A valuable heterocyclic ring transformation: From isoxazolin-5(2H)-ones to quinolines

Article abstract of DOI:10.1016/j.tet.2003.10.053

A new synthesis of quinoline derivatives was achieved by catalytic hydrogenation of 3,4-disubstituted 2-(2-formylphenyl)-isoxazolin-5(2H)-ones. In the same way, 2,3-disubstituted [1,8]naphthyridine was obtained.

Full text of DOI:10.1016/j.tet.2003.10.053

Tetrahedron 59 (2003) 9887–9893
A valuable heterocyclic ring transformation:
from isoxazolin-5(2H)-ones to quinolines
b
a
Giorgio Abbiati,a Egle M. Beccalli,a Gianluigi Broggini and Caterina Zoni
,
*
a
`
`
Istituto di Chimica Organica “A.Marchesini”, Facolta di Farmacia, Universita di Milano, via Venezian 21, 20133 Milano, Italy
`
Dipartimento di Scienze Chimiche, Fisiche e Matematiche, Universita dell’Insubria, via Valleggio 11, 22100 Como, Italy
b
Received 25 July 2003; revised 18 September 2003; accepted 16 October 2003
Abstract—A new synthesis of quinoline derivatives was achieved by catalytic hydrogenation of 3,4-disubstituted 2-(2-formylphenyl)-
isoxazolin-5(2H)-ones. In the same way, 2,3-disubstituted [1,8]naphthyridine was obtained.
q 2003 Elsevier Ltd. All rights reserved.
The development of new methods for the synthesis of
nitrogen-containing heterocycles is of extreme importance
in organic chemistry. We reported in the past years, the
synthesis of pyrroles,1 oxazinones,2 imidazoles,3 2-pyra-
zinones,4 isoxazoles5 starting from isoxazolin-5-ones. As a
part of our ongoing interest in the study of the reactivity of
the isoxazolone nucleus as a synthon to obtain different
heterocyclic systems, we describe now a new and easy
approach to the quinoline nucleus starting from 2-aryl-3,4-
disubstituted isoxazolin-5(2H)-ones. The presence of the
quinoline scaffold in the framework of various pharmaco-
logically active compounds with antiasthmatic,6 antiinflam-
matory7 and tyrosine kinase inhibiting properties8 continues
to spur synthetic efforts regarding their acquisition.9
corresponding salt. On the basis of our research on the
5(2H)-isoxazolones as nucleophiles12 we have considered
the reaction of the isoxazolyl anion with a proper aryl halide
in a nucleophilic aromatic substitution to give the 2-aryl
derivatives 3 (Scheme 1 and Table 1). The nucleophilic
substitution was possible only when the aryl halide was
activated by an electron-withdrawing group in the para
position to the halogen atom. The reaction was performed
with 2-fluoro-5-nitrobenzaldehyde 2a and with 2-fluoro-5-
trifluoromethylbenzaldehyde 2b. Better yields were
obtained with 2a in comparison to 2b.
It is known that catalytic hydrogenation of the isoxazolin-5-
ones favours the N–O bond cleavage.13 Consequently, the
ring opening gave the enamine intermediate 4 susceptible to
The synthesis of quinolines has been a focus of organic
chemistry for more than 100 years.10 Most of the classical
synthetic routes are limited to certain substitution patterns
and suffer from harsh reaction conditions and poor yields. A
precedent paper describing the synthesis of the 2,4-
dichloroquinolines starting from 3-arylisoxazol-5(4H)-
ones via Vilsmeier–Haack reaction is available.11 The
overall synthetic sequence to obtain quinolines consisted of
three very simple steps: (a) isolation of the 3,4-disubstituted
isoxazolin-5(2H)-one salt 10a–g; (b) nucleophilic substi-
tution with the 2-fluorobenzaldehyde derivatives 2a or 2b to
give the adducts 3; (c) catalytic hydrogenation reaction to
give directly the desired quinoline derivatives 5.
Owing to the strong acidity of the isoxazolin-5(4H)-one
nucleus, the reaction with a base (TEA or EtONa) gave the
Keywords: quinolines; isoxazolones; catalytic hydrogenation;
naphthyridine.
*
Corresponding author. Tel.: þ39-0250314479; fax: þ39-0250314476;
Scheme 1.
e-mail: egle.beccalli@unimi.it
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.053

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G. Abbiati et al. / Tetrahedron 59 (2003) 9887–9893
Table 1. Data for Scheme 1
Substrate
R
R1
Substrate R2 Product Yield
(%)
1a
1b
1c
1d
1e
1f
1g
1a
1b
1c
1d
1e
1f
CH3
CH3
CH2Ph
Ph
2a
2a
2a
2a
NO2 3aa
NO2 3ba
NO2 3ca
NO2 3da
NO2 3ea
NO2 3fa
NO2 3ga
CF3 3ab
CF3 3bb
CF3 3cb
CF3 3db
CF3 3eb
CF3 3fb
CF3 3gb
99
78
70
95
83
99
87
70
75
68
62
68
67
68
Scheme 3.
CH2CH2CH3 CH2Ph
Ph
Ph
–(CH2)4–
–CH2CH2SCH2–
CH3
CH3
CH2CH2CH3 CH2Ph
Ph
Ph
–(CH2)4–
–CH2CH2SCH2–
CH3
CH2CH3 2a
2a
was tested with the isoxazolone salt 10a and 2-fluoro-3-
formylpyridine. The adduct 8 was submitted to the
hydrogenation process and the reaction gave the
[1,8]naphthyridine 9 in good yield. Besides the fully
aromatic product, the reductive process gave also the
[1,8]tetrahydronaphthyridine 10 arising from the partial
hydrogenation of the pyridine ring (Scheme 4). The ratio
between the two products depends on the reaction
conditions. Performing the hydrogenation with Pd/C in
ethyl acetate the ratio was 6:1 in favour of the naphthyridine
9, with Pd/C in ethanol the result was opposite with a ratio
1:3 in favour of the tetrahydronaphthyridine 10.
2a
2b
2b
2b
2b
CH2Ph
Ph
CH3
CH2CH3 2b
2b
2b
1g
decarboxylation and subsequent intramolecular cyclocon-
densation on the formyl group. The hydrogenation reaction
was performed with different catalysts and solvents. Better
yields were obtained with palladium on charcoal in ethanol
as a solvent. In the case of the substrates 3aa–ga containing
the nitro group, in all conditions, the 6-aminoquinoline
derivatives 6 were obtained as major product, accompanied by
a minor amount of the quinolines 5. In the case of substrates
3da, 3ea, 3ga only the corresponding aminoquinolines 6da,
6ea and 6ga were isolated (Scheme 2 and Table 2).
Scheme 4.
Scheme 2.
In conclusion, this paper shows a new and easy synthetic
pathway to the quinoline system allowing a very large
substitution patterns. Furthermore, starting from suitable
substrate, the synthesis of other heterocyclic systems is
possible.
Only in the case of compound 3ga containing a sulfur atom,
the quinoline 5ga was the only product. With the substrates
3ab-gb including the trifluoromethyl group on the aromatic
ring, besides the desired quinolines 5 tetrahydroquinolines 7
were also isolated, with the exception of 5gb (Scheme 3 and
Table 2). The relative configuration of the two stereocentres
was assumed to be cis on the basis of the vicinal coupling
constants, whenever detectable.14
1. Experimental
1.1. General
With the aim to extend the synthetic procedure for the
preparation of different heterocyclic systems, the reaction
Melting points were determined on a Buchi 510 or an
Table 2. Data for Schemes 2 and 3
Substrate
R
R1
Product 5
Yield (%)
Product 6
Yield (%)
Product 7
Yield (%)
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ab
3bb
3cb
3db
3eb
3fb
3gb
CH3
CH3
CH2CH2CH3
Ph
Ph
–(CH2)4–
–CH2CH2SCH2–
CH3
CH2Ph
Ph
CH2Ph
CH3
CH2CH3
5aa
5ba
5ca
5da
5ea
5fa
5ga
5ab
5bb
5cb
5db
5eb
5fb
5gb
8
6
10
–
–
6aa
6ba
6ca
6da
6ea
6fa
84
66
64
97
98
55
–
–
84
45
41
58
38
61
32
77
6ga
CH2Ph
Ph
CH2Ph
CH3
CH2CH3
7ab
7bb
7cb
7db
7eb
7fb
14
41
23
48
28
40
–
CH3
CH2CH2CH3
Ph
Ph
–(CH2)4–
–CH2CH2SCH2–
7gb

G. Abbiati et al. / Tetrahedron 59 (2003) 9887–9893
9889
Electrothermal 9100 apparatus and are uncorrected. IR
spectra were recorded on a Jasco IR Report 100 spectro-
photometer, in nujol mull for solids and as a liquid film for
1377 cm21; 1H NMR: 2.31 (s, 3H), 7.41–7.65 (m, 6H), 8.58
(dd, 1H, J¼2.5, 8.8 Hz), 8.91 (d, 1H, J¼2.5 Hz), 10.51 (s,
1H); 13C NMR: 13.5 (CH3), 124.9, 129.5 (CHAr), 127.4
(2£CHAr), 128.6 (2£CHAr), 129.1 (2£CHAr), 107.5,
128.3, 133.2, 144.1, 148.3, 158.8 (C), 168.7 (CO), 186.7
(CHO). Anal. calcd for C17H12N2O5: C, 62.96; H, 3.73; N,
8.64. Found: C, 63.03; H, 3.80; N, 8.52.
1
oils. H NMR and 13C NMR spectra were recorded on a
Varian Gemini 200, Bruker AC 200 and Bruker Avance 300
spectrometer in CDCl3 solution unless otherwise stated.
Column chromatography was performed on Merck Kieselgel
60, 0.063–0.2 mm. Evaporation was carried out under
vacuum in a rotary evaporator.
From 1c and 2a, heated for 2 h, 3ca, mp 85–878C (yellow
crystals from Et2O–hexane); IR: 1722, 1613, 1528 cm21
;
Compounds 1a,15 1b,16 1c,17 1d,18 1e,19 1f,20 were prepared
according to the literature procedures.
1H NMR: 0.82 (t, 3H, J¼7.3 Hz), 1.20–1.40 (m, 2H), 2.36
(t, 2H, J¼7.3 Hz), 3.75 (s, 2H), 7.33 (m, 5H), 7.40 (d, 1H,
J¼8.8 Hz), 8.52 (dd, 1H, J¼2.5, 8.8 Hz); 8.87 (d, 1H,
J¼2.5 Hz), 10.51 (s, 1H); 13C NMR 14.1 (CH3), 21.6, 28.5,
28.8 (CH2), 124.6, 127.3, 127.8, 129.2, 129.3, 129.6
(CHAr), 128.6 (2£CHAr), 107.7, 134.2, 138.3, 145.6,
148.8, 154.8 (C), 164.8 (CO), 186.9 (CHO). Anal. calcd
for C20H18N2O5: C, 65.57; H, 4.95; N, 7.65. Found: C,
65.42; H, 5.03; N, 7.60.
1.1.1. Synthesis of 1,4,6,7-tetrahydrothiopyrano[4,3-c]iso-
xazol-3-one 1g. To a solution of 4-oxo-tetrahydro-thio-
pyran-3-ethylcarboxylate21 (5.6 g, 30 mmol) in EtOH
(80 ml)
a mixture of hydroxylamine hydrochloride
(3.12 g, 45 mmol) and AcONa (3.69 g, 45 mmol) in water
(20 ml) was added. After heating to reflux for 2 h, the
solvent was evaporated, water was added (60 ml) and the
mixture extracted with CH2Cl2 (2£40 ml). The organic
layer was dried, filtered and evaporated and the residue
purified by silica gel column chromatography, eluent
CH2Cl2 to give 1g, 90% yield, mp 107–1088C (white
From 1d and 2a, heated for 2 h, 3da, mp 153–1558C dec.
(light yellow crystals from Et2O); IR: 1724, 1681, 1622,
;
1519, 1380 cm21 1H NMR: 2.14 (s, 3H), 7.06 (d, 1H,
J¼8.8 Hz), 7.42 (m, 2H), 7.50 (m, 3H), 8.26 (dd, 1H, J¼2.5,
8.8 Hz), 8.80 (d, 1H, J¼2.5 Hz), 10.68 (s, 1H); 13C NMR:
11.2 (CH3), 105.3, 124.5, 134.9, 145.2, 146.9, 157.3 (C),
116.8, 122.6, 127.2, 127.7 (CHAr), 126.2 (2£CHAr), 128.4
(2£CHAr), 170.3 (CO), 186.4 (CHO). Anal. calcd for
C17H12N2O5: C, 62.96; H, 3.73; N, 8.64. Found: C, 62.80;
H, 3.89; N, 8.48.
1
crystals from CH2Cl2–hexane); IR 1720, 1692 cm21; H
NMR (CD3COCD3): 2.78 (t, 2H, J¼5.5 Hz), 2.96 (t, 2H,
J¼5.5 Hz), 3.29 (s, 2H), 10.30 (br s, 1H, D2O); 13C NMR
(CD3COCD3): 19.7, 23.8, 23.9 (CH2), 96.6, 164.7 (C),
170.4 (CO). Anal. calcd for C6H7NO2S: C, 45.86; H, 4.46;
N, 8.92. Found: C, 45.69; H, 4.52; N, 8.80.
1.1.2. Sodium salts 10 of 3,4-disubstituted 5(2H)-isoxazo-
lones 1: general procedure. A methanolic solution of
NaOMe, prepared from MeOH (5 ml) and Na (92 mg,
4 mmol) was added to a solution of the isoxazolin-5-one 1
(4 mmol) in MeOH (10 ml). After evaporation of the
solvent, the residue was dried for 1 h at 608C/5 mbar.
From 1e and 2a, heated for 24 h, 3ea, mp 143–1458C (light
yellow crystals from Et2O–hexane); IR: 1740, 1682, 1530,
1377 cm21; 1H NMR: 1.28 (t, 3H, J¼7.3 Hz), 2.54 (q, 2H,
J¼7.3 Hz), 7.09 (d, 1H, J¼8.4 Hz), 7.38 (m, 2H), 7.50 (m,
3H), 8.24 (dd, 1H, J¼2.5, 8.4 Hz), 8.78 (d, 1H, J¼2.5 Hz),
10.64 (s, 1H); 13C NMR: 13.3 (CH3), 16.4 (CH2), 111.2,
127.2, 133.0, 146.0, 147.4, 160.3 (C), 124.1, 126.5, 126.9,
128.3, 129.8, 131.6 (CHAr), 128.8 (2£CHAr), 170.1 (CO),
186.6 (CHO). Anal. calcd for C18H14N2O5: C, 63.90; H,
4.17; N, 8.28. Found: C, 64.08; H, 4.31; N, 8.15.
1.1.3. Synthesis of 2-aryl-3,4-disubstituted isoxazolin-
5(2H)-ones 3: general procedure. To a solution of
isoxazolin-5(2H)-ones sodium salt 10 (2 mmol) in DMF
(3 ml), the 5-substituted-2-fluorobenzaldehyde 2a or 2b
(3 mmol) was added. The mixture was heated to 45–508C
under stirring for the reported time (see below) and diluted
with brine: (i) for the compounds 3aa–ga, the solid formed
was filtered and purified by crystallization, (ii) for the
compounds 3ab–gb, the mixture was extracted with Et2O
(2£20 ml), the organic layer dried (Na2SO4), filtered,
evaporated and the residue purified by crystallization or
by silica gel column chromatography (eluent see below).
From 1f and 2a, heated for 5 h, 3fa, mp 1568C dec. (cream
crystals from acetone); IR: 1749, 1688, 1377 cm21 1H
;
NMR (CD3OD): 1.83 (m, 4H), 2.86 (m, 4H), 7.51 (d, 1H,
J¼8.8 Hz), 8.33 (dd, 1H, J¼2.6, 8.8 Hz), 8.64 (d, 1H,
J¼2.6 Hz), 10.56 (s, 1H); 13C NMR: 18.3, 21.3, 21.7, 22.7
(CH2), 92.8, 122.7, 124.4 (CHAr), 101.8, 140.8, 141.8,
148.8, 165.5 (C), 171.3 (CO), 186.9 (CHO). Anal. calcd for
C14H12N2O5: C, 58.33; H, 4.20; N, 9.72: Found: C, 58.20;
H, 4.29; N, 9.73.
From 1a and 2a, heated for 0.5 h, 3aa, mp 46–478C (yellow
crystals from hexane); IR: 1748, 1698, 1610, 1490 cm21; 1H
NMR: 3.72 (s, 3H), 5.32 (s, 2H), 7.33 (m, 5H), 7.46 (d, 1H,
J¼8.8 Hz), 8.52 (dd, 1H, J¼2.5, 8.8 Hz), 8.86 (d, 1H,
J¼2.5 Hz), 10.45 (s, 1H); 13C NMR: 16.8 (CH3), 29.2
(CH2), 116.8, 122.6, 125.5, 127.2 (CHAr), 128.4 (2£CHAr),
129.2 (2£CHAr), 127.3, 130.2, 137.7, 143.6, 154.2, 158.2
(C), 168.5 (CO), 186.2 (CHO). Anal. calcd for C18H14N2O5:
C, 63.90; H, 4.17; N, 8.28. Found: C, 63.79; H, 4.33; N, 8.23.
From 1g and 2a, heated for 5 h, 3ga, mp 125–1278C (ochre
crystals from AcOEt–hexane); IR:1722, 1672, 1590,
1
1380 cm21; H NMR: 2.59 (t, 2H, J¼5.9 Hz), 2.90 (t, 2H,
J¼5.9 Hz), 3.52 (s, 2H), 7.56 (d, 1H, J¼8.8 Hz), 8.56 (dd,
1H, J¼2.5, 8.8 Hz), 8.87 (d, 1H, J¼2.5 Hz), 10.44 (s, 1H);
13C NMR: 19.9, 23.9, 25.3 (CH2), 101.7, 133.0, 144.5,
148.3, 163.4 (C), 124.1, 127.5, 129.1 (CHAr), 168.1 (CO),
187.7 (CHO). Anal. calcd for C13H10N2O5S: C, 50.98; H,
3.29; N, 9.15. Found: C, 50.91; H, 3.41; N, 9.08.
From 1b and 2a, heated for 2 h, 3ba, mp 154–1568C
(orange crystals from Et2O); IR: 1720, 1686, 1613, 1530,
From 1a and 2b, heated for 24 h, SiO2 eluent: hexane–Et2O

9890
G. Abbiati et al. / Tetrahedron 59 (2003) 9887–9893
2:1, 3ab, mp 154–1568C (cream crystals from AcOEt); IR:
1730, 1612, 1463, 1374 cm21; 1H NMR: 2.04 (s, 3H), 3.72
(s, 2H), 7.27–7.34 (m, 5H), 7.39 (d, 1H, J¼8.4 Hz), 7.95
(dd, 1H, J¼2.2, 8.4 Hz), 8.31 (d, 1H, J¼2.2 Hz), 10.47 (s,
1H). 13C NMR: 13.5 (CH3), 28.4 (CH2), 106.5, 133.1, 127.8,
144.2, 160.3 (C), 123.1 (CF3), 132.4 (C–CF3), 126.7, 127.1,
128.5, 131.8 (CHAr), 128.3 (2£CHAr), 129.6 (2£CHAr),
169.3 (CvO), 187.6 (CHO). Anal. calcd for C19H14F3NO3:
C, 63.16; H, 3.91; N, 3.88. Found: C, 63.17; H, 3.77; N,
4.03.
164.2 (C), 123.2 (CF3), 131.8 (C–CF3), 125.4, 126.3, 131.9
(CHAr), 170.2 (CvO), 187.7 (CHO). Anal. calcd for
C15H12F3NO3: C, 57.88; H, 3.89; N, 4.50. Found: C, 57.98;
H, 3.94; N, 4.36.
From 1g and 2b, heated for 5 h, SiO2 eluent: hexane–Et2O
1:1, 3gb, mp 95–988C (ochre crystals from Et2O–hexane);
1
IR: 1730, 1679, 1630, 1597 cm21; H NMR: 2.56 (t, 2H,
J¼5.8 Hz), 2.93 (t, 2H, J¼5.8 Hz), 3.58 (s, 2H), 7.54 (d, 1H,
J¼8.4 Hz), 8.02 (dd, 1H, J¼2.2, 8.4 Hz), 8.37 (d, 1H,
J¼2.2 Hz), 10.41 (s, 1H); 13C NMR: 20.6, 24.5, 25.5 (CH2),
103.3, 132.7, 133.0, 143.1, 163.3 (C), 123.2 (CF3), 126.5,
126.8, 132.2 (C–CF3), 168.9 (CvO), 187.6 (CHO). Anal.
calcd for C14H10F3NO3S: C, 51.06; H, 3.06; N, 4.25. Found:
C, 51.14; H, 3.21; N, 4.30.
From 1b and 2b, heated for 24 h, SiO2 eluent: hexane–Et2O
3:1, 3bb, mp 998C (orange crystals from Et2O); IR: 1732,
1
1698, 1613 cm21; H NMR: 2.28 (s, 3H), 7.38–7.59 (m,
6H), 8.01 (d, 1H, J¼8.2 Hz), 8.33 (s, 1H), 10.47 (s, 1H); 13C
NMR: 13.4 (CH3), 122.9 (CF3), 126.6, 127.1, 128.4, 131.8
(CHAr), 128.3 (2£CHAr), 128.9 (2£CHAr), 106.7, 133.3,
126.9, 142.4, 159.1 (C), 132.7 (C–CF3), 168.9 (CvO),
187.4 (CHO). Anal. calcd for C18H12F3NO3: C, 62.25; H,
3.48; N, 4.03; Found: C, 62.31; H, 3.51; N, 4.08.
1.1.4. Synthesis of quinolines 5, 6 and tetrahydroquino-
lines 7: general procedure. The compound 3 (1 mmol) was
dissolved in EtOH (15 ml), 10% Pd/C (40 mg) was added
and the mixture hydrogenated under atmospheric pressure at
rt. After 5 h the catalyst was filtered off, the solvent
evaporated and the crude material was crystallized or
chromatographed (see below).
From 1c and 2b, heated for 5 h, SiO2 eluent: hexane–
CH2Cl2 10:1 to CH2Cl2, 3cb, mp 91–938C (white crystals
from hexane–Et2O); IR: 1746, 1698, 1613 cm21; 1H NMR:
0.89 (t, 3H, J¼7.3 Hz), 1.35 (tq, 2H, J¼7.3, 7.3 Hz), 2.34 (t,
2H, J¼7.3 Hz), 3.74 (s, 2H), 7.26–7.40 (m, 6H), 7.95 (dd,
1H, J¼1.8, 8.4 Hz), 8.32 (d, 1H, J¼1.8 Hz), 10.51 (s, 1H);
13C NMR: 13.9 (CH3), 21.5, 28.3, 28.6 (CH2), 107.0, 133.8,
138.4, 143.7, 165.1 (C), 123.0 (CF3), 126.4, 127.1, 127.4,
131.9 (CHAr), 128.5 (2£CHAr), 129.1 (2£CHAr), 131.1
(C–CF3), 171.2 (CvO), 187.7 (CHO). Anal. calcd for
C21H18F3NO3: C, 64.78; H, 4.66; N, 3.60. Found: C, 64.86;
H, 4.81; N, 3.46.
From 3aa, reaction time 6 h, SiO2 eluent: CH2Cl2–Et2O
1:1, afforded compounds 5aa, mp 1908C (beige crystals
1
from Et2O–hexane); IR: 1442, 1360 cm21; H NMR: 2.77
(s, 3H), 4.21 (s, 2H), 7.20 (m, 2H), 7.36 (m, 3H), 7.92 (s,
1H), 8.17 (d, 1H, J¼9.1 Hz), 8.44 (dd, 1H, J¼2.5, 9.1 Hz),
8.70 (d, 1H, J¼2.5 Hz); 13C NMR: 24.4 (CH3), 39.4 (CH2),
122.7, 124.4, 127.3, 130.4, 137.3 (CHAr), 129.3 (2£CHAr),
128.5 (2£CHAr), 126.4, 135.7, 138.2, 145.5, 149.1, 163.6
(C). Anal. calcd for C17H14N2O2: C, 73.37; H, 5.07; N,
10.07. Found: C, 73.45; H, 5.17; N, 9.98; and 6aa, mp 195–
1968C (ochre crystals from Et2O–hexane). IR: 3230, 3140,
1620, 1597, 1440 cm21; 1H NMR: 2.62 (s, 3H), 3.90 (br s,
2H, D2O), 4.11 (s, 2H), 6.84 (d, 1H, J¼2.5 Hz), 7.20 (m,
3H), 7.30 (m, 3H), 7.58 (s, 1H), 7.90 (d, 1H, J¼8.8 Hz); 13C
NMR: 24.9 (CH3), 39.2 (CH2), 107.2, 120.8, 125.5, 127.9,
125.5, 127.9, 128.4, 129.2, 134.5 (CHAr), 128.5, 135.1,
137.4, 141.9, 144.7, 155.9 (C). Anal. calcd for C17H16N2: C,
82.22; H, 6.49; N, 11.28. Found: C, 82.09; H, 6.42; N, 11.15.
From 1d and 2b, heated for 1 h, SiO2 eluent: hexane–Et2O
3:1, 3db, mp 98–1008C (white crystals from hexane); IR:
1722, 1690, 1608 cm21; 1H NMR: 2.13 (s, 3H), 7.02 (d, 1H,
J¼8.4 Hz), 7.37–7.49 (m, 5H), 7.68 (dd, 1H, J¼2.2,
8.4 Hz), 8.25 (d, 1H, J¼2.2 Hz), 10.73 (s, 1H); 13C NMR:
8.3 (CH3), 105.8, 133.2, 127.8, 144.9, 161.1 (C), 123.1
(CF3), 132.0 (C–CF3), 126.2, 126.7, 131.4, 131.6 (CHAr),
128.5 (2£CHAr), 129.8 (2£CHAr), 171.1 (CvO), 187.8
(CHO). Anal. calcd for C18H12F3NO3: C, 62.25; H, 3.48; N,
4.03; Found: C, 62.37; H, 3.53; N, 3.84.
From 3ba, reaction time 2 h, SiO2 eluent: from hexane to
Et2O, afforded compounds 5ba, mp 1908C (yellow crystals
from Et2O–hexane); IR: 1601, 1521, 1376 cm21; 1H NMR:
2.74 (s, 3H), 7.40–7.55 (m, 5H), 8.14 (s, 1H), 8.18 (d, 1H,
J¼9.1 Hz), 8.48 (dd, 1H, J¼2.5, 9.1 Hz), 8.79 (d, 1H,
J¼2.5 Hz); 13C NMR: 25.4 (CH3), 123.2, 124.7, 129.4,
130.6, 137.7 (CHAr), 128.7 (2£CHAr), 129.1, (2£CHAr),
126.1, 138.2, 139.0, 145.6, 149.4, 162.4 (C). Anal. calcd for
C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C, 72.81;
H, 4.73; N, 10.31; and 6ba mp 122–1248C (cream crystals
from Et2O–hexane); IR: 3318, 3191, 1628, 1462,
From 1e and 2b, heated for 2 h, SiO2 eluent: hexane–
CH2Cl2 1:1, 3eb, mp 114–1168C (white crystals from
Et2O–hexane); IR: 1737, 1698, 1607 cm21; 1H NMR: 1.28
(t, 3H, J¼7.3 Hz), 2.54 (q, 2H, J¼7.3 Hz), 7.05 (d, 1H,
J¼8.4 Hz), 7.38–7.49 (m, 5H), 7.70 (dd, 1H, J¼1.8,
8.4 Hz), 8.23 (d, 1H, J¼1.8 Hz), 10.69 (s, 1H); 13C NMR:
13.4 (CH3), 16.4 (CH2), 110.8, 129.1, 128.9, 144.6, 160.9
(C), 126.0, 126.4, 131.2, 131.4 (CHAr), 128.3 (2£CHAr),
129.7 (2£CHAr), 123.1 (CF3), 132.9 (C–CF3), 170.6
(CvO), 187.6 (CHO). Anal. calcd for C19H14F3NO3: C,
63.16; H, 3.91; N, 3.88. Found: C, 63.25; H, 3.99; N, 3.90.
1
1377 cm21; H NMR: 2.64 (s, 3H), 3.90 (br s, 2H, D2O),
6.91 (d, 1H, J¼2.5 Hz), 7.18 (dd, 1H, J¼2.5, 9.1 Hz), 7.40–
7.75 (m, 5H), 7.77 (s, 1H), 7.94 (d, 1H, 9.1 Hz); 13C NMR:
24.3 (CH3), 107.8, 121.9, 128.4, 128.7, 134.8 (CHAr), 127.0
(2£CHAr), 129.1 (2£CHAr), 129.2, 136.4, 140.6, 142.3,
144.7, 153.7 (C). Anal. calcd for C16H14N2: C, 82.02; H,
6.02; N, 11.96. Found: C, 82.16; H, 6.11; N, 11.81.
From 1f and 2b, heated for 2 h, SiO2 eluent: hexane–
CH2Cl2 1:1, 3fb, mp 117–1198C (cream crystals from
1
Et2O); IR: 1754, 1613 cm21; H NMR: 1.82 (m, 4H), 2.27
(m, 2H), 2.42 (m, 2H), 7.48 (d, 1H, J¼8.4 Hz), 7.95 (dd, 1H,
J¼1.8, 8.4 Hz), 8.31 (d, 1H, J¼1.8 Hz), 10.40 (s, 1H); 13C
NMR: 18.8, 21.5, 21.6, 23.3 (CH2), 105.3, 131.4, 143.9,
From 3ca, reaction time 4 h, SiO2 eluent: hexane–Et2O 1:1,

G. Abbiati et al. / Tetrahedron 59 (2003) 9887–9893
9891
afforded compounds 5ca, mp 135–1388C (yellow crystals
from Et2O–hexane); IR: 1599, 1380 cm21;1H NMR: 1.05 (t,
3H, J¼7.3 Hz), 1.83 (tq, 2H, J¼7.3, 7.3 Hz), 3.00 (t, 2H,
J¼7.3 Hz), 4.24 (s, 2H), 7.20 (m, 2H), 7.38 (m, 3H), 7.90 (s,
1H), 8.17 (d, 1H, J¼9.1 Hz), 8.42 (dd, 1H, J¼2.5, 9.1 Hz),
8.67 (d, 1H, J¼2.5 Hz); 13C NMR: 14.6 (CH3), 22.5, 38.6,
38.9 (CH2), 122.6, 124.4, 127.3, 129.3, 129.4, 130.6, 137.8
(CHAr), 129.2 (2£CHAr), 126.2, 135.4, 18.7, 145.4, 149.2,
166.8 (C). Anal. calcd for C19H18N2O2: C, 74.49, H, 5.92; N,
9.14. Found: C, 74.60; H, 5.99; N, 9.05; and 6ca, mp 163–
1658C (beige from Et2O–hexane); IR: 3405, 3250, 1610,
1580, 1440 cm21; 1H NMR: 1.02 (t, 3H, J¼7.3 Hz), 1.74 (tq,
2H, J¼7.3, 7.3 Hz), 2.91 (t, 2H, J¼7.3 Hz), 3.93 (br s, 2H,
D2O), 4.15 (s, 2H), 6.82 (d, 1H, J¼2.2 Hz), 7.15 (m, 3H), 7.30
(m, 3H), 7.59 (s, 1H), 7.96 (d, 1H, J¼9.1 Hz); 13C NMR: 14.7
(CH3), 23.2, 38.2, 39.1 (CH2), 107.6, 121.2, 126.7, 128.8,
128.9, 129.2, 129.3, 129.9, 134.9 (CHAr), 129.1, 133.0, 140.1,
142.0, 144.4, 158.8 (C). Anal. calcd for C19H20N2: C, 82.57;
H, 7.29; N, 10.14. Found: C, 82.66; H, 7.38; N, 10.02.
From 3ab, reaction time 4 h, SiO2 eluent: from CH2Cl2–
hexane 1:1 to CH2Cl2–Et2O, afforded compounds 5ab, mp
84–868C (cream crystals from hexane); IR: 1452 cm21; 1H
NMR: 2.72 (s, 3H), 4.19 (s, 2H), 7.20 (m, 2H), 7.38 (m, 3H),
7.82 (m, 2H), 8.04 (s, 1H), 8.13 (d, 1H, J¼8.8 Hz); 13C
NMR: 24.0 (CH3), 39.3 (CH2), 124.4 (CF3), 124.8, 125.4,
127.0, 129.7, 136.5 (CHAr), 129.1 (2£CHAr), 129.2
(2£CHAr), 127.9 (C–CF3), 126.3, 134.7, 138.4, 147.8,
161.7 (C). Anal. calcd for C18H14F3N: C, 71.75; H, 4.68, N,
4.65. Found: C, 71.86; H, 4.77; N, 4.63; and 7ab, oil; IR:
3413, 1619, 1519 cm21; 1H NMR: 1.26 (d, 3H, J¼6.6 Hz),
2.20–2.80 (m, 5H), 3.60 (m, 1H), 4.16 (br s, 1H, D2O), 6.49
(d, 1H, J¼8.4 Hz), 7.15–7.37 (m, 7H); 13C NMR: 22.2
(CH3), 31.0, 34.7 (CH2), 38.9, 54.7 (CH), 112.9, 124.2,
126.9, 127.2 (CHAr), 128.5 (2£CHAr), 128.7 (2£CHAr),
118.8 (CF3), 121.9 (C–CF3), 123.8, 140.9, 146.6 (C). Anal.
calcd for C18H18F3N: C, 70.81; H, 5.94; N, 4.59. Found: C,
70.92; H, 5.99; N, 4.52.
From 3bb, reaction time 12 h, SiO2 eluent: from CH2Cl2–
hexane 1:10 to CH2Cl2, afforded compounds 5bb, mp 156–
1588C (yellow crystals from Et2O–hexane); IR:
From 3da, reaction time 6 h, SiO2 eluent: CH2Cl2–Et2O
1:1, afforded compound 6da, mp 150–1528C (ochre crystals
from Et2O–hexane); IR: 3410, 3240, 1640, 1557 cm21; 1H
NMR: 2.42 (s, 3H), 3.90 (br s, 2H, D2O), 6.88 (d, 1H,
J¼2.5 Hz), 7.14 (dd, 1H, J¼2.5, 9.1 Hz), 7.48 (m, 3H), 7.60
(m, 2H), 7.83 (s, 1H), 8.04 (dd, 1H, J¼2.5, 9.1 Hz); 13C
NMR: 21.0 (CH3), 107.0, 121.3, 129.3, 130.8, 135.0
(CHAr), 128.6 (2£CHAr), 128.2 (2£CHAr), 129.8, 129.5,
141.5, 142.2, 145.0, 157.3 (C). Anal. calcd for C16H14N2: C,
82.02; H, 6.02; N, 11.96. Found: C, 82.11; H, 6.09; N, 11.82.
1
1450 cm21; H NMR: 2.72 (s, 3H), 7.40–7.53 (m, 5H),
7.91 (dd, 1H, J¼1.9, 8.8 Hz), 8.06 (s, 1H), 8.13 (d, 1H,
J¼1.9 Hz), 8.18 (d, 1H, J¼8.8 Hz); 13C NMR: 24.9 (CH3),
122.9 (CF3), 125.1, 125.3, 128.3, 129.7, 137.0 (CHAr),
128.8 (2£CHAr), 129.3 (2£CHAr), 126.1 (C–CF3), 127.9,
137.4, 139.3, 148.1, 160.4 (C). Anal. calcd for C17H12F3N:
C, 71.08; H, 4.21; N, 4.88. Found: C, 71.19; H, 4.29; N,
1
4.99; and 7bb, oil; IR: 3411, 1620, 1521 cm21; H NMR:
0.99 (d, 3H, J¼6.6 Hz), 3.14 (m, 2H), 3.25 (m, 1H), 3.78 (m,
1H), 4.25 (br s, 1H, D2O), 6.56 (d, 1H, J¼8.8 Hz), 7.17–
7.35 (m, 7H); 13C NMR: 19.9 (CH3), 33.1 (CH2), 46.3, 59.2
(CH), 113.0, 124.2, 126.3, 127.3 (CHAr), 128.5 (2£CHAr),
128.9 (2£CHAr), 119.2 (CF3), 120.6 (C–CF3), 123.5,
141.2, 146.2 (C). Anal. calcd for C17H16F3N: C, 70.09; H,
5.54; N, 4.81. Found: C, 69.93; H, 5.73; N, 4.70.
From 3ea, reaction time 3 h, SiO2 eluent: CH2Cl2–Et2O
1:1, afforded compound 6ea, mp 160–1628C (beige crystals
from Et2O–hexane); IR: 3328, 3212, 1620, 1454 cm21; 1H
NMR: 1.19 (t, 3H, J¼7.3 Hz), 2.77 (q, 2H, J¼7.3 Hz), 2.98
(br s, 2H, D2O), 6.93 (d, 1H, J¼2.2 Hz), 7.16 (dd, 1H,
J¼2.2, 9.1 Hz), 7.50 (m, 5H), 7.87 (s, 1H), 8.07 (d, 1H,
J¼9.1 Hz) manca 1H; 13C NMR: 16.5 (CH3), 22.6 (CH2),
107.2, 121.5, 127.2, 128.5, 135.3 (CHAr), 127.1 (2£CHAr),
129.0 (2£CHAr), 129.9, 141.5, 142.5, 144.7, 157.6 (C).
Anal. calcd for C17H16N2: C, 82.22; H, 6.49; N, 11.28.
Found: C, 82.30; H, 6.58; N, 11.08.
From 3cb, reaction time 6 h, SiO2 eluent: CH2Cl2–hexane
1:2, afforded compounds 5cb, mp 68–698C (beige crystals
;
from hexane); IR: 1449 cm21 1H NMR: 1.04 (t, 3H,
J¼7.3 Hz), 1.81 (tq, 2H, J¼7.3, 7.3 Hz), 2.99 (t, 2H,
J¼7.3 Hz), 4.23 (s, 2H), 7.20 (m, 2H), 7.34 (m, 3H), 7.82
(m, 2H), 8.03 (s, 1H), 8.18 (d, 1H, J¼9.1 Hz); 13C NMR:
14.2 (CH3), 23.2, 38.2, 39.2 (CH2), 124.2, 125.2, 127.5,
129.2, 136.2 (CHAr), 128.4 (2£CHAr), 129.2 (2£CHAr),
122.9 (CF3), 126.6 (C–CF3), 125.9, 134.1, 138.0, 147.7,
161.5 (C). Anal. calcd for C20H18F3N: C, 72.93; H, 5.51; N,
From 3fa, reaction time 5 h, SiO2 eluent: from CH2Cl2–
AcOEt 3:1 to AcOEt, afforded compound 6fa,22 mp 111–
1128C (beige crystals from i-Pr2O); IR: 3329, 3198, 1634,
1457 cm21; 1H NMR: 1.93 (m, 4H), 2.94 (t, 2H, J¼6.6 Hz),
3.08 (t, 2H, J¼6.6 Hz), 3.80 (br s, 2H, D2O), 6.83 (d, 1H,
J¼2.6 Hz), 7.08 (dd, 1H, J¼2.6, 8.8 Hz), 7.59 (s, 1H), 7.81
(d, 1H, J¼8.8 Hz); 13C NMR: 23.4, 23.7, 29.7, 33.5 (CH2),
107.3, 121.3, 129.6, 133.4 (CHAr), 128.9, 131.6, 142.1,
144.2, 155.8 (C). Anal. calcd for C13H14N2: C, 78.75; H,
7.12; N, 14.13. Found: C, 78.83; H, 7.19; N, 14.04.
1
4.25. Found: C, 73.03; H, 5.60; N, 4.17; and 7cb, oil; H
NMR: 0.94 (t, 3H, J¼6.6 Hz), 1.51 (m, 4H), 2.07 (m, 1H),
2.49 (m, 2H), 2.75 (m, 2H), 3.12 (m, 1H), 3.43 (br s, 1H,
D2O), 6.55 (d, 1H, J¼8.7 Hz), 7.13–7.37 (m, 7H); 13C
NMR: 14.5 (CH3), 19.2, 29.2, 34.4, 39.2 (CH2), 36.6, 54.3
(CH), 113.1, 124.5, 126.5, 127.3 (CHAr), 128.8 (2£CHAr),
129.5 (2£CHAr), 118.2 (CF3), 119.7 (C–CF3), 118.9,
140.6, 146.5 (C). Anal. calcd for C20H22F3N: C, 72.05; H,
6.65; N, 4.20. Found: C, 72.12; H, 6.79; N, 4.13.
From 3ga, reaction time 6 h, afforded compound 5ga, mp
168–1708C (ochre crystals from CH2Cl2–pentane); IR:
1580, 1530 cm21; 1H NMR: 3.16 (t, 2H, J¼6.3 Hz), 3.48 (t,
2H, J¼6.3 Hz), 4.00 (s, 2H), 8.06 (s, 1H), 8.14 (d, 1H,
J¼9.3 Hz), 8.45 (dd, 1H, J¼2.4, 9.3 Hz), 8.76 (d, 1H,
J¼2.4 Hz); 13C NMR: 26.0, 26.4, 34.8 (CH2), 122.5, 124.7,
130.6, 135.2 (CHAr), 126.5, 132.4, 146.2, 149.3, 163.0 (C).
Anal. calcd for C12H10N2O2S: C, 58.52; H, 4.09; N, 11.37.
Found: C, 58.66; H, 4.17; N, 11.30.
From 3db, reaction time 10 h, SiO2 eluent: from hexane–
Et2O 5:1 to Et2O, afforded compounds 5db, mp 134–1368C
(white crystals from Et2O–hexane); IR: 1440, 1360 cm21
;
1H NMR: 2.54 (s, 3H), 7.52 (m, 3H), 7.62 (m, 2H), 7.85 (d,
1H, J¼8.4 Hz), 8.13 (m, 2H), 8.26 (d, 1H, J¼8.4 Hz); 13C

9892
G. Abbiati et al. / Tetrahedron 59 (2003) 9887–9893
NMR: 21.1 (CH3), 124.8, 125.1, 129.0, 130.9, 137.8
(CHAr), 128.8 (2£CHAr), 129.2 (2£CHAr), 126.1 (CF3),
129.0 (C–CF3), 126.9, 131.2, 140.7, 148.0, 163.1 (C). Anal.
calcd for C17H12F3N: C, 71.08; H, 4.21; N, 4.88. Found: C,
71.16; H, 4.33; N, 4.80; and 7db, mp 78–808C (white
34.8 (CH2), 124.2 (CF3), 125.2, 125.6, 130.0, 134.5 (CHAr),
128.0 (C–CF3), 126.5, 130.9, 148.2, 160.9 (C). Anal. calcd
for C13H10F3NS: C, 57.98; H, 3.74; N, 5.20. Found: C,
58.10; H, 3.83; N, 5.10.
crystals from hexane); IR: 3400, 1610, 1529 cm21
;
1H
1.1.5. Synthesis of 2-(4-benzyl-3-methyl-5-oxo-5H-isoxa-
zol-2-yl)-pyridine-3-carbaldehyde 8. To a solution of 10a
(5 mmol) in DMF (4 ml) the 2-fluoro-pyridine-3-carbalde-
hyde23 was added. The mixture was heated to 508C for 4 h,
then the reaction was diluted with brine (20 ml) and
extracted with Et2O (2£20 ml). The organic layer was
dried, filtered and evaporated and the residue purified by
silica gel column chromatography, eluent hexane–Et2O 1.1
to give compound 8, yield 60%, mp 1088C (white crystals
NMR: 0.84 (d, 3H, J¼7.0 Hz), 2.33 (m, 1H), 2.54 (dd, 1H,
J¼7.3, 16.2 Hz), 2.95 (dd, 1H, J¼4.4, 16.2 Hz), 4.51 (br s,
1H, D2O), 4.58 (d, 1H, J¼3.6 Hz), 6.58 (d, 1H, J¼8.8 Hz),
7.25–7.35 (m, 6H), 7.70 (m, 1H); 13C NMR: 15.8 (CH3),
31.7, 59.7 (CH), 33.3 (CH2), 113.1, 124.6, 127.1, 128.6
(CHAr), 127.5 (2£CHAr), 127.8 (2£CHAr), 118.0 (CF3),
119.5 (C–CF3), 119.9, 142.2, 147.2 (C). Anal. calcd for
C17H16F3N: C, 70.09; H, 5.54; N, 4.81. Found: C, 70.20; H,
5.63; N, 4.70.
1
from Et2O). IR: 1738, 1690, 1633, 1490 cm21; H NMR:
2.40 (s, 3H), 3.74 (s, 2H), 7.34 (m, 5H), 7.47 (m, 1H), 8.38
(dd, 1H, J¼2.2, 8.8 Hz), 8.63 (dd, 1H, J¼2.2, 4.8 Hz), 10.55
(s, 1H); 13C NMR: 14.1 (CH3), 28.6 (CH2), 107.2, 126.7,
138.6, 152.7, 160.9, (C), 170.7 (CO), 124.5, 127.0, 138.4,
153.3 (CHAr), 128.7 (2£CHAr), 129.1 (2x CHAr), 188.9
(CHO). Anal. calcd for C17H14N2O3: C, 69.38; H, 4.79; N,
9.52. Found: C, 69.25; H, 4.88; N, 9.45.
From 3eb, reaction time 6 h, SiO2 eluent: hexane–CH2Cl2
1:1, afforded compounds 5eb, oil; IR: 1453 cm21; 1H NMR:
1.28 (t, 3H, J¼7.3 Hz), 2.27 (q, 2H, J¼7.3 Hz), 7.58 (m,
5H), 7.87 (dd, 1H, J¼1.8, 9.1 Hz), 8.21 (d, 1H, J¼1.8 Hz),
8.28 (s, 1H), 8.49 (d, 1H, J¼9.1 Hz); 13C NMR: 16.9 (CH3),
24.6 (CH2), 120.7 (CF3), 125.2, 125.9, 127.9, 129.5, 137.2
(CHAr), 127.8 (2£CHAr), 129.3 (2£CHAr), 127.1 (C–
CF3), 126.3, 137.5, 139.0, 147.9, 160.2 (C). Anal. calcd for
C18H14F3N: C, 71.75; H, 4.68; N, 4.65. Found: C, 71.84; H,
4.79; N, 4.59; and 7eb, mp 85–878C (cream crystals from
Et2O–hexane); IR: 3311, 1665, 1454 cm21; 1H NMR: 0.94
(t, 3H, J¼7.3 Hz), 1.95 (m, 1H), 2.05 (m, 1H), 2.39 (1H, m),
2.53 (dd, 1H, J¼9.1, 16.2 Hz), 2.88 (dd, 1H, J¼4.4,
16.2 Hz), 3.55 (br s, 1H, D2O), 4.60 (d, 1H, J¼3.7 Hz),
6.60 (m, 1H), 7.20–7.40 (m, 7H); 13C NMR: 15.7 (CH3),
24.1, 32.4 (CH2), 35.2, 60.1 (CH), 113.7, 124.9, 127.5,
128.4 (CHAr), 128.2 (2£CHAr), 128.3 (2£CHAr), 119.0
(CF3), 121.5 (C–CF3), 120.1, 142.3, 147.5 (C). Anal. calcd
for C18H18F3N: C, 70.81; H, 5.94; N, 4.59. Found: C, 70.90;
H, 6.02; N, 4.49.
1.1.6. Synthesis of [1,8]naphthyridine 9 and tetrahydro-
naphthyridine 10. To a solution of compound 8 (2 mmol)
in AcOEt (25 ml) 10% Pd/C was added and the mixture was
hydrogenated under atmospheric pressure and rt. After 4 h
the catalyst was filtered off, the solvent evaporated and the
crude material was chromatographed, eluent CH2Cl2–Et2O
3:1, to give compound 9,24 yield 68%, mp 123–1258C
(white crystals from Et2O–hexane); IR: 1630, 1490 cm21
;
1H NMR: 2.77 (s, 3H), 4.20 (s, 2H), 7.20 (m, 2H), 731–7.47
(m, 4H), 7.78 (s, 1H), 8.10 (dd, 1H, J¼2.2, 8.0 Hz), 9.06
(dd, 1H, J¼2.2, 4.4 Hz), 13C NMR: 24.1 (CH3), 39.0 (CH2),
121.6, 126.9, 136.4, 136.5, 152.9 (CHAr), 129.0 (2£CHAr),
129.1 (2£CHAr), 121.7, 134.4, 138.6, 155.2, 162.9 (C).
Anal. calcd for C16H14N2: C, 82.02; H, 6.02, N, 11.96.
Found: C, 82.13; H, 6.10; N, 11.89; and compound 10, yield
From 3fb, reaction time 6 h, SiO2 eluent: from hexane–
Et2O 10:1 to Et2O, afforded compounds 5fb, mp 47–488C
1
13%, oil; H NMR: 1.91 (tt, 2H, J¼5.9, 6.2 Hz), 2.31 (s,
1
(crystals from Et2O–hexane); IR: 1452 cm21; H NMR:
3H), 2.69 (t, 2H, J¼6.2 Hz), 3.41 (t, 2H, J¼5.9 Hz), 3.84 (s,
2H), 5.36 (br s, 1H, D2O), 6.95 (s, 1H), 7.18 (m, 2H), 7.26–
7.36 (m, 3H); 13C NMR: 31.3 (CH3), 20.5, 26.0, 36.8, 41.3
(CH2), 127.0, 141.9 (CHAr), 128.4 (2£CHAr), 129.2
(2£CHAr), 120.6, 121.6, 138.4, 155.3, 160.4 (C). Anal.
calcd for C16H18N2: C, 80.63; H, 7.61; N, 11.75. Found: C,
80.71; H, 7.70; N, 11.69.
1.96 (m, 4H), 3.03 (t, 2H, J¼6.6 Hz), 3.17 (t, 2H,
J¼6.6 Hz), 7.80 (dd, 1H J¼1.8, 8.8 Hz), 7.90 (s, 1H),
8.04 (d, 1H J¼1.8 Hz), 8.08 (d, 1H, J¼8.8 Hz); 13C NMR:
20.5, 25.6, 27.5, 27.7 (CH2), 124.5, 125.9, 127.2, 136.1
(CHAr), 122.7 (CF3), 127.0 (C–CF3), 123.9, 131.2, 147.1,
161.2 (C). Anal. calcd for C14H12F3N: C, 66.93; H, 4.81; N,
5.57. Found: C, 67.01; H, 4.90; N, 5.50; and 7fb, mp 98–
998C (crystals from Et2O–hexane); IR: 3424, 1619,
When the catalytic hydrogenation reaction was performed
in EtOH the ratio between 9 and 10 was 24 and 74%.
1
1519 cm21; H NMR: 1.45 (m, 4H), 1.62 (m, 4H), 1.99
(m, 1H), 2.56 (dd, 1H, J¼4.0, 16.2 Hz), 2.91 (dd, 1H,
J¼5.5, 16.2 Hz), 3.57 (m, 1H, J¼3.7 Hz), 3.91 (br s, 1H,
D2O), 6.45 (d, 1H, J¼8.8 Hz), 7.19 (d, 1H, J¼8.8 Hz), 7.17
(s, 1H); 13C NMR: 20.8, 24.8, 27.3, 31.8, 32.7 (CH2), 32.5,
50.2 (CH), 118.9, 146.9 (C), 127.0, 124.2, 112.5 (CHAr),
122.1 (CF3) 120.9 (C–CF3), Anal. calcd for C14H16F3N: C,
65.87; H, 6.32; N, 5.49. Found: C, 65.96; H, 6.40; N, 5.37.
Acknowledgements
The authors gratefully acknowledge the Ministero
`
dell’Istruzione, dell’Universita e della Ricerca (MIUR)
for financial support.
From 3gb, reaction time 18 h, SiO2 eluent: hexane–CH2Cl2
1:1, afforded compound 5gb, mp 231–2338C (cream
1
crystals from hexane); IR: 1458 cm21; H NMR: 3.14 (t,
References
2H, J¼6.6 Hz), 3.46 (t, 2H, J¼6.6 Hz), 3.99 (s, 2H), 7.86
(dd, 1H, J¼1.8, 9.1 Hz), 7.97 (s, 1H), 8.10 (d, 1H,
J¼1.8 Hz), 8.13 (d, 1H, J¼9.1 Hz); 13C NMR: 26.6, 30.1,
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