An improved, safe, and efficient conversion of triarylpyrylium perchlorates to corresponding cyanodienones using Amberlite IRA 910[CN]

Article abstract of DOI:10.1007/s00706-012-0825-2

Triarylpyrylium perchlorates are readily converted into new aromatic cyanodienones by using cyanide impregnated on anion exchange resin as a safe and efficient reagent.

Full text of DOI:10.1007/s00706-012-0825-2

Monatsh Chem (2013) 144:375–379
DOI 10.1007/s00706-012-0825-2
ORIGINAL PAPER
An improved, safe, and efficient conversion of triarylpyrylium
perchlorates to corresponding cyanodienones using Amberlite
IRA 910[CN]
•
Arash Mouradzadegun Fatemeh Abadast
Received: 10 December 2011 / Accepted: 10 July 2012 / Published online: 7 August 2012
Ó Springer-Verlag 2012
Abstract Triarylpyrylium perchlorates are readily con-
verted into new aromatic cyanodienones by using cyanide
impregnated on anion exchange resin as a safe and efficient
reagent.
various triarylpyrylium perchlorates with aqueous sodium
cyanide is still a challenge to investigate. In continuation of
our ongoing work to develop selective, preparatively and
synthetically useful methodology for the preparation [16],
application [17, 18], and transformation of pyrylium and
thiopyrylium salts [19–23], besides the importance of
biological active aromatic butenolides [24–28], we decided
to synthesize new aromatic cyanodienones from the reaction
of cyanide anion with various triarylpyrylium perchlorates
carrying electron-donating and -withdrawing groups in the
para position of substituted phenyl rings.
Keywords Anion exchange resin Á Cyanodienones Á
Green chemistry Á Heterocycles Á Nucleophilic additions
Introduction
Butenolides are ubiquitous moieties in many natural
products [1–5]. These compounds are potent antibiotics
[6, 7], often show interesting antimicrobialactivity [8], appear
as substructures in peptide analogues and HIV-1 protease
inhibitors [9, 10], and can also be main materials for the
development of new asymmetric methodologies [11, 12].
The reaction of substituted pyrylium salts 1 with aqueous
alkali cyanides affords the corresponding cyanodienones 2,
which are utilized as key intermediates for butenolides 3
[13] (Scheme 1).
Because of the toxicity of the cyanide anion, which
leads to vomiting, convulsions, loss of consciousness, and
eventual death [29–31], and in the interest of developing
green chemistry, we also tried to use a new strategy where
the cyanide anion is impregnated on anion exchange resin
as a safe and efficient reagent. Resins are very important in
circumventing major environmental problems and serious
separation difficulties encountered with many current
methods. In addition, they can be used as effective catalysts
in various organic reactions, e.g., azidation of a,b-unsatu-
rated ketones [32], protection of carbonyl groups [33],
reduction of 4-nitrophenol [34], sampling and preservation
of sulfoxyanions in natural waters [35], and highly regio-
selective conversion of epoxides to b-hydroxynitriles [36].
Therefore, the design of new and improved methods for
the synthesis of cyanodienones is of interest. The majority
of the work reported in this area has concentrated on al-
kylpyrylium compounds [13, 14], and in the case of
arylpyrylium, this reaction is restricted only to triphenyl-
pyrylium perchlorates [15]; in this sense, the reaction of
Results and discussion
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-012-0825-2) contains supplementary
material, which is available to authorized users.
Reactions of triarylpyrylium perchlorates 4 containing
electron-donating and -withdrawing groups in the para
position of substituted phenyl rings with sodium cyanide
afford the corresponding cyanodienones 6 via intermediate
2-cyanopyrans 5 which could not be isolated (Scheme 2).
A. Mouradzadegun (&) Á F. Abadast
Department of Chemistry, Faculty of Science,
Shahid Chamran University, Ahvaz, Iran
e-mail: arash_m@scu.ac.ir
123

376
A. Mouradzadegun, F. Abadast
CH3
O
CH3
O
were obtained when 2 mmol of nucleophile and 1 mmol of
substrate were used.
CH3 CN
CH3
NaCN
CN
H3C
CH3
The scope and generality of this process are illustrated
with various triarylpyrylium perchlorates and new aromatic
cyanodienones were synthesized in good yields (Table 1).
The structures of all products were determined from their
H3C
H3C
O
CH3
2
1
CH3
CH3
O
+ 2 H2O
- NH3
H3C
1
spectral data (IR, H NMR, 13C NMR).
CH3
O
H3COCH2C
H3C
O
COOH
The data in Table 1 clearly show that electron-donating
groups cause the reactions to become slow (e.g., entries 1–6).
This may be rationalized by considering the fact that these
groups decrease the positive charge on the a-position of the
heterocyclic ring. Stronger electron-donating groups exhibit
longer reaction times. In contrast electron-withdrawing
groups (e.g., entries 7 and 8) accelerate the reaction.
As stated earlier, because of the toxicity of the cyanide
anion in the traditional method and in order to shed more
light on the mechanism, these conversions were done in the
presence of Amberlite IRA 910[CN] as an improved
reagent. This reagent was prepared by simple mixing
sodium cyanide and Amberlite IRA 910[Cl] in H2O. The
capacity of the resin was determined with a potentiometric
method. Then the conversion of various triarylpyrylium
perchlorates to the corresponding cyanodienones was
investigated in the presence of this reagent and in the tra-
ditional method (Table 1).
3
Scheme 1
Ar2
Ar2
Ar2 1CN
H1
NaCN
4
2
Ar1
CN
Ar1
5
6
3
H2
Ar1
O
Ar1
Ar1
O
Ar1
O
4
5
6
ClO4
Ar1 : C6H5, C6H4OMe
Ar2 : C6H5, C6H4Me, C6H4OMe, C6H4NMe2, C6H4Cl, C6H4NO2
Scheme 2
Preliminary tests were carried out to survey the requisite
reaction conditions and establish the modifications required
for this methodology. Triphenylpyrylium perchlorate was
chosen as the model compound to identify and optimize the
reaction conditions.
This resin has a highly developed structure with sites
that easily trap the starting materials and accelerate the
reaction. In particular the workup and handling of the
reaction were very easy and the pure products could be
isolated with simple filtering; the filtered resin could be
used several times without any loss in its capacity and
efficiency.
Initially, reaction of the model compound with sodium
cyanide was followed in different solvent. In the presence
of protic solvents such as ethanol, the reaction was not
successful and noticeable amounts of starting material
remained intact. In low polarity solvents such as tetrahy-
drofuran or dichloromethane, starting material could not
completely dissolve. In acetonitrile the reaction was very
fast and gave the corresponding cyanodienone in 78 %
yield within 30 min, so acetonitrile appeared to be the
solvent of choice giving the best results.
In conclusion, we describe a novel and general protocol
for the synthesis of new aromatic cyanodienones from the
reaction of triarylpyrylium perchlorates with Amberlite
IRA 910[CN] as a safe and highly efficient reagent. This
environmentally friendly methodology offers several
advantages including decrease of toxicity, easy workup and
handling, short reaction times, and reusability of the resin.
Following these tests, the relative molar ratio of nucle-
ophile and substrate was also optimized. The best results
Table 1 Conversion of various
Entry
Ar1
Ar2
Product
Reaction time
with NaCN
Reaction time
with IRA 910[CN]
Yield/%
triarylpyrylium salts into
corresponding cyanodienones in
acetonitrile at room temperature
(Scheme 2)
1
2
3
4
5
6
7
8
C6H5
C6H5
6a
6b
6c
6d
6e
6f
30 min
1 h
25 min
40 min
30 min
40 min
50 min
2 h
78
81
91
95
93
88
70
72
C6H5
p-Me-C6H4
p-MeO-C6H4
p-Me-C6H4
p-MeO-C6H4
p-Me2N-C6H4
p-Cl-C6H4
p-NO2-C6H4
C6H5
4 h
p-MeO-C6H4
p-MeO-C6H4
C6H5
10 h
16 h
23 h
C6H5
6g
6h
25 min
20 min
20 min
15 min
C6H5
123

Conversion of triarylpyrylium perchlorates to corresponding cyanodienones
377
Experimental
N(Me)3 CN
IRA 910[CN]
KI
N(Me)3 I
KCN
Chemicals were purchased from Fluka, Merck, and Aldrich
chemical companies. Monitoring of the reactions was
accomplished by TLC. IR spectra were obtained on a
IRA 910[I]
Fig. 2 Estimation the capacity of the polymer-supported cyanide via
anion exchange of IRA 910[CN] with iodide
1
Bomen MB:102 FT-IR spectrophotometer. H NMR and
13C NMR spectra were recorded on a 400 MHz Bruker
spectrometer using CDCl3 as the solvent and TMS as the
internal standard. All triarylpyrylium perchlorates were
synthesized from the corresponding aldehydes and ketones
by the method previously described [37, 38] (and refer-
ences therein).
room temperature in acetonitrile (10 mmol) and the reac-
tions were followed by TLC (similar to the previous
procedure). After completion of the reaction, the resin was
removed by filtering and the product recrystallized from
EtOH.
(2Z,4E)-6-Oxo-2,4,6-triphenyl-2,4-hexadienenitrile
(6a, C24H17NO)
General procedure for the reaction of triarylpyrylium
perchlorates 4 with sodium cyanide
Yield 78 %; yellow crystals; m.p.: 103–105 °C (from
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,645 (CO) cm-1; H
1
The triarylpyrylium perchlorates (1 mmol) were stirred with
sodium cyanide (2 mmol) at room temperature in acetoni-
trile (10 mmol). The reactions were monitored by TLC using
ether/n-hexane (1:4) as eluent. After completion of the
reaction, the solvent was evaporated under vacuum and the
residue was worked up in aqueous ethyl acetate (in order to
remove excess cyanide), then recrystallized from EtOH.
NMR (400 MHz, CDCl3): d = 7.33 (s, 1H, H1), 7.45–8.05
(m, 15H, Ar–H), 8.40 (s, 1H, H2) ppm; 13C NMR
(100 MHz, CDCl3): d = 115.9 (C-2), 119.6 (C-1), 126.2
(C-5), 126.9, 128.8, 129.1, 129.2, 129.4, 129.5, 130.3,
130.6, 133.6 (ArC), 134.1, 138.8, 139.4 (ArCq), 141.8
(C-3), 151.9 (C-4), 190.6 (C-6) ppm.
(2Z,4E)-4-(4-Methylphenyl)-6-oxo-2,6-diphenyl-2,4-
hexadienenitrile (6b, C25H19NO)
Preparation of polymer-supported cyanide anion
Yield 81 %; yellow crystals; m.p.: 116–118 °C (from
1
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,644 (CO) cm-1; H
Amberlite IRA 910[Cl] (100 g) was stirred for 12 h with
32 g sodium cyanide in 450 cm3 water. The resin was fil-
tered off, washed successively with water, and dried under
vacuum at 40 °C (Fig. 1).
NMR (400 MHz, CDCl3): d = 2.46 (s, 3H, CH3), 7.32 (s,
1H, H1), 7.45–8.04 (m, 14H, Ar–H), 8.37 (s, 1H, H2) ppm;
13C NMR (100 MHz, CDCl3): d = 21.5 (CH3), 115.7
(C-2), 118.9 (C-1), 124.8 (C-5), 126.4, 128.4, 128.6, 128.7,
129.0, 129.7, 129.8, 133.1 (ArC), 133.7, 136.1, 138.5,
140.7 (ArCq), 142.0 (C-3), 151.6 (C-4), 190.2 (C-6) ppm.
Estimation the capacity of the polymer-supported cyanide
A sample of 1.00 g dry resin was stirred for 12 h with
830 mg potassium iodide in 10 cm3 water. The resin was
filtered off, washed with water, and the combined filtrate
and washings titrated against silver nitrate solution using a
potentiometer. The capacity generally was found to be
1.4 mmol/g (Fig. 2).
(2Z,4E)-4-(4-Methoxyphenyl)-6-oxo-2,6-diphenyl-2,4-
hexadienenitrile (6c, C25H19NO2)
Yield 91 %; yellow crystals; m.p.: 112–114 °C (from
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,643 (CO) cm-1; H
1
NMR (400 MHz, CDCl3): d = 3.89 (s, 3H, OCH3), 7.30 (s,
1H, H1), 7.00–7.02, 7.43–8.03 (m, 14H, Ar–H), 8.35 (s,
1H, H2) ppm; 13C NMR (100 MHz, CDCl3): d = 55.4
(OCH3), 114.4 (C-5), 115.2 (C-2), 118.8 (C-1), 123.5,
126.4, 128.3, 128.7, 129.0, 129.8, 130.2 (ArC), 131.2
(ArCq), 133.0 (ArC), 133.6, 138.6 (ArCq), 142.5 (C-3),
151.3 (ArCq), 161.5 (C-4), 190.1 (C-6) ppm.
General procedure for the reaction of triarylpyrylium
perchlorates 4 with cyanide impregnated on anion
exchange resin
The triarylpyrylium salts (1 mmol) were stirred with
cyanide impregnated on Amberlite IRA 910 (2 mmol) at
(2Z,4E)-2,6-Bis(4-methoxyphenyl)-4-(4-methylphenyl)-
6-oxo-2,4-hexadienenitrile (6d, C27H23NO3)
Yield 95 %; yellow crystals; m.p.: 129–131 °C (from
1
EtOH); IR (neat): vꢀ = 2,217 (CN), 1,638 (CO) cm-1; H
N(Me)3 Cl
NaCN
N(Me)3 CN
NaCl
NMR (400 MHz, CDCl3): d = 2.44 (s, 3H, CH3), 3.86,
3.89 (2 s, 6H, OCH3), 7.25 (s, 1H, H1), 6.95–6.99,
7.23–7.28, 7.43–8.02 (m, 12H, Ar–H), 8.31 (s, 1H, H2)
ppm; 13C NMR (100 MHz, CDCl3): d = 21.5 (CH3), 55.4,
IRA 910[Cl]
IRA 910[CN]
Fig. 1 Preparation of polymer-supported cyanide anion from IRA
910[Cl]
123

378
A. Mouradzadegun, F. Abadast
Acknowledgments This work was supported by the Research
Council at the University of Shahid Chamran. Thanks are expressed
to Mr. A.T. Balaban for providing some references.
55.5 (OCH3), 113.9 (C-5), 114.4 (ArC), 115.8 (C-2), 118.3
(C-1), 124.9 (ArC), 126.4 (ArCq), 127.9, 128.6, 129.6,
130.7 (ArC), 131.7, 136.6 (ArCq), 139.5 (C-3), 140.3
(ArCq), 151.1 (C-4), 160.9, 163.5 (ArCq), 188.7 (C-6) ppm.
References
(2Z,4E)-2,4,6-Tris(4-methoxyphenyl)-6-oxo-2,4-
hexadienenitrile (6e, C27H23NO4)
1. Villemin D, Cheikh N, Mostefa-Kara B, Bar N, Choukchou-
Braham N, Didi MA (2006) Tetrahedron Lett 47:5519
2. Karade NN, Gampawar SV, Kondre JM, Shinde SV (2008)
Tetrahedron Lett 49:4402
3. De Rosa M, Citro L, Soriente A (2006) Tetrahedron Lett 47:8507
4. Fakova H, Pour M, Kunes J, Senel P (2005) Tetrahedron Lett
46:8137
5. Sabitha G, Prasad MN, Ramesh M, Yadav JS (2010) Monatsh
Chem 141:1245
6. Renard M, Ghosez LA (2001) Tetrahedron 57:2597
7. Harris LJ, Alexander NJ, Saparno A, Blackwell B, McCormick
Yield 93 %; yellow crystals; m.p.: 131–133 °C (from
1
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,636 (CO) cm-1; H
NMR (400 MHz, CDCl3): d = 3.87, 3.88, 3.90 (3 s, 9H,
OCH3), 7.22 (d, J = 1.0 Hz, 1H, H1), 6.95–7.01, 7.49–8.03
(m, 12H, Ar–H), 8.29 (d, J = 1.0 Hz, 1H, H2) ppm; 13C
NMR (100 MHz, CDCl3): d = 55.2, 55.3, 55.4 (OCH3),
113.7 (C-5), 113.9, 114.4 (ArC), 115.9 (C-2), 118.2 (C-1),
123.7 (ArC), 126.4 (ArCq), 127.8, 127.9, 129.2, 130.3
(ArC), 141.0 (ArCq), 150.8 (C-3), 157.1, 160.9, 161.2
(ArCq), 163.4 (C-4), 188.7 (C-6) ppm.
´
SP, Desjardins AE, Robert LS, Tinker N, Hattori J, Piche C,
Schernthaner JP, Watson R, Ouellet T (2007) Fungal Genet Biol
44:293
8. Burger K, Hennig L, Fuchs A, Greif D, Spengler J, Albericio F
(2005) Monatsh Chem 136:1763
9. Suzuki Y, Nishimaki R, Ishikawa M, Murata T, Takao K, Tadano
K (2000) J Org Chem 65:8595
10. Fan WY, Wang ZL, Zhang ZG, Li HC, Deng WP (2011) Tet-
rahedron 67:5596
(2Z,4E)-4-[4-(Dimethylamino)phenyl]-6-oxo-2,6-
diphenyl-2,4-hexadienenitrile (6f, C25H19N2O)
Yield 88 %; red crystals; m.p.: 174–176 °C (from EtOH);
IR (neat): vꢀ = 2,215 (CN), 1,628 (CO) cm-1; H NMR
1
(400 MHz, CDCl3): d = 3.07 (s, 6H, N(CH3)2), 7.30 (d,
J = 1.0 Hz, 1H, H1), 6.74–6.76, 7.41–8.03 (m, 14H,
Ar–H), 8.32 (d, J = 1.0 Hz, 1H, H2) ppm; 13C NMR
(100 MHz, CDCl3): d = 40.1 (N(CH3)2), 111.9 (C-5),
116.1 (C-2), 118.0 (C-1), 119.8 (ArC), 125.7 (ArCq), 126.4,
128.2, 128.6, 129.0, 129.5, 130.0, 132.5 (ArC), 133.8,
139.2 (ArCq), 144.0 (C-3), 151.9 (ArCq), 152.2 (C-4),
190.0 (C-6) ppm.
11. Lipka E, Vaccher MP, Vaccher C, Lens C (2005) Bioorg Med
Chem Lett 15:501
12. Len C, Selouane A, Weilling A, Coicon F, Postel D (2003)
Tetrahedron Lett 44:663
13. Balaban AT, Nenitzescu CD (1961) J Chem Soc 3566
14. Balaban AT, Tudose A, Caproiu MT (2003) Tetrahedron 59:3291
15. Balaban AT, Silhan W (1970) Tetrahedron 26:743
16. Mouradzadegun A, Gheitasvand N (2005) Phosphorus Sulfur
Silicon 180:1385
17. Ganjali MR, Norouzi P, Emami M, Golmohamadi M, Pirelahi H,
Mouradzadegun A (2006) J Chin Chem Soc 53:1209
18. Ganjali MR, Akbar V, Daftari A, Norouzi P, Pirelahi H, Mou-
radzadegun A (2004) J Chin Chem Soc 51:309
19. Mouradzadegun A, Pirelahi H (2001) J Photochem Photobiol A
Chem 138:203
20. Mouradzadegun A, Pirelahi H (2000) Phosphorus Sulfur Silicon
165:149
21. Mouradzadegun A, Pirelahi H (2000) Phosphorus Sulfur Silicon
157:193
22. Mouradzadegun A, Dianat S (2009) J Heterocycl Chem 46:778
23. Mouradzadegun A, Ghasem Hezave F, Karimnia M (2010)
Phosphorus Sulfur Silicon 185:84
24. Ortega MJ, Zubia E, Ocana JM, Naranjo S, Salva J (2000) Tet-
rahedron 56:3963
(2Z,4E)-4-(4-Chlorophenyl)-6-oxo-2,6-diphenyl-2,4-
hexadienenitrile (6g, C24H16ClNO)
Yield 70 %; yellow crystals; m.p.: 109–111 °C (from
1
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,647 (CO) cm-1; H
NMR (400 MHz, CDCl3): d = 7.29 (s, 1H, H1), 7.41–8.03
(m, 14H, Ar–H), 8.35 (s, 1H, H2) ppm; 13C NMR
(100 MHz, CDCl3): d = 115.5 (C-2), 119.4 (C-1), 126.0
(C-5), 126.4, 128.4, 128.8, 129.1, 129.3, 129.9 (ArC),
130.0 (ArCq), 133.3, 133.4 (ArC), 136.4, 137.3, 138.3
(ArCq), 140.9 (C-3), 150.2 (C-4), 190.0 (C-6) ppm.
25. Clark B, Capon RJ, Lacey E, Tennant S, Gill JH, Bulheller B,
Bringmann G (2005) J Nat Prod 68:1226
26. Bellina F, Anselmi C, Viel S, Mannina L, Rossi R (2001) Tet-
rahedron 57:9997
27. Ma S, Shi Z, Wu S (2001) Tetrahedron Asymmetry 12:193
28. Wu J, Zhu Q, Wang L, Fathi R, Yang Z (2003) J Org Chem
68:670
29. Kim YH, Hong JI (2002) Chem Commun 512
30. Tomasulo M, Sortino S, White AJP, Raymo FM (2006) J Org
Chem 71:744
(2Z,4E)-4-(4-Nitrophenyl)-6-oxo-2,6-diphenyl-2,4-
hexadienenitrile (6h, C24H16N2O3)
Yield 72 %; brown crystals; m.p.: 151–153 °C (from
EtOH); IR (neat): vꢀ = 2,218 (CN), 1,651 (CO), 1,518,
1,345 (NO2) cm-1; 1H NMR (400 MHz, CDCl3): d = 7.30
(s, 1H, H1), 7.24, 7.44–8.34 (m, 14H, Ar–H), 8.39 (s, 1H,
H2) ppm; 13C NMR (100 MHz, CDCl3): d = 115.4 (C-2),
120.0 (C-1), 124.2 (C-5), 126.5, 128.3, 128.5, 128.9, 129.2,
129.7, 130.4 (ArC), 133.1 (ArCq), 133.7 (ArC), 137.9
(ArCq), 139.4 (C-3), 145.2, 148.5 (ArCq), 148.8 (C-4),
189.8 (C-6) ppm.
31. Lee KS, Kim HJ, Kim GH, Shin I, Hong JI (2008) Org Lett 10:49
32. Castrica L, Fringuelli F, Gregoli L, Pizzo F, Vaccaro L (2006) J
Org Chem 71:9536
33. Niknam K, Kiasat AR, Karimi S (2005) Synth Commun 35:2231
123

Conversion of triarylpyrylium perchlorates to corresponding cyanodienones
379
34. Praharaj S, Nath S, Ghosh SK, Kundu S, Pal T (2004) Langmuir
20:9889
Advances in heterocyclic chemistry, vol 2, suppl 1. Academic,
New York
35. Druschel GK, Schoonen MA, Nordstrom DK, Ball JW, Xu Y,
Cohn CA (2003) Geochem Trans 4:12
36. Tamami B, Iranpoor N, Rezaei R (2003) Synth Commun 33:3153
37. Balaban AT, Dinculescu A, Dorofeenko GN, Fischer GW, Koblik
AV, Mezheritskii VV, Schroth W (1982) In: Katritzky AR (ed)
38. Balaban AT, Schroth W, Fischer GW (1969) Pyrylium Salts. In:
Katritzky AR (ed) Advances in heterocyclic chemistry, vol 10.
Academic, New York, p 241
123