New Straightforward Quinoline Synthesis from the Mannich Reaction of α-Ketohydrazones

Article abstract of DOI:10.1081/SCC-120027244

The addition of α-ketohydrazones to 2-acetamidobenzaldehyde proceeds efficiently in the presence of N-benzylpiperazine to afford in good to high yields the expected Mannich adducts; these are easily converted to quinoline derivatives under acidic conditio

Full text of DOI:10.1081/SCC-120027244

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New Straightforward Quinoline Synthesis from the
Mannich Reaction of α‐Ketohydrazones
Vincent Bailliez a , Laurent El Kaim a & Valérie Michaut a
a Laboratoire Chimie et Procédés , Ecole Nationale Supérieure de Techniques Avancées ,
32 Bd. Victor, 75015, Paris, France
Published online: 16 Aug 2006.
To cite this article: Vincent Bailliez , Laurent El Kaim & Valérie Michaut (2004) New Straightforward Quinoline Synthesis
from the Mannich Reaction of α‐Ketohydrazones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:1, 109-118, DOI: 10.1081/SCC-120027244
To link to this article: http://dx.doi.org/10.1081/SCC-120027244
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 109–118, 2004
New Straightforward Quinoline Synthesis
from the Mannich Reaction of
a-Ketohydrazones
*
Vincent Bailliez, Laurent El Kaim, and Valerie Michaut
´
´ ´ ´
Laboratoire Chimie et Procedes, Ecole Nationale Superieure de
´
Techniques Avancees, Paris, France
ABSTRACT
The addition of a-ketohydrazones to 2-acetamidobenzaldehyde proceeds
efficiently in the presence of N-benzylpiperazine to afford in good to high
yields the expected Mannich adducts; these are easily converted to
¨
quinoline derivatives under acidic conditions in a new Azo–Friedlander
reaction.
¨
Key Words: Azo–Friedlander reaction; Quinoline; Mannich reaction;
a-Ketohydrazone.
*
´ ´
Correspondence: Laurent El Kaim, Laboratoire Chimie et Procedes, Ecole Nationale
´ ´
Superieure de Techniques Avancees, 32 Bd. Victor, 75015 Paris, France;
Fax: 33.1.45.52.83.22; E-mail: elkaim@ensta.fr.
109
DOI: 10.1081/SCC-120027244
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

110
Bailliez, El Kaim, and Michaut
INTRODUCTION
Among the various heterocyclic compounds used in medical chemistry,
the quinoline derivatives have a long tradition of biologically relevant
compounds with such activities as cardiovascular, bactericidal or anti-
malarial.[1]
Synthesis of the heterocyclic core most often use aniline derivatives as
¨
starting materials. In the classical Friedlander synthesis, the quinoline system
is formed by an aldol reaction between protected 2-aminobenzaldehyde and
various ketones followed by cyclisation.[2] The selectivity problems
encountered in the final cyclisation have stimulated some recent improve-
ments such as the use of a-ketophosphonates.[3,4] Despite their first prepara-
tion at the end of the nineteenth century, new synthetic approaches for their
preparation will still be needed to meet the demand for new biologically active
quinolines.
Following our ongoing interest in hydrazone chemistry, we recently
described a Mannich coupling of a-ketohydrazones with aldehydes in the
presence of N-benzylpiperazine.[5] This coupling reaction initially limited to
formaldehyde (Keil and Ried reaction)[6] proved in our hand to be successful
with a wide range of aldehydes (Sch. 1).
If efficient with protected 2-aminobenzaldehyde, we imagined that this
coupling reaction could give an easy access to quinolines.
RESULTS AND DISCUSSION
When a 2 M solution of 2-acetamidobenzaldehyde 1a (prepared in two
steps from 2-aminobenzyl alcohol) in toluene was heated at 808C with
hydrazone 2a and N-benzylpiperazine, the expected Mannich adduct 4a was
obtained in a 93% isolated yield. Hydrazone 2b behaved similarly to give 4b
with the same yield (Sch. 2). Deprotection of the N-acetyl group of 4a and 4b
was easily performed as usual in hot aqueous hydrochloric acid solutions; to
our delight, under these conditions, deprotection, cyclisation and elimination
Scheme 1.

New Straightforward Quinoline Synthesis
111
Scheme 2.
of the N-benzylpiperazine were carried out in a single step giving the
quinolines 5a and 5b in good yield (Sch. 2).
Elimination of N-benzylpiperazine from these Mannich adducts was
performed previously in our group under alkylating conditions (1,2-
dibromoethane) to generate transient azoalkenes trapped in situ by various
nucleophiles;[7] in this case, final aromatisation to quinoline ensures easy
elimination of piperazine. Though hydrazo-noester analogue 2c gave a
successful Mannich coupling with aldehyde 1a, the resulting hydrazone 4c
gave a complex mixture under treatment with aqueous hydrochloric acid. 4c
was finally cleanly converted to indole 6 when treated with an excess of HCl in
hot MeOH (Sch. 3). This new indole synthesis is however of lower synthetic
value as similar indoles are more easily prepared from malonate derivatives.[8]
In contrast to this indole formation, the new quinoline synthesis brings a
valuable access to 2-alkyl-3-amino derivatives. Our procedure coupled with
the Japp–Klingemann reaction[8] allows a straightforward formation of
various 2-alkyl derivatives as shown by the preparation of quinoline 5c from
ethyl acetoacetate without any purification of synthetic intermediates in a 25%
unoptimized overall yield (Sch. 4).
The use of formylating reactions of aniline analogues also allows
structural variations on the starting aldehyde 1a. Naphthyridine 5d, for
instance, was obtained in low yields from 2-aminopyridine. Though the
application of a tert-butyloxycarbonyl protecting group allowed easy
Scheme 3.

112
Bailliez, El Kaim, and Michaut
Scheme 4.
formylation, it was in this case associated with problems in the Mannich
coupling and cyclisation [BOC is displaced during the reaction and two
equivalents of N-benzylpiperazine are needed, cyclisation of the resulting
carbamate is only observed in low yield under 1,2-dibromoethane alkylation
(Sch. 5)].
This work is a new demonstration of the synthetic interest of umpolung
reactions involving hydrazones.[10–14] This new heterocyclic synthesis gives a
general access to 3-azoquinoline derivatives; easily converted into amino
group through reduction, the azo function could be further used to construct
more complex quinoline derivatives by nucleophilic attack on the 4
heterocyclic position.[19] These features as well as other applications of
umpolung reactions of N-arylhydrazones are still under study in our research
group.
EXPERIMENTAL
1H and 13C NMR were recorded on an Bruker Advance 400 (400 MHz)
spectrometer using chloroform-d as a solvent. IR spectra were recorded on a
Perkin–Elmer 299 using a CaF2 cell. Melting points were obtained on a
Scheme 5.

New Straightforward Quinoline Synthesis
113
Reichert apparatus and are uncorrected. Mass spectra were obtained on a MS
50 spectrometer. Chromatography was performed using Merck silica gel or
Aldrich activated neutral aluminum oxide (Brockmann I). Analytical TLC
was performed using 0.25 mm Merck Kieselgel 60 P254 precoated silica gel
plates. All solvents are reagent grade. Aldehydes 1a,[20] 2a[21] and hydrazones
2a,[18] 2b,[19] 2c[20] were prepared according reported procedures.
Preparation of Mannich adducts 4a–d. To a solution of starting
hydrazones 2a–c (2 mmol) in 1 mL of toluene at room temperature were
added aldehyde 1a–b (2.2 mmol), and N-benzylpiperazine (2.2 mmol). The
resulting mixture was heated at 808C for 8 hours. Solvents were evaporated,
and the crude purified by flash chromatography on silica gel with Et2O/
petroleum ether (PE) The following compounds were obtained.
N-f2-[1-(4-Benzyl-piperazin-1-yl)-3-oxo-2-(phenyl-hydrazono)-butyl]-
phenylg-acetamide (4a). Yield 93%. Brown oil. Rf : 0.60 (Et2O/PE, 50 : 50).
1H NMR (CDCl3, 400 MHz) d 13.11 (s, 1H, NH-Ph), 9.51 (s, 1H, NH-Ac),
7.84 (dd, J ¼ 8.1, 0.8 Hz, 1H), 7.56 (dd, J ¼ 8.0, 1.0 Hz, 1H), 7.42
(t, J ¼ 7.9 Hz, 2H), 7.35–7.25 (m, 8H, Har), 7.10 (t, J ¼ 7.4 Hz, 2H), 5.02
(s, 1H), 3.58 (d, J ¼ 13.0 Hz, 1H), 3.54 (d, J ¼ 13.0 Hz, 1H), 2.90–2.73
(m, 4H), 2.46 (s, 3H, Me–C55O), 2.37 (td, J ¼ 11.4, 2.0 Hz, 1H), 2.34 (s, 3H,
NH–CO-Me), 2.20 (td, J ¼ 11.4, 2.0 Hz, 2H), 1.94 (td, J ¼ 11.4, 2.0 Hz,
1H).13C NMR (CDCl3, 100.6 MHz) d 200.2, 169.3 (Cq, HN–C55O), 143.2,
138.5, 137.8, 136.4, 130.0, 129.7, 129.5, 128.9, 128.7, 127.6, 127.3, 126.1,
125.9, 123.3, 114.5, 63.2, 63.1, 53.8, 53.6, 52.8, 51.4, 25.0 (CH3, NHAc), 24.6
(CH3, Me–C55O). IR (CCl4, CaF2) n (cm21): 3317, 2810, 1698, 1650, 1602,
1554, 1453, 1367, 1296, 1264, 1231, 1003. Mass (ID ICP NH3) m/z 484
(MHþ), 307, 249, 178. Exact Mass (CI, CH4) m/z calculated: 484.2713;
found: 484.2705 (MHþ).
N-f2-[1-(4-Benzyl-piperazin-1-yl)-3-oxo-3-phenyl-2-(phenylhydrazono)-
propyl]-phenylg-acetamide (4b). Yield 93%. Brown solid M.p. 95–978C.
Rf : 0.60 (Et2O/PE, 50 : 50). 1H NMR (CDCl3, 400 MHz) d 13.44 (s, 1H, NH-
Ph), 9.64 (s, 1H, NH-Ac), 7.86 (d, J ¼ 10.9 Hz, 2H), 7.84 (d, J ¼ 7.4 Hz, 2H),
7.66–7.64 (m, 1H), 7.56–7.52 (m, 1H), 7.44 (t, J ¼ 7.4 Hz, 2H), 7.39 (t,
J ¼ 7.8 Hz, 2H), 7.35–7.27 (m, 6H), 7.16–7.11 (m, 3H), 7.09 (t, J ¼ 7.3 Hz,
1H), 5.23 (s, 1H), 3.60 (d, J ¼ 13.0 Hz, 1H), 3.54 (d, J ¼ 13.0 Hz, 1H), 3.00–
2.93 (m, 2H), 2.89–2.86 (m, 1H), 2.82–2.80 (m, 1H), 2.53–2.48 (m, 1H),
2.39 (s, 3H, O55C–Me), 2.30–2.22 (m, 2H), 2.07–2.02 (m, 1H). 13C NMR
(CDCl3, 100.6 MHz) d 194.3, 169.4, 143.3, 138.5, 138.0, 137.8, 136.6, 132.0,
131.1, 130.1, 129.5, 129.0, 128.7, 127.9, 127.8, 127.4, 126.4, 126.2, 123.4,
114.7, 64.4, 63.1, 53.9, 53.6, 53.1, 51.4, 24.8 (O55C–CH3). IR (CCl4, CaF2) n
(cm21): 3325, 3064, 3030, 2940, 2810, 1698, 1548, 1452, 1296, 1238. Mass
(ID ICP NH3) m/z 545 (Mþ.), 369, 310, 178. Micro analysis: found: C 74.91,
H 6.63, calculated: C 74.84, H 6.47.

114
Bailliez, El Kaim, and Michaut
3-(2-Acetylaminophenyl)-3-(4-benzylpiperazin-1-yl)-2-(phenylhydra-
zono)-propionic acid methyl ester (4c). Yield 58%. Brown solid. M.p. 155–
1
1578C. Rf : 0.25 (EtOAc/PE, 60 : 40). H NMR (CDCl3, 400 MHz) d 12.30
(s, 1H, NHPh), 11.19 (s, 1H, NHAc), 8.50 (dd, J ¼ 8.2, 0.8 Hz, 1H), 7.35–
7.24 (m, 8H), 7.20–7.15 (m, 3H), 7.03 (tt, J ¼ 7.4, 1.0 Hz, 1H), 9.67 (td,
J ¼ 7.5, 1.2 Hz, 1H), 4.72 (s, 1H), 3.83 (s, 3H, OMe), 3.58 (s, 2H), 2.80–2.50
(brs, 8H), 2.14 (s, 3H, O55C–CH3). 13C NMR (CDCl3, 100.6 MHz) d 168.6
(Cq, C55O), 163.9, 143.3, 138.8, 138.0, 130.5, 129.8, 129.6, 128.8, 128.7,
127.6 (CHar), 126.0, 125.3, 123.3, 123.2, 120.6, 114.7, 70.3, 63.3, 54.0, 52.2
(CH3, OMe), 51.4, 25.9 (CH3, O55C–Me). IR (CCl4, CaF2) n (cm21): 3062,
3030, 2952, 2810, 2766, 1692, 1603,1591, 1536, 1445, 1290, 1227, 1169,
1132, 1004. Mass (ID ICP NH3) m/z 500 (MHþ), 323, 265, 178. Micro
analysis: found: C 69.32, H 6.71, calculated: C 69.72, H 6.66.
4-Benzylpiperazine-1-carboxylic acid f3-[1-(4-benzylpiperazin-1-yl)-
3-oxo-2-(phenylhydrazono)-butyl]-pyridin-2-ylg-amide (4d). Was obtained
as a brown oil (yield 74%) after 4 hr heating using 2.2 eq. of N-benzyl-
piperazine and purified on silica gel (EtOH/CH2Cl2). Rf : 0.45 (EtOH/
CH2Cl2, 5 : 95). 1H NMR (CDCl3, 400 MHz) d 13.14 (s, 1H, NHPh), 8.90 (s,
1H, NH–C55O), 8.46 (dd, J ¼ 4.7, 1.7 Hz, 1H), 7.84 (dd, J ¼ 7.8, 1.7 Hz, 1H)
7.43–7.23 (m, 14H), 7.10 (t, J ¼ 7.4 Hz, 1H), 6.99 (dd, J ¼ 7.8, 4.7 Hz, 1H),
4.98 (s, 1H), 3.80–3.66 (m, 4H), 3.60 (m, 2H), 3.54 (s, 2H), 2.89–2.54 (m,
8H), 2.41 (s, 3H, CH3–C55O), 2.39–2.05 (m, 4H). 13C NMR (CDCl3,
100.6 MHz) d 199.9, 155.1, 151.3, 149.3, 143.1, 138.4, 138.3, 137.8, 136.2,
130.1, 129.6, 129.4, 128.7, 127.7, 127.6, 125.4, 123.4, 120.5, 114.4, 63.4,
63.4, 63.0, 53.7, 53.5, 53.3, 52.9, 51.3, 24.9 (CH3–C55O). IR (CCl4, CaF2) n
(cm21): 3334, 2934, 2809, 1676, 1555, 1495, 1233, 1003. Mass (ID ICP NH3)
m/z 378, 296, 246, 207, 178, 95. HRMS (FAB): Calc 645.3665; Found
645.3662 (MHþ).
Cyclization Procedures
(2-Methyl-quinolin-3-yl)-phenyldiazene (5a). A solution of 1.00 g
(2.07 mmol, 1.0 eq.) of Mannich adduct 4a in HCl 6M (5 mL) was heated at
808C for 40 mn. The mixture was cooled to 08C, and quenched with NaOH.
Et2O was added, and the aqueous phase was extracted three times with
Et2O. The combined organic layers were washed with brine, dried over
anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the
crude product by flash chromatography on silica gel with Et2O/PE (30%) gave
373 mg (73%) of compound 5a as an orange solid M.p. 95–968C
1
(cyclohexane). Rf : 0.70 (EtOAc/PE, 40 : 60). H NMR (CDCl3, 400 MHz) d
8.19 (s, 1H), 8.01 (d, J ¼ 8.1 Hz, 1H), 7.94–7.91 (m, 2H), 7.83 (d, J ¼ 8.1 Hz,

New Straightforward Quinoline Synthesis
115
1H), 7.66 (t, J ¼ 8.1 Hz, 1H), 7.52–7.42 (m, 4H), 3.04 (s, 3H). 13C NMR
(CDCl3, 100.6 MHz) d 158.9, 153.3, 149.2, 145.1, 132.0, 130.9, 130.0, 129.6,
128.9, 127.6, 126.8, 123.6, 120.9, 22.4. IR (CCl4, CaF2) n (cm21): 3065, 2960,
2923, 2859, 1612, 1585, 1453, 1411, 1369, 1184, 1147. Mass (ID ICP NH3)
m/z 248 (MHþ), 190. Micro analysis: found: C 77.88, H 5.29, calculated: C
77.71, H 5.30. Analogously the following compounds were obtained:
Phenyl-(2-phenyl-quinolin-3-yl)-diazene (5b). Yield 82%. Orange
solid. M.p. 118–1208C (cyclohexane). Rf : 0.80 (EtOAc/PE, 60 : 40). 1H
NMR (CDCl3, 400 MHz) d 8.42 (s, 1H), 8.27 (d, 1H, J ¼ 8.5 Hz), 8.00 (d, 1H,
J ¼ 8.0 Hz), 7.94–7.90 (m, 4H), 7.81 (ddd, J ¼ 8.5, Hz, 1H), 7.60 (ddd,
J ¼ 8.0, 7.1, 1.0 Hz, 1H), 7.56–7.50 (m, 6H). 13C NMR (CDCl3, 100.6 MHz)
d 157.9, 153.2, 149.4, 144.9, 140.0, 132.0, 131.6 (CHar), 131.2, 130.0, 129.9,
129.7, 129.3, 128.3, 122.4, 127.5, 123.9, 122.4. IR (thin film): 3057, 1715,
1613, 1586, 1545, 1484, 1450, 1416, 1369, 1247, 1186, 1152, 1131, 1070. (ID
ICP NH3) m/z 310 (MHþ). Micro analysis: found: C 81.81, H 4.92,
calculated: C 81.53, H 4.89.
3-Methoxy-1H-indole-2-carboxylic acid methyl ester (6). To a solu-
tion of HCl 1M in ethanol (9.0 mL) was added 115 mg (0.23 mmol, 1.0 eq.) of
hydrazone 4c. The resulting mixture was heated at 808C for 40 min, then
cooled to 08C and quenched with NaOH. Et2O was added, and the aqueous
phase was extracted three times with Et2O. The combined organic layers were
washed with brine, dried over anhydrous MgSO4, filtered and concentrated in
vacuo. Purification of the crude product by flash chromatography on silica gel
with EtOAc/PE (10%) gave 39 mg (83%) of indole 6[21] as a pale solid M.p.
1
102–1048C (Lit[21] m.p. 1068C). Rf : 0.45 (EtOAc/PE, 40 : 60). H NMR
(CDCl3, 400 MHz) d 8.61 (s, 1H, NH), 7.80 (dd, J ¼ 8.2, 0.8 Hz, 1H), 7.37–
7.31 (m, 2H), 7.13 (ddd, J ¼ 8.2, 5.6, 2.3 Hz, 1H), 4.17 (s, 3H), 4.00 (s, 3H).
13C NMR (CDCl3, 100.6 MHz) d 162.4, 145.4, 134.8, 126.6, 120.8, 120.7,
120.4, 114.6, 112.6, 62.8, 52.4. IR (CCl4, CaF2) n (cm21): 3461, 3336, 2952,
1726, 1698, 1474, 1338, 1252, 1004. Mass (ID ICP NH3) m/z 223
(M þ NHþ4 ), 206 (MHþ). Micro analysis: found: C 64.34, H 5.69, calculated:
C 64.38, H 5.40.
(2-But-3-enyl-quinolin-3-yl)-phenyldiazene (5c). To a stirred solution
of LDA (50 mmol, 2.0 eq.), prepared from diisopropylamine (7 mL, 50 mmol,
2.0 eq.) and n-BuLi (50 mmol, 2.0 eq.), in dry THF (50 mL), was added ethyl
acetoacetate (3.2 ml, 25.0 mmol, 1.0 eq.) at 08C. After 30 mn, allyl bromide
(2.2 mL, 25 mmol, 1.0 eq.) was added and the resulting solution was stirred for
an additional 30 mn at 08C, then at room temperature overnight, followed by
addition of acetic acid (2.8 mL, 50 mmol, 2.0 eq.), ether and water. Organic
layers were extracted with ether, washed with brine, dried with MgSO4, and
concentrated in vacuo to give the crude keto ester (3.9 g, 75% crude yield) as a
colorless oil. To a solution of this ester in ethanol (25 mL, 1M) was added

116
Bailliez, El Kaim, and Michaut
sodium acetate (6.2 g, 3 eq.) followed by a controlled (the temperature should
be kept under 108C) addition of a phenyl diazonium chloride water solution
(prepared from 25 mmol of aniline, HCl and NaNO2 in water). The resulting
solution was brought to pH ¼ 7, ethanol was evaporated under reduced
pressure and the resulting solution extracted with CH2Cl2. After evaporation
of the solvents, the crude hydrazone was diluted in MeOH and H2O (25 mL of
each), and sodium hydroxide (3.0 g, 75 mmol, 3.0 eq.) was added. The result-
ing solution was stirred overnight at room temperature, the solution was
brought to pH 7 with HCL (1M) and the solvents were evaporated. The solid
mixture was then heated under argon 1h30 at 1508C. To the crude hydrazone
was added toluene (12 ml), N-(2-formylphenyl)-acetamide 1a (4.1 g,
25 mmol) and N-benzylpiperazine (4.7 mL, 27 mmol, 1.1 eq) and the resulting
mixture heated under argon at 808C for 8 hours. After evaporation of the
solvent, a 2M water solution of HCl (200 mL) was added and the mixture
heated at 808C for 2 hours. Neutralisation with NaOH, extraction with Et2O
and flash chromatography on silica gel (Et2O/PE 10/90) gave quinoline 5d
(2.2 g, 25%). Orange solid. M.p. 72–748C (petroleum ether). Rf : 0.35 (Et2O/
PE, 10 : 90). 1H NMR (CDCl3, 400 MHz) d 8.21 (s, 1H), 8.02 (d, J ¼ 8.1 Hz,
1H), 7.93–7.89 (m, 2H), 7.82 (d, J ¼ 8.1 Hz, 1H), 7.65 (td, J ¼ 8.1, 1.2 Hz,
1H), 7.50–7.40 (m, 4H, Har), 5.92 (ddt, J ¼ 17.0, 10.2, 6.7 Hz, 1H), 5.02 (dd,
J ¼ 17.0, 1.4 Hz, 1H), 4.91 (dd, J ¼ 10.2, 1.4 Hz, 1H), 3.50 (t, J ¼ 7.9 Hz,
2H), 2.62–2.57 (m, 2H). 13C NMR (CDCl3, 100.6 MHz) d 161.6, 153.3,
149.4, 144.7, 138.5, 132.0, 130.9, 130.1, 129.6, 129.2, 127.6, 126.9, 123.6,
121.1, 115.4, 35.1, 34.6. IR (CCl4, CaF2) n (cm21): 3066, 2929, 1640, 1617,
1591, 1561, 1496, 1153, 1131. Mass (ID ICP NH3) m/z 287 (M), 195. Micro
analysis: found: C 79.61, H 6.11, calculated: C 79.41, H 5.96.
(2-Methyl-[1,8]naphthyridin-3-yl)-phenyldiazene (5d). To a solution
of 283 mg (0.439 mmol, 1.0 eq.) of Mannich adduct 4d in 1.0 mL of toluene at
room temperature was added 75 mL (0.88 mmol, 2.0 eq.) of 1,2-dibromo-
ethane. The resulting mixture was heated to reflux under argon for 4 h. H2O
was added and the aqueous phase was extracted with CH2Cl2. The combined
organic layers were washed with brine, dried over anhydrous NaSO4, filtered
and concentrated in vacuo. Purification by flash chromatography on silica gel
with 10% EtOAc/CH2Cl2, gave 23 mg (21%) of naphthyridine 5d as a pale
yellow solid along with 11% of starting material. M.p. 106–1088C. 1H NMR
(CDCl3, 400 MHz) d 9.12 (dd, J ¼ 4.2, 1.9 Hz, 1H), 8.29 (dd, J ¼ 8.1, 1.9 Hz,
1H), 8.26 (s, 1H), 8.02–7.99 (m, 2H), 7.60–7.55 (m, 3H), 7.48 (dd, J ¼ 8.1,
4.2 Hz, 1H), 3.17 (3H, Me). 13C NMR (CDCl3, 100.6 MHz) d 162.8, 156.9,
154.5, 153.2, 145.5, 139.1, 132.4, 129.7, 123.8, 122.5, 122.0, 120.9, 22.9
(CH3, Me). IR (CCl4, CaF2) n (cm21): 2926, 2354, 1605, 1553, 1490, 1467,
1264, 1151. Mass (ID ICP NH3) m/z 249 (MHþ). HRMS (CI, CH4) calc
249.1140, found 249.1143.

New Straightforward Quinoline Synthesis
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Received in Poland May 26, 2003