. Transl.)].
22. HoubenꢀWeyl, Methoden der organischen Chemie, Verlag
Georg Tieme, Stuttgart, 1953.
23. Analiz nefti i nefteproduktov [Analysis of Petroleum and Petroꢀ
leum Products], Ed. B. M. Rybak, Gostoptekhizdat, Mosꢀ
cow, 1962, 5, 887 pp. (in Russian).
25. R. M. Kuznetsov, A. S. Balueva, I. A. Litvinov, A. T.
Gubaidullin, G. N. Nikonov, A. A. Karasik, and O. G.
Sinyashin, Izv. Akad. Nauk, Ser. Khim., 2002, 142 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 151].
26. B. A. Arbuzov, O. A. Erastov, G. N. Nikonov, I. A. Litvinov,
D. S. Yufit, and Yu. T. Struchkov, Dokl. Akad. Nauk SSSR,
1981, 257, 127 [Dokl. Chem., 1981 (Engl. Transl.)].
27. N. D. Cheronis, Micro and Semimicro Methods, Intersci.
Publ., New York, 1954.
28. Spravochnik khimika [Chemist's Handbook], Ed. B. P.
Nikol´skii, Khimiya, Moscow—Leningrad, 1964, 3, 1008 pp.
(in Russian).
29. G. M. Sheldrick, SHELXTL PLUS, PC Version, System of
Computer Programs for the Determination of Crystal Structure
from Xꢀray Diffraction Data, Rev. 502, Siemens Analytical
XꢀRay Instruments, Inc., Germany, 1994.
24. G. CadenasꢀPliego, M. J. RosalesꢀHoz, R. Contreras, and
A. FloresꢀParra, Tetrahedron Asymmetry, 1994, 5, 633.
Received March 20, 2006;
in revised form July 4, 2006