Regioselective addition of Grignard reagents to 2,6-dicyanoanilines and cyclization to new quinazoline derivatives under thermal/microwave irradiation conditions

Article abstract of DOI:10.1016/j.jfluchem.2006.01.003

Two strategies have been developed for the synthesis of novel quinazoline derivatives. 2,6-Dicyanoanilines were reacted with Grignard reagents followed by cyclization to give two quinazoline regioisomers 2 and 3. Alternately 2,6-dicyanoanilines on reactio

Full text of DOI:10.1016/j.jfluchem.2006.01.003

Journal of Fluorine Chemistry 127 (2006) 351–359
www.elsevier.com/locate/fluor
Regioselective addition of Grignard reagents to 2,6-dicyanoanilines
and cyclization to new quinazoline derivatives under
thermal/microwave irradiation conditions§
D. Maitraie a, T. Yakaiah a, K. Srinivas a, G. Venkat Reddy a, S. Ravikanth a,
a
b
b
B. Narsaiah a, , P. Shanthan Rao , K. Ravikumar , B. Sridhar
*
a Fluoroorganic Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
b X-ray Crystallography Laboratory, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 17 November 2005; received in revised form 28 December 2005; accepted 13 January 2006
Available online 23 February 2006
Abstract
Two strategies have been developed for the synthesis of novel quinazoline derivatives. 2,6-Dicyanoanilines were reacted with Grignard reagents
followed by cyclization to give two quinazoline regioisomers 2 and 3. Alternately 2,6-dicyanoanilines on reaction with Grignard reagents gave
imine regioisomers 4 and 5. Each imine regioisomer was separated and independently cyclized to give new quinazoline derivatives 6, 7 and 8, 9,
respectively, under different microwave irradiation conditions.
# 2006 Elsevier B.V. All rights reserved.
Keywords: 2,6-Dicyanoanilines; Regioisomers; Quinazolines; Grignard reagents
1. Introduction
enamines via aza Wittig reaction [9], electrocyclic ring closures
[10,11] and 1,3-dimethoxybenzenes [12].
The quinazoline nucleus features in many alkaloids and is
known to show awide range of biological activity [1]. A few non-
classical quinazoline analogues of folic acid have remarkable
antibacterial and antimalarial effects and most prominent is
trimetrexate [2]. It is also considered as an anticancer agent and
has similar levels of inhibitory potency as methotrexate towards
dihydrofolate reductase (DHFR). Prazosin, a quinazoline-based
drug, is used as an antihypertensive agent [3]. The prime
requirement for any organic molecule to act as a potential drug is
low dosage, low toxicity and effective binding to the specific
disease causing receptor site with high solubility. In order to
target the requirements, specific substituents at appropriate
positions of a molecule are desirable. One such group is fluorine
[4] or trifluoromethyl [5,6] which, at a strategic position in the
molecule, alters the properties of molecule by promoting activity
due to high lipid solubility. Previous syntheses of quinazolines
are mainly from o-aminoketones [7], o-aminonitriles [8],
Based on the importance of quinazoline derivatives and our
continued interest in fluorinated molecules [13], we have
selected 2,6-dicyanoanilines (1) [14,15], interesting trifunc-
tional intermediates and subjected them to Grignard addition in
two ways. One way was addition of Grignard reagents followed
by cyclization in a single step to quinazoline derivatives (2 and
3). Another way was addition of Grignard reagents to
compounds 1 to give imine regioisomers (4 and 5). Then,
each isomer was separated and independently cyclized to
quinazolines 6, 7 and 8, 9, respectively, under microwave
irradiation conditions.
2. Results and discussion
Unsymmetrical 2,6-dicyanoanilines (1) were reacted with
various Grignard reagents and the resulted reaction mixture was
treated with trifluoroacetic/acetic anhydrides in situ to give
quinazoline regioisomers (2 and 3) in different proportions. The
yields were in the range 60–70%. The main reaction is addition
of Grignard reagents to the less hindered nitrile (CN) carbon in
preference to highly hindered and followed by cyclization in
presence of trifluoroacetic/acetic anhydride resulted two
§
IICT Communication No. 040932.
* Corresponding author. Tel.: +91 40 27193185; fax: +91 40 27160757.
E-mail address: narsaiah@iict.res.in (B. Narsaiah).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.01.003

352
D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
quinazoline regioisomers, as one isomer in major and another
isomer in minor depending upon the substituents used. The role
of substituents on reaction time, yield and ratio of products
formed was established. Thus, the methyl substituent in
compound 1 promotes formation of product 2 as the major,
whereas the phenyl substituent reverses the formation of
products. Regioselectivity is high with phenyl substitution in
compound 1 and also in the Grignard reagents. The reaction is
schematically drawn in Scheme 1.
imine derivatives (4 and 5) are exclusively formed. Thus,
unsymmetrical 2,6-dicyanoanilines (1) on reaction with
Grignard reagents gave two imine regioisomers (4 and 5).
The reaction trend is similar to the first strategy and obtained
one of the isomer major and another minor. The regioisomers
are with close polarity, separated by column and identified
based on spectral data (Scheme 2).
The 1H NMR spectra of two regioisomers (4a and 5a) show
characteristic differences in the chemical shift of CH3 and NH2
signals of one isomer to other isomer are varied due to
electronic factors. It depends on mainly two groups, i.e., CF3
and CN. If CF3 and CN are para to each other, the NH2 signal
appears more upfield. Similarly, the CH3 signal when it is ortho
to CN appeared downfield as in compound 3a and para to nitrile
appeared in upfield. It is presumed that the ortho nitrile has
more influence on CH3 than para and as a result the signals for
CH3 group appeared in downfield and upfield, respectively
(Table 2).
The regioisomers 2 and 3 were separated and identified
based on characteristic differences in their 1H NMR spectra. In
a specific example of 2a and 3a, we observed a change in
chemical shift of CH3 and C–H proton on C-6 carbon. In 3a the
methyl group as well as C–H proton on C-6 carbon appeared
downfield with reference to 2a. It is attributed to the ortho
nitrile (CN) effect on the methyl group and the ortho CF3 group
effect on the C-6 proton in line with C-4 phenyl group as a result
appeared in downfield in comparison to 2a isomer. Similar
trend is followed in other isomers. The products synthesised are
tabulated in Table 1.
In a typical reaction, one of the compounds 4a was reacted
with benzaldehyde in acetic acid under thermal conditions at
110 8C for 4 h to give a number of products. As a result mixture
of products 6 and 7 formed in a low yield of 35%. As an
alternate method, the same reaction of 4a with benzaldehyde
was conducted under microwave irradiation conditions with
300 W power in 4 min, to give exclusively 1,2-dihydroquina-
zolines 6a and no further reaction even at longer time and
higher concentration of aldehyde. In contrast with 450 W
power of microwave irradiation, quinazoline 7a was obtained
directly. Quinazoline was identified based on spectral data and
confirmed by single crystal X-ray analysis (Fig. 1).
The reaction of compound 1 with Grignard reagents
followed by aryl aldehydes is further extended in order to
obtain 2-arylsubstituted quinazolines; however, in all the cases
Table 1
Quinazoline regioisomers
Entry
1
Product
R
R0
R00
Ratio (%)
Yield (%)
2a
3a
CH3
CH3
Ph
Ph
CF3
CF3
65
35
42
22
Thus, all four compounds 4–5 were independently reacted
with various aldehydes under two sets of microwave irradiation
conditions to obtain 1,2-dihydroquinazolines (6 and 8) and
quinazolines (7 and 9). Thus, the reaction using 300 W
microwave irradiation gave exclusively compounds 6 and 8,
whereas with 450 W microwave irradiation gave compounds 7
and 9. The reaction involved formation of Schiff’s base
2
3
4
2b
3b
Ph
Ph
Ph
Ph
CF3
CF3
28
72
22
56
2c
3c
Ph
Ph
Ph
Ph
CH3
CH3
25
75
15
46
2d
3d
Ph
Ph
C2H5
C2H5
CF3
CF3
40
60
23
35

D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
353
Scheme 1.
Scheme 2.
Table 2
Imine regioisomers of 4 and 5
S. no.
1
Entry
R
Ratio (%)
Yield (%)
4a
5a
CH3
CH3
75
25
59
20
2
4b
5b
Ph
Ph
17
83
15
73
Table 3
7-Trifluoromethyl-1,2-dihydroquinazolines (6)/quinazolines (7)
S. no.
Entry
R
R0
Time (min)
Yield (%)
5
6
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
CH3
CH3
CH3
CH3
Ph
Ph
4
3
6
3
4
7
6
9
6
6
62
63
55
61
60
73
75
69
70
70
p-Cl-C6H4
p-CH3-C6H4
p-F-C6H4
Ph
7
8
9
10
11
12
13
14
CH3
CH3
CH3
CH3
Ph
Ph
p-Cl-C6H4
p-CH3-C6H4
p-F-C6H4
Ph
Fig. 1. X-ray crystal structure 7a. Displacement ellipsoids are drawn at 30%
probability level and H atoms are shown as small spheres of arbitrary radii.

354
D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
Scheme 3.
Scheme 4.
Table 4
4. Experimental
5-Trifluoromethyl-1,2-dihydroquinazolines (8)/quinazolines (9)
1H NMR spectra were recorded in CDCl3 on Bruker AV 300
and Unity 400 spectrometers, chemical shifts are reported in
ppm relative to 0 for TMS. Melting points were recorded on
VMP-AM melting point apparatus and are uncorrected.
Elemental analyses were carried out on Elemental Vario EL
(Germany) apparatus. IR spectra were recorded on FT-IR
Schimadzu Perkin-Elmer 1310 infrared spectrometer. Electron
impact (EI) and chemical ionization mass spectra (CIMS) were
recorded on VG 7070 H ev instrument at 70 ev. During usual
workup, all organic extracts were dried over Na2SO4 and
evaporated. All reactions were monitored by thin layer
chromatography (TLC) on precoated silica gel 60 F254 (Merck);
spots were visualized with UV light. Merck silica gel (100–
200 mesh) was used for chromatography.
S. no.
Entry
R
R0
Time (min)
Yield (%)
15
16
17
18
19
20
21
22
23
24
25
26
27
28
8a
8b
8c
8d
8e
8f
8g
9a
9b
9c
9d
9e
9f
CH3
CH3
CH3
CH3
Ph
Ph
4
3
6
3
4
3
6
7
6
9
6
7
6
9
65
64
59
61
63
65
58
83
82
78
80
85
88
82
p-Cl-C6H4
p-CH3-C6H4
p-F-C6H4
Ph
Ph
p-Cl-C6H4
p-CH3-C6H4
Ph
Ph
CH3
CH3
CH3
CH3
Ph
p-Cl-C6H4
p-CH3-C6H4
p-F-C6H4
Ph
Ph
p-Cl-C6H4
p-CH3-C6H4
9g
Ph
4.1. General procedure
followed by cyclization to 1,2-dihydroquinazolines and further
to quinazolines.
4.1.1. 2-Trifluoromethyl/methyl-4-phenyl/ethyl-5-methyl/
phenyl-7-trifluoromethyl-quinazoline-8-carbonitrile (2), 2-
trifluoromethyl/methyl-4-phenyl/ethyl-5-trifluoro methyl-7-
methyl/phenyl-quinazoline-8-carbonitrile (3)
The yields of quinazoline products are comparatively higher
than the 1,2-dihydroquinazolines. Each set of reactions and
products formed has been schematically drawn in Scheme 3,
Table 3 and Scheme 4, Table 4.
2,6-Dicyanoanilines 1 (1 mmol) dissolved in dry THF
(2 mL) and added dropwise to a well-stirred solution of RMgBr
(alkyl/aryl bromide, 2 mmol and magnesium, 2 mmol) in THF
(2 mL) at 0 8C. After complete addition, the reaction mixture
was further stirred at room temperature for 1 h; trifluoroacetic
anhydride/acetic anhydride (1 mL) in THF (3 mL) was added
dropwise under cooling (0–5 8C). The reaction mixture was
slowly brought to room temperature and stirred for 2 h. The
THF was removed, residue was cooled to 5 8C and quenched
with NH4Cl solution, then stirred for 0.5 h, and the residue was
extracted with ether. The ether layer was washed with water
3. Conclusion
In conclusion, two strategies have been developed to
synthesise quinazoline derivatives. One of the strategies is the
regioselective addition of Grignard reagents followed by
cyclization under thermal conditions and another is isolation of
imine followed by cyclization under microwave irradiation
conditions. Both strategies provide useful route to different
quinazolines.

D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
355
until washings were neutral to pH and dried over Na2SO4. The
solvent was evaporated in vacuum and the residue was purified
through column chromatography using silica gel (100–
200 mesh) in n-hexane:chloroform (70:30) as eluents, to give
title compounds of good purity.
(200 MHz, CDCl3): d 3.05 (s, 3H, CH3), 7.0–7.12 (m, 8H,
aromatic), 7.2–7.28 (m, 2H, aromatic), 7.32 (s, 1H, aromatic-
H). MS: m/z (%) 390 (M+, 54). Anal. Calcd for C23H14F3N3: C,
70.95; H, 3.62; N, 10.79. Found: C, 71.13; H, 3.84; N, 10.55%.
4.1.8. 4-Ethyl-5-phenyl-2,7-
bis(trifluoromethyl)quinazoline-8-carbonitrile (2d)
Yield: 90 mg (23%), a pale yellow solid, mp: 138 8C. IR
4.1.2. 5-Methyl-4-phenyl-2,7-
bis(trifluoromethyl)quinazoline-8-carbonitrile (2a)
Yield: 160 mg (42%), a pale yellow solid, mp: 149 8C. IR
(KBr) (cmꢀ1): 2238, 1568 and 1470. 1H NMR (200 MHz,
CDCl3): d 2.32 (s, 3H, CH3), 7.5–7.63 (m, 5H, aromatic), 7.85
(s, 1H, aromatic-H). MS: m/z (%) 382 (M+, 51). Anal. Calcd for
C18H9F6N3: C, 56.70; H, 2.38; N, 11.02. Found: C, 56.91; H,
2.56; N, 10.78%.
1
(KBr) (cmꢀ1): 3450, 2942, 2239, 1601, 1562 and 1140. H
NMR (200 MHz, CDCl3): d 1.4 (t, 3H, CH3), 3.5 (q, 2H, CH2),
7.5–7.58 (m, 3H, aromatic), 7.6–7.7 (m, 2H, aromatic), 8.2 (s,
1H, aromatic-H). MS: m/z (%) 396 (M+, 61). Anal. Calcd for
C19H11F6N3: C, 57.73; H, 2.80; N, 10.63. Found: C, 57.57; H,
2.59; N, 10.81%.
4.1.3. 7-Methyl-4-phenyl-2,5-
bis(trifluoromethyl)quinazoline-8-carbonitrile (3a)
Yield: 80 mg (22%), a pale yellow solid, mp: 162 8C. IR
4.1.9. 4-Ethyl-7-phenyl-2,5-
bis(trifluoromethyl)quinazoline-8-carbonitrile (3d)
Yield: 130 mg (35%), a pale yellow solid, mp: 159 8C. IR
1
1
(KBr) (cmꢀ1): 3384, 2930, 2220, 1545 and 1476. H NMR
(KBr) (cmꢀ1): 3449, 2987, 2236, 1570, 1460 and 1375. H
(200 MHz, CDCl3): d 2.95 (s, 3H, CH3), 7.47–7.6 (m, 5H,
aromatic), 8.03 (s, 1H, aromatic-H). MS: m/z (%) 382 (M+, 34).
Anal. Calcd for C18H9F6N3: C, 56.70; H, 2.38; N, 11.02. Found:
C, 56.49; H, 2.19; N, 11.20%.
NMR (200 MHz, CDCl3): d 1.15 (t, 3H, CH3), 2.65 (q, 2H,
CH2), 7.36–7.42 (m, 2H, aromatic), 7.55–7.62 (m, 3H,
aromatic), 7.92 (s, 1H, aromatic-H). MS: m/z (%) 396 (M+,
66). Anal. Calcd for C19H11F6N3: C, 57.73; H, 2.80; N, 10.63.
Found: C, 57.98; H, 2.62; N, 10.48%.
4.1.4. 4,5-Diphenyl-2,7-bis(trifluoromethyl)quinazoline-8-
carbonitrile (2b)
4.2. General procedure for the preparation of compounds
(4 and 5)
Yield: 0.1 mg (22%), a pale yellow solid, mp: 125 8C. IR
1
(KBr) (cmꢀ1): 3442, 2973, 2228, 1558 and 1449. H NMR
(200 MHz, CDCl3): d 7.52–7.7 (m, 8H, aromatic), 7.81–7.89
(m, 2H, aromatic), 8.32 (s, 1H, aromatic-H). MS: m/z (%) 444
(M+, 50). Anal. Calcd for C23H11F6N3: C, 62.31; H, 2.51; N,
9.48. Found: C, 62.57; H, 2.30; N, 9.32%.
A solution of o-aminonitrile 1 (1 mmol) in THF (3 mL)
was added dropwise to a well-stirred solution of phenyl
magnesium bromide (from bromobenzene, 2 mmol and
magnesium, 2 mmol) in THF (3 mL) at 0 8C. The reaction
mixture was further stirred at room temperature for 2 h,
quenched with cold diluted HCl solution (5 mL) and extracted
with CHCl3. The combined extracts were washed with brine,
dried on Na2SO4 and evaporated to obtain crude product
mixture of two isomers. The isomers were separated by
column chromatography on 100–200 silica gel (eluent:hex-
ane/ethylacetate 93:7).
4.1.5. 4,7-Diphenyl-2,5-bis(trifluoromethyl)quinazoline-8-
carbonitrile (3b)
Yield: 250 mg (56%), a pale yellow solid, mp: 132 8C.
IR (KBr) (cmꢀ1): 3440, 2979, 2232, 1569 and 1458. 1H
NMR (200 MHz, CDCl3): d 7.1–7.22 (m, 8H, aromatic),
7.35–7.42 (m, 2H, aromatic), 8.12 (s, 1H, aromatic-H). MS:
m/z (%) 444 (M+, 53). Anal. Calcd for C23H11F6N3: C,
62.31; H, 2.51; N, 9.48. Found: C, 62.13; H, 2.76; N,
9.18%.
4.2.1. 2-Amino-3-[imino(phenyl)methyl]-4-methyl-6-
(trifluoromethyl)benzonitrile (4a)
Yield: 180 mg (59%), a white solid, mp: 141 8C. IR (KBr)
1
4.1.6. 2-Methyl-4,5-diphenyl-7-trifluoromethyl-
quinazoline-8-carbonitrile (2c)
(cmꢀ1): 3407, 3260, 3162, 2216, 1649, 1609 and 1450. H
NMR (200 MHz, CDCl3): d2.13 (s, 3H, CH3), 4.82 (br., s, 2H,
NH2), 6.95 (s, 1H, aromatic-H), 7.4–7.52 (m, 3H, aromatic),
7.62–7.66 (m, 2H, aromatic). MS: m/z (%) 304 (M+, 69). Anal.
Calcd for C16H12F3N3: C, 63.36; H, 3.99; N, 13.86. Found: C,
63.20; H, 4.22; N, 14.03%.
Yield: 60 mg (15%), a pale yellow solid, mp: 120 8C. IR
(KBr) (cmꢀ1): 3440, 2976, 2227, 1569 and 1449. H NMR
1
(200 MHz, CDCl3): d 3.01 (s, 3H, CH3), 7.46–7.52 (m, 5H,
aromatic), 7.59–7.63 (m, 3H, aromatic), 7.75–7.79 (m, 2H,
aromatic), 8.04 (s, 1H, aromatic-H). MS: m/z (%) 390 (M+, 36).
Anal. Calcd for C23H14F3N3: C, 70.95; H, 3.62; N, 10.79.
Found: C, 71.18; H, 3.46; N, 10.96%.
4.2.2. 2-Amino-3-[imino(phenyl)methyl]-6-methyl-4-
(trifluoromethyl)benzonitrile (5a)
Yield: 60 mg (20%), a white solid, mp: 135 8C. IR (KBr)
1
4.1.7. 2-Methyl-4,7-diphenyl-5-trifluoromethyl-
quinazoline-8-carbonitrile (3c)
(cmꢀ1): 3437, 3334, 3222, 2217, 1649 and 1447. H NMR
(200 MHz, CDCl3): d2.6 (s, 3H, CH3), 4.62 (br., s, 2H, NH2),
6.97 (s, 1H, aromatic-H), 7.38–7.5 (m, 3H, aromatic), 7.62–7.7
(m, 2H, aromatic). MS: m/z (%) 304 (M+, 41). Anal. Calcd for
Yield: 180 mg (46%), a pale yellow solid, mp: 111 8C. IR
(KBr) (cmꢀ1): 3446, 2956, 2231, 1562 and 1437. H NMR
1

356
D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
C16H12F3N3: C, 63.36; H, 3.99; N, 13.86. Found: C, 63.57; H,
4.15; N, 13.67%.
(200 MHz, CDCl3): d1.95 (s, 3H, CH3), 2.41 (s, 3H, CH3), 5.31
(s, 1H, N–H), 5.65 (s, 1H, C–H), 6.9 (s, 1H, aromatic-H), 7.2–
7.23 (m, 2H, aromatic), 7.39–7.48 (m, 7H, aromatic). MS: m/z
(%) 406 (M+, 51). Anal. Calcd for C24H18F3N3: C, 71.10; H,
4.48; N, 10.36. Found: C, 71.27; H, 4.70; N, 10.17%.
4.2.3. 3-Amino-2-[imino(phenyl)methyl]-5-
(trifluoromethyl)biphenyl-4-carbonitrile (4b)
Yield: 50 mg (15%), a white solid, mp: 148 8C. IR (KBr)
(cmꢀ1): 3404, 3248, 2215, 1608 and 1131. 1H NMR (200 MHz,
CDCl3): d 4.75 (br., s, 2H, NH2), 7.12 (s, 1H, aromatic-H),
7.42–7.57 (m, 5H, aromatic), 7.6–7.62 (m, 3H, aromatic), 7.78–
7.82 (m, 2H, aromatic). MS: m/z (%) 366 (M+, 45). Anal. Calcd
for C21H14F3N3: C, 69.04; H, 3.86; N, 11.50. Found: C, 68.80;
H, 4.04; N, 11.70%.
4.3.4. 2-(4-Fluorophenyl)-5-methyl-4-phenyl-7-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(6d)
Yield: 70 mg (61%), a pale yellow solid, mp: 250 8C. IR
(KBr) (cmꢀ1): 3370, 2925, 2218 and 1578. 1H NMR (200 MHz,
CDCl3): d 1.95 (s, 3H, CH3), 5.27 (s, 1H, N–H), 5.64 (s, 1H, C–
H), 6.92 (s, 1H, aromatic-H), 7.1–7.14 (m, 2H, aromatic), 7.38–
7.42 (m, 5H, aromatic), 7.54–7.58 (m, 2H, aromatic). MS: m/z
(%) 410 (M+, 63). Anal. Calcd for C23H15F4N3: C, 67.48; H,
3.69; N, 10.26. Found: C, 67.25; H, 3.85; N, 10.45%.
4.2.4. 3-Amino-4-[imino(phenyl)methyl]-5-
(trifluoromethyl)biphenyl-2-carbonitrile (5b)
Yield: 260 mg (73%), a white solid, mp: 167 8C. IR (KBr)
1
(cmꢀ1): 3438, 3248, 2216, 1610, 1443 and 1132. H NMR
(200 MHz, CDCl3): d 5.52 (br., s, 2H, NH2), 7.02 (s, 1H,
aromatic-H), 7.12–7.15 (m, 10H, aromatic). MS: m/z (%) 366
(M+, 46). Anal. Calcd for C21H14F3N3: C, 69.04; H, 3.86; N,
11.50. Found: C, 69.19; H, 3.66; N, 11.32%.
4.3.5. 7-(Trifluoromethyl)-2,4,5-triphenyl-1,2-
dihydroquinazoline-8-carbonitrile (6e)
Yield: 80 mg (60%), a pale yellow solid, mp: 172 8C. IR
(KBr) (cmꢀ1): 3071, 2834, 2221, 1683 and 1291. H NMR
1
(200 MHz, CDCl3): d 5.46 (s, 1H, N–H), 5.48 (s, 1H, C–H),
7.19 (s, 1H, aromatic-H), 7.62–7.67 (m, 13H, aromatic), 8.1–
8.15 (m, 2H, aromatic). MS: m/z (%) 454 (M+, 44). Anal. Calcd
for C28H18F3N3: C, 74.16; H, 4.01; N, 9.27. Found: C, 74.34; H,
4.22; N, 9.11%.
4.3. Preparation of 1,2-dihydroquinazolines (6 and 8)
In a sealed tube compound 4 or 5 (0.3 mmol) and
benzaldehyde (0.45 mmol) was irradiated in the microwave
oven at 300 W for 4–6 min. After completion of the reaction, the
contentsarecooledtoroomtemperatureandunsealedthetubefor
isolation of crude product. It is purified by column chromato-
graphy on 60–120 silica gel (eluent:hexane/ethylacetate 95:5).
4.3.6. 7-Methyl-2,4-diphenyl-5-(trifluoromethyl)-1,2-
dihydroquinazoline-8-carbonitrile (8a)
Yield: 80 mg (65%), a pale yellow solid, mp: 167 8C. IR
1
(KBr) (cmꢀ1): 3310, 2223, 1594, 1276 and 1122. H NMR
4.3.1. 5-Methyl-2, 4-diphenyl-7-(trifluoromethyl)-1,2-
dihydroquinazoline-8-carbonitrile (6a)
(200 MHz, CDCl3): d 2.63 (s, 3H, CH3), 5.25 (s, 1H, NH), 5.4
(s, 1H, C–H), 6.95 (s, 1H, aromatic-H), 7.32–7.35 (m, 5H,
aromatic), 7.42–7.45 (m, 3H, aromatic), 7.6–7.63 (m, 2H,
aromatic). MS: m/z (%) 392 (M+, 38). Anal. Calcd for
C23H16F3N3: C, 70.58; H, 4.12; N, 10.74. Found: C, 70.79; H,
3.93; N, 10.92%.
Yield: 70 mg (62%), a pale yellow solid, mp: 215 8C. IR
(KBr) (cmꢀ1): 3376, 3061, 2214, 1612, 1509, 1444, 1358 and
1125. 1H NMR (200 MHz, CDCl3): d 1.95 (s, 3H, CH3), 5.32 (s,
1H, NH), 5.68 (s, 1H, C–H), 6.9 (s, 1H, aromatic-H), 7.38–7.45
(m, 8H, aromatic), 7.54–7.58 (m, 2H, aromatic). MS: m/z (%)
392 (M+, 28). Anal. Calcd for C23H16F3N3: C, 70.58; H, 4.12;
N, 10.74. Found: C, 70.42; H, 4.38; N, 10.95%.
4.3.7. 2-(4-Chlorophenyl)-7-methyl-4-phenyl-5-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(8b)
4.3.2. 2-(4-Chlorophenyl)-5-methyl-4-phenyl-7-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(6b)
Yield: 80 mg (63%), a pale yellow solid, mp: 186 8C. IR
(KBr) (cmꢀ1): 3302, 2919, 2217 and 1589. 1H NMR (200 MHz,
CDCl3): d 1.93 (s, 3H, CH3), 5.28 (s, 1H, NH), 5.65 (s, 1H, C–
H), 6.91 (s, 1H, aromatic-H), 7.36–7.4 (m, 5H, aromatic), 7.42–
7.44 (m, 2H, aromatic), 7.51–7.54 (m, 2H, aromatic). MS: m/z
(%) 426 (M+, 32). Anal. Calcd for C23H15ClF3N3: C, 64.87; H,
3.55; N, 9.87. Found: C, 64.68; H, 3.38; N, 10.11%.
Yield: 80 mg (64%), a pale yellow solid, mp: 162 8C. IR
(KBr) (cmꢀ1): 3304, 2922, 2219 and 1592. 1H NMR (200 MHz,
CDCl3): d 2.62 (s, 3H, CH3), 5.31 (s, 1H, NH), 5.41 (s, 1H, C–
H), 6.98 (s, 1H, aromatic-H), 7.32–7.36 (m, 4H, aromatic),
7.38–7.42 (m, 3H, aromatic). MS: m/z (%) 426 (M+, 52). Anal.
Calcd for C23H15ClF3N3: C, 64.87; H, 3.55; N, 9.87. Found: C,
65.12; H, 3.38; N, 9.68%.
4.3.8. 7-Methyl-2-(4-methylphenyl)-4-phenyl-5-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(8c)
4.3.3. 5-Methyl-2-(4-methylphenyl)-4-phenyl-7-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(6c)
Yield: 70 mg (59%), a pale yellow solid, mp: 158 8C. IR
1
(KBr) (cmꢀ1): 3310, 2922, 2224, 1531 and 1129. H NMR
(200 MHz, CDCl3): d 2.38 (s, 3H, CH3), 2.61 (s, 3H, CH3), 5.32
(s, 1H, N–H), 5.41 (s, 1H, C–H), 6.98 (s, 1H, aromatic-H), 7.32–
7.36 (m, 4H, aromatic), 7.48–7.52 (m, 3H, aromatic), 7.6–7.62
Yield: 70 mg (55%), a pale yellow solid, mp: 214 8C. IR
1
(KBr) (cmꢀ1): 3312, 2921, 2222, 1529 and 1127. H NMR

D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
357
(m, 2H, aromatic). MS: m/z (%) 406 (M+, 55). Anal. Calcd for
4.4.1. 5-Methyl-2,4-diphenyl-7-
(trifluoromethyl)quinazoline-8-carbonitrile (7a)
C24H18F3N3: C, 71.10; H, 4.48; N, 10.36. Found: C, 71.25; H,
4.70; N, 10.18%.
Yield: 80 mg (73%), a pale yellow solid, mp: 193 8C. IR
(KBr) (cmꢀ1): 3074, 2229, 1568 and 1141. 1H NMR (200 MHz,
CDCl3): d 2.28 (s, 3H, CH3), 7.5–7.59 (m, 8H, aromatic), 7.61
(s, 1H, aromatic-H), 8.73–8.79 (m, 2H, aromatic). MS: m/z (%)
390 (M+, 35). Anal. Calcd for C23H14F3N3: C, 70.95; H, 3.62;
N, 10.79. Found: C, 70.77; H, 3.87; N, 10.58%.
4.3.9. 2-(4-Fluorophenyl)-7-methyl-4-phenyl-5-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(8d)
Yield: 70 mg (61%), a pale yellow solid, mp: 169 8C. IR
(KBr) (cmꢀ1): 3372, 2923, 2221 and 1599. 1H NMR
(200 MHz, CDCl3): d 2.6 (s, 3H, CH3), 5.25 (s, 1H, N–H),
5.4 (s, 1H, C–H), 6.97 (s, 1H, aromatic-H), 7.47–7.5 (m, 4H,
aromatic), 7.57–7.62 (m, 3H, aromatic), 7.76–7.8 (m, 2H,
aromatic). MS: m/z (%) 410 (M+, 36). Anal. Calcd for
C23H15F4N3: C, 67.48; H, 3.69; N, 10.26. Found: C, 67.69; H,
3.52; N, 10.45%.
4.4.1.1. X-ray crystallography. Compound 7a. C23H14F3N3:
Mw = 389.37, pale yellow block crystal 0.35 mm ꢁ 0.25
˚
˚
mm ꢁ 0.12 mm, a = 6.2910(4) A, b = 24.2900(15) A, c =
3
˚
˚
12.6105(8) A, b = 103.313(1)8, V = 1875.2(2) A , monoclinic,
space group P21/c, rcalc = 1.379 mg mꢀ3, l = 0.71073 A,
˚
m(Mo Ka) = 0.104 mmꢀ1, F0 0 0 = 800, T = 273(2) K. Data
collection yielded 15,902 reflections resulting in 4376 unique,
averaged reflections, 3561 with I > 2s(I), u range: 1.68–25.008.
Full-matrix least-squares refinement led to a final R = 0.0470,
wR ¼ 0:1249 and GOF = 1.061. Intensity data were measured
on Bruker Smart Apex with CCD area detector. CCDC 273388
contains supplementary crystallographic data for the stru-
cture 7a.
4.3.10. 2,4,7-Triphenyl-5-(trifluoromethyl)-1,2-
dihydroquinazoline-8-carbonitrile (8e)
Yield: 80 mg (63%), a pale yellow solid, mp: 160 8. IR (KBr)
(cmꢀ1): 3069, 2829, 2224, 1681 and 1291. 1H NMR (200 MHz,
CDCl3): d 5.64 (s, 1H, N–H), 5.85 (s, 1H, C–H), 6.95–6.99 (m,
2H, aromatic), 7.03–7.12 (m, 5H, aromatic), 7.14–7.18 (m, 3H,
aromatic), 7.2 (s, 1H, aromatic-H), 7.44–7.49 (m, 2H,
aromatic), 7.57–7.59 (m, 2H, aromatic). MS: m/z (%) 454
(M+, 28). Anal. Calcd for C28H18F3N3: C, 74.16; H, 4.01; N,
9.27. Found: C, 74.34; H, 4.25; N, 9.07%.
4.4.2. 2-(4-Chlorophenyl)-5-methyl-4-phenyl-7-
(trifluoromethyl)quinazoline-8-carbonitrile (7b)
Yield: 90 mg (75%), a pale yellow solid, mp: 260 8C. IR
(KBr) (cmꢀ1): 3479, 2912, 2225, 1522 and 1126. H NMR
1
4.3.11. 2-(4-Chloro-phenyl)-4,7-diphenyl-5-
(trifluoromethyl)-1,2-dihydroquinazoline-8-carbonitrile
(8f)
(200 MHz, CDCl3): d 2.25 (s, 3H, CH3), 7.45–7.49 (m, 2H,
aromatic), 7.52–7.59 (m, 5H, aromatic), 7.62 (s, 1H, aromatic-
H), 8.68–8.72 (m, 2H, aromatic). MS: m/z (%) 424 (M+, 48).
Anal. Calcd for C23H13ClF3N3: C, 65.18; H, 3.09; N, 9.91.
Found: C, 64.99; H, 2.88; N, 10.06%.
Yield: 90 mg (65%), a pale yellow solid, mp: 195 8C. IR
(KBr) (cmꢀ1): 3304, 2815, 2222, 1683, 1597, 1293 and 1136.
1H NMR (200 MHz, CDCl3): d 5.6 (s, 1H, N–H), 5.81 (s, 1H,
C–H), 6.9–6.98 (m, 2H, aromatic), 7.02–7.1 (m, 8H, aromatic),
7.19 (s, 1H, aromatic-H), 7.41–7.45 (m, 2H, aromatic), 7.57–
7.62 (m, 2H, aromatic). MS: m/z (%) 488 (M+, 40). Anal. Calcd
for C28H17ClF3N3: C, 68.93; H, 3.51; N, 8.61. Found: C, 68.70;
H, 3.70; N, 8.78%.
4.4.3. 5-Methyl-2-(4-methylphenyl)-4-phenyl-7-
(trifluoromethyl)quinazoline-8-carbonitrile (7c)
Yield: 80 mg (69%), a pale yellow solid, mp: 236 8C. IR
1
(KBr) (cmꢀ1): 3480, 2915, 2222, 1528 and 1130. H NMR
(200 MHz, CDCl3): d 2.25 (s, 3H, CH3), 2.5 (s, 3H, CH3), 7.29–
7.32 (m, 2H, aromatic), 7.52–7.59 (m, 5H, aromatic), 7.6 (s, 1H,
aromatic-H), 8.6–8.65 (m, 2H, aromatic). MS: m/z (%) 404
(M+, 54). Anal. Calcd for C24H16F3N3: C, 71.46; H, 4.00; N,
10.42. Found: C, 71.63; H, 4.23; N, 10.19%.
4.3.12. 4,7-Diphenyl-2-p-tolyl-5-(trifluoromethyl)-1,2-
dihydroquinazoline-8-carbonitrile (8g)
Yield: 80 mg (58%), a pale yellow solid, mp: 152 8C. IR
(KBr) (cmꢀ1): 2919, 2851, 2545, 2227, 1679, 1531 and 1142.
1H NMR (200 MHz, CDCl3): d 2.47 (s, 3H, CH3), 5.54 (s, 1H,
N–H), 5.8 (s, 1H, C–H), 6.92–6.97 (m, 2H, aromatic), 7.18 (s,
1H, aromatic-H), 7.21–7.28 (m, 5H, aromatic), 7.36–7.4 (m,
3H, aromatic), 7.52–7.59 (m, 4H, aromatic). MS: m/z (%) 468
(M+, 43). Anal. Calcd for C29H20F3N3: C, 74.51; H, 4.31; N,
8.99. Found: C, 74.70; H, 4.10; N, 8.75%.
4.4.4. 2-(4-Fluorophenyl)-5-methyl-4-phenyl-7-
(trifluoromethyl)quinazoline-8-carbonitrile (7d)
Yield: 80 mg (70%), a pale yellow solid, mp: 140 8C. IR
1
(KBr) (cmꢀ1): 2930, 2230, 1535, 1473 and 1126. H NMR
(200 MHz, CDCl3): d 2.25 (s, 3H, CH3), 7.21–7.26 (m, 2H,
aromatic), 7.55–7.62 (m, 5H, aromatic), 7.62 (s, 1H, aromatic-
H), 8.78–8.82 (m, 2H, aromatic). MS: m/z (%) 408 (M+, 67).
Anal. Calcd for C23H13F4N3: C, 67.81; H, 3.22; N, 10.32.
Found: C, 67.63; H, 3.42; N, 10.51%.
4.4. Preparation of quinazolines (7 and 9)
A mixture of compound 4 or 5 (0.3 mmol) and benzaldehyde
(0.45 mmol) was taken in a sealed tube and irradiated in the
microwave oven at 450 W for 4–9 min. Reaction mixture was
cooled and purified by column chromatography (eluent:hexane/
ethylacetate 97:3).
4.4.5. 7-(Trifluoromethyl)-2,4,5-triphenyl-quinazoline-8-
carbonitrile (7e)
Yield: 90 mg (70%), a pale yellow solid, mp: 245 8C. IR
1
(KBr) (cmꢀ1): 3069, 2832, 2222, 1682 and 1289. H NMR

358
D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
(200 MHz, CDCl3): d 7.43 (s, 1H, aromatic-H), 7.45–7.52 (m,
7H, aromatic), 7.59–7.63 (m, 3H, aromatic), 8.11–8.17 (m, 5H,
aromatic). MS: m/z (%) 452 (M+, 41). Anal. Calcd for
C28H16F3N3: C, 74.49; H, 3.57; N, 9.31. Found: C, 74.67; H,
3.35; N, 9.11%.
4.4.11. 2-(4-Chlorophenyl)-4,7-diphenyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9f)
Yield: 130 mg (88%), a pale yellow solid, mp: 214 8C. IR
1
(KBr) (cmꢀ1): 3303, 2825, 2221, 1682, 1293 and 1132. H
NMR (200 MHz, CDCl3): d 7.08–7.13 (m, 8H, aromatic), 7.32–
7.37 (m, 2H, aromatic), 7.53–7.57 (m, 2H, aromatic), 7.86 (s,
1H, aromatic-H), 8.73–8.78 (m, 2H, aromatic). MS: m/z (%)
486 (M+, 42). Anal. Calcd for C28H15ClF3N3: C, 69.21; H, 3.11;
N, 8.65. Found: C, 69.37; H, 2.92; N, 8.86%.
4.4.6. 7-Methyl-2,4-diphenyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9a)
Yield: 100 mg (83%), a pale yellow solid, mp: 287 8C. IR
1
(KBr) (cmꢀ1): 3461, 2922, 2220, 1737 and 1126. H NMR
(200 MHz, CDCl3): d 2.92 (s, 3H, CH3), 7.5–7.55 (m, 5H,
aromatic), 7.57–7.6 (m, 3H, aromatic), 7.8 (s, 1H, aromatic-H),
8.71–8.75 (m, 2H, aromatic). MS: m/z (%) 390 (M+, 42). Anal.
Calcd for C23H14F3N3: C, 70.95; H, 3.62; N, 10.79. Found: C,
70.76; H, 3.79; N, 10.56%.
4.4.12. 4,7-Diphenyl-2-p-tolyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9g)
Yield: 110 mg (82%), a pale yellow solid, mp: 193 8C. IR
1
(KBr) (cmꢀ1): 3304, 2819, 2219, 1680, 1290 and 1136. H
NMR (200 MHz, CDCl3): d 2.49 (s, 3H, CH3), 7.05–7.16 (m,
8H, aromatic), 7.32–7.39 (m, 4H, aromatic), 7.8 (s, 1H,
aromatic-H), 8.67–8.72 (m, 2H, aromatic). MS: m/z (%) 466
(M+, 45). Anal. Calcd for C29H18F3N3: C, 74.83; H, 3.90; N,
9.03. Found: C, 74.65; H, 4.14; N, 8.86%.
4.4.7. 2-(4-Chlorophenyl)-7-methyl-4-phenyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9b)
Yield: 100 mg (82%), a pale yellow solid, mp: 282 8C. IR
1
(KBr) (cmꢀ1): 3478, 2915, 2220, 1528 and 1128. H NMR
(200 MHz, CDCl3): d 2.92 (s, 3H, CH3), 7.45–7.52 (m, 5H,
aromatic), 7.54–7.6 (m, 2H, aromatic), 7.84 (s, 1H, aromatic-
H), 8.65–8.71 (m, 2H, aromatic). MS: m/z (%) 424 (M+, 60).
Anal. Calcd for C23H13ClF3N3: C, 65.18; H, 3.09; N, 9.9.
Found: C, 64.97; H, 2.94; N, 10.09%.
Acknowledgements
The authors are grateful to Dr. J.S. Yadav, Director, IICT,
and Shri S. Narayan Reddy, Head Fluoroorganic Division, for
their constant encouragement. DM, TY, KS, GVR and SRK are
also thankful to Council of Scientific and Industrial Research
(CSIR), New Delhi, India, for the financial support in the form
of Senior Research Fellowship (SRF) grant.
4.4.8. 7-Methyl-2-(4-methylphenyl)-4-phenyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9c)
Yield: 90 mg (78%), a pale yellow solid, mp: 278 8C. IR
1
(KBr) (cmꢀ1): 3480, 2918, 2221, 1530 and 1132. H NMR
References
(200 MHz, CDCl3): d 2.45 (s, 3H, CH3), 2.9 (s, 3H, CH3), 7.29–
7.31 (m, 2H, aromatic), 7.45–7.51 (m, 3H, aromatic), 7.53–7.59
(m, 2H, aromatic), 7.78 (s, 1H, aromatic-H), 8.59–8.62 (m, 2H,
aromatic). MS: m/z (%) 404 (M+, 29). Anal. Calcd for
C24H16F3N3: C, 71.46; H, 4.00; N, 10.42. Found: C, 71.70; H,
3.82; N, 10.56%.
[1] S. Coffey (Ed.), second ed., Rodd’s Chemistry of Carbon Compounds, vol.
4, Elsevier, Amsterdam, 1978 (Chapter 46).
[2] B.J. Hynes, A. Tomazic, A. Kumar, V. Kumar, J. Heterocycl. Chem. 28
(1991) 1981–1986.
[3] J.W. Constantine, H.J. Hess, Eur. J. Pharmacol. 74 (1981) 227.
[4] L.W. Hertel, J.S. Kroin, J.W. Misner, J.M. Tustin, J. Org. Chem. 53 (1988)
2406–2409.
[5] R. Filler, et al. (Eds.), Organo Fluorine Compounds in Medicinal Chem-
istry and Biomedical Applications, Studies in Organic Chemistry, vol. 48,
1993, p. 362.
4.4.9. 2-(4-Fluorophenyl)-7-methyl-4-phenyl-5-
(trifluoromethyl)quinazoline-8-carbonitrile (9d)
Yield: 100 mg (80%), a pale yellow solid, mp: 276 8C.
IR (KBr) (cmꢀ1): 3074, 2925, 2359, 2214, 1536, 1472 and
1126. 1H NMR (200 MHz, CDCl3): d 2.92 (s, 3H, CH3),
7.18–7.22 (m, 2H, aromatic), 7.49–7.58 (m, 5H, aromatic),
7.8 (s, 1H, aromatic-H), 8.72–8.78 (m, 2H, aromatic). MS:
m/z (%) 408 (M+, 43). Anal. Calcd for C23H13F4N3: C,
67.81; H, 3.22; N, 10.32. Found: C, 67.62; H, 3.42; N,
10.54%.
[6] J. Chae, T. Konno, T. Ishihara, H. Yamanaka, Chem. Lett. 33 (2004) 314–
315.
[7] K. Schofield, J. Chem. Soc. 9 (1952) 1927–1929.
[8] (a) J. Bergman, A. Brynolf, B. Elman, E. Vuorinen, Tetrahedron 42
(1986) 3697–3706;
(b) L. Strekowski, M.T. Cegla, D.B. Harden, J.L. Mokrosz, M.J. Mokrosz,
Tetrahedron Lett. 29 (1988) 4265–4268;
(c) B. Kokel, G. Menichi, M. Hubert-Habart, Tetrahedron Lett. 25 (1984)
1557–1560;
(d) T. Mizuno, N. Okamoto, T. Ito, T. Miyata, Tetrahedron Lett. 41 (2000)
1051–1053;
4.4.10. 2,4,7-Triphenyl-5-(trifluoromethyl)quinazoline-8-
carbonitrile (9e)
(e) J.A. Seijas, P.M. Vazquez-Tato, M.M. Martinez, Tetrahedron Lett. 41
(2000) 2215–2217;
Yield: 110 mg (85%), a pale yellow solid, mp: 255 8C. IR
(f) W. Szczepankiewicz, J. Suwinski, R. Bujok, Tetrahedron 56 (2000)
9343–9349.
1
(KBr) (cmꢀ1): 3068, 2832, 2223, 1681 and 1288. H NMR
[9] (a) E. Rossi, R. Stradi, P. Visentin, Tetrahedron 46 (1990) 3581–3592;
(b) S. Jayakumar, V. Kumar, M.P. Mahajan, Tetrahedron Lett. 42 (2001)
2235–2237.
(200 MHz, CDCl3): d 7.05–7.11 (m, 8H, aromatic), 7.33–7.38
(m, 2H, aromatic), 7.55–7.59 (m, 3H, aromatic), 7.84 (s, 1H,
aromatic-H), 8.81–8.85 (m, 2H, aromatic). MS: m/z (%) 452
(M+, 39). Anal. Calcd for C28H16F3N3: C, 74.49; H, 3.57; N,
9.31. Found: C, 74.72; H, 3.72; N, 9.50%.
[10] E. Rossi, D. Calabrese, F. Farma, Tetrahedron 47 (1991) 5819–5834.
[11] E. Rossi, G. Celentano, R. Stradi, A. Stradi, Tetrahedron Lett. 31 (1990)
903–906.

D. Maitraie et al. / Journal of Fluorine Chemistry 127 (2006) 351–359
359
[12] Y. Bathini, I. Sidhu, R. Singh, R.G. Micetich, P.L. Toogood, Tetrahedron
Lett. 43 (2002) 3295–3296.
R. Yadla, S.N. Reddy, B. Narsaiah, P. Shanthan Rao, J. Fluorine Chem.
124 (2003) 203–209.
[13] (a) A.C.S. Reddy, B. Narsaiah, R.V. Venkataratnam, Tetrahedron Lett. 37
(1996) 2829–2832;
[14] E. Gudriniece, A.V. Guttsaif, S.V. Belyakou, Latv. PSR Zinat. Akad.
Vertis. Kim. Ser. 2 (1983) 245 (Chem. Abstr. (1983), 99, 53298d).
[15] D. Maitraie, G. Venkat Reddy, V.V.V.N.S. Rama Rao, S. Ravi Kanth,
P. Shanthan Rao, B. Narsaiah, J. Fluorine Chem. 118 (2002) 73–
79.
(b) A.C.S. Reddy, P. Shanthan Rao, R.V. Venkataratnam, Tetrahedron 53
(1997) 5847–5854;
(c) G. Venkat Reddy, V.V.V.N.S. Rama Rao, D. Maitraie, S. Ravi Kanth,