Three-component reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates and furan-2-carboxylic acid arylidene-hydrazides

Article abstract of DOI:10.3184/030823410X12674470482572

The adduct produced in the reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates was trapped by furan-2-carboxylic acid arylidene-hydrazides to afford highly functionalised ketenimines in good yields. The reaction is characterised by mild

Full text of DOI:10.3184/030823410X12674470482572

178 RESEARCH PAPER
MARCH, 178–180
JOURNAL OF CHEMICAL RESEARCH 2010
Three-component reaction of alkyl isocyanides, dialkyl
acetylenedicarboxylates and furan-2-carboxylic acid arylidene-hydrazides
Mohammad Hossein. Mosslemina*, Mohammad Reza Nateghia, Alireza Hassanabadib and
Mohsen Zarea
aDepartment of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
bDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
The adduct produced in the reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates was trapped by
furan-2-carboxylic acid arylidene-hydrazides to afford highly functionalised ketenimines in good yields. The reaction
is characterised by mild conditions, high selectivity, and tolerance to various functional groups.
Keywords: ketenimines, acetylenic esters, isocyanides, NH-acids, three-component reaction, furan-2-carboxylic acid arylidene-
hydrazide
Ketenimines have been extensively used in organic synthesis
as versatile building blocks for the preparation of a large
variety of cyclic compounds via inter- or intramolecular cyclo-
addition reactions.1,2 There has been intense interest in their
addition reactions, such as cycloaddition3–5 and nucleophilic,6,7
electrophilic,8,9 and radical addition.10–13 In addition, novel
synthetic approaches to carbocyclic and N-heterocyclic four-,
five-, and six-membered rings using ketenimine transition-
metal complexes have been developed.14,15 A general way to
improve synthetic efficiency and also to address other criteria,
such as atom-economy, procedural simplicity, and the number
of accessible backbones, is through the development of types
of multicomponent reactions.16 Multicomponent reactions
(MCRs), by virtue of their convergence, productivity, facile
execution, and generally high yields of products, have attracted
much attention in the area of combinatorial chemistry,17–19 of
pivotal importance are the isocyanide-based MCRs.17–21 The
trapping of the 1:1 intermediate formed between dialkyl acety-
lenedicarboxylates and isocyanides with OH, NH, and CH
acids has been widely studied.22–27 In continuation of our work
on the reaction between isocyanides and acetylenic esters in
the presence of organic acids28–30, we now report the results
of our studies on the reaction between alkyl isocyanides and
dialkyl acetylenedicarboxylates, in the presence of furan-
2-carboxylic acid arylidene-hydrazides. Thus, alkyl isocya-
nides 1 and dialkyl acetylenedicarboxylates 2 in the presence
of furan-2-carboxylic acid arylidene-hydrazides 3 undergo a
smooth 1:1:1 addition reaction in dichloromethane at ambient
temperature to produce dialkyl 2-[N′-arylidene-N-(2-furoyl)
hydrazino]-3-(alkyliminomethylene)succinate derivatives 4a–f
in excellent yields (Scheme 1).
The structures of compounds 4a–f were deduced from their
1
elemental analyses and their IR, H NMR, 13C NMR spectra.
The mass spectrum of 4a displayed the molecular ion peak at
m/z = 465 which is consistent with the formation of a 1:1:1
adduct of dimethyl acetylenedicarboxylate, cyclohexyl isocya-
nide, and furan-2-carboxylic acid benzylidene-hydrazide.
The IR spectrum of 4a exhibited the absorption band for the
ketenimine moiety at 2060 cm–1and for the ester carbonyl
groups at 1748 and 1662 cm−1.
1
The H NMR spectrum of compound 4a exhibited three
sharp singlet signals readily recognised as arising from
methoxy (δ = 3.74 and 3.76), and CH (δ = 5.82) protons. The
NCH proton was appeared as a multiplet at 3.91 ppm and the
Scheme 1
* Correspondent. E-mail: mhmosslemin@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2010 179
Scheme 2
s, N=CH) ppm. 13C NMR (125.7MHz, CDCl ): δ = 23.94, 25.21, and
33.03 (5 CH2 of cyclohexyl), 51.68 (OCH3), 533.06 (OCH3), 54.51 (CH
of cyclohexyl), 58.24 (N=C=C), 60.44 (CH), 111.75, 120.69, 143.58
and 145.72(C Furan),127.79, 128.86, 130.06 and 134.52 (C aromatic),
145.97 (N=CH), 159.19 (N=C=C), 161.15 (CON), 167.82 (CO2Me),
170.81 (CO2Me) ppm.
signals related to methylene groups of cyclohexyl moiety were
observed as multiplets at 1.26–2.05 ppm.
The protons of the aryl and furyl groups exhibited character-
istic signals in the aromatic region of the spectrum. A single
signal was observed at 8.35 ppm which arises from N=CH
proton. The 13C NMR spectrum of compound 4a showed 21
distinct resonances in agreement with the proposed structure.
The sp2- hybridised carbon atom of the ketenimine residue
appears at δ = 58.24 ppm, as a result of strong electron delo-
calisation. Partial assignments of these resonances are given in
the experimental section.
Although we have not established the mechanism of the
reaction between an isocyanide and an acetylenic ester in
the presence of furan-2-carboxylic acid arylidene-hydrazides 3
experimentally a possible explanation is proposed in Scheme
2. On the basis of the well-established chemistry of isocya-
nides,1,2,6,7 it is reasonable to assume that the functionalised
ketenimine 4 results from the initial addition of the isocyanide
to the acetylenic ester and subsequent protonation of the 1:1
adduct 5 by furan-2-carboxylic acid arylidene-hydrazides.
Then, the positively charged ion 6 is attacked by anion 7 to
give the product 4 (Scheme 2).
Dimethyl 2-[N'-benzylidene-N-(2-furanoyl)hydrazino]–3–(ter-buty
liminomethylene)succinate (4b): White powder; m.p. 150–152 °C. IR
(KBr) (νmax, cm−1): 2090 (N=C=C), 1751, 1669 (C=O). Anal. Calcd for
C23H25N3O6: C, 62.86; H, 5.73; N, 9.56. Found: 62.7; H, 5.8; N, 9.7%.
1
MS (m/z, %): 439 (M+, 5). H NMR (500.1 MHz, CDCl ): δ = 1.45
(9 H, s, 3 CH3), 3.73 (3 H, s, OCH3), 3.75 (3 H, s, OCH )3, 5.78 (1 H,
s, CH), 6.57(1H, m, CH furan), 7.44 (1H, s, CH furan),37.63 (1H, d,
3JHH = 2 HZ, CH furan), 7.42–7.74 (5 H, m, aromatic), 8.29 (1 H,
s, N=CH) ppm. 13C NMR (125.7MHz, CDCl ): δ = 30.01 (3 CH3),
51.71 (OCH3), 52.93 (OCH3), 54.24 (C), 59.75 3(N=C=C), 62.50 (CH),
111.73, 120.68, 143.28 and 145.74(C Furan),127.70, 128.83, 130.04
and 134.43 (C aromatic), 145.85 (N=CH), 159.06 (N=C=C), 162.23
(CON), 167.85 (CO2Me), 170.79 (CO2Me) ppm.
Dimethyl 2-[N'-4-chlorobenzylidene-N-(2-furanoyl)hydrazino]-3–
(cyclohexyliminomethylene)succinate (4c): White powder; m.p. 168–
170 °C. IR (KBr) (νmax, cm−1): 2080 (N=C=C), 1742, 1662 (C=O).
Anal. Calcd for C25H26ClN3O6: C, 60.06; H, 5.24; N, 8.40. Found:
1
60.2; H, 5.1; N, 8.5%. MS (m/z, %): 499 (M+, 7). H NMR (500.1
MHz, CDCl3): δ = 1.26–2.02 (10 H, m, 5 CH2 of cyclohexyl), 3.40
(3 H, s, OCH3), 3.73 (3 H, s, OCH ), 3.80 (1 H, m, CH of cyclohexyl),
5.78 (1 H, s, CH), 6.58(1H, m, CH3furan), 7.45 (1H, s, CH furan), 7.64
(1H, d, 3JHH = 2 HZ, CH furan),7.39 (2H, d, 3JHH = 7 HZ, aromatic), 7.68
In summary, the simple one-pot reaction between alkyl iso-
cyanides and dialkyl acetylenedicarboxylates in the presence
of furan-2-carboxylic acid arylidene-hydrazides provides
access to stable ketenimine derivatives of potential synthetic
interest. The presented method has the advantage of being
performed under neutral conditions and requires no activation
or modification of the reagents.
3
(2H, d, JHH = 7 HZ, aromatic), 8.32 (1 H, s, N=CH) ppm. 13C NMR
(125.7MHz, CDCl3): δ = 23.82, 25.13, and 32.93 (5 CH of cyclo-
hexyl), 51.60 (OCH3), 53.37 (OCH3), 54.55 (CH of cyclohe2xyl), 58.03
(N=C=C), 60.43 (CH), 111.71, 120.64, 139.94 and 142.83 (C Furan),
128.80, 129.13, 133.05 and 135.86 (C aromatic),145.87 (N=CH),
159.14 (N=C=C), 167.62 (CON), 170.63 (CO2Me), 170.82 (CO2Me)
ppm.
Experimental
Melting points were determined with an electrothermal 9100 appara-
tus. Elemental analyses were performed using a Heraeus CHN-
O-Rapid analyser. Mass spectra were recorded on a FINNIGAN-MAT
8430 mass spectrometer operating at an ionisation potential of 70 eV.
Diethyl 2-[N'-4-chlorobenzylidene-N-(2-furanoyl)hydrazino]-3-
(cyclohexyliminomethylene)succinate (4d): White powder; m.p. 134–
136 °C. IR (KBr) (νmax, cm−1): 2075 (N=C=C), 1744, 1680 (C=O).
Anal. Calcd for C27H30ClN3O6: C, 61.42; H, 5.73; N, 7.96. Found:
C, 61.5; H, 5.6; N, 7.8%. MS (m/z, %): 527 (M+, 5). 1H NMR (500.1
MHz, CDCl3): δ = 1.24–2.05 (10 H, m, 5 CH2 of Cy),1.22 (6H, m,
2CH3), 3.92–3.95 (1 H, m, CHN), 4.17–4.30 (4H, m, 2OCH2), 5.79
(1 H, s, CH), 6.58 (1H, m, CH furan), 7.44 (1H, s, CH furan), 7.64
(1H, d, 3JHH = 2 HZ, CH furan), 7.42 (2 H, d, 3J = 7 Hz, aromatic), 7.68
1
IR spectra were recorded on a Shimadzu IR-470 spectrometer. H
and 13C NMR spectra were recorded on Bruker DRX-500 Avance
spectrometer at solution in CDCl using TMS as internal standard.
The chemicals used in this wor3k purchased from Fluka (Buchs,
Switzerland) and were used without further purification.
3
(2 H, d, J = 7 Hz, aromatic), 8.34 (1 H, s, N=CH) ppm. 13C NMR
General procedure
(125.7MHz, CDCl ): δ = 14.42 (CH3),14.83 (CH ), 24.13, 25.67, and
33.35 (5 CH2 of 3 cyclohexyl), 55.16 (CH of 3cyclohexyl), 58.87
(N=C=C), 60.79 (OCH ), 62.68 (OCH2), 63.39 (CH), 112.09, 120.80,
139.87 and 142.51 (C2 Furan), 129.26, 129.53, 133.61 and 136.24
(C aromatic),146.13 (N=CH), 146.43 (N=C=C), 159.56 (CON),
167.55 (CO2Et), 170.87 (CO2Et) ppm .
To a magnetically stirred solution of dialkyl acetylenedicarboxylate
(2 mmol) and furan-2-carboxylic acid arylidene-hydrazide (2 mmol)
in dichloromethane (10 mL) was added a solution of alkyl isocyanide
(2 mmol) in dichloromethane (5 mL) dropwise at r.t. over 10 min.
The mixture was then stirred for 24 h. The solvent was removed under
reduced pressure, and the residue was separated by column chroma-
tography (silica gel, hexane–EtOAc, 3:1) to afford the pure title
compounds.
Di-tert-butyl 2-[N'-4-chlorobenzylidene-N-(2-furanoyl)hydrazino]-
3-(cyclohexyliminomethylene)succinate (4e): White powder; m.p.
162–164 °C. IR (KBr) (νmax, cm−1): 2075 (N=C=C), 1730, 1661 (C=O).
Anal. Calcd for C31H38ClN3O6: C, 63.74; H, 6.56; N, 7.19. Found:
Dimethyl 2-[N'-benzylidene–N-(2-furanoyl)hydrazino]-3-(cyclohe
xyliminomethylene)succinate (4a): White powder; m.p. 131–133 °C.
IR (KBr) (νmax, cm−1): 2060 (N=C=C), 1748, 1662 (C=O). Anal. Calcd
for C25H27N3O6: C, 64.50; H, 5.85; N, 9.03. Found: 64.6; H, 5.7;
1
63.8; H, 6.7; N, 7.3%. MS (m/z, %): 583 (M+, 3). H NMR (500.1
MHz, CDCl3): δ = 1.27–2.02 (10 H, m, 5 CH2 of cyclohexyl), 1.43 (s,
1
N, 9.1%. MS (m/z, %): 465 (M+, 3). H NMR (500.1 MHz, CDCl ):
9 H), 1.45 (s, 9 H), 3.88 (1 H, m, CH of cyclohexyl), 5.70 (1 H, s, CH),
δ = 1.26–2.05 (10 H, m, 5 CH2 of cyclohexyl), 3.74 (3 H, s, OCH3),
3.76 (3 H, s, OCH ), 3.91 (1 H, m, CH of cyclohexyl), 5.82 (1 H,3s,
CH), 6.58(1H, m, 3CH furan), 7.46 (1H, s, CH furan), 7.65 (1H, d,
3JHH = 2 HZ, CH furan),7.42–7.76 (5 H, m, aromatic), 8.35 (1 H,
6.56 (1H, m, CH furan), 7.41 (1H, s, CH furan), 7.63 (1H, d, JHH
=
3
2 HZ, CH furan), 7.39 (2 H, d, 3J = 7 Hz, aromatic), 7.66 (2 H, d, 3J =
7 Hz, aromatic), 8.25 (1 H, s, N=CH) ppm. 13C NMR (125.7MHz,
CDCl3): δ = 23.84, 25.32, and 33.06 (5 CH2 of cyclohexyl), 27.90

180 JOURNAL OF CHEMICAL RESEARCH 2010
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N, 8.9 %. MS (m/z, %): 473 (M+, 5). H NMR (500 MHz, CDCl ):
δ =1.46 (9 H, s, 3 CH3), 3.74 (3 H, s, OCH ), 3.76 (3 H, s, OCH33),
6.24 (1 H, s, CH), 6.85 (1H, m, CH furan), 37.55 (1H, s, CH furan),
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7.85 (2 H, d, 3J = 7 Hz, aromatic), 8.55 (1 H, s, N=CH) ppm. 13C NMR
(125.7 MHz, CDCl3): δ = 29.02 (3 CH ), 51.10 (OCH ), 52.17 (OCH3),
52.64 (C), 59.95 (N=C=C), 61.59 (C3H), 111.72, 1230.14, 141.92 and
144.53 (C Furan), 128.51, 128.74, 132.47 and 134.23 (C aromatic),
146.33 (N=CH), 157.51 (N=C=C), 163.46 (CON), 166.84 (CO2Me),
168.93 (CO2Me) ppm.
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Received 15 September 2009; accepted 12 January 2010
Paper 090792 doi: 10.3184/030823410X12674470482572
Published online: 23 March 2010
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