Reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin- 7-ones with aryl bromomethyl ketones and benzyl bromide

Article abstract of DOI:10.1007/s10593-005-0221-5

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4] triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]tria

Full text of DOI:10.1007/s10593-005-0221-5

Chemistry of Heterocyclic Compounds, Vol. 41, No. 6, 2005
REACTION OF 2-ARYL-5-R-5,6-DIHYDRO-7H-[1,2,4]-
TRIAZOLO[5,1-b][1,3]THIAZIN-7-ONES WITH ARYL
BROMOMETHYL KETONES AND BENZYL BROMIDE
V. N. Britsun, A. N. Esipenko, and M. O. Lozinskii
The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones
with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl
ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on
the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones
with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide.
Keywords: aryl bromomethyl ketones, 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-
ones, 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones, benzyl bromide, 3-benzylsulfanil-5-aryl-4H-
1,2,4-triazoles, 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles, 3-phenyl-2-propenoic acid, recyclization.
We have recently proposed a new method for the synthesis of 2,5-diaryl-5,6-dihydro-7H-
[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones involving the condensation of 3-aryl-4,5-dihydro-1H-1,2,4-triazole-5-
thiones with 3-aryl-2-propenoyl chlorides [1,2]. Ali and Soliman [3] have reported the preparation of 2-aryl-5,6-
dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by heating 3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanil)-
propanoic acids with acetic anhydride and the reactions of these [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with
nucleophilic reagents such as amines and hydrazine. In the present work, we have investigated the reactions of
2,5-diaryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones synthesized in our laboratory and 2-aryl-5,6-
dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones described by Ali and Soliman [3] with aryl bromomethyl
ketones and benzyl bromide, which were used in light of their high reactivity and thermal stability.
We have found that 5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 1a-g react with aryl
bromomethyl ketones 2a,b under vigorous conditions (fusion at 150-200°C). The direction of this reaction
depends on the structure of substituent R in 1a-g. When R = H, dehydrogenation of [1,2,4]triazolo[5,1-b]-
[1,3]thiazin-7-ones 1a-c occurs leading to 2-aryl-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones 3a-c and aryl
methyl ketones 4a,b. On the other hand, when R = Ph, thiazinones 1d-g recyclize at 150°C to give 2-Ar1-5-Ar2-
[1,3]thiazolo[3,2-b][1,2,4]triazoles 5a-e as well cinnamic acid (6) (Scheme 1).
Benzyl bromide 7 does not react with [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 1a-c even at 200°C, while
this bromide reacts with [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 1d-f already at 150°C. The products of this
reaction are 3-benzylthio-5-aryl-4H-1,2,4-triazoles 8a-c and 3-phenyl-2-propenoyl bromide (9) (Scheme 2).
The yields, melting points, and elemental analysis data of the reaction products are given in Table 1.
2-Phenyl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one (3a) was previously obtained by the cyclization of
3-(5-phenyl-4H-1,2,4-triazol-3-ylsulfanil)-2-propenoic acid in the presence of thionyl chloride [4], while
__________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 02094 Kiev, Ukraine.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905-909, June, 2005. Original article
submitted April 1, 2004.
782
0009-3122/05/4106-0782©2005 Springer Science+Business Media, Inc.

Scheme 1
Ar2
CH2Br
O
O
Ar2
Me
N
N
2a,b
Ar1
+
+
HBr
HBr
O
O
R
+
S
R = H, 200 o
C
N
N
3a–c
4a,b
N
Ar1
Ar 2
R
S
N
N
N
2a,b
N
Ar1
R
1a–g
+
COOH
S
R = Ph, 150 oC
.
6
5a–e
1a,d, 3a, 5a Ar1 = Ph, 1b,f, 3b, 5c Ar1 = р-ClC6H4, 1c,g, 3c, 5d Ar1 = р-FC6H4,
1e, 5b,e Ar1 = р-MeOC6H4; 2a, 4a, 5a-d Ar2 = Ph, 2b, 4b, 5e Ar2 = р-ClC6H4;
1a-c, 3a-c R = H, 1d-g, 6 R = Ph
Scheme 2
PhCH2Br
N
N
7
Ar1
COBr
1d–f
+
Ph
S
Ph
150 oC
.
N
H
9
8a–c
8 a Ar1 = Ph, b Ar1 = р-ClC6H4 , c Ar1 = р-MeОC6H4
[1,3]thiazolo[3,2-b][1,2,4]triazoles 5a-c,e have been synthesized by heating 1-aryl-2-(5-aryl-4H-1,2,4-triazol-3-
ylsulfanil)-1-ethanones in absolute ethanol at reflux [5] or in the thermal decomposition of 4-aryl-2-(5-aryl-1H-
1,2,3,4-tetrazol-1-yl)-1,3-thiazoles [6]. Since the compounds described by Potts [5] and Ramachandraiah [6]
1
were not characterized by spectral methods, we found it necessary to give the H NMR and IR spectral data of
the compounds synthesized in the present work (Table 2).
The reaction temperatures indicate the relative stability of the 1,3-thiazine ring in the starting
[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones lacking a substituent at C(5) (1a-c, R = H) and with a phenyl substituent
at this position (1d-g). Thiazinones 1d-f react with aryl methyl ketones 2a,b at 150°C, while thiazinones 1a-c
react with these ketones only at 200°C.
In all likelihood, the alkylation of [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 1a-c and 1d-g initially occurs
at S(4) with formation of unstable sulfonium salt A, which loses a proton and converts to intermediate B.
Then, the direction of the decomposition of B depends on the structure of substituent R at C(5). If R = H,
intermediate B probably transforms into [1,2,4]triazolo[5,1-b][1,3]thiazin-7-one 3 and aryl methyl ketone 4. On
the other hand, if R = Ph, the S–C(5) is cleaved, and the amide of 3-aryl-2-propenoic acid C may possibly be
formed, which then likely is converted into [1,3]thiazolo[3,2-b][1,2,4]triazole 5 and 3-phenyl-2-propenoic
acid 6.
783

O
O
7
6
N
N
5
N
–
N
R = H
Ar1
R
1
+
S
R
+
Ar
3 + 4
– HBr
S
N
N
O
O
Br
Ar
Ar
R = Ph
B
A
O
N
N
Ar1
5
6
+
R
S
N
O
Ar
C
TABLE 1. Characteristics of Synthesized Compounds
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °C
Yield, %
35
С
H
N
3a
C11H7N3OS
57.47
57.63
3.31
3.08
18.10
18.33
260-262
264-266 [4]
3b
3c
4a
C11H6ClN3OS
C11H6FN3OS
C8H8O
50.32
50.10
53.67
53.44
79.70
79.97
2.20
2.29
2.69
2.45
6.49
6.71
16.22
15.93
17.29
17.00
268-270
37
33
45
250-252
—
17-18
20-20.5 [7]
4b
5a
C8H7ClO
62.31
62.15
4.33
4.56
—
16-18
20 [8]
42
43
C16H11N3S
69.58
69.29
4.29
4.00
15.39
15.15
135-137
137-139 [5, 6]
5b
5c
C17H13N3OS
C16H10ClN3S
66.76
66.43
4.41
4.26
13.45
13.67
140-141
153 [6]
40
39
61.78
61.64
3.46
3.23
13.19
13.48
150-152
158 [6]
5d
5e
C16H10FN3S
65.29
65.07
59.96
59.74
3.70
3.41
3.70
3.54
13.94
14.23
12.57
12.29
138-140
45
41
C17H12ClN3OS
170-172
171 [6]
6
C9H8O2
72.71
72.96
5.31
5.44
—
131-133
135 [9]
50
8a
8b
8c
9
C15H13N3S
C15H12ClN3S
C16H15N3OS
C9H7BrO
67.61
67.39
59.52
59.70
64.33
64.62
51.51
51.22
4.61
4.90
4.31
4.01
4.81
5.08
3.07
3.34
15.43
15.72
13.81
13.92
13.85
14.13
—
78-80
115-117
87-89
45
42
40
38
39-40
43 [10]
784

TABLE 2. IR and 1H NMR Spectral Data of Products
Com-
pound*
IR spectrum, ν, cm-1
1Н NMR spectrum, δ, ppm. (J, Hz)
3a
—
6.99 (1H, d, J = 9.5, Н-6); 7.57 (3Н, m, С6Н5);
8.17 (2H, m, С6Н5); 8.38 (1H, d, J = 9.5, Н-5)
3b
3050, 1700 (C=O), 1605
C=N), 1560, 1520, 1480,
1410, 1370, 1310
6.99 (1H, d, J = 9.4, Н-6); 7.61 (2Н, d, J = 7.6, m-HAr);
8.16 (2H, d, J = 7.6, о-HAr); 8.42 (1H, d, J = 9.4, Н-5)
3c
3050, 1700 (C=O), 1620
C=N), 1560, 1490, 1450,
1420, 1370
6.99 (1H, d, J = 9.6, Н-6); 7.40 (2Н, m, m-H Ar);
8.19 (2H, m, о-HAr); 8.42 (1H, d, J = 9.6, Н-5)
5a
5b
3100, 1610, 1550, 1500, 1480, 7.45-7.59 (6Н, m, HAr); 7.96 (1Н, s, Н-6);
1460, 1400, 1330, 1300, 1290 8.16 (2Н, m, HAr); 8.32 (2Н, m, HAr)
3100, 2830, 1620, 1590, 1530, 3.82 (3H, s, СН3О); 7.07 (2Н, d, J = 8.9, m-HAr);
1500, 1470, 1430, 1320, 1310 7.59 (3Н, m, НAr); 7.90 (1Н, s, H-6);
8.07 (2Н, d, J = 8.9, о-HAr); 8.28 (2Н, m, HAr)
5c
5d
5е
3100, 3050, 1600, 1550, 1500, 7.61 (5Н, m, HAr); 7.96 (1Н, s, Н-6);
1470, 1450, 1410, 1320
3100, 1610, 1530, 1500, 1470, 7.40 (2Н, m, HAr); 7.64 (3Н, m, HAr); 7.95 (1Н, s, H-6);
1420, 1320, 1280, 1230 8.16 (2Н, m, HAr); 8.30 (2Н, m, HAr)
8.09 (2Н, d, J = 9.0, o-HAr); 8.29 (2Н, m, HAr)
3050, 1610, 1580, 1530, 1500, 3.84 (3H, s, СН3О); 7.11 (2Н, d, J = 8.4, m-HAr);
1470, 1430, 1320, 1310, 1270 7.70 (2Н, d, J = 8.1, m-HAr); 7.99 (1Н, s, H-6);
8.09 (2Н, d, J = 8.4, o-HAr); 8.36 (2Н, d, J = 8.1, o-HAr)
8b
3000, 1620, 1500, 1460, 1410, 4.44 (2H, s, SCH2); 7.28-7.68 (7Н, m, HAr);
1340, 1280
7.99 (2Н, d, J = 9.1, o-HAr)
8с
3000, 1610, 1590, 1510, 1460, 3.80 (3Н, s, СН3О); 4.40 (2H, s, SCH2);
1410, 1350, 1300, 1270
7.09 (2Н, d, J = 8.9, m-HAr); 7.31 (3Н, m, C6H5);
7.42 (2Н, m, C6H5); 7.89 (2Н, d, J = 8.9, o-HAr)
_______
* The IR spectrum of 3a corresponds to the spectrum reported by Heindel
1
[4]. The IR and H NMR spectra of 8a correspond to the spectra given by
Barbier et al. [11].
We note that, in both cases, reaction products 3a-c and 5a-e contain aromatic heterocyclic systems,
while starting compounds 1a-g have a single thiazole ring. This is evidence of the greater chemical and
thermodynamic stability of heteroaromatic compounds in comparison with alicyclic heterocycles.
EXPERIMENTAL
1
The H NMR spectra were taken on a Varian 300 spectrometer at 300 MHz for solutions in DMSO-d6
with TMS as the internal standard. The IR spectra were taken for KBr pellets on a UR-20 spectrometer.
2-Aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3a-c and Aryl Methyl Ketones 4a,b. A mixture
of 2-aryl[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one 1a-c (10 mmol) and aryl bromomethyl ketones 2a or 2b
(10 mmol) was heated for 4 min at 200°C and then cooled. The reaction mixture was extracted with three 7-ml
ether portions. The precipitate of 3a-c was filtered off, dried, and recrystallized from acetic acid. The ethereal
extract containing ketone 4a or 4b was evaporated and the resultant oil was extracted with three 5-ml hot hexane
portions. Hexane was evaporated and 4a or 4b was distilled in vacuum. The yields and physical constants of 3a-
c, 4a,b are given in Table 1.
2,5-Diaryl[1,3]thiazolo[3,2-b][1,2,4]triazolo[5,1-b][1,3]-triazoles 5a-e and 3-Phenyl-2-propenoic
Acid (6). A mixture of 2,5-diaryl[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one 1d-g and aryl bromomethyl ketone 2a
or 2b (10 mmol) was heated for 7 min at 150°C and cooled. The reaction mixture was treated with three 10-ml
785

portions of 10% aq. sodium bicarbonate. Products 5a-e, which are insoluble in the sodium bicarbonate solution,
were filtered off and recrystallized from acetic acid. The aqueous sodium bicarbonate solution containing acid 6
was acidified by adding concentrated hydrochloric acid and maintained for 6 h in the cold. Cinnamic acid 6 was
filtered off, dried, and recrystallized from 4:1 aqueous ethanol.
5-Aryl-3-benzylthio-4H-1,2,4-triazoles 8a-c and 3-Phenyl-2-propenoyl Bromide (9). A mixture of
2,5-diaryl[1,2,4]triazolo[5,1-b][1,3]thiazin-7-one 1d-f (10 mmol) and benzyl bromide 7 (11 mmol) was heated
for 10 min at 150°C and cooled. The reaction mixture was extracted with three 10-ml dry ether portions. The
insoluble residue of 8a-c was filtered off, dried, and recrystallized from ethanol. The ethereal extracts were
combined and evaporated to yield bromide 9.
REFERENCES
1.
2.
3.
4.
5.
V. N. Britsun, V. V. Pirozhenko, and M. O. Lozinskii, Zh. Org. Khim., 37, 1102 (2001).
V. N. Britsun and M. O. Lozinskii, Khim. Geterotsikl. Soedin., 1256 (2004).
M. I. Ali and A. A. Soliman, J. Prakt. Chem., 325, 869 (1993).
N. D. Heindel and J. R. Reid, J. Org. Chem., 45, 2479 (1980).
K. T. Potts and S. Husain, J. Org. Chem., 36, 10 (1971).
G. Ramachandraiah and K. K. Reddy, Indian J. Chem., Sect. B, 24(B), 808 (1985).
Beilstein, 7, 271 (1925).
6.
7.
8.
Beilstein, 7, 281 (1925).
9.
Beilstein, 9, 225 (1932).
10.
11.
Beilstein, 9, 233 (1932).
F. Malbec, R. Milcent, and G. Barbier, J. Heterocycl. Chem., 21, 1689 (1984).
786