(N-isocyanimino)triphenylphosphorane as an efficient reagent for the preparation of N-benzyl-1-Phenyl-1-(5-Phenyl-1,3,4-Oxadiazol-2-yl)methanamine derivatives via in-Situ generation of densely functionalized iminophosphoranes

Article abstract of DOI:10.1080/10426507.2011.568026

A novel isocyanide-based four-component reaction between (N-isocyanimino) triphenylphosphorane, benzyl amine, benzaldehyde derivatives, and various carboxylic acids efficiently provides N-benzyl-1-phenyl-1-(5-phenyl-1,3,4- oxadiazol-2-yl)methanamine deriv

Full text of DOI:10.1080/10426507.2011.568026

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Phosphorus, Sulfur, and Silicon and the
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(N-Isocyanimino)Triphenylphosphorane
as an Efficient Reagent for the
Preparation of N-Benzyl-1-Phenyl-1-
(5-Phenyl-1,3,4-Oxadiazol- 2-
yl)Methanamine Derivatives via in-Situ
Generation of Densely Functionalized
Iminophosphoranes
Ali Ramazani a , Aram Rezaei a & Yavar Ahmadi b
a Chemistry Department, Zanjan University, Zanjan, Iran
b Young Researchers Club, Zanjan Branch, Islamic Azad University,
Zanjan, Iran
Version of record first published: 06 Dec 2011.
To cite this article: Ali Ramazani , Aram Rezaei & Yavar Ahmadi (2012): (N-
Isocyanimino)Triphenylphosphorane as an Efficient Reagent for the Preparation of N-Benzyl-1-
Phenyl-1-(5-Phenyl-1,3,4-Oxadiazol- 2-yl)Methanamine Derivatives via in-Situ Generation of Densely
Functionalized Iminophosphoranes, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:1,
22-31
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Phosphorus, Sulfur, and Silicon, 187:22–31, 2012
Copyright ꢀC 2011 Islamic Azad University
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.568026
(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE
AS AN EFFICIENT REAGENT FOR THE PREPARATION
OF N-BENZYL-1-PHENYL-1-(5-PHENYL-1,3,4-OXADIAZOL-
2-YL)METHANAMINE DERIVATIVES VIA IN-SITU
GENERATION OF DENSELY FUNCTIONALIZED
IMINOPHOSPHORANES
Ali Ramazani,1 Aram Rezaei,1 and Yavar Ahmadi2
1Chemistry Department, Zanjan University, Zanjan, Iran
2Young Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran
GRAPHICAL ABSTRACT
Abstract A novel isocyanide-based four-component reaction between (N-isocyanimino)
triphenylphosphorane, benzyl amine, benzaldehyde derivatives, and various carboxylic
acids efficiently provides N-benzyl-1-phenyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)methanamine
derivatives in good yields without using any catalyst or activation. The reaction can be carried
out as a simple one-pot protocol at room temperature.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: NMR Spectra for 5i.]
Keywords 1,3,4-Oxadiazole; four-component reaction; aza-wittig; iminophosphorane; hete-
rocyclization
Received 22 January 2011; accepted 27 February 2011.
This research was supported by the “Zanjan University” and the “Iran National Science Foundation: INSF”.
Address correspondence to Ali Ramazani, Chemistry Department, Zanjan University, 4537138111, P O Box
45195-313, Zanjan, Iran. E-mail: aliramazani@gmail.com
22

(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE AS AN EFFICIENT REAGENT
23
Figure 1 Examples of some biologically active 2,5-disubstituted-1,3,4-oxadiazole derivatives.
INTRODUCTION
1,3,4-Oxadiazoles have been an important pharmacophore in the pharmaceutical in-
dustry.1 The therapeutic applications of 1,3,4-oxadizoles include HIV integrase inhibitor,2
tyrosinase inhibitor,3 anti-inflammatory,4 antihypoglycemic,5 anticancer,6 antimalarial,7 an-
giogenesis inhibitor,8 anticonvulsive, antiemetic, diuretic,9 and dopamine transporters.10
Furthermore, 1,3,4-oxadiazole derivatives with an amine and an alkyl tail have been ap-
plied as electroluminescent materials.11 In 1990, it was found that 2-(biphenyl-4-yl)-5-
(4-tert-butylphenyl)-1,3,4-oxadiazole (PBD) functioned very well as an excellent electron
transport material (ETM) in an organic multilayer EL diode.12 1,3,4-Oxadiazoles are also
important starting materials for cycloaddition reactions13 in the synthesis of furans and
natural products (Figure 1).14
The aza-Wittig reactions of iminophosphoranes have attracted much attention in view
of their usefulness in the synthesis of nitrogen-containing heterocyclic compounds since
they were first prepared in 1919 by Staudinger and Meyer.15 Several interesting heterocy-
clization reactions involving iminophosphoranes have been reviewed. These compounds
can easily be altered through aza-Wittig reaction with carbon disulfide, isocyanates, or
carbon dioxide into functionalized heterocumulenes which display a wealthy chemistry of
of an uncommon synthetic covenant.16 The nucleophilicity at nitrogen is a factor of neces-
sary mechanistic importance in the use of these iminophosphoranes as aza-Wittig reagents.
Iminophosphoranes are significant reagents in synthetic organic chemistry, specially in the
synthesis of naturally occurring products, compounds with biological and pharmacological
activity.17 There are several reports for the utility of (N-isocyanimino)triphenylphosphorane
4 in the synthesis of metal complexes. Nevertheless, the organic chemistry of 4 remains
relatively unexplored. The (N-isocyanimino)triphenylphosphorane 4 is presumed to have
synthetic potential because it prepares a reaction system in which the iminophosphorane
group can react with a reagent having a carbonyl functionality (Scheme 1).18
RESULTS AND DISCUSSION
Recently, 1,3,4-oxadiazoles have been the object of intense research in organic syn-
thesis and medicinal chemistry, and several procedures have been reported for the synthesis
of these heterocyclic compounds which are multistep in nature.19 Accordingly, development
of a synthetic procedure that could be used to prepare a diversity of these templates re-
mains an significant task. In the last years, several synthetic approaches have been reported
for the preparation of (N-isocyanimino)triphenylphosphorane (CNNPPh3) 4.18 There are
several reports on the use of (N-isocyanimino)triphenylphosphorane 4 in the synthesis of
metal complexes.18 Nevertheless, application of 4 in the synthesis of organic compounds

24
A. RAMAZANI ET AL.
Scheme 1 Synthesis of N-benzyl-1-phenyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)methanamine derivatives 5a–k.
is scarce.20 As part of our ongoing program to develop efficient and robust methods for the
preparation of heteroatom-containing organic compounds,21 we sought to develop a conve-
nient preparation of sterically congested 2,5-disubstituted 1,3,4-oxadiazoles 5 by a multi-
component reaction between (N-isocyanimino)triphenylphosphorane (4), benzyl amine (2),
benzaldehyde derivatives (1), and various carboxylic acids (3), followed by an aza-Wittig
cyclization in CH2Cl2 at ambient temperature in excellent yields (Scheme 1 and Figure 2).
This route permits us to introduce great molecular diversity under mild reaction
conditions, including substitution and scaffold diversity. A large number of derivatives
can be rapidly synthesized in excellent purity and high yield by using this method. The
structures of the products were deduced from their IR, mass, H NMR, and 3C NMR spectra.
The mass spectra of these compounds displayed molecular ion peaks at the appropriate m/z
values. The H NMR spectrum of 5a consisted of an AB-quartet for CH2 of benzyl group at
3.87 and 3.93 (2JHH = 13.25 Hz), a singlet at δ = 5.26 for CH, and a multiplet at 7.30–7.77
1
and 8.01–8.18 for aromatic hydrogens. The H-decoupled 13C NMR spectrum of 5a is
in agreement with the proposed structure. In view of the success of the above-mentioned
reaction, we explored the scope of this promising reaction by varying the structure of
1
the benzaldehyde and carboxylic acid component (Table 1). As an example, the H and
13C NMR spectra for 5i are given in the Supplemental Materials (Figures S1 and S2). As
indicated in Figure 2 and Scheme 1, the reaction proceeds very cleanly under mild reaction
conditions at room temperature and no undesirable by-products were observed. Owing to
the great diversity of substitution patterns, this reaction may be used in the production of
combinatorial libraries.

(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE AS AN EFFICIENT REAGENT
25
Figure 2 Synthesis of N-benzyl-1-phenyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)methanamine derivatives 5a–k.
Table 1 Synthesis of N-benzyl-1-phenyl-1-(5-phenyl-1,3,4-oxaddiazol-2-yl)methanamine derivatives 5a–k
from benzaldehyde 1, amine 2, and carboxylic acid 3 in the presence of (N-isocyanimino)triphenylphosphorane 4
Aldehyde 1
benzaldehyde
benzaldehyde
benzaldehyde
benzaldehyde
benzaldehyde
4-fluoro benzaldehyde
benzaldehyde
4-fluoro benzaldehyde
benzaldehyde
Amine 2
Carboxylic acid 3
Product
1
2
3
4
5
6
7
8
9
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
benzyl amine
biphenyl-4-carboxylic acid
benzoic acid
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-fluorobenzoic acid
3-fluorobenzoic acid
4-bromobenzoic acid
4-bromobenzoic acid
3-bromobenzoic acid
3-bromobenzoic acid
4-chlorobenzoic acid
4-chlorobenzoic acid
2-chloro-4-nitrobenzoic acid
10
11
4-fluoro benzaldehyde
benzaldehyde
5g
5k

26
A. RAMAZANI ET AL.
Scheme 2 A possible mechanism for the formation of products 5a–k.
A mechanistic rationalization for this reaction is provided in Scheme 2. It is con-
ceivable that, the initial event is the condensation of the benzaldehyde 1, benzyl amine
2, and carboxylic acid 3 entities to an intermediate imine 7. Nucleophilic addition of the
(N-isocyanimino)triphenylphosphorane 4 to the imine intermediate 7, leads to nitrilium
intermediate 8. This intermediate may be attacked by the conjugate base of acid 3 to form
1:1:1 adduct 9. This adduct may undergo intramolecular aza-Wittig reaction of iminophos-
phorane moiety with the ester carbonyl group to afford the isolated 2,5-disubstituted 1,3,4-
oxadiazole 5 by removal of triphenylphosphine oxide 6 from intermediate 10.20e
To the best of our knowledge, this is the first report in which (N-isocyanimino)
triphenylphosphorane is used in a four-component condensation in the presence of benzyl
amine followed by an intramolecular aza-Wittig22,23 ring closure of the iminophosphorane
moiety with the ester carbonyl. In conclusion, we are reporting a new IMCR,24 yielding
2,5-disubstituted 1,3,4-oxadiazole derivatives, by a sequence of a multicomponent reaction,
and an intramolecular aza-Wittig closure. Due to the easy availability of the synthetic
approach and the neutral ring closure conditions, this new synthetic approach discussed
here has the potential to synthesize various 2,5-disubstituted 1,3,4-oxadiazoles, which are
of considerable interest as potential biological active compounds or pharmaceuticals. Other
aspects of this process are under investigation.
EXPERIMENTAL
General
Starting materials and solvents were obtained from Merck (Germany) and Fluka
(Switzerland) and were used without further purification. The methods used to follow

(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE AS AN EFFICIENT REAGENT
27
the reactions are TLC and NMR. TLC and NMR indicated that there is no side product.
Melting points were measured on an Electrothermal 9100 apparatus and were uncorrected.
1
IR spectra were measured on a Jasco 6300 FTIR spectrometer. H and 13C NMR spectra
were measured (CDCl3 solution) with a BRUKER DRX-250 AVANCE spectrometer at
250.0 and 62.5 MHz, respectively. Elemental analyses were performed using a Heraeus
CHN-O-Rapid analyzer. Mass spectra were recorded on a FINNIGAN-MATT 8430 mass
spectrometer operating at an ionization potential of 20 eV. Flash chromatography columns
were prepared from Merck silica gel powder.
General Procedure for the Preparation of Compounds 5a–k; General
Procedure Exemplified for 5a
To a magnetically stirred solution of benzylamine (1 mmol), benzaldehyde (1mmol),
and (N-isocyanimino)triphenylphosphorane (1 mmol) in CH2Cl2 (5 mL) was added drop-
wise of a solution of biphenyl-4-carboxylic acid (1 mmol) in CH2Cl2 (5 mL) at room
temperature over 15 min. The mixture was stirred for 2 h. The solvent was removed under
reduced pressure, and the viscous residue was purified by flash column chromatography
(silica gel powder; petroleum ether-ethyl acetate (2:1)) to afford 5a (93%) as a yellow oil.
The characterization data of the compounds are given below:
N-Benzyl-1-(5-(Biphenyl-4-yl)-1,3,4-Oxadiazol-2-yl)-N-Methyl-1-Phenyl
methanamine (5a). Yellow Oil (yield 88%), IR (KBr) (νmax/cm−1): 3030, 2924, 2374,
2345, 1547, 1451, 1051, 845. 1H NMR (CDCl3, 250 MHz): δH (ppm) 2.17 (1H, br, s, NH,
2
exchanged by D2O addition), 3.87 and 3.93 (AB quartet, 2H, JHH = 13.25 Hz, CH2 of
Benzyl), 5.26 (s, 1H, CH), 7.30–7.77 and 8.01–8.18 (m, 19 H, arom). 13C NMR (CDCl3,
62.5 MHz): δC (ppm) 51.37 (CH2 of Benzyl), 57.84 (CH), 127.1, 127.4, 127.6, 127.7,
128.2, 128.5, 128.6, 128.7, 129.0, 139.8, and 144.5 (19 CH of arom), 122.5, 137.5, and
138.4 (5 Cipso(C C) of 3 C6H5 and C6H4), 165.2 and 166.5 (2 C N). MS m/z: 418 (M+, 2),
312 (100), 269 (6), 194 (21), 178 (18), 151 (23), 106 (33), 90 (67), 76 (15), 65 (7). Anal.
Calcd for C28H23N3O: C, 80.55; H, 5.55; N, 10.06; Found: C, 80.57; H, 5.53; N, 10.03.
N-Benzyl-1-Phenyl-1-(5-Phenyl-1,3,4-Oxadiazol-2-yl)Methanamine (5b).
Orange Powder (yield 77%), mp: 106.1 ◦C–107.8 ◦C. IR (KBr) (νmax/cm−1): 3304, 2924,
1
2375, 2345, 1558, 1482, 1452, 1121, 834. H NMR (CDCl3, 250 MHz): δH (ppm) 2.37
(1H, br, s, NH, exchanged by D2O addition), 3.83–3.94 (m, 2H, CH2 of Benzyl), 5.24 (s,
1H, CH), 7.16–7.53, and 8.01–8.02 (m, 15 H, arom). 13C NMR (CDCl3, 62.5 MHz): δC
(ppm) 51.4 (CH2 of Benzyl), 57.9 (CH), 127.0, 127.4, 127.7, 128.4, 128.6, 128.6, 129.0,
and 131.7 (15 CH of arom), 123.7, 137.6, and 138.7 (3 Cipso(C
of 3 C6H5), 165.2 and
C)
166.6 (2 C N). MS m/z: 342 (M+, 1), 249 (1), 236 (100), 193 (23), 179 (16), 132 (12), 105
(93), 76 (36), 65 (12), 51 (14). Anal. Calcd for C22H19N3O: C, 77.40; H, 5.61; N, 12.31;
Found: C, 77.46; H, 5.59; N, 12.33.
N -Benzyl-1-(5-(4-Fluorophenyl)-1,3,4-Oxadiazol-◦2-yl)-1-Phenylmethana
◦
mine (5c). White Powder (yield 90%), mp: 111.0 C–113.3 C. IR (KBr) (νmax/cm−1):
3287, 2925, 2372, 2345, 1610, 1499, 1454, 1235, 1078, 856. 1H NMR (CDCl3, 250 MHz):
δH (ppm) 2.33 (1H, br s, NH, exchanged by D2O addition), 3.81–3.92 (m, 2H, CH2 of
Benzyl), 5.22 (s, 1H, CH), 7.13–7.53 and 7.97–8.13 (m, 14 H, arom). 13C NMR (CDCl3,
62.5 MHz): δC (ppm) 51.4 (CH2 of Benzyl), 57.9 (CH), 116.3 (d, 2JCF = 22.0 Hz), 120.1
4
(d, JCF = 3.6 Hz), 129.2 (d, 3JCF = 8.8 Hz), 164.7 (d, 1JCF = 252.1 Hz), 127.4, 127.6,
128.4, 128.5, 128.6, and 129.0 (10 CH of arom), 137.7 and 138.9 (2 Cipso(C C) of 2 C6H5),
164.4 and 165.6 (2 C N). MS m/z: 360 (M+, 1), 254 (99), 211 (17), 196 (20), 122 (35),

28
A. RAMAZANI ET AL.
106 (100), 95 (17), 65 (13), 50 (8). Anal. Calcd for C22H18FN3O: C, 73.52; H, 5.05; N,
11.69; Found: C, 73.55; H, 5.06; N, 11.66.
N-Benzyl-1-(5-(3-Fluorophenyl)-1,3,4-Oxadiazol-2-yl)-1-Phenylmethana
mine (5d). Yellow Powder (yield 80%), mp: 103.8 ◦C–105.4 ◦C. IR (KBr) (νmax/cm−1):
1
3309, 2922, 2374, 2345, 1561, 1488, 1453, 1120, 870. H NMR (CDCl3, 250 MHz):
δH (ppm) 2.17 (1H, br s, NH, exchanged by D2O addition), 3.81–3.92 (m, 2H, CH2 of
Benzyl), 5.23 (s, 1H, CH), 7.04–8.01 (m, 14 H, arom). 13C NMR (CDCl3, 62.5 MHz): δC
(ppm) 51.5 (CH2 of Benzyl), 58.0 (CH), 114.0 (d, 2JCF = 24.5 Hz), 118.8 (d, 2JCF = 21.3
Hz), 122.7 (d, 4JCF = 3.1 Hz), 125.6 (d, 3JCF = 9.1 Hz), 130.8 (d, 3JCF = 8.2 Hz), 164.9
(d, 1JCF = 269.8 Hz), 127.4, 127.6, 127.8, 128.3, 128.6, 128.7, and 129.0 (10 CH of arom),
137.7 and 138.9 (2 Cipso(C
of C6H5), 164.7 and 165.7 (2 C N). MS m/z: 360 (M+, 1),
C)
254 (88), 211 (13), 132 (14), 123 (27), 106 (95), 90 (100), 76 (20), 65 (13), 50 (11). Anal.
Calcd for C22H18FN3O: C, 73.52; H, 5.05; N, 11.69; Found: C, 73.53; H, 5.07; N, 11.72.
N-Benzyl-1-(5-(4-Bromophenyl)-1,3,4-Oxadiazol-2-yl)-1-Phenylmethana
◦
◦
mine (5e). White powder (yield 87%), mp: 123.1 C–125.2 C. IR (KBr) (νmax/cm−1):
3285, 2924, 2376, 2345, 1604, 1482, 1452, 1078, 1006, 830. 1H NMR (CDCl3, 250 MHz):
δH (ppm) 2.39 (1H, br, s, NH, exchanged by D2O addition), 3.81–3.93 (m, 2H, CH2 of
Benzyl), 5.22 (s, 1H, CH), 7.16–7.65 and 7.83–7.97 (m, 14 H, arom). 13C NMR (CDCl3,
62.5 MHz): δC (ppm) 51.4 (CH2 of Benzyl), 57.8 (CH), 122.6 (CAr–Br of C6H4Br), 126.4
(Cipso(C
of C6H4Br), 127.4, 127.7, 128.3, 128.4, 128.6, 128.7, 129.0, and 132.3 (14 CH
C)
of arom), 137.4 and 138.6 (2 Cipso(C
of 2 C6H5), 164.5 and 166.8 (2 C N). MS m/z:
C)
422 (M++2, 1), 316 (31), 236 (9), 183 (14), 132 (13), 106 (88), 90 (100), 76 (33), 65 (17),
50 (15). Anal. Calcd for C22H18BrN3O: C, 62.87; H, 4.32; N, 10.00; Found: C, 62.84; H,
4.36; N, 9.97.
N-Benzyl-1-(5-(4-Bromophenyl)-1,3,4-Oxadiazol-2-yl)-1-(4-Fluorophenyl)
Methanamine (5f). White Oil (yield 74%). IR (KBr) (νmax/cm−1): 3288, 2925, 2376,
2345, 1603, 1490, 1452, 1236, 835. 1H NMR (CDCl3, 250 MHz): δH (ppm) 2.17 (1H, br s,
NH, exchanged by D2O addition), 3.82 and 3.89 (AB quartet, 2H, 2JHH = 13.25 Hz, CH2
of Benzyl), 5.21 (s, 1H, CH), 7.04–7.97 (m, 13 H, arom). 13C NMR (CDCl3, 62.5 MHz):
2
4
δC (ppm) 51.3 (CH2 of Benzyl), 57.1 (CH), 116.0 (d, JCF = 22.0 Hz), 119.4 (d, JCF
=
3.4 Hz), 129.5 (d, 3JCF = 8.8 Hz), 163.7 (d, 1JCF = 251.8 Hz), 122.5 (CAr–Br of C6H4Br),
126.5 (Cipso(C C) of C6H4Br), 127.5, 128.3, 128.4, 128.5, 128.6, 132.4, and 132.5 (9 CH of
arom), 138.5 (Cipso(C
of C6H5), 164.1 and 164.6 (2 C N). MS m/z: 438 (M+, 1), 334
C)
(24), 272 (12), 198 (5), 183 (16), 122 (21), 106 (100), 90 (89), 75 (19), 65 (10), 50 (7).
Anal. Calcd for C22H17BrFN3O: C, 60.29; H, 3.91; N, 9.59; Found: C, 60.33; H, 3.93; N,
9.61.
N-Benzyl-1-(5-(3-Bromophenyl)-1,3,4-Oxadiazol-2-yl)-1-Phenylmethana
mine (5g). Colorless Oil (yield 81%). IR (KBr) (νmax/cm−1): 3286, 2925, 2376, 2345,
1
1604, 1488, 1451, 1073, 830. H NMR (CDCl3, 250 MHz): δH (ppm) 2.17 (1H, br s,
NH, exchanged by D2O addition), 3.81–3.93 (m, 2H, CH2 of Benzyl), 5.23 (s, 1H, CH),
7.11–7.70 and 7.93–8.12 (m, 14 H, arom). 13C NMR (CDCl3, 62.5 MHz): δC (ppm) 51.4
(CH2 of Benzyl), 57.9 (CH), 123.0 (CAr–Br of C6H4Br), 125.6 (Cipso(C
of C6H4Br),
C)
125.5, 127.4, 127.6, 128.4, 128.6, 128.7, 129.0, 129.8, 130.5, and 134.7 (14 CH of arom),
135.0 and 137.5 (2 Cipso(C C) of 2 C6H5), 163.9 and 167.1 (2 C N). MS m/z: 316 (4), 224
(3), 183 (8), 157 (7), 105 (35), 91 (86), 76 (100), 62 (35), 50 (52), 41 (17). Anal. Calcd for
C22H18BrN3O: C, 62.87; H, 4.32; N, 10.00; Found: C, 62.84; H, 4.28; N, 10.04.
N-Benzyl-1-(5-(3-Bromophenyl)-1,3,4-Oxadiazol-2-yl)-1-(4-Fluorophenyl)
Methanamine (5h). Orange Oil (yield 72%). IR (KBr) (νmax/cm−1): 3321, 3066, 2927,

(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE AS AN EFFICIENT REAGENT
29
1
2383, 2346, 1605, 1550, 1512, 1230, 1107, 833. H NMR (CDCl3, 250 MHz): δH (ppm)
2.17 (1H, br, s, NH, exchanged by D2O addition), 3.82 and 3.90 (m, 2H, CH2 of Benzyl),
5.22 (s, 1H, CH), 7.05–7.71 and 7.92–8.50 (m, 13 H, arom). 13C NMR (CDCl3, 62.5 MHz):
2
4
δC (ppm) 51.3 (CH2 of Benzyl), 57.1 (CH), 116.0 (d, JCF = 21.7 Hz), 119.2 (d, JCF
=
3.7 Hz), 129.6 (d, 3JCF = 8.7 Hz), 163.4 (d, 1JCF = 251.9 Hz), 123.0 (CAr–Br of C6H4Br),
125.4 (Cipso(C
of C6H4Br), 125.5, 127.6, 128.4, 128.6, 129.8, 130.6, and 134.8 (9 CH
C)
of arom), 138.5 and 139.9 (2 Cipso(C
of 2 C6H5), 164.0 and 166.7 (2 C N). MS m/z:
C)
224 (45), 183 (42), 168 (12), 155 (17), 88 (100), 75 (51), 62 (38), 50 (28), 41 (7). Anal.
Calcd for C22H17BrFN3O: C, 60.29; H, 3.91; N, 9.59; Found: C, 60.32; H, 3.93; N, 9.57.
N-Benzyl-1-(5-(4-Chlorophenyl)-1,3,4-Oxadiazol◦-2-yl)-1-Phenylmethana
mine (5i). Yellow Powder (yield 85%), mp: 118.4–120.0 C. IR (KBr) (νmax/cm−1):
1
3283, 2925, 2373, 2345, 1606, 1484, 1452, 1094, 861. H NMR (CDCl3, 250 MHz):
δH (ppm) 2.34 (1H, br s, NH, exchanged by D2O addition), 3.81–3.86 (m, 2H, CH2 of
Benzyl), 5.22 (s, 1H, CH), 7.34–7.51 and 7.91–8.04 (m, 14 H, arom). 13C NMR (CDCl3,
62.5 MHz): δC (ppm) 51.5 (CH2 of Benzyl), 57.9 (CH), 122.2 (Cipso(C
of C6H4Cl),
C)
127.4, 127.6, 128.2, 128.4, 128.6, 128.7, 129.0, and 129.4 (19 CH of arom), 137.6, 138.0,
and 138.9 (2 Cipso(C
of 2 C6H5 and CAr–Cl of C6H4Cl), 164.4 and 166.9 (2 C N). MS
C)
m/z: 376 (M+, 1), 270 (50), 236 (6), 179 (15), 149 (22), 139 (28), 106 (98), 91 (100), 77
(34), 65 (20), 50 (22), 41 (12). Anal. Calcd for C22H18ClN3O: C, 70.30; H, 4.83; N, 11.18;
Found: C, 70.33; H, 4.85; N, 11.20.
N-Benzyl-1-(5-(4-Chlorophenyl)-1,3,4-Oxadiazol◦-2-yl)-1-Phenylmethana
◦
mine (5j). Yellow Powder (yield 71%), mp: 110 C–113 C. IR (KBr) (νmax/cm−1):
1
3283, 2927, 2376, 2345, 1609, 1482, 14.45, 1093, 857. H NMR (CDCl3, 250 MHz): δH
(ppm) 2.17 (1H, br s, NH, exchanged by D2O addition), 3.82 and 3.90 (AB quartet, 2H,
2JHH = 13.25 Hz, CH2 of Benzyl), 5.21 (s, 1H, CH), 7.04–7.52 and 7.90–8.05 (m, 13 H,
arom). 13C NMR (CDCl3, 62.5 MHz): δC (ppm) 51.3 (CH2 of Benzyl), 57.1 (CH), 116.0
(d, 2JCF = 21.4 Hz), 119.2 (d, 4JCF = 3.1 Hz), 129.5 (d, 3JCF = 8.8 Hz), 164.7 (d, 1JCF
=
252.1 Hz), 122.1 (Cipso(C
of C6H4Cl), 127.6, 128.2, 128.4, and 128.6 (19 CH of arom),
C)
133.1, 138.2, and 139.3 (2 Cipso(C
of 2 C6H5 and CAr–Cl of C6H4Cl), 164.4 and 165.6
C)
(2 C N). MS m/z: 394 (M+, 1), 288 (30), 272 (12), 180 (27), 139 (49), 122 (29), 106
(100), 91 (70), 74 (23), 62 (12), 50 (17), 41 (6). Anal. Calcd for C22H17ClFN3O: C, 67.09;
H, 4.35; N, 10.67; Found: C, 67.05; H, 4.37; N, 10.68.
N-Benzyl-1-(5-(2-Chloro-4-Nitrophenyl)-1,3,4-Oxadiazol-2-yl)-1-Phenylme
thanamine (5k). Colorless Oil (yield 69%). IR (KBr) (νmax/cm−1): 3288, 2927, 2374,
1
2344, 1609, 1482, 14.45, 1093, 836. H NMR (CDCl3, 250 MHz): δH (ppm) 2.17 (1H,
2
br s, NH, exchanged by D2O addition), 3.85 and 3.93 (AB quartet, 2H, JHH = 13.25
Hz, CH2 of Benzyl), 5.29 (s, 1H, CH), 7.24–7.66 and 8.16–8.40 (m, 13 H, arom). 13C
NMR (CDCl3, 62.5 MHz): δC (ppm) 51.4 (CH2 of Benzyl), 57.9 (CH), 121.8 (Cipso(C
C)
of C6H4Cl), 126.4, 127.5, 127.7, 128.4, 128.6, 128.9, 129.1, and 132.0 (13 CH of arom),
133.6, 134.3, and 138.1 (3 Cipso(C
of 2 C6H5 and CAr–Cl), 149.3 (C(NO2)), 165.2 and
C)
166.5 (2 C N). MS m/z: 421 (M+, 1), 270 (50), 236 (6), 179 (15), 149 (22), 139 (28),
106 (98), 91 (100), 77 (34), 65 (20), 50 (22), 41 (12). Anal. Calcd for C22H17ClN4O3: C,
62.79; H, 4.07; N, 13.31; Found: C, 62.80; H, 4.09; N, 13.33.
REFERENCES
1. Ambrosi G.; Formica M.; Fusi V.; Giorgi L.; Macedi E.; Micheloni M.; Piersanti G.; Pontellini
R. Org. Biomol. Chem. 2010, 8, 1471-1478.

30
A. RAMAZANI ET AL.
2. Johns B. A. PCT International Application WO 2004101512.
3. Hassan Khan M. T.; Choudhary M. I.; Mohammed Khan K.; Rani M.; Rahman A. Bioorg. Med.
Chem. 2005, 13, 3385-3395.
4. Deshmukh A. A.; Sattur P. B.; Sheth U. K. Indian. J. Exp. Biol. 1976, 14, 166-168.
5. Goankar S. L.; Rai K. M. L.; Prabhuswamy B. Eur. J. Med. Chem. 2006, 41, 841-846.
6. Sengupta P.; Deepak D. K.; Yeligar V. C.; Murugesh K.; Rajalingam D.; Singh J.; Maity T. K.
Indian J. Chem. 2008, 47B, 460-462.
7. Mogilaiah K.; Ramesh B. H.; Babu R. R. Indian. J. Heterocycl. Chem. 2000, 10, 109-112.
8. Piatnitski E.; Kiselyov A.; Doody J.; Hadari Y.; Ouyang S.; Chen X., PCT International Appli-
cation WO 2004052280.
9. Thomas J. Ger. Pat. 2,403, 357/1974 [Chem. Abstr., 1974, 81, 136153g].
10. Carroll F. I.; Gray J. L.; Abrahm P.; Kuzemko M. A.; Lewin A. H.; Boja J. W.; Kuhar M. J. J.
Med. Chem. 1993, 36, 2886-2890.
11. Mochizuki H.; Hasui T.; Kawamoto M.; Shiono T.; Ikeda T.; Adachi C.; Taniguchi Y.; Shirota
Y. Chem. Commun. 2000, 1923-1924.
12. Adachi C.; Tsutsui T.; Saito S. Appl. Phys. Lett. 1990, 56, 799-801.
13. Vasil’ev N. V.; Romanov D. V.; Bazhenov A. A.; Lyssenko K. A.; Zatonsky G. V. J. Fluorine
Chem. 2007, 128, 740-747.
14. Wolkenberg S. E. and Boger D. L. J. Org. Chem. 2002, 67, 7361-7364.
15. Staudinger H. and Meyer J. J. Helv. Chim. Acta 2 1919, 635-646.
16. Palacios F.; Aparicio D.; Rubiales G.; Alonso C.; de los Santos J. M. Curr. Org. Chem. 2009, 13,
808-826.
17. Palacios F.; Alonso C.; Aparicio D.; Rubiales G.; de los Santos J. M. Tetrahedron 2007, 63,
523-575.
18. (a) Stolzenberg H.; Weinberger B.; Fehlhammer W. P.; Pu¨hlhofer F. G.; Weiss R. Eur. J. Inorg.
Chem. 2005, 21, 4263-4271; (b) Chiu T. W.; Liu Y. H.; Chi K. M.; Wen Y. S.; Lu K. L. Inorg.
Chem. 2005, 44, 6425-6430.
19. Sutherland S. H.; Blaser A.; Kmentova I.; Franzblau S. G.; Wan B.; Wang Y.; Ma Z.; Palmer B.
D.; Denny W. A.; Thompson A. M. J. Med. Chem. 2010, 53, 855-866; (b) Tong Y.; Bouska J.
J.; Ellis P. A.; Johnson E. F.; Leverson J.; Liu X.; Marcotte P. A.; Olson A. M.; Osterling D. J.;
Przytulinska M.; Rodriguez L. E.; Shi Y.; Soni N.; Stavropoulos J.; Thomas S.; Donawho C. K.;
Frost D. J.; Luo Y.; Giranda V. L.; Penning T. D. J. Med. Chem. 2009, 52, 6803-6813.
20. (a) Souldozi A.; Ramazani A.; Bouslimani N.; Welter R. Tetrahedron Lett. 2007, 48, 2617-2620;
(b) Souldozi A. and Ramazani A. Tetrahedron Lett. 2007, 48, 1549-1551; (c) Ramazani A. and
Souldozi A. Phosphorus, Sulfur, Silicon Relat. Elem. 2009, 184, 3191-3198; (d) Ramazani A.
and Souldozi A. Phosphorus, Sulfur, Silicon Relat. Elem. 2009, 184, 2344-2350; (e) Ramazani A.
and Rezaei A. Org. Lett. 2010, 12, 2852-2855; (f) Ramazani A. and Souldozi A. Arkivoc. 2008,
´
xvi, 235-242; (g) Souldozi A.; Slepokura K.; Lis T.; Ramazani A. Z. Z. Naturforsch., B: Chem.
Sci. 2007, 62b, 835-840; (h) Ramazani A.; Rouhani M.; Rezaei A.; Shajari N.; Souldozi A. Helv.
Chim. Acta 2011, 94, 282-288; (i) Ramazani A.; Ahmadi Y.; Rouhani M.; Shajari N.; Souldozi
A. Heteroat. Chem. 2010, 21, 368-372; (j) Ramazani A.; Ahmadi Y.; Tarasi R. Heteroat. Chem.
2011, 22, 79-84; (k) Ramazani A.; Shajari N.; Mahyari A.; Ahmadi Y. Mol. Divers 2011, 15,
doi:10. 1007/s11030-010-9275-0; (l) Ramazani A.; Zeinali Nasrabadi F.; Ahmadi Y. Helv. Chim.
Acta 2011, 94, doi: 10.1002/hlca.201000356; (m) Ramazani A.; Ahmadi Y.; Zeinali Nasrabadi F.
Z. Naturforsch. 2011, 66b, 184-190; (n) Ramazani A.; Salmanpour S.; Souldozi A. Phosphorus,
Sulfur, Silicon Relat. Elem. 2010, 185, 97-102; (o) Ramazani A.; Shajari N.; Tofangchi Mahyari
A.; Khoobi M.; Ahmadi Y.; Souldozi A. Phosphorus, Sulfur, Silicon Relat. Elem. 2010, 185,
2496-2502.
21. (a) Ramazani A.; Kazemizadeh A. R.; Ahmadi E.; Noshiranzadeh N.; Souldozi A. Curr. Org.
Chem. 2008, 12, 59-82; (b) Ramazani A.; Mahyari T. M.; Rouhani M.; Rezaei A. Tetrahedron
Lett. 2009, 50, 5625; (c) Ramazani A. and Bodaghi A. Phosphorus, Sulfur, Silicon Relat. Elem.
2004, 179, 1615-1620; (d) Ramazani A.; Kazemizadeh A. R.; Ahmadi E. Phosphorus, Sulfur,

(N-ISOCYANIMINO)TRIPHENYLPHOSPHORANE AS AN EFFICIENT REAGENT
31
Silicon Relat. Elem. 2005, 180, 1781-1784; (e) Ramazani A. and Ahmadi E. Phosphorus, Sulfur,
Silicon Relat. Elem. 2006, 181, 2725-2729; (f) Heshmati-Gonbari M.; Ramazani A.; Souldozi
A. Phosphorus, Sulfur, Silicon Relat. Elem. 2009, 184, 309-314; (g) Kazemizadeh A. R. and
Ramazani A. Arkivoc 2008, xv, 159-165; (h) Kazemizadeh A. R. and Ramazani A. J. Braz.
Chem. Soc. 2009, 20, 309-312; (i) Shajari N. and Ramazani A. Phosphorus, Sulfur, Silicon
Relat. Elem. 2010, 185, 1850-1857; (j) Noshiranzadeh N.; Ramazani A.; Tofangchi Mahyari
´
A.; Slepokura K.; Lis T. Z. Z. Naturforsch. 2008, 63b, 65-70; (k) Ramazani A.; Noshiranzadeh
´
N.; Ghamkhari A.; Slepokura K.; Lis T. Helv. Chim. Acta 2008, 91, 2252-2261; (l) Ramazani
A.; Rezaei A.; Mahyari A. T.; Rouhani M.; Khoobi M. Helv. Chim. Acta 2010, 93, 2033-2036;
(m) Ramazani A. and Mahyari A. Helv. Chim. Acta 2010, 93, 2203-2209; (n) Ramazani A. and
Rahimifard M. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2675-2678; (o) Ramazani A.
and Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 529; (p) Ramazani A. and
Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 2663-2666; (q) Ramazani A.
and Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 1325-1328; (r) Ramazani A.
and Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 1329-1332; (s) Ramazani
A. and Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 2189-2192; (t) Morsali
A. and Ramazani A. Z. Anorg. Allg. Chem. 2005, 631, 1759-1760; (u) Morsali A. and Ramazani
A. J. Coord. Chem. 2005, 58, 751-758; (v) Morsali A.; Mahjoub A. R.; Ramazani A. J. Coord.
Chem. 2004, 57, 347-352; (w) Morsali A.; Ramazani A.; Mahjoub A. R.; Soudi A. A. Z. Z.
Anorg. Allg. Chem. 2003, 629, 2058-2061; (x) Ramazani A.; Amini I.; Massoudi A. Phosphorus,
Sulfur Silicon Relat. Elem. 2006, 181, 2373-2376; (y) Souldozi A.; Ramazani A.; Noshiranzadeh
N. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 1271-1275; (z) Souldozi A.; Ramazani
A.; Noshiranzadeh N. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 587-589.
22. Maughan M. A. T.; Davies I. G.; Claridge T. D. W.; Courtney W. S.; Hay P.; Davis B. G. Angew.
Chem., Int. Ed. 2003, 42, 3788-3792.
23. Davis B. G.; Maughan M. A. T.; Chapman T. M.; Villard R.; Courtney S. Org. Lett. 2002, 4,
103-106.
´
24. (a) Tofangchi Mahyari A.; Shajari N.; Kazemizadeh A. R.; Slepokura K.; Lis T.; Ramazani A.
Z. Naturforsch. 2007, 62b, 829-834; (b) Noshiranzadeh N.; Morsali A. Ramazani,A.; Hunter A.
D.; Zeller M. Inorg. Chem. Commun. 2007, 10, 738-742; (c) Noshiranzadeh N.; Ramazani A.;
Morsali A.; Hunter A. D.; Zeller M. Inorg. Chim. Acta 2007, 360, 3603-3609; (d) Youseftabar-
Miri L.; Ramazani A.; Ahmadi E.; Morsali A. Anal. Sci. 2007, 23, x97-x98; (e) Ramazani A.;
´
Kazemizadeh A. R.; Ahmadi E.; Slepokura K.; Lis T. Z. Naturforsch. 2006, 61b, 1128-1133;
(f) Ramazani A.; Kazemizadeh A. R.; Marandi F. Phosphorus, Sulfur Silicon Relat. Elem. 2005,
180, 1541-1544; (g) Ramazani A.; Yousefi L.; Ahmadi E.; Souldozi A. Phosphorus, Sulfur
Silicon Relat. Elem. 2004, 179, 1459-1464; (h) Ramazani A.; Rahimifard M.; Noshiranzadeh
N.; Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182, 413-417; (i) Pakravan
P.; Ramazani A.; Noshiranzadeh N.; Sedrpoushan A. Phosphorus, Sulfur Silicon Relat. Elem.
2007, 182, 545-549; (j) Ramazani A.; Rahimifard M.; Souldozi A. Phosphorus, Sulfur Silicon
Relat. Elem. 2007, 182, 1-5; (k) Ramazani A.; Rahimifard M.; Noshiranzadeh N.; Souldozi A.
Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182, 413-417; (l) Ramazani A. and Mohammadi-
Vala M. Phosphorus, Sulfur Silicon Relat Elem. 2001, 176, 223-229; (m) Ramazani A.; Amini I.;
Massoudi A. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2225-2229; (n) Ramazani A.;
Morsali A.; Ganjeie B.; Kazemizadeh A. R.; Ahmadi E.; Kempe R.; Hertle I. Z. Naturforsch. 2005,
60b, 569-571; (o) Ahmadi E.; Ramazani A.; Nekomanesh Haghighi M. Tetrahedron Lett. 2007,
48, 6954-6957; (p) Ramazani A.; Ahmadi E.; Kazemizadeh A. R.; Dolatyari L.; Noshiranzadeh
N.; Eskandari I.; Souldozi A. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 2419-2422;
(q) Ramazani A. and Holagh M. V. Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184, 171-178;
(r) Ramazani A. and Bodaghi A. Tetrahedron Lett. 2000, 41, 567-568.