Reaction of diimines and azines with diphenylcyclopropenone

Article abstract of DOI:10.1039/b109711n

1-Cyclohexyl-2-cyclohexylaminomethylene-4,5-diphenyl-1,2-dihydropyrrol-3-one 4a and 1-aryl-2-arylamino-methylene-4,5-diphenyl-1,2-dihydropyrrol-3-ones 4b,c as the E-form are synthesized by the reaction between N,N′-dicyclohexylethane-1,2-diylidenediamine

Full text of DOI:10.1039/b109711n

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Reaction of diimines and azines with diphenylcyclopropenone
Mohsen Abdel-Motaal Gomaa
Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt
1
Received (in Cambridge, UK) 24th October 2001, Accepted 4th December 2001
First published as an Advance Article on the web 10th January 2002
1-Cyclohexyl-2-cyclohexylaminomethylene-4,5-diphenyl-1,2-dihydropyrrol-3-one 4a and 1-aryl-2-arylamino-
methylene-4,5-diphenyl-1,2-dihydropyrrol-3-ones 4b,c as the E-form are synthesized by the reaction between
N,NЈ-dicyclohexylethane-1,2-diylidenediamine 2a and N,NЈ-diarylethane-1,2-diylidenediamines 2b,c with
diphenylcyclopropenone 1 through a formal [2 ϩ 3] cycloaddition reaction. The structure assignment of 4a
is confirmed on the basis of an X-ray crystal-structure determination. Similarly, diaryl azines 8a–c react with
1 through a formal [2 ϩ 3] cycloaddition reaction to give the non-isolable product ∆4-pyrrolin-3-ones 10a–c
which undergo oxidative rearrangement to afford ultimately the indenone derivatives 9a–c.
Introduction
The fascinating chemistry of cyclopropenones has attracted
the attention of numerous researchers over the past three
decades,1,2 with special emphasis on the behaviour of diphenyl-
cyclopropenone 1.3 Diphenylcyclopropenone has been found
to react with a wide range of imines, amidines, guanidines and
other compounds containing the C᎐N moiety to form aza-
᎐
cyclopentenones (pyrrolinones) via a formal [2 ϩ 3] cyclo-
addition reaction (Fig. 1).4–9 Similarly, 2-amino-1-azetines
Fig. 1
reacted with 1 to afford azeto[1,2-a]pyrroles.10 Diphenyl-
cyclopropenone 1 was used to synthesize the annelated hetero-
cycles by its reaction with cyclic amidines to give rise
to bi- and tricyclic pyrrolinones (Fig. 2).11 Moreover, thi-
azolo[3,2-a]pyrimidones were synthesized from the reaction of
diphenylcyclopropenone 1 with 2-aminothiazoles.12 Similarly,
tetrasubstituted 4(3H )-pyridones were produced from the
reaction of 1 with 3-amino-2,2-dimethyl-2H-azirines (Fig. 3).13
As part of our programme to develop efficient procedures for
the synthesis of heterocyclic compounds via the nucleophilic
Fig. 2
reactions of an amidine group (–HN–CR᎐N–) with π-deficient
᎐
compounds14–17 we have synthesized trisubstituted pyridin-
2(1H )-ones from the reaction of N 1,N 2-diarylacetamidines
with π-deficient dibenzoylacetylene.18 Recently we also
prepared 1,4,5,6-tetrahydropyridines by reaction of N 1,N 2-
diarylacetamidines with benzylidenemalononitriles.19
Fig. 3
cyclopropenone 1 were heated in ethanol for 2–5 h to give the
pyrrolinone derivatives 4a–c in 42–67% yield (Scheme 1). 13C
NMR spectra showed a characteristic peak at δC 175.96–177.33
for the carbonyl groups, and the aliphatic carbon atoms (of 4a)
of the cyclohexyl rings appeared as two peaks at δC 56.05 and
56.33 for the cyclohexyl tertiary carbon atoms (CH) adjacent to
the nitrogen atoms. A 13C DEPT spectrum of 4a showed six
peaks with a negative amplitude that were assigned for the
Results and discussion
Herein I report the reaction of the diimines 2a–c and the
aromatic azines 8a–c with the selected π-deficient diphenyl-
cyclopropenone 1.
First we undertook to investigate the reaction of N,NЈ-
dicyclohexyl- 2a and diaryl-ethane-1,2-diylidenediamines 2b,c
with diphenylcyclopropenone 1. Thus diimines 2a–c and the
1
cyclohexyl-CH2 carbon atoms. H NMR spectroscopy showed
signals between δ 7.42–7.98 that were assigned to the NH
group. IR spectroscopy showed absorptions at 3380–3410 cmϪ1
DOI: 10.1039/b109711n
J. Chem. Soc., Perkin Trans. 1, 2002, 341–344
This journal is © The Royal Society of Chemistry 2002
341

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Scheme 1
for the amino groups and at 1645–1650 cmϪ1 for the C᎐O
᎐
groups for structures 4. We expected to obtain the structures
1
3a–c but, in the H NMR spectra, the H-2 methine hydrogen
atom was not observed. To distinguish between arrangements
of the tautomeric structure of 3a–c, i.e. 4a–c, and an altern-
ative, e.g., 5 an X-ray crystal-structure analysis of 4a was
carried out (Fig. 4). It clearly demonstrates the five-membered
Scheme 2
of dienophilic compounds to yield 1,5-diazabicyclo[3.3.0]-
octane derivatives (derivatives of pyrazolo[1,2-a]pyrazoles),
while the addition of equimolar amounts of the same reagents
leads to the formation of the corresponding azomethine imines
and pyrazoles. Recently, aromatic azines have been shown to
react with dibenzoylacetylene to afford unexpected [4 ϩ 2]
cycloadducts such as 4,5-dibenzoyl-3,6-diarylpyridazines.22
From the above findings it may be appropriate to investigate
the reactivity of diarylaldazines 8a–c towards the diphenyl-
cyclopropenone 1 to compare their reactivity with 2a–c. Thus
two mol equivalents of 1 together with one mol equivalent of
an aldazine 8a–c were kept in ethanol at reflux for 12 h to afford
solid inden-1-one derivatives 9a–c (Scheme 3). The structure of
Fig. 4 Molecular structure of 4a in the crystal phase (the crystallo-
graphic numbering does not reflect the systematic numbering).
structure and shows that the adduct is a tautomer (enamine-like
structure) of 3a–c in the E-configuration.
It is clear that the pyrrolinone structures 3a–c tautomerize to
the enaminone structures 4a–c which are more stable, having
extended conjugation and hydrogen bonding.
Scheme 3
Formation of ∆4-pyrrolinones 4a–c may be rationalized as an
initial attack of one of the imino nitrogen atoms of 2a–c on the
electrophilic carbon C-2 or C-3 of cyclopropenone 1 giving
the immoniumbetaine 6a–c, followed by ring opening to afford
the ketene intermediate 7a–c. Subsequent cyclization by attack
of the ketene onto the iminium function (electrocyclization)
leads to imines 3a–c and hence to isomeric enaminones 4a–c
(Scheme 2).
products 9a–c was assigned on the basis of their spectral data.
1H NMR spectra showed only one imine-proton (CH᎐N),
᎐
at δ 7.97–8.03. 13C NMR spectra showed a signal between
δC 195.80–195.94 that was assigned for the carbonyl group of
the indenone system, and another signal at higher field between
δC 170.44 and 170.72 was assigned to the amidic carbonyl
group, in addition to a signal between δC 144.22–145.28 that
was attributed to the imine carbon atom.
The reaction of dienophilic compounds with diaryl azines
represents a valuable enlargement to synthetic heterocyclic
chemistry.20,21 Aldazines derived from aromatic aldehydes
undergo the so-called criss-cross addition with two mol equiv.
The formation of products 9a–c was rationalized as a formal
[2 ϩ 3] cycloaddition reaction between 1 and 8a–c to give
the ∆4-pyrrolin-3-ones 10a–c, which undergo an oxidative
rearrangement to afford ultimately the indenone derivatives 9a–
342
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Starting materials
N,NЈ-Diarylethane-1,2-diylidenediamines 2b,c and N,NЈ-
dicyclohexylethane-1,2-diylidenediamine 2a24,25 and diaryl
azines 8a–c26 were prepared as reported.
Reaction of N,NЈ-dicyclohexylethane-1,2-diylidenediamine 2a
and N,NЈ-diarylethane-1,2-diylidenediamines 2b,c with diphenyl-
cyclopropenone 1 (general procedure)
A solution of 1 (206 mg, 1.0 mmol) in ethanol (10 cm3) was
added to solutions of a diimine 2a–c (1.0 mmol) in ethanol
(20 cm3). The mixture was heated to reflux temperature for
2–5 h. After this period, orange crystals of the corresponding
enaminone 4a–c precipitated, which were filtered off and
recrystallized from ethanol and identified as follows.
(E )-1-Cyclohexyl-2-cyclohexylaminomethylene-4,5-diphenyl-
1,2-dihydropyrrol-3-one [(E )-4a]. Yield 180 mg (42%), mp 259–
260 ЊC as orange crystals (from ethanol); 1H NMR (d6-DMSO)
δ 0.95–1.92 (m, 20 H, cyclohexyl-CH2), 3.52–3.54 (m, 2 H,
cyclohexyl-CH), 6.99 (s, 1 H, CH), several multiplets at 7.03,
7.13, 7.27 and 7.27 (10 H, ArH), 7.98 (s, 1 H, NH); 13C NMR
(d6-DMSO)
δ 24.10, 24.35, 24.97, 26.10, 31.63, 33.97
(cyclohexyl-CH2), 56.05 and 56.33 (cyclohexyl-CH), 111.42,
114.05, 124.04, 127.34, 128.24, 127.66, 128.96, 129.64 (all
Ar–CH and vinylic CH), 129.18, 132.56, 134.20, 140.99, 148.82,
176.39; IR (KBr) 3380 (NH), 1645 (CO) cmϪ1; MS (70 eV) m/z
(%) 426 (Mϩ, 100), 425 (15), 409 (5), 383 (7), 369 (5), 344 (51),
327 (57), 261 (19), 248 (14), 178 (15), 55 (24), 41 (14), [Calc. for
C29H34N2O (426.6): C, 81.65; H, 8.03; N, 6.57. Found: C, 81.50;
H, 7.95; N, 6.51%].
(E )-1-(4-Methylphenyl)-2-(4-methylphenylaminomethylene)-
4,5-diphenyl-1,2-dihydropyrrol-3-one [(E )-4b]. Yield 264 mg
(60%), mp 208–210 ЊC as orange crystals (from ethanol); H
1
Scheme 4
NMR (d6-DMSO) δ 2.22 (s, 3 H, CH3), 2.25 (s, 3 H, CH3), 6.95
(s, 1 H, CH), several multiplets at 7.07, 7.13, 7.17 and 7.23
(18 H, ArH), 7.46 (s, 1 H, NH);
20.63 (2 × CH3), 116.40, 125.18, 127.72, 128.39, 128.46, 129.06,
129.92, 130.14, 130.28 and 131.0 (all Ar–CH and vinylic CH),
113.39, 120.86, 128.5, 131.15, 132.71, 134.20, 137.17, 137.95,
152.14, 177.33; IR (KBr) 3400 (NH), 1650 (CO) cmϪ1; MS
(70 eV) m/z (%) 442 (Mϩ, 100), 336 (7), 221 (6), 212 (4), 178 (5),
118 (9), 91 (11), 65 (4) [Calc. for C31H26N2O (442.6): C, 84.13;
H, 5.92; N, 6.33. Found: C, 84.31; H, 5.83; N, 6.30%].
c via the intermediates 11a–c–13a–c (Scheme 4). Eicher et al.
have isolated indenones as a result of oxidative processes during
the reaction of benzylidene azines with 1.23 Thus the aldazines
8a–c react with the dienophiles like 1 as do imines via a [2 ϩ 3]
cycloaddition reaction but not as azines via the criss-cross
addition reaction.
13C NMR (d6-DMSO) δ 20.33,
Conclusions
The present investigation clearly indicates that diaryl azines
react with diphenylcyclopropenone through a formal [3 ϩ 2]
cycloaddition reaction giving the non-isolable ∆4-pyrrolin-3-
ones 10a–c products, which undergo oxidative processes to
afford ultimately the indenone derivatives 9a–c. Similarly,
diimines react with diphenylcyclopropenone to afford the
∆4-pyrrolin-3-one derivatives which are more stable against air
oxidation due to high conjugation.
(E )-1-(4-Methoxyphenyl)-2-(4-methoxyphenylaminomethyl-
ene)-4,5-diphenyl-1,2-dihydropyrrol-3-one [(E )-4c]. Yield 315
mg (67%), mp 170–172 ЊC as orange crystals (from ethanol);
1H NMR (d6-DMSO) δ 3.70 (s, 3 H, OCH3), 3.71 (s, 3 H,
OCH3), 6.68 (s, 1 H, CH), several multiplets at 6.89, 7.0, 7.10,
7.18 and 7.25 (18 H, ArH), 7.42 (s, 1 H, NH); 13C NMR
(d6-DMSO) δ 55.19, 55.30 (2 × OCH3), 114.31, 114.58, 114.97,
117.84, 123.22, 124.94, 127.57, 128.24, 128.80, 129.92, 130.04,
and 131.94 (all Ar–CH and vinylic CH), 112.81, 120.71, 129.09,
130.94, 132.92, 133.82, 151.12, 157.51, 158.25, 175.96; IR (KBr)
3410 (NH), 1650 (CO) cmϪ1; MS (70 eV) m/z (%) 474 (Mϩ, 100),
458 (6), 352 (7), 237 (4), 178 (5), 134 (6), 123 (3), 77 (5) [Calc. for
C31H26N2O3 (474.6): C, 78.46; H, 5.52; N, 5.90. Found: C, 78.62;
H, 5.40; N, 5.81%].
Experimental
Uncorrected melting points were determined on a Griffin &
George apparatus. Elemental analyses were carried out by the
Microanalysis Center at Cairo University. IR spectra (KBr)
were recorded on a Shimadzu 470 spectrophotometer. 400 MHz
1H NMR and 100 MHz 13C NMR spectra were observed
on a Bruker AM 400 spectrometer. Mass spectra (70 eV,
electron-impact mode) were recorded on a JEOL JMS600
instrument. Preparative thin-layer chromatography (PLC)
used air-dried 1.0 mm thick layers of slurry-applied silica gel
Merck PF254 on 48 cm wide and 20 cm high glass plates and
toluene–ethyl acetate (2 : 1) as developing solvent. Zones
were detected by the colour or by quenching of indicator
fluorescence upon exposure to 254 nm light and eluted with
acetone.
Reaction of diarylaldazines 8a–c with diphenylcyclopropenone 1
(general procedure)
A solution of 1 (206 mg, 1.0 mmol) in ethanol (10 cm3) was
added to a solution of an aldazines 8a–c (0.5 mmol) in ethanol
(20 cm3) or toluene (30 cm3). The mixture was heated to reflux
temperature for 12 h before being concentrated and the residue
was subjected to PLC using toluene–ethyl acetate (2 : 1) as the
developing solvent to give one or two main zones. The faster
J. Chem. Soc., Perkin Trans. 1, 2002, 341–344
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moving one contained 9a, 9b or 9c respectively, while the more
slowly moving one contained the unchanged cyclopropenone
1. The zonal components were extracted, crystallized, and
identified as follows.
Data collection and processing. Nonius-Kappa CCD diffract-
ometer, graphite-monochromator Mo-Kα (radiation; 6293
reflections measured (θ = 24.18Њ), 4039 unique) merging at
R = 0.0317, linear and approx. isotropic crystal decay, ca. 23%
corrected during processing. Refinements on F 2, R1 = 0.0769
for 2411 reflections with I > 2σ(I ), 291 variables, wR2 = 0.2018
for all unique data, SHELXL program package.
Atomic coordinates, bond lengths and angles, and parameters
have been deposited at the Cambridge Crystallographic Data
Centre.†
3-[1Ј-(4-Methylbenzoyl)-2Ј-(4-methylbenzylidene)hydrazino]-
2-phenylinden-1-one 9a. Yield 120 mg (52%), mp 118–119 ЊC as
1
yellow crystals (from cyclohexane); H NMR (CDCl3) δ 2.34
(s, 3 H, CH3), 2.41 (s, 3 H, CH3), several multiplets at 7.11, 7.16,
7.24, 7.49, 7.53 and 7.61 (17 H, ArH), 8.03 (s, 1 H, CH᎐N);
᎐
13C NMR (CDCl3) δ 21.12, 21.35, 91.75, 108.75, 125.59, 126.07,
126.87, 127.84, 127.91, 129.07, 129.14, 129.36, 129.81, 130.52,
130.60, 131.60, 132.17, 138.69, 139.51, 144.27, 170.65, 195.96;
IR (KBr) 1690 (CO), 1645 (CO) cmϪ1; MS (70 eV) m/z (%) 457
(1), 456 (Mϩ, 48), 440 (14), 429 (4), 412 (2), 341 (72), 337 (58),
325 (44), 310 (65), 222 (68), 191 (28), 177 (82), 164 (18), 120
(37), 118 (100), 105 (37), 91 (87) [Calc. for C31H24N2O2 (456.6):
C, 81.55; H, 5.30; N, 6.14. Found: C, 81.42; H, 5.18; N, 6.10%].
Acknowledgements
The author is deeply indebted to the referees for their help in
revising the manuscript; also, thanks are due to Prof. Dr G.
Henkel, Duisburg University, Germany, for carrying out the
X-ray structure refinement and to Prof. Dr I. Farag, National
Research Center, Gizza, Egypt, for collecting the X-ray data.
3-[1Ј-(4-Methoxybenzoyl)-2Ј-(4-methoxybenzylidene)-
† CCDC reference number(s) 170858. See http://www.rsc.org/suppdata/
p1/b1/b109711n/ for crystallographic files in .cif or other electronic
format.
hydrazino]-2-phenylinden-1-one 9b. Yield 118 mg (48%), mp
85–89 ЊC as yellow crystals (from cyclohexane); 1H NMR
(CDCl3) δ 3.75 (s, 3 H, OCH3), 3.77 (s, 3 H, OCH3), several
multiplets at 6.75, 6.88, 7.09, 7.11, 7.24, 7.35, 7.49, 7.53, 7.58
References
and 7.85 (17 H, ArH), 7.99 (s, 1 H, CH᎐N); 13C NMR (CDCl3)
᎐
δ 55.26, 55.27, 91.52, 108.55, 113.89, 114.54, 126.15, 126.48,
127.12, 127.63, 127.92, 127.99, 128.43, 129.37, 130.58, 131.53,
132.73, 144.22, 158.96, 160.67, 170.72, 195.80; IR (KBr) 1690
(CO), 1645 (CO) cmϪ1; MS (70 eV) m/z (%) 489 (1), 488 (Mϩ,
20), 467 (14), 354 (18), 340 (44), 326 (65), 223 (68), 209 (12), 196
(20), 152 (82), 150 (18), 137 (100), 123 (70), 121 (48), 105 (33),
91 (77) [Calc. for C31H24N2O4 (488.6): C, 76.21; H, 4.95; N, 5.74.
Found: C, 76.11; H, 4.89; N, 5.63%].
1 T. Eicher and J. L. Weber, Top. Curr. Chem., 1975, 57, 1.
2 M. L. Deem, Synthesis, 1982, 701.
3 B. Musicki, J. Org. Chem., 1991, 56, 110.
4 T. Eicher and J. L. Weber, Tetrahedron Lett., 1974, 1381.
5 T. Eicher, F. Abdesakan, G. Franke and J. L. Weber, Tetrahedron
Lett., 1975, 3918.
6 T. Eicher, J. L. Weber and G. Chatila, Justus Liebigs Ann. Chem.,
1975, 1203.
7 T. Eicher and D. Krause, Tetrahedron Lett., 1979, 1213.
8 T. Eicher and G. Franke, Liebigs Ann. Chem., 1981, 1337.
9 M. Takahashi, T. Funaki, H. Honda, Y. Yokoyama and
H. Takimoto, Heterocycles, 1982, 19, 1921.
10 F. Stierli, R. Prewo, H. Bieri and H. Heimgartner, Helv. Chim. Acta,
1983, 66, 1366.
11 T. Eicher and R. Rohde, Synthesis, 1985, 916.
12 A. Kascheres, J. L. Reyes and S. M. Fonesca, Heterocycles, 1984, 22,
2529.
13 S. Chaloupka and H. Heimgartner, Chimia, 1978, 32, 468.
14 D. Döpp, M. A.-M. Gomaa, G. Henkel and A. M. Nour El-Din,
J. Heterocycl. Chem., 1995, 32, 603.
15 D. Döpp, M. A.-M. Gomaa, G. Henkel and A. M. Nour El-Din,
J. Chem. Soc., Perkin Trans. 2, 1996, 573.
16 M. A.-M. Gomaa, S. K. Mohamed and A. M. Nour El-Din,
J. Chem. Res. (S), 1997, 284.
17 M. A.-M. Gomaa and D. Döpp, J. Heterocycl. Chem., 1998, 35, 339.
18 M. A.-M. Gomaa, J. Chem. Res., 1997, (S) 444; M. A.-M. Gomaa,
J. Chem. Res., 1997, (M) 2679.
19 M. A.-M. Gomaa, A. M. Nour El-Din and A. A. Mohamed, Bull.
Chem. Soc. Jpn., 1999, 72, 471.
3-{1Ј-[4-(Dimethylamino)benzoyl]-2Ј-[4-(dimethylamino)-
benzylidene]hydrazino}-2-phenylinden-1-one 9c. Yield 130 mg
(50%), mp 176–178 ЊC as orange crystals (from cyclohexane);
1H NMR (CDCl3) δ 2.91 (s, 6H, NCH3), 2.92 (s, 6H, NCH3),
several multiplets at 6.52, 6.55, 6.67, 6.69, 7.11, 7.22, 7.26, 7.35,
7.44, 7.58, 7.60 (17 H, ArH), 7.97 (s, 1 H, CH᎐N); 13C NMR
᎐
(CDCl3) δ 40.21, 40.33 (4 × NCH3), 91.88, 107.81, 111.67,
112.70, 121.70, 123.07, 125.81, 126.68, 127.83, 127.88, 128.34,
129.08, 129.86, 130.30, 130.68, 131.02, 145.28, 150.62, 151.23,
170.44, 195.94; IR (KBr) 1690 (CO), 1645 (CO) cmϪ1; MS
(70 eV) m/z (%) 514 (Mϩ, 20), 499 (2), 484 (2), 471 (8), 425 (11),
365 (80), 338 (65), 322 (18), 294 (18), 282 (11), 264 (11), 263
(27), 193 (13), 178 (25), 164 (32), 149 (100), 134 (55), 121 (32),
105 (50), 91 (17), 84 (54), 77 (49) [Calc. for C33H30N4O2 (514.6):
C, 77.02; H, 5.88; N, 10.89. Found: C, 76.91; H, 5.79; N,
10.73%].
20 M. Häring and T. Wagner-Jauregg, Helv. Chim. Acta, 1957, 40, 852.
21 T. Wagner-Jauregg, Helv. Chim. Acta, 1969, 52, 1672.
22 M. A.-M. Gomaa and A. A. Aly, unpublished results.
23 T. Eicher, J. L. Weber and G. Chatila, Liebigs Ann. Chem., 1978,
1203.
24 J. M. Kliegman and R. K. Barnes, J. Org. Chem., 1970, 35, 3140.
25 J. M. Kliegman and R. K. Barnes, Tetrahedron, 1970, 26, 2555.
26 B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell,
Vogel’s Textbook of Practical Organic Chemistry, Longman,
London, 5th edn., 1991.
Crystal structure determination of compound 4a
Crystal data. C29H34N2O, M = 426.60. Trigonal, a =
32.814(2), c = 12.309(1) Å, α = 90.00Њ, T = 293 K, V = 11
478.1(14) Å3, Mo-Kα radiation (λ = 0.710 73 Å), space group
R-3, Z = 18, Dx = 1.111 Mg mϪ3. Dark orange prisms. Crystal
dimensions: 0.50 × 0.43 × 0.25 mm, µ(Mo-Kα) = 0.067 mmϪ1
F(000) = 4140.
,
344
J. Chem. Soc., Perkin Trans. 1, 2002, 341–344