Organic selenium compounds, Part IV: Synthesis and applications of some new diaryl selenides containing azomethine and oxazole moieties

Article abstract of DOI:10.1080/10426500903241747

3,3'-Diacetyloxy (2), 3,3'-dihydroxy (3), 4,4'-diamino (4), and 4-amino (5) diphenylselenide derivatives were prepared as new precursors for the title studies. Compound 6 was obtained by condensation of 4 with an appropriate aromatic aldehyde. Unsymmetrical diphenylselenides 7 and 8 were obtained by condensation of 4 and/or 5 with an aromatic aldehyde. Compound 7 undergoes facile condensation with the same aldehyde present in its arylidene moiety to yield 6, while condensation with another different aromatic aldehyde yielded unsymmetrical 4-arylideneamino diphenylselenide derivative 9. Oxidation of 6, 8, and 9 using lead tetra acetate and/or N-bromosuccinimide yielded symmetrical bis-(2-aryl benzoxazol-6-yl) (10), unsymmetrical 3'-hydroxy, 2-aryl benzoxazol-6-yl selenides (11), and 2-aryl benzoxazol-6-yl, 2'-aryl' benzoxazol-6'-yl selenide derivatives (12), respectively. Compound 10 was prepared in one-pot unequivocal synthesis by fusion of 4 with the appropriate aromatic aldehyde, while 12 was prepared by fusion of 4 with two different aromatic aldehydes. In certain cases, 6 and 9 were heated on a direct flame until complete homogeneity afforded the corresponding 10 and 12. The structures of the synthesized compounds are based on physical data, IR, 1H NMR, 13C NMR, chemical means, and mass spectral data. Some of the synthesized compounds were biologically tested. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903241747

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Organic Selenium Compounds, Part IV:
Synthesis and Applications of Some New
Diaryl Selenides Containing Azomethine
and Oxazole Moieties
M. A. Abbady a , M. M. Kandeel a , Sh. H. Abdel-Hafez a & M.-A. M.
Abou-Omar a
a Chemistry Department, Faculty of Science, Assiut University,
Assiut, Egypt
Version of record first published: 02 Aug 2010.
To cite this article: M. A. Abbady , M. M. Kandeel , Sh. H. Abdel-Hafez & M.-A. M. Abou-Omar (2010):
Organic Selenium Compounds, Part IV: Synthesis and Applications of Some New Diaryl Selenides
Containing Azomethine and Oxazole Moieties, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:8, 1708-1725
To link to this article: http://dx.doi.org/10.1080/10426500903241747
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Phosphorus, Sulfur, and Silicon, 185:1708–1725, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903241747
ORGANIC SELENIUM COMPOUNDS, PART IV:
SYNTHESIS AND APPLICATIONS OF SOME NEW DIARYL
SELENIDES CONTAINING AZOMETHINE
AND OXAZOLE MOIETIES
M. A. Abbady, M. M. Kandeel, Sh. H. Abdel-Hafez,
and M.-A. M. Abou-Omar
Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
3,3ꢀ-Diacetyloxy (2), 3,3ꢀ-dihydroxy (3), 4,4ꢀ-diamino (4), and 4-amino (5) diphenylselenide
derivatives were prepared as new precursors for the title studies. Compound 6 was obtained by
condensation of 4 with an appropriate aromatic aldehyde. Unsymmetrical diphenylselenides
7 and 8 were obtained by condensation of 4 and/or 5 with an aromatic aldehyde. Compound
7 undergoes facile condensation with the same aldehyde present in its arylidene moiety to
yield 6, while condensation with another different aromatic aldehyde yielded unsymmetrical
4-arylideneamino diphenylselenide derivative 9. Oxidation of 6, 8, and 9 using lead tetra
acetate and/or N-bromosuccinimide yielded symmetrical bis-(2-aryl benzoxazol-6-yl) (10),
unsymmetrical 3ꢀ-hydroxy, 2-aryl benzoxazol-6-yl selenides (11), and 2-aryl benzoxazol-6-yl,
2ꢀ-arylꢀ benzoxazol-6ꢀ-yl selenide derivatives (12), respectively. Compound 10 was prepared
in one-pot unequivocal synthesis by fusion of 4 with the appropriate aromatic aldehyde, while
12 was prepared by fusion of 4 with two different aromatic aldehydes. In certain cases, 6
and 9 were heated on a direct flame until complete homogeneity afforded the corresponding
10 and 12. The structures of the synthesized compounds are based on physical data, IR,
1H NMR, 13C NMR, chemical means, and mass spectral data. Some of the synthesized
compounds were biologically tested.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Azomethines; diarylselenides; organic selenium compounds; oxazoles
INTRODUCTION
Organoselenium compounds have been found to function as antioxidants, enzyme in-
hibitors, and anti-tumor and anti-infective agents.1 Moreover, introduction of selenium into
organic compounds often permits modification of their chemical properties and biological
activities.2,3 On the other hand, oxazole moieties are widely used as solutes in liquid scintil-
lators,4–6 pharmaceuticals,7–9 and photography.10,11 In view of these reported applications
and in continuation of our interest in the chemistry of diarylsulfides, -sulfones, -oxides,
Received 24 May 2009; accepted 4 August 2009.
Address correspondence to M. A. Abbady, Chemistry Department, Faculty of Science, Assiut University,
P.O. Pox 71516, Assiut, Egypt. E-mail: maabbady@aun.edu.eg
1708

ORGANIC SELENIUM COMPOUNDS, PART IV
1709
-selenides, and -selenones containing different heterocyclic and other organic moieties,12–19
we report in this article a study on the synthesis of some new diarylselenides containing
azomethine and oxazole moieties, and we also investigated their biological activities.
RESULTS AND DISCUSSION
In this article, we describe the synthetic studies of a series of hitherto unreported
diarylselenides containing azomethine and oxazole moieties. The starting compound of
the forthcoming synthesis and studies is the reported 4-chloro-2-hydroxy nitrobenzene
(1a), which was prepared according to our modified procedure by diazotization of m-
chloroaniline (1) in the presence of excess conc. HNO3 (68%). The nitro diazonium salt
formed in situ was steam distilled to produce 1a. Attempt to condense 2 moles of 1a
with K2Se in refluxing absolute ethanol via condensation using bimolecular nucleophilic
aromatic substitution reaction (nucleophiles: KSe− and/or ArSe−) depending on the effect
of NO2 group to produce the expected 3,3ꢁ-dihydroxy-4,4ꢁ-dinitro diphenylselenide (3)
has failed, whereby an unidentified resinous substance was formed. The formed resinous
substance is probably due to the fact that two reactive sites are present in 1a ( OH and
Cl) and are ready to react with K2Se. We thought to protect the ( OH) group in 1a
by acetylation to produce 2-acetyloxy-4-chloro nitrobenzene 1b. Two moles of 1b were
smoothly condensed with 1 mole of K2Se in refluxing absolute ethanol. The condensation
product was thoroughly investigated, and it was proven that it is a mixture of the following
three substances: elemental selenium, 3,3ꢁ-diacetyloxy-4,4ꢁ-dinitro diphenylselenide (2),
and 3,3ꢁ-dihydroxy-4,4ꢁ-dinitro diphenylselenide (3). The formed three substances were
easily isolated separately by means of fractional crystallization and recrystallization to
form pure, well-defined compounds. Compound 2 was also obtained by acetylation of 3
(Scheme 1).
3,3ꢁ-Diacetyloxy-4,4ꢁ-dinitro diphenylselenide (2) was treated with 20% NaOH fol-
lowed by neutralization with H2SO4 to give 3,3ꢁ-dihydroxy-4,4ꢁ-dinitro diphenylselenide
(3) in nearly quantitative yield. Reduction of 3 using sodium dithionite (8.0–10.0 mol) in the
presence of ammonium hydroxide (33%) yielded 4,4ꢁ-diamino-3,3ꢁ-dihydroxy diphenylse-
lenide (4), while its partial reduction using sodium dithionite (3.0 mol) in the presence of
ammonium hydroxide (33%) furnished 4-amino-4ꢁnitro-3,3ꢁ-dihydroxy diphenylselenide
(5).
Compound (4) was condensed with 4 moles of aromatic aldehydes in absolute ethanol
and in the presence of a catalytic amount of dry piperidine that gave symmetrical se-
lenides in the form of a new bis-azomethines namely, 4,4ꢁ-di arylideneamino-3,3ꢁ-dihydroxy
diphenylselenides (6). When 4 was condensed with 1 mole of aromatic aldehyde in absolute
ethanol and in the presence of the same catalyst, mono-azomethines were obtained, namely
4ꢁ-amino-4-arylideneamino-3,3ꢁ-dihydroxy diphenylselenides (7). Compounds 6a–d were
obtained by another unequivocal synthetic route (stepwise); this was carried out by con-
densation of compound 7 with 1 mole of aromatic aldehyde (the same aromatic aldehyde
present in arylidene moiety in 7), using the same previously mentioned conditions to yield
6a–d. The obtainable 6a–d by two different routes are identical (mp, mixed mp, physical
and spectral data).
Condensation of 7 with another different aromatic aldehyde (not present in arylidene
moiety in 7) using the same conditions and procedure gave unsymmetrical selenides

1710
M. A. ABBADY ET AL.
_
_
_
_
NH2
N+ NNO3
OH
O2N
O2N
1a
moles of
K2Se
2
Excess conc. HNO3
Steam distill.
NaNO2 / H2O
Cooling
Cl
Cl
Cl
_
Abs. ethanol
1
(
)
( 1 )
a
OCOCH3
Cl
O2N
(CH3CO)2O
Unidentified substance
( 1
)
b
mole of
K2Se
2
1
b
Abs. ethanol
O2N
NO2
OCOCH3
O2N
HO
NO2
OH
Se
+
+
H3COCO
Se
Se
2
( )
( 3 )
Acetylation
-
% NaOH
i
20
- Neutralization,
ii
H2SO4
H2N
HO
NH2
OH
moles of
8 - 10
Na2S2O4
NH4OH
Se
4
( )
O2N
HO
NH2
OH
moles of Na S O
4
3
2
2
NH4OH
Se
( 5 )
Scheme 1
namely, 4-arylideneamino-4ꢁ-arylideneꢁamino-3,3ꢁ-dihydroxy diphenylselenides (9a–c)
(Scheme 2).
Attempts to obtain 9 by condensation of 4 with two different aromatic aldehydes
spontaneously, using the solvent method as previously discussed, have failed and gave
undefined substances. These results may be attributed to the variation of the reactivity
of each reacted aldehyde toward the applied reactions, and this fact is under our further
consideration. Condensation of 5 with aromatic aldehydes in the presence of piperidine
and absolute ethanol furnished the expected aldimines, namely 4-arylideneamino-4ꢁ-nitro-
3,3ꢁ-dihydroxy diphenylselenides (8a–c). The structures of the prepared compounds 1b–5
and 6–9 were established on the basis of elemental analyses, IR, NMR, chemical means,
and mass spectral data (see the Experimental section).
Oxidation of bis-aldimines (6) using lead tetra acetate (LTA)20 and/or N-bromo
succinimide (NBS)21 in refluxing dry benzene or glacial acetic acid for 20 min, as a

ORGANIC SELENIUM COMPOUNDS, PART IV
1711
Piperidine
HC=N
HO
N=CH
OH
4
( )
ArCHO
(2 - 3 moles)
R
+
R
Abs. ethanol
Se
(
)
6
a ;
R = H
b ; R = N(CH3)2
c ;
a - d
R = Cl
d ; R = Br
Piperidine
Abs. ethanol
ArCHO(1 mole)
H2N
HO
N=CH
OH
R
(1 mole)
ArCHO
Piperidine
Abs. ethanol
Se
(
)
7
Piperidine
Abs. ethanol
Ar CHO(1 mole)
ArCHO(1 mole)
Ar CHO
HC=N
N=CH
OH
a ;
R
R
(1 mole)
Piperidine
Abs. ethanol
HO
Se
(
)
9
R = H,
R = H,
= OCH3
= NO2
R
R
a - c
b ;
c ;
R = NO2
,
= OCH
R
3
O2N
HO
N=CH
OH
R
Piperidine
ArCHO (1 mole)
+
( 5 )
Abs. ethanol
Se
(
)
a ;
8
R = H
a - c
b ; R = NO2
c ;
R = OCH3
Scheme 2
result of dehydrogenation and ring closure, furnished the expected symmetrical bis-(2-aryl
benzoxazol-6-yl) selenides (10).
Another route to synthesize 10 was accomplished by fusion of 4 with 4 moles of
aromatic aldehydes and/or by melting 6 for 2 min. The oxazoles (10) obtained by three
different routes (Scheme 3) are identical (mp, mixed mp, spectral data, and chemical
means).
Unsymmetrical diarylselenides of type 11 were obtained by oxidation of 8 using LTA
and/or NBS in refluxing dry benzene or glacial acetic acid and furnished the unsymmet-
rical diarylselenides namely, 3ꢁ-hydroxy-4ꢁ-nitrophenyl, 2-aryl benzoxazol-6-yl selenides
(11a–c) in moderate yields.
Attempts to obtain 11 by direct fusion of 5 with the corresponding aromatic aldehyde
and/or by melting 8 for 2 min were unsuccessful, and only unidentifiable substances were
produced.

1712
M. A. ABBADY ET AL.
Melting for (1-2) min.
or
LTA NBS
6
( )
( 6 )
Dry benzene
Reflux for 20 min.
a ;
b ;
c ;
R = H
N
O
N
O
R = N(CH3)2
R = Cl
R
R
Se
d ; R = Br
(
)
10
a - d
moles
4
ArCHO
4
( )
Fusion
Melting for (1-2) min.
or
LTA NBS
9
( )
9
( )
Dry benzene
Reflux for 20 min.
a ;
b ;
c ;
R = H ,
= OCH3
= NO2
R
R
N
O
N
O
R
R
R = H ,
Se
R = NO ,
= OCH3
R
2
(
)
12
a - c
,
,
ArCHO Ar CHO
ArCHO Ar CHO
( 4 )
( 4 )
,
Piperidine Abs. ethanol
Fusion
a ;
R = H
O2N
HO
N
O
or
LTA NBS
( 8 )
R
b ;
c ;
R = NO2
R = OCH3
Dry benzene
Se
Reflux for 15 min.
(
)
11
a - c
Melting for (1-2) min.
ArCHO
Fusion
( 8 )
( 5 )
Scheme 3
It should be pointed out that 3ꢁ-hydroxy-4ꢁ-nitrophenyl, 2-(p-nitrophenyl)
benzoxazol-6-yl selenide (11b) was obtained by interaction of 5 with p-nitro benzaldehyde
in refluxing n-butanol, in the presence of dry piperidine as a basic catalyst for 5 h, then
the reaction mixture was left overnight in an open container. Repeating this procedure
using other aldehydes free from electron-withdrawing groups, such a nitro group, was
unsuccessful. Here the nitro group exerts influence, depending on its catalyzation role of
oxidation by removing the needed azomethine hydrogen to the ring closure of the formed in
situ aldimine (8b) to the corresponding oxazole (11b) with access to air oxidation (oxygen
atom behaves as a free biradical).22 It is believed that, this reaction proceeds via a free
radical mechanism. The presence of a nitro group considerably increases the probability of
delocalization of the cloud of the odd electron of the free radical that is developed on the

ORGANIC SELENIUM COMPOUNDS, PART IV
1713
(5 )
OHC
+
NO2
Reflux Piperidine
n-butanol
(4-5) hrs.
O2N
HO
NO2
N=CH
Se
OH
( not isolated )
)
(
8
b
O
.
N
+
O2N
N=C
O
_
.
.
O
O
Se
(
)
8
bi
.
O
N
+
O2N
N=C
O
_
.
.
O
Se
O
.
(
)
3 H
+
8
bii
O2N
HO
N
O
NO2
Se
(
)
11
b
.
.
.
:
2 H
+
O
H2O
+
3-O
H
3-OH
Scheme 4
azomethine linkage; the latter has become more stable through its contributing resonance
structures 8bi and 8bii (Scheme 4).
Another type of unsymmetrical oxazole, namely 2-aryl benzoxazol-6-yl, 2ꢁ-arylꢁ
benzoxazol-6ꢁ-yl selenides (12), was obtained by oxidation of 9a–c under refluxing dry
benzene using LTA and/or NBS for 20 min. Moreover two additional different routes to
synthesize 12 were carried out. The first one was accomplished by fusion of 4 with a mixture
of two different aromatic aldehydes (1.5 mol of each) for 3 min. The second route was carried
out by melting 9 for 3 min. The obtainable oxazoles (12) by the last three different routes
(Scheme 3) are identical (mp, mixed mp, and spectral data). The prepared oxazoles 10–12
as expected are characterized by lower λmax. than that their corresponding aldimines; this

1714
M. A. ABBADY ET AL.
behavior is apparently attributed to the absence of an azomethine chromophore in 10–12 as
a result of the previously mentioned oxidation, which must be described as a hypsochromic
reaction under the given conditions (representative examples given below).
The formed oxazoles (10–12) are highly crystalline compounds with sharp melting
points, and gave a pink-red colors in conc. H2SO4, while compound 10b gave a blue color,
which could be interpreted via inspection of the charged contributing resonance structure
of 10b),23 as follows (Scheme 5).
N
O
N
( C H 3 )2 N
N ( C H 3 )2
O
S e
1 0
(
)
b
2 H 2 S O 4
H
N
H
N
+
+
( C H 3 )2 N
N ( C H 3 )2
O
O
S e
_
(L U M O )
2 H S O 4
H
N
H
N
+
+
( C H 3 )2 N
N ( C H 3 )2
O
O
S e
_
1 0
(
)
(H O M O )
b -A
2 H S O 4
o r
H
N
+
N
O
( C H 3 )2 N
N ( C H 3 )2
O
S e
+
H
_
(L U M O )
2 H S O 4
H
N
+
+
N
O
( C H 3 )2 N
N ( C H 3 )2
O
S e
H
_
1 0
(H O M O )
)
(
(B lu e co lo u r)
b -B
2 H S O 4
Scheme 5
Structure 10b-B has been suggested, depending on the capability of aromatic selenide
linkage to form selenonium compounds, in the form of bisulfate salt.
It is worth noting that the oxidation of 6 and 9 to the corresponding 10 and 12
was achieved without any accompanying any side reactions or process (for example see
Figure 1). In some cases, the previously used oxidation of 6, 8, and 9 to 10–12 proceeded
near quantitatively; this was proven by using spectral means as follows.
A solution of 2 × 10−4 g/mol of 6d in dry benzene was prepared, and the equivalent
amount of NBS was added to this solution, which was refluxed for 20 min. The mixture was

ORGANIC SELENIUM COMPOUNDS, PART IV
1715
6
4
2
0
( 1 )
( 2 )
( 3 )
400
500
600
700
800
900
Wave Length (nm)
Figure 1 The UV-visible spectrum of compounds 6d and 10d. (1) Schiff’s base 6d; (2) the generated in situ
oxazole 10d; (3) separately prepared oxazole 10d.
cooled, and then its UV-visible spectrum was measured. In fact, at the end of oxidation,
this mixture represents a solution of 2 × 10−4 g/mol of the generated in situ oxazole
(10d). Another solution of 2 × 10−4 g/mol of already synthesized oxazole (10d) by a
separate procedure (see the Experimental section) was prepared in the same solvent, and
its UV-visible spectrum was carried out. By comparison between the two spectra, we
observed that both spectra coincided completely on each other. The obtainable result was
chemical evidence to prove that the above oxidation in the given example proceeded nearly
quantitatively.
The structures of the prepared compounds 10–12 were established by elemental
analysis, IR, NMR, and mass spectral data (see the Experimental section).
Antimicrobial Activities
The results obtained from the antimicrobial screening of some newel synthesized
compounds (6b, 6c, 7a, 8a, 9a, 10b, 10c, 11a, 12a, and 12b) against representatives of
bacteria and fungi are listed in Table S1 (Supplemental Materials, available online).
EXPERIMENTAL
Measurements
The times required for the completion of the reactions and the purity of the prepared
compounds was monitored by thin layer chromatography (TLC). Melting points were
determined on a Gallenkamp Melting Point apparatus with a digital thermometer type
MFB-595–010M and are uncorrected. The elemental analyses were performed on a Perkin-
Elmer 240 C elemental analyzer and a GmbH VAR IDEL V2.3 elemental Analysis System
in CHNS Mode. IR Spectra were measured on an IR-470 spectrophotometer (Shimadzu)

1716
M. A. ABBADY ET AL.
using a KBr wafer technique. 1H NMR spectra were recorded on INM-A (400 MHz) NMR
spectrophotometer using the appropriate deuterated solvent and TMS as an internal standard
(chemical shifts expressed in δ ppm). Mass spectra were recorded on a JEOL JMS-600
mass spectrometer.
4-Chloro-2-hydroxy Nitrobenzene (1a)
This compound was prepared according to the method given in the literature,24 with
some modification in which the mother-liquor of the desired compound was successively
extracted by chloroform, and the collected extracts were evaporated under vacuum to small
volume, cooled, filtered, and crystallized from commercial ethanol, mp 38◦C, in literature
41◦C; yield 26%. (This modified procedure leads an increase in the yield by 10%).
2-Acetyloxy-4-chloro Nitrobenzene (1b)
A solution of 4-chloro-2-hydroxy nitrobenzene (1a) (10 g, 0.057 mol) in acetic
anhydride (35 mL, 0.370 mol) was refluxed for 45 min. The solution was poured in cold
water (150 mL) with vigorous stirring, and was kept in the refrigerator overnight, in which
the present oil solidifies. The product was filtered off and crystallized from petroleum ether
(60–80◦C), mp 44◦C; yield 85%.
IR: 3100 cm−1 (Ar C H), 2950, 2850 cm−1 (CH3), 1665 cm−1 (C O), 1520,
1335 cm−1 (NO2), 1178 cm−1 (Ar O). 1H NMR in CDCl3: at δ 2.35 (s, 3H, OCOCH3),
δ 7.30–8.25 (Ar H). Anal. Calc. for C8H6ClNO4 (215.59) (%): C, 44.57; H, 2.80; N, 6.49;
Cl, 16.44; Found (%): C, 44.32; H, 3.02; N, 6.84; Cl, 16.08.
3,3ꢀ-Diacetyloxy-4,4ꢀ-dinitro Diphenylselenide (2)
To a solution of 2-acetyloxy-4-chloro nitrobenzene (1b) (12 g, 0.055 mol) in absolute
ethanol (180 mL), potassium selenide (7.2 g, 0.045 mol) was added, which was prepared
by fusion of a mixture of metallic selenium (3.65 g) and potassium hydroxide (5.19 g)
in an oil bath for 2 h at 140◦C. Then the mixture was boiled under reflux with stirring
for 7 h. The precipitate which formed upon cooling (which also contains the unreacted
selenium) was filtered off, dried, and dissolved by heating in aqueous ethanol. The solution
was filtered, which separated about 2.42 g of metallic selenium, which was quite suitable
for repeat preparations. After that the solvent was evaporated, and the dihydroxy compound
(3) (3.50 g) was obtained. The mother-liquor of the reaction, which contained the desired
diacetyloxy compound (2), was distilled off, and the formed crude product was crystallized
from abs. ethanol, mp > 300◦C decomp.; yield (83%).
IR: 3080 cm−1 (Ar. C H), 2900 cm−1 (CH3), 1690 cm−1 (C O), 1540,1325 cm−1
1
(NO2), 1150 cm−1 (Ar O), 738, 685 cm−1 (Ar Se Ar). H NMR in DMSO: at δ 2.35
(s, 3H, OCOCH3), δ 6.60–8.20 (Ar H). Anal. Calc. for C16H12N2O8Se (439.24) (%): C,
43.75; H, 2.75; N, 6.37; Found (%): C, 43.98; H, 2.88; N, 6.24.
3,3ꢀ-Dihydroxy-4,4ꢀ-dinitro Diphenylselenide (3)
Diacetyloxy compound 2 (10 g, 0.022 mol) was boiled with a solution of sodium
hydroxide (30 g) in distilled water (150 mL) for 1.5 h. Dilute sulfuric acid was added
with stirring to the cold alkaline solution, until the solution was acidic to litmus paper.
The crude product was filtered off and recrystallized from ethanol, mp (> 300)◦C decomp;
yield (68%).

ORGANIC SELENIUM COMPOUNDS, PART IV
1717
IR: 3450 cm−1 (OH), 3080 cm−1 (Ar H str.), 1530, 1320 cm−1 (NO2), 1150 cm−1
(Ar O), 738, 685 cm−1 (Ar Se Ar). 1H NMR in DMSO: at δ 5.88–7.63 (the Ar. protons
at the Ar Se Ar moiety), δ 8.67 (s, 2H, OH). MS: 355 (M+, 4%), 172 (20%), 142 (19%),
62 (25%), 43 (100%). Anal. Calc. for C12H8N2O6Se (355.16) (%): C, 40.58; H, 2.27; N,
7.88; Found C, 40.76; H, 2.45; N, 7.72.
4,4ꢀ-Diamino-3,3ꢀ-dihydroxy Diphenylselenide (4)
To a heated solution of 3,3ꢁ-dihydroxy-4,4ꢁ-dinitro diphenylselenide (3) (5 g,
0.014 mol) in distilled water (75 mL) and concentrated ammonium hydroxide solution
(20 mL), a solution of sodium dithionite (24.5 g, 0.14 mol) in distilled water (about 300
mL) was added in three portions. The deep red color of the solution changed to a pale
yellow. The whole reaction mixture (unfiltered) was extracted several times with ether.
The extracts were collected, dried over anhydrous sodium sulfate, and evaporated, which
furnished a brown product, which by crystallization from absolute ethanol yielded brown
crystals, mp 150–152◦C; yield (60%).
IR: 3450,3300 cm−1 (NH2), 2550–3200 cm−1 (OH), 1140 cm−1 (Ar O), 752,
1
700 cm−1 (Ar Se Ar). H NMR in DMSO: δ 4.62 (s, 4H, 2NH2), δ 6.34–6.84 (the
Ar. protons at the Ar Se Ar moiety), δ 9.47 (s, 2H, OH). MS: 296 (M+, 25%), 142
(89%), 79 (100%), 62 (52%). Anal. Calc. for C12H12N2O2Se (295.20) (%): C, 48.82; H,
4.09; N, 9.49; Found (%): C, 49.12; H, 3.86; N, 9.68.
4-Amino-4ꢀ-nitro-3,3ꢀdihydroxy Diphenylselenide (5)
To a heated solution of 3,3ꢁ-dihydroxy-4,4ꢁ-dinitro diphenylselenide (3) (2 g,
0.0056 mol) in distilled water (30 mL) and concentrated ammonium hydroxide solution (8
mL), a solution of sodium dithionite (2.940 g, 0.0168 mol) in distilled water (35 mL) was
added in three portions. The deep red color of the solution changed to orange. The whole
reaction mixture (unfiltered) was extracted several times with ether. The extracts were
collected, dried over anhydrous sodium sulfate, and evaporated to small volume, whereby
brown crystals were separated and recrystallized from absolute ethanol, mp 122◦C, yield
40%.
IR: 3300, 3380 cm−1 (NH2), 2550–3050 cm−1 (OH), 1500, 1330 cm−1 (NO2) and
1
710 cm−1 (Ar Se Arꢁ). H NMR in DMSO: δ 4.60 (s, 2H, NH2), δ 6.0–7.40 (the Ar.
protons at the Ar Se Arꢁ moiety), δ 9.15 (s, 2H, OH). Anal. Calc. for C12H10N2O4Se
(325.18) (%): C, 44.32; H, 3.09; N, 8.61; Found (%): C, 44.71; H, 3.28; N, 8.92.
Symmetrical 4,4ꢀ-Diarylideneamino-3,3ꢀ-dihydroxy Diphenylselenides
(6a–d)
Method A. A mixture of 4,4ꢁ-diamino-3,3ꢁ-dihydroxy diphenyl selenide (4) (1.0 g,
0.0033 mol), the appropriate aromatic aldehyde (0.0070 mol), and dry piperidine [2–3
drops in absolute ethanol (30 mL)] was heated under reflux for 5 h, evaporated to a small
volume, and cooled, and the precipitate that formed was collected and washed with cold
ethanol (10 mL). The crude product was crystallized from the proper solvent; the results
are listed in Table I.

1718

1719

1720

1721

1722
M. A. ABBADY ET AL.
4ꢀ-Amino-4-arylideneamino-3,3ꢀ-dihydroxy Diphenylselenides (7)
A mixture of 4,4ꢁ-diamino-3,3ꢁ-dihydroxy diphenyl selenide (4) (1.0 g, 0.0033 mol),
the appropriate aromatic aldehyde (0.0033 mol), and dry piperidine [2–3 drops in absolute
ethanol (30 mL)] was heated under reflux for 5 h, evaporated to a small volume, and cooled,
and the formed precipitate was collected and washed with cold ethanol (15 mL). The crude
product was crystallized from the proper solvent; the results are listed in Table I.
Symmetrical 4,4ꢀ-diarylideneamino-3,3ꢀ-dihydroxy Diphenylselenides
(6a–d)
Method B. A mixture of 4ꢁ-amino-4-arylideneamino-3,3ꢁ-dihydroxy diphenylse-
lenide (7) (0.0026 mol), an aromatic aldehyde (the same aldehyde present in the arylidene
moiety of 7) (0.0026 mol), and dry piperidine [2–3 drops in absolute ethanol (30 mL)] was
refluxed for 5 h, evaporated to a small volume, and cooled, and the formed precipitate was
collected and washed with cold ethanol (10 mL). The crude product was crystallized from
the proper solvent; the results are listed in Table I.
Unsymmetrical 4-Arylideneamino-4ꢀ-arylideneꢀamino-3,3ꢀ-dihydroxy
Diphenyl Selenides (9a–c)
A mixture of 4ꢁ-amino-4-arylideneamino-3,3ꢁ-dihydroxy diphenylselenide (7)
(0.0026 mol), different aromatic aldehydes (not present in the arylidene moiety in 7a–c)
(0.0026 mol), and dry piperidine [2–3 drops in absolute ethanol (30 mL)] was refluxed for
5 h, evaporated to a small volume, and cooled, and the formed precipitate was collected
and washed with cold ethanol (15 mL). The crude product was crystallized from the proper
solvent; the results are listed in Table I.
4-Arylideneamino-4ꢀ-nitro-3,3ꢀ-dihydroxy Diphenylselenides (8a–c)
A mixture of 4-amino-4ꢁ-nitro-3,3ꢁ-dihydroxy diphenylselenide (5) (1.0 g, 0.0030
mol), the appropriate aromatic aldehyde (0.0040 mol), and dry piperidine (2–3 drops) in
absolute ethanol (30 mL) was heated under reflux for 5 h, evaporated to a small volume,
and cooled, and the formed product was collected, washed with ethanol (20 mL), and
crystallized from absolute ethanol. The results are given in Table I.
Symmetrical Bis-(2-aryl benzoxazol-6-yl) Selenides (10a–d)
Method A. A mixture of symmetrical Schiff’s base 4,4ꢁ-di-arylideneamino-3,3ꢁ-
dihydroxy diphenylselenides (6a–d) (0.0020 mol) and LTA (0.0070 mol) in dry benzene
(40 mL) was refluxed for 15 min. The reaction mixture was allowed to stand for 1 h at room
temperature, then the separated solid was filtered and washed with water, and the crude
product was crystallized from the proper solvent. The results are listed in Table I.
Method B: Fusion method. A mixture of 4,4ꢁ-diamino-3,3ꢁ-dihydroxy
diphenylselenide (4) (1.0 g, 0.0033 mol) and equimolar quantities of two identical aromatic
aldehydes (0.0040 mol of each aldehyde) were mixed thoroughly and heated for 4 min
on direct flame until complete homogeneity of the reaction mixture was achieved. The
reaction was dried in a current of air, and the viscous residue was triturated with absolute

ORGANIC SELENIUM COMPOUNDS, PART IV
1723
ethanol, then concentrated and cooled. The deposited crystalline product was collected
and recrystallized from absolute ethanol. The results are listed in Table I.
Method C: Melting method. Symmetrical Schiff’s base 4,4ꢁ-di-arylideneamino-
3,3ꢁ-dihydroxy diphenylselenides (6a–d) (0.0020 mol) was melted in a dry porcelain cru-
cible on a direct flame and in the presence of a current of air. The formed solid product
was dissolved in absolute ethanol and evaporated to small volume and cooled Then the
deposited crystalline product was collected and crystallized from the proper solvent (see
Table I).
Unsymmetrical 3ꢀ-Hydroxy-4ꢀ-nitrophenyl, 2-Aryl Benzoxazol-6-yl
Selenides (11a–c)
A mixture of Schiff’s base 4-arylideneamino-4ꢁ-nitro-3,3ꢁ-dihydroxy diphenylse-
lenides (8a–c) (0.0025 mol) and LTA (0.0040 mol) in dry benzene (40 mL) was refluxed
for 15 min. The reaction mixture was allowed to stand for 1 h at room temperature, then the
separated solid was filtered and washed with water, and the crude product was crystallized
from the proper solvent. The results are listed in Table I.
Application of methods B and C for the preparation of 10a-d to produce 11a–c failed.
3ꢀ-Hydroxy-4ꢀ-nitrophenyl, 2-(p-Nitrophenyl) Benzoxazol-6-yl Selenide
(11b)
A mixture of 4-amino-4ꢁ-nitro-3,3ꢁ-dihydroxy diphenylselenide (5) (1.0 g, 0.0030
mol), p-nitrobenzaldehyde (0.6 g, 0.0040 mol), and dry piperidine (2–3 drops) in n-butanol
(30 mL) was refluxed for 5 h on an oil bath. Then the mixture was cooled, and the product
was collected and washed thoroughly with water, and the crude product was crystallized
from absolute ethanol. The results are given in Table I. When the same method was carried
out with other aromatic aldehydes, e.g., C6H5CHO and p-C6H4-OCH3, no product was
formed.
Unsymmetrical 2-Aryl Benzoxazol-6-yl, 2ꢀ-Arylꢀ Benzoxazol-6ꢀ-yl
Selenides (12a–c)
Method A. Unsymmetrical Schiff’s base 4-arylideneamino-4ꢁ-arylideneꢁamino-
3,3ꢁ-dihydroxy diphenylselenides (9a–c) (0.0020 mol) and NBS (0.0070 mol) in dry ben-
zene (40 mL) were refluxed for 15 min. The reaction mixture was allowed to stand for 1
h at room temperature. Then the deposited product was filtered and washed with water,
crystallized, and recrystallized as usual. The results are given in Table I.
Method B: Fusion method. 4,4ꢁ-Diamino-3,3ꢁ-dihydroxy diphenylselenide (4)
(1.0 g, 0.0033 mol) and equimolar quantities of two different aromatic aldehydes (0.0040
mol of each) where mixed thoroughly and heated for 4 min on direct flame until complete
homogeneity of the reaction mixture was achieved. The reaction was dried in a current of
air. The viscous residue was triturated with absolute ethanol, then concentrated and cooled.
The deposited crystalline product was collected and recrystallized from absolute ethanol.
The results are listed in Table I.
It must be noted that repeating this method using the solvent method was unsuccessful,
apparently due to the difference of the reactivity of each aldehyde under the applied
conditions.

1724
M. A. ABBADY ET AL.
Method C: Melting method. Unsymmetrical Schiff’s base 4-arylideneamino-
4ꢁ-arylidene amino-3,3ꢁ-dihydroxy diphenylselenides (9a–c) (0.0020 mol) were melted in
a dry porcelain crucible on direct flame and in the presence of a current of air with stirring.
The formed solid product was dissolved in absolute ethanol, evaporated to a small volume,
and cooled. Then the deposited crystalline product was collected and crystallized from the
proper solvent; see Table I.
Note: The o-amino compounds formed during this investigation should be used
momentarily for the subsequent chemical reactions in order to avoid their partial oxidation
by atmospheric oxygen.
Preparation of Solvents for Spectral Measurements
The solvent of an oxidation reaction of selected Schiff’s bases to corresponding
oxazoles must possesses a wide range of solubility to dissolve all the ingredients present
and generated in the reaction mixture, without formation of any turbidity or precipitates
during the whole reaction time. Factors, such as spectral purity, volume, and quantity of
selected solvents, besides the concentrations of the solutes, must be taken in consideration.
Antibacterial and Antifungal Screening
Biological screening of some prepared compounds was carried out to evaluate their
antibacterial properties. Preliminary screening of the tested compounds against different
strains of both Gram-positive and Gram-negative bacteria and fungi were determined using
the agar diffusion technique.25 (See the Supplemental Materials.)
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