Cyclothiomethylation of carboxylic acid hydrazides with aldehydes and H2S

Article abstract of DOI:10.1007/s11172-010-0096-1

The cyclothiomethylation of carboxylic acid hydrazides RCONHNH₂ (R = C₅H₄N, Ph, 2-MeOC₆H₄, or 4-HOC₆H₄CH₂) with formaldehyde and H ₂S at 70 °C affords predo

Full text of DOI:10.1007/s11172-010-0096-1

Russian Chemical Bulletin, International Edition, Vol. 59, No. 2, pp. 425—433, February, 2010
425
Cyclothiomethylation of carboxylic acid hydrazides
with aldehydes and H2S
V. R. Akhmetova,a R. R. Khairullina,a T. V. Tyumkina,a Yu. V. Nelyubina,b A. F. Smol´yakov,b
I. S. Bushmarinov,b Z. A. Starikova,b M. F. Abdullin,c and R. V. Kunakovad
aInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences,
141 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347 2) 84 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
cInstitute of Organic Chemistry, Ufa Research Center of the Russian Academy of Sciences,
71 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347 2) 35 6066. Eꢀmail: elmolek@anrb.ru
dUfa State Academy of Economy and Service,
145 ul. Chernyshevskogo, 450077 Ufa, Russian Federation.
Fax: +7 (347 2) 52 0806. Eꢀmail: nis_utis@bashnet.ru
The cyclothiomethylation of carboxylic acid hydrazides RCONHNH2 (R = C5H4N, Ph,
2ꢀMeOC6H4, or 4ꢀHOC6H4CH2) with formaldehyde and H2S at 70 °C affords predominantly the
–
corresponding Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)amides, whereas this reaction at 0— 50 °C gives a
mixture of the latter compounds with 3ꢀacylꢀ1,3,4ꢀthiadiazolidines. Nꢀ(1,3,5ꢀDithiazinanꢀ5ꢀyl)ꢀ
amides were selectively synthesized by the reaction of carboxylic acid hydrazides with formalꢀ
dehyde and H2S in the presence of BuONa in BuOH.
Key words: cyclothiomethylation, carboxylic acid hydrazides, 1,3,5ꢀdithiazinanes, 1,3,4ꢀthiaꢀ
diazolidines, formaldehyde, acetaldehyde, hydrogen sulfide, Xꢀray diffraction study.
Cyclic acid amides and hydrazides, including cyclic
peptides, have found use as antibiotics.1,2 Sulfurꢀcontainꢀ
ing cyclic amides exhibit also antituberculosis, radioꢀ
protective, antidepressant, diuretic,3 and antibacterial
properties.2
1,3,4ꢀThiadiazolidine derivatives have antifungal acꢀ
tivity against Candida spp.,4 and substituted 1,3,5ꢀdiꢀ
thiazinanes are effective sorbents for platinum, gold, and
silver.5
Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)amides, we investigated the
condensation of carboxylic acid hydrazides, viz., isonicoꢀ
tinic acid hydrazide (1a), benzhydrazide (1b), oꢀmethoxyꢀ
benzhydrazide (1c), and pꢀhydroxybenzhydrazide (1d),
with the CH2O—H2S thiomethylating mixture(see Ref. 9)
under different conditions, and also investigated the
cyclothioalkylation with acetaldehyde and propionaldehyde
for isonicotinic acid hydrazide 1a.
Previously,6,7 we have described the selective synthesis
of 5ꢀacylꢀ1,3,5ꢀdithiazinanes by the cyclothiomethylation
of carboxamides with CH2O and H2S in aqueous butanol
in the presence of BuONa. By contrast, the cyclothiomeꢀ
thylation of pꢀtoluenesulfonic acid hydrazide with CH2O and
H2S affords a mixture of 1,3,4ꢀthiadiazolidine, 1,3,5ꢀdiꢀ
thiazinane, and 1,5,3,7ꢀdithiadiazaoctane regardless of the
reaction conditions used (pH, the temperature mode).8
Before we started our research, carboxylic acid hydrazides
have not been subjected to cyclothiomethylation with alꢀ
dehydes and H2S.
Results and Discussion
By analogy with sulfonic acid hydrazides,8 carboxylic
acid hydrazides would be expected to undergo heteroꢀ
cyclization with CH2O and H2S at the βꢀnitrogen atom,
as well as at both the αꢀ and βꢀnitrogen atoms of hydrꢀ
azides. Actually, the cyclothiomethylation of isonicotinic
acid hydrazide (1a) affords a mixture of 4ꢀ(isonicotinoyl)ꢀ
1,3,4ꢀthiadiazolidine (2a) and Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀ
yl)isonicotinamide (3a) (Scheme 1, Table 1). It should be
noted that at 0, –10, and –50 °C, the yield of 3ꢀacylꢀ
1,3,4ꢀthiadiazolidine 2a increases, whereas at 70 °C the
reaction produces predominantly Nꢀ(1,3,5ꢀdithiazinꢀ
In the present study, with the aim of performing the
selective synthesis of Nꢀacylꢀ1,3,4ꢀthiadiazolidines and
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 416—424, February, 2010.
1066ꢀ5285/10/5902ꢀ0425 © 2010 Springer Science+Business Media, Inc.

426
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Akhmetova et al.
Scheme 1
R = C5H4N (a), Ph (b), 2ꢀMeOC6H4 (c), 4ꢀHOC6H4CH2 (d)
anyl)amide 3a. However, the cyclothiomethylation of benzꢀ
hydrazide (1b) in the temperature range of 0—70 °C gives
Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)benzamide (3b) as the major
product, whereas the cyclothiomethylation of oꢀmethoxyꢀ
benzhydrazide (1c) and pꢀhydroxybenzhydrazide (1d)
yields mixtures of the corresponding 3ꢀacylꢀ1,3,4ꢀthiadiꢀ
azolidines 2c,d and Nꢀ(1,3,5ꢀdithiazinanyl)amides 3c,d
(see Scheme 1 and Table 1). A change in the order of
mixing of the reagents (the reaction of 1a with CH2O)
results in the formation of imine 4 (90%), and the subseꢀ
quent bubbling of H2S (20 °C) through a mixture of imine
4 and CH2O affords a mixture of compounds 2a and 3a in
a ratio of 2 : 3.
Previously, the reaction temperature,10 as well as the
nature and the arrangement of the substituents in the aroꢀ
matic rings of anilines,11,12 have been found to have
a similar effect on the cyclothiomethylation pathway.
Therefore, the heterocyclization of carboxylic acid
hydrazides 1a—d with CH2O and H2S involves two comꢀ
petitive reactions. One reaction occurs at both N atoms of
the hydrazide group and affords 1,3,4ꢀthiadiazolidines 2,
whereas another reaction proceeds with the involvement
of the NH2 group of the hydrazide moiety and gives 1,3,5ꢀdiꢀ
thiazinanes 3, the pathway of cyclothiomethylation being
dependent on the nature of the solvent and the reaction
temperature.
It should be noted that, in some cases, this reaction
under reflux conditions in ethanol (70—80 °C) occurs with
a higher selectivity. Thus, isonicotinic acid hydrazide (1a)
and benzhydrazide (1b) were selectively transformed into
the corresponding dithiazinanes 3a,b (see Table 1).
Compounds 2a—d and 3a—d were separated by colꢀ
umn chromatography on silica gel.
In the 13C NMR spectra of thiadiazolidines 2a,c,d, the
signals for the carbon atoms of the rings are magnetically
nonequivalent. The 2D HMBC spectra show crossꢀpeaks
corresponding to the C(2)—H(5) (C(5)—H(2)) coupling.
1
The H NMR spectra have, in addition to the signals of
Table 1. Influence of the temperature and the nature of the
reaction medium on the yield and the composition of the cyꢀ
clothiomethylation products of acid hydrazides 1a—d with CH2O
and H2S
the rings and the aromatic substituent, signals for the proꢀ
tons of the secondary amino group of 1,3,4ꢀthiadiazoꢀ
lidines (δ 9.33—10.54).
The mass spectra of compounds 2a—d and 3a—d conꢀ
tain the corresponding molecular ion peaks [M]+ and peaks
of fragmentation ions produced by the successive eliminaꢀ
tion of CH2S and CH2SCH2S fragments from [M]+.
The structures of 1,3,5ꢀdithiazinanes 3a—d were esꢀ
Hydrꢀ
azide
T/°C
Medium
Yield (%)
2
3
1a
–50
–10
0
70
70
–10
0
70
70
–10
0
70
70
–10
0
H2O
H2O
H2O
56
53
44
22
—
21
18
16
—
34
39
18
35
36
37
10
31
22
23
35
58
62
46
55
60
57
47
51
55
48
49
51
61
47
1
tablished by H and 13C NMR spectroscopy and Xꢀray
diffraction. Thus, the signals for the carbon atoms of the
methylene fragments S—CH2—S and S—CH2—N are obꢀ
served at δ 30.90—33.57 and 53.30—57.86, respectively.
The chemical shifts are similar to those described in the
literature13 for other 1,3,5ꢀdithiazinane derivatives. Analꢀ
ogously, the 1H NMR spectra of compounds 3a—d show
signals for the methylene groups as broadened singlets due
to the rapid heterocyclic ring inversion on the NMR time
scale. The crystal structures of compounds 3a—c were
studied by Xꢀray diffraction (Figs 1—5).
In dithiazinane 3a, the Py—CO—NH fragment is nonꢀ
planar. The dihedral angle between the planes of the pyriꢀ
dine ring and CONH is 35.4°. The dithiazinane ring is
twisted around the N(1)—N(2) bond by 87.5°, i.e., the
H2O
EtOH—H2O
H2O
H2O
H2O
EtOH—H2O
H2O
H2O
H2O
EtOH—H2O
H2O
H2O
H2O
EtOH—H2O
1b
1c
1d
70
70

Cyclothiomethylation of carbohydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
427
a
C(7)
N(3)
O(1)
C(6)
O(2B)
H(1AB)
N(1B)
O(2)
N(1) C(4)
S(2)
C(2)
C(3)
H(1A)
N(1)
C(5)
O(1B)
H(9AC)
O(1AA)
N(2)
O(1)
H(9AA)
N(1A)
C(1)
S(1)
H(9AB)
O(1A)
C(9)
C(8)
C(8)
N(1AA)
H(1AC)
O(2AA)
H(1AA)
O(2A)
b
O(2)
S(1)
Fig. 3. Molecular chains in the crystal structure of 3c.
C(3)
C(4)
C(2)
C(10)
C(9)
(S(2)...H(3), 2.93 Å) hydrogen bonds to form double layꢀ
ers parallel to the ac plane (see Fig. 2).
C(7)
S(2)
C(11)
C(1)
C(5)
C(6)
N(1)
In molecule 3c, the Ph—CO—NH fragment is strongꢀ
ly flattened, as opposed to molecule 3a (the flattening is
associated with the formation of the strong intramolecular
N(1)—H(1N)...O(2)Me hydrogen bond with the methoxy
group (H(1N)...O(2), 2.003 Å)). The similar bond was
found in 18 structures of hydrazones containing the
oꢀmethoxy group14 (H...N, 1.79—2.02 Å). The dithiazinꢀ
ane ring is twisted around the N(1)—N(2) bond line by
92.6° and adopts the conformation identical to that obꢀ
served in 3a. The angles between the bottom of the chair
N(2)
O(1)
Fig. 1. Molecular structures of Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)ꢀ
isonicotinamide (3a) (a) and Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)ꢀoꢀmethꢀ
oxybenzamide (3c) (b) in the crystals (displacement ellipsoids
are drawn at the 50% probability level).
aromatic substituent is in the axial position. The ring
adopts the classical chair conformation slightly flattened
at the N(1) atom (the deviations of the C(2) and N(1)
atoms from the mean plane of the ring are 0.90 and 0.64
Å, respectively). The dihedral angles between the bottom
of the chair (C(1)—S(1)—S(2)—C(3)) and the
N(1)C(1)C(3) and C(2)S(1)S(2) planes are 55.2 and 63.7°,
respectively (see Fig. 1). In the crystal structure, the molꢀ
ecules are linked through the N(2)—H(2N)...N(1)
(H(2N)...N(1), 2.18 Å) and S(2)...H(3)—C(3)
O(1)
C(4)
S(1)
C(2)
C(11)
C(6)
N(2)
C(1)
C(10)
O(2)
C(5)
N(1)
C(3)
C(9)
S(2)
C(7)
C(8)
Fig. 4. Molecular structure of Nꢀ(1,3,5ꢀdithiazinanꢀ5ꢀyl)ꢀpꢀhydrꢀ
oxybenzamide (3d) in the crystal.
a
0
c
S(2A)
O(2B)
S(1)
C(2)
H(2N)
N(2)
H(2OB)
O(1)
S(2)
C(3)
C(1)
N(1)
C(4)
C(5)
C(6)
O(2)
b
H(2O)
Fig. 5. Hydrogen bonds in the crystal structure of 3d.
Fig. 2. Double layers in the crystal packing of 3a.

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Akhmetova et al.
Table 2. Selected bond lengths (d) and torsion angles (τ) in molꢀ
ecules 3а,c,d and 8
(C(1)—S(1)—S(2)—C(3)) and the N(2)C(11)C(9) and
C(10)S(1)S(2) planes are 56.0 and 62.3°, respectively (the
deviations of the C(10) and N(2) atoms from the mean
plane are 0.89 and 0.65 Å, respectively) (see Fig. 1).
In the crystal structure, molecules 3c are linked to
each other through the weak C(9)—H(9a)...O(1) hydroꢀ
gen bonds (H(9a)...O(1), 2.36 Å) to form zigzag chains
running along the a axis (see Fig. 3).
Parameter
3a
3c
3d
8
Bond
d/Å
N—N
1.410(3) 1.406(3) 1.402(2) 1.389(3),
1.384(4),
1.389(3),
The NH—CO group in molecule 3d, unlike those
in 3a,c, has a fixed cis conformation (see Fig. 4).
This is associated with the formation of the strong
O(2)—H(2O)...O(1) (H(2O)...O(1), 1.90 Å) and
N(1)—H(1N)...S(2) (H(1N)...S(2), 2.52 Å) hydrogen
bonds (see Fig. 5). The N(1)N(2)C(4)O(1) group is plaꢀ
nar and orthogonal to the dithiazinane ring (the dihedral
angle is 88.7°). The conformation of the dithiazinane rings
is identical to that in compounds 3a,c. The angles beꢀ
tween the bottom of the chair (C(1)—S(1)—S(2)—C(3))
and the N(1)C(1)C(3) and C(2)S(1)S(2) planes are 55.4
and 63.8°, respectively (the deviations of the C(2) and
N(1) atoms from the mean plane are 0.90 and 0.64 Å,
respectively).
The bond lengths are given in Table 2. As can be seen
from the aboveꢀconsidered data, the molecules have simiꢀ
lar geometric characteristics, which are close to the stanꢀ
dard values.
We found that the reaction of hydrazide 1a with CH2O
and H2S in the presence of HCl (–50—20 °C) occurs with
the involvement of the NH2 group of protonated form 1a.
As a result, 1,3,5ꢀdithiazinane 3a and linear oligomer 5
were obtained after the neutralization of the reaction mixꢀ
ture (NaOH) (Scheme 2, Table 3). Compounds 3a and 5
were separated by column chromatography.
1.397(3)
N—C(=O)
C=O
1.351(4) 1.341(3) 1.341(3) 1.333(4),
1.342(4),
1.326(4),
1.331(4)
1.220(3) 1.217(3) 1.232(3) 1.235(3),
1.231(3),
1.241(3),
1.234(4)
С—S*
1.833(2), 1.826(3), 1.828(2),
1.829(3) 1.824(3) 1.827(2)
1.820(3), 1.812(3), 1.812(2),
1.829(4) 1.800(3) 1.809(2)
—
C—S**
—
Angle
τ/deg
N—N—C—O 0.0(4)
2.5(4)
–5.9(2)
–4.2(5),
–3.9(4),
–1.0(4),
–4.1(4)
* The bottom of the chair.
** The SCH2S fragment.
protons of the S—CH2—S fragment. The mass specꢀ
trum of compound 5 shows a molecular ion peak [M]–
at m/z 378 and a characteristic fragmentation pattern
corresponding to the successive elimination of the
CH2CH2NNHCOC5H4N
(m/z
184)
and
CH2NNHCOC5H4N (m/z 148) fragments.
Scheme 2
Liquid chromatography mass spectrometry (LCMS)
of a mixture of reaction products 3a and 5 also revealed
the cyclic oligomer of formaldehyde and CH2S, viz.,
1,3,5,7,9ꢀoxatetrathiecane 6 (~10%).
The selective cyclothiomethylation
of hydrazides 1a—d to dithiazinylamides
3a—d was carried out with the use of the
CH2O—H2S thiomethylating mixture in
the presence of BuONa in BuOH (see Tabꢀ
le 3) by analogy with the cyclothiomeꢀ
thylation of carboxamides.6,7 The activation of hydrazide
1a with sodium metal in refluxing benzene15 followed by
the thiomethylation with the CH2O—H2S system affords
the mixture 2a + 3a.
Alkylꢀsubstituted nitrogenꢀ and sulfurꢀcontaining hetꢀ
erocyclic systems were synthesized by the cyclothioalkyꢀ
lation of hydrazide 1a with acetaldehyde or propionaldeꢀ
hyde and H2S. Unlike the reactions with CH2O and H2S,
the reaction of 1a with these aldehydes under usual condiꢀ
tions (20 °C in ethanol) produces exceptionally Schiff bases
7 and 8 in 72 and 50% yields, respectively (Scheme 3).
The HMBC spectrum of linear product 5 contains
crossꢀpeaks between the C(10) (C(10´)) atoms and the

Cyclothiomethylation of carbohydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
429
Table 3. Influence of the reaction temperature and the pH of the
reaction mixture on the yield and the composition of the cyꢀ
clothioalkylation products of carboxylic acid hydrazides 1a—d
N(3A)
C(4A)
H(1NA)
C(11A)
C(1A)
C(6A)
C(2A)
C(5A)
N(9A)
Hydrꢀ T
azide /°C hyde
Aldeꢀ
Medium
Reagent
ratio
Yield (%)
2а 3а 5
C(12A)
C(13A)
9
N(10A)
O(8A)
C(7A)
1a
20 CH2O HCl
20 CH2O HCl
–50 CH2O HCl
40 CH2O BuONa/BuOH 1 : 3 : 3
40 MeCHO BuONa/BuOH 1 : 3 : 3
1 : 2 : 1
1 : 2 : 3
1 : 2 : 3
—
—
—
—
—
39 11
56 14
40 12
—
—
—
—
Fig. 6. Molecular structure of N´ꢀ(propylidene)isonicotinic acid
hydrazide (8) (displacement ellipsoids are drawn at the 50% probꢀ
ability level).
68
—
—
— 41
20 CH2O Na/C6H6
1 : 3 : 1
24 35
—
—
—
—
—
—
—
—
1b
1c
1d
40 CH2O BuONa/BuOH 1 : 3 : 3
40 CH2O BuONa/BuOH 1 : 3 : 3
40 CH2O BuONa/BuOH 1 : 3 : 3
—
—
—
57
59
55
tion of two CHCH3SCHCH3 fragments from [M – H]–
(m/z 413) and the successive fragments C5H4NCONCHꢀ
CH3SCHCH3NCHCH3SCHCH3S (m/z 281) and
C5H4NCONCHCH3SCHCH3N (m/z 223) were observed.
The stereoselective synthesis of (cis,cisꢀ2,4,6ꢀtrimethꢀ
ylꢀ1,3,5ꢀdithiazinanꢀ5ꢀyl)isonicotinamide (9) was carried
out in the presence of BuONa/BuOH (pH 11.25) at 40 °C
(see Scheme 3 and Table 3).
The 13C and 1H NMR spectra of compound 9 contain
one set of signals. A comparison of the 13C NMR spectra
of compound 9 with the corresponding data for two stereoꢀ
isomers of 2ꢀmethylꢀ1,3ꢀdithiane16 showed that the meꢀ
thyl group at the C(2) atom in the dithiazinane ring is in
the equatorial position, because its chemical shift (δ 19.72)
agrees well with the corresponding chemical shift (δ 20.80)
of the equatorial methyl group of 2ꢀmethylꢀ1,3ꢀdithiane,
whereas the corresponding resonance of the axial isomer
should appear at much lower field (δ 25.4). It is also
known17 that under these reaction conditions, the
condensation of Nꢀnitrosodimethylamine, acetaldehyde,
and NaSH affords the 2,4,6ꢀcis,cis stereoisomer. Hence,
it can be said with certainty that heterocycle 9 is the stereoꢀ
1
Imines 7 and 8 were identified by H and 13C NMR
spectroscopy. The structure of compound 8 was estabꢀ
lished also by Xꢀray diffraction (Fig. 6).
It should be noted that the Py—CO—NH fragment in
molecule 8 is structurally similar to that in dithiazinane
3a. This fragment is nonplanar; the dihedral angle beꢀ
tween the planes of the pyridine ring and CONH is 32.4°.
The reaction of imine 7 with MeCHO and H2S affords
a mixture of the heterocycles Nꢀ(2,4,6ꢀtrimethylꢀ1,3,5ꢀ
dithiazinanꢀ5ꢀyl)isonicotinamide (9) and 1,1ꢀbis[4ꢀ(isoꢀ
nicotinoylꢀ2,5ꢀdimethylꢀ1,3,4ꢀthiadiazolidinꢀ3ꢀyl)ethylꢀ
sulfanyl]ethane (10) in a ratio of ~5 : 1 both upon refluxꢀ
ing in ethanol and in the presence of BuONa/BuOH (see
Scheme 3).
The liquid chromatography mass spectra show moꢀ
lecular ion peaks [M – H]– at m/z 283 and 591 for
compounds 9 and 10, respectively, and fragmentation
ion peaks. For molecule 10, the characteristic eliminaꢀ
Scheme 3
or
R = Me (7, 9, 10), Et (8)
Reagents and conditions: i. RCHO—H2S (3 : 2), 20 °C, EtOH. ii. RCHO—H2S (3 : 2), EtOH, refluxing. iii. RCHO—H2S (3 : 2),
1) BuONa/BuOH, 2) HCl.

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Akhmetova et al.
benzene (15 mL) were placed into a reactor at room temperaꢀ
ture. The reaction mixture was refluxed with stirring for 2 h and
then divided into two aliquots. Imine 4 was isolated from one
aliquot. Another aliquot was saturated with hydrogen sulfide for
5 h. After bubbling with H2S, the products were extracted with
chloroform and separated by column chromatography on silica
gel (CHCl3—AcOEt—EtOH, 5 : 1 : 1, as the eluent; compounds
2a and 3a).
Cyclothiomethylation of isonicotinic acid hydrazide (1a) with
H2S and CH2O in the presence of the Na/C6H6 system. Isonicoꢀ
tinic acid hydrazide (1a) (1 mol), benzene (20 mL), and sodium
metal (1 mol) were mechanically stirred in a reactor until
a homogeneous creamꢀlike substance was obtained. Then paraꢀ
formaldehyde (1 mol) was added. The mixture was stirred at
70 °C for 3 h, and then hydrogen sulfide was bubbled through the
reaction mixture for 4 h. The benzene was decanted, and a mixꢀ
ture of heterocycles 2a and 3a was isolated from the residue by
extraction with CHCl3.
4ꢀ(Isonicotinoyl)ꢀ1,3,4ꢀthiadiazolidine (2a). The yield was 56%
(method A), m.p. 185—187 °C, Rf 0.35 (CHCl3—AcOEt—EtOH,
5 : 1 : 1). IR, ν/cm–1: 690, 900, 1080, 1270, 1440—1520, 1660,
2900, 3385. 1H NMR (DMSOꢀd6), δ: 4.35 (s, 2 H, C(2)H2); 4.53
(s, 2 H, C(5)H2); 7.64—7.70 (d, 2 H, C(10)H, C(12)H, J = 5.6 Hz);
8.68—8.75 (d, 2 H, C(9)H, C(13)H, J = 5.6 Hz); 10.09 (s, 1 H,
N(3)H). 13C NMR (DMSOꢀd6), δ: 55.5 (t, C(2)); 74.0 (t, C(5));
121.6 (d, C(9), C(11)); 140.8 (d, C(7)); 150.2 (d, C(8), C(12));
163.7 (s, C(6)). MS, m/z (Irel (%)): 196 [M + 1]+ (10); 151
[M – CH2S]+ (100); 120 [M – CH2SCH2NH]+ (15); 106
[M – CH2SCH2NHN]+ (12). Found (%): C, 49.83; H, 4.64;
N, 21.87; S, 16.67. C8H9N3OS. Calculated (%): C, 49.23;
H, 4.62; N, 21.54; S, 16.41.
isomer with the 2,4,6ꢀcis,cis configuration of the methyl
substituents.
To sum up, the cyclothiomethylation of carboxylic acid
hydrazides with aldehydes (CH2O, MeCHO) and H2S in
the presence of BuONa/BuOH (pH 11.25) selectively gives
Nꢀ(1,3,5ꢀdithiazinꢀ5ꢀyl)amides of carboxylic acids in
55—68% yields. 3ꢀAcylꢀ1,3,4ꢀthiadiazolidines were synꢀ
thesized by the reactions of carboxylic acid hydrazides
–
with formaldehyde and H2S at 0— 50 °C in 21—56% yields.
Experimental
Experiments were carried out with the use of the starting
compounds with a purity of 95%. The solvents were purified,
dried, and distilled according to known procedures.18
The 1H and 13C NMR spectra were recorded on a Bruker
Avanceꢀ400 spectrometer operating at 400.13 and 100.62 MHz,
respectively, in DMSOꢀd6 (δ , 39.50) and CDCl3 (δ , 77.10).
C
C
The IR spectra were measured on a Specord 75 IR spectrometer
as Nujol mulls. The LCꢀmassꢀspectrometric analysis of comꢀ
pounds 2b and 3b was carried out on a Finnigan 4021 instrument
(50000×0.25 mm glass capillary column, HPꢀ5 stationary phase,
helium as the carrier gas, temperatureꢀprogrammed from 50 to
300 °C at a rate of 5 deg min–1, the temperature of the vaporizer
was 280 °C, the temperature of the ion source was 250 °C).
Compounds 2a,c,d, 3a,c,d, and 4—10 were analyzed on a Shiꢀ
madzu LCMSꢀ2010 EV instrument by atmospheric pressure
chemical ionization (APCI) mass spectrometry; the maximum
temperature of the APCI probe was 500 °C; the temperature of
the heating source was 200 °C, the temperature of the vaporizer
was 250 °C; nitrogen that was produced by an NM18L ultraꢀhigh
purity nitrogen generator was used as the nebulizing gas; the
liquid flow rate was 0.05 mL min–1, the nebulizing gas flow rate
was 2.5 mL min–1; the ion source voltage was as follows: (+),
4.5 kV; (–), 3 kV.
4ꢀBenzoylꢀ1,3,4ꢀthiadiazolidine (2b). The yield was 21%
(method A), m.p. 223—225 °C, Rf 0.40 (diethyl ether—AcOEt,
5 : 1, as the eluent). IR, ν/cm–1: 670, 1100, 1265, 1360—1450,
1
1620, 1670, 2900, 3315. H NMR (DMSOꢀd6), δ: 4.63 (s, 2 H,
C(5)H2); 5.05 (s, 2 H, C(2)H2); 7.60—7.80 (m, 4 H, Ph); 9.83
(s, 1 H, N(3)H). 13C NMR (DMSOꢀd6), δ: 55.0 (t, C(5)); 73.5
(t, C(2)); 127.7 (d, C(8), C(12)); 128.6 (d, C(9), C(11)); 132.0
(d, C(10)); 132.8 (d, C(7)); 166.2 (s, C(6)). MS, m/z (Irel (%)):
194 [M]+ (2); 149 [M – CH2S]+ (43); 119 [M – CH2SCH2NH]+
(61); 105 [PhCO]+ (100); 45 [CH2S]+ (17). Found (%): C, 56.48;
H, 5.74; N, 14.87; S, 15.97. C9H10N2OS. Calculated (%):
C, 55.65; H, 5.19; N, 14.42; S, 16.51.
4ꢀ(oꢀMethoxybenzoyl)ꢀ1,3,4ꢀthiadiazolidine (2c). The yield was
34% (method A), m.p. 110—112 °C, Rf 0.09 (CHCl3—AcOEt—
—acetone, 10 : 1 : 1, as the eluent). IR, ν/cm–1: 740, 1005, 1165,
1280, 1470—1480, 1595, 1640, 2840, 2950, 3295. 1H NMR
(DMSOꢀd6), δ: 3.65 (br.s, 3 H, C(13)H3); 3.92 (s, 2 H, C(5)H2);
4.25 (s, 2 H, C(2)H2); 7.10—7.95 (m, 4 H, Ph); 9.33 (s, 1 H,
N(3)H). 13C NMR (DMSOꢀd6), δ: 56.0 (s, C(13)); 56.5 (t, C(5));
74.0 (t, C(2)); 112.1 (d, C(12)); 120.8 (d, C(11)); 121.7 (d, C(10));
131.2 (d, C(9)); 133.5 (d, C(8)); 157.5 (d, C(7)); 164.4 (s, C(8)).
MS, m/z (Irel (%)): 225 [M + 1]+ (50); 193 [M – S]+ (10);
180 [M – SCH2]+ (100); 165 [M – SCH2N]+ (20); 136 [M –
– CH2SCH2NNH]+ (10); 93 [M – CH2SCH2NNHCO,Me]+
(15). Found (%): C, 53.58; H, 5.29; N, 14.87; S, 15.18.
C10H12N2O2S. Calculated (%): C, 53.57; H, 5.36; N, 12.50;
S, 14.29.
The elemental analysis was carried out on a Carlo Erba (modꢀ
el 1106) elemental analyzer. The melting points were deterꢀ
mined on a PHMK 80/2617 instrument; the refractive index of
compound 9 was measured on an IRFꢀ22 refractometer; the pH
values of solutions were measured and adjusted using a pHꢀ340
pHꢀmeter.
Cyclothioalkylation of acid hydrazides with aldehydes and H2S
(general procedure). A solution of aldehyde (2 or 3 mol) was
saturated with H2S by bubbling for 30 min until the required
aldehyde : H2S ratio (2 : 1 or 3 : 2) was achieved. Then a solution
of isonicotinic acid hydrazide (1 mol) in water (method A), in
EtOH (method B), in aqueous 37% HCl (1 : HCl = 1 : 3) (methꢀ
od C), or in BuONa/BuOH (1 : BuONa = 1 : 3) (method D) was
added dropwise to the thiomethylating mixture, and the reaction
solution was stirred for 5 h at a specified temperature (–50, –10,
0, 20, or 70 °C). In the method C, the mixture was neutralized
with NaOH; in the method D, with HCl. The reaction products
were extracted with chloroform and separated by column chroꢀ
matography on silica gel (CHCl3—AcOEt—EtOH, 5 : 1 : 1 (2a, 3a),
diethyl ether—AcOEt, 5 : 1 (2b, 3b), CHCl3—AcOEt—acetone,
10 : 1 : 1 (2c, 3c), and CHCl3—AcOEt, 10 : 1 (2d, 3d) as
the eluents).
Cyclothiomethylation of isonicotinic acid hydrazide (1a) with
H2S and CH2O by the reverse mixing procedure. Paraformalꢀ
dehyde (1 mol), isonicotinic acid hydrazide (1a) (1 mol), and
4ꢀ(4ꢀHydroxybenzylcarbonyl)ꢀ1,3,4ꢀthiadiazolidine (2d).
The yield was 36% (method A), m.p. 183—185 °C, Rf 0.15
(CHCl3—AcOEt, 10 : 1, as the eluent). IR, ν/cm–1: 670, 1100,

Cyclothiomethylation of carbohydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
431
1
1265, 1360—1450, 1620, 1670, 2900, 3315. H NMR (DMSOꢀ
130.2 (d, C(10), C(14)); 156.1 (d, C(9)); 168.4 (s, C(8)). MS,
m/z (Irel (%)): 271 [M + 1]+ (49); 179 [M ꢀ SCH2SCH2]+ (100);
151 [M – SCH2SCH2N]+ (9); 107 [M – CH2SCH2SNNCH2]+
(12). Found (%): C, 49.12; H, 5.47; N, 10.39; S, 24.28.
C11H14N2O2S2. Calculated (%): C, 48.86; H, 5.22; N, 10.36;
S, 23.72.
N´ꢀ(Methylidene)isonicotinic acid hydrazide (4). The yield
was 90% (method A), m.p. 156—158 °C, Rf 0.58 (CHCl3—EtOH,
5 : 1, as the eluent). IR, ν/cm–1: 1060, 1160, 1300, 1530, 1650,
2905, 3150, 3250. 1H NMR (DMSOꢀd6), δ: 4.20 (br.s, 2 H,
C(10)H); 7.67 (d, 2 H, C(2)H, C(6)H, J = 5.6 Hz); 8.72 (d, 2 H,
C(3)H, C(5)H, J = 5.6 Hz); 10.33 (s, 1 H, N(8)H). 13C NMR
(DMSOꢀd6), δ: 121.6 (d, C(2), C(6)); 140.60 (d, C(4)); 149.7
(d, C(10)); 150.4 (d, C(3), C(5)); 163.9 (s, C(7)). MS, m/z (Irel (%)):
150 [M]+ (100); 138 [M – CH2]+ (20); 123 [M – CH2N]+ (10).
Found (%): C, 56.11; H, 4.71; N, 27.85. C7H7N3O. Calculatꢀ
ed (%): C, 56.37; H, 4.73; N, 28.17.
d6), δ: 4.56 (s, 1 H, OH(13)); 4.15 (s, 2 H, C(5)H2); 4.81 (s, 2 H,
C(2)H2); 6.71—7.00 (m, 4 H, Ph); 9.35 (s, 1 H, N(3)H).
13C NMR (DMSOꢀd6), δ: 55.9 (t, C(5)); 70.9 (t, C(2)); 115.1
(s, C(9), C(11)); 126.5 (d, C(10)); 130.0 (d, C(8), C(12)); 155.9
(d, C(7)); 169.9 (s, C(6)). MS, m/z (Irel (%)): 224 [M]+ (15); 180
[M – SCH2]+ (100); 150 [M – CH2SCH2NH]+ (11); 135
[M – CH2SCH2NNH]+ (5). Found (%): C, 53.47; H, 5.29.
C10H12N2O2S. Calculated (%): C, 53.55; H, 5.39.
Nꢀ(1,3,5ꢀDithiazinanꢀ5ꢀyl)isonicotinamide (3a). The yield
was 62% (method B), 68% (method D), m.p. 200—202 °C, Rf 0.35
(CHCl3—AcOEt—EtOH, 5 : 1 : 1). IR, ν/cm–1: 700, 1070, 1270,
1460—1540, 1650, 2905, 3390. 1H NMR (DMSOꢀd6), δ: 4.59
(s, 2 H, C(2)H2); 5.06 (s, 4 H, C(4)H2, C(6)H2); 8.12—8.17
(d, 2 H, C(11)H, C(13)H, J = 4.7 Hz); 9.14—9.19 (d, 2 H,
C(10)H, C(14)H, J = 4.7 Hz); 9.74 (s, 1 H, N(7)H). 13C NMR
(DMSOꢀd6), δ: 30.9 (t, C(2)); 57.7 (t, C(4), C(6)); 121.5
(d, C(11), C(13)); 141.2 (d, C(9)); 150.3 (d, C(10), C(14)); 163.2
(s, C(8)). MS, m/z (Irel (%)): 242 [M]+ (5); 150 [M – SCH2SCH2]+
Bis[4ꢀ(isonicotinoylaminohydrazino)methylsulfanyl]methane
(5a). The yield was 14% (method C), Rf 0.05 (CHCl3—AcOEt—
—EtOH, 10 : 1 : 1, as the eluent). IR, ν/cm–1: 740, 1020, 1190,
1280, 1370—1410, 1500, 1590, 1650, 2905, 3280. 1H NMR
(DMSOꢀd6), δ: 3.97 (s, 2 H, C(12)H2); 4.27 (s, 4 H, C(10)H2,
C(10´)H2); 7.49 (s, 1 H, N(9)H, N(9´)H); 7.78 (d, 4 H, C(2)H,
C(2´)H, C(6)H, C(6´)H, J = 4.4 Hz); 8.83 (d, 4 H, C(3)H,
C(3´)H, C(5)H, C(5´)H), J = 4.4 Hz); 9.29 (s, 2 H, N(8)H,
N(8´)H). 13C NMR (DMSOꢀd6), δ: 33.7 (t, C(12));
56.6 (t, C(10), C(10´)); 120.6 (d, C(2), C(2´), C(6), C(6´));
140.9 (d, C(4), C(4´)); 151.5 (d, C(3), C(3´), C(5), C(5´));
162.9 (s, C(7), C(7´)). MS, m/z (Irel (%)): 378 [M]– (50); 184
(100); 122 [M
– –
CH2SCH2SCH2N]+ (13); 108 [M
– CH2SCH2SCH2NHN]+ (6). Found (%): C, 46.18; H, 4.74;
N, 17.97; S, 25.97. C9H11N3OS2. Calculated (%): C, 44.81;
H, 4.56; N, 17.43; S, 26.55.
Nꢀ(1,3,5ꢀDithiazinanꢀ5ꢀyl)benzamide (3b). The yield was
57% (method B), 57% (method D), m.p. 240—242 °C, Rf 0.43
(diethyl ether—AcOEt, 5 : 1, as the eluent). IR, ν/cm–1: 700,
1070, 1250, 1360—1450, 1615, 1670, 2900, 3310. 1H NMR
(DMSOꢀd6), δ: 4.20 (s, 2 H, C(2)H2); 4.66 (s, 4 H, C(4)H2,
C(6)H2); 7.60—7.80 (m, 4 H, Ph); 8.86 (s, 1 H, N(7)H).
13C NMR (DMSOꢀd6), δ: 30.9 (t, C(2)); 58.1 (t, C(4), C(6));
127.3 (d, C(11), C(13)); 128.8 (d, C(10), C(14)); 131.9 (d, C(12));
148.5 (d, C(9)); 155.6 (s, C(8)). MS, m/z (Irel %): 240 [M]+ (25);
162 [M – SCH2S]+ (5); 121 [M – PhCONH]+ (6); 105 [PhCO]+
(100); 45 [CH2S]+ (10). Found (%): C, 49.47; H, 4.99; N, 11.84;
S, 25.37. C10H12N2OS2. Calculated (%): C, 49.97; H, 5.03;
N, 11.66; S, 26.68.
[M
–
–
CH2SCH2NHNHCOC5H4N]– (100); 148 [M
CH2SCH2SCH2NHNHCOC5H4N]– (37). Found (%):
–
C, 48.58; H, 4.54; N, 20.17; S, 17.23. C15H18N6O2S2. Calculatꢀ
ed (%): C, 47.60; H, 4.79; N, 22.21; S, 16.94.
1,3,5,7,9ꢀOxatetrathiecane (6). The yield was 10%. MS,
m/z (Irel (%)): 217 [M]+ (87); 201 [M – CH2]+ (100); 185 [M –
– CH2O]+ (44); 182 [M – S]+ (87); 138 [M – CH2SCH2O]+ (87).
N´ꢀ(Ethylidene)isonicotinic acid hydrazide (7). The yield was
72% (method A), m.p. 150—151 °C, Rf 0.69 (CHCl3—EtOH,
5 : 1, as the eluent). IR, ν/cm–1: 1020, 1120, 1290, 1455—1540,
1610, 1650, 2900, 3050, 3210. 1H NMR (CDCl3), δ: 1.94 (m, 3 H,
C(11)H3); 7.67 (d, 2 H, C(2)H, C(6)H, J = 6.0 Hz); 7.78 (q, 1 H,
C(10)H, J = 5.2 Hz); 8.61 (d, 2 H, C(3)H, C(5)H, J = 6.0 Hz);
10.97 (s, 1 H, N(8)H). 13C NMR (CDCl3), δ: 18.6 (s, C(11));
121.0 (d, C(2), C(6)); 140.4 (d, C(4)); 150.3 (d, C(3), C(5));
150.9 (t, C(10)); 162.7 (s, C(7)). MS, m/z (Irel (%)): 164 [M]+
(100); 138 [M – CH3CH]+ (20); 121 [M – CH3CHN]+ (17);
78 [M – CH3CHNHNCO]+ (8). Found (%): C, 58.18; H, 5.71;
N, 25.97. C8H9N3O. Calculated (%): C, 58.88; H, 5.56; N, 25.75.
N´ꢀ(Propylidene)isonicotinic acid hydrazide (8). The yield was
50% (method A), m.p. 134—135 °C, Rf 0.73 (CHCl3—EtOH,
5 : 1, as the eluent). IR, ν/cm–1: 1000, 1130, 1295, 1450—1530,
1615, 1650, 2905, 3035, 3190. 1H NMR (CDCl3), δ: 1.04 (m, 3 H,
C(12)H3); 2.27 (m, 2 H, C(11)H2); 7.70 (d, 2 H, C(2)H, C(6)H,
J = 4.4 Hz); 7.77 (t, 1 H, C(10)H, J = 5.2 Hz); 8.61 (d, 2 H,
C(3)H, C(5)H, J = 4.4 Hz); 10.06 (s, 1 H, N(8)H). 13C NMR
(CDCl3), δ: 10.6 (s, C(12)); 26.0 (s, C(11)); 121.5 (d, C(2),
C(6)); 140.4 (d, C(4)); 150.3 (d, C(3), C(5)); 156.0 (t, C(10));
162.8 (s, C(7)). MS, m/z (Irel (%)): 178 [M]+ (100); 150
[M – CH3CH2]+ (6); 135 [M – CH3CH2CH]+ (79); 121
[M – CH3CH2CHN]+ (6). Found (%): C, 61.18; H, 6.34;
N, 24.07. C9H11N3O. Calculated (%): C, 61.00; H, 6.26; N, 23.71.
Nꢀ(1,3,5ꢀDithiazinanꢀ5ꢀyl)ꢀoꢀmethoxybenzamide (3c).
The yield was 59% (method D), m.p. 105—107 °C, Rf 0.50
(CHCl3—AcOEt—acetone, 10 : 1 : 1, as the eluent). IR, ν/cm–1
:
740, 1005, 1100, 1265, 1370—1445, 1595, 1640, 2840, 2900,
3340. H NMR (DMSOꢀd6), δ: 3.51 (br.s, 3 H, C(15)H3); 4.05
1
(s, 2 H, C(2)H2); 4.54 (s, 4 H, C(4)H2, C(6)H2); 7.11 (t, 1 H,
C(11)H, J = 7.6 Hz); 7.15 (d, 1 H, C(10)H, J = 8.6 Hz); 7.57
(t, 1 H, C(12)H, J = 7.4 Hz); 7.99 (d, 1 H, C(13)H, J = 7.4 Hz);
10.23 (s, 1 H, N(7)H). 13C NMR (DMSOꢀd6), δ: 30.9 (t, C(2));
56.7 (t, C(4), C(6)); 58.1 (s, C(15)); 112.6 (d, C(13)); 120.5
(d, C(12)); 121.1 (d, C(11)); 131.2 (d, C(14)); 136.1 (d, C(10));
157.1 (d, C(9)); 164.4 (s, C(8)). MS, m/z (Irel (%)): 271 [M + 1]+
(100); 179 [M – SCH2SCH2]+ (72); 151 [M – SCH2SCH2N]+
(8); 135 [M – SCH2SCH2NNH]+ (13). Found (%): C, 49.42;
H, 5.57; N, 10.37; S, 24.28. C11H14N2O2S2. Calculated (%):
C, 48.88; H, 5.19; N, 10.37; S, 23.70.
Nꢀ(1,3,5ꢀDithiazinanꢀ5ꢀyl)ꢀ2ꢀ(hydroxyphenyl)acetamide (3d).
The yield was 55% (method D), m.p. 209—210 °C, Rf 0.52
(CHCl3—AcOEt, 10 : 1, as the eluent). IR, ν/cm–1: 700, 1070,
1250, 1360—1450, 1615, 1670, 2900, 3310. 1H NMR (DMSOꢀd6),
δ: 3.89 (s, 2 H, C(2)H2); 4.44 (s, 4 H, C(4)H2, C(6)H2);
6.63—6.73 (d, 2 H, C(12)H, C(14)H, J = 8.5 Hz); 7.04—7.14
(d, 2 H, C(11)H, C(15)H, J = 8.5 Hz); 8.94 (s, 1 H, N(7)H);
9.26 (s, 1 H, OH(15)). 13C NMR (DMSOꢀd6), δ: 31.2 (t, C(2));
57.9 (t, C(4), C(6)); 115.2 (d, C(11), C(13)); 126.0 (d, C(12));

432
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Akhmetova et al.
Nꢀ(2,4,6ꢀTrimethylꢀ1,3,5ꢀdithiazinanꢀ5ꢀyl)isonicotinamide
CH3SCHCH3SCHCH3]– (24); 190 [M – C5H4NCONCHꢀ
CH3SCHCH3NCHCH3SCHCH3SCHCH3,S]– (29).
20
(9). The yield was 32% (method C), 41% (method D), nD
1.4990, Rf 0.78 (CHCl3—AcOEt—EtOH, 5 : 1 : 1, as the eluent).
IR, ν/cm–1: 700, 1050, 1255, 1450—1510, 1600, 1695, 2935,
3370. 1H NMR (CDCl3), δ: 1.39 (m, 3 H, C(15)H3); 1.64 (m, 6 H,
C(16)H3, C(17)H3); 3.54 (s, 2 H, C(2)H2); 4.28 (s, 4 H, C(4)H2,
C(6)H2); 7.30 (d, 2 H, C(11)H, C(13)H), J = 4.2 Hz); 7.66
(d, 2 H, C(10)H, C(14)H, J = 4.2 Hz); 8.71 (s, 1 H, N(7)H).
13C NMR (CDCl3), δ: 19.5 (s, C(15)); 23.6 (s, C(16), C(17));
44.2 (s, C(2)); 68.9 (s, C(4), C(6)); 121.1 (d, C(11), C(13));
140.2 (d, C(9)); 150.6 (d, C(10), C(14)); 164.9 (s, C(8)). MS,
m/z (Irel (%)): 284 [M + 1]+ (100); 224 [M – CH3CHSCHCH3]+
Xꢀray diffraction study of compounds 3a,c,d and 8. Crystals of
3a were grown by crystallization from a 5 : 1 : 1 CHCl3—AcOEt—
—EtOH mixture; crystals of 3c, by crystallization from a 10 : 1 : 1
CHCl3—AcOEt—acetone mixture; crystals of 3d, by crystallizaꢀ
tion from a 10 : 1 CHCl3—AcOEt mixture; crystals of 8, by
crystallization from a 5 : 1 CHCl3—EtOH mixture.
The Xꢀray diffraction data sets for compounds 3a,c,d and 8
were collected on Bruker SMART CCD Area Detector (3c,d, 8)
and Bruker APEX 2 CCD Area Detector (3a) diffractometers
(MoꢀKα radiation) at 100, 295, 100, and 120 K for compounds
3a,c,d and 8, respectively. For compounds 3a,c,d, semiempiriꢀ
cal absorption corrections were applied; the transmission coeffiꢀ
cients Tmax and Tmin were determined using the SADABS proꢀ
gram.19 The structures were solved by direct methods. All nonꢀ
hydrogen atoms were located in different electron density maps
(5); 164 [M
– –
SCHCH3SCHCH3]+ (25); 107 [M
– CH3CHSCHCH3SCHCH3]+ (7). Found (%): C, 50.52;
H, 6.09; N, 14.57; S, 22.78. C12H17N3OS2. Calculated (%):
C, 50.85; H, 6.05; N, 14.83; S, 22.63.
1,1ꢀBis[4ꢀ(isonicotinoylꢀ2,5ꢀdimethylꢀ1,3,4ꢀthiadiazolidinꢀ3ꢀ
yl)ethylsulfanyl]ethane (10). The yield was 6% (method C). MS,
m/z (Irel (%)): 591 [M – H]– (53); 531 [M – SCHCH3]– (100); 515
[M – CHCH3SCHCH3]– (58); 413 [M – 2 CHCH3SCHCH3]–
(41); 281 [M – C5H4NCONCHCH3SCHCH3NCHCH3SCHꢀ
CH3]– (29); 223 [M – C5H4NCONCHCH3SCHCH3NCHꢀ
and refined based on F 2 with anisotropic displacement paꢀ
hkl
rameters. The hydrogen atoms of the NH and OH groups were
located in difference electron density maps. The H(C) atoms
were positioned geometrically. All hydrogen atoms were refined
using a riding model with U(H) = 1.2U(Ci), where U(X) are the
Table 4. Crystallographic characteristics and the structure refinement statistics for 3a,c,d and 8
Parameter
3a
3c
3d
8
Molecular formula
M
Space group
a/Å
b/Å
C9H11N3OS2
241.33
Pccn
12.083(1)
20.398(2)
9.0115(9)
90
С11H14N2O2S2
270.36
Pbca
C11H14N2O2S2
270.36
P21/c
12.754(3)
7.864(2)
13.496(3)
90
111.675(6)
90
C9H11N3O
177.21
P–1
8.778(1)
12.143(1)
23.483(3)
90
9.893(2)
14.219(2)
15.123(2)
93.022(4)
106.224(3)
109.655(3)
1898.1(5)
8
c/Å
α/deg
β/deg
γ/deg
90
90
90
90
3
V/Å
2221.1(4)
8
1.443
2502.9(5)
8
1.435
1258.0(5)
4
1.428
Z
dcalc/g cm–3
1.240
Crystal color and shape
Crystal dimensions/mm
μ/mm–1
Colorless prism
0.25×0.20×0.20
0.40×0.30×0.20
0.417
0.20×0.20×0.15
0.25×0.21×0.18
0.456
0.414
0.085
Absorption correction
Tmin/Tmax
2θmax/deg
SADABS
0.851/0.921
58
—
—
56
0.896/0.914
56
0.923/0.940
58
Number of reflections
23456
14083
7927
19578
Number of independent
2658 (0.0803)
3284 (0.0397)
3333 (0.0559)
9133 (0.0582)
reflections (Rint
)
R1 (based on F for
reflections
0.0509 (1932)
0.0525 (2143)
0.1555
0.0485 (2186)
0.0671 (3829)
with I > 2σ(I))
wR2 (based on F 2 for
all reflections)
Number of refined
parameters
Weighting scheme
A
0.1341
136
0.1048
154
0.2206
490
155
2
2
w
–1 = σ (Fo2) + (aP)2 + bP, P = 1/3(Fo2 + 2Fc
)
0.0533
4.8523
1.000
1008
0.0313
2.5802
1.023
1136
0.0350
0.2000
1.000
568
0.0918
0.2650
1.001
752
B
GOOF
F(000)

Cyclothiomethylation of carbohydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
433
equivalent thermal parameters of the corresponding parent atꢀ
oms; for the hydrogen atoms of the methyl groups, U(H) =
= 1.5U(Ci). All calculations were carried out with the use of the
SHELXTL PLUS 5.10 program package.14
Principal Xꢀray data collection and refinement statistics are
given in Table 4. The atomic coordinates, bond lengths, bond
angles, and thermal parameters were deposited with the Camꢀ
bridge Crystallographic Data Centre (CCDC 716620—716623)
and can be obtained, free of charge, on application to
www.ccdc.cam.uk/conts/retrieving.html (or CCDC, 12 Union
Road, Cambridge CB2 1EZ; fax: +44 1223 335 033; or depoꢀ
sit@ccdc.cam.ac.uk).
7. V. R. Akhmetova, R. R. Khairullina, G. R. Nadyrgulova,
R. V. Kunakova, U. M. Dzhemilev, Zh. Org. Khim., 2008,
200 [Russ. J. Org. Chem. (Engl. Transl.), 2008, 44].
8. 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].
9. A. Wohl, Ber., 1886, 19, 2344.
10. V. R. Akhmetova, R. A. Vagapov, G. R. Nadyrgulova, T. V.
Tyumkina, Z. A. Starikova, M. Y. Antipin, R. V. Kunakova,
U. M. Dzhemilev, Tetrahedron, 2007, 47, 11702.
11. V. R. Akhmetova, G. R. Nadyrgulova, Z. T. Niatshina, R. R.
Khairullina, Z. A. Starikova, A. O. Borisova, M. Yu. Anꢀ
tipin, R. V. Kunakova, U. M. Dzhemilev, Heterocycles, 2009,
78, 45.
12. S. R. Khafizova, V. R. Akhmetova, R. V. Kunakova, U. M.
Dzhemilev, Izv. Akad. Nauk, Ser. Khim., 2003, 1722 [Russ.
Chem. Bull., Int. Ed., 2003, 52, 1817].
13. S. R. Khafizova, V. R. Akhmetova, L. F. Korzhova, T. V.
Khakimova, G. R. Nadyrgulova, R. V. Kunakova, E. A. Kruꢀ
glov, U. M. Dzhemilev, Izv. Akad. Nauk, Ser. Khim., 2005,
423 [Russ. Chem. Bull., Int. Ed., 2005, 54, 432].
We thank Corresponding Member of the Russian Acadꢀ
emy of Sciences U. M. Dzhemilev for helpful discussion.
This study was financially supported by the Council on
Grants of the President of the Russian Federation (Proꢀ
gram for State Support of Leading Scientific Schools of
the Russian Federation, Grant NShꢀ3019.2008.3).
References
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Received May 5, 2009;
in revised form August 5, 2009