β-Amino Carbonyl Compounds from Iodine-Catalyzed Three Component Mannich Reactions and Evaluation of Their Antioxidant Activity

Full text of DOI:10.1080/00304948.2019.1677443

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
β-Amino Carbonyl Compounds from Iodine-
Catalyzed Three Component Mannich Reactions
and Evaluation of Their Antioxidant Activity
Hasniye Yaşa, Belma Hasdemir & Özge Erken
To cite this article: Hasniye Yaşa, Belma Hasdemir & Özge Erken (2019): β-Amino Carbonyl
Compounds from Iodine-Catalyzed Three Component Mannich Reactions and Evaluation
of Their Antioxidant Activity, Organic Preparations and Procedures International, DOI:
10.1080/00304948.2019.1677443
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Organic Preparations and Procedures International, 0:1–10, 2019
# 2019 Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2019.1677443
b-Amino Carbonyl Compounds from
Iodine-Catalyzed Three Component Mannich
Reactions and Evaluation of Their
Antioxidant Activity
1
1
2
€
Hasniye Yas¸a, Belma Hasdemir, and Ozge Erken
1Chemistry Department, Engineering Faculty, Istanbul University-Cerrahpas¸a,
34320 Avcilar, Istanbul, Turkey
2Chemistry Department, Science Institute, Istanbul University, Fatih,
Istanbul, Turkey
The multicomponent Mannich reaction is one of the most important carbon-carbon
bond formation types in organic chemistry1,2 and plays a key step in the synthesis of
many nitrogen-containing natural products and pharmaceuticals.3 Mannich bases have a
very important place in the synthesis of anti-inflammatory,4,5 antimicrobial,6–8 antimal-
arial,9 and anticancer drugs.10,11 They are used in the petroleum, paper and recycling
industries. Several methods have been reported in the literature for the synthesis of
12
b-amino carbonyl compounds using Amberlyst-15, Bronsted acids, Lewis acids13 and
€
bases.14 However; these methods have some drawbacks, including the use of expensive
metal salts as catalysts. In view of these findings, we wanted to broaden the possibility
of iodine15,16 as the catalyst for the synthesis of b-amino carbonyl compounds. In this
work, we describe a mild, convenient, efficient and one-pot method for preparation of
b-amino carbonyl compounds, using molecular iodine as a catalyst at room temperature,
from ketones, aromatic aldehydes, and aromatic amines (Scheme 1).
The synthesized b-amino carbonyl compounds (4a-o) were purified by crystalliza-
1
tion or column chromatography and were characterized by elemental analysis, IR, H
NMR, 13C NMR, and GC-MS methods. A number of these compounds (4f-i, 4k-n) are
novel. All of the compounds were evaluated for their antioxidant activity using the 1,1-
diphenyl-2-picryl-hydrazyl (DPPH) assay.
The Mannich reaction of aniline, benzaldehyde and cyclohexyl methyl ketone was
selected as a model and several catalysts have been tried (Table 1). The highest yield
was obtained with I2 (Table 1, entry 2). In preliminary trials, several common organic
solvents (acetone, ethanol, THF, toluene, and DCM) had been used to optimize the
reaction conditions. Ethanol was found to be the most suitable solvent for the reaction
in terms of availability, cost, and over-all yield.
Different molar ratios of iodine catalyst were investigated to find the best yield.
The optimum value was 10 mol % of I2 catalyst (Table 2).
Received May 14, 2018; in final form July 4, 2019.
Address correspondence to Hasniye Yas¸a, Chemistry Department, Engineering Faculty, Istanbul
University-Cerrahpas¸a, 34320 Avcilar, Istanbul, Turkey. E-mail: hhasniye@gmail.com
1

2
Yas¸a et al.
R4
Kat.
O
H
NH2
R3
O
O
I2
+
+
R2
R1
N
H
R1
C2H5OH
r.t.
R3
R4
R2
4
3
2
1
Scheme 1. Iodine-catalyzed direct Mannich reaction of ketones, aldehydes, and amines.
Table 1
Mannnich Reaction with Different Catalysts
Entry
Catalysta
Time (h)
Yieldb (%)
1
2
3
4
7
8
9
10
11
13
14
18
No catalyst
I2
48
24
24
24
12
20
24
24
24
6
No reaction
88
78
Bi(NO3)2.
Al(NO3)3 9H2O
No reaction
No reaction
No reaction
63
2,4,6-Trichloro-1,3,5-triazine(TCT)
AlCl3
TCT þ PEG 400
Sodium dodecyl sulfate (SDS)
65
PPH3
TiCl4
MoCl5
TFAA
No reaction
20
No reaction
10
24
24
aAll catalysts were at 10 mol %.
bIsolated yield. Mannich reaction; 2.0 mmol of aldehyde, 2.0 mmol of amine and 2.2 mmol of
cyclohexyl methyl ketone in 5 mL of ethanol in the presence of catalyst at room temperature.
Table 2
Screening of Molar Ratios of I2 for 4l
Entry
I2 %
Time (h)
Yielda (%)
1
2
3
4
5
6
2.5
5
7.5
10
15
20
24
24
24
24
24
24
42
54
61
88
72
76
aIsolated yield. Mannich reaction; cyclohexyl methyl ketone (2.2 mmol), benzaldehyde
(2.0 mmol), aniline (2.0 mmol) in 5 mL of ethanol by I2 catalyst at r.t.
Our results are summarized in Table 3. We found that the reactivity of aliphatic
ketones appeared to be better than that of aromatic ketones in our system. By way of
contrast to aromatic ketones, aliphatic ketones gave the desired product in good to
excellent yields using only 10% iodine as the catalyst within 24 h. The Mannich reac-
tion of cyclohexyl methyl ketone with benzaldehyde and aniline gave 88% yield within

b-Amino Carbonyl Compounds
3

4
Yas¸a et al.
24 h (Table 3, entry 12). In the case of both 4f and 4g, we found a 2:1 ratio of anti to
syn by 1H-NMR spectra according to the literature (Scheme 2).17,18
For all of our compounds, determination of antioxidant activity was done by the
scavenging of the stable radical DPPH (see Experimental Section). Of the b-amino car-
bonyl compounds we prepared, 4a showed moderate antioxidant activity. Compounds
4h, which includes a methoxy-substituted aromatic ring, 4j, and 4k, for both of which
R1 ¼ 2-furyl, showed very good activities similar to the reference antioxidant com-
pounds, ascorbic acid, BHA and BHT. These results suggest that the antioxidant activ-
ity may be increased by aromatics or heteroromatics with electron donating groups.
Compounds 4h, 4j, and 4k showed the best DPPH radical scavenging activity at all
concentrations, followed by 4a. As shown in Table 4, the compounds obtained have
radical scavenging activity between 7% and 93% in the concentration ranges studied.
R4
R4
O
H
R3
R3
NH2
O
O
O
I2
R2
+
+
+
R1
R1
R1
N
H
N
H
C2H5OH
25oC
R3
R2
R2
R4
anti
syn
Scheme 2. Syn- and anti-diastereomers of the b-amino carbonyl compounds.
Table 4
Antioxidant Scavenging Activity of Compounds 4a-o at Different Concentrations
DPPHꢀ Scavenging Activitya
Compounds
250 lM/mL
500 lM/mL
1000 lM/mL
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
BHA
22.07 0.26
10.96 1.12
7.11 0.44
8.08 0.44
8.44 0.44
8.15 0.68
10.22 0.68
67.26 0.68
12.25 0.68
66.96 0.27
68.88 0.27
7.85 0.93
10.45 0.44
8.89 0.44
11.26 0.68
94.57 0.71
95.81 0.47
96.90 0.27
36.29 0.26
20.89 1.18
9.78 0.44
10.25 0.44
10.07 1.28
13.78 0.00
15.88 0.27
81.78 0.44
17.28 0.27
90.67 0.44
92.12 0.44
7.26 0.68
13.12 0.44
11.11 0.44
5.33 0.44
96.12 0.71
96.12 0.54
97.36 0.54
61.03 0.93
37.78 0.89
14.37 1.03
15.37 0.44
1.33 0.44
19.56 1.18
23.28 0.44
93.48 0.51
25.58 0.44
88.44 0.89
89.44 0.89
13.63 0.93
25.26 0.44
19.11 0.44
4.29 1.36
97.83 0.27
98.29 0.27
98.29 0.27
BHT
Ascorbic Acid
aValues were the means of three replicates S.D.

b-Amino Carbonyl Compounds
5
In summary, we have reported a useful synthesis of the title compounds using a
simple system based on iodine catalysis. A number of the compounds are new. We
determined the antioxidant activity of our b-amino carbonyl compounds (4a-o).
Compounds 4j, 4k and 4h have been found to be effective in terms of their antioxidant
activity. Other activities of these compounds and further structure modification to
improve the antioxidant activity are under current investigation in our laboratory and
will be reported in due course.
Experimental Section
The chemicals used in this study were commercially available from Merck and Aldrich
and were used without further purification. The obtained compounds were purified by
column chromatography on silica gel (particle sizes 0.063-0.200 mm and 0.040-
1
0.063 mm, respectively) with hexane/EtOAc (15:1) as the eluent. H and 13C NMR
(500 and 125 MHz, respectively) spectra were recorded using Me4Si as the internal
standard in CDCl3 on a VarianUNITY INOVA spectrometer. Gas chromatography–mass
spectrometry (GC-MS) data were recorded on a Shimadzu QP2010 Plus using a GC-
MS column, Teknokroma TRB-5MS (30 m x 0.25 mm x 0.25lm I.D.). The operating
conditions were as follows: injection temperature 250 ꢁC, helium carrier gas flow:
20 psi. Split ratio: 1/100. E.I:70 eV. Temperature programming: 80 ꢁC (5 min) ꢂ 250 ꢁC
at 5 ꢁC/min, hold 30 min. FT-IR spectra were recorded on Bruker Vertex 70. The
anti/syn ratio of obtained compounds (4a-o) was determined by 1H-NMR spectra
according to the literature.17,18
General Method for the Synthesis of b-Amino Carbonyl Compounds
Ketone (2.2 mmol), aldehyde (2 mmol) and amine (2 mmol) and 10 mol % iodine15,16
were added to a one-necked round bottom flask. The reaction mixture was stirred
vigorously with a magnetic stirrer at room temperature (r.t.) for 24 hours. Running the
reactions at 50 ꢁC and at 80 ꢁC led to lower yields and the formation of side products.
The reactions were monitored by TLC with hexane/ethyl acetate, 15:1. After reaction
completion, NaHCO3 was added, the mixture was filtered and the crude mixture was
either purified by column chromatography (hexane/ethyl acetate, 15:1) or recrystallized
from ethanol or an ethanol–acetone mixture (3/2, v/v) to afford the corresponding com-
pounds. Compounds (4a-e)12,19–25 are known in the literature and their melting points
are in accordance with the literature. Although 4j2,26 and 4o27,28 were synthesized
before, spectrometric data were not available, so we treated them as new compounds.
The analytical and spectral data of the novel products (4f-o) were as follows.
2-Methyl-1-phenyl-1-(phenylamino)hexan-3-one (4f)
Yield 45%; pale yellow oil. IR (neat, cmꢂ1): 3382 (-NH), 3051, 3022, 2944, 2920, 1696
1
(-CO), 1177 (C-N), 1275, 745, 691. H-NMR (500 MHz, CDCl3, d/ppm, a mixture of
ꢃ
(anti/syn) isomers in 66/34 ratio; the minor one is marked with an asterisk : 0.81 (3H, t,
ꢃ
ꢃ
J¼ 7.4 Hz, -CH3), 0.84 (1.33H, t, J¼ 5.6 Hz, -CH3), 1.13 (1.33H, d, J¼ 7.0 Hz, -CH3),
ꢃ
1.20 (3H, d, J¼ 7.1 Hz, -CH3), 1.30 (1H, s, -NH), 1.43-1.53 (2H, m, -CH2-CH3), 2.01
(0.93H, m, -CO-CH2-CH2), 2.30 (2H, m, -CO-CH2-CH2-), 3.07 (1H, m, -CO-CH-CH-

6
Yas¸a et al.
ꢃ
NH-), 4.53 (1H, d, J ¼ 6.3 Hz, -CO -CH-CH-NH-), 4.71 (0.50H, d, J ¼ 5.8 Hz, -CO -CH-
CH-NH-), 6.55 (2H, m -CH-), 6.67 (1H, m, -CH-), 7.10 (2H, m, -CH-), 7.24 (1H, m,
-CH-), 7.31–7.34 (4H, m, -CH-). 13C-NMR (125 MHz, CDCl3, d/ppm) : 11.6 (CH3-), 13.
ꢃ
ꢃ
ꢃ
6 (CH3-), 15.3 (CH3-), 15.4 (CH3-), 29.7 (-CH2-), 43.6 (-COCH2-), 44.7 (-COCH2-), 52.9
ꢃ
(-CHCO-), 58.7 (-CHNH-), 60.1 (CHNH-), 113.1 (2 x arom.-CH-), 113.9 (2 x
arom.-CH-), 117.1 (arom.-CH-), 126.4 (arom.-CH-), 127.0 (arom.-CH-), 128.5 (arom.-CH-),
ꢃ
129.1 (2 x arom.-CH-), 141.8 (arom.-CH-), 146.9 (arom.-CH-), 212.7 (-C¼O), 214.6
(-C¼O). GC-MS (m/z): 51, 57, 77, 91, 104, 117, 131, 153, 182, 208, 270, 281 (Mþ).
Anal. Calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found: C, 81.08; H, 8.26;
N, 4.97.
2-Methyl-1-phenyl-1-(p-tolyl amino)-hexan-3-one (4g)
Yield 64%; orange oil. IR (neat, cmꢂ1): 3395 (-NH), 3050, 2985, 2920, 2900, 1690(-
1
CO), 1170 (C-N), 1295, 750, 680. H-NMR (500 MHz, CDCl3, d/ppm, a mixture of
ꢃ
(anti/syn) isomers in 66/34 ratio; the minor one is marked with an ): 0.82 (3H, t, J¼
ꢃ
ꢃ
5.6 Hz, -CH3), 0.84 (3H, t, J¼ 7.4 Hz, -CH3), 1.13 (3H, d, J¼ 7.0 Hz, -CH3), 1.18
ꢃ
(3H, d, J¼ 7.1 Hz, -CH3), 1.52 (2H, m, -CH2-CH3), 2.21 (3H, s, -CH3), 2.23 (3H, s,
ꢃ
-CH3), 2.31 (2H, m, -CH2-CH3), 2.43 (2H, t, J¼ 7.3 Hz, -COCH2-CH2-), 3.05 (1H, m,
ꢃ
-CO-CH-CH-NH-), 4.52 (1H, d, J ¼ 6.7 Hz, CH2-CH-NH-), 4.70 (1H, d, J¼ 5.8 Hz,
CH2-CH-NH-) , 6.48 (2H, m -CH-), 6.93 (2H, d, J¼ 8.4 Hz, -CH-), 7.27 (1H, m, -CH-),
7.33–7.35 (4H, m, -CH-).13C-NMR (125 MHz, CDCl3, d/ppm) : 11.4 (CH3-),
ꢃ
ꢃ
ꢃ
13.6 (CH3-), 15.4(CH3-), 15.5 (CH3-), 16.5(-CH2-), 16.9 (CH2-), 20.4 (CH3-),
20.5 (CH3-), 44.2 (-COCH2-), 44.7 (-COCH2-), 52.5 (-CHCO-), 59.3 (-CHNH-),
62.9 (-CHNH-), 113.5 (arom.-CH-), 113.8 (arom.-CH-), 126.5 (arom.-CH-), 126.7
(arom.-CH-), 126.8 (arom.-CH-), 126.9 (arom.-CH-), 127.3 (arom.-CH-), 128.6 (arom.-
CH-), 129.6 (arom.-CH-), 141.5 (arom.-CH-), 141.8 (arom.-CH-), 144.7 (arom.-CH-),
ꢃ
ꢃ
ꢃ
ꢃ
212.7 (-C¼O), 214.9 (-C¼O). GC-MS (m/z): 43, 65, 71, 91, 106, 118, 128, 145, 165,
180, 196, 222, 248, 262, 277, 295 (Mþ).
Anal. Calcd. for C20H25NO: C, 81.31; H, 8.53; N, 4.74. Found: C, 81.28; H, 8.55;
N, 4.70.
1-(4-Methoxyphenyl)-4-phenyl-4-(phenylamino)butan-2-one (4h)
Yield 64%; yellow oil. IR (neat, cmꢂ1): 3393 (-NH), 3046, 3030, 2920, 2851, 1704
1
(-CO), 1504 (C-N), 1242, 748, 683. H-NMR (500 MHz, CDCl3, d/ppm): 2.82 (1H, t,
J ¼ 6.3Hz, CH2-CH-NH-), 3.43 (2H, d, J ¼ 2.2Hz, -CO-CH2-CH-NH-), 3.71 (3H, s,
OCH3), 4.72 (2H, s, -CH2-CO), 6.40 (2H, m, arom. -CH-), 6.55 (1H, m -CH-), 6.92
(2H, m, arom.-CH-), 6.98-7.01 (4H, m, arom. -CH-), 7.20 (5H, m, arom. -CH-).13C-
NMR (125 MHz, CDCl3, d/ppm): 48.9 (-COCH2-), 50.2 (-CH2CO-), 54.5 (-CHNH-),
55.3(-OCH3), 113.7 (2 x arom.-CH-), 114.3(2 x arom.-CH-), 117.7 (arom.-CH-), 125.3
(2 x arom.-CH-), 126.3 (arom.-CH-), 127.3 (arom.-CH-), 128.8 (2 x arom.-CH-), 129.1
(2 x arom.-CH-), 130.5 (2 x arom.-CH-), 142.4 (arom.-CH-), 146.9 (arom.-CH-), 158.8
(arom -CH-OCH3), 207.0 (-C¼O). GC-MS (m/z): 51, 65, 77, 91, 104, 121, 131, 152,
164, 180, 196, 211, 224, 250, 267, 281, 310, 327, 345 (Mþ).
Anal. Calcd. for C23H23NO: C, 79.97; H, 6.71; N, 4.05. Found: C, 79.80; H, 6.69;
N, 4.06.

b-Amino Carbonyl Compounds
7
7-Chloro-1-phenyl-1-(phenylamino)heptan-3-one (4i)
Yield 59%; brown crystals; Mp.: 176,8- 178,1 ꢁC. IR (neat, cmꢂ1): 3382 (-NH), 3070,
1
3026, 2941, 2851, 1691(-CO), 1504 (C-N), 1291, 752 C-Cl, 687. H-NMR (500 MHz,
CDCl3, d/ppm): 1.66 (4H, m, -CH2-), 2.37 (2H, m, -CH2-CO), 2.93 (2H, dd, J ¼ 6.4
and 3.3Hz, -CO-CH2-CH-NH-), 3.46 (2H, t, J ¼ 6.3 Hz, ClCH2-), 4.86 (1H, t,
J ¼ 6.5 Hz, CH2-CH-NH-), 6.55 (2H, m -CH-), 6.68 (1H, m, -CH-), 7.11 (2H, m, -CH-),
7.32-7.37 (5H, m, -CH-). 13C-MR (125 MHz, CDCl3, d/ppm): 20.6 (-CH2-), 31.7
(-CH2-), 42.5 (-COCH2-), 44.7 (ClCH2-), 47.6 (-CH2CO-), 50.2 (-CHNH-), 113.7 (2 x
arom.-CH-), 117.9 (2 x arom.-CH-), 127.4 (2 x arom.-CH-), 128.9 (arom.-CH-), 129.1
(3 x arom.-CH-), 142.3 (arom.-CH-), 146.6 (arom.-CH-), 208.7 (-C¼O). GC-MS (m/z):
43, 66, 77, 93, 104, 119, 131, 152, 165, 182, 209, 227, 253, 281, 315 (Mþ).
Anal. Calcd. for C19H22ClNO: C, 72.25; H, 7.02; Cl, 11.23; N, 4.43. Found: C,
72.17; H, 7.00; Cl, 11.20; N, 4.45.
1-(Furan-2-yl)-3-phenyl-3-(phenylamino)propan-1-one (4j)
Yield 51%; pale yellow crystals; Mp.: 117.1–118.8 ꢁC. IR (neat, cmꢂ1): 3390 (-NH),
3065, 3035, 2995, 2895, 1680(-CO), 1605 (C-N), 1405, 750, 700, 685. 1H-NMR
(500 MHz, CDCl3, d/ppm): 3.27 (1H, dd, J ¼ 15.1 and 8.1 Hz, -CO-CH2a-CH-NH-),
3.36 (1H, dd, J ¼ 15.1 and 5.2 Hz, -CO-CH2b-CH-NH-), 4.98 (1H, dd, J ¼ 8.1 and
5.2 Hz, -CH2-CHNH-), 6.53 (1H, dd, J ¼ 3.6 and 1.7 Hz, furan -CH-) 6.56 (2H, m,
arom. -CH-), 6.68 (1H, t, J ¼ 7.3 Hz, furan -CH-), 7.10 (2H, dd, J ¼ 8.6 and 7.4 Hz,
arom. -CH-), 7.16–7.26 (2H, m, arom. -CH-), 7.33 (2H, t, J ¼ 7.6 Hz, arom. -CH-), 7.44
(2H, d, J ¼ 8.8 Hz, arom. -CH-), 7.59 (1H, m, furan -CH-). 13C-NMR (125 MHz,
CDCl3, d/ppm) : 46.5 (-CH-), 55.0 (-CH2-), 112.5 (-COCO-), 113.8 (3 x arom.-CH-),
117.7 (furan-CH-), 126.3 (2 x arom.-CH-), 127.4 (arom.-CH-), 128.8 (2 x arom.-CH-),
129.2 (2 x arom.-CH-), 142.7 (arom.-CH-), 146.8 (arom.-CH- and CH-CH-O-), 152.7
(-O-C-CO-), 187.1 (-C ¼ O). GC-MS (m/z): 40, 51, 66, 77, 95, 104, 115, 131, 141, 154,
182, 197, 223, 251, 267, 291(Mþ).
Anal. Calcd. for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 78.37; H, 5.90; N, 4.78.
1-Furan-2-yl-3-(2-chloro-phenylamino)-3-phenyl-propan-1-one (4k)
Yield 46%; red crystals; Mp.: 139.3–141.3 ꢁC. IR (neat, cmꢂ1): 3398 (-NH), 3078,
3048, 2985, 2877, 1684(-CO), 1600 (C-N), 1409, 754, 700, 687 (-Cl). 1H-NMR
(500 MHz, CDCl3, d/ppm): 3.32 (1H, dd, J ¼ 15.1 and 5.3 Hz, -CO-CH2a-CH-NH-),
3.41 (1H, dd, J ¼ 14.5 and 7.4 Hz, -CO-CH2b-CH-NH-), 5.25 (1H, d, J ¼ 6.1 Hz, CH2-
CH-NH-), 6.49 (1H, dd, J ¼ 8.2 and 1.4 Hz, furan -CH-), 6.54 (1H, dd,J ¼ 3.6 and
1.7 Hz, arom. -CH-), 6.58 (1H, dd, J ¼ 7.9 and 1.5 Hz, furan -CH-), 6.62 (1H, dd,
J ¼ 3.6 and 1.7 Hz, arom. -CH-), 6.90 (1H, m, arom. -CH-), 7.22–7.26 (2H, m, arom.
-CH-), 7.32–7.35 (2H, m, arom. -CH-), 7.42–7.45 (2H, m, arom. -CH-), 7.60 (1H, dd,
J¼ 1.7 and 0.8 Hz, furan -CH-). 13C-NMR (125 MHz, CDCl3, d/ppm): 46.2 (-CH-),
54.7 (-CH2-), 111.9 (furan -CH-), 112.2 (arom.-CH-), 117.7 (furan -CH-), 119.2 (arom.-
CH-), 121.1 (arom.-CH-), 126.2 (arom.-CH-), 127.6 (arom.-CH-), 128.7 (arom.-CH-),
128.9 (arom.-CH-), 131.0 (2 x arom.-CH-), 142.7 (2 x arom.-CH-), 144.0 (arom.-CH-).
146.6 (-CH-CH-O-), 178.1 (-O-C-CO-), 186.6 (-C¼O). GC-MS (m/z): 40, 51, 63, 77,
95, 111, 112, 141, 157, 180, 197, 216, 290, 325 (Mþ).

8
Yas¸a et al.
Anal. Calcd. for C19H16ClNO: C, 70.05; H, 4.95; Cl, 10.88; N, 4.30. Found: C,
70.02; H, 4.98; Cl, 10.94; N, 4.31.
1-Cyclohexyl-3-phenyl-3-(phenylamino)propan-1-one (4l)
Yield 46%; orange crystals; Mp.: 132.0–133.2 ꢁC. IR (neat, cmꢂ1): 3385 (-NH), 3051,
3026, 2920, 2875, 1668 (-CO), 1594 (C-N), 1291, 740, 704. 1H-NMR (500 MHz,
CDCl3, d/ppm): 1.22 (5H, m, -CH2-), 1.65 (1H, m, -CH2-), 1.74 (4H, m, -CH2-), 2.23
(1H, m, -CH-), 2.95 (2H, d, J ¼ 6.4Hz, -CO-CH2-CH-NH-), 4.60 (1H, s, -NH-), 4.85
(1H, t, J ¼ 6.3Hz, CH2-CH-NH-), 6.56 (2H, dd, J ¼ 8.6 and 1.0 Hz, -CH-) 6.67 (1H, m
-CH-), 7.10 (2H, m, arom. -CH-), 7.24 (1H, m, -CH-), 7.34 (4H, m, -CH-).13C-NMR
(125 MHz, CDCl3, d/ppm): 25.5 (-CH2-), 25.5 (-CH2-), 25.8 (-CH2-), 27.9 (-CH2-),
28.0 (-CH2-), 48.1 (-COCH2-), 51.4 (-CHCO-), 54.5 (-CHNH-) 113.8 (2 x arom.-CH-),
117.7 (2 x arom.-CH-), 126.3 (2 x arom.-CH-), 127.2 (arom.-CH-), 128.7 (2 x arom.-
CH-), 129.1 (2 x arom.-CH-), 142.9 (arom.-CH-), 146.9 (-C¼O). GC-MS (m/z): 41, 55,
77, 93, 104, 131, 182, 196, 214, 307 (Mþ).
Anal. Calcd. for C21H25NO: C, 82.04; H, 8.20; N, 4.56. Found: C, 82.01; H, 8.19;
N, 4.58.
1-Cyclohexyl-3-(2-chlorophenylamino)-3-phenylpropan-1-one (4m)
Yield 72%; black crystals; Mp.: 155.4–156.9 ꢁC. IR (neat, cmꢂ1): 3382 (-NH), 3070,
1
3026, 2941, 2851, 1691(-CO), 1504 (C-N), 1291, 752 (C-Cl), 687. H-NMR (500 MHz,
CDCl3, d/ppm): 1.18–1.31 (6H, m, alicyclic -CH2-), 1.67 (4H, m, -CH2-), 2.26 (1H, m,
-CH2-), 2.88 (1H, dd, J ¼ 16.1 and 5.6 Hz, -CO-CH2a-CH-NH-), 3.06 (1H, dd, J ¼ 16.1
and 7.1 Hz, -CO-CH2b-CH-NH-), 4.96 (1H, t, J ¼ 6.8 Hz, CH2-CH-NH-), 6.52 (1H, dd,
J ¼ 8.2 and 1.4 Hz -CH-), 6.61 (1H, m, -CH-), 7.01 (1H, m, -CH-), 7.26 (2H, m, -CH-),
7.32-738 (4H, m, -CH-).13C-NMR (125 MHz, CDCl3, d/ppm): 25.5 (2xalicyclic -CH2-),
25.6 (alicyclic -CH2-), 25.8 (alicyclic -CH2-), 27.9 (alicyclic -CH2-), 48.4 (-CH2CO-),
51.6 (alicyclic -CH-), 54.2 (-CHNH-), 112.7 (arom.-CH-), 117.6 (arom.-CH-), 119.5
(arom.-CH-), 126.3 (2 x arom.-CH-), 127.4 (arom.-CH-), 127.7 (arom.-CH-), 128.8 (2 x
arom.-CH-), 129.0 (arom.-CH-), 142.4 (arom.-CH-), 142.8 (arom.-CH-), 211.8 (-C¼O).
GC-MS (m/z): 41, 55, 65, 83, 92, 103, 127, 140, 159, 180, 194, 216, 230, 341 (Mþ).
Anal. Calcd. for C21H24ClNO: C, 73.78; H, 7.08; Cl, 10.37; N, 4.10. Found: C,
73.80; H, 7.05; Cl, 10.35; N, 4.13.
1-Cyclohexyl-3-(p-tolyl amino)-3-phenylpropan-1-one (4n)
Yield 88%; white crystals; Mp.: 139.5–140.6 ꢁC. IR (neat, cmꢂ1): 3316 (-NH), 3058,
3022, 2941, 2924, 1650(-CO), 1195 (C-N), 1275, 745, 691. 1H-NMR (500 MHz,
CDCl3, d/ppm): 1.13–1.27 (6H, m, alicyclic -CH2-), 1.62 (H, m, -CH2-), 1.75 (4H, m,
-CH2-), 2.20 (3H, s, -CH3-), 2.97 (2H, d, J ¼ 7.6 Hz, -CO-CH2-CH-NH-), 4.81 (1H, t,
J ¼ 6.4 Hz, CH2-CH-NH-), 6.51 (2H, d, J ¼ 8.3 Hz -CH-), 6.92 (2H, d, J ¼ 8.1 Hz,
-CH-), 7.23 (1H, m, -CH-), 7.31–738 (5H, m, -CH-).13C-NMR (125 MHz, CDCl3,
d/ppm): 20.39 (-CH3-), 25.49 (alicyclic -CH2-), 25.54 (alicyclic -CH2-), 25.75 (alicyclic
-CH2-), 27.93 (alicyclic -CH2-), 28.03 (alicyclic -CH2-), 47.50 (-CH2CO-), 47.99 (ali-
cyclic -CH-), 51.41 (-CHNH-), 112.69 (arom.-CH-), 114.59 (arom.-CH-), 126.23

b-Amino Carbonyl Compounds
9
(arom.-CH-), 126.49 (2 x arom.-CH-), 127.30 (arom.-CH-), 127.91 (arom.-CH-), 128.36
(2 x arom.-CH-), 129.13 (arom.-CH-), 129.61 (arom.-CH-), 129.84 (arom.-CH-), 212.34
(-C¼O). GC-MS (m/z): 41, 55, 65, 77, 91, 106, 118, 131, 152, 165, 180, 194, 214, 249,
321 (Mþ).
Anal. Calcd. for C22H27NO: C, 82.20; H, 8.47; N, 4.36. Found: C, 82.18; H, 8.50;
N, 4.35.
1,5-Diphenyl-1-(phenylamino)pentan-3-one (4o)
Yield 55%; white crystals; Mp.: 202–203.4 ꢁC. IR (neat, cmꢂ1): 3382 (-NH), 3070,
3026, 2941, 2851, 1691(-CO), 1504 (C-N), 1291, 752, 687. 1H-NMR (500 MHz,
CDCl3, d/ppm): 1.56 (1H, s, -NH-), 2.67 (2H, t, J ¼ 7.6 Hz, -CH2-CH2CO-), 2.83 (2H,
t, J ¼ 7.6 Hz, -CH2-CH2CO-), 2.91 (2H, dd, J ¼ 6.4 and 2.8Hz, -CO-CH2-CH-NH-),
4.85 (1H, t, J ¼ 6.4 Hz, CH2-CH-NH-), 6.54 (2H, m, -CH-), 6.69 (1H, t, J ¼ 7.4 and
1.0 Hz, -CH-), 7.09–7.13 (4H, m, -CH-), 7.25–7.27 (4H, m, -CH-), 7.32–7.34 (4H, m,
-CH-).13C-NMR (125 MHz, CDCl3, d/ppm): 29.40 (-CH2-), 45.18 (-CH2-) 50.43
(-CH2CO-), 54.42 (-CHNH-), 113.74 (2 x arom.-CH-), 117.83 (arom.-CH-), 126.24 (2 x
arom.-CH-), 127.36 (arom.-CH-), 128.24 (2 x arom.-CH-), 128.49 (2 x arom.-CH-),
128.80 (2 x arom.-CH-), 129.12 (2 x arom.-CH-), 140.66 (arom.-CH-), 142.44 (arom.-
CH-), 146.74 (arom.-CH-), 146.58 (arom.-CH-), 208.28 (-C ¼ O). GC-MS (m/z): 43,
65, 77, 91, 105, 115, 131, 148, 158, 180, 196, 218, 236, 252, 267, 283, 309, 329 (Mþ).
Anal. Calcd. for C23H23NO: C, 83.85; H, 7.04; N, 4.25. Found: C, 83.81; H, 7.07;
N, 4.27.
Determination of Antioxidant Activity by the Scavenging of the Stable
Radical DPPH
Equal volumes of 0.02% DPPH in methanol were added to different concentrations of
test compounds (250 – 1000 lM/mL) in methanol, mixed well and kept in the dark for
30 min. The absorbance at 517 nm was measured. Plotting the percentage DPPHꢀ scav-
enging against concentration gave the standard curve and the percentage scavenging
was calculated from the following equation:
DPPH radical scavenging activity ð%Þ ¼ ðA0– A1=A0Þ ꢄ 100%
A0 and A1 are the absorbance of blank (without sample) and test sample, respect-
ively.29,30 Ascorbic acid, BHA and BHT were used as standards for comparison.
Acknowledgments
This work was supported by the Scientific Research Projects Coordination Unit of
Istanbul University. Project number: FYL-2016-23127.
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