Synthesis of new 3-substituted and spiro 1,5-benzodiazepin-2-ones under phase-transfer catalysis conditions

Article abstract of DOI:10.1081/SCC-100105132

1,3-Dihydro-4-phenyl-1,5-benzodiazepin-2-one 1 was treated with bromine in 1:1 molar ratio to get the corresponding 3-bromo derivative 2 which in turn reacted with different nucleophiles to get the corresponding 3-substituted derivatives 3-11. The cyclize

Full text of DOI:10.1081/SCC-100105132

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SYNTHESIS OF NEW 3-SUBSTITUTED AND SPIRO 1,5-
BENZODIAZEPIN-2-ONES UNDER PHASE-TRANSFER
CATALYSIS CONDITIONS
H. Abdel-Ghany , A. M. El-Sayed , A. Khodairy & H. Salah
Published online: 09 Nov 2006.
To cite this article: H. Abdel-Ghany , A. M. El-Sayed , A. Khodairy & H. Salah (2001) SYNTHESIS OF NEW 3-SUBSTITUTED
AND SPIRO 1,5-BENZODIAZEPIN-2-ONES UNDER PHASE-TRANSFER CATALYSIS CONDITIONS, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:16, 2523-2535, DOI: 10.1081/
SCC-100105132
To link to this article: http://dx.doi.org/10.1081/SCC-100105132
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SYNTHETIC COMMUNICATIONS, 31(16), 2523–2535 (2001)
SYNTHESIS OF NEW 3-SUBSTITUTED
AND SPIRO 1,5-BENZODIAZEPIN-2-ONES
UNDER PHASE-TRANSFER
CATALYSIS CONDITIONS
H. Abdel-Ghany,* A. M. El-Sayed, A. Khodairy,
and H. Salah
Department of Chemistry, Faculty of Science, Sohag, Egypt
ABSTRACT
1,3-Dihydro-4-phenyl-1,5-benzodiazepin-2-one 1 was treated
with bromine in 1:1 molar ratio to get the corresponding
3-bromo derivative 2 which in turn reacted with different
nucleophiles to get the corresponding 3-substituted deriva-
tives 3–11. The cyclized compounds 4a, 5a, 7a,b, and 9a–c
were achieved on refluxing compounds 4, 5, 6a,b, or 8a–c
respectively in diphenyl ether. Compound 1 was benzoylated
with benzoyl chloride to give the corresponding 1-benzoyl
derivative 12 which reacted with bromine in 1:2 molar ratio
to yield the corresponding 3,3-dibromo derivative 13. Spiro
benzodiazepines 14a–d–16 were obtained by reacting com-
pound 13 with the proper bidentates. Compound 1 was trea-
ted with formaldehyde and secondary amines or thiols to give
Mannich bases or sulphides 17–21, respectively.
*Corresponding author.
2523
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
2524
ABDEL-GHANY ET AL.
The pharmacological activities1-7 of 1,5-benzodiazepin-2-ones pro-
mpted us to continuate our previous work on the synthesis of fused and
3-substituted-1,5 benzodiazepines8,9
.
RESULTS AND DISCUSSION
3-Bromo-1,3-dihydro-1,5-benzodiazepin-2-one 2 was prepared from
the reaction of 1,3-dihydro-4-phenyl-1,5 benzodiazepin-2-one 1 with an
equimolar amount of bromine in chloroform as a solvent. This compound
is proven to be a good starting material for the synthesis of 4-phenyl-3-
substituted-1(H)-1,5-benzodiazepin-2-ones, where it was reacted with phtha-
limidoethanol, cystamine hydrochloride, guanidine hydrochloride, ethyl
mercaptoacetate, ethyl glycinate hydrochloride, o-phenylenediamine,
o-aminothiophenol, catechol, p-phenylenediamine, p-aminobenzoic acid,
hydroquinone or resorcinol to give the corresponding 3-substituted deriva-
tives 3, 4, 5, 6a,b, 8a-c, 10a-c or 11, respectively (cf. Scheme 1, Table 1).
The reaction was performed under phase-transfer catalysis conditions
using solid-liquid phase system, where the reactants in dioxane formed the
organic phase in which potassium carbonate was suspended. The reaction
was catalyzed with tetrabutylammonium bromide (TBAB). The reaction
pathway was assumed to proceed via two catalytic cycles. The first one,
namely proton abstraction, takes place on the surface of solid carbonate.
The formed anion then migrates as an ion pair with the catalyst cation into
the organic phase where the second cycle concerned with the substitution
reaction takes place in order of reactivity Sꢀ>Nꢀ>Oꢀ.
On refluxing compounds 4, 5, 6a,b or 8a-c in diphenyl ether gave the
corresponding cyclized products 4a, 5a, 7a,b or 9a-c, respectively.
Treatment of compound 1 with benzoyl chloride in pyridine as a
solvent and catalyst afforded 1-benzoyl-4-phenyl-3(H)-1,5-benzodiazepin-
2-one 12, which in turn reacted with bromine in 1:2 molar ratio at room
temperature in chloroform to give 1-benzoyl-3,3-dibromo-4-phenyl-1,5-ben-
zodiazepin-2-one 13. This compound is a building block for the synthesis of
spiro heterocyclic systems attached to benzodiazepine moeity, where it was
treated with ethylenediamine, ethanolamine, cystamine hydrochloride,
2-mercaptoethanol, o-phenylenediamine, o-aminophenol, o-aminothio-
phenol, catechol or thiosemicarbazide using phase-transfer catalysis tech-
nique [dioxane/potassium carbonate/tetrabutylammonium bromide (TBAB)]
to give the corresponding spiro (1, 5) benzodiazepin-2-one derivatives
14a-d–16, respectively (cf. Scheme 2, Table 1).
The reaction mechanism should be followed as explained before and
can be illustrated as in Figure A.

ORDER
REPRINTS
SPIRO 1,5-BENZODIAZEPIN-2-ONES
2525
Scheme 1.

ORDER
REPRINTS
2526
ABDEL-GHANY ET AL.
Table 1. Analytical and Spectral Data of the Prepared Compounds
M.P.(ꢁC)a
Crystaliz.
Solvent
Analytical Data (cal./found)b
Comp.
No.
Yield
(%)
Mol. From.
(Mol.wt.)
C
H
N
S
3
4
90
ethanol
108
ethanol
165
ethanol
145
methanol
171
ethanol
185
methanol
101
ethanol
187
methanol
182
ethanol
130
dioxane
117
ethanol
177
ethanol
240
ethanol
192
methanol
280
methanol
160
methanol
154
62
80
68
82
70
67
42
60
30
76
89
45
68
76
34
60
30
32
C25H19N3O4
(425.45)
C17H17N3O S
(311.41)
C17H15N3S
(293.39)
C16H15N5O
(293.34)
C16H13N5
(275.32)
C19H18N2O3S
(354.43)
C19H19N3O3
(337.38)
C17H12N2O2S
(308.36)
C17H13N3O2
(291.31)
C21H18N4O
(342.4)
C21H17N3O S
(359.45)
C21H16N2O3
(344.37)
C21H16N4
(324.39)
C21H15N3S
(341.44)
C21H14N2O2
(326.36)
C21H18N4O
(342.41)
70.58
70.30
65.57
65.80
69.60
69.83
65.51
65.30
69.80
69.63
64.39
64.61
67.64
67.81
66.22
66.50
70.09
70.33
73.66
73.81
70.17
70.40
73.24
73.60
77.76
77.43
73.87
73.63
77.29
77.00
73.66
73.83
71.15
71.35
73.24
73.54
4.50
4.22
5.5
9.88
9.66
13.49
13.65
14.32
14.60
23.88
23.60
25.44
24.13
7.90
10.30
10.51
10.93
10.71
5.71
5.15
5.31
5.15
5.35
4.76
4.95
5.12
5.35
5.68
5.63
3.92
3.63
4.50
4.73
5.3
5.52
4.77
4.44
4.68
4.81
4.97
4.67
4.43
4.73
4.32
4.63
5.20
5.60
4.61
4.83
4.68
4.93
4a
5
5a
6a
6b
7a
7b
8a
8b
8c
9.05
9.30
7.60
12.46
12.30
9.08
10.40
10.23
9.31
14.42
14.75
16.36
16.60
11.69
11.83
8.14
8.92
8.70
8.35
9a
9b
9c
17.27
17.00
12.31
12.53
8.58
9.39
9.14
8.71
10a
10b
10c
16.36
16.02
11.31
11.61
8.14
C22H17N3O3
(371.40)
C21H16N2O3
(344.37)
dioxane
151
methanol
8.39
(continued)

ORDER
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SPIRO 1,5-BENZODIAZEPIN-2-ONES
2527
Table 1. Continued
Analytical Data (cal./found)b
Mol. From.
M.P.(ꢁC)a
Crystaliz.
Solvent
Comp.
No.
Yield
(%)
(Mol.wt.)
C
H
N
S
11
12
260
ethanol
170
ethanol
298
benzene
95
ethanol
275
ethanol
123
methanol
284
ethanol
270
ethanol
258
methanol
120
ethanol
113
ethanol
84
ethanol
104
benzene
138
benzene
132
ethanol
152
dioxane
196
ethanol
45
90
72
52
79
81
63
65
60
84
71
40
63
60
52
92
88
C21H16N2O3
(344.37)
C22H16N2O2
(340.38)
C22H14N2O2Br2
(498.19)
C24H20N4O2
(396.46)
C24H19N3O3
(397.44)
C24H19N3O2S
(413.50)
C24H18N2O3S
(414.49)
C28H20N4O2
(444.50)
C28H19N3O3
(445.48)
C28H19N3O2S
(461.55)
C28H18N2O4
(446.47)
C23H17N5O2S
(427.49)
C21H23N3O
(333.43)
C20H21N3O2
(335.41)
C36H34N6O2
(582.70)
C23H17N3O2S
(399.47)
73.24
73.00
77.63
77.44
53.04
53.30
72.71
72.52
72.53
72.69
69.71
69.92
69.55
69.31
75.66
75.45
75.49
75.31
72.86
72.95
75.33
75.00
64.62
64.31
75.65
75.41
71.62
71.82
74.21
71.52
69.15
69.35
72.49
72.33
4.68
4.90
4.74
4.94
2.83
2.66
5.08
5.30
4.82
4.62
4.63
4.78
4.38
4.75
4.53
4.75
4.30
4.51
4.15
4.35
4.06
4.31
4.01
4.40
6.95
6.75
6.31
6.08
5.88
5.97
4.29
4.00
6.64
6.80
8.14
8.35
8.32
8.45
5.62
5.45
14.13
14.40
10.57
10.79
10.16
10.35
6.76
13
14a
14b
14c
14d
15a
15b
15c
15d
16
7.75
7.90
7.74
7.95
6.81
12.60
12.85
9.43
9.69
9.10
9.35
6.28
6.00
16.38
16.20
12.60
12.82
12.53
12.75
14.42
14.62
10.52
10.69
4.68
6.95
6.61
7.50
7.69
17
18
19
20
8.03
8.30
8.80
8.63
21
C22H24N2O S
(364.51)
7.88
b
aUncorrected; Satisfactory microanalysis obtained C; Æ0.35, H; Æ0.40, N; Æ0.30.
(continued)

ORDER
REPRINTS
2528
ABDEL-GHANY ET AL.
Table 1. Continued
1H-NMR
Com.
No.
IR
(cmꢀ1 c
)
(d, ppm)d
3
3230(NH); 1692,
1672(2CO).
9.60 (s, 1H, NH); 7.90-6.70
(m, 13H, arom.); 4.80
(s, 1H, CH); 3.90-3.40
(m, 4H, 2CH2).
4
3374, 3310,
33205(NH, NH2);
1678(CO).
9.30 (s, 1H, NH); 7.60-6.50
(m, 9H, arom.); 4.80
(s, 1H, CH); 3.60-3.30
(m, 4H, 2CH2);
3.20-2.80 (br, 2H, NH2).
10.30 (s, 1H, NH); 9.70
(s, 1H, NH); 7.80-6.10
(m, 9H, arom); 3.10-2.80
(m, 4H, 2CH2).
4a
3413, 3280(2NH).
5
3383, 3360, 3150, 3300,
3254(3NH, NH2);
1665(CO).
10.55 (s, 1H, NH);
9.85 (s, 1H, NH); 7.70-6.60
(m, 10H, arom. þ NH);
6.25 (s, 2H, NH2);
4.15 (s, 1H, CH).
5a
6a
3415, 3300, 3190,
3120(2NH, NH2).
9.90 (s, 1H, NH); 9.30
(s, 1H, NH); 7.80-6.70
(m, 9H, arom.); 5.80 (s, 2H, NH2).
10.55 (s, 1H, NH); 8.30-7.10
(m, 9H, arom.); 4.70-4.10
(m, 3H, CH þ CH2);
3420(NH); 1724,
1668(2CO).
3.70 (s, 2H, CH2); 1.30-0.80
(t, 3H, CH3).
6b
3340, 3260(2NH);
1720, 1674(2CO).
10.30 (s, 1H, NH); 9.80
(s, 1H, NH); 8.30-6.90
(m, 9H, arom.); 4.50-4.10
(q, 2H, CH2); 3.80 (s, 1H, CH),
3.40 (s, 2H, CH2);
1.40-1.00 (t, 3H, CH3).
10.10 (s, 1H, NH); 7.80-6.30
(m, 9H, arom.); 4.40 (s, 2H, CH2).
10.25 (s, 1H, NH); 9.35 (s, 1H, NH);
8.10-7.10 (m, 9H, arom.);
4.30 (s, 2H, CH2).
7a
7b
3342(NH); 1701(CO).
3321, 3211(2NH),
1711(CO).
(continued)

ORDER
REPRINTS
SPIRO 1,5-BENZODIAZEPIN-2-ONES
Table 1. Continued
2529
Com.
No.
IR
(cmꢀ1 c
1H-NMR
(d, ppm)d
)
8a
3416, 3360, 3259,
3157(NH2);
1686(CO).
10.30 (s, 1H, NH); 9.55
(S, 1H, NH); 8.30-6.90
(m, 13H, arom.); 5.85 (s, 2H, NH2);
3.65 (s, 1H, CH).
8b
8c
9a
3345(NH); 3310,
3200, (NH2); 1686(Co).
10.35 (s, 1H, NH); 9.90-6.30
(m, 13H, arom.); 4.50
(s, 2H, NH2); 3.10 (s, 1H, CH).
10.85 (s, 1H, NH); 8.40-7.10
(m, 13H, arom.); 3.60
(s, 1H, OH); 3.40 (s, 1H, CH).
10.35 (s, 1H, NH); 9.70-9.40
(br, 2H, 2NH); 7.80-6.30
(m, 13H, arom.).
3441(OH); 3320(NH);
1674 (CO).
3417, 3286, 3274(3NH).
9b
9c
3414, 3240(NH2).
3396(NH).
9.90 (s, 1H, NH); 9.15 (s, 1H, NH);
7.80-6.20 (m, 13H, arom.).
10.25 (s, 1H, NH); 8.20-7.10
(m, 13H, arom.).
10a
3424, 3350, 3232,
3120(2NH, NH2);
1691(CO).
10.50 (s, 1H, NH); 9.70
(s, 01H, NH); 8.00-6.80
(m, 13H, arom.);
4.80 (s, 2H, NH2); 3.60
(s, 1H, CH).
10b
3421(OH); 3188,
3140(2NH);
1715, 1685(2CO).
11.45 (s, 1H, OH); 10.30
(s, 1H, NH); 9.20 (s, 1H, NH);
8.20-6.80 (m, 13H, arom.);
3.60 (s, 1H, CH).
10c
11
3410(OH); 3200(NH);
1682(CO).
10.85 (s, 1H, OH); 10.40
(s, 1H, NH); 7.90-6.20
(m, 13H, arom.); 3.40 (s, 1H, CH).
10.75 (s, 1H, OH); 9.75 (s, 1H, NH);
8.10-6.20 (m, 13H, arom.); 3.40
(s, 1H, CH).
3412(OH); 3220(NH);
1684(CO).
12
13
1741, 1674(2CO).
8.60-7.10 (m, 14H, arom.),
6.00 (s, 1H, Ha), 5.60 (s, 1H, Hb).
8.60-7.30 (m, 14H, arom.).
1751, 1695(2CO),
603(C-Br).
(continued)

ORDER
REPRINTS
2530
ABDEL-GHANY ET AL.
Table 1. Continued
Com.
No.
IR
(cmꢀ1 c
1H-NMR
(d, ppm)d
)
14a
3310, 3308(2NH);
1720, 1688(2CO).
9.60-9.30 (br, 2H, 2NH); 8.30-7.10
(m, 14H, arom.); 3.20-2.70
(br, 4H, 2CH2).
14d
15a
15b
15c
1723, 1686(2CO).
8.10-6.40 (m, 14H, arom.); 3.90-3.60
(t, 2H, OCH2). 3.20-2.80 (t, 2H, sCH2).
9.50-9.10 (br, 2H, 2NH);
8.10-7.60 (m, 18H, arom.).
9.70 (s, 1H, NH); 8.30-6.70
(m, 18H, arom.).
3164, 3161(2NH);
1725, 1690(2CO).
3163(NH); 1726,
1697(2CO).
3165(NH); 1727,
1692(2CO).
9.60 (s, 1H, NH); 8.20-6.50
(m, 18H, arom.).
15d
16
1719, 1684(2CO).
3420, 3314,
3210(NH, NH2);
1718, 1684(2CO).
1670(CO).
8.20-6.60 (m, 18H, arom.).
9.30 (S, 1H, NH); 8.20-7.10
(m, 14H, arom.);
6.20 (s, 2H, NH2).
8.60-7.10 (m, 9H, arom); 4.30
(s, 2H, N-CH2-N);
3.70-3.30 (br, 2H, CH);
2.00-1.40 [br, 4H, N(CH2)2];
1.20-0.60 (m, 6H, 3CH2).
8.50-7.10 (m, 9H, arom.); 4.70
(s, 2H, N-CH2-N); 4.25
(s, 2H, CH2); 4.15-3.80
17
18
19
1662(CO).
1670(CO).
[t, 4H, O(CH2)2];
3.40-3.10 [t, 4H, N(CH2)2].
8.70-7.00 (m, 18H, arom.); 4.60
(s, 4H, 2N-CH2-N)
3.45 (s, 4H, 2CH2); 2.05-1.60
[br, 8H, N(CH2)4 N)].
20
21
1666(CO).
1668(CO).
8.10-7.10 (m, 13H, arom.); 4.70
(s, 2H, N-CH2-S); 3.50 (s, 2H, CH2).
8.00-7.50 (m, 4H, arom.); 4.50
(s, 2H, N-CH2-S);
3.50-2.90 (t, 1H, CH), 2.50-1.60
(m, 10H, 5CH2).
cMeasured by Nicolet FT-IR 710 spectrophotometer.
dMeasured by a varian EM 360 L spectrometer at 60 MHzusing TMS as internal
standard and DMSO as a solvent.

ORDER
REPRINTS
SPIRO 1,5-BENZODIAZEPIN-2-ONES
2531
Scheme 2.
Also, compound 1 was subjected to react with formaldehyde and
piperidine, morpholine, piperazine, 2-mercaptobenzoxazole or cyclohexyl-
mercaptane, the corresponding Mannich bases 17–21 were obtained (cf.
Scheme 3, Table 1).
EXPERIMENTAL
Synthesis of 3-bromo-1,3-dihydro-4-phenyl-
1,5-benzodiazepin-2-one 2
To a stirred solution of compound 1 (4.72 g, 0.02 mol) in chloroform
(50 mL), solution of bromine (1.91 mL, 0.02 mol) in chloroform (15 mL) was
added dropwise. Stirring was continued until the evolution of HBr gas

ORDER
REPRINTS
2532
ABDEL-GHANY ET AL.
Figure A.
ceased. The precipitated solid was filtered off and crystallized from chloro-
form (cf. Table 1, Scheme 1).
Synthesis of 4-phenyl-3-substituted-1(H)-1,5 benzodiazepin-2-one
3, 4, 5, 6a,b, 8a-c, 10a-c and 11: (General procedure)
A mixture of anhydrous potassium carbonate (3 g), dry dioxane
(30 mL), compound 2 (0.003 mol), the appropriate reactant (0.003 mol),
namely phthalimidoethanol (0.57 g), cystamine hydrochloride (0.94 g), gua-
nidine hydrochloride (0.28 g), ethyl mercaptoacetate (0.33 g), ethyl glycinate
hydrochloride (0.41 g), o-phenylenediamine (0.32 g), o-aminothiophenol
(0.32 g), catechol (0.33 g), p-phenylenediamine (0.33 g), p-aminobenzoic
acid (0.41 g), hydroquinone (0.33 g) or resorcinol (0.33 g) and a catalytic
amount of tetrabutylammonium bromide [TBAB] (0.003 g) was stirred
over different periods of time at the appropriate temperature (cf. Table 1),
till completion of the reaction (TLC). The reaction mixture was filtered off

ORDER
REPRINTS
SPIRO 1,5-BENZODIAZEPIN-2-ONES
2533
Scheme 3.
and the filtrate evaporated in vacuo. The residue was triturated with pet.
ether (40–60ꢁC) to give a solid crystallized from the appropriate solvent
(cf. Table 1, Scheme 1)
Note: Compound 11 was obtained by dissolving the carbonate in water
(30 mL) followed by acidification and collected by filtration.

ORDER
REPRINTS
2534
ABDEL-GHANY ET AL.
Synthesis of Compounds 4a, 5a, 7a,b, and 9a-c: (General Procedure)
0.005 Mol of compound 4 (1.55 g), 5 (1.64 g), 6a (1.77 g), 6b (1.68 g), 8a
(1.71 g), 8b (1.77 g) or 8c (1.72 g) were dissolved in diphenyl ether (15 mL)
and refluxed for 90 min. After cooling, the reaction mixture was poured into
pet. ether 40–60ꢁC. The separated solid was collected by filtration and crys-
tallized from the suitable solvent (cf. Table 1, Scheme 3).
Synthesis 1-benzoyl-4-phenyl-3(H)-1,5-benzodiazepin-2-one 12
To a stirred solution of compound 1 (4.72 g, 0.02 mol) in dry pyridine
(20 mL), benzoyl chloride (2.32 mL, 0.02 mol) was added dropwise at room
temperature. The stirring was continued for 30 min. and the reaction
mixture was refluxed for 7 hr, poured into ice cold water. The separated
solid was collected by filtration and crystallized from absolute ethanol
(cf. Table 1, Scheme 1).
Synthesis 1-benzoyl-3,3-dibromo-4-phenyl-
1,5-benzodiazepin-2-one 13
To a solution of compound 12 (7.47 g, 0.015 mol) in chloroform
(50 mL), a solution of bromine (2.68 mL, 0.03 mol) in chloroform (25 mL)
was added dropwise during the stirring. The stirring was continued till the
evolution of HBr gas ceased. The precipitated solid was filtered off and
crystallized from chloroform (cf. Table 1, Scheme 2).
Synthesis of Compounds 14a-d, 15a-d and 16: (General Procedure)
A mixture of compound 13 (0.99 g, 0.002 mol), dry dioxane (30 mL),
anhydrous potassium carbonate (3 g), catalytic amount of tetrabutylammo-
nium bromide [TBAB] (0.003 g) was treated with the suitable reactant
(0.002 mol) namely, ethylenediamine (0.13 mL), ethanolamine (0.12 mL),
cystamine hydrochloride (0.22 g), 2-mercaptoethanol (0.41 mL), o-phenyl-
enediamine (0.21 g), o-aminophenol (0.21 g), o-aminothiophenol (0.21 mL),
catechol (0.22 g) or thiosemicarbazide (0.18 g). The reaction mixture was
stirred over different periods of time at the appropriate temperature
(cf. Table 1, Scheme 3), till the completion of the reaction (TLC).The reac-
tion mixture was filtered off and the filtrate evaporated in vacuo. The solid

ORDER
REPRINTS
SPIRO 1,5-BENZODIAZEPIN-2-ONES
2535
residue was washed with water and crystallized from the appropriate solvent
(cf. Table 1, Scheme 1).
Synthesis of Compounds 17–21: (General Procedure)
To a stirred solution of compound 1 (0.003 mol) in dioxane (20 mL),
formaline solution (1 mL) and the suitable reagent (0.003 mol) including,
piperidine (0.3 mL), morpholine (0.26 mL), piprazine (0.12 g, 0.0015 mol),
cyclohexylmercaptane (0.36 mL) or 2-mercaptobenzoxazole (0.45 g) were
added. The reaction mixture was refluxed for 3 hr. The precipitated solid
was filtered off, washed with water and crystallized from the appropriate
solvent (cf. Table 1, Scheme 3).
REFERENCES
1. Guidan, C.; Greiveldinger, F.; Balette, B.; Loppinet, V. Soc. Pharm.
Biol. Lorraine, 1975, 1, 29.
2. Bauer, A.; Weber, K.H.; Dannlberg, F. Ger. Offen. 1974, 2, 306. C.A.
1975, 32, 43312.
3. Nawrocka, W.; Liszkiewicz, H.; Nawojsk, A.; Wilimowski, M.;
Kdzierska-Godzik, L.; Barezyska, J.; Wojew dzki, W.; Du, E.;
Szel, G.A.; Ruthowska, M. Pol. Pharmacol. Pharm. 1991, 43(6), 495.
4. Khan, H.; Bano, Q.; Nizamuddin, J. Agric. Food Chem. 1995, 43(10),
2719.
5. Fray, M.J.; Cooper, K.; Parry, M.J.; Richardsan, K.; Steele, J. J. Med.
Chem. 1995, 38(18), 3514.
6. Nawrocka, W.; Rutkowska, M.; Szelag, A.; Barczynska, J.; Kedzierska-
Gozdzik, L. Acta. Pol. Pharm. 1996, 53(6), 425.
7. Nawocka, W.; Sztuba, B.; Rutkowska, M.; Barczynska, J.; Opolski, A.;
Wietrzyk, J. Acta. Pol. Pharm. 1998, 55(5), 397.
8. Abdel-Ghany, H.; El-Sayed, A.M.; Sultan, A.A.; El-Shafei, A.K. Synth.
Comm. 1990, 20(6), 893.
9. El-Sayed, A.M.; Abdel-Ghany, H.; and El-Saghier, A.M.M. Synth.
Comm. 1999, 29(20), 3561.
Received in the USA November 10, 2000

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