Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solvent-free conditions and their anti-fungal activity

Article abstract of DOI:10.1016/j.jfluchem.2004.10.015

A rapid one-pot solvent-free procedure has been developed for the synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones by neat three-component cyclocondensation of anthranilic acid, phenyl acetyl chloride and substituted anilines under microwa

Full text of DOI:10.1016/j.jfluchem.2004.10.015

Journal of Fluorine Chemistry 126 (2005) 307–312
www.elsevier.com/locate/fluor
Green chemical multi-component one-pot synthesis of
fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under
solvent-free conditions and their anti-fungal activity
*
Anshu Dandia , Ruby Singh, Pritima Sarawgi
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
Received 31 March 2004; accepted 26 October 2004
Available online 8 March 2005
Abstract
A rapid one-pot solvent-free procedure has been developed for the synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones by neat
three-component cyclocondensation of anthranilic acid, phenyl acetyl chloride and substituted anilines under microwave irradiation. The
experimental methodology and microwave conditions described here are well established, allowing significant rate enhancement and good
yields compared to conventional reaction conditions. The reaction is generalized for o-, m- and p-substituted anilines with electron-donating
and -withdrawing groups to give quinazolin-4(3H)-ones. Synthesized compounds have been screened for their anti-fungal activity.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Quinazolines; Three-component system; Microwave irradiation
1. Introduction
patents mention the utility of fluorinated quinazolines as
important anti-fungal [6], herbicidal [7], pesticidal [8], CNS
depressant [9] and AMPA inhibitors [10], etc. Thus, their
synthesis has been of great interest in the elaboration of
biologically active heterocyclic compounds.
Quinazoline compounds are reported to be physiologi-
cally and pharmacologically active and find applications in
the treatment of several diseases like leprosy and mental
disorder and also exhibit a wide range of activities [1]. A
well known methaquolone [2] having quinazoline nucleus, is
a sedative and hypnotic drug and reported to possess
anticonvulsant activity.
Microwave-induced rate enhancement of various reac-
tions is becoming popular with organic chemists [11].
However, recently, more interest has been focussed on ‘dry
media’ synthesis and particularly on solvent-free procedure
using various mineral oxides [12] and solvent-less reactions
with neat reactants in the absence of a catalyst or solid
support [13]. Recently, the diversity generating potential of
multi-component reactions (MCRs) has been recognized
and their utility in preparing libraries to screen for functional
molecules is well appreciated. Consequently, the design of
novel MCRs is an important field of research [14].
Recently, several scientists elucidated that quinazoline
system possess variable sites at positions 2 and 3 which can
be suitably modified by the introduction of different
heterocyclic moieties to yield the potential anticonvulsant
agents [3].
Incorporation of fluorine atoms or CF3 group to
heterocycles is known to influence the biological activity
[4]. Fluorinated quinazoline has been the attraction of
pharmacologists and chemists during last several years due
to wide variety of activity possessed by them [5]. Number of
Conventional synthesis of disubstituted quinazolin-
4(3H)-ones involves two steps [15] i.e. (i) cyclodehydration
of 2-benzamidobenzoic acid (I) with excess of acetic
anhydride under anhydrous conditions and removal of
excess of acetic anhydride under reduced pressure gave
benzoxazin-4-one (II) (ii) refluxing the II with amines in
* Corresponding author. Tel.: +91 141 520301; fax: +91 141 523637.
E-mail address: dranshudandia@eth.net (A. Dandia).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.10.015

308
A. Dandia et al. / Journal of Fluorine Chemistry 126 (2005) 307–312
Table 1
Comparative studies for the synthesis of IVa
Method
A
Medium
MW power (W)
Time (min)
Yield (%)
Temperaturea (8C)
(a) Acidic alumina
640
640
640
640
640
4 + 10
82
88
92
91
90
132
141
165
162
164
(b) Montmorillonite KSF
Neat (without solvent and support)
Neat (path I)
3 + 7
B
C
5
4
5
Neat (path II)
Time 4 + 10 indicates that first irradiation for 4 min gives compound II (detected by TLC) and then further irradiation after adding 3-trifluoromethyl aniline for
10 min yield IVa.
a
Measured immediately after the reaction using a glass thermometer.
Scheme 1.
glacial acetic acid/pyridine [16]. The products were
obtained in moderate yield and require 10–12 h refluxing.
Although the synthesis of 3H-quinazolin-4-one core
nucleus under microwaves is reported involving the reaction
of anthranilic acid with formamide [17]. But to the best of
our knowledge no report is available in the literature for
fluorinated disubstituted quinazolines involving multi-
component reaction for the synthesis of series of compounds
to make them available for bioactivity evaluation.
2. Results and discussion
In method A, the intermediate benzoxazin-4-one (II) was
synthesized ‘in situ’ by the cyclodehydration of I with acetic
anhydride using inorganic solid supports. The method is
environmentally friendly, as acetic anhydride remains
adsorbed over the solid support and there is no evaporation
into the atmosphere.
The condensation reaction of II with para-/meta-/ortho-
substituted fluorinated anilines have been studied. Meta-/
para-substituted anilines gave cyclized product quinazoline
(IV). While the ortho-substituted anilines gave an inter-
mediate o-acylaminobenzanilide (III), which is in contrast
to earlier report of Mishra et al. [15] where they reported the
formation of cyclized quinazolones in case of ortho-
substituted anilines also.
For the afore-mentioned reasons and in view of our
general interest in the development of environmentally
friendlier synthetic alternatives using microwaves [18], we
studied extensively the synthesis of fluorine containing
quinazolin-4(3H)-ones under microwave irradiation by
various methods (Table 1) i.e. (A) using inorganic solid
support montmorillonite KSF/acidic alumina (Scheme 1);
(B) neat one-pot synthesis without using any dehydrating
agent, solvent or support (Schemes 2 and 3). The best
results obtained from neat synthesis (method B) have been
reported.
Although, the solvent-free procedure using inorganic
support under microwaves is an attractive ecofriendly
methodology, it requires appreciable amount of solvent for
adsorption of reactants and elution of products.
Further, in view of our aim to synthesize a series of
fluorinated 2,3-disubstituted quinazolones with pharmaco-
phoric groups and to establish structure activity relationship
in quinazolones, we have developed a ‘green chemistry
procedure’ using neat multi-component reaction conditions,
which aims at complete elimination of the solvent as well as
Scheme 2.

A. Dandia et al. / Journal of Fluorine Chemistry 126 (2005) 307–312
309
Scheme 3.
solid support from the reaction. These no-solvent reactions,
when coupled with microwave irradiation prove to be
advantageous for environmental reasons as well, due to their
uniforating effect and shorter reaction time.
any dehydrating agent, solvent or support. Reaction
occurred in shorter time with easier work-up process and
this method was applicable even when o-substituted anilines
were used, while conventional methods failed to give IV in
case of o-substituted anilines.
Experimentally, anthranilic acid, phenyl acetyl chloride
and corresponding amines are admixed and irradiated inside
the microwave oven. The formation of final product
quinazolone (IV) can proceed via two pathways I and II
(Scheme 3).
The formation of o-acyl aminobenzanilide (III) and
quinazoline 4(3H)-ones (IV) have been confirmed on the
basis of spectral studies. The IR spectra of IIIa,b (Table 2)
showed characteristic absorption bands at 3360–3400 (NH),
1
Path I involves first N-phenylacetylation of anthranilic
acid and condensation of resultant 2-benzamidobenzoic acid
(I) with the amines and then intramolecular amidation of the
intermediate amidine (V) afforded the desired final product
IV. While another path II involves N-phenylacetylation of
amines instead of anthranilic acid. The possibility of all
routes are confirmed by isolation of intermediates in some
cases or the reaction of 2-benzamidobenzoic acid (I) with
3-trifluoromethylaniline and the condensation of VI with
anthranilic acid were conducted under microwave irradia-
tion, the desired product IVa was obtained in few minutes.
Thus, N-phenylacetylation step occurs very quickly.
Attempts to use PhCH2COOH instead of PhCH2COCl were
not successful.
1700–1680 (both C O). The H NMR spectra of IIIa,b
showed broad peaks at d 8.92 and 9.25 ppm due to two
NHCO protons (exchangeable with D2O) and a singlet at d
4.22–4.26 ppmdue to COCH2Ph protons. 13C NMR spectrum
of IIIa also showed the presence of two carbonyl signals at d
169.9 and 169.2 ppm. The remaining signals were obtained at
d 140.8, 133.9, 133.6, 133.4, 130.7, 128.8, 128.3, 127.9,
126.4, 126.3, 125.5, 125.3, 125.3, 121.8, 120.1, 119.2
(aromatic and CF3 carbon) and 45.0 (CO–CH2) ppm.
IR spectra of quinazolones IVa–f (Table 3) showed the
only one carbonyl absorption band at 1695–1700 cmÀ1
and 1605–1610 (C N) cmÀ1 confirms the ring closure in
all compounds. It was further confirmed on the basis of
13C NMR spectrum of IVd which showed only one signal
at d 169.7 (C O) ppm along with other peaks at 155.4
(C N), 139.5, 138.6, 137.5, 135.8, 131.3, 130.9, 129.3,
128.6, 127.3, 126.4, 125.6, 123.3, 122.0, 120.7, 119.5
In conclusion, we have introduced a simple one-pot
multi-component cyclocondensation reaction for the synth-
esis of disubstituted quinazolin-4(3H)-ones without using
Table 2
Physical and analytical data of o-acylaminobenzanilide (IIIa,b)
Compound
R
Time (min)
Yield (%)
Temperaturea (8C)
Melting point (8C)
Molecular formula
IIIa
IIIb
a
2-CF3C6H4
2-F. C6H4
3 + 7
3 + 6
89
85
140
139
160
168
C22H17F3N2O2
C21H17FN2O2
Measured immediately after the reaction using a glass thermometer.

310
A. Dandia et al. / Journal of Fluorine Chemistry 126 (2005) 307–312
Table 3
Physical and analytical data of 2-phenylmethyl-3-(substituted-phenyl)-quinazolin-4(3H)-ones (IVa–f)
Compound
R
Method A
Method B
Melting
Molecular
formula
point (8C)
Time
(min)
Yield
(%)
Temperaturea
Time
(min)
Yield
(%)
Temperature
(8C)
(8C)
IVa
IVb
IVc
IVd
IVe
IVf
3-CF3ÁC6H4
3-FÁC6H4
3 + 7
3 + 6
3 + 7
–
88
82
81
–
141
142
137
–
5
5
5
4
6
5
92
87
88
92
91
90
165
165
164
159
150
155
101
185
166
129
182
142
C22H15F3N2O
C21H15FN2O
C22H14ClN2O
C22H15F3N2O
C21H15FN2O
C21H15FN2O
3-CF3Á4-ClÁC6H3
2-CF3ÁC6H4
2-FÁC6H4
–
–
–
4-FÁC6H4
–
–
–
Method A: using inorganic solid support; method B: neat one-pot synthesis. All compounds gave satisfactory elemental analysis (C, H and N) within Æ0.25% of
theoretical value.
a
Measured immediately after the reaction using a glass thermometer.
(aromatic and CF3 carbon) and 24.1 (CH2Ph) ppm.
Further, the disappearance of NH peaks in IVa–f peaks
at (d 8.92 and 9.25 ppm) showed the formation of
quinazolones (IV). The presence of fluorine attached to
phenyl ring has been confirmed by 19F NMR. The detailed
spectral data of compound IIIa,b and IVa–f are given in
Table 6. In the mass spectrum of representative
compounds the molecular ion peak at m/z 398 and 380
(100%) was corresponding to the molecular weight of
compounds IIIa and IVd, respectively.
prepared in flasks and sterilized. To this medium, a requisite
quantity of solution was added and then the medium was
poured into Petri plates in three replication. A culture of test
fungus was grown on PDA for 6–7 days. Small disc (4 mm)
of fungus culture was cut with a sterile cork-borer and
transferred asceptically, upside-down in the center of
petridishes containing the medium and fungicides. Plates
were incubated at 25 Æ 1 8C for 6 days. Colony diameter
was measured and data was statistically analysed (Table 4).
2.3. Pot trial method
2.1. Evaluation of anti-fungal activity
White-seeded sorghum grains were soaked in water for
about 12 h [20]. Hundred and sixty grams of the soaked
kernels were placed in 500 ml flasks and 20 ml of water was
added to each. The material was autoclaved twice on
successive days before inoculation. After sterilization,
fungus bits were inoculated in each flask and flasks were
kept for 10 days at 25–27 8C. Hundred seeds of okra were
taken for one treatment of each compound. Inoculum was
added at 2 g/kg of soil, 3 days prior to sowing. Sowing was
done after 3 days and germination data were recorded after
7, 15 and 25 days of sowing. Suitable checks were
maintained and the data was statistically analysed
(Table 5). ‘Baynate’ and ‘Thiram’ are standard fungicides
used as seed dressers to control this disease. ‘Baynate’ was
found best in reducing the plant mortality.
The synthesized compounds were screened for anti-
fungal activity against three pathogenic fungi, namely
Rhizoctonia solani, causing root rot of okra, Fusarium
oxysporum, causing wilt of mustard and Colletotrichum
capsici causing leaf spot and fruit rot of chilli. It was done by
two methods (Tables 4–6).
2.2. Poison plate technique
The compounds synthesized were dissolved in acetone
and compounds were prepared in 1000 and 500 ppm
concentrations [19]. Potato–dextrose–agar medium was
Table 4
Effect of concentrations of different chemicals on the mean radial growth
(cms) of different fungi in vitro
Table 5
Evaluation of quinazolin-4(3H)-ones derivatives as seed dressers against
Rhizoctonia solani causing root rot of okra (in pot trial)
Compound
Rhizoctonia
solani
Fusarium
Colletotrichum
capsici
oxysporum
Compound
Percent
Plant stand
25 DAS
1000
ppm
500
1000
ppm
500
1000
ppm
500
germination 7 DAS
ppm
ppm
ppm
IVa
IVb
IVc
IVd
Ve
Vf
42.00
63.00
70.00
58.00
28.00
59.00
98.00
79.00
12.00
95.00
48.00
45.00
42.00
41.00
21.00
40.00
64.00
68.00
4.00
IVa
IVb
IVc
IVd
IVe
IVf
Check
CD 1%
1.08a
2.58
1.83
2.08
6.67
1.92
9.00
1.22
1.75
1.50a
2.58
7.67
8.25
3.83
9.00
1.02
1.58
1.60
2.25
2.92
1.08a
1.25
8.17
0.77
1.83
3.92
4.25
5.00
1.67
1.58a
8.17
1.14
1.33
2.58
1.75
1.50
0.75a
2.50
7.33
1.03
2.17
3.67
3.25
3.50
1.25a
4.08
7.33
1.08
Baynate (0.2%)
Thiram (0.3%)
Check with inoculum
Check without inoculum
90.00
At par with minimum value.
a
Minimum value.
DAS: days after sowing.

A. Dandia et al. / Journal of Fluorine Chemistry 126 (2005) 307–312
311
Table 6
Spectral data of compounds IIIa,b and IVa–f
Compound
IR (cmÀ1
)
1H NMR (d, ppm)
19F NMR (d, ppm)
À64.21 (s, CF3)
IIIa
3365–3395 (2Â NH), 3060, 2940, 2850
(aromatic and aliphatic C–H), 1700,
1680 (2Â C O), 1490 (NO2)
d 4.22 (s, 2H, CH2Ph), 6.90–8.35
(m, 13H, Ar–H), 8.92 and 9.25
(2Â bs, 2Â 1H, 2Â NH exchangeable with D2O)
d 4.26 (s, 2H, CH2Ph), 6.98–8.26
IIIb
IVa
IVb
IVc
IVd
IVe
IVf
3360–3400 (2Â NH), 3060, 2955, 2860
(aromatic and aliphatic C–H),1700,
1685 (2Â C O), 680, 720.
À119.90 (s, 2-F)
À63.38 (s, CF3)
À119.61 (s, 3-F)
À63.21 (s, CF3)
À64.45 (s, CF3)
À119.61 (s, 2-F)
118.88 (s, 4-F)
(m, 13H, Ar–H), 8.95 and 9.22 (2Â bs, 2Â
1H, 2Â NH exchangeable with D2O)
d 3.96 (s, 2H, CH2Ph), 6.88–7.19
3050, 2940, 2840 (aromatic and aliphatic C–H),
1700 (C O), 1605 (C N)
(m, 5H, phenyl ring protons of CH2Ph),
7.22–8.18 (m, 7H, Ar–H), 8.40 (dd, 1H, 5-H)
d 3.95 (s, 2H, CH2Ph), 6.84–7.10
3050, 2980, 2860 (aromatic and aliphatic C–H),
1695 (CO), 1605 (C N)
(m, 5H, phenyl ring protons of CH2Ph),
7.19–8.14 (m, 7H, Ar–H), 8.39 (dd, 1H, 5-H)
d 3.98 (s, 2H, CH2Ph), 6.86–7.12
3040, 2970, 2860 (aromatic and aliphatic C–H),
1705 (C O), 1608 (C N)
(m, 5H, phenyl ring protons of CH2Ph),
7.25–8.15 (m, 6H, Ar–H), 8.38 (dd, 1H, 5-H)
d 3.95 (s, 2H, CH2Ph), 6.82–7.15
3040, 2970, 2860 (aromatic and aliphatic C–H),
1700 (C O), 1608 (C N)
(m, 5H, phenyl ring protons of CH2Ph), 7.31–8.25
(m, 7H, Ar-H), 8.45 (dd, 1H, 5-H)
3050, 2980, 2850 (aromatic and aliphatic C–H),
d 3.96 (s, 2H, CH2Ph), 6.85–7.18
1700 (C O), 1610 (C N)
(m, 5H, phenyl ring protons of CH2Ph),
7.21–8.10 (m, 7H, Ar–H), 8.40 (dd, 1H, 5-H)
3.97 (s, 2H, CH2Ph), 6.88–7.19
3060, 2980, 2860 (aromatic and aliphatic C–H),
1700 (C O), 1615 (C N)
(m, 5H, phenyl ring protons of CH2Ph), 7.10–8.10
(m, 7H, Ar–H), 8.39 (dd, 1H, 5-H)
3. Experimental
the reaction mixture and irradiated for appropriate time
(Table 1). The product was extracted into ethanol and the
excess solvent was evaporated on a roto-evaporator to give
compound, which was purified by methanol and identified as
IVa (Scheme 1).
From the comparative results, it has been observed that
the montmorillonite KSF is the best solid support as
compared to acidic alumina (Table 1). The remaining
compounds IVb,c and IVf (in case of meta-/ para-
substituted anilines) and IIIa,b (in case of ortho-
substituted anilines) were similarly prepared by using
montmorillonite KSF.
Melting points were determined in open glass capillary
and were uncorrected. IR spectra were recorded on a Perkin-
Elmer (Model-577) in KBr pellets. 1H NMR and 13C NMR
were recorded on Jeol model FX 90Q and Bruker-DRX-300
using CDCl3 as solvent and TMS as internal reference at
89.55 and 75.47 MHz, respectively. 19F NMR was recorded
on Jeol model FX 90Q at 84.25 MHz, using CDCl3 as
solvent and/or hexafluorobezene as external reference. Mass
spectrum of representative compound was recorded on
Kratos 50 mass spectrometer at 70 eV. Purity of all
compounds was checked by TLC using silica gel ‘G’-
coated glass plates and benzene–ethylacetate (8:2) as eluent.
The microwave-induced reactions were carried out in BMO-
700T modified domestic oven fitted with a condenser and a
magnetic stirrer. Montmorillonite KSF and acidic alumina
were Aldrich product and used as received. 2-Benzamido-
benzoic acid has been synthesized by literature method [21].
2-Phenylmethyl-3-(3-trifluoromethylphenyl)-quinazolin-
4(3H)-one (IVa) was prepared by three different procedures
under microwave irradiation.
3.2. Method B: neat three-component
cyclocondensation
An equimolar mixture of anthranilic acid (2 mmol),
phenyl acetyl chloride (2 mmol) and 3-trifluoromethylani-
line (2 mmol) contained in a Erlenmeyer flask fitted with
condensor was placed in the microwave oven and irradiated
for 5 min (TLC) at 640 W. The reaction mixture was cooled
at room temperature to give solid mass, which was
crystallized from ethanol (Scheme 2).
3.1. Method A: using inorganic solid supports
3.3. Method C: alternative procedure for
preparation of IVa
A mixture of 2-benzamidobenzoic acid (I) (2 mmol) and
acetic anhydride (2.5 mmol) was adsorbed on acidic
alumina/montmorillonite KSF (2 g), mixed thoroughly
and irradiated inside the microwave oven at 640 W until
the completion of reaction (TLC). After completion of
reaction the 3-trifluoromethylaniline (2 mmol) was added to
A mixture of I (2 mmol) and 3-triflouromethyl aniline
(2 mmol) was irradiated for 4 min (TLC) at 640 W. After
cooling, the resultant residue was crystallized from
methanol yielding 91% of IVa (path I) (Scheme 3).

312
A. Dandia et al. / Journal of Fluorine Chemistry 126 (2005) 307–312
(b) S. Myies-gardiner, E. Russellphilip, M.A. Webb, R.J. Williams,
In order to verify the viability of path II under the above
Chem. Abst. 131 (1999) 311840d.
conditions, a mixture of phenyl acetyl anilide (VI) (2 mmol)
and anthranilic acid (2 mmol) was irradiated (5 min, TLC).
The resultant residue was crystallized from ethanol to give
IVa yield of 90%.
[7] (a) D.J. Nevill, Ger. Offen. DE 19,834, 627 (1998);
(b) D.J. Nevill, Chem. Abstr. 130 (1999) 48703m.
[8] (a) S.D. Mistry, C.M. Amey, PCT Int. Appl. WO 9929, 169 (1999);
(b) S.D. Mistry, C.M. Amey, Chem. Abstr. 131 (1999) 15176j.
[9] (a) B.L. Chenard, F.S. Mennit, W.M. Welch, Eur. Pat. Appl., EP 900,
567 (1999);
The identity of compounds synthesized by various
1
methods was established by their mixed mp, IR and H
NMR spectral studies.
(b) B.L. Chenard, F.S. Mennit, W.M. Welch, Chem. Abstr. 130 (1999)
209717m.
All compounds IVb–f listed in Table 3 were similarly
synthesized by neat three-component method comparatively
in high yield and reduced time.
[10] (a) B.L. Chenard, K.D. Shenk, Eur. Pat. Appl., EP 934, 934 (1999);
(b) B.L. Chenard, K.D. Shenk, Chem. Abstr. 131 (1999) 144610v.
[11] (a) S. Caddick, Tetrahedron 51 (1995) 10403;
(b) A. Loupy, A. Petit, J. Hamelin, F.T. Boullet, P. Jacquault, D.
Mathe, Synthesis (1998) 1213.
[12] (a) R. Varma, Green Chem. 43 (1999) 1;
(b) P. Lidstron, J. Tierney, B. Wathey, J. Weasman, Tetrahedron 57
(2001) 9199.
Acknowledgements
[13] (a) F. Toda, ACC Chem. Res. 28 (1995) 480;
(b) M. Jeselnik, R.S. Varma, S. Polanc, M. Kocevar, Green Chem. 4
(2002) 35.
Financial assistance from CSIR and UGC, New Delhi is
gratefully acknowledged. We are also thankful to Depart-
ment of Pathology, Durgapura, Jaipur for anti-fungal
screening and RSIC, CDRI, Lucknow, for the elemental
and spectral analyses.
[14] (a) L.F. Tietze, U. Beifuss, Angew. Chem. Int. Ed. Engl. 32 (1993)
131;
(b) R.W. Armstrong, A.P. Combs, P.A. Tempest, S.D. Brown, T. A.
Acc. Chem. Res. 29 (1996) 123;
(c) A. Domling, I. Ugi, Angew. Chem. Int. Ed. Engl. 39 (2000) 3168;
(d) H. Bienayme, C. Hulme, G. Oddon, P. Schmit, Chem. -Eur. J. 6
(2000) 3321.
References
[15] P. Mishra, S. Jain, S. Jain, J. Indian Chem. Soc. 74 (1997) 816.
[16] (a) P. Mishra, P.N. Gupta, A.K. Shakya, J. Indian Chem. Soc. 68
(1991) 618;
[1] (a) W. Nowrocka, J.J. Stasko, Chem. Abstr. 132 (2000) 87507m;
(b) A.G. EI-helpy, J. Pharm. Sci. 14 (1994) 193;
(c) V.K. Srivastava, S. Singh, A. Gulati, K. Sanker, Indian J. Chem.
26B (1987) 652;
(b) P. Mishra, P. Paneerselvam, S. Jain, J. Indian Chem. Soc. 72 (1995)
559.
(d) J. Sarvanan, S. Mohan, K.S. Manjunatha, Chem. Abstr. 130 (1999)
81477;
[17] F.R. Alexandre, A. Berecibar, T. Besson, Tetrahedron Lett. 43 (2002)
3911.
(e) R. Khanna, A.K. Saxena, V.K. Srivastava, K. Shanker, Indian J.
Chem. 29B (1990) 1056.
[18] (a) A. Dandia, H. Sachdeva, R. Singh, C.S. Sharma, Indian J. Chem.
42 (2003) 140;
[2] J.G. Swift, E.A. Dickens, B.A. Beacker, Arch. Int. Pharmacodyn. 128
(1960) 112.
(b) A. Dandia, M. Sati, A. Loupy, Green Chem. 4 (2002) 599;
(c) A. Dandia, R. Singh, H. Sachdeva, K. Arya, J. Fluor. Chem. 111
(2001) 61;
[3] (a) M.S. Amine, Indian J. Chem. 37B (1998) 303;
(b) E. Feky, Said, Pharmazie 48 (1993) 894.
[4] R. Filler, Chem. Tech. 4 (1974) 752.
(d) A. Dandia, H. Sachdeva, R. Singh, J. Chem. Res. (s) (2002)
272;
[5] (a) G. Romas, M. Cuenca-Estrella, A. Monzon, J.L. Rodriguez-
Tudela, J. Antimicrob. Chemother. 44 (1999) 283;
(b) R. Tyagi, B. Goel, V.K. Srivastava, A. Kumar, Indian J. Pharm.
Sci. 60 (1998) 283.
(e) A. Dandia, K. Arya, M. Sati, P. Sarawgi, J. Fluor. Chem., in press.
[19] Y.L. Nene, P.N. Thapliyal, Fungicides in Plant Disease Control,
Oxford and IBH Publishing Co., New Delhi, 1993.
[20] M.D. Whitehead, Phytopathology 47 (1952) 450.
[21] A.I. Vogel, Textbook of Practical Organic Chemistry, 3rd ed. Long-
mans Green, London, 1956.
[6] (a) S. Myies-gardiner, E. Russellphilip, M.A. Webb, R.J. Williams,
Ger. Offen. DE 19,918, 574 (1999);