Novel 4-aryl-2-amino-6-(naphthalene-1-yl)-3-cyanopyridine derivates as potential organic fluorescent materials prepared under microwave irradiation via three-component domino reactions

Article abstract of DOI:10.1080/00397911.2014.891239

A green and efficient method for direct preparation of 3-cyanopyridine from aromatic aldehydes is reported. A series of novel 4-aryl-2-amino-6- (naphthalene-1-yl)-3-cyanopyridine derivates were successfully prepared by one-pot synthesis of three-component domino reactions including aromatic aldehydes, 1-acetylnaphthalene, and dicyanomethane in the presence of ammonium acetate in a solution of ethanol under microwave irradiation. This synthetic method for these compounds possesses many advantages including greater yield and shorter reaction times compared with traditional methods. The structures of these compounds were confirmed by means of high-resolution mass spectrometry, ¹H NMR, ¹³C NMR, and infrared. Moreover, the results of their fluorescent spectra showed that these compounds have good fluorescence intensity excited by the visible light wavelength of 416 nm. Copyright

Full text of DOI:10.1080/00397911.2014.891239

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Novel 4-Aryl-2-amino-6-(naphthalene-1-
yl)-3-cyanopyridine Derivates as
Potential Organic Fluorescent Materials
Prepared Under Microwave Irradiation
via Three-Component Domino Reactions
Jianqiang Wang a , Jianlin Zhu a , Jie Zhong a , Jun Sun a , Shigui
Tang b & Cheng Guo a
a College of Sciences , Nanjing Tech University , Jiangsu , Nanjing ,
China
b Biotechnology and Pharmaceutical Engineering , Nanjing Tech
University , Jiangsu , Nanjing , China
Accepted author version posted online: 03 Apr 2014.Published
online: 06 Jun 2014.
To cite this article: Jianqiang Wang , Jianlin Zhu , Jie Zhong , Jun Sun , Shigui Tang & Cheng Guo
(2014) Novel 4-Aryl-2-amino-6-(naphthalene-1-yl)-3-cyanopyridine Derivates as Potential Organic
Fluorescent Materials Prepared Under Microwave Irradiation via Three-Component Domino Reactions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 44:15, 2205-2214, DOI: 10.1080/00397911.2014.891239
To link to this article: http://dx.doi.org/10.1080/00397911.2014.891239
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Synthetic Communications1, 44: 2205–2214, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2014.891239
NOVEL 4-ARYL-2-AMINO-6-(NAPHTHALENE-1-
YL)-3-CYANOPYRIDINE DERIVATES AS POTENTIAL
ORGANIC FLUORESCENT MATERIALS PREPARED
UNDER MICROWAVE IRRADIATION VIA
THREE-COMPONENT DOMINO REACTIONS
Jianqiang Wang,1 Jianlin Zhu,1 Jie Zhong,1 Jun Sun,1
Shigui Tang,2 and Cheng Guo1
1College of Sciences, Nanjing Tech University, Jiangsu, Nanjing, China
2Biotechnology and Pharmaceutical Engineering, Nanjing Tech University,
Jiangsu, Nanjing, China
GRAPHICAL ABSTRACT
Abstract A green and efficient method for direct preparation of 3-cyanopyridine from
aromatic aldehydes is reported. A series of novel 4-aryl-2-amino-6-(naphthalene-1-yl)-3-
cyanopyridine derivates were successfully prepared by one-pot synthesis of three-component
Received July 9, 2013.
Address correspondence to Cheng Guo, College of Sciences, Nanjing Tech University, 30 Puzhu
South Road, Jiangsu, Nanjing 211816, China. E-mail: guocheng@njtech.edu.cn
Color versions of one or more of the figures in the article can be found online at www.tandfonline.
com/lsyc.
2205

2206
J. WANG ET AL.
domino reactions including aromatic aldehydes, 1-acetylnaphthalene, and dicyanomethane
in the presence of ammonium acetate in a solution of ethanol under microwave irradiation.
This synthetic method for these compounds possesses many advantages including greater
yield and shorter reaction times compared with traditional methods. The structures of these
compounds were confirmed by means of high-resolution mass spectrometry, H NMR, 13
1
C
NMR, and infrared. Moreover, the results of their fluorescent spectra showed that these
compounds have good fluorescence intensity excited by the visible light wavelength of
416 nm.
Keywords 3-Cyanopyridine derivates; microwave irradiation; one-pot synthesis; organic
fluorescent material; three-component domino reactions
INTRODUCTION
3-Cyanopyridine is an important heterocycle with great applicability in med-
icinal chemistry. The special heterocycle structure can be found in many biologically
active compounds with diverse medicinal properties. Because of the various potential
biological and pharmacological activities of its derivatives, many 3-cyanopyridine
derivatives are often used to construct the alkaloid intermediates, and they also play
an important role in cardiotonic agents for the treatment of heart failure,[1] selective
farnesyl protein inhibitors, and pilicides with novel antibacterial properties.[2] Even
the relatively simple structure of 4,6-diaryl-2-pyridone can become an effective leu-
kotriene B4 antagonists (LTB4).[3] Besides, the heterocyclic compounds are widely
used in the synthesis of natural products. For example, they are also used as calcium
ion channel modulators[4] and human GABAA receptor modulators.[5]
Because of the importance of 3-cyanopyridine in the pharmaceutical, dye, and
photo industries, many synthetic methods for these compounds have been widely
reported.[6–11] However, most of these methods have significant drawbacks such as
long reaction time, harsh reaction conditions, and difficult workup. In recent years,
microwave irradiation, a new and useful method of synthesis of the compounds, has
been applied in organic synthetic chemistry.[12–18] Microwave-assisted organic syn-
thesis has received much attention because of its faster chemistry, formation of clea-
ner products, and greater yields compared with standard thermal conduction.[19,20]
Many drug intermediates have been manufactured with the assistance of microwave
irradiation.[21–23] Thus, microwave irradiation is chosen as our heating source to
develop more new products in combinational synthesis.
In this article, we report a facile, rapid, and green method for the synthesis of
4-aryl-2-amino-6-(naphthalene-1-yl)-3-cyanopyridine derivates by three-component
domino condensations under microwave irradiation. To the best of our knowledge,
this is a new synthetic route to build the structure. Meanwhile, a relative good result
is concluded by the comparison between microwave irradiation and conventional
heating. On the other hand, the fluorescence intensities of these compounds are
detected in the excited wavelength to observe their fluorescent characteristics.
RESULTS AND DISCUSSION
Effects of Microwave Irradiation (MWI) Time
To optimize the reaction conditions, the effects of different reaction time and
microwave irradiation (MWI) power were investigated in the preparation of compound

THREE-COMPONENT DOMINO REACTION
2207
4a. The amounts of all the reactants including benzaldehyde 1a (2 mmol),
1-(naphthalen-1-yl)ethanone 2 (2 mmol), ethyl cyanocaetate 3 (2 mmol), and
ammonium acetate (2 mmol) were the same in ethanol under microwave irradiation
at 100 ꢀC. Figure 1 indicates the difference in the yields of product 4a resulting from
the MWI time. The results showed that the yield of product 4a was improved with
the increasing of the MWI time in the range from 2 to 6 min. However, the yield of
4a decreased when MWI time was further increased to 12min. Therefore, the
MWI time of 6 min was chosen as the optimized time for the preparation of the other
compounds.
Effects of Microwave Irradiation (MWI) Power
The different MWI powers were used in the one-pot synthesis of these com-
pounds. It is well known that a low irradiation power cannot give sufficient energy
to drive the reaction, but it does not mean the greater power can result in the better
yield of the product. To get the relatively suitable MWI power, we change the differ-
ent power to drive the reaction. The powers from 200 W to 600 W in 100-W incre-
ments every 6 min were selected in the preparation of compound 4a. As shown in
Fig. 2, the yield of compound 4a is the greatest when the MWI power is 400 W. How-
ever, when the power was further increased to 500 W or 600 W, the yield decreased.
The special change of yield in the different MWI powers is clearly observed because
the vigorous reaction in the flask produces a lot of side products. Moreover, some
products are carbonized under the greater power. Therefore, the optimized MWI
power of compound 4a is 400 W.
Effects of Different Synthesis Methods
Compared to the conventional heating, the reaction time is very short under
MWI. In this study, the reaction time and yield of the product were compared
Figure 1. Effect of MWI time on the yield of 4a.

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J. WANG ET AL.
Figure 2. Effects of MWI power on the yield of 4a.
between the MWI method and the conventional heating method. All of the reactions
were carried out under the same optimized conditions including reaction power,
reaction time, and reaction temperature under the MWI method. Furthermore,
the conventional heating temperature was 100 ꢀC, equal to the MWI temperature.
However, the reaction time of conventional heating was 180 min, which is longer
than the microwave reaction time. As shown in Table 1, there is an obvious differ-
ence between the MWI and the conventional heating. The yield of compounds 4
under MWI is greater than the one under conventional heating. So, MWI seems
to be an effective method to drive the reaction because of the shorter reaction time
and the longer yield.
Fluorescent Spectra of Compounds 4a–4f
Figure 3 shows the change of fluorescent intensity of compound 4a in the
different solvents. To discuss the effect of the different solvent in the fluorescent
Table 1. Comparison of reaction times and yields for compounds 4 using microwave and classical
methods
Reaction time
Yield (%)
Classical heating
Compound
Microwave (min)
Classical heating (min)
Microwave
4a
4b
4c
4d
4e
4f
6
6
6
6
6
6
180
180
180
180
180
180
59
68
67
72
53
36
43
62
54
56
27
30

THREE-COMPONENT DOMINO REACTION
2209
Figure 3. Florescent spectra of 4a in different solvents (c ¼ 2.0 ꢁ 10ꢂ5 mol=L).
spectrum of 4a, four compounds including methanol, ethanol, dimethyl formamide
(DMF), and dimethyl sulfoxide (DMSO) were selected as the solvents. The
fluorescent intensity of 4a is the greatest in the solution of methanol in Fig. 3. The
fluorescent intensity of 4a becomes low in the other three solvents. Moreover,
the maximum emission wavelength is shifted to the long wave because of the hydro-
gen bond and different polarities of the other three solvents. Thus, methanol is
the best solvent in the detection of fluorescent spectrum of these compounds
3-cyanopyridines.
The fluorescent spectra of compounds 4a–4f were detected in the methanol. As
shown in Fig. 4, all of the compounds 4a–4f possesses good fluorescent intensity in
the same exited wavelength. The results indicate that these compounds can be used
as the potential fluorescent material because of their good fluorescent intensity.
Moreover, the difference of fluorescent intensity is tightly related to the structure
of 3-cyanopyridines. The fluorescent intensity of compound 4e is the strongest of
Figure 4. Fluorescent spectra of 4a–4f in methanol (c ¼ 2.0 ꢁ 10ꢂ5 mol=L).

2210
J. WANG ET AL.
the compounds because of the larger p conjugated structure and plenty of p electrons
are formed by the linked furyl group in the compound 4a. However, the compound
4d possesses weak fluorescent intensity due to fluorescent quenching resulting from
the internal heavy-atom effect of two chlorine groups. Additionally, the different
positions of substituted groups also largely affect the fluorescent intensity of these
compounds. As shown in Fig. 4, the fluorescent intensity of compounds 4e and 4c
are stronger than one of the compounds 4b and 4f because the ortho-position and
para-position of aromatic cycle can enhance the fluorescent intensity. Conversely,
the meta-position of aromatic cycle decreases the fluorescent intensity.[24,25]
The fluorescence quantum yields of these compounds were obtained by using
L-tryptophane as a reference. The fluorescence quantum yield of compound 4e is
0.56. It is the greatest in all of the compounds studied here. However, the fluores-
cence quantum yield of compound 4d is only 0.33. The results indicate that the
compound 4e possesses good fluorescent performance. The fluorescent quantum
yields of the other compounds 4a, 4b, 4c, and 4f are respectively 0.52, 0.50, 0.51,
and 0.53. These differences of fluorescence quantum yield are in accord with the
fluorescent intensity showed in Fig. 4. Furthermore, these compounds can be used
as the potential fluorescent materials.
Scheme 1. Possible reaction mechanism for the synthesis of 3-cyanopyridine.

THREE-COMPONENT DOMINO REACTION
2211
Reaction Mechanism of 3-Cyanopyridine Compounds
During the reaction, the possible mechanism of the reaction was studied. It may
be assumed to proceed via a mechanism of Knoevenagel condensation, Michael
addition, cyclization, and elimination. First, two-component reaction between the
reagent of aldehyde 1 and the reagent of malononitrile 3 gave a desired intermediate
2-aromatic methylene malononitrile 6. At the same time, the intermediate imine 5 is pre-
pared by the reaction between 1-acetylnaphthalene and NH4OAc. When the compound
6 met with the compound 5, the key intermediate compound 7 was speculated by the
next two-component reaction. Finally, the compound 2-amino-3-cyanopyridine 4 is
obtained by the speculated compound 7 via cyclization, isomerization, and aromati-
zation. The possible reaction mechanism was showed in Scheme 1. Moreover, the
mechanism indicates that the targeted compound 4 is prepared by the domino reactions.
EXPERIMENTAL
General Method for the Synthesis of 4-Aryl-2-amino-6-
(naphthalene-1-yl)-3-cyanopyridine Under Microwave Irradiation
According to Scheme 2, the aromatic aldehyde 1 (2 mmol), 1-acetylnaphthalene
2 (2 mmol), malononitrile 3 (2 mmol), NH4OAc (16 mmol), and absolute ethanol
(2 mL) were added to a 50-mL, three-necked, round-bottomed flask. The mixtures
were placed into the microwave reaction system. The reaction condition was
controlled at 100 ꢀC and the microwave power was 400 W for 6–7 min. A small
amount of reaction mixture was used to monitor the reaction progress with
thin-layer chromatography (TLC). Then, the reaction mixture was cooled for several
hours and filtered to the crude product. The solid product was crystallized with
ethanol to obtain the compound 4.
General Method for the Synthesis of 4-Aryl-2-amino-6-
(naphthalene-1-yl)-3-cyanopyridine Under Classical Conditions
The aromatic aldehyde 1 (2 mmol), 1-acetylnaphthalene 2 (2 mmol), malono-
nitrile 3 (2 mmol), NH4OAc (16 mmol), and absolute ethanol (2 mL) were added
Scheme 2. Preparation of 4-aryl-2-amino-6-(naphthalene-1-yl)-3-cyanopyridine derivates 4a–4f.

2212
J. WANG ET AL.
to a 50-mL, three-necked, round-bottomed flask. The mixture was heated in the oil
bath and kept refluxing at 100 ꢀC for 4 h. Then, the reaction mixture was cooled and
filtered. The compound 4 was obtained by crystallizing with ethanol.
Compound Characterization
Microwave reaction was carried out in WF-4000C microwave system. Melting
1
points were measured on X-4 digital display melting-point meter. The H NMR
spectra were recorded on Bruker AC-300 (300-MHz) NMR spectrometer using
CDCl3 as the solvent. All of the chemical shifts were reported in parts per million
relative to internal standard Tetramethylsilane (TMS); positive chemical shifts
denote greater frequency from the given reference. The 13C NMR spectra were
recorded on Bruker AV-400 (100-MHz) NMR spectrometer using CDCl3 as the sol-
vent. The Fourier transform infrared (FTIR) spectrum were determined using
FTIR-8400S spectrometer in the region from 4000 to 400 cmꢂ1 at 298 K, and all
of the samples were mixed with KBr at the ratio of 3:97 (mol=mol) and then pressed.
The mass spectra (MS) [electrospray ionization (ESI)] were detected on an Aglient
6550 iFunnel Q-TOF. The elemental analysis (C, H, and N analysis) was done on
a German Elementar Vario EL. Purity of the compounds was checked by thin-layer
chromatography (TLC). The fluorescence spectra were done on a Perkin-Elmer LS55
luminescence spectrometer.
The fluorescence quantum yield was obtained by comparing the integrated area
of the corrected emission spectrum of the samples with the reference under the same
excited wavelength. The concentration of the reference L-tryptophane (U ¼ 0.14)[26]
in aqueous solution was adjusted to match the absorbance of the test sample. The
quantum yields of compounds 4a–4f were tested by using a methanol solution con-
taining 2 ꢁ 10ꢂ5 M. Emission for all of the compounds was integrated from 290 to
490 nm. The quantum yields were calculated with the following equation[27]
:
R
emissionsample
Areference
R
Usample ¼ Ureference
ꢁ
ꢁ
emissionreference Asample
CONCLUSIONS
A series of 4-aryl-2-amino-6-(naphthalene-1-yl)-3-cyanopyridine has been
synthesized successfully under the condition of MWI, which makes the small-scale
high-speed synthesis possible. In addition, the 3-cyanopyridine derivates are
obtained by domino reactions in good yields. Moreover, these compounds are used
as the potential fluorescent materials because of their good fluorescent characteristic
at special excited wavelength in the range of visible light.
FUNDING
The authors thank the National Natural Science Foundation of China (No.
21106069) and Science Foundation for Young Scientists of Nanjing University of
Technology (No. 39704011).

THREE-COMPONENT DOMINO REACTION
2213
SUPPLEMENTARY INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.
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