Triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcones: Synthesis of 3-(2-aminoethylthio)-1-(aryl)-3-(thiophen-2-yl) propan-1-ones and 5,7-diaryl-2,3,6, 7-tetrahydro-1,4-thiazepines

Article abstract of DOI:10.1080/00397911.2016.1152585

The triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcone analogs was investigated. This addition, bearing a 2-thienyl group at the 3-position, gave the only addition adduct at room temperature in 3 h, whereas the chalcones bearing the 2-furyl group at the 1-position gave an addition-cyclization product (1, 4-thiazepine) in the same conditions. The effect of the groups to the reaction was investigated by changing the 1- and 3-position groups. The chalcones bearing the 2-thienyl group at the 1-position and the others afforded the mixture of products in different ratio at rt for 0.5-24 h. Moreover, the addition-cyclization products (1,4-thiazepine) were obtained under reflux conditions in 36 h. The structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, infrared, and elemental analysis.

Full text of DOI:10.1080/00397911.2016.1152585

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Triethylamin-Mediated Addition of 2-
aminoethanethiol Hydrochloride to Chalcones:
Synthesis of 3-(2-aminoethylthio)-1-(Aryl)-3-
(Thiophen-2-yl) Propan-1-ones and 5,7-
diaryl-2,3,6,7-tetrahydro-1,4-thiazepines
Meliha Burcu Gürdere, Ali Cemal Emeç, Osman Nuri Aslan, Yakup Budak &
Mustafa Ceylan
To cite this article: Meliha Burcu Gürdere, Ali Cemal Emeç, Osman Nuri Aslan, Yakup
Budak & Mustafa Ceylan (2016): Triethylamin-Mediated Addition of 2-aminoethanethiol
Hydrochloride to Chalcones: Synthesis of 3-(2-aminoethylthio)-1-(Aryl)-3-(Thiophen-2-yl)
Propan-1-ones and 5,7-diaryl-2,3,6,7-tetrahydro-1,4-thiazepines, Synthetic Communications,
DOI: 10.1080/00397911.2016.1152585
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1152585
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Date: 23 February 2016, At: 04:30

Triethylamin-Mediated Addition of 2-Aminoethanethiol hydrochloride to
Chalcones: Synthesis of 3-(2-Aminoethylthio)-1-(aryl)-3-(thiophen-2-yl) propan-1-
ones and 5,7-Diaryl-2,3,6,7-tetrahydro-1,4-thiazepines
Meliha Burcu Gürdere1,, Ali Cemal Emeç1, Osman Nuri Aslan1, Yakup Budak1, Mustafa
Ceylan1
1Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa University,
Tokat, Turkey
Corresponding author, E-mail: burcu.gurdere@gop.edu.tr
Abstract
The triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcone
analogues was investigated. This addition - bearing a 2-thienyl group at the 3-position
gave the only addition adduct at room temperature for 3 hours, whereas the chalcones
bearing the 2-furyl group at the 1-position gave an addition-cyclization product (1, 4-
thiazepine) in the same conditions. The effect of the groups to the reaction was
investigated by changing the 1- and 3-position groups. The chalcones bearing the 2-
thienyl group at the 1-position and the others afforded the mixture of products in different
ratio at r.t. for 0.5-24 hours. Moreover, the addition-cyclization products (1, 4-thiazepine)
were obtained under reflux conditions for 36 hours. The structures of the synthesized
compounds were elucidated by 1H NMR, 13C NMR, IR, and the elemental analysis.
1

KEYWORDS: 1,4-thiazephines, Chalcones, Triethylamin, 2-aminoethanethiol
hydrochloride
1. INTRODUCTION
1, 4-Thiazepinones and 1, 4-thiazepines are important compounds whose biological and
pharmacological properties have received much attention.1,2 1,4-Thiazepinones
derivatives such as 1,4-thiazepin-5-one3,4 and -2,4-dione5 have been developed for the
treatment of cancer, heart and inflammatory diseases. Most of these derivatives act as an
enzyme inhibitor.6-8 For the synthesis of these compounds, there have been are various
methods developed such as addition,9 condensation,10 coupling11,12 and rearrangement.13
For example, some 1,4-thiazepin-5-ones have been obtained from the ring expansion of
acetylenic thiazoles.3 Highly functionalized 2,3,4,7-tetrahydro[1,4]thiazepines have been
synthesized from the addition-condensation of sodium 2,2-dicyanoethene-1,1-
bis(thiolate) to 2-chloroethylamine hydrochloride in water6 and from thiazolidines and -
enaminonitriles.1 However, 5,7-disubstituted-2,3,6,7-[1,4] thiazepine derivatives have
generally been synthesized by the thia-Michael addition of 2-aminoethanethiol to
2
-

unsaturated carbonyls.14 According to our knowledge, a few studies have reported on the
relationship to the thia-Michael addition of 2-aminoethanethiol (1) to chalcone.15,16 It has
also previously been reported that the reaction of 2-aminoethanethiol (1) with chalcone in
benzene gives a mixture of two mono-adducts (2 and 3) or a bisadduct (1,4-thiazepine)
(4), depending on the molar ratios used.17 Recently, Kodomari et al. have reported18 that
when the reaction was carried out in the presence of silica-gel under solvent-free
condition, the a cyclization product (1,4-thiazepine) (4), was obtained as a sole product,
but only one example was reported.
In this paper, we revisited the thia-Michael addition of 2-aminoethanethiol hydrochloride
(5) to chalcones. The triethylamin-mediated addition of 2-aminoethanethiol
hydrochloride (5) to particular chalcones bearing 2-thienyl and 2-furyl groups at the 1-
and/or 3-position and synthesis of the novel mono adduct products (3-(2-
Aminoethylthio)-1-(aryl)-3-(thiophen-2-yl)propan-1-ones) (9a-o) and the novel (5,7-
diaryl-2,3,6,7-tetrahydro-1,4-thiazepines) (10a-o) are reported.
2. RESULTS AND DISCUSSION
The starting compounds (chalcone analogues) (8a-o) were obtained by base-catalyzed
condensation of the appropriately substituted acetophenone, 2-furyl methyl ketone and 2-
thienyl methyl ketone with substituted benzaldehydes, furfural, and thiophene-2-
3

carbaldehyde in the presence of NaOH in EtOH at room temperature in yields of 82–
98%.19 The structures of all the synthesized chalcone derivatives were assigned on the
basis of spectroscopic (IR, 1H-, 13C-NMR and elemental analysis) data, and comparison
with their authentic sample.20,21
In the second stage of study, the in thia-Michael additions (1,4-addition) of 2-
aminoethanethiol hydrochloride (5) to chalcone analogues (8a-o) was investigated. The
reaction between chalcone (8a) and 2-aminoethanethiol hydrochloride (5) was chosen as
the model reaction (Scheme 2) in order to determine optimum conditions. The results are
summarized in Table 1. When the reaction was performed in the solvent (such as
CH3OH, THF, DMSO and CH2Cl2) without catalyst (entries 1-6, Table 1), and aqueous
NaOH (as a catalyst) in CH3OH (entry 7, Table 1), the addition failed. In the case of
CH2Cl2 aqueous NaOH or KOH and CH2Cl2, I2, TEA (triethylamine) at r.t for 3h. and/or
CH2Cl2, I2, TEA under the reflux condition for 3h, the addition product, 3-(2-
aminoethylthio)-1-(4-methoxyphenyl)-3-(thiophen-2-yl)propan-1-one (9a), was occurred
but chalcone (8a) was unconsumed and the product rates determined from the 1H NMR
spectrum was given in Table 1 (entries 8-12). When the reaction was performed in
CH2Cl2 in the presence of TEA at room temperature for 3 hours, the adduct 9a was
obtained as the sole product in yield of 91% (entry 13, Table 1). The reaction was
continued for 24 hours at r.t.; and obtained the mixture of products at a ratio of 3:1 (entry
14, Tab. 1). The same reaction was repeated under reflux conditions for 3, 24 and 36
hours. The mixtures of products (9a and 10a) were obtained at a ratio of 2.5:1 and 1:1.5
for 3 and 24 hours, respectively, (entry 15, 16, Tab. 1). Finally, refluxing for 36 hours
4

afforded the only addition-cyclization product (E)-5-(4-methoxyphenyl)-7-(thiophen-2-
yl)-2,3,6,7-tetrahydro-1, 4-thiazepine (10a) in a good yield (86%) (Entry 17, Tab.1).
After the optimized conditions, we continued with the reactions with the other chalcones
(8b-o). The reaction of chalcones 8a-e, bearing 2-thienyl group at the 3-position, with 2-
aminoethanethiol hydrochloride (5) in the presence of TEA in CH2Cl2 at room
temperature for 3 hours gave the only addition products, 3-(2-aminoethylthio)-1-(aryl)-3-
(thiophen-2-yl)propan-1-one 9a-e, (Scheme 3; entry 1-5, Table 2).
The reaction of the chalcones 8l-o, bearing 2-furyl group at the 1-position, with 5 was
surprising. The addition of 5 to chalcones 8l-o in the same conditions gave the only
cyclisation products, (E)-5-(aryl)-7-(thiophen-2-yl)-2,3,6,7-tetrahydro-1,4-thiazepine 10l-
o, (Scheme 3; entry 12-15, Table 2).
In order to investigate the effect of the groups to the reaction, the reactions were
continued by changing the 1- and 3-position groups. Chalcones 8f-i (bearing 2-thienyl
group at the 1-position and phenyl, 4-MeOPh, 4-ClPh and 2-thienyl group at the 3-
position, respectively) and chalcones 8j, k (bearing 2-furyl and phenyl group both at the
1- and 3-position, respectively) were submitted to the reaction with 2-aminoethanethiol
hydrochloride (5) in the presence of TEA in CH2Cl2 at room temperature. The reactions
were monitored by TLC and NMR. After 0.5-3 hours, it was observed that the mixture of
products (9 and 10) occurred approximately at a ratio of 7:1, respectively, and the
obtained yields from the 1H NMR were given (Scheme 3, entry 6-11, Table 2) (entries 6-
5

11). The reactions were stopped after 0.5-3 hours for separation of products (9f-k) from
the mixture. The mixture was submitted on a silica gel column and eluting with n-
hexane/CH2Cl2 (3:1). During chromatography, it is observed that the product 9 converted
to starting chalcone by elimination of 2-aminoethanethiol, so some of the products 9f-k
could not be isolated as purely.
Then, the same reactions were repeated in the same conditions for 24 hours, and the
mixture of products (9 and 10) occurred as an approximately ratio of 1:4, respectively,
(Scheme 3, entry 6-11, Table 2).
Finally, the chalcones (8a, b, 8d, 8f-i and 8k) were reacted with 2-aminoethanethiol
hydrochloride (5) under reflux conditions for 36 hours to obtain the addition-cyclization
products (1,4-thiazepines) (10a, b, 10d, 10f-i, and 10k) (Scheme 3, entry 16-23, Table 2).
After the reactions were completed, the addition-cyclization products (10a, b, 10d, 10f-i
and 10k) were obtained as a sole product in high yields (Scheme 3, entry 16-23, Table 2).
All the synthesized compounds, except for 9k and 10k, are novel as our literature
surveys. The structures of all the synthesized compounds were determined on the basis of
spectral and literature data. All the spectral data are in good agreement with the proposed
structures.
After all these results, we observed that the addition of 2-aminoethanethiol to the thienyl
group containing, particularly 1-position, chalcones gave the addition products at room
6

temperature and the short reaction times. On the contrary, the furyl group containing
chalcones gave the addition-cyclization products in the same conditions. This situation
can be explained by the electronic interactions. For this, we calculated some parameters
of the model compounds A-D as theoretically. The theoretical calculations (HyperChem
7.05 Semi-empirical (AM1), Molecular Mechanic (MM+)) showed that compounds C
and D are more stable than compounds A and B (Table 3). According to the results, it can
be said that the repulsion between sulfur atoms and/or sulphur and nitrogen atom is
greater than the repulsion between oxygen atoms and/or oxygen and nitrogen atom. The
strong repulsion in the molecules A and B are increased to the strain energy and the heat
of formation of them. Thus cyclization cannot occur at room temperature and short
reaction times.
3. CONCLUSIONS
In summary, the triethylamin-mediated addition of 2-aminoethanethiol hydrochloride (5)
to chalcone analogues was investigated. The addition of 2-aminoethanethiol
hydrochloride (5) to chalcones (8a-e) bearing 2-thienyl group at the 3-position gave the
only addition adduct (9a-e) at room temperature for 3 hours, whereas the chalcones (8l-o)
bearing 2-furyl group at the 1-position gave the addition-cyclization product (10l-o) (1, 4-
thiazepine) in the same conditions. The effect of the groups to the reaction was
investigated by changing the 1- and 3-position groups. The chalcones bearing 2-thienyl
group at the 1-position, and the others, afforded the mixture of products a different ratio
at r.t. for 0.5-24 hours. Further, the addition-cyclization products (1, 4-thiazepine) were
obtained under reflux conditions for 36 hours.
7

4. EXPERIMENTAL
All the chemicals and solvents employed in the synthesis were supplied by Merck
(Germany) and Fluka (Germany) and used without purification. The melting points were
measured on an Electrothermal 9100 apparatus. The IR spectrums (KBr disc or CHCl3)
were recorded on a Jasco FT/IR-430 spectrometer. The 1H and 13C NMR spectra were
recorded on a Bruker Avance DPX-400 instrument. As internal standards served TMS (
0.00) for 1H NMR and CDCl3 ( 77.0) for 13C NMR spectroscopy J values are given in
Hz. The multiplicities of the signals in the 1H NMR spectra are abbreviated by s (singlet),
d (doublet), t (triplet), q (quarted), m (multiplet), br (broad) and combinations thereof.
The elemental analyses were obtained from a LECO CHNS 932 Elemental Analyzer.
4.1. General Procedure For The Synthesis Of 9a-E
The chalcone derivatives (1 equiv.) were dissolved in CH2Cl2 and stirred at room
temperature for 5 min. To a stirred solution of chalcone were added to the solution of 2-
aminoethanethiol hydrochloride (1.2 equiv.) and trimethylamine (1.2 equiv.) in 10 mL
CH2Cl2 for a period of 15 min. The mixture was stirred at room temperature for 3 h. The
progress of the reaction was followed by TLC. The reaction mixture was then diluted
with water and extracted with CH2Cl2. Subsequently, the organic layer was dried over
anhydrous sodium sulfate. The evaporating of the solvent under reduced pressure gave
the corresponding solid products. The crude products were purified by recrystallization
from n-hexane-CH2Cl2.
8

4.1.1. 3-(2-Aminoethylthio)-1-(4-Methoxyphenyl)-3-(Thiophen-2-Yl)Propan-1-One
(9a)
Yellow crystals, Yield (91%); mp: 106-1080C. IR (KCl cm-1): 3286, 3100, 2974, 2928,
2376, 1660, 1585, 1467, 1423, 1365, 1312, 1201, 1056, 1002, 965, 812, 715, 580. 1H-
NMR (400 MHz, DMSO-d6) (ppm): 7.98 (d, J = 8.8 Hz, 2H, AA’), 7.42 (dd, J = 5.2,
1.2 Hz, 1H), 7.13 (d, J = 3.6 Hz, 1H), 7,05 (d, J = 8.8 Hz, 2H, XX’), 6.93 (dd, J = 5.2, 3.6
Hz, 1H), 4.85 (t, J = 6.8 Hz, 1H), 3.84 (s, 3H), 3.71 (dd, J = 17.2, 8.0 Hz, 1H, A), 3.60
(dd, J = 17.2, 6.4 Hz, 1H, B), 3.35 (s ,–NH2), 2.95-2.85 (m, 2H), 2.75-2.65 (m, 2H). 13C-
NMR (100 MHz, DMSO-d6) (ppm): 195.2, 163.8, 146.5, 140.9, 130.9 (2C), 127.1,
126.4, 125.7, 114.4 (2C), 56.1, 45.2, 38.9, 28.4; 21.8. Anal. Cald for C16H19NO2S2: C,
59.78; H, 5.96; N, 4.36; S, 19.95. Found: C, 59.77; H, 5.74; N, 4.23; S, 19.89.
4.2. General Procedure For The Synthesis Of 9f-K
The chalcone derivatives (1 equiv.) were dissolved in CH2Cl2 and stirred at room
temperature for 5 min. To a stirred solution of chalcone were added to the solution of 2-
aminoethanethiol hydrochloride (1.2 equiv.) and trimethylamine (1.2 equiv.) in 10 mL
CH2Cl2 for a period of 15 min. The mixture was stirred at room temperature for 0.5 or 3
h. The progress of the reaction was followed by TLC. After 0.5-3 hours, the reaction
mixture was diluted with water and extracted with CH2Cl2. Subsequently, the organic
layer was dried over anhydrous sodium sulfate. The evaporating of the solvent under
reduced pressure gave the corresponding solid products. The crude products were
subjected to on a silica gel column.
9

4.2.1. 3-((2-Aminoethyl)Thio)-3-Phenyl-1-(Thiophen-2-Yl)Propan-1-One (9f)
Viscous oil, Yield (58%). IR (KCl cm-1): 3075, 3026, 2929, 2843, 2030, 1652, 1617,
1540, 1517, 1490, 1450, 1433, 1414, 1352, 1330, 1278, 1232, 1217, 1182, 1065, 1044.
1H-NMR (400 MHz, CDCl3) (ppm): 7.70 (d, J = 3.6, 1H), 7.62 (d, J = 4.8 Hz, 1H),
7.43-7.41 (m, 2H), 7.34-7.29 (m, 2H), 7.23 (dd, J = 4.8, 3.6 Hz, 1H), 7.11-7.09 (m, 1H),
4.54 (t, J = 7.2 Hz, 1H), 3.55-3.39 (m, 2H), 2.82-2.71 (m, 2H), 2.51-2.39 (m, 2H), 1.32
(bs, 2H, -NH2). 13C-NMR (100 MHz, CDCl3) (ppm): 186.8, 142.5, 130.2, 128.9, 128.5,
128.2, 128.1, 127.9, 127.8, 127.5, 127.1, 55.8, 42.0, 36.6, 29.5. Anal. Cald for
C15H17NOS2: C, 61.82; H, 5.88; N, 4.81; S, 22.01. Found: C, 61.76; H, 5.79; N, 4.69; S,
21.98.
4.3. General Procedure For The Synthesis Of 10a, B, 10d, 10f-I And 10k:
The chalcone derivatives (1 equiv.) were dissolved in CH2Cl2 and stirred at room
temperature for 5 min. To a stirred solution of chalcone were added to the solution of 2-
aminoethanethiol hydrochloride (1.2 equiv.) and trimethylamine (1.2 equiv.) in 10 mL
CH2Cl2 for a period of 15 min. The mixture was stirred at reflux temperature for 36 h.
The progress of the reaction was followed by TLC. The reaction mixture was then diluted
with water and extracted with CH2Cl2. Subsequently, the organic layer was dried over
anhydrous sodium sulfate. The evaporating of the solvent under reduced pressure gave
the corresponding solid products. The crude products were purified by recrystallization
from n-hexane-CH2Cl2.
10

4.3.1. 5-(4-Methoxyphenyl)-7-(Thiophen-2-Yl)-2,3,6,7-Tetrahydro-1,4-Thiazepine
(10a)
Colorless crystals, Yield (86%); mp: 154-1570C. IR (KCl cm-1): 3070, 2926, 2847, 2035,
1891, 1615, 1581, 1511, 1455, 1423, 1353, 1317, 1300, 1246, 1180, 1109, 1081, 1066,
1
1027. H-NMR (400 MHz, CDCl3) (ppm): 7.42 (d, J = 4.8 Hz, 1H), 7.33 (d, J = 8.4
Hz, 2H, AA’), 7.20 (d, J = 3.6 Hz, 1H),7.02 (dd, J = 4.8, 3.6 Hz, 1H), 6.91 (d, J = 8.4
Hz, 2H, XX’), 4.47 (dd, J = 10.8, 6.0 Hz, 1H), 4.17-4.11 (dd, J = 12.6, 10.0 Hz, 1H),
3.95 (d, J = 10.4 Hz, 1H), 3.84 (s, 3H), 3.79-3.73 (dd, J = 14.4, 10.4 Hz, 1H), 3.56 (d, J
= 14.0 Hz, 1H), 3.04-2.98 (dd, J = 14.8, 9.2 Hz, 1H), 2.72-2.67 (dd, J = 14.6, 6.4 Hz,
1H). 13C-NMR (100 MHz, CDCl3) (ppm): 166.1, 159.1, 146.8, 134.6, 130.2, 128.2
(2C), 127.7, 127.5, 114.2 (2C), 55.3, 54.5, 42.2, 41.3, 29.6. Anal. Cald for C16H17NOS2:
C, 63.33; H, 5.65; N, 4.62; S, 21.13. Found: C, 63.16; H, 5.58; N, 4.49; S, 21.08.
4.4. General Procedure For The Synthesis Of 10l-O
The chalcone derivatives (1 equiv.) were dissolved in CH2Cl2 and stirred at room
temperature for 5 min. To a stirred solution of chalcone were added to the solution of 2-
aminoethanethiol hydrochloride (1.2 equiv.) and trimethylamine (1.2 equiv.) in 10 mL
CH2Cl2 for a period of 15 min. The mixture was stirred at room temperature for 3 h. The
progress of the reaction was followed by TLC. The reaction mixture was then diluted
with water and extracted with CH2Cl2. Subsequently, the organic layer was dried over
anhydrous sodium sulfate. The evaporating of the solvent under reduced pressure gave
the corresponding solid products. The crude products were purified by recrystallization
from n-hexane-CH2Cl2.
11

4.4.1. (E)-5-(Furan-2-Yl)-7-(4-Methoxyphenyl)-2,3,6,7-Tetrahydro-1,4-Thiazepine
(10l)
Colorless crystals, Yield (98%); mp: 121-123 0C. IR (KCl cm-1): 3100, 3073, 2974, 2925,
2845, 1639, 1596, 1568, 1503, 1461, 1409, 1241, 1196, 1165, 1009, 819, 763, 491. 1H-
NMR (400 MHz, CDCl3) (ppm): 7.49 (m, 1H), 7.30 (d, J = 8.4 Hz, 2H, AA’), 6.86 (d, J
= 8.4 Hz, 2H, BB’), 6.68 (d, J = 3.6 Hz, 1H), 6.41 (dd, J = 3.2, 2.0 Hz, 1H), 4.50 (dd, J =
12.4, 6.4 Hz, 1H), 4.12 (t, J = 12 Hz, 1H), 3.87 (d, J = 6.4 Hz, 1H), 3.74 (s, 3H, -OCH3),
3.63 (t, J = 6.4 Hz, 1H), 3.39 (d, J = 14.0 Hz, 1H), 2.96 (dd, J = 14.0, 10.0 Hz, 1H), 2.65
(dd, J = 14.0, 6.8 Hz, 1H). 13C-NMR (100 MHz, CDCl3) (ppm): 161.8, 159.0, 153.2,
145.1, 134.5, 128.4 (2C), 118.8 (2C), 114.1, 111.7, 55.3, 55.2, 41.5, 41.4, 29.5. Anal.
Cald for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87; S, 11.16. Found: C, 66.74; H, 5.88; N,
4.80; S, 11.08.
ACKNOWLEDGEMENT
The authors are indebted to the Gaziosmanpasa University, Scientific Research Projects
Commission (Project No: BAP2009/31) for financial supports.
SUPPLEMENTAL MATERIAL
Experimental procedures, characterization data, and NMR spectra of all compounds for
this article can be accessed on the publisher’s website.
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12

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15

Table 1. Optimization studies of reaction condition
Entry Chalcon HS(CH2)2HN3 Solvent,
Temp. Time Products
e
Cl (equiv.)
Catalyst
(h)
9a:10a:8a
(equiv.)
1
2
3
4
5
6
7
1
1
1
1
1
1
1
1
CH3OH
CH3OH
CH3OH
DMSO
THF
r.t
r.t
ref.
r.t
r.t
r.t
r.t
3
-
-
-
-
-
-
-
1
24
3
1
1
3
1
3
1
CH2Cl2
CH3OH,
NaOH
3
1.2
12
8
1
1
1
1
1
1
1.2
2
CH2Cl2,
KOH
r.t
r.t
r.t
r.t
ref.
r.t
3
3:0:1
9
CH2Cl2,
KOH
3
2:0:1
10
11
12
13
2
CH2Cl2,
KOH
24
3
1:0:1.5
3:0:1
1.2
1.2
1.2
CH2Cl2,
I2,TEA
CH2Cl2,
I2,TEA
CH2Cl2,
3
2:0:1
3
9a (91%)
16

TEA
14
15
16
17
1
1
1
1
1.2
1.2
1.2
1.2
CH2Cl2,
TEA
r.t
24
3
3:1:0
CH2Cl2,
TEA
ref.
ref.
ref.
2:1:0
CH2Cl2,
TEA
24
36
1:1.5:0
10a (86%)
CH2Cl2,
TEA
-Not reaction
17

Table 2. Synthesized compounds 9 and 10
Entry
Chalcone Ar
Ar’
Temp.
Time
(h)
Product (yield)
9
10
-
1
4-
2-thienyl r.t.
3
9a (91)
8a
CH3OPh
4-ClPh
4-BrPh
2
3
4
5
6
2-thienyl r.t.
2-thienyl r.t.
3
9b (89)
9c (82)
9d (86)
9e (89)
9f (59)
9f (15)
-
8b
8c
8d
8e
8f
3
-
4-CH3Ph 2-thienyl r.t.
4-HOPh 2-thienyl r.t.
3
-
3
-
2-thienyl Ph
r.t.
0.5-3
24
10f (9)
10f (60)
7
8
2-thienyl 4-
r.t.
0.5-3
9g (63) 10g (9)
8g
8h
CH3OPh
24
9g (14) 10g (62)
2-thienyl 4-ClPh
r.t.
0.5-3
9h (70)
9h (16)
10h
(10)
24
10h
(64)
9
2-thienyl 2-thienyl r.t.
0.5-3
24
9i (60)
9i (13)
9j (57)
9j (12)
10i (8)
10i (55)
10j (8)
10j (54)
8i
8j
10
2-furyl
2-furyl
r.t.
0.5-3
24
18

11
Ph
Ph
r.t.
0.5-3
9k (74)
8k
10k
(11)
24
3
9k (12)
10k
(76)
12
13
14
2-furyl
2-furyl
2-furyl
4-
r.t.
r.t.
r.t.
-
-
-
10l (98)
8l
CH3OPh
4-ClPh
3
8m
8n
10m
(84)
4-BrPh
3
10n
(89)
15
16
2-furyl
4-
4-CH3Ph r.t.
2-thienyl ref.
3
-
-
10o (94)
10a (86)
8o
8a
36
CH3OPh
4-ClPh
17
18
2-thienyl ref.
36
36
-
-
8b
8d
10b
(89)
4-CH3Ph 2-thienyl ref.
10d
(93)
19
20
2-thienyl Ph
2-thienyl 4-
ref.
ref.
36
36
-
-
10f (83)
10g (94)
8f
8g
CH3OPh
2-thienyl 4-ClPh
21
22
ref.
36
36
-
-
8h
8i
10h
(84)
2-thienyl 2-thienyl ref.
19
10i (85)

23
Ph
Ph
ref.
36
-
8k
10k
(95)
20

Table 3. The Calculated Total Energy (TE), Bonding Energy (BE), Heats of Formation
(Hf) and Strain Energy (SE) for Compounds A, B, C and D
Compd. TE (kcal/mol) BE (kcal/mol) Hf (kcal/mol) SE (kcal/mol)
A
B
C
D
-73732.88
-73731.74
-76617.15
-76616.64
-3886.83
-3885.74
-3903.86
-3902.35
38.69
39.59
15.63
16.14
29.98
29.29
25.45
24.30
21

Scheme 1. Synthesis of chalcone analogues
22

Scheme 2. Reaction of chalcone (8a) with 2-aminoethanethiol hydrochloride (5)
23

Scheme 3. Synthetic routes of compounds 9a-o and 10a-o
24