Green and Sustainable Chemistry, 2011, 1, 176-181
doi:10.4236/gsc.2011.14027 Published Online November 2011 (http://www.SciRP.org/journal/gsc)
Solar Thermochemical Reactions IV: Unusual Reaction of
Nitrones with Acetonitrile Derivatives Induced by
Solar Thermal Energy
Ramadan Ahmed Mekheimer1*, Khadijah Mohamed Al-Zaydi1, Asma Al-Shamary1,
Kamal Usef Sadek2
1Department of Chemistry, Faculty of Science for Girls, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia
2Chemistry Department, Faculty of Science, El-Minia University, El-Minia, AR Egypt
Received June 13, 2011; revised July 15, 2011; accepted July 28, 2011
Abstract
The behaviour of cyanothioacetamide 1 and the acetonitrile derivatives 6 and 10, respectively, towards the
nitrones 2a-i induced by free solar thermal energy is reported. Structures and reaction mechanisms are also
discussed.
Keywords: Nitrones, Cyanothioacetamide, 2-(Hetaryl)Acetonitrile Derivatives, Synthesis, Solar Thermal
Energy
1. Introduction
Nitrones are used as useful reagents or intermediates in
the synthesis of a variety of nitrogen-containing com-
pounds which find application as agro-chemicals and/or
pharmaceuticals [1]. Generally, nitrones easily undergo
1,3-dipolar cycloaddition reactions with a large variety
of substituted alkenes including both electron-rich and
electron-poor dipolarophiles [2,3]. The resulting five-
membered isoxazolidine derivatives may be converted
into amino alcohols, precursors to biologically impor-
tant amino acids, alkaloids or β-lactams [4-8]. In addi-
tion to the well-known cycloaddition chemistry of ni-
trones, there are several reports on nucleophilic addi-
ctions to nitrones promoted and/or catalyzed by Lewis
acids [9-11].
Recently, we have designed a new strategy aiming at
the synthesis of pharmacologically interesting heterocy-
clic systems using solar energy as eco-friendly energy
source [12-14]. In continuation of this work, we report
herein the behaviour of some acetonitrile derivatives to-
wards differently substituted open-chain C-aryl(or hetaryl)-
N-phenylnitrones under the effect of solar thermal energy.
To the best of our knowledge, the use of free solar ther-
mal energy to accomplish such study has not so far been
reported in the literature.
2. Results and Discussion
The reactions between cyanothioacetamide 1 with the
nitrones 2 were first investigated. Thus, the reaction of
cyanothioacetamide 1a, which is completely enthiolized
in liquid phase (Figure 1), with the diphenylnitrone 2a in
absolute ethanol under solar heating for 2h (TLC control)
did not afford 5-amino-5-mercapto-2,3-diphenylisoxa-
zolidine-4-carbonitrile 3a, as a final product, but furni-
shed instead the unexpected 2-cyano-3-phenylprop-2-
enethioamide 5a, in good yield (Scheme 1). Although
the synthesis of arylmethylenecyanothioacetamide de-
rivatives has been reported [15-18], compound 5a was
not previously isolated as a solid and always generated in
situ. Therefore, it seems to be very interesting to report
the first isolation of 2-cyano-3-phenylprop-2-enethioa-
mide 5a. The structure of 5a was assigned on the basis of
consistent elemental and spectral data. Thus, the IR spe-
ctrum showed the presence of absorption bands at
Figure 1. The equilibrium between cyanothioacetamide (1a)
and 3-amino-3-mercapto-acrylonitrile (1b).

177 R. A. MEKHEIMER ET AL.
Scheme 1. Synthetic route used for preparing the 3-aryl-2-cyanothio-acrylamides 5a-h from nitrones and cyanothioacetamide
and proposed mechanism for their synthesis.
Figure 2. The equilibrium between 2-(5-ethylthio-4-phenyl-
4H-1,2,4-triazol-3-yl)acetonitrile (6a) and 2-(3-ethylthio-4-
phenyl-1H-1,2,4-triazol-5(4H)-ylidene)acetonitrile (6b).
3400 cm–1, 3300 cm–1, 3200 cm–1 and 2220 cm–1 assign-
able to NH2 and CN functions, while the 1H NMR spec-
trum contained two singlet signals at 7.95 ppm and 9.57
ppm, attributable to the olefinic proton and the thioamide
protons respectively, in addition to five aromatic protons
at 7.43 ppm - 7.61 ppm. Furthermore, its structure was
supported by 13C NMR, MS and analytical data analysis
which confirmed the proposed structure. Formation of 5a
could be achieved by an initial 1,3-dipolar cycloaddition
of the nitrone 2a and compound 1b giving the isoxa-
zolidines intermediate 3. This adduct undergoes an in-
ternal proton shift and ring-opening to yield a further
intermediate 4 which then undergoes a proton shift and
carbon-nitrogen fission to afford the final product 5a
(Scheme 1).
The generality of the method is demonstrated by using
different C-aryl (or hetaryl)-N-phenylnitrones. Thus, rea-
ction of 1b with 2b-h under the same reaction conditions
gave the corresponding 3-aryl-2-cyanothio-acrylamides
5b-h. Their structures were confirmed by comparison of
their physical properties (mp, mixed mp, IR, 1H NMR)
with those of authentic samples prepared as previously
described [15].
To develop this reaction into a more general method,
other acetonitrile derivatives, containing a heterocyclic
sub-structure at position 2, were also tried. Thus, the re-
action of 2-(5-ethylthio-4-phenyl-4H-1,2,4-triazol-3-yl)-
acetonitrile 6b (Figure 2), with the nitrones 2a,b,i gave
the corresponding derivatives 9a-c (Scheme 2). The
compound 9a thus obtained was identical in all respects
(mp, mixed mp, IR, 1H NMR) with that previously pre-
pared by Mekheimer et al. [19]. The structures of 9b,c
were deduced from their IR, NMR and correct elemental
analyses as well as mass spectra. Thus, the IR spectra of
9b,c revealed the presence of absorption band at 2220
cm-1 due to cyano function. The 1H NMR spectra con-
tained a singlet signal at 7.88 ppm and 8.45 ppm assign-

R. A. MEKHEIMER ET AL.
178
able to the olefinic proton in 9b and 9c, respectively, in
addition to signals due to ethyl, phenyl and aryl protons.
Additionally, their structures were supported by 13C NMR
and correct mass spectra and analytical data, which were
all compatible with the assigned structures (see Experi-
mental). The formation of 9a-c may take place through an
initial 1,3-dipolar cycloaddition of 2 to the olefinic π bond
of 6b to yield the spiro intermediate 7 which was con-
verted to 9 by a similar mechanism to that discussed above
for the formation of 5 (see Sc heme 2).
Other acetonitriles derivatives in which the 2-position
is substituted with benzothiazole moiety were also used.
Thus, the nitrones 2a,b,i reacted with 2-(benzo-thiazol-
2(3H)-ylidene)acetonitrile 10b, under the same reaction
conditions, to afford 3-aryl-2-(benzothiazol-2-yl)acrylo-
nitrile derivatives 11a-c (Scheme 3), presumably by a
mechanism similar to that discussed above for the for-
mation of 9. The structures of the benzothiazole deriva-
tives 11a-c were established by comparison with authen-
tic samples (mp, mixed mp, IR, 1H NMR) prepared as
previously reported [20].
In order to investigate the exact effect of solar energy
in accelerating the reaction whether it is a thermal or a
photochemical one, we carried out the reaction in dark
under conventional heating and for the same reaction
time. It afforded the same products obtained under solar
Scheme 2. Synthetic route used for preparing the 3-aryl-2-(5-ethylthio-4-phenyl-4H-1,2,4-triazol-3-yl)acrylonitrile 9a-c from
nitrones 2a,b,f and 2-(3-ethylthio-4-phenyl-1H-1,2,4-triazol-5(4H)-ylidene)acetonitrile (6b) and proposed mechanism for their
synthesis.
Scheme 3. Synthetic route used for preparing the 3-aryl-2-(benzothiazol-2-yl)acrylonitrile derivatives 11a-c from nitrones
2a,b,f and 2-(benzothiazol-2(3H)-ylidene)acetonitrile (10b).

179 R. A. MEKHEIMER ET AL.
energy. At the same time, we performed the same reac-
tion at a low temperature (10˚C) under the effect of arti-
ficial visible light and the reactants were recovered, un-
changed even when exposure was performed for a longer
reaction time. This rules out the possibility of a photo-
chemical reaction.
3. Conclusions
In this fourth-generation version of our strategy, we have
shown that the reaction between nitrones and some ace-
tonitrile derivatives under solar heating efficiently leads
the unexpected 3-aryl-2-cyanothioacrylamide and 3-aryl-
2-(hetaryl)acrylonitrile derivatives. The significant ad-
vantages of this procedure are green, high yields, a sim-
ple work-up procedure. Further studies in our laboratory
aimed at the synthesis of new heterocyclic ring systems
induced by solar thermal energy are now in progress and
will be published in due course.
4. Experimental
4.1. General
Melting points were measured on a Gallenkamp appara-
tus and were not corrected. IR spectra were recorded
with a Nicollet Magna 520FT IR spectrophotometer.
Peaks are reported in cm–1. 1 H and 13C NMR spectra
were recorded on a Bruker DPX (600 MHz for 1H NMR
and 150 MHz for 13C NMR) spectrometer in DMSO-d6
using TMS as an internal standard; the chemical shifts
are given in δ units (ppm). Mass spectra were measured
on a GCMS-QP1000EX mass spectrometer. Analytical
thin-layer chromatography (TLC) was performed on al-
uminum sheets precoated with silica gel (Merck, Kie-
selgel 60F-254). Visualization was accomplished by UV
light. Micro-analyses were performed at the Microana-
lytical Data Unit at Cairo University.
4.2. Synthesis of 3-Aryl-2-cyanothioacrylamides
5a-h, General Procedure
To a solution of cyanothioacetamide (1) (2.5 mmole) in
absolute EtOH (10 mL), nitrones 2a-h (2.5 mmole) were
added. Then, the reaction mixture was exposed to direct
sunlight for 1-3 h, until the TLC showed the disappea-
rance of the starting materials. The maximum tempera-
ture of the reaction mixture was determined and cited in
Table 1. The excess of solvent was removed in vacuo.
The resulting solid product was collected by filtration
and recrystallized from EtOH to yield 5a-h. The products
5b-h were characterized by IR, NMR and through com-
parison of their physical properties with those reported in
literature.
Table 1. Solar thermal energy synthesis of 3-aryl-2-cyanothioacrylamides 5a-h and 3-aryl-2-(hetaryl)acrylonitrile derivatives
9a-c and 11a-c.
Product Ar Time (h) Yield (%)M. P. (˚C) Lit. M. P. (˚C)Maximum reaction temperature (˚C)
5a Ph 2 63 145 - 147 ___ 53
5b 4-MeOC6H4 2 73 189 - 190 190 - 19115 48
5c 4-NO2C6H4 3 69 187 - 188 188 - 18915 58
5d 2-NO2C6H4 5 66 179 - 180 180 - 18115 58
5e 3,4-methylenedioxyphenyl 2 67 216 - 217 215 - 21615 55
5f 4-Me2NC6H4 1 65 229 - 231 231 - 23215 57
5g 2-thienyl 3 54 168 - 169 169 - 17015 57
5h 2-furyl 3 52 156 - 157 15815 51
9a Ph 14 98 149 - 150 149 - 15019 56
9b 4-MeOC6H4 5 67 172 - 173 ___ 58
9c 4-ClC6H4 11 66 169 - 170 ___ 59
11a Ph 6 64 121 - 122 121 - 12320 56
11b 4-MeOC6H4 4 81 142 - 143 143 - 14420 59
11c 4-ClC6H4 4 73 148 - 150 148 - 15020 56

R. A. MEKHEIMER ET AL.
180
4.3. 2-Cyano - 3 -p h en y lp r op -2 - en e th i oa mide (5a)
1H NMR (600 MHz, DMSO-d6): δ =7.43 - 7.61 (m, 5H),
7.95 (s, 1H), 9.57 (br s, 2H). 13C NMR (150 MHz,
DMSO-d6): δ =102.2, 118.0, 128.0, 128.4, 129.0, 129.2,
129.6, 130.4, 136.5, 195.5. IR (KBr):  = 3410, 3295,
3200, 2185, 1619 cm–1. Found: C, 63.67; H, 4.37; N,
15.0; S, 16.85; anal. calcd for C10H8N2S: C, 63.80; H,
4.28; N, 14.88; S, 17.03. MS: m/z = 188 (M+, 60), 187
(M+-1, 100), 172 (3), 162 (4), 161 (4), 160 (7), 155 (12),
128 (14), 102 (20), 101 (11), 100 (7), 78 (8), 77 (24), 76
(14), 75 (13), 74 (11), 60 (49), 51 (42), 50 (29).
4.4. Synthesis of 3-Aryl-2-(hetaryl)acrylonitriles
9a-c and 11a-c; General Procedure
To a solution of compounds 6 or 10 (2.5 mmole) in ab-
solute EtOH (12 mL), nitrones 2a,b,i (2.5 mmole) were
added. The flask was exposed to direct sunlight for a
period determined by TLC control (see Table 1). The
maximum temperature of the reaction mixture was de-
termined and cited in Table 1. Then, the reaction mix-
ture was worked up as described above for 5a-h to give
the products 9a-c and 11a-c, respectively.
4.5. 2-(5-Ethylthio-4-phenyl-4H-1,2,4-triaz ol-3-yl)-
3-(4-methoxyphenyl)acrylonitrile (9b)
1H NMR (600 MHz, DMSO-d6): δ =1.43 (t, 3J = 7.2 Hz,
3H), 3.28 (q, 3J = 7.2 Hz, 2H), 3.86 (s, 3H), 6.93 (d, 3J =
7.8 Hz, 2H), 6.97 (m, 1H), 7.33 (m, 2H), 7.53 (m, 1H),
7.58 (m, 1H), 7.82 (d, 3J = 7.8 Hz, 2H), 7.88 (s, 1H). 13C
NMR (150 MHz, DMSO-d6): δ =14.7, 29.7, 55.5, 93.6,
114.5, 115.1, 121.3, 127.4, 129.0, 130.1, 132.3, 132.7,
146.3, 149.3, 153.9, 157.6. IR (KBr):  = 2922, 2200
cm–1. MS: m/z = 362 (M+, 12), 361 (45), 333 (7), 118
(12), 115 (7), 114 (14), 108 (2), 88 (7), 78 (11), 77 (100),
65 (11), 64 (15), 63 (21), 61 (7), 60 (12), 51 (72), 50 (20).
Found: C, 66.41; H, 4.89; N, 15.29; S 9.07; anal. calcd
for C20H18N4OS: C, 66.28; H, 5.01; N, 15.46; S, 8.85.
4.6. 3-(4-Chlorophenyl)-2-(5-ethylthio-4-phenyl-
4H-1,2,4-triazol-3-yl)acrylonitrile (9c)
1H NMR (600 MHz, DMSO-d6): δ =1.43 (t, 3J = 7.2 Hz,
3H), 4.06 (q, 3J = 7.2 Hz, 2H), 6.93 (m, 2H), 7.23 (m,
3H), 7.44 (d, 3J = 8.4 Hz, 2H), 7.82 (d, 3J = 8.4 Hz, 2H),
8.45 (s, 1H). IR: (KBr):  = 3050, 2970, 2200. MS: m/z =
368 (M+, 4), 366 (M+, 8), 337 (9), 255 (3), 244 (2), 230
(2), 189 (3), 161 (5), 137 (7), 126 (9), 118 (10), 113 (3),
112 (3), 105 (9), 100 (5), 99 (9), 91 (12), 77 (99), 65 (22),
64 (12), 63 (17), 61 (10), 60 (19), 59 (24), 51 (100), 50
(28). Found: C, 62.01; H, 4.25; Cl, 9.59; N, 15.38; S,
8.68; anal. calcd for C19H15ClN4S: C, 62.20; H, 4.12; Cl,
9.66; N, 15.27; S, 8.74.
5. Acknowledgements
The authors are grateful to King Abdul-Aziz University,
Jeddah, Kingdom of Saudi Arabia, for the financial sup-
port and necessary facilities which enabled this research
to be completed.
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