Azines and azoles: CXXIII. Three-component condensation of 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione with o-phenylenediamine and carbonyl compounds as a convenient synthesis of substituted 1,5-benzodiazepines

Article abstract of DOI:10.1134/S1070363206050240

Readily accessible 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione reacted with an equimolar amount of o-phenylenediamine under mild conditions (propan-2-ol, 5 min, reflux) to give the corresponding Schiff base. Reactions of the latter with aldeh

Full text of DOI:10.1134/S1070363206050240

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 5, pp. 801 813.
Pleiades Publishing, Inc., 2006.
Original Russian Text V.N. Yuskovets, Berzhe Uankpo, B.A. Ivin, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 5, pp. 839 849.
Azines and Azoles: CXXIII.1 Three-component Condensation
of 5-Acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione
with o-Phenylenediamine and Carbonyl Compounds
as a Convenient Synthesis of Substituted 1,5-Benzodiazepines
V. N. Yuskovets, Berzhe Uankpo, and B. A. Ivin
St. Petersburg State Chemical and Pharmaceutical Academy,
ul. Professora Popova 14, St. Petersburg, 197376 Russia
Received September 16, 2005
Abstract Readily accessible 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione reacted with an
equimolar amount of o-phenylenediamine under mild conditions (propan-2-ol, 5 min, reflux) to give the
corresponding Schiff base. Reactions of the latter with aldehydes and ketones in propan-1-ol in the
presence of a catalytic amount of trifluoroacetic acid or in acetic acid led to the formation of 4-hydroxy-5-
(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-diones.
DOI: 10.1134/S1070363206050240
We recently developed a very simple and con-
venient procedure for the synthesis of 5-acetyl-4-
azepin-4-yl)-4-hydroxy-2H-1,3-thiazine-2,6-dione
(IIIs) rather than the expected Schiff base which
could be formed via condensation at the free amino
group of o-phenylenediamine. It turned out that the
observed reaction is general and that it is catalyzed
by acids.
hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione
(I)
from malonic acid, potassium thiocyanate, and acetic
anhydride in acetic acid [1 3]. We also found that
thiazine I very readily reacts with various aliphatic
and aromatic amines in ethanol or propan-2-ol at the
acetyl carbonyl group without opening of the thiazine
ring to afford only the corresponding Schiff bases
[1, 2]. Reactions of 5-acetyl-4-hydroxy-3,6-dihydro-
2H-1,3-thiazine-2,6-dione (I) with diamines were not
studied. Therefore, it was not surprising that the reac-
tion of thiazine I with an equimolar amount of o-
phenylenediamine in boiling propan-2-ol (reaction
time 5 min) gave 98% of compound II. It should be
noted that heating of thiazine I with 1 equiv of o-
phenylenediamine in boiling DMF was accompanied
by extrusion of COS and formation of a 6-methyl-
uracil derivative, 1-(2-aminophenyl)-6-methyluracil
[1, 2] (Scheme 1).
1,5-Benzodiazepine derivatives [4 7] constitute an
important class of biologically active substances w
hich exhibit a broad spectrum of activity, depending
on their structure [8]. Undoubtedly, preparation of
previously unknown 1,5-benzodiazepine derivatives,
especially of those containing pharmacophoric hetero-
cyclic substituents, is of particular importance. In the
present communication we describe the synthesis of
2,3-dihydro-1H-1,5-benzodiazepine derivatives having
a 1,3-thiazine substituent in the 4-position.
2-Substituted 2,3-dihydro-1H-1,5-benzodiazepines
IIIa IIIt (Table 1) are formed by heating a mixture
of compound II with a 1.5 2-fold excess of the cor-
responding aldehyde or ketone in boiling methanol,
ethanol, propan-2-ol or propan-1-ol over a period of
1 3 h in the presence of a catalytic amount of trifluo-
roacetic acid. Propan-1-ol is the most preferred; it
ensures the reaction to be complete in 1 1.5 h. A
strong advantage of this procedure is very simple iso-
lation of the product, which includes filtration of the
cooled reaction mixture and washing of the precipitate
Our attention was attracted by the fact that a solu-
tion of II in acetone (prepared for TLC analysis) very
quickly turned yellow (over a period of 2 3 days).
According to the TLC data, a substance characterized
by a higher Rf value than that of II (hexane acetone,
2:1) accumulated in the acetone solution. This sub-
stance showed a bright yellow fluorescence under UV
irradiation. We found that the product has the struc-
ture of 5-(2,2-dimethyl-2,3-dihydro-1H-1,5-benzodi-
1
with alcohol. According to the TLC data, H and 13C
NMR, and mass spectra, and elemental analyses, the
crude products were sufficiently pure. Under the given
conditions, , -unsaturated aldehydes, such as croto-
1
For communication CXXII, see [1].
801

802
YUSKOVETS et al.
Scheme 1.
NH2
H
H
N
O
O
O
O
NH2
i-PrOH
+
NH
NH
H3C
H3C
5 min
NH2
O
O
O
S
S
I
II
R
R
p-PrOH
DMF 1 h
O
F3CCOOH
O
H
O
N
NH
NH
HN
R
O
H3C
O
N
S
R
NH2
O
IIIa IIIt
III, R = H; R = Ph (a), 4-MeC6H4 (b), 4-HOC6H4 (c), 3,4-(HO)2C6H3 (d), 4-MeOC6H4 (e), 3-MeO-4-NO2C6H3 (f),
-piperonyl (g), 4-Me2NC6H4 (h), 4-ClC6H4 (i), 2-ClC6H4 (j), 4-NCC6H4 (k), 4-NO2C6H4 (l), 2-furyl (m), 3-indolyl (n),
(E)-MeCH=CH (o), (E)-PhCH=CH (p), (E)-(2-furyl) CH=CH (q), i-Pr (r); R = R = Me (s); RR = (CH2)5 (t).
naldehyde, cinnamaldehyde, and 3-(2-furyl)acrolein,
and various heterocyclic aldehydes readily reacted
with compound II. Among ketones, the reaction with
cyclohexanone gave the best results; in the reaction of
cyclopentanone a complex mixture consisting of five
compounds was formed, and the composition of that
mixture was not studied in the present work. From
anthracene-9-carbaldehyde we obtained only Schiff
base IV which did not undergo cyclization to the cor-
responding benzodiazepine even on prolonged heating
(boiling propan-1-ol, 6 h).
presence of trifluoroacetic acid were unsuccessful: the
yields were as low as 2 5%. By heating isobutyral-
dehyde with compound II in boiling acetic acid over
a period of 40 min we succeeded in isolating the
corresponding benzodiazepine in 84% yield.
Benzodiazepine IIIp was also synthesized in 67%
yield by an independent method (Scheme 2) from
compound V and o-phenylenediamine in boiling
propan-1-ol (reaction time 1.5 h). Compound V was
prepared in 74% yield by heating a mixture of thiazine
I and cinnamaldehyde in chloroform in the presence
of catalytic amounts of pyridine and piperidine (it was
isolated as lustrous leaflets resembling potassium
dichromate in color); an analogous reaction with
dehydroacetic acid was described in [9].
H
N
N
O
O
S
Me
NH
Scheme 2.
O
H
H
O
IV
O
S
O
NH
The largest yields were obtained from aromatic
aldehydes, especially from those having donor sub-
stituents in the aromatic ring. 4-Nitrobenzaldehyde
failed to produce benzodiazepine derivative even on
prolonged boiling in propan-1-ol (5 h). However, this
problem was circumvented by heating a mixture of
compound II with a small excess of 4-nitrobenzalde-
hyde in glacial acetic acid under reflux over a period
of 1 h. Our attempts to effect the reaction with ali-
phatic aldehydes in boiling lower alcohols in the
I
CHCl3, 2 h
O
O
V
NH2
NH2
IIIp.
PrOH, F3CCOOH
The structure of the isolated products was con-
1
firmed by the analytical data and H and 13C NMR,
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AZINES AND AZOLES: CXXIII.
803
Table 1. Yields, melting points, Rf values, and elemental analyses of 4-hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-
4-yl)-2H-1,3-thiazine-2,6-diones IIIa IIIt, 4-hydroxy-5-{1-N-[2-(9-anthrylmethylideneamino)phenyl]ethanimidoyl}-2H-
1,3-thiazine-2,6-dione (IV), and 4-hydroxy-5-[(2E,4E)-5-phenylpenta-2,4-dienoyl]-2H-1,3-thiazine-2,6-dione (V)
Found, %
H
Calculated, %
Rf
(acetone hexane,
1: 2)
Comp. Yield,
no.
mp,
C
Formula
%
C
N
C
H
N
II
98 197 198 (decomp.)
70 239 240 (decomp.)
75 236 237 (decomp.)
68 245 246 (decomp.)
65 238 239 (decomp.)
78 223 224
92 237 238 (decomp.)
76 219 221 (decomp.)
81 247 248 (decomp.)
60 244 245 (decomp.)
54 205 206
60 284 285 (decomp.)
49 257 258 (decomp.)
63 191 192
65 255 256 (decomp.)
57 192 193
0.34
0.46
0.51
0.30
0.14
0.42
0.28
0.43
0.51
0.41
0.41
0.37
0.43
0.43
0.30
0.41
0.46
0.45
0.61
0.46
0.73
0.46
0.53a
51.92 3.99 15.16 C12H11N3O3S
62.57 4.13 11.38 C19H15N3O3S
63.38 4.51 11.09 C20H17N3O3S
59.71 3.97 10.99 C19H15N3O4S
57.38 3.81 10.56 C19H15N3O5S
60.68 4.33 10.61 C20H17N3O4S
58.43 4.15 10.22 C20H17N3O5S
58.71 3.68 10.22 C20H15N3O5S
61.81 4.93 13.74 C21H20N4O3S
51.98 4.00 15.15
62.45 4.14 11.50
63.31 4.52 11.07
59.83 3.96 11.02
57.42 3.80 10.57
60.75 4.33 10.63
58.38 4.16 10.21
58.67 3.69 10.26
61.75 4.94 13.72
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
IIIm
IIIn
IIIo
IIIp
IIIq
IIIr
IIIs
IIIt
IV
56.89 3.52 10.53 C19H14ClN3O3S 57.01 3.53 10.51
56.91 3.53 10.50 C19H14ClN3O3S 57.01 3.53 10.51
61.59 3.60 14.33 C20H14N4O3S
55.65 3.43 13.67 C19H14N4O5S
57.34 3.68 11.80 C17H13N3O4S
62.23 3.98 13.87 C21H16N4O3S
58.22 4.58 12.78 C16H15N3O3S
64.55 4.36 10.74 C21H17N3O3S
59.71 3.94 10.99 C19H15N3O4S
58.06 5.15 12.66 C16H17N3O3S
56.65 4.76 13.26 C15H15N3O3S
61.50 5.68 11.33 C19H21N3O3S
61.53 3.61 14.35
55.60 3.44 13.65
57.46 3.69 11.82
62.36 3.99 13.85
58.34 4.59 12.76
64.43 4.38 10.73
59.83 3.96 11.02
57.99 5.17 12.68
56.77 4.76 13.24
61.44 5.70 11.31
72 205 206
71 220 222 (decomp.)
84 210 211
43 232 233 (decomp.)
60 227 228 (decomp.)
76 217 218
69.78 4.10
59.64 3.69
9.04 C27H19N3O3S
4.64 C15H11NO4S
69.66 4.11
59.79 3.68
9.03
4.65
V
74 215 216 (decomp.)
a
Eluent benzene acetic acid, 10:1.
UV, IR, and mass spectra. The mass spectra of com-
pounds II, IIIa IIIt, IV, and V are given in Table 2.
Almost all these showed the molecular ion peak in the
mass spectrum. In addition, [M 60]+ ion peak was
present due to expulsion of COS molecule from the
molecular ion. The mass spectra also contained peaks
from fragment ions arising from cleavage of the bonds
between C2 in the benzodiazepine ring and aryl sub-
stituent ([M R]+) and between C4 in the benzodi-
azepine ring and C5 in the thiazine ring ([M 144]+,
m/z 144). In some cases, the fragmentation patterns
were complicated by thermal decomposition of sam-
Table 2. Mass spectra of 4-hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-diones IIIa IIIt,
4-hydroxy-5-{1-N-[2-(9-anthrylmethylideneamino)phenyl]ethanimidoyl}-2H-1,3-thiazine-2,6-dione (IV), and 4-hydroxy-
5-[(2E,4E)-5-phenylpenta-2,4-dienoyl]-2H-1,3-thiazine-2,6-dione (V)
Comp.
no.
m/z (Irel, %)
II
277 (M+, 27%), 266 (85), 219 (12), 217 (7), 202 (15), 178 (4), 174 (4), 159 (15), 145 (7), 133 (100), 132 (80),
131 (40), 104 (7), 92 (24), 80 (12), 65 (29), 60 (20)
IIIa
366 (M+ + 1, 23%), 365 (M+, 100), 350 (4), 332 (15), 305 (10), 304 (15), 288 (8), 276 (9), 274 (12), 261 (21),
233 (21), 221 (36), 219 (36), 195 (51), 194 (59), 158 (15), 144 (19), 133 (17), 119 (34), 103 (25), 92 (21), 77
(29), 65 (27), 60 (23), 51(15), 39 (17)
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804
YUSKOVETS et al.
Table 2. (Contd.)
Comp.
no.
m/z (Irel, %)
IIIb
380 (M+ + 1, 23%), 379 (M+, 100), 346 (19), 318 (10), 319 (12), 274 (19), 281 (19), 247 (19), 235 (38), 233
(28), 209 (71), 208 (72), 158 (19), 144 (19), 130 (19), 119 (47), 115 (19), 103 (33), 91 (33), 77 (28), 65 (43), 60
(12), 51 (11)
IIIc
IIId
381 (M+, 10%), 321 (15), 320 (15), 277 (10), 235 (71), 210 (5), 159 (7), 134 (19), 118 (10), 115 (5), 103 (10),
93 (19), 77 (10), 65 (20), 60 (100), 51 (10)
397 (M+, 18%), 363 (4), 337 (19), 336 (13), 319 (15), 301 (14), 293 (15), 278 (20), 277 (38), 253 (20), 252
(51), 251 (86), 233 (6), 227 (6), 217 (8), 205 (12), 168 (6), 159 (7), 158 (7), 144 (8), 136 (20), 134 (33), 132
(30), 119 (7), 110 (29), 103 (40), 92 (28), 77 (30), 64 (40), 60 (100)
IIIda
IIIe
337 (M+ COS, 8%), 251 (20), 243 (6), 227 (6), 217 (8), 200 (8), 182 (3), 174 (6), 158 (16), 144 (4), 134 (52),
110 (30), 106 (24), 92 (10), 90 (8), 79 (24), 78 (24), 64 (28), 60 (8), 51 (10), 43 (100)
395 (M+, 71%), 362 (17), 335 (133), 334 (15), 291 (13), 271 (12), 263 (14), 251 (42), 239 (30), 225 (65), 224
(67), 201 (13), 185 (8), 159 (14), 144 (21), 134 (100), 121 (38), 119 (33), 103 (25), 91 (25), 77 (21), 65 (29), 60
(83), 51 (13)
IIIf
411 (M+, 62%), 378 (10), 368 (4), 378 (10), 351 (38), 350 (34), 336 (4), 333 (7), 307 (19), 265 (45), 251 (14),
241 (38), 240 (40), 217 (24), 201 (14), 150 (57), 144 (15), 134 (17), 137 (12), 119 (22), 103 (20), 92 (10), 82
(10), 77 (17), 65 (22), 60 (100)
IIIg
410 (M+ + 1, 28%), 409 (M+, 100), 394 (5), 381 (4), 380 (5), 377 (7), 376 (17), 366 (9), 349 (19), 348 (19), 332
(6), 330 (9), 305 (20), 277 (24), 265 (40), 239 (68), 238 (82), 224 (8), 219 (11), 205 (10), 199 (8), 185 (9), 160
(12), 159 (14), 158 (13), 148 (74), 144 (30), 135 (34), 132 (20), 130 (18), 119 (16), 103 (26), 92 (18), 89 (18),
77 (24), 76 (16), 65 (30), 60 (32), 51 (16), 44 (15), 43 (56), 39 (24)
IIIh
IIIi
IIIj
409 (M+ + 1, 28%), 408 (M+, 100), 380 (8), 375 (10), 365 (5), 348 (35), 347 (25), 304 (20), 276 (18), 264 (58),
262 (30), 238 (10), 237 (9), 191 (10), 166 (11), 158 (10), 147 (98), 134 (70), 121 (15), 119 (15), 103 (15), 92
(8), 91 (9), 77 (18), 65 (13), 60 (30)
401 (M+, 41%), 400 (M+, 25), 399 (M+, 100), 366 (18), 339 (18), 338 (21), 327 (10), 310 (8), 295 (15), 274 (23),
267 (18), 257 (49), 255 (44), 228 (67), 227 (51), 219 (13), 220 (10), 200 (8), 185 (10), 159 (23), 144 (28), 132
(26), 119 (41), 103 (31), 93 (30), 77 (31), 65 (44), 60 (67), 51 (23)
401 (M+, 40%), 400 (M+, 26), 399 (M+, 100), 384 (4), 368 (5), 366 (16), 364 (24), 356 (4), 339 (22), 338 (14),
323 (4), 322 (4), 321 (4), 310 (6), 304 (8), 295 (12), 288 (10), 274 (24), 265 (18), 261 (22), 255 (42), 229 (50),
228 (74), 219 (50), 214 (10), 200 (8), 190 (8), 185 (12), 158 (24), 144 (18), 130 (24), 119 (70), 103 (36), 102
(34), 92 (36), 77 (34), 65 (46), 60 (64), 51 (22), 44 (14), 43 (12), 39 (30)
IIIk
390 (M+, 29%), 374 (2), 372 (2), 357 (4), 347 (2), 330 (21), 329 (16), 313 (3), 289 (11), 274 (4), 258 (7), 246
(24), 245 (29), 244 (84), 220 (21), 219 (19), 214 (4), 202 (3), 185 (3), 171 (2), 159 (7), 158 (6), 144 (6), 140 (4),
134 (11), 131 (7), 122 (6), 119 (21), 116 (6), 108 (6), 103 (9), 102 (7), 93 (17), 92 (13), 77 (11), 65 (20), 60
(100), 52 (7), 51 (9), 45 (19), 44 (27), 43 (11)
IIIl
410 (M+, 20%), 393 (11), 350 (9), 333 (2), 306 (4), 277 (8), 266 (7), 265 (15), 264 (37), 240 (6), 239 (8), 231
(4), 218 (28), 217 (10), 206 (4), 193 (4), 185 (2), 172 (2), 159 (6), 158 (7), 144 (8), 134 (12), 132 (11), 119 (10),
103 (8), 91 (10), 77 (9), 60 (100), 51 (9), 43 (25)
IIIm
355 (M+, 61%), 338 (4), 327 (3), 322 (7), 312 (3), 395 (5), 294 (5), 274 (11), 267 (3), 261 (11), 250 (7), 223 (9),
211 (23), 185 (34), 158 (12), 156 (10), 144 (9), 130 (10), 119 (13), 103 (16), 94 (18), 81 (21), 77 (14), 65 (27),
60 (91), 45 (100)
IIIn
IIIo
404 (M+, 57%), 371 (7), 344 (25), 327 (8), 300 (16), 272 (15), 260 (35), 258 (25), 234 (30), 233 (23), 210 (8),
158 (12), 143 (100), 130 (40), 117 (20), 115 (22), 103 (12), 90 (12), 60 (35)
329 (M+, 100%), 314 (15), 301 (5), 296 (5), 288 (5), 286 (5), 274 (8), 269 (5), 261 (6), 254 (9), 237 (7), 230 (6),
225 (9), 215 (10), 211 (12), 197 (13), 185 (22), 183 (15), 169 (19), 159 (24), 158 (25), 144 (10), 132 (15), 119
(28), 108 (6), 103 (10), 92 (17), 91 (19), 77 (20), 65 (18), 60 (13), 51 (10), 45 (11), 41 (12), 39 (15)
391 (M+, 100%), 331 (10), 287 (10), 274 (15), 259 (13), 247 (25), 221 (15), 219 (15), 169 (37), 158 (15), 146
(10), 132 (20), 130 (25), 119 (25), 117 (20), 115 (25), 103 (15), 91 (20), 77 (23), 65 (25), 60 (50)
381 (M+, 100%), 353 (4), 348 (3), 338 (6), 321 (5), 282 (6), 277 (8), 274 (17), 249 (17), 237 (27), 219 (14), 211
(18), 196 (8), 183 (13), 177 (5), 169 (21), 158 (14), 144 (11), 132 (20), 120 (38), 119 (40), 107 (12), 103 (27),
102 (16), 92 (22), 91 (44), 81 (33), 77 (32), 65 (49), 51 (24), 44 (25), 43 (19), 41 (25), 39 (47)
IIIp
IIIq
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AZINES AND AZOLES: CXXIII.
805
Table 2. (Contd.)
Comp.
no.
m/z (Irel, %)
IIIr
331 (M+, 36%), 288 (100), 271 (1), 270 (1), 260 (1), 254 (2), 245 (15), 228 (24), 211 (25), 201 (4), 185 (9), 170
(4), 157 (8), 156 (7), 155 (7), 143 (17), 119 (29), 102 (4), 92 (7), 77 (7), 65 (10), 60 (6), 51 (4), 45 (5), 43 (5),
41 (6), 39 (8)
IIIs
IIIt
IV
V
318 (M+ + 1, 19%), 317 (M+, 100), 302 (58), 274 (44), 261 (7), 259 (9), 242 (16), 225 (11), 199 (14), 185 (7),
173 (23), 157 (18), 144 (11), 133 (51), 103 (9), 92 (18), 77 (13), 65 (20), 41(20), 39 (16)
358 (M+ + 1, 22%), 357 (M+, 100), 315 (13), 314 (48), 301 (8), 286 (13), 274 (6), 254 (13), 213 (35), 183 (11),
169 (31), 159 (11), 160 (15), 145 (27), 132 (27), 119 (11), 102 (11), 92 (13), 77 (15), 65 (17), 60 (4)
405 (M+ COS, 3%), 361 (1), 334 (2), 320 (29), 319 (17), 262 (9), 216 (8), 202 (15), 178 (10), 160 (8), 133
(20), 132 (57), 131 (22), 92 (8), 85 (8), 65 (9), 60 (100), 43 (22)
301 (M+, 22%), 283 (22), 258 (3), 255 (12), 241 (5), 240 (3), 224 (8), 223 (5), 214 (5), 112 (7), 198 (15), 197
(17), 184 (17), 173 (20), 170 (18), 157 (35), 145 (20), 141 (27), 130 (40), 129 (100), 128 (95), 127 (33), 118
(13), 115 (40), 102 (17), 91 (17), 77 (30), 69 (13), 60 (10), 51 (29), 44 (25), 43 (18), 39 (20)
a
Vaporizer temperature 250 C.
ples during vaporization with elimination of COS; this
was typical of high-melting and low-volatile com-
pounds III having an aryl substituent in the 2-position.
For example, the mass spectrum of compound IIId
recorded at a higher vaporizer temperature was the
same as the mass spectrum of the product of thermal
extrusion of COS from IIId.
azepines IIIa IIIt exist as conformer A rather than B
(Scheme 3, a view along the C3 C2 bond). Otherwise
(the dihedral angles HXC2C3HA and HXC2C3HB in
conformer B are similar), the JAX and JBX values
would approach each other, which is inconsistent with
the experimental data (Table 3).
Scheme 3.
In the 1H NMR spectra of 1,5-benzodiazepines
IIIa IIIt in DMSO-d6 (Table 3) we observed singlets
from protons of the OH ( 13.80 14.07 ppm) and NH
groups ( 11.65 11.85 ppm) in the thiazine ring, a
relatively narrow singlet of the diazepine NH proton
( 5.54 6.35 ppm), overlapping multiplets from pro-
tons in the benzene ring and aryl groups on C2 in the
benzodiazepine ring ( 6.25 7.41 ppm). Also, an ABX
pattern (not always clearly resolved) from the benzo-
diazepine 2-H and 3-H protons was present; it in-
cluded a doublet of doublets from 2-H (X, 4.80
5.23 ppm; JAX 9.6 10.7, JBX 2.2?3.7 Hz); a doublet
of doublets from 3-H (B, 3.55 4.17 ppm; JAB 11.8
13.0, JBX 2.2 3.7 Hz; in some cases, the latter coupl-
ing constant is close to zero, obviously because the
dihedral angle HXC2C3HB approaches 90 ; therefore,
the doublet of doublets is reduced to a pseudodoublet);
HX
HA
H
HA
H
R
HB
HB
N
N
HX
N
R
N
Tz
Tz
A
B
The 13C NMR spectra of solutions of IIIa IIIt in
DMSO-d6 (Table 4) contain signals typical of
1,5-benzodiazepine ring system,
60.6 67.3 (C2)
C
and 33.6 39.5 ppm (C3) (no such signals were present
in the spectra of initial compounds), as well as signals
from carbon atoms in the 1,3-thiazine ring and sub-
stituent on C2.
1,5-Benzodiazepines IIIa IIIt showed in the IR
spectra (KBr, Table 3) absorption bands in the regions
corresponding to stretching and bending vibrations of
NH and OH groups involved in hydrogen bonding
(3120 3380 cm ) and stretching vibrations of C=O
and C=N groups (1600 1700 cm ).
and a doublet of doublets from 3-HA
(
2.99
3.23 ppm; JAB 11.8?13.0, JAX 9.6 10.7 Hz; due to
similar values of JAB and JAX, a pseudotriplet is some-
1
1
1
times observed). The H NMR spectra of IIIa IIIt
lack signal from acetyl protons, in contrast to initial
compound II ( 2.38 ppm, s, 3H).
As noted above, all 1,5-benzodiazepines IIIa IIIt
show bright yellow to yellow-green fluorescence
under UV irradiation. The UV spectra of solutions of
IIIa IIIt in 96.5% ethanol (Table 3) contain 4 5 ab-
sorption bands with their maxima at 208 218, 262
281, 312 316, and 359 382 nm; by contrast, initial
The large difference between the coupling con-
stants JAX and JBX (JAX >> JBX, the dihedral angle
HXC2C3HAapproaches 180 , and the angle
HXC2C3HB is close to 70 ) suggests that 1,5-benzodi-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

806
YUSKOVETS et al.
1
Table 3. UV, IR, and H NMR spectra of 4-hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-
diones IIIa IIIt, 4-hydroxy-5-{1-N-[2-(9-anthrylmethylideneamino)phenyl]ethanimidoyl}-2H-1,3-thiazine-2,6-dione (IV),
and 4-hydroxy-5-[(2E,4E)-5-phenylpenta-2,4-dienoyl]-2H-1,3-thiazine-2,6-dione (V)
AH
N1
N
R
H
H
HB
O
H
HX
N3
H
S
H
H
O
O
H
UV spec-
trum,
1H NMR spectrum (DMSO-d6), , ppm (J, Hz)
Comp.
no.
IR spectrum (KBr),
(EtOH),
max, nm
1
, cm
OH
N3H
N1H
Hx
Hb
Ha
Ar, R
(
104)
II
210 (2.70), 3470, 3395, 3320, 3225, 13.65 s 11.78 s 5.34 s
2.38 s (3H)
7.11 d.t (1H,
234 (2.18), 3120, 2946, 2790, 2360, (1H)
301 (2.29) 2340, 1665, 1620, 1544,
1350, 1248, 890, 755,
(1H)
(2H)
J
1.2, 7.5),
7.03 d.d (1H,
1.2, 8.1),
6.82 d.d (1H,
1.2, 8.1),
6.62 d.t (1H,
1.2, 7.5)
IIIaa 208 (1.91), 3365, 3030, 2985, 1677, 13.98 s 11.58 s 6.13 s 5.26 d.d 3.94 pse- 3.16 d.d 7.38 d (2H, J
J
687, 540, 434
J
J
240 (1.02), 1607, 1588, 1567, 1490, (1H)
315 (0.87), 1455, 1408, 1369, 1340,
377 (0.68) 1300, 872, 758, 692,
638, 561, 446
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
10.7, Jbx Jab 11.8) 11.8, Jax
7.5), 7.32 t (2H,
J 7.5), 7.25 t
3.2)
10.7)
(1H,
7.12 7.18
J
7.5),
m
(3H), 6.90 d.t
(1H, J 1.2, 7.5)
IIIb 210 (2.45), 3365, 2975, 2360, 1668, 13.80 s 11.82 s 6.28 s 5.16 d.d 3.78 d.d 2.99 d.d
7.18 7.24
m
240 (1.55), 1632, 1591, 1567, 1460, (1H)
276 (0.98), 1410, 1370, 1340, 1295,
315 (1.26) 1160, 862, 815, 740,
705, 630, 547, 470, 444
(1H)
(1H) (1H, Jax (1H, Jab (1H, Jab
10.4, Jbx 12.7, Jbx 12.7, Jax
(4H), 7.10
7.16 m (3H),
6.92 d.t (1H, J
1.2, 7.5), 2.27
s (3H)
2.3)
2.3)
10.4)
IIIc 218 (2.72), 3330, 3020, 2880, 2360, 13.82 s 11.81 s 6.20 s 5.09 d.d 3.78 pse- 3.04 d.d
9.38 s (1H),
279 (1.62), 1685, 1615, 1560, 1515, (1H)
315 (1.95), 1480, 1453, 1340, 1222,
376 (1.51) 860, 828, 740, 632, 538,
450
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
10.4, Jbx Jab 12.4) 12.4, Jax
7.17 7.22
(2H), 7.07
m
2.8)
10.4)
7.13 m (3H),
6.90 d.t (1H, J
1.3, 7.5), 6.72
d (2H, J 8.6)
8.62 s (1H),
8.42 s (1H),
IIId 212 (2.19), 3420, 3377, 3320, 3300, 13.96 s 11.53 s 5.88 s 5.06 d.d 3.96 pse- 2.83 d.d
281 (0.91), 3048, 2360, 1682, 1652, (1H)
313 (1.14), 1590, 1567, 1475, 1370,
376 (0.85) 1290, 833, 765, 743,
638, 550, 485
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
10.4, Jbx Jab 12.1) 12.1, Jax
7.09 7.18
(3H), 6.87 d.t
(1H, 1.3,
7.5), 6.76
(1H, 2.1),
m
2.8)
10.4)
J
d
J
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

AZINES AND AZOLES: CXXIII.
807
Table 3. (Contd.)
UV spec-
1H NMR spectrum (DMSO-d6), , ppm (J, Hz)
trum,
Comp.
IR spectrum (KBr),
(EtOH),
no.
1
, cm
max, nm
OH
N3H
N1H
Hx
Hb
Ha
Ar, R
(
104)
IIId
6.68 d (1H, J
8.6), 6.63 d.d
(1H, J 2.1, 8.6)
IIIea 216 (2.63), 3362, 2990, 2835, 1670, 13.97 s 11.57 s 6.02 s 5.20 d.d 3.92 pse- 2.93 d.d
7.27 d (2H, J
277 (1.05), 1632, 1610, 1590, 1563, (1H)
314 (1.23), 1510, 1457, 1407, 1363,
374 (1.00) 1240, 1174, 1030, 825,
740, 433
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
9.6, Jbx Jab 11.8) 11.8, Jax
8.6),
7.10
7.18 m (3H),
6.89 d.t (1H, J
1.6, 7.5), 6.84
d (2H, J 8.6),
3.78 s (3H)
3.2)
9.6)
IIIfa 212 (2.26), 3508, 3440, 3359, 3315, 13.98 s 11.58 s 6.01 s 5.14 d.d 3.90 d.d 2.99 d.d
8.56 s (1H),
281 (0.94), 3276, 2929, 2360, 1675, (1H)
314 (1.18), 1663, 1619, 1694, 1566,
375 (0.89) 1520, 1480, 1447, 1410,
1368, 1279, 857, 761,
(1H)
(1H) (1H, Jax (1H, Jab (1H, Jab
9.6, Jbx 11.8, Jbx 11.8, Jax
7.11 7.18
(3H), 6.85
6.90 m (2H),
6.76 d.d (1H,
m
2.2)
2.2)
9.6)
743, 687, 643, 550, 490,
J
2.1, 8.6),
432
6.71 d (1H, J
8.6), 3.79
(3H)
s
IIIg 205 (2.31), 3370, 3354, 3250, 3140, 13.77 s 11.84 s 6.26 s 5.12 d.d 3.74 pse- 3.11 d.d
7.21 t (2H, J
8.0), 7.10
(1H, 8.0),
6.92 d.t (1H, J
1.3, 7.5), 6.87
d (1H, J 8.0),
6.82 d (1H, J
2.0), 6.79 d.d
237 (1.55), 3028, 2980, 2928, 2867, (1H)
313 (1.38), 2848, 1665, 1594, 1567,
367 (0.87) 1486, 1447, 1405, 1369,
1240, 1117, 1042, 923,
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
10.0, Jbx Jab 13.0) 13.0, Jax
d
J
2.8)
10.0)
869, 845, 749, 636, 455
(1H,
J
2.0,
8.0), 5.98
(2H)
s
IIIh 208 (2.39), 3368, 3155, 3030, 2895, 13.96 s 11.55 s 5.88 s 5.13 d.d 3.95 pse- 2.86 d.d
7.08 7.19
m
262 (1.78), 2810, 1693, 1660, 1605, (1H)
312 (1.09), 1560, 1524, 1492, 1450,
379 (0.74) 1412, 1362, 1337, 1311,
1265, 1160, 810, 752,
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
10.7, Jbx Jab 12.9) 12.9, Jax
(5H), 6.88 d.t
(1H, 1.3,
7.5), 6.65
(2H, 8.6),
J
3.2)
10.7)
d
J
618, 542, 453, 430
2.92 s (6H)
IIIi
213 (2.45), 3375, 3350, 2995, 2850, 13.80 s 11.83 s 6.36 s 5.23 d.d 3.68 d.d 3.23 d.d
7.40 d (2H, J
241 (1.38), 2365, 1670, 1633, 1610, (1H)
312 (1.23), 1590, 1560, 1459, 1408,
366 (0.81) 1365, 1336, 1088, 847,
820, 740, 632, 531, 420
(1H)
(1H) (1H, Jax (1H, Jab (1H, Jab
10.0, Jbx 12.5, Jbx 12.5, Jax
8.1), 7.33 d
(2H,
7.20 7.24
J
8.1),
m
2.2)
2.2)
10.0)
(2H), 7.12 d
(1H, 8.1),
J
6.92 d.t (1H, J
1.3, 7.5)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

808
YUSKOVETS et al.
Table 3. (Contd.)
UV spec-
1H NMR spectrum (DMSO-d6), , ppm (J, Hz)
trum,
Comp.
IR spectrum (KBr),
(EtOH),
no.
1
, cm
max, nm
OH
N3H
N1H
Hx
Hb
Ha
Ar, R
(
104)
IIIja 216 (2.71), 3361, 3154, 3041, 1676, 14.05 s 11.48 s 6.09 d 5.63
3.54 d.d 3.83 d.d
(1H, 5.67 m (1H, Jab (1H, Jab
J 2.1) (1H) 12.9, Jbx 12.9, Jax
3.2) 7.5)
7.51 7.55
m
239 (1.52), 1642, 1610, 1593, 1570, (1H)
278 (0.78), 1492, 1457, 1403, 1363,
317 (1.10), 1337, 1302, 1056, 873,
374 (0.96) 752, 727, 677, 637, 562,
462, 447
(1H)
(1H),
7.39 m (1H),
7.23 7.28
(2H), 7.13
7.34
m
7.18 m (2H),
7.04 d (1H, J
8.6), 6.94 d.t
(1H, J 1.2, 7.5)
8.83 d (2H, J
IIIk 205 (2.66), 3440, 3356, 3175, 3050, 13.78 s 11.85 s 6.48 s 5.34 d.d 3.63 pse- 3.40 d.d
219 (2.54), 2928, 2810, 2238, 1664, (1H)
237 (2.48), 1600, 1570, 1486, 1445,
276 (1.57), 1408, 1365, 1294, 850,
314 (1.72), 830, 745, 674, 632, 526,
376 (1.59) 478, 423
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
9.6, Jbx Jab 12.9) 12.9, Jax
8.6), 7.52
(2H, 8.6),
7.24 t (2H, J
8.6), 7.12
(1H, 8.6),
d
J
3.2)
9.6)
d
J
6.95 t (1H, J
7.3)
IIIl
207 (2.76), 3372, 3150, 2990, 2850, 13.98 s 11.62 s 6.33 s 5.41 d.d 3.82 d.d 3.19 d.d
8.18 d (2H, J
214 (2.59), 1666, 1634, 1610, 1590, (1H)
244 (2.01), 1665, 1515, 1485, 1460,
269 (2.02), 1410, 1343, 1295, 854,
315 (1.35), 749, 694, 653, 631, 619,
376 (1.11) 565, 472
(1H)
(1H) (1H, Jax (1H, Jab (1H, Jab
10.0, Jbx 13.0, Jbx 13.0, Jax
9.0), 7.64 d
(2H,
7.14 7.22
J
9.0),
m
2.0)
2.0)
10.0)
(3H), 6.93 d.t
(1H, J 1.6, 7.0)
7.42 s (1H),
IIIm 205 (2.14), 3325, 3150, 3015, 1670, 13.91 s 11.65 s 5.83 s 5.26 d.d 3.96 d.d 2.97 d.d
214 (1.91), 1640, 1608, 1594, 1565, (1H)
272 (0.61), 1481, 1456, 1410, 1364,
316 (0.89), 1340, 1141, 1005, 836,
363 (0.93) 745, 640, 596, 549, 461,
435
(1H)
(1H) (1H, Jax (1H, Jab (1H, Jab
10.6, Jbx 12.3, Jbx 12.3, Jax
7.13 7.19
(2H), 7.05 d.d
(1H, 1.2,
8.1), 6.97 d.t
m
3.7)
3.7)
10.6)
J
(1H,
7.6),
J
1.3,
6.31
6.33 m (1H),
6.26 d (1H, J
3.5)
IIIn 205 (2.59), 3369, 3358, 3305, 3130, 14.05 s 11.59 s 5.83 s 5.54 d.d 4.29 pse- 2.89 d.d
10.80 s (1H),
220 (2.35), 2990, 2845, 1639, 1609, (1H)
249 (1.24), 1593, 1561, 1458, 1408,
312 (0.98), 1362, 1342, 1291, 1108,
371 (0.86) 1061, 837, 743, 691,
668, 637, 550, 461, 446,
(1H)
(1H) (1H, Jax udo-d (1H, (1H, Jab
7.63
Jax J 8.6), 7.34 d
(1H, 8.6),
7.23 d (1H, J
3.2), 7.13
d (1H,
10.4, Jbx Jab 12.4) 12.4,
2.9)
10.4)
J
432
7.20 m (3H),
7.09 t (1H, J
7.5), 6.95
d
(1H, 7.5),
J
6.92 d.t (1H, J
1.6, 7.5)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

AZINES AND AZOLES: CXXIII.
809
Table 3. (Contd.)
UV spec-
1H NMR spectrum (DMSO-d6), , ppm (J, Hz)
trum,
Comp.
IR spectrum (KBr),
(EtOH),
no.
1
, cm
max, nm
OH
N3H
N1H
Hx
Hb
Ha
Ar, R
(
104)
IIIo 216 (2.72), 3340, 3130, 2988, 2909, 13.82 s 11.87 s 5.88 s 4.50
3.55 d.d 2.89 d.d
(1H) 4.56 m (1H, Jab (1H, Jab
(1H) 12.9, 12.9,
7.17 t (2H, J
7.3), 7.05
(1H, 8.1),
6.89 d.t (1H, J
1.2, 7.3), 5.64
238 (2.26), 2875, 2850, 1681, 1607, (1H)
275 (1.79), 1590, 1562, 1483, 1462,
314 (2.09), 1408, 1367, 1340, 1284,
365 (1.88) 962, 865, 851, 758, 750,
720, 640, 567, 461, 438
(1H)
d
J
Jbx 3.2) Jax 9.6)
d.q (1H,
J
15.0, 6.9),
5.52 d.d (1H,
J 6.9, 15.0),
1.64 d (3H, J
6.9)
IIIpa 208 (2.55), 3370,
3337,
3318, 14.01 s 11.57 s 5.83 s 4.81
3.67 d.d 3.12 d.d
7.37 d (2H, J
248 (1.95), 3023, 2827, 1685, 1610, (1H)
314 (0.74), 1594, 1557, 1470, 1452,
365 (0.67) 1406, 1353, 1339, 1282,
967, 821, 747, 693, 637,
(1H)
(1H) 4.87 m (1H, Jab (1H, Jab
(1H) 12.4, Jbx 12.4, Jax
7.5), 7.38
(2H, 7.5),
7.19 t (1H, J
7.5), 7.10
t
J
3.1)
10.6)
483, 425
7.17 m (3H),
6.91 d.t (1H, J
1.3, 7.5), 6.62
d (1H, J 16.1),
6.31 d.d (1H,
J 6.4, 16.1)
IIIq 215 (2.53), 3450, 3356, 3172, 3053, 13.85 s 11.89 s 6.10 s 4.73
3.51 d.d 3.21 d.d
7.61 s (1H),
7.19 t (2H, J
269 (2.76), 2836, 1669, 1569, 1470, (1H)
312 (1.69), 1415, 1369, 1327, 1282,
367 (1.31) 1115, 1012, 958, 882,
810, 745, 426
(1H)
(1H) 4.79 m (1H, Jab (1H, Jab
(1H) 12.6, Jbx 12.6, Jax
7.5), 7.09
(1H, 8.1),
6.92 d.t (1H, J
d
2.9)
9.1)
J
1.3,
6.42 6.48
8.1),
m
(3H), 6.15 d.d
(1H,
J
6.9,
16.1)
IIIr 217 (2.18), 3395, 3155, 2967, 2875, 14.07 s 11.49 s 5.38 s 3.88 d.d 4.04 pse- 2.38 d.d
6.99 7.09
m
237 (1.67), 2360, 2340, 1668, 1634, (1H)
282 (1.21), 1610, 1592, 1575, 1465,
314 (1.66), 1408, 1370, 1333, 1263,
374 (1.16) 867, 832, 740, 547, 482,
427
(1H)
(1H) (1H, J udo-d (1H, (1H, Jab
2.7, 4.3, Jab 12.0) 12.0, Jax
(3H), 6.79 d.t
(1H, J 1.3, 7.5),
1.91 m (1H),
1.02 d (3H, J
10.3)
10.3)
6.4), 0.94
(3H, J 6.4)
7.16 7.21
d
IIIs 205 (2.69), 3450, 3314, 3160, 3055, 14.08 s 11.89 s 5.59 s
3.28 s (2H)
m
215 (1.92), 3034, 2985, 2955, 2925, (1H)
237 (1.45), 1674, 1655, 1613, 1590,
312 (1.24), 1561, 1455, 1355, 1335,
359 (0.93) 1287, 1248, 1161, 836,
766, 709, 600, 486, 438
(1H)
(1H)
(2H), 6.98 d
(1H, 8.1),
6.92 d.t (1H, J
1.2, 8.1),
J
1.27 s (6H)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

810
YUSKOVETS et al.
Table 3. (Contd.)
UV spec-
1H NMR spectrum (DMSO-d6), , ppm (J, Hz)
trum,
Comp.
IR spectrum (KBr),
(EtOH),
no.
1
, cm
max, nm
OH
N3H
N1H
Hx
Hb
Ha
Ar, R
(
104)
IIIt 212 (2.39), 3366, 2927, 2848, 2363, 14.04 s 11.85 s 5.54 s
3.33 s (2H)
7.15 7.22
m
276 (1.43), 2340, 1693, 1630, 1604, (1H)
313 (0.98), 1571, 1483, 1459, 1398,
362 (0.72) 1369, 1298, 1259, 868,
842, 750, 640, 631, 542,
(1H)
(1H)
(2H), 7.08 d
(1H, 8.1),
6.91 d.t (1H, J
J
1.2, 8.1),
485, 445
1.26 1.69
(10H)
m
IV
208 (2.69), 3450, 3160, 3030, 1668, 14.31 s 11.92 s
9.86 s (1H)
8.89 d (2H, J
8.4), 8.83
(1H), 8.18 d
(2H, 6.9),
7.75 d.d (1H,
1.2, 7.9),
7.54 7.65
(6H), 7.48 d.t
(1H, 1.2,
218 (2.70), 1616, 1588, 1570, 1455, (1H)
259 (3.79), 1345, 1248, 1070, 887,
305 (1.95), 834, 766, 730, 695, 558,
406 (1.48) 533, 476, 440
(1H)
s
J
J
m
J
7.5), 2.51
(3H)
s
V
216 (1.14), 3450, 3258, 3099, 3029,
247 (1.13) 2362, 1684, 1625, 1608,
1599, 1589
7.84 d.d.d (1H, J 1.8, 8.3, 14.8), 7.61 7.67 m (3H), 7.35
7.42 m (3H), 7.27 7.34 m (2H)
Vb
340 391
1423, 1401, 1315, 1302, 17.07 s 8.26 7.92 d.d (1H, J 9.8, 14.6), 7.74 d (1H, J 14.6), 7.53 d.d (2H,
(1.18 1.14), 1279, 1003, 952, 905, (1H)
411 (0.88), 888, 777, 750, 725, 685,
br.s J 1.8, 8.0), 7.36 7.42 m (3H), 7.09 7.16 m (2H)
(1H)
432
640, 613, 549, 505, 451
a
b
In DMSO-d CCl , 1:1.
In CDCl .
3
6
4
compound II is characterized by three strong absorp-
tion bands at 210, 234, and 301 nm, and it shows
no fluorescence.
on an FSM-1201 Fourier spectrometer. The mass
spectra (electron impact, 70 eV) were run on an MKh-
1320 instrument. The progress of reactions and the
purity of products were monitored by TLC on Sorbfil
plates using acetone hexane (1:2) as eluent.
Thus we have developed a new efficient prepara-
tive procedure for the synthesis of 4-hydroxy-5-(2-R-
2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thia-
zin-2,6-diones IIIa IIIt from readily accessible start-
ing compounds.
5-Acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-
2,6-dione (I) was synthesized by the procedure des-
cribed in [1 3]. Acetic anhydride, 45 ml, was added
to a solution of 21 g of malonic acid in 100 ml of
acetic acid. The mixture was stirred for 15 min at 20
25 C, 19 g of potassium thiocyanate was added in one
portion, and the mixture was stirred for 1 h at 20
25 C. The resulting yellow transparent solution was
left to stand for 48 h at 20 C, and the mixture crys-
tallized. It was diluted with 300 ml of water, and the
crystals were filtered off, dried in air, and recrystal-
lized from benzene. It is advisable to use a Soxhlet
EXPERIMENTAL
The UV spectra were recorded from solutions in
96.5% ethanol on an SF-2000 spectrophotometer. The
1H and 13C NMR spectra were measured on a Bruker
AM-500 spectrometer (500 and 125 MHz, respec-
tively) using DMSO-d6 as solvent. The IR spectra
were obtained from samples prepared as KBr pellets
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AZINES AND AZOLES: CXXIII.
811
Table 4. 13C NMR spectra ( C, ppm) of 4-hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-
diones IIIa IIIt, 4-hydroxy-5-{1-N-[2-(9-anthrylmethylideneamino)phenyl]ethanimidoyl}-2H-1,3-thiazine-2,6-dione (IV),
and 4-hydroxy-5-[(2E,4E)-5-phenylpenta-2,4-dienoyl]-2H-1,3-thiazine-2,6-dione (V)
7
6
5a
8
9
H
O
N
9a
4
NH
2
S
4
HN
5
2 3
O
6
R
O
Comp.
no.
C2
C3
C4
C2
C4
C5
C6
C5a, C6, C7, C8, C9, C9a
R
II
20.1 180.3 174.9 168.4
37.4 180.8 170.2 167.8
37.5 180.8 170.2 167.8
37.7 180.7 170.3 167.8
37.9 181.2 170.2 167.7
37.6 180.8 170.3 167.8
97.9
97.1
97.1
96.9
96.9
97.1
96.9
97.3
97.1
97.0
97.3
97.2
97.2
97.2
97.1
96.9
97.1
97.1
96.7
163.1 143.8, 129.3, 126.9, 120.2,
116.1, 115.8
162.8 141.4, 128.6, 124.8, 124.4, 144.5, 128.3, 127.5, 125.6
120.9, 119.8
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
66.3
66.1
65.5
66.7
65.8
162.8 141.3, 128.5, 125.5, 124.4, 141.6, 136.6, 128.8, 124.8,
120.9, 119.8
20.5
162.8 141.3, 128.5, 124.8, 124.2, 156.7, 135.1, 126.7, 114.9
120.9, 119.6
162.6 141.4, 128.1, 124.3, 124.1, 144.9, 144.6, 136.1, 116.2,
121.3, 119.5
162.8 141.3, 128.5, 126.8, 124.8, 158.6, 136.7, 126.8, 113.7,
120.9, 119.7 55.1
162.6 141.4, 128.1, 124.4, 124.2, 147.2, 146.1, 135.6, 117.9,
121.1, 119.6 115.1, 109.8, 55.4
163.1 141.4, 128.8, 125.0, 124.5, 147.3, 146.7, 138.7, 120.1,
121.1, 119.1 108.1, 106.3, 101.1
162.9 141.4, 128.4, 124.8, 124.1, 149.9, 132.4, 126.2, 112.2,
121.1, 119.6 40.1
162.5 141.1, 128.2, 124.8, 124.3, 143.3, 132.3, 128.0, 127.3
121.3, 120.0
162.7 140.2, 128.6, 124.9, 124.4, 141.4, 131.2, 129.2, 129.1,
120.7, 119.9
162.8 141.1, 128.7, 125.0, 124.6, 149.5, 132.3, 126.9, 120.2,
120.9, 118.7 110.2
162.7 141.0, 128.7, 127.2, 125.0, 151.5, 146.7, 124.7, 120.9
123.5, 120.3
162.9 140.5, 128.4, 126.2, 124.4, 155.5, 142.1, 110.2, 105.5
122.0, 121.2
162.9 141.4, 128.5, 124.9, 124.6, 136.2, 124.8, 121.9, 121.4,
121.2, 120.1
162.9 140.8, 128.3, 125.3, 124.6, 132.6,
121.3, 120.1
162.9 140.8, 128.4, 124.9, 124.7, 136.2, 130.9, 129.2, 128.5,
121.4, 120.2 127.6, 126.3
162.9 140.7, 128.4, 124.8, 124.7, 151.5, 142.7, 128.9, 118.1,
121.3, 120.2 111.6, 108.8
162.5 141.4, 127.8, 124.3, 123.9, 31.3, 18.4, 17.1
121.0, 119.1
115.2, 113.0
66.55 37.7 181.1 170.2 167.9
66.3
66.1
66.0
63.7
37.6 181.0 170.3 167.9
37.8 180.7 170.3 167.8
37.2 181.2 169.8 167.8
33.6 180.3 169.8 167.5
IIIj
IIIk
IIIl
127.8, 126.9
65.96 36.4 180.8 169.8 167.7
65.8
60.8
60.6
64.9
65.4
64.7
68.4
36.3 180.8 169.7 167.6
34.7 180.7 170.3 167.7
37.3 180.9 170.7 167.8
35.6 180.7 170.9 167.9
35.2 180.8 170.8 167.9
35.2 180.8 170.6 167.8
35.0 181.1 171.9 168.0
IIIm
IIIn
IIIo
IIIp
IIIq
IIIr
119.0, 118.9, 118.6, 111.5
124.8,
17.2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

812
YUSKOVETS et al.
Table 4. (Contd.)
Comp.
C2
C3
C4
C2
C4
C5
C6
C5a, C6, C7, C8, C9, C9a
R
no.
IIIs
IIIt
IV
V
66.3
67.3
39.5 180.9 170.6 168.3
38.3 180.8 170.5 168.1
21.0 180.3 173.7 168.3
183.9 180.7 173.3
97.3
97.5
97.5
99.6
162.8 140.7, 128.4, 125.4, 124.4, 29.6
121.2, 120.2
162.8 140.3, 128.2, 125.5, 124.4, 37.6, 25.1, 21.2
121.9, 120.1
162.9 162.3, 147.5, 131.6, 130.7, 130.2, 130.0, 129.7, 129.0,
127.5, 127.1, 126.98, 125.8, 125.6, 124.7, 119.9
163.0 148.9, 144.9, 135.6, 129.87, 128.86, 127.89, 127.4,
123.79
extractor for recrystallization. Yield 25 g (46%), mp
198 200 C.
plete, 2/3 of the solvent was removed under reduced
pressure, and the product was then isolated following
the general procedure. In the synthesis of compounds
IIIs and IIIt we used a large excess of acetone and
cyclohexanone, respectively (3 ml per gram of II).
5-[N-(2-Aminophenyl)ethanimidoyl]-4-hydroxy-
2H-1,3-thiazine-2,6-dione (II). A mixture of 1 g of
finely powdered 5-acetyl-4-hydroxy-1,3-thiazine-2,6-
dione I and 580 mg of o-phenylenediamine in 25 ml
of propan-2-ol was heated for 5 10 min under reflux.
As a rule, the reactants initially dissolved, and (in
1 2 min after the mixture became boiling), almost
colorless fine needle-shaped crystals began to quickly
separate from the solution. After cooling, the crystals
were filtered off, washed with propan-2-ol, and dried
in air. The product was analytically pure, and no ad-
ditional purification was necessary. Yield 1.45 g
(98%), mp 197 198 C.
b. A mixture of 1 g of 5-acetyl-4-hydroxy-1,3-thi-
azine-2,6-dione (I) and 580 mg of o-phenylenedi-
amine in 20 ml of propan-1-ol was heated for 5 min
under reflux. The mixture was cooled, 1.5 2 equiv of
the corresponding aldehyde and 5 7 drops of trifluo-
roacetic acid were added, and the mixture was heated
for 1.5 2 h under reflux and was then treated as de-
scribed above in a. The yields of the products ob-
tained by methods a and b were almost similar.
4-Hydroxy-5-[2-(4-nitrophenyl)-2,3-dihydro-1H-
1,5-benzodiazepin-4-yl]-2H-1,3-thiazine-2,6-dione
(IIIl). A mixture of 1 g of compound II and 600 mg
of 4-nitrobenzaldehyde in 15 ml of acetic acid was
heated for 1 h under reflux. The solvent was removed
on a rotary evaporator, 7 ml of ethanol was added to
the residue, and the mixture was heated to the boiling
point. After cooling, the crystals were filtered off.
washed with 2 3 small portions of ethanol, and dried
in air. Yield 725 mg (49%), mp 257 258 C (decomp).
4-Hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodi-
azepin-4-yl)-2H-1,3-thiazine-2,6-diones IIIa IIIt
(general procedure). a. Trifluoroacetic acid, 5
7 drops, was added to a mixture of 1 g of compound
II and 1.5 2 equiv of the corresponding aldehyde in
15 ml of propan-1-ol, and the mixture was heated for
1.5 2 h under reflux until initial compound II dis-
appeared completely. During the process, poorly
soluble compound II was gradually converted into
poorly soluble product which was as a rule a yellow
finely crystalline powder. In some cases, e.g., in the
reaction with vanillin, the reactants dissolved com-
pletely during the first 15 min, and only then product
IIIf began to crystallize from the solution. The mix-
ture was cooled, and the crystals were filtered off and
washed with 2 3 portions of propan-1-ol. As a rule,
the product was analytically pure, and no additional
purification was required. If necessary, benzodiaxe-
pines III can be recrystallized from dioxane (however,
the solvent is difficult to remove from the substance;
the recrystallized product should be dried under
reduced pressure on heating). Compound IIIj ob-
tained from o-chlorobenzaldehyde is readily soluble
in propan-1-ol; therefore, when the reaction was com-
5-[2-(4-Chlorophenyl)-2,3-dihydro-1H-1,5-
benzodiazepin-4-yl]-4-hydroxy-2H-1,3-thiazine-2,6-
dione (IIIi), 5-[2-(4-cyanophenyl)-2,3-dihydro-1H-
1,5-benzodiazepin-4-yl]-4-hydroxy-2H-1,3-thiazine-
2,6-dione (IIIk), and 4-hydroxy-5-(2-isopropyl-2,3-
dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thia-
zine-2,6-dione (IIIr) were synthesized as described
above for compound IIIl.
4-Hydroxy-5-[(2E,4E)-5-phenylpenta-2,4-di-
enoyl]-2H-1,3-thiazine-2,6-dione
(V). Pyridine,
5 drops, and piperidine, 5 drops, were added to a mix-
ture of 1 g of 5-acetyl-4-hydroxy-1,3-thiazine-2,6-di-
one (I) and 0.7 ml of cinnamaldehyde in 15 ml of
chloroform. The mixture was heated for 2 h
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006

AZINES AND AZOLES: CXXIII.
813
under reflux and cooled, and the orange plates were
filtered off, washed with a small amount of chloro-
form, and dried in air. Yield 1.2 g (74%), mp 215
216 C (decomp.)
4. Lloyd, D. and McNab, H., Adv. Heterocycl. Chem.,
1998, vol. 71, p. 1.
5. Chimirri, A., Gitto, R., Grasso, S., Monforte, A.M.,
Romeo, G., and Zappala, M., Heterocycles, 1993,
vol. 36, p. 601.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 5 2006