Azines and azoles: CXXIX. Synthesis, structure, and some reactions of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones

Article abstract of DOI:10.1134/S1070363209100223

Reactions of 2-aryl-4-chloro-6H-1,3-thiazin-6-ones with sodium sulfide in aqueous alcohol at 18-20°C led to the formation of a readily separable mixture of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts (yield >70%) and bis(2-aryl-6-oxo-6H-1,3-thiazi

Full text of DOI:10.1134/S1070363209100223

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 10, pp. 2212–2219. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.N. Kuklin, L.E. Mikhailov, G.A. Mironova, B.A. Ivin, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 10,
pp. 1718–1725.
Azines and Azoles: CXXIX.1 Synthesis, Structure, and Some
Reactions of 2-Aryl-4-sulfanyl-6H-1,3-thiazin-6-ones
V. N. Kuklin, L. E. Mikhailov, G. A. Mironova†, and B. A. Ivin
St. Petersburg State Chemical and Pharmaceutical Academy, ul. Professora Popova 14, St. Petersburg, 197376 Russia
e-mail: kuklin-prof@yandex.ru
Received February 19, 2009
Abstract—Reactions of 2-aryl-4-chloro-6H-1,3-thiazin-6-ones with sodium sulfide in aqueous alcohol at 18–
20°C led to the formation of a readily separable mixture of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts
(yield >70%) and bis(2-aryl-6-oxo-6H-1,3-thiazin-4-yl) sulfides (<10%). The latter can also be obtained in
more than 50% yield by treatment of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts with 2-aryl-4-chloro-
6H-1,3-thiazin-6-ones. Methylation of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones afforded the corresponding
methylsulfanyl derivatives (yield >90%) regardless of the alkylating agent, solvent, temperature, reactant
concentration, and their ratio. 2-Aryl-4-sulfanyl-6H-1,3-thiazin-6-ones in the crystalline state and in solutions
in polar and nonpolar protic and aprotic solvents exist preferentially as 4-sulfanyl-6-oxo tautomers, and they
undergo almost complete ionization in neutral aqueous, alcoholic, and aqueous–alcoholic media (pKa = 4.3).
Reactions of 4-sulfanyl-2-phenyl-6H-1,3-thiazin-6-one with ammonia, amines, and difunctional N-centered
nucleophiles involve cleavage of the C6–S bond in the thiazine ring and subsequent recyclization of linear
intermediates to pyrimidines and diazole derivatives. The structure of the isolated compounds was confiirmed
by 1H and 13C NMR, IR, and UV spectra.
DOI: 10.1134/S1070363209100223
While studying the reactivity and biological activity
of substituted 6-oxo-1,3-thiazines, we showed that 2-
aryl-4-hydroxy-1,3-thiazin-6-ones in the crystalline
state and in solutions in various solvents exist
preferentially as 4-hydroxy-6-oxo tautomers [2–5].
Like 4-halogen-substituted 1,3-thiazin-6-ones, 2-aryl-
4-hydroxy-6H-1,3-thiazin-6-ones readily react with N-,
C-, and O-centered nucleophiles to give the
corresponding malonamic acid derivatives as a result
of opening of the thiazine ring at the C6–bond [6, 7].
Depending on the nucleophile nature, malonamic acids
thus obtained are capable of undergoing recyclization
to substituted azines or azoles [8, 9]. The product
composition and the direction of nucleophilic attack
(on C2 or C6) are determined by both substituent on C4
and C5 of the thiazine ring [6, 7] and nucleophile
nature [8]. Substituent in the benzene ring of 2-aryl-
1,3-thiazin-6-ones affect only the reaction rate.
with nucleophiles may take different pathways,
depending on the nature of substituent both on C5 and
in the benzene ring [9–13]. Reactions of compounds I
with soft nucleophiles are orbital-controlled, whereas
their reactions with hard nucleophiles are charge-
controlled, and nucleophilic replacement of the chlo-
rine atom at C4 may be accompanied by cleavage of
the thiazine ring or not [14].
4-Thio analogs III of 2-aryl-4-hydroxy-6H-1,3-
thiazin-6-ones have not been reported so far;
consequently, neither their structure nor reactivity was
studied. We tried to synthesize such compounds and
examine their structure in the crystalline state and in
solution and some chemical transformations.
2-Aryl-4-chloro-6H-1,3-thiazin-6-ones I seemed to
be the most convenient starting compounds for the
synthesis of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones
III [15]. We found that compounds I readily reacted
with sodium sulfide in 85% aqueous ethanol at 18–20°
C to give mixtures of the corresponding 2-aryl-4-
sulfanyl-6H-1,3-thiazin-6-one sodium salts II and
dithiazinyl sulfides, 2-aryl-4-(2-aryl-6-oxo-6H-1,3-
thiazin-4-ylsulfanyl)-6H-1,3-thiazin-6-ones IV. Com-
On the other hand, reactions of previously
synthesized 2-aryl-4-chloro-6H-1,3-thiazin-6-ones I
1
For communication CXXVIII, see [1].
† Deceased.
2212

AZINES AND AZOLES: CXXIX.
2213
pounds II and IV can readily be separated. Mercapto-
thiazines III were isolated by acidification of aqueous
or aqueous–alcoholic solution of their salts II with
hydrochloric acid; their yield ranged from 55 to 70%,
while the yield of dithiazinyl sulfides IV did not
exceed 10%. Sulfides IV can be obtained in a higher
yield (>50%) by reaction of sodium salts II with 4-
chlorothiazines I.
SCH3
SCH3
S
N
S
N
N
S
N
S
CH3NH2
Ph
Ph
Ph
Ar
N
O
O
O
O
CH3
VII
Vа, Vb
IV
Cl
O
N
S
Na2S
Ar
(CH3)2SO4 or
CH2N2
Iа, Ib
SH
S
SH
N
N
S
N
S
HCl
NaOH
CH3NH2
+
Na
−
Ar
Ar
Ar
N
O
O
O
CH3
IIIа, IIIb
IIа, IIb
VI
CHO
F
N
NH2NHPh
CH2
C
O
NH NH
Ph
NO2
Ph
N
N
Ph
IX
CHO
NH(i-C4H9)2
Ph
C
S
S
NH
C
S
NO2
CH2
C N(C4H9-i)2
N
O
Ph
VIII
S
O
X
Ar = C6H5 (a), p-CH3OC6H4 (b).
Aryl-4-sulfanyl-6H-1,3-thiazin-6-ones III, like
their oxygen-containing analogs, may exist as four
tautomers A–D.
atom is replaced by methyl group. Attempted methyla-
tion of mercaptothiazines III or their sodium salts II
did not led to the desired results. Despite variation of
alkylating agents [CH2N2, CH3I, (CH3O)2SO2] and
reaction conditions (solvent, temperature, reactant ratio
and concentration), in all cases the major products
(90% and more) were 4-methylsulfanyl derivatives V
Unfortunately, we did not succeed in obtaining the
complete set of compounds with “fixed” structures as
models of tautomers A–D in which the labile hydrogen
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

2214
KUKLIN et al.
S
S
S−
SH
O
N
S
H+N
S
N
S
N
S
−
Ar
Ar
Ar
Ar
OH
O
O
A
B
C
D
(model of structure A), and the product mixtures were
very difficult to separate. With some assumptions, 2-
aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts II
may be regarded as models of zwitterionic structure D;
however, it should be taken into account that
association with counterion may “distort” spectral
parameters of the anionic 1,3-dicarbonyl fragment.
In the region corresponding to stretching vibrations
of multiple bonds compounds III displayed a strong
broadened νC=O band (~1660 cm–1), νC=N (1610 cm–1)
and νC=C bands (1530 cm–1) typical of thiazine ring,
and aromatic νC=C band (1500 cm–1); the position of
these bands only slightly differs from the position of
the corresponding bands in the IR spectra of 4-methyl-
sulfanyl derivative V (1650, 1580, 1530, 1500 cm–1)
and 4-hydroxy- (1600, 1563, 1500, 1480 cm–1) and 4-
methoxy-6-oxothiazines (1665, 1600, 1594, 1500 cm–1).
On the other hand, the observed spectral pattern is
considerably different from those typical of 4,6-dioxo-
and 4-oxo-6-methoxythiazines (1728, 1590, 1564,
1500 cm–1 and 1640, 1594, 1568, 1500 cm–1,
respectively). As might be expected, ionization of mer-
captothiazines III is accompanied by appreciable
displacement of the νC=O, νC=N, and νC=C(thiazine)
bands. In the IR spectra of salts II (1610, 1590, 1520,
1500 cm–1), the corresponding bands are displaced by
10–40 cm–1 toward lower frequencies, as compared to
neutral compounds V. It should be noted that the IR
spectra of dilute (0.002 M) solutions of thiazines III in
chloroform are very similar to the spectra of their
crystalline samples (the same applies to their 4-
hydroxy analogs), but the νS–H band appears at higher
Crystalline mercaptothiazines III (see table) are
most likely to have structure A, i.e., they exist as 2-
aryl-4-sulfanyl-6H-1,3-thiazin-6-ones. In fact, the IR
spectra of crystalline compounds IIIa and IIIb
(dispersed in mineral or perfluorinated oil) are quite
similar to the spectra of the corresponding S-methyl
derivatives V simulating structure A; on the other
hand, the spectra of III differ from the spectra of
sodium salts II. In the IR spectra of IIIa and IIIb we
observed absorption bands in the region of X–H
stretching vibrations only near 2500 cm–1, which
should be assigned to vibrations of S–H bond. As in
the spectra of sodium salts II and 4-hydroxy analogs
[5], no absorption bands assignable to stretching
vibrations of C5H2 group (4-thioxo-6-oxo tautomer B)
or C6–OH bond (3400–3600 cm–1, 4-thioxo-6-hydroxy
tautomer C) were present.
UV, 1H and 13C NMR, and IR spectra of compounds IIa, IIIa, Va, VI, and VII
UV spectrum
(EtOH),
λmax, nm
1H and 13C NMR spectra, δ, δC, ppm
Comp.
no.
IR spectrum, ν, cm–1
1H
13C
217, 263, 345
270, 300
297, 322
234, 258
244
4.3 (SH), 6.2 (С5Н), 107.5 (С5), 127.4, 129.1, 133.3, 136.1 (Ph), 165.9, 1640 (С=О), 1610 (С=С),
7.5– 8.0 (Ph) 1570 (С=N), 2500 (SH)
173.9, 177.6 (С2, С4, С6 )
IIIа
Vа
6.0 (С5Н), 7.6 7.5–8.0 104.8 (С5), 14.4 (SCH3), 127.44, 129.05, 133.1, 136.1 1660 (C=O), 1630 (C=C),
(Ph)
(Ph), 171.35, 172.4, 177.6 (С2, С4, С6)
1570 (C=N)
IIаа
VI
6.3, (С5Н), 7.4–8.1 (Ph)
–
1610 (C=O), 1595 (C=C),
1520 (C=N)
6.52 (C5Н), 6.01 (SH), 33.0 (NCH3), 106.6 (C5), 128.3, 128.4, 131.8, 133.8 2450 (SH), 1630 (C=O),
7.5–7.8 (Ph)
6.23 (C5Н)
(Ph), 158.5, 160.6, 173.6 (C2, С4, С6)
13.2 (SCH3), 33.2 (NCH3), 104.2 (C5), 128.2, 128.4, 1650 (C=O), 1610 (C=C),
130.2, 154.3 (Ph), 159.2, 160.5, 166.7 (С2, С4, С6)
1580 (C=N)
1600 (C=C), 1575 (C=N)
VII
a
The 1H NMR spectrum was recorded in DMF-d7.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

AZINES AND AZOLES: CXXIX.
frequency (by almost 100 cm–1). These findings
2215
2
4
1
4
ε×10–
6
indicate strong association of mercaptothiazines III in
the crystalline state via hydrogen bonding, as in the
case of 2-aryl-4-hydroxy-6-oxothiazines [5]. The larger
displacement of the νS–H band upon ionization of 4-
sulfanylthiazines III, as compared to νO–H of analogous
4-hydroxy derivatives, is consistent with the higher
acidity of compounds III (see below). We can
conclude that compounds III in the crystalline state,
like their oxygen-containing analogs [5], exist
preferentially as 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-
ones (structure A) and that the fraction of tautomers
B–D is small (or the latter are absent at all).
2.0
5
1.0
3
As already noted, similarity of the IR spectra of
solutions and crystalline samples of mercaptothiazines
III and those of methylsulfanyl derivative V suggests
that compounds III in weakly polar aprotic solvents
240
280
320
λ, nm
UV spectra of solutions of 2-phenyl-4-sulfanyl-6H-1,3-
thiazin-6-one (IIIa) in (1) ethanol, (2) chloroform, (3)
hexane, (4) 0.01 M aqueous–alcoholic KOH, and (5) 0.01 M
aqueous–alcoholic HCl and (6) of 4-methylsulfanyl-2-
phenyl-6H-1,3-thiazin-6-one (Va) in ethanol.
1
also have structure A. In fact, the H NMR spectra of
IIIa and IIIb in chlorooform-d contain a broadened
singlet assignable to SH proton (δ 4.3 ppm), a singlet
at δ 6.1–6.2 ppm due to 5-H, and a set of signals from
aromatic protons with an intensity ratio of 1:1:5 (IIIa)
or 1:1:4 (IIIb). The spectra lack signal in the δ region
of 3.5 ppm (typical of methylene protons in structure
B), vinylic 5-H proton in the anionic fragment of
tautomer D (δ > 6.3 ppm), or hydroxy proton of
tautomer C. As follows from the data given in table,
the positions of the 5-H signal and signals from
protons in the benzene ring of potentially tautomeric
compounds III and methylsulfanyl derivatives V are
almost similar. In addition, the UV spectra of these
compounds in chloroform and dioxane almost coincide
(see figure). Structure A of mercaptothiazines III is
retained in polar aprotic solvents. The 1H NMR
spectrum of compound IIIa in DMF-d7 is
characterized by the same set of signals as in CDCl3,
but the 5-H and SH signals are displaced downfield
(by 0.2 and 1.9 ppm, respectively). On the other hand,
the position of signals in the spectra of sodium salt IIa
remains unchanged. The UV spectra of thiazine IIIa in
ethanol and 40% aqueous ethanol (see table and figure)
strongly differ from the spectra recorded from
solutions in nonpolar aprotic solvents and from the
spectra of alcoholic solutions of model S-methyl
derivative, but they are almost identical to the
spectrum of a solution of IIIa in 0.01 M aqueous–
alcoholic alkali (40% of ethanol). Acidification of the
alkaline solution to pH 1 gives a spectrum resembling
that of the solution in chloroform. These findings
indicate that thiazines III and alcoholic and aqueous–
alcoholic solutions undergo almost complete ionization
and that they have structure A in acid medium. The
pKa values of thiazines IIIa and IIIb in aqueous
ethanol were estimated at 3.29 and 3.41, respectively,
i.e., they are stronger acids than their 4-hydroxy
analogs by an order of magnitude (the pKa values of 2-
phenyl- and 2-p-methoxyphenyl-4-hydroxy-6H-1,3-
thiazin-6-ones are 4.20 and 4.33, respectively [5] ).
The 13C NMR spectra of 4-sulfanyl-2-phenyl-6H-
1,3-thiazin-6-one (IIIa) and its S-methyl derivative Va
in DMSO-d6 are almost superimposable. The spectra
contain a signal from C5 (δC 107.5 and 104.8 ppm,
respectively), signals from aromatic carbon atoms (δC
127.4, 129.1, 133.3, 136.1 and 127.44, 129.05, 133.1,
136.1 ppm), and signals from C2, C4, and C6 in the
thiazine ring (δC 165.9, 173.9, 177.6 and 171.4, 172.4,
177.6 ppm). It should be noted that the C5 signal of 4-
methylsulfanylthiazinone V appears in a weaker field
(ΔδC = 2.7 ppm). The positions of one of the C2, C4,
and C6 signals are also slightly different (see table).
Unfortunately, thiazines III and V are poorly soluble
in water, alcohol, and chloroform; therefore, we failed
to record their NMR spectra in these solvents.
Like 4-hydroxy(chloro)-1,3-thiazines [8], 4-sul-
fanyl-2-phenyl-6H-1,3-thiazin-6-one (IIIa) reacted with
a solution of methylamine on heating to give 1-methyl-
2-phenyl-4-sulfanylpyrimidin-6(1H)-one (VI). 4-Methyl-
sulfanylthiazine (Va) reacted with methylamine in a
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

2216
KUKLIN et al.
similar way, yielding 1-methyl-4-methylsulfanyl-2-
phenylpyrimidin-6(1H)-one (VII). Unlike 4-hydroxy
analogs, no pyrimidine derivatives were formed in the
reactions of thiazines III and V with an ammonia
solution; in the reaction mixture we identified
ammonium sulfide and benzoic acid derivatives.
Secondary amines reacted with 4-sulfanyl-1,3-thiazine
IIIa to afford open-chain thiomalonamic acid
derivatives like VIII (analogous products were formed
in reactions of secondary amines with 4-hydroxy-
thiazines).
oxo-6H-1,3-thiazin-4-ylsulfanyl)benzaldehyde (X). In
the reaction of 4-sulfanylthiazine IIIa with the same
aldehyde in 30% sodium hydroxide the yield of sulfide
X did not exceed 15%. The structure of sulfide X was
confirmed by the 1H NMR, UV, and IR spectra.
Thus the results of our experimental study showed
that 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones in the
crystalline state and in solution exist as 4-sulfanyl-6-
oxo tautomers A. Reactions of thiazines III and V with
nitrogen-centered nucleophiles (methylamine, diiso-
butylamine, and phenylhydrazine) lead to the forma-
tion of cyclic (pyrimidine and 1,2,4-triazole
derivatives) or open-chain products (thiomalonamic
acid derivatives), depending on the nucleophile nature.
Sodium 6-oxo-2-phenyl-6H-1,3-thiazin-4-thiolate reacts
with 5-nitro-2-fluorobenzaldehyde to give product of
nucleophilic replacement of the fluorine atom. The
newly synthesized compounds attract interest as
models for studying properties of 6-oxothiazine
systems and as potential biologically active substances.
The structure of pyrimidines VI and VII was
confirmed by spectral data. The 13C NMR spectra of
compounds VI and VII in DMSO-d6 contained signals
from carbon atoms in the phenyl substituent on C2 (δC
127–134 ppm), C5 (δC 104, 107 ppm), and methyl
carbon atoms, as well as three weak signals from C2,
1
C4, and C6 in the pyrimidine ring. In the H NMR
spectra of these compounds, aromatic protons
resonated at δ ~7.6 ppm, the 5-H proton in the
pyrimidine ring appeared at δ 6.52 (VI) and 6.23 ppm
(VII), and the SH signal of VI was located at
δ 6.01 ppm; also, signals from protons in the methyl
groups were present. It should be noted that the 5-H
and C5 signals of VI appear in a weaker field relative
to the corresponding signals of pyrimidine VII (by 0.3
and 2.5 ppm, respectively). Also, the chemical shifts of
one carbon atom in the pyrimidine ring of VI and VII
are different. Analogous pattern is observed in the
spectra of initial thiazines IIIa and Va. Compound
EXPERIMENTAL
The electronic absorption spectra were measured
from 1×10–4 M solutions in hexane, chloroform,
ethanol, and aqueous–alcoholic buffers on an SF-56
spectrophotometer using 1-cm quartz cells. The 1H and
13C NMR spectra were recorded from solutions in
CDCl3, DMSO-d6, and DMFA-d7 on a Bruker AM-500
1
spectrometer at 500.17 MHz for H and 83 MHz for
13C. The IR spectra were obtained on a Specord IR-75
spectrometer from 2×10–3 M solutions in CDCl3 (CaF2
cells with a cell path length of 98–490 μm) and
suspensions in mineral or pefluorinated oil. The purity
of the products was checked, and the progress of
reactions was monitored, by thin-layer chromato-
graphy using Silufol UV-254 plates; spots were
detected under UV light.
1
VIII displayed in the H NMR spectrum (DMSO-d6)
signals from protons in the CH, CH2, and NH groups
and aromatic ring. The UV spectrum of pyrimidine VI
in ethanol contained two absorption maxima; one
maximum was observed in the UV spectrum of VII,
and three maxima were present in the spectrum of
VIII. Crystalline compounds VI, VII, and VIII
showed in the IR spectra absorption bands typical of
stretching vibrations of C=O, SH, and NH groups,
which were consistent with their structure.
2-Phenyl-4-sulfanyl-6H-1,3-thiazin-6-one (IIIa).
A solution of 4.5 mmol of sodium sulfide nonahydrate
(Na2S·9H2O) in 5 ml of water was added under
stirring at 18–20°C to a solution of 4.5 mmol of 4-
chloro-2-phenyl-6H-1,3-thiazin-6-one (I) [15] in 50 ml
of ethanol. The mixture was stirred for 20 min, the
precipitate of dithiazinyl sulfide IV was filtered off,
and the filtrate was adjusted to weakly acidic reaction
by adding dilute hydrochloric acid. The precipitate of
sulfanylthiazinone IIIa was filtered off and recrys-
tallized from benzene–hexane (1:3). Yield 76%, mp
131–133°C, Rf 0.47 (EtOH–CHCl3, 1:9). UV spectrum
The reaction of 2-phenyl-4-sulfanyl-6H-1,3-thiazin-
6-one (IIIa) with phenylhydrazine gave N′,3-diphenyl-
1,2,4-triazol-5-ylacetohydrazide (IX) which was
reported previously [8]. 4-Hydroxy- and 4-chloro-1,3-
thiazines react with phenylhydrazine in a similar way.
The reaction of sodium 6-oxo-2-phenyl-6H-1,3-thi-
azine-4-thiolate (IIa) with 2-fluoro-5-nitrobenzal-
dehyde under mild conditions involved nucleophilic
replacement of the fluorine atom in the benzene ring of
the aldehyde with formation of 5-nitro-2-(2-phenyl-6-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

AZINES AND AZOLES: CXXIX.
2217
(EtOH), λmax, nm (ε×10–4): 217 (0.77), 263 (1.09), 345
(0.40). H NMR spectrum (CDCl3), δ, ppm: 4.3 s (1H,
C20H12N2O2S3. Calculated, %: C 51.3; H 2.6; N 5.9; S
20.9.
1
SH), 6.2 s (1H, 5-H), 7.6 m (5H, C6H5). 13C NMR
spectrum, δC, ppm: 107.5 (C5); 127.4, 129.1, 133.3,
136.1 (Carom); 165.9, 173.9, 177.6 (C2, C4, C6); IR
spectrum (mineral oil), ν, cm–1: 1640 (C=O), 1610
(C=C), 1570 (C=N), 2500 (SH). Found, %: C 54.1;
H 3.2; N 6.2; S 28.7. C10H7NOS2. Calculated, %: C
54.3; H 3.2; N 6.3; S 28.9.
4-Methylsulfanyl-2-phenyl-6H-1,3-thiazin-6-one
(Va). a. 2-Phenyl-4-sulfanyl-6H-1,3-thiazin-6-one (IIIa),
4.6 mmol, was dissolved in 30 ml of 10% aqueous
sodium hydroxide, 4.6 mmol of dimethyl sulfate was
added, and the precipitate was filtered off, washed with
water, dried under reduced pressure, and recrystallized
from petroleum ether. Yield 74%.
2-p-Methoxyphenyl-4-sulfanyl-6H-1,3-thiazin-6-
one (IIIb) was synthesized in a similar way. Yield
55%, decomposition point 220°C, Rf 0.66 (EtOH–
CHCl3, 1:9). UV spectrum (EtOH), λmax, nm (ε×10–4):
244 sh (0.71), 270 sh (0.64), 312 (1.26), 342 (1.02). 1H
NMR spectrum (CDCl3), δ, ppm: 3.9 s (1H, CH3O),
4.4 s (1H, SH), 6.1 s (1H, 5-H), 7.4 (4H, C6H4). IR
spectrum (mineral oil), ν, cm–1: 1640 (C=O), 1610
(C=C), 1530 (C=N), 2450 (SH). Found, %: C 52.3; H
3.8; N 5.5; S 25.4. C11H9NO2S2. Calculated, %: C 52.6;
H 3.6; N 5.6; S 25.5.
b. Compound IIIa, 2.0 mmol, was treated with 50
ml of a solution of diazomethane (prepared from 1.0 g
of N-nitroso-N-methylurea) in diethyl ether. The
mixture was left to stand for 24 h at 18–20°C and
evaporated, and the residue was recrystallized from
hexane. Yield 91%, mp 110–112°C, Rf 0.7 (CCl4–
Me2CO, 10:1). UV spectrum (EtOH), λmax, nm (ε×10–4):
1
270 (2.40), 300 (1.14). H NMR spectrum (CDCl3), δ,
ppm: 2.5 (3H, SCH3), 6.0 s (1H, 5-H), 7.6 m (5H,
C6H5). 13C NMR spectrum, δC, ppm: 14.4 (SCH3);
104.8 (C5); 127.4, 129.1, 133.1, 136.1 (Carom); 171.35,
172.4, 177.6 (C2, C4, C6). IR spectrum (mineral oil), ν,
cm–1: 1660 (C=O), 1630 (C=C), 1530 (C=N). Found,
%: C 56.2; H 3.6; N 5.8; S 27.6. C11H9NOS2.
Calculated, %: C 56.2; H 3.8, N 6.0; S 27.2.
Sodium 2-phenyl-6-oxo-6H-1,3-thiazine-4-thiolate
(II). A solution of 4.5 mmol of sodium hydroxide in
4 ml of water was gradually added at 18–20°C to a
solution of 4.5 mmol of 2-phenyl-4-sulfanyl-6H-1,3-
thiazin-6-one (IIIa) in 50 ml of ethanol. The solvent
was removed under reduced pressure (~20 mm) at 20°C,
and the solid residue was washed with several portions
of hot chloroform. Yield 68%, decomposition point
246–248°C, Rf 0.44 (EtOH–CHCl3, 1:9). UV spectrum
(EtOH), λmax, nm (ε×10–4): 297 (1.80), 322 sh (0.85).
1H NMR spectrum (DMF-d7), δ, ppm: 6.3 s (1H, 5-H),
7.6 m (5H, C6H5). IR spectrum (mineral oil), ν, cm–1:
1610 (C=O), 1595 (C=C), 1520 (C=N). Found, %: C
49.0; H 2.7; N 6.0; S 26.7. C10H6NOS2Na. Calculated,
%: C 49.4; H 2.5; N 5.8; S 26.3.
2-p-Methoxyphenyl-4-methylsulfanyl-6H-1,3-
thiazin-6-one (Vb) was synthesized in a similar way
(method a) from compound IIIb. Yield 63%, mp 225–
227°C, Rf 0.74 (CCl4–Me2CO, 10:1). UV spectrum
(EtOH), λmax, nm (ε×10–4): 232 (1.05), 270 (1.32), 332
1
(1.60), 378 (1.05). H NMR spectrum (CDCl)3, δ,
ppm: 2.6 (3H, CH3S), 3.8 s (3H, CH3O), 5.9 s (1H,
5-H), 7.4 m (4H, C6H4). IR spectrum (mineral oil), ν,
cm–1: 1650 (C=O), 1610 (C=C), 1530 (C=N). Found,
%: C 54.5; H 4.1; N 5.7; S 24.1. C12H11NO2S2.
Calculated, %: C 54.3; H 4.1; N 5.3; S 24.2.
2-Phenyl-4-(2-phenyl-6-oxo-6H-1,3-thiazin-4-yl-
sulfanyl)-6H-1,3-thiazin-6-one (IV). Compound Ia,
4.5 mmol, was dissolved under stirring and heating in
20 ml of ethanol, the solution was cooled to 18–20°C,
and a solution of sodium 2-phenyl-6-oxo-6H-1,3-
thiazine-4-thiolate (IIa) in 4 ml of 40% aqueous
ethanol was added under stirring. The mixture was
kept for 24 h at 18–20°C, and an amorphous material
separated. It was filtered off and recrystallized from
chloroform. Yield 53%, decomposition point 252–254°C,
Rf 0.34 (EtOH–CHCl3, 1:9). UV spectrum (CHCl3),
1-Methyl-4-sulfanyl-2-phenylpyrimidin-6(1H)-
one (VI). Compound IIIa, 1.0 mmol, was dissolved in
5 ml of 25% aqueous methylamine. The solution was
heated for 2 h at 60°C under stirring and was left to
stand for 24 h at 18–20°C. The mixture was filtered,
the filtrate was acidified to pH 2 with 2 M hydro-
chloric acid, and the precipitate was filtered off,
washed with water until neutral washings (pH 7),
dried, and recrystallized from benzene–hexane (1:1).
Yield 71%, mp 210–211°C, Rf 0.35 (benzene–ethyl
acetate, 1:1). UV spectrum (EtOH), λmax, nm (ε×10–4):
234 (0.58), 258 (0.56). 1H NMR spectrum (DMSO-d6),
δ, ppm: 6.01 s (1H, SH), 6.52 s (1H, 5-H), 7.64 m (5H,
C6H5). 13C NMR spectrum, δC, ppm: 33.0 (NCH3);
λ
max, nm (ε×10–4): 280 (2.1), 330 (1.99). IR spectrum
(mineral oil), ν, cm–1: 1650 (C=O), 1645 (C=C), 1530
(C=N). Found, %: C 51.2; H 2.8; N 5.8; S 21.1.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

2218
KUKLIN et al.
106.6 (C5); 128.3, 128.4, 131.8, 134.8 (Carom); 158.5,
160.6, 173.6 (C2, C4, C6). IR spectrum (mineral oil), ν,
cm–1: 1575 (C=N), 1600 (C=C), 1630 (C=O), 2450
(SH). Found, %: C 61.4; H 4.8; N 12.2; S 14.0.
C11H10N2OS. Calculated, %: C 60.6; H 4.6; N 12.8; S
14.7.
left to stand for 24 h at 18–20°C, and filtered from
impurities, the filtrate was acidified to pH 2 with 2 M
hydrochloric acid, and the precipitate was filtered off,
washed with water until neutral washings (pH 7),
dried, and recrystallized from acetic acid. Yield 65%,
mp 241–242°C; published data [8]: mp 242–244°C.
1-Methyl-4-methylsulfanyl-2-phenylpyrimidin-
6(1H)-one (VII). Thiazine Va, 1.0 mmol, was
dissolved at 60°C in 2 ml of 25% aqueous methyl-
amine. The mixture was stirred for 4 h at 60–70°C and
cooled, and the precipitate was filtered off, dried, and
recrystallized from heptane. Yield 72%, mp 134–135°C,
Rf 0.47 (benzene–ethyl acetate, 1:1). UV spectrum
5-Nitro-2-(2-phenyl-6-oxo-6H-1,3-thiazin-4-yl-
sulfanyl)benzaldehyde (X). A solution of 1.0 mmol of
2-fluoro-5-nitrobenzaldehyde in 2 ml of ethanol was
added under stirring to a solution of 1.0 mmol of
sodium 6-oxo-2-phenyl-6H-1,3-thiazine-4-thiolate (IIa)
in 5 ml of ethanol. The mixture was stirred for 3 h at
18–20°C, the precipitate was filtered off, washed with
water, dried, and recrystallized from dioxane. Yield
63%, decomposition point 244–246°C, Rf 0.49
(acetone–hexane, 1:2). UV spectrum (EtOH): λmax 264
1
(EtOH): λmax 244 nm (ε = 0.31×104). H NMR
spectrum (DMSO-d6), δ, ppm: 2.43 s (3H, SCH3), 3.25
s (3H, NCH3), 6.23 s (1H, 5-H), 7.58 m (5H, C6H5).
13C NMR spectrum, δC, ppm: 13.2 (SCH3), 33.2
(NCH3); 104.2 (C5); 128.2, 128.4, 130.2, 134.3 (Carom);
159.2, 160.5, 166.7 (C2, C4, C6). IR spectrum (mineral
oil), ν, cm–1: 1580 (C=N), 1610 (C=C), 1660 (C=O).
Found, %: C 62.5; H 4.9; N 12.5; S 13.9. C12H12N2OS.
Calculated, %: C 62.1; H 5.2; N 12.1; S 13.8.
1
nm (ε = 1.03×104). H NMR spectrum (DMSO-d6), δ,
ppm: 6.47 s (1H, 5-H), 7.75 m (5H, C6H5), 8.5 (3H,
C6H3), 10.5 s (1H, CHO). IR spectrum (mineral oil), ν,
cm–1: 1650 (C=O), 1710 (CHO). Found, %: C 57.5; H
3.0; N 9.7; S 17.9. C17H10N2O3S2. Calculated, %: C
57.6; H 2.8; N 9.9; S 18.0.
N,N-Diisobutyl-3-(phenylcarbonothioylamino)-
REFERENCES
3-thioxopropanamide
(VIII).
Diisobutylamine,
1.5 mmol, was added to a solution of 1.0 mmol of
thiazine IIIa in 25 ml of toluene. The mixture was
heated for 6 h under reflux and cooled, the solvent was
distilled off under reduced pressure (~20 mm) at 40°C,
and the residue was subjected to column chromato-
graphy on silica gel (40–100 μm) using petroleum
ether as eluent. Yield 21%, mp 64–65°C, Rf 0.27
(benzene). UV spectrum (EtOH), λmax, nm (ε×10–4):
1. Shutov, R.V., Kuklina, E.V., and Ivin, B.A., Russ. J.
Gen. Chem., 2009, vol. 79, no. 5, p. 1049.
2. Krylov, A.I., Kuklin, V.N., and Ivin, B.A., Khim.
Geterotsikl. Soedin., 1987, no. 10, p. 1409.
3. Belyaeva, K.F., Kuklin, V.N., Smorygo, N.A.,
Biyushkin, V.N., and Malinovskii, T.I., Zh. Strukt.
Khim., 1986, vol. 27, no. 3, p. 127.
1
4. Kuklin, V.N., Belyaeva, K.F., Biyushkin, V.N., Ivin, B.A.,
and Malinovskii, T.I., Zh. Strukt. Khim., 1991, vol. 32,
no. 5, p. 103.
224 (0.78), 278 (0.49), 393 (0.07). H NMR spectrum
(DMSO-d6), δ, ppm: 0.9 m (12H, CH3), 1.8 m (2H,
CH), 4.15 s (2H, CH2), 7.0 s (1H, NH), 7.75 m (5H,
C6H5).2 IR spectrum (mineral oil), ν, cm–1: 1740
(C=O); 3150, 3330 (NH). Found, %: C 60.9; H 7.1; N
8.3; S 17.8. C18H26N2OS2. Calculated, %: C 61.7; H
7.4; N 8.0; S 18.3.
5. Kuklin, V.N., Yakovlev, I.P., Smorygo, N.A., Strelko-
va, L.F., and Ivin, B.A., Russ. J. Gen. Chem., 1996,
vol. 66, no. 6, p. 985.
6. Kuklin, V.N., Belyaeva, K.F., Chan Khyu Byu,
Kirillova, E.N., Gindin, V.A., and Ivin, B.A., Zh. Org.
Khim., 1992, vol. 28, no. 12, p. 2597.
N′-Phenyl(1,3-diphenyl-1,2,4-triazol-5-yl)aceto-
hydrazide (IX). Freshly distilled phenylhydrazine,
1.2 mmol, was added under stirring to a solution of
1.0 mmol of 2-phenyl-4-sulfanyl-6H-1,3-thiazin-6-one
(IIIa) in 4 ml of 5% aqueous sodium hydrogen
carbonate. The mixture was heated for 1 h at 50–60°C,
7. Kuklin, V.N., Anisimova, N.A., Pastushenkov, L.V., and
Ivin, B.A., Khim.-Farm. Zh., 1996, no. 3, p. 37.
8. Kuklin, V.N., Suntsov, A.G., Sakaev, M.R., and Ivin, B.A.,
Zh. Obshch. Khim., 1995, vol. 65, no. 6, p. 1022.
9. Kuklin, V.N., Kirillova, E.N., and Ivin, B.A., Zh.
Obshch. Khim., 1995, vol. 65, no. 6, p. 1015.
10. Kaluzhskikh, A.N., Mikhailov, L.E., Kuklin, V.N., and
Ivin, B.A., Russ. J. Gen. Chem., 1997, vol. 67, no. 7,
p. 1126.
2
Signals from the methylene protons in the isobutyl groups are
overlapped by the solvent signal.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009

AZINES AND AZOLES: CXXIX.
2219
11. Chena, M., Pradere, J.P., Vicens, J., Tonpet, L., and
14. Kuklin, V.N., Mironova, G.V., Chumakov, Yu.M.,
Biyushkin, V.N., Malinovskii, T.I., and Ivin, B.A., Zh.
Org. Khim., 1993, vol. 29, no. 3, p. 611.
Qunion, H., Bull. Soc. Chim. Fr., 1988, no. 5, p. 897.
12. Mikhailov, L.E., Kuklin, V.N., and Ivin, B.A., Russ. J.
Gen. Chem., 1998, vol. 68, no. 3, p. 493.
15. Mironova, G.A., Kuklin, V.N., Kirillova, E.N., and
Ivin, B.A., Khim. Geterotsikl. Soedin., 1984, no. 10,
p. 1328.
13. Mikhailov, L.E., Kaluzhskikh, A.N., Kuklin, V.N.,
Studentsov, E.P., and Ivin, B.A., Russ. J. Gen. Chem.,
2004, vol. 74, no. 1, p. 150.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 10 2009