Synthetic approaches towards 1,2,4-triazines utilizing wittig and wittig-horner reagents

Article abstract of DOI:10.1080/10426500802077606

The reaction of 5-aroyl-1,2,4-triazin-6(1H)-ones 2a, 2b with methoxycarbonyl-, ethoxycarbonyl-, methylenetriphenylphosphorane (1a,1b) gave olefinic adducts 4a-4d, pyranotriazine products 5a-5d, and triphenylphosphine oxide. Moreover, benzoylmethylenetriph

Full text of DOI:10.1080/10426500802077606

This article was downloaded by: [The Aga Khan University]
On: 26 November 2014, At: 05:24
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Synthetic Approaches Towards
1,2,4-Triazines Utilizing Wittig
and Wittig-Horner Reagents
Mona H. N. Arsanious a & Maysa E. Moharam b
a Organometallic and Organometalloid Chemisrty
Department , National Research Centre , Dokki,
Cairo, Egypt
b Microbial Chemistry Department , National
Research Centre , Dokki, Cairo, Egypt
Published online: 12 Aug 2008.
To cite this article: Mona H. N. Arsanious & Maysa E. Moharam (2008) Synthetic
Approaches Towards 1,2,4-Triazines Utilizing Wittig and Wittig-Horner Reagents,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9, 2344-2359, DOI:
10.1080/10426500802077606
To link to this article: http://dx.doi.org/10.1080/10426500802077606
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,

and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 183:2344–2359, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802077606
Synthetic Approaches Towards 1,2,4-Triazines Utilizing
Wittig and Wittig-Horner Reagents
Mona H. N. Arsanious,1 and Maysa E. Moharam2
1Organometallic and Organometalloid Chemisrty Department, National
Research Centre, Dokki, Cairo, Egypt
2Microbial Chemistry Department, National Research Centre, Dokki,
Cairo, Egypt.
The reaction of 5-aroyl-1,2,4-triazin-6(1H)-ones 2a, 2b with methoxycarbonyl-,
ethoxycarbonyl-, methylenetriphenylphosphorane (1a,1b) gave olefinic adducts
4a-4d, pyranotriazine products 5a-5d, and triphenylphosphine oxide. More-
over, benzoylmethylenetriphenylphosphorane (1c) reacts with 5-[(4-methoxyphenyl)
carbonyl]-3-phenyl-1,2,4-triazin-6(1H)-one (2b) to yield 4e and triphenylphosphine
oxide. On the other hand, the application of phosphorus ylides on 5-[(hydroxyimino)
(4-methoxyphenyl)methyl]-3-phenyl-1,2,4-triazin-6(1H)-one (3b) render the new
product tetraazabenzocyclohepten-8-one oxide 6, and triphenylphosphine oxide.
Trimethylphosphonoacatate 7 reacts with 5-aroyl-1,2,4-triazin-6(1H)-ones 2a, 2b to
afford 5,6-dihydro-5-hydroxy-3,5-diarylpyrano[3,2-e][1,2, 4]-triazin-7-ones 8a, 8b
and alkylated adducts 9a, 9b. Moreover, 5-[(hydroxyimino)aryl methyl]-3- phenyl-
1,2,4-triazin-6(1H)-ones 3a, 3b react with Wittig-Horner reagent to give alkylated
products 10a, 10b and isoxazolo [4,5-e]-1,2,4-triazines 11a, 11b. The biological
activity of the new synthesized compounds was also examined. Possible reaction
mechanisms are considered and the structural assignments are based on analyti-
cal and spectroscopic results.
Keywords 5-Aroyl-1,2,4-triazinones; 5-[(hydroxyimino)arylmethyl]-3-phenyl-1,2,4-
triazin-6(1H)-ones; phosphonium ylides; Wittig-Horner reagent
INTRODUCTION
Microorganisms of the genus Pseudomonas produce a wide spectrum
of heterocyclic antibiotics, including phenazine, quinoline, and pyrrole
derivatives.1 Many of these substances are synthesized by strains of P.
fluorescens, one of the most prolific producers of antibiotic in the genus.2
Triazine derivatives represent one of these substances, which exhibits
Received 19 December 2007; 8 February 2008.
Address correspondence to Mona H. N. Arsanious, National Research Center, Dokki,
Cairo, Egypt. E-mail: mona.arsanious@gmail.com.
2344

Utilizing Witting and Wittig-Horner Reagents
2345
FIGURE 1
biological activities.3–6 This, together with our interest in organophos-
phorus chemistry,7–13 triggered the synthesis of new organophospho-
rus compounds incorporating such important nuclei that may pos-
sibly lead to biological activity. The present study deals with the
reaction of stabilized phosphonium ylides 1a–1c with 5-aroyl-1,2,4-
triazinones 2a, 2b and 5-[(hydroxyimino)arylmethyl]-3-phenyl-1,2,4-
triazinones 3a, 3b (Figure 1).
RESULTS AND DISCUSSION
When 3-phenyl-5-benzoyl-1,2,4-triazin-6(1H)-one (2a) was treated with
one mol equivalent of methoxycarbonylmethylene triphenylphospho-
rane (1a) in boiling toluene for 4 h, adduct 4a, triphenylphosphine ox-
ide, and the starting triazinone, 2a, were isolated.
Compound 4a was chromatographically pure and exhibited a sharp
melting point. The IR spectrum of 4a, in KBr, revealed the presence
of strong absorption bands at ν = 3230 (NH), 1736 (C O ester) and
1
1617 (C C, Ar) cm−1 14
.
The H NMR spectrum of 4a exhibits signals
centered at 3.61 (s, 3H, COOCH3), 6.50 (s,1H, CH), and 10.62 (s,1H,
NH). The mass spectrum of 4a yielded a prominent peak for M+ at m/z =
333, which corroborates the structure 4a . The 13C NMR spectrum of 4a
supports the established structure (see Experimental section). Carrying
out the reaction using 2 mol of the phosphonium ylide 1a instead of 1
mol led to the formation of 4a, 5a, and triphenylphosphine oxide.
It is worth mentioning that when compounds 4a–4d were allowed to
react with 1 mol equivalent of phosphorus ylides, 1a–1b, 5a–5d, and
triphenylphosphine oxide were obtained.

2346
M. H. N. Arsanious and M. E. Moharam
Compound 5a was chromatographically pure and exhibited a sharp
melting point. The 1H NMR spectrum of 5a consisted of signals at 3.79
as singlet for methyl ester. The exocyclic methine proton appeared as
singlet at 5.91, whereas the cyclic CH proton exhibits a singlet at 8.57.
Moreover, the 13C NMR spectrum of 5a shows signals at 101.2 ppm,
corresponding to exocylic methine carbon, 166.5 ppm to carbonyl ester,
and at 127.9 for cyclic CH carbone.14Actually, the mass spectrum of
5a contains a prominent peak for M+ at m/z = 357, which supports
structure 5a.
Next, the reaction of 2b with methoxycarbonyl-(1a) and ethoxycar-
bonyl-, methylenetriphenylphosphorane (1b) was also investigated. We
have found that when 2b reacts with 1 mol equivalent of 1a and/or 1b,
adducts 4c and 4d were obtained together with triphenylphosphine
oxide.
Moreover, when 2b reacts with 2 mol equivalents of 1a and/or 1b, in
boiling toluene, products 4c, 4d, 5c, and 5d were isolated. Triphenyl-
phosphine oxide is also obtained from each reaction and identified.
Structure of products 4c, 4d, 5c, and 5d from correct microanaly-
sis, IR,1H NMR, 13C NMR, and MS spectral data (see Experimental
section).
When 2b was treated with benzoylmethylenetriphenylphosphorane
(1c) in boiling toluene for 10–12 h, compound 4e was isolated. 5-(1-
(4-methoxyphenyl) -3-oxo-3-phenylprop-1-enyl)-3-phenyl-1,2,4-triazin-
6 (1H)-one (4a) was obtained irrespective where 1 or 2 mol equivalents
of 1c were used (Scheme 1). Its elemental analysis and spectroscopic
results were consistent with the assigned structure 4e. The IR spectrum
of 4e revealed the presence of strong absorption band at 1721 cm−1
(COPh), 3180 (NH), and 1611cm−1(C C,Ar).14 The mass spectrum of
4e contains a prominent peak for M+at m/z = 409, which corroborates
the structure 4e.
A possible explanation for the course of the reaction of the phospho-
nium ylides 1a–1c with 2a and 2b is shown in Scheme 1. Formation
of adducts 4a–4e can be explained in terms of carbonyl olefination15
of 2a and 2b by the Wittig reagents 1a–1c with expulsion of triph-
enylphosphine oxide.The olefinic compounds 4a–4d reacted with an-
other molecule of phosphorus ylides 1a and 1b to give products
5a–5d presumably through loss of one mol alcohol and expulsion of
triphenylphosphine oxide (Scheme 1).16
Furthermore, this study was extended to include the behavior of
3b toward phosphonium ylides 1a and 1b. We found that 5-[(hydroxy-
imino)(4-methoxyphenyl)methyl]-3-phenyl-1,2,4-triazin-6(1H)-one
(3b) reacts with 2 mol equivalents methoxycarbonyl- (1a), and
ethoxycarbonyl-, methylenetriphenylphosphorane (1b) in refluxing

Utilizing Witting and Wittig-Horner Reagents
2347
SCHEME 1
xylene, to give yellowish green crystalline product assigned struc-
ture 6. Triphenylphosphine was isolated from the reaction medium
(Scheme 2). Structural support for 5-(4-methoxyphenyl)-3-phenyl-5H-
9-oxa-1,2,4,6-tetraazabenzocyclohepten-8-one-6-oxide (6) was based
upon correct elemental analysis spectroscopic data. The IR spectrum
of 6 revealed the presence of strong absorption bands at 1565 cm−1
(N → O), 1740 (C O, lactone).14 Its 1H NMR spectrum aromatic
protons at δ = 7.47–8.14 ppm (m, 9H, Ar), 7.28 (s,1H,N CH). The
1H NMR spectrum of compound 6 disclosed the presence of signal at

2348
M. H. N. Arsanious and M. E. Moharam
SCHEME 2
δ = 12.25 (s, 1H, N OH) ppm. The mass spectrum of 6 showed
prominent peak for M+ at m/z = 362, which supports the nitrogen
oxide structure 6. A possible explanation of the course of the reaction
of the ylides 1a and 1b with 3b is shown in Scheme 2.17
Moreover, we have also studied the reactions of Wittig-Horner
reagent 7 with 5-aroyl-1,2,4-triazinones 2a and 2b. We have found that
reaction of 2a and 2b with 2 mol equivalents of trimethylphosphonoac-
etate 7 in the presence of DMF/ NaH suspension with stirring at room
temperature gave 5,6-dihydro-5-hydroxy-3,5-diarylphenylpyrano[3,2-
e][1,2,4] triazin-7-ones 8a–8b and alkylated products 9a–9b (Fig-
ure 2).18
The possible explanation for the course of the reaction of Wittig-
Horner reagent 7 with 2a and 2b is show in Scheme 3. Forma-
tion of adducts 8a, 8b can be explained in terms of nucleophilic at-
tack of the carbanion Wittig-Horner reagent 7 at the carbonyl group
with the formation of intermediate (A), followed by hydrolysis with
molecule of water to give intermediate (B).19 5,6-Dihydro-5-hydroxy-
3,5-diarylphenyl-pyrano[3, 2-e][1,2,4]triazin-7-ones 8a, 8b were de-
rived by loss a methanol moity Scheme 3.19
The reaction of trimethylphosphonoacetate (7) with 5-
[(hydroxylimino) arylmethyl]-3-phenyl-1,2,4-triazin-6(1H)-ones 3a, 3b
was also investigated. We have found that reaction with 3a, 3b, in the

Utilizing Witting and Wittig-Horner Reagents
2349
FIGURE 2
SCHEME 3

2350
M. H. N. Arsanious and M. E. Moharam
SCHEME 4
presence of alcoholic sodium methoxide, at refluxing temperature gave
products 10a, 10b, and 11a, 11b (Scheme 4). The structure of the new
compounds is confirmed through elemental analysis, IR, 1H NMR, 13
NMR, and MS spectral data (see Experimental section).
C
A possible explanation for the course of the reaction of 3a, 3b with
trimethylphosphonoacetate 7 is shown in (Scheme 4).
CONCLUSIONS
From the results of the present investigation it could be concluded
that 5-aroyl-1,2,4-triazin-6(1H)-ones 2a and 2b react with one mol of
phosphonium ylides 1a and 1b to give the corresponding olefinic prod-
ucts 4a–4d and triphenylphosphine oxide. Moreover, when 2a and 2b
react with two mol equivalents of ylides, the olefinic compounds,5a–
5d and triphenylphosphine oxide were isolated.16 On the other hand,
benzoylmethylenetriphenylphosphorane (1c) reacts with 2b to yield
the olefinic adduct 4e. Moreover, the behavior of 5-[(hydroxyimino)(4-
methoxyphenyl)methyl]-3-phenyl-1,2,4-triazin-6(1H)-one 3b towards
phosphorans ylide 1a and or 1b leading to 5-(4-methoxyphenyl)-3-
phenyl-5H-9-oxa-1,2,4,6-tetraazabenzocyclohepten-8-one-6-oxide (6).
Trimethylphosphonoacetate (7) reacts with 2a and 2b to give adducts
8a, 8b and 9a,9b. Moreover,5-[(hydroxyimino)(aryl) methyl]-3-phenyl-
1,2,4-triazin-6 (1H)-ones 3a, 3b react with 7 to yield products 10a, 10b
and 11a, 11b, respectively.
EXPERIMENTAL
All melting points are uncorrected. 5-aroyl-1,2,4-triazin-6(1H)-ones 2a–
2b were prepared according to Nalepa et al.20 The IR spectra were mea-
sured in KBr pellets with a Perkin-Elmer Infrared Spectrophotometer

Utilizing Witting and Wittig-Horner Reagents
2351
1
Model 157 (Grating). The H and 13C NMR spectra were recorded in
CDCl3/and DMSO as solvent, with a Varian Spectrometer at 270 and
67.5MHz using TMS as internal reference. The mass spectra were per-
formed at 70 eV on a Shimadzu GCS-OP 1000 Ex Spectrometer provided
with a data system. Elemental analyses were performed using the El-
mentar Varu EL Germany Instrument. Their value agreed favorably
with the calculated ones.
Reaction of 3-phenyl-5-benzoyl-1,2,4-triazin-6(1H)-one (2a)
with pho-sphonium ylides 1a and 1b.
A mixture of 2a (0.27g; 0.001 mol), and 0.002 mol phosphonium ylide 1a
and 1b in 30 cm3dry toluene was refluxed for 6 h. After evaporation of
the volatile materials under reduced pressure, the residue was applied
to silica gel column chromatography. The eluent, yield, and m.p. are
given below for adducts 4a,5a, 4b, and 5b.
Methyl-3-(6-oxo-3-phenyl-1,6-dihydro-1,2,4-triazin-5-yl)3-
phenyl acrylate 4a
Eluent: petroleum ether/ethyl acetate (80/20, v/v). Product 4a was
separated as pale yellow crystals, m.p. 222–223◦C, yield (35%). Anal.
calcd. for C19H15N3O3(333.34):C,68.46;H,4.54;N,12.61. Found: C, 68.52;
H, 4.64; N, 12.54%. IR (KBr): 1736 (C O ester) 3230 (NH), and
1
1617(C C, Ar.), cm−1; H NMR (CDCl3): δ = 3.61 (s, 3H, COOCH ),
3
6.50 (s,1H, = CH), 6.90–6.93 (d, 2H, J = 7.4 Hz, Ar), 7.37–7.40 (m, 3H,
Ar), 8.13–8.16 (m, 5H, Ar), 10.62 (b, 1H, NH) ppm;13C NMR(CDCl3):
δ = 55.1 (COOCH3), 167.8 (COO CH3), 140.2 (C CH), 100.6 (C CH),
161.8 (C O NH), 161.3, 158.6 (C N), 124.6, 126.7, 127.8, 129.2, 128.8,
131.2, 130.83, 134.2 (C Ar) ppm; MS m/z (%) 333 (100) [M+].
Methyl(3,5-diphenyl-7H-pyrano[3,2-e][1,2,4]triazin-7-ylidene)
acetate 5a
Eluent: petroleum ether/ethyl acetate (80/20, v/v). Product 5a was
separated as yellow crystals, m.p. 209–211◦C, yield (55%). Anal. calcd.
for C21 H15N3O3(357.36): C, 70.58; H, 4.23; N, 11.76. Found: C, 70.67;
H, 4.34; N, 11.84%. IR (KBr): 1670 (C O ester) cm−1;1H NMR(CDCl3):
δ = 3.79 (s, 3H, COOCH ), 5.91 (s, 1H, exo CH), 7.84–7.65 (2H, d,
3
J = 7.8Hz, Ar), 7.83–7.86 (m, 3H, Ar), 8.37–8.41 (m, 5H, Ar), 8.57 (s,
1H, pyrano C CH) ppm; 13C NMR(CDCl3): δ = 51.6 (COOCH3), 166.5
(COOCH3), 140.3 (C CH), 127.9 (C CH), 101.2 (C CH, exo), 160.8
(C CH), 158.6 (CO, pyrano), 161.3, 158.3 (C N), 139.8, 126.4, 128.7,
128.0, 130.7, 129.3, 127.5, 132.1 (C Ar) ppm; MS: m/z (%) 357 (70)
[M+].

2352
M. H. N. Arsanious and M. E. Moharam
Ethyl-3-(6-oxo-3-phenyl-1,6-dihydro-1,2,4-triazin-5-yl)-3-
phenyl acrylate 4b
Eluent: petroleum ether/ethyl acetate (88/12, v/v). Product 4b was
separated as pale yellow crystals, m.p. 189–190◦C, yield (35%). Anal.
calcd. for C20H17N3O3 (347.37): C,69.15; H, 4.93; N, 12.10. Found: C,
69.28; H, 4.89; N, 12.25%. IR (KBr): 3230 (NH), 1700 (C O ester) cm−1
;
1H NMR (CDCl3): δ = 1.20 (t, 3H, J = 7.1Hz, CH2CH ), 4.25 (q, 2H,
3
J = 7.1Hz, CH CH3), 6.50 (s, 1H, =CH), 6.90–6.93 (d, 2H, Ar), 7.37–
2
7.42 (m, 5H, Ar), 8.13–8.18 (m, 3H, Ar), 11.30 (b, 1H, NH) ppm; 13C
NMR(CDCl3): δ = 14.2 (CH3), 64.2 (CH2), 167.8 (CO), 140.8 (C CH),
100.3 (C CH), 161.7 (C O NH), 161.3, 158.6 (C N), 129.6, 126.7,
127.4, 114.8, 131.0, 130.0, 132.2, 126.4 (C Ar) ppm; MS: m/z (%) 347
(48) [M+].
Ethyl(3,5-diphenyl-7H-pyrano[3,2-e][1,2,4]triazin-7-ylidene)
acetate 5b
Eluent: petroleum ether/ethyl acetate (92/8, v/v). Product 5b was
separated as yellow crystals, m.p.173–174◦C, yield (35%). Anal. calcd.
for C22H17N3O3(371.39): C, 71.15; H, 4.61; N, 11.31. Found: C, 71.01;
H, 4.68; N, 11.20%. IR (KBr): 1710 (C Oester)cm−1; 1H NMR(CDCl3):
δ = 1.30 (t, 3H, J = 7.3Hz, CH2CH ), 4.19 (q, 2H, J = 7.3Hz, CH CH3),
3
2
5.06 (s, 1H, exo CH), 7.80–7.75 (d, 2H, Ar), 7.83–7.86 (m, 3H, Ar), 8.37–
8.41 (m, 5H, Ar), 8.51 (s, 1H, pyrano C CH) ppm; 13C NMR(CDCl3): δ
= 14.2 (OCH2CH ), 61.4 (OCH2 CH3), 167.5 (CO-ester), 139.0 (C CH),
3
124.6 (C CH,pyrano), 161.2 (O C CH), 100.9 ( CH, exo), 161.3, 161.6,
158.7 (C-triazine), 140.0, 125.6, 128.4, 127.8, 131.4, 129.3, 128.5, 127.5
(C Ar) ppm; MS: m/z (%) 371 (80) [M+].
Reaction of 5-(4-methoxybenzoyl)-3-phenyl-1,2,4-triazin-6(1H)
one (2b) with phosphonium ylides 1a and 1b
A mixture of 0.001 mol 2b and 0.002 mol phosphonium ylide1a and 1b
in 30 cm3dry toluene was refluxed for 6 h. The volatile materials were
evaporated under reduced pressure. The residue was subjected to silica
gel column chromatography to give 4c, 5c, 4d and 5d.
Methyl-3-(4-methoxyphenyl)-3-(6-oxo-3-phenyl-1,6-dihydro-
1,2,4-triazin-5-yl) acrylate 4c
Eluent: petroleum ether/ethyl acetate (75/25, v/v). Product 4c was
separated as yellow crystals, m.p. 197–198◦C, yield (25%). Anal. calcd.
for C20H17N3O4(363.37): C, 66.11; H, 4.72; N, 11.56. Found: C, 66.23; H,
4.80; N, 11.50%. IR (KBr): 1664 (CO NH), 3230 (NH), 1670 (C O ester)
cm−1; 1H NMR(CDCl3): δ = 3.67 (s, 3H, COOCH3), 3.79 (s, 3H, OCH3),

Utilizing Witting and Wittig-Horner Reagents
2353
6.56 (s, 1H, CH), 6.89–6.94 (d, 2H, J = 6.90 Hz, Ar), 7.37–7.45 (m, 5H,
Ar), 8.13–8.16 (m, 2H, Ar), 10.60 (b, 1H, NH) ppm;13C NMR(CDCl3): δ
= 55.1 (COOCH3), 55.4 (OCH3), 167.8 (COOCH3), 140.2 (C CH), 100.6
(C CH), 161.8 (CO NH), 161.3, 158.6 (C N), 159.0, 124.6, 126.7, 127.8,
113.8, 129.6, 130.8, 128.2 (C Ar) ppm; MS: m/z (%) 363 (100) [M+].
Methyl-(5-(4-methoxyphenyl)-3-phenyl-7H-pyrano[3,2-
e][1,2,4] triazin-7-ylidene acetate 5c
Eluent: petroleum ether/acetone (96/4, v/v). Product 5c was sepa-
rated as yellow crystals, m.p. 214–215◦C, yield (65%). Anal. calcd. for
C22 H17N3O4 (387.39): C, 68.21; H, 4.42; N, 10.85. Found: C, 68.07; H,
4.56; N, 10.76%. IR (KBr): 1730 (C Oester) cm−1; 1H NMR(CDCl3): δ =
3.92 (s, 3H, COOCH3), 3.79 (s, 3H, OCH3), 5.87 (s, 1H, CHCOOCH3),
7.05–7.08 (d, 2H, J = 9.0 Hz, Ar), 7.51–7.53 (m, 3H, Ar), 7.88–7.85 (d,
2H, J = 9.0 Hz, Ar), 8.39–8.42 (m, 2H, Ar), 8.54 (s, 1H, N CH) ppm;13C
NMR (CDCl3): δ = 51.5 (COOCH3), 55.4 (OCH3), 166.7 (COOCH3), 139.0
(C CH, pyrano), 124.6 (C CH), 161.2 ( O C CH), 100.4 ( CH, exo),
157.5 (N C-O), 161.3, 158.6 (C N), 158.5, 128.0, 126.7, 127.4, 114.5,
129.2, 130.8, 133.2 (C Ar) ppm; MS: m/z (%) 387 (100) [M+].
Ethyl-3-(4-methoxyphenyl)-3-(6-oxo-3-phenyl-1,6-dihydro-
1,2,4-triazin-5-yl)acrylate 4d
Eluent: petroleum ether/ethyl acetate (85/15, v/v). Product 4d was
separated as pale yellow crystals, m.p. 190–191◦C, yield (30%). Anal.
calcd. for C21H19N3O4(377.39): C, 66.83; H, 5.07; N, 11.13. Found:
C, 66.75; H, 5.16; N, 11.24%. IR(KBr): 2930 (NH), 1748 (C O ester)
cm−1;1H NMR(CDCl3):δ = 1.24 (t, 3H, J = 7.0 Hz, CH2CH3), 4.24 (q,
2H, J = 7.0 Hz, CH2CH3), 3.85 (s, 3H, OCH ), 6.59 (s, 1H, CH), 6.89–
3
6.93 (m, 3H, Ar), 7.42–7.48 (m, 4H, Ar), 8.16–8.12 (m, 2H, Ar), 11.38
(b, 1H, NH) ppm;13C NMR (CDCl3): δ = 55.4 (OCH3), 14.2 (CH3), 60.3
(CH2), 166.5 (CO ester), 139.2 (C CH), 100.1 (C CH), 161.8 (CONH),
161.3, 158.6 (C N), 129.6, 124.6, 126.7, 127.8, 113.8, 130.8, 134.2, 158.4
(C Ar) ppm; MS m/z (%) 377 (90) [M+].
Ethyl-(5-(4-methoxyphenyl)-3-phenyl-7H-pyrano[3,2-e]
[1,2,4]triazin-7-ylidene) acetate 5d
Eluent: petroleum ether/acetone (96/4, v/v). Product 5d was sep-
arated as yellow crystals, m.p. 177–179◦C, yield (55%). Anal. calcd.
C23H19N3O4(401.41): C, 68.82; H, 4.77; N, 10.47. Found: C, 68.74; H,
1
4.86; N, 10.34%. IR (KBr): 1700 (C O ester) cm−1; H NMR (CDCl3):
δ 1.35 (t, 3H, J = 7.2 Hz, CH2CH ), 4.24 (q, 2H, J 7.2Hz, CH CH3),
3
2
3.92 (s, 3H, OCH3), 5.85 (s, 1H, exo CH), 7.05–7.07 (d, 2H, J = 7.2
Hz, Ar), 7.50–7.52 (m, 3H, Ar), 7.85–7.88 (m, 2H, J = 7.2 Hz, Ar),

2354
M. H. N. Arsanious and M. E. Moharam
8.40–8.43 (m, 2H, Ar), 8.54 (s,1H, pyrano C CH),13C NMR(CDCl3): δ
= 14.2 (OCH2CH3), 60.4 (OCH2CH3), 55.4 (OCH3), 166.2 (CO ester),
141.3 (C CH, pyrano), 121.6 (C CH, pyrano), 161.2 (O C CH), 100.9
(exo, = CH), 161.3, 162.7 (C N azine), 158.7 (N C-O), 158.4, 114.2,
127.4, 132.9, 127.5, 129.3, 130.7, 128.8 (C Ar) ppm; MS: m/z (%) 401
(80) [M+].
Reaction of 2b with benzoylmethylenetriphenylphosphorane
(1c)
To a solution of triazinone 2b (0.30g; 0.001 mol) in dry xylene, was
added ylide 1c (0.001 mol) and the reaction mixture was refluxed for
10 h. The solution was evaporated under reduced pressure and the
residue subjected to silica gel column chromatography to give 4e.
5-[1-(4-Methoxyphenyl)-3-oxo-3-phenylprop-1-en-1-yl]-3-
phenyl-1,2,4-triazin-6(1H)-one 4e
Eluent: petroleum ether/ethyl acetate (25/75, v/v). Product 4e was
separated as colorless crystals, m.p. 202–203◦C, yield 80%. Anal. calcd.
C25 H19N3O3(409.44): C, 73.34; H, 4.68; N, 10.26. Found: C, 73.25; H,
4.73; N, 10.12%. IR (KBr): 1721 (COPh), 3180 (NH), 1611 (C C, Ar)
cm−1; 1H NMR(CDCl3):δ = 3.89 (s, 3H, OCH3), 6.85 (s,1H, CH), 6.72–
7.19 (m, 5H, Ar), 7.81–7.54 (m, 5H), 7.3–7.42 (m, 4H, Ar), 8.57 (b, 1H,
NH); 13C NMR(CDCl3): δ = 54.2(OCH3), 186.3 (CO Ph), 143.0 (C CH),
123.6 (C CH), 161.3, 161.6, 158.7 (C-triazinon), 165.1 (CONH), 164.0,
155.0 (C N), 159.9, 114.2, 127.4, 124.9 (C6H4), 137.9, 129.9, 128.7,
134.6 (COC6H5), 127.9, 131.9, 128.7, 129.2 (C6H5) ppm; MS: m/z (%)
409 (100) [M+].
Reaction of triphenylphosphorane 1a-1 b with 3b
A mixture of 0.002 mol of 1a or 1b and 0.001 mol of 3b in 30 cm3
xylene was refluxed for 3–4 h. The reaction mixture was evaporated
under reduced pressure and then applied to silica gel column chroma-
tography to give adduct 6.
5-(4-Methoxyphenyl)-3-phenyl-5H-9-oxa-1,2,4,6-tetraaza-
benzocyclohepten-8-one-6-oxide 6
Eluent: petroleum ether/acetone (85/15, v/v). Product 6 was sep-
arated as yellow crystals, m.p. 220–221◦C, yield 80%. Anal. calcd.
C19 H14N4O4(362.34):C, 62.98; H, 3.89; N, 15.46. Found: C, 62.87;
H, 3.94; N, 15.50%. IR (KBr): 1565 (O←N CH), 1740 (CO lactone)

Utilizing Witting and Wittig-Horner Reagents
2355
1
cm−1; H NMR(CDCl3): δ = 3.92 (s, 3H, OCH3), 6.89 (s, 1H, CH), 7.28
(s, 1H, N CH), 7.42–7.43 (d, 2H, J = 8.7 Hz, Ar), 7.47–7.45 (m, 3H,
Ar), 8.02–7.99 (d, 2H, J = 8.7 Hz, Ar), 8.14–8.11 (m, 2H, Ar) ppm;
13C NMR(CDCl3): δ = 55.49 (OCH3), 103.9 (HC N→O), 163.0 (O←N
= CH), 158.9 (O CO), 159.4, 162.4 (C N), 153.2 (= C O ), 156.8,
119.5, 125.6, 126.7, 127.8, 123.8, 132.7, 114.3 (C Ar) ppm; MS: m/z
(%) 362 (80) [M+].
Reaction of Trimethylphosphonoacetate 7 with 2a and 2b
A suspension of NaH (0.048 g; 0.002mol) in 15 ml of anhydrous DMF
was added slowly to a stirred solution of reagent 7 (0.36g, 0.002 mol) in
anhydrous DMF at 0◦C. After the addition was completed (15 min), a
solution of 2a or 2b (0.001 mol) in anhydrous DMF (10 ml) was added
and the resulting mixture was allowed to warm at r.t., and then stirred
for additional 10–15 h (TLC). To the reaction mixture, few drops of
water was added, and extracted with CHCl3 and the combined organic
phase was dried over anhydrous Na2SO4. After removal of the solvent
under vacuum, the resulting residue was applied to silica gel column
chromatography to give products 8a, 8b, 9a and 9b.
5-Hydroxy-3,5-diphenyl-5,6-dihydro-7H-pyrano[3,2-e]
[1,2,4]triazin-7-one 8a
Eluent: petroleum ether/ethyl acetate (15/85, v/v). Product 8a was
separated as colorless crystals, m.p. 272–273◦C, yield (35%). Anal.calcd.
C18H13N3O3(319.31): C, 67.71; H, 4.10; N, 13.16. Found: C, 67.82;
H, 4.18; N, 13.29%. IR(KBr): 3540 (OH), 1720 (CO, lactone) cm−1;1H
NMR(DMSO): δ = 3.50 (s, 2H, CH2), 7.82–7.81 (m, 5H, Ar), 7.49–7.48
(m, 5H, Ar), 12.5 (b, 1H, OH) ppm. 13C NMR(DMSO): δ = 55.0 (CH2),
78.1 (C OH), 168.0 (CO lactone), 155.5, 154.7, 146.9 (C N), 143.8,
129.1, 126.9, 127.8, 123.8, 132.7, 129.9, 128.9 (C Ar) ppm; MS : m/z
(%) 319 (25) [M+].
(6-Methoxy-3-phenyl-1,2,4-triazin-5-yl)(phenyl)methanone 9a
Eluent: petroleum ether/ethyl acetate (92/8, v/v). Product 9a was sep-
arated as pale yellow crystals, m.p. 178–180◦C, yield 55%. Anal.calcd.
C17H13N3O2(291.30): C, 70.09; H, 4.50; N, 14.42. Found: C, 70.16; H,
1
4.62; N, 14.34%. IR(KBr): 1730 (CO) cm−1; H NMR(DMSO): δ = 3.92
(s, 3H, OCH3), 7.45–7.68 (m, 6H, Ar), 7.79–8.01 (d, 2H, J = 7.8 Hz, Ar),
8.01–8.16 (d, 2H, J = 7.8 Hz, Ar) ppm; 13C NMR(DMSO): δ = 52.4
(OCH3), 176.8 (CO), 155.1, 154.7, 164.9 (C N), 134.8, 129.1, 126.9,

2356
M. H. N. Arsanious and M. E. Moharam
127.8, 123.8, 132.7, 129.4, 128.1 (C Ar) ppm; MS: m/z (%) 291 (85)
[M+].
5-Hydroxy-5-(4-methoxyphenyl)-3-phenyl-5,6-dihydro-7H-
pyrano [3,2-e][1,2,4]triazin-7-one 8b
Eluent: petroleum ether/ethyl acetate (20/80,v/v). Product 8b was
separated as colorless crystals, m.p. 234–235◦C, yield (40%). Anal.calcd.
C19H15 N3O4 (349.34): C, 65.32; H, 4.33; N, 12.03. Found: C, 65.16;
H, 4.46; N, 12.12%. IR(KBr): 3530 (OH), 1724 (CO, lactone) cm−1;1H
NMR(DMSO):δ = 3.91 (s, 3H, OCH3), 3.16 (s, 2H, CH2), 6.97–7.00 (d,
2H, J = 9.0 Hz, Ar), 7.44–7.47 (m, 3H, Ar), 7.95–7.98 (d, 2H, J = 9.0 Hz,
Ar), 8.12–8.16 (m, 2H, Ar), 2.50 (b, 1H, OH) ppm; 13C NMR(DMSO): δ
= 53.4 (OCH3), 55.0 (CH2), 78.5 (C—OH), 158.8 (CO lactone), 156.5,
155.7, 147.9 (C N), 159.6, 134.8, 129.1, 126.9, 127.8, 132.7, 129.6, 114.6
(C Ar) ppm; MS: m/z (%) 349 (25) [M+].
(6-Methoxy-3-phenyl-1,2,4-triazin-5-yl)(4-
methoxyphenyl)methanone 9b
Eluent: petroleum ether/ethyl acetate (95/5, v/v). Product 9b was
separated as pale yellow crystals, m.p. 200–201◦C yield (45%). Anal.
calcd. C18H15 N3O3 (321.33): C, 67.28; H, 4.71; N, 13.08. Found: C, 67.16;
1
H, 4.82; N, 13.22%. IR(KBr): 1730 (CO) cm−1; H NMR(DMSO): δ =
3.91 (s, 6H, OCH3), 6.97–7.00 (d, 2H, J = 7.2 Hz, Ar), 7.46–7.47 (m, 3H,
Ar), 7.95–7.98 (d, 2H, J = 7.2 Hz, Ar), 8.12–8.16 (m, 2H, Ar) ppm;13C
NMR(DMSO): δ = 53.6 (O CH3), 54.4 (p-OCH3), 179.4 (CO), 155.5,
154.7, 149.9 (C N), 160.2, 134.8, 129.1, 126.9, 127.8, 127.0, 132.7, 114.3
(C Ar) ppm; MS: m/z (%) = 321 (90) [M+].
Reaction of Trimethylphosphonoacetate (7) with 3a and 3b
A solution of 0.002 mol of sodium methoxide in absolute methanol was
treated with an equimolar amount of the phosphonate 7 (0.36g; 0.002
mol), after 5 min, 3a or 3b (0.001 mol) was added, the reaction mixture
was boiling under reflux for 4 h. To the reaction mixture, a few drops
of water were added, and extracted with ethyl acetate. The extract was
evaporated under reduced pressure and the residue subjected to silica
gel column chromatography to give products 10a, 11a, 10b, and 11b.
5-[Methoxyimino(phenyl)methyl]-3-phenyl-1,2,4-triazin-
6(1H)-one 10a
Eluent: petroleum ether/ethyl acetate (82/18, v/v). Product 10a was
separated as pale yellow crystals, m.p.230–231◦C, yield (60%). Anal.

Utilizing Witting and Wittig-Horner Reagents
2357
calcd. C17H14N4O2(306.32): C, 66.66; H, 4.61; N, 18.29. Found: C, 66.58;
H, 4.70; N, 18.35%. IR(KBr): 1730 (CO), 3240 (NH) cm−1 1H NMR
;
(DMSO): δ = 3.92 (s, 3H, N OCH3), 7.20(s, 1H, NH), 7.37–7.64 (m, 5H,
Ar), 7.93–8.20 (m, 5H, Ar) ppm;13C NMR(DMSO): δ = 160.5 (C N), 61.6
(N OCH3), 164.3 (CO), 155.5, 154.7 (C N), 134.8, 129.1, 126.9, 127.8,
125.8, 130.7, 114.9, 128.9 (C Ar) ppm; MS: m/z (%) 306 (75) [M+].
3,5-Diphenylisoxazolo[4,5-e]-1,2,4-triazine 11a
Eluent: petroleum ether/ethyl acetate (95/5, v/v). Product 11a was
separated as yellow crystals, m.p. 180–183◦C, yield (30%). Anal. calcd.
C16H10N4O(274.28): C, 70.06; H, 3.67; N, 20.43. Found: C, 70.15; H,
1
3.60; N, 20.35%. IR(KBr): 1570 (C NO) cm−1; H NMR(CDCl3): δ =
7.37–7.60 (m, 5H, Ar), 7.83–8.02 (m, 5H, Ar) ppm;13C NMR(DMSO): δ
= 156.4 (C O N), 152.2 (C N), 151.5, 161.7 (C N), 131.0, 134.8, 128.1,
125.9, 127.8, 123.8, 132.7, 126.9 (C Ar)ppm; MS: m/z (%) 274 (75) [M+].
5-[Methoxyimino(4-methoxyphenyl)methyl]-3-phenyl-12,4-
triazin-6(1H)-one 10b
Eluent: petroleum ether/acetone (82/18, v/v). Product 10b was sepa-
rated as pale yellow crystals, m.p. 214–215◦C, yield (65%). Anal. calcd.
C18H16N4O3(336.34): C, 64.28; H, 4.79; N, 16.66. Found: C, 64.34; H,
4.84; N, 16.71%. IR (KBr): 1730 (CO), 3240 (NH) cm−1;1H NMR(CDCl3):
δ = 3.91 (s, 3H, OCH3), 3.86 (s, 3H, N OCH3), 7.16 (s, 1H, NH), 6.88–
7.03 (m, 3H, Ar), 7.42–7.57 (m, 3H, Ar) 8.17–8.19 (m, 3H, Ar) ppm;
13C NMR(DMSO):δ = 55.7 (OCH3), 162.5 (C N), 61.6 (N OCH3), 165.1
(CO), 160.5, 154.7 (C N), 161.2, 134.8, 129.1, 126.9, 127.8, 125.8, 130.7,
114.9 (C Ar) ppm; MS: m/z (%) 336 (75) [M+].
3(4-Methoxyphenyl)-5-phenylisoxazolo[4,5-e]-1,2,
4-triazine 11b
Eluent: petroleum ether/acetone (95/5, v/v). Product 11b was sep-
arated as yellow crystals, m.p. 220–222◦C, yield 30%. Anal. calcd.
C17H12N4O2(304.30): C, 67.10; H, 3.97; N, 18.41. Found: C, 67.24; H,
1
3.86; N, 18.52%. IR (KBr): 1568 (C NO) cm−1; H NMR (CDCl3): δ =
3.95 (s, 3H, OCH3), 7.13–7.62 (m, 2H, Ar), 7.60–7.62 (m, 3H, Ar) 8.53–
8.56 (m, 2H, Ar) 8.65–8.68 (m, 2H, Ar) ppm; 13C NMR(DMSO): δ = 55.4
(OCH3), 158.4 (N O C), 152.5 (C N), 160.1, 154.7(C N), 159.2, 134.8,
129.1, 126.9, 127.8, 123.8, 132.7, 114.9 (C Ar) ppm; MS: m/z (%) 304
(25) [M+].
Biological Activity
The antibacterial and antifungal activities were carried out in the
Microbial Department, National Research Centre, using the diffusion

2358
M. H. N. Arsanious and M. E. Moharam
TABLE I The Antibacterial and Antifungal Activities of the
Synthesized Compounds
Inhibition zone diameter mm/mg sampl
Gram
Strain
reaction Chloroform
Compound No
2b 5d
Control
Reference
Micro-organism
5c
11b antibiotic
Bacillus subtilis
Bacillus cereus
Escherichia coli
Pseudomonas aeruginose
Staphylococcus aureus
Candida albicans
+ve
+ve
0.0
0.0
0.0
0.0
0.0
0.0
0.0 0.0 0.0
0.0 0.0 0.0
30
0.0
11
0.0
0.0
10
40
30
20
35
50
44
−ve
16
11
11
−ve
0.0 0.0 0.0
+ve
16
15
0.0 0.0
12 10
fungus
plate method.21–24 A filter paper sterilized disc saturated with mea-
sured quantity (1ml, mg/ml) of the sample is placed on a plate (9 cm
diameter) containing a solid bacterial medium (nutrient agar broth) or
a fungal medium (Dox’s medium) which has been seeded with the spore
suspension of the test organism. After incubation at 37◦C for 24 h for
bacteria (in case of fungi, at 25◦C for 72 h), the diameter of the clear
zone of inhibition surrounding the sample is taken as a measure of the
inhibitory power of the sample against the particular test organism
(% inhibition = sample inhibition zone (cm)/plate diameter × 100). All
measurements were done in chloroform as a solvent which has zero inhi-
bition activity. The antimicrobial activity of the tested compounds were
examined with gram positive bacteria Bacillus subtilis, Bacillus cereus
and Staphylococcus aureus and gram negative bacteria Escherichia coli,
Pseudomonas aeruginose and fungus Candida albicans. The obtained
results are compared with reference antibiotics that were purchased
from Egyptian markets.
As shown in (Table 1), the compounds 5c, 2b,5d, 11b were found
be active against gram negative bacteria Escherichia and Candida al-
bicans. Compound 11b was found to be active against gram positive
bacteria Bacillus subtilis, while the other derivatives have inhibitory
effect against the same microorganism.
REFERENCES
[1] a)V.V. Smirnov and E.A. Kiprianova Bacteria of the Pseudomonas Genus (in Russian)
100–121(1990) Naukova Dunika, Kliev; b) Deepti Dwivedi and B.N. Johri; Current
Science 85(12), 1693 (2003).
[2] V.V. Simirnov, E.A. Kiprianova, A.D. Garagulya, S.E. Esipov, and S.A. Dovjenko FEMS
Microbiology 153, 357 (1997); C.A.127, 231635t (1997).

Utilizing Witting and Wittig-Horner Reagents
2359
[3] D. Christian, C. Micheal, and G. Susanne, Heterocycles 20, 1581 (1983).
[4] R.G. Glushkov, L.A. Nikolaeva, O.V. Kozlova, L.N. Dronova, V.A. Chernov, and S.M.
Minakova, Khim-Farm Zh 18(6), 674 (1984); C.A. 102, 6372u (1985).
[5] J.P. Van Wauwe, and P.A.J. Janssen J. Med. Chem. 32, 2231(1989), P.A. Cole, and C.H.
Robinson, J. Med. Chem. 32, 2933(1990); L.J. Brown, C. Gude, H. Rodriguez, and
R.E. Steele, J. Med. Chem. 34, 725(1991).
[6] B.H. Vanden, H. Moereels, and L.M.H. Koymans, Breast Cancer Res. Treat. 30, 43
(1994); C.A. 123, 160775t (1995); J.M. O’Reilly, and R.W. Brueggemeier, Curr. Med.
Chem. 3, 11(1996); C.A. 124, 306219j (1996).
[7] L.S. Boulos, and M.H.N. Arsanious, Tetrahedron 53, 3649(1997).
[8] L.S. Boulos, and M.H.N. Arsanious, Synthetic Communications 32, 2779(2001).
[9] L.S. Boulos, and M.H.N. Arsanious, Heteroatom Chemistry 12, 511(2002).
[10] L.S. Boulos, M. A.Yakout, and M.H.N. Arsanious, Phosphorus Sulfur, Silicon 181 (7):
1615(2006).
[11] L.S. Boulos, N.K. El Din, and M.H.N. Arsanious Phosphorus, Sulfur Silicon 181 (6):
1467(2006).
[12] M.H.N. Arsanious, and L.. Boulos; Mh Chem 137: 1177(2006).
[13] L.S. Boulos, M.H.N. Arsanious and M. A. Yakout, Mh Chem 138: 979 (2007).
[14] M. Hesse, H. Meier, and B. Zech, Spektroskopische Methoden in der Organischen
Chemie G, Thieme Stuttgart (1979).
[15] G. Wittig, and K. Schollkopf, Chem. Ber. 87,1318(1954).
[16] a) V.O. Koz’minykh, N.M. Igidov, E.N. Koz’minykh, L.O. Kon’shina, Z.N.
Semenova, N.V. Lyadova, A.N. Plaksina and Yu.S. Andreichikov, Pharm. Chem.
J. (Engl Transl),25, 891(1991); C.A. 116, 105997x(1992): b) Yu.S. Andreichikov,
V.O. Koz’minykh and E.N. Manelova, J Org. Chem. USSR(Engl Transl),21,363
(1985); C.A. 103, 37302w(1985): c) V.O.Koz’minykh, E.N. Koz’minykh, and
Yu.S.Andreichikov, Chemistry Heterocyclic Compound (Engl Transl), 25, 862(1989);
C.A. 111, 7391x (1989).
[17] H.J. Bestmann, Angew Chem, 77, 850(1965); Angew Chem Int. Ed. Engl. 4,
830(1965).
[18] M. Mercey, and P. ToubeJ Chem Res Synop 63, 13 (1987), Chem Abstr 107:
236149x(1988).
[19] J. Villieras, and Ramboud,Synthesis 924(1982),.
[20] K. Nalepa and J. Slouka, Coll. Czech, Chemistry Communication 42, 2182(1977).
[21] R.J. Grager and J.B. Harbone, Phytochemistry 37, 19 (1994).
[22] O.N. Irob, M. Moo-Young, and W.A. Anderson, Internat. J Pharmacog. 34,87(1996).
[23] E. Jawetz, J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology Lang
Medical Publication, Los Altos, California (1974).
[24] D.N. Muanza, B.W. Kim, K.L. Euler, and L. Williams, Internat J Pharmacog. 32,
337(1994).