Reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates with 4-hydroxy quinoline: Synthesis of 1-azabuta-1,3-dienes

Article abstract of DOI:10.2174/157017812800221762

The 1:1 reactive intermediates generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates were trapped by 4-hydroxy quinoline to yield highly functionalized 1-azabuta-1,3-dienes.

Full text of DOI:10.2174/157017812800221762

150
Letters in Organic Chemistry, 2012, 9, 150-153
Reaction of Alkyl Isocyanides, Dialkyl Acetylenedicarboxylates with 4-
Hydroxy Quinoline: Synthesis of 1-Azabuta-1,3-Dienes
Bita Mohtat*,a, Somayeh Rezazadeha, Mahnaz Matinfara, Vale Arabzadehb, Hoorieh Djahanianic and
Zinatossadat Hossainid
aDepartment of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
bDepartment of Chemistry, Jooybar Branch, Islamic Azad University, Mazandaran, Iran
cDepartment of Chemistry, East Tehran Branch, Islamic Azad University, Tehran, Iran
dDepartment of Chemistry, Qaemshahr Branch, Islamic Azad University, Mazandaran, Iran
Received September 02, 2011: Revised October 14, 2011: Accepted October 25, 2011
Abstract: The 1:1 reactive intermediates generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates
were trapped by 4-hydroxy quinoline to yield highly functionalized 1-azabuta-1,3-dienes.
Keywords: Acetylenic esters, alkyl isocyanides, 1-Azabuta-1,3-dienes, 4-Hydroxy quinoline, multi-component reaction.
INTRODUCTION
productivity, facile execution, and generally high yields of
products, have attracted much attention in the context of
combinatorial chemistry. Of pivotal importance in this area
are the isocyanide based MCRs such as the versatile Ugi and
Passerini reactions [3-10].
Isocyanides are compounds with an extraordinary
functional group; their unusual valence structure and
reactivity have been discussed for over one and a half
century [1]. Isocyanides are the only class of stable organic
compounds with a formally divalent carbon. Owing to its
reactivity, the isocyanide group differs fundamentally from
The reactions of 1-azadienes with various chiral
dienophiles, which lead to substituted pyridines, have been
O
CO2R'
N
R
N
C
+
+
N
CO2R'
CHCO2R'
RN
OH
CO2R'
2
1
3
4
4
R
yield %
R'
3
R'
R
1
a
b
c
d
e
f
a
b
t-Butyl
Me
Et
a
b
c
t-Butyl
c-Hexyl
1,1,3,3-tetra metyl Butyl
83
78
65
79
70
62
Me
Me
Me
Et
c-Hexyl
1,1,3,3-tetra metyl Butyl
t-Butyl
c-Hexyl
Et
1,1,3,3-tetra metyl Butyl
Et
Scheme 1. Typical procedure for compounds 4.
other functional groups. The fascinating chemistry that stems
from the addition of isocyanides to activated acetylenic
compounds has evoked considerable interest [2]. Multi-
component reactions (MCRs), by virtue of their convergence,
reported [11]. Recently, we have described a convenient
method for the preparation of 1-azadienes, by three-
component reaction of 2-pyridinol and 1-isoquinolinol with
dialkyl acetylenedicarboxylates and alkyl isocyanide [12]. In
continuation of our interest in the application of isocyanides
in MCRs, [13, 14] we extend this methodology using 4-
hydroxyquinoline. Thus, the reaction of alkyl isocyanides 1
and dialkyl acetylenedicarboxylates 3 in the presence
of strong NH-acid, such as 4-hydroxy quinoline 2 leads
*Address correspondence to this author at the Karaj Branch, Islamic Azad
University, Karaj, Iran; Tel: +989122937695; Fax: +982122921610;
E-mail: b.mohtat@jooyan.org
1875-625512 $58.00+.00
© 2012 Bentham Science Publishers

Synthesis of 1-Azabuta-1,3-Dienes
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
151
1
to dimethyl 2-((tert-butylimino)(4-oxoquinolin-1(4H)-yl)
measured on a Shimadzu IR-460 spectrometer. H and 13C
NMR spectra were measured with a Bruker DRX-300
Avance instrument with CDCl3 at (300.1 and 75.5 MHz,
respectively). Mass spectra were recorded on a Finnigan-
Matt 8430 mass spectrometer operating at an ionization
potential of 70 eV. Alkyl isocyanides, dialkyl
acetylenedicarboxylates, and compounds 2 were obtained
from (Fluka) and were used without further purification.
methyl)but-2-enedioate 4 in good yields (Scheme 1).
RESULT AND DISCUSSION
The reaction proceeded spontaneously in CH2Cl2, and
was completed within a few hours. The structures of
1
compounds 4a–4f were deduced from their IR, H-NMR,
and 13C-NMR spectra. The mass spectra of these compounds
displayed molecular ion peaks at appropriate m/z values, the
1H-NMR spectrum of 4a exhibited four sharp lines for tert-
butyl (ꢀ = 1.32 ppm), methoxy (ꢀ = 3.67 and 3.69 ppm), and
vinyl (ꢀ = 6.66 ppm) protons. The quinolinol moiety
appeared at ꢀ = 6.31–8.29 ppm. The 13C-NMR spectrum of
4a showed 18 distinct resonances in agreement with
the dimethyl 2-((tert-butylimino)(4-oxoquinolin-1(4H)-yl)
methyl)but-2-enedioate. Structure partial assignments of
these resonances are given in the experimental section. The
1H-NMR spectra of 4b–4f are similar to that of 4a, except
for the signals of the alkyl, and alkoxy moieties. The
structural assignments of compounds 4a–4f made on the
basis of their NMR spectra were supported by their IR
spectra. Of special interest are the imine absorption bands at
about 1620 cm-1 in all compounds.
General Procedure for the Preparation of Compounds 4
To a stirred solution of 4-quinolinol (2 mmol) and tert-
butyl isocyanide (2 mmol) in 10 mL of CH2Cl2, dimethyl
acetylenedicarboxylate (DMAD) (2 mmol) was added
dropwise at -10 ºC over 10 min. The reaction mixture was
then allowed to warm to room temperature and stand for 24
h. The solvent was removed under reduced pressure, and the
residual was purified by preparative TLC on silica gel
(Merck silica gel DC-Fertigplatten 60/Kieselgur F254)
20ꢀ20 cm plates using n-hexane-EtOAc (1:1) as an eluent.
Dimethyl 2-((tert-butylimino)(4-oxoquinolin-1(4H)-yl)
methyl)but-2-enedioate (4a)
Yellow oil, yield 0.66 g (83%), IR (neat) (ꢁmax/cm-1):
1735, 1666 (C=O), 1632 (C=N). 1H NMR (300 MHz,
CDCl3): ꢀ 1.32 (s, 9H, 3CH3), 3.67 (s, 3H, OCH3), 3.69 (s,
3H, OCH3), 6.31 (t, 1H, J = 7.4 Hz, CH), 6.66 (s, 1H, CH),
7.37 (m, 1H, CH), 7.67 (m, 2H, 2CH), 8.03 (d, 1H, J = 7.4
Hz, CH), 8.29 (d, 1H, J = 8.8 Hz, CH). 13C NMR (75 MHz,
CDCl3): ꢀ 28.6 (3 CH3), 52.3 (OCH3), 52.5 (OCH3), 56.2 (C-
N), 109.5 (CH=), 119.1 (CH=), 124.3 (CH=), 126.0 (CH=),
126.5 (C=), 128.6 (C=), 129.3 (CH=), 132.7 (CH=), 140.6
(CH), 141.1 (C=), 141.7 (C=), 165.1 (C=O), 169.4 (C=O),
178.7 (C=O). MS (EI, 70 eV): m/z (%) = 398 (M+, 7 ), 262
(73), 146 (100), 71 (65), 58 (62). Anal. calcd. for
C20H22N2O5 (370.41): C, 64.85, H, 5.99, N, 7.56, found: C,
64.89, H, 5.94, N, 7.60.
A
plausible mechanism for the formation of
polyfunctionalized 1-azadienes 4a–4f is shown in Scheme 2.
The reaction proceeds by addition of the isocyanide to the
activated acetylene to produce the zwitterionic intermediate
5, which is protonated by the NH acid 3 [15]. Then, the
positively charged ion is attacked by the carbon atom of the
bidentate anion of the NH acid, direct addition leads to 1-
azadiene 4 (Scheme 2). The absence of the strong ketenimine
absorption bands at about 2060 cm-1 in all compounds
excludes the conjugate addition of the anion 7 to the
intermediate 6.
CONCLUSION
Dimethyl 2-((cyclohexylimino)(4-oxoquinolin-1(4H)-yl)
methyl)but-2-enedioate (4b)
In conclusion, the reaction of alkyl isocyanide with
electron-deficient acetylenic esters in the presence of some
NH acid provides a simple one-pot entry into the synthesis of
polyfunctionalized 1-azadienes of potential synthetic
interest. The present procedure carries the advantage that not
only is the reaction performed under neutral conditions, but
also the substances can be mixed without any activation or
modification.
Yellow oil, yield 0.62 g (78%), IR (neat) (ꢁmax/cm-1):
1732, 1660 (C=O), 1622 (C=N). 1H NMR (300 MHz,
CDCl3): ꢀ 1.28-2.08 (m, 10H, 5CH2), 3.62 (s, 3H, OCH3),
3.65(s, 3H, OCH3), 3.79 (m, 1H, CH), 6.25 (t, 1H, J = 7.8
Hz, CH), 6.62 (s, 1H, CH), 7.21 (m, 1H, CH), 7.42 (m, 2H,
2CH), 7.76 (d, 1H, J = 7.5 Hz, CH), 8.30 (d, 1H, J = 8.1 Hz,
CH). 13C NMR (75 MHz, CDCl3): ꢀ 22.8 (CH2), 24.0 (CH2),
25.7 (CH2), 32.0 (CH2), 32.2 (CH2), 51.9 (CH-N), 52.8
(OCH3), 54.0 (OCH3), 108.3 (CH=), 119.0 (CH=), 124.7
(CH=), 126.3 (CH=), 126.9 (C=), 127.1 (C=), 130.8 (CH=),
132.1 (CH=), 140.2 (CH), 141.2 (C=), 141.4 (C=), 163.3
(C=O), 164.9 (C=O), 178.4 (C=O). MS (EI, 70 eV): m/z (%)
EXPERIMENTAL
General
Elemental analyses for C, H, and N were performed
using a Heraeus CHNO-Rapid analyzer. IR spectra were
N
C-CO2R'
CHCO2R'
Direct Addition
+3
4
1
R
N
C
2
+
R
N
C
+
CO2R'
CO2R'
O
5
6
7
Scheme 2. A possible mechanism for the preparation of compound 4.

152 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Mohtat et al.
= 396 (M+, 10), 288 (100), 146 (49), 71 (85), 43 (77). Anal.
Calcd. For C22H24N2O5: C, 66.65, H, 6.10, N, 7.07, found: C,
66.70, H, 6.07, N, 7.05.
Diethyl 2-((2,4,4-trimethylpentan-2-ylimino)(4-oxoquino-
lin-1(4H)-yl)methyl)but-2-enedioate (4f)
Yellow oil, yield 0.56 g (62%), IR (neat) (ꢁmax/cm-1):
1735, 1665 (C=O), 1624 (C=N). 1H NMR (300 MHz,
CDCl3): ꢀ 1.04 (s, 9 H, 3CH3), 1.22 (t, 3H, J = 7.1 Hz, CH3),
1.34 (t, 3H, J = 7.1 Hz, CH3), 1.43 (s, 3H, CH3), 1.47 (s, 3H,
CH3), 1.82 (m, 2H, 2CH), 4.04-4.23 (m, 4H, 2 OCH2), 6.23
(d, 1H, J = 7.4 Hz, CH), 6.74 (s, 1H, CH), 7.34 (m, 1H, CH),
7.65 (m, 2H, 2CH), 7.98 (d, 1H, J = 7.4 Hz, CH), 8.26 (d,
1H, J = 7.9 Hz, CH). 13C NMR (75 MHz, CDCl3): ꢀ 14.3
(CH3), 14.4 (CH3), 30.6 (3 CH3), 31.6 (2 CH3), 31.7 (C),
34.0 (CH2), 56.2 (C-N), 61.4 (OCH2), 62.5 (OCH2), 109.7
(CH=), 119.1 (CH=), 124.1 (CH=), 126.2 (CH=), 126.9
(C=), 129.3 (C=), 131.0 (CH=), 132.6 (CH=), 140.0 (CH),
141.2 (C=), 141.9 (C=), 164.4 (C=O), 164.7 (C=O), 178.4
(C=O). MS (EI, 70 eV): m/z (%) = 454, (M+, 6), 310 (37),
198 (29), 145 (100), 57 (63), 29 (72). Anal. calcd for
C26H34N2O5: C, 68.70, H, 7.54, N, 6.16%, Found: C, 68.73,
H, 7.50, N, 6.18.
Dimethyl 2-((2,4,4-trimethylpentan-2-ylimino)(4-oxoquino-
lin-1(4H)-yl)methyl)but-2-enedioate (4c)
Yellow oil, yield 0.55 g (65%), IR (neat) (ꢁmax/cm-1):
1731, 1670 (C=O), 1633 (C=N). 1H NMR (300 MHz,
CDCl3): ꢀ 1.02 (s, 9H,3 CH3), 1.42 (s, 3H, CH3), 1.48 (s, 3H,
CH3), 1.85 (m, 2H, 2CH), 3.73 (s, 3H, OCH3), 3.77 (s, 3H,
OCH3), 6.29 (d, 1H, J = 7.4 Hz, CH), 6.72 (s, 1H, CH), 7.39
(m, 1H, CH), 7.67 (m, 2H, CH), 8.03 (d, 1H, J = 7.3 Hz,
CH), 8.30 (d, 1H, J = 8.1 Hz, CH). 13C NMR (75 MHz,
CDCl3): ꢀ 31.4 (3 CH3), 31.6 (CH3), 31.7 (CH3), 31.8 (C),
34.0 (CH2), 52.2 (OCH3), 52.5 (OCH3), 56.2 (C-N), 109.6
(CH=), 119.2 (CH=), 124.3 (CH=), 126.0 (CH=), 126.7
(C=), 128.6 (C=), 130.3 (CH=), 132.7 (CH=), 140.9 (CH),
141.2 (C=), 141.6 (C=), 165.2 (C=O), 169.4 (C=O), 178.6
(C=O). MS (EI, 70 eV): m/z (%) = 426 (M+, 8), 388 (54),
318 (100), 146 (100), 71 (48), 58 (81). Anal. calcd for
C24H30N2O5: C, 67.59, H, 7.09, N, 6.57%, Found: C, 67.64,
H, 6.92, N, 6.54.
DISCLOSURE
Some part of information included in this article has been
previously published in "Synthetic Communications Volume
41, Issue 6, 2011".
Diethyl 2-((tert-butylimino)(4-oxoquinolin-1(4H)-yl)
methyl)but-2-enedioate (4d)
Yellow oil, yield 0.63 g (79%), IR (neat) (ꢁmax/cm-1):
1
1733, 1665 (C=O), 1628 (C=N). H NMR (300 MHz,
ACKNOWLEDGEMENT
CDCl3): ꢀ 1.16 (t, 3H, J = 7.1 Hz, CH3), 1.25 (t, 3H, J = 7.1
Hz, CH3), 1.40 (s, 9H, 3CH3), 4.00-4.35 (m, 4H, 2OCH2),
6.16 (d, 1H, J = 7.5 Hz, CH), 6.67 (s, 1H, CH), 7.34 (m, 1H,
CH), 7.64 (m, 2H, 2CH), 7.65 (d, 1H, J = 7.5 Hz, CH), 7.94
(d, 1H, J = 8.0 Hz, CH) . 13C NMR (75 MHz, CDCl3): ꢀ 14.1
(CH3), 14.3 (CH3), 28.5 (3 CH3), 51.9 (C-N), 61.6 (OCH2),
62.4 (OCH2), 109.9 (CH=), 119.0 (CH=), 123.9 (CH=),
126.2 (CH=), 127.1 (C=), 129.3 (C=), 129.6 (CH=), 132.5
(CH=), 139.9 (CH), 141.3 (C=), 141.9 (C=), 164.6 (C=O),
164.7 (C=O), 178.5 (C=O). MS (EI, 70 eV): m/z (%) = 398
(M+, 2), 310 (24), 254 (23), 198 (35), 145 (82), 57 (100), 41
(30). Anal. Calcd. for C22H26N2O5: C, 68.71, H, 7.56, N,
6.14, found: C, 68.73, H, 7.50, N, 6.12.
Declared none.
CONFLICT OF INTEREST
Declared none.
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Synthesis of 1-Azabuta-1,3-Dienes
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