Synthesis and characterization of unsaturated diacyl and alkyl-acyl piperazine derivatives

Article abstract of DOI:10.3906/kim-1907-16

The aim of this study is to obtain new unsaturated piperazine compounds by the reactions of piperazine (1a) and piperazine derivatives (1b–1d) with acylation reactive groups (2a–2j). Methacryloyl piperazine (1b) was synthesized from the reaction of methacrylic anhydride with piperazine (1a). Acyl chlorides (2b–2d) were prepared from the reaction of thionyl chloride with carboxylic acids (3a–3c) obtained as a result of the reaction with malonic acid and suitable aldehyde (5-methylfuran-2-carbaldehyde for 3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde for 3c), respectively, by literature methods. Acyl chlorides 2e and 2f were obtained from the reaction of commercially purchased carboxylic acids 3d and 3e with thionyl chloride. Acyl chlorides (2g–2j) were synthesized from the reaction of thionyl chloride with carboxylic acids (3d–3g) transformed from hydrolyzation of esters (4a–4d) obtained as a result of the reaction of triethyl phosphonoacetate with a suitable ketone (acetophenone for 4a, benzophenone for 4b, 1-(5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d), respectively, by literature methods. Unsaturated piperazine derivatives 5a and 5b were obtained from the reaction of 1b with 2b and 2e, respectively. In addition, from the reaction of 1b and acyl chlorides (2b–2j), unsaturated piperazines (5c–5k) were synthesized in medium to good yields (63%–84%). Also, 5l–5g and 5r–5w were obtained from the reaction of allyl piperazine (2c) and cinnamyl piperazine (2d) with acyl chlorides (2a–2f).

Full text of DOI:10.3906/kim-1907-16

Turkish Journal of Chemistry
Turk J Chem
2019) 43: 1656 –
TÜBİTAK
doi:10.3906/kim-1907-16
(
©
http://journals.tubitak.gov.tr/chem/
Research Article
Synthesis and characterization of unsaturated diacyl and alkyl-acyl piperazine
derivatives
∗
Sait SARI,, Seda ÜNALAN,, Mehmet YILMAZ ,
Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, Umuttepe, Kocaeli, Turkey
Received: 08.07.2019
•
Accepted/Published Online: 07.11.2019
•
Final Version: 09.12.2019
Abstract: The aim of this study is to obtain new unsaturated piperazine compounds by the reactions of piperazine
1a) and piperazine derivatives (1b–1d) with acylation reactive groups (2a–2j). Methacryloyl piperazine (1b) was
(
synthesized from the reaction of methacrylic anhydride with piperazine (1a). Acyl chlorides (2b–2d) were prepared
from the reaction of thionyl chloride with carboxylic acids (3a–3c) obtained as a result of the reaction with malonic
acid and suitable aldehyde (5-methylfuran-2-carbaldehyde for 3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde
for 3c), respectively, by literature methods. Acyl chlorides 2e and 2f were obtained from the reaction of commercially
purchased carboxylic acids 3d and 3e with thionyl chloride. Acyl chlorides (2g–2j) were synthesized from the reaction
of thionyl chloride with carboxylic acids (3d–3g) transformed from hydrolyzation of esters (4a–4d) obtained as a result
of the reaction of triethyl phosphonoacetate with a suitable ketone (acetophenone for 4a, benzophenone for 4b, 1-
(
5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d), respectively, by literature methods.
Unsaturated piperazine derivatives 5a and 5b were obtained from the reaction of 1b with 2b and 2e, respectively.
In addition, from the reaction of 1b and acyl chlorides (2b–2j), unsaturated piperazines (5c–5k) were synthesized in
medium to good yields (63%–84%). Also, 5l–5g and 5r–5w were obtained from the reaction of allyl piperazine (2c) and
cinnamyl piperazine (2d) with acyl chlorides (2a–2f).
Key words: Piperazine, acylation, heterocycle
1. Introduction
Heterocycles are organic molecules that have great importance both biologically and industrially. Many synthetic
and naturally occurring drugs contain heterocyclic moieties [1–3]. Heterocycles bearing nitrogen (piperazine,
thiazole, imidazole, etc.) have drawn much attention due to their biological properties [4,5]. In medicinal
chemistry the piperazine scaffold is considered a privileged structure for its capability of binding to multiple
receptors with high affinity [6] and it can be found in drugs such as imatinib [7], sildenafil [8], indinavir [9],
and gatifloxacin [10] (Figure 1). Piperazine is also a useful linker for bioactive structures. Many biological
activity studies were performed on piperazine-containing structures, such as anticonvulsant [11], antibacterial
[
[
12], antituberculosis [13], antiviral [14], anticancer [15], antimalarial [16], and acetylcholine esterase inhibition
17].
Cinnamyl piperazine derivatives were reported to show anticonvulsant activity [18], monoacylglycerol
lipase inhibition [19], and antimicrobial [20] and antiinflammatory activity [21]. Some acrylamide piperazine
∗Correspondence: mehmet.yilmaz@kocaeli.edu.tr
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This work is licensed under a Creative Commons Attribution 4.0 International License.

SARI et al./Turk J Chem
Figure 1. Structure of imatinib, sildenafil, indinavir, and gatifloxacin.
derivatives were also reported to show antimycobacterial [22], antiischemic [23], and antiparasitic activities [24].
Additionally, some dienoyl-substituted piperazines were reported to show γ -aminobutyric acid receptor [25],
monoamine oxidase [26], and Staphylococcus aureus [27] inhibition. In this study, based on these properties of
piperazines, we obtained various unsaturated diacyl and alkyl-acyl cinnamyl, ally, and acrylamide piperazines
bearing unsaturated moieties, which are potential bioactive compounds and starting reagents for synthesizing
1
13
many other potential bioactive molecules. All new synthesized compounds were characterized by H NMR,
C
NMR, HRMS, and FTIR spectroscopy. Other compounds that are available in the literature were characterized
1
by H NMR spectroscopy.
2. Results and discussion
Synthesis of methacryloyl piperazine (1b) was performed by the reaction of piperazine (1a) and methacryloyl
chloride as an acylating reagent in the literature [28]. However, we did not succeed in synthesizing 1b using this
method; dimethacryloyl piperazine was obtained instead. In this study, synthesis of 1b (77%) was achieved by
the reaction of methacrylic anhydride (2a) with piperazine (1a) in mild conditions (Figure 2).
Figure 2. Synthesis of methacryloyl piperazine (1b).
Unsaturated acyl chlorides (2b–2j) were prepared from the reaction of suitable carboxylic acid and
SOCl2 according to literature (see Section 3). Diacyl (5a–5k) and alkyl-acyl (5l–5w) piperazine compounds
were obtained from the reactions of these acyl chlorides with piperazine (1a) and piperazine derivatives (1b–1d).
As can be seen in Table 1, symmetrical unsaturated piperazine derivatives 5a (84%) and 5b (66%) were
synthesized from the reactions of piperazine (1a) and (E)-3-(5-methylfuran-2-yl)acryloyl chloride (2b) and
(2E ,4E)-hexa-2,4-dienoyl chloride (2e), respectively.
Reactions of 1b with (2E ,4E)-5-phenylpenta-2,4-dienoyl chloride (2c) and 2e gave 5c (72%) and 5d
66%) in high yields, respectively. Additionally, reactions of 1b with 2b and (E)-3-(thiophen-2-yl)acryloyl
(
chloride (2d) gave piperazine derivatives 5e (75%) and 5f (81%), respectively.
Diacyl piperazine compounds 5g (65%), 5h (79%), and 5i (70%) were obtained from the reaction of 1b
with cinnamoyl chloride (2f), (E)-3-phenylbut-2-enoyl chloride (2g), and 3,3-diphenylacryloyl chloride (2h) in
medium to high yields, respectively (Table 2).
Similarly, 5j (65%) and 5k (63%) were synthesized from the reaction of 1b with (E)-3-(5-methylfuran-
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Table 1. Synthesis diacyl piperazine compounds 5a-f.
Diacyl piperazine
Product and
a
Yield (%)
Entry Piperazine
Acylating reagent
product
1
5a, 84
5b, 66
2
3
5c, 72
4
5
5d, 66
5e, 75
6
5f, 81
a) Isolated yields are based on piperazine derivative (1a or 1b).
2
-yl)but-2-enoyl chloride (2i) and (E)-3-(thiophen-2-yl)but-2-enoyl chloride (2j), respectively.
Synthesis of alkyl-acyl piperazine (5l–5q) compounds obtained from the reactions of allyl piperazine (1c)
and suitable acyl chloride (2a–2f) can be seen in Table 3.
Piperazine compounds 5l (63%) and 5m (70%) were obtained from the reaction of 1c with 2b and 2d,
respectively. Treatments of 1c with 2f and 2a also gave piperazine derivatives 5n (90%) and 5o (76%) in high
yields, respectively. Moreover, reactions of 1c with 2c and 2e gave 5p (75%) and 5q (81%), respectively.
Syntheses of alkyl-acyl piperazines (5r–5w) were obtained from the reactions of cinnamyl piperazine (1d)
and suitable acyl chloride (2a–2f) (Table 4).
Reactions of 1d with 2b and 2d gave piperazine compounds 5r (87%) and 5s (81%) in high yields,
respectively. Additionally, 5t (87%) and 5u (94%) were obtained from the reactions of 1d with 2f and 2a.
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Table 2. Synthesis diacyl piperazine compounds 5g-k.
Diacyl piperazine
product
Product and
a
Yield (%)
Entry
1
Piperazine
Acylating reagent
5g, 65
5h, 79
5i, 70
2
3
4
5
5j, 65
5k, 63
a) Isolated yields are based on piperazine derivative (1b).
Moreover, 5v (75%) and 5w (81%) were synthesized from the reactions of 1d with 2c and 2e in high yields.
In conclusion, novel diacyl (5a–5k) and alkyl-acyl (5l–5w) unsaturated piperazine compounds were
synthesized by the acylation reactions of piperazine (1a), methacryloyl piperazine (1b), allyl piperazine (1c),
and cinnamyl piperazine (1d) with suitable acyl chlorides and methacrylic anhydride in medium to high yields for
1
13
the first time. All new compounds were characterized by H NMR, C NMR, HRMS, and FTIR spectroscopy.
1
The others were characterized by only H NMR.
Many piperazine derivatives are known for their bioactive properties and can be used as linkers for many
other bioactive structures like imatinib [7], sildenafil [8], indinavir [9], and gatifloxacin [10]. On the other hand,
these diacyl (5a–5k) and alkyl-acyl (5l–5w) piperazine compounds bear unsaturated moieties and for that
reason they are potential starting reagents for many reactions such as Heck coupling, polymerizations, and α-β
unsaturated Michael additions.
These compounds are also starting reagents for Mn(OAc)3 mediated radical cyclization reactions for
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Table 3. Synthesis of allyl-acyl piperazine compounds (5l-q).
Alkly-Acyl piperazine
product
Product and
a
Yield (%)
Entry
1
Piperazine
Acylating reagent
5l, 63
2
3
4
5m, 70
5n, 90
5o, 76
5
6
5p, 75
5q, 81
a) Isolated yields are based on piperazine derivative (1c).
synthesizing acetylcholine esterase inhibitor dihydrofuran-piperazine molecules and this work is an ongoing
research interest of our group.
3
3
. Experimental
.1. Equipment and used chemicals
Melting points were determined on a Gallenkamp capillary melting point apparatus. IR spectra (ATR) were
−
1
−1
1
obtained with a Bruker Tensor27 spectrophotometer in the 400–4000 cm range with 2 cm
resolution. H
1
3
NMR and C NMR spectra were recorded on Varian Mercury-400 High Performance Digital FT-NMR and
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Table 4. Synthesis of cinnamyl-acyl piperazine compounds (5r-w).
Alkly-Acyl piperazine
product
Product and
a
Yield (%)
Entry
1
Piperazine
Acylating reagent
5r, 87
5s, 81
2
3
4
5t, 87
5u, 94
5
6
5v, 75
5w, 81
a) Isolated yields are based on piperazine derivative (1d).
Varian Oxford NMR300 spectrometers. High-resolution mass time-of-flight spectra (TOF) were measured on
an Agilent 1200/6210 LC/MS spectrophotometer. Thin-layer chromatography (TLC) was performed on Merck
aluminum-packed silica gel plates. Purification of products was performed by column chromatography on
silica gel (Merck silica gel 60, 40–60 µm) or preparative TLC on silica gel (Merck, PF254−366 nm). All sol-
vents (chloroform, methanol, ethyl acetate, hexane, THF, diethyl ether, ethanol, HCl) were of the highest pu-
rity and anhydrous. Malonic acid, 5-methyl-2-carbaldehyde, cinnamaldehyde, thiophene-2-carbaldehyde, pyri-
dine, piperidine, SOCl2 , NaH, triethyl phosphonoacetate, acetophenone, benzophenone, 2-acetyl-5-methylfuran,
2
-acetyl-thiophene, NaOH, Na2 SO4 , 2,4-hexadienoic acid, cinnamic acid, piperazine, 1-allypiperazine, 1-
1
cinnamylpiperazine, and metacrylic anhydride were purchased from Sigma Aldrich. Please note that the
H
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1
13
NMR spectra for known compounds and H NMR, C NMR, and HRMS spectra for all novel compounds can
be found in the Supplementary information.
3
.2. General synthesis of unsaturated acyl chlorides (2b–2j)
Thionyl chloride (22 mL, 0.3 mol, freshly distilled) was added to a solution of suitable carboxylic acid (3a–3g)
0.1 mol) in 100 mL of chloroform at room temperature. The mixture was allowed to stand for 12 h. Then
(
the solvent and excess SOCl2 were distilled in vacuo. The residue was pure enough to be used as an acylating
reagent without further purification.
All necessary carboxylic acids (except 2,4-hexadienoic acid and cinnamic acid) were prepared according
to methods described in Sections 3.3 and 3.4.
3.3. General synthesis of (E)-3-(5-methylfuran-2-yl)acrylic acid (3a), (2E,4E)-5-phenylpenta-2,4-
dienoic acid (3b), and (E)-3-(thiophen-2-yl)acrylic acid (3c)
Molecular structures of carboxylic acids (3a–3c) are given in Figure 3.
Figure 3. Carboxylic acids (3a–3c).
Malonic acid (20 g, 0.2 mol), the corresponding aldehyde (0.1 mol), (5-methylfuran-2-carbaldehyde for
3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde for 3c), 50 mL of freshly distilled pyridine, and 1
mL of piperidine were put into a two-necked reaction flask. The mixture was heated for 2 h to a temperature
◦
not exceeding 90–95 C and boiled for 5 min after that. The mixture was left to cool and diluted with water.
After cooling, concentrated HCl was added dropwise. Formed precipitates were filtered and crystallized in
EtOH-water.
◦
◦
(
E)-3-(5-Methylfuran-2-yl)acrylic acid (3a) [29]: Yield: 13 g, 85%. Mp: 155–156 C, (lit: 154–155 C).
1
H NMR (400 MHz, CDCl3), δ (ppm): 7.43 (1H, d, J = 15.6 Hz), 6.56 (1H, d, J = 3.2 Hz), 6.22 (1H, d, J =
1
5.6 Hz), 6.10 (1H, d, J = 3.2 Hz), 2.35 (3H, s).
◦
(2E ,4E)-5-Phenylpenta-2,4-dienoic acid (3b) [30]: Yield: 12 g, 70%. Mp: 164–166 C, (lit: 164–166
◦
1
C). H NMR (400 MHz, CDCl3), δ (ppm): 7.57–7.46 (3H, m), 7.39–7.30 (3H, m), 6.98–6.87 (2H, m), 6.00
1H, d, J = 15.2 Hz).
E)-3-(Thiophen-2-yl)acrylic acid (3c) [31]: Yield: 13.8 g, 90%. Mp: 140–141 C, (lit: 140–142 C).
H NMR (400 MHz, CDCl3), δ (ppm): 7.88 (1H, d, J = 15.6 Hz), 7.42 (1H, d, J = 4.8 Hz), 7.30 (1H, d, J
3.2 Hz), 7.07 (1H, dd, J = 4.8, 3.2 Hz), 6.24 (1H, d, J = 15.6 Hz).
(
◦
◦
(
1
=
3.4. General synthesis of substituted carboxylic acids (3d–3g)
Carboxylic acids (3d–3g) were prepared from the hydrolysis of esters (4a–4d) synthesized from the reaction of
suitable ketones and triethyl phosphonoacetate in NAH/THF (Figure 4).
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Figure 4. Synthesis of unsaturated esters (4a–4d) and carboxylic acids (3d–3g).
3.4.1. General synthesis of unsaturated esters (4a–4d)
To a suspension of NaH (60%, 8.3 g, 0.12 mol) in THF, a solution of triethyl phosphonoacetate (34.5 mL, 0.12
mol) in THF was added dropwise in an ice bath. After instillation the mixture was stirred for 30 min at room
temperature and a solution of corresponding ketone (0.1 mol) (acetophenone for 4a, benzophenone for 4b,
1
-(5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d) in THF was poured into the
reaction mixture and stirred for 2–3 h. The reaction was monitored with TLC, and in the case of remaining
ketone, the mixture was heated until no more ketone remained. THF was evaporated and water was added.
The mixture was extracted with diethyl ether. The combined organic phase was dried with Na2 SO4 and ether
was evaporated. The crude product was purified with column chromatography with hexane/ethyl acetate (5:1)
as eluent.
1
(
E)-Ethyl 3-phenylbut-2-enoate (4a) [32]: Yield: 17.81 g, 94%. Oily product. H NMR (400 MHz,
CDCl3), δ (ppm): 7.51 (2H, m), 7.40 (3H, m), 6.17 (1H, m), 4.25 (2H, q, J = 7.2 Hz), 2.62 (3H, d, J = 1.2
Hz), 1.36 (3H, t, J = 7.2 Hz).
1
Ethyl 3,3-diphenylacrylate (4b) [32]: Yield: 23.5 g, 93%. Oily product. H NMR (400 MHz, CDCl3), δ
(
ppm): 7.27–7.45 (10H, m), 6.44 (1H, s), 4.11 (2H, q, J = 7.2 Hz), 1.17 (3H, t, J = 7.2 Hz).
Ethyl (E)-3-(5-methylfuran-2-yl)but-2-enoate (4c): Yield: 17.9, g 92%. Oily product. H NMR (400
MHz, CDCl3), δ (ppm): 6.52 (1H, d, J = 3.6 Hz), 6.28 (1H, d, J = 1.2 Hz), 6.03 (1H, d, J = 3.6 Hz), 4.17
1
1
3
(
2H, q, J = 7.2 Hz), 2.40 (3H, d, J = 1.2 Hz), 2.30 (3H, s), 1.28 (3H, t, J = 7.2 Hz).
C NMR (100 MHz,
CDCl3), δ (ppm): 167.35, 154.35, 152.78, 142.24, 112.71, 110.82, 108.36, 59.57, 14.48, 14.33, 13.74.
1
Ethyl (E)-3-(thiophen-2-yl)but-2-enoate (4d) [33]: Yield: 16 g, 93%. Oily product. H NMR (400 MHz,
CDCl3), δ (ppm): 7.34 (2H, d, J = 4.2 Hz), 7.06 (1H, t, J = 4.2 Hz), 6.22 (1H, d, J = 1.2 Hz), 4.22 (2H, q,
J = 7.2 Hz), 2.63 (3H, d, J = 1.2 Hz), 1.34 (3H, t, J = 7.2 Hz).
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3.4.2. General synthesis of unsaturated carboxylic acids (3d–3g)
Unsaturated esters (4a–4d) obtained by the method described above were transformed into their corresponding
carboxylic acids (3d–3g) by the method described below.
Unsaturated ester (4a–4d) (0.1 mol) was boiled with 5 N NaOH under a reflux condenser for 2–3 h and
left to stir at room temperature overnight. The formed carboxylate salt was dissolved in water and diluted HCl
was added. The obtained solid product was filtered and crystallized with EtOH-water.
◦
◦
1
(
E)-3-Phenylbut-2-enoic acid (3d) [34]: Yield: 15 g, 94%. Mp: 90–92 C, (lit: 90–92 C). H NMR
(
(
400 MHz, CDCl3), δ (ppm): 7.51–7.49 (3H, m), 7.40–7.38 (2H, m), 6.18 (1H, s), 2.61 (3H, s).
◦
◦
1
3
,3-Diphenylacrylic acid (3e) [35]: Yield: 14.5 g, 65%. Mp: 159–161 C (lit: 161–162 C). H NMR
400 MHz, CDCl3), δ (ppm): 7.38–7.19 (10H, m), 6.33 (1H, s).
E)-3-(5-Methylfuran-2-yl)but-2-enoic acid (3f): Yield: 10 g, 60%. Mp: 138–140 C. H NMR (400
MHz, CDCl3), δ (ppm): 6.08 (1H, d, J = 3.2 Hz), 6.33 (1H, d, J = 1.2 Hz), 6.07 (1H, d, J = 3.2 Hz), 2.43
◦
1
(
1
3
(
3H, d, J = 1.2 Hz), 2.43 (3H, s).
C NMR (100 MHz, CDCl3), δ (ppm): 172.3, 155, 152.6, 144.5, 113.7,
1
09.8, 108.6, 14.8, 13.8.
E)-3-(Thiophen-2-yl)but-2-enoic acid (3g) [36]: Yield: 11 g, 65%. Mp: 113–115 C (lit: 114–114.8 C).
H NMR (400 MHz, CDCl3), δ (ppm): 7.37 (2H, d, J = 4.4 Hz), 7.07 (1H, t, J = 4.4 Hz), 6.29 (1H, s), 2.63
3H, s).
◦
◦
(
1
(
3.5. Synthesis procedure for 2-methyl-1-(piperazin-1-yl)prop-2-en-1-one (1b) [28]
Piperazine (1a) (20 g, 0.232 mol) was dissolved in 50 mL of chloroform in a reaction flask. The solution was
stirred in an ice-salt bath for 15 min. Then a dilute solution of methacrylic anhydride (2a) (18 g, 0.116 mol)
was added. After instillation, the reaction was removed from the ice-salt bath and allowed to stir overnight.
Water was added and crude product was extracted with chloroform. Combined organic phases were dried over
anhydrous Na2 SO4 and evaporated. The crude product was purified by column chromatography on silica gel
1
using EtOAc-methanol (1:1) as eluent. Yield: 30 g, 77%. Oily product. H NMR (400 MHz, CDCl3) δ (ppm):
5
.16 (1H, q, J = 1.6 Hz), 5.00 (1H, q, J = 1.2 Hz) 3.55 (4H, s) 2.84 (4H, s), 1.93 (3H, t, J = 1.2 Hz).
3.6. General synthesis procedure for symmetrical diacyl piperazine compounds (5a, 5b)
Piperazine (2a) (860 mg, 10 mmol) and Et3 N (22 mmol) were dissolved in 10 mL of chloroform in a reaction
flask. The solution was stirred in an ice bath for 15 min. Then a dilute solution of the related acylating agent
(
1a, 1b) (22 mmol) in CHCl3 was added dropwise. After instillation, the reaction was removed from the
ice bath and allowed to stir overnight. Water was added and crude product was extracted with chloroform.
Combined organic phases were dried over anhydrous Na2 SO4 and evaporated. The crude product was purified
by column chromatography on silica gel using EtOAc-methanol (1:1) as eluent.
(
2E,2’E)-1,1’-(Piperazine-1,4-diyl)bis(3-(5-methylfuran-2-yl)prop-2-en-1-one) (5a): Yield: 3.1
◦
−1
1
g, 84%. Mp: 275–277 C. IR (ATR): 980, 1209, 1426, 1603, 1644, 1748, 2850, 2921, 3686 cm
.
H NMR (400
MHz, CDCl3), δ (ppm): 7.43 (2H, d, J = 14.8 Hz), 6.69 (2H, d, J = 14.8 Hz), 6.47 (2H, d, J = 2.8 Hz), 6.07
1
3
(
1
3
2H, d, J = 2.8 Hz), 3.74 (8H, s), 2.35 (6H, s). C NMR (100 MHz, CDCl3), δ (ppm): 165.80, 154.83, 150.09,
+
30.48, 116.06, 111.81, 108.75, 45.6, 42.3, 13.89. HRMS (ESI): (m/z) calcd. for C20 H22 N2 O4 , (M+Na)
77.14717, found: 377.14695.
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(
2E,2’E,4E,4’E)-1,1’-(Piperazine-1,4-diyl)bis(hexa-2,4-dien-1-one) (5b): Yield: 1.9 g, 66%.
◦
−1
1
Mp: 153–155 C. IR (ATR): 938, 1207, 1236, 1426, 1620, 1648, 2336, 2912 cm
.
H NMR (400 MHz,
CDCl3), δ (ppm): 7.28 (2H, dd, J = 14.8, 10 Hz), 6.25–6.07 (6H, m), 3.64 (8H, s), 1.85 (6H, d, J = 6.4 Hz).
1
3
C NMR (100 MHz, CDCl3), δ (ppm): 166.02, 143.99, 138.40, 129.99, 117.07, 41.99, 38.70, 18.59. HRMS
+
(ESI): (m/z) calcd. for C16 H22 N2 O2 , (M+Na) 297.15734, found: 297.15706.
3.7. General synthesis procedure for nonsymmetrical diacyl piperazine compounds (5c-k)
Methacryloyl piperazine (1b, 10 mmol) and Et3 N (22 mmol) was dissolved in 10 mL of chloroform in a reaction
flask. The solution was stirred in an ice bath for 15 min. Then a dilute solution of the related acylating agent
(
2c–2j) (22 mmol) in CHCl3 was added dropwise. After instillation, the reaction was removed from the ice bath
and allowed to stir overnight. Water was added and crude product was extracted with chloroform. Combined
organic phases were dried over anhydrous Na2 SO4 and evaporated. The crude product was purified by column
chromatography on silica gel using EtOAc-methanol (1:1) as eluent.
(
2E ,4E)-1-(4-Methacryloylpiperazine-1-yl)-5-phenylpenta-2,4-dien-1-one (5c): Yield: 2.2 g,
◦
−1
1
7
2%. Mp: 178–180 C. IR (ATR): 759, 989, 1194, 1225, 1430, 1460, 1615, 2861, 2908 cm
.
H NMR (400
MHz, CDCl3), δ (ppm): 7.51–7.44 (3H, m), 7.36–7.25 (3H, m), 6.89 (2H, t, J = 15.2 Hz), 6.43 (1H, d, J
1
3
=
15.2 Hz), 5.24 (1H, s), 5.06 (1H, s), 3.63 (8H, s), 1.96 (3H, s).
C NMR (100 MHz, CDCl3), δ (ppm):
1
71.38, 165.71, 143.75, 139.71, 136.18, 128.78, 127.04, 126.52, 119.39, 116.12, 45.22, 41.56, 20.47. HRMS (ESI):
+
(m/z) calcd. for C19 H22 N2 O2 , HRMS (ESI): (m/z) calcd. for C19 H22 N2 O2 , (M+H) 311.17540, found:
3
11.17543.
2E ,4E)-1-(4-Methacryloylpiperazine-1-yl)hexa-2,4-dien-1-one (5d): Yield: 1.78 g, 66%. Mp:
(
◦
−1
1
1
10–112 C. IR (ATR): 924, 1198, 1253, 1432, 1614, 1645, 2912 cm
.
H NMR (400 MHz, CDCl3), δ (ppm):
7
.30 (1H, t, J = 14.8 Hz), 6.24–6.09 (3H, m), 5.24 (1H, t, J = 1.6 Hz), 5.05 (1H, t, J = 1.2 Hz), 3.60 (8H,
1
3
s), 1.96 (3H, t, J = 1.6 Hz), 1.84 (3H, d, J = 6.4 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 171.38,
1
66.03, 144.10, 139.97, 138.49, 129.97, 116.99, 116.08, 42, 46, 20.46, 18.60. HRMS (ESI): (m/z) calcd. for
+
C14 H20 N2 O2 , (M+Na) 271.14169, found: 271.14216.
E)-1-(4-Methacryloylpiperazine-1-yl)-3-(5-methylfuran-2-yl)prop-2-en-1-one (5e): Yield: 2.33
g, 75%. Mp: 142–144 C IR (ATR): 977, 1196, 1247, 1426, 1606, 1644, 1705, 2859, 2919, 3047 cm
(
◦
−1
1
.
H NMR
(400 MHz, CDCl3), δ (ppm): 7.40 (1H, d, J = 15.2 Hz), 6.66 (1H, d, J = 15.2), 6.45 (1H, d, J = 3.2 Hz),
6
Hz).
.05 (1H, m) 5.23 (1H, t, J = 1.2 Hz), 5.05 (1H, t, J = 1.2 Hz), 3.66 (8H, s), 2.33 (3H, s), 1.96 (3H, t, J = 1.2
1
3
C NMR (100 MHz, CDCl3), δ (ppm): 171.36, 165.75, 154.81, 150.05, 139.97, 130.49, 116.06, 111.75,
+
1
08.75, 45.47, 42.19, 20.46, 13.87. HRMS (ESI): (m/z) calcd. for C16 H20 N2 O3 , (M+Na) 311.13661, found:
3
11.13582.
(
E)-1-(4-Methacryloylpiperazine-1-yl)-3-(thiophen-2-yl)prop-2-en-1-one (5f): Yield: 2.5 g,
◦
−1
1
8
1%. Mp: 101–103 C. IR (ATR): 967, 1202, 1271, 1433, 1606, 1642, 2190, 2860, 2923, 2997 cm
.
H
NMR (400 MHz, CDCl3), δ (ppm): 7.84 (1H, d, J = 15.2 Hz), 7.51 (1H, dd, J = 5.2, 3.6 Hz), 7.34 (1H, d, J =
5
3
1
.2 Hz), 7.24 (1H, d, J = 3.6 Hz), 6.65 (1H, d, J = 15.2 Hz), 5.25 (1H, t, J = 1.6 Hz), 5.07 (1H, t, J = 1.6 Hz),
.66 (8H, s), 1.98 (3H, t, J = 1.2 Hz). C NMR (100 MHz, CDCl3), δ (ppm): 171.38, 165.33, 140.13, 139.94,
1
3
36.46, 130.67, 128,08, 127.57, 116.13, 114.96, 46, 42, 20.4. HRMS (ESI): (m/z) calcd. for C15 H18 N2 O2 S,
+
(M+Na) 313.09811, found: 313.09941.
1
665

SARI et al./Turk J Chem
(
E)-1-(4-Cinnamoylpiperazine-1-yl)-2-methylprop-2-en-1-one (5g):
◦
Yield: 1.9 g, 65%. Mp: 100–102 C. IR (ATR): 748, 996, 1133, 1209, 1367, 1436, 1618, 1739, 2362, 3003
−
1
1
cm
6
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.71 (1H, d, J = 16 Hz), 7.54–7.52 (2H, m), 7.41–7.36 (3H, m),
1
3
.86 (1H, d, J = 16 Hz), 5.26 (1H, s), 5.08 (1H, s), 3.60 (8H, s), 1.98 (3H, s).
C NMR (100 MHz, CDCl3),
δ (ppm): 171,38, 165.68, 143.66, 139.94, 134.97, 129.88, 128.85, 127.82, 116.39, 116.14, 42, 46, 20.47. HRMS
+
(
ESI): (m/z) calcd. for C17 H20 N2 O2 , (M+Na) 307.14169, found: 307.14038.
(
E)-1-(4-Methacryloylpiperazine-1-yl)-3-phenylbut-2-en-1-one (5h):
◦
−1
Yield: 2.6 g, 79%. Mp: 84–86 C. IR (ATR): 766, 910, 1208, 1433, 1460, 1612, 2867, 2917, 2995 cm
.
1
H NMR (400 MHz, CDCl3), δ (ppm): 7.46–7.43 (2H, m), 7.38–7.33 (3H, m), 6.25 (1H, t, J = 1.2 Hz), 5.24
(
1H, d, J = 1.2 Hz), 5.06 (1H, d, J = 1.2 Hz), 3.62 (8H, s), 2.28 (3H, d, J = 1.2 Hz), 1.96 (3H, t, J = 1.2
1
3
Hz).
1
C NMR (100 MHz, CDCl3), δ (ppm): 171.4, 167.3, 146.9, 141.4, 140, 128.54, 128.51, 125.9, 118.83,
+
16.1, 46.89, 42.29, 20.47, 18.05. HRMS (ESI): (m/z) calcd. for C18 H22 N2 O2 , (M+Na) 337.13129, found:
3
37.13041.
1
-(4-Methacryloylpiperazine-1-yl)-3,3-diphenylprop-2-en-1-one (5i):
◦
−1
Yield: 2.7 g, 70%. Mp: 126–128 C. IR (ATR): 760, 916, 1199, 1431, 1592, 1628, 2856, 2890, 2978 cm
.
1
H NMR (400 MHz, CDCl3), δ (ppm): 7.37–7.27 (10H, m), 6.30 (1H, s), 5.171 (1H, s), 4.94 (1H, s), 3.5 (2H,
1
3
s), 3.30 (4H, s), 2.91 (2H, s), 1.88 (3H, s).
C NMR (100 MHz, CDCl3), δ (ppm): 171.09, 167.31, 147.68,
1
40.54, 139.84, 138.65, 129.50, 128.84, 128.77, 128.44, 128.40, 128.08, 120.11, 115.92, 46.20, 41.32, 20.39. HRMS
+
(ESI): (m/z) calcd. for C23 H24 N2 O2 , (M+Na) 383.17300, found: 383.17366.
(
E)-1-(4-Methacryloylpiperazine-1-yl)-2-methyl-3-(5-methylfuran-2-yl)prop-2-en-1-one (5j):
◦
Yield: 2.1 g, 65%. Mp: 142–144 C. IR (ATR): 988, 1195, 1219, 1421, 1441, 1611, 1631, 1738, 2854,
923, 3013 cm
−
1
1
2
.
H NMR (400 MHz, CDCl3), δ (ppm): 6.45 (1H, d, J = 1.2 Hz), 6.39 (1H, d, J = 2.8
Hz), 6.00 (1H, m), 5.21 (1H, t, J = 1.6 Hz), 5.03 (1H, t, J = 1.2 Hz), 3.62 (8H, s), 2.3 (3H, s), 2.19 (3H, d, J
1
3
=
1.2 Hz), 1.94 (3H, t, J = 1.2 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 171.33, 167.03, 153.45, 152.67,
1
40, 136.70, 115.98, 112.15, 111,12, 108.10, 46.66, 41.54, 20.46, 14.93, 13.78. HRMS (ESI): (m/z) calcd. for
+
C17 H22 N2 O3 , (M+Na) 325.15226, found: 325.15113.
(
E)-1-(4-Methacryloylpiperazine-1-yl)-2-methyl-3-(thiophen-2-yl)prop-2-en-1-one (5k):
◦
−1
1
Yield: 2 g, 63%. Mp: 102–104 C. IR (ATR): 856, 1196, 1428, 1462, 1616, 2911, 2974 cm
.
H
NMR (400 MHz, CDCl3), δ (ppm): 7.26 (1H, d, J = 1.2 Hz), 7.19 (1H, dd, J = 3.6, 1.2 Hz), 7.02 (1H, dd,
J = 5.2, 3.6 Hz), 6.37 (1H, d, J = 1.2 Hz), 5.24 (1H, t, J = 1.2 Hz), 5.06 (1H, t, J =1.6 Hz), 3.61 (8H, s),
1
3
2
.33 (3H, d, J = 1.2 Hz), 1.96 (3H, t, J = 1.2 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 171.37, 166.61,
1
45.17, 140.69, 139.96, 127.80, 125.82, 125.54, 116.2,3 116.09, 46, 42, 20.5, 17.8. HRMS (ESI): (m/z) calcd. for
+
C16 H20 N2 O2 S, (M+Na) 327.11376, found: 327.11506.
3.8. General synthesis procedure for alkyl-acyl piperazine compounds (5l–5w)
Ally piperazine (2c) or cinnamyl piperazine (2d) (10 mmol) and Et3 N (20 mmol) were dissolved in 10 mL
of chloroform. The solution was stirred in an ice bath for 15 min. Then a dilute solution of related acylating
reagents (13 mmol) in CHCl3 was added dropwise. After instillation, the reaction was removed from the ice bath
and allowed to stir overnight. Water was added and crude product was extracted with chloroform. Combined
1
666

SARI et al./Turk J Chem
organic phases were dried over anhydrous Na2 SO4 and evaporated. The crude product was purified by column
chromatography on silica gel using EtOAc-methanol (1:1) as eluent.
3.8.1. (E)-1-(4-Allylpiperazine-1-yl)-3-(5-methylfuran-2-yl)prop-2-en-1-one (5l):
−
1
1
Yield: 1.7 g, 63%. Oily product. IR (ATR): 1001, 1220, 1367, 1428, 1647, 1739, 2360, 2799, 2943 cm
.
H
NMR (400 MHz, CDCl3), δ (ppm): 7.39 (1H, d, J = 14.8 Hz), 6.69 (1H, d, J = 14.8 Hz), 6.44 (1H, d, J = 3.2
Hz), 6.05 (1H, d, J = 3.2 Hz), 5.87 (1H, ddt, J = 17.2, 10, 6 Hz), 5.24 (1H, dd, J = 17.2, 1.2 Hz), 5.20 (1H, dd,
1
3
J = 10, 1.2 Hz), 3.73 (4H, s) 3.06 (2H, d, J = 6.8 Hz), 2.51 (4H, t, J = 5.2 Hz), 2.34 (3H, s). C NMR (100
MHz, CDCl3), δ (ppm): 165.45, 154.47, 150.24, 133.94, 129.87, 118.90, 115.50, 112.40, 108.60, 61.42, 53.16,
+
5
2.58, 45.45, 41.88, 14. HRMS (ESI): (m/z) calcd. for C15 H20 N2 O2 , (M+Na) 283.1417, found: 283.14169.
(
E)-1-(4-Allylpiperazine-1-yl)-3-(thiophen-2-yl)prop-2-en-1-one (5m):
◦
Yield: 1.9 g, 70%. Mp: 64–66 C. IR (ATR): 971, 1223, 1366, 1441, 1582, 1630, 1739, 2359, 2818, 2941
−
1
1
cm
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.80 (1H, d, J = 15.2 Hz), 7.31 (1H, d, J = 5.2 Hz), 7.20 (1H,
d, J = 3.6 Hz), 7.03 (1H, dd, J = 5.2, 3.6 Hz), 6.67 (1H, d, J = 15.2 Hz), 5.87 (1H, ddt, J = 17.2, 10.8, 6 Hz),
.21 (1H, dd, J = 17.2, 1.2 Hz), 5.19 (1H, dd, J = 10.8, 1.2 Hz), 3.70 (4H, s), 3.04 (2H, d, J = 6 Hz), 2.49
5
1
3
(4H, s). C NMR (100 MHz, CDCl3), δ (ppm): 164.96, 140.42, 135.60, 134.13, 130.20, 127.96, 127.15, 118.73,
+
1
15.70, 61.45, 53.16, 52.62, 45.60, 42.02. HRMS (ESI): (m/z) calcd. for C14 H18 N2 OS, (M+Na) 285.10321,
found: 285.10448.
E)-1-(4-Allylpiperazine-1-yl)-3-phenylprop-2-en-1-one (5n):
(
◦
−1
1
Yield: 2.5 g, 90%. Mp: 85–87 C. IR (ATR): 987, 1221, 1436, 1590, 1643, 1739, 2360, 2943 cm
NMR (400 MHz, CDCl3), δ (ppm): 7.66 (1H, d, J = 15.2 Hz), 7.51 (2H, d, J = 1.6 Hz), 7.39–7.33 (3H, m),
.87 (1H, d, J = 15.2 Hz), 5.86 (1H, ddt, J = 17.2, 10.4, 6.4 Hz), 5.23 (1H, dd, J = 17.2, 1.2 Hz), 5.18 (1H,
.
H
6
1
3
dd, J = 10.4, 1.2 Hz), 3.71 (4H, s), 3.03 (2H, dd, J = 6.4, 1.2 Hz) 2.48 (4H, s). C NMR (100 MHz, CDCl3),
δ (ppm): 165.39, 142.69, 135.29, 134.42, 129.56, 128.76, 127.71, 118.48, 117.12, 61.52, 53.24, 52.67, 45.79, 42.13,
+
2
9.66. HRMS (ESI): (m/z) calcd. for C16 H20 N2 O, (M+Na) 279.14678, found: 279.14752.
◦
1
-(4-Allylpiperazine-1-yl)-2-methylprop-2-en-1-one (5o): Yield: 1.48 g, 76%. Mp: 128–130 C.
−
1
1
IR (ATR): 791, 920, 998, 1207, 1368, 1435, 1624, 1739, 2360, 2967 cm
.
H NMR (400 MHz, CDCl3), δ
(
ppm): 5.82 (1H, ddt, J = 17.2, 10, 6 Hz), 5.20 (1H, d, J = 1.2 Hz), 5.16 (2H, m), 5.00 (1H, d, J = 1.2
1
3
Hz), 3.57 (4H, s), 2.99 (2H, dd, J = 6, 1.2 Hz), 2.41 (4H, s), 1.96 (3H, t, J = 1.2 Hz).
C NMR (100 MHz,
CDCl3), δ (ppm): 171.04, 140.42, 134.36, 118.37, 115.27, 61.49, 52.88, 42, 46, 20.44. HRMS (ESI): (m/z) calcd.
+
for C11 H18 N2 O, (M+H) 195.14919, found: 195.14906.
(
2E,4E)-1-(4-Allylpiperazine-1-yl)-5-phenylpenta-2,4-dien-1-one (5p):
Yield: 2.1 g, 76%. Oily product. IR (ATR): 758, 1009, 1227, 1447, 1595, 1636, 1739, 2360, 2792, 3005
−
1
1
cm
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.48–7.42 (3H, m), 7.36–7.26 (3H, m), 6.88 (2H, q, J = 14.4
Hz), 6.44 (1H, d, J = 14.4 Hz), 5.85 (1H, ddt, J = 17.2, 10.4, 6.4 Hz), 5.22 (1H, dd, J = 17.2, 1.2 Hz), 5.19 (1H,
1
3
dd, J = 10.4, 1.2 Hz), 3.73 (2H, s), 3.61 (2H, s), 3.03 (2H, d, J = 6.4 Hz), 2.47 (4H, t, J = 5.2 Hz). C NMR
(
1
100 MHz, CDCl3), δ (ppm): 165.42, 142.88, 138.99, 136.35, 134.39, 128.74, 128.66, 126.97, 126.81, 120.19,
18.53, 61.53, 53.21, 52.68, 45.68, 41.99. HRMS (ESI): (m/z) calcd. for C18 H22 N2 O, (M+H) 283.18049,
+
found: 283.18153.
2E,4E)-1-(4-Allylpiperazine-1-yl)hexa-2,4-dien-1-one (5q):
(
1
667

SARI et al./Turk J Chem
◦
Yield: 2 g, 84%. Mp: 62–64 C. IR (ATR): 923, 1228, 1266, 1421, 1621, 1648, 1739, 2360, 2810, 2958
−
1
1
cm
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.25 (1H, dd, J = 14.8, 10.4 Hz), 6.23–6.04 (3H, m), 5.85
(
2
1
1H, ddt, J = 17.2, 10.4, 6.4 Hz), 5.23–5.16 (2H, m), 3.70 (2H, s), 3.58 (2H, s), 3.01 (2H, d, J = 6.4 Hz),
1
3
.45 (4H, t, J = 5.2 Hz), 1.83 (3H, d, J = 6.4 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 165.71, 143.17,
37.55, 134.27, 130.12, 118.56, 117.68, 61.49, 53.14, 52.66, 45.51, 41.86, 18.53. HRMS (ESI): (m/z) calcd. for
+
C13 H20 N2 O, (M+Na) 243.14678, found: 243.14626.
(
E)-1-(4-Cinnamylpiperazine-1-yl)-3-(5-methylfuran-2-yl)prop-2-en-1-one (5r):
◦
Yield: 3.1 g, 87%. Mp: 122–124 C. IR (ATR): 969, 1212, 1366, 1432, 1647, 1739, 2360, 2801, 2944
−
1
1
cm
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.39 (1H, d, J = 14.8 Hz), 7.37–7.21 (5H, m), 6.69 (1H, d, J =
1
4.8 Hz), 6.53 (1H, d, J = 16 Hz), 6.42 (1H, d, J = 3.2 Hz), 6.26 (1H, dt, J = 16, 6.8 Hz), 6.04 (1H, d, J = 3.2
1
3
Hz), 3.75 (2H, s), 3.60 (2H, s), 3.18 (2H, d, J = 6.8 Hz), 2.52 (4H, t, J = 4.8 Hz), 2.33 (3H, s). C NMR (100
MHz, CDCl3), δ (ppm): 165.46, 154.44, 150.29, 136.70, 133.51, 129.82, 128.59, 127.64, 126.33, 115.44, 112.53,
+
1
3
08.60, 60.89, 53.44, 52.86, 45.66, 42.11, 13.86. HRMS (ESI): (m/z) calcd. for C21 H24 N2 O2 , (M+Na)
59.173, found: 359.17447.
(
E)-1-(4-Cinnamylpiperazine-1-yl)-3-(thiophen-2-yl)prop-2-en-1-one (5s): Yield: 2.9 g, 81%.
◦
−1
1
Mp: 111–113 C. IR (ATR): 965, 1208, 1230, 1421, 1587, 1629, 2152, 2941 cm
.
H NMR (400 MHz,
CDCl3), δ (ppm): 7.80 (1H, d, J = 14.8 Hz), 7.38–7.20 (7H, m), 7.02 (1H, dd, J = 5.2, 3.6 Hz), 6.67 (1H, d, J
=
=
14.8 Hz), 6.53 (1H, d, J = 16.4 Hz), 6.25 (1H, dt, J = 16.4, 7.2 Hz), 3.70 (2H, s), 3.60 (2H, s), 3.18 (2H, d, J
1
3
7.2 Hz), 2.53 (4H, t, J = 4.8 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 165.01, 140.47, 136.70, 135.60,
1
33.52, 130.20, 128.60, 127.98, 127.64, 127.14, 126.33, 125.89, 115.76, 60.88, 53.44, 52.86, 44.1. HRMS (ESI):
+
(m/z) calcd. for C20 H22 N2 OS, (M+Na) 361.13451, found: 361.13598.
(
E)-1-(4-Cinnamylpiperazine-1-yl)-3-phenylprop-2-en-1-one (5t):
◦
−1
1
Yield: 3 g, 87%. Mp: 104–106 C. IR (ATR): 978, 1226, 1428, 1648, 1738, 2358, 2949 cm
.
H NMR
(
(
(
400 MHz, CDCl3), δ (ppm): 7.67 (1H, d, J = 15.2 Hz), 7.51 (2H, dd, J = 7.6, 2 Hz), 7.39–7.22 (8H, m), 6.87
1H, d, J = 15.2 Hz), 6.54 (1H, d, J = 16 Hz), 6.26 (1H, dt, J = 16, 6.8 Hz), 3.73 (2H, s), 3.62 (2H, s), 3.19
1
3
2H, d, J = 6.8 Hz), 2.54 (4H, t, J = 4.8 Hz). C NMR (100 MHz, CDCl3), δ (ppm): 165.40, 142.75, 136.70,
1
35.29, 133.50, 129.57, 128.77, 128.60, 127.73, 127.65, 126.33, 125.91, 117.11, 60.89, 53.40, 52.86, 45.85, 42.17.
+
HRMS (ESI): (m/z) calcd. for C22 H24 N2 O, (M+Na) 355.17918, found: 355.17952.
(
E)-1-(4-Cinnamylpiperazine-1-yl)-2-methylprop-2-en-1-one (5u):
◦
Yield: 2.7 g, 94%. Mp: 100–102 C. IR (ATR): 748, 996, 1133, 1209, 1367, 1436, 1618, 1739, 2362, 3003
−
1
1
cm
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.36–7.35 (2H, m), 7.34–7.19 (3H, m), 6.5 (1H, d, J = 16 Hz),
6
=
.22 (1H, dt, J = 16, 6.8 Hz), 5.15 (1H, t, J = 1.6 Hz), 5.00 (1H, t, J = 1.2 Hz), 3.60 (4H, s), 3.15 (2H, dd, J
6.4, 1.2 Hz), 2.46 (4H, s), 1.93 (3H, t, J = 1.6 Hz). C NMR (100 MHz, CDCl3), δ (ppm): 171.09, 140.33,
1
3
1
36.64, 133.53, 128.57, 127.64, 126.32, 125.78, 115.40, 60.87, 53.45, 52.78, 46.85, 41.30, 20.5. HRMS (ESI):
+
(m/z) calcd. for C17 H22 N2 O, (M+Na) 293.16243, found: 293.16291.
(
2E,4E)-1-(4-Cinnamylpiperazine-1-yl)-5-phenylpenta-2,4-dien-1-one (5v):
◦
Yield: 2.8 g, 75%. Mp: 120–121 C. IR (ATR): 787, 1000, 1241, 1437, 1596, 1640, 1738, 2359, 2803,
945 cm
−
1
1
2
.
H NMR (400 MHz, CDCl3), δ (ppm): 7.49–7.22 (11H, m), 6.91 (1H, d, J = 14.8 Hz), 6.87 (1H,
d, J = 14.8 Hz), 6.53 (1H, d, J = 15.6 Hz), 6.44 (1H, d, J = 14.8 Hz), 6.26 (1H, dt, J = 15.6, 7.2 Hz), 3.68
1
668

SARI et al./Turk J Chem
1
3
(4H, s), 3.18 (2H, d, J = 7.2 Hz), 2.52 (4H, t, J = 5.2 Hz).
C NMR (100 MHz, CDCl3), δ (ppm): 165.44,
1
6
3
42.94, 139.03, 136.68, 136.35, 133.57, 128.76, 128.68, 128.61, 127.68, 126.99, 126.81, 126.35, 125.82, 120.17,
0.88, 53.33, 52.85, 45.68, 42.03. HRMS (ESI): (m/z) calcd. for C24 H26 N2 O, (M+Na) 381.19373, found:
81.19241.
+
(
2E,4E)-1-(4-Cinnamylpiperazine-1-yl)hexa-2,4-dien-1-one (5w):
◦
−1
Yield: 2.5 g, 81%. Mp: 85–87 C. IR (ATR): 787, 1048, 1242, 1433, 1617, 1734, 2359, 2764, 2907 cm
.
1
H NMR (400 MHz, CDCl3), δ (ppm): 7.36–7.18 (6H, m), 6.49 (1H, d, J = 15.6 Hz), 6.22 (1H, dt, J = 15.6,
7
Hz).
.2 Hz), 6.18–6.00 (3H, m), 3.61 (4H, s), 3.13 (2H, d, J = 7.2 Hz), 2.46 (4H, t, J = 5.2 Hz), 1.80 (3H, d, J = 6.8
1
3
C NMR (100 MHz, CDCl3), δ (ppm): 165.70, 143.15, 137.50, 136.69, 133.40, 130.16, 128.57, 127.61,
1
26.31, 125.96, 117.75, 60.85, 53.31, 52.85, 45.61, 41.97, 18.55. HRMS (ESI): (m/z) calcd. for C19 H24 N2 O,
+
(M+Na) 319.17808, found: 319.17952.
Acknowledgments
The authors are indebted to the Scientific and Technological Research Council of Turkey (TÜBİTAK, TBAG-
1
16Z455) and Kocaeli University BAP (2018/056). Sait Sarı thanks TÜBİTAK for doctoral fellowship.
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671

SUPPLEMENTARY INFORMATION
Synthesis and characterization of unsaturated diacyl and alkyl-acyl
piperazine derivatives
Sait SARI, Seda ÜNALAN, Mehmet YILMAZ*
Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, 41380
Umuttepe, Kocaeli, Turkey
*
Correspondence: mehmet.yilmaz@kocaeli.edu.tr
1
13
H-NMR and C-NMR spectra
1
1
b. H-NMR
1

1
18
3a. H-NMR
1
3
b. H-NMR
2

1
3
c. H-NMR
1
3
d. H-NMR
3

1
3
e. H-NMR
1
3
f. H-NMR
4

1
3
3
f. C-NMR
1
3
g. H-NMR
5

1
4
a. H-NMR
1
4
b. H-NMR
6

1
4
c. H-NMR
1
3
4
c. C-NMR
7

1
4
d. H-NMR
1
5
a. H-NMR
8

1
3
5
a. C-NMR
,
0
1
5
b. H-NMR
9

1
3
5
b. C-NMR
1
5
c. H-NMR
1
0

1
3
5
c C-NMR
1
5
d. H-NMR
1
1

1
3
5
d. C-NMR
1
5
e. H-NMR
1
2

5
e. 13C-NMR
1
5
f. H-NMR
1
3

1
3
5
f. C-NMR
1
5
g. H-NMR
1
4