An efficient synthesis of fluorine-containing substituted spiro[piperidine-4,4′-pyrano[3,2-c]quinoline]-3′-carbonitrile by nonconventional methods

Article abstract of DOI:10.1016/j.jfluchem.2007.08.002

A series of fluorine-containing substituted spiro[piperidine-4,4′-pyrano[3,2-c]quinolines] were synthesized through a rapid one-pot multi-component reaction under microwave irradiation and sonication. The method has the advantages of excellent yields (80-96%) and short reaction time (3-10 min). We provide a series of fluorinated quinoline derivatives interesting for biological screening tests.

Full text of DOI:10.1016/j.jfluchem.2007.08.002

Journal of Fluorine Chemistry 128 (2007) 1454–1460
www.elsevier.com/locate/fluor
An efficient synthesis of fluorine-containing substituted spiro[piperidine-4,
40-pyrano[3,2-c]quinoline]-30-carbonitrile by nonconventional methods
*
Anshu Dandia , Sangeeta Gautam, Anuj Kumar Jain
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
Received 28 February 2007; received in revised form 30 July 2007; accepted 6 August 2007
Available online 10 August 2007
Abstract
A series of fluorine-containing substituted spiro[piperidine-4,40-pyrano[3,2-c]quinolines] were synthesized through a rapid one-pot multi-
component reaction under microwave irradiation and sonication. The method has the advantages of excellent yields (80–96%) and short reaction
time (3–10 min). We provide a series of fluorinated quinoline derivatives interesting for biological screening tests.
# 2007 Published by Elsevier B.V.
Keywords: Fluorinated pyrano[3,2-c]quinoline; Spiropiperidine; Microwave irradiation; Ultrasound waves
1. Introduction
The fluorine-containing heterocycles are now widely
recognized as important organic materials showing interesting
biological activities for their potential use in medicinal and
agricultural scientific fields [11–14]. The fluoro quinolones
have proven to be the most successful economically and
clinically, notable clinical examples are world wide patented
drugs, e.g., norfloxacin, ciprofloxacin, ofloxacin, enooxacin,
perfloxacin, grepafloxacin, etc., as antimicrobial, antibacterial
[15], anticonvulsant, CNS depressing [16] and hypotensive
agents. They are orally and parenterally active, have a broad
antimicrobial spectrum that includes many frequently encoun-
tered pathogens, are bactericidal in clinically achievable doses,
generate comparatively tolerable resistance levels, and possess
a fascinating molecular mode of action. That is not to say that
they are perfect drugs [17].
Substituted pyrano quinolines have been synthesized in a
search for new physiologically active compounds, drugs,
pesticides and other compounds of practical significance [1,2].
Pyrano quinoline moiety is also present in many naturally
occurring bioactive alkaloids such as flindersine, oricine and
vesprisine [3], simulenoline [4,5], huajiaosimuline [6] and
zanthodioline.
Among several scaffolds, spiropiperidines showed to be an
interesting and promising class of nociceptin (NOP) ligands.
They are structurally related to lofentanyl, a m-selective opiate
ligand having also affinity for the NOP (nociceptin) receptor.
Spiropiperidines [7] are also useful tools for the elucidation of
the mechanism of interaction of small nonpeptidic molecules.
Most of the spiropiperidines have been reported to possess high
agonistic activity and selectivity as Ro64-619814, which also
exhibited anxiolytic properties [8]. Substituted piperidin-4-
ones are important synthetic intermediate for the preparation of
various alkaloids and pharmaceuticals [9]. This nucleus is also
frequently recognized in the structure of numerous naturally
occurring alkaloid and synthetic compounds with interesting
biological and pharmacological properties [10].
Inspite of the immense biological activities of pyrano
quinolines and spiropiperidine derivatives no report is yet
available on the synthesis of fluorinated spiro derivatives
incorporating both biolabile nuclei in a single framework.
Hence, promoted by this observation and in continuation of
our earlier interest on the green chemical synthesis of
biodynamic spiro derivatives using a nontraditional approach
[18] an attempt has been made to synthesize fluorinated novel
20-amino-1,70,90-trimethyl-50-oxo-spiro[piperidine-4,40-pyr-
ano[3,2-c]quinoline]-30-carbonitrile with the assumption that
the incorporation of more than one bioactive heterocycle
moiety into a single framework may result in the production of
novel heterocycles with enhance/altered bioactivity.
* Corresponding author.
E-mail address: dranshudandia@yahoo.co.in (A. Dandia).
0022-1139/$ – see front matter # 2007 Published by Elsevier B.V.
doi:10.1016/j.jfluchem.2007.08.002

A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
1455
Table 1
2. Results and discussion
Comparative study for synthesis of compound (6)
Entry Reaction conditions Method
Time/yield
For synthesis of novel spiro derivatives, at first we attempted
to obtain unsaturated nitrile (Scheme 1) by the condensation of
piperidin-4-one (2a) and malononitrile (3), but the resulting
compound is unstable and dimerized at room temperature to
form spiropiperidinoisoquinoline (4a)[19,20] within 2–3 min
after mixing the reactants (chromatographic monitoring).
To overcome this problem and encouraged by the potential
of multi-component reactions (MCR) [21,22] in organic
synthesis specially when intermediates are unstable, we studied
the three component condensation of substituted piperidin-4-
ones (2), malononitrile (3a) and substituted 4-hydroxy
quinolones (5), which afforded the required product spiro[pi-
peridine-4,40-pyrano[3,2-c]quinoline]-30-carbonitrile (6) exclu-
sively in good yield (80–90%). To optimize the method, the
reaction was studied under different reaction conditions to find
out the best results (Table 1).
1
Ethanol (MCR)
D
No reaction*
12 h/76%
8 min/92%
7 min/94%
7 h/90%
2
3
4
5
6
7
8
Ethanol + TEA (MCR)
Ethanol (MCR)
D
MW
Ethanol + TEA (MCR)
Ethanol + TEA (MCR)
Ethanol (MCR)
MW
US (80 8C)
US (80 8C)
D
8 h/86%
ꢀ
Neat + eDMF
5 h/68%
ꢀ
Neat + eDMF
MW
7 min/70%
ꢀ
e= few drops of DMF, TEA = triethylamine, US = ultrasound, No reac-
tion* = no reaction after formation of intermediate (4).
From the results obtained as shown in (Table 1), it is clear
that the MCR of (5), (3) and (2) occurred successfully in ethanol
without using any catalyst under microwaves and ultrasound,
which are well-known nonconventional energy sources for
carrying out green chemical synthesis [23–31]. However,
Scheme 1.
Scheme 2.

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A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
Scheme 3.
Scheme 4.
formation of spiro product under conventional condition
required the prolonged refluxing in ethanol in the presence
of triethylamine.
Compound (6) was obtained in pure form after washing with
ethanol.
Further, to study this reaction more thoroughly, we
introduced indol-2,3-dione (9) (isatin) and model cage
compound adamantan-2-one (12) into the described three-
component condensation instead of the piperidin-4-ones. In
case of isatin, the reaction occurs successfully to give expected
spiro derivative (14) involving the intermediate formation of (2-
oxo-1,2-dihydro-3H-indol-3-ylidene)malononitrile (13), which
can be separated out and did not dimerize after prolonged
refluxing in ethanol (Scheme 4).
The reaction was also performed under neat conditions in the
absence of any solvent or catalyst under microwave irradiation
and it was found that at low power level only intermediate was
found while at higher power charring occurs. Hence, reaction
could be made successful by adding a few drops of DMF, but it
can be concluded that under microwaves the reaction is very
fast giving required product in 8 min. While, the ultrasonic
process is more regioselective, the product of the reaction is
analytically pure and does not require further recrystallization.
A plausible mechanism for the multi-component reaction of
(5), (3) and (2) is given in (Scheme 2). Probably such
regioselectivity has been determined by the stringent reaction
sequence. That is, the initially formed unsaturated nitrile (1a),
which acts as electrophile reacts with the ‘‘in situ’’ generated
nucleophile anion of 4-hydroxy quinolones to give Michael
adduct (7). Subsequent intramolecular cyclization and tauto-
meric transformation lead to the desired product (6).
In the MCR of (2), (3) and (5) although the another route is
also possible as shown in (Scheme 3), which involves the
formation of intermediate (8), which may react with
malononitrile to give finally the spiro[piperidine-4,40-pyr-
ano[3,2-c]-quinoline (6).
While in case of adamantan-2-one (12), the reaction occurs,
to form stable Michael adduct (11), but due to some steric
But in the present studies the possibility of occurrence of the
reaction by path i (Scheme 2) is important and TLC studies also
indicated the formation of dimer along with the compound (6).
Scheme 5.

A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
1457
Table 2
Method and yield of substituted spiro[piperidine-4,40-pyrano[3,2-c]quinoline] 6
Entry
1
Reactant 2/9/12
Reactant 3
Reactant 5
Method
Time
Product 6/11/14
Yield (%)
2b
3a
5a
X = F, Y = Z = H
A
B
C
D
5 h
6a
82
86
70
87
8 min
12 min
10 min
2
3
2a
2a
2a
2a
2a
2a
2a
2b
2b
3a
3a
3a
3a
3a
3a
3b
3a
3a
5a
X = F, Y = Z = H
A
B
C
D
5 h
6b
6c
6d
6e
6f
72
82
75
76
5 min
15 min
8 min
5b
A
B
C
D
4 h
86
96
80
92
Y = F, X = Z = H
4 min
16 min
8 min
4
5c
Y = CF3, X = Z = H
A
B
C
D
5 h
81
92
85
90
5 min
9 min
8 min
5
5d
X = CF3, Y = Z = H
A
B
C
D
9 h
80
94
80
90
6 min
11 min
9 min
6
5e
Z = F, X = Y = H
A
B
C
D
6 h
80
90
85
91
10 min
9 min
9 min
7
5f
Y = H, X = Z = CH3
A
B
C
D
6 h
6g
6h
6i
76
92
70
86
3 min
5 min
5 min
8
5f
Y = H, X = Z = CH3
A
B
C
D
7 h
75
82
76
81
6 min
8 min
11 min
9
5g
Y = X = Z = H
A
B
C
D
4 h
81
90
76
88
4 min
6 min
7 min
10
5h
Z = Cl, X = Y = H
A
B
C
D
6 h
6j
83
92
72
90
7 min
12 min
9 min
11
12
13
9a
9b
12
3a
3a
3a
5g
Y = X = Z = H
B
5 min
14a
14b
11a
80%
5g
Y = X = Z = H
B
2 min
81%
5g
Y = X = Z = H
A
B
D
9 h
70%
80%
82%
9 min
12 min
14
12
3a
5a
X = F, Y = Z = H
A
B
D
5 h
11b
88%
92%
89%
10 min
17 min
Method A: reflux in EtOH, TEA, Method B: MW in EtOH, Method C: MW in DMF, Method D: sonication.
hindrance Michael adduct (11) did not cyclized to pyran
derivative (10) upon prolonged refluxing in ethanol in the
presence of triethylamine or under microwave irradiation/
sonication (Scheme 5) (Table 2).
3. Conclusion
In conclusion, the reported one pot procedure is attrac-
tive methodology for the facile rapid synthesis of novel

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A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
spiro[piperidine-4,40-pyrano[3,2-c]quinolines] involving the
Michael and Knoevenagel condensations.
appropriate time at 300 W. The mixture was then cooled and
product separated was filtered and washed with ethanol
thoroughly. It was found that the product is pure by TLC
analysis in most cases.
The reaction course, that is formation of either compound 4
or 6 depends on the structure of the intermediate and the
conditions. It is difficult to predict the reaction course
unambiguously but on the basis of comparative studies with
other cyclic ketone, e.g., isatin and adamantan-2-one and
isolation of intermediates it appears that reaction occur
regioselectively by path i. We can say that the study of
cross-condensation of this type is very important because it
leads to the development of one-pot methods for synthesis of
complicated and interesting organic compounds.
4.2.3. Method C
An equimolar mixture (1 mmol) of (5), (2) and (3) with few
drops of DMF, in an open tall beaker was irradiated inside
microwave oven for an appropriate time (monitored by TLC).
The solid mass obtained poured into water to give product,
which was recrystallized from ethanol.
4.2.4. Method D
4. Experimental
An equimolar mixture (1 mmol) of (5), (2) and (3)
dissolved in minimum quantity of ethanol in a conical flask,
which was immersed in the water bath of an ultrasonic cleaner.
The flask was positioned 0.5 cm above the bottom of the bath
and the level of the water was adjusted to that of the solvent
level inside the flask. The mixture was treated with ultrasound
(operating at 230 V generating 33 KHz output frequencies) for
appropriate time (TLC). The product started to separate out
during the course of the reaction The solid that separate out
was filtered, washed with ethanol and found to be pure by TLC
analysis.
4.1. General
Melting points were determined on a Toshniwal apparatus.
The purity of compounds was checked by thin layer of silica
gel. IR spectra (KBr) were recorded on a Shimadzu FT IR-
8400s spectrophotometer and H NMR and 13C NMR spectra
1
were recorded on
a Bruker DRX-300 instrument at
300.15 MHz for 1H and 89.55 MHz for 13C NMR, respectively,
in CDCl3 relative to tetramethylsilane as a internal reference.
The mass spectrum of a representative compound was recorded
on a Kratos 50 mass spectrometer at 70 eV. The microwave-
assisted reactions were carried out in a multimode MW oven
(Panasonic-NN-781JF) equipped with inverter technology
(generating fixed frequency throughout the required time)
for realistic control of the microwave operating at 1000 W
generating 2450 MHz frequency and ultrasound enhanced
reactions were carried out in an ultrasonic bath (Bandelin
Sonorex) operating at 230 V and generating 33 KHz output
frequency.
Although pure crystalline product was obtained under
microwaves and sonication (TLC), for analytical purpose the
product was further recrystallized from ethanol.
The identification of substituted 20-amino-1-benzyl/methyl-
50-oxo-spiro[piperidine-4,40-pyrano[3,2-c]quinoline]-30-carbo-
nitrile or carboxyethyl synthesized was established by their mp,
1
IR, H NMR, 13C NMR and Mass (representative compound)
spectral studies.
6a. Mp: 310 8C. 1H NMR (CDCl3) d 10.69 (s, 1H, NH, D2O
exchangeable), 8.07–6.83 (m, 10H, Ar–H, NH2 D2O exchange-
able), 3.54 (s, 2H, CH2Ph), 2.59 (m, 2H), 2.42 (m, 2H), 2.16 (m,
2H), 1.81 (m, 2H). IR (cmꢀ1) 3395, 3350 (NH2), 2345 (CBB N),
1687 (C O), 1180 (C–O), 760 (C–F). 13C NMR d 171.22,
161.87, 154.36, 137.81, 135.96, 128.81, 127.21, 126.91,
126.61, 125.46, 123.41, 120.32, 107,36, 65.71, 58.49, 46.10,
45.96, 26.56, 26.54, 19.18. 19F NMR d 120.42 (s, C–F). Anal
calcd. for C24H21FN4O2: C, 69.22; H, 5.08; N,13.45. Found C,
69.02; H, 5.06; N, 13.41.
Substituted 4-hydroxy quinolines (5a–h) were prepared by
improved method under microwaves developed in our
laboratory [32].
4.2. General procedures for the synthesis of compounds
(6a–j)
4.2.1. Method A
An equimolar mixture of ketone (2), (1 mmol) malononitrile
(1 mmol) and corresponding 4-hydroxy quinoline (1 mmol)
and triethylamine (0.5 ml) in absolute ethanol was refluxed for
6 h or stirred for 12 h at room temperature. TLC monitored the
progress of the reaction. The precipitate that formed was
filtered off, indicated intermediate along with required product.
This precipitate was passed through a silica gel column with a
mixture of ethyl acetate and petroleum ether (1:15, v/v) as an
eluent to give pure product.
6b. Mp: 223 8C. 1H NMR (CDCl3) d 9.61 (s, 1H, NH, D2O
exchangeable), 7.16–6.89 (m, 5H, Ar–H, NH2, D2O exchange-
able), 2.60 (m, 2H), 2.57 (s, 3H, CH3), 2.42 (m, 2H), 2.11 (m,
2H), 1.81 (m, 2H). IR (cmꢀ1) 3380, 3310 (NH2) 2352 (CBB N),
1685 (C O), 1180 (C–O), 780 (C–F). 13C NMR d 171.16,
162.80, 154.39, 134.91, 126.96, 125.47, 123.49, 116.26,
107.32, 65.74, 48.79, 48.46, 38.01, 25.26, 26.16, 19.22. 19F
NMR d 119.20 (s, C–F). Anal calcd. for C18H17FN4O2: C,
63.52; H, 5.03; N,16.46. Found C, 63.33; H, 5.02; N, 16.41.
6c. Mp; 265 8C. 1H NMR (CDCl3) d 10.51 (s, 1H, NH, D2O
exchangeable), 7.89–7.51 (m, 5H, Ar–H, NH2, D2O exchange-
able), 2.61 (m, 2H), 2.60 (s, 3H, CH3), 2.41 (m, 2H), 2.15 (m,
2H), 1.50 (m, 2H). IR (cmꢀ1) 3392, 3320 (NH2), 2347 (CBB N),
1688 (C O), 1185 (C–O), 760 (C–F). 13C NMR d170.81,
160.82, 152.19, 133.96, 126.94, 125.49, 122.49, 119.34,
4.2.2. Method B
An equimolar mixture (1 mmol) of (5), (2) and (3) was
introduced in a beaker and minimum quantity of ethanol
sufficient to make slurry was added in the absence of catalyst.
The mixture was placed in a microwave oven and irradiated for

A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
1459
116.24, 107.34, 65.94, 48.79, 48.64, 38.34, 26.19, 19.11. 19F
NMR d 118.05 (s, C–F). Anal calcd. for C18H17FN4O2: C,
63.52; H, 5.03; N, 16.46. Found C, 63.51; H, 5.04; N, 16.42.
6d. Mp: 280 8C. 1H NMR (CDCl3) d 10.16 (s, 1H, NH, D2O
exchangeable), 7.50–7.47 (m, 5H, Ar–H, NH2, D2O exchange-
able), 2.60 (m, 2H), 2.50 (s, 3H, CH3), 2.38 (m, 2H), 2.30 (m,
2H), 1.87 (m, 2H). IR (cmꢀ1) 3390, 3350 (NH2), 2355 (CBBN),
1695 (C O), 1195 (C–O), 770 (C–F). 13C NMR d 170.92,
160.84, 153.94, 132.96, 125.41, 124.96, 123.49, 119.39,
116.29, 112.64, 107.39, 65.99, 48.79, 48.26, 39.12, 26.24,
26.02, 19.11. 19F NMR d 64.01 (s, C–CF3). Anal calcd. for
C19H17F3N4O2: C, 58.46; H, 4.39; N, 14.60. Found C, 58.65; H,
4.38; N, 14.56.
6e. Mp: 145 8C. 1H NMR (CDCl3) d 10.16 (s, 1H, NH, D2O
exchangeable), 7.50–7.47 (m, 5H, Ar–H, NH2, D2O exchange-
able), 2.61 (m, 2H), 2.52 (s, 3H, CH3), 2.38 (m, 2H), 2.30 (m,
2H), 1.87 (m, 2H). IR (cmꢀ1) 3390, 3350 (NH2), 2355 (CBBN),
1695 (C O), 1195 (C–O), 760 (C–F). 13C NMR d171.01,
162.81, 154.91, 132.54, 128.79, 125.69, 123.19, 116.24,
109.65, 107.91, 65.64, 48.59, 48.26, 38.04, 26.64, 26.51,
19.07. 19F NMR d 63.24 (s, C–CF3). Anal calcd. for
C19H17F3N4O2: C,60.59; H, 4.39; N, 15.70. Found C, 58.63;
H, 4.40; N, 60.40.
(NH2), 2355 (CBBN), 1696 (C O), 1190 (C–O). 13C NMR
d171.26, 162.87. 154.10, 135.35, 133.21, 129.36, 128.01,
127.36, 126.72, 125.27, 124.06, 116.21, 107.06, 65.74, 57.46,
47.19, 47.12, 27.56, 27.42, 19.30. Anal calcd. for C24H22N4O2:
C, 72.34; H, 5.57; N, 14.02. Found C, 72.13; H, 5.55; N, 14.02.
1
6j. Mp: 215 8C. H NMR (CDCl3) d 9.52 (s, 1H, NH, D2O
exchangeable), 7.59–7.26 (m, 8H, Ar–H); 6.70 (br, s, 2H, NH2,
D2O exchangeable), 3.71 (s, 2H, CH2Ph), 2.63 (m, 2H), 2.38
(m, 2H), 2.20 (m, 2H), 1.81 (m, 2H). IR (cmꢀ1) 3392, 3330
(NH2), 2356 (CBBN), 1697 (C O), 1195 (C–O), 735 (C–Cl).
13C NMR d 170.21, 163.84, 155.90, 135.32, 128.36, 128.32,
127.10, 127.01, 126.36, 125.71, 124.01, 115.20, 106.01, 64.72,
56.41, 47.16, 46.10, 26.51, 26.06, 19.12. Anal calcd. for
C24H21N4ClO2: C, 72.34; H, 5.60; N, 14.05. Found C, 72.11; H,
5.60; N, 14.01.
14a. Mp: 258 8C. 1H NMR (CDCl3) d 9.19 (s, 1H, NH, D2O
exchangeable), 8.60–7.02 (m, 11H, Ar–H, NH and NH2, D2O
exchangeable). IR (cmꢀ1) 3370, 3200 (NH2 and NH), 2100
(CBB N), 1725, 1695 (two C O), 1170 (C–O). 13C NMR d
177.06, 166.63, 162.49, 157.91, 141.82, 133.53, 132.33,
129.49, 128.10, 127.41, 127.36, 126.77, 126.12, 121.42,
116.78, 97.04, 56.70, 46.70. Anal calcd. for C20H12N4O3,: C,
67.41; H, 3.39; N 15.72. Found C, 67.21; H, 3.38; N 15.67.
14b. Mp: 220 8C. 1H NMR (CDCl3) d 9.24 (s, 1H, NH, D2O
exchangeable), 8.28–6.83 (m, 10H, Ar–H, NH and NH2, D2O
exchangeable), 2.21 (s, 3H, CH3). IR (cmꢀ1) 3360, 3200 (NH2
and NH), 2100 (CBBN), 1720, 1690 (two C O), 1170 (C–O).
13C NMR d 176.29, 167.32, 162.78, 158.67, 140.91, 134.29,
133.38, 129.24, 128.73, 127.67, 126.34, 125.49, 123.05,
119.43, 116.72, 98.04, 56.64, 46.61, 20.42. Anal calcd. for
C21H14N4O3: C, 68.10; H, 3.81; N 15.13. Found C, 67.90; H,
3.80; N 15.08.
6f. Mp: 275 8C. 1H NMR (CDCl3) d 10.70 (s, 1H, NH, D2O
exchangeable), 7.80–7.02 (m, 5H, Ar–H, NH2, D2O exchange-
able), 2.60 (m, 2H), 2.56 (s, 3H, CH3), 2.35 (m, 2H), 2.20 (m,
2H), 1.87 (m, 2H). IR (cmꢀ1) 3385, 3300 (NH2), 2350 (CBBN),
1692 (C O) 1180 (C–O), 780 (C–F). 13CNMR d 170.71,
162.72, 156.72, 154.09, 130.86, 126.64, 122.59, 116.34,
106.24, 65.64, 48.76, 48.61, 38.21, 26.21, 26.09, 19.10. Anal
calcd. for C18H17FN4O2: C, 63.52; H, 5.03; N, 16.46. Found C,
63.71; H, 5.02; N, 16.41.
6g. Mp: 140 8C. 1H NMR (CDCl3) d 10.20 (s, 1H, NH, D2O
exchangeable), 7.84–7.49 (m, 4H, Ar–H, NH2, D2O exchange-
able), 2.62 (m, 2H), 2.50 (s, 3H, N–CH3), 2.40 (m, 2H), 2.27,
11a. Mp: 133 8C. H NMR (CDCl3) d 10.93 (bs, 1H, OH,
1
D2O exchangeable), 9.42 (s, 1H, NH, D2O exchangeable),
7.60–7.28 (m, 4H, Ar–H), 3.58 (s, 1H, CH), 2.07–1.25 (m,
14H, adamantanyl protons). IR (cmꢀ1) 3275 (NH), 2200 (two
CBB N), 1725 (C O). 13C NMR d162.81, 160.34, 134.86,
127.41, 126.97, 123.81, 119.32, 117.69, 100.83, 37.27, 31.16,
29.33, 29.21, 28.84, 28.46, 28.06, 19.42. Anal calcd. for
C22H21N3O2: C, 73.52; H, 5.89; N 11.69. Found C, 73.42; H,
5.87; N 11.65.
2.26 (2s, 6H, Ar–CH3), 2.20 (m, 2H), 1.87 (m, 2H). IR (cmꢀ1
3380, 3300 (NH2), 2350 (CBB N), 1690 (C O), 1190 (C–O). 13
)
C
NMR d 170.11, 161.01, 154.64, 132.91, 128.46, 123.11,
116.21, 107.32, 65.74, 48.74, 48.21, 39.54, 26.21, 26.01, 21.64,
19.17, 12.54. m/z (%) 350 (15, M+), 349 (10), 323 (20), 311
(100), 293 (40), 288 (30), 190 (60), 105 (35). Anal calcd. for
C20H22N4O2: C, 68.55; H, 6.33; N, 15.99. Found C, 68.34; H,
6.31; N, 15.94.
1
11b. Mp: 186 8C. H NMR (CDCl3) d 10.52 (bs, 1H, OH,
D2O exchangeable), 9.62 (s, 1H, NH, D2O exchangeable),
7.55–6.92 (m, 3H, Ar–H), 3.55 (s, 1H, CH), 2.10–1.52 (m, 14H,
adamantanyl protons). IR (cmꢀ1) 3270 (NH), 2210 (two CBBN),
1720 (C O), 785 (C–F). 13C NMR d 161.80, 159.54, 134.62,
126.45, 124.91, 124.69, 120.34, 116.40, 101.53, 36.51, 32.45,
30.61, 29.43, 28.54, 28.29, 28.09, 20.05. Anal calcd. for
C22H20FN3O2: C, 70.01; H, 5.34; N 11.13. Found C, 69.81; H,
5.35; N, 11.10.
6h. Mp: 300 8C. 1H NMR (CDCl3) d 10.69 (s, 1H, NH, D2O
exchangeable), 8.55–7.20 (m, 4H, Ar–H, NH2, D2O exchange-
able) 4.41 (q, 2H, CH2), 2.62 (m, 2H), 2.38 (m, 2H), 2.58 (s, 3H,
CH3), 2.27,2.26 (2s, 6H, CH3), 2.14 (m, 2H), 1.81 (m, 2H), 1.44
(t, 3H, CH3). IR (cmꢀ1) 3385, 3350 (NH2), 1685, 1680 (2C O),
1170 (C–O). 13C NMR d164.94, 163.84, 160.94, 153.09,
132.64, 128.49, 124.64, 107.64, 88.94, 58.91, 49.24, 49.16,
38.91, 26.94, 26.64, 20.69, 19.07, 12.74, 11.51. Anal calcd. for
C22H27N2O4: C, 66.48; H, 6.85; N, 10.57. Found C, 66.28; H,
6.83; N, 10.54.
Acknowledgements
1
6i. Mp: 181 8C. H NMR (CDCl3) d 9.50 (s, 1H, NH, D2O
Financial assistance from CSIR [No. 01 (1907)/03/EMR-II]
and UGC New Delhi is gratefully acknowledged. We are also
thankful to RSIC, CDRI, Lucknow for the elemental and
spectral analyses.
exchangeable), 8.56–7.21 (m, 9H, Ar–H), 6.50 (s, 2H, NH2,
D2O exchangeable), 3.72 (s, 2H, CH2Ph), 2.62 (m, 2H), 2.37
(m, 2H), 2.12 (m, 2H), 1.80 (m, 2H). IR (cmꢀ1) 3390, 3300

1460
A. Dandia et al. / Journal of Fluorine Chemistry 128 (2007) 1454–1460
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