Vinyltriphenylphosphonium salt-mediated preparation of fully substituted furans and electron-poor imides from benzoic acid, cyclohexyl isocyanide, and acetylenic esters

Article abstract of DOI:10.1080/10426500701852646

Protonation of the reactive intermediates produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by benzoic acid leads to vinyltriphenylphosphonium salts, which undergo complex reactions with cyclohexyl isocyanide to produ

Full text of DOI:10.1080/10426500701852646

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Vinyltriphenylphosphonium
Salt-Mediated Preparation
of Fully Substituted Furans
and Electron-Poor Imides
from Benzoic acid, Cyclohexyl
Isocyanide, and Acetylenic
Esters
Mohsen Valizadeh Holagh a , Ebrahim Ahmadi a & Ali
Ramazani a
a Department of Chemistry , University of Zanjan ,
Zanjan, Iran
Published online: 12 Aug 2008.
To cite this article: Mohsen Valizadeh Holagh , Ebrahim Ahmadi & Ali Ramazani (2008)
Vinyltriphenylphosphonium Salt-Mediated Preparation of Fully Substituted Furans and
Electron-Poor Imides from Benzoic acid, Cyclohexyl Isocyanide, and Acetylenic Esters,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9, 2173-2180, DOI:
10.1080/10426500701852646
To link to this article: http://dx.doi.org/10.1080/10426500701852646
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Phosphorus, Sulfur, and Silicon, 183:2173–2180, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701852646
Vinyltriphenylphosphonium Salt-Mediated Preparation
of Fully Substituted Furans and Electron-Poor Imides
from Benzoic acid, Cyclohexyl Isocyanide,
and Acetylenic Esters
Mohsen Valizadeh Holagh, Ebrahim Ahmadi,
and Ali Ramazani
Department of Chemistry, University of Zanjan, Zanjan, Iran
Protonation of the reactive intermediates produced in the reaction between triph-
enylphosphine and dialkyl acetylenedicarboxylates by benzoic acid leads to vinylt-
riphenylphosphonium salts, which undergo complex reactions with cyclohexyl iso-
cyanide to produce corresponding densely functionalized furans and imides in fairly
good yields in neutral conditions. The formulas of the products were deduced from
1
13
their IR, H NMR, and C NMR spectra. The reaction is completely stereoselective.
Keywords Acetylenic ester; densely functionalized furan; electron-poor imide; phospho-
rus ylide; triphenylphosphine
INTRODUCTION
Organophosphorus compounds1,2 have been extensively employed in
organic synthesis as useful reagents as well as ligands in a number of
transition metal catalysts.3 Phosphorus ylides are a class of special type
of zwitterions, which bear strongly nucleophilic electron rich carban-
ions. The electron distribution around the P+–C− bond and its conse-
quent chemical implications had been probed and assessed through the-
oretical, spectroscopic and crystallographic investigations.4 They are
excellent ligands and excel in their ligating functions the unstabilized
ylides because of their ambidentate and chemically differentiating char-
acter. Proton affinity of these ylides can be used as a molecular guide to
assess their utility as synthetic reagents and their function as ligands
in coordination and organometallic chemistry.3,5 The nucleophilicity at
the ylidic carbon is a factor of essential mechanistic importance in the
Received 11 November 2007; accepted 14 November 2007.
This work was supported by the Zanjan University.
Address correspondence to Ali Ramazani, Department of Chemistry, University of
Zanjan, P O Box 45195-313, Zanjan, Iran. E-mail: aliramazani@gmail.com
2173

2174
M. V. Holagh et al.
use of these ylides as Wittig reagents. Phosphorus ylides are important
reagents in synthetic organic chemistry, especially in the synthesis of
naturally occurring products, compounds with biological and pharmaco-
logical activity.1,2 In recent years, we have established a one-pot method
for the synthesis of stabilized ylides.6–15
For several years, acetylenic esters have attracted the attention
of organic chemists and are reactive systems that can take part in
many chemical syntheses,16 almost as a Michael acceptor in the organic
reactions.17 In recent years, there has been increasing interest on the
applications of acetylenic esters in the multi-component16–19 synthesis.
Due to the atom economy, convergent character and simplicity of one-
pot procedures, multi-component condensation reactions (MCRs) have
an advantageous position among other reactions. The development of
novel MCRs is receiving growing interest from industrial chemistry re-
search groups and represents a challenge for organic chemists.20–23 As
part of our ongoing program to develop efficient and robust methods for
the preparation of heterocyclic compounds,24–26 we sought to develop a
convenient preparation of densely functionalized furans 5 and imides
4 in fairly good yields in neutral conditions.
RESULTS AND DISCUSSION
Protonation of the reactive intermediates produced in the reaction be-
tween triphenylphosphine and dialkyl acetylenedicarboxylates 2 by
benzoic acid 3 leads to vinyltriphenylphosphonium salts 7, which un-
dergo complex reactions with cyclohexyl isocyanide 1 to produce corre-
sponding densely functionalized furans 5 and imides 4 in fairly good
yields in neutral conditions (Scheme 1 and Scheme 2). TLC indicated
the formation of products 4 and 5 at room temperature. The reaction
proceeds smoothly and cleanly under reaction conditions and no side
reactions were observed. The reactions were completed in 48 h. and
densely functionalized furans 5 observed as major products (Table I).
In this reaction, triphenylphosphine acts as a catalyst. In the absence
of the triphenylphosphine, the reactions were completed after 72 h in
CH2Cl2 at room temperature and imides 4 observed as major prod-
ucts (Table I).22,23 The 1H NMR (CDCl3) spectra of compounds 4 show
the presence of one stereoisomer (E) for each imides 4. Z isomers of the
imides 4 were not isolated. It seems that Z isomers 12 are reactive than
E isomers toward formation of adduct 13 with cyclohexyl isocyanide 1
and act as intermediate in the formation of furans 5 (Scheme 2). The
reaction is completely stereoselective.
The mechanism of the reaction between the triphenylphosphine, cy-
clohexyl isocyanide (1), dialkyl acetylenedicarboxylates (2), and benzoic

Substituted Furans and Electron-Poor Imides
2175
SCHEME 1
acid (3) has not been established experimentally. However, a possible
explanation is proposed in Scheme 2. The formulas of the products were
1
deduced from their IR, H NMR, and 13C NMR spectra (See Experi-
mental section). The IR spectrum of 4a showed strong adsorptions at
1730 (OCNCO), 1685 (CO2Me), 1615 (C C), 1538 and 1453 (Ph), and
1369, 1261, 1207, and 1161 (C O) cm−1 indicating the presence of the
mentioned functionalities in its formula. The 1H NMR spectrum of 4a
compound exhibited five signals readily recognized as arising from cy-
clohexyl group (δ = 0.89–2.40, m), two OMe groups (δ = 3.76 and 3.81
ppm), NH (δ = 6.53 ppm, s) and aromatic moieties (δ = 7.24–7.72 ppm,
m). The 1H decoupled 13C NMR spectrum of 4a showed 15 distinct res-
onances in agreement with the 4a formula. Partial assignment of these
resonances is given in the spectral analysis section (See experimental
1
section). The H and 13C NMR spectra of compound 4b are similar to
those of 4a, except for the ester groups (1H and 13C NMR), which exhibit
characteristic signals with appropriate chemical shifts (see spectral
analysis section).22–26 The IR spectrum of 5a showed strong adsorp-
tions at 3461 (NH), 1738 (CO2Me), 1676 (CO2Me), 1607 (CON), 1238
(C O) cm−1 indicating the presence of the mentioned functionalities
1
in its formula. The H NMR spectrum of 5a compound exhibited five
signals readily recognized as arising from cyclohexyl group (δ = 0.90–
2.40, m), two OMe groups (δ = 3.65 and 3.70 ppm), NH (δ = 6.53 ppm, d,

2176
M. V. Holagh et al.
SCHEME 2
3JHH = 8.0) and aromatic moieties (δ = 7.24–7.72 ppm, m). The 1H de-
coupled 13C NMR spectrum of 5a showed 18 distinct resonances in
agreement with the 5a formula. Partial assignment of these resonances
is given in the spectral analysis section (See Experimental section). The
1H and 13C NMR spectra of compound 5b are similar to those of 5a,
except for the ester groups (1H and 13C NMR), which exhibit charac-
teristic signals with appropriate chemical shifts (see spectral analysis
section).22–26
CONCLUSION
In summary, we have found a new and efficient method for preparing
electron-poor imides (4) and fully substituted furans (5) from triph-
enylphosphine, cyclohexyl isocyanide (1) dialkyl acetylenedicarboxy-
lates (2) and benzoic acid (3) in neutral conditions (Scheme 1, Scheme 2,
and Table I). We believe the reported method offers a simple and effi-
cient route for the preparation of electron-poor imides (4) and fully
substituted furans (5) (Scheme 1). Its ease of work up and fairly good
yields make it a useful addition to modern synthetic methodologies.
Other aspects of this process are under investigation.

Substituted Furans and Electron-Poor Imides
2177
TABLE I Synthesis of Imides 4 and Furans 5 (See Scheme 1)
In the presence of PPh3
(r. t., 48 h.): Total isolated
yield % (4 + 5);
In the absence of PPh3
(r. t., 72 h.): Total isolated
yield % (4 + 5);
Entry Products
Ratio of 4/5
Ratio of 4/5
1
2
4a/5a
4b/5b
88; 30/70
82; 35/65
83; 83/17
83; 85/15
EXPERIMENTAL
1H (250.13 MHz) and 13C (62.90 MHz) NMR measurements were
recorded on a Brucker 250 spectrometer in CDCl3 with tetramethyl-
silane as internal standard. IR spectra were measured on a Mattson-
1000 FTIR spectrophotometer. Starting materials and solvents were ob-
tained from Merck (Germany) and Fluka (Switzerland) and were used
without further purification. Flash chromatography columns were pre-
pared from Merck silica gel powder.
General Procedure for the Preparation
of Compounds 4a–b and 5a–b
To a magnetically stirred solution of triphenylphosphine (0.262 g,
1.00 mmol) and benzoic acid 3 (0.140 g, 1.00 mmol) in dry CH2Cl2
(1.00 ml) was added dropwise a solution of 2 (1.00 mmol) in CH2Cl2
(2.00 ml) at −10◦C over 15 min. The mixture was allowed to warm
to room temperature and added dropwise a solution of cyclohexyl iso-
cyanide 1 (1.00 mmol) in CH2Cl2 (1.00 ml) over 10 min. The mixture
was allowed to stirred for 48 h. The solvent was removed under reduced

2178
M. V. Holagh et al.
pressure, and the viscous residue was purified by flash column chro-
matography (silica gel; light petroleum ether-ethyl acetate). Charac-
terization data are given below:
Dimethyl (E)-2-{[benzoyl(cyclohexyl)amino]carbonyl}-
2-butenedioate 4a
Viscose yellow oil, IR (KBr) (υmax, cm−1): 1730 (OCNCO), 1685
(CO2Me), 1615 (C C), 1538 and 1453 (Ph), 1369, 1261, 1207, and 1161
1
(C O). H NMR (250.13 MHz, CDCl3): δH 0.89–2.4 (11 H, m, cyclo-
hexyl), 3.76 (3 H, s, OMe), 3.81 (3 H, s, OMe), 6.53 (1 H, s, NH), 7.24–
7.72 (5 H, m, arom).13C NMR (62.90 MHz, CDCl3): δC24.71 (CH2 of cy-
clohexyl), 26.33 (CH2 of cyclohexyl), 29.29 (CH2 of cyclohexyl), 52.33
(OMe), 52.97 (OMe), 60.39 (CH of cyclohexyl), 128.44 (2 CHortho of
C6H5), 128.58 (C CH), 132.55 (CHpara of C6H5), 135.34 (Cipso of C6H5),
142.46 (C CH), 163.14 (PhCONCO), 164.58 (CO2Me), 165.72 (CO2Me),
175.12 (PhCON).
Diethyl (E)-2-{[benzoyl(cyclohexyl)amino]carbonyl}-
2-butenedioate 4b
Viscose yellow oil, IR (KBr) (υmax, cm−1): 1731 (OCNCO), 1669
(CO2Me), 1608 (C C), 1530 and 1453 (Ph), 1373, 1261, 1200 and 1161
1
3
(C-O). H NMR (250.13 MHz, CDCl3): δH 1.25 (3 H, t, JHH = 7.0 Hz,
3
CH3), 1.32 (3 H, t, JHH = 7.0 Hz, CH3), 1.5–2.4 (11 H, m, cyclohexyl),
4.2 (2 H, q, 3JHH = 7.0 Hz, OCH2), 4.28 (2 H, q, 3JHH = 7.0 Hz, OCH2),
6.52 (1 H, s, NH), 7.2–8.1 (5 H, m, arom).13C NMR (62.90 MHz, CDCl3):
δC 13.94 (CH3), 14.04 (CH3), 24.61 (CH2 of cyclohexyl), 26.35 (CH2 of
cyclohexyl), 29.29 (CH2 of cyclohexyl), 60.35 (OCH2), 61.40 (OCH2),
62.17 (CH of cyclohexyl), 128.45 (2 CHortho of C6H5), 128.52 (C CH),
129.51 (CHpara of C6H5), 135.49 (Cipso of C6H5), 142.65 (C CH), 162.65
(PhCONCO), 164.22 (CO2Me), 165.91 (CO2Me), 175.05 (PhCON).
Dimethyl 2-[Benzoyl(cyclohexyl)amino]-5-(cyclohexylamino)-
3,4-furandicarboxylate 5a
Viscose yellow oil, IR (KBr) (υmax, cm−1): 3461 (NH), 1738 (CO2Me),
1676 (CO2Me), 1607 CON), 1238 (C O). 1H NMR (250.13 MHz, CDCl3):
δH 0.9–2.4 (11 H, m, cyclohexyl), 3.65 (3 H, s, OMe), 3.70 (3 H, s, OMe),
3
6.53 (1 H, d, JHH = 8.0, NH), 7.24–7.72 (5 H, m, arom).13C NMR
(62.90 MHz, CDCl3): δC 24.45 (CH2 of cyclohexyl), 25.37 (CH2 of cyclo-
hexyl), 33.29 (CH2 of cyclohexyl), 50.96 (CH of cyclohexyl), 51.54 (OMe),
51.81 (OMe), 56.73 (CH of cyclohexyl), 85.48 (C4 of furan), 114.05 (C3
of furan), 127.28 (CHpara of C6H5), 127.62 (2 CHortho of C6H5), 130.14
(2 CHmeta of C6H5), 136.45 (Cipso of C6H5), 138.73 (C5 of furan), 159.46
(C2 of furan), 162.29 (CO2Me), 164.96 (CO2Me), 171.23 (NCO).

Substituted Furans and Electron-Poor Imides
2179
Diethyl 2-[Benzoyl(cyclohexyl)amino]-5-(cyclohexylamino)-
3,4-furandicarboxylate 5b
Viscose yellow oil, IR (KBr) (υmax, cm−1): 3353 (NH), 1723 (CO2Me),
1669 (CO2Me), 1607 (CON), 1238 (C O). 1H NMR (250.13 MHz, CDCl3):
3
3
δH 1.21 (3 H, t, JHH = 7.3 Hz, CH3), 1.26 (3 H, t, JHH = 7.3 Hz,
CH3), 0.8–2.4 (11 H, m, cyclohexyl), 3.49–4.51 (4 H, m, OCH2), 6.64
(1 H, d, 3JHH = 8.3, NH), 7.2–8.2 (5H, m, arom). 13C NMR (62.90 MHz,
CDCl3): δC 14.05 (CH3), 14.22 (CH3), 24.44(CH2 of cyclohexyl), 24.59
(CH2 of cyclohexyl), 24.70 (CH2 of cyclohexyl), 25.38 (CH2 of cyclohexyl),
51.49 (CH of cyclohexyl), 56.77 (CH of cyclohexyl), 59.68 (OCH2), 61.01
(OCH2), 85.76 (C4 of furan), 114.54 (C3 of furan), 127.43 (CHpara of
C6H5), 127.73 (2 CHortho of C6H5), 130.11 (2 CHmeta of C6H5), 136.35
(Cipso of C6H5), 137.99 (C5 of furan), 159.36 (C2 of furan), 162.20
(CO2Me), 164.62 (CO2Me), 171.26 (NCO).
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