The cycloacylation - 1,3-acylrearrangement sequence as tool for highly substituted pyrrolones

Article abstract of DOI:10.1002/jhet.5570450332

(Chemical Equation Presented) The cyclization reactions between bis-imidoylchlorides 1 and ketones, which possess different CH-acidity, were investigated. Diphenylacetone 2 reacts under mild conditions via C,O-cyclization of the preformed enolate to yield the iminofurane derivative 3. Upon treatment with trifluoroacetic acid, the latter can be rearranged quantitatively into the pyrrolone 5. In contrast, 1,3-acetonedicarboxylate 9 and cyclohexanone 12 immediately lead to highly substituted pyrrolones 11 and 14. Obviously, the primarily formed cyclization products undergo a very fast 1,3-acyl rearrangement (Dimroth-/Mumm-Rearrangement). The structures of the maleiimide 11 and the indolone 14 were determined by single crystal X-ray structure analysis. Due to its amino/imino substructure, compound 3 is an efficient ligand for metal complexation reactions, exemplified by the synthesis of two different Zn-complexes 7 and 8.

Full text of DOI:10.1002/jhet.5570450332

May-Jun 2008
845
The Cycloacylation - 1,3-Acylrearrangement Sequence as Tool for
Highly Substituted Pyrrolones
Gunther Buehrdel [a], Rainer Beckert [a]*, Birgit Friedrich [a], Helmar Goerls [b]
[a] Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University Humboldtstr. 10, D-
07743 Jena, Germany. Fax: +49 3641 948212; Tel: +49 3641 948230; E-mail: c6bera@uni-jena.de
[b] Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University August-Bebelstr. 2, D-07743
Jena, Germany
Received October 22, 2007
TolN
NTol
Cl
Cl
Ph
Ph
O
O
KOtBu
NHTol
Ph
NHTol
O
Ph
Ph
NHTol
O
F3CCOOH
HCl aq
N
NTol
O
Ph
Tol
Ph
Ph
The cyclization reactions between bis-imidoylchlorides 1 and ketones, which possess different CH-
acidity, were investigated. Diphenylacetone 2 reacts under mild conditions via C,O-cyclization of the
preformed enolate to yield the iminofurane derivative 3. Upon treatment with trifluoroacetic acid, the latter
can be rearranged quantitatively into the pyrrolone 5. In contrast, 1,3-acetonedicarboxylate 9 and
cyclohexanone 12 immediately lead to highly substituted pyrrolones 11 and 14. Obviously, the primarily
formed cyclization products undergo
a very fast 1,3-acyl rearrangement (Dimroth-/Mumm-
Rearrangement). The structures of the maleiimide 11 and the indolone 14 were determined by single
crystal X-ray structure analysis. Due to its amino/imino substructure, compound 3 is an efficient ligand for
metal complexation reactions, exemplified by the synthesis of two different Zn-complexes 7 and 8.
J. Heterocyclic Chem., 45, 845 (2008).
for derivatives of type f are described [5], for example the
gallium(III) chloride catalyzed insertion of isocyanides into
epoxides [2a].
INTRODUCTION
During recent years derivatives of γ-butyrolactone have
increased in interest and significance, due to the fact that this
cyclic template is present in many highly bioactive
molecules and especially in sesquiterpene lactones of type a
(Figure 1) [1]. The α-hydroxy- γ-lactones and their α-amino
analogs represent structural units of many biologically
active materials and natural products [1b] and in addition,
several of their unsaturated derivatives are versatile building
blocks for the synthesis of natural products [1c]. For
example, sotolone b is used as a food additive as well as in
tobacco industries as an important aroma. Compound c is
believed to be its biological precursor [2]. Substituted
pyrrolidones, especially 5-alkylidene-2,5-dihydropyrrol-2-
ones which occur in a variety of natural products such as
pukeleimides A-G (type d Figure 1) [3], are of considerable
pharmacological relevance [3a]. The simple replacement of
oxo- and hydroxyl groups in derivatives e by imino- and
amino groups should lead to α amino-γ imino-lactones f
(Figure 1) for which a high biological activity can also be
expected. Comparable to type e they should easily be
transformed to yield novel products with interesting
properties. Furthermore, they might undergo a 1,3 (O→N)
migration reaction (Dimroth-Rearrangement) [4] to finally
give α-amino-pyrrolidones of type g. Only few syntheses
During the course of our past work, we demonstrated
that bis-arylimidoyl chlorides 1 [6] are excellent (and
selective) bis-electrophiles that can be employed in a wide
range as C2-building blocks for heterocyclic as well as for
carbocyclic compounds [7]. Due to their 1,4-
diazabutadiene substructures, the cyclization products
offer good requirements for the formation of metal
complexes [8]. Our aim was therefore to develop a short
and new synthetic route to derivatives of type f by
cycloacylation reactions of ketones with bis-imidoyl-
chlorides derived from oxalic acid 1 [6].
OMe
NH2
Me
N
OH
O
O
O
O
N
O
c
O
O
b
O
d
O
Stolone
precursor
a
OH
Pukeleimid A
Stolone
Alantolactone
NH2
OH
NH2
NH
O
N
H
O
O
e
O
f
g
Figure 1

846
G. Buehrdel, R. Beckert, B. Friedrich, H. Goerls
Vol 45
RESULTS AND DISCUSSION
isomerisation process takes place and a (E/Z)-isomer
mixture is formed (1H NMR, E:Z = 2:1). In chloroform
immediately the isomerisation take place. The yellow
solution of compound 5 (CHCl3: λmax: 380 nm, lg ε: 4.2)
display a yellow fluorescence with a large stokes shift
(CHCl3: λEm: 577nm).
Diphenylacetone 2 reacts with the bis-electrophile 1
under quite mild conditions (THF in the presence of
KO-tBu at -78°C) forming a yellow crystalline product in
a satisfactory yield. Elemental analysis and MS data
confirmed the presence of a 1:1 cyclisation product.
1H and 13C NMR spectra with the presence of double sets
of signals suggest an unsymmetrical structure. NMR
correlation spectroscopy proved that the cyclisation
product displays the structure of the 3-amino-2-imino-γ-
lactone 3 (Scheme 1). A single crystal X-ray analysis of 3
confirmed this molecular structure (Figure 2). Compound
3 is a monomer in the solid state with the bond lengths
and angles being in the expected range (Table 1).
According to our expectations, 3 was formed via an O,C-
cycloacylation reaction of the preformed enolate of 2. The
cyclisation reaction proceeds in a highly stereoselective
manner, whereby only the (Z)-isomer is formed. The
furan derivative 3 is soluble even in nonpolar solvents
forming dark yellow solutions. In addition, 3 show an
amphoteric character upon treatment with acids (HCl) and
bases (KO-tBu, n-BuLi). In each case, the color changes
reversibly to deep red under the formation of
cations/anions. Derivative 3 is electrochemically active
and can be oxidized reversibly. Employing square wave
measurements, two peaks at 1.162 V and at 1.538 V can
be ascribed to two different electron transfer steps. The
quasi-reversibility of the oxidation was confirmed by
We also tested an independent synthetic entry to
compounds 3, 4 and 5 via the aminolysis reaction of 3-
hydroxy-4-phenyl-5-phenylmethylene-2(5H)-furanone
6
[9] with p-toluidine. Despite a broad variation of the
reaction conditions, only the decomposition of the
heterocycle to ketone 2 and the corresponding oxanilide
was observed, this is most likely due to the retro-aldol
reaction. Only when acetic acid was used as solvent the
formation of pyrrolone 5 was observed. The two samples
of 5 show identical properties.
Scheme 1
TolN
Cl
NTol
Ph
OH
1
2
Cl
Ph
Ph
O
O
O
Ph
6
H2NTol
NHTol
KOtBu
NHTol
Ph
Ph
Ph
NHTol
O
F3CCOOH
HCl aq
cyclovoltammetric measurements ΔE1
= 0.081 V
NTol
O
N
RED,OX
O
3
O
4
Ph
and ΔE2
= 0.097 V and the semiquinone formation
Ph
Tol
RED,OX
Ph
constant is KSEM = 1.2*106.
5
Thereafter, we studied various synthetic trans-
formations of the γ-imino lactone 3. Imino groups can
often easily be hydrolysed yielding the parent carbonyl
compounds. In a mixture of THF/aqueous hydrochloric
acid, the lactone 3 easily undergoes hydrolysis. In a
straight forward reaction only the imino group is
converted to an oxo group giving 3-amino-γ-lactone 4 in
high yield. In compound 4 the (Z)-configuration is
maintained showing almost the same properties
(solubility, amphotheric behaviour) as derivative 3.
In the past we often employed the Dimroth
rearrangement of cyclic isothiourea substructures in order
to synthesize new thioxo derivatives [10]. This valuable
1,3 (S→N)-migration reaction can be induced by acids as
well as by bases, and in addition, is not only restricted to
S,N-compounds. Accordingly, the furan derivative 3 was
converted by treatment with anhydrous trifluoroacetic
acid via 1,3 (O→N)-rearrangement into alkylidene-2,5-
dihydropyrrol-2-one 5. Compound 5 was isolated in the
(E)-configuration in high yield as pale yellow crystals. In
cold DMSO-d6 it was possible to measure the NMR-
spectra of the (E)-isomer. Upon irradiation by sunlight or
by heating the pure solution of the (E)-isomer, an
Figure 2. ORTEP-plot (50% probability ellipsoids) of the solid state
molecular structure of 3.
Another interesting feature of heterocycles 3 is their
vicinal amino/imino substructure, which has been used
recently in our group for the preparation of redox-active
group VIII metal complexes [8a]. Upon addition of ZnEt2
to a solution of 3 (two parts of 3: one part of ZnEt2) and
heating of the resulting mixture, the complex 7 was

May-Jun 2008
1,3-Acylrearrangement Sequence as Tool for Highly Substituted Pyrrolones
847
Table 1. selected bond length for 3 and 8
isolated. Using
a
1:1 stoichiometry at ambient
temperature, the coordinative unsaturated zinc complex 8
was isolated in the shape of red crystals. The temperature
depending exchange of alkyl-groups in similar zinc
complexes was reported in the aminotropone series. These
complexes proved to be efficient and selective pre-
catalysts for hydroamination reactions [11].
The solid-state structure of 8 was established by single-
crystal X-ray diffraction. Compound 8 is a monomer in
the solid state, and therefore the zinc atom has a trigonal-
planar coordination sphere (Figure 3). The bond lengths
and angles at the zinc centre are in the expected range.
The changes of the bond lengths and angles between
ligand 3 and complex 8 are rather small (Table 1). In
contrast to the pyrophoric starting material, complex 8 is
relatively stable towards moisture and air. The reasons for
this stability of compounds of the general formula
[LZnEt] (L = ligand) was described earlier [12].
Ligand 3 d in Å
1.362(4)
1.270(4)
1.386(3)
1.400(3)
1.471(4)
1.368(4)
1.465(4)
1.339(4)
Complex 8 d in Å
N2-C2
N1-C1
O-C1
1.354(4)
1.282(4)
1.365(3)
1.415(4)
1.456(4)
1.382(4)
1.445(4)
1.347(4)
1.952(3)
2.115(2)
1.953(3)
O-C4
C1-C2
C2-C3
C3-C4
C4-C5
Zn-C32
Zn-N1
Zn-N2
bond lengths and NMR signals in the furan 3 with those in
complex 8 suggests that part of the negative charge is
stabilized in the furane ring.
Analogously, dimethyl 1,3-acetonedicarboxylate
9
reacts with the bis-electrophile 1 under the similar mild
conditions giving a yellow crystalline product in good
yield. Elemental analysis, MS data and NMR spectra
confirmed the presence of a formal 1:1 cyclisation
product. However, also the elimination of a methyl group
occurred. The X-ray structure analysis revealed that in the
course of a cascade reaction, the maleinimide 11 was
formed (Scheme 3). The bond lengths and angles in
compound 11, which exist as a monomer in the solid state
are in the expected range (Figure 4). Obviously, only one
CH-acidic methylene group of 9 was integrated into the
heterocyclic system of 11 and we propose the following
mechanism. In the first step, the ester-enolate of 9 is
acylated by 1 to form an open-chained intermediate which
then attacks the ester group with its second acyl unit. This
O-acylation leads to the lactone 10 which finally was
converted via 1,3 (O→N)-migration (Mumm-Rearrange-
ment) [13] into the maleinimide 11 (Scheme 3).
Scheme 2
Tol
Tol
N
Ph
N
Ph
Zn
ZnEt2
ZnEt2
RT
Zn
3
O
N
N
Ph
O
8
Tol
Ph
Tol
2
7
Scheme 3
O
COOMe
NHTol
TolN
Cl
NTol
Cl
MeOOC
NHTol
O
O
1
O
MeOOC
COOMe
N
O
NTol
O
10
O
9
Tol
11
Figure 3. ORTEP-plot (50% probability ellipsoids) of the solid state
molecular structure of 8.
Encouraged by these results, less CH acidic carbonyl
systems were integrated in these cyclization
investigations. Cyclohexanone 12 reacted smoothly with 1
in the presence of KOtBu forming a crystalline product in
good yield. Elemental analysis and MS data were in
agreement with the structure of the 1:1 cyclization
product. The 1H and 13C NMR spectra indicated the
presence of a double bond in the cyclohexane ring system.
The result of the X-ray analysis of pale yellow single
crystals of 14 is shown in Figure 5. Hence, the
cycloacylation product has the structure of a 4,5,6-
1
The H and 13C NMR spectra of complexes 7 and 8
show the expected sets of signals for the ligands.
Compared to the starting material ZnEt2, the signals of the
Zn-Et group of 8 (1H: δ = 0.40, 1.28; 13C: δ = 6.1, 13.6
ppm) are shifted towards higher field. The signals of the
benzyl-CH and the two methyl groups in 7 and 8 were
detected as singlets and their chemical shifts are in the
range of those for ligand 3. This fact is somewhat
surprising with respect to the different coordination
spheres of the central zinc atoms. The comparison of the

848
G. Buehrdel, R. Beckert, B. Friedrich, H. Goerls
Vol 45
3-5, 11 and 14 with the appropriate aryl substituents can
be isolated as main products.
Figure 4. ORTEP-plot (50% probability ellipsoids) of the solid state
molecular structure of 11, selected bond lengths in Å: O1-C4
1.212(3), O2-C1 1.205(4), O3-C5 1.240(3), N1-C1 1.387(3), N1-C4
1.429(4), N2-C2 1.314(4), C1-C2 1.514(4), C2-C3 1.389(4), C3-C4
1.450(4), C3-C5 1.439(4).
Figure 5. ORTEP-plot (50% probability ellipsoids) of the solid state
molecular structure of 14, selected bond length in : N1-C1 1.380(2),
N1-C8 1.421(3), N2-C2 1.380(3), C1-C2 1.479(3), C2-C3 1.354(3), C3-
C8 1.457(3), C7-C8 1.334(3).
trihydro-indolone. This cyclic hydro-isatine derivative 14
is a dimer in the solid state in which the two units are
connected via NH-O bridges. The bond lengths and angles
are in the expected range (Figure 5).
CONCLUSION
The reaction between cyclopentanone and 1 under
similar conditions resulted in a complex reaction mixture.
As in the previously reported cases, the enolate of 12
reacts with 1 to give the 2-imino furan derivative (imino-
γ-lactone) 13 which could be neither isolated nor detected.
In a fast rearrangement sequence 13 was then transformed
into indolone 14 (Scheme 4). The synthesis of 14 and of
its phenyl analogue was described earlier by a two-step
protocol [14]. Previously, the reaction between 1 and 1,3-
dicarbonyl compounds in the presence of LDA has been
employed for the preparation of 5-alkylidene-2,5-
dihydropyrrol-2-ones [7b]. Accordingly to our observa-
tions these enolates reacted with 1 to give 2-imino furan
derivatives (imino-γ-lactones) which fast rearrange into
the pyrrolones. We could substitute the base LDA by
KO-tBu which is easier to handle and needs no special
reaction techniques.
An short and efficient synthesis for highly substituted
iminofuranes and pyrrolones based on the cyclisation
reaction of different enolates with bis-imidoylchlorides 1
was developed. Whereas diphenylacetone 2 reacted to
iminofurane
3
1,3-acetonedicarboxylate
9
and
cyclohexanone 12 immediately formed via subsequent
1,3-acyl-rearangment reactions the pyrrolones 11 and 14.
The proton induced Dimroth-Rearrangment of
3
quantitatively yields the pyrrolone 5. Due to its vicinal
amino-imino substructure derivative 3 proved to be an
excellent chelating ligand, exemplified by the preparation
of two Zn complexes. The solid state structures of the new
products were determined by single crystal X-ray
diffraction.
EXPERIMENTAL
General. The reagents described in the following section
were purchased from commercial sources and were used directly
unless otherwise stated in the text. The bis-imidoylchloride 1 [6]
and lactone 6 [9] were synthesized according to literature
procedures. All solvents were of reagent grade and were dried
according to common practice and were distilled prior to use.
Reactions were monitored by TLC, carried out on 0.2 mm
Scheme 4
TolN
Cl
NTol
Cl
NHTol
O
NHTol
NTol
1
N
1
Merck silica gel plates (60 F254). The H and 13C NMR spectra
O
14
13
Tol
O
were recorded on Bruker AVANCE 250 and 400 spectrometers,
shifts are relative to the signals of the solvent.
12
Melting points were measured with a Galen III apparatus
(Boëtius system) and are uncorrected.
It is noteworthy that not only the bis-
tolylimidoylchloride 1 but also bis-imidoylchlorides,
which possess other aryl moieties e.g. Ar = 4-BrC6H4,
3-CF3C6H4 or 4-tertBuC6H4, can be employed as
cyclization partners. Analogously, heterocycles of type
3-Tolylamino-4-phenyl-5-phenylmethylen-2(5H)-furan-
tolylimine 3. The solution of 2.00 g (9.5 mmol) diphenylacetone
2 in 100 mL of dry THF was cooled down to -78 °C and 6.00 g
(54 mmol) KO-tBu was added. To the solution 4.60 g (15.1
mmol) bis-tolylimidoylchloride 1 was added. The deep red

May-Jun 2008
1,3-Acylrearrangement Sequence as Tool for Highly Substituted Pyrrolones
849
reaction mixture was stirred at -30 °C for 30 minutes. The
mixture was acidified by addition of HCl/isopropyl alcohol to
pH 7. The mixture was concentrated in vacuo to dryness. The
remaining solid was dissolved in CHCl3/n-heptane and was dried
over Na2SO4. Upon removal of the solvent in vacuo, the residue
was purified by column chromatography on silica gel (CHCl3/n-
heptane) and the crude product was purified by recrystallization
from CHCl3/n-heptane to yield 3 as yellow crystals.
vacuo, the crude product was purified by recrystallization from
CHCl3/ n-heptane to yield 5 as pale yellow crystals, yield: 0.41 g
(82%).
Method B. A mixture of 0.50 g (1.9 mmol) 6 and 0.50 g
(4.7 mmol) p-toluidine in 5 mL of acetic acid was heated to
80°C for one day. Upon cooling the product crystallised. The
crude product was colleted by filtration, was washed with
diethyl ether and was purified by recrystallization from
CHCl3/n-heptane to yield 5 as pale yellow crystals, yield: 0.53 g
(70%).
Yellow crystals, yield: 1.83 g (43%), mp 146°C (CHCl3/
1
n-heptane). H NMR (400MHz, DMSO-d6): δ = 8.26 (s, 1H,
Pale yellow crystals, mp 226°C (CHCl3/n-heptane). 1H NMR
((E/Z)-mixer, 250MHz, CDCl3): δ = 7.35-6.50 (m, 18H,
CH-Ar), 6.24 + 6.23 (s, 1H, CH-Benzal), 2.45 + 2.22 + 2.18 +
2.14 (s, 6H, CH-Tol) ppm. 1H NMR ((E)-isomer, 250MHz,
DMSO-d6): δ = 8.09 (s, 1H, NH), 7.26 (s, 5H, CH-Ph), 6.97-
6.83 (m, 9H, CH-Ar), 6.67 (d, 2H, J = 8 Hz CH-Tol), 6.57 (d,
2H, J = 8 Hz CH-Tol), 6.08 (s, 1H, CH-Benzal), 2.15 (s, 3H,
CH-Tol), 2.08 (s, 3H, CH-Tol) ppm. 13C NMR ((E)-isomer,
63MHz, DMSO-d6): δ = 167.4 (C-2), 138.5, 138.4, 136.0, 134.7,
134.1, 132.7, 130.1, 129.7, 129.6, 129.4, 128.9, 128.6, 128.5,
128.0, 127.4, 127.3, 126.4, 120.0, 119.3, 110.2(C-Benzal), 21.0,
20.7 ppm. MS(EI) m/z: 442 (100) [M+], 191 (50), 91 (30)
NH), 7.58 (d, 2H, J = 8 Hz CH-Ph), 7.36 (d, 2H, J = 8 Hz CH-
Tol), 7.28-7.18 (m, 10H, CH-Ar), 6.68 (d, 2H, J = 8 Hz CH-
Tol), 6.62 (d, 2H, J = 8 Hz CH-Tol), 5.66 (s, 1H, CH-Benzal),
2.36 (s, 3H, CH-Tol), 2.08 (s, 3H, CH-Tol) ppm. (250MHz,
THF-d8): δ = 7.63-7.06 (m, 14H, CH-Ar), 6.68 (d, 2H, J = 8 Hz
CH-Tol), 6.59 (d, 2H, J = 8 Hz CH-Tol), 5.69 (s, 1H, CH-
Benzal), 2.37 (s, 3H, CH-Tol), 2.11 (s, 3H, CH-Tol) ppm. 13C
NMR (100MHz, DMSO-d6): δ = 152.7 (C-1), 152.0 (C-2),
142.4, 137.0, 134.7, 134.0, 131.13, 131.10, 130.05, 129.4, 128.9,
128.5, 128.3, 128.05, 128.01, 127.7, 126.4, 123.4, 119.7, 116.7
(C-3), 101.2 (C-Benzal), 20.6, 20.2 ppm. MS(EI) m/z: 442 (60)
+
[M+], 365 (20), 191 (100), 91 (50) [C7H7 ]. Elemental analysis
+
calculated for C31H26N2O (442.57) C 84.13, H 5.92, N 6.33;
found C 83.83, H 5.95, N 6.32%. IR(ATR): νmax/cm-1 3331 (NH),
3022, 2916, 1667, 1610, 1590, 1530, 1442, 1105, 813, 750, 690.
UV/VIS (CCl3H): λmax (lg ε) = 405 (4.41) nm.
[C7H7 ]. Elemental analysis calculated for C31H26N2O (442.57) C
84.13, H 5.92, N 6.33; found C 83.70, H 5.98, N 6.27%.
IR(ATR): νmax/cm-1 3298 (NH), 3058, 2915, 1692, 1620, 1596,
1534, 1411, 816, 695, 656. UV/VIS (CCl3H): λmax (lg ε) = 380
(4.22) nm.
3-Tolylamino-4-phenyl-5-phenylmethylen-2(5H)-furanone
4. The solution of 0.50 g (1.1 mmol) of 3 in 30 mL of THF was
treated with 3 mL of hydrochloric acid and heated to 60°C. The
reaction was monitored by TLC and when no starting material
was detected (after 5 minutes) the reaction mixture was
neutralised by addition of diluted sodium hydroxide solution and
the mixture was then concentrated in vacuo to dryness. The
remaining solid was dissolved in CHCl3/n-heptane and was dried
over Na2SO4. Upon removal of the solvent in vacuo, the crude
product was purified by recrystallization from CHCl3/n-heptane
to yield 4 as yellow crystals.
Preparation of zinc complex 7. The solution of 0.50 g
(1.1 mmol) of 3 in 10 mL of dry THF and 20 mL of dry
n-heptane was treated at ambient temperature with 0.6 mL of a
hexane solution of ZnEt2 (1 M, 0.6 mmol). The mixture was
stirred for 30 minutes at room temperature and then was heated
briefly under reflux. The solvent was removed and the
remaining orange solid was washed twice with dry n-pentane
and dried in vacuo. Yield 0.46 g (89%).
1H NMR (250MHz, Benzol-d6): δ = 7.72-6.80 (m, 18H, CH-
Ar), 5.94 (s, 1H, CH-Benzal), 2.07 (s, 3H, CH3), 2.03 (s, 3H,
CH3), ppm. 13C NMR (63MHz, Benzol-d6): δ = 165.5 (C-1),
155.1 (C-2), 145.2, 139.2, 138.6, 136.1, 135.6, 133.2, 130.0,
129.6, 128.9, 128.7, 128.5, 126.8, 126.3, 123.7, 122.2, 109.4,
102.9 (C-Benzal), 20.6, 20.5 ppm. MS (EI) m/z: 951 (4) + 950
(5) + 949 (7) + 948 (5) and 947 (8) [M + H+], 442 (100)
calculated and measured isotope patterns for C62H51N4O2Zn+ are
conform.
Yellow crystals, yield: 0.34 g (87%), mp 202°C (CHCl3/
n-heptane). 1H NMR (250MHz, DMSO-d6): δ = 8.56 (s, 1H, NH),
7.67 (d, 2H, J = 8 Hz CH-Ph), 7.40-7.21 (m, 8H, CH-Ar), 6.72 (d,
2H, J = 8 Hz CH-Tol), 6.57 (d, 2H, J = 8 Hz CH-Tol), 5.86 (s, 1H,
CH-Benzal), 2.09 (s, 3H, CH-Tol) ppm. 13C NMR (63MHz,
DMSO-d6): δ = 165.7 (C-2), 148.0 (C-3), 137.2, 133.9, 130.2,
130.1, 129.4, 129.0, 128.6, 128.3, 128.2, 127.5, 126.3, 123.2,
119.1, 105.9 (C-Benzal), 20.2 ppm. MS(EI) m/z: 353 (100) [M+],
Preparation of zinc complex 8. The solution of 250 mg
(0.56 mmol) of 3 in 5 mL of dry THF and 20 mL of dry
n-heptane was treated at ambient temperature with 0.6 mL of a
solution of ZnEt2 in hexane (1 M, 0.6 mmol). The mixture was
stirred for 30 minutes at room temperature and then was treated
with 80 mL of dry n-heptane. The solution was cooled at –16°C
over one month, yielding the zinc complex 8 as dark red
crystals. Yield 201 mg (67%).
1H NMR (250MHz, THF-d8): δ = 7.30-7.05 (m, 14H, CH-Ar),
6.58-6.45 (m, 4H, CH-Tol), 5.78 (s, 1H, CH-Benzal), 2.39 (s,
3H, CH-Tol), 2.08 (s, 3H, CH-Tol), 1.28 (t, 3H, J = 8 Hz
CH3-Ethyl), 0.40 (q, 2H, J = 8 Hz CH2-Ethyl) ppm. 13C NMR
(63MHz, THF-d8): δ = 164.5 (C-1), 154.0 (C-2), 143.7, 138.0,
137.3, 135.1, 134.5, 131.9, 128.2, 127.6, 127.4, 127.1, 126.9,
126.4, 125.5, 125.1, 124.6, 123.1, 120.4, 108.9, 102.2
(C-Benzal), 20.2, 19.9, 13.6 (CH3-Ethyl), 6.1 (CH2-Ethyl) ppm.
Preparation of maleinimide 11. The solution of 2.00 g
(11.5 mmol) ketone 9 in 100 mL of dry THF was cooled down
+
324 (20), 191 (60), 91 (30) [C7H7 ]. Elemental analysis calculated
for C24H19NO2 (353.42) C 81.65, H 5.42, N 3.96; found C 81.51,
H 5.39, N 3.89%. IR(ATR): νmax/cm-1 3333 (NH), 3037, 2916,
1745 (conjugated lactone C=O), 1620, 1591, 1528, 1255, 751,
693. UV/VIS (CCl3H): λmax (lg ε) = 394 (4.42) nm.
1-Tolyl-3-tolylamino-4-phenyl-5-phenylmethylene-2(5H)-pyr-
rolidone 5.
Method A. The solution of 0.50 g (1.1 mmol) 3 in 30 mL of
dry THF was treated with a mixture consisting of 10 mL of
trifluoroacetic acid and 0.2 mL of trifluoroacetic anhydride and
then heated to 70°C. The reaction was monitored by TLC and
when no starting material was detected (after 40 minutes) the
reaction mixture was neutralised by addition of diluted sodium
hydroxide solution and the mixture was concentrated in vacuo to
dryness. The remaining solid was dissolved in CHCl3/n-heptane
and was dried over Na2SO4. Upon removal of the solvent in

850
G. Buehrdel, R. Beckert, B. Friedrich, H. Goerls
Vol 45
to -78 °C and 4.00 g (35.7 mmol) of KO-tBu was added. To the
solution 3.70 g (12.1 mmol) bis-tolylimidoylchloride 1 was
added. The deep red reaction mixture was stirred at -30 °C for
30 minutes. The mixture was acidified by addition of
hydrochloric acid to pH 7. Then the mixture was concentrated in
vacuo to dryness. The remaining solid was dissolved in
CHCl3/n-heptane and was dried over Na2SO4. Upon removal of
the solvent in vacuo, the residue was purified by column
chromatography on silica gel (CHCl3/n-heptane) and the crude
product was purified by recrystallization from CHCl3/n-heptane
to yield 11 as yellow crystals.
included at calculated positions with fixed thermal parameters. All
non hydrogen atoms were refined anisotropically [18]. The
program XP (SIEMENS Analytical X-ray Instruments, Inc.) was
used for structure representations.
CCDC-661235 (3), CCDC-661236 (8), CCDC-661237 (11), and
CCDC-661238 (14) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2
1EZ, UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
Crystal Data for 3 (CCDC-661235): C31H26N2O, Mr = 442.54
gmol-1, yellow prism, size 0.05 x 0.05 x 0.04 mm3, monoclinic,
space group P21, a = 13.9374(8), b = 6.3810(3), c = 15.3665(9) Å,
β = 107.320(3)°, V = 1304.6(1) Å3, T= -90 °C, Z = 2, ρcalcd. = 1.127
gcm-3, µ (Mo-Kα) = 0.68 cm-1, F(000) = 468, 8972 reflections in
h(-16/18), k(-8/7), l(-19/19), measured in the range 2.96° ≤ Θ ≤
Yellow crystals, yield: 2.62 g (58%), mp 140°C (CHCl3/
1
n-heptane). H NMR (250MHz, CDCl3): δ = 9.30 (s, 1H, NH),
7.57-7.18 (m, 8H, CH-Tol), 4.05 (s, 2H, CH2), 3.81 (s, 3H,
OCH3), 2.38 (s, 3H, CH-Tol), 2.36 (s, 3H, CH-Tol) ppm.
13C NMR (63MHz, CDCl3): δ = 189.5 (C=O), 157.4, 152.7,
138.5, 138.2, 135.3, 133.7, 132.7, 129.8, 129.6, 126.3, 124.6,
119.8, 99.9, 52.3 (CH3-ester), 46.6 (CH2), 21.1, 21.0 ppm.
MS(EI) m/z: 392 (80) [M+], 318 (80), 216 (50), 158 (100), 107
27.47°, completeness
reflections, Rint = 0.0430, 4105 reflections with Fo > 4σ(Fo), 315
Θ
= 99%, 5227 independent
max
parameters, 1 restraints, R1obs = 0.0642, wR2 = 0.1688, R1all
=
obs
0.0882, wR2 = 0.1871, GOOF = 1.083, Flack-parameter -4(2),
+
(30), 91 (90) [C7H7 ]. Elemental analysis calculated for
all
largest difference peak and hole: 0.754 / -0.257 e Å-3.
C22H20N2O5 (392.42) C 67.34, H 5.14, N 7.15; found C 67.47, H
5.53, N 7.17%. IR(ATR): νmax/cm-1 3184 (NH), 2956, 1714,
1638, 1593, 1511, 1358, 1155, 797. UV/VIS (CCl3H): λmax (lg ε)
= 415 (3.73) nm.
Crystal Data for 8 (CCDC-661236): C33H30N2OZn, Mr = 535.96
gmol-1, red prism, size 0.06 x 0.06 x 0.06 mm3, triclinic, space
group Pī, a = 7.3782(6), b = 12.5394(11), c = 15.6793(15) Å, α =
110.074(4), β = 95.163(5), γ = 100.185(5)°, V = 1323.1(2) Å3 , T=
-90 °C, Z = 2, ρcalcd. = 1.345 gcm-3, µ (Mo-Kα) = 9.57 cm-1, F(000)
= 560, 9074 reflections in h(-9/9), k(-15/16), l(-20/20), measured
1-Tolyl-3-tolylamino-4,5,6-trihydro-indolone 14. The
solution of 1.00 g (10.2 mmol) cyclohexanone 12 in 100 mL of
dry THF was cooled down to -78 °C and 3.80 g (40.0 mmol) of
KO-tBu was added. To the solution 3.20 g (10.5 mmol) of bis-
tolylimidoylchloride 1 was added. The deep red reaction mixture
was stirred at -30 °C for 30 minutes. The mixture was acidified
by addition of hydrochloric acid to pH 7. The mixture was
concentrated in vacuo to dryness. The remaining solid was
dissolved in CHCl3/n-heptane and was dried over Na2SO4. Upon
removal of the solvent in vacuo, the crude product was purified
by recrystallization from CHCl3/n-heptane to yield 14 as pale
yellow crystals.
in the range 1.81° ≤ Θ ≤ 27.49°, completeness Θ
= 96.6%,
5879 independent reflections, Rint = 0.0446, 4032 reflections
max
with Fo > 4σ(Fo), 342 parameters, 0 restraints, R1obs = 0.0527,
wR2 = 0.1081, R1all = 0.0926, wR2all = 0.1251, GOOF = 1.006,
obs
largest difference peak and hole: 0.329 / -0.556 e Å-3.
Crystal Data for 11 (CCDC-661237): C22H20N2O5, Mr = 392.40
gmol-1, yellow prism, size 0.06 x 0.06 x 0.05 mm3, monoclinic,
space group P21/c, a = 7.0583(2), b = 12.1473(5), c = 22.5441(9)
Å, β = 96.933(3)°, V = 1918.78(12) Å3 , T= -90 °C, Z = 4, ρcalcd.
=
1.358 gcm-3, µ (Mo-Kα) = 0.97 cm-1, F(000) = 824, 11305
reflections in h(-9/8), k(-15/14), l(-29/29), measured in the range
Pale yellow crystals, yield: 2.42 g (72%), mp 213°C (CHCl3/
n-heptane), Lit. [14b] 211°C (ethanol). 1H NMR (250MHz,
DMSO-d6): δ = 7.74 (s, 1H, NH), 7.28 (d, J = 8 Hz, 2H, CH-Tol),
7.15 (d, J = 8 Hz, 2H, CH-Tol), 7.02 (d, J = 8 Hz, 2H, CH-Tol),
6.81 (d, J = 8 Hz, 2H, CH-Tol), 5.34 (t, J = 5 Hz, 1H, CH-cycle),
2.34 (s, 3H, CH-Tol), 2.29-2.23 (m, 7H, CH2-cycle + CH-Tol),
2.20 (quint., J = 6 Hz, 2H, CH2-cycle) ppm. 13C NMR (63MHz,
DMSO-d6): δ = 165.8, 140.1, 138.9, 136.9, 132.2, 130.0, 129.5,
127.4, 126.9, 120.8, 118.8, 115.6, 106.9, 24.4 (CH-cycle), 23.8
(CH-cycle), 23.5 (CH-cycle), 21.1 (CH-Tol), 20.7 (CH-Tol) ppm.
MS(EI) m/z: 330 (100) [M+], 268 (90), 135 (40), 106 (100), 91
2.91° ≤ Θ ≤ 27.49°, completeness Θ
= 96.8%, 4263
independent reflections, Rint = 0.0556, 2950 reflections with Fo >
max
4σ(Fo), 266 parameters, 0 restraints, R1obs = 0.0702, wR2
=
obs
0.1714, R1all = 0.1042, wR2 = 0.1875, GOOF = 1.073, largest
all
difference peak and hole: 0.300 / -0.289 e Å-3.
Crystal Data for 14 (CCDC-661238): C22H22N2O, Mr = 330.42
gmol-1, colourless prism, size 0.06
x 0.06 x
0.06 mm3,
orthorhombic, space group Pbca, a = 12.3420(4), b = 16.5660(6), c
= 17.1098(6) Å, V = 3498.2(2) Å3 , T= -90 °C, Z = 8, ρcalcd. = 1.255
gcm-3, µ (Mo-Kα) = 0.77 cm-1, F(000) = 1408, 22277 reflections
in h(-15/16), k(-19/21), l(-22/22), measured in the range 2.38° ≤
+
(90) [C7H7 ]. Elemental analysis calculated for C22H22N2O
(330.43) C 79.97, H 6.71, N 8.48; found C 79.87, H 6.55, N
8.39%. IR(ATR): νmax/cm-1 3292 (NH), 2949, 2933, 2863, 1677,
1639, 1609, 1531, 1511, 1404, 1325, 1170, 821. UV/VIS
(CCl3H): λmax (lg ε) = 301 (4.06), 349 (3.89) nm.
Θ ≤ 27.48°, completeness Θ
= 99.9%, 3998 independent
reflections, Rint = 0.0753, 2622 reflections with Fo > 4σ(Fo), 232
max
parameters, 0 restraints, R1obs = 0.0550, wR2 = 0.1386, R1all
=
obs
0.0965, wR2 = 0.1663, GOOF = 0.904, largest difference peak
all
Crystal Structure Determination for 3, 8, 11 and 14. The
intensity data for the compounds were collected on a Nonius
KappaCCD diffractometer, using graphite-monochromated
Mo-Kα radiation. Data were corrected for Lorentz and polarization
effects, but not for absorption effects [15, 16]. The structure was
solved by direct methods (SHELXS [17]) and refined by full-
matrix least squares techniques against Fo2 (SHELXL-97 [18]). For
the amino groups of 3, 11 and 14 as well as the CH2-protons at C32
of 8 the hydrogen atoms were located by difference Fourier
synthesis and refined isotropically. The other hydrogen atoms were
and hole: 0.535 / -0.392 e Å-3.
Acknowledgement. We are grateful to the Free State of
Thuringia for financial support of the work of G. Buehrdel.
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