Reactivity of ketene dithiolates toward alkyl bromides

Article abstract of DOI:10.1002/jhet.484

Figure represented. The reactivity of barbituric/thiobarbituric ketene dithiolates with bromoacetic ester and phenacyl bromide is studied.

Full text of DOI:10.1002/jhet.484

July 2011
Reactivity of Ketene Dithiolates toward Alkyl Bromides
973
Venkatapuram Padmavathi,* Guda Dinneswara Reddy, Gali Sudhakar Reddy,
Konda Mahesh, and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
*E-mail: vkpuram2001@yahoo.com
Received January 27, 2010
DOI 10.1002/jhet.484
Published online 12 May 2011 in Wiley Online Library (wileyonlinelibrary.com)
The reactivity of barbituric/thiobarbituric ketene dithiolates with bromoacetic ester and phenacyl
bromide is studied.
J. Heterocyclic Chem., 48, 973 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
The chemistry of activated olefins has gained impor-
tance because of their utility as synthons for the synthe-
sis of a variety of carbocyclic and heterocyclic systems.
In fact, we have reported a simple approach for the syn-
thesis of E,Z-bis(styryl)sulfones [1]. We have also stud-
ied the reaction of vinyl chloride with aroyl and arylsul-
fonyl chlorides under Friedel-crafts conditions which
afforded unsaturated oxosulfones and bissulfones [2].
This methodology has been extended to prepare bis un-
saturated oxosulfones and bissulfones [3]. These acti-
vated mono and bis unsaturated olefins have been used
to develop different heterocyclic systems [4]. In continu-
ation of our interest on the synthesis of new activated
olefins, the following Scheme 1 has been taken up.
The reaction of active methylene compounds with car-
bon disulfide in the presence of a base followed by alkyl-
ation produced thioesters and ketene mercaptols [5]. Var-
ious acyclic and cyclic aliphatic and aromatic ketones
have been utilized for this purpose. However, the reaction
with less activated compounds like aliphatic aldehydes or
ketones resulted in low yield [6] (10–25%). On the other
hand, barbituric acid and thiobarbituric acid have not
been explored as active methylene compounds to gener-
ate a variety of thioesters and ketene mercaptols. The
present communication deals with the reactivity of barbi-
turic acid and thiobarbituric acid with carbon disulfide in
the presence of a base followed by alkylation with ethyl
bromoacetate and phenacyl bromide.
The barbituric acid (1) was treated with carbon disul-
fide in the presence of sodium hydride and was subse-
quently alkylated with ethyl bromoacetate. The reaction
mixture was stirred for 8 h at room temperature and
extracted with dichloromethane. The product obtained
was identified as 5-oxo-2-(2,4,6-trioxopyrimidin-5-yli-
dene)-[1,3]dithiane-4-carboxylic acid ethyl ester (3)
(Scheme 1). It seems that the initially formed [ethoxy-
carbonylmethylsulfanyl-(2,4,6-trioxopyrimidin-5-ylidene)
methyl-sulfanyl]acetic acid ethyl ester undergoes Die-
ckmann cyclization resulting in the formation of 3.
Similarly, the reaction of thiobarbituric acid (2) with
carbon disulfide in the presence of sodium hydride fol-
lowed by alkylation with ethyl bromoacetate produced
5-oxo-2-(4,6-dioxo-2-thioxopyrimidin-5-ylidene)-
[1,3]dithiane-4-carboxylic acid ethyl ester (4). On the
other hand, the reaction of barbituric acid/thiobarbituric
acid 1/2 with carbon disulfide in the presence of sodium
hydride followed by treatment with phenacyl bromide
resulted in 5-[bis-(2-oxo-2-aryl-ethylsulfanyl)methyle-
ne]pyrimidine-2,4,6-trione (5)/5-[bis-(2-oxo-2-arylethyl-
sulfanyl)methylene]-2-thioxopyrimidine-4,6-dione (6).
The Knoevenagel reaction of 5 and 6 with araldehydes
in the presence of benzylamine in acetic acid gave
5-[bis-(1-aroyl-2-arylvinylsulfanyl)-methylene]pyrimi-
dine-2,4,6-trione (7) and 5-[bis-(1-aroyl-2-arylvinylsul-
fanyl)-methylene]-2-thioxo-pyrimidine-4,6-dione (8)
(Scheme 1, Table 1). The structures of all the new
C
V
2011 HeteroCorporation

Scheme 1
Table 1
Physical and analytical data of compounds 3–8.
Analysis (%) calcd./found
Compound
Mp (ꢀC)
168–170
Yield (%)
67
Ar
–
Ar0
–
Molecular formula
C
H
N
3
C11H10N2O6S2 (330.34)
39.99
39.92
38.14
38.21
57.26
57.22
58.96
59.03
49.52
49.58
55.24
55.30
57.00
57.06
48.00
48.07
68.16
68.21
69.62
69.70
55.72
55.76
66.43
66.37
68.00
68.07
54.55
54.49
3.05
2.98
2.91
2.89
3.66
3.63
4.30
4.25
2.77
2.81
3.53
3.55
4.16
4.21
2.69
2.72
3.92
3.90
4.79
4.75
2.67
2.70
3.82
3.86
4.68
4.65
2.62
2.66
8.48
8.52
8.09
8.17
6.36
6.41
5.98
6.04
5.50
5.45
6.14
6.08
5.78
5.82
5.33
5.40
4.54
4.60
4.16
4.20
3.71
3.76
4.43
4.48
4.07
4.01
3.64
3.67
4
182–184
182–184
176–178
230–232
175–177
184–186
192–194
159–161
164–166
197–199
161–163
167–169
185–187
65
76
80
85
75
82
77
71
76
80
74
80
75
–
–
C11H10N2O5S3 (346.41)
C21H16N2O5S2 (440.49)
C23H20N2O5S2 (468.55)
C21H14Cl2N2O5S2 (509.38)
C21H16N2O4S3 (456.56)
C23H20N2O4S3 (484.61)
C21H14Cl2N2O4S3 (525.45)
C35H24N2O5S2 (616.71)
C39H32N2O5S2 (672.81)
C35H20Cl4N2O5S2 (754.49)
C35H24N2O4S3 (632.77)
C39H32N2O4S3 (688.88)
C35H20Cl4N2O4S3 (770.55)
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
C6H5
–
4-MeC6H4
4-ClC6H4
C6H5
–
–
–
4-MeC6H4
4-ClC6H4
C6H5
–
–
C6H5
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
C6H5
4-MeC6H4
4-ClC6H4
4-MeC6H4
4-ClC6H4

July 2011
Reactivity of Ketene Dithiolates toward Alkyl Bromides
975
Table 2
compounds were confirmed by spectral parameters
and elemental analyses which are depicted in Tables 2
and 3.
IR data of compounds 3–8.
IR (KBr) cmꢁ1
Compounds C¼S C¼C
C¼O
NH
CONCLUSIONS
3
4
–
1485
–
–
–
1752, 1735, 1710, 1685 3263
The reaction of barbituric acid/thiobarbituric acid
with CS2 followed by treatment with ethyl bromoacetate
led to directly Dieckmann cyclized product. However,
with phenacyl bromide bisalkylation takes place which
are used as synthons to develop a new class of olefins
by Knovenagel condensation with different araldehydes.
1759, 1735, 1681
1720, 1703, 1685
1722, 1695, 1682
1733, 1702, 1686
1726, 1712
3216
3282
3274
3290
3284
3310
3300
3285
3290
3295
3251
3295
3300
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
–
–
–
–
–
1488
1492
1495
–
–
–
1720, 1704
1712, 1725
–
1606
1612
1610
1672, 1680, 1730
1724, 1682, 1675
1720, 1684, 1677
1733, 1686
–
–
EXPERIMENTAL
1487 1588
1498 1594
1510 1610
1730, 1680
1724, 1704
Melting points were determined in open capillaries on a
Mel-Temp apparatus and are uncorrected. The purity of the
compounds was checked by TLC (silica gel H, BDH, ethyl
Table 3
1H and 13C NMR data of compounds 3–8.
Compound
1H NMR (CDCl3/DMSO-d6) d (ppm)
13C NMR (CDCl3/DMSO-d6) d (ppm)
3
1.25 (t, 3H, ACH2ACH3, J ¼ 7.2 Hz), 3.25
(s, 2H, ASCH2ACO), 4.14 (q, 2H, ACH2ACH3,
J ¼ 7.2 Hz), 4.44 (s, 1H, [ASCHACO(CO)],
10.25 (bs, 2H, NH)
13.8 (ACH2ACH3), 40.5 (ASCH2ACO), 59.6 (OCH2ACH3),
65.3 (ASCHACO), 104.6 (C-5), 159.4 (C-2), 168.6 (C-4
and C-6), 173.4 (COAO), 175.2 [¼CAS(S)], 205.4 (CO)
4
1.19 (t, 3H, ACH2ACH3, J ¼ 6.9 Hz), 3.23
(s, 2H, ASCH2ACO), 4.18 (q, 2H, ACH2ACH3,
J ¼ 6.9 Hz), 4.39 (s, 1H, [ASCHACO(CO)],
9.86 (bs, 2H, NH)
13.5 (ACH2ACH3), 39.8 (ASCH2ACO), 58.9
(AOCH2ACH3), 64.5 (ASCHACO), 105.5 (C-5), 169.3
(C-4 and C-6), 172.6 (COAO), 174.5 [¼CAS(S)], 181.6
(C-2), 207.2 (C¼O)
5a
5b
5c
6a
6b
6c
7a
3.89 (s, 4H, ASCH2ACO), 7.35–7.84 (m, 10H,
Ar-H), 10.32 (s, 2H, NH)
46.2 (ASCH2ACO), 113.4 (C-5), 156.7 (C-2), 168.3 (C-4 and
C-6), 174.6 [C¼CAS(S)], 198.4 (C¼O)
2.24 (s, 6H, Ar-CH3), 3.85 (s, 4H, ASCH2ACO),
7.24–7.85 (m, 8H, Ar-H), 11.29 (s, 2H, NH)
3.81 (s, 4H, ASCH2ACO), 7.41–7.95 (m, 8H,
Ar-H), 11.22 (s, 2H, NH)
21.4 (Ar-CH3), 45.9 (ASCH2ACO), 112.8 (C-5), 156.5 (C-2),
167.5 (C-4 and C-6), 175.3 [C¼CAS(S)], 197.9 (C¼O)
47.5 (ASCH2ACO), 114.2 (C-5), 158.4 (C-2), 166.5 (C-4 and
C-6), 175.5 [C¼CAS(S)], 196.8 (C¼O)
3.85 (s, 4H, ASCH2ACO), 7.26–7.52 (m, 10H,
Ar-H), 9.98 (s, 2H, NH)
2.26 (s, 6H, Ar-CH3), 3.87 (s, 4H, ASCH2ACO),
7.19–7.43 (m, 8H, Ar-H), 9.89 (s, 2H, NH)
3.86 (s, 4H, ASCH2ACO), 7.24–7.80 (m, 8H,
Ar-H), 9.96 (s, 2H, NH)
48.4 (ASCH2ACO), 112.4 (C-5), 168.5 (C-4 and C-6), 176.4
[C¼CAS(S)], 188.4 (C-2), 198.3 (C¼O)
21.2 (Ar-CH3), 47.6 (-SCH2-CO), 112.8 (C-5), 168.8 (C-4
and C-6), 175.8 [C¼C-S(S)], 187.9 (C-2), 197.6 (C¼O)
48.5 (ASCH2ACO), 114.3 (C-5), 168.2 (C-4 and C-6), 175.3
[C¼CAS(S)], 189.3 (C-2), 197.5 (C¼O)
6.94 (s, 2H, Ar-CH¼C), 7.19-7.78 (m, 20H,
120.5 (C-5), 136.8 (Ar-CH¼C), 138.5 (Ar-CH¼C),
157.5 [C¼CAS(S)], 159.2 (C-2), 168.4 (C-4 and C-6),
186.9 (CO)
Ar-H), 9.87 (s, 2H, NH)
7b
7c
8a
8b
8c
2.21 (s, 12H, Ar-CH3), 6.89 (s, 2H, Ar-CH¼C),
21.5 (Ar-CH3), 121.2 (C-5), 136.3 (Ar-CH¼C), 139.2
(Ar-CH¼C), 156.2 [C¼CAS(S)], 158.5 (C-2), 169.3
(C-4 and C-6), 188.2 (CO)
7.14–7.26 (m, 16H, Ar-H), 9.88 (s, 2H, NH)
6.98 (s, 2H, Ar-CH¼C), 7.25–7.80 (m, 16H,
121.2 (C-5), 136.3 (Ar-CH¼C), 138.9 (Ar-CH¼C), 158.4
[C¼CAS(S)], 159.8 (C-2), 167.5 (C-4 and C-6), 185.8
(CO)
Ar-H), 9.85 (s, 2H, NH)
6.96 (s, 2H, Ar-CH¼C), 7.22–7.81 (m, 20H,
120.2 (C-5), 135.9 (Ar-CH¼C), 139.4 (Ar-CH¼C), 156.8
[C¼CAS(S)], 166.8 (C-4 and C-6), 182.4 (C-2), 186.5
(CO)
21.3 (Ar-CH3), 121.5 (C-5), 136.2 (Ar-CH¼C), 139.8
(Ar-CH¼C), 156.2 [C¼CAS(S)], 167.2 (C-4 and C-6),
181.8 (C-2), 185.9 (CO)
Ar-H), 9.79 (s, 2H, NH)
2.18 (s, 12H, Ar-CH3), 6.92 (s, 2H, Ar-CH¼C),
7.19–7.82 (m, 16H, Ar-H), 9.75 (s, 2H, NH)
6.90 (s, 2H, Ar-CH¼C), 7.25–7.79 (m, 16H,
122.2 (C-5), 136.9 (Ar-CH¼C), 138.4 (Ar-CH¼C),
157.2 [C¼CAS(S)], 166.9 (C-4 and C-6), 182.2 (C-2),
185.5 (CO)
Ar-H), 9.79 (s, 2H, NH)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

976
V. Padmavathi, G. D. Reddy, G. S. Reddy, K. Mahesh, and A. Padmaja
Vol 48
acetate/hexane-2:1). The IR spectra were recorded on a Nicolet
IR 200 FTIR spectrometer using KBr pellets (m in cmꢁ1). The
1H NMR spectra were recorded in CDCl3/DMSO-d6 on a Jeol
JNM k-300 MHz. The 13C NMR spectra were recorded in
CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
75.5 MHz. All chemical shifts were reported in d (ppm) using
TMS as an internal standard. The microanalyses were per-
formed on Perkin-Elmer 240C elemental analyzer. All the sol-
vents and reagents were obtained from commercial sources
and purified before use if necessary. Column chromatography
was performed in silica gel (60–120 mesh).
5-Oxo-2-(2,4,6-trioxopyrimidin-5-ylidene)-[1,3]dithiane-4-
carboxylic acid ethyl ester (3)/5-oxo-2-(4,6-dioxo-2-thioxo-
pyrimidin-5-ylidene)-[1,3]dithiane-4-carboxylic acid ethyl
ester (4): general procedure. To a solution of barbituric acid/
thiobarbituric acid (1, 1.28 g/2, 1.44 g, 10 mmol) dissolved in
DMSO (15 mL), sodium hydride (0.46 g, 20 mmol) was added
slowly while stirring at room temperature. To this carbon di-
sulfide (1.14 g, 15 mmol) in DMSO (4 mL) was added and the
stirring was continued for 1 h. Then ethyl bromoacetate (5.01
g, 30 mmol) was added dropwise to the stirred solution. After
stirring at room temperature for 7–8 h, the reaction mixture
was diluted with water and extracted with dichloromethane.
The organic layer was washed with water followed by brine
solution and dried over an. sodium sulfate. Removal of the sol-
vent under vacuum gave 3/4.
5-[Bis-(1-aroyl-2-arylvinylsulfanyl)methylene]pyrimidine-
2,4,6-trione (7)/5-[bis-(1-aroyl-2-aryl-vinylsulfanyl)methylene]-
2-thioxopyrimidine-4,6-dione (8): general procedure.. A mix-
ture of 5/6 (4.40 g/4.56 g, 10 mmol), araldehyde (2.12 g, 20
mmol), benzylamine (0.5 mL), and glacial acetic acid was
refluxed for 7–8 h. The reaction mixture was cooled, treated
with dry ether (50 mL), and refrigerated overnight. Any prod-
uct separated was collected by filtration. The filtrate was
extracted with ether, washed with sodium bisulfite solution,
dilute hydrochloric acid, and finally with water. Evaporation of
the ethereal layer gave yellow solid product 7/8 which was
recrystallized from 2-propanol.
Acknowledgments. The authors are grateful to Council of Sci-
entific and Industrial Research (CSIR), New Delhi, for financial
assistance under major research project.
REFERENCES AND NOTES
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5-[Bis-(2-oxo-2-arylethylsulfanyl)methylene]-pyrimidine-
2,4,6-trione (5)/5-[bis-(2-oxo-2-arylethylsulfanyl)methylene]-
2-thioxopyrimidine-4,6-dione (6): general procedure. To a
solution of barbituric acid/thiobarbituric acid (1, 1.28 g/2, 1.44
g, 10 mmol) in DMSO (15 mL), sodium hydride (0.46 g, 20
mmol) was added slowly while stirring at room temperature.
To this carbon disulfide (1.14 g, 15 mmol) in DMSO (4 mL)
was added at the same temperature. The solution was stirred
for 1 h. Then, phenacyl bromide (3.98 g, 20 mmol) was added
in portions and continued stirring for 10–12 h. The reaction
mixture was diluted with water and extracted with dichlorome-
thane. The organic layer was washed with water followed by
brine solution and dried over an. sodium sulfate. Removal of
the solvent in vaccuo gave a solid which was purified by col-
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DOI 10.1002/jhet