Antimicrobial activities of some synthesized pyridines, oxazines and thiazoles from 3-aryl-1-(2-naphthyl)prop-2-en-1-ones

Article abstract of DOI:10.3797/scipharm.0804-09

3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which were treated with ethyl chloroacetate to give the corresponding ester. Treatment of the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and benzoxazines. The hydrazides were reacted with benzaldehyde or phenylisothiocyanate to afford the corresponding hydrazone and thiosemicarbazide derivatives, which were cyclized with chloroacetic acid or thioglycolic acid to the corresponding thiazole derivatives. 3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were either condensed with malononitrile under different conditions to produce carbonitrile derivatives or treated with active methylene reagents to afford the substituted cyclohexene derivatives. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. Some of these compounds exhibited antimicrobial activities comparable to Ampicillin as reference drug. Oesterreichische Apotheker-Verlagsgesellschaft m. b. H.

Full text of DOI:10.3797/scipharm.0804-09

Sci Pharm. 2008; 76: 279–303
doi:10.3797/scipharm.0804-09
279
© Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria
Reproduction is permitted for non-commercial purposes.
Antimicrobial Activities of some Synthesized
Pyridines, Oxazines and Thiazoles from
3-Aryl-1-(2-naphthyl)prop-2-en-1-ones
2
Salwa F. MOHAMED * 1, Mohamed M. YOUSSEF ,
1
3
Abd El-Galil E. AMR , Eman R. KOTB
1 Applied Organic Chemistry, National Research Center, Dokki, Cairo, Egypt
2 Chemistry Department, Faculty of Science, Cairo University, Egypt
3 Photochemistry Department, National Research Center, Dokki, Cairo, Egypt
Abstract
3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate
to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which
were treated with ethyl chloroacetate to give the corresponding ester. Treatment of
the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and
benzoxazines. The hydrazides were reacted with benzaldehyde or
phenylisothiocyanate to afford the corresponding hydrazone and thiosemicarbazide
derivatives, which were cyclized with chloroacetic acid or thioglycolic acid to the
corresponding thiazole derivatives. 3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were
either condensed with malononitrile under different conditions to produce
carbonitrile derivatives or treated with active methylene reagents to afford the
substituted cyclohexene derivatives. The structure assignment of the new
compounds is based on chemical and spectroscopic evidence. Some of these
compounds exhibited antimicrobial activities comparable to Ampicillin® as reference
drug.
Keywords
α,β-Unsaturated ketones • Hydrazones • Thiazoles • Benzoxazine •
Antimicrobials
* Corresponding author. Fax.: +202+33370-931.
E-mail: salwa.fahim@hotmail.com (S. F. Mohamed).

280
S. F. Mohamed et al.:
Introduction
In previous works we reported that certain substituted pyridines, pyrimidines
and their chiral macrocyclic derivatives have antidepressant, antimicrobial,
anticancer, analgesic, and anticonvulsant activities [1–7]. α,β-Enones are widely
used as versatile precursors for synthesis of several types of heterocyclic
compounds, such as isoxazoles [8], thiazoles [9], thiadiazoles [10],
oxazolopyridines, pyrans, pyridines and pyrimidines [11, 12], triazines [13], and
flavonoids [14]. In view of these observations and as continuation of our previous
work in heterocyclic chemistry, we synthesized some new heterocyclic derivatives
and tested their antimicrobial activities.
Results and Discussion
Chemistry
Ar
O
CN
Ar CHO
Me
CH2 COOEt
N
H
O
CN
1
Ar
Ar CHO
CN
OH
O
CN
Ar
CH2 COOEt
N
2a,b
3a,b
Ar
CN
ClCH2COOEt
N
OCH2COOEt
4a,b
a, Ar = Ph; b, Ar = C H OMe(p)
6 4
Sch. 1.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
281
3-Aryl-1-(2-naphthyl)prop-2-en-1-ones (2a,b) were reacted with ethyl
cyanoacetate in refluxing ethanol in the presence of ammonium acetate to produce
dihydropyridinecarbonitriles 3a,b. One-step synthesis [15] was used to synthesize
compounds 3a,b in good yields by refluxing of 2-acetylnaphthalene, aromatic
aldehyde and ethyl cyanoacetate in ethanol containing ammonium acetate as a
catalyst. The latter compounds 3a,b were reacted with ethyl chloroacetate in dry
acetone, in the presence of anhydrous potassium carbonate to afford the ethyl
glycolate derivatives 4a,b (Scheme 1).
The esters 4a,b were reacted with hydrazine hydrate in refluxing ethanol to
give the corresponding hydrazides 5a,b, which were refluxed with benzaldehyde in
ethanol to produce the corresponding hydrazone derivatives 6a,b, followed by
cyclization with thioglycollic acid to thiazoles 7a,b. While, compounds 5a,b were
reacted with phenylisothiocyanate in dry dioxane to obtain thiosemicarbazides 8a,b,
which were cyclized with chloroacetic acid in ethanol to produce 2-N-
phenylthiazoles 9a,b. But, compounds 4a,b were fused with anthranilic acid at
110°C to give oxazinone derivatives (10a,b) (Scheme 2).
Condensation of 2a,b with malononitrile in acetic acid under reflux afforded the
oxapentanoic acid nitrile derivatives 11a,b, which cyclized by refluxing in acetic acid
in the presence of anhydrous sodium acetate or ammonium acetate to afford the
corresponding cyanoaminopyranes 12a,b or cyanoaminopyridines 13a,b,
respectively. However, the later compounds 12a,b and 13a,b were also prepared
directly from the chalcone derivatives 2a,b by reacting it with malononitrile in acetic
acid in the presence of sodium acetate or ammonium acetate (Scheme 3).

282
S. F. Mohamed et al.:
X
COOH
NH2
O
CN
O
Ar
N
OCH2
N
10a,b
X
X
CN
O
CN
O
NH2NH2.H2O
CH2COOEt
CH2CONHNH2
Ar
Ar
N
N
4a,b
5a,b
PhNCS
PhCHO
X
X
CN
O
CN
O
CH2CONHNHCSNHPh
CH2CONHN=CHPh
Ar
Ar
N
8a,b
N
6a,b
ClCH2COOH
HSCH2COOH
X
X
S
S
CN
O
CN
O
N
NPh
O
N
Ph
CH2CONH
CH2CONH
Ar
Ar
N
O
N
9a,b
7a,b
a, X = H;
b, X = OMe
Ar =
Sch. 2.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
283
AcOH
AcOH
2a,b
+ CH (CN)
2
2
AcONH4
AcONa
NH2
Ar
CN
O
AcOH
CN
Ar
N
NH2
12a,b
NC
O
CN
13a,b
AcOH
Ar
AcOH
AcONa
AcONH4
11a,b
a, Ar = Ph; b, Ar = C H OMe(p)
6 4
Sch. 3.
Moreover, naphthyl chalcones 2a,b were reacted with ethyl acetoacetate in
ethanolic sodium ethoxide solution to give cyclohexenone ethyl esters 14a,b. While,
compounds 2a,b were reacted with acetoacetanilide (15) or acetonedicarboxylic
acid dianilide (16) in ethanolic sodium hydroxide solution to yield the corresponding
cyclohexenone carboxylic acid phenylamides 17a,b and cylohexenone-1,3-
dicarboxilic acid diphenylamides 18a,b, respectively. Finally, cyclocondensation of
17a,b with hydrazine hydrate, phenyl hydrazine and hydroxylamine in glacial acetic
acid in the presence of sodium acetate afforded the corresponding benzopyrazol-3-
ones 19a,b, 2-phenylbenzopyrazol-3-ones 19c,d and benzisoxazol-3-ones 19e,f,
respectively (Scheme 4).

284
S. F. Mohamed et al.:
Ar
COOEt
CH3COCH2COOEt
O
Ar
14a,b
CONHPh
CH3COCH2CONHPh
O
1
15
17a,b
PhNHCOCH2COCH2CONHPh
NH2 XH
16
Ar
Ar
O
X
CONHPh
N
H
O
CONHPh
19a-f
19a, X = NH, Ar = Ph
18a,b
a, Ar = Ph;
19b, X = NH, Ar = C H OMe(p)
6 4
b, Ar = C H OMe(p)
6 4
19c, X = NPh, Ar = Ph
19d, X = NPh, Ar = C H OMe(p)
6 4
19e, X = O, Ar = Ph
19f, X = O, Ar = C H OMe(p)
6 4
Sch. 4.
Antimicrobial evaluation
The newly synthesized heterocyclic compounds, shown in Table 1 were tested
for their antimicrobial activity against the following microorganisms: Escherichia
coli, Pseudomonas putide, Bacillus subtilis, Streptococcus lactis, Aspergillus niger,
Penicillium sp. and Candida albicans. The preliminary screening of the investigated
compounds was performed using the filter paper disc-diffusion method. The most
active compounds were: 5b, 8b and 17b and the results are summarized in
Table 1.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
285
Tab. 1. Antimicrobial activities of some newly synthesized compounds.
Inhibition zone (mm)
Comp.
No.
Gram-negative
Gram-positive
Fungi
Yeast
E.
coli
0
P.
Putide
0
B.
Subtilis
0
S.
lactis
0
A.
P.
Sp.
0
C.
Albicans
0
niger
3a
4a
0
0
12
0
0
18
0
0
17
0
0
17
0
0
18
0
0
10
0
0
0
5b
7b
0
8b
12
0
10
0
14
0
13
0
8
6
0
11a
13b
15b
17c
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
20
20
18
18
18
10
13
Chloram-
phenicol®
Ampicilin®
22
24
21
20
18
19
19
22
20
24
12
14
0
14
E. coli = Escherichia coli; P. Putide = Pseudomonas Putide; B. Subtilis = Bacillus Subtilis; S. lactis
= Streptococcus lactis; A. niger = Aspergillus niger; P. Sp. = Penicillium Sp; C. Albicans = Candida
Albicans
The sensitivity of microorganisms to the tested compounds is identified in the following manner *:
Highly sensitive = Inhibition zone 15–20 mm
Moderately sensitive = Inhibition zone: 10–15 mm
Slightly sensitive = Inhibition zone: 5–10 mm
Not sensitive = Inhibition zone: 0 mm
* Each result represents the average of triplicate readings.
Experimental
Chemistry
All melting points are uncorrected and were taken on Electrothermal IA 9000
series digital melting point apparatus. Elemental analytical data (in accordance with
the calculated values) were obtained from the microanalytical unit, Cairo University,
Cairo, Egypt. The IR spectra (KBr) were recorded on a Pye Unicam SP-1000

286
S. F. Mohamed et al.:
1
1
spectro-photometer. The H-NMR spectra were recorded at a Varian H-Gemini
200 Spectro-meter using TMS as an internal standard. The mass spectra were
performed using GC-MSQP 1000 EX spectrometer (70eV). All reactions were
followed by TLC (silica gel, aluminum sheets 60 F254, Merck). Compound 2a,b was
prepared from 2-acetyl-naphthalene 1 according to the literature method [16].
Physical and spectral data are shown in Tables 2 and 3.
6-(2-Naphthyl)-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3a) and 4-(4-
Methoxyphenyl)-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (3b)
Method A: A mixture of 1 (0.17 g, 1 mmol), aromatic aldehyde, namely,
benzaldehyde or 4-methoxybenzaldehyde (1 mmol), ethyl cyanoacetate (0.113 g, 1
mmol) and ammonium acetate (0.062 g, 8 mmol) in 40 ml ethanol was heated
under reflux for 3 h. The obtained precipitate was filtered off, dried and crystallized
from the proper solvent to give compounds 3a,b (Tables 2 and 3).
Method B. A mixture of 2a,b (1 mmol), ethyl cyanoacetate (0.113 g, 1 mmole)
and ammonium acetate (0.062 g, 8 mmol) in 40 ml ethanol was heated under reflux
for 10 h. The obtained precipitate was filtered off, dried and crystallized the proper
solvent to give 3a,b in 56% yield.
Ethyl {[3-cyano-6-(2-naphthyl)-4-phenylpyridin-2-yl]oxy}acetate (4a) and Ethyl
{[3-cyano-4-(4-methoxyphenyl)-6-(2-naphthyl)pyridin-2-yl]oxy}acetate (4b)
A mixture of 3a,b (1 mmol), ethyl chloroacetate (0.123 g, 1 mmol) and
anhydrous potassium carbonate (0.55 g, 4 mmol) in 30 ml dry acetone was refluxed
for 20 h. The reaction mixture was evaporated under reduced pressure, the residue
was dissolved in water, the produced was extracted with ether, dried over sodium
sulphate anhydrous and filtered off, then evaporated and crystallized the proper
solvent to give 4a,b (Tables 2 and 3).

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
287
2-{[3-Cyano-6-(2-naphthyl)-4-phenylpyridin-2-yl]oxy}acetohydrazide (5a) and
2-{[3-Cyano-4-(4-methoxyphenyl)-6-(2-naphthyl)pyridin-2-
yl]oxy}acetohydrazide (5b)
A solution of 4a,b (1 mmol) in 50 ml ethanol and 4 ml of hydrazine hydrate (8
mmol) was refluxed for 6 h. After cooling, the separated solid was filtered off, dried
and crystallized the proper solvent to give 5a,b (Tables 2 and 3).
N'-Benzylidene-2-{[3-cyano-6-(2-naphthyl)-4-phenylpyridin-2-
yl]oxy}acetohydrazide (6a) and N'-Benzylidene-2-{[3-cyano-4-(4-
methoxyphenyl)-6-(2-naphthyl)pyridin-2-yl]oxy}acetohydrazide (6b)
A mixture of 5a,b (1 mmol) in 30 ml ethanol, three drops of piperidine and
benzaldehyde (0.106 g, 1 mmol) was refluxed with stirring for 5 h. After cooling, the
formed solid was filtered off and crystallized the proper solvent to give 6a,b (Tables
2 and 3).
2-{[3-Cyano-6-(2-naphthyl)-4-phenylpyridin-2-yl]oxy}-N-(4-oxo-2-phenyl-1,3-
thiazolidin-3-yl)acetamide (7a) and 2-{[3-Cyano-4-(4-methoxyphenyl)-6-(2-
naphthyl)pyridin-2-yl]oxy}-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)acetamide
(7b)
To a stirred solution of 6a,b (1 mmol) in 30 ml dry benzene, thioglycollic acid
(~0.1 g, 1 mmol) in 5 ml dry benzene was added. The reaction mixture was refluxed
for 10 h, evaporated under reduced pressure. The residue was solidified with
petroleum ether, the obtained solid was filtered off, dried and crystallized the proper
solvent to give 7a,b (Tables 2 and 3).
2-({[3-Cyano-6-(2-naphthyl)-4-phenylpyridin-2-yl]oxy}acetyl)-N-
phenylhydrazinecarbothioamide (8a) and 2-({[3-Cyano-4-(4-methoxyphenyl)-6-
(2-naphthyl)pyridin-2-yl]oxy}acetyl)-N-phenylhydrazinecarbothioamide(8b)
A mixture of 5a,b (1 mmol) and phenylisothiocyanate (0.135 g, 1 mmol) in 50
ml dry dioxane was refluxed for 5 h. The reaction mixture was concentrated under

288
S. F. Mohamed et al.:
reduced pressure and the obtained solid was filtered off and crystallized the proper
solvent to give 8a,b (Tables 2 and 3).
2-{[3-Cyano-6-(2-naphthyl)-4-phenylpyridin-2-yl]oxy}-N-[4-oxo-2-
(phenylimino)-1,3-thiazolidin-3-yl]acetamide (9a) and 2-{[3-Cyano-4-(4-
methoxyphenyl)-6-(2-naphthyl)pyridin-2-yl]oxy}-N-[4-oxo-2-(phenylimino)-1,3-
thiazolidin-3-yl]acetamide (9b)
A mixture of 8a,b (1 mmol) and chloroacetic acid (~0.1 g, 1 mmol) in 20 ml
absolute ethanol was refluxed for 4 h. After cooling, the formed solid was filtered
off, dried and crystallized the proper solvent to give 9a,b (Tables 2 and 3).
6-(2-Naphthyl)-2-[(4-oxo-4H-3,1-benzoxazin-2-yl)methoxy]-4-
phenylnicotinonitrile (10a) and 4-(4-Methoxyphenyl)-6-(2-naphthyl)-2-[(4-oxo-
4H-3,1-benzoxazin-2-yl)methoxy]nicotinonitrile (10b)
Equimolar amounts of anthranilic acid (0.13 g, 1 mmol) and 4a,b (1 mmol)
were fused at 110°C on an oil bath for 5 h. The reaction mixture was triturated with
ethanol, the formed precipitate was filtered off and crystallized the proper solvent to
give 10a,b (Tables 2 and 3).
[3-(2-Naphthyl)-3-oxo-1-phenylpropyl]malononitrile (11a) and [1-(4-
Methoxyphenyl)-3-(2-naphthyl)-3-oxopropyl]malononitrile (11b)
A mixture of 2a,b (1 mole) and malononitrile (~0.1 g, 1 mmol) in 50 ml glacial
acetic acid was refluxed for 30 min. After cooling, the reaction mixture was poured
onto water with stirring. The formed solid was filtered off, dried and crystallized the
proper solvent to give 11a,b (Tables 2 and 3).
2-Amino-6-(2-naphthyl)-4-phenyl-4H-pyran-3-carbonitrile (12a) and 2-Amino-4-
(4-methoxyphenyl)-6-(2-naphthyl)-4H-pyran-3-carbonitrile (12b)
2-Amino-6-(2-naphthyl)-4-phenylnicotinonitrile (13a) and
2-Amino-4-(4-methoxyphenyl)-6-(2-naphthyl)nicotinonitrile (13b)
Method A. A solution of 11a,b (1 mmol) in 50 ml acetic acid in the presence of
1 g sodium acetate or ~0.1 g ammonium acetate was refluxed for 6 h. The reaction

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
289
mixture was poured onto ice-water, the formed solid was filtered off, dried and
crystallized the proper solvent to give 12a,b and 13a,b, respectively (Tables 2 and
3).
Method B. A mixture of 2a,b (1 mmol) and malononitrile (~0.1 g, 1 mmol) in 50
ml acetic acid in the presence of 1 g sodium acetate or ~0.1 g ammonium acetate
was refluxed for 3 h. The reaction mixture was poured onto ice-water, the formed
solid was filtered off, dried and crystallized the proper solvent to give 12a,b and
13a,b, respectively (Tables 2 and 3).
Ethyl 4-(2-naphthyl)-2-oxo-6-phenylcyclohex-3-ene-1-carboxylate (14a) and
Ethyl 6-(4-methoxyphenyl)-4-(2-naphthyl)-2-oxocyclohex-3-ene-1-carboxylate
(14b)
To sodium ethoxide solution [prepared by dissolving sodium metal (0.03 g) in
15 ml absolute ethanol], ethyl acetoacetate (0.13 g, 1 mmol) was added and stirred
for 1 hr. 2a,b was added to the reaction mixture and the resulting solution was
refluxed for 3 h, after cooling, it was poured onto ice-water and acidified with
hydrochloric acid. The product was extracted with ether, washed with water, dried
over anhydrous MgSO4, and then evaporated under reduced pressure. The
obtained solid was crystallized the proper solvent to give 14a,b (Tables 2 and 3).
4-(2-Naphthyl)-2-oxo-N,6-diphenylcyclohex-3-ene-1-carboxamide (17a) and
6-(4-Methoxyphenyl)-4-(2-naphthyl)-2-oxo-N-phenylcyclohex-3-ene-1-
carboxamide (17b)
4-(2-Naphthyl)-6-oxo-N,N',2-triphenylcyclohex-4-ene-1,3-dicarboxamide (18a)
and 2-(4-Methoxyphenyl)-4-(2-naphthyl)-6-oxo-N,N'-diphenylcyclohex-4-ene-
1,3-dicarboxamide (18b)
A mixture of 2a,b (1 mmol) and acetoacetanilide (15) (0.18 g, 1 mmol) or
acetonedicarboxylic acid dianilide (16) (0.3 g, 1 mmol) in 50 ml ethanol containing
sodium hydroxide (~0.1 g, 2 mmol) was refluxed for 6 h. The reaction mixture was
poured onto acidified ice-water, the formed precipitate was filtered off and

290
S. F. Mohamed et al.:
crystallized the proper solvent to give 17a,b and 18a,b, respectively (Tables 2
and 3).
6-(2-Naphthyl)-4-phenyl-1,2,4,5-tetrahydro-3H-indazol-3-one (19a) and
4-(4-Methoxyphenyl)-6-(2-naphthyl)-1,2,4,5-tetrahydro-3H-indazol-3-one (19b)
6-(2-Naphthyl)-2,4-diphenyl-1,2,4,5-tetrahydro-3H-indazol-3-one (19c) and
4-(4-Methoxyphenyl)-6-(2-naphthyl)-2-phenyl-1,2,4,5-tetrahydro-3H-indazol-3-
one (19d)
6-(2-Naphthyl)-4-phenyl-4,5-dihydro-2,1-benzisoxazol-3(1H)-one (19e) and
4-(4-Methoxyphenyl)-6-(2-naphthyl)-4,5-dihydro-2,1-benzisoxazol-3(1H)-one
(19f)
A mixture of 17a,b (1 mmol) and aminoreagents, namely, hydrazine hydrate,
phenyl hydrazine or hydroxylamine hydrochloride (1 mmol) in 30 ml acetic acid
containing 2 g of sodium acetate was refluxed for 4 h. The reaction mixture was
allowed to cool, poured onto water and the formed solid was filtered off and
crystallized the proper solvent to give 19a,b, 19c,d and 19e,f, respectively (Tables
2 and 3).

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
291
Tab. 2. Physical properties of the new synthesized compounds
Comp.
No.
M.P. (oC)
Solvent of cryst.
300–301
(AcOH)
Yield
(%)
80
Mol. formula
(M. wt)
Analysis Calcd (Found)
C
H
N
3a
C22H14N2O
(322.37)
81.97
81.95
78.39
78.34
76.46
76.40
73.96
73.91
73.08
73.02
70.74
70.68
77.16
77.12
74.99
74.94
71.21
71.18
69.61
69.55
68.24
68.18
4.38
4.33
4.58
4.54
4.94
4.90
5.06
5.00
8.69
8.64
7.95
7.90
6.86
6.80
6.39
6.34
3b
4a
4b
5a
5b
6a
6b
7a
7b
8a
360–361
(AcOH);
72
70
75
70
65
65
62
52
55
60
C23H16N2O2
(352.39)
165–167
(MeOH)
C26H20N2O3
(408.46)
175–177
(MeOH)
C27H22N2O4
(438.48)
200–201
(MeOH)
C24H18N4O2
(394.43)
4.60 14.20
4.56 14.15
4.75 13.20
4.70 13.15
4.60 11.61
4.55 11.56
4.72 10.93
4.68 10.88
4.35 10.07
4.30 10.00
205–206
(MeOH)
C25H20N4O3
(424.46)
242–244
(AcOH)
C31H22N4O2
(482.54)
251–252
(AcOH)
C32H24N4O3
(512.57)
225–227
(DMF)
C33H24N4O3S
(556.64)
220–222
(DMF)
C34H26N4O4S
(586.66)
4.47
4.42
9.55
9.50
145–146
(CHCl3/pet. ether)
C31H23N5O3S
(545.62)
4.25 12.84
4.20 12.78

292
S. F. Mohamed et al.:
Tab. 2. (Cont.)
Comp.
M.P. (oC)
Yield
(%)
60
Mol. formula
Analysis Calcd (Found)
No.
8b
Solvent of cryst.
160–162
(M. wt)
C32H25N5O3S
(559.64)
C
H
N
68.68
68.62
69.58
69.52
68.10
68.00
77.33
77.28
75.14
75.05
81.46
81.40
77.95
77.90
81.46
81.40
77.95
77.90
81.71
81.65
78.16
78.10
81.06
81.00
4.50 12.51
4.44 12.46
4.07 12.29
4.00 12.24
4.20 11.68
4.14 11.62
(CHCl3/pet. ether)
170–172
9a
60
60
60
65
65
55
65
60
70
68
25
C33H23N5O3S
(569.64)
(CHCl3/pet. ether)
210–212
9b
C34H25N5O4S
(599.66)
(CHCl3/pet. ether)
182–184
10a
10b
11a
11b
12a
12b
13a
13b
14a
C31H19N3O3
(481.51)
3.98
3.94
4.14
4.10
4.97
4.94
5.12
5.05
4.97
4.92
5.12
5.06
8.73
8.68
8.21
8.16
8.64
8.60
7.90
7.84
8.64
8.58
7.90
7.85
(EtOH)
195–196
C32H21N3O4
(511.54)
(EtOH)
245–247
C22H16N2O
(324.38)
(AcOH)
260–262
C23H18N2O2
(354.41)
(AcOH)
245–247
C22H16N2O
(324.38)
(AcOH)
262–263
C23H18N2O2
(354.41)
(AcOH)
230–232
C22H17N3
(323.40)
5.30 12.99
5.24 12.95
5.42 11.89
5.38 11.84
5.99
(dioxane)
290–292
C23H19N3O
(353.42)
(dioxane)
90–92
C25H22O3
(370.45)
(MeOH)
5.94

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
293
Tab. 2. (Cont.)
Comp.
M.P. (oC)
Yield
(%)
25
Mol. formula
(M. wt)
Analysis Calcd (Found)
No.
14b
Solvent of cryst.
135–137
(MeOH)
220–222
(AcOH)
C
H
N
C26H24O4
(400.47)
77.98
77.90
83.43
83.36
80.51
80.46
80.58
80.52
78.43
78.38
81.63
81.56
78.24
78.20
84.03
83.98
81.06
80.96
81.40
81.32
78.03
77.97
6.04
5.98
5.55
5.50
5.63
5.58
5.26
5.20
5.34
5.28
5.36
5.30
5.47
5.42
5.35
5.30
5.44
5.40
5.05
4.98
5.18
5.10
17a
17b
18a
18b
19a
19b
19c
19d
19e
19f
70
70
70
70
65
60
70
65
65
60
C29H23NO2
(417.51)
3.35
3.30
3.13
3.06
5.22
5.18
4.94
4.88
8.28
8.22
7.60
7.55
6.76
6.70
6.30
5.96
4.13
4.05
3.79
3.72
230–232
(EtOH)
C30H25NO3
(447.53)
240–242
(EtOH)
C36H28N2O3
(536.63)
260–262
(EtOH)
C37H30N2O4
(566.66)
160–162
(dioxane)
190–192
(dioxane)
220–222
(dioxane)
255–257
(dioxane)
180–182
(EtOH)
C23H18N2O
(338.41)
C24H20N2O2
(368.44)
C29H22N2O
(414.51)
C30H24N2O2
(444.53)
C23H17NO2
(339.39)
200–202
(EtOH)
C24H19NO3
(369.42)

294
S. F. Mohamed et al.:
Tab. 3. Spectral data of newly synthesized compounds
Comp
No.
Spectral data
1H NMR (DMSO-d6, δ)
IR (ν,cm-1)
MS (m/z,
%)
3a
3b
4a
4b
3150 (NH),
2220 (CN),
1650 (CO)
3150 (NH),
2220 (CN),
1658 (CO)
2220 (CN),
1745 (CO)
322 [M+,
6.95 (s, 1H, pyrimidine-H5), 7.55-8.50 (m, 12H,
Ar-H), 12.85 (bs, 1H, NH, exchangeable with
D2O).
100].
352 [M+,
29],
3.75 (s, 3H, OCH3), 6.95 (s, 1H, pyrimidine-
H5), 7.55-8.50 (m, 12H, Ar-H), 12.90 (bs, 1H,
NH, exchangeable with D2O).
304 [100].
408 [M+, 4], 1.21 (t, 3H,CH3), 4.32 (q, 2H, CH2), 5.20 (s,
332 [100].
2H, CH2), 7.50-8.65 (m, 13H, Ar-H + pyridine-
H5)
2220 (CN),
1745 (CO)
438 [M+, 3], 1.20 (t, 3H, CH3), 3.85 (s, 3H, OCH3), 4.29 (q,
411 [100].
2H, CH2), 5.20 (s, 2H, CH2), 7.15, 7.75 (2d, 4H,
Ar-H), 7.90 (s, 1H, pyridine-H5), 8.00-8.90 (m,
7H, Ar-H).
5a
5b
6a
3250, 3160
(NH2+NH),
2220 (CN),
1675 (CO)
3240, 3155
(NH2, NH),
2220 (CN),
1675 (CO)
3220 (NH),
2215 (CN),
1670 (CO)
394 [M+,
37],
4.35 (s, 2H, NH2, exchangeable with D2O),
5.13 (s, 2H, CH2), 7.40-8.79 (m, 13H, Ar-H +
pyridine-H5), 9.60 (s, 1H, NH, exchangeable
with D2O)
362 [100].
424 [M+,
100].
3.90 (s, 3H, OCH3), 4.33 (s, 2H, NH2,
exchangeable with D2O), 5.11 (s, 2H, CH2),
7.10-8.75 (m, 12H, Ar-H + pyridine-H5), 9.59
(s, 1H, NH, exchangeable with D2O).
5.22 (s, 2H, CH2), 7.40-8.55 (m, 19H, Ar-H +
pyridine-H5 + benzylidene-H), 12.93 (s, 1H,
NH, exchangeable with D2O).
482 [M+,
100].

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
295
Tab. 3. (Cont.)
Comp.
No.
Spectral data
IR
MS
1H NMR (DMSO-d6, δ)
(ν, cm-1)
3220 (NH),
2220 (CN),
1675 (CO)
(m/z, %)
6b
512 [M+, 4], 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 7.25-
372 [100].
8.59 (m, 18H, Ar-H+ pyridine-H5
benzylidene-H), 12.95 (s, 1H,
exchangeable with D2O).
+
NH,
7a
3225 (NH),
2220 (CN),
1730,1685
(2CO)
556 [M+,
18],
3.75 (d, 1H, thiazolidine-H5), 3.95 (d, 1H,
thiazolidine-H5), 5.13, 5.21 (2d, 2H, 2
methylene-H), 5.73 (s, 1H, thiazolidine-H2),
7.25-8.75 (m, 18H, Ar-H + pyridine-H5), 10.66
(s, 1H, NH, exchangeable with D2O).
451 [100].
7b
3225 (NH),
2220 (CN),
1730,1685
(2CO)
586 [M+, 2], 3.75, 3.95 (2d, 2H, 2 thiazolidine-H5), 3.90 (s,
402 [100].
3H, OCH3), 5.15, 5.20 (2d, 2H, 2 methylene-
H), 5.75 (s, 1H, thiazolidine-H2), 7.25-8.75
(m, 17H, Ar-H + pyridine-H5), 10.69 (s, 1H,
NH, exchangeable with D2O).
8a
8b
3330,3200
(NH), 2220
(CN), 1680
(CO)
529 [M+, 5], 5.10 (s, 2H, CH2), 7.10-8.30 (m, 13H, 12 Ar-H
386 [100].
+ pyridine-H5), 9.20, 9.42, 9.81 (3s, 3H, 3NH,
exchangeable with D2O).
3330,3200
(NH), 2220
(CN), 1685
(CO)
559 [M+, 5], 3.91 (s, 3H, OCH3), 5.10 (s, 2H, CH2), 7.00-
520 [100].
8.10 (m, 12H, Ar-H +pyridine-H5), 9.20, 9.40,
9.80 (3s, 3H, 3NH, exchangeable with D2O).

296
S. F. Mohamed et al.:
Tab. 3. (Cont.)
Comp.
No.
Spectral data
IR
MS
(m/z, %)
1H NMR
(ν, cm-1)
3300,3200
(NH),
(DMSO-d6, δ)
9a
9b
569 [M+, 3], 3.52 (s, 2H, CH2 thiazolidine), 5.41, 5.71 (2d,
386 [100]. 2H, 2 methylene-H), 7.20-8.80 (m, 18H, Ar-H
pyridine-H5), 9.50 (s, 1H, NH,
exchangeable with D2O).
2220 (CN),
1720,1685
(2CO)
+
3300, 3200
(NH),
599 [M+, 3], 3.50 (s, 2H, CH2 thiazolidine), 3.90 (s, 3H,
465 [100].
OCH3), 5.40, 5.70 (2d, 2H, 2 methylene-H),
7.00-8.50 (m, 17H, Ar-H + pyridine-H5), 9.50
(s, 1H, NH, exchangeable with D2O).
2220 (CN),
1725, 1685
(2CO
10a
10b
11a
11b
2220 (CN),
1725 (CO)
481 [M+,
22],
5.30 (s, 2H, CH2), 7.10-8.35 (m, 17H, Ar-H +
pyridine-H5).
288 [100].
511 [M+,
20],
2220 (CN),
1725 (CO)
3.61 (s, 3H, OCH3), 5.22 (s, 2H, CH2), 6.90-
8.10 (m, 16H, Ar-H + pyridine-H5)
480 [100].
324 [M+,
20],
2210 (CN),
1680 (CO)
3.10 (m, 1H, H3), 4.20 (dd, 1H, H4), 4.40 (dd,
1H, H4), 5.10 (d, 1H, H2), 7.00-8.10 (m, 12H,
Ar-H).
318 [100].
354 [M+,
20],
2210 (CN),
1680 (CO)
3.10 (m, 1H, H3), 3.76 (s, 3H, OCH3), 4.21
(dd, 1H, H4), 4.32 (dd, 1H, H4), 5.15 (d, 1H,
H2), 6.88-8.00 (m, 11H, Ar-H).
349 [100].

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
297
Tab. 3. (Cont.)
Comp.
No.
Spectral data
IR
MS
(m/z, %)
324 [M+,
77],
1H NMR
(ν, cm-1)
3450, 3240
(NH2), 2180
(CN)
(DMSO-d6, δ)
12a
12b
13a
2.50 (d, 1H, pyran-H4), 5.00 (s, 2H, NH2,
exchangeable with D2O), 7.20-8.35 (m, 13H,
Ar-H + pyran-H5).
300 [100].
354 [M+,
75],
3455,3245
(NH2), 2190
(CN)
2.50 (d, 1H, pyran-H4), 3.80 (s, 3H, OCH3),
5.00 (s, 2H, NH2, exchangeable with D2O),
7.00-8.08 (m, 12H, Ar-H + pyran-H5).
2.60 (d, 1H, pyridine-H4), 4.12 (s, 2H, NH2,
exchangeable with D2O), 7.35-8.50 (m, 13H,
Ar-H + pyridine-H5), 12.85 (s, 1H, NH,
exchangeable with D2O).
425 [100].
323 [M+,
100].
3420,3250
(NH, NH2),
2190 (CN)
13b
14a
3420,3245
(NH, NH2),
2200 (CN)
353 [M+,
100].
2.60 (d, 1H, pyridine-H4), 3.80 (s, 3H, OCH3),
4.10 (s, 2H, NH2, exchangeable with D2O),
7.20-8.30 (m, 12H, Ar-H + pyridine-H5), 12.80
(s, 1H, NH, exchangeable with D2O).
1.10 (t, 3H, CH3), 3.33 (d, 2H, cyclohexene-
H5), 3.70 (m, 1H, cyclohexene-H6), 3.90 (q,
2H, CH2), 4.20 (d, 1H, cyclohexene-H1), 6.80
(s, 1H, cyclohexene-H3), 7.20-8.50 (m, 12H,
Ar-H).
1720, 1670
(2CO)
370 [M+,
100].
14b
1720, 1670
(2CO)
400 [M+,
100].
1.01 (t, 3H, CH3), 3.35 (d, 2H, cyclohexene-
H5), 3.70 (m, 1H, cyclohexene-H6), 3.76 (s,
3H, OCH3), 3.90 (q, 2H, CH2), 4.20 (d, 1H,
cyclohexene-H1), 6.80 (s, 1H, cyclohexene-
H3), 7.00-8.10 (m, 11H, Ar-H);

298
S. F. Mohamed et al.:
Tab. 3. (Cont.)
Comp.
No.
Spectral data
IR
MS
1H NMR
(ν, cm-1)
3260 (NH),
1740, 1640
(2CO)
(m/z, %)
417 [M+,
100].
(DMSO-d6, δ)
17a
17b
3.20 (d, 2H, CH2), 3.90 (m, 1H, cyclohexene-
H6), 4.00 (d, 1H, cyclohexene-H1), 6.50 (s,
1H, cyclohexene-H3), 7.10-8.35 (m,17H,Ar-
H), 10.15 (s,1H,NH, exchange-able with
D2O).
3260 (NH),
1740,1645
(2CO)
447 [M+,
100].
3.20 (d, 2H, CH2), 3.75 (s, 3H, OCH3), 3.90
(m, 1H, cyclohexene-H6), 4.00 (d, 1H,
cyclohexene-H1), 6.50 (s, 1H, cyclohexene-
H3), 6.90-8.00 (m, 17H, Ar-H), 10.10 (s, 1H,
NH, exchangeable with D2O).
18a
18b
3300-3200
(NH),
536 [M+,
100].
3.05 (d, 2H, CH2), 4.10 (m, 1H, cyclohexene-
H4), 4.50 (d, 1H, cyclohexene-H3), 6.75-8.25
(m, 22H, Ar-H), 10.10, 10.30 (2s, 2H, 2NH,
exchangeable with D2O).
1710,1680,
1645(3CO)
3310-3200
(NH),
566 [M+,
100]
3.05 (d, 2H, CH2), 3.75 (s, 3H, CH3), 4.10 (m,
1H, cyclohexene-H4), 4.50 (d, 1H,
cyclohexene-H3), 6.67-8.15 (m, 22H, Ar-H),
10.10, 10.30 (2s, 2H, 2NH, exchangeable
with D2O).
1720,1685,
1650(3CO)
19a
3420 (NH),
1700 (CO)
338 [M+,
100]
3.00 (d, 2H, CH2), 4.25 (t, 1H,
cyclohexadiene-H4), 7.00-8.10 (m, 13H, Ar-
H+ cyclohexadiene-H7), 11.00, 11.30 (2s, 2H,
2NH, exchangeable with D2O).

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
299
Tab. 3. (Cont.)
Comp.
No.
Spectral data
IR
MS
(m/z, %)
368 [M+,
100]
1H NMR
(ν, cm-1)
3420 (NH),
1700 (CO)
(DMSO-d6, δ)
19b
19c
19d
19e
19f
3.00 (d, 2H, CH2), 3.60 (s, 3H, OCH3), 4.25 (t,
1H, cyclo-hexadiene-H4), 6.90-8.00 (m, 12H,
Ar-H + cyclo-hexadiene-H7), 11.00,11.30 (2s,
2H, 2NH, exchangeable with D2O).
3400 (NH),
1705 (CO)
414 [M+,
100]
3.10 (d, 2H, CH2), 4.40 (t, 1H,
cyclohexadiene-H4), 7.00-8.10 (m, 18H, Ar-H
+ cyclohexadiene-H7), 11.40 (s, 1H, NH,
exchangeable with D2O).
3440 (NH),
1710 (CO)
444 [M+,
100]
3.10 (d, 2H, CH2), 3.60 (s, 3H, OCH3), 4.40 (t,
1H, cyclohexadiene-H4), 6.70-8.00 (m, 17H,
Ar-H + cyclohexadiene-H7), 11.40 (s, 1H, NH,
exchangeable with D2O).
3400 (NH),
1710 (CO)
339 [M+,
100]
3.00 (d, 2H, CH2), 4.25 (t, 1H,
cyclohexadiene-H4), 7.00-8.10 (m, 13H, Ar-H
+ cyclohexadiene-H7), 11.40 (s, 1H, NH,
exchangeable with D2O).
3400 (NH),
1710 (CO)
369 [M+,
100].
3.00 (d, 2H, CH2), 3.60 (s, 3H, OCH3), 4.30 (t,
1H, cyclohexadiene-H4), 6.90-8.00 (m, 12H,
Ar-H + cyclohexadiene-H7), 11.40 (s, 1H, NH,
exchangeable with D2O).

300
S. F. Mohamed et al.:
Antimicrobial screening
The newly synthesized heterocyclic compounds were tested for their
antimicrobial activity against the following microorganisms: (a) Gram-negative:
Escherichia coli and Pseudomonas putide; (b) Gram-positive: Bacillus subtilis and
Streptococcus lactis; (c) Fungi: Aspergillus niger and Penicillium sp.; (d) Yeast:
Candida albicans
Mediums: Three types of specific media were used in this study:
Medium (1): For bacteria (Nutrient Medium), consisting of (g/l distilled water):
peptone, 5 and meat extract, 3. pH was adjusted to 7.0.
Medium 2: For fungi (Potato Dextrose Medium), consisting of (g/l distilled
water): Infusion from potatoes, 4 and D(+)glucose, 20. pH was adjusted to 5.5.
Medium 3: For yeast (Universal Medium), consisting of (g/l distilled water):
yeast extract, 3; malt extract, 3; peptone, 5 and glucose, 10. pH was adjusted to
5.5.
For solid media, 2% agar was added. All media were sterilized at 121°C for 20
minutes.
Procedure (Filter paper diffusion method) [17]
Proper concentrations of microbial suspensions were prepared from 1 (for
bacteria to 3 (for yeast and fungi)-day-old liquid stock cultures incubated on a rotary
shaker (100 rbm). In the case of fungi, 5 sterile glass beads were added to each
culture flask. The mycelia were then subdivided by mechanical stirring at speed No.
1 for 30 minutes. Turbidity of microorganisms was adjusted with a spectro-
photometer at 350 nm to give an optical density of 1.0. Appropriate agar plates
were aseptically surface inoculated uniformly by a standard volume (ca. 1 ml) of the
microbial broth culture of the tested microorganism, namely E. coli, P. putide, B.
subtilis, S. Lactis. A. Niger, Penicillium sp. And C. albicans.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
301
Whatman No. 3 filter paper discs of 10 mm diameter were sterilized by
autoclaving for 15 minutes at 121°C. Test compounds were dissolved in 80% ethyl
alcohol to give final concentration of 5 μg/ml. The sterile discs were impregnated
with the test compounds (5 μg/disc). After the impregnated discs have been air
dried, they were placed on the agar surface previously seeded with the organism to
be tested. Discs were gently pressed with forceps to insure thorough contact with
the media. Three discs were arranged per dish, suitably spaced apart, i.e. the discs
should be separated by a distance that is equal to or slightly greater than the sum
of the diameters of inhibition produced by each disc alone. Each test compound
was conducted in triplicate. Plates were kept in the refrigerator at 5°C for 1 hour to
permit good diffusion before transferring them to an incubator at 37°C for 24 hours
for bacteria and at 30°C for 72 hours for yeast and fungi.
Conclusion
In order to reveal a potential activity of nine newly obtained compounds, they
were tested on seven bacterial species: Escherichia coli, Pseudomonas putide,
Bacillus subtilis, Streptococcus lactis, Aspergillus niger, Penicillium sp., Candida
albicans. The obtained results are shown in Table 1. Many of the investigated
derivatives presented interesting antibacterial activity.
References
[1]
Abdel-Latif NA.
Synthesis and antidepressant activity of some new coumarin derivatives.
Sci Pharm. 2005; 74: 193–216.
[2]
Amr AE, Abdel-Latif NA, Abdalla MM.
Synthesis of some new testosterone derivatives fused with substituted
pyrazoline ring as 5α-reductase inhibitors.
Acta Pharm. 2006; 56: 203–218.
[3]
Amr AE, Abdel-Latif NA, Abdalla MM.
Synthesis and antiandrogenic activity of some new 3-substituted
androstano[17,16-c]-5`-aryl-pyrazoline and their derivatives.
Bioorg Med Chem. 2006; 14: 373–384.
[doi:10.1016/j.bmc.2005.08.024]

302
S. F. Mohamed et al.:
[4]
Amr AE.
Synthesis of some new linear and chiral macrocyclic pyridine carbazides as
analgesic and anticonvulsant agents.
Z Naturforsch. 2005; 60b: 990–998.
[5]
[6]
Amr AE, Sayed HH, Abdulla MM.
Synthesis and reactions of some new substituted pyridine and pyrimidine
derivatives as analgesic, anticonvulsant and antiparkinsonian agents.
Arch Pharm Chem Life Sci. 2005; 338: 433–440.
[doi:10.1002/ardp.200500982]
Abo-Ghalia MH, Amr AE.
Synthesis and investigation of a new cyclo-(Nα-dipicolinoyl)pentapeptide of a
breast and CNS cytotoxic activity and an ionophoric specifity.
Amino Acids. 2004; 26: 283–289.
[doi:10.1007/s00726-003-0042-8]
[7]
[8]
Hammam AG, Fahmy AF, Amr AE, Mohamed AM.
Synthesis of novel tricyclic heterocyclic compounds as potential anticancer
agents using chromanone and thiochromanone as synthons.
Ind J Chem. 2003; 42B: 1985–1993.
Lakhvich FA, Koroleva EV, Akhrem AA.
Synthesis, chemical transformation, and application of isoxazole derivatives
in the total chemical synthesis of natural compounds.
Chem Heterocycl Comp. 1989; 25: 359–375.
[doi:10.1007/BF00480746]
[9]
Mukhtar S, Ramadan M, Ansari W, Lemiere G, De Groot A, Dommisse R.
Bifunctional derivative of p,p`-dichlorochalcone Part II. Synthesis of a novel
compound 2-[2-carboxymethylthio-2-(4-chlorophenyl)ethyl]-2-(4-
chlorophenyl)-4-thiazolidinone.
Molecules. 1999; 4: 232–237.
[10] Bae SH, Kim KS, Park Y.
Reactions of Tetrasulfur Tetranitride Antimony Pentachloride Complex
(S4N4•SbCl5) with Primary β-Enaminones and β-Enamino Esters: Synthesis
of 4-Substituted 3-Aroyl- and 3-Ethoxycarbonyl-1,2,5-thiadiazoles.
Heterocycles. 2000; 53: 159–172.
[11] Swellem RH, Allam YA, Nawwar GA.
Synthesis of 3-Phenylisoxazolo[3,4-a]carbazoles.
Z Naturforsch. 1999; 54b: 1197–2201.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and …
303
[12] Bakhite EA.
Convenient heterocyclization reactions with 2-functionalized 3-amino-4-aryl-
5,6,7,8-tetrahydrothieno[2,3-b]quinolines: Synthesis of new thienoquinolines,
pyridothienoquinolines, pyranothienoquinolines and
pyrimidothienoquinolines.
J Chem Res Synop. 2000; 11: 500–501.
[13] Al-Shikh MA, El-Din AMS, Hafez EA, Elnagdi MH.
α-Enones in heterocyclic synthesis, part I. Classical synthetic and
environmentally friendly synthetic approaches to alkyl and acyl azoles and
azines.
J Chem Res. 2004; 174–179.
[14] Lim SS, Jung SH, Ji J, Shin KH, Keum SR.
Synthesis of flavonoids and their effects on aldose reductase and sorbitol
accumulation in streptozotocin-induced diabetic rat tissues.
J Pharm Pharmacol. 2001; 53: 653–668.
[doi:10.1211/0022357011775983]
[15] Nehad AA, Amr EA, Alhusien AI.
Synthesis, reactions and pharmacological screening of heterocyclic
derivatives Using nicotinic acid as a natural synthon.
Monatsh Chem. 2007; 138: 559–567.
[doi:10.1007/s00706-007-0628-z]
[16] Attia A, Abdel-Salam OI, Abo-Ghalia MH, Amr EA.
Chemical and biological reactivity of newly synthesized 2-chloro-6-ethoxy-4-
acetylpyridine.
Egypt J Chem. 1995; 38: 543–553.
[17] Coffen DL, Korzan DG.
Synthetic quinine analogs. III. Frangomeric and anchimeric processes in the
preparation and reactions of α,β-epoxy ketones.
J Org Chem. 1971; 36: 390–395.
[doi:10.1021/jo00802a006]
Received April 8th, 2008
Accepted (after revision) May 16th, 2008
Available online at www.scipharm.at May 19th, 2008