Novel trichloroindolizine derivatives via intramolecular acylation of a bis(chloroacyl)bipyridine

Article abstract of DOI:10.1039/b202616n

3,3′-Bis(alkyloxycarbonyl)-2,2′-bipyridines are produced from the reaction of alcohols with 3,3′-bis(chlorocarbonyl)-2,2′-bipyridine which is generated from the corresponding dicarboxylic acid and thionyl chloride. When the dicarboxylic acid is reacted with a SOCl₂-Cl₂ mixture, significant amounts of trichloroindolizines are produced. This reaction is likely to take place via initial intramolecular N-chloroacylation of bipyridine 3.

Full text of DOI:10.1039/b202616n

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Novel trichloroindolizine derivatives via intramolecular acylation
of a bis(chloroacyl)bipyridine
Najat Sam,a Sghir Elkadiri,a Hubert Le Bozec,b Loic Toupet,c Maria Daoudi,d Najib Bitit,d
Taibi Ben Hadda*a and Pierre H. Dixneuf*b
1
a Laboratoire d’activation Moléculaire, Faculté des Sciences d’Oujda, Université Mohamed 1er,
60000 Oujda, Morocco. E-mail: benhadda@sciences.univ-oujda.ac.ma
b Institut de Chimie de Rennes, UMR 6509 CNRS-Université de Rennes 1,
Organométalliques et Catalyse: Chimie et Electrochimie Moléculaires, Campus de Beaulieu,
35042 Rennes Cedex, France. E-mail: dixneuf@univ-rennes1.fr
c UMR CNRS 6626, Groupe de la Matière condensée et Matériaux, Campus de Beaulieu,
35042 Rennes Cedex, France
d Faculté des Sciences Dhar El Mehraz, Département de Chimie, 30000 Fès, Morocco
Received (in Cambridge, UK) 14th March 2002, Accepted 23rd May 2002
First published as an Advance Article on the web 24th June 2002
3,3Ј-Bis(alkyloxycarbonyl)-2,2Ј-bipyridines are produced from the reaction of alcohols with 3,3Ј-bis(chlorocarbonyl)-
2,2Ј-bipyridine which is generated from the corresponding dicarboxylic acid and thionyl chloride. When the
dicarboxylic acid is reacted with a SOCl2–Cl2 mixture, significant amounts of trichloroindolizines are produced.
This reaction is likely to take place via initial intramolecular N-chloroacylation of bipyridine 3.
diesters 4 from the diacid precursors 2 and thionyl chloride in
Introduction
the presence of alcohols7,8 was considered. The 2,2Ј-bipyridine-
Polyfunctional indolizine derivatives have recently attracted
3,3Ј-dicarboxylic acid 2, prepared in 67% yield by oxidation of
interest due to their biological activity,1 especially in the field
1,10-phenanthroline
1 with aqueous alkaline potassium
of agrochemicals2 and as anticancer and antiviral agents.3
Functionalised indolizines are usually obtained via initial
alkylation of a pyridine nitrogen atom, for example by 1,3-
dipolar additions to pyridinium N-ylides,4 or via initial
addition of chloro carbenes.5 We report herein the formation of
new trichloroindolizine derivatives of type I which were also
formed during our attempts to produce 3,3Ј-diester-2,2Ј-
bipyridines from 2,2Ј-bipyridine-3,3Ј-dicarboxylic acids. These
additional products are a result of 3,3Ј-bis(chlorocarbonyl)-
2,2Ј-bipyridine reacting with the diacid and a mixture of
thionyl chloride and chlorine via acylation of one pyridine
nitrogen atom, and chlorination of the neighbouring double
bond. This new two step reaction offers potential access to
a variety of indolizines. The initial chloroacylation is in con-
trast to the usual intramolecular C-acylations for this class
of compound as illustrated by the C-acylation occurring
in the formation of 4,5-diazafluoren-9-one; a by-product in
the synthesis of the same 2,2Ј-bipyridine-3,3Ј-dicarboxylic
acid.6
permanganate,8 was first reacted with a large excess of old thio-
nyl chloride containing chlorine at reflux for 5 h in an attempt
to generate the diacyl dichloride derivative 3 (Scheme 1).
Excess thionyl chloride was eliminated under vacuum to
afford a yellow residue which was dissolved in toluene before
the addition of methanol. The mixture was refluxed for 3 h in
order to produce the diester 4a. Chromatography on silica
with petroleum ether–dichloromethane separated 5a (31%), 6a
(7%) and the diester 4a (52%) successively, as white solids
(Scheme 1). Analogously, the same intermediate, obtained from
2 and SOCl2 was reacted with ethanol which led to the form-
ation of 5b (13%), 6b (5%) and 4b (83%). When the same
reaction was performed after reflux in isobutanol, chrom-
atography also afforded 5c (16%), 6c (6%) and 4c (79%)
(Scheme 1). The structures of compounds 4–6 have been
established on the basis of elemental analysis, IR, NMR
spectroscopy and on an X-ray diffraction study of 5b. The IR
and NMR spectra of diesters 4 correspond to those of diacid
2 and of related diesters.8 The elemental analyses and mass
spectra of derivatives 5and 6 are consistent with a reaction
resulting from one acylation and the addition of three chlorine
1
atoms. The H NMR spectra of compounds 5 and 6 show a
typical array of signals for the consecutive protons of a disub-
stituted pyridine ring [H2 (d), H3 (dd), H4 (d); see Chart 1 for
NMR assignments]. The protons at higher field for 5a
show very small vicinal coupling constants, typical of axial–
equatorial or equatorial–equatorial positions,9 and thus indi-
cate a consecutive trans–trans configuration for the chlorine
atoms (Table 1). The spectra of derivatives 5b and 5c show
similar sets of signals to 5a. The spectrum of 6a also shows
similar signals to 5a but with significantly larger J values
(Table 1), thus consistent with axial–axial (3J = 9.8 Hz) and
axial–equatorial (3J = 3.1 Hz) couplings.9 The 2D {13C–1H
CORR} spectrum of 5b has enabled the correlation of each
Results and discussion
Synthesis
The diesters 4 are key starting molecules for the building of
3,3Ј-disubstituted-2,2Ј-bipyridine metal complexes.7 Modifi-
cation of the initial procedure in order to directly produce the
1688
J. Chem. Soc., Perkin Trans. 1, 2002, 1688–1692
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b202616n

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Table 1 Comparison of J values for derivatives 5a and 6a
δ H7 (ppm) [3J, 4J/Hz]
δ H8 (ppm) [3J/Hz]
δ H9 (ppm) [3J/Hz]
5a
6a
6.49 (dd) [1.33, 2.1]
6.47 (d) [3.0]
5.35 (t) [1.33]
4.52 (dd) [3.0, 9.8]
5.03 (dd) [1.33, 2.1]
5.26 (d) [9.8]
Scheme 1
Fig. 1 X-Ray crystal structure of 5b.
atom C(8) stays above the average plane ca. N(2)–C(7)/C(10)–
C(9). The carboxylate group is linked to carbon atom C(11).
Chart 1 Labelling used for NMR assignments.
Acylation–chlorination mechanism
proton to each carbon nucleus of molecule 5b. The structure of
5b was further confirmed by an X-ray diffraction study.
Formation of the trichlorinated indolizines may be rationalized
as shown in Scheme 2 by the initial formation of the expected
bis(acyl chloride) 3. A subsequent intramolecular acylation
of one pyridine nitrogen atom could give access to the cation
b which, after addition of ClϪ could afford the neutral inter-
mediates c and cЈ. The next step is expected to be a classical
chlorination of a double bond which preferentially gives the
trans intermediate d rather than the cis intermediate f. Trans
addition of ClϪ to the chloronium ion d would preferentially
produce the acyl chloride e, the precursor of 5 and not the
cis derivative g, the precursor of 6.
X-Ray diffraction study
The structure of derivative 5b was determined by an X-ray dif-
fraction study (Fig. 1, Tables 2 and 3). This confirms that one
pyridine ring remains unchanged while the other pyridine
nitrogen atom has been acylated. Moreover, it shows that the
ring containing the acylated nitrogen has been trichlorinated at
consecutive carbon atoms C(7), C(8) and C(9) in a relative
trans–trans configuration as shown in Scheme 1. The carbon
J. Chem. Soc., Perkin Trans. 1, 2002, 1688–1692
1689

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According to the proposed mechanism, the presence of Cl2
is needed to explain the unexpected formation of 5 and 6. This
was further confirmed by carrying out the following experi-
ments: the use of freshly distilled thionyl chloride in the
presence of ethanol gave the diester 4b in 87% yield with only
traces of compounds 5b (5%) and 6b (2%), whereas upon
bubbling Cl2 gas into the precedent mixture considerably
increased yields of 5b (45%) and 6b (12%) were observed at the
expense of 4b (39%).
Table 2 Crystallographic data for 5b
Formula
C14H11N2O3Cl3
361.61
Monoclinic
P21/a
MW/g molϪ1
Crystal system
Space group
Conclusion
a/Å
b/Å
c/Å
α/Њ
13.536(2)
7.787(1)
14.769(2)
90
The above results show, due to the unexpected presence
of chlorine in thionyl chloride, a novel transformation of
3,3Ј-diacid-2,2Ј-bipyridine into new, highly chlorinated indol-
izines. The mechanism suggests an initial intramolecular
chloroacylation of the diacyl dichloride affording the inter-
mediates b and c, with chlorination of c.These key, two step
reactions, offer potential for the design of novel indolizines.
β/Њ
97.62(1)
90
1543.0(5)
4
6.067
1.557
γ/Њ
Volume/Å3
Z
µ/cmϪ1
ρcalc/g cmϪ3
Crystal size/mm
T /K
2θmax/Њ
0.35 × 0.25 × 0.20
294
54
Experimental
The 3,3Ј-bis(hydroxycarbonyl)-2,2Ј-bipyridine 2 used in this
work was prepared from 1,10-phenanthroline 1 by a procedure
described previously.8 1H and 13C NMR spectra were recorded
on a Bruker WP-80 operating at 200.131 MHz, an AC 250 at
250.14 MHz or an AM 300 at 300.134 MHz. Mass spectra
(electrospray) were recorded on a Platform II Micro Mass
Reflections measured
Reflections observed (I > σ(I ))
R
3942
2347
0.057
0.1699
1.094
Rw
Sw
Max residual (e ÅϪ3
)
0.37
Table 3 Selected bond distances and bond angles for 5b
Bond lengths/Å
Bond angles/Њ
C1–C7
N1–C1
C1–C5
C5–C6
O1–C6
N2–C6
N2–C7
N2–C8
1.480(5)
1.325(4)
1.387(5)
1.471(5)
1.211(4)
1.392(5)
1.406(4)
1.418(5)
Cl1–C8
C8–C9
1.810(4)
1.515(5)
1.785(4)
1.533(5)
1.811(4)
1.494(5)
1.489(5)
1.325(5)
C6–N2–C8
124.5(3)
110.7(3)
110.2(3)
107.0(3)
107.5(3)
111.3(3)
110.0(3)
116.4(3)
121.0(3)
Cl1–C8–N2
Cl1–C8–C9
Cl2–C9–C8
Cl2–C9–C10
Cl3–C10–C9
Cl3–C10–C11
C10–C11–C12
C7–C11–C10
Cl2–C9
C9–C10
Cl3–C10
C10–C11
C11–C12
C12–O3
Scheme 2
1690
J. Chem. Soc., Perkin Trans. 1, 2002, 1688–1692

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spectrometer, and FTIR spectra were measured on a Nicolet
205 spectrometer.
as described in the general procedure. Three compounds were
obtained; 5b (398 mg, 45%), 6b (106 mg, 12%) and 4b (314 mg,
39 %).
Crystallography
Compound 4a. Mp = 135–136 ЊC; anal. calc. (found) for
C14H12N2O4: C, 61.76 (61.13); H, 4.42 (4.45); N, 10.29 (9.82);
m/z 273.0 (Mϩ ϩ H, C14H13N2O4 requires 273.09); IR (KBr)
ν/cmϪ1 1720 (C᎐O, s), 1582 (C᎐C, m), 1440 (C᎐N, m), 1307,
Crystal data and refinement details for derivative 5b are
presented in Table 1. All measurements were made on an
automatic diffractometer CAD4 NONIUS with graphite
monochromatized Mo-Kα radiation.10 The data collection
(2θmax = 54Њ, scan ω/2θ = 1, tmax = 60 s, range hkl: h 0.17, k 0.9,
l Ϫ18.18) gives 3749 unique reflections from which 1614 with
I > 3.0 σ(I ) were considered reliable. After Lorentz and polar-
ization corrections,11 the structure was solved with SIR-9712
which reveals the non-hydrogen atoms. After anisotropic
refinement, all the hydrogen atoms were found with a Fourier
difference. The whole structure was refined with SHELXL 9713
by the full-matrix least-square techniques with the resulting
R = 0.052, Rw = 0.047 and Sw = 1.24 (residual ∆ρ = 0.32 e AϪ3).
Atomic scattering factors were obtained from International
Tables14 and ORTEP views realized with PLATON 98.15
CCDC reference number 181455. See http://www.rsc.org/
suppdata/p1/b2/b202616n/ for crystallographic files in .cif or
other electronic format.
᎐
᎐
᎐
1
1299 (C–O, m); H NMR (250.14 MHz, CDCl3) δ (ppm) 8.74
(dd, 2 H, H6,H6Ј, 3JH6–H5 = 4.83 Hz, 4JH6–H4 = 1.62 Hz), 8.37 (dd,
2 H, H4,H4Ј, 3JH4–H5 = 7.94 Hz, 4JH4–H6 = 1.62 Hz), 7.44 (dd, 2 H,
3
3
H5,H5Ј, JH5–H4 = 7.94 Hz, JH5–H6 = 4.83 Hz), 3.66 (s, 6 H, 2
CH3).
Compound 5a. Mp = 121–122 ЊC; anal. calc. (found) for
C13H9N2O3Cl3: C, 44.94 (44.98); H, 2.59 (2.63); N, 8.06 (7.99);
m/z 347.0 (Mϩ ϩ H, C13H10N2O3Cl3 requires 346.98); IR (KBr)
ν/cmϪ1 1744 (C᎐O, s), 1717 (C᎐O, s), 1601, 1581 (C᎐C, w), 1434
᎐
᎐
᎐
(C᎐N, m), 1297 (C–O, w); 1H NMR (250.14 MHz; CDCl3)
᎐
3
4
δ (ppm) 8.9 (dd, 1H, H2, JH2–H3 = 4.9 Hz, JH2–H4 = 1.6
3
4
Hz), 8.2 (dd, 1 H, H4, JH4–H3 = 7.8 Hz, JH4–H2 = 1.6 Hz),
7.53 (dd, 1 H, H3, 3JH3–H4 = 7.8 Hz, 3JH3–H2 = 4.9 Hz), 6.49 (dd,
3
4
1 H, H7, JH7–H8 = 1.33 Hz, JH7–H9 = 2.1 Hz), 5.35 (t, 1 H, H8,
3JH8–H7 = 1.33 Hz, 3JH8–H9 = 1.33 Hz), 5.03 (dd, 1 H, H9, 3JH9–H8
1.33 Hz, 4JH7–H9 = 2.1 Hz), 4.0 (s, 3 H, CH3).
=
Compound 6a. m/z 347.0 (Mϩ ϩ H, C13H10N2O3Cl3 requires
346.98); 1H NMR (200.13 MHz; CDCl3) δ (ppm) 8.86 (dd, 1 H,
H2, 3JH2–H3 = 4.9 Hz, 4JH2–H4 = 1.6 Hz), 8.14 (dd, 1 H, H4, 3JH4–H3
= 7.8 Hz, 4JH4–H2 = 1.6 Hz), 7.48 (dd, 1 H, H3, 3JH3–H4 = 7.8 Hz,
Synthesis of 3,3Ј-bis(alkoxycarbonyl)-2,2Ј-bipyridine (4) and
alkyl 7,8,9-trichloro-5-oxo-5,7,8,9-tetrahydropyrido[2,3-a]-
indolizine-10-carboxylates (5 and 6)
3
General procedure. To 10 mL of thionyl chloride, was added
600 mg (2.5 mmol) of 3,3Ј-bis(hydroxycarbonyl)-2,2Ј-bipyridine
2 and the mixture was refluxed for 5 h. The excess SOCl2 was
removed under vacuum to leave a yellow residue. Toluene
(20 mL) and then alcohol (ROH, 1 mL) were added and the
solution was heated at reflux for 3 h. Chloroform (40 mL) was
added and the organic phase was washed with a cooled solution
of sodium hydrogencarbonate (2.5%), and dried on sodium
sulfate. The crude product was chromatographed on a silica
column (l = 30 cm, id = 3 cm) and three white solids
were successively obtained: a mixture of petroleum ether–
dichloromethane (10 : 90) eluted 5 first and then, in a ratio of
5 : 95, 6 was recovered. The diester 4 was extracted by elution
with ether–acetone (40 : 60).
1. With ROH = methanol: 5a (310 mg, 31%), 6a (70 mg, 7%)
and 4a (450 mg, 52%) were obtained.
2. With ROH = ethanol: 5b (115 mg, 13%), 6b (46 mg, 5%)
and 4b (668 mg, 80%) were obtained.
3. With ROH = isobutanol: 5c (155 mg, 16%), 6c (58 mg, 6%)
and 4c (769 mg, 78%) were obtained.
3JH3–H2 = 4.9 Hz), 6.47 (d, 1 H, H7, JH7–H8 = 3 Hz), 5.26 (d,
1 H, H9, 3JH9–H8 = 9.8 Hz), 4.52 (dd, 1 H, H8, 3JH8–H7 = 3.05 Hz,
3JH8–H9 = 9.75 Hz), 3.96 (s, 3 H, CH3).
Compound 4b. Mp = 89–90 ЊC; anal. calc. (found) for
C16H16N2O4: C, 64.01 (63.56.); H, 5.33 (5.62); N, 9.33 (9.13);
m/z 301.10 (Mϩ ϩ H, C16H17N2O4 requires 301.12); IR (KBr)
ν/cmϪ1 1724 (C᎐O, s), 1578, 1565 (C᎐C, w), 1423 (C᎐N, m),
᎐
᎐
᎐
1
1277 (C–O, w); H NMR (250.14 MHz; CDCl3) δ (ppm) 8.74
(dd, 2 H, H6,H6Ј, 3JH6–H5 = 4.80 Hz, 4JH6–H4 = 1.56 Hz), 8.36 (dd,
2 H, H4,H4Ј, 3JH4–H5 = 7.93 Hz, 4JH4–H6 = 1.56 Hz), 7.42 (dd, 2 H,
H5,H5Ј, JH5–H4 = 7.93 Hz, JH5–H6 = 4.80 Hz), 4.08 (q, 4 H,
2 CH2, JCH2–CH3 = 7.15 Hz), 1.02 (t, 6 H, 2 CH3, JCH3–CH2
3
3
3
3
=
7.15 Hz).
Compound 5b. Mp = 102–103 ЊC; anal. calc. (found) for
C14H11N2O3Cl3: C, 46.97 (47.44); H, 3.05 (3.33); N, 7.74 (7.35);
m/z 360.9 (Mϩ ϩ H, C14H12NO3Cl3 requires 360.99); IR (KBr)
ν/cmϪ1 1750 (C᎐O, s), 1716 (C᎐O, s), 1609, 1580 (C᎐C, w), 1457
᎐
᎐
᎐
(C᎐N, m); 1H NMR (300.13 MHz; CDCl ) δ (ppm) 8.90 (dd, 1
᎐
3
3
4
H, H2, JH2–H3 = 4.8 Hz, JH2–H4 = 1.6 Hz), 8.21 (dd, 1 H, H4,
3JH4–H3 = 7.8 Hz, 4JH4–H2 = 1.6 Hz), 7.53 (dd, 1 H, H3, 3JH3–H4
=
3
3
7.8 Hz, JH3–H2 = 4.8 Hz), 6.49 (dd, 1 H, H7, JH7–H8 = 1.45 Hz,
Acylation–chlorination mechanism. 1. Use of pure SOCl2.
The preparation of a mixture of 4b, 5b and 6b is described
in the general procedure: 10 mL of pure SOCl2, 600 mg
(2.5 mmol) of 3,3Ј-bis(hydroxycarbonyl)-2,2Ј-bipyridine 2 and
1 mL of EtOH afforded a mixture of 5b (46 mg, 5%), 6b (18 mg,
2%) and the diester 4b (702 mg, 87%).
4JH7–H9 = 2.04 Hz), 5.35 (t, 1 H, H8, 3JH8–H7 = 1.42 Hz, 3JH8–H9
=
3
4
1.45 Hz), 5.00 (dd, 1 H, H9, JH9–H8 = 1.45 Hz, JH9–H7 = 2.04
3
3
Hz), 4.48 (m, 2 H, CH2, J = 7.12 Hz), 1.39 (t, 3 H, CH3, J =
7.12 Hz).
Compound 6b. m/z 360.9 (Mϩ ϩ H, C14H12NO3Cl3 requires
360.99); 1H NMR (200.13 MHz; CDCl3) δ (ppm) 8.85 (dd, 1 H,
H2, 3JH2–H3 = 4.8 Hz, 4JH2–H4 = 1.6 Hz), 8.14 (dd, 1 H, H4, 3JH4–H3
= 7.8 Hz, 4JH4–H2 = 1.6 Hz), 7.48 (dd, 1 H, H3, 3JH3–H4 = 7.8 Hz,
2. Use of SOCl2–Cl2 mixture. The synthetic method used to
produce Cl2 has been adapted from the procedure described in
the literature.16 Commercial HCl was added (15 mL; d = 1.7)
dropwise to crystalline powder of KMnO4 (10 g, 63 mmol)
and the temperature of the reaction mixture was increased to
35–45 ЊC. The mixture was then magnetically stirred for 5 h.
The mixture of gases produced (Cl2–H2O–HCl–ClO2) was dried
by bubbling the mixture through a saturated aqueous solution
of NaCl. HCl gas was then eliminated by bubbling the remain-
ing gas mixture (Cl2–HCl–ClO2) through a second tube
containing CuSO4 powder. Pure Cl2 was finally obtained by
bubbling the (Cl2–ClO2) gas mixture into a third tube contain-
ing H2SO4. The freshly prepared Cl2 was then progressively
bubbled into a mixture containing 6 mL of thionyl chloride
and 600 mg (2.5 mmol) of 3,3Ј-bis(hydroxycarbonyl)-2,2Ј-
bipyridine 2. The mixture was refluxed for 5 h and then treated
3JH3–H2 = 4.8 Hz), 6.46 (d, 1 H, H7, JH7–H8 = 3.2 Hz), 5.30 (d,
3
3
3
1 H, H9, JH9–H8 = 9.8 Hz), 4.53 (dd, 1 H, H8, JH8–H7 = 3.2 Hz,
3JH8–H9 = 9.8 Hz), 4.46 (m, 2 H, CH2, 3J = 7.12 Hz), 1.37 (t, 3 H,
CH3, 3J = 7.12 Hz).
Compound 4c. Mp = 88–89 ЊC; anal. calc. (found) for
C20H24N2O4: C, 67.42 (67.55); H, 6.74 (6.82); N, 7.86 (7.87); m/z
357.10 (Mϩ ϩ H, C20H25N2O4 requires 357.18); IR (KBr)
ν/cmϪ1 1713 (C᎐O, s), 1589, 1561 (C᎐C, w), 1470 (C᎐N, m),
᎐
᎐
᎐
1
1289 (C–O, w); H NMR (250.14 MHz; CDCl3) δ (ppm) 8.74
(dd, 2 H, H6,H6Ј, 3JH6–H5 = 4.83 Hz, 4JH6–H4 = 1.66 Hz), 8.37 (dd,
2 H, H4,H4Ј, 3JH4–H5 = 7.93 Hz, 4JH4–H6 = 1.66 Hz), 7.44 (dd, 2 H,
H5,H5Ј, 3JH5–H4 = 7.93 Hz, 3JH5–H6 = 4.83 Hz), 3.84 (d, 2 H, CH2,
3JCH–CH2 = 6.6 Hz), 1.68 (m, 2 H, 2 CH), 0.76 (d, 12 H, 4 CH3,
3JCH3–CH = 6.6 Hz).
J. Chem. Soc., Perkin Trans. 1, 2002, 1688–1692
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1992, pp. 52–53.
Compound 5c. Mp = 96–97 ЊC; anal. calc. (found) for
C16H15N2O3Cl: C, 49.32 (49.23); H, 3.85(3.89); N, 7.19 (6.99);
m/z 388.90 (Mϩ ϩ H, C16H16N2O3Cl3 requires 389.02); IR
(KBr) ν/cmϪ1 1750 (C᎐O, s), 1715 (C᎐O, s), 1582 (C᎐C, w), 1473
᎐
᎐
᎐
1
(C᎐N, m); H NMR (200.131 MHz; CDCl ) δ (ppm) 8.88 (dd,
᎐
3
1 H, H2, 3JH2–H3 = 4.86 Hz, 4JH2–H4 = 1.6 Hz), 8.21 (dd, 1 H, H4,
3JH4–H3 = 7.8 Hz, 4JH4–H2 = 1.6 Hz), 7.52 (dd, 1 H, H3, 3JH3–H4
=
7.8 Hz, 3JH3–H2 = 4.86 Hz), 6.50 (dd, 1 H, H7, 3JH7–H8 = 1.39 Hz,
4JH7–H9 = 2.04 Hz), 5.36 (t, 1 H, H8, 3JH8–H7 = 1.39 Hz, 3JH8–H9
=
3
4
1.39 Hz), 5.03 (dd, 1 H, H9, JH9–H8 = 1.39 Hz, JH9–H7 = 2.04
Hz), 4.22 (m, 2 H, CH2, 3J = 6.7 Hz), 2.09 (m, 1 H, H13, 3J = 6.7
Hz), 1.0 (d, 6 H, 2 CH3, 3J = 6.7 Hz).
Compound 6c. m/z 388.90 (Mϩ ϩ H, C16H16N2O3Cl3 requires
389.02); IR (KBr) ν/cmϪ1 1750 (C᎐O, s), 1715 (C᎐O, s), 1582
᎐
᎐
1
(C᎐C, w), 1473 (C᎐N, m); H NMR (200.131 MHz; CDCl )
᎐
᎐
3
δ (ppm) 8.90 (dd, 1 H, H2, 3JH2–H3 = 4.86 Hz, 4JH2–H4 = 1.6 Hz),
8.18 (dd, 1 H, H4, 3JH4–H3 = 7.8 Hz, 4JH4–H2 = 1.6 Hz), 7.52 (dd, 1
3
3
H, H3, JH3–H4 = 7.8 Hz, JH3–H2 = 4.86 Hz), 6.52 (d, 1 H, H7,
3JH7–H8 = 3.07 Hz), 5.26 (d, 1 H, H9, 3JH9–H8 = 9.75 Hz), 4.56 (dd,
3
3
1 H, H8, JH8–H7 = 3.08 Hz, JH8–H9 = 9.75 Hz), 4.21 (m, 2 H,
CH2, 3J = 6.67 Hz), 2.09 (m, 1 H, CH, 3J = 6.7 Hz), 1.04 (d, 6 H,
2 CH3, 3J = 6.7 Hz).
10 MOLEN, An Interactive Intelligent System for Crystal Structure
Analysis, User Manual, C. K. Fair, Enraf–Nonius, Delft, The
Netherlands, 1990.
11 HELENA, Program for the handling of CAD4-Diffractometer
output SHELX(S/L), A. L. Spek, University of Utrecht, The
Netherlands, 1997.
12 A. Altomare, M. C. Burla, M. Camalli, G. Cascarano,
C. Giacovazzo, A. Guagliardi, A. G. G. Molitemi, G. Polidori and
R. Spagna, Sir 97: a new tool for crystal structure determination and
refinement,J. Appl. Crystallogr., 1998, 31, 74.
13 SHELX93-Program for the Refinement of Crystal Structures,
G. M. Sheldrick, University of Gottingen, Germany, 1993.
14 International Tables for X-ray Crystallography, Kynoch Press,
Birmingham, Vol. IV, 1974.
15 PLATON, A multipurpose crystallographic tool, A. L. Spek,
Utrecht University, Utrecht, The Netherlands, 1998.
16 P. Pascal, Nouveau Traité de Chimie Minérale, Tome XVI, Edit
Masson, 1960, 153.
Acknowledgements
We thank the “Programme Thématique d’Appui à la Recherche
Scientifique PROTARS NЊ P1T2/27”, the “Programme
Régional de Recherche et de dévelopement de la Willaya
d’Oujda” and the France–Morocco cooperation program
“Action Intégrée 98/160/SM” for financial support.
References
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