Synthesis of Fluorescent 2,6-Dicyano-3,5-Disubstituted Anilines Using Cellulose Sulfuric Acid in Aqueous Media

Article abstract of DOI:10.1002/hlca.201500242

The synthesis of some fluorescent 2,6-dicyano-3,5-disubstituted anilines using cellulose sulfuric acid (Cellulose-SA) as an environmentally benign catalyst in H₂O is described. The one-pot reaction of 1,3-diketone and three equiv. of malononitrile was carried out in the presence of one equiv. of a secondary amine, Cellulose-SA as catalyst, and H₂O as solvent. The photophysical properties (λ_Abs., λ_Flu.) of the synthesized compounds in CH₂Cl₂, MeCN, and MeOH have been measured. The emission spectra of the new compounds in the solid state are also reported.

Full text of DOI:10.1002/hlca.201500242

Helv. Chim. Acta 2016, 99, 355 – 360
355
FULL PAPER
Synthesis of Fluorescent 2,6-Dicyano-3,5-Disubstituted Anilines Using Cellulose
Sulfuric Acid in Aqueous Media
by Afsaneh Zonouzi*a)b), Zakieh Izakiana)b), Khosrou Abdic), and Seik Weng Ngd)e)
a) School of Chemistry, University College of Science, University of Tehran, Tehran, Iran (phone: +98-21-61112988;
e-mail: zonouzi@khayam.ut.ac.ir)
b) Pharmaceutical and Cosmetic Research Center (PCRC), University of Tehran, Enghelab Ave., 141556455, Tehran, Iran
c) Department of Medicinal Chemistry and Radio pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences,
Tehran, Iran, 14155-6153
d) Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
e) Chemistry Department, Faculty of Science, King Abdulaziz University, Abdullah Solayman Ave., 80200, Jeddah,
Saudi Arabia
The synthesis of some fluorescent 2,6-dicyano-3,5-disubstituted anilines using cellulose sulfuric acid (Cellulose-SA) as an
environmentally benign catalyst in H2O is described. The one-pot reaction of 1,3-diketone and three equiv. of malononitrile
was carried out in the presence of one equiv. of a secondary amine, Cellulose-SA as catalyst, and H2O as solvent. The
photophysical properties (kAbs., kFlu.) of the synthesized compounds in CH2Cl2, MeCN, and MeOH have been measured. The
emission spectra of the new compounds in the solid state are also reported.
Keywords: Cellulose sulfuric acid, Fluorescence, 2,6-Dicyanoaniline, Photophysical properties, Thorpe–Ziegler reaction.
report the synthesis of fluorescent 2,6-dicyano-3,5-dialkyl
anilines using environmentally benign cellulose sulfuric
acid as the catalyst in aqueous media (Scheme 1).
Introduction
One of the key areas of ‘green chemistry’ is the elimina-
tion of solvents or the replacement of hazardous solvents
by relatively benign solvents in chemical processes, espe-
cially for industrial compounds. The best solvent for this
purpose is H2O [1][2]. In addition, cellulose sulfuric acid
(Cellulose-SA) is one of the common organic polymers
which can be used as an inexpensive and biodegradable
heterogeneous catalyst in organic reactions. Recently, it
has attracted attention from both environmental and eco-
nomic points. Cellulose-SA can be easily separated from
reaction mixtures, has a high turnover number, and since
it can replace liquid homogenous acids, it is desirable in
chemical industry. In recent years, Cellulose-SA as an
Results and Discussion
In 2007, Tu et al. [18] used the condensation reaction of
1,3-diphenylprop-2-en-1-one, malononitrile, and primary
amines in DMF under microwave irradiation for the syn-
thesis of 2,6-dicyanoaniline derivatives [18]. They postu-
lated that amines in non-acidic or basic media acted only
as a base for deprotonation of reactants and intermedi-
ates. They also reported the synthesis of 2-aminopyridine
derivatives using the same reactants in DMF and the
presence of AcOH and microwave irradiation. They sug-
environmentally benign catalyst has been used for the gested that under acidic conditions, contrary to basic
synthesis of some heterocyclic compounds [3 – 9].
media, the primary amines which could not act as a base,
Optoelectronic devices, such as fiber switches, tunable reacted as a reactant and appeared in the structure of the
lasers and amplifiers, modulators with various applica- products. In agreement to their suggestion, we have
tions, require compounds emitting in the blue spectral
region [10][11]. Cyanobenzene derivatives are good candi-
dates for producing nonlinear optical materials [12] and
recently reported the synthesis of some new fluorescent
2-amino-3-cyanopyridines using pentane-1,4-dione, malono
nitrile, and amines in the presence of organic acids
molecular switches [13]. It seems that designing a highly (N-hydroxybenzamide or TsOH) [14]. When Cellulose-SA
efficient environmentally benign procedure for the prepa- was used as the catalyst, the only products were 2,6-dicya-
ration of fluorescent-substituted cyanobenzene derivatives
is of great interest. Following our interest in the synthesis
of fluorescent compounds [14 – 17], here we wish to
noaniline derivatives instead of 2-amino-3-cyano pyri-
dines. We have already used some acidic catalysts in
organic synthesis [14 – 17]. In this report, we used 1,3-
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
DOI: 10.1002/hlca.201500242

356
Helv. Chim. Acta 2016, 99, 355 – 360
Scheme 1. Synthesis of 2,6-dicyano-3,5-disubstitued anilines 2a – c
diketones 1 and malononitrile in the aqueous media and
can be considered as a catalytic cycle (Scheme 2). On the
presence of secondary amines (Me2NH, Et2NH, and other hand, Cellulose-SA allows the use of H2O as the
piperidine) for the synthesis of some fluorescent 2,6-dicya- solvent instead of organic solvents without the need of
noanilines 2. We used Cellulose-SA as the catalyst in this
procedure. Cellulose-SA changed the reaction path com-
pletely. It performed its role as an acidic catalyst which
microwave irradiation used in the previous report by
Tu et al. [18]. The more effective role of H2O on the
Scheme 2. The proposed mechanism for the synthesis of compounds 2
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
www.helv.wiley.com

Helv. Chim. Acta 2016, 99, 355 – 360
357
synthesis of 2a is compared with MeCN, EtOH, MeOH,
and DMF (Table 1).
The reaction did not proceed in the absence of
amines. For exploring the role of the amine in the above
reaction, we replaced the secondary amine with Et3N and
other tertiary amines, but no products were observed.
Therefore, we guessed that the amine not only acts as a
base in the first stage of the reaction, but also can assist
Cellulose-SA to proceed the reaction. Replacing one of
the Me groups or both of them in pentane-2,4-dione by
Ph moieties produced 2b – c in high yields by the present
procedure. Compound 2b has attracted a lot of interest. It
has been the subject of many studies in recent years, and
some approaches have been reported for its synthesis
[19 – 21]. Here, we report the Cellulose-SA catalyzed
synthesis of 2b using 1-phenylbutane-1,3-dione as reactant
in H2O as solvent. The present procedure meets the
‘green chemistry’ using Cellulose-SA as a biodegradable
catalyst and H2O as the best environmentally benign
solvent.
Fig. 1. X-Ray crystal structure of 2a.
malononitrile produced adduct 3, which exist in equilib-
rium with its enolic form, and in the presence of the sec-
ondary amine afforded the conjugated enamine 4.
Cellulose-SA was added in this stage of the reaction.
Thus, enamine 4 was protonated to produce 5. Michael
addition of malononitrile anion to 5 produced adduct 6,
which is stabilized by the anion of Cellulose-SA. Addition
of a third anion of malononitrile and elimination of the
secondary amine yields 7. The acidic proton of 7 can be
Compound 2c, which also had been the subject of
some previous reports [22 – 24], is also synthesized by
this new procedure. The Ph groups do not seem to affect
the role of catalytic activity of Cellulose-SA in this syn-
thetic procedure (85% yield). Optimal times, yields, and
melting points of the synthesized compounds 2a – c using
this procedure are compared in Table 2.
Structures of compounds 2a – c were assigned on the
basis of their elemental analysis, IR, 1H- and 13C-NMR, and
MS data. Single crystals of 2a were obtained from a mixture
of AcOEt and hexane, and its X-ray crystal structure
confirms unambiguously the proposed structure (Fig. 1).
A plausible reaction mechanism which can explain the
catalytic role of Cellulose-SA is shown in Scheme 2 and
the final step is very similar to the Thorpe–Ziegler reac-
tion [19]. Primary condensation of 1,3-diketone 1 and
removed and intermediate
8 was produced by an
intramolecular cyclization (Thorpe–Ziegler reaction).
Intermediate 8 was converted to 9 by the aid of the amine
and finally product 2 was obtained by a second Thorpe–
Ziegler reaction. This part of mechanism is closely related
to the one reported by Yi et al. [19]. In contrast to our
previous report, the amine did not act as the reactant; it
played its interesting role twice, first, by producing enam-
ine 4 as precursor of the more effective Michael acceptor
5 in the presence of Cellulose-SA, and second, by depro-
tonation of intermediates 7 and 8. Comparing our previ-
ous report on 2-aminopyridines using the same reactants
[14], in the present reaction, Cellulose-SA prevents nucle-
ophilic addition to the nitrile group and controls the reac-
tion path.
Table 1. Solvent effect on the Cellulose-SA catalyzed synthesis of
2,6-dicyano-3,5-dimethylaniline (2aa))
Cellulose-SA has already been used as a catalyst for
the reaction between amines and other reactants [9][25]
[26].
The reusability of cellulose sulfuric acid was checked
by recovering the Cellulose-SA from the reaction mixture
of the synthesis of 2a. Simple filtration and washing the
recovered Cellulose-SA with 5 ml of 10% H2SO4, then
with 5 ml of CH2Cl2 for 2 – 3 times, and drying in a
Entry
Solvent
Time [h]
Yield [%]
1
2
3
4
5
MeCN
EtOH
MeOH
DMF
16
12
12
14
8
55
75
70
66
92
H2O
a) 0.05 g of cellulose-SA has been used.
Table 2. Reaction times and yields of the synthesis and melting points of 2,6-dicyano-3,5-disubstitued anilines 2a – c
Entry
Compound
R
R0
Time [h]
Yield [%]a)
M.p. [°]
1
2
3
2a
2b
2c
Me
Me
Ph
Me
Ph
Ph
8
11
10
92
72
85
211 – 212 ([29]: 211 – 213)
179 – 180 ([20]: 191; [21],188 – 190)
224 – 225 ([23]: 216 – 218)
a) Yield of isolated product.
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
www.helv.wiley.com

358
Helv. Chim. Acta 2016, 99, 355 – 360
vacuum oven at about 60 °C for 6 h were enough. The
recovered Cellulose-SA was used for at least four addi-
tional times for the proposed reaction without any signifi-
cant loss in the product yield (Fig. 2).
5 nm. The fluorescence emission intensity of compounds
after excitation at 290 nm is shown in Fig. 3.
Conclusions
The products 2a – c have shown fluorescent properties
in the solid state and in solution. In the literature, 3,5-dis- Biodegradable cellulose sulfuric acid catalyzed the forma-
ubstituted-2,6-dicyano anilines have been the subject of tion of some 2,6-disubstituted dicyanoaniline derivatives
many fluorescent studies [27]. The synthesis of 2a has in aqueous media in excellent yields. The reaction workup
been reported by Hull et al., using 1-acetyl-2-aminopro- is very simple because of the aqueous media. The catalyst
pen and malononitrile [28]. Also photophysical properties can be easily separated from the reaction mixture and
of compound 2a were previously reported via quantum reused several times in subsequent reactions without sig-
mechanical calculations by Kolek et al. [29].
nificant loss in the yields of products. The present proce-
dure meets the ‘green chemistry’ using Cellulose-SA as a
reusable biodegradable catalyst and H2O as the best envi-
ronmentally benign solvent. Further investigation of this
Fluorescence properties of 2a – c including kAbs. (nm),
kFlu. (nm) have been measured in CH2Cl2, MeCN, and
MeOH (2 9 10ꢀ5 M conc.). The results in Table 3 show
that the fluorescence maxima (kFlu.) of 2a and 2b are method is currently in progress to establish its scope and
shifted to longer wavelength by increasing the solvent
utility. The products showed fluorescence properties in
polarity. On the other hand, kFlu. of 2c in MeOH is at solution and in the solid state. Photophysical properties of
lowest wavelength than in MeCN, probably as a result of
the presence of two Ph groups in its structure lowering
the stability in MeOH as a protic solvent.
We were delighted to find that the synthesized com-
pounds not only showed strong fluorescence in different
the synthesized compounds (kAbs., kFlu.) in CH2Cl2,
MeCN, and MeOH are measured. The fluorescence emis-
sion intensity of compounds after excitation at 290 nm is
reported too. We are hopeful that the synthesized fluores-
cent compounds can play a significant role in biochemical
solvents, but also two of them are highly fluorescent even research and technology upgrading, probably useful for
in the solid state that is necessary for the development of
electronic devices, such as solid-state organic lasers. Fluo-
rescence molecular spectroscopy of the new compounds
electronic devices, such as organic lasers.
The support of this study by the Research Council at the
has been studied. Each sample (0.5 ml) in CHCl3 University of Tehran is gratefully acknowledged.
(10ꢀ10 M) was first coated on a glass sheet and dried at
room temperature, then placed in a 1 cm length quartz
cell. The excited and emission slits were adjusted to
Experimental Part
General
Chemicals and solvents were obtained from Merck (Ger-
many) and Fluka (Switzerland). M.p. was measured on a
Barnstead Electrothermal melting point apparatus and was
not corrected. IR Spectra were measured on a Bruker
EQUINOX 55 spectrophotometer using the ATR
1
method. H- and 13C-NMR spectra were determined on a
Bruker spectrometer at 500 MHz and 128 MHz, respec-
tively. Mass spectra were recorded on a Finnigan-MAT
8430 spectrometer at an ionization potential of 70 ev. All
fluorescence intensity measurements and fluorescence
emissions were obtained by a luminescence PERKIN
Fig. 2. Reusability of Cellulose-SA as catalyst in the preparation of
2,6-dicyano-3,5-dimethyl aniline 2a.
ELMER LS 50B spectrometer. The photo is taken under
a lamp at k = 366 nm (TL8W/08F8T5/BLC Philips made
Table 3. The photophysical data, electronic absorption (Abs.) and fluorescence (Flu.) of 2a – c in solution
Entry
Compound
kAbs.
(CH2Cl2)
kFlu.
(CH2Cl2)
kAbs.
(MeCN)
kFlu.
(MeCN)
kAbs.
(MeOH)
kFlu.
(MeOH)
1
2
3
2a
2b
2c
340
340
345
366
396
396
335
342
344
375
416
409
341
360
333
386
431
391
kAbs. [nm], kFlu. [nm] have been measured for 2 9 10ꢀ5 M in CH2Cl2, MeOH, MeCN.
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
www.helv.wiley.com

Helv. Chim. Acta 2016, 99, 355 – 360
359
Fig. 3. Left: The fluorescence emission spectra of the synthesized compounds in the solid state after excitation at 290 nm. Right: Photos of
compounds 2a – c in the solid phase under the same fluorescence lamp k = 366 nm.
in Holland, the Netherlands). Elemental analysis for C,
H, and N were performed using a Thermo Finnigan Flash perature for 8 – 11 h (Table 1). The progress of the reac-
EA1112 instrument. Crystallographic data for the struc- tion was monitored by TLC. When the enamine spot was
the above mixture. The mixture was stirred at room tem-
ture of compound 2a have been deposited with the Cam- disappeared and the spot of the product was reached to
bridge Crystallographie Data Center as CCDC-941206, its maximum (Rf ꢁ 0.6 on silica gel, hexane/AcOEt 2:1),
which contains the supplementary crystallographic data
for this work. These data can be obtained free of charge
via http://www.ccdc.com.ac.uk/data_request/cif.
the product was extracted with AcOEt. Colorless crystals
of the products were obtained by recrystallization in
AcOEt/hexane 1:3.
Preparation of Cellulose Sulfuric Acid
Recovering the Catalyst (Cellulose-SA)
Cellulose-SA was prepared by the method described in To recover the catalyst, the solid residue was washed
[9]. To a magnetically stirred mixture of 5.0 g of cellulose using 5 ml of 10% H2SO4 and then 5 ml of CH2Cl2 for
in 20 ml of hexane, 1.0 g of chlorosulfonic acid (10 mmol) three times. The separated cellulose sulfuric acid was
was added dropwise at 0 °C during a 3 h period. HCl gas dried in the vacuum oven and it can be used at least
was removed from the reaction vessel immediately. The
mixture was stirred for 3 h at room temperature until
HCl gas was removed completely. Then the mixture was
stirred for 3 h, filtered, and washed with 30 ml of MeCN
and dried at room temperature; 5.25 g of Cellulose-SA
was obtained as a white powder. The sulfur content of
the synthesized samples of Cellulose-SA was 0.55 mmol/g
determined by conventional elemental analysis. The num-
ber of H+ sites on the cellulose-SO3H was determined by
acid–base titration and was found to be 0.50 meq/g. This
value corresponds to about 90% of the sulfur content
indicating that most of the sulfur species are in the form
of sulfonic acid [9].
another four times without significant loss of activity.
REFERENCES
[1] C. J. Li, T. H. Chan, Organic Reactions in Aqueous Media,
John Wiley and Sons, New York, 1997.
[2] M. C. Pirrung, K. D. Sarma, J. Am. Chem. Soc. 2004, 126, 444.
[3] A. Shaabani, A. Rahmati, Z. Badri, Catal. Commun. 2008, 9,
13.
[4] J. Safari, S. H. Banitaba, S. D. Khalili, J. Mol. Catal. A: Chem.
2011, 335, 46.
[5] A. Rahmatpour, React. Funct. Polym. 2011, 71, 80.
[6] A. Rajack, K. Yuvaraju, C. Praveen, Y. L. N. Murthy, J. Mol.
Catal. A: Chem. 2013, 370, 197.
[7] J. V. Madhav, Y. T. Reddy, P. N. Reddy, M. N. Reddy, S.
Kuarm, P. A. Crooks, B. Rajitha, J. Mol. Catal. A: Chem. 2009,
304, 85.
General Procedure for the Synthesis of Compounds
2a – c
[8] H. Alinezhad, A. H. Haghighi, F. Salehian, Chin. Chem. Lett.
2010, 21, 183.
[9] A. Shaabani, A. Maleki, Appl. Catal. A: Gen. 2007, 331, 149.
[10] H. Kanbara, M. Asobe, K. Kubodera, T. Kaino, T. Kurihara,
Appl. Phys. Lett. 1992, 61, 2290.
To a mixture of 1,3-diketone 1 (1 mmol) and malononi-
trile (3 mmol) in H2O (3 ml) was added a secondary
amine 3 (1 mmol). The mixture was stirred for 5 min.
When the synthesis of the conjugated enamine 4 was
completed, cellulose sulfuric acid (0.05 g) was added to
[11] F. J. Duarte, Appl. Opt. 1994, 33, 3857.
[12] T. M. Cardozo, M. A. C. Nascimento, J. Mater. Sci. 2005, 40,
3549.
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
www.helv.wiley.com

360
Helv. Chim. Acta 2016, 99, 355 – 360
[13] R. L. Carroll, C. B. Gorman, Angew. Chem., Int. Ed. 2002, 41,
4378.
[24] V. Raghukumar, P. Murugan, V. T. Ramakrishnan, Synth. Com-
mun. 2001, 31, 3497.
[14] A. Zonouzi, Z. Izakian, S. W. Ng, Heterocycles 2012, 85, 2713.
[15] A. Zonouzi, R. Mirzazadeh, S. W. Ng, Molbank 2012, M775.
[16] A. Zonouzi, F. Hosseinzadeh, N. Karimi, R. Mirzazadeh, S. W.
Ng, A. C. S. Comb. Sci. 2013, 15, 240.
[25] A. Shaabani, M. Seyyedhamzeh, A. Maleki, F. Rezazadeh,
Appl. Catal. A: Gen. 2009, 358, 146.
[26] H. Mofakham, Z. Hezarkhani, A. Shaabani, J. Mol. Catal. A:
Chem. 2012, 360, 26.
ꢀ
[27] B. Szczepanik, S. Styrcz, M. Gora, Spectrochim. Acta 2008, 71,
403.
[17] A. Zonouzi, Z. Izakian, H. Salehi, K. Abdi, S. W. Ng, Molbank
2014, M831.
[18] S. Tu, B. Jiang, Y. Zhang, R. Jia, J. Zhang, C. Yao, F. Shi, Org.
Biomol. Chem. 2007, 5, 355.
[19] C. Yi, C. Blum, S.-X. Liu, G. Frei, A. Neels, P. Renaud, S.
Leutwyler, S. Decurtins, J. Org. Chem. 2008, 73, 3596.
[20] M. Adib, B. Mohammadi, S. Ansari, H. R. Bijanzadeh, L.-G.
Zhu, Synthesis 2010, 1526.
[28] R. Hull, N. Campbell, W. H. Stafford, J. F. K. Wilshire, L. H.
Briggs, G. A. Nicholls, A. W. Johnson, N. Sheppard, A. R.
Todd, J. Ratcliffe, D. Bryce-Smith, K. E. Howlett, L. H.
Groves, G. A. Swan, J. Chem. Soc. (Res.) 1951, 1136.
[29] P. Kolek, P. Gajdek, T. Motylewski, M. Tulej, J. Najbar, J. Flu-
orescence 1999, 9, 123.
[21] S.-L. Cui, X.-F. Lin, Y.-G. Yang, J. Org. Chem. 2005, 70, 2866.
[22] X. Xin, Y. Wang, W. Xu, Y. Lin, H. Duan, D. Dong, Green
Chem. 2010, 12, 893.
Received September 19, 2015
Accepted March 7, 2016
[23] A.-G. Ying, X.-Z. Chen, C.-L. Wu, R.-H. Zheng, H.-D. Liang,
C.-H. Ge, Synth. Commun. 2012, 42, 3455.
€
© 2016 Verlag Helvetica Chimica Acta AG, Zurich
www.helv.wiley.com