Facile Synthesis of Novel Amino Acids Derivatives as Potential Antibacterial Agents using Sustainable Materials

Article abstract of DOI:10.1002/jccs.201700054

Following the principles of green chemistry, cardanol derivatives have been used as renewable, low-cost, and available natural starting materials to construct a variety of protected and unprotected amino acids derivatives. The reaction of cardanol derivat

Full text of DOI:10.1002/jccs.201700054

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Facile Synthesis of Novel Amino Acids Derivatives as Potential Antibacterial Agents
using Sustainable Materials
*
Mohamed S. Behalo
Chemistry Department, Faculty of Science, Benha University, Benha P. O. Box 13518, Egypt
(Received: February 14, 2017; Accepted: June 4, 2017; DOI: 10.1002/jccs.201700054)
Following the principles of green chemistry, cardanol derivatives have been used as renewable,
low-cost, and available natural starting materials to construct a variety of protected and unpro-
tected amino acids derivatives. The reaction of cardanol derivatives with different phthaloylamino
acids including glycine, alanine, phenylalanine, and valine in the presence N,N’-dicyclohexylcarbo-
diimide (DCC) as coupling reagent afforded high yields of the target compounds. Deprotection of
phthaloylamino acids derivatives was achieved by heating with hydrazine hydrate. The chemical
1
structures of all products were confirmed by spectral data (IR, MS, H NMR, 13C NMR) and ele-
mental analyses. Antibacterial evaluation of the synthesized products was performed, which exhib-
ited potent to weak activity in comparison with a standard drug.
Keywords: Cardanol; Hydrogenated cardanol; Phthaloylamino acids; Hydrazide; Antibacterial.
INTRODUCTION
Recently, the utilization of renewable feedstock is
antioxidant,19 pseudo analogs of the naturally occurring
antibiotic sparsomyci,20 anti-inflammatory,21 and anti-
convulsant agents.22 They are used also as reactive sub-
strates in the design of bioactive molecules for cancer
treatment.23–25
Guided by the previous observations, and in con-
tinuation of our ongoing interest in the synthesis of bio-
logically active molecules,26–30 several new cardanol
derivatives conjugated with flexible protected and
unprotected amino acids as side chains have been
designed. This combination has been suggested as an
effective means of evaluating the effect of different
amino acids on the bioactivity of cardanol derivatives,
and therefore these products were tested for their anti-
bacterial activity.
one of the most important green chemistry principles
used in the development of chemicals and organic
synthesis.1–4 Cardanol is a renewable and inexpensive
natural organic molecule that can be easily obtained via
the vacuum distillation of cashew nut shell liquid
(CNSL) obtained from the spongy mesocarp of cashew
nut shells (Anacardium occidentale L.).5 The oil CNSL
and cardanol have a high potential uses in chemical
reactions, resulting in products with innumerable appli-
cations like surface-active agents, pesticides, insecti-
cides, phenolic resins and surface coatings, biocides,
antioxidants, and pharmaceuticals.6–13 Cardanol is the
main component (about 84%) of CNSL, besides smaller
percentages of cardol (11%) and methylcardol (4%)
(Figure 1). Cardanol itself is a mixture of 3-(pentadeca-
8-enyl)phenol, 3-n-pentadecylphenol, 3-(pentadeca-8,11-
dienyl)phenol, and 3-(pentadeca-8,11,14-trienyl)phenol
(1a–1d, respectively).5 Purification of cardanol afforded
3-(pentadeca-8-enyl)phenol (1a) as the main component
(95%), so this monoolefinic phenol will be referred to as
cardanol.
RESULTS AND DISCUSSION
Chemistry
The reaction of cardanol and hydogenated cardanol
(3-n-pentadecylphenol) (1a and 1b) with N-protected
amino acids, namely phthaloylglycine, phthaloylalanine,
phthaloylphenylalanine, and phthaloylvaline (2a–
2d) in tetrahydrofuran in the presence of N,N’-
dicyclohexylcarbodiimide (DCC) afforded the target
products 3a–3d and 5a–5d, respectively. DCC has
Amino acid derivatives have been reported to be
biologically active as antibacterial,14–16 antifungal,17,18
*Corresponding author. Email: mohamed.behalo@fsc.bu.edu.eg
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Article
Behalo
Fig. 1. Main components of cashew nut shell liq-
uid (CNSL).
Scheme 2. Synthesis of protected and unprotected
achieved popularity mainly because of its high-
yielding amide and ester coupling reactions and the fact
that it is quite inexpensive. Deprotection of phthaloyla-
mino acids derivatives 3a–3d and 5a–5d by hydrazine
hydrate under refluxing in ethanol afforded the free
amino acids derivatives 4a–4d and 6a–6d, (Schemes 1
and 2). The structures of compounds were established by
both spectral and elemental analyses. The infrared spec-
tra of free amino acids derivatives 4a–4d and 6a–6d
showed the absorption peaks of amino group at
3335–3180 cm−1 and the absence of imide carbonyls in
1775–1725 cm−1 range. Also, disappearance of hydroxyl
signal of cardanol and hydrogenated cardanol in 1H
NMR spectra and the presence of amino signal con-
firmed the chemical structures.
amino acids from cardanol 1b.
same protected amino acids 2a–2c to illustrate the effect
of the combination of amino acids with different carda-
nol derivatives in their antibacterial activities.
Thus, the reaction of hydrogenated cardanol 1b
with ethyl chloroacetate in dry acetone in the presence
of anhydrous potassium carbonate furnished ethyl-2-(3-
pentadecylphenoxy)acetate 7. The structure of ester
7 was established by its infrared spectrum, which
showed the absorption peak of the ester group at
1
1745 cm−1. Also, the H NMR spectrum exhibited tri-
plet and quartet signals at 1.11 and 4.15 ppm besides a
singlet signal at 4.72 ppm of the methylene protons. 13C
NMR detected the presence of the carbonyl group at
169.5 ppm. Treatment of ester 7 with hydrazine hydrate
gave the target structure 2-(3-pentadecylphenoxy)aceto-
hydrazide 8. Its infrared spectrum showed the charac-
teristic absorption peaks of NH2 and NH groups and
the absence of the absorption peak of the ester group
(Scheme 3).
An extension of this study, 2-(3-pentadecylphe-
noxy)acetohydrazide 8 was allowed to react with the
Treatment of hydrazide 8 with phthaloylamino
acids 2a–2c under the same conditions described above
afforded the protected amino acids 9a–9c. Deprotection
Scheme 1. Synthesis of protected and unprotected
Scheme 3. Synthesis of 2-(3-pentadecylphenoxy)
amino acids from cardanol 1a.
acetohydrazide 8.
2
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Amino Acid Derivatives with Antibacterial Activity
the starting materials cardanol, saturated cardanol, and
hydrazide enhanced their antibacterial activity, espe-
cially against Gram-negative bacteria.
EXPERIMENTAL
Materials and instruments
The chemical reagents were purchased from
Sigma-Aldrich. Solvents were commercially available
from El-nasr Chemicals Co. in analytical grade and
were used without further purification. Thin-
layerchromatography (TLC) was performed on pre-
coated silica gel polyester sheets (Kieselgel 60 F254,
0.20 mm; Merck).
Melting points reported are uncorrected. FT-IR
spectra were recorded on a JASCO FT-IR 660 Plus
spectrometer; NMR spectra were recorded on a Bruker
Avance 400 (400 MHz) spectrometer using DMSO and
CDCl3 as solvents; and mass spectra were obtained
Scheme 4. Synthesis of protected and unprotected
amino acids from hydrazide 8.
of 9a–9c by hydrazine hydrate furnished free amino
acids derivatives 10a–10c (Scheme 4).
using
a
Shimadzu GCMS-QP 1000 EX mass
spectrometer.
Antibacterial activity
The synthesized products were evaluated for their
antibacterial activity against two Gram-positive bacte-
ria Streptococcus spp. and Bacillus subtilis and two
Gram-negative bacteria Escherichia coli and Pseudomo-
nas aeruginosa. Ampicillin was used as the standard
drug to evaluate the potency of the tested compounds
under the same conditions.
Agar diffusion method31 was used for the determi-
nation of the preliminary antibacterial activity, and the
results were recorded for each tested compound as the
average diameter of inhibition zones (d) of bacterial
growth around the disks in millimeters at the concentra-
tion of 100 μg/mL in dimethyl sulfoxide. The observed
data on the antibacterial activity of the compounds and
the control drug are given in Table 1.
From the results given in Table 1, it is seen that
the synthesized products show varying degrees of inhi-
bition against the tested microorganisms. Most of the
tested compounds exhibit high activity against both
E. coli and P. aeruginosa, comparable to that of the
standard drug ampicillin. Among the tested products,
compounds 4a, 6a, 6b, and 10a are more potent against
all bacteria. Also, the presence of the hydrazide moiety
in compounds 8, 9a, 10a, and 10b enhanced their anti-
bacterial activity against both E. coli and P. aeruginosa.
It is clear that coupling of amino acid derivatives with
General procedure for the synthesis of 3a–3d and 5a–5d
A mixture of cardanol derivatives 1a and 1b
(0.01 mol) and phthaloylamino acids 2a–2d, namely
glycine, alanine, phenylalanine, and valine (0.01 mol),
was dissolved in tetrahydrofuran (THF) (30 mL).
The mixture was cooled to 0ꢀC, and then N,N-
dicyclohexylcarbodiimide (DCC) (0.01 mol) dissolved
in THF (10 mL) was added. The reaction mixture was
stirred for 24 h at 0ꢀC, which was continued for
another 24 h at room temperature. The precipitated
N,N-diclohexylurea was filtered off and removed. The
filtrate was evaporated in vacuo and the residue was tri-
trated with 25 mL ethyl acetate. The formed mixture
was filtrated off again from N,N-dicyclohexylurea. The
products obtained after evaporation of the filtrate in
vacuo were filtered off and recrystallized to give 3a–3d
and 5a–5d.
General procedures for the synthesis of free amino acids
4a–4d and 6a–6d
A mixture of protected amino acid derivatives 3a–
3d or 5a–5d (0.01 mol) and hydrazine hydrate (0.8 ml)
in ethanol (20 mL) was refluxed for 2 h on a water bath
and left for 24 h at room temperature. Evaporation of
the solvent under vacuum gave a solid material, to
which was added water (10 mL), and the solution was
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
3

Article
Behalo
Table 1. Antibacterial activity of compounds 1–10a
Compounds
Streptococcus spp.
Bacillus subtilis
Escherichia coli
Pseudomonas aeruginosa
1a
1b
++
++
+
++
+
++
+
-
3a
3b
3c
4a
4b
4c
5a
5c
6a
6b
8
9a
++
++
++
+++
+++
+++
++
+++
++
+++
+++
++
+++
+++
+++
+++
+++
++
++
+++
++
++
+
+
+++
++
+++
+++
+++
+++
+++
+++
+++
+++
+++
++
++
+++
+++
+++
+++
+++
+++
+++
+++
+++
+++
++
+++
+++
++
+++
++
+++
+++
+++
+
++
++
+++
9b
10a
10b
Ampicillin
+++
+++
+++
+++
a Inhibition zone diameter: +++ (d > 12 mm, highly active); ++ ( d = 9–12 mm, moderately active); + (d = 6–9 mm, slightly
active); − (d < 6 mm, inactive).
acidified with AcOH till pH = 6. The reaction mixture
was heated for 1 h on a water bath, and the suspension
was diluted with water (25 mL), cooled to room tem-
perature, and filtrated off. The filtrate was concentrated
and cooled to give a solid, which was recrystallized to
give pure powder of 4a–4d and 6a–6d.
3-(Pentadec-8-en-1-yl)phenyl-2-(1,3-dioxoisoindolin-2-yl)
propanoate 3b
Yield: 83%; m.p. 77–79ꢀC. IR spectrum (KBr, ν,
1
cm−1): 2920, 2851 (CH aliphatic), 1773–1726 (CO); H
NMR (CDCl3, δ ppm): 1.05 (t, 3H, CH3, J = 7.1 Hz),
1.40 (d, 3H, CHCH3, J = 7.1 Hz), 1.30–2.20 (m, 22H,
11CH2), 2.53 (t, 2H, benzylic CH2, J = 7.3 Hz),
4.12–4.17 (q, 1H, CHCH3, J = 7.1 Hz), 6.50–6.80 (dd,
2H, vinylic protons), 6.95–7.80 (m, 8H, Ar-H); 13C
NMR, 16.2, 18.7, 21.5, 23.2, 25.4, 25.8, 26.3, 28.1,
28.6, 28.9, 32.1, (aliphatic carbon chain), 55.5
(CH alanine), 115.2, 115.7, 120.0, 121.2, 125.1, 125.4,
126.2, 126.5, 127.0, 127.5, 128.1, 128.4, 129.2, 145.3,
155.3 (aromatic and vinylic carbons), 167.5, 170.2
(CO); MS: m/z = 503 (M+); Anal. calcd. for
C32H41NO4 (503.68): C, 76.31%; H, 8.21%; N, 2.78%.
Found: C, 76.24%; H, 8.15%; N, 2.69%.
3-(Pentadec-8-en-1-yl)phenyl-2-(1,3-dioxoisoindolin-2-yl)
acetate 3a
Yield: 79%; m.p. 72–74ꢀC. IR spectrum (KBr, ν,
1
cm−1): 2922, 2852 (CH aliphatic), 1772–1719 (CO); H
NMR (DMSO, δ ppm): 1.00 (t, 3H, CH3, J = 7.2 Hz),
1.08–2.27 (m, 22H, 11CH2), 2.51 (t, 2H, benzylic CH2),
3.74 (s, 2H, COCH2), 5.30–5.80 (dd, 2H, vinylic pro-
tons), 7.12–7.56 (m, 8H, Ar-H); 13C NMR, 15.6, 22.3,
23.1, 25.7, 26.2, 26.8, 27.5, 28.3, 29.3, 31.5, (aliphatic
carbon chain), 42.2 (CH2 glycine), 114.5, 116.3, 121.5,
122.3, 125.5, 126.4, 126.8, 127.5, 128.3, 128.8, 129.3,
130.5, 131.5, 144.3, 155.5 (aromatic and vinylic car-
bons), 169.5, 171.3 (CO); MS: m/z = 489 (M+); Anal.
calcd. for C31H39NO4 (489.66): C, 76.04%; H,
8.03%; N, 2.86%. Found: C, 75.95%; H,
7.95%; N, 2.75%.
3-(Pentadec-8-en-1-yl)phenyl-2-(1,3-dioxoisoindolin-2-
yl)-3-phenylpropanoate 3c
Yield: 77%; m.p. 80–82ꢀC. IR spectrum (KBr, ν,
1
cm−1): 2925, 2848 (CH aliphatic), 1775–1723 (CO); H
NMR (DMSO, δ ppm): 1.12 (t, 3H, CH3, J = 7.2 Hz),
1.39–2.12 (m, 22H, 11CH2), 2.46 (t, 2H, benzylic CH2,
4
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Amino Acid Derivatives with Antibacterial Activity
J = 7.4 Hz), 2.91 (d, 2H, CHCH2, J = 7.2 Hz), 4.42 (t,
1H, CHCH2, J = 7.1 Hz), 5.22–5.53 (dd, 2H, vinylic
protons), 6.90–7.80 (m, 13H, Ar-H); 13C NMR, 14.5,
22.5, 27.3, 28.2 28.5, 29.5, 29.8, 31.3, 32.5, 35.2, 36.3
(aliphatic carbon chain), 41.5 (CH2 phenylalanine),
56.5 (CH phenylalanine), 117.5, 118.2, 122.5, 126.5,
127.5, 128.3, 130.5, 132.5, 146.6, 155.1, (aromatic car-
bons), 167.2, 170.0 (CO); MS: m/z = 579 (M+),
580 (M+1); Anal. calcd. for C38H45NO4 (579.78): C,
78.72%; H, 7.82%; N, 2.42%. Found: C, 78.64%; H,
7.74%; N, 2.35%.
3-(Pentadec-8-en-1-yl)phenyl alaninate 4b
Yield: 69%; m.p. 113–115ꢀC. IR spectrum
(KBr, ν, cm−1): 3315–3155 (NH2), 2930, 2862
(CH aliphatic), 1745 (CO); 1H NMR (CDCl3, δ
ppm): 0.97 (t, 3H, CH3, J = 7.1 Hz), 1.12 (d, 3H,
CHCH3, J = 7.0 Hz), 1.25–2.20 (m, 22H, 11CH2),
2.48(t, 2H, benzylic CH2, J = 7.2 Hz), 4.10–4.13 (q,
1H, CHCH3, J = 8.2 Hz), 5.42 (s, 2H, NH2,
exchangeable), 6.48–6.81 (dd, 2H, vinylic protons),
7.12–8.02 (m, 4H, Ar-H); 13C NMR, 15.2, 22.3,
22.8, 28,2, 28.5, 29.3, 30.5, 31.7, 32.2, 34.5, 36.5 (ali-
phatic carbon chain), 18.5 (CH3 alanine), 49.5
(CH alanine), 115.3, 121.5, 126.3, 127.2, 128.5,
129.2, 135.5, 144.3, 148.5 (aromatic carbons), 169.5
(CO); MS: m/z = 373 (M+), 374 (M+1); Anal. calcd.
for C24H39NO2 (373.58): C, 77.16%; H, 10.52%; N,
3.75%. Found: C, 77.07%; H, 10.45%; N, 2.65%.
3-(Pentadec-8-en-1-yl)phenyl-2-(1,3-dioxoisoindolin-2-
yl)-3-methylbutanoate 3d
Yield: 84%; m.p. 77–79ꢀC. IR spectrum (KBr, ν,
1
cm−1): 2918, 2849 (CH aliphatic), 1774–1721 (CO); H
NMR (CDCl3, δ ppm): 0.96 (t, 3H, CH3, J = 7.2 Hz),
1.05 (d, 6H, 2CH3, J = 7.1 Hz), 1.15–2.10 (m, 22H,
11CH2), 2.57 (t, 2H, benzylic CH2, J = 7.3 Hz),
2.90–2.93 (m, 1H, CH(CH3)2), 4.20 (d, 1H, CH),
5.55–5.68 (dd, 2H, vinylic protons), 7.25–7.80 (m, 8H,
Ar-H); 13C NMR, 14.4, 22.5, 23.2, 25.6, 28.3, 29.5,
30.6, 31.2, 32.5, 35.3, 36.7 (aliphatic carbon chain),
18.8 (2CH3 valine), 27.8 (CH valine), 51.2 (CH valine),
118.5, 122.4, 127.5, 127.8, 128.2, 129.3, 136.3, 145.2,
152.5 (aromatic carbons), 170.2, 172.6 (CO); MS: m/
z = 531 (M+); Anal. calcd. for C34H45NO4 (531.74): C,
76.80%; H, 8.53%; N, 2.63%. Found: C, 76.72%; H,
8.42%; N, 2.55%.
3-(Pentadec-8-en-1-yl)phenyl phenylalaninate 4c
Yield: 67%; m.p. 110–112ꢀC. IR spectrum (KBr,
ν, cm−1): 3418–3180 (NH2), 2961, 2850 (CH aliphatic),
1717 (CO); 1H NMR (CDCl3, δ ppm): 0.90 (t, 3H,
CH3, J = 7.1 Hz), 1.12–2.28 (m, 22H, 11CH2), 2.49 (t,
2H, benzylic CH2, J = 7.4 Hz), 2.90 (d, 2H, CHCH2),
4.02 (t, 1H, CHCH2, J = 7.2 Hz), 5.13–5.50 (dd, 2H,
vinylic protons), 6.69–7.70 (m, 9H, Ar-H), 8.62 (s, 2H,
NH2, exchangeable); 13C NMR, 14.2, 22.3, 26.5, 27,5,
28.3, 29.5, 30.5, 31.3, 31.5, 32.2, 36.4 (aliphatic carbon
chain),
37.2
(CH2
phenylalanine),
49.5
(CH phenylalanine) 117.3, 121.5, 126.4, 127.5, 127.8,
128.2, 129.5, 130.2, 131.5, 138.2, 145.7, 156.2 (aromatic
and vinylic carbons ), 168.4 (CO); MS: m/z = 449
(M+), 450 (M+1); Anal. calcd. for C30H43NO2
(449.68): C, 80.13%; H, 9.64%; N, 3.11%. Found: C,
80.06%; H, 9.57%; N, 3.03%.
3-(Pentadec-8-en-1-yl)phenyl glycinate 4a
Yield: 75%; m.p. 106–108ꢀC. IR spectrum (KBr,
ν, cm−1): 3352–3192 (NH2), 2927, 2853 (CH aliphatic),
1738 (CO); 1H NMR (CDCl3, δ ppm): 1.05 (t, 3H,
CH3, J = 7.1 Hz), 1.18–2.27 (m, 22H, 11CH2), 2.53(t,
2H, benzylic CH2), 4.28 (s, 2H, COCH2), 5.55 (s, 2H,
NH2, exchangeable), 6.52–6.73 (dd, 2H, vinylic pro-
tons), 7.05–7.92 (m, 4H, Ar-H); 13C NMR, 16.5, 22.2,
23.5, 27.5, 28.2, 29.5, 30.8, 31.5, 32.5, 33.3, 35.2 (ali-
phatic carbon chain), 42.5 (CH2 glycine), 114.3, 119.3,
122,5, 126.5, 127.3, 128,2, 136.3,, 144.5, 147.2 (aro-
matic carbons), 170.5 (CO); MS: m/z = 359 (M+); Anal.
calcd. for C23H37NO2 (359.55): C, 76.83%; H,
10.37%; N, 3.90%. Found: C, 76.74%; H,
10.30%; N, 3.82%.
3-(Pentadec-8-en-1-yl)phenyl valinate 4d
Yield: 70%; m.p. 108–110ꢀC. IR spectrum (KBr,
ν, cm−1): 3334–3165 (NH2), 2925, 2855 (CH aliphatic),
1728 (CO); 1H NMR (CDCl3, δ ppm): 0.97 (t, 3H,
CH3, J = 7.2 Hz), 1.18 (d, 6H, 2CH3, J = 7.1 Hz),
1.21–2.24 (m, 22H, 11CH2), 2.32–2.35 (m, 1H,
CH(CH3)2), 2.51 (t, 2H, benzylic CH2, J = 7.3 Hz),
5.20 (d, 1H, CH, J = 7.1 Hz), 5.59–5.64 (dd, 2H,
vinylic protons), 5.82 (s, 2H, NH2, exchangeable),
6.85–7.42 (m, 4H, Ar-H); 13C NMR, 14.6, 22.2, 23.5,
26.5, 28.8, 29.2, 30.2, 31.5, 32.5, 35.2, 36.5 (aliphatic
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
5

Article
Behalo
carbon chain), 17.5 (2CH3 valine), 28.2 (CH valine),
48.3 (CH valine), 116.3, 122.5, 126.3, 127.2, 128.5,
135.2,, 146.8, 154.5 (aromatic and vinylic carbons),
167.8 (CO); MS: m/z = 401 (M+), 402 (M+1); Anal.
calcd. for C26H43NO2 (401.64): C, 77.75%; H,
10.79%; N, 3.49%. Found: C, 77.68%; H,
10.71%; N, 3.43%.
6.72–8.25 (m, 13H, Ar-H); 13C NMR, 18.5, 23.2, 26.5,
28.8, 29.3, 30.0, 30.7, 32.3, 32.6, 36.3 (aliphatic carbon
chain),
36.8
(CH2
phenylalanine),
59.2
(CH phenylalanine), 114.5, 116.2, 117.1, 118.5, 121.5,
126.3, 127.2, 127.8, 128.1, 130.2, 138.2, 147.5, 154.5,
158.2 (aromatic carbons), 167.2, 170.0 (CO); MS: m/
z = 581 (M+); Anal. calcd. for C38H47NO4 (581.80): C,
78.45%; H, 8.14%; N, 2.41%. Found: C, 78.36%; H,
8.07%; N, 2.32%.
3-Pentadecylphenyl-2-(1,3-dioxoisoindolin-2-yl)
acetate 5a
Yield: 76%; m.p. 102–104ꢀC. IR spectrum (KBr,
ν, cm−1): 2933, 2852 (CH aliphatic), 1775–1723 (CO);
1H NMR (DMSO, δ ppm): 1.09 (t, 3H, CH3,
J = 7.2 Hz), 1.24–2.29 (m, 26H, 13CH2), 2.37 (t, 2H,
benzylic CH2, J = 7.2 Hz), 4.50 (s, 2H, COCH2),
7.10–7.90 (m, 8H, Ar-H); 13C NMR, 15.8, 21.5, 25.3,
27.5, 28.2, 29.3, 31.3, 31.7, 32.3, 36.2 (aliphatic carbon
chain), 45.8 (CH2 glycine) 116.3, 122.0, 123.5, 125.5,
127.2, 128.5, 135.2, 145.5, 154.3 (aromatic carbons),
170.2, 171.5 (CO); MS: m/z = 491 (M+); Anal. calcd.
for C31H41NO4 (491.67): C, 75.73%; H, 8.41%; N,
2.85%. Found: C, 75.60%; H, 8.31%; N, 2.73%.
3-Pentadecylphenyl-2-(1,3-dioxoisoindolin-2-yl)-3-
methylbutanoate 5d
Yield: 76%; m.p. 132–134ꢀC. IR spectrum (KBr,
ν, cm−1): 2948, 2850 (CH aliphatic), 1771–1738 (CO);
1H NMR (CDCl3,
δ ppm): 0.91 (t, 3H, CH3,
J = 7.1 Hz), 1.01 (d, 6H, 2CH3, J = 7.1 Hz), 1.21–2.12
(m, 26H, 13CH2), 2.15–2.30 (m, 1H, CH(CH3)2), 2.56
(t, 2H, benzylic CH2, J = 7.3 Hz), 4.96–5.02 (d, 1H,
CH, J = 7.1 Hz), 6.70–7.63 (m, 8H, Ar-H); 13C NMR,
15.3, 21,8, 23.5, 28.5, 29.4, 30.3, 30.6, 31.6, 32.2, 35.5
(aliphatic carbon chain), 18.2 (2CH3 valine), 26.5
(CH valine), 53.5 (CH valine), 115.3, 122.5, 123.5,
126.2, 128.3, 1229.5, 135.2, 146.5, 156.3 (aromatic car-
bons), 167.3, 170.5 (CO); MS: m/z = 533 (M+),
534 (M+1); Anal. calcd. for C34H47NO4 (533.75): C,
76.51%; H, 8.88%; N, 2.62%. Found: C, 76.43%; H,
8.77%; N, 2.50%.
3-Pentadecylphenyl-2-(1,3-dioxoisoindolin-2-yl)
propanoate 5b
Yield: 80%; m.p. 112–114ꢀC. IR spectrum (KBr,
ν, cm−1): 2923, 2855 (CH aliphatic), 1770–1725 (CO);
1H NMR (CDCl3,
δ ppm): 0.96 (t, 3H, CH3,
J = 7.1 Hz), 1.21–2.23 (m, 26H, 13CH2), 1.53 (d, 3H,
CHCH3, J = 7.0 Hz), 2.55 (t, 2H, benzylic CH2,
J = 7.4 Hz), 5.24 (q, 1H, CHCH3, J = 7.2 Hz),
6.87–7.65 (m, 8H, Ar-H); 13C NMR, 14.3, 22.5, 25.5,
28.3, 29.1, 29.5, 30.2, 31.5, 32.5, 35.3 (aliphatic carbon
chain), 15.5 (CH3 alanine), 55.4 (CH alanine) 117.5,
121.2, 123.2, 126.3, 127.5, 128.4, 136.5, 148.2, 155.3
(aromatic carbons), 169.5, 171.3 (CO); MS: m/z = 505
(M+); Anal. calcd. for C32H43NO4 (505.70): C,
76.00%; H, 8.57%; N, 2.77%. Found: C, 75.92%; H,
8.46%; N, 2.68%.
3-Pentadecylphenyl glycinate 6a
Yield: 70%; m.p. 135–137ꢀC. IR spectrum (KBr,
ν, cm−1): 3327–3156 (NH2), 2928, 2898 (CH aliphatic),
1726 (CO); 1H NMR (CDCl3, δ ppm): 0.98 (t, 3H,
CH3, J = 7.2 Hz), 1.16–2.21 (m, 26H, 13CH2), 2.46 (t,
2H, benzylic CH2, J = 7.4 Hz), 4.42 (s, 2H, COCH2),
5.53 (s, 2H, NH2, exchangeable), 7.10–7.82 (m, 4H, Ar-
H); 13C NMR, 16.3, 21.3, 25.5, 28.2, 28.6, 29.2, 30.7,
31.3, 32.5, 36.5 (aliphatic carbon chain), 45.2 (CH2 gly-
cine), 115.5, 120.2, 125.3, 126.3, 144.5, 154.5 (aromatic
carbons), 169.5 (CO); MS: m/z = 361 (M+); Anal.
calcd. for C23H39NO2 (361.57): C, 76.40%; H,
10.87%; N, 3.87%. Found: C, 76.33%; H,
10.78%; N, 3.76%.
3-Pentadecylphenyl-2-(1,3-dioxoisoindolin-2-yl)-3-
phenylpropanoate 5c
Yield: 79%; m.p. 121–123ꢀC. IR spectrum (KBr,
ν, cm−1): 2980, 2860 (CH aliphatic), 1767–1704 (CO);
3-Pentadecylphenylalaninate 6b
1H NMR (CDCl3,
δ
ppm): 0.98 (t, 3H, CH3,
Yield: 66%; m.p. 142–144ꢀC. IR spectrum (KBr,
ν, cm−1): 3315–3195 (NH2), 2932, 2856 (CH aliphatic),
1740 (CO); 1H NMR (CDCl3, δ ppm): 1.02 (t, 3H,
CH3, J = 7.1 Hz), 1.42 (d, 3H, CHCH3, J = 7.1 Hz),
J = 7.0 Hz), 1.25–2.20 (m, 26H, 13CH2), 2.54 (t, 2H,
benzylic CH2, J = 7.3 Hz), 2.90 (d, 2H, CHCH2,
J = 7.0 Hz), 4.85 (t, 1H, CHCH2, J = 7.2 Hz),
6
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Amino Acid Derivatives with Antibacterial Activity
1.20–2.18 (m, 26H, 13CH2), 2.50 (t, 2H, benzylic CH2,
J = 7.4 Hz), 4.65 (q, 1H, CHCH3, J = 7.2 Hz), 5.76 (s,
2H, NH2, exchangeable), 7.23–7.88 (m, 4H, Ar-H); 13C
NMR, 15.5, 22.2, 26.3, 28.5, 29.3, 29.6, 30.5, 31.2,
32.3, 35.2 (aliphatic carbon chain), 17.3 (CH3 alanine),
46.5 (CH alanine) 117.2, 121.5, 126.5, 128.8, 146.5,
152,3 (aromatic carbons), 166.7 (CO); MS: m/z = 375
(M+), 376 (M+1); Anal. calcd. for C24H41NO2
(375.60): C, 76.75%; H, 11.00%; N, 3.73%. Found:
C, 76.66%; H, 10.91%; N, 3.65%.
cm−1): 2919, 2850 (CH aliphatic), 1745 (CO), 1594
(C C); 1H NMR (DMSO-d6, δ ppm): 0.85 (t, 3H,
CH3, J = 7.1 Hz), 1.11 (t, 3H, OCH2CH3,
J = 7.1 Hz), 1.23–1.53 (m, 26H, 13CH2), 2.49 (t, 2H,
benzylic CH2, J = 7.3 Hz), 4.15–4.17 (q, 2H,
OCH2CH3, J = 7.2 Hz), 4.72 (s, 2H, OCH2),
6.69–7.17 (m, 4H, Ar-H); 13C NMR, 14.9, 15.1, 22.5,
29.9, 30.0, 30.2, 31.5, 32.5, 36.2, 36.5 (aliphatic carbon
chain), 59.2 (OCH2), 65.3 (OCH2CO), 112.2, 115.8,
120.7, 129.9, 145.1, 156.3 (aromatic carbons), 169.5
(CO); MS: m/z = 390 (M+); Anal. calcd. for C25H42O3
(390.61): C, 76.87%; H, 10.84%. Found: C,
76.78%; H, 10.72%.
3-Pentadecylphenylphenylalaninate 6c
Yield: 65%; m.p. 155–157ꢀC. IR spectrum (KBr,
ν, cm−1): 3321–3200 (NH2), 2922, 2855 (CH aliphatic),
1737 (CO); 1H NMR (CDCl3, δ ppm): 0.98 (t, 3H,
CH3, J = 7.1 Hz), 1.20–2.18 (m, 26H, 13CH2), 2.58
(t, 2H, benzylic CH2, J = 7.2 Hz), 3.10 (d, 2H, CHCH2,
J = 7.2 Hz), 3.85 (t, 1H, CHCH2, J = 7.3 Hz), 5.85
(s, 2H, NH2, exchangeable), 7.11–7.95 (m, 9H, Ar-H);
13C NMR, 13.8, 22.5, 26.1, 28.3, 29.6, 30.2, 31.7, 32.5,
35.2 (aliphatic carbon chain), 42.5 (CH2 phenylalanine),
52.5 (CH phenylalanine) 118.5, 122.5, 127.3, 127.5, 128.5,
130.5, 131.2, 138.5, 144.5, 155.5 (aromatic carbons), 169.2
(CO); MS: m/z = 451 (M+), 452 (M+1); Anal. calcd. for
C30H45NO2 (451.70): C, 79.77%; H, 10.04%; N, 3.10%.
Found: C, 79.83%; H, 10.10%; N, 3.07%.
Synthesis of 2-(3-pentadecylphenoxy)acetohydrazide 8
Hydrazine hydrate (0.01 mol) was added to ester
7 (0.01 mol) in absolute ethanol (20 mL). The reaction
mixture was heated under reflux for 6 h. The separated
solid after cooling was collected by filtration, dried, and
crystallized from ethanol to give the pure powder of
hydrazide 8.
Yield: 84%; m.p. 103–105ꢀC. IR spectrum (KBr,
ν, cm−1): 3350–3187 (NH, NH2), 2923, 2854
1
(CH aliphatic), 1680 (CO); H NMR (DMSO, δ ppm):
0.83 (t, 3H, CH3, J = 7.2 Hz), 1.23–1.53 (m, 26H,
13CH2), 2.43 (t, 2H, benzylic CH2, J = 7.3 Hz), 4.91 (s,
2H, OCH2), 6.53–7.05 (m, 4H, Ar-H), 6.56 (s, 2H,
NH2, exchangeable), 9.15 (s, 1H, NH, exchangeable);
13C NMR, 18.7, 22.5, 27.1, 28.8, 29.1, 29.5, 30.0, 31.5,
31.8, 36.1 (aliphatic carbon chain), 112.5, 116.1, 121.2,
129.3, 130.1, 159.5 (aromatic carbons), 173.3 (CO);
MS: m/z = 376 (M+), 377 (M+1); Anal. calcd. for
C23H40N2O2 (376.59): C, 73.36%; H, 10.71%; N,
7.44%. Found: C, 73.29%; H, 10.63%; N, 7.33%.
3-Pentadecylphenyl valinate 6d
Yield: 68%; m.p. 138–140ꢀC. IR spectrum (KBr,
ν, cm−1): 3370–3160 (NH2), 2917, 2849 (CH aliphatic),
1730 (CO); 1H NMR (CDCl3, δ ppm): 0.95 (t, 3H,
CH3, J = 7.2 Hz), 1.11 (d, 6H, 2CH3, J = 7.2 Hz),
1.22–2.23 (m, 26H, 13CH2), 2.32–2.36 (m, 1H,
CH(CH3)2), 2.61 (t, 2H, benzylic CH2, J = 7.3 Hz),
4.92 (d, 1H, CH, J = 7.0 Hz), 6.70–7.63 (m, 4H, Ar-
H), 8.52 (s, 2H, NH2, exchangeable); MS: m/z = 403
(M+), 404 (M+1); Anal. calcd. for C26H45NO2
(403.65): C, 77.37%; H, 11.24%; N, 3.47%. Found: C,
77.32%; H, 11.17%; N, 3.39%.
General procedures for the synthesis of 9a–9c
The same procedures described for the synthesis of
3a–3d and 5a–5d were used.
2-(1,3-Dioxoisoindolin-2-yl)-N-(2-(3-pentadecylphenoxy)
acetyl)acetohdrazide 9a
Synthesis of ethyl-2-(3-pentadecyl phenoxy) acetate 7
A mixture of cardanol 1b (0.01 mol), ethyl chlor-
oacetate (0.01 mol) in dry acetone (30 mL) containing
anhydrous potassium carbonate (0.5 g) was heated
under reflux for 24 h. After cooling, the reaction mix-
ture was poured into cold water and the formed solid
was filtered off, dried and crystallized from ethanol.
Yield: 76%; m.p. 95–97ꢀC. IR spectrum (KBr, ν,
Yield: 79%; m.p. 111–113ꢀC. IR spectrum (KBr,
ν, cm−1): 3463–3270 (NH), 2931, 2866 (CH aliphatic),
1
1772–1726 (CO), 1682 (CO amide), H NMR (CDCl3,
δ ppm): 0.97 (t, 3H, CH3, J = 7.2 Hz), 1.18–2.23 (m,
26H, 13CH2), 2.54 (t, 2H, benzylic CH2, J = 7.3 Hz),
4.31 (s, 2H, COCH2), 4.93 (s, 2H, OCH2), 6.95–7.92
(m, 8H, Ar-H), 8.55, 9.34 (2 s, 2H, 2NH,
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
7

Article
Behalo
exchangeable); 13C NMR, 15.3, 21.5, 27.2, 28.5, 29.5,
30.3, 31.5, 31.2, 32.6, 35.5 (aliphatic carbon chain),
46.5 (CH2 glycine), 51.3 (OCH2), 116.3, 121.5, 122.2,
125.5, 127.3, 128.5, 135.5, 148.3, 151.5 (aromatic car-
bons), 167.5, 168.7, 175.5 (CO); MS: m/z = 563 (M+);
Anal. calcd. for C33H45N3O5 (563.74): C, 70.31%; H,
8.05%; N, 7.45%. Found: C, 70.24%; H,
7.96%; N, 7.39%.
General procedures for synthesis of free amino acids
10a–10c
The same procedures described for the synthesis of
free amino acids 4a–4d and 6a–6d were used.
2-Amino-N-(2-(3-pentadecylphenoxy)acetyl)
acetohdrazide 10a
Yield: 67%; m.p. 150–152ꢀC. IR spectrum (KBr, ν,
cm−1):
3430–3175
(NH2,
NH),
2933,
2863
(CH aliphatic), 1680, 1665 (CO amide); 1H NMR
(DMSO, δ ppm): 0.81 (t, 3H, CH3, J = 7.2 Hz),
1.18–1.46 (m, 26H, 13CH2), 2.42 (t, 2H, benzylic CH2,
J = 7.3 Hz), 4.40 (s, 2H, COCH2), 5.25 (s, 2H, OCH2),
5.60 (s, 2H, NH2, exchangeable); 6.52–6.96 (m, 4H, Ar-
H), 8.60, 9.20 (2 s, 2H, 2NH, exchangeable); Anal.
calcd. for C25H43N3O3 (433.64): C, 69.25%; H,
10.00%; N, 9.69%. Found: C, 69.12%; H,
9.83%; N, 9.56%.
2-(1,3-Dioxoisoindolin-2-yl)-N-(2-(3-pentadecylphenoxy)
acetyl)propanehdrazide 9b
Yield: 76%; m.p. 123–125ꢀC. IR spectrum (KBr,
ν, cm−1): 3344–3200 (NH), 2927, 2853 (CH aliphatic),
1
1770–1730 (CO), 1685 (CO amide), H NMR (CDCl3,
δ ppm): 0.93 (t, 3H, CH3, J = 7.2 Hz), 1.16 (d, 3H,
CH3CH, J = 7.3 Hz), 1.25–2.25 (m, 26H, 13CH2), 2.50
(t, 2H, benzylic CH2, J = 7.4 Hz), 4.75 (q, 1H,
CHCH3, J = 7.2 Hz), 5.35 (s, 2H, OCH2), 6.70–7.98
(m, 8H, Ar-H), 8.25, 8.40 (2s, 2H, 2NH, exchangeable);
13C NMR, 14.5, 22.3, 28.5, 28.9, 29.2, 29.7, 31.6, 31.8,
32.8, 36.3 (aliphatic carbon chain), 16.2 (CH3 alanine),
56.2 (CH alanine) 118.8, 122.5, 123.5, 126.2, 128.5,
128.7, 136.2, 149.5, 155.5 (aromatic carbons), 168.4,
169.5, 172.2 (CO); MS: m/z = 577 (M+), 578 (M+1);
Anal. calcd. for C34H47N3O5 (577.77): C, 70.68%; H,
8.20%; N, 7.27%. Found: C, 70.61%; H,
8.11%; N, 7.17%.
2-Amino-N-(2-(3-pentadecylphenoxy)acetyl)
propanehdrazide 10b
Yield: 63%; m.p. 146–148ꢀC. IR spectrum (KBr,
ν, cm−1): 3425–3151 (NH2, NH), 2925, 2845
(CH aliphatic), 1683, 1676 (CO amide); 1H NMR
(CDCl3, δ ppm): 0.97 (t, 3H, CH3, J = 7.1 Hz), 1.18 (d,
3H, CH3CH, J = 7.0 Hz), 1.23–2.18 (m, 26H, 13CH2),
2.57 (t, 2H, benzylic CH2, J = 7.4 Hz), 4.22 (q, 1H,
CHCH3, J = 7.3 Hz), 5.16 (s, 2H, OCH2), 5.89 (s, 2H,
NH2, exchangeable); 7.05–7.65 (m, 4H, Ar-H), 8.45,
8.96 (2s, 2H, 2NH, exchangeable); 13C NMR, 14.3,
22.8, 28.3, 28.7, 29.5, 29.8, 31.5, 32.5, 32.7, 36.5 (ali-
phatic carbon chain), 17.4 (CH3 alanine), 50.3
(CH alanine) 118.3, 122.2, 123.7, 126.5, 128.5, 129.3,
136.5, 148.5, 155.2 (aromatic carbons), 167.5, 168.2,
171.7 (CO); Anal. calcd. for C26H45N3O3 ( 447.66): C,
69.76%; H, 10.13%; N, 9.39%. Found: C, 69.64%; H,
9.98%; N, 9.26%.
2-(1,3-Dioxoisoindolin-2-yl)-N-(2-(3-pentadecylphenoxy)
acetyl)-3-phenylpropane hydrazide 9c
Yield: 78%; m.p. 135–137ꢀC. IR spectrum (KBr,
ν, cm−1): 3436–3185 (NH), 2923, 2853 (CH aliphatic),
1
1773–1725 (CO), 1678 (CO amide); H NMR (CDCl3,
δ ppm): 0.99 (t, 3H, CH3, J = 7.1 Hz), 1.18–2.23 (m,
26H, 13CH2), 2.52, (t, 2H, benzylic CH2, J = 7.4 Hz),
2.90 (d, 2H, CH2, J = 7.2 Hz), 4.72 (t, 1H, CHCH2,
J = 7.1 Hz), 5.40 (s, 2H, OCH2), 6.70–8.10 (m, 8H,
Ar-H), 8.30, 8.52 (2s, 2H, 2NH, exchangeable); 13C
NMR, 15.2, 22.5, 27.8, 28.5, 29.5, 30.3, 31.5, 32.2,
33.5, 35.2 (aliphatic carbon chain), 37.1 (CH2 phenyl-
alanine), 56.4 (CH phenylalanine), 116.5, 117.3, 117.8,
118.2, 122.5, 126.5, 127.6, 128.2, 128.5, 131.5, 138.5,
148.3, 155.2, 156.5 (aromatic carbons), 167.8, 171.3,
172.5 (CO); MS: m/z = 653 (M+); 654 (M+1); Anal.
calcd. for C40H51N3O5 (653.86): C, 73.48%; H,
7.86%; N, 6.43% Found: C, 73.37%; H,
7.71%; N, 6.32%.
2-Amino-N-(2-(3-pentadecylphenoxy)acetyl)-3-
phenylpropanehydrazide 10c
Yield: 65%; m.p. 131–133ꢀC. IR spectrum (KBr,
ν, cm−1): 3430–3170 (NH2, NH), 2928, 2850
(CH aliphatic), 1680, 1672 (CO amide), 1H NMR
(CDCl3, δ ppm): 0.98 (t, 3H, CH3, J = 7.2 Hz),
1.23–2.18 (m, 26H, 13CH2), 2.10 (d, 2H, CH2CH,
J = 7.2 Hz), 2.47 (t, 2H, benzylic CH2, J = 7.3 Hz),
4.16 (t, 1H, CHCH2, J = 7.2 Hz), 5.27 (s, 2H, OCH2),
6.11 (s, 2H, NH2, exchangeable); 6.88–7.79 (m, 9H, Ar-
8
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Amino Acid Derivatives with Antibacterial Activity
13. J. Chen, Z. Liu, X. Li, P. Liu, J. Jiang, X. Nie, Polym.
Degrad. Stab. 2016, 126, 58.
14. R. P. Hicks, Bioorg. Med. Chem. 2016, 24, 4056.
15. L. H. Abdel-Rahman, A. M. Abu-Dief, M. Ismael,
M. A. A. Mohamed, N. A. Hashem, J. Mol. Struct. 2016,
1103, 232.
16. H. Wang, H. Yuan, S. Li, Z. Li, M. Jiang, Bioorg. Med.
Chem. Lett. 2016, 26, 809.
17. A. Shete, S. Murthy, S. Korpale, A. Yadav, S. Sajane,
S. Sakhare, R. Doijad, J. Drug Deliv. Sci. Tech. 2015,
28, 46.
18. Y. A. Issac, I. G. El-Karim, S. G. Donia, M. S. Behalo,
Sulf. Lett. 2002, 25, 183.
19. D. E. Lee, G. R. Shin, S. Lee, E. S. Jang, H. W. Shin,
B. S. Moon, Food Res. Int. 2016, 87, 10.
20. T. Amagata, K. Minoura, A. Numata, J. Nat. Prod.
2006, 69, 1384.
21. L. Rosa, G. Scainia, C. B. Furlanetto, L. S. Galant,
F. Vuolo, D. M. Dall’Igna, P. F. Schuckd,
G. C. Ferreirad, F. Dal-Pizzol, E. L. Streck, Int. J. Dev.
Neurosci. 2016, 48, 24.
H), 8.15, 9,23 (2s, 2H, 2NH, exchangeable); MS: m/
z = 523 (M+), 524 (M+1); Anal. calcd. for C32H49N3O3
(523.76): C, 73.38%; H, 9.43%; N, 8.02%. Found: C,
73.24%; H, 9.30%; N, 7.90%.
CONCLUSIONS
I reported the facile and convenient synthesis of a
new series of cardanol derivatives conjugated with pro-
tected and unprotected amino acids as a suitable side
chain using DCC. In addition, the synthesized products
were examined for their antibacterial activity, which
was comparable to that of ampicillin.
ACKNOWLEDGMENTS
The author wishes to thank Dr. Reyad
M. El-Sharkawy, Department of Botany, who carried
out antibacterial activity tests. This work was supported
by the Chemistry Department, Faculty of Science,
Benha University.
22. R. Torregrosa, X. F. Yang, E. T. Dustrude,
T. R. Cummins, R. Khanna, H. Kohn, Bioorg. Med.
Chem. 2015, 23, 3655.
23. D. S. Agarwal, H. S. Anantaraju, D. Sriram,
P. Yogeeswari, S. H. Nanjegowda, P. Mallu, R. Sakhuja,
Steroids 2016, 107, 87.
24. G. Gopinath, V. Sankeshi, S. Perugu, M. D. Alaparthi,
S. Bandaru, V. K. Pasala, P. R. Chittineni,
G. L. D. Krupadanam, S. R. Sagurthi, Eur. J. Med.
Chem. 2016, 124, 750.
25. A. Wang, L. Gui, S. Lu, L. Zhou, J. Zhou, S. Wei, Dyes
Pigm. 2016, 126, 239.
REFERENCES
1. J. A. Linthorst, Found. Chem. 2010, 12, 55.
2. P. T. Anastas, J. C. Warner, Green Chemistry: Theory
and Practice, Oxford University Press, New York, 1998.
3. R. A. Sheldon, I. W. Arends, U. Hanefeld, Green Chemis-
try and Catalysis, Wiley, New York, 2007.
4. K. Sanderson, Nature 2011, 469, 18.
5. R. Paramashivappa, P. P. Kumar, P. J. Vithayathil,
A. S. Rao, J. Agric. Food Chem. 2001, 49, 2548.
6. A. R. Menon, C. K. S. Pillai, J. D. Sudha,
A. G. Mathew, J. Sci. Ind. Res. 1985, 44, 324.
7. K. I. Suresh, V. S. Kishanprasad, Ind. Eng. Chem. Res.
2005, 44, 4504.
26. M. S. Behalo, I. G. El-Karim, Y. A. Issac, M. A. Farag,
J. Sulf. Chem. 2014, 35, 661.
8. E. Darroman, N. Durand, B. Boutevin, S. Caillol, Prog.
Org. Coat. 2016, 91, 9.
9. N. N. Ghosh, B. Kiskan, Y. Yagci, Prog. Polym. Sci.
2007, 32, 1344.
10. M. Himejima, I. Kubo, J. Agric. Food Chem. 1991, 39, 418.
11. C. N. Subbarao, K. M. Krishna, V. S. Prasad, Pharm.
Res. J. 2011, 6, 21.
12. S. Shukla, A. Ghosh, P. K. Roy, S. Mitra, B. Lochab,
Polymer 2016, 99, 349.
27. M. S. Behalo, J. Sulf. Chem 2010, 31, 287.
28. A. A. Aly, M. S. Behalo, J. Chem. Res. 2010, 34, 571.
29. M. S. Behalo, RSC Adv. 2016, 6, 103132.
30. M. S. Behalo, M. S. Amine, I. M. Fouda, Phosphorus,
Sulfur and Silicon and the Related Elements, 2017,
192, 410.
31. C. Leifert, S. Chidbouree, S. Hampson, S. Workman,
D. Sigee, H. A. S. Epton, A. Harbour, J. Appl. Bacteriol.
1995, 78, 97.
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
9