One-pot, three-component reaction of N-isocyanimino-triphenylphosphorane (Ph 3PNNC), acenaphthoquinone, and an aromatic carboxylic acid in water

Article abstract of DOI:10.1080/10426507.2015.1054933

Water was used as an efficient green solvent for the synthesis of sterically congested 1,3,4-oxadiazoles derivatives via a one-pot, three-component reaction of various aromatic carboxylic acids, acenaphthoquinone, and N-isocyanimino-triphenylphosphorane (

Full text of DOI:10.1080/10426507.2015.1054933

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
One-Pot Three-Component Reaction of N-
Isocyanimino-Triphenylphosphorane (Ph3Pnnc),
Acenaphthoquinone and An Aromatic Carboxylic
Acid in Water
Ali Jafari, Ali Ramazani, Fariba Sadri & Sang Woo Joo
To cite this article: Ali Jafari, Ali Ramazani, Fariba Sadri & Sang Woo Joo (2015): One-
Pot Three-Component Reaction of N-Isocyanimino-Triphenylphosphorane (Ph3Pnnc),
Acenaphthoquinone and An Aromatic Carboxylic Acid in Water, Phosphorus, Sulfur, and Silicon
and the Related Elements, DOI: 10.1080/10426507.2015.1054933
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1054933
Accepted online: 06 Oct 2015.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [Monash University Library]
Date: 09 October 2015, At: 22:35

ACCEPTED MANUSCRIPT
ONE-POT THREE-COMPONENT REACTION OF N-ISOCYANIMINO-
TRIPHENYLPHOSPHORANE (Ph3PNNC), ACENAPHTHOQUINONE AND AN
AROMATIC CARBOXYLIC ACID IN WATER
Ali Jafari1, Ali Ramazani*,1, Fariba Sadri2 and Sang Woo Joo3
1Department of Chemistry, University of Zanjan, P O Box 45195-313, Zanjan, Iran,
2Department of Chemistry, Payame Noor University, P O BOX 19395-4697 Tehran, Iran
3School of Mechanical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of
Korea, E-mail: swjoo@yu.ac.kr
*Corresponding Author Email: aliramazani@gmail.com
Keywords
N-isocyanimino-triphenylphosphorane (Ph3PNNC); water; 1,3,4-oxadiazoles; aza-Wittig
reaction; aromatic carboxylic acid.
Abstract
Water was used as an efficient green solvent for the synthesis of sterically congested 1,3,4-
oxadiazoles derivatives via a one-pot, three component reaction of various aromatic carboxylic
acids, acenaphthoquinone and N-isocyanimino-triphenylphosphorane (Ph3PNNC) at RT (20–26
°C) for 15 h. The remarkable features of this “green” methodology include high yield of
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
products, water as the solvent, short reaction time, operational simplicity, environmentally
benign and the absence of any volatile or hazardous organic solvents.
N
N
HO
O
O
O
Ar
O
H2O
ArCO2H
+
Ph3PO
Ph3P
N
C
+
N
+
r.t., 15 h
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
The aza-Wittig-type reaction has attracted much attention recently because of its high
potential for the synthesis of a wide variety of nitrogen heterocycles, which can be attributed in
the preparation of functionalized iminophosphoranes.1 Through aza-Wittig reaction,
iminophosphoranes with isocyanates, carbon dioxide, or carbon disulfide can easily be converted
into functionalized hetero-cumulenes.1 The nucleophilicity at the nitrogen is an important factor
in the use of these iminophosphoranes as aza-Wittig reagents. Iminophosphoranes are important
reagents in organic chemistry, especially in the producing of naturally occurring products,
compounds with biological and pharmacological activity.1 In the last years, several preparative
procedures have been reported for the preparations and synthetic applications of
iminophosphoranes.1 It is expected N-isocyanimino-triphenylphosphorane (Ph3PNNC) 3 to have
synthetic potential because it develops a reaction system in which the iminophosphorane group
can react with a reagent having a carbonyl functionality. 1
There is increasing interest in the chemistry of heterocyclic compounds because of their
vast distribution in natural compounds, their applications in pharmaceuticals, agrochemicals, and
industrial chemicals, etc. 1,3,4-Oxadiazole derivatives are an important class of heterocycles,
which possess pharmaceutical and biological activities, such as antimicrobial,2,3
antimycobacterial,4 anti-inflammatory,5 anti-allergic,6 antifungal and genotoxic activities.7
Nowadays, many organic compounds can be synthesized in multicomponent reactions (MCRs).8
An important class of MCRs are the isocyanides-based multicomponent reactions (IMCRs).
IMCRs are especially interesting because they are more diverse and versatile than non-IMCRs.9–
18 Several methods have been reported in the literature for the synthesis of 1,3,4-oxadiazoles.
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
These protocols are multistep in nature.19–21 In recent years, a one-pot method for the synthesis
of 1,3,4-oxadiazole derivatives from N-isocyanimino-triphenylphosphorane (Ph3PNNC) has been
established.22–26
One important aspect of green chemistry is the elimination of solvents in chemical processes or
the replacement of hazardous solvents with relatively benign solvents. Water being the most
environmentally benign, cleanest, cheapest, nonflammable, and naturally occurring solvent
having high specific heat capacity is the primary choice. Moreover, in water significant rate
enhancement was observed in many reactions,27 because of hydrophobic interactions that induce
a favorable aggregation of polar components in water.28
In continuation of our ongoing effort to develop new methods using water in organic
synthesis,29 in this paper we describe the one-pot reaction between various aromatic carboxylic
acids (1), acenaphthoquinone (2) and N-isocyanimino-triphenylphosphorane (Ph3PNNC) (3) in
water at RT (20–26 °C) to give sterically congested 1,3,4-oxadiazole derivatives (4, Scheme 1).
RESULTS AND DISCUSSION
Herein, the sterically congested 2,5-disubstituted 1,3,4-oxadiazoles derivatives (4) were
synthesized via a one-pot three-component reaction of various aromatic carboxylic acids (1),
acenaphthoquinone (2) and N-isocyanimino-triphenylphosphorane (Ph3PNNC) (3) in water as a
green solvent at RT (20–26 °C) in 15 h (Scheme 1). The N-isocyanimino-triphenylphosphorane
(Ph3PNNC) 3 was prepared based on reported procedure.30,31
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
In our initial investigation to study the solvent effect, the reaction of benzoic acid,
acenaphthoquinone and N-isocyanimino-triphenylphosphorane (as a model reaction) was studied
in different solvents, like ethanol, methanol, dichloromethane, toluene, acetonitrile and water
(Table 1, entries 1-6). Isolated yield of the desired product (4a) was 84% when the reaction was
carried out in water as a solvent at RT (20–26 °C) for 15 h (Table 1, entry 6). Consequently,
water was selected as the best reaction solvent. The results of this study are summarized in Table
1.
After selecting an appropriate solvent, to explore the scope of water effect as reaction solvent in
the preparation of sterically congested 1,3,4-oxadiazoles derivatives, one-pot three-component
reaction of an aromatic carboxylic acid derivative (1 mmol) with acenaphthoquinone (1 mmol)
and N-isocyanimino-triphenylphosphorane (Ph3PNNC) (1 mmol) were investigated in water at
RT (20–26 °C). The reaction proceeds smoothly and cleanly under mild conditions in water that
is considerable to be a green chemistry method.
All of the prepared products are known compounds and were identified by comparing
their physical and spectral data with those reported in the literature.32 The data of the prepared
compounds are similar to their previously reported data32 under the same analytical conditions.
A proposed mechanism for the formation of products 4a-p is shown in Scheme 2. On the
basis of the chemistry of isocyanides,33 it is reasonable to assume that the first step may involve
nucleophilic addition of the N-isocyanimino-triphenylphosphorane (Ph3PNNC) (3) to
acenaphthoquinone (2), which is facilitated by its protonation with the aromatic acid (1), leading
to nitrilium intermediate 6. This intermediate may be attacked by the conjugate base of acid (1)
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
to form 1:1:1 adduct (7). This adduct may undergo intramolecular aza-Wittig reaction of
iminophosphorane moiety with the ester carbonyl to afford the sterically congested 1,3,4-
oxadiazole derivatives (4) by removal of triphenylphosphine oxide (5) from intermediate (8) (See
Scheme 2).
EXPERIMENTAL
N-isocyanimino-triphenylphosphorane (Ph3PNNC) 3 was prepared based on reported
procedure.30,31 Other starting materials and solvents were obtained from Merck (Germany) and
Fluka (Switzerland) and were used without further purification. The progress of the reaction was
monitored by thin layer chromatography (TLC) technique. Melting points were measured on an
Electrothermal 9100 apparatus and are uncorrected. IR spectra were measured on a Jasco 6300
FT-IR spectrometer. 1H and 13C NMR spectra (CDCl3) were recorded on a BRUKER DRX-250
AVANCE spectrometer at 250.0 and 62.5MHz, respectively. Mass spectra were recorded on a
FINNIGAN-MATT 8430 mass spectrometer operating at an ionization potential of 20 eV.
Preparative layer chromatography (PLC) plates were prepared from Merck silica gel (F254
powder.
)
General Procedure for the synthesis of sterically congested 2,5-disubstituted 1,3,4-
oxadiazoles derivatives (4a-p)
A mixture of N-isocyanimino-triphenylphosphorane (Ph3PNNC) (1.0 mmol, 0.302 g),
acenaphthoquinone (1.0 mmol, 0.182 g) and an aromatic carboxylic acid (1.0 mmol (1a: 0.136 g,
1b: 0.201 g, 1c: 0.147 g, 1d: 0.136 g, 1e: 0.178 g, 1f: 0.173 g, 1g: 0.214 g, 1h: 0.215 g, 1i: 0.172
g, 1j: 0.157 g, 1k: 0.140 g, 1l: 0.136 g, 1m: 0.152 g, 1n: 0.182 g, 1o: 0.136 g, 1p: 0.150 g.)) in
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
distilled water (5 mL) was stirred at RT (20–26 °C) for 15 h. After completing the reaction, the
resulting mixture was extracted in dichloromethane. The solvent was removed under reduced
pressure, and the viscous residue was purified by preparative layer chromatography (PLC) (silica
gel powder, F254; petroleum ether-ethyl acetate (4:1)).
2-hydroxy-2-(5-phenyl-1,3,4-oxadiazol-2-yl)-1(2H)-acenaphthylenone (4a, C20H12N2O3)
Yellow powder; yield 84%; Rf = 0.36 (petroleum ether/ethyl acetate, 4/1); mp: 162-164 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.59 (br s, OH); 7.40 - 8.30 (m, 11CHarom) ppm. 13C NMR
(62.53 MHz, CDCl3) δ = 87.74 (C-OH); 122.56, 123.88, 126.97, 127.13, 128.79 and 132.85
(6CH of naphthalene ring); 128.96, 129.07 and 132.02 ( 5CH of phenyl group); 129.60 (C of
phenyl group); 123.22, 127.80, 135.12 and 142.96 (4C of naphthalene ring); 161.05 and 166.13
(2C=N of oxadiazole); 198.51 (C=O) ppm. IR (KBr, υ max) = 3366, 3073, 1718, 1603, 1448 and
1012 cm-1. MS (EI, 20 eV): m/z (%)= 328 (M+), 198 (16), 182 (34), 154 (83), 126 (100), 98 (28),
85 (28), 76 (39), 62 (38) and 43 (45).
2-[5-(4–bromophenyl)-1,3,4–oxadiazol–2–yl]–2–hydroxy–1(2H)–acenaphthylenone (4b,
C20H11BrN2O3)
Yellow powder; yield 81%; Rf = 0.33 (petroleum ether/ethyl acetate, 4/1); mp: 151-153 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.57 (br s, OH); 7.57 (d, 3JHH = 8.3 Hz, 2CHarom); 8.03 (d, 3JHH
=
8.3 Hz, 2CHarom); 7.69 - 7.86 and 8.09-8.30 (m, 6CHarom) ppm. 13C NMR (62.53 MHz, CDCl3) δ
= 86.50 (C-OH); 122.59, 123.96, 127.03, 128.51, 128.83 and 132.94 (6CH of naphthalene ring);
129.08 and 132.33 (4CH of benzene ring); 126.80 and 129.50 (2C of benzene ring); 122.12,
130.98, 134.22 and 140.25 (4C of naphthalene ring); 164.02 and 165.03 (2C=N of oxadiazole);
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
202.02 (C=O) ppm. IR (KBr, υ max) = 3204, 3077, 1733, 1600, 1481 and 1007 cm-1. MS (EI, 20
eV): m/z (%) = 407 (M+), 198 (8), 182 (37), 154 (78), 126 (100), 98 (22), 85 (22), 75 (55), 62
(45) and 50 (18).
4-[5-(1-hydroxy-2-oxo-1,2-dihydro-1-acenaphthylenyl)-1,3,4-oxadiazol-2-yl]benzonitrile
(4c, C21H11N3O3)
Yellow powder; yield 74%; Rf = 0.30 (petroleum ether/ethyl acetate, 4/1); mp: 161-163 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 3.63 (s, OH); 7.71 - 8.33 (m, 10CHarom) ppm. 13C NMR (62.53
MHz, CDCl3) δ = 77.31 (C-OH); 122.07, 127.13, 127.60, 128.45, 129.09 and 132.75 (6CH of
naphthalene ring); 115.51 and 132.62 (4CH of benzene ring); 109.98 and 128.90 (2C of benzene
ring); 124.00, 133.02, 135.05 and 143.03 (4C of naphthalene ring); 161.03 and 165.13 (2C=N of
oxadiazole); 192.21 (C=O) ppm. IR (KBr, υ max) = 3439, 3209, 1729, 1604, 1495 and 1014 cm-1.
MS (EI, 20 eV): m/z (%) = 353 (M+), 197 (17), 182 (32), 154 (73), 130 (100), 126 (85), 101 (90),
75 (86), 62 (47), 50 (48) and 42 (30).
2–hydroxy–2-[5-(3–methylphenyl)-1,3,4-oxadiazol–2-yl]-1(2H)–acenaphthylenone (4d,
C21H14N2O3)
Yellow powder; yield 85%; Rf = 0.36 (petroleum ether/ethyl acetate, 4/1); mp: 169-171 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 2.37 (s, CH3); 4.50 (br s, OH); 7.26 - 8.30 (m, 10CHarom) ppm.
13C NMR (62.53 MHz, CDCl3) δ = 21.21 (CH3); 76.57 (C-OH); 122.55, 124.29, 126.84, 128.44,
128.78 and 132.86 (6CH of naphthalene ring); 122.06, 127.58, 129.07 and 132.60 (4CH of
benzene ring); 128.81 and 129.10 (2C of benzene ring); 123.82, 130.91, 134.80 and 143.35 (4C
of naphthalene ring); 164.18 and 166.75 (2C=N of oxadiazole); 198.87 (C=O) ppm. IR (KBr, υ
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
max) = 3399, 3073, 1723, 1603, 1490 and 1073 cm-1. MS (EI, 20 eV): m/z (%) = 342 (M+), 198
(6), 182 (24), 154 (54), 126 (60), 105 (100), 91 (18), 76 (54), 62 (23) and 50 (24).
2-{5-[4-(tert-butyl)phenyl]-1,3,4–oxadiazol–2-yl}–2-hydroxy-1(2H)–acenaphthylenone (4e,
C24H20N2O3)
Yellow powder; yield 89%; Rf = 0.33 (petroleum ether/ethyl acetate, 4/1); mp: 176-178 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 1.30 (s, 3CH3); 5.30 (br s, OH); 7.41 (d, 3JHH = 8.3 Hz,
2CHarom); 7.98 (d, 3JHH = 8.3 Hz, 2CHarom); 7.71 - 7.86 and 8.05-8.20 (m, 6CHarom) ppm. 13C
NMR (62.53 MHz, CDCl3) δ = 31.03 (3CH3); 35.03(C); 76.60 (C-OH); 122.53, 123.74, 126.98,
128.70, 129.03 and 132.73 (6CH of naphthalene ring); 125.89 and 126.79 (4CH of benzene
ring); 128.43 and 129.75 (2C of benzene ring); 122.04, 130.88, 135.51 and 142.33 (4C of
naphthalene ring); 164.28 and 166.00 (2C=N of oxadiazole); 198.17 (C=O) ppm. IR (KBr, υ max
= 3209, 2965, 1738, 1614, 1495 and 1010 cm-1. MS (EI, 20 eV): m/z (%) = 384 (M+), 182 (11),
163 (25), 148 (14), 120 (38), 103 (17), 91 (73), 76 (35), 57 (18) and 43 (100).
)
2-[5-(3-chlorophenyl)–1,3,4-oxadiazol–2-yl]–2–hydroxy–1(2H)–acenaphthylenone (4f,
C20H11ClN2O3)
Yellow powder; yield 79%; Rf = 0.30 (petroleum ether/ethyl acetate, 4/1); mp: 174-176 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.06 (br s, OH); 7.33- 8.29 (m, 10CHarom) ppm. 13C NMR
(62.53 MHz, CDCl3) δ = 77.25 (C-OH); 122.06, 123.98, 127.02, 128.44, 129.09 and 132.94
(6CH of naphthalene ring); 125.24, 130.34, 132.09 and 132.62 (4CH of benzene ring); 128.83
and 148.62 (2C of benzene ring); 122.59, 129.50, 133.82 and 135.12 (4C of naphthalene ring);
158.50 and 164.82 (2C=N of oxadiazole); 198.27 (C=O) ppm. IR (KBr, υ max) = 3379, 3080,
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1718, 1602, 1551 and 1068 cm-1. MS (EI, 20 eV): m/z (%) = 362 (M+), 197 (18), 182 (44), 154
(95), 126 (100), 98 (23), 85 (19), 75 (47), 62 (34) and 50 (17).
2–hydroxy–2-[5-(3–phenoxyphenyl)-1,3,4–oxadiazol–2-yl]-1(2H)–acenaphthylenone (4g,
C26H16N2O4)
Yellow powder; yield 75%; Rf = 0.26 (petroleum ether/ethyl acetate, 4/1); mp: 153-155 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.81 (br s, OH); 6.96- 8.29 (m, 15CHarom) ppm. 13C NMR
(62.53 MHz, CDCl3) δ = 85.02 (C-OH); 117.19, 119.14, 121.80, 123.88, 129.95, 130.45 and
130.92 (9CH of benzene rings); 122.05, 123.97, 126.95, 128.77, 129.04 and 132.84 (6CH of
naphthalene ring); 122.52, 129.62, 135.22 and 145.30 (4C of naphthalene ring); 128.44, 156.20
and 157.85 (3C of benzene rings); 165.45 and 164.71 (2C=N of oxadiazole); 198.17 (C=O) ppm.
IR (KBr, υ max)= 3307, 3082, 1743, 1563, 1485 and 1225 cm-1; MS (EI, 20 eV): m/z (%) = 420
(M+), 214 (27), 197 (29), 182 (80), 154 (80), 126 (100), 98 (21), 85 (15), 76 (29), 62 (29) and 50
(22).
2-{5-[4-(bromomethyl)phenyl]-1,3,4–oxadiazol–2-yl}–2–hydroxy-1(2H)-acenaphthylenone
(4h, C21H13BrN2O3)
Yellow powder; yield 85%; Rf = 0.33 (petroleum ether/ethyl acetate, 4/1); mp: 163-165 ºC. 1H
NMR (250.13 MHz, CDCl3) δ: 4.46 (s, CH2); 4.98 (br s, OH); 7.43 (d, 3JHH = 8.3 Hz, 2CHarom);
7.90 (d, 3JHH = 8.3 Hz, 2CHarom); 7.70- 7.86 and 7.99-8.29 (m, 6CHarom) ppm. 13C NMR (62.53
MHz, CDCl3) δ = 32.09 (CH2); 76.77 (C-OH); 122.56, 123.89, 126.95, 127.55, 129.07 and
132.87 (6CH of naphthalene ring); 129.61 and 132.62 (4CH of benzene ring); 128.44 and 128.79
(2C of benzene ring); 123.10, 130.92, 135.24 and 141.80 (4C of naphthalene ring); 165.12 and
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
166.22 (2C=N of oxadiazole); 198.15 (C=O) ppm. IR (KBr, υ max) = 3343, 3072, 1717, 1603,
1486 and 1012 cm-1.
2-hydroxy-2-[5-(1-naphthyl)-1,3,4-oxadiazol-2-yl]-1(2H)-acenaphthylenone (4i,
C24H14N2O3)
Yellow powder; yield 78%; Rf = 0.36 (petroleum ether/ethyl acetate, 4/1); mp: 154-156 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.84 (br s, OH); 7.42- 9.07 (m, 13CHarom) ppm. 13C NMR
(62.53 MHz, CDCl3) δ = 76.39 (C-OH); 122.60, 124.67, 125.95, 126.71, 126.96, 128.22, 128.59,
128.75, 128.79, 129.08 and 132.88 (13CH naphthalene rings); 123.91, 128.35, 129.90, 131.92,
133.80, 135.22 and 142.26 (7C of naphthalene rings); 162.32 and 166.25 (2C=N of oxadiazole);
198.17 (C=O) ppm. IR (KBr, υ max) = 3433, 3186, 1741, 1604, 1538 and 1089 cm-1.
2-[5-(4–chlorophenyl)-1,3,4–oxadiazol–2–yl]–2–hydroxy-1(2H)–acenaphthylenone (4j,
C20H11ClN2O3)
Yellow powder; yield 73%; Rf = 0.30 (petroleum ether/ethyl acetate, 4/1); mp: 169-171 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.58 (br s, OH); 7.77 (d, 3JHH = 8.3 Hz, 2CHarom); 8.24 (d, 3JHH
=
8.3 Hz, 2CHarom); 7.40 - 7.73 and 7.83-8.13 (m, 6CHarom) ppm. 13C NMR (62.53 MHz, CDCl3) δ
= 83.23 (C-OH); 122.07, 122.58, 128.40, 128.45, 129.09 and 132.94 (6CH of naphthalene ring);
129.37 and 132.63 (4CH of benzene ring); 127.02 and 137.52 (2C of benzene ring); 123.95,
128.83, 135.02 and 138.45 (4C of naphthalene ring); 164.12 and 165.23 (2C=N of oxadiazole);
202.12 (C=O) ppm. IR (KBr, υ max) = 3227, 3022, 1732, 1604, 1486 and 1078 cm-1.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2-[5-(4–fluorophenyl)-1,3,4–oxadiazol–2–yl]–2-hydroxy-1(2H)–acenaphthylenone (4k,
C20H11FN2O3)
Yellow powder; yield 80%; Rf = 0.33 (petroleum ether/ethyl acetate, 4/1); mp: 156-158 ºC. 1H
NMR (250.13 MHz, CDCl3) δ = 4.40 (s, OH); 7.10 - 8.31 (m, 10CHarom) ppm. 13C NMR (62.53
MHz, CDCl3) δ = 82.65 (C-OH); 116.38 (d, 2JCF = 20.1 Hz, 2CH of benzene ring); 122.06,
122.55, 127.00, 128.44, 129.09 and 132.62 (6CH of naphthalene ring); 129.53 (d, 3JCF = 12.5 Hz,
2CH of benzene ring); 123.93, 128.94, 135.02 and 140.74 (4C of naphthalene ring); 127.00 (C of
benzene ring); 160.52 (d, 1JCF = 252.0 Hz, CF of benzene ring); 164.48 and 166.53 (2C=N of
oxadiazole); 189.51 (C=O) ppm. IR (KBr, υ max) = 3375, 3082, 1725, 1606, 1497 and 1013 cm-1.
2–hydroxy–2-[5-(4–methylphenyl)-1,3,4-oxadiazol–2–yl]-1(2H)–acenaphthylenone (4l,
C21H14N2O3)
Yellow powder; yield 83%; Rf = 0.36 (petroleum ether/ethyl acetate, 4/1); mp: 170-172 ºC. 1H
NMR (250.13 MHz, CDCl3) δ= 2.37 (s, CH3); 4.30 (br s, OH); 7.20 - 8.29 (m, 10CHarom) ppm.
13C NMR (62.53 MHz, CDCl3) δ= 21.61 (CH3); 76.64 (C-OH); 122.05, 123.81, 127.07, 128.44,
129.05 and 132.80 (6CH of naphthalene ring); 129.64 and 132.61 (4CH of benzene ring);
122.52, 128.75, 135.22 and 142.85 (4C of naphthalene ring); 126.89 and 128.60 (2C of benzene
ring); 162.08 and 164.13 (2C=N of oxadiazole); 198.10 (C=O) ppm. IR (KBr, υ max) = 3355,
3068, 1725, 1603, 1498 and 1012 cm-1.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2–hydroxy–2-[5-(4–methoxyphenyl)-1,3,4–oxadiazol–2–yl]-1(2H)-acenaphthylenone (4m,
C21H14N2O4)
Yellow powder ; yield 73%; Rf = 0.26 (petroleum ether/ethyl acetate, 4/1); mp: 195-197 ºC. 1H
NMR (250.13 MHz, CDCl3) δ= 3.84 (s, CH3); 4.33 (s, OH); 6.85 - 8.31 (m, 10CHarom) ppm. 13C
NMR (62.53 MHz, CDCl3) δ = 55.55 (OCH3); 77.55 (C-OH); 122.54, 123.92, 126.92, 128.93,
128.95 and 132.89 (6CH of naphthalene ring); 114.40 and 132.50 (4CH of benzene ring);
122.54, 131.04, 135.22 and 140.04 (4C of naphthalene ring); 128.86 and 158.82 (2C of benzene
ring); 164.08 and 166.53 (2C=N of oxadiazole); 194.51 (C=O) ppm. IR (KBr, υ max) = 3244,
3083, 1739, 1614, 1500 and 1185 cm-1.
2-[5-(3,5–dimethoxyphenyl)-1,3,4–oxadiazol–2-yl]–2–hydroxy-1(2H)- acenaphthylenone
(4n, C22H16N2O5)
Yellow powder; yield 71%; Rf = 0.20 (petroleum ether/ethyl acetate, 4/1); mp: 168-170 ºC. 1H
NMR (250.13 MHz, CDCl3) δ= 3.80 (s, 2OCH3); 4.43 (s, OH); 6.56 - 8.30 (m, 9CHarom) ppm.
13C NMR (62.53 MHz, CDCl3) δ= 55.64 (2OCH3); 87.00 (C-OH); 122.04, 123.94, 127.00,
128.43, 132.59 and 132.84 (6CH of naphthalene ring); 105.00 and 107.05 (3CH of benzene
ring); 124.75, 131.04, 135.03 and 142.10 (4C of naphthalene ring); 127.00 and 162.15 (3C of
benzene ring); 164.02 and 166.43 (2C=N of oxadiazole); 189.51 (C=O) ppm. IR (KBr, υ max) =
3380, 3094, 1725, 1604, 1463 and 1162 cm-1.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2–hydroxy–2-[5-(2–methylphenyl)-1,3,4–oxadiazol–2–yl]-1(2H)-acenaphthylenone (4o,
C21H14N2O3)
Yellow powder; yield 77%; Rf = 0.34 (petroleum ether/ethyl acetate, 4/1); mp: 154-156 ºC. 1H
NMR (250.13 MHz, CDCl3) δ= 2.57 (s, CH3); 4.09 (br s, OH); 7.06 - 8.64 (m, 10CHarom) ppm.
13C NMR (62.53 MHz, CDCl3) δ= 22.32 (CH3); 77.70 (C-OH); 122.06, 123.82, 126.98, 128.44,
129.09 and 132.80 (6CH of naphthalene ring); 126.06, 129.13, 131.50 and 132.61 (4CH of
benzene ring); 123.82, 131.65, 138.62 and 140.35 (4C of naphthalene ring); 128.60 and 132.00
(2C of benzene ring); 164.18 and 166.73 (2C=N of oxadiazole); 198.03 (C=O) ppm. IR (KBr, υ
max) = 3416, 3072, 1725, 1604, 1491 and 1014 cm-1.
2-[5-(3,4–dimethylphenyl)-1,3,4–oxadiazol–2–yl]–2–hydroxy-1(2H)–acenaphthylenone (4p,
C22H16N2O3)
Yellow powder; yield 75%; Rf = 0.32 (petroleum ether/ethyl acetate, 4/1); mp: 167-169 ºC. 1H
NMR (250.13 MHz, CDCl3): δ= 2.26 and 2.28 (s, 2CH3); 4.42 (br s, OH); 7.07 - 8.75 (m,
9CHarom) ppm. 13C NMR (62.53 MHz, CDCl3): δ= 19.65 and 19.93 (2CH3); 80.00 (C-OH);
122.05, 122.54, 126.89, 128.59, 128.85 and 132.75 (6CH of naphthalene ring); 128.43, 130.16
and 132.61 (3CH of benzene ring); 122.05, 129.02, 135.32 and 145.90 (4C of naphthalene ring);
123.92, 127.50 and 128.05 (3C of benzene ring); 164.18 and 166.33 (2C=N of oxadiazole);
188.07 (C=O) ppm. IR (KBr, υ max) = 3376, 3083, 1721, 1603, 1494 and 1184 cm-1.
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
CONCLUSION
In conclusion, in the present paper an efficient green procedure for the synthesis of sterically
congested 2,5-disubstituted 1,3,4-oxadiazole derivatives (4) via a one-pot three-component
reaction of an aromatic carboxylic acid (1), acenaphthoquinone (2) and N-isocyanimino-
triphenylphosphorane (Ph3PNNC) (3) in water as a green reaction solvent at RT (20–26 °C) for
15 h has been developed. The remarkable features of this “green” methodology include high
yield of products, water as the solvent, short reaction time, operational simplicity,
environmentally benign and the absence of any volatile or hazardous organic solvents.
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
[1] Palacios, F.; Aparicio, D.; Rubiales, G.; Alonso, C.; de los Santos, J. M. Curr. Org.
Chem. 2009, 13, 810–828.
[2] Rollas, S.; Gulerman, N.; Erdeniz, H. Farmaco 2002, 57, 171-174.
[3] Holla, B. S.; Gonsalves, R.; Shenoy, S. Eur. J. Med. Chem. 2000, 35, 267-271.
[4] Mamolo, M. G.; Zampieri, D.; Vio, L.; Fermeglia, M.; Ferrone, M.; Pricl, S.; Scialino,
G.; Banfi, E. Bioorg. Med. Chem. 2005, 13, 3797-3809.
[5] Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N. T.; Altinok, G. Farmaco 2002, 57, 101-107.
[6] Musser, J. H.; Brown, R. E.; Loev, B.; Bailey, K.; Jones, H.; Kahen, R.; Huang, F.;
Khandwala, A.; Leibowitz, M. J. Med. Chem. 1984, 27, 121-125.
[7] Maslat, A. O.; Abussaud, M.; Tashtoush, H.; AL-Talib, M. Pol. J. Pharmacol. 2002, 54,
55-59.
[8] Zhu, J. Multicomponent Reactions, Wiley-VCH, Weinheim, Germany, 2005
[9] Dömling, A. Chem. Rev. 2006, 106, 17-89.
[10]
[11]
Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51-80.
Shaabani, A.; Maleki, A.; Rezayan, A. H.; Sarvary, A. Mol. Divers. 2011, 15, 41-
68.
[12]
Ramazani, A.; Tofangchi Mahyari, A.; Rouhani, M.; Rezaei, A. Tetrahedron Lett.
2009, 50, 5625-5627.
[13]
[14]
[15]
Yavari, I.; Khalili, G.; Mirzaei, A. Tetrahedron Lett. 2010, 51, 1190-1192.
Azizian, J.; Ramazani, A.; Haji, M. Helv. Chim. Acta 2011, 94, 371-375.
Sadjadi, S.; Heravi, M. M. Tetrahedron 2011, 67, 2707-2752.
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
[16]
[17]
Ramazani, A.; Mahyari, A. Helv. Chim. Acta, 2010, 93, 2203-2209.
Shoaei, S. M.; Kazemizadeh, A. R. Ramazani, A. Chin. J. Struct. Chem. 2011, 30,
568-574.
[18]
[19]
[20]
[21]
Kazemizadeh, A. R.; Ramazani, A. Arkivoc 2008, xv, 159-165.
Baxendale, I. R.; Ley, S. V.; Martinelli, M. Tetrahedron 2005, 61,5323-5349.
Brown, B. J.; Clemens, I. R. Neesom, J. K., Synlett 2000, 1, 131-133.
Coppo, F. T.; Evans, K. A.; Graybill, T. L.; Burton, G. Tetrahedron Lett. 2004,
45, 3257-3260.
[22]
[23]
[24]
Ramazani, A.; Ahmadi, Y.; Tarasi, R. Heteroat. Chem. 2011, 22, 79-84.
Ramazani, A.; Rezaei, A. Org. Lett. 2010, 12, 2852-2855.
Ramazani, A.; Shajari, N.; Mahyari, A.; Ahmadi, Y. Mol. Divers. 2011, 15, 521-
527.
[25]
Ramazani, A.; Rouhani, M.; Rezaei, A.; Shajari, N.; Souldozi, A. Helv. Chim.
Acta 2011, 94, 282-288.
[26]
[27]
[28]
[29]
Zeinali Nasrabadi, F.; Ramazani, A.; Ahmadi, Y. Mol. Divers. 2011, 15, 791-798.
Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102, 7816-7817.
Bailey, W. J.; Hermes, M. E. J. Am. Chem. Soc. 1962, 27, 2732-2736.
Sadri, F.; Ramazani, A.; Massoudi, A.; Khoobi, M.; Tarasi, R.; Shafiee, A.;
Azizkhani, V.; Dolatyari, L.; Joo, S. W. Green Chem. Lett. Rev. 2014, 7, 257–264. (b)
Sadri, F.; Ramazani, A.; Massoudi, A.; Khoobi, M.; Azizkhani, V.; Tarasi, R.; Dolatyari,
L.; Min, B.-K. Bull. Korean Chem. Soc. 2014, 35, 2029-2032. (c) Ramazani, A.; Rezaei,
A.; Tofangchi Mahyari, A.; Rouhani, M.; Khoobi, M. Helv. Chim. Acta 2010, 93, 2033-
17
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2036. (d) Vessally, E.; Ramazani, A.; Yaaghubi, E. Monatsh Chem 2011, 142,1143–
1147.
[30]
Eur. J. Inorg. Chem. 2005, 21, 4263-4271.
[31] Chiu, T. W.; Liu, Y. H.; Chi, K. M.; Wen, Y. S.; Lu, K. L. Inorg. Chem. 2005, 44,
6425-6430.
[32] Ramazani, A.; Zeinali Nasrabadi, F.; Mashhadi Malekzadeh, A.; Ahmadi, Y.
Monatsh Chem. 2011, 142, 625-630.
Stolzenberg, H.; Weinberger, B.; Fehlhammer, W. P.; Pühlhofer, F. G.; Weiss, R.
[33]
Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168–3210.
18
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 1 Effect of solvent for the synthesis of sterically congested 1,3,4-oxadiazoles derivatives
Yield (%) a,
b
Entry Solvent
Time (h)
EtOH
24
24
24
26
24
15
62
41
59
69
80
84
1
2
3
4
5
6
MeOH
CH2Cl2
Toluene
CH3CN
Water
a Reaction conditions: N-isocyanimino-triphenylphosphorane (1.0 mmol), acenaphthoquinone
(1.0 mmol) and benzoic acid (1.0 mmol) in solvent (5 mL) at RT (20–26 °C).
b Isolated yields.
19
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Scheme 1 Synthesis of sterically congested 2,5-disubstituted 1,3,4-oxadiazole derivatives (4a:
Ar=C6H5; 4b: Ar=4-BrC6H4; 4c: Ar=4-CNC6H4; 4d: Ar=3-MeC6H4; 4e: Ar=4-t-BuC6H4; 4f:
Ar=3-ClC6H4; 4g: Ar=3-PhOC6H4; 4h: Ar=4-BrCH2C6H4; 4i: Ar=C10H7 (1-Naphthyl); 4j: Ar=4-
ClC6H4; 4k: Ar=4-FC6H4; 4l: Ar=4-MeC6H4; 4m: Ar=4-MeOC6H4; 4n: Ar=3,5-diMeOC6H4; 4o:
Ar=2-MeC6H4; 4p: Ar=3,4-diMeC6H4).
20
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
O
HO
O
Ar
HO
O
1
O
N N C
(Ph)3P
O
N
3
N
C
(Ph)3P
Ar
O
2
6
(Ph)3HP
N
(Ph)3HP
O
N
HO
N
O
N
N
OH
OH
N
O
O
O
Ar
O
O
O
Ph PO
+
3
Ar
Ar
5
4
7
8
Scheme 2 Proposed mechanism for the formation of sterically congested 2,5-disubstituted 1,3,4-
oxadiazole derivatives 4 in water.
21
ACCEPTED MANUSCRIPT