Novel synthesis of 1,2-dihydro-4H-3,1-benzoxazine-4-thiones by the reaction of newsynthesized methyl dithioanthranilate hydrobromide with carbonyl compounds and the synthesis of another new class of 1,2-dihydro-4H-3,1-benzothiazine-4-thiones from the same

Article abstract of DOI:10.3987/COM-15-13336

Methyl dithioanthranilate hydrobromide (6) was synthesized by the deprotection of Z-protected methyl dithioanthranilate (5) which was obtained by treatment of Z-protected methylthioiminium iodide 4 with H2S. The 1,2-dihydro-4H-3,1-benzoxazine-4-thiones 10

Full text of DOI:10.3987/COM-15-13336

HETEROCYCLES, Vol. 91, No. 12, 2015
2327
HETEROCYCLES, Vol. 91, No. 12, 2015, pp. 2327 - 2342. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 6th October, 2015, Accepted, 2nd November, 2015, Published online, 20th November, 2015
DOI: 10.3987/COM-15-13336
NOVEL
1,2-DIHYDRO-4H-3,1-BENZOXAZINE-4-THIONES BY THE REACTION
OF NEWSYNTHESIZED METHYL DITHIOANTHRANILATE
HYDROBROMIDE WITH CARBONYL COMPOUNDS AND THE
SYNTHESIS OF ANOTHER NEW CLASS OF
1,2-DIHYDRO-4H-3,1-BENZOTHIAZINE-4-THIONES FROM THE SAME
REACTANTS IN THE PRESENCE OF EXCESS SODIUM
HYDROGENSULFIDE
SYNTHESIS
OF
Tatsuo Yamamoto* and Motomu Muraoka
Department of Chemistry, Faculty of Science, Josai University, 1-1, Keyaki-Dai,
Sakado, Saitama 350-0295㸪Japan
E-mail: yukidai2㸾josai.ac.jp
Abstract 㸫 Methyl dithioanthranilate hydrobromide (6) was synthesized by the
deprotection of Z-protected methyl dithioanthranilate (5) which was obtained by
treatment of Z-protected methylthioiminium iodide 4 with H2S.
The
1,2-dihydro-4H-3,1-benzoxazine-4-thiones 10a-m were first synthesized by the
reaction of methyl dithioanthranilate hydrobromide (6) with each aldehyde or
ketone. Formaldehyde, in this reaction, gave N-(methylthio)methyl-4H-3,1-
benzoxazine-4-thione (11). Another new class of 1,2-dihydro-4H-3,1-
benzothiazine-4-thiones 12a-e were synthesized from the same reactants in the
presence of two equivalents of sodium hydrogensulfide.
INTRODUCTION
To the best of our knowledge, neither free dithioanthranilic acid (2-aminodithiobenzoic acid) nor its alkyl
or aryl ester has been synthesized so far. Stable 3-amino-2,3-unsaturated alicyclic dithiocarboxylic acids,
such as 2-aminocyclopent-1-ene-1-dithiocarboxylic and -cyclohex-1-ene-1-dithiocarboxylic acids were
first synthesized by Takeshima and co-workers.1,2ꢀ
Muraoka et al. also reported the synthesis of stable 3-amino-2-cyanodithiocrotonic acid, the parent

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HETEROCYCLES, Vol. 91, No. 12, 2015
3-amino-2-cyanodithiocinnamic acid and its homologous dithioacids bearing an alkyl substituent on the
aromatic ring.3
Reactions of 3-amino-2,3-unsaturated alicyclic dithiocarboxylic acids, 3-amino-2-cyanodithiocrotonic
and -2-cyanodithiocinnamic acids with carbonyl compounds, carbon disulfide, or phenyl isothiocyanate to
give 1,3-thiazine-6-thiones2,4,5-7 or -2,6-dithiones4,8,9 have been reported by Takeshima, Muraoka, and
their co-workers. Unstable 2-thioxodithiocarboxylic acids generated during the procedure of reaction
mixture were oxidized by air to give 1,2-dithiol-3-thiones.9 Subsequently 1,2,4-trithiols were formed by
the oxidation of stable 2-imino-1-dithiocarboxylic acids with I2.2,3 The 1,3-dithietanes2,3 were produced by
the intramolecular elimination of H2S with DCC or upon heating to about 70 °С. The 1,3-
benzodithiols2,3,6 were produced by the reaction of these dithiocarboxylic acids with picryl chloride.
Pyrazole derivatives6 were also obtained when the iminodithiocarboxylic acids were treated with
hydrazine.
In addition to the above-mentioned reactions of the dithioacids to form various heterocyclic compounds,
addition reactions of 2-aminocyclopent-1-ene-1-dithiocarboxylic acid to strongly electrophilic olefins to
form stable dithioesters were also reported.10
No further studies regarding the synthesis of heterocyclic compounds using 3-amino-2,3-unsaturated
alicyclic dithiocarboxylic acids or 3-amino-2-cyanodithiocinnamic acids have thus been reported for over
36 years until we began to study the synthesis and reactions of methyl dithioanthranilate.
Dithioanthranilic acid is considered to be a special case of 3-amino-2,3-unsaturated dithiocarboxylic acids,
and is expected to give rise to some new types of heterocyclic compounds fused to benzene ring by
allowing it to react with electrophilic reagents such as carbonyl compounds.
Jourdan and co-workers11 reported the formation of sodium dithioanthranilate by the reaction of
2-aminobenzotrifluoride with sodium sulfide in boiling dimethyl sulfoxide, but they isolated neither free
dithioanthranilic acid nor any of its esters. The synthesis of the regioisomer of methyl dithioanthranilate,
methyl 4-aminodithiobenzoate, which is utilized as a precursor compound for dyeing keratin fibers, was
reported by Leon and co-worker.12 Mckinnon and co-workers reported the synthesis of N-methyl
derivative of methyl dithioanthranilate.13
RESULTS AND DISCUSSION
We are strongly interested in the physical and chemical properties and reactions of dithioanthranilic acid
and its ester with electrophiles. These do not seem to be any way to introduce dithiocarboxyl group to the

HETEROCYCLES, Vol. 91, No. 12, 2015
2329
2-position of aniline and vice versa. Alkyl dithioanthranilate is expected to be useful as a reagent for the
synthesis of N,O- or N,S-containing fused heterocyclic compounds. Therefore, we converted ethyl
anthranilate into methyl dithioanthranilate hydrobromide (6) to use as a starting material for synthesizing
N,O- or N,S-containing fused heterocyclic compounds (Scheme 1).
Thus, Z-protected ethyl anthranilate 1 was tert-amidated by treating it with lithium piperidide. Then, the
tert-amide 214 was changed to the thioamide 3 by sulfurization with diphosphorus pentasulfide in
1,4-dioxane under Ar-bubbling and ultrasonic irradiation.15 Purified thioamide 3 was dissolved in
iodomethane and converted into 2-benzyloxycarbonylamino(α-methylthio)benzylidenepiperidinium
iodide (4). This salt 4 was then dissolved in pyridine and to this solution was added iodomethane. H2S gas
continued to be passed through the solution until the solution no longer absorbed the gas. Some amount of
thioamide 3 was inevitably reproduced on preparation of Z-protected methyl dithioanthranilate (5). The
yield of compound 5 was improved a little by adding iodomethane to the solution of the salt 4 through
partial re-formation of compound 4 from the thioamide 3 formed by the elimination of methanethiol from
intermediate A (Scheme 2).

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Methyl dithioanthranilate (7) was obtained by neutralizing the hydrobromide 6 with sodium
1
hydrogensulfide and its structure was confirmed by the IR, H- and 13C NMR spectra as well as its
elemental analysis. Both the NMR and IR spectra of compounds 3, 5, and 6 were in good agreement with
the proposed structures for these compounds.
The formation of sodium dithioanthranilate (8) in N,N-dimethylformamide was attained by allowing a
solution of compound 6 and two equivalents of sodium hydrogensulfide in N,N-dimethylformamide to
stand overnight with gently warming under Ar. The existence of sodium dithioanthranilate (8) in the
solution was confirmed by the intense bluish purple coloration upon the addition of one drop of very
dilute aqueous Ni(II)(NO3)2 or Ni(II)Cl2 to a highly diluted solution of the reaction mixture with acetone.
This coloration indicates that the dithiocarboxyl group and amino group are at ortho positions to each
other on benzene ring and form a chelate-type complex with Ni(II) ion. Similar deep purple complex
formations were observed whenever one drop of dilute aqueous Ni(II)(NO3)2 was added to highly diluted
alcoholic or acetonic solution of each alicyclic D-amino-D,E-unsaturated dithiocarboxylic acid.1,3,16
Aiming to obtain free dithioanthranilic acid, dilute hydrochloric acid was added to a solution containing
sodium dithioanthranilate in aqueous N,N-dimethylformamide, but no trace of dithioanthranilic acid was
found. Instead, 2-(2-aminophenyl)-4H-3,1-benzothiazine-4-thione (9) was isolated by immediate
decomposition of the generated dithioanthranilic acid (Scheme 3).
S
CSSH
NH2
CSSNa
NH2
S
NaSH
DMF
H
HCl
6
N
H2S
H2N
8
9
Scheme 3
Jourdan and co-workers first reported the formation and isolation of compound 9 in high yield upon the
acidification of the reaction mixture obtained by the reaction of 2-aminobenzotrifluoride with sodium

HETEROCYCLES, Vol. 91, No. 12, 2015
2331
sulfide in dimethyl sulfoxide.11 They did not try to obtain any alkyl esters of dithioanthranilic acid, but
applied the reaction mixture containing sodium dithioanthranilate to the synthesis of trithioisatoic
anhydride and isothiazole derivatives.
R1
H
R2
Me
Yields(%)
CSSMe
NH2
74
61
65
37
52
54
10a
10b
10c
R1COR2/ THF
OH
C
6
H
Et
Ph
+
R1
R2
H
p-MeC6H4
10d
10e
10f
H
p-MeOC6H4
H
H
1-C10H7
10g
10h
2-C10H7
Me
H
50
57
S
Me
CSSMe
O
Me
Et
Et
Et
10i
10j
88
57
Br
R1
R2
NH2 CR1R2OH
N
H
MeSH
57
7
10k Me
10l
Ph
B
(CH2)4
(CH2)5
10
43
10m
Scheme 4
When methyl dithioanthranilate hydrobromide (6) was refluxed with each aldehyde or ketone in
tetrahydrofuran or methanol, 2-substituted or 2,2-disubstituted 1,2-dihydro-4H-3,1-benzoxazine-4-
thiones 10a-m were obtained as a new series of heterocyclic compounds fused with benzene ring.
These benzoxazine-4-thiones 10a-m were probably formed via the cyclization of intermediates B, which
may have arisen from the addition of deprotonated methyl dithioanthranilate to a protonated carbonyl
compound formed by proton transfer (Scheme 4).
It is somewhat curious that cyclopentanone afforded 4-thioxo-1,2-dihydro-4H-3,1-benzoxazine-2-
spirocyclopentane (10l) in very low yield. One explanation for this abnormally low yield may be that the
proton transfer from the hydrobromide 6 to cyclopentanone would be difficult, and another one for the
extraordinary low yield is that the amino group of free methyl dithioanthranilate is very weak nucleophile
and is slow to add to the carbonyl of protonated cyclopentanone, which is more planar and having less
space for the reaction to take place than that of cyclohexanone. By these reasons, the majority of the
intermediate B would decompose before the formation of the benzoxazine 101.
In the reaction of methyl dithioanthranilate hydrobromide (6) with formaldehyde, the parent
1,2-dihydro-4H-3,1-benzoxazine-4-thione was never formed, but only N-(methylthio)methyl-
1,2-dihydro-4H-3,1-benzoxazine-4-thione (11) was obtained.

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HETEROCYCLES, Vol. 91, No. 12, 2015
CSSMe
NH3Br
CSSMe
NH2
H2C O
H2C OH Br
6
7
S
CSSMe
HBr
O
H2C O , HBr
MeSH
N
H
NHCH2OH
(R1= R2 = H)
10
S
S
O
O
OH2
MeSCH2
Br
+
74%
N
N
H
CH2SMe
11
Scheme 5
The route for forming N-(methylthio)methylbenzoxazinethione 11 was arbitrarily proposed as follows:
formaldehyde reacted first with the hydrobromide 6 to give parent 1,2-dihydoro-4H-3,1-
benzoxazine-4-thione (10; R1=R2=H), but the excess formaldehyde existing in situ is so reactive that it
also reacted with methanethiol liberated from the protonated intermediate B (in this case, R1=R2=H) to
form protonated methylthiomethanol, which reacted rapidly with the parent 4H-3,1-benzoxazine-4-thione
to give N-(methylthio)methylbenzoxazine-4-thione 11 (Scheme 5).
On the other hand, when a mixture of methyl dithioanthranilate hydrobromide (6) was warmed with
equimolar aromatic aldehyde or an aliphatic ketone and two equivalents of sodium hydrogensulfide in
mixed solvent of ethanol and tetrahydrofuran, another new class of fused heterocyclic compounds,
2-substituted or 2,2-disubstituted 1,2-dihydro-4H-3,1-benzothiazine-4-thiones 12a-e, were obtained as
deep red to reddish orange products in relatively high yields. Salem and Soliman first reported
2-[4-(chlorobenzoyl)vinyl]-4H-3,1-benzothiazine-4-thione17 which corresponds to an example of dehydro
type derivative of 1,2-dihydro-4H-3,1-benzothiazine-4-thiones synthesized by us.
Compared with high to medium yields of compounds 12a-d, the yield of compound 12e is below 50%
and is markedly lower than that of compound 12d. This large difference may be the steric hindrance of
ethyl group of the reactant, ethyl methyl ketone. Each step of the reaction forming the intermediate C and
intramolecular cyclization of the intermediate C by losing water would be, therefore, slow and this may
lead to lowering the yield of compound 12e.

HETEROCYCLES, Vol. 91, No. 12, 2015
2333
These benzothiazine-4-thione derivatives 12a-e may have been yielded via intermediates C, which were
formed by the hydrolysis of methyl dithioanthranilate with sodium hydrogensulfide (Scheme 6).
S
.
2NaSH / EtOH THF
CSSNa
R1COR2
S
6
R1
R2
NHCR1R2OH
H2O
N
H
C
12
R1
R2
yields(%)
12a
12b
H
H
Ph
p-MeC6H4
76
69
p-MeOC6H4
12c
12d
12e
H
59
90
47
Me
Me
Me
Et
Scheme 6
1
13
The H- and C NMR and IR spectra of the 4H-3,1-benzoxazinethiones 10a-m, N-(methylthio)methyl-
1,2-dihydro-4H-3,1-benzoxazinethione 11, and -benzothiazinethiones 12a-e were all in good agreement
with the proposed structures (See EXPERIMENTAL).
EXPERIMENTAL
Melting points were determined on a Mettler FP62 and a Yanagimoto MP-J melting point apparatuses and
are uncorrected. NMR spectra were taken on a Nihondenshi model JEOL EX270 spectrometer and IR
spectra were obtained with a Nihonbunko (JASCO) FT/IR-5000 spectrometer.
Low-pressure chromatographic separations were achieved by utilizing Oyobunko UVLOG/ALPC-100.
Pure anhydrous sodium hydrogensulfide was obtained by recrystallizing reagent grade NaSH࣭nH2O
(Wako) from ethanol and diethyl ether and then by drying the resulting pure NaSH࣭nH2O crystals over
silica gel in vacuo.
Diphosphorus pentasulfide (Aldrich) was used as purchased. All solvents such as benzene, Et2O, THF,
and CH2Cl2 were distilled just before use.
Ethyl N-benzyloxycarbonylanthranilate (1). To a stirred solution of ethyl anthranilate (1.652 g, 10
mmol) and ethyldi- isopropylamine (3.87 g, 30 mmol) dissolved in 50 mL of CH2Cl2, was added benzyl
chloroformate (2.56 g, 15 mmol) dropwise at 0 °С. The resulting mixture was continued to warm at 30 °С
for 19 h. After 100 mL of saturated aqueous NH4Cl solution was added to the cooled reaction mixture, the
solution was extracted three times with each 30 mL of CH2Cl2. The combined CH2Cl2 extract was dried

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HETEROCYCLES, Vol. 91, No. 12, 2015
(MgSO4), and evaporated in vacuo to give reddish viscous residue. Ethyl anthranilate remaining in the
viscous residue was removed in vacuo at 130 °С. The solidified residue (2.95 g, 98.6%) was washed with
cooled EtOH, then was recrystallized from hot EtOH to give white crystals of compound 1; mp
25.5-28.0 °С ; IR (KBr) : 3297 (NH), 1738 (Ph-COO), 1690 (NHCOO) cm-1. 1H NMR (CDCl3) : δ 10.64
(br. s, NH), 8.47 (d,1H, J=7.5 Hz, 6-H), 8.01 (d, J=7.5 Hz, 1H, 3-H), 7.35 (m, 5H, phenyl protons), 7.02 (t,
1H, J=7.5 Hz, 4-H), 5.20 (s, 2H, N-CH2), 4.34 (q, 3H, J=7.3 Hz, OCH2), 1.37 ppm (t, 3H, J=7.3 Hz, CH3).
Anal. Calcd for C17H17N O4: C, 68.21; H, 5.73; N, 4.68. Found: C, 68.50; H, 5.64; N, 4.50.
N-Benzyloxycarbonylanthraniloyl piperidine (2). To ice-cooled solution of butyllithium (4.48 g, 70
mmol) in THF (120 mL), was added dropwize piperidine (6.13 g, 72 mmol) diluted with THF (20 mL),
and to this mixture was added ethyl N-benzyloxycarbonylanthranilate (5.99 g, 20 mmol) in THF (40 mL)
at -15 °С.ꢀ The mixture was kept for 2 h at -15 °С and kept for an additional 1 h at 0 °С under Ar, then
MeOH (20 mL) was added to this reaction mixture. After adding saturated aqueous NH4Cl solution (400
mL) to the subsequent mixture at 0 °С, the water layer, which was separated, was extracted with Et2O
(120 mL×3). The combined Et2O extract was dried (MgSO4), evaporated in vacuo to give yellow oil,
which was column-chromatographed [silica gel (Fuji-Davison, BW-350), EtOAc-hexane:1:4] to give 5.46
g (91.2%) of pale yellow crystals of 2. Recrystallization from CH2Cl2-hexane gave white crystals of
Z-protected anthraniloyl piperidine (2); mp 71.8-74.6 °С.
N-Benzyloxycarbonylthioanthraniloyl piperidine (3). A mixture of N-benzyloxycarbonylanthraniloyl
piperidine (2) (1.69 g, 5 mmol) and diphosphorus pentasulfide (2.23 g, 5 mmol) in 1,4-dioxane (50 mL)
was mechanically stirred under Ar and ultrasonic irradiation (24 kHz) at room temperature for 1 h. The
resulting reaction mixture was continued to stir at 60 °С for 2 h under Ar. To a clear orange solution after
removing the insoluble matters from the reaction mixture by filtration, was added water (100 mL) and the
resulting aqueous solution was extracted with Et2O (30 mL×3). The combined Et2O extract was washed
with water (100 mL), dried (MgSO4), and evaporated in vacuo to give an oily matter, which was
column-chromatographed [silica gel, (Fuji-Davison, BW-350), CH2Cl2] to give 4.75 g (89.4%) of
greenish yellow crystals of compound 3. Recrystallization from acetone-hexane gave white crystals of
compound 3; mp 101.5-102.0 °С㸹IR (KBr): 3335 (NH), 3063, 2942, 2859, 1736 (C=O), 1584 and 1518
(aromatic ring conjugated with R2NC=S), 1447, 1290, 1244, 1215, 980, 855, 745 cm-1. Both CH2 bonded
to N-atom and neighboring CH2 to it in piperidino group of compound 3 showed magnetic anisotropy by
the restricted rotation of piperidino group in both 1H- and 13C NMR spectra. 1H NMR (CDCl3) : δ 7.95 (d,
1H, J=7.5 Hz, 6-H), 7.53 (br. s., 1H, NH), 7.33 (m, 6H, phenyl protons and 3-H), 6.98 (t, 1H, J=7.5 Hz,

HETEROCYCLES, Vol. 91, No. 12, 2015
2335
4-H), 7.05 (t, 1H, J=7.5 Hz, 5-H), 5.20 and 5.15 (each d, J=9.5 Hz, CH2Ph), 4.30 and 3.45 (m, 4H,
13
N-CH2×2), 1.74 and 1.63 (m, 4H, NCH2CH2), 1.40 ppm (m, 2H, NCH2CH2CH2); C NMR (CDCl3) : δ
194.9 (C=S), 153.5 (C=O), 136.1-122.0 (9 peaks, phenyl carbons), 66.9, 53.0, 49.9, 26.8, 25.6, 24.0 ppm.
Anal. Calcd for C20H22O2N2S: C, 67.76; H, 6.26; N, 7.90. Found: C, 67.63; H, 6.61; N, 8.07.
2-Benzyloxycarbonylamino-(D-methylthio)benzylidenepiperidinium iodide (4). N-Benzyloxy-
carbonylthioanthraniloyl piperidine (1.77 g, 5 mmol) was dissolved in iodomethane (10 mL) and the
solution was allowed to stand overnight at room temperature. The resulting solution did not show any
other components than the iminium salt 4 by TLC check. Excess iodomethane was removed thoroughly in
vacuo to give D-methylthiobenzylidene-piperidinium iodide 4 as yellow glassy solid in quantitative yield;
mp 223 °С (decomposition). This compound could not be recrystallized from any solvents, but always
separated as an oily matter); IR (KBr): 3433 (NH), 3150, 2944, 2863, 1722 (C=O), 1601, 1578, and 1516
cm-1. Anal. Calcd for C21H25O2N2SI: C, 50.81; H, 5.08; N, 5.64; S, 6.46. Found: C, 50.38; H, 5.01; N,
5.65; S, 6.47.
Methyl N-benzyloxycarbonyldithioanthranilate (5). To a solution of 2-benzyloxycarbonylamino-
D-methylthiobenzylidenepiperidinium iodide 4 (2.48 g, 5 mmol) in iodomethane (20 mL), was added
pyridine (20 mL) and then hydrogen sulfide was babbled to this solution for 1 h at -15 °С, followed by
stirring for an additional 1 h. After removing pyridine under reduced pressure, CH2Cl2 (100 mL) was
added to the residue and the insoluble matter was filtered off. This CH2Cl2 extract was washed with water
(50 mL×2), dried (MgSO4), and evaporated in vacuo to yield orange to red oily matter, which was
purified by flash column chromatography [silica gel ( Fuji-Davison, BW-350), eluent; EtOAc-hexane: 1:
4] to give 1.02 g (64.3%) of orange oil of 5 and 0.49 g (25.5%) of Z-protected thioanthraniloyl piperidine
(3). Fractional distillation with Kugelrohl in vacuo gave pure compound 5; bp 186 °С (2.67 hPa); IR
(potassium bromide) 3328 (NH), 3065 ,3032, 1736 (C=O), 1599, 1520, 1442, 1373, 1305, 1207, 1165,
1121, 1069, 1028, 889, 839, 756, 698 cm-1; 1H NMR (CDCl3) : δ 8.95 (br. s, 1H, NH), 8.18 (d, 1H, J=7.5
Hz, 3-H), 7.55 (d, 1H, J=7.5 Hz, 6-H), 7.35 (m, 6H, phenyl protons and 4-H), 7.05 (t, 1H, J=7.5 Hz, 5-H),
5.15 (s, 2H, CH2), 2.73 ppm (s, 3H, CH3); 13C NMR (CDCl3) : δ 230.3 (C=S), 153.5 (C=O), 136.0-121.2
(9 peaks; phenyl carbons), 67.0, 20.9 ppm.ꢀ Anal. Calcd for C16H15NO2S2: C, 60.54; H, 4.76; N, 4.41.
Found: C, 60.27; H, 4.84; N, 4.47.
Methyl dithioanthranilate hydrobromide (6). To a solution of methyl N-benzyloxycarbonyl-
dithioanthranilate (5) (1.60 g, 5 mmol) in acetic acid (25 mL), was added HBr in acetic acid (47%, 25
mL) dropwise at room temperature under mechanical stirring and the solution was stirred for additional

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HETEROCYCLES, Vol. 91, No. 12, 2015
30 min. The solvent of the reaction mixture was evaporated in vacuo at 40 °С to leave crude solid, which
was washed 3 times with Et2O, dried (silica gel) to give 1.30 g (98.5%) of methyl dithioanthranilate
hydrobromide (6) as orange solid (chromatographically pure). Recrystallization from 1-propanol and
hexane gave orange crystals; mp 191.6 °С; IR (KBr): 3440 and 3325 (NH2), 3063, 2990, 2821, 2724,
1
2535, 1555, 1483, 1252 1073, 1022, 905, 891, 760 cm-1; H NMR (DMF-d6) : δ 7.77-7.49 (m, 4H,
+
aromatic protons), 7.12 (s, 3H, NH3 ), 2.85 ppm (s, 3H, SCH3); 13C NMR (DMF-d6) : δ225 (C=S), 162,
161, 136, 134, 131, 122, 29 ppm. Anal. Calcd for C8H10NS2Br: C, 36.37; H, 3.82; N, 5.30. Found: C,
36.32; H, 3.75; N, 5.18.
Methyl dithioanthranilate (7). An aqueous solution (15 mL) of pure methyl dithioanthranilate
hydrobromide (6) (0.793 g, 3 mmol) was neutralized with aqueous sodium hydrogensulfide (ca. 1M), then
extracted with Et2O (20 mL×2). The combined Et2O extract was dried (MgSO4) and evaporated to
dryness in vacuo to afford red viscous oil (chromatographically pure), yield 0.35 g (64%); IR (KBr) 3445
and 3325 (NH2), 3063, 2938, 2855, 1612, 1586, 1480, 1451, 1213, 1163, 1015, 905, 889 and 750 cm-1; 1H
NMR (CDCl3) : δ 7.81 (dd, 1H, J=1 Hz and 7.6 Hz, 6-H), 7.19 (dt, 1H, J=1 Hz and 7.6 Hz, 4-H), 6.69 (d,
1H, J=7.6 Hz, 3-H), 6.67 (t, 1H, J=7.6 Hz, 5-H), 5.83 (br. s, 2H, NH2), and 2.69 ppm (s, 3H, SCH3); 13C
NMR (CDCl3) : δ 227.9 (C=S), 145.9, 132.5, 128.9, 128.1, 117.9, 116.7, and 20.0 ppm. ꢀ
Confirmation of Formation of Sodium dithioanthranilate (8). Methyl dithioanthranilate hydrobromide
(6) (0.186 g, 1 mmol) was dissolved in DMF (10 mL) and to this was added sodium hydrogensulfide
(0.19 g, 3.3 mmol) in DMF (10 mL) dropwise at 0 °С to give a black solution, which was warmed
gradually to 40 °С㸬After 1 h, a drop of the solution was highly diluted with acetone and to this was added
one drop of 0.1% aqueous NiCl2. The solution was colored immediately to thick deep bluish purple,
indicating the formation of a complex between Ni(II) ion and sodium dithioanthranilate (8).
2-(2-Aminophenyl)-4H-3,1-benzothiazine-4-thione (9). After dilution of above reaction mixture with
water (20 mL), the aqueous solution was washed with Et2O (20 mL×5) to remove DMF thoroughly, and
the aqueous layer was acidified (pH ca. 5) with 1M-HCl to separate red oily matter, which was extracted
with Et2O (20 mL×2). The combined Et2O extract was dried (MgSO4), evaporated in vacuo to afford red
oil, which solidified on standing overnight, yield 0.145 g (49%). Recrystallization from hot EtOH gave
1
red crystals of compound 9; mp 152-153 °С; the δ values of H NMR of compound 9 were in good
13
agreement with those reported by Jourdan et al. ; C NMR (CDCl3) : δ 211 (C=S), 164, 148, 141, 136,
132, 130, 129, 128, 127, 126, 118, 117, 116 ppm; IR (KBr): 3420 and 3275 (NH2), 1616, 1578, 1522,
1454, 1236, 1197, 1153, and 1013 cm-1. Anal. Calcd for C14H10N2S2: C, 62.19; H,3.73; N, 10.36.

HETEROCYCLES, Vol. 91, No. 12, 2015
2337
Found: C, 62.19; H, 3.75; N, 10.39.
General procedure for the synthesis of 2-substituted or 2,2-disubstituted 1,2-dihydro-4H-3,1-
benzoxazine-4-thiones (10a-m). A mixture of 1 mmol of methyl dithioanthranilate hydrobromide (6), 1
to 2 mmol of appropriate aldehyde or ketone, and 10 mL of THF (for 10a-c,10e) or MeOH (for 10f-g,
10k-l) was refluxed at 66 °С for 24 h. The reaction mixture was cooled and then diluted with water (30
mL) and extracted with Et2O (50 mL×3). The combined Et2O extract was washed once with water (50
mL), dried (MgSO4), evaporated, and the residue obtained was separated by chromatography (the residue
was pre-absorbed on silica gel, eluent:1:10 C6H6-C5H12). Orange to yellow crystals of crude compounds
10 were recrystallized from benzene-pentane (10c,e, h-m) or -hexane (10a,b,f,g). For the synthesis of
compound 10d, EtOH was used as solvent and refluxed at 80 °С for 24 h. For the syntheses of
1,2-dihydro-4H-3,1-benzoxazine-4-thiones, 10h-j and 10m, each large excess of the corresponding
ketone was used under refluxing at 60 to 80 °С for 24 h. ꢀ
2-Methyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10a). Paraldehyde was used in place of MeCHO
for the synthesis of compound 10a. Yellow crystals: yield 0.13 g (74%); mp 90.5-92 °С; IR (KBr) 3312
1
(NH), 3067, 2979, 2965, 2881, 1616, 1505 (hetero ring), 1481, 1280, 1119, 930, 760 cm-1; H NMR
(CDCl3): δ 7.92 (quasi d, 1H, J=6.8 Hz, 5-H), 7.40 (dd, 1H, J=1 Hz and 8.1Hz, 7-H), 6.85 (t, 1H, J=7.3
Hz, 6-H), 6.75 (dd, 1H, J=1 Hz and 8 Hz, 8-H), 5.22 (q, 1H, J=6.5 Hz, 2-H), 4.30㸦br s, 1H, NH, 1.65
13
ppm (d, 3H, J=6.5 Hz, CH3); C NMR (CDCl3): δ 188 (C=S), 148.7, 134.8, 127.9, 120.6, 119.4, 117.6,
55.1, 20.9 ppm. Anal. Calcd for C9H9NOS: C, 60.31; H, 5.06; N, 7.82; S, 17.87. Found: C, 60.06; H,
4.79; N, 7.91; S,17.65.
2-Ethyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10b). Orange viscous oil: yield 0.12 g (61%); IR
(KBr) 3323 (NH), 3065, 2968, 2933, 2875, 1614, 1504, 1484, 1269, 1192, 1157, 1126, 932, 764 cm-1; 1H
NMR (CDCl3): δ 7.90 (dd, 1H, J=1.6Hz and 8.1Hz, 5-H), 7.31 (t, 1H, J= 8.1 Hz , 7-H), 6.80 (m, 2H, 6-H
and 8-H), 5.01 (t, 1H, J=6.75 Hz, 2-H), 4.80 (br. s, 1H, NH), 2.02 (q, 2H, J=6.75 Hz, -CH2-), 1.09 ppm (t,
3H, J=6.75Hz, CH3); 13C NMR (CDCl3): δ 188.2 (C=S), 48.7, 134.9, 127.7, 120.6, 119.2, 117.7, 61.0,
28.2, 9.91 ppm. Anal. Calcd for C10H11NOS: C, 62.15, H,5.74; N,7.25: S,16.59. Found: C, 61.81; H,5.95,
N,7.54, S,16.20.
2-Phenyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10c). Yellow crystals: yield 0.16 g (65%); mp
1
163.5-164 °С; IR (KBr): 3310 (NH), 1615, 1599, 1481, 1275, 1155, 1103, 934, 770 cm-1; H NMR
(CDCl3): δ 7.92 (d,1H, J=8.1 Hz, 5-H), 7.60 (dd, J=1 Hz and 7.0 Hz, 7-H), 7.43-7.25 (m,5H, phenyl
protons), 6.875 (t, 1H, J=7.6Hz, 6-H), 6.75 (d, 1H, J=8.1 Hz, 8-H), 6.18 (s, 1H, 2-H), 4.82 ppm (br. s, 1H,

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HETEROCYCLES, Vol. 91, No. 12, 2015
NH); 13C NMR (CDCl3): δ 187.7 (C=S) 148.7, 136.5, 135.1, 129.9, 129.2, 128.3, 128.0, 127.6, 120.2,
119.7, 63.3 ppm. Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80; S, 13.29. Found: C, 69.70; H,
4.52; N, 5.70; S, 13.24.
2-(p-Tolyl)-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10d). Yellow crystals: yield 0.095 g (37%); mp
137.5-138 °С; IR (KBr): 3267 (NH), 1599 (vs, phenyl and hetero ring), 1503, 1481, 1279, 1155, 1103,
936 cm-1; 1H NMR (CDCl3): δ 7.90 (d, 1H, J=7.5 Hz, 5-H), 7.48 and 7.25 (each d, 4H, J=8.1 Hz, 2’, 3’ 5’,
6’-protons), 7.35 (t, 1H, J=7.5 Hz, 7-H), 7.28 (d, 1H, J=7.5 Hz, 6-H), 6.86 (t, 1H, J=7.5 Hz, 8-H), 6.14
(s,1H, 2-H), 4.81 (br. s, 1H, NH), 2.40 ppm (s, 3H, CH3); 13C NMR (CDCl3): δ 187.7 (C=S), 148.8, 140.0,
135.0, 129.8, 128.3, 128.0, 127.5, 120.2, 119.6, 117.5, 63.1, 21.3 ppm. Anal. Calcd for C15H13NOS: C,
70.56; H, 5.13; N, 5.49; S, 12.56. Found: C, 70.44; H, 5.05; N, 5.36; S, 12.84.
2-(p-Methoxyphenyl)-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10e). Yellow crystals: yield 0.14 g
(52%); mp 156.7-157.2 °С; IR (KBr): 3316 (NH), 1618, 1599, 1512, 1497, 1483, 1279, 1248, 1177, 1032,
936, 837, 768 cm-1; 1H NMR (CDCl3): δ 7.75 (d, 2H, J=7.6 Hz, 2’-H and 6’-H); 7.59 (d, 2H, J=7.6 Hz, 5
and 8-H); 7.39 (t, 1H, J=7.6 Hz, 7-H); 7.03 (d, 3H, J=7.6.Hz, 3’-H, 5’-H, and NH)), 6.79 (t, 1H, J=7.6.Hz,
6-H), 6.35 (s, 1H, 2-H), 3.78 ppm (s, 3H, OCH3); 13C NMR (CDCl3): δ 186.8 (C=S), 159.9, 150.1, 134.9,
129.0, 128.9, 126.7, 118.6, 117.9, 117.8, 114.0, 61.5, 55.2 ppm. Anal. Calcd for C15H13NO2S: C, 66.40; H
4.83; N, 5.16: S, 11.82. Found: C, 66.38; H, 4.73; N, 5.13; S, 11.74.
2-(1-Naphthyl)-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10f). Yellow crystals: yield 0.16 g (54%);
mp 210.5-212.4 °С; IR (KBr): 3280 (NH), 1623, 1597, 1499, 1481, 1277, 1193, 1109, 933, 782, 765 cm-1;
1H NMR (DMSO-d6): δ 8.05-7.09 (m, 11H, aromatic protons), 6.85 (quasi s, 2-H), 6.17 ppm (br. s, 1H,
NH); 13C NMR (DMSO-d6): δ 186.9 (C=S), 150.5, 135.0, 133.5, 132.2, 129.8, 129.7, 128.8, 128.2, 126.9,
126.4, 126.2, 125.3, 124.0, 118.7, 117.9, 59.8 ppm. Anal. Calcd for C18H13NOS: C, 74.20; H; 4.50; N,
4.81; S, 11.00. Found: C, 74.31; H, 4.63; N, 4.59; S, 10.96.
2-(2-Naphthyl)-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10g). Yellow crystals: yield 0.145 g (50%);
mp 201.4-201.9 °С; IR (KBr): 3303 (NH), 1612, 1503, 1481, 1280, 1190, 1155, 1103, 934, 863, 826, 754
cm-1; 1H NMR (acetone-d6): δ 8.01-6.83 (m, 11H, aromatic protons), 6.53 (s, 2-H), 6.17 ppm (s, 1H, 2-H).
13C NMR (acetone-d6): δ187.2 (C=S), 151.0, 135.9, 135.7, 134.6, 134.1, 129.6, 129.0, 128.6, 127.8, 127.7,
127.6, 125.7, 120.5, 119.5, 118.8, 63.8 ppm. Anal. Calcd for C18H13NOS: C, 74.20; H, 4.50; N, 4.81; S,
11.00. Found: C, 73.95; H, 4.55; N, 4.77; S, 10.78.
2,2-Dimethyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10h). Orange crystals: yield 0.11 g (57%); mp
105.8-106.3 °С; IR (KBr): 3306 (NH), 1601, 1505, 1481, 1285, 1227, 1161, 934, 766 cm-1; UV (EtOH)

HETEROCYCLES, Vol. 91, No. 12, 2015
2339
λmax 236.6 (log ε 4.30), 254 (sh, 3.87), 274.6 (sh, 3.54), 378.6 nm (3.48); 1H NMR (CDCl3): δ 7.80 (d ,1H,
J=8.1 Hz, 5-H), 7.36 (t, 1H, J=7.0 Hz, 7-H), 6.79 (t, 1H, J=7.3 Hz, 6-H), 6.90 (d, 1H, J=8.1 Hz, 8-H),
13
6.50 (br. s, 1H, NH), 1.75 ppm (s, 6H, CH3×2); C NMR (CDCl3): δ 187.3 (C=S), 149.1, 135.7, 127.5,
119.4, 118.9, 118.7, 64.1, 30.6 ppm. Anal. Calcd for C10H11NOS: C, 62.15, H,5.74; N,7.25: S,16.59.
Found: C, 61.90; H,5.71, N,7.17, S,16.75.
2-Ethyl-2-methyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10i). Orange crystals: yield 0.18 g (88%);
mp 66.6-67.1 °С; IR (KBr): 3326 (NH), 3065, 2971, 2934, 2878, 1598, 1482, 1285, 1155, 1106, 955, 855,
764 cm-1; UV (EtOH) λmax 238 (log ε 4.34), 258 (sh,3.91), 273 (sh,3.63), 383 nm (3.52); 1H NMR
(CDCl3): δ 7.90 (d, 1H, J=8.1 Hz, 5-H), 7.33 (t, 1H, J=7.0 Hz, 7-H), 7.26 (d, 1H, J=8.1 Hz, 8-H), 6.815 (t,
1H, J=7.3 Hz, 6-H), 4.59 (br. s, 1H, NH), 2.03 (m, 2H, CH2Me), 1.69 (s, 3H, CH3), 1.02 ppm (t, 3H,
13
CH2CH3); C NMR (CDCl3): δ 188.0 (C=S), 147.0, 135.1, 127.5, 119.4, 118.9, 117.9, 67.1, 35.4, 27.8,
9.0 ppm. Anal. Calcd for C11H13NOS: C, 63.74, H, 6.32; N, 6.76: S, 15.47. Found: C, 63.79; H,6.32;
N,6.73; S,15.31.
2,2-Diethyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10j). Orange crystals: yield 0.125 g (57%); mp
77.5-78.0 °С; IR (KBr) 3287 (NH), 2972, 2938, 1595, 1516, 1481, 1380, 1290, 1253, 1147, 1106, 988,
942, 856, 765 cm-1; UV(EtOH) λmax 239 (log ε 4.38), 258 (sh, 3.95), 280 (sh, 3.58), 387 nm (3.53); 1H
NMR (CDCl3) δ7.88 (d, 1H, J=7.8 Hz, 5-H), 7.32 (t, 1H, J=7.6 Hz, 7-H), 6.785 (t, 1H, J=7.6 Hz, 6-H),
7.75 (d, 1H, J=7.6 Hz, 8-H), 4.77 (s, 1H, NH), 2.03 (q, 4H, J=7.6 Hz, CH2×2), 0.99 ppm (t, 6H, J=7.6 Hz,
CH3×2); 13C NMR (CDCl3) δ 188.2 (C=S), 147.2, 135.1, 127.2, 119.4, 118.6, 117.9, 71.0, 32.2, 8.7, 8.4
ppm. Anal. Calcd for C12H15NOS: C, 65.12; H, 6.83; N, 6.33; S, 14.49. Found: C, 64.96; H, 6.79; N, 6.29;
S, 14.26.
2-Methyl-2-phenyl-l,2-dihydro-4H-3,1-benzoxazine-4-thione (10k). Orange crystals: yield 0.145 g
(57%); mp 127.1-127.6 °С; IR (KBr): 3314 (NH), 3060, 3033, 2985, 2923, 1601, 1481, 1444, 1281, 1254,
1203, 1145, 956, 929, 762, 698 cm-1; UV (EtOH): λmax 236 (log ε 4.56), 258 (sh, 4.10), 282 (sh, 3.71),
378 nm (3.68). Anal. Calcd for C15H13NOS: C, 70.56; H, 5.13; N, 5.49; S,12.56. Found: C, 70.30; H,
5.14; N,5.50; S,12.45.
4-Thioxo-l,2-dihydro-4H-3,1-benzoxazine-2-spirocyclopentane (10l). Orange crystals: yield 0.015 g
(7%); mp 84.6-85.1 °С; IR (KBr): 3299 (NH), 3069, 2925, 2850, 1611, 1590, 1508, 1480, 1282, 1144,
933, 769 cm-1; UV (EtOH): λmax 238 (logε 4.29), 258 (sh, 3.89), 281 (sh, 3.53), 306 (3.19), 382 nm
(3.47); 1H NMR (CDCl3): δ7.83-6.75 (m, 4H, aromatic protons), 4.49 (br.s, 1H, NH), 2.23-1.475 ppm (m,
8H, C4H8). Anal. Calcd for C12H13NOS: C, 65.72; H, 5.97; N, 6.39 S, 14.62. Found: C, 64.81; H, 6.30; N,

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HETEROCYCLES, Vol. 91, No. 12, 2015
6.30; S,14.59.
4-Thioxo-l,2-dihydro-4H-3,1-benzoxazine-2-spirocyclohexane (10m). Yellow crystals㸸yield 0.10 g
(43%); mp 191.8-192.3 °С; IR (KBr): 3299 (NH), 3070, 2925, 2850, 1610, 1591, 1508, 1480, 1282, 1210,
1143, 933, 769 cm-1; UV (EtOH): λmax 238 (log ε 4.16) 258 (sh, 3.72), 277 (sh, 3.40), 384 nm (3.28); 1H
NMR (CDCl3): δ 7.88 (d, 1H, J=7.6 Hz, 5-H), 7.33 (t, 1H, J=7.3 Hz, 7-H), 6.82 (t, 1H, J=7.6 Hz, 6-H),
6.74 (d, 1H, J=8.1 Hz, 8-H), 4.49 (br. s, 1H, NH), 2.20-1.44 ppm (m, 10H, cyclo-C5H10) ; 13C NMR
(CDCl3): δ 187.7 (C=S), 146.6, 135.0, 127.4, 120.1, 119.1, 118.0, 66.9, 38.7, 25.0, 22.0 ppm. Anal. Calcd
for C13H15NOS: C,66.92; H,6.48; N,6.00; S,13.74. Found: C,66.62; H,6.59; N,5.83; S,13.42.
N-Methylthiomethyl-1,2-dihydro-4H-3,1-benzoxazine-4-thione (11).
A
mixture of methyl
dithioanthranilate hydrobromide (6) (0.265g, 1 mmol), paraformaldehyde (0.88g, 6.7 mmol), THF (10
mL) was refluxed at 66 Υ for 24 h. To the cooled reaction mixture, was added water (30 mL) and Et2O
(50 mL), and then was shaken vigorously. After separating organic layer, the water layer was extracted
with Et2O (50 mL×3). The combined Et2O extract was dried (MgSO4), evaporated in vacuo to give oily
matter, which was chromatographed (silica gel, 400 mesh, 1:4 EtOAc-pentane) to give 0.13 g (74%) of
crude yellow crystals of compound 11. Recrystallization from benzene-hexane gave yellow crystals of
compound 11; mp 90.5-92 °С; IR (KBr): 3065, 2968, 2919, 2877, 2834, 1596, 1631, 1596, 1474, 1283,
1
1125, 984, 929, 892, 772 cm-; H NMR (CDCl3): δ 8.01 (d, 1H, J=7.6 Hz, 5-H), 7.50 (t, 1H, J=7.6 Hz,
7-H), 6.99 (t, 2H, J=7.3 Hz, 6-H and 8-H), 4.94 (s, 2H, 2-H), 4.94 (s, 2H, NCH2O), 4.58 (s, 2H, NCH2S),
2.24 (s, 3H, CH3); 2.24 ppm (s, 3H, CH3); 13C NMR (CDCl3): δ 188.0 (C=S)., 148.7, 134.7, 128.4, 123.8,
120.9, 118.8, 57.2, 50.9, 15.0 ppm. Anal. Calcd for C10H11NOS2: C, 53.30; H, 4.92; N, 6.22; S, 28.46.
Found: C, 53.36; H, 4.96; N, 6.27; S, 28.44.
General procedure for the synthesis of 2-substituted or 2,2-disubstituted 1,2-dihydro-4H-3,1-
benzothiazine-4-thiones (12a-e). To a three-necked flask containing EtOH (10 mL) and finely powdered
pure NaSH (0.56 g, 10 mmol), was added 0.5 mmol of the appropriate aldehyde or ketone dissolved in
THF (10 mL) and methyl dithioanthranilate (0.132 g, 0.5 mmol) in THF (10 mL), which was obtained by
neutralizing methyl dithioanthranilate hydrobromide with ethyldiisopropylamine, and the resulting
mixture was warmed to 40~50 °С for 18 h under Ar. The mixture turned deep red. Water (150 mL) was
added to the reaction mixture, and the organic layer was separated. The water layer was extracted with
Et2O (60 mL×3). The organic layer and each Et2O extract were combined, dried (MgSO4), and evaporated
in vacuo to remain deep red oily matter, which was chromatographed (silica gel, 400 mesh, 1:10
EtOAc-pentane) to give deep red crystals or oil which solidified under storage in a desiccator.

HETEROCYCLES, Vol. 91, No. 12, 2015
2341
1,2-Dihydro-4H-3,1-benzothiazinethiones 12a-c obtained as crude red crystals were recrystallized from
benzene-pentane.
2-Phenyl-1,2-dihydro-4H-3,1-benzothiazine-4-thione (12a). Red crystals: yield 0.098 g (76%); mp
116.5-117.0 °С; IR (KBr): 3449 (NH), 1605, 1562, 1491, 1472 cm-1; 1H NMR (CDCl3): δ 8.36 (dd, 1H,
J=1.5 Hz and 7Hz, 5-H), 7.58 (quasi dt, 1H, J=7.3 Hz, 7-H), 7.45 - 7.41 (m, 5H, phenyl protons), 6.87 (t,
1H, J=8.1 Hz, 6-H), 6.73 (d, 1H, J=8.1 Hz, 8-H), 6.00 (s, 1H, 2-H), 4.96 ppm (br. s, 1H, NH); 13C NMR
(CDCl3): δ 217.6 (C=S), 144.6, 135.4 135.3, 130.1, 130.0, 129.3, 128.0, 127.7, 120.0, 117.8, 63.7 ppm.
Anal. Calcd for C14H11NS2: C, 65.33; H, 4.31; N, 5.44; S, 24.92. Found: C, 65.32; H, 4.31; N, 5.15; S,
24.64.
2-(p-Tolyl)-1,2-dihydro-4H-3,1-benzothiazine-4-thione (12b). Red crystals: yield 0.094 g (69%); red
viscous oil; IR (KBr): 3449 (NH), 1611, 1561, 1477 cm-1; 1H NMR (CDCl3): 8.37 (d, 1H, J=7.5 Hz, 5-H),
7.47 (d, 2H, J=8.1 Hz, 2’-H and 6’-H), 7.36 (m, 1H, 7-H), 7.25 (d, 1H, J=8.1 Hz, 3’-H and 5’-H), 6.87 (t,
1H, J=7.5 Hz, 6-H), 6.715 (d, 1H, J=8.1 Hz), 5.98 (s, 1H, 2-H), 4.92 ppm (br. s, 1H, NH), 2.37(s, 3H,
CH3); 13C NMR (CDCl3): δ 217.9 (C=S), 144.6, 140.2, 135.2, 132.4, 130.2, 129.9, 128.1, 127.6, 120.0,
117.7, 63.5, 21.3 ppm. Anal. Calcd for C15H13NS2: C, 66.38; H, 4.83; N, 5.16; S, 23.62. Found: C, 66.21;
H, 4.95; N, 4.99; S, 23.32.
2-(p-Methoxyphenyl)-1,2-dihydro-4H-3,1-benzothiazine-4-thione (12c). Red crystals: yield 0.085 g
(59%); mp 162.1-163.2 °С; IR (KBr): 3453 (NH), 1607, 1561, 1489, 1472 cm-1 ;1H NMR (CDCl3): δ 8.36
(d, 1H, J=8.1 Hz, 5-H), 7.51 (d, 2H, J=8.4 Hz, 3’-H and 5’-H), 7.38 (t, 1H, J=7.4 Hz, 7=H), 6.95 (d, 2H,
J=8.4 Hz, 2’-H and 6’-H), 6.87 (t, 2H, J=7.6 Hz, 6-H), 6.72 (d, 2H, J=8.1 Hz, 8-H), 5.97 (s, 1H, 2-H),
4.90 (s, 1H, NH), 3.84 ppm (s, 3H, OCH3); 13C NMR (CDCl3): δ 218.1 (C=S), 160.8, 144.7, 135.2, 130.2,
129.1, 128.1, 127.2, 120.0, 117.7, 114.6, 63.3, 55.4 ppm. Anal. Calcd for C15H13NOS2: C,62.68; H,4.56;
N,4.88; S,22.31. Found: C,62.35; H,4.38; N,4.64; S,22.08.
2,2-Dimethyl-1,2-dihydro-4H-3,1-benzothiazine-4-thione (12d). Deep red crystals: yield 0.094 g
1
(90%); mp 163.2-163.4 °С; IR (KBr): 3279 (NH), 1605, 1561, 1495, 1474 cm-1; H NMR (CDCl3): δ
8.37-6.70, (m, 4H, aromatic protons), 4.93 (s, 1H, NH), 1.68 ppm (s, 6H, CH3×2); 13C NMR (CDCl3): δ
216.5 (C=S), 142.6, 130.0, 127.3, 119.7, 118.3, 117.9, 62.4, 29.1 ppm. Anal. Calcd for C10H11NS2:
C,57.38; H,5.30; N,6.69; S,30.64. Found: C, 57.48; H,5.31; N,6.58; S, 30.16.
2-Ethyl-2-methyl-1,2-dihydro-4H-3,1-benzothiazine-4-thione (12e). Orange crystals: yield 0.053 g
1
(47%); mp 66.6-67.1 °С; IR (KBr): 3491(NH), 1607, 1564, 1497, 1474 cm-1; H NMR (CDCl3): δ
8.36-6.69 (m, 4H, aromatic protons), 4.83 (s, 1H, NH), 1.95 (q, 2H, J=7.3 Hz, CH2Me), 1.68 (s, 3H,

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HETEROCYCLES, Vol. 91, No. 12, 2015
2-CH3), 0.96 ppm (t, 3H, J=7.3 Hz, CH3); 13C NMR (CDCl3): δ 217.9 (C=S), 142.5, 135.4, 130.9, 129.7,
127.4, 118.2, 68.2, 38.7, 26.2, 11.0 ppm. Anal. Calcd for C11H13NS2: C, 59.14; H,5.87; N,6.28; S, 28.71.
Found: C, 59.53; H, 5.69; N, 6.45; S, 28.30.
REFERENCES AND NOTES
1. T. Takeshima, M.Yokoyama; T. Imamoto, M. Akano, and H. Asaba, J. Org. Chem., 1969, 34, 730.
2. T. Takeshima, A. Yano, N. Fukada, Y. Hirose, and M. Muraoka, J. Chem. Res. (S), 1979, 140; idem,
ibid., (M), 1979, 1732.
3. M. Muraoka, T. Yamamoto, S. Yamaguchi, F. Tonosaki, T. Takeshima, and N. Fukada, J. Chem. Soc.,
Perkin Trans. 1, 1977, 1273.
4. T. Takeshima, T. Hayashi, M. Muraoka, and T. Matsuoka, J. Org. Chem., 1967, 32, 980.
5. M. Muraoka, M. Yokoyama, K. Yamamoto, and T. Takeshima, Bull. Chem. Soc. Jpn., 1970, 43, 2134.
6. T. Takeshima, T. Miyauchi, N. Fukada, S. Koshizawa, and M. Muraoka, J. Chem. Soc., Perkin Trans.
1, 1973, 1009.
7. T. Miyauchi, Y. Kadokura, N. Fukada, and T. Takeshima, Bull. Chem. Soc. Jpn., 1974, 47, 1678.
8. M. Muraoka, T. Yamamoto, and T. Takeshima, Bull. Chem. Soc. Jpn., 1975, 48, 2462.
9. M. Muraoka, T. Yamamoto, T. Ebisawa, W. Kobayashi, and T. Takeshima, J. Chem. Soc., Perkin
Trans. 1, 1978, 1019.
10. T. Takeshima, M. Muraoka, N. Fukada, A. Takayama, and T. Yamamoto, J. Org. Chem., 1977, 42,
3383.
11. G. P. Jourdan and B. A. Dreikorn, J. Org. Chem., 1982, 47, 5255.
12. N. H. Leon and J. A. Swift, Brit. (1975), GB 1416255 A 19751203 (Chem. Abstr., 1976, 84,
166232m.)
13. D. M. Mckinnon, K. A. Duncan, and L. M. Millar, Can. J. Chem., 1982, 60, 440.
14. This compound is commercially available from ACOS or Scientific Exchange Inc.
15. G. J. Price, ‘Current Trends in Sonochemistry’, The Royal Society of Chemistry, Cambridge, 1992.
16. M. Yokoyama and T. Takeshima, Anal. Chem., 1968, 40, 1344.
17. M. A. I. Salem and E. A. Soliman, Egyptian J. Chem., 1985, 27, 779.