Preparation of quinolines substituted at the 2 or 3 position by an alkenyl or alkynyl chain

Article abstract of DOI:10.1081/SCC-120006472

Quinolines substituted by a functionalized alkenyl or an alkynyl chain, either at the 2 or 3 position, were efficiently synthesized from 2-quinaldehyde and 3-bromoquinoline, respectively.

Full text of DOI:10.1081/SCC-120006472

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PREPARATION OF QUINOLINES SUBSTITUTED AT THE 2
OR 3 POSITION BY AN ALKENYL OR ALKYNYL CHAIN
Mohamed A. Fakhfakh a , Xavier Franck a , Alian Fournet b , Reynald Hocquemiller a & Bruno
Figadère c
a Laboratoire de Pharmacognosie, associé au CNRS (BIOCIS), Faculté de Pharmacie, rue J.B.
Clément, Université Paris-Sud, Châtenay-Malabry, F-92296, France
b Institute de Recherche pour le Développement (I.R.D.), 213 rue La Fayette, Paris, F-75480,
France
c Laboratoire de Pharmacognosie, associé au CNRS (BIOCIS), Faculté de Pharmacie, rue J.B.
Clément, Université Paris-Sud, Châtenay-Malabry, F-92296, France
Published online: 18 Oct 2011.
To cite this article: Mohamed A. Fakhfakh , Xavier Franck , Alian Fournet , Reynald Hocquemiller & Bruno Figadre (2002)
PREPARATION OF QUINOLINES SUBSTITUTED AT THE 2 OR 3 POSITION BY AN ALKENYL OR ALKYNYL CHAIN, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:18, 2863-2875, DOI:
10.1081/SCC-120006472
To link to this article: http://dx.doi.org/10.1081/SCC-120006472
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 18, pp. 2863–2875, 2002
PREPARATION OF QUINOLINES
SUBSTITUTED AT THE 2 OR 3 POSITION
BY AN ALKENYL OR ALKYNYL CHAIN
Mohamed A. Fakhfakh,1 Xavier Franck,1
Alian Fournet,1,2 Reynald Hocquemiller,1
and Bruno Figadere1,
*
1Laboratoire de Pharmacognosie, associe au CNRS
(BIOCIS), Universite Paris-Sud, Faculte de Pharmacie,
rue J.B. Clement, F-92296 Chatenay-Malabry France
2Institute de Recherche pour le Developpement
(I.R.D.), 213 rue La Fayette, F-75480 Paris, France
ABSTRACT
Quinolines substituted by a functionalized alkenyl or an alky-
nyl chain, either at the 2 or 3 position, were efficiently synthe-
sized from 2-quinaldehyde and 3-bromoquinoline, respectively.
Several 2-alkenylquinolines, the chimanies, with very promising activity
against several leishmania strains, have been isolated form Galipea longi-
flora[1] and have shown oral leismanicidal property.[2,3] A few of them also
expressed some activity against Plasmodium vinckei petteri.[4] Therefore, we
were interested in establishing some structure-activity relationships, based on
*Corresponding author. E-mail: bruno.figadere@cep.u-psud.fr
2863
DOI: 10.1081/SCC-120006472
Copyright & 2002 by Marcel Dekker, Inc.
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2864
FAKHFAKH ET AL.
the nature of the alkenyl chain branched at the 2 position of quinoline. Then
we also prepared some 3-substituted quinolines for further comparisons.
Several methods have been reported for the preparation of 2-alkylpyridines,[5]
however very few reports have appeared in the literature concerning the syn-
thesis of 2- or 3-substituted quinolines.[6] We thought that 2-quinaldehyde (1)
could be engaged in Wittig reactions to afford the unsaturated adducts[7]
(Scheme 1), whereas 3-bromoquinoline (2) could be a suitable starting
material for cross-coupling reactions with organomagnesium species[8]
(Scheme 3). For the preparation of 2-alkenylquinolines, we first performed
the separated addition of several phosphonium bromides on 2-quinaldehyde
(1) in toluene in the presence of tBuOK at 0ꢀC for 1 h, and after usual workup
and purification by flash chromatography through evaporation of the sol-
vents under a slight vacuum (>30 mm Hg), the desired 2-alkenylquinolines
(3a–e) were obtained in 46–84% yield as the E isomers (Table 1).
Interestingly compounds (3a–e) were obtained with high stereoselectivity,
maybe due to isomerisation of the double bond during the work-up and
purification steps. With phosphorus ylides possessing a stabilized carbanion,
the temperature was brought to 100ꢀC, and the desired compound (3f,g)
obtained as E major isomers in 60 and 80% yield, respectively (Scheme 1).
Then when (1) was treated under McKelvie conditions[9] (PPh3, CBr4,
CH2Cl2, room temperature, 2 h) the desired 1,1-dibromo-2-(2-quinolyl)-
ethylene (3h) was obtained in 89% yield.
We then prepared several derivatives from these compounds such
as the dienic ester (4) by a second Wittig reaction from (3f) and the
corresponding phosphorus ylide (63% yield), and the carboxylic acid (5)
Scheme 1.

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2865
Table 1.
Entry
Products
Yield (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
46
57
84
54
58
60
80
89
3g
3h
Scheme 2.
Scheme 3.
through saponification of (3h) (90% yield). The allylic alcohol (6) was also
prepared by reduction of (3f) (1 equivDibal-H) in good yield (85%). It is
interesting to note that compound (3a) was previously synthesized by addi-
tion of a Grignard reagent (vinylmagnesium bromie) on N-oxyisobutyl-
oxycarbonylquinolinium chloride in 82% yield, as already reported.[10] It
is worth noting that it is also a complementary approach to the iron cata-
lyzed Grignard reduction-coupling reactions of 1,1-dibromo-2-(2-
quinolyl)ethylene (3h)[11] (see Scheme 2). Furthermore, it allows one to
synthesize functionalized 2-alkenyl quinolines.

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2866
FAKHFAKH ET AL.
Scheme 4.
For the preparation of 3-substituted quinolines, we chose 3-bromo-
quinoline (2) as starting material. Thus compound (7a) was prepared in
30% yield from (2) by coupling reaction with the desired Grignard reagent
[12]
in the presence of a catalytic amount of Ni(acac)2
in THF/NMP.
Whereas, compound (7b) was best obtained from (2) and phenylmagnesium
bromide in the presence of 5% molar of Fe(acac)3, in 35% yield (see
Scheme 3). It is worth noting that it is the first reported coupling reaction
between a heteroaryl bromide and a Grignard reagent, catalyzed by an iron
salt.[8e,11]
Compounds (7c) and (7d) were obtained by Sonogashira coupling
reactions with the required alkynes,[13] in the presence of pyrrolidine and
a catalytic amount of Pd(PPh3)4 and CuI, in 99 and 70% yield, respectively
(see Scheme 3).
Finally, the bis-quinoline (8) was easily obtained by the Perkin reaction
of 2-quinaldehyde (1) with 2-quinaldine (9) in 50% yield (see Scheme 4).[14]
In conclusion, we have successfully synthesized several quinolines
conjugated to functionalized alkenyl chains from easily accessible
starting materials. The coupling reaction between a Grignard reagent and
3-bromoquinoline will probably find further applications in this field. These
structurally related compounds were then engaged in several biological tests,
and the results will be published in due course.
EXPERIMENTAL
Solvents were purified according to the procedures described.[15] Infra
red spectra (IR) were recorded on a Pekin-Elmer-257 apparatus (ꢀ expressed
1
in: cmꢁ1). H and 13C NMR spectra were recorded with a Bruker AC-200
(200 MHz) and Bruker AM-400 (400 MHz). Chemical shifts (ꢁ) are
expressed in ppm with the protonated solvent as reference. Patterns are
described according to Hoye et. al.,[16] and coupling constants (J) are
given in hertz (Hz). Mass spectra (MS) have been recorded on: Nermag-
Sidar R10-10C (CIMS) with either CH4 or NH3 and for the electronic
impacts (EIMS) at 70 eV. Electrospray mass spectra (ESIMS) were recorded

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2867
on a Bruker-Esquire. Flash chromatography was performed with silica gel
60 (9385 Merck), silica gel S (31607 Riedel-de-Haen), and silica gel 60H
(7736 Merck). TLC was performed on plates coated with silica gel 60F254
(554 Merck).
General procedure for the preparation of products (3a–e): In a round
bottom flask under a nitrogen atmosphere, 19.1 mmol of alkyltriphenylphos-
phonium bromide are introduced, followed by 20 mL of anhydrous toluene.
The temperature was brought to 0ꢀC (ice cold bath) and 20.3 mmol of
t-BuOK are added. After 15 min of stirring, 6.37 mmol of quinaldehyde (1),
in 10 mL of anhydrous THF, was added. The reaction mixture was stirred
at 0ꢀC for 1 h and 20 mL of water added. After the temperature has reached
20ꢀC, the two layers were separated, and the aqueous layer extracted with
EtOAc (4 ꢂ 50 mL); the combined organic layers were washed with a satu-
rated aqueous solution of NaHCO3, then brine and dried over MgSO4.
After filtration and concentration, the crude material was purified by flash
chromatography (eluant: cyclohexane/EtOAc: 92/8) (for the yields, see in
the text).
2-(2-Quinolyl)-ethylene (3a): [CAS number 772-03-2]. 1H NMR
(200 MHz, CDCl3)-ꢁ ppm: 5.66 (d, J ¼ 10.9 Hz, 1H, H-30), 6.26 (d, J ¼ 17.7
Hz, 1H, H-40), 7.04 (dd, J ¼ 17.7, 10.9 Hz, 1H, H-10), 7.49 (dd, J ¼ 7.2, 6.9 Hz,
1H, H-6), 7.60 (d, J ¼ 8.7 Hz, 1H, H-3), 7.69 (ddd, J ¼ 7.0, 8.3, 0.6 Hz, 1H,
H-7), 7.77 (d, J ¼ 7.9 Hz, 1H, H-5), 8.06 (d, J ¼ 9.9 Hz, 1H, H-8 or H-4), 8.08
(d, J ¼ 8.8 Hz, 1H, H-4 or H-8); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 118.26
(C-3), 119.68 (C-20), 126.17 (C-6), 126.90 (C-10), 127.34 (C-5), 129.22 (C-8),
129.46 (C-7), 136.17 (C-4), 136.87 (C-10), 147.93 (C-9), 155.96 (C-2); CIMS
(NH4þ) 156 (MHþ, 100); IR (cmꢁ1): 3060, 1595, 1555, 1505, 1425, 1310, 1140,
1120, 1015, 990, 925, 830, 760, 730, 714, 615.
E-1-(2-quinolyl)-butene (3b): [CAS number 36680-24-7]. 1H NMR
(400 MHz, CDCl3)-ꢁ ppm : 1.17 (t, J ¼ 7.5 Hz, 3H, H-40), 2.36 (dqd,
J ¼ 7.5, 6.3, 1.5 Hz, 1H, H-30), 6.72 (dt, J ¼ 15.9, 1.5 Hz, 1H, H-10), 6.88
(dd, J ¼ 15.9, 6.3 Hz, 1H, H-20), 7.45 (ddd, J ¼ 6.9, 6.9, 1.2 Hz, 1H, H-6),
7.52 (d, J ¼ 8.6 Hz, 1H, H-3), 7.66 (ddd, J ¼ 6.9, 6.9, 1.5 Hz, 1H, H-7), 7.74
(dd, J ¼ 8.01, 1.3 Hz, 1H, H-5), 8.03 (d, J ¼ 9.4 Hz, 1H, H-8), 8.06 (d,
J ¼ 9.0 Hz, 1H H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 12.90 (C-40),
25.80 (C-30), 118.46 (C-3), 125.54 (C-6), 126.90 (C-10), 127.18 (C-5),
128.88 (C-8), 129.21 (C-7), 129.92 (C-10), 135.84 (C-4), 139.00 (C-20),
147.87 (C-9), 156.30 (C-2); ESIMS: 184 (MHþ, 100); IR (cmꢁ1): 2965,
1650, 1615, 1595, 1555, 1505, 1460, 1425, 1315, 1115, 965, 855, 815, 750, 620.
E-1-(2-quinolyl)-pentene (3c): [CAS number 128396-36-1]. 1H NMR
(200 MHz, CDCl3)-ꢁ ppm: 0.99 (t, J ¼ 6.7 Hz, 3H, H-50), 1.58 (sext,
J ¼ 6.8 Hz, 2H, H-40), 2.31 (q, J ¼ 6.8 Hz, 2H, H-30), 6.70 (d, J ¼ 15.9 Hz,
1H, H-10), 6.83 (dt, J ¼ 15.9, 60 Hz, 1H, H-20), 7.45 (t, J ¼ 8.3 Hz, 1H, H-6),

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2868
FAKHFAKH ET AL.
7.51 (d, J ¼ 8.9 Hz, 1H, H-3), 7.66 (t, J ¼ 7.5 Hz, 1H, H-7), 7.74 (d, J ¼ 8.4 Hz,
1H, H-5), 8.02 (d, J ¼ 8.3 Hz, 1H, H-8), 8.05 (d, J ¼ 8.2 Hz, 1H, H-4);
13C NMR (50 MHz, CDCl3)-ꢁ ppm: 13.40 (C-50), 21.67 (C-40), 34.68 (C-30),
118.28 (C-3), 125.31 (C-6), 126.71 (C-10), 126.98 (C-5), 128.70 (C-8), 128.99
(C-7), 130.87 (C-20), 135.56 (C-4), 137.11 (C-20), 147.69 (C-9), 155.99 (C-2);
ESIMS: 198 (MHþ, 100); IR (cmꢁ1): 2960, 2930, 2870, 1695, 1650, 1615,
1595, 1555, 1505, 1460, 1425, 1310, 1140, 1115, 970, 835, 805, 770, 620.
E-1-(2-quinolyl)-hexene (3d): [CAS number 183968-28-7]. 1H NMR
(200 MHz, CDCl3)-ꢁ ppm: 0.94 (t, J ¼ 6.8 Hz, 3H, H-60), 1.47 (m, 4H,
H-50, 40), 2.33 (q, J ¼ 6.7 Hz, 2H, H-30), 6.70 (d, J ¼ 16.0 Hz, 1H, H-10),
6.84 (dt, J ¼ 16.0, 6.1 Hz, 1H, H-20), 7.45 (t, J ¼ 7.1 Hz, 1H, H-6), 7.51
(d, J ¼ 8.9 Hz, 1H, H-3), 7.66 (ddd, J ¼ 7.2, 7.2, 1.2 Hz, 1H, H-7), 7.74
(d, J ¼ 8.1 Hz, 1H, H-5), 8.02 (d, J ¼ 8.5 Hz, 1H, H-8), 8.07 (d, J ¼ 8.6 Hz,
1H, H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 13.54 (C-60), 21.91 (C-50),
30.62 (C-40), 32.28 (C-30), 118.22 (C-3), 125.25 (C-6), 126.92 (C-10),
126.89 (C-5), 128.70 (C-8), 128.95 (C-7), 130.65 (C-20), 135.53 (C-4),
137.28 (C-20), 147.66 (C-9), 155.96 (C-2); ESIMS: 212 (MHþ, 100); IR
(cmꢁ1): 2960, 2930, 2870, 1695, 1650, 1615, 1595, 1555, 1505, 1460, 1425,
1375, 1312, 1140, 1115, 970, 835, 805, 750, 620.
E-1-(2-quinolyl)-heptene (3e): 1H NMR (200 MHz, CDCl3)-ꢁ ppm: 0.91
(t, J ¼ 6.5 Hz, 3H, H-60), 1.29 (m, 6H, H-60, 50, 40), 2.32 (q, J ¼ 6.9 Hz, 2H,
H-30), 6.70 (d, J ¼ 16.1 Hz, 1H, H-10), 6.84 (dt, J ¼ 16.0, 6.1 Hz, 1H, H-20),
7.45 (t, J ¼ 8.4 Hz, 1H, H-6), 7.52 (d, J ¼ 8.8 Hz, 1H, H-3), 7.66 (dd, J ¼ 7.6,
7.2 Hz, 1H, H-7), 7.74 (d, J ¼ 7.8 Hz, 1H, H-5), 8.02 (d, J ¼ 8.4 Hz, 1H, H-8),
8.05 (d, J ¼ 8.3 Hz, 1H, H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 13.92
(C-70), 22.43 (C-60), 28.50 (C-50), 31.38 (C-40), 32.88 (C-30), 118.59 (C-3),
125.67 (C-6), 127.04 (C-10), 127.29 (C-5), 129.04 (C-8), 129.35 (C-7),
130.96 (C-20), 135.95 (C-4), 137.90 (C-20), 147.99 (C-9), 156.42 (C-2);
ESIMS: 226 (MHþ, 100); IR (cmꢁ1): 2955, 2925, 2855, 1650, 1615, 1595,
1555, 1505, 1460, 1425, 1375, 1310, 1140, 1115, 1015, 965, 830, 810, 750, 620.
3-(2-Quinolyl)-propenal (3f): [CAS number 201928-74-7]. In a round
bottom flask, equipped with a condensor, under a nitrogen atmosphere,
1.27 mmol (0.2 g) of quinaldehyde (1) are introduced, followed by 10 mL
of anhydrous toluene. Then, 1.52 mmol (0.46 g) of triphenylphosphoranyli-
dene acetaldehyde are added, and the reaction mixture heated under reflux
for 90 min. After cooling to room temperature, 10 mL of water were added.
The two layers were separated, and the aqueous layer extracted with EtOAc
(4 ꢂ 50 mL); the combined organic layers were washed with a saturated
aqueous solution of NaHCO3, then brine and dried over MgSO4. After
filtration and concentration, the crude material was purified by flash chro-
matography (eluant: cyclohexane/EtOAc: 75/25) to afford 0.149 g (76%) of
1
(3f). H NMR (400 MHz, CDCl3)-ꢁ ppm: 7.13 (ddd, J ¼ 16.2, 7.7, 0.7 Hz,

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2869
1H, H-20), 7.59 (dd, J ¼ 7.0, 7.0 Hz, 1H, H-6), 7.69 (d, J ¼ 8.5 Hz, 1H, H-3),
7.73 (d, J ¼ 16.1 Hz, 1H, H-10), 7.76 (dd, J ¼ 7.2, 7.5 Hz, 1H, H-7), 7.84
(d, J ¼ 8.1 Hz, 1H, H-5), 8.12 (d, J ¼ 8.5 Hz, 1H, H-8), 8.22 (d, J ¼ 8.5 Hz,
1H, H-4), 9.86 (dd, J ¼ 7.7, 0.7 Hz, 1H, H-30); 13C NMR (50 MHz, CDCl3)-ꢁ
ppm: 119.85 (C-3), 127.52 (C-5), 127.78 (C-6), 128.11 (C-10), 129.91 (C-8),
130.22 (C-7), 132.54 (C-20), 136.84 (C-4), 148.28 (C-9), 151.75 (C-10), 152.84
(C-2), 193.52 (C-30); ESIMS: 184 (MHþ, 100); IR (cmꢁ1): 3050, 1670, 1630,
1595, 1555, 1500, 1430, 1290, 1125, 1110, 980, 900, 825, 785, 625, 590.
Methyl E-3-(2-quinolyl)-propenoate (3g): [CAS number 81124-46-1].
In a round bottom flask, equipped with a condensor, under a nitrogen atmo-
sphere, 1.27 mmol (0.2 g) of quinaldehyde (1) are introduced, followed by
10 mL of anhydrous toluene. Then 1.52 mmol (0.51 g) of methyltriphenyl-
phosphoranylidene acetate are added, and the reaction mixture heated
under reflux for 90 min. After cooling to room temperature, 10 mL of water
were added. The two layers were separated, and the aqueous layer extracted
with EtOAc (4 ꢂ 50 mL); the combined organic layers were washed with a
saturated aqueous solution of NaHCO3, then brine and dried over MgSO4.
After filtration and concentration, the crude material was purified by flash
chromatography (eluant: cyclohexane/EtOAc: 70/30) to afford 0.217 g (80%)
of (3g). 1H NMR (400 MHz, CDCl3)-ꢁ ppm: 3.85 (s, 3H, OMe), 7.00
(d, J ¼ 14.9 Hz, 1H, H-20), 7.54 (t, J ¼ 7.9 Hz, 1H, H-6), 7.57 (d, J ¼ 8.7 Hz,
1H, H-3), 7.72 (dd, J ¼ 7.2, 8.1 Hz, 1H, H-7), 7.78 (d, J ¼ 8.1 Hz, 1H, H-5),
7.89 (d, J ¼ 16.0 Hz, 1H, H-10), 8.10 (d, J ¼ 8.5 Hz, H-8), 8.14 (d, J ¼ 8.5 Hz,
H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 51.67 (OMe), 120.12 (C-3), 123.01
(C-20), 127.11 (C-6), 127.033 (C-5), 127.87 (C-10), 129.67 (C-8), 129.83 (C-7),
136.48 (C-4), 144.11 (C-1 ), 148.06 (C-9), 152.88 (C-2), 166.74 (C-30); ESIMS:
214 (MHþ, 100); IR (cmꢁ1): 1740, 1725, 1650, 1595, 1560, 1500, 1435, 1345,
1245, 1195, 1155, 975, 825, 755, 715, 620. El. An.: (Calculated: C 73.22,
H, 5.20, N, 6. 57). Found: C, 72.96; H, 5.26; N, 6.35.
1,1 Dibromo-2-(2-quinolyl)-ethylene (3h): [CAS number 218902-66-0].
In a round bottom flask, under a nitrogen atmosphere, 3.18 mmol (0.5 g)
of quinaldehyde (1) are introduced, followed by 20 mL of anhydrous
CH2Cl2. The temperature was brought to 0ꢀC (ice cold bath) and
4.42 mmol (1.47 g) of CBr4 are added, followed by 6.37 mmol (1.67 g) of
triphenylphosphine. After 2 h of stirring, triphenylphosphine oxide was pre-
cipitated by adding pentane, and the surnactant filtered through a short pad
of silica gel. The remaining solid was dissolved in CH2Cl2, and pentane
added. The surnactant again was filtered through a short pad of silica gel,
and the combined filtrates were concentrated under vacuum at 70ꢀC. The
crude material was then purified by flash chromatography (eluant:
cyclohexane/EtOAc: 90/10) to afford 0.866 g (89%) of (3h). 1H NMR
(400 MHz, CDCl3)-ꢁ ppm: 7.54 (dd, J ¼ 8.0, 7.1 Hz, 1H, H-6), 7.71 (ddd,

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2870
FAKHFAKH ET AL.
J ¼ 8.3, 7.1, 1.2 Hz, 1H, H-7), 7.78 (dd, J ¼ 8.4, 7.4 Hz, 2H, H-3, 5), 7.83
(s, 1H, H-10), 8.10 (d, J ¼ 8.5 Hz, 1H, H-8), 8.12 (d, J ¼ 8.6 Hz, 1H, H-4);
13C NMR (50 MHz, CDCl3)-ꢁ ppm: 93.94 (C-20), 120.24 (C-3), 126.57 (C-6),
127.06 (C-5), 127.15 (C-10), 128.93 (C-8), 129.43 (C-7), 135.61 (C-4), 137.19
(C-10), 147-28 (C-9), 153.21 (C-2); ESIMS: 315 (MHþ, 49); 313 (MHþ, 100),
311 (MHþ, 44); IR (cmꢁ1): 3020, 1590, 1555, 1500, 1430, 1340, 1310, 1255,
1230, 1205, 1120, 955, 880, 855, 835, 820, 785, 755, 710, 665, 590.
Methyl E, E-5-(2-quinolyl)-penta-2,4-dienoate (4): In a round bottom
flask, under a nitrogen atmosphere, 0.55 mmol (0.1 g) of aldehyde (3f) are
introduced, followed by 5 mL of anhydrous toluene. Then, 0.66 mmol (0.22 g)
of methyltriphenylphosphoranylidene acetate are added, and the reaction
mixture stirred at room temperature for 5 h 30 min. Then 10 mL of water
were added. The two layers were separated, and the aqueous layer extracted
with EtOAc (4 ꢂ 50 mL); the combined organic layers were washed with a
saturated aqueous solution of NaHCO3, then brine and dried over MgSO4.
After filtration and concentration, the crude material was purified by flash
chromatography (eluant: cyclohexane/EtOAc: 60/40) to afford 0.082 g (63%)
of (4). 1H NMR (200 MHz, CDCl3)-ꢁ ppm: 3.80 (s, 3H, OMe), 6.18
(d, J ¼ 14.6 Hz, 1H, H-20), 7.16 (d, J ¼ 14.5 Hz, 1H, H-40), 7.50 (m, 4H,
H-10, 30, 3, 6), 7.72 (t, J ¼ 7.0 Hz, 1H, H-7), 7.79 (d, J ¼ 8.1 Hz, 1H, H-5),
8.07 (d, J ¼ 8.4 Hz, 1H, H-8), 8.14 (d, J ¼ 8.9 Hz, 1H, H-4); 13C NMR
(50 MHz, CDCl3)-ꢁ ppm: 51.53 (OMe), 119.81 (C-3), 123.52 (C-20), 126.06
(C-10), 126.66 (C-6), 127.40 (C-5), 129.36 (C-8), 129.82 (C-7), 131.25 (C-40),
136.37 (C-4), 139.80 (C-30), 143.64 (C-10), 148.16 (C-9), 154.32 (C-2),
166.86 (C-50); ESIMS: 239 (Mþ, 21), 180 (100), 167 (33), 143 (23), 128 (31);
IR (cmꢁ1): 3055, 1730, 1590, 1505, 1485, 1310, 1180, 1115, 1070, 995, 745,
720, 695.
3-(2-Quinolyl)-propenoic acid (5): [CAS number 81124-50-7]. In a round
bottom flask, 1.17 mmol (0.25 g) of methyl ester (3g) are introduced, followed
by 10 mL of methanol. The temperature was brought to 0ꢀC (ice cold bath)
and 3.52 mmol (17.6 mL of aqueous 20% M solution) of KOH are added.
After 3 h of stirring, the solution was extracted with Et2O and the aqueous
layer acidified to pH ¼ 5 with a saturated aqueous solution of NH4Cl. Then
the mixture was extracted with CHCl3 (4 ꢂ 50 mL), and the organic layer
dried over MgSO4, filtered and concentrated. The crude material was purified
by crystallization in Et2O to afford 0.150 g (60%) of (5). 1H NMR (200 MHz,
DMSO)-ꢁ ppm: 7.28 (d, J ¼ 16 Hz, 1H, H-20), 7.80 (dd, J ¼ 7.7, 7.4 Hz, 1H,
H-6), 7.98 (dd, J ¼ 7.8, 7.4 Hz, 1H, H-7), 7.96 (d, J ¼ 15.8 Hz, 1H, H-10), 8.18
(d, J ¼ 8.2 Hz, 1H, H-5), 8.31 (d, J ¼ 10.1 Hz, 1H, H-8 or 4), 8.36
(d, J = 9.2 Hz, 1H, H-8 or 4), 8.83 (d, J ¼ 8.6 Hz, 1H, H-3); 13C NMR
(50 MHz, CDCl3)-ꢁ ppm: 119.11 (C-3), 123.42 (C-20), 126.73 (C-10), 127.14
(C-6), 127.50 (2C), 131.39 (C), 136.87 (C-10), 140.43 (C-4), 141.04 (C-9),

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2871
149.87 (C-2), 165.22 (C-30); IEMS (CH2Cl2, 70 eV): 199 (Mþ, 15), 198 (24),
155 (31), 154 (100), 153 (74), 128 (66); IR (cmꢁ1): 3355, 3090, 2685, 1885,
1700, 1635, 1600, 1490, 1455, 1420, 1390, 1300, 1270, 1214, 1195, 1155, 985,
950, 900, 880, 850, 780, 765, 725, 665, 620. El. An.: (Calculated: C, 72.35;
H, 4.55; N, 7. 03). Found: C, 71.99; H, 4.66; N, 7.13.
E-3-(2-quinolyl)-prop-2-en-1-ol (6): [CAS number 150294-54-5]. In a
round bottom flask, under a nitrogen atmosphere, 0.93 mmol (0.2 g) of
aldehyde (3f) are introduced, followed by 10 mL of anhydrous toluene.
Then temperature was brought to ꢁ78ꢀC and 1.87 mmol (1.87 mL of a
1 M solution in toluene) of Dibal-H were added. After 2 h of stirring 5 mL
of methanol were added and the temperature is allowed to reach 20ꢀC. Then
50 mL of EtOAc are introduced and the reaction mixture stirred overnight
at room temperature. The reaction mixture was then filtered over a short
pad of celite. The filtrate was then washed with a saturated aqueous solution
of NaHCO3, then brine and dried over MgSO4. After filtration and concen-
tration, the crude product was purified by flash chromatography (eluant:
cyclohexane/EtOAc:60/40)toafford0.085 g(49%)of(6).1H NMR(400 MHz,
CDCl3)-ꢁ ppm: 4.44 (d, J ¼ 3.9 Hz, 2H, H-30), 6.87 (dt, J ¼ 16.8, 4.3 Hz, 1H,
H-20), 7.01 (d, J ¼ 16.3 Hz, 1H, H-10), 7.44 (m, 2H), 7.67 (m, 2H), 7.57 (m,
2H); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 62.60 (C-30), 118.90 (C-3), 126.15
(C-6), 127.21 (C-5), 127.40 (C-8), 128.73 (C-7), 129.73 (C-10), 136.48 (C-20),
137.21 (C-4), 147.67 (C-2), 155.71 (C-9); ESIMS: 208 (M þ Na, 12), 186
(MHþ, 100); IR (cmꢁ1): 3145, 2835, 1650, 1615, 1600, 1560, 1505, 1430,
1370, 1315, 1150, 1120, 1095, 965, 930, 840, 810, 770, 745, 635, 605.
E-1-(3-quinolyl)-propene (7a): [CAS number 104967-49-9]. In a round
bottom flask, under a nitrogen atmosphere, 2.40 mmol (0.500 g) of
3-bromoquinoline (2) are introduced, followed by 0.48 mmol (0.123 g) of
Ni(acac)2 and 5 mL of anhydrous THF with 5 mL of anhydrous NMP.
The temperature was brought to ꢁ10ꢀC and 2.4 mmol (6.31 mL of a 0.38 M
solution in THF) of propenylmagnesium bromide were added. After 12 h
30 min of stirring 20 mL of water were added and the temperature allowed
to reach 20ꢀC. After separation of the two layers, the aqueous solution was
extracted with Et2O (3 ꢂ 50 mL) and the combined organic layers were
washed with a saturated aqueous solution of NaHCO3, then brine and
dried over MgSO4. After filtration and concentration, the crude product
was purified by flash chromatography (eluant: cyclohexane/EtOAc: 87/13)
1
to afford 0.120 g (30%) of (7a). H NMR (400 MHz, CDCl3)-ꢁ ppm: 1.89
(d, J ¼ 4.5 Hz, 3H, H-30), 6.40 (m, 1H, H-20), 6.47 (d, J ¼ 16.5 Hz, 1H, H-10),
7.43 (dd, J ¼ 7.7, 6.9 Hz, 1H, H-6), 7.58 (dd, J ¼ 8.1, 7.0 Hz, 1H, H-7), 7.68
(d, J ¼ 8.5 Hz, 1H, H-5), 7.87 (s, 1H, H-2), 8.02 (d, J ¼ 8.2 Hz, 1H, H-8),
8.90 (s, 1H, H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 18.62 (C-30), 126.64
(C-20), 127.53 (C-6), 127.76 (C-5), 128.04 (C-10), 128.38 (C-8), 128.61

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2872
FAKHFAKH ET AL.
(C-7), 128.99 (C-10), 130.65 (C-3), 131.29 (C-2), 146.99 (C-9), 149.09 (C-4);
ESIMS: 170 (Mþ þ 1, 49), 169 (Mþ, 100), 168 (84), 156 (71), 128 (66); IR
(cmꢁ1): 2910, 2855, 1655, 1570, 1490, 1445, 1370, 1335, 1125, 1015, 960, 910,
860, 800, 785, 750, 720, 615, 570.
3-Phenyl-quinoline (7b): [CAS number 166-96-2]. In a round bottom
flask, under a nitrogen atmosphere, 2.40 mmol (0.500 g) of 3-bromoquino-
line (2) are introduced, followed by 0.12 mmol (0.042 g) of Fe(acac)3 and
5 mL of anhydrous THF with 5 mL of anhydrous NMP. The temperature
was brought to ꢁ10ꢀC and 2.6 mmol (3.52 mL of a 0.75 M solution in THF)
of phenylmagnesium bromide were added. After 3 h of stirring 20 mL of
water were added and the temperature allowed to reach 20ꢀC. After separa-
tion of the two layers, the aqueous solution was extracted with Et2O
(3 ꢂ 50 mL) and the combined organic layers were washed with a saturated
aqueous solution of NaHCO3, then brine and dried over MgSO4. After
filtration and concentration, the crude product was purified by flash chro-
matography (eluant: cyclohexane/EtOAc: 90/10) to afford 0.172 g (35%) of
(7b). H NMR (200 MHz, CDCl3)-ꢁ ppm: 7.49 (m, 4H, H-20, 30, 50, 60), 7.71
1
(m, 3H, H-6, 7, 40), 7.84 (d, J ¼ 8.0 Hz, 1H, H-5), 8.16 (d, J ¼ 8.9 Hz, 1H,
H-8), 8.26 (d, J ¼ 2.0 Hz, 1H, H-2), 9.19 (d, J ¼ 2.1 Hz, 1H, H-4); 13C NMR
(50 MHz, CDCl3)-ꢁ ppm: 126.49 (C-6), 126.89 (C-5), 127.62 (C-8, 7), 128.68,
128.89, 132.62 (C-2), 133.23 (C-3), 137.26 (C-10), 146.84 (C-9), 149.33 (C-4);
ESIMS: 170 (M þ Naþ, 30), 206 (MHþ, 100); IR (cmꢁ1); 3060, 1570, 1495,
1450, 1415, 1365, 1340, 1125, 1015, 1025, 955, 905, 860, 785, 760, 695,
615, 560.
(3-Quinolyl)-decyne (7c): In a round bottom flask, under a nitrogen
atmosphere, 1 mmol (0.208 g) of 3-bromoquinoline (2) are introduced, fol-
lowed by 3 mL of anhydrous pyrrolidine. Then 0.05 mmol (0.057 g) of
Pd(PPh3)4 and 2 mmol (0.36 mL) of 1-decyne and 0.1 mmol (0.019 g) of CuI
are added. After 20 h of stirring at room temperature, 5 mL of water were
added. After separation of the two layers, the two layers, the aqueous solution
was extracted with Et2O (3 ꢂ 50 mL) and the combined organic layers were
washed with a saturated aqueous solution of NaHCO3, then brine and dried
over MgSO4. After filtration and concentration, the crude product was pur-
ified by flash chromatography (eluant: cyclohexane/EtOAc: 90/10) to afford
0.262 g (99%) of (7c). 1H NMR (400 MHz, CDCl3)-ꢁ ppm: 0.89 (t, J ¼ 6.9 Hz,
3H, H-100), 1.32 (m, 8H, H-90, 80, 70, 60), 1.48 (m, 2H, H-50), 1.66 (quint,
J ¼ 7.3 Hz, 2H, H-40), 2.47 (t, J ¼ 7.1, 1H, H-30), 7.54 (ddd, J ¼ 8.0, 7.0,
1.0 Hz, 1H, H-6), 7.68 (ddd, J ¼ 8.4, 7.0, 1.4 Hz, 1H, H-7), 7.75 (d,
J ¼ 8.3 Hz, 1H, H-5), 8.07 (d, J ¼ 8.0 Hz, 1H, H-8), 8.16 (d, J ¼ 1.8 Hz, 1H,
H-2), 8.88 (d, J ¼ 2.1 Hz, 1H, H-4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm: 14.07
(C-100), 19.53 (C-30), 22.61 (C-90), 28.59 (C-70), 29.12 (C-60), 31.81 (C-50, 40),
77.89 (C-10), 94.15 (C-20), 118.22 (C-3), 127.04 (C-6), 127.35 (C-5), 127.53

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2873
(C-10), 129.25 (C-8), 129.56 (C-7), 137.86 (C-2), 146.44 (C-9), 152.48 (C-4);
ESIMS: 266 (MHþ, 100); IR (cmꢁ1): 3060, 2925, 2855, 2360, 2230, 1580,
1490, 1465, 1355, 1325, 1250, 1225, 1195, 1125, 1070, 945, 895, 860, 850,
780, 750, 625, 585.
1,6-Bis-(3-quinolyl)-hexa-1,5-diyne (7d): In a round bottom flask, under
a nitrogen atmosphere, 5.12 mmol (1.065 g) of 3-bromoquinoline (2) are
introduced, followed by 7.5 mL of anhydrous pyrrolidine. Then 0.25 mmol
(0.295 g) of Pd(PPh3)4, 2.56 mmol (0.25 mL) of 1,5-hexadiyne and 0.25 mmol
(0.048 g) of CuI are added. After 20 h of stirring at room temperature, 5 mL
of water were added. After separation of the two layers, the aqueous sol-
ution was extracted with Et2O (3 ꢂ 50 mL) and the combined organic layers
were washed with a saturated aqueous solution of NaHCO3, then brine and
dried over MgSO4. After filtration and concentration, the crude product was
purified by flash chromatography (eluant: cyclohexane/EtOAc: 90/10) to
1
afford 0.59 g (70%) of (7d). H NMR (200 MHz, CDCl3)-ꢁ ppm: 2.86 (s,
4H, H-30), 7.54 (ddd, J ¼ 8.0, 7.2, 1.2 Hz, 2H, H-6), 7.70 (td, J ¼ 8.3,
1.5 Hz, 2H, H-7), 7.75 (d, J ¼ 7.7 Hz, 2H, H-5), 8.07 (d, J ¼ 8.6 Hz, 2H,
H-8), 8.21 (d, J ¼ 2.3 Hz, 2H, H-2), 8.91 (d, J ¼ 2.2 Hz, 2H, H-4);
13C NMR (50 MHz, CDCl3)-ꢁ ppm: 19.40 (C-30), 78.88 (C-10), 91.33
(C-20), 117.18 (C-3), 126.73 (C-6), 126.77 (C-10), 127.04 (C-5), 128.89
(C-8), 129.41 (C-7), 137.78 (C-2), 146.26 (C-9), 151.91 (C-4); ESIMS:
355 (M þ Na, 3), 333 (MHþ, 100); IR (cmꢁ1): 3055, 2230, 1710, 1565,
1485, 1465, 1415, 1345, 1285, 1260, 1190, 1125, 1020, 950, 895, 860, 785,
745, 640.
E-1,2-Bis-(2-quinolyl)-ethylene (8): [CAS number 97871-25-5]. In a
round bottom flask, equipped with a condensor, under a nitrogen atmo-
sphere, 5 mmol (0.720 g) of quinaldehyde (1) are introduced, followed by
5 mmol (0.790 g) of 2-methylquinoline (9) and 3 mL of acetic anhydride. The
reaction mixture was then heated under reflux. After 20 min of stirring, the
solution was cooled to 20ꢀC and the pH was brought to 9 by addition of a
saturated aqueous solution of NaHCO3. After separation of the two layers,
the aqueous solution was extracted with toluene (3 ꢂ 50 mL) and the com-
bined organic layers were washed with brine and dried over MgSO4. After
filtration and concentration, the crude product was purified by crystalliza-
tion in ethanol to afford 0.589 g (42%) of (8). 1H NMR (200 MHz, CDCl3)-ꢁ
ppm: 7.51 (dd, J ¼ 7.6, 7.2 Hz, 2H, H-3), 7.71 (dd, J ¼ 7.9, 7.1 Hz, 2H, H-7),
7.81 (d, J ¼ 9.6, 4H, H-3, 5), 7.87 (s, 2H, H-10), 8.08 (d, J ¼ 8.4 Hz, 2H, H-8
or 4), 8.19 (d, J ¼ 8.6 Hz, 2H, H-8 or 4); 13C NMR (50 MHz, CDCl3)-ꢁ ppm:
119.50 (C-3), 126.49 (C-3), 126.97 (C-10), 127.45 (C-5), 129.37 (C-7), 129.72
(C-8), 134.52 (C-10), 136.39 (C-4), 148.22 (C-9), 155.29 (C-2); ESIMS: 282
(M+, 57), 281 (Mþꢁ1, 100), 280 (68), 253 (18), 179 (18), 128 (16); IR (cmꢁ1):
3090, 2180, 1590, 1550, 1500, 1455, 1425, 1375, 1305, 1260, 1235, 1140, 1115,

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2874
FAKHFAKH ET AL.
1050, 1015, 945, 870, 835, 815, 785, 755, 750, 675, 615. El. An.: (Calculated:
C, 85.08; H, 5.00; N, 9.92). Found: C, 84.96; H, 5.26; N, 9.85.
ACKNOWLEDGMENTS
We wish to thank J.-C. Jullian for NMR experiments.
REFERENCES
1. Fournet, A.; Hocquemiller, R.; Roblot, F.; Cave, A.; Richomme, P.;
Bruneton, J. J. Nat. Prod. 1993, 56, 1547–1553.
2. Fournet, A.; Barrios, A.A.; Munoz, V.; Hocquemiller, R.; Cave, A.;
Bruneton, J. Antimicrob. Agents Chemother. 1993, 37, 859–863.
3. Fournet, A.; Ferreira, M.E.; Rojas de Arias, A.; Torres de Ortiz, S.;
Fuentes,S.;Nakayama, H.;Schinini,A. Antimicrob. AgentsChemother.
1996, 40, 2447–2451.
4. Gantier, J.C.; Fournet, A.; Munos, M.H.; Hocquemiller, R. Planta
Med. 1996, 62, 285–286.
5. (a) Ochiai, E. Aromatic Amine Oxides; Elsevier: Amsterdam, 1996; p 269;
(b) Fife, W.K. J. Org. Chem. 1983, 48, 1375–1377; (c) Eisner, U.;
Kuthan, J. Chem. Rev. 1972, 72, 1–42; (d) von Doering, W.E.;
Pasternack, V.Z. J. Am. Chem. Soc. 1950, 72, 143–147; (e) Benkeser,
R.A.; Holtar, D.S. J. Am. Chem. Soc. 1951, 73, 5861–5863; (f)
Giam, C.S.; Knaus, E.E.; Pasutto, F.M. J. Org. Chem. 1974, 39,
3565–3568; (g) Frankel, G.; Cooper, J.W.; Fink, C.M. Angew. Chem.
Int. Ed. Engl. 1970, 9, 523–524; (h) Lyle, R.E.; Marshall, J.L.; Comins,
D.L. Tetrahedron Lett. 1977, 1005–1018.
6. (a) Mani, N.S.; Chen, P.; Jones, T.K. J. Org. Chem. 1999, 64,
6911–6914 and ref. cited therein; (b) Webb, T.R. Tetrahedron Lett.
1985, 26, 3191–3194.
7. (a) Carsky, P.; Hunig, S.; Stemmler, I.; Scheutzow, D. Liebigs Ann.
Chem. 1980, 291–304; (b) Minowa, N.; Imamura, K.-I.; Machinami, T.;
Shibahara, S. Biosci. Biotech. Biochem. 1996, 60, 1510–1512.
8. For coupling reactions of Grignard reagents with vinyl bromides (and
in some cases aryl bromides), see : a) with FeCl 3 : Tamura, M. ; Kochi,
J.K. Synthesis 1971, 303-305; Smith, R.S. ; Kochi, J.K. J. Org. Chem.
1976, 41, 502-509; b) with (dppp)NiCl2 : Tamao, K. ; Zembayashi, M. ;
Kiso, Y. ; Kumada, M. J. Organomet. Chem. 1973, 55C91; c) with
CoI2 : Elsom, L.F. ; Hunt, J.D. ; McKillop, A. Organomet. Chem.

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QUINOLINES SUBSTITUTED BY ALKENYL OR ALKYNYL CHAIN
2875
Rev. Sect. A 1972, 8, 135; d) with MnCl2 and Fe(acac) 3 : Cahiez, G. ;
Marquais, S. Tetrahedron Lett. 1996, 37, 1773-1776; e) with Fe(acac)3 :
Cahiez, G. ; Avedissian, H. Synthesis, 1998, 1199-1205; e) with
Co(acac)2 : Cahiez, G. ; Avedissian, H. Tetrahedron Lett. 1998, 39,
6159; and Defretin, J. ; Saez, J. ; Franck, X. ; Hocquemiller, R. ;
Figadere, B. Tetrahedron Lett. 1999, 40, 4041-4044.
9. Ramirez, F.; Desai, N.B.; McKelvie, N. J. Am. Chem. Soc. 1962, 84,
1745.
10. Fakhfakh, M.A.; Fournet, A.; Franck, X.; Hocquemiller, R.; Figadere,
B. Tetrahedron Lett. 2001, 42, 3847–3850.
11. Fakhfakh, M.A.; Franck, X.; Hocquemiller, R.; Figadere, B.
J. Organomet. Chem. 2001, 624, 131–135.
12. Urabe, H.; Sato, F. In Handbook of Grignard Reagents; Silverman,
G.S., Rakita, P.E., Eds.; Marcel Dekker Inc.: New York-Basel-Hong
Kong, 1996; p. 2159; Comins, D.L.; Herrick, J.J. Heterocycles 1987,
26, 2159.
13. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467–4470.
14. (a) Irving, H.; Pinnington, A.R. J. Chem. Soc. 1954, 3782–3785;
(b) Mekouar, K.; Mouscadet, J.-F.; Desmaele, D.; Subra, F.; Leh,
H.; Savoure, D.; Auclair, C.; d’Angelo, J. J. Med. Chem. 1998, 41,
2846–2857; (c) Walker, A.; Baldwin, W.E.; Thayer, H.I.; Corson, B.B.
J. Org. Chem. 1951, 16, 1805.
15. Purification of Common Laboratory Chemicals; Perrin, Amaredo and
Perrin, Pergamon: Oxford, U.K., 1966.
16. Hoye, T.R.; Hanson, P.R.; Vyvyan, J.R. J. Org. Chem. 1994, 59,
4096–4103.
Received in the UK August 6, 2001