Heterocycles from Ylides. Part XI. Synthesis of 2-Substituted Quinoline Derivatives

Article abstract of DOI:10.3987/COM-07-S(W)78

The reaction of 2-N-phenylsulfonylaminobenzaldehyde (1) with stabilized alkylidene phosphoranes (2) gives, through a Wittig condensation followed by reduction of intermediate alkenes and cyclization with PPA, quinoline derivatives (5).

Full text of DOI:10.3987/COM-07-S(W)78

HETEROCYCLES, Vol. 74, 2007
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HETEROCYCLES, Vol. 74, 2007, pp. 1015 - 1018. © The Japan Institute of Heterocyclic Chemistry
Received, 26th September, 2007, Accepted, 6th November, 2007, Published online, 9th November, 2007. COM-07-S(W)78
HETEROCYCLES FROM YLIDES. PART XI.1 SYNTHESIS OF
2-SUBSTITUTED QUINOLINE DERIVATIVES §
Giuseppe Cremonesi,a Piero Dalla Croce,b,* Francesco Fontana,b and
Concetta La Rosaa
a
Institute of Organic Chemistry “Alessandro Marchesini”, Faculty of Pharmacy,
Via Venezian 21, I-20133 Milano, Italy
b
Department of Organic and Industrial Chemistry, C.N.R. - I.S.T.M.,
Via Venezian 21, I-20133 Milano, Italy
Abstract – The reaction of 2-N-phenylsulfonylaminobenzaldehyde (1) with
stabilized alkylidene phosphoranes (2) gives, through a Wittig condensation
followed by reduction of intermediate alkenes and cyclization with PPA,
quinoline derivatives (5).
INTRODUCTION
A part of our researches deals with the synthesis of heterocyclic systems from ylides. Some our recent
papers describe the preparation of 1-phenylsulfonyl-2,3-disubstituted-2,3-dihydroindoles2 and 1-
phenylsulfonyl-3-hydroxy-2,3-dihydroindoles1 starting from sulfonium ylides. Taking into account the
easy availability of 2-N-phenylsulfonylaminobenzaldehyde (1), in our opinion stable synthetic equivalent
of 2-aminobenzaldehyde, we report a new method of preparation of quinoline derivatives according to a
Friedländer-type synthesis.
RESULTS AND DISCUSSION
The treatment of 1 with preformed stabilized phosphonium ylides (2), in acetonitrile solution, leads to the
corresponding (E) alkenes (3) according to a typical Wittig reaction. The selective catalytic reduction of
C-C double bond gives 4 which, treated with PPA at 120 °C for 2-4 h in presence of air, cyclize to
quinoline system. The loss of phenylsulfonyl group and the final oxidation allow to gain aromaticity.
(Scheme 1).
§ This paper is dedicated to Prof. Ekkehard Winterfeldt in the occasion of his 75th birthday.
* Corresponding author: piero.dallacroce@unimi.it

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HETEROCYCLES, Vol. 74, 2007
Scheme 1
O
O
C
H
C
R
O
C
C
H2, Pd/C
MeCN
H
H
+
(Ph)3P CH C R
NH
NH
SO2Ph
SO2Ph
1
2
3
O
C
R
2a, 3a, 4a : R = Me
2b, 3b, 4b : R = Ph
2c, 3c, 4c : R = OEt
5a : R = Me
CH2 CH2
PPA, O2
120°C
5b : R = Ph
5c : R = OH
NH
N
R
2d, 3d, 4d : R = CO2Et 5d : R = CO2Et
SO2Ph
4
5
Analytical and spectroscopic data of all the new compounds isolated are consistent with the assigned
structure.
EXPERIMENTAL
Melting points were determined on a Büchi B-540 apparatus and are uncorrected. Elemental analyses
were performed by the Microanalytical Laboratory of the Department. 1H NMR spectra were recorded in
CDCl3 solution using a Bruker AMX 300 MHz spectrometer, and chemical shifts are given in ppm relative
to TMS. IR spectroscopy was performed using a Jasco FT-IR 4100 spectrometer.
2-N-phenylsulfonylaminobenzaldehyde (1) was prepared according to the reported procedure.3
Ylides 2a, 2b, 2c, 2d are commercially available.
Preparation of alkenes (3a-d): general procedure.
To a solution of ylide 2a-d (6.0 mmol) in MeCN (20 mL), a solution of (1) (3.0 mmol) in the same
solvent was added dropwise. The mixture was stirred 16 h at rt and then heated at 50 °C for 4 h. The
solvent was evaporated off and the residue taken up with AcOEt (20 mL) and HCl 5% solution (10 mL)
to pH 6. The organic layer was separated, dried (Na2SO4), filtered and the solvent was evaporated off.
The residue was purified by column chromatography (SiO2 – toluene/AcOEt : 80/20). In this way were
prepared.
N-[2-(3-Oxo-but-1-enyl)phenyl]benzenesulfonamide (3a): Solid, mp 182-184 °C (toluene). Yield 85%.
1H NMR δ : 2.35 (s, 3H, CH3); 6.45 (d, 1H, J = 15.2 Hz, H-2); 6.55 (d, 1H, J = 15.2 Hz, H-1); 7.00 (s, 1H,

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NH); 7.25-7.80 (m, 9H, Ar). IR (nujol, cm-1): 3280 (NH). Anal. Calcd for C16H15NO3S: C, 63.77; H, 5.02;
N, 4.65. Found: C, 63.65; H, 4.95; N, 4.75.
N-[2-(3-Oxo-3-phenylprop-1-enyl)phenyl]benzenesulfonamide (3b): Solid, mp 127-129 °C (toluene).
Yield 75%. 1H NMR δ : 7.00 (s, 1H, NH); 7.15-7.95 (m, 16H, Ar, H-1, H-2). IR (Nujol, cm-1): 3270 (NH).
Anal. Calcd for C21H17NO3S: C, 69.40; H, 4.71; N, 3.85. Found: C, 69.62; H, 4.80; N, 3.78.
Ethyl 3-(2-benzenesulfonylaminophenyl)acrylate (3c): Solid, mp 125-127 °C (toluene). Yield 50%. 1H
NMR δ : 1.30 (t, 3H, J = 7.5 Hz, CH3); 4.22 (q, 2H, J = 7.5 Hz, CH2); 6.25 (d, 1H, J = 15.8 Hz, H-2);
6.90 (s, 1H, NH); 7.20-7.90 (m, 10H, Ar, H-3). IR (Nujol, cm-1): 3295 (NH). Anal. Calcd for
C17H17NO4S: C, 61.61; H, 5.17; N, 4.23. Found: C, 61.70; H, 5.10; N, 4.12.
Ethyl 4-(2-benzenesulfonylaminophenyl)-2-oxo-3-butenoate (3d): Solid, mp 168-170 °C (toluene).
Yield 65%. 1H NMR δ : 1.41 (t, 3H, J = 7.5 Hz, CH3); 4.44 (q, 2H, J = 7.5 Hz, CH2); 6.82 (s, 1H, NH);
7.10 (d, 1H, J = 15.6 Hz, H-3) 7.40-7.80 (m, 10H, Ar, H-4). IR (Nujol, cm-1): 3310 (NH). Anal. Calcd for
C18H17NO5S: C, 60.15; H, 4.77; N, 3.90. Found: C, 60.25; H, 4.68; N, 3.82.
Preparation of compounds (4a-d): general procedure.
A mixture of 3 (1.5 mmol) in AcOEt (20 mL) was treated with catalytic amount of 5% Pd/C and
hydrogenated at rt and 1 atm until the requested amount of hydrogen was consumed. The catalyst was
filtered on a celite pad and the solvent evaporated off. The residue was purified by crystallization.
1
N-[2-(3-Oxo-butyl)phenyl]benzenesulfonamide (4a): Solid, mp 85-86 °C (toluene). Yield 95%. H
NMR δ : 2.05 (s, 3H, CH3); 2.25 (t, 2H, J = 6.3 Hz, CH2-2); 2.72 (t, 2H, J = 6.3 Hz, CH2-1); 7.10-7.80 (m,
9H, Ar); 8.50 (s, 1H, NH). IR (Nujol, cm-1): 3305 (NH). Anal. Calcd for C16H17NO3S: C, 63.34; H, 5.65;
N, 4.62. Found: C, 63.28; H, 5.62; N, 4.58.
N-[2-(3-Oxo-3-phenylpropyl)phenyl]benzenesulfonamide (4b): Solid, mp 131-132 °C (toluene). Yield
1
96%. H NMR δ : 2.55 (t, 2H, J = 6.5 Hz, CH2-2); 3.25 (t, 2H, J = 6.5 Hz, CH2-1); 7.05-7.95 (m, 14H,
Ar); 8.71 (s, 1H, NH). IR (Nujol, cm-1): 3295 (NH). Anal. Calcd for C21H19NO3S: C, 69.02; H, 5.24; N,
3.83. Found: C, 68.95; H, 5.25; N, 3.78.
Ethyl 3-(2-benzenesulfonylaminophenyl)propionate (4c): Solid, mp 78-80 °C (toluene). Yield 94%. 1H
NMR δ : 1.25 (t, 3H, J = 7.5 Hz, CH3); 2.50 (m, 4H, H-2, H-3); 4.15 (q, 2H, J = 7.5 Hz, CH2); 7.00-7.95
(m, 9H, Ar); 8.20 (s, 1H, NH). IR (Nujol, cm-1): 3315 (NH). Anal. Calcd for C17H19NO4S: C, 61.24; H,
5.74; N, 4.20. Found: C, 61.18; H, 5.65; N, 4.25.
Ethyl 4-(2-benzenesulfonylaminophenyl)-2-oxobutyrate (4d): Solid, mp 154-156 °C (toluene). Yield
90%. 1H NMR δ : 1.39 (t, 3H, J = 7.5 Hz, CH3); 2.61 (t, 2H, J = 6.7 Hz, H-3); 3.09 (t, 2H, J = 6.7 Hz, H-
4); 4.42 (q, 2H, J = 7.5 Hz, CH2); 7.25-7.85 (m, 9H, Ar); 8.02 (s, 1H, NH). IR (Nujol, cm-1): 3295 (NH).
Anal. Calcd for C18H19NO5S: C, 59.82; H, 5.30; N, 3.88. Found: C, 59.76; H, 5.21; N, 3.82.

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Preparation of quinolines (5a-d): general procedure.
A mixture of 4 (0.5 g) and PPA (2.5 g) was heated at 120 °C for 3 h in air current. The reaction mixture
was cooled to rt, diluted with water (10 mL), and extracted with AcOEt. The organic phase was dried
(Na2SO4), filtered and the solvent evaporated off. The residue was purified by distillation or
crystallization. All the products are known compounds and the physical constants are in satisfactory
agreement with literature data.
2-Methylquinoline (5a): Oil, bp 120-125 °C / 20 mmHg. Yield 80%. Lit.,4 bp 105-107 °C / 10 mmHg.
2-Phenylquinoline (5b): Solid, mp 82-84 °C (hexane). Yield 85%. Lit.,5 84-86 °C.
2-Hydroxyquinoline (5c): Solid, mp 198-200 °C (H2O). Yield 82%. Lit.,6 195-200 °C.
Ethyl 2-quinolinecarboxylate (5d): Oil, bp 120-125 °C / 0.5 mmHg. Yield 70%. Lit.,7 180 °C/ 14
mmHg.
REFERENCES
1. Part X. G. Cremonesi, P. Dalla Croce, F. Fontana, and C. La Rosa, Heterocycles, 2007, 73, 873.
2. G. Cremonesi, P. Dalla Croce, and C. La Rosa, Heterocycles, 2005, 66, 557.
3. M. Hechavarria Fonseca, E. Eibler, M. Zabel, and B. Konig, Tetrahedron: Asymmetry, 2003, 14,
1989.
4. R. C. Myerly and K. G. Weinberg, J. Org. Chem., 1966, 31, 2008.
5. T. Joh and N. Hagihara, Tetrahedron Lett., 1967, 4199.
6. P. G. Gassman and H. R. Drewes, J. Am. Chem. Soc. 1978, 100, 7600.
7. P. H. Dirstine and F. W. Bergstrom, J. Org. Chem., 1946, 11, 55.