Four-component reaction of α-naphthol, an arylglyoxal, aniline and a dialkyl acetylenedicarboxylate: A Michael addition of enamines to α,β-unsaturated γ-dicarbonyl compounds

Article abstract of DOI:10.3184/174751916X14744659642971

Seven new tetracyclic diesters [dialkyl 1-Anilino-4-Aryl-3-(1-hydroxynaphthalen-2-yl)-4-oxobut-1-ene-1,2-dicarboxylates] have been prepared in good yield by a one-pot four-component reaction between enamine intermediates (as Michael donors) generated from aniline and a dialkyl acetylenedicarboxylate and α,β-unsaturated β-dicarbonyl intermediates (as Michael acceptors) generated fromα-naphthol and an arylglyoxal without using a catalyst in ethanol at reflux conditions.

Full text of DOI:10.3184/174751916X14744659642971

640 RESEARCH PAPER
VOL. 40 OCTOBER, 640–642
JOURNAL OF CHEMICAL RESEARCH 2016
Four-component reaction of α-naphthol, an arylglyoxal, aniline and a dialkyl
acetylenedicarboxylate: a Michael addition of enamines to α,β-unsaturated
γ-dicarbonyl compounds
Hossein Mehrabi*, Mohadeseh Fadaei and Ashrafosadat Beheshti Zadeh
Department of Chemistry, Vali-e-Asr University of Rafsanjan, Rafsanjan, 77176, Iran
Seven new tetracyclic diesters [dialkyl 1-anilino-4-aryl-3-(1-hydroxynaphthalen-2-yl)-4-oxobut-1-ene-1,2-dicarboxylates] have been
prepared in good yield by a one-pot four-component reaction between enamine intermediates (as Michael donors) generated from aniline
and a dialkyl acetylenedicarboxylate and α,β-unsaturated γ-dicarbonyl intermediates (as Michael acceptors) generated from α-naphthol
and an arylglyoxal without using a catalyst in ethanol at reflux conditions.
Keywords: α-naphthol, arylglyoxal, acetylenedicarboxylate, aniline, multi-component reaction, Michael addition
The Michael addition is one of the most powerful tools for
Results and discussion
the formation of carbon–carbon bonds in organic synthesis.1–6
The arylglyoxals 2 were prepared from the corresponding
One type of Michael addition is the conjugate addition of an
acetophenone derivatives by oxidation with selenium dioxide.25
enolate to an α,β-unsaturated carbonyl compound affording a
The optimised conditions for the condensation, using as model
1,5-dioxo compound. It is generally carried out under strongly
compounds phenylglyoxal and diethyl acetylenedicarboxylate,
basic conditions.7,8 However, such base-catalysed methods are
were 1.0 mmol α-naphthol (1), 1.0 mmol phenylglyoxal
(2, R1 = H), 1.2 mmol aniline (3) and 1.2 mmol diethyl
acetylenedicarboxylate (4) without using a catalyst in ethanol (10
mL) at reflux. To explore the scope of this transformation, other
substituted arylglyoxals and dialkyl acetylenedicarboxylates
were reacted under the same conditions and the results are
shown in Table 1.
All the synthesised compounds were unknown to the best
of our knowledge and were characterised by IR, H and 13C
NMR, CHN analysis and melting points. Thus, the IR spectrum
sometimes detrimental9,10 to base-sensitive functionalities and
often lead to side reactions like auto-oxidation or retro-Michael
type decompositions.11 In order to circumvent this problem,
considerable attention has been directed towards the search for
more convenient methods.12–15 The related enamines constitute
an important class of Michael donors that have been utilised in
complicated syntheses.16–19
Aliteraturesurveyrevealedthat, incomparisontoenolates, the
use of enamines as Michael donors is less common. The major
disadvantage associated with enamines is their susceptibility
to hydrolysis,20,21 causing restrictions to their general use in
Michael reactions. Consequently, the development of the use
of enamines in Michael reactions that are efficient and offer
operational advantages remains a challenging problem to
organic chemists.
In continuation of our studies on one-pot multi-component
reactions,22–24 we report here a one-pot four-component
reaction of aniline and a dialkyl acetylenedicarboxylate (to
form enamines as Michael donors) and α-naphthol and an
arylglyoxal (to form α,β-unsaturated γ-dicarbonyl compounds
as Michael acceptors) without using a catalyst in ethanol at
reflux conditions (Scheme 1).
1
Table 1 Yields of compounds 5a–g prepared by a four-component
reaction of compounds 1, 2, 3 and 4 (Scheme 1)
Product
R1
R2
Et
Et
Et
Yield/%a
5a
H
75
82
85
74
78
80
85
5b
Cl
5c
5d
5e
Br
Me
H
Et
Me
Me
Me
5f
Cl
5g
Me
aIsolated yields.
OH
R1
O
H
O
OH
O
R1
CH3CH2OH
24 h
COOR2
COOR2
+
COOR2
NH2
HN
Reflux,
COOR2
5a–g
3
4
Scheme 1
* Correspondent. E-mail: mehraby_h@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2016 641
R1
R1
O
OH
O
O
OH
Knoevenagel
condensation
H
+
O
R1
O
-
H
2O
O
B
1
2
Michael
addition
R1
A
R1
( )
COOR
O
OH
O
OH
COOR2
NH2
COOR2
COOR2
C
COOR2
HN
COOR
+
COOR2
COOR2
N
HN
3
4
A
5
Scheme 2
Bruker FTIR Equinax-55 spectrophotometer in KBr with absorption in
cm–1. Elemental analyses were performed using a Carlo Erba EA 1108
instrument.
of compound 5a contained absorption bands at 3271 (NH and
1
OH), 1736 and 1668 (C=O, esters and ketone) cm–1. The H
NMR spectrum of compound 5a consisted of two triplets at 1.10
and 1.31 ppm due to the two methyl groups and two quartets at
4.16 and 4.20 ppm due to the two attached methylene groups.
The methine proton was discernible as a singlet at 5.39 ppm
and the NH and OH groups were observed as two singlets at
9.70 and 15.50 ppm. There was a multiplet at 6.94–8.52 ppm
for the aromatic protons of the phenyl and naphthyl rings. The
1H decoupled 13C NMR spectrum of compound 5a showed 28
distinct signals in agreement with the proposed structure. There
were two methyl carbons at 13.6 and 14.3 ppm, a characteristic
methine carbon at 29.7 ppm and two methylene carbons at 59.9
and 62.0 ppm. The two alkene carbons were at 93.7 and 109.6
and 18 signals from 118.0 to 136.2 ppm were due to the aromatic
carbons of the phenyl and naphthyl rings. Three signals at 164.6,
169.4 and 194.0 ppm were due to the esters and ketone carbonyl
groups. Assignment of these resonances for the other products
is given in the experimental section.
A possible mechanism for the synthesis of compound 5 is
illustrated in Scheme 2. The initial reaction of aniline (3) and
dialkyl acetylenedicarboxylate 4 results in the formation of
enamine A. Knoevenagel condensation of α-naphthol (1) with
arylglyoxal 2 and then dehydration gives α,β-unsaturated
γ-dicarbonyl compound B. Michael addition of enamine A (as
Michael donor) to intermediate B (as Michael acceptor) provides
intermediate C which then undergoes an intramolecular H-shift
to form the product 5.
Representative experimental procedure
A mixture of aniline (3) (1.2 mmol) and acetylenedicarboxylate (4)
(1.2 mmol) in ethanol (5 mL) was added dropwise at room temperature
over 10 min to a magnetically stirred solution of α-naphthol (1)
(1 mmol) and arylglyoxal 2 (1 mmol) in ethanol (5 mL). The reaction
mixture was then stirred at reflux for 24 h. After completion of
the reaction (determined by TLC) the solvent was removed under
reduced pressure and the residue was purified by silica gel (Merck
230–240 mesh) column chromatography using n-hexane/EtOAc (3:1)
as eluent to afford the pure product.
Diethyl
1-anilino-4-phenyl-3-(1-hydroxynaphthalen-2-yl)-4-
IR (ν/cm–1) (KBr):
oxobut-1-ene-1,2-dicarboxylate (5a): Yellow oil
.
3271, 3058, 2981, 2935, 1736, 1668, 1597, 1269, 1208; 1H NMR
(300 MHz, CDCl3): δ 1.10 (3H, t, J = 7.2 Hz, OCH2CH3), 1.31 (3H, t,
J = 7.2 Hz, OCH2CH3), 4.16 (2H, q, J = 7.2 Hz, OCH2CH3), 4.20 (2H,
q, J = 7.2 Hz, OCH2CH3), 5.39 (1H, s, CH), 6.94–8.52 (16H, m, ArH),
9.70 (1H, s, NH), 15.50 (1H, bs, OH); 13C NMR (75 MHz, CDCl3): δ
13.6, 14.3, 29.7, 59.9, 62.0, 93.7, 109.6, 118.0, 119.2, 121.0, 122.3, 124.2,
124.3, 125.0, 125.7, 126.0, 126.4, 127.4, 128.9, 129.0, 129.4, 129.6,
134.4, 134.8, 136.2, 164.6, 169.4, 194.0. Anal. calcd for C32H29NO6
(523.59): C, 73.41; H, 5.58; N, 2.68; found: C, 73.82; H, 5.63; N, 2.62%.
Diethyl 1-anilino-4-(4-chlorophenyl)-3-(1-hydroxynaphthalen-2-
yl)-4-oxobut-1-ene-1,2-dicarboxylate (5b): Yellow oil; IR (ν/cm–1)
1
(KBr): 3275, 2981, 2935, 1739, 1668, 1597, 1274, 1208; H NMR
(300 MHz, CDCl3): δ 1.09 (3H, t, J = 7.2 Hz, OCH2CH3), 1.31 (3H, t,
J = 7.2 Hz, OCH2CH3), 4.16 (2H, q, J = 7.2 Hz, OCH2CH3), 4.20 (2H,
q, J = 7.2 Hz, OCH2CH3), 5.39 (1H, s, CH), 6.91–8.51 (15H, m, ArH),
9.68 (1H, s, NH), 15.34 (1H, bs, OH); 13C NMR (75 MHz, CDCl3): δ
13.6, 14.3, 29.9, 59.9, 62.0, 93.7, 109.5, 118.2, 121.0, 122.2, 124.2, 124.7,
125.8, 126.1, 127.4, 129.0, 129.5, 129.7, 130.6, 132.7, 136.2, 140.3, 141.4,
144.5, 148.4, 164.4, 169.5, 192.9. Anal. calcd for C32H28ClNO6 (558.03):
C, 68.88; H, 5.06; N, 2.51; found: C, 69.22; H, 5.14; N, 2.46%.
Diethyl 1-anilino-4-(4-bromophenyl)-3-(1-hydroxynaphthalen-2-
yl)-4-oxobut-1-ene-1,2-dicarboxylate (5c): Yellow oil; IR (ν/cm–1)
(KBr): 3271, 3057, 2980, 2926, 1735, 1675, 1615, 1274.79, 1209;
1H NMR (400 MHz, CDCl3): δ 1.12 (3H, t, J = 7.2 Hz, OCH2CH3),
1.33 (3H, t, J = 7.2 Hz, OCH2CH3), 4.19 (2H, q, J = 7.2 Hz, OCH2CH3),
4.23 (2H, q, J = 7.2 Hz, OCH2CH3), 5.42 (1H, s, CH), 6.95–8.57 (15H,
m, ArH), 9.71 (1H, s, NH), 15.40 (1H, bs, OH); 13C NMR (100 MHz,
CDCl3): δ 13.6, 14.3, 29.7, 60.0, 62.0, 93.8, 109.6, 118.30, 121.7, 122.2,
124.2, 124.7, 125.9, 126.1, 127.5, 129.1, 129.7, 130.4, 130.7, 132.5,
133.2, 136.2, 140.4, 144.5, 148.4, 164.0, 169.0, 193.2. Anal. calcd for
In conclusion, we have reported an efficient Michael addition
of enamines with α,β-unsaturated γ-dicarbonyl compounds by a
one-pot four-component reaction of α-naphthol, an arylglyoxal,
aniline and a dialkyl acetylenedicarboxylate. The reaction was
accomplished without using additional base or catalyst. The
advantages of the reaction are the simple reaction conditions,
readily available starting materials and the high yields of
products.
Experimental
Chemicals purchased from Aldrich or Merck were high-grade quality
and used without any purification. All melting points were obtained
on a Bamslead Electrothermal 9200 apparatus and are uncorrected.
The reactions were monitored by TLC and all yields refer to isolated
products. 1H and 13C NMR spectra were recorded in CDCl3 on a Bruker
300 or 400 MHz spectrometer. Infrared spectra were recorded on a

642 JOURNAL OF CHEMICAL RESEARCH 2016
C32H28BrNO6 (602.48): C, 63.79; H, 4.68; N, 2.32; found: C, 63.06; H,
4.47; N, 2.40%.
125.9, 127.4, 129.0, 129.2, 129.6, 129.8, 132.1, 136.2, 140.2, 144.4,
146.2, 148.0, 164.6, 169.6, 193.5. Anal. calcd for C31H27NO6 (509.56):
C, 73.07; H, 5.34; N, 2.75; found: C, 72.44; H, 5.19; N, 2.84%.
Diethyl 1-anilino-4-(4-methylphenyl)-3-(1-hydroxynaphthalen-2-
yl)-4-oxobut-1-ene-1,2-dicarboxylate (5d): Yellow oil; IR (ν/cm–1)
(KBr): 3291, 3056, 2980, 2925, 1735, 1668, 1598, 1274.89, 1209;
1H NMR (400 MHz, CDCl3): δ 1.12 (3H, t, J = 7.2 Hz, OCH2CH3),
1.33 (3H, t, J = 7.2 Hz, OCH2CH3), 2.38 (3H, s, ArCH3), 4.19 (2H, q,
J = 7.2 Hz, OCH2CH3), 4.23 (2H, q, J = 7.2 Hz, OCH2CH3), 5.42 (1H, s,
CH), 6.94–8.57 (15H, m, ArH), 9.70 (1H, s, NH), 15.64 (1H, bs, OH);
13C NMR (100 MHz, CDCl3): δ 13.6, 14.3, 21.9, 29.7, 60.0, 62.1, 93.8,
109.7, 117.9, 121.0, 122.3, 124.3, 125.1, 125.7, 125.9, 127.4, 129.0, 129.1,
129.6, 129.8, 132.1, 136.2, 140.4, 144.4, 146.2, 148.4, 164.6, 169.6,
193.5. Anal. calcd for C33H31NO6 (537.61): C, 73.73; H, 5.81; N, 2.61;
found: C, 73.11; H, 5.64; N, 2.62%.
Received 1 July 2016; accepted 3 August 2016
Paper 1604174 doi: 10.3184/174751916X14744659642971
Published online: 27 September 2016
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Dimethyl 1-anilino-4-(4-methylphenyl)-3-(1-hydroxynaphthalen-
2-yl)-4-oxobut-1-ene-1,2-dicarboxylate (5g): Yellow oil; IR (ν/cm–1)
(KBr): 3291, 3056, 2951, 2924, 1740, 1671, 1615, 1598, 1279, 1216;
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21.9, 29.7, 51.2, 52.8, 93.6, 109.7, 117.9, 120.7, 122.3, 124.3, 125.1, 125.7,
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