A new synthesis of bis-enaminones via acylation of ketones

Article abstract of DOI:10.1055/s-2008-1067269

A short and efficient synthesis for a series of 1,6-diaryl-3,4- diarylaminohexa-2,4-diene-1,6-diones was developed. Based on the acylation-prototropism sequence during the reaction of various aryl methyl ketones with bis-imidoyl chlorides, the products were isolated in good yields. Substituted acetophenones, acetylthiophene, 3-acetylpyridine, and acetylferrocene can be integrated into this reaction as ketone component. Similarly, α-tetralone can be transformed with bis-electrophiles into the corresponding bis-enaminones. Treatment of 2-acetylpyridine with N,N′-bis(4-tolyl)ethanebis(imidoyl) dichloride yielded not only the expected bis-enaminone, but also a new quinolizine derivative which was structurally characterized by single crystal X-ray analysis. Analogously, pinacolone and cyclopropyl methyl ketone can readily be converted into bis-enaminones. Monoimidoyl chlorides showed the same reactivity, providing derivatives in high yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067269

PAPER
3071
A New Synthesis of Bis-Enaminones via Acylation of Ketones
S
ynthesis of Bis-E
u
naminones nther Buehrdel,a Rainer Beckert,*a Eva Petrlikova,b Petra Herzigova,b Vera Klimesova,b Jan Fleischhauer,a
Helmar Goerlsc
a
Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstr. 10, 07743 Jena, Germany
Fax +49(3641)948212; E-mail: c6bera@uni-jena.de
Faculty of Pharmacy, Charles University Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University, August-Bebelstr. 2, 07743 Jena, Germany
b
c
Received 28 May 2008; revised 16 June 2008
Dedicated to Prof. Branko Stanovnik, Ljubljana, on the occasion of his 70th birthday
carbocyclic compounds.4 In many cases, during acylation
of substrates with 4 a very fast prototropic shift takes
place forming enamino substructures. Our aim was there-
fore to develop a short and efficient route to derivatives of
Abstract: A short and efficient synthesis for a series of 1,6-diaryl-
3,4-diarylaminohexa-2,4-diene-1,6-diones was developed. Based
on the acylation-prototropism sequence during the reaction of vari-
ous aryl methyl ketones with bis-imidoyl chlorides, the products
were isolated in good yields. Substituted acetophenones, acetyl- type 2 exploiting this acylation–prototropism cascade.
thiophene, 3-acetylpyridine, and acetylferrocene can be integrated
into this reaction as ketone component. Similarly, a-tetralone can be
transformed with bis-electrophiles into the corresponding bis-
enaminones. Treatment of 2-acetylpyridine with N,N¢-bis(4-
tolyl)ethanebis(imidoyl) dichloride yielded not only the expected
bis-enaminone, but also a new quinolizine derivative which was
structurally characterized by single crystal X-ray analysis. Analo-
gously, pinacolone and cyclopropyl methyl ketone can readily be
converted into bis-enaminones. Monoimidoyl chlorides showed the
same reactivity, providing derivatives in high yields.
H
R2
R3
O
N
R1
R
1
H
Ar
N
O
N
NAr
O
3
Cl
R
R
Cl
R
2
3
4
O
NAr
O
Ar
H
Key words: acylations, ketones, tautomerism, enaminones, bis-
imidoyl chlorides
Scheme 1
Generally, the bis-imidoyl chlorides 4 are available by
chlorination of appropriate oxanilides 5 with phosphorus
pentachloride in toluene.4a However, the favored way of
obtaining oxanilides – the aminolysis of oxalyl chloride
with substituted anilines5 – has several disadvantages.
Thus, an additional base (triethylamine) for the binding of
HCl is necessary, which results in a mixture of oxanilides
and amine hydrochloride. In the course of time-consum-
ing purification steps and drying, the pure oxanilide is
converted into 4 by treatment with PCl5 in the final step.
In addition, the oxanilides 5 were obtained as large crys-
tals, which needed substantial longer chlorination times
than in a fine disperse, amorphous state due to their insol-
ubility. We have now optimized this process in the form
of a two-step one-pot protocol for the preparation of the
bis-electrophiles 4. In the first step, the oxanilides 5 were
prepared by the addition of oxalyl chloride (one equiva-
lent) to aniline (two equivalents) in toluene without any
additional base. Within a few minutes, a slurry of pure 5
in toluene was obtained, which was directly chlorinated
(PCl5) without further purification. After recrystallization,
the bis-arylimidoyl chlorides 4a–c were obtained in good
yields (70–80%) as yellow crystals (Scheme 2). In order
to achieve better solubility of the products, derivative 4d
was synthesized. It can be isolated by the same improved
procedure as a viscous yellow oil.
Enaminones 1 are versatile and readily obtainable build-
ing blocks and their chemistry has received considerable
attention in recent years, mainly for the synthesis of het-
erocyclic compounds.1 In contrast, data for bis-enamin-
ones 2 (Figure 1) are quite rare. These bifunctional
compounds might offer the possibility of synthesizing
new and interesting bis-heterocycles. In addition, bis-
enaminones 2 should be of interest for the preparation of
dinuclear metal complexes. 1,6-Diaryl/alkyl-1,3,4,6-
tetrones,2 which are easily available by Claisen condensa-
tion of aryl/alkyl methyl ketones with diethyl oxalate, pro-
vide a synthetic entry via aminolysis reactions to
compounds of type 2. However, their aminolysis is only
described with vicinal diamines such as o-phenylenedi-
amine or 1,2-diaminocyclohexane and resulted in the for-
mation of cyclic products of the piperazine type.3
Based on our previous experiences, another synthetic
pathway to compounds of type 2 should consist in the acy-
lation reaction of aryl methyl ketones 3 with bis-arylimi-
doyl chlorides 4 (Scheme 1). During the last decade, we
demonstrated that the latter derivatives are excellent (and
selective) bis-electrophiles that can be employed in a wide
range as C2-building blocks for heterocyclic as well as for
Acetophenone (3a, R = Ph) reacts readily with the bis-
electrophile 4b. Under quite mild conditions (THF in the
presence of t-BuOK at –30 °C), a single product (TLC)
SYNTHESIS 2008, No. 19, pp 3071–3080
Advanced online publication: 05.09.2008
DOI: 10.1055/s-2008-1067269; Art ID: Z12908SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
8

3072
G. Buehrdel et al.
PAPER
toluene
r.t.
PCl5
toluene, 110 °C
H
Ar
Cl
O
ArHN
O
ArN
Cl
Cl
O
N
ArNH2
+
R
O
R
2
O
Cl
O
NHAr
NAr
NAr
5
4
t-BuOK
THF, –78 °C
N
O
R
Ar
H
3
Cl
+
4a Ar = Ph (82%)
4b Ar = 4-Tol (93%)
4c Ar = 4-BrC6H4 (81%)
O
Cl
4
H
Ar
O
N
NAr
4d Ar = 3,5-(n-C8H17OOC)2C6H3 (94%)
4e Ar = 4-MeOC6H4 (77%)
3i
N
O
Scheme 2
Ar
H
2p–r
was isolated in high yields as yellow crystals and recrys-
tallized from DMF. Due to the existence of intermolecular
hydrogen bonds, the product is relatively insoluble in oth-
er common solvents. Elemental analysis (and MS data,
see discussion below, Scheme 3) confirmed the presence
of a 2:1 acylation product 2a. Evidence for the high sym-
metry in this novel 1,6-diphenyl-3,4-ditolylaminohexa-
2,4-diene-1,6-dione (2a) (Scheme 3) was provided by sin-
Scheme 3
and the signals for the methine protons were observed at
2.24 ppm. In the 13C NMR spectrum, the signal for the
carbonyl carbons was observed at 189.9 ppm whereas the
signal for the methine groups appeared at higher fields at
96.1 ppm.
gle sets of signals in its 1H and 13C NMR spectra. The NH Employing the same procedure, the bis-imidoyl chlorides
protons of derivative 2a showed resonance at 12.40 ppm, 4a–e as well as the acetophenone derivatives 3b–d were
Table 1 Bis-enaminones of Type 2
2
3
4
R
Ar
Mp (°C)6
232
242
218
240
254
236
238
oil
2a
2b
2c
2d
2e
2f
3a
3b
3a
3a
3c
3d
3d
3b
3e
3f
4b
4b
4a
4b
4b
4b
4c
4d
4b
4b
4b
4c
4b
4c
4e
4a
4b
4c
4a
4b
4a
4b
4e
Ph
4-MeC6H4
4-MeC6H4
Ph
4-MeC6H4
Ph
4-MeC6H4
4-BrC6H4
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
2-thienyl
3-pyridyl
ferrocenyl
4-MeC6H4
2-pyridyl
2-pyridyl
4-MeOC6H4
see text
see text
see text
t-Bu
Ph
4-MeC6H4
4-MeC6H4
4-BrC6H4
3,5(n-C8H17OOC)2C6H3
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-BrC6H4
4-MeC6H4
4-BrC6H4
4-MeOC6H4
Ph
2g
2h
2i
256
223
dec.
254
233
237
196
198
204
246
167
146
186
181
162
2j
2k
2l
3g
3a
3h
3h
3d
3i
2m
2n
2o
2p
2q
2r
2s
2t
3i
4-MeC6H4
4-BrC6H4
Ph
3i
3j
3j
t-Bu
4-MeC6H4
Ph
2u
2v
2w
3k
3k
3k
c-Pr
c-Pr
4-MeC6H4
4-MeOC6H4
c-Pr
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis-Enaminones
3073
integrated into this reaction (Table 1). The derivatives Other methyl ketones such as 2-acetylthiophene (3e), 3-
2b–g were isolated as yellow crystalline compounds, acetylpyridine (3f) and acetylferrocene (MeCOFc) 3g re-
which showed chemical properties similar to those of 2a. acted with 4b under similar mild conditions to yield the
The reaction of 4d with 4-methylacetophenone (3b) re- corresponding 1,6-diaryl-3,4-ditolylaminohexa-2,4-di-
sulted in the soluble derivative 2h, caused by the existence ene-1,6-diones 2 (Table 1). Analogously, a-tetralone (3i)
of four lipophilic n-octyl ester substructures.
was transformed with bis-electrophiles 4 into the corre-
sponding enaminones of types 2p–r (Scheme 2), which in
contrast to those of the acetophenone series are well solu-
ble in most common solvents.
The mass spectra (EI) of derivatives 2 showed some inter-
esting features: on the one hand, no [M]+ peak was detect-
ed in any of the cases. However, at mild ionization
conditions and application of relatively large probe The presence of an additional electrophilic center in 2-
amounts, a weak peak for the molecule ion was detected. acetylpyridine (3h) guaranteed the formation of a further
On the other hand, the base peak measured in all cases was product. Using TLC, not only the expected yellow hexa-
assigned to pyrylium ion 6 (Scheme 4), which resulted 2,4-diene-1,6-diones 2m,n but also a red side product 7
from the extrusion reaction of an acyl residue from [M]+. was detected; both products were separated by column
As a result of two donor-acceptor chromophores in the chromatography. After recrystallization, 7 was obtained
molecule, compounds 2 formed dark yellow solutions as red, green shining crystals. Elemental analysis as well
(Table 1); for example 2b absorbed in CHCl3 at lmax = 396 as MS data confirmed the presence of a 2:1 acylation
nm, (log e = 3.9).
product. However, the 1H as well as the 13C NMR spectra
only showed complex sets of signals located mainly in the
part of aromatic protons/carbons. The structure of 7 was
established by single crystal X-ray analysis (Figure 2).
Thus, compound 7 can be regarded as a derivative of 1H-
1-oxoquinolizine (Scheme 5). The bond lengths and an-
gles are in the expected range for this structure; only the
bond N3–C3 was somewhat shortened. The solutions of 7
are dark red which could be interpreted as result of its
cross-conjugated system. Compound 7 showed a broad
and strong absorption between 450 and 550 nm in its
UV/vis spectrum (CHCl3), with a maximum at 515 nm
(log e = 4.3). Furthermore, 7 is electrochemically active
and could be reduced reversibly. Employing square wave
measurements, two peaks at –0.718 V and at –1.196 V can
be ascribed as two different electron transfer steps. The
quasi-reversibility of the reduction was confirmed by cy-
clovoltammetric measurements (DE1RED,OX = 0.122 V,
DE2RED,OX = 0.085 V). The resulting semiquinone forma-
tion constant is relatively high (KSEM = 1.26 × 108).
H
Ar
H
Ar
N+
N
ArHN
ArHN
2+•
•
RCO
O+
6
R
–
O
6'
R
Scheme 4
Further structural details were obtained from a single
crystal X-ray analysis of 2e. The result of this analysis
showed that 2e is a monomer in the solid state (Figure 1).
The bond lengths and angles were in the expected range;
only the bonds between N1–C3/C4–N2 were somewhat
shortened. Due to a strong hydrogen bridge between the
NH groups and the oxygen atoms of the carbonyl groups,
the cis configuration predominated in the solid state.
Figure 2 ORTEP plot (50% probability ellipsoids) of the solid state
molecular structure of 7, selected bond lengths in Å: O1–C1 1.237(2),
O2–C12 1.235(2), N–C4 1.419(2), N–C6 1.388(3), N–C10 1.400(2),
N2–C4 1.273(2), N3–C3 1.350(2), C1–C2 1.415(3), C2–C3 1.367(3),
C3–C4 1.488(3), C6–C7 1.340(3), C7–C8 1.442(3), C8–C9 1.437(3),
C9–C10 1.353(3), C1–C10 1.494(3), C8–C11 1.381(3), C11–C12
1.441(3).
Figure 1 ORTEP plot (50% probability ellipsoids) of the solid state
molecular structure of 2e, selected bond lengths in Å: O1–C1
1.250(6), O2–C6 1.249(6), N1–C3 1.345(6), N2–C4 1.350(6), C1–C2
1.438(6), C2–C3 1.372(6), C3–C4 1.499(6), C4–C5 1.372(6), C5–C6
1.436(6).
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

3074
G. Buehrdel et al.
PAPER
The formation of bicyclic 7 can be rationalized by the fol- BuOK under the formation of turquoise solutions of delo-
lowing mechanism: initial attack of the enolate of 3h at 4 calized anions, the neutral form being regenerated upon
resulted in the intermediate A. A second enolate then at- treatment with acids. Generally, these derivatives showed
tacks the 4-position (A¢) of the pyridine ring forming in- the characteristic chemical behavior of isatines which
termediate B, which finally was oxidized to yield 7 were already prepared earlier starting from 4.7 Their for-
(Scheme 5).
mation can be explained by intramolecular ortho-attack of
the firstly formed acylation product C¢, followed by pro-
ton shift and rearomatization (Scheme 6). The 1H as well
as the 13C NMR spectra of 8 displayed complex sets of
signals due to dynamic interconversion processes of E/Z
forms.
O
O
C+
4b
+
3h
2m
+
N+
A
N
A'
NHTol
NHTol
NHTol
Py
NTol
O
NTol
Finally, we tested the synthetic concept on ‘simple’ imi-
doyl chlorides. For this reason, the imidoyl chloride 10
was synthesized from benzanilide 9. Recently, this con-
cept was successfully applied for the synthesis of b-bro-
modifluoromethyl b-enaminoketones,8a as well as for a
short way to quinolones starting from acetophenones and
trifluoroacetimidoyl chlorides.8b In both cases sodium hy-
dride had been used as the base. We substituted this base
by the cheaper and easier to handle t-BuOK. Thus, 4-
methylacetophenone (3b) reacted under similar mild con-
ditions as described above readily with 10 yielding only a
single product (TLC), which was isolated in high yield as
yellow crystals. Elemental analysis and MS data con-
firmed the presence of a 1:1 acylation product 11d. In its
1H NMR, characteristic signals for the NH proton at
12.79 ppm, and the methine proton at 6.03 ppm were de-
tected. The 13C NMR signals at 189.9 ppm (C=O) and at
86.9 ppm (CH=) gave further evidence for the structure of
an enaminone. Analogously, pinacolone (3j), cyclopropyl
methyl ketone (3k) and acetone (3l) could successfully be
transformed into the corresponding enaminone 11
(Scheme 7).
O
Py
O
Ox
H
O
N
7
N
B
NHTol
NTol
NTol
Scheme 5
The synthetic concept presented here is not only restricted
to aryl methyl ketones. In a smooth reaction, pinacolone
(3j) and cyclopropyl methyl ketone (3k) were converted
into 1,6-dialkyl-3,4-diarylaminohexa-2,4-diene-1,6-di-
ones of type 2. These new bis-enaminones were isolated
as yellow, well soluble crystalline compounds (Table 1).
Whereas in the case of ketone 3j, only traces of a red by-
product (derivatives of isatine) were detected, the use of
3k allowed the isolation of compounds 8b,c as red crys-
tals. Elemental analysis and MS data confirmed the pres-
ence of 1:1 cyclization products 8b,c (Scheme 6). In the
1H NMR spectrum of 8b, a singlet at 2.4 ppm indicated an
intramolecular acylation reaction within the diimino sub-
structure. Dark red 8 was easily deprotonated with t-
Based on the acylation reaction of aryl methyl ketones 3
with bis-imidoyl chlorides 4, a short and efficient synthe-
sis for a series of 1,6-diaryl-3,4-diarylaminohexa-2,4-di-
ene-1,6-diones 2 was developed. The products 2 were
isolated as yellow crystalline compounds in high yields.
The chemical nature of the starting ketone can be varied
in a wide range from substituted acetophenones to
acetylthiophene (3e), 3-acetylpyridine (3f) and acetylfer-
rocene 3g. As a cyclic version of acetophenones, a-tetra-
lone (3i) was successfully transformed with 4 into the
corresponding enaminones of type 2. Whereas most ke-
tones gave only one main product, the use of 2-acetylpy-
ridine (3h) additionally yielded the quinolizine derivative
Y
Y
N–
O
C–
Cl
N
O
4
3k
2u–w
+
+
Cl
R
R
C
C'
NAr
NAr
NAr
Y
N
R
H
O
8
Y = Me, MeO
Scheme 6
O
H
O
Tol
H
Tol
N
NTol
O
N
R
t-BuOK
THF, –78°C
PCl5
Cl
R
11
CF3
CF3
CF3
9
11a R = Me (69%)
11b R = c-Pr (82%)
11c R = t-Bu (79%)
11d R = 4-Tol (86%)
10
Scheme 7
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis-Enaminones
3075
Bis-imidoyl Chloride 4d
Yield: 94%; yellow oil.
7. Its formation can easily be explained due to the exist-
ence of the electrophilic g-carbon in the acylated pyridine
ring. The synthetic concept is not only restricted to aryl 1H NMR (250 MHz, CDCl3): d = 7.99 (s, 2 H), 7.95 (s, 4 H), 4.37
(t, J = 7 Hz, 8 H, OCH2), 1.81–0.86 (m, 60 H).
13C NMR (63 MHz, CDCl3): d = 165.1 (C=O), 146.0, 132.2, 132.1,
126.0, 125.3, 65.8 (OCH2), 31.8, 29.2, 28.6, 26.0, 22.6, 14.0.
MS (EI): m/z (%) = 902 (2, [M+]), 450 (10), 320 (10), 69 (80), 43
(100).
methyl ketones. Pinacolone (3j) as well as cyclopropyl
methyl ketone (3k) were readily converted into enamin-
ones 2. Monoimidoyl chlorides such as 10 showed the
same reactivity. The reaction is exemplified with four dif-
ferent ketones giving the corresponding products 11 in
high yields.
1,6-Diaryl/alkyl-3,4-diarylaminohexa-2,4-diene-1,6-diones 2;
General Procedure
The reagents described in the following section were purchased
from commercial sources and were used directly unless otherwise
stated in the text. All solvents were of reagent grade and were dried
according to common practice and were distilled prior to use. The
N,N¢-bis-(4-methoxyphenyl)oxaldiimidoyl chloride (4e) was syn-
thesized according to literature.4a Reactions were monitored by
TLC, carried out on 0.2 mm Merck silica gel plates (60 F254). The
1H and 13C NMR spectra were recorded on Bruker Avance 250 and
400 spectrometers; shifts are relative to the signals of the solvent.
Melting points were measured with a Galen III apparatus (Boëtius
system) or with the Kofler apparatus and are uncorrected.
A solution of the corresponding aryl/alkyl ketone 3 (12 mmol) in
anhyd THF (50 mL) was cooled down to –30 °C and t-BuOK (2.7
g, 24 mmol) was added. To the solution was added the correspond-
ing bis-arylimidoyl chloride 4 (6 mmol). The deep red mixture was
stirred at 10 °C for 30 min. The mixture was acidified by addition
of HCl to pH 7 and then diluted with H2O (500 mL). The yellow
precipitate was collected by filtration, washed with Et2O (20 mL)
and dried. Recrystallization from DMF gave pure derivatives of
type 2. The following purification was employed for 2h, 2k, 2m–w:
The crude product was dissolved in CHCl3 (100 mL) and the solu-
tion was dried (Na2SO4) and filtered over a short column of SiO2.
After removing the solvent in vacuo, the product was purified by
column chromatography on silica gel (CHCl3–n-heptane) or by re-
crystallization from CHCl3–n-heptane (Table 1).
Bis-imidoyl Chlorides 4; General Procedure
To a solution of the corresponding aniline (0.5 mol) in toluene (400
mL) was added oxalyl chloride (33.0 g, 0.26 mol) over 10 min. A
slurry of 5 was formed, and the mixture was stirred for 20 min at r.t.
To the slurry PCl5 (105 g, 0.505 mol) was added. The mixture was
refluxed until no further HCl evolved. The dark yellow mixture was
concentrated in vacuo to dryness and the crude product was recrys-
tallized from toluene–n-heptane.
1,6-Diphenyl-3,4-ditolylaminohexa-2,4-diene-1,6-dione (2a)
Yield: 83%; yellow crystals; mp 232 °C.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.40 (s, 2 H, NH),
8.00 (m, 4 H, CHphenyl), 7.57 (m, 4 H, CHphenyl), 7.51 (m, 2 H,
CHphenyl), 7.03 (d, J = 8 Hz, 4 H, CHtolyl), 6.81 (d, J = 8 Hz, 4 H,
CHtolyl), 6.41 (s, 2 H, =CH), 2.24 (s, 6 H, CH3).
Bis-imidoyl Chloride 4a
Yield: 82%; yellow crystals; mp 115 °C.
1H NMR (250 MHz, CDCl3): d = 7.53–7.44 (m, 4 H), 7.33–7.27 (m,
2 H), 7.16–7.13 (m, 4 H).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 189.9 (C=O), 154.5,
139.3, 135.9, 134.8, 132.8, 129.8, 129.0, 127.8, 122.0, 96.1, 20.8.
Anal. Calcd for C32H28N2O2: C, 81.33; H, 5.97; N, 5.93. Found: C,
81.12; H, 5.95; N, 5.97.
13C NMR (63 MHz, CDCl3): d = 145.8, 138.7, 129.0, 127.0, 120.4.
1,6-Ditolyl-3,4-ditolylaminohexa-2,4-diene-1,6-dione (2b)
Yield: 91%; yellow crystals; mp 242 °C.
Bis-imidoyl Chloride 4b
Yield: 93%; yellow crystals; mp 111 °C.
IR (ATR): 3025, 2921, 1585, 1550, 1512, 1465, 1253, 1049, 772,
689 cm–1.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.45 (s, 2 H, NH),
7.89 (d, J = 8 Hz, 4 H, CHtolyl), 7.30 (d, J = 8 Hz, 4 H, CHtolyl), 7.01
(d, J = 8 Hz, 4 H, CHtolyl), 6.79 (d, J = 8 Hz, 4 H, CHtolyl ), 6.41 (s,
2 H, =CH), 2.37 (s, 6 H, CH3), 2.20 (s, 6 H, CH3).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 189.7 (C=O), 162.5
(C-1), 154.3, 136.7, 136.0, 134.6, 129.8, 129.6, 127.9, 121.8, 96.0
(CH), 21.5, 20.8.
1H NMR (250 MHz, CDCl3): d = 7.17 (d, J = 8 Hz, 4 H), 6.99 (d,
J = 8 Hz, 4 H), 2.30 (s, 6 H, CH3).
13C NMR (63 MHz, CDCl3): d = 143.0, 137.8, 136.8, 129.5, 120.9,
21.1.
Bis-imidoyl Chloride 4c
Yield: 81%; yellow crystals; mp 191 °C.
1H NMR (250 MHz, CDCl3): d = 7.58 (d, J = 8 Hz, 4 H), 7.02 (d,
J = 8 Hz, 4 H).
13C NMR (63 MHz, CDCl3): d = 144.4, 139.1, 132.2, 122.3, 120.4.
MS (EI): m/z (%) = 500 (1, [M+]), 482 (5, [M – H2O+]), 381 (90),
119 (100, [C8H7O+]).
UV/vis (CHCl3): lmax (log e) = 396 nm (3.9).
Oxanilide 5d
Yield: 89%; white crystals; mp 184 °C (toluene–n-heptane).
1H NMR (250 MHz, CDCl3): d = 9.51 (s, 2 H, NH), 8.53 (s, 6 H),
4.37 (t, J = 7 Hz, 8 H, OCH2), 1.81–0.86 (m, 60 H).
Anal. Calcd for C34H32N2O2: C, 81.57; H, 6.44; N, 5.66. Found: C,
81.28; H, 6.68; N, 5.73.
1,6-Diphenyl-3,4-diphenylaminohexa-2,4-diene-1,6-dione (2c)
Yield: 85%; yellow crystals; mp 218 °C.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.44 (s, 2 H, NH),
8.03–6.89 (m, 20 H, CHphenyl), 6.48 (s, 2 H, =CH).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 190.2 (C=O), 154.2
(C-1), 139.3, 138.4, 132.4, 129.8, 129.3, 127.8, 125.3, 121.9, 96.7
(CH).
13C NMR (63 MHz, CDCl3): d = 165.1 (C=O), 157.4, 136.5, 132.2,
127.6, 124.6, 65.9 (OCH2), 31.8, 29.2, 28.6, 26.0, 22.6, 14.1.
MS (EI): m/z (%) = 864 (1, [M+]), 405 (30), 293 (40), 43 (80,
+
[C7H7 ]).
Anal. Calcd for C50H76N2O10: C, 69.41; H, 8.85; N, 3.24. Found: C,
69.34; H, 8.87; N, 3.10.
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

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PAPER
1,6-Ditolyl-3,4-bis(3,5-dicarboxyoctylphenylamino)hexa-2,4-
Anal. Calcd for C30H24N2O2: C, 81.06; H, 5.44; N, 6.30. Found: C,
80.95; H, 5.48; N, 6.37.
diene-1,6-dione (2h)
Yield: 63%; yellow oil.
1,6-Ditolyl-3,4-diphenylaminohexa-2,4-diene-1,6-dione (2d)
Yield: 87%; yellow crystals; mp 240 °C.
1H NMR (250 MHz, CDCl3): d = 12.36 (s, 2 H, NH), 7.94 (d, J = 8
Hz, 4 H, CHarom), 7.52 (s, 4 H, CHarom), 7.31 (d, J = 8 Hz, 4 H,
CHarom), 7.26 (s, 2 H, CHarom), 6.54 (s, 2 H, =CH), 4.19 (t, J = 7 Hz,
8 H, CO2CH2), 2.45 (s, 6 H, CH3), 1.62–0.86 (m, 60 H, CH2).
13C NMR (63 MHz, CDCl3): d = 190.7 (C=O), 164.7 (C=O), 153.0,
143.1, 138.4, 136.1, 131.7, 129.3, 127.7, 127.0, 126.5, 97.2, 65.6
(OCH2), 31.8, 29.1, 28.6, 28.4, 25.8, 22.6, 21.6 (ArCH3), 14.1
(CH3).
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.43 (s, 2 H, NH),
7.91 (d, J = 8 Hz, 4 H, CHarom), 7.37–6.88 (m, 14 H, CHarom), 6.43
(s, 2 H, =CH), 2.39 (s, 6 H, CH3).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 190.0 (C=O), 153.9
(C-1), 142.7, 138.5, 136.7, 129.8, 129.6, 129.3, 127.9, 121.8, 96.6,
21.5.
Anal. Calcd for C32H28N2O2: C, 81.33; H, 5.97; N, 5.93. Found: C,
81.38; H, 6.96; N, 5.88.
MS (EI): m/z (%) = 1096 (1, [M+]), 1012 (10), 978 (100), 405 (30),
119 (60, [C7H7 ]).
+
MS (ESI, MeOH–CHCl3): m/z = 1119 (100%, [M + Na+]).
1,6-Bis(4-bromophenyl)-3,4-ditolylaminohexa-2,4-diene-1,6-di-
one (2e)
Yield: 90%; yellow crystals; mp 254 °C.
Anal. Calcd for C68H92N2O10: C, 74.42; H, 8.45; N, 2.55. Found: C,
74.01; H, 8.29; N, 2.45.
IR (ATR): 3024, 2923, 1583, 1560, 1513, 1461, 1249, 1070, 1005,
778 cm–1.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.43 (s, 2 H, NH),
7.97 (d, J = 8 Hz, 4 H, CHarom), 7.70 (d, J = 8 Hz, 4 H, CHarom),
7.00 (d, J = 8 Hz, 4 H, CHarom), 6.73 (d, J = 8 Hz, 4 H, CHtolyl), 6.47
(s, 2 H, =CH), 2.21 (s, 6 H, CH3).
1,6-Bis(2-thienyl)-3,4-ditolylaminohexa-2,4-diene-1,6-dione (2i)
Yield: 81%; yellow crystals; mp 256 °C.
IR (ATR): 3076, 3020, 2917, 1590, 1553, 1512, 1461, 1409, 1304,
1260, 1064, 789, 766, 719 cm–1.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.04 (s, 2 H, NH),
8.01 (d, J = 4 Hz, 2 H, CHthienyl), 7.90 (d, J = 4 Hz, 2 H, CHthienyl),
7.19 (m, 2 H, CHthienyl), 6.99 (d, J = 8 Hz, 4 H, CHtolyl), 6.74 (d, J = 8
Hz, 4 H, CHtolyl), 6.38 (s, 2 H, =CH), 2.21 (s, 6 H, CH3).
MS (EI): m/z (%) = 632 (2), 630 (5), 628 (2, [M+]), 447 (50), 445
(100), 315 (10), 183 (50).
UV/vis (CHCl3): lmax (log e) = 400 nm (3.7).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 183.1 (C=O), 153.8,
146.4, 135.8, 134.6, 133.5, 130.9, 129.8, 129.0, 121.8, 96.1, 20.8
(CH3).
Anal. Calcd for C34H26Br2N2O2: C, 60.97; H, 4.16; Br, 25.35; N,
4.44. Found: C, 61.00; H, 4.16; Br, 25.01; N, 4.08.
UV/vis (CHCl3): lmax (log e) = 403 nm (4.1).
1,6-Bis(4-methoxyphenyl)-3,4-ditolylaminohexa-2,4-diene-1,6-
dione (2f)
Yield: 83%; yellow crystals; mp 236 °C.
Anal. Calcd for C28H24N2O2S2: C, 69.35; H, 4.99; N, 5.78; S, 13.23.
Found: C, 69.08; H, 5.03; N, 5.97; S, 13.09.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.44 (s, 2 H, NH),
8.01 (d, J = 8 Hz, 4 H, CHarom), 7.02 (d, J = 8 Hz, 4 H, CHarom), 6.98
(d, J = 8 Hz, 4 H, CHarom), 6.74 (d, J = 8 Hz, 4 H, CHtolyl), 6.40 (s,
2 H, =CH), 3.83 (s, 6 H, OCH3), 2.20 (s, 6 H, CH3).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 188.8 (C=O), 162.8,
153.9, 135.9, 134.3, 131.7, 130.0, 129.7, 121.6, 114.3, 95.6, 55.9
(OCH3), 20.8 (CH3).
1,6-Bis(3-pyridyl)-3,4-ditolylaminohexa-2,4-diene-1,6-dione
(2j)
Yield: 82%; yellow crystals; mp 223 °C.
IR (ATR): 3025, 2917, 1584, 1547, 1515, 1462, 1258, 1016, 780,
685 cm–1.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.42 (s, 2 H, NH),
9.20 (s, 2 H, CHpyridyl), 8.74 (m, 2 H, CHpyridyl), 8.36 (m, 2 H,
CHpyridyl), 7.53 (m, 2 H, CHpyridyl), 7.03 (d, J = 8 Hz, 4 H, CHtolyl),
6.81 (d, J = 8 Hz, 4 H, CHtolyl), 6.52 (s, 2 H, =CH), 2.25 (s, 6 H,
CH3).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 188.3 (C=O), 154.9,
152.8, 149.1, 135.5, 135.3, 135.1, 134.3, 129.8, 124.1, 122.2, 96.3
(CH), 20.8 (CH3).
MS (EI): m/z (%) = 532 (1, [M+]), 514 (10, [M – H2O+]), 397 (100),
+
135 (100, [C8H7O2 ]).
Anal. Calcd for C34H32N2O4: C, 78.67; H, 6.06; N, 5.26. Found: C,
78.40; H, 5.94; N, 5.22.
1,6-Bis(4-methoxyphenyl)-3,4-bis(4-bromophenylamino)hexa-
2,4-diene-1,6-dione (2g)
Yield: 86%; yellow crystals; mp 238 °C.
UV/vis (CHCl3): lmax (log e) = 397 nm (4.5).
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.23 (s, 2 H, NH),
8.03 (d, J = 8 Hz, 4 H, CHarom), 7.36 (d, J = 8 Hz, 4 H, CHarom), 7.04
(d, J = 8 Hz, 4 H, CHarom), 6.81 (d, J = 8 Hz, 4 H, CHarom), 6.51 (s,
2 H, =CH), 3.86 (s, 6 H, OCH3).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 189.4 (C=O), 163.2
(C-1), 152.8, 138.0, 132.1, 131.8, 130.2, 123.6, 117.1, 114.5, 97.5
(CH), 56.0 (OCH3).
Anal. Calcd for C30H26N4O2: C, 75.93; H, 5.52; N, 11.81. Found: C,
75.93; H, 5.53; N, 11.85.
1,6-Diferrocenyl-3,4-ditolylaminohexa-2,4-diene-1,6-dione (2k)
Yield: 91%; red crystals; mp >250 °C (dec.)
IR (ATR): 3078, 2917, 2859, 1603, 1559, 1519, 1475, 1264, 1094,
816, 798 cm–1.
1H NMR (250MHz, CDCl3): d = 12.21 (s, 2 H, NH), 6.99 (d, J = 8
Hz, 4 H, CHtolyl), 6.88 (d, J = 8 Hz, 4 H, CHtolyl), 5.70 (s, 2 H, =CH),
4.79 (s, 4 H, C5H5), 4.47 (s, 4 H, C5H5), 4.16 (s, 10 H, C5H5), 2.25
(s, 6 H, CH3).
13C NMR (63 MHz, CDCl3): d = 194.5 (C=O), 152.1, 136.1, 134.1,
129.4, 121.3, 96.8 (CH), 81.6 (1-C5H5), 71.7 (C5H5), 69.9 (C5H5),
68.7 (C5H5), 20.8.
MS (EI): m/z (%) = 664 (1), 662 (2), 660 (1, [M+]), 646 (2), 644 (5),
642 (2, [M – H2O+]), 529 (50), 527 (100), 625 (50, [M – C8H7O2 ]),
+
+
173 (70), 135 (90, [C8H7O2 ]).
Anal. Calcd for C32H26Br2N2O4: C, 58.03; H, 3.96; N, 4.23. Found:
C, 58.02; H, 3.92; N, 4.18.
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

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Synthesis of Bis-Enaminones
3077
MS (EI): m/z (%) = 690 (20), 689 (30), 688 (80), 687 (30, [M+]), 583
(20), 475 (100), 228 (20).
1,6-Bis(4-methoxyphenyl)-3,4-bis(4-methoxyphenyl)amino-
hexa-2,4-diene-1,6-dione (2o)
Yield: 89%; yellow crystals; mp 196 °C.
UV/vis (CHCl3): lmax (log e) = 389 (4.5), 487 nm (3.8).
1H NMR (250 MHz, CDCl3): d = 12.40 (s, 2 H, NH), 7.99 (d, J = 8
Hz, 4 H, CHarom), 6.98 (d, J = 8 Hz, 4 H, CHarom), 6.72 (d, J = 8 Hz,
4 H, CHarom), 6.65 (d, J = 8 Hz, 4 H, CHarom), 6.29 (s, 2 H, =CH),
3.90 (s, 6 H, OCH3), 3.76 (s, 6 H, OCH3).
13C NMR (63 MHz, CDCl3): d = 189.1 (C=O), 162.6, 157.0, 154.7,
132.1, 131.3, 129.3, 123.3, 114.4, 113.8, 94.7, 55.44 (OCH3), 55.36
(OCH3).
Anal. Calcd for C40H36Fe2N2O2: C, 69.79; H, 5.27; N, 3.83. Found:
C, 69.35; H, 5.15; N, 3.83.
1,6-Ditolyl-3,4-bis(4-bromophenylamino)hexa-2,4-diene-1,6-di-
one (2l)
Yield: 82%; yellow crystals; mp 254 °C.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.24 (s, 2 H, NH),
7.94 (d, J = 8 Hz, 4 H, CHarom), 7.37 (d, J = 8 Hz, 4 H, CHarom), 7.32
(d, J = 8 Hz, 4 H, CHarom), 6.83 (d, J = 8 Hz, 4 H, CHtolyl), 6.52 (s,
2 H, =CH), 2.39 (s, 6 H, CH3).
Anal. Calcd for C34H32N2O6: C, 72.33; H, 5.71; N, 4.96. Found: C,
72.54; H, 5.62; N, 4.81.
Bis[1-(anilinomethylene)-2-oxotetrahydronaphthalene] (2p)
Yield: 83%; yellow crystals; mp 198 °C.
13C NMR (100 MHz, DMSO-d6, 343 K): d = 189.5 (C=O), 162.3,
153.3, 136.9, 136.1, 132.2, 129.7, 128.1, 127.9, 123.7, 97.6, 21.5.
1H NMR (250 MHz, acetone-d6): d = 13.70 (s, 2 H, NH), 8.00–7.97
(m, 2 H, =CH), 7.41–7.12 (m, 16 H, CHarom), 2.72–2.43 (m, 8 H,
CH2).
13C NMR (63 MHz, acetone-d6): d = 187.6 (C=O), 148.1, 142.5,
138.6, 134.7, 132.6, 132.0, 128.3, 127.3, 127.0, 122.9, 117.0, 104.2,
28.5, 25.3.
MS (EI): m/z (%) = 632 (1), 630 (3), 628 (1, [M+]), 614 (5), 612
(10), 610 (5, [M – H2O+]), 513 (50), 511 (100), 509 (50, [M –
C8H7O+]), 173 (90), 119 (95, [C8H7O+]).
Anal. Calcd for C32H26Br2N2O2: C, 60.97; H, 4.16; N, 4.44. Found:
C, 60.90; H, 4.17; N, 4.47.
1,6-Bis(2-pyridyl)-3,4-ditolylaminohexa-2,4-diene-1,6-dione
(2m)
MS (EI): m/z (%) = 496 (80, [M+]), 403 (90), 376 (90), 351 (90), 248
(80), 230 (80), 115 (90), 77 (100, [C6H5 ]).
+
Yield: 69%; yellow crystals; mp 233 °C.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.39 (s, 2 H, NH),
8.71–6.62 (m, 16 H, CHarom), 6.07 (s, 2 H, =CH), 2.24 (s, 6 H, CH3).
Anal. Calcd for C34H28N2O2: C, 82.23; H, 5.68; N, 5.64. Found: C,
82.22; H, 5.81; N, 5.64.
Bis[1-(4-tolylaminomethylene)-2-oxotetrahydronaphthalene]
(2q)
Yield: 90%; yellow crystals; mp 204 °C.
13C NMR (100 MHz, DMSO-d6, 343 K): d = 188.5 (C=O), 154.9,
149.5, 138.1, 138.0, 136.8, 135.5, 133.7, 129.8, 123.5, 122.9, 94.9,
21.0.
IR (ATR): 3026, 2969, 2836, 1585, 1555, 1513, 1454, 1299, 1233,
1161, 807, 736 cm–1.
1H NMR (250 MHz, DMSO-d6): d = 13.56 (s, 2 H, NH), 7.88 (m, 2
H, CHarom), 7.41–7.32 (m, 4 H, CHarom), 7.19 (m, 2 H, CHarom), 7.08
(m, 8 H, CHtolyl), 2.75–2.60 (m, 4 H, CH2), 2.45–2.25 (m, 4 H, CH2),
2.18 (s, 6 H, CH3).
13C NMR (63 MHz, DMSO-d6): d = 186.9 (C=O), 149.6, 142.2,
136.5, 134.8, 134.4, 132.6, 130.3, 128.2, 127.2, 126.7, 120.8, 102.4,
28.4, 25.0, 20.7.
MS (EI): m/z (%) = 474 (60, [M+]), 368 (100), 354 (60), 91 (50,
[C7H7 ]), 78 (80).
+
Anal. Calcd for C30H26N4O2: C, 75.93; H, 5.52; N, 11.81. Found: C,
75.57; H, 5.48; N, 11.72.
Quinolizine Derivative 7
Yield: 8%; red crystals; mp 193 °C.
IR (ATR): 3245, 2994, 1584, 1515, 1275, 1244, 1071, 1073, 812,
795 cm–1.
1H NMR (250 MHz, CDCl3): d = 8.66 (m, 1 H, =CH), 8.11–7.78
(m, 4 H, CHarom), 7.41–7.11 (m, 9 H, CHarom), 6.84 (d, J = 8 Hz, 2
H, =CH), 6.25 (s, 1 H, =CH), 2.38 (s, 6 H, CH3).
MS (EI): m/z (%) = 524 (10, [M+]), 418 (90), 262 (100), 91 (80,
+
[C7H7 ]).
UV/vis (CHCl3): lmax (log e) = 416 nm (4.2).
13C NMR (63 MHz, CDCl3): d = 188.5 (C=O), 175.1 (C=O), 156.1,
148.5, 154.9, 148.5, 142.9, 136.8, 136.5, 135.4, 135.1, 134.3, 130.9,
130.6, 130.3, 129.4, 125.8, 123.8, 122.0, 119.8, 119.5, 112.4, 109.1,
100.6, 21.0.
Anal. Calcd for C36H32N2O2: C, 82.41; H, 6.15; N, 5.34. Found: C,
82.26; H, 6.15; N, 5.39.
Bis[1-(4-bromophenylaminomethylene)-2-oxotetrahydronaph-
thalene] (2r)
Yield: 76%; yellow crystals; mp 246 °C.
MS (FAB, NBA): m/z (%) = 473 (40, [M + H+]), 356 (20), 241 (60).
UV/vis (CHCl3): lmax (log e) = 444 (4.2), 516 nm (4.3).
1H NMR (250 MHz, DMSO-d6): d = 13.37 (s, 2 H, NH), 7.94 (m, 2
H, CHarom), 7.63–7.40 (m, 4 H, CHarom), 7.38–7.35 (m, 4 H, CHarom),
7.24 (d, J = 8 Hz, 2 H, CHarom), 7.11 (d, J = 8 Hz, 4 H, CHarom),
2.78–2.72 (m, 2 H, CH2), 2.63–2.50 (m, 6 H, CH2).
13C NMR (63 MHz, DMSO-d6): d = 187.6 (C=O), 148.1 (C-1),
142.5, 138.6, 134.7, 132.6, 132.0, 128.3, 127.3, 127.0, 122.9, 117.0,
104.2, 28.5, 25.3.
Anal. Calcd for C30H24N4O2: C, 76.25; H, 5.12; N, 11.86. Found: C,
75.99; H, 5.07; N, 11.65.
1,6-Bis(2-pyridyl)-3,4-bis(4-bromophenyl)aminohexa-2,4-di-
ene-1,6-dione (2n)
Yield: 74%; yellow crystals; mp 237 °C.
1H NMR (400 MHz, DMSO-d6, 343 K): d = 12.35 (s, 2 H, NH),
8.65–6.83 (m, 16 H, CHarom), 6.66 (s, 2 H, =CH).
13C NMR (100 MHz, DMSO-d6, 343 K): d = 189.6 (C=O), 154.2,
148.9, 140.2, 137.1, 137.0, 134.8, 132.2, 131.8, 127.0, 112.5, 96.3.
MS (EI): m/z (%) = 656 (5), 654 (10), 652 (5, [M+]), 482 (100), 326
(100).
Anal. Calcd for C34H26Br2N2O2: C, 62.40; H, 4.00; N, 4.28. Found:
C, 62.26; H, 4.02; N, 4.51.
Anal. Calcd for C28H20Br2N4O2: C, 55.65; H, 3.34; N, 9.27. Found:
C, 55.66; H, 3.32; N, 9.13.
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

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1,6-Di(tert-butyl)-3,4-diphenylaminohexa-2,4-diene-1,6-dione
(2s)
Yield: 83%; yellow crystals; mp 167 °C.
1H NMR (250 MHz, CDCl3): d = 12.00 (s, 2 H, NH), 7.12–6.95 (m,
6 H, CHarom), 6.78–6.75 (m, 4 H, CHarom), 5.60 (s, 2 H, =CH), 1.16
(s, 18 H, CH3).
13C NMR (63 MHz, CDCl3): d = 206.8 (C=O), 153.1, 138.3, 128.6,
124.4, 121.4, 95.1, 42.5, 27.3 (CH3).
1H NMR (250 MHz, CDCl3): d (major isomer) = 10.33 (s, 1 H, NH),
7.57–6.70 (m, 7 H, CHarom), 6.44 (s, 1 H, =CH), 2.41 (s, 3 H, CH3),
2.04 (s, 3 H, ArCH3), 1.71–1.62 (m, 1 H, CHcylopropyl), 1.13–0.91 (m,
4 H, CH2).
13C NMR (63 MHz, CDCl3): d (major isomer) = 201.4 (C=O),
159.9, 149.4, 148.3, 147.5, 134.3, 130.7, 129.9, 129.7, 126.9, 119.8,
118.2, 117.6, 110.7, 94.7, 21.9, 20.8, 10.6.
MS (EI): m/z = 316 (80, [M+]), 247 (100), 231 (40), 91 (30,
+
[C7H7 ]).
MS (EI): m/z (%) = 404 (1, [M+]), 319 (100), 263 (40), 77 (15), 57
(25).
UV/vis (CHCl3): lmax (log e) = 487 nm (4.0).
Anal. Calcd for C26H32N2O2: C, 77.19; H, 7.97; N, 6.92. Found: C,
77.10; H, 8.03; N, 6.89.
Anal. Calcd for C21H20N2O: C, 79.72; H, 6.37; N, 8.85. Found: C,
79.48; H, 6.56; N, 8.82.
1,6-Di(tert-butyl)-3,4-ditolylaminohexa-2,4-diene-1,6-dione (2t)
Yield: 87%; yellow crystals; mp 146 °C.
1,6-Di(Cyclopropyl)-3,4-bis(4-methoxyphenyl)aminohexa-2,4-
diene-1,6-dione (2w)
Yield: 67%; yellow crystals; mp 162 °C.
1H NMR (250 MHz, CDCl3): d = 11.98 (s, 2 H, NH), 6.90 (d, J = 8
Hz, 4 H, CHtolyl), 6.67 (d, J = 8 Hz, 4 H, CHtolyl), 5.55 (s, 2 H, =CH),
2.25 (s, 6 H, ArCH3), 1.15 (s, 18 H, CH3).
13C NMR (63 MHz, CDCl3): d = 206.6 (C=O), 153.6, 135.8, 134.1,
129.2, 121.5, 94.6, 42.3, 27.4 [C(CH3)3], 20.8 (ArCH3).
MS (EI): m/z = 433 (1, [M + H+]), 347 (80, [C23H27N2O+]), 291 (20),
216 (10), 174 (10), 91 (15), 57 (100).
1H NMR (250 MHz, CDCl3): d = 11.75 (s, 2 H, NH), 6.60 (m, 8 H,
CHtolyl), 5.69 (s, 2 H, =CH), 3.74 (s, 6 H, OCH3), 1.91–1.84 (m, 2
H, CHc-Pr), 0.91–0.87 (m, 8 H, CH2).
13C NMR (63 MHz, CDCl3): d = 199.7 (C=O), 156.8, 152.4, 131.4,
123.0, 113.8, 98.3, 55.4 (OCH3), 21.1, 10.1.
MS (EI): m/z (%) = 432 (1, [M+]), 416 (1), 363 (100), 216 (40, [M+/
2]).
Anal. Calcd for C28H36N2O2: C, 77.74; H, 8.39; N, 6.48. Found: C,
77.53; H, 8.56; N, 6.36.
Anal. Calcd for C26H28N2O4: C, 72.20; H, 6.53; N, 6.48. Found: C,
72.15; H, 6.53; N, 6.36.
1,6-Di(cyclopropyl)-3,4-diphenylaminohexa-2,4-diene-1,6-di-
one (2u)
Yield: 78%; yellow crystals; mp 186 °C.
1-Cyclopropyl-2-(5-methyl-3-tolyliminoindoline-2-ylidene)eth-
anone (8c)
Yield: 7%; red crystals; mp 146 °C.
1H NMR (250 MHz, CDCl3): d = 11.82 (s, 2 H, NH), 7.44–6.64 (m,
10 H, CHphenyl), 5.74 (s, 2 H, =CH), 1.94–1.84 (m, 2 H, CHc-Pr),
1.09–0.90 (m, 8 H, CH2).
IR (ATR): 3348, 3290, 3007, 2933, 1651, 1606, 1567, 1473, 1367,
1285, 1184, 1113, 1026, 808 cm–1.
13C NMR (63 MHz, CDCl3): d = 200.1 (C=O), 151.6, 138.1, 128.6,
1H NMR (250 MHz, CDCl3): d (major isomer) = 10.29 (s, 1 H, NH),
7.74–6.33 (m, 7 H, CHarom), 5.99 (s, 1 H, =CH), 3.93 (s, 3 H), 3.49
(s, 3 H), 1.70–1.65 (m, 1 H, CHc-Pr), 1.12–0.85 (m, 4 H, CH2).
13C NMR (63 MHz, CDCl3): d (major isomer) = 201.2 (C=O),
157.3, 154.1, 149.7, 143.8, 124.2, 122.5, 121.2, 120.0 117.9, 114.3,
113.3, 111.4, 94.6, 55.6, 55.5, 21.8, 10.6.
124.3, 121.3, 99.1 (CH), 21.2, 10.4.
MS (EI): m/z (%) = 372 (1, [M+]), 303 (100), 186 (20, [M+/2]).
Anal. Calcd for C24H24N2O2: C, 77.39; H, 6.49; N, 7.52. Found C,
77.12; H, 6.77; N, 7.53.
1,6-Di(cyclopropyl)-3,4-ditolylaminohexa-2,4-diene-1,6-dione
MS (EI): m/z (%) = 348 (10, [M+]), 255 (40), 134 (80), 122 (100).
(2v)
UV/vis (CHCl3): lmax (log e) = 514 nm (3.8).
Yield: 72%; yellow crystals; mp 181 °C.
Anal. Calcd for C21H20N2O3: C, 72.40; H, 5.79; N, 8.04. Found: C,
72.11; H, 5.83; N, 8.28.
IR (ATR): 3316, 3002, 2919, 1592, 1563, 1514, 1464, 1383, 1242,
1123, 1025, 801 cm–1.
1H NMR (250 MHz, CDCl3): d = 11.80 (s, 2 H, NH), 7.20 (d, J = 8
Hz, 4 H, CHtolyl), 6.86 (d, J = 8 Hz, 4 H, CHtolyl), 5.67 (s, 2 H, =CH),
2.24 (s, 6 H, ArCH3), 1.91–1.81 (m, 2 H, CHc-Pr), 1.07–0.88 (m, 8
H, CH2).
13C NMR (63 MHz, CDCl3): d = 199.8 (C=O), 152.0, 135.6, 134.1,
129.1, 121.3, 98.6 (CH), 21.1, 20.8, 10.2.
N-Tolyl-4-trifluoromethylbenzamide (9)
To a solution of 4-toluidine (10.8 g, 101 mmol) in toluene (100 mL)
and Et3N (10.2 g, 101 mmol) was added 4-trifluoromethylbenzoyl
chloride (21.4 g, 102 mmol) over 10 min. The mixture was stirred
for 20 min at r.t. and the solvent was removed in vacuo. The precip-
itate was treated with H2O, collected by filtration, and dried over
CaCl2. The crude product was recrystallized from CHCl3–n-heptane
to yield pure 9; yield: 73%; white crystals; mp 238 °C.
1H NMR (250 MHz, DMSO-d6): d = 10.37 (s, 1 H, NH), 8.12 (d,
J = 8 Hz, 2 H, CHarom), 7.89 (d, J = 8 Hz, 2 H, CHarom), 7.64 (d,
J = 8 Hz, 2 H, CHarom), 7.16 (d, J = 8 Hz, 2 H, CHarom), 2.27 (s, 3 H,
CH3).
MS (EI): m/z (%) = 400 (1, [M+]), 357 (10), 307 (100), 200 (40, [M+/
2]).
UV/vis (CHCl3): lmax (log e) = 369 nm (4.3).
Anal. Calcd for C26H28N2O2: C, 77.97; H, 7.05; N, 6.99. Found: C,
77.70; H, 7.14; N, 6.95.
13C NMR (63 MHz, DMSO-d6): d = 164.6, 139.3, 136.7, 133.5,
133.1 (q, 2J = 32 Hz, CF3), 129.5, 128.9, 125.7 (q, 3J = 4 Hz), 123.1
(q, 1J = 273 Hz), 120.9, 21.0 (ArCH3).
1-Cyclopropyl-2-(5-methyl-3-tolyliminoindoline-2-ylidene)eth-
anone (8b)
Yield: 5%; red crystals; mp 152 °C.
+
MS (EI): m/z (%) = 279 (5, [M+]), 173 (70), 145 (100, [C7H5F3 ]),
IR (ATR): 3344, 3304, 3011, 2922, 1653, 1605, 1570, 1409, 1364,
1183, 1111, 914, 824 cm–1.
77 (50).
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis-Enaminones
UV/vis (CHCl3): lmax (log e) = 361 nm (4.2).
3079
Anal. Calcd for C15H12F3NO: C, 64.51; H, 4.33; N, 5.02. Found: C,
64.37; H, 4.52; N, 5.00.
Anal. Calcd for C20H18F3NO: C, 69.56; H, 5.25; N, 4.06. Found: C,
69.55; H, 5.16; N, 4.06.
N-Tolyl-4-trifluoromethylbenzimidoyl Chloride (10)
Compound 9 (10.0 g, 36 mmol) was suspended in toluene (50 mL)
and PCl5 (7.7 g, 37 mmol) was added. The mixture was heated un-
der reflux until no further HCl evolved. After removal of the solvent
in vacuo, the crude product was recrystallized from n-heptane;
yield: 93%; white crystals; mp 107 °C.
1H NMR (250 MHz, CDCl3): d = 8.29 (d, J = 8 Hz, 2 H, CHarom),
7.74 (d, J = 8 Hz, 2 H, CHarom), 7.25 (d, J = 8 Hz, 2 H, CHarom), 6.99
(d, J = 8 Hz, 2 H, CHarom), 2.40 (s, 3 H, CH3).
1-tert-Butyl-3-tolylamino-3-(4-trifluoromethylphenyl)prop-2-
ene-1-one (11c)
Yield: 79%; yellow crystals; mp 114 °C.
1H NMR (250 MHz, CDCl3): d = 12.36 (s, 1 H, NH), 7.56 (d, J = 8
Hz, 2 H, CHarom), 7.44 (d, J = 8 Hz, 2 H, CHarom), 6.90 (d, J = 8 Hz,
2 H, CHarom), 6.58 (d, J = 8 Hz, 2 H, CHarom), 5.52 (s, 1 H, =CH),
2.22 (s, 3 H, ArCH3), 1.23 (s, 9 H, CH3).
13C NMR (63 MHz, CDCl3): d = 206.2 (C=O), 158.8, 139.9, 136.6,
133.8, 131.4 (q, 2J = 32 Hz), 129.4, 128.7, 125.4, 123.1 (q, 1J = 273
Hz, CF3), 123.0, 96.0, 42.4, 27.6, 20.7 (ArCH3).
13C NMR (63 MHz, CDCl3): d = 144.4, 141.0, 138.9, 135.4, 133.4
(q, 2J = 32 Hz), 129.7, 129.5, 125.4 (q, 3J = 4 Hz), 123.7 (q, 1J = 273
Hz, CF3), 120.6, 21.0 (CH3).
MS (EI): m/z (%) = 361 (5, [M+]), 304 (100, [C17H13F3NO+]), 41
MS (EI): m/z (%) = 299 (109), 297 (20, [M+]), 262 (90), 91 (100,
(20, [C4H5O+]).
+
[C7H7 ]).
Anal. Calcd for C21H22F3NO: C, 69.79; H, 6.14; N, 3.88. Found: C,
69.61; H, 5.80; N, 3.74.
Anal. Calcd for C15H11ClF3N: C, 60.52; H, 3.72; N, 4.70. Found: C,
60.40; H, 3.79; N, 4.83.
1-Tolyl-3-tolylamino-3-(4-trifluoromethylphenyl)prop-2-ene-1-
one (11d)
Yield: 86%; yellow crystals; mp 105–106 °C.
1-Aryl/alkyl-3-tolylamino-3-(4-trifluoromethylphenyl)prop-2-
ene-1-ones 11; General Procedure
A solution of the corresponding aryl/alkyl ketone 3 (8 mmol) in an-
hyd THF (30 mL) was cooled down to –30 °C and t-BuOK (1.8 g,
16 mmol) was added. To this mixture was added 10 (2.4 g, 8 mmol).
The deep red mixture was stirred at 10 °C for 30 min. The mixture
was acidified to pH 7 and the solvent was removed in vacuo. The
yellow residue was dissolved in CHCl3 (100 mL) and the solution
was dried (Na2SO4), and filtered over a short column of SiO2. After
removal of the solvent, the crude product was purified by column
chromatography on silica gel (CHCl3–n-heptane) or alternatively,
was purified by recrystallization from CHCl3–n-heptane.
IR (ATR): 3032, 2922, 1596, 1561, 1512, 1320, 1163, 1123, 1048,
861, 773 cm–1.
1H NMR (250 MHz, CDCl3): d = 12.79 (s, 1 H, NH), 7.88 (d, J = 8
Hz, 2 H, CHarom), 7.60 (d, J = 8 Hz, 2 H, CHarom), 7.51 (d, J = 8 Hz,
2 H, CHarom), 7.25 (d, J = 8 Hz, 2 H, CHarom), 6.95 (d, J = 8 Hz, 2
H, CHarom), 6.66 (d, J = 8 Hz, 2 H, CHarom), 6.03 (s, 1 H, =CH), 2.42
(s, 3 H, ArCH3), 2.25 (s, 3 H, ArCH3).
13C NMR (63 MHz, CDCl3): d = 189.6 (C=O), 159.6, 142.0, 139.8,
2
137.0, 136.5, 134.2, 131.4 (q, J = 32 Hz), 129.5, 129.1, 128.8,
127.3, 125.5 (q, 3J = 4 Hz), 123.8 (q, 1J = 273 Hz, CF3), 123.3, 96.9
(CH), 21.5 (ArCH3), 20.8 (ArCH3).
4-Tolylamino-4-(4-trifluoromethylphenyl)but-3-ene-2-one
(11a)
Yield: 69%; yellow crystals; mp 42–46 °C.
1H NMR (250 MHz, CDCl3): d = 13.08 (s, 1 H, NH), 8.00 (d, J = 8
Hz, 2 H, CHarom), 7.68 (d, J = 8 Hz, 2 H, CHarom), 7.19 (d, J = 8 Hz,
2 H, CHarom), 7.08 (d, J = 8 Hz, 2 H, CHarom), 5.86 (s, 1 H, =CH),
2.37 (s, 3 H, ArCH3), 2.13 (s, 3 H, CH3).
MS (EI): m/z (%) = 395 (40, [M+]), 394 (40, [M – H+]), 276 (100),
119 (100, [C8H7O+]).
UV/vis (CHCl3): lmax (log e) = 386 nm (4.3).
Anal. Calcd for C24H20F3NO: C, 72.90; H, 5.10; N, 3.54. Found: C,
72.65; H, 5.13; N, 3.58.
13C NMR (63 MHz, CDCl3): d = 186.6 (C=O), 163.7, 143.3, 136.2,
2
Crystal Structure Determination of 2e and 7
135.6, 132.2 (q, J = 32 Hz, CF3), 129.8, 127.3, 125.3, 124.0 (q,
1J = 273 Hz), 124.9, 93.9, 20.9, 20.3.
The intensity data for the compound were collected on a Nonius
KappaCCD diffractometer, using graphite-monochromated Mo-Ka
radiation. Data were corrected for Lorentz and polarization effects,
but not for absorption effects.9 The structure was solved by direct
methods (SHELXS)10 and refined by full-matrix least squares tech-
niques against Fo2 (SHELXL-97).11 For the amine groups on N1,
N2, the methine groups on C2, C5 of 2e and all hydrogen atoms of
7 without the methyl groups were located by difference Fourier syn-
thesis and refined isotropically. The other hydrogen atoms were in-
cluded at calculated positions with fixed thermal parameters. All
nonhydrogen atoms were refined anisotropically.11 XP (Siemens
Analytical X-ray Instruments, Inc.) was used for structure represen-
tations.12
MS (EI): m/z (%) = 319 (60, [M+]), 173 (50), 146 (100).
Anal. Calcd for C18H16F3NO: C, 67.70; H, 5.05; N, 4.39. Found: C,
67.35; H, 5.01; N, 4.48.
1-Cyclopropyl-3-tolylamino-3-(4-trifluoromethylphenyl)prop-
2-ene-1-one (11b)
Yield: 82%; yellow crystals; mp 125 °C.
IR (ATR): 3013, 2945, 2923, 2858, 1604, 1565, 1519, 1322, 1275,
1163, 1121, 1108, 1060, 851, 775 cm–1.
1H NMR (250 MHz, CDCl3): d = 12.19 (s, 1 H, NH), 7.56 (d, J = 8
Hz, 2 H, CHarom), 7.46 (d, J = 8 Hz, 2 H, CHarom), 6.90 (d, J = 8 Hz,
2 H, CHarom), 6.57 (d, J = 8 Hz, 2 H, CHarom), 5.51 (s, 1 H, =CH),
2.22 (s, 3 H, ArCH3), 1.91–1.81 (m, 1 H, CHc-Pr), 1.13–0.87 (m, 4
H, CH2).
Crystal Data for 2e
C32H26Br2N2O2, Mr = 630.37 gmol–1, yellow prism, size
0.05 × 0.05 × 0.05 mm3, monoclinic, space group C2/c,
a = 21.4503(6), b = 12.0702(5), c = 21.6890(9) Å, b = 105.919(3)°,
V = 5400.1(4) Å3, T = –90 °C, Z = 8, rcalcd = 1.551 gcm–3, m (Mo-
Ka) = 30.35 cm–1, F(000) = 2544, 17887 reflections in h(–27/23),
k(–15/15), l(–23/28), measured in the range 1.95° ≤ Q ≤ 27.47°,
13C NMR (63 MHz, CDCl3): d = 199.4 (C=O), 157.1, 139.5, 136.6,
2
3
133.8, 131.2 (q, J = 32 Hz), 129.4, 128.7, 125.4 (q, J = 4 Hz),
123.8 (q, 1J = 273 Hz, CF3), 123.6, 100.4 (CH), 21.0 (ArCH3), 20.7,
10.0.
completeness
Qmax = 99.4%, 6141 independent reflections,
MS (EI): m/z (%) = 345 (70, [M+]), 344 (30, [M – H+]), 304 (70),
Rint = 0.066, 4205 reflections with Fo > 4s(Fo), 361 parameters, 0
276 (100), 69 (40, [C4H5O+]).
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York

3080
G. Buehrdel et al.
PAPER
restraints, R1obs = 0.0598, wR2obs = 0.1458, R1all = 0.0967,
wR2all = 0.1645, GOOF = 1.065, largest difference peak and hole:
1.980/–0.721 e Å–3.
Weston, J.; Goerls, H. Eur. J. Chem. 2007, 5404.
(d) Buehrdel, G.; Beckert, R.; Raabe, D.; Görls, H. J. Sulfur
Chem. 2006, 5, 401. (e) Anders, J. T.; Nyngen, V. T. H.;
Langer, P. Synlett 2004, 2779. (f) Atzrodt, J.; Brandenburg,
J.; Käpplinger, C.; Beckert, R.; Günther, W.; Görls, H.;
Fabian, J. J. Prakt. Chem./Chem.-Ztg. 1997, 339, 729.
(g) Wuckelt, J.; Döring, M.; Langer, P.; Görls, H.; Beckert,
R. Tetrahedron Lett. 1998, 39, 1135. (h) Faust, R.; Göbelt,
B.; Weber, C.; Krieger, C.; Gross, M.; Gisselbrecht, J.;
Bondon, C. Eur. J. Org. Chem. 1999, 205. (i) Pufky, D.;
Beckert, R.; Döring, M.; Walther, O. Heterocycles 2002, 57,
1257. (j) Welzel, T.; Beckert, R.; Fischer, R.; Rau, S.;
Walther, D.; Görls, H. Tetrahedron 2006, 62, 731.
(5) (a) Stylianides, N.; Danopoulos, A.; Pugh, D.; Zanotti-
Gerosa, A. Organometallics 2006, 22, 5226.
Crystal Data for 7
C30H24N4O2, Mr = 472.53 gmol–1, red prism, size 0.04 ´ 0.04 ´ 0.04
mm3, orthorhombic, space group Pbca, a = 16.8170(6),
b = 14.9217(5), c = 19.3258(6) Å, V = 4849.6(3) Å3, T = –90 °C,
Z = 8, rcalcd = 1.294 gcm–3, m (Mo-Ka) = 0.83 cm–1, F(000) = 1984,
31431 reflections in h(–21/17), k(–19/19), l(–23/25), measured in
the range 2.11° ≤ Q ≤ 27.48°, completeness Qmax = 99.9%, 5549 in-
dependent reflections, Rint = 0.0994, 3449 reflections with Fo
>
4s(Fo), 399 parameters,
0
restraints, R1obs = 0.0535,
wR2obs = 0.1131, R1all = 0.1069, wR2all = 0.1374, GOOF = 0.950,
largest difference peak and hole: 0.267/–0.204 e Å–3.
(b) Winkelmann, O.; Näther, C.; Lüning, U. Eur. J. Org.
Chem. 2006, 871. (c) Kim, H.; Livinghousee, T.; Shim, J.
H.; Lee, S. G.; Lee, P. H. Adv. Synth. Catal. 2002, 347, 601.
(6) Derivatives 2 melt under the formation of dark green liquids;
at about 260 °C formation of a colorless liquid takes place.
(7) (a) Lindauer, D.; Beckert, R.; Görls, H.; Fehling, P.; Döring,
M. J. Prakt. Chem./Chem.-Ztg. 1995, 337, 143. (b) Anders,
J. T.; Langer, P. Eur. J. Org. Chem. 2004, 5020.
(8) (a) Wu, Y.-M.; Li, Y.; Deng, J. Tetrahedron Lett. 2005, 42,
5356. (b) Lopez, S. E.; Rebollo, O.; Salazar, J.; Charris, J.
E.; Yanez, C. J. Fluorine Chem. 2003, 110, 61.
(9) (a) COLLECT, Data Collection Software; Nonius, B.V.:
Delft, 1998. (b) Otwinowski, Z.; Minor, W. Processing of X-
Ray Diffraction Data Collected in Oscillation Mode, In
Methods in Enzymology, Macromolecular Crystallography,
Part A, Vol. 276; Carter, C. W.; Sweet, R. M., Eds.;
Academic Press: New York, 1997, 307–326.
Acknowledgment
We are grateful to the Friedrich Schiller University Jena for finan-
cial support for G. Buehrdel by a grant.
References
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(12) CCDC-688639 (2e) and CCDC-688640 (7) contain the
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data can be obtained free of charge via
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Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336 033; or
deposit@ccdc.cam.ac.uk).
Synthesis 2008, No. 19, 3071–3080 © Thieme Stuttgart · New York