Formation of novel 1,2,3,4-tetrasubstituted 3-pyrrolines via cyclisation of γ-halo-β-ketoesters with aromatic amines and aldehydes

Article abstract of DOI:10.1016/j.tetlet.2011.09.072

Cyclisation of γ-halo-β-ketoesters with aromatic amines and aldehydes in methanol gave novel polysubstituted 3-pyrroline derivatives. A plausible mechanism for the reaction has been proposed. The structures of 1,2,3,4-tetrasubstituted 3-pyrrolines were co

Full text of DOI:10.1016/j.tetlet.2011.09.072

Tetrahedron Letters 52 (2011) 6246–6249
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Formation of novel 1,2,3,4-tetrasubstituted 3-pyrrolines via cyclisation
of c-halo-b-ketoesters with aromatic amines and aldehydes
Brigita Cekavicus, Kintija Kore, Liva Jakovele, Aiva Plotniece, Karlis Pajuste, Marina Petrova,
⇑
Sergey Belyakov, Arkadij Sobolev
Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclisation of c-halo-b-ketoesters with aromatic amines and aldehydes in methanol gave novel polysub-
Received 25 March 2011
Revised 2 September 2011
Accepted 16 September 2011
Available online 21 September 2011
stituted 3-pyrroline derivatives. A plausible mechanism for the reaction has been proposed. The struc-
tures of 1,2,3,4-tetrasubstituted 3-pyrrolines were confirmed by NMR spectroscopy and X-ray
crystallography.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Nitrogen heterocycles
3-Pyrrolines
Cyclisation
c
-Halo-b-ketoesters
Nitrogen containing, highly-substituted, five-membered het-
but-2-ynedioate, cyclohexylamine, formaldehyde and aniline
which leads to tetrasubstituted 3-pyrroline derivatives. Various
reaction conditions were studied with the best result being
obtained using ethanol with AcOH as an additive at room temper-
ature for 30 min. A four-component synthesis of pentasubstituted
3-pyrrolines was also performed, using aliphatic or aromatic
aldehydes instead of formaldehyde. This multicomponent reaction
proceeds via a hydroamination, amidation, intramolecular cyclisa-
tion and an imine–enamine tautomerism sequence.14
The copper-catalysed three-component reaction of sulfonyl
azides, methylphenylacetylene and aziridine derivatives is another
approach for the construction of 2-imino-5-arylidene-pyrrolines.15
A convenient method for the synthesis of a range of 3-pyrro-
lines has been recently achieved from primary amines via alkyl-
ation giving alkylidene carbene derivatives, followed by 1,5-CH
insertion to form the desired compounds.16
The classical Hantzsch synthesis and its variations remain the
most common methods for the synthesis of a wide variety of
1,4-dihydropyridines (1,4-DHPs).17–19 The formation of by-products
under Hantzsch conditions is a rare occurrence.20 Besides 1,4-DHPs
Hantzsch synthesis and its modifications can lead to cyclohexenes,
pyridines, 1,2-dihydropyridines and 1,2,3,4-tetrahydropyri-
dines.21–23
There are several methods for the synthesis of 2-bromomethyl-
and 2,6-bis(bromomethyl)-substituted 1,4-DHP derivatives. The
synthesis of unsymmetrical 2-halomethyl-substituted 1,4-DHPs
was performed via condensation of 3-aminobut-2-enoic acid ester
erocyclic derivatives, such as pyrrole, pyrroline and pyrrolidine in-
clude several classes of natural and synthetic compounds that
exhibit a wide spectrum of biological activity.1
Synthetic approaches to these five-membered heterocycles are
mainly based on cyclocondensations. The Hantzsch pyrrole synthe-
sis involves cyclocondensation of b-ketoesters with ammonia (or
primary amines) and
curs via condensation of
pound containing active
a
-haloketones.2–4 Knorr pyrrole synthesis oc-
a
-aminoketones with a carbonyl com-
a
-methylene groups.5
Dieckmann-type annulation is the most common method for
the synthesis of pyrrolidinones6,7 which can be easily further con-
verted into 3-pyrrolines.6,8 Three-component cyclisations of
sodium alkyl oxaloacetate with a variety of arylaldehydes and
primary amines under various reaction conditions leading to
2,3-dioxopyrrolidines have been described in the literature.9,10
There are several examples of efficient, stereoselective gold
chloride11 and silver nitrate12 catalysed cycloisomerisations of
a
-aminoallenes to 3-pyrrolines. It has also been reported that the
formation of 3-pyrrolines from simple unactivated allenes bearing
a protected amino group was performed in the absence of transi-
tion metals, albeit promoted by potassium carbonate.13
Concise and versatile multicomponent syntheses of multi-
substituted polyfunctional 3-pyrrolines have been reported. The
approach involves a four-component hydroamination, nucleophilic
addition and amidation–cyclisation domino reactions of diethyl
(b-aminocrotonate), m-nitrobenzaldehyde and ethyl
c-haloacetoac-
⇑
Corresponding author. Tel.: +371 67014928; fax: +371 67550338.
E-mail address: arkady@osi.lv (A. Sobolev).
etate.24 Methyl 4-chloroacetoacetate readily forms a Knoevenagel
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.072

B. Cekavicus et al. / Tetrahedron Letters 52 (2011) 6246–6249
6247
yield (Table 1, entry 2). Changing o-phenetidine (3a) to aniline
(3b) led to the formation of 3-pyrroline 4b in 18% yield (Table 1,
entry 3). Almost no 3-pyrroline product was found when this cyc-
NH2
R1
O
H
R
lisation was performed with c-chloro-b-ketoester 1b, aniline (3b)
2a (R1=NO2-m)
and aldehyde 2a (Table 1, entry 4). No other cyclisation products
were isolated from this reaction. LC–MS of the reaction mixtures
(Table 1, entries 1–4) showed the presence of molecular ion peaks
matching the corresponding 1,4-dihydropyridine structures in
amounts not higher than 2–4%. The low yield of this cyclisation
can be explained by the fact that o-phenetidine (3a) as HCl or
HBr salts (Table 1, entries 1 and 2) was isolated as by-products.
Crystallisation of the reaction mixtures from acetone or ethyl
acetate instead of methanol afforded reaction products, together
with HCl or HBr salts of o-phenetidine.
Performing this reaction in methanol was crucial as no cyclisa-
tion occurred when chloroform or acetic acid was used.
Having established the structure of the reaction product, this
reaction was next performed with 1 equiv of b-ketoester 1a,b, 1
equiv of aldehyde 2a and 2 equiv of amine 3a,b (Table 1, entries
5–8). The highest yield of 3-pyrroline 4a was obtained when the
R
H
N
O
2b (R1=H)
O
+
NH2
N
R1
R
R
O
O
O
3a (R=OCH2CH3-o)
3b (R=H)
3c (R=Cl-p)
3d (R=NO2-m)
3e (R=CH3-p)
X
4a-g
1a (X=Br)
1b (X=Cl)
Scheme 1. Synthesis of 1,2,3,4-tetrasubstituted 3-pyrrolines 4a–g.
reaction of c-bromo derivative 1a, aldehyde 2a and o-phenetidine
condensation product with various aromatic aldehydes, which on
reaction with enamines form 2-chloromethyl-2-hydroxy-1,2,3,
4-tetrahydropyridine derivatives or 2-chloromethylene-1,2,3,4-
tetrahydropyridine derivatives as successive intermediates of 2-
chloromethyl-1,4-dihydropyridines depending on the reaction
conditions (solvent and/or temperature).25
Bromination of 4-aryl-3,5-dialkoxycarbonyl-2,6-dimethyl-1,4-
dihydropyridines with NBS can lead to both 2-mono and 2,6-
bis(bromomethyl)-substituted 1,4-DHP derivatives depending on
the amount of brominating agent used.26–28
(3a) was carried out in methanol at room temperature for one day
(Table 1, entry 5).30
When this reaction was performed at reflux temperature
(Table 1, entry 6), the 3-pyrroline was isolated from a deeply-
coloured mixture in 21% yield only. Reaction of
ter 1b with o-phenetidine (3a) and m-nitrobenzaldehyde (2a),
compared to the -bromo derivative 1a, was slower and gave a
c-chloro-b-ketoes-
c
lower yield (Table 1, entry 7). When this cyclisation was performed
with aniline (3b), 3-pyrroline 4b was obtained in 30% yield (Table 1,
entry 8).31
In this Letter, we report an unexpected cyclisation of
c-bromo-
Analysis of the above results (Table 1, entries 1–8) shows that
or
c-chloro-b-ketoesters, aromatic aldehydes and aromatic amines
the best result was observed when
c-bromo-b-ketoester 1a, m-
to give 3-pyrroline derivatives instead of the expected 2,6-bis(bro-
momethyl)-substituted 1,4-DHPs.
nitrobenzaldehyde (2a) and o-phenetidine (3a) (1:1:2) were re-
acted in methanol at room temperature (Table 1, entry 5). These
reaction conditions were applied to the synthesis of derivatives
The starting ethyl
bromination of ethyl acetoacetate according to a reported meth-
od.29 As mentioned above,24
-bromo- or -chloro-b-ketoesters
c-bromoacetoacetate (1a) was prepared by
4c–g using
c-bromo-b-ketoester 1a and a range of aromatic
c
c
amines and benzaldehyde (2b). The reactions proceeded in a sim-
ilar fashion in yields of 19–71%. Thus, the condensation of 1a, 3a
and benzaldehyde (2b) led to the formation of 3-pyrroline 4c in
58% yield (Table 1, entry 9). 3-Pyrroline 4d was obtained in 37%
yield using 1a, 3b and 2b as substrates (Table 1, entry 10). Reaction
of 1a, 2b and p-chloroaniline (3c) gave 3-pyrroline 4e in 19% yield
(Table 1, entry 11). 3-Pyrroline 4f was obtained by reaction of 1a,
2b and m-nitroaniline (3d) in 63% yield (Table 1, entry 12). The cor-
responding reaction with p-toluidine (3e) proceeded to afford 4g in
71% yield (Table 1, entry 13).
1a,b can be used for the synthesis of 2-halomethyl-substituted
1,4-dihydropyridines. From a synthetic point of view, 2,6-bis(bro-
momethyl)-substituted 1,4-DHP derivatives can be synthesised
from 2 equiv of a
c-halo-b-ketoester, an aromatic amine and an
aldehyde under Hantzsch dihydropyridine synthesis conditions.
Thus, we initially attempted the reaction of two equivalents of
c-bromo-b-ketoester 1a with 1 equiv each of m-nitrobenzaldehyde
(2a) and o-phenetidine (3a) in methanol at room temperature for
one day (Scheme 1), resulting in formation of 1,2,3,4-tetrasubsti-
tuted 3-pyrroline 4a in 23% yield (Table 1, entry 1), which pro-
duced an orange precipitate during the reaction. This product
A plausible mechanism for the formation of 1,2,3,4-tetrasubsti-
tuted 3-pyrrolines is proposed in Scheme 2. Instead of proceeding
was also obtained using
c-chloro-b-ketoester 1b, but in a lower
Table 1
Synthesis of 1,2,3,4-tetrasubstituted 3-pyrrolines 4a–g
Entry
X=
R=
R1=
Conditions
Ratio (1:2:3)
Product
Yield (%)
1
2
3
4
5
6
7
8
Br
Cl
Br
Cl
Br
Br
Cl
Cl
Br
Br
Br
Br
Br
o-CH3CH2O
o-CH3CH2O
H
m-NO2
m-NO2
m-NO2
m-NO2
m-NO2
m-NO2
m-NO2
m-NO2
H
H
H
H
H
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, reflux, 6 h
MeOH, rt, 72 h
MeOH, rt, 48 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
MeOH, rt, 24 h
2:1:1
2:1:1
2:1:1
2:1:1
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
4a
4a
4b
4b
4a
4a
4a
4b
4c
4d
4e
4f
23
12
18
2
67
21
42
30
58
37
19
63
71
H
o-CH3CH2O
o-CH3CH2O
o-CH3CH2O
H
o-CH3CH2O
H
p-Cl
m-NO2
p-CH3
9
10
11
12
13
4g

6248
B. Cekavicus et al. / Tetrahedron Letters 52 (2011) 6246–6249
O
O
NH2
X
X
O
O
R1
O
H
1a,b
R
2a,b
3a-e
OH
O
O
O
O
X
..
R1
H
N
N
R1
R
R
5
6
- HX
O
R
NH2
H
N
O
O
O
O
R
R1
R1
N
N
- H2O
R
R
4a-g
7
Figure 1. ORTEP representation of the structure of 4a.
Scheme 2. A plausible mechanism for the formation of 1,2,3,4-tetrasubstituted 3-
pyrrolines 4a–g.
In summary, we have developed a new and convenient four-
component synthesis of highly-substituted 3-pyrrolines. The
methodology might be practical for the synthesis of novel hetero-
cycles with useful pharmacological properties. The synthesised
compounds and their derivatives will be subjected to pharmaco-
logical screening. The synthesis of other 3-pyrroline derivatives
using this approach is currently underway at our laboratory.
via the formation of a Knoevenagel condensation product from the
c-halo-b-ketoester and aldehyde, and formation of an enamine
from the second molecule of -halo-b-ketoester and aromatic
c
amine, followed by Michael addition and intramolecular condensa-
tion to afford the 1,4-dihydropyridine derivative, the reaction pro-
ceeds via a different pathway.
Mechanistically, the condensation seems to proceed via initial
formation of the Schiff base 5 from aromatic amine 3a–e and alde-
hyde 2a,b, after which intermediate 5 reacts with an enolised form
Acknowledgment
This research work was supported by the European Social Foun-
dation (ESF), Project No. 2009/0197/1DP/1.1.1.2.0/09/APIA/VIAA/
014.
of c-halo-b-ketoester 1a or 1b forming intermediate 6. Intramolec-
ular condensation of 6 affords 4-oxopyrrolidine 7 (Scheme 2). The
final step involves the reaction with a second molecule of the aro-
matic amine 3a-e, affording 1,2,3,4-substituted 3-pyrrolines 4a–g.
Supplementary data
It is known from the literature that
der basic conditions cyclises to five-membered cycle—tetronic
acid.29 Also in our case halogen atom of
-halo-b-ketoester 1a,b
c-bromo-b-ketoester 1a un-
Supplementary data associated with this Letter can be found, in
the online version, at doi:10.1016/j.tetlet.2011.09.072.
c
under Hantzsch reaction conditions is involved in cyclisation
changing the course of the reaction.
References and notes
The structure of 1,2,3,4-tetrasubstituted 3-pyrroline 4a was
proved by 1D (1H, 13C) and NMR 2D NMR (1H–1H COSY, 1H–1H
NOESY, 1H–13C HMBC, 1H–13C HSQC) spectroscopy, MS and X-ray
diffraction analysis.32
1. Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213–7256.
2. Hantzsch, A. Ber. 1890, 23, 1474–1483.
3. Trautwein, A. W.; Süßmuth, R. D.; Jung, G. Bioorg. Med. Chem. Lett. 1998, 8,
2381–2384.
Suitable crystals of 4a were obtained by slow crystallisation from
methanol–chloroform. The structure with atomic numbering is
shown in Figure 1 and is characterised by a bifurcated intramolecu-
lar hydrogen bond of NHꢀ ꢀ ꢀO type (seeFig. 1). The parameters of this
bond are: N29ꢀ ꢀ ꢀO25 = 2.740(2) Å (Hꢀ ꢀ ꢀO = 1.97 Å, N–Hꢀ ꢀ ꢀO = 132°),
N29ꢀ ꢀ ꢀO36 = 2.546(2) Å (Hꢀ ꢀ ꢀO = 2.07 Å, N–Hꢀ ꢀ ꢀO = 107°). All frag-
ments of the molecule, except the m-nitrophenyl substituent, lie
approximately in a plane. The m-nitrophenyl group is almost
perpendicular to the molecular plane: the dihedral angle between
these planes is 84.1(5)°. Spectroscopic data of 3-pyrroline deriva-
tives 4b–g (IR, 1H NMR, 13C NMR, MS) were in agreement with the
structures.
4. Demir, A. S.; Akhmedov, I. M.; Sesenoglu, O. Tetrahedron 2002, 58, 9793–9799.
5. Knorr, L. Ber. 1884, 17, 1635–1642.
6. Southwick, P. L.; Seivard, L. L. J. Am. Chem. Soc. 1949, 71, 2532–2538.
7. Hargrave, J. D.; Allen, J. C.; Kociok-Köhn, G.; Bish, G.; Frost, C. G. Angew. Chem.,
Int. Ed. 2010, 49, 1825–1829.
8. Southwick, P. L.; Madhav, R.; Fitzgerald, J. A. J. Heterocycl. Chem. 1969, 6, 507–
516.
9. Merchant, J. R.; Srinivasan, V. Recl. Trav. Chim. Pays-Bas 1962, 81, 144–155.
10. Metten, B.; Kostermans, M.; Van Baelen, G.; Smet, M.; Dehaen, W. Tetrahedron
2006, 62, 6018–6028.
11. Morita, N.; Krause, N. Org. Lett. 2004, 6, 4121–4123.
12. Dieter, R. K.; Chen, N.; Gore, V. K. J. Org. Chem. 2006, 71, 8755–8760.
13. Ohno, H.; Kadoh, Y.; Fujii, N.; Tanaka, T. Org. Lett. 2006, 8, 947–950.
14. Zhu, Q.; Jiang, H.; Li, J.; Liu, S.; Xia, C.; Zhang, M. J. Comb. Chem. 2009, 11, 685–
696.

B. Cekavicus et al. / Tetrahedron Letters 52 (2011) 6246–6249
6249
15. Cui, S.-L.; Wang, J.; Wang, Y.-G. Org. Lett. 2007, 9, 5023–5025.
16. Green, M. P.; Prodger, J. C.; Sherlock, A. E.; Hayes, J. C. Org. Lett. 2001, 3, 3377–
3379.
17. Kuthan, J.; Kurfurst, A. Ind. Eng. Chem. Prod. Res. Dev. 1982, 21, 191–261.
18. Sausins, A.; Duburs, G. Heterocycles 1988, 27, 269–289.
19. Natale, N. R. Chem. Innovat. 2000, 30, 22–28.
20. Eisner, U.; Kuthan, J. Chem. Rev. 1972, 72, 1–42.
21. Goldmann, S.; Stoltefuss, J. Angew. Chem., Int. Ed. Engl. 1991, 30, 1559–1578.
22. Görlitzer, K.; Buß, D. Arch. Pharm. 1984, 317, 1029–1037.
23. Frigerio, M.; Zaliani, A.; Riva, C.; Palmisano, G.; Pilati, T.; Gandolfi, C. A.
Tetrahedron Lett. 1988, 29, 6335–6338.
(dd, 3J = 8.0 and 4J = 1.8 Hz, 1H), 7.35 (t, 3J = 8.0 Hz, 1H), 7.71 (ddd, 3J = 8.1,
4J = 2.0 and 5J = 1.1 Hz, 1H), 7.99 (ddd, 3J = 8.1, 4J = 2.0 and 5J = 1.0 Hz, 1H), 8.26
(t, 4J = 2.0 Hz, 1H), 9.78 (br s, 1H). 13C NMR (CDCl3, 100 MHz): 14.25 (CH3CH2),
14.81 (CH030 ), 15.06 (CH03), 57.31 (C5), 59.28 (CH2), 64.17 (CH200 ), 64.48 (CH02),
66.69 (C2), 98.98 (C3), 112.26 (C30), 113.27 (C600), 116.90 (C300), 118.33 (C60),
120.55 (C400), 120.76 (C40), 121.14 (C500), 121.87 (C4000), 123.31 (C2000), 123.70
(C50), 128.42 (C5000), 129.86 (C20), 134.23(C6000), 135.56 (C200), 146.51(C1000),
147.89 (C3000), 149.22 (C10), 149.66 (C100), 154.49 (C4), 165.65 (C@O); IR (film)
1629, 1668, 3277 cmꢁ1; MS (+ESI) m/z (relative intensity) 518 ([M+H]+, 100).
Anal. calcd for C29H31N3O6: C, 67.30; H, 6.04; N, 8.12; found: C, 66.95; H, 5.98; N,
8.02.
24. Lehmann, J.; Kahlich, R.; Gottesberge, C. M. Z.; Fricke, U. Arch. Pharm. 1997, 330,
247–252.
25. Chekavichus, B.; Popelis, Y.; Shebenina, E.; Sausins, A.; Verkhe, R.; Duburs, G.
Khim. Geterotsikl. Soedin. 1997, 915–920 [Chem. Heterocycl. Comp. (Engl. Ed.)
1997, 37, 799–804].
26. Skrastinsh, I. P.; Kastron, V. V.; Chekavichus, B. S.; Sausins, A. E.; Zolotoyabko, R.
M.; Dubur, G. J. Khim. Geterotsikl. Soedin. 1991, 1230–1235 [Chem. Heterocycl.
Comp. (Engl. Ed.) 1991, 27, 989–994].
27. 27. Urtti, A.; Hyvonen, Z.; Plotniece, A.; Makarova, N.; Reine, I.; Tirzitis, G.;
Vigante, B.; Cekavicus, B.; Shmidlers, A.; Krauze, A.; Zhalubovskis, R.; Duburs,
G.; Turunen, M.; Yla-Herttuala, S.; Jaaskelainen, I.; Toppinen, M.-R. WO 01/
62946 A1, 2001; Chem. Abstr. 2001, 135, 206419h.
31. General procedure for the synthesis of 3-pyrrolines 4b–g: To a solution of
benzaldehyde (2b) (0.24 ml; 2.4 mmol) in MeOH (10 mL), ethyl 4-
bromoacetoacetate (1a) (0.50 g, 2.4 mmol) and the corresponding aromatic
amine 3a–e (4.8 mmol) were added, after which the mixture was stirred at
room temperature for 24–48 h. After cooling, the precipitated product was
filtered and crystallised from MeOH. Spectral data of 3-pyrrolines 4b–g can be
found in the Supplementary data.
32. Diffraction data were collected at ꢁ80 °C on
a
Bruker-Nonius KappaCCD
diffractometer using graphite
monochromated Mo-K radiation
a
(k = 0.71073 Å). The crystal structure of 4a was solved by direct methods33
and refined by full-matrix least squares.34 All non-hydrogen atoms were
refined in anisotropical approximation, all H-atoms were refined using the
riding model. Crystal data for 4a: monoclinic; a = 19.7995(4), b = 16.3084(4),
28. Pajuste, K.; Plotniece, A.; Kore, K.; Intenberga, L.; Cekavicus, B.; Kaldre, D.;
Duburs, G.; Sobolev, A. Cent. Eur. J. Chem. 2011, 9, 143–148.
c = 16.8738(5) Å, b = 99.939(1)°; V = 5366.8(2) Å3, Z = 8,
l
= 0.09 mmꢁ1
total of 7053 reflection
intensities were collected; for structure refinement, 3669 independent
reflections with I > 3 (I) were used. The final R-factor is 0.058. For further
,
29. Svendsen, A.; Bolla, P. M. Tetrahedron 1973, 29, 4251–4258.
30. Ethyl 1-(2-ethoxyphenyl)-4-(2-ethoxyphenylamino)-2-(3-nitrophenyl)-2,5-dihydro-
1H-pyrrole-3-carboxylate (4a). To a solution of m-nitrobenzaldehyde (2a) (0.36 g,
2.4 mmol) in MeOH (10 mL), ethyl 4-bromoacetoacetate (1a) (0.50 g, 2.4 mmol)
and 2-ethoxyaniline (3a) (0.63 mL, 4.8 mmol) were added, after which the
resulting mixture was stirred at room temperature for 24 h. After cooling, the
orange precipitate was filtered and crystallised from MeOH to give 4a (0.83 g,
67%) as orange crystals, mp 95–97 °C. 1H NMR (CDCl3, 400 MHz): 1.15 (t,
3J = 7.1 Hz, 3H), 1.49 (t, 3J = 7.1 Hz, 3H), 1.51 (t, 3J = 7.1 Hz, 3H), 4.02 (q,
3J = 7.1 Hz, 2H), 4.10 (q, 3J = 7.1 Hz, 2H), 4.15 (q, 3J = 7.1 Hz, 2H), 4.63 (dd,
2J = 15.8 and 4J = 1.8 Hz, 1H), 5.52 (dd, 2J = 15.8 and 4J = 4.6 Hz, 1H), 6.01 (dd,
4J = 4.2 and 4J = 1.8 Hz, 1H), 6.78 (m, 4H), 6.92 (dd, 3J = 8.0 and 4J = 1.8 Hz, 1H),
6.94 (dt, 3J = 8.0 and 4J = 1.8 Hz, 1H), 7.04 (dt, 3J = 8.0 and 4J = 1.8 Hz, 1H), 7.12
Dcalc = 1.281 g cm–3
; space group is C 2/c. A
r
details, see crystallographic data for 4a deposited with the Cambridge
Crystallographic Data Centre as Supplementary Publication Number CCDC
814887. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.
33. Altomare, A.; Burla, M.; Camalli, M.; Cascarano, G.; Giacovazzo, C.; Guagliardi,
A.; Moliterni, A.; Spagna, R. J. Appl. Cryst. 1999, 32, 115–119.
34. Mackay, S.; Dong, W.; Edwards, C.; Henderson, A.; Gilmore, C.J.; Stewart, N.;
Shankland, K.; Donald, A. maXus, Integrated Crystallography Software, 2003,
Bruker-Nonius and University of Glasgow.