Novel 1,5,3-dithiazepanes: Three-component synthesis, stereochemistry, and fungicidal activity

Article abstract of DOI:10.1007/s11172-012-0301-5

Three-component heterocyclization of hydrazine with formaldehyde and ethane-1,2-dithiol gave previously unknown 3,3′-bi(1,5,3-dithiazepane). Its stereochemistry was determined by X-ray diffraction. The reaction with higher aliphatic aldehydes RCHO (R = Me

Full text of DOI:10.1007/s11172-012-0301-5

Russian Chemical Bulletin, International Edition, Vol. 61, No. 11, pp. 2140—2148, November, 2012
2140
Novel 1,5,3ꢀdithiazepanes: threeꢀcomponent synthesis,
stereochemistry, and fungicidal activity
V. R. Akhmetova,a N. N. Murzakova,a T. V. Tyumkina,a G. R. Khabibullina,a I. S. Bushmarinov,b
L. F. Korzhova,c and N. F. Galimzyanovad
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: ib@ineos.ac.ru
cBashkir Republic Research Center of Ecology,
147 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347) 284 3503. Eꢀmail: ecocnt@diaspro.ru
dInstitute of Biology, Ufa Research Center of the Russian Academy of Sciences,
69 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347) 235 6247. Eꢀmail: ib@anrb.ru
Threeꢀcomponent heterocyclization of hydrazine with formaldehyde and ethaneꢀ1,2ꢀdithiol
gave previously unknown 3,3´ꢀbi(1,5,3ꢀdithiazepane). Its stereochemistry was determined by
Xꢀray diffraction. The reaction with higher aliphatic aldehydes RCHO (R = Me, Et, Prn, and
Bun) yielded 2,4ꢀdialkylꢀ3ꢀalkylideneaminoꢀ1,5,3ꢀdithiazepanes. The stereochemistry of the
latter was determined by 1H and 13C NMR spectroscopy and confirmed by quantum chemical
calculations. Heterocyclizations of phenylhydrazine and benzylhydrazine with ethaneꢀ1,2ꢀ
dithiol gave 3ꢀaminoꢀ1,5,3ꢀdithiazepanes only with CH2O and MeCHO as the aldehyde comꢀ
ponent. 3,3´ꢀBi(1,5,3ꢀdithiazepane) and its Nꢀadduct with MeI were found to exhibit fungicidal
activity against microscopic fungi.
Key words: heterocyclization, hydrazines, aldehydes, ethaneꢀ1,2ꢀdithiol, 1,5,3ꢀdithiazeꢀ
panes, stereochemistry, Xꢀray diffraction analysis, fungicides.
In the last few years, multicomponent and domino
studied threeꢀcomponent condensation between hydrꢀ
azines, ethaneꢀ1,2ꢀdithiol, and aliphatic aldehydes RCHO
(R = H, Me, Et, Prn, and Bun). The stereochemistry of
the compounds obtained was examined both theoretically
and experimentally. In addition, they were tested for funꢀ
gicidal activity against the microscopic fungi Bipolaris soꢀ
rokiniana, Fusarium oxysporium, Aspergillus fumigatus,
Aspergillus niger, and Paecilomyces variotii.
reactions have given strong impetus to the development of
"one pot" methods for the regiocontrolled synthesis of
heterocycles. In particular, threeꢀcomponent reactions of
hydrazines with formaldehyde and H2S are used to obtain
1,3,4ꢀthiadiazolidines,1,2 which are valuable bactericides,
fungicides, and drugs.3—5
We assumed that the use of ethaneꢀ1,2ꢀdithiol in the
thiomethylation of hydrazine would extend the synthetic
scope of this reaction and afford novel biologically active
heterocyclic systems containing the methylenethioethylꢀ
ene fragments —CH2SCH2CH2—.
The literature data on threeꢀcomponent condensation
of ethaneꢀ1,2ꢀdithiol with aldehydes and hydrazine are
lacking. However, it has been reported6 that baseꢀcataꢀ
lyzed threeꢀcomponent heterocyclization between ethaneꢀ
1,2ꢀdithiol, CH2O, and ketones produces 6ꢀacylꢀ1,4ꢀdiꢀ
thiepanes as mixtures with polymeric ꢀoxo bissulfides.
The present work was intended to develop methods for
the synthesis of dialkyldithiazepanes. For this purpose, we
Results and Discussion
Recently,7 we have demonstrated that the regiospeciꢀ
ficity of threeꢀcomponent heterocyclization between hydrꢀ
azine, H2S, and acetaldehyde substantially depends on
the reaction conditions. By optimizing the reaction conꢀ
ditions, we succeeded in the selective synthesis of 2,4,6,8ꢀ
tetramethylꢀ1,3,4ꢀthiadiazolo[3,4ꢀc]ꢀ1,3,4ꢀthiadiazole or
5ꢀaminoꢀ2,4,6ꢀtrimethylꢀ1,3,5ꢀdithiazinane.8
Here, we carried out a reaction between hydrazine (1),
CH2O (2), and ethaneꢀ1,2ꢀdithiol (3) by varying several
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2123—2131, November, 2012.
1066ꢀ5285/12/6111ꢀ2140 © 2012 Springer Science+Business Media, Inc.

Novel 1,5,3ꢀdithiazepanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2141
factors (temperature, concentration of the starting reꢀ
agents, order of mixing, and pH) to examine their effect
on the reaction pathway.
tives: 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4), 3ꢀaminoꢀ1,5,3ꢀ
dithiazepane (5), and 3ꢀmethylideneaminoꢀ1,5,3ꢀdithiaꢀ
zepane (6). According to our experimental data, the
heterocyclization is only selective in the synthesis of
3,3´ꢀbi(1,5,3ꢀdithiazepane) (4); at 20—25 C, its yield
is 80%.
It turned up that this reaction produces no annulated
heterocycles, in contrast to similar reactions between hydrꢀ
azine, H2S, and aldehydes RCHO (R = H and Me). For
instance, condensation of hydrazine (1) with formaldeꢀ
hyde (2) and ethaneꢀ1,2ꢀdithiol (3) in a ratio of 1 : 4 : 2 at
0—70 C without any acid or base (pH 3.15—3.20) and in
the presence of a base (pH 11.50—11.70) selectively gives
3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) in 81 and 79% yields, reꢀ
spectively. An increase in the reaction temperature to 80 C
leads to a 1 : 2 mixture of compound 4 and 3ꢀaminoꢀ1,5,3ꢀ
dithiazepane (5) in a total yield of 93%. Heterocyclization
in the presence of HCl (pH 0.45—0.5) gives 3ꢀmethylideneꢀ
aminoꢀ1,5,3ꢀdithiazepane (6) and sulfurꢀcontaining prodꢀ
ucts 7—9 derived from CH2O and ethaneꢀ1,2ꢀdithiol in
a total yield of 99% (Scheme 1). Note that the range of
products in the above reactions does not vary with the
concentrations or order of mixing of the starting reagents.
The structure of 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) was
1
proved by H and 13C NMR spectroscopy and Xꢀray difꢀ
1
fraction. The H NMR spectra show narrow singlets for
the protons at the C(2) and C(4) atoms (H 4.55) as well
as for the protons at the C(6) and C(7) atoms (H 2.94).
This suggests a rapid inversion of the rings on the NMR
time scale. In the 13C NMR spectra, the corresponding
carbon atoms resonate at C 56.18 and 37.84, respectively.
In the crystal, both dithiazepane rings adopt the
twistꢀchair conformation;9 the torsion angle C(1)—N(1)—
N(2)—C(5) is 82.1(1) (Fig. 1).
The C(4)—S(2) and C(5)—S(3) bonds are longer by
0.03—0.04 Å than the topologically equivalent C(1)—S(1)
and C(8)—S(4) bonds. In conjunction with the nearꢀ180
pseudotorsion angles lp—N—C—S (lp stands for the lone
electron pair), this suggests the presence of strong stereoꢀ
electronic couplings lp—N—C—S in structure 4. At the
same time, the N(2)—C(5) and N(2)—C(8) bond lengths
differ only by 0.003(1) Å, although the N(2)—C(8) bond
is involved in the coupling lp—N—C—S and hence should
have been shortened by 0.02 Å (Table 1). Apparently, the
coupling lp—N(1)—N(2)—C(8) is also effective here, thus
lengthening the N(2)—C(8) bond. Analogous reasoning
holds for the N(1)—C(1) bond, although its shortening
relative to the N(1)—C(4) bond is more appreciable
(0.01(1) Å).
Scheme 1
1
The H NMR spectra exhibit two singlets at H 2.87
and 3.61, with an integral intensity ratio of 1 : 1, for the
methylene protons of the dithiazepane ring in compound 5,
which suggests a rapid inversion of the sevenꢀmembered
ring in CDCl3. The signals for the C(2), C(4) and C(6),
C(7) atoms of compound 5 are shifted upfield compared
to the corresponding signals for bicyclane 4. In the
13C NMR spectrum, compound 6 is manifested as three
characteristic signals at C 35.13 (C(2), C(4)), 59.01 (C(6),
C(7)), and 130.00 (methylidene C(9)).
The IR spectra of compounds 4—6 show absorption
bands at 1020—1150 (C—N stretching) and 580—750 cm–1
(C—S stretching). The mass spectrum of compound 6
Reagents and conditions:i. 1—2—3, 1 : 4 : 2, 0—70 C (рН 3.15—3.20);
ii. 1—BuONa—2—3, 1 : 4 : 4 : 2, 0—70 C (рН 11.50—11.70);
iii. 1—2—3, 1 : 4 : 2, 80 C, (рН 3.15—3.20); iv. 1—HСl—2—3,
1 : 4 : 4 : 2, 20 C, (рН 0.45—0.5).
C(4)
C(8)
S(2)
C(7)
S(4)
C(3)
C(2)
N(2)
S(1)
S(3)
C(6)
C(1)
Thus, by varying the conditions for the threeꢀcompoꢀ
nent reaction between hydrazine, ethaneꢀ1,2ꢀdithiol, and
CH2O, we obtained three types of dithiazepane derivaꢀ
C(5)
Fig. 1. Structure of 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) in the crystal.

2142
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012
Akhmetova et al.
Table 1. Selected bond lengths in compound 4
tained as major heterocyclization products. Only the reꢀ
actions with acetaldehyde and propanal gave 2,4ꢀdialkylꢀ
3ꢀ(2,4ꢀdialkylꢀ1,3ꢀoxazetanꢀ3ꢀyl)ꢀ1,5,3ꢀdithiazepanes 18
and 19 as minor products (5—7%) (GCꢀMS). Apparently,
the synthesis of tetraalkylated 3,3´ꢀbi(1,5,3ꢀdithiazepanes)
is precluded by steric hindrances. At the same time, since
higher aliphatic aldehydes are less electrophilic than formꢀ
aldehyde, the threeꢀcomponent reaction between hydrꢀ
azine, aldehydes, and ethaneꢀ1,2ꢀdithiol proceeds more
slowly and involves several steps. Initially, a nucleophilic
N atom of intermediate aldazine A is attacked by intermeꢀ
diate B or C, probably giving adduct D (Scheme 3). The
alkyl substituents make intermediates B—D less reactive;
consequently, the reaction stops to yield monodithiazꢀ
epanes 14—17.
Bond
d/Å
Bond
d/Å
S(1)—C(1)
S(1)—C(2)
S(2)—C(3)
S(2)—C(4)
S(3)—C(6)
S(3)—C(5)
1.8020(3)
1.8162(4)
1.8102(4)
1.8393(3)
1.8145(4)
1.8395(3)
S(4)—C(8)
S(4)—C(7)
S(1)—C(2)
N(1)—C(4)
N(1)—C(1)
1.8062(3)
1.8167(4)
1.4250(3)
1.4485(3)
1.4603(4)
contains a molecular ion peak with m/z 162 ([M]+) and
characteristic peaks with m/z 101 ([M – CHNN(CH2)2S]+),
92 ([SCH2CH2S]+), 73 ([NNCHS]+), 60 ([NCHS]+),
55 ([CHNNCH2]+), and 27 ([NCH]+).
The formation of 2,4ꢀdialkylꢀ3ꢀalkylideneaminoꢀ1,5,3ꢀ
dithiazepanes 14a and 15—17 was confirmed by IR specꢀ
troscopy, 1H and 13C NMR spectroscopy, and mass
spectrometry. The mass spectra of this homologous series
contain the corresponding molecular ion peaks with
m/z 204, 246, 288, and 330 ([M]+) and characteristic peaks
due to the fragmentation of [M]+. The 13C NMR spectra
of compounds 14a and 15—17 show characteristic signals
for the AlkCH=N— group as well as signals for the diꢀ
thiazepane ring at C 34—36 (S(CH2)2S) and 63—68
(NCH(R)S). According to GCꢀMS data, 3ꢀethylideneꢀ
aminoꢀ2,4ꢀdimethylꢀ1,5,3ꢀdithiazepane (14) was detectꢀ
ed as isomer 14a only, while compounds 15—17 form
three stereoisomers, one of them being dominant (13C and
1H NMR data). For the major stereoisomers of compounds
14—17, we determined the Kovats indices (IK).10
The use of higher aliphatic aldehydes 10—13 (acetꢀ
aldehyde, propanal, butanal, and pentanal) in threeꢀcomꢀ
ponent heterocyclization with hydrazine and ethaneꢀ
1,2ꢀdithiol under optimized conditions (0 C,
N2H4 : RCHO : (CH2SH)2 = 1 : 4 : 2) selectively gives the
corresponding 2,4ꢀdialkylꢀ3ꢀalkylideneaminoꢀ1,5,3ꢀdiꢀ
thiazepanes 14—17 (R = methyl, ethyl, propyl, and butyl;
alkylidene is ethylidene, propylidene, butylidene, and
pentylidene) in 63, 69, 74, and 76% yields, respectively.
Note that this reaction produces dimethyldithiazepane as
the only isomer 14a, while ethyl, propyl, and butyl derivaꢀ
tives 15—17 are mixtures of three stereoisomers (Scheme 2).
Scheme 2
The use of phenylhydrazine (20) and benzylhydrazine
(21) in threeꢀcomponent reactions with ethaneꢀ1,2ꢀdiꢀ
thiol and formaldehyde (or acetaldehyde) leads to 3ꢀaniliꢀ
noꢀ and 3ꢀbenzylaminoꢀ1,5,3ꢀdithiazepanes 22 and 24 or
the corresponding 2,4ꢀdimethylated derivatives 23 and 25,
regardless of the pH of the medium. Higher aliphatic alꢀ
dehydes RCHO (R = Et, Prn, and Bun) under these reacꢀ
tion conditions yield dithio acetals 26—28 and the correꢀ
sponding hydrazones 29—31, probably because of the lowꢀ
er reactivity of aliphatic aldehydes 11—13 (Scheme 4).
1
The H NMR spectrum of compound 22 shows sinꢀ
glets at H 3.08 (—CH2CH2—) and 4.31 (—NCH2S—)
and multiplets at H 6.86—7.28 (Ph). In the 13C NMR
spectrum of compound 22, the signal at C 35.46 is due to
the carbon atoms of the fragment —SCH2CH2S— in the
dithiazepane ring. The mass spectrum of compound 22
contains a molecular ion peak with m/z 226 ([M]+) and
characteristic peaks with m/z 180 ([M – CH2S]+), 118
([C6H5NHNCH]+), 106 ([C6H5NHN]+), 91 ([C6H5N]+),
77 ([C6H5]+), 51 ([CN—NC]+), and 46 ([CH2S]+). The
formation of three diastereomers of 3ꢀanilinoꢀ2,4ꢀdiꢀ
methylꢀ1,5,3ꢀdithiazepane 23 is evident from triple sets
R = Me (10, 14, 18), Et (11, 15, 19), Prn(12, 16), Bun(13, 17)
Attempted synthesis of tetraalkylated 3,3´ꢀbi(1,5,3ꢀ
dithiazepanes) at elevated temperature through involveꢀ
ment of both the amino groups of hydrazine failed under
the chosen reaction conditions. Imines 14—17 were obꢀ
1
of signals in the H and 13C NMR spectra, which remain
unchanged in a temperature range from 20 to 40 C.

Novel 1,5,3ꢀdithiazepanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2143
Scheme 3
R = Me (10, 14), Et (11, 15), Prn (12, 16), Bun (13, 17)
Scheme 4
The Kovats indices were determined for compounds 22
and 23b.
1
In the H NMR spectrum of a mixture of stereoisoꢀ
mers 23a—c, the signal for the ring H(2) and H(4) protons
in the major isomer 23b appears as a quartet at H = 4.51
(J = 6.8 Hz). In the two other isomers 23a,c, these proꢀ
tons are manifested as broadened singlets because of
a rapid (on the NMR time scale) conformational change.
Note that their chemical shifts differ largely (H 4.90 and
4.15, respectively; Fig. 2). According to the integral intenꢀ
sity ratio of the signals, isomers 23a,c are minor products
(23a : 23b : 23c = ~1 : 5 : 1). Therefore, major isomer 23b
in CDCl3 predominantly exists as one conformer, in conꢀ
trast to minor isomers 23a,c, the configurations of which
are described below.
R´ = Ph (20, 22, 23, 29—31), Bz (21, 24, 25); R = H (22, 24),
Me (23, 25), Et (26, 29), Prn (27, 30), Bun (28, 31)
In the 13C NMR spectrum of stereoisomers 23a—c,
the chemical shifts of the signals for the C(2) and C(4)
atoms can easily be differentiated as well. A heteronucleꢀ
ar HSQC experiment gave the following correlations:
Reagents and conditions: i. 20—RCHO (2, 10—13)—(CH2SH)2,
1 : 2 : 1, 0—70 C (pH 3.15—3.20); ii. 20—BuONa—RCHO—
(CH2SH)2, 1 : 2 : 1, 0—70 C (pH 11.50—11.70).
4.495
4.512
H(4.90)  C(67.01), H(4.51)  C(72.26), and H(4.15)
 C(68.10). For each stereoisomer, all signals were asꢀ
signed from heteronuclear spinꢀspin couplings (HMBC)
(see Fig. 2).
For stereochemical identification of compounds 23a—c,
we compared experimental and theoretical data. Conforꢀ
mational analysis of 2,4ꢀsubstituted isomers 23a—c with
axialꢀaxial (aa), axialꢀequatorial (ae), and equatorialꢀ
4.529
4.478
4.152
4.908
5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1

Fig. 2. 1H NMR spectrum of a mixture of isomers 23a—c (the
fragment containing the signals for the H(2) and H(4) protons is
shown only) and heteronuclear HMBC spinꢀspin couplings in
compounds 23a—c.

2144
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012
Akhmetova et al.
equatorial (ee) arrangements of the methyl substituents
was performed using the quantum chemical DFT approach
(B3LYP, 6ꢀ31G(d,p)) (Table 2).
There are three minima on the potential energy surface
for two isomeric structures 23a and 23c which correspond
to the conformations chair F, twist Q, and boat H (Fig. 3).
But there are only two minima for isomer 23b. The
F
Q
global minimum corresponds to the chair conformer F
298
(Grel
= 6.5 kcal mol–1). This makes it evident that
stereoisomer 23b with the diaxially arranged substituents
must incur the conformational shift F Q observed in the
1H and 13C NMR spectra. In addition, the energy barrier
to the forward conformational change is higher (TSFQ
=
= 7.5 kcal mol–1) than the barriers in the other isomers
(TSFQ = 6.7 kcal mol–1 (23a); TSFH = 6.0 kcal mol–1
(23c)). The differences between the G values of the
stereoisomers in their most stable conformations are
H
Fig. 3. Conformers F, Q, and H of compounds 14, 17, and 23.
Grel298(aa—ae) = 2.1 kcal mol–1 and Grel298(aa—ee) =
= 5.5 kcal mol–1 (see Table 2). Therefore, it is isomer 23b
that should be expected to form under thermodynamꢀ
ic control.
Table 2. Relative thermodynamic parameters of the stable conꢀ
formers of compounds 14, 17, and 23 (the lowestꢀenergy rotaꢀ
mers formally derived by rotation about the N—N bond of the
substituent are cited)
Thus, the methyl substituents in stereoisomers 23a and
23c are arranged ae and ee, respectively. This is confirmed
by a moderate upfield shift of the signal for the characterꢀ
istic H(2) and H(4) protons in the heterocycle of stereoꢀ
isomer 23c because of a 1,3ꢀcoupling between the axial
protons in any of its conformers. Based on theoretical and
experimental data, we concluded that aa stereoisomer 23b
in the chair conformation is the major reaction product.
Similar calculations performed for imines 14 and 17
showed that the aa stereoisomer is most stable for
compound 17 as well. However, the energy differences
between the isomers of imine 17 are small (G = 2.2 and
3.2 kcal mol–1, see Table 2) and the integral intensities of
the corresponding signals in the 1H and 13C NMR spectra
are almost equal. As for compound 14, the formation of
the only stereoisomer is probably due to steric hindrances.
Based on our calculations, we identified 3ꢀethylideneꢀ
aminoꢀ2,4ꢀdimethylꢀ1,5,3ꢀdithiazepane as ae stereoꢀ
isomer 14a.
298
Comꢀ Conforꢀ Confiꢀ
pound mation guration /Hartree
E
Grel
for the
G298
for the
conformers isomers
kcal mol–1
14
17
23
14
17
23
14
17
23
F
chair
ае
аа
ее
1180.831408
1180.840919
1180.835589
0
5.9
2.6
0
ае
аа
ее
1337.997151
1337.994537
1337.998869
1.6
0
2.7
0
0
ае
аа
ее
1373.737276
1373.728564
1373.731834
5.7
0
9.6
Q
twist
ае
аа
ее
1180.877092
1180.835316
1180.838171
3.6
0
4.2
2.5
3.2
ае
аа
ее
1337.994865
1337.997097
1337.994524
0
1.6
3.9
Because accessible starting materials and easy syntheꢀ
sis make 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) most promisꢀ
ing for practical application, we studied the fungicidꢀ
al activity of its solution in DMF and waterꢀsoluble
adduct 32 prepared by Nꢀquaternization of compound 4
with MeI.
ае
аа
ее
1373.736679
1373.736767
1373.739866
0
6.5
5.9
2.1
H
boat
ае
аа
ее
1180.847046
1180.841021
1180.841021
9.8
0
6.0
3.4
2.2
Scheme 5
ае
аа
ее
1338.005521
1337.785633
1337.996441
5.7
4.6
0
ае
аа
ее
1373.865347
13.2
—
0
1373.864379
5.5

Novel 1,5,3ꢀdithiazepanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2145
Fungicidal activity was examined in tests with the
microscopic fungi Bipolaris sorokiniana, Fusarium oxyꢀ
sporium, Aspergillus fumigatus, Aspergillus niger, and Paecꢀ
ilomyces variotii, which cause various diseases in crops
(including root rot in cereals and wood11). The mold
species Aspergillus fumigatus and Aspergillus niger are
also common contaminants of various natural and
synthetic materials, which can provoke allergic reacꢀ
tions and mycosis in people with weakened immune
systems.12
above fungi. The effect of a solution of bi(dithiazepane) 4
in DMF on the test cultures is speciesꢀspecific and depenꢀ
dent on the concentration of compound 4. For instance,
compound 4 completely suppresses the growth of Paeciloꢀ
myces variotii in a concentration of 0.13% and inhibits
the growth of the other test cultures in a concentration
range from 0.04 to 0.2% (Table 3).
Waterꢀsoluble adduct 32 proved to be ineffective
against the growth of the test cultures of the microscopic
fungi (Table 4).
First, we tested the solvent (DMF) and revealed no
negative effect on the growth of the test cultures of the
To sum up, 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) has a fungꢀ
istatic effect on Bipolaris sorokiniana, Fusarium oxysporium,
Table 3. Effect of 3,3´ꢀbi(1,5,3ꢀdithiazepane) (4) on the growth of test fungi (incubation period 7 days)a
Test culture
Processes occurring at the concentration of 4 in DMF
0.04%
0.09%
0.13%
0.16%
0.2%
Bipolaris
sorokiniana
Sporogenesis
Growth
inhibition
Growth
suppression,
d = 13.0 2.9
Growth
suppression,
d = 17.3 5.6
Growth
suppression,
d = 21.3 3.1b
Growth
Growth
suppression,
d = 12.8 0.8b
Growth
suppression,
d = 17.8 4.2
No growth
Growth
inhibition
Fusarium
oxysporum
Growth
Growth
inhibition
Growth
suppression,
d = 16.3 7.8c
Growth
suppression,
d = 23.3 4.1c
Growth
suppression,
d = 19.0 2.7b
No growth
suppression,
d = 11.7 3.1c
Growth
suppression,
d = 14.3 3.1
Sporogenesis
Aspergillus
fumigatus
Growth
inhibition
A.niger
Growth
inhibition
No growth
No growth
inhibition
Paecilomyces
variotii
Sporogenesis
Growth
inhibition
No growth
a In a control group, sporogenesis always occurs; d is the diameter of the growth suppression zone.
b Outside the effective area of compound 4, the growth of fungi is inhibited.
c Within the effective area of compound 4, the growth of fungi is inhibited; outside, sporogenesis occurs.
Table 4. Fungicidal activity of aqueous solutions of quaternized 3,3´ꢀbi(1,5,3ꢀdithiazepane) derivative
32 (incubation period 7 days)a
Test culture
Processes occurring at the concentration of adduct 32 in water
0.04%
0.09%
0.13%
0.16%
0.2%
Bipolaris
Sporogenesis
Sporogenesis
Growth
inhibition
Growth
Growth
inhibition
Growth
Growth
inhibition
Growth
suppression,
d = 15.3 1.6c
Sporogenesis
sorokiniana
Fusarium
oxysporum
Sporogenesis
Sporogenesis
inhibition
inhibition
Aspergillus
fumigatus
A.niger
Sporogenesis
Sporogenesis
Sporogenesis
Growth
inhibition
Sporogenesisb
Sporogenesis
Sporogenesis
Sporogenesis
Sporogenesis
Sporogenesis
Sporogenesisb
Sporogenesisb
Paecilomyces
variotii
Sporogenesisb Sporogenesisb
aIn a control group, sporogenesis always occurs.
bThe color of sporeꢀproducing colonies is atypical of this species.
cOutside the effective area of compound 32, typical sporogenesis occurs.

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Akhmetova et al.
Table 5. Crystallographic parameters and the data collecꢀ
tion and refinement statistics for compound 4
Aspergillus fumigatus, and Aspergillus niger and a fungicidal
effect on Paecilomyces variotii.
Parameter
Value
Experimental
Molecular formula
Molecular mass
C8H16N4S4
268.51
1
H and 13C NMR spectra were recorded on a Bruker Avance
T/K
100
Tricl–inic
P1
400 spectrometer (400.13 and 100.62 MHz, respectively) in CDCl3.
IR spectra were recorded on a Specord 75 IR spectrophotometer
(Nujol, KBr). GCꢀMS analysis was carried out on a Finnigan
4021 instrument (glass capillary column 50 000×0.25 mm, HPꢀ5
stationary phase, helium as a carrier gas, programmed temꢀ
perature rise from 50 to 300 C, heating rate 5 deg min–1, inꢀ
jector temperature 280 C, ion source temperature 250 C,
70 eV). Elemental analysis was done on a Carlo Erba 1106 anaꢀ
lyzer. Reaction products were separated by column chromꢀ
atography on SiO2. Thinꢀlayer chromatography was carried
out on Silufol Wꢀ254 plates; spots were visualized with the
iodine vapor.
Crystal system
Space group
Z
a/Å
b/Å
2
6.61880(10)
8.9581(2)
11.0195(2)
68.4428(8)
75.5200(8)
88.4911(10)
586.802(19)
1.520
c/Å
/deg
/deg
/deg
3
V/Å
dcalc/g cm–3
/cm–1
7.73
284
115
91041
An Xꢀray diffraction study of compound 4 was carried out on
a SMART APEX II CCD diffractometer (MoꢀK radiation,
graphite monochromator,  scan mode). The structure was
F(000)
2max/deg
Number of measured
reflections
Number of unique
reflections
Number of reflections
with I < 2(I)
Number of parameters
refined
solved by the direct methods and refined anisotropically on F2
hkl
by the fullꢀmatrix leastꢀsquares method. The hydrogen atoms
were located in the difference electronꢀdensity maps and refined
isotropically. The crystallographic parameters and data collecꢀ
tion and refinement statistics for compound 4 are summarized in
Table 5. All calculations were performed with the SHELXTL
PLUS program package.13
16128
13750
191
Heterocyclization of hydrazine hydrate with aldehydes and
ethaneꢀ1,2ꢀdithiol. A threeꢀnecked flask equipped with a stirrer,
a reflux condenser, and a dropping funnel was maintained at
a given temperature and charged with acetaldehyde, propanal,
butanal, or pentanal (0.2 mol). Ethaneꢀ1,2ꢀdithiol (0.1 or
0.07 mol) was added dropwise with stirring for 3 h to a desired
RCHO : 3 ratio of 2 : 1 or 3 : 2. Then hydrazine hydrate
(0.05 mol) was added dropwise and the reaction mixture was
stirred at a specific temperature (0, 20, 40, or 70 C) for 3.5 h
(see Scheme 1, pathway i). Alternative pathways involved
BuONa—BuOH (1 : BuONa = 1 : 2) (see Scheme 1, pathway
ii), water at 80 C (see Scheme 1, pathway iii), and aqueous 37%
HCl (1 : HCl = 1 : 2) (see Scheme 1, pathway iv). After compleꢀ
tion of the reaction, the mixture was neutralized with HCl (pathꢀ
way ii) or NaOH (pathway iv). The products were extracted with
chloroform, the extracts were dried with CaCl2 and concentratꢀ
ed on a rotary evaporator, and the residues were separated by
R1
wR2
GOOF
Residual electron density
/e Å–3, min/
0.0218
0.0643
1.003
0.667/0.331
max
(70); 60 [NCH2S]+ (40); 57 [N2CH2CH2]+ (100); 45
[NH2NHCH2]+ (20).
3ꢀMethylideneaminoꢀ1,5,3ꢀdithiazepane (6). Yield 49%
1
(pathway iv), Rf 0.54. H NMR (20 C), : 3.32 (s, 4 H, CH2);
4.15 (s, 4 H, CH2); 6.72 (s, 2 H, CH2). 13C NMR, : 35.13;
59.01; 131.00. IK = 1493. MS, m/z (Irel (%)): 162 [M]+ (60); 106
[CH2SCH2CH2S]+ (70); 73 [NNCH2S]+ (25); 60 [NCHS]+
(100); 55 [CHNNCH2]+ (50); 27 [NCH]+ (45).
1,3ꢀDithiolane (7). Yield 30% (pathway iv). The product obꢀ
tained is identical with 1,3ꢀdithiolane described earlier.14 MS,
m/z (Irel (%)): 106 [M]+ (95); 78 [SCH2S]+ (56); 60 [CH2CH2S]+
(94); 45 [CHS]+ (100).
1,4ꢀDithiane (8). Yield 9% (pathway iv). The product obꢀ
tained is identical with 1,4ꢀdithiane described earlier.15 MS, m/z
(Irel (%)): 120 [M]+ (80); 92 [SCH2CH2S]+ (20); 60 [CH2CH2S]+
(40); 45 [CHS]+ (60).
1,3,6,8ꢀTetrathiecane (9). Yield 12% (pathway iv). MS, m/z
(Irel (%)): 212 [M]+ (80); 106 [CH2SCH2CH2S]+ (70); 92
[SCH2CH2S]+ (35); 60 [CH2CH2S]+ (100); 45 [CHS]+ (60).
3ꢀEthylideneaminoꢀ2,4ꢀdimethylꢀ1,5,3ꢀdithiazepane (14a).
Light yellow oil, yield 63% (pathway i). 1H NMR (20 C), : 1.42
(s, 6 H, Me); 1.89 (m, 3 H, Me); 2.88 (m, 4 H, CH2); 4.85 (m, 2 H,
CH); 7.12 (m, H, CHAr). 13C NMR, : 19.14; 22.06; 35.61;
63.27; 146.02. IK = 1560. MS, m/z (Irel (%)): 204 [M]+ (40);
column chromatography on SiO2 (C6H6—AcOEt—CHCl3
=
= 5 : 1 : 1 (for compounds 5 and 6)).
3,3´ꢀBi(1,5,3ꢀdithiazepane) (4). Yield 81 (pathway i) and
79% (pathway ii). Colorless crystals, Rf 0.55 (CHCl3), m.p.
121—122 C. 1H NMR (20 C), : 2.94 (s, 8 H, CH2); 4.55
(s, 8 H, CH2). 13C NMR, : 37.84; 56.18. IK = 2526. MS, m/z
(Irel (%)): 268 [M]+ (40); 162 [CH2N2CH2CH2SCH2CH2S]+
(70); 106 [CH2SCH2CH2S]+ (100); 92 [SCH2CH2S]+ (15);
60 [NCH2S]+ (35); 57 [N2CH2CH2]+ (12); 42 [CH2NCH2]+ (12).
Found (%): C, 35.50; H, 5.43; N, 10.24; S, 47.48. C8H16N2S4.
Calculated (%): C, 35.79; H, 6.01; N, 10.43; S, 47.77.
3ꢀAminoꢀ1,5,3ꢀdithiazepane (5). Yield 37% (pathway iii),
1
Rf 0.75. H NMR (20 C), : 2.87 (s, 4 H, CH2); 3.61 (s, 2 H,
NH2); 4.67 (s, 4 H, CH2). 13C NMR, : 31.61; 65.85. MS, m/z
(Irel (%)): 149 [M – H]+ (50); 105 [NH2NHCH2SCH2CH2]+

Novel 1,5,3ꢀdithiazepanes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2147
162 [NCH(CH3)SCH2CH2S CH(CH3)]+ (13); 120
[CH(CH3)SCH2CH2S]+ (35); 105 [CHSCH2CH2S]+ (100); 92
[SCH2CH2S]+ (30); 69 [CH3CHNNCH]+ (52); 59 [NCHS]+
(57); 57 [N2CH2CH2]+ (12); 45 [CHS]+ (40); 42 [CH3NCH]+
(72). Found (%): C, 46.92; H, 7.56; N, 13.69; S, 31.24. C8H16N2S2.
Calculated (%): C, 47.02; H, 7.89; N, 13.71; S, 31.38.
flask equipped with a stirrer, a reflux condenser, and a dropping
funnel was maintained at a given temperature and charged with
formaldehyde, acetaldehyde, propanal, butanal, and pentanal
(0.1 mol). Ethaneꢀ1,2ꢀdithiol (0.05 mol) was added dropwise
with stirring for 3 h to a desired RCHO : 3 ratio of 2 : 1. Then
phenylhydrazine or benzylhydrazine (0.05 mol) was added dropꢀ
wise and the reaction mixture was stirred at a specific temperaꢀ
ture (0, 20, 40, or 70 C) for 3.5 h (see Scheme 4, pathway i). An
alternative pathway involved BuONa—BuOH (20 : BuONa =
= 1 : 2) (see Scheme 4, pathway ii). After completion of
the reaction, the mixture was neutralized with HCl (pathꢀ
way ii). The products were extracted with chloroform, the
extracts were dried with CaCl2 and concentrated on a rotary
2,4ꢀDiethylꢀ3ꢀpropylideneaminoꢀ1,5,3ꢀdithiazepanes (15a—c)
(5 : 1 : 1). Light yellow oil, yield 69% (pathway i). 1H NMR
(20 C), : 0.94 (t, 6 H, Me, 3J = 7.5 Hz); 1.03 (t, 3 H, Me,
3J = 7.5 Hz); 1.66 (sextet, 2 H each, CH2a, J = 7.2 Hz (15b,c));
1.72 (sextet, 2 H, CH2a, J = 7.5 Hz (15a)); 1.81 (sextet, 2 H each,
CH2b, J = 7.2 Hz (15b,c)); 2.01 (sextet, 2 H, CH2b, J = 7.5 Hz
(15a)); 2.24 (m, 2 H, CH2); 2.82—2.97 (m, 4 H, CH2); 4.76 (t, 4 H,
CH2(2), CH2(4), J = 6.2 Hz); 6.90 (t, H, CHAr
13C NMR, : 11.48; 11.58; 26.64; 28.54; 34.78; 68.32 (15b);
74.26 (15a); 72.12 (15c); 143.18 (15b); 147.00 (15a,c). IK
,
3J = 5.0 Hz).
evaporator, and the residues were separated by column chromaꢀ
tography on SiO2 (C6H6—AcOEt—CHCl3 = 5 : 1 : 1 (comꢀ
pounds 29—31)).
=
= 1776 (15a). 15a. MS, m/z (Irel (%)): 246 [M]+ (5); 190
[NCH(C2H5)SCH2CH2SCH(C2H5)]+ (7); 134 [CH(C2H5)ꢀ
SCH2CH2S]+ (23); 112 [CH3CH2CHNNCH(C2H5)]+ (25); 105
[CHSCH2CH2S]+ (100); 83 [CH3CH2CH2NNCH]+ (60); 56
[CH3CH2CHN]+ (30); 45 [CHS]+ (22); 41 [CH2CH2CH]+ (41).
3ꢀButylideneaminoꢀ2,4ꢀdipropylꢀ1,5,3ꢀdithiazepane (16a).
Light yellow oil, yield 74% (pathway i). 1H NMR (20 C),
: 0.81—0.90 (m, 9 H, Me); 1.28—1.62 (m, 6 H, CH2); 2.63—2.65
(m, 4 H, CH2); 2.65—2.79 (m, 2 H, CH2); 3.50—3.70 (m, 4 H,
CH2); 4.70—4.80 (m, 4 H, CH2); 6.85 (m, H, CHAr). 13C NMR,
: 13.63; 13.77; 20.06; 20.56; 28.66; 34.62; 37.57; 66.23; 141.77.
IK = 1996. MS, m/z (Irel (%)): 288 [M]+ (3); 148 [CH(C3H7)Sꢀ
CH2CH2S)]+ (20); 105 [CHSCH2CH2S]+ (100); 97 [CH3CH2ꢀ
CH2CHNNCH]+ (50); 70 [CH3CH2 CH2CHN]+ (18); 55
[CH3CH2 CH2C]+ (45); 43 [CH2CH2CH2]+ (30). Found (%):
C, 58.07; H, 9.63; N, 9.59; S, 22.11. C14H28N2S2. Calculatꢀ
ed (%): C, 58.28; H, 9.78; N, 9.71; S, 22.23.
2,4ꢀDibutylꢀ3ꢀpentylideneaminoꢀ1,5,3ꢀdithiazepanes (17a—c)
(Faa). Light yellow oil, yield 76% (pathway i). 1H NMR (20 C),
: 1.61—1.67 (m, 9 H, Me); 2.42—2.61 (m, 18 H, CH2); 4.72
(t, 2 H, CH2, J = 6.2 Hz (17b)); 4.79—4.82 (t, 2 H each, CH2
(17a,c)); 6.41—6.42 (m, H, CHAr). 13C NMR, : 18.62; 20.26;
24.48; 25.26; 28.57; 31.32; 33.80; 34.82; 67.95 (17b); 74.08 (17a);
73.32 (17c); 131.85 (17b); 131.91 (17a); 131.81 (17c). IK = 2258
(17a). 17a. MS, m/z (Irel (%)): 330 [M]+ (3); 162 [CH(C4H9)Sꢀ
CH2CH2S)]+ (20); 111 [CH3CH2CH2CH2CHNNCH]+ (35);
105 [CHSCH2CH2S]+ (100); 84 [CH3CH2CH2CH2CHN]+
(26); 69 [CH3CH2CH2CH2C]+ (30); 56 [CH3CH2CH2CH2]+
(19); 43 [CH2CH2CH2]+ (28).
3ꢀ(2,4ꢀDimethylꢀ1,3ꢀoxazetanꢀ3ꢀyl)ꢀ2,4ꢀdimethylꢀ1,5,3ꢀ
dithiazepane (18) (pathway i). MS, m/z (Irel (%)): 248 [M]+ (40);
162 [NCH(CH3)SCH2CH2SCH(CH3)]+ (15); 120 [CH(CH3)Sꢀ
CH2CH2S]+ (37); 105 [CHSCH2CH2S]+ (100); 92 [SCH2CH2S]+
(32); 86 [NCH(CH3)OCH(CH3)]+ (32); 69 [CH3CHNNCH]+
(54); 59 [NCHS]+ (57); 57 [N2CH2CH2]+ (12); 45 [CHS]+ (40);
42 [CH3NCH]+ (72).
3ꢀ(2,4ꢀDiethylꢀ1,3ꢀoxazetanꢀ3ꢀyl)ꢀ2,4ꢀdiethylꢀ1,5,3ꢀdithiazeꢀ
pane (19) (pathway i). MS, m/z (Irel (%)): 304 [M]+ (5); 190
[NCH(C2H5)SCH2CH2SCH(C2H5)]+ (5); 134 [CH(C2H5)ꢀ
SCH2CH2S]+ (21); 115 [NCH(C2H5)OCH(C2H5)]+ (31); 112
[CH3CH2CHNNCH(C2H5)]+ (23); 105 [CHSCH2CH2S]+ (100);
83 [CH3CH2CH2NNCH]+ (58); 56 [CH3CH2CHN]+ (28);
45 [CHS]+ (20); 41 [CH2CH2CH]+ (39).
3ꢀAnilinoꢀ1,5,3ꢀdithiazepane (22). Light yellow oil, yield 87
(pathway i) and 66% (pathway ii). 1H NMR (20 C), : 3.08 (s, 4 H,
CH2); 4.31 (s, 4 H, CH2); 6.18 (s, H, NH); 6.96 (d, 4 H, CH2,
J = 8 Hz); 6.88 (t, 2 H, CH2, J1 = 7.6 Hz, J2 = 7.2 Hz); 7.26
(t, 4 H, CH2, J1 = 7.6 Hz, J2 = 8 Hz). 13C NMR, : 35.46; 61.19;
114.51; 120.15; 129.35; 146.02. IK = 2118. MS, m/z (Irel (%)):
226 [M]+ (60); 147 [NNCH2SCH2CH2SCH]+ (50); 120
[NCH2SCH2CH2S]+ (100); 106 [C6H5NHN]+ (15); 91
[C6H5N]+ (35); 77 [C6H5]+ (23); 75 [NHNCH2S]+ (25); 60
[NCH2S]+ (25); 46 [CH2S]+ (10). Found (%): C, 52.94; H, 6.16;
N, 12.24; S, 28.18. C10H14N2S2. Calculated (%): C, 53.06;
H, 6.23; N, 12.38; S, 28.33.
3ꢀAnilinoꢀ2,4ꢀdimethylꢀ1,5,3ꢀdithiazepanes (23a—c). Orange
oil, yield 75 (pathway i) and 73% (pathway ii). 1H NMR (20 C),
: 1.45 (d, 6 H, Me, J = 6.8 Hz); 3.02—3.18 (m, 4 H, CH2); 4.51
(q, 2 H, CH, 2J = 6.8 Hz (23b)); 4.90 (br.s, 2 H, CH2 (23a));
4.15 (br.s, 2 H, CH2 (23c)); 6.03 (s, H, NH (23b)); 5.76 (s, H,
NH (23a,c)); 6.91—6.94 (m, 3 H, CHAr (23b)); 6.75—6.89
(m, 3 H each, CHAr (23a,c)); 7.19—7.29 (m, 2 H, CHAr).
13C NMR, : 21.59; 34.47; 72.26 (23b); 67.10 (23a); 68.10 (23c);
112.33; 118.22; 129.13 (23b); 129.25 (23a,c); 150.44 (23b); 148.32
(23a,c). IK = 2144 (23a). MS, m/z (Irel (%)): 254 [M]+ (8); 161
[NCH(CH3)SCH2CH2SCHCH2]+ (25); 134 [NCH(CH3)Sꢀ
CH2CH2S]+ (100); 106 [C6H5NN]+ (25); 78 [C6H6]+ (5); 60
[NCH2S]+ (10).
3ꢀBenzylaminoꢀ1,5,3ꢀdithiazepane (24). Light yellow oil,
yield 77 (pathway i) and 69% (pathway ii). 1H NMR (20 C),
: 2.51 (s, 4 H, CH2); 3.52 (s, 2 H, CH2); 4.71 (s, 4 H, CH2); 6.15
(br.s, 1 H, NH); 7.09—7.24 (m, 5 H, CHAr). 13C NMR, : 37.35;
53.80; 59.15; 122.24; 125.41; 127.97; 141.65. Found (%): C, 54.33;
H, 6.13; N, 11.09; S, 26.57. C11H16N2S2. Calculated (%):
C, 54.96; H, 6.71; N, 11.65; S, 26.68.
3ꢀBenzylaminoꢀ2,4ꢀdimethylꢀ1,5,3ꢀdithiazepane (25). Light
yellow oil, yield 69 (pathway i) and 63% (pathway ii). 1H NMR
(20 C), : 1.43 (br.s, 6 H, Me); 2.67 (s, 4 H, CH2); 3.99 (s, 2 H,
CH2); 4.23 (m, 4 H, CH2); 6.35 (br.s, 1 H, NH); 7.11—7.33
(m, 5 H, CHAr). 13C NMR, : 22.55; 34.76; 53.82; 61.15; 121.77;
124.39; 126.37; 142.24. Found (%): C, 58.01; H, 7.35; N, 10.22;
S, 23.61. C13H20N2S2. Calculated (%): C, 58.16; H, 7.51;
N, 10.44; S, 23.89.
2ꢀEthylꢀ1,3ꢀdithiolane (26). Yield 35% (pathway i). The
product obtained is identical with 2ꢀethylꢀ1,3ꢀdithiolane deꢀ
scribed earlier.16 MS, m/z (Irel (%)): 134 [M]+ (70); 105 [CHSꢀ
CH2CH2S]+ (100); 74 [CH3CH2CHS]+ (10); 59 [CHSCH2]+
(20); 45 [CHS]+ (65).
Heterocyclization of phenylꢀ and benzylhydrazines with aldeꢀ
hydes and ethaneꢀ1,2ꢀdithiol (general procedure). A threeꢀnecked

2148
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012
Akhmetova et al.
2ꢀPropylꢀ1,3ꢀdithiolane (27). Yield 27% (pathway i). The
product obtained is identical with 2ꢀpropylꢀ1,3ꢀdithiolane deꢀ
scribed earlier.16 MS, m/z (Irel (%)): 148 [M]+ (50); 105 [CHSꢀ
CH2CH2S]+ (100); 77 [SCHS]+ (10); 55 [CH2CH2CH2CH]+
(25); 45 [CHS]+ (35).
2ꢀButylꢀ1,3ꢀdithiolane (28). Yield 10% (pathway i). The
product obtained is identical with 2ꢀbutylꢀ1,3ꢀdithiolane
described earlier.16 MS, m/z (Irel (%)): 162 [M]+ (20); 105
[CHSCH2CH2S]+ (100); 69 [CH2CH2CH2CH2CH]+ (10); 61
[SCH2CH2]+ (20); 45 [CHS]+ (15).
References
1. N. P. Neureiter, J. Am. Chem. Soc., 1959, 81, 2910.
2. V. R. Akhmetova, R. A. Vagapov, G. R. Nadyrgulova, T. V.
Tyumkina, Z. A. Starikova, M. Yu. Antipin, R. V. Kunaꢀ
kova, U. M. Dzhemilev, Tetrahedron, 2007, 63, 11702.
3. M. R. Stillings, A. P. Welbourn, D. J. Walter, J. Med. Chem.,
1986, 29, 2280.
4. M. Kidwai, N. Negi, S. R. Chaudhary, Acta Pharm., 1995,
45, 511.
Propanal Nꢀphenylhydrazone (29). Yield 60% (pathway i),
Rf 0.35. The product obtained is identical with propanal Nꢀphenꢀ
ylhydrazone described earlier.17 1H NMR (20 C), : 1.14 (m, 3 H,
Me); 1.98 (m, 2 H, CH2); 3.15 (s, 1 H, NH); 6.79—7.31 (m, 5 H,
CHAr). 13C NMR, : 10.77; 28.13; 113.68; 119.12; 129.20; 147.50;
149.81. MS, m/z (Irel (%)): 148 [M]+ (100); 119 [C6H5NHNCH]+
(15); 106 [C6H5NHN]+ (15); 92 [C6H5NH]+ (80); 77 [C6H5]+
(30); 41 [CHCH2CH2]+ (10).
Butanal Nꢀphenylhydrazone (30). Yield 70% (pathway i),
Rf 0.30. The product obtained is identical with butanal Nꢀphenꢀ
ylhydrazone described earlier.17 1H NMR (20 C), : 1.02
(m, 3 H, Me); 1.61 (m, 2 H, CH2); 2.33 (m, 2 H, CH2); 6.03
(m, 1 H, CH); 6.21 (s, 1 H, NH); 6.83—7.31 (m, 5 H, CHAr).
13C NMR, : 13.92; 21.19; 34.53; 113.68; 112.93; 118.20;
129.25; 147.40; 149.85. MS, m/z (Irel (%)): 162 [M]+ (100); 133
[C6H5NHNCHCH2]+ (30); 119 [C6H5NHNCH]+ (15); 106
[C6H5NHN]+ (45); 92 [C6H5NH]+ (95); 77 [C6H5]+ (50); 41
[CHCH2CH2]+ (10).
Pentanal Nꢀphenylhydrazone (31). Yield 90% (pathway i),
Rf 0.27. The product obtained is identical with pentanal Nꢀpheꢀ
nylhydrazone described earlier.17 1H NMR (20 C), : 0.92
(m, 3 H, Me); 1.53 (m, 2 H, CH2); 2.29 (m, 2 H, CH2); 6.00
(m, 1 H, CH); 6.15 (s, 1 H, NH); 6.79—7.26 (m, 5 H, CHAr).
13C NMR, : 13.22; 21.89; 25.89; 33.94; 116.78; 121.12;
126.55; 147.37; 149.07. MS, m/z (Irel (%)): 176 [M]+ (80); 147
[C6H5NHNCHCH2CH2]+ (10); 133 [C6H5NHNCHCH2]+
(60); 119 [C6H5NHNCH]+ (50); 106 [C6H5NHN]+ (50); 92
[C6H5NH]+ (100); 77 [C6H5]+ (50); 41 [CHCH2CH2]+ (10).
3ꢀ(1,5,3ꢀDithiazepanꢀ3ꢀyl)ꢀ3ꢀmethylꢀ1,5,3ꢀdithiazepanium
iodide (32). A flask equipped with a mechanical stirrer was
charged with 3,3´ꢀbi(1,5,3ꢀdithiazepane) 4 (10 mmol) in CHCl3.
Iodomethane (10 mmol) was added and the reaction mixture
was stirred at ~20 C for 6 h. Then water (5 mL) was added. The
aqueous phase was concentrated to give compound 32. On coolꢀ
ing, it was recrystallized from water. The yield was 88%. 1H NMR
(20 C), : 2.50 (s, 3 H, Me); 2.94 (s, 8 H, CH2); 4.55 (s, 8 H,
CH2). 13C NMR, : 15.01; 37.84; 56.18. Calculated (%):
C, 26.34; H, 4.67; N, 6.83; S, 31.24; I, 30.92. C9H19N2S4I.
Found (%): C, 26.16; H, 4.43; N, 6.24; S, 31.20; I, 30.92.
5. N. A. Tyukavkina, S. E. Zurabyan, V. L. Beloborodov, Orgaꢀ
nicheskaya khimiya [Organic Chemistry], Drofa, Moscow,
2008, p. 66 (in Russian).
6. V. I. Dronov, R. F. Nigmatullina, L. M. Khalilov, Yu. E.
Nikitin, Zh. Org. Khim., 1979, 15, 1709 [J. Org. Chem. USSR
(Engl. Transl.), 1979, 15].
7. V. R. Akhmetova, G. R. Khabibullina, E. B. Rakhimova,
R. A. Vagapov, R. R. Khairullina, Z. T. Niatshina, N. N.
Murzakova, Mol. Divers., 2010, 14, 463 (Published online:
10.1007 Is 11030ꢀ010ꢀ9248ꢀ3).
8. V. R. Akhmetova, G. R. Nadyrgulova, N. N. Murzakova,
Z. A. Starikova, M. Yu. Antipin, R. V. Kunakova, Russ. Chem.
Bull. (Int. Ed.), 2009, 58, 1091 [Izv. Akad. Nauk, Ser. Khim.,
2009, 1063].
9. J. B. Hendrikson, J. Am. Chem. Soc., 1961, 83, 4537.
10. M. S. Vigdergauz, L. V. Semenchenko, V. A. Ezrets, Yu. N.
Bogoslovskii, Kachestvennyi gazokhromatograficheskii analiz
[Qualitative Gas Chromatography Analysis], Nauka, Moscow,
1978, 244 pp. (in Russian).
11. V. I. Bilai, Mikroorganizmy — vozbuditeli boleznei rastenii
[Plant Pathogens], Naukova Dumka, Kiev, 1988, p. 552.
(in Russian).
12. D. Satton, A. Fothergill, M. Rinaldi, Guide to Clinically Sigꢀ
nificant Fungi, Williams and Wilkins, Baltimore, 1998, 471 pp.
13. G. M. Sheldrick, SHELXTL Plus, PC Version, a. System of
Computer Programs for the Determination of Crystal Structure
from Xꢀray Diffraction Data, Rev. 502, Siemens Analytical
XꢀRay Instruments Inc., Germany, 1994.
14. D. T. Gibson, J. Org. Chem., 1969, 34, 473.
15. H. J.ꢀM. Dou, M. Ludwikow, P. Hassanaly, J. Kister,
J. Metzger, J. Heterocycl. Chem., 1980, 13, 393.
16. A. R. Hajipour, A. Zarei, L. Khazdooz, S. A. Pourmousavi,
S. Zahmatkesh, A. E. Ruoho, J. Sulfur Chem., 2004, 25, 389.
17. A. N. Kost, I. I. Grandberg, Usp. Khim., 1959, 922 [Russ.
Chem. Rev. (Engl. Transl.), 1959, 28].
This work was financially supported by the Division of
Chemistry and Materials Science of the Russian Academy
of Sciences (Program No. 7, 2011).
Received April 7, 2011;
in revised form July 3, 2012