Rapid and efficient synthesis of new deoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwaves

Article abstract of DOI:10.2174/157017811796505016

An efficient and simple method for the synthesis of new deoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave irradiation has been developed. Its main advantages are short reaction times, good conversions, highly selective and the environment friendly nature of the process. Their structures were elucidated by IR, ¹H NMR, ESI-Mass and elemental analyses. The preliminary results indicate that some of these compounds possess inhibitory effects against Escherichia coli.

Full text of DOI:10.2174/157017811796505016

Letters in Organic Chemistry, 2011, 8, 515-519
515
Rapid and Efficient Synthesis of New Deoxycholic Acid Thiosemicarba-
zone Derivatives under Solvent-Free Conditions using Microwaves
Zhi-Chuan Shi, Zhi-Gang Zhao*, Xing-Li Liu and Li-Ying Qiu
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu
610041, P.R. China
Received July 05, 2010: Revised April 30, 2011: Accepted June 06, 2011
Abstract: An efficient and simple method for the synthesis of new deoxycholic acid thiosemicarbazone derivatives under
solvent-free conditions using microwave irradiation has been developed. Its main advantages are short reaction times,
good conversions, highly selective and the environment friendly nature of the process. Their structures were elucidated by
1
IR, H NMR, ESI-Mass and elemental analyses. The preliminary results indicate that some of these compounds possess
inhibitory effects against Escherichia coli.
Keywords: Antimicrobial activity, deoxycholic acid, microwave irradiation, solvent-free, steroids, thiosemicarbazone.
1. INTRODUCTION
under microwave irradiation (MWI) in solvent-free condi-
tions using neutral aluminum oxide as a mineral support. The
synthetic route is depicted in Scheme 1.
The biological activity of thiosemicarbazones was ex-
ploited in the 1960s using 1-methylisatin- 3-
thiosemicarbazone, which was effective as prophylactic
against smallpox [1] and vaccinia [2]. 3-Aminopyridine-2-
carboxaldehyde thiosemicarbazone is now being evaluated in
clinical trials against several malignancies [3]. Currently,
derivatives of thiosemicarbazones and their metal complexes
have been reported as antibacterial, antitumor, antiviral and
antimalarial agents [4-7]. In addition, steroidal thiosemicar-
bazones and their derivatives have attracted considerable
interest due to their wide biological activities [8]. Steroidal
Schiff bases showed in vitro inhibitory effect against bacteria
such as Staphylococcus aureus, Staphylococcus pyogenes,
Salmonella typhimurium and Escherichia coli [9,10].
2. RESULTS AND DISCUSSION
As shown in Table 1, we carried out a comparison of the
synthesis of 4a-l between MWI in the solvent-free conditions
and conventional heating. It was easily shown that MWI
greatly decreased the reaction time from 300-540 min to 1.5-
3.0 min. Furthermore, the yields increased from 51%-64% to
84%-94%. Consequently, the use of microwave technology
in conjunction with the use of solvent-free conditions allows
expeditious and efficient procedures in organic synthesis.
The structures of all the compounds 4a-l were confirmed
1
by IR, Mass, H NMR and elemental analysis. Their mass
spectra showed the expected molecular peaks at high inten-
sity. The IR spectra of these compounds exhibited a charac-
teristic strong absorption at 3268-3286 cm-1 due to N-H
stretching vibration. Strong absorption bands falling within
the range of 1518-1550 cm-1 and the range of 1045-1064
cm-1 were assigned to the C=N and C=S groups, respec-
With an increasing public concern over environmental
degradation, the use of environmentally benign solvents like
water and solvent-free reactions represents important green
procedures from both the economic and synthetic point of
view. Microwave-assisted organic synthesis has proven to be
a valuable tool for reducing reaction times, giving cleaner
reactions, improving yields, simplifying work-up and design-
ing energy-saving protocols. Moreover, with the develop-
ment of "green chemistry", the focus has now shifted to less
cumbersome solvent-free methods, undergoing facile reac-
tions to provide high yields of pure products, thus eliminat-
ing or minimizing the use of organic solvents [11,12].
1
tively. In the H NMR spectra, the singlet between ꢀ 8.91-
9.32 ppm can be assigned to the protons of the NHN. Peaks
due to the other NH proton were observed at 8.54-8.64 ppm.
In addition, the singlet peaks at 1.05 ppm, 1.09-1.10 ppm
and the doublet at 0.86 ppm were the characteristics of ster-
oidal structure. The singlet at 3.67 ppm was assigned to the
protons of COOCH3.
Our research group has worked on microwave-assisted sol-
vent-free synthesis [13-14]. As far as we know, no one has
examined so far the microwave-assisted solvent-free synthe-
sis of deoxycholic acid thiosemicarbazone derivatives. In
order to extend our research, we now report good yields in
the synthesis of new deoxycholic acid thiosemicarbazones
The compounds 4a-d, 4f and 4i were tested for their anti-
bacterial activities by disc-diffusion method using nutrient
broth medium. The Gram-positive and Gram-negative bacte-
ria utilized in this study consisted of S. aureus, S. pyogenes,
E. coli. In the disc-diffusion method, sterile paper discs (5
mm) were impregnated with compound dissolved in DMSO
at concentration 0.01% (mass fraction). The plates were in-
cubated at 35 ˚C for 24 h. The result is presented in Table 2.
The compounds investigated have good biological activity
against E. coli. Further antibacterial activities are under
study.
*Address correspondence to this author at the College of Chemistry and
Environmental Protection Engineering, Southwest University for Nationali-
ties, Chengdu 610041, P.R. China; Tel: +86-28-85522315; Fax: +86-28-
85524382; E-mail: zzg63129@yahoo.com.cn
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers

516 Letters in Organic Chemistry, 2011, Vol. 8, No. 7
Shi et al.
CH3OH
COOCH3
COOH
OH
OH
CH3COCl, MWI
OH
OH
1
S
H
N
H
R
C
N
NH2
3a-3l
COOCH3
PCC, CH2Cl2
r.t.
O
MWI
solvet-free
O
2
R=
COOCH3
OCH3
Cl
Br
F
CH3
4b
O
N
4a
4c
4d
4e
4f
NH
C
CH3
CH3
OCH3
S
F
Br
Cl
NH
R
CH3
4i
4g
4h
4l
4a-4l
4j
4k
Scheme 1. Synthesis of the deoxycholic acid thiosemicarbazone derivatives 4a-l.
3. CONCLUSIONS
known procedures [15,16]. Thiosemicarbazides 3a-l was also
prepared by known procedures [17].
In conclusion, we have developed a rapid and efficient
eco-friendly method for the preparation of thiosemicarba-
zone derivatives. The reaction was conducted in the presence
of neutral aluminum oxide, without using solvent, and as-
sisted by MWI. The salient features of this method include
the simple reaction set-ups, high yields of products, and
short reaction time.
4.2. Methyl (5ꢀ)-3,12-dioxocholan-24-oate (2)
Pyridinium chlorochromate [18] (PCC) (3.03 mmol) was
added to a solution of Methyl (3ꢀ,5ꢁ,12ꢀ)-3,12-dihydroxy-
cholan-24-oate (1) (0.25 g, 0.615 mmol) in dried CH2Cl2 (20
ml) at room temperature. The reaction was completed in 24
h. The solvent was removed under reduced pressure, and the
crude product was purified by column chromatography on
silica gel using ethyl acetate as eluant to give 2 as white
solid; yield 84%; Mp: 135-136ꢀ (Lit [19] Mp: 133-135 ˚C).
4. EXPERIMENTAL
4.1. General
= +12.15 (c 0.12, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
Melting points were determined on a micro-melting point
apparatus and are uncorrected. IR spectra were obtained on
CDCl3) ꢀ 0.86 (d, 3H, J = 6.4 Hz, 21-CH3), 1.06 (s, 3H, 18-
CH3), 1.11 (s, 3H, 19-CH3), 3.69 (s, 3H, COOCH3); ESI-MS
m/z (%): 827 ([2M+23]+, 100). IR (KBr, cm-1): 2967, 2930,
2868, 1738, 1709, 1220, 1175; Elemental analysis: Found
(%): C, 74.48; H, 9.54 Calcd. For C25H38O4: C, 74.59; H,
9.51.
1
1700 PerkinElmer FTIR using KBr disks. H NMR spectra
were recorded on a Varian INOVA 400 MHz spectrometer
using CDCl3 as solvent and TMS as internal standard. Mass
spectra were determined on FinniganLCQDECA instrument.
Elemental analyses were performed on a Carlo-Erba-1106
auto analyzer. Optical rotation was measured on a Wzz-2B
polarimeter. All reactions were performed in a commercial
microwave apparatus (XH-100A, 100-1000W, Beijing
Xianghu Science and Technology Development Co. Ltd,
Beijing, China). All the solvents were purified before use.
Methyl (3ꢀ,5ꢁ,12ꢀ)-3,12-dihydroxycholan-24-oate (1) and
Methyl (5ꢁ)-3,12-dioxocholan-24-oate (2) were prepared by
4.3. Microwave Procedure for the Preparation of Steroi-
dal Thiosemicarbazones 4a-l
The steroidal diketone 2 (1 mmol), the thiosemicar-
bazides 3a-l (1 mmol) and neutral aluminium oxide (0.8 g)
were placed in a porcelain mortar, then concentrated acetic
acid (two drops) was added. After grinding, the mixture was

Rapid and Efficient Synthesis of New Deoxycholic Acid
Letters in Organic Chemistry, 2011, Vol. 8, No. 7
517
Table 1. Synthetic Comparison of the Deoxycholic acid Thiosemicarbazone Derivatives 4a-l Between MWI and Conventional
Heating
Compd.
Conventional method
T/min
Microwave method
T/min
Tca/Tmwb
Solvent(ml)
Yield/%
Solvent(ml)
Yield/%
4a
4b
4c
4d
4e
4f
20
20
20
20
20
20
20
20
20
20
20
20
360
450
380
500
420
450
300
360
420
450
540
500
58
51
57
58
60
59
61
62
64
58
60
61
/
/
/
/
/
/
/
/
/
/
/
/
2
1.5
2
91
87
84
91
94
89
86
90
85
92
90
92
180
300
190
200
280
225
150
180
140
180
180
167
2.5
1.5
2
4g
4h
4i
2
2
3
4j
2.5
3
4k
4l
3
aTime of conventional heating.
bTime of MWI.
Table2.
Antibacterial Activities of Compounds 4a-d, 4f and 4i
Compounds
S. aureus
S. pyogenes
E. coli
4a
4b
++
+
+
+
++
++
++
++
++
++
-
4c
++
+
++
+
4d
4f
+
+
4i
++
-
+
DMSO
-
++: strong; +: moderate; -: weak or no.
put in round-bottom flask (25 ml) in a microwave oven. It
was irradiated for 1.5~3.0 min at 240~500 W. The reaction
mixture was cooled to room temperature, dissolved in
DMSO and filtered. The filtrate was added of water and the
product was formed. It was recrystallized from ethanol and
obtained in 84~94% yields. The physical and spectra data of
the compounds 4a-l are as follows.
69.57; H, 8.16; N, 7.65 Calcd. For C32H45N3O3S: C, 69.65;
H, 8.22; N, 7.62.
4.3.2. Methyl (5ꢀ)-3-[2-[[(4-methylphenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4b)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +153.85 (c 0.14,
yield 87%; Mp
:
200-201 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
2.36 (s, 3H, Ar-CH3), 3.67 (s, 3H, COOCH3), 7.18 (d, 2H, J
= 8.0 Hz, ArH), 7.47-7.50 (m, 2H, ArH), 8.54 (d, 1H, J =
11.6 Hz, NH), 9.17 (s, 1H, NH); IR (KBr, cm-1): 3278, 2925,
2866, 1736, 1699, 1586, 1524, 1379, 1329, 1269, 1172,
1061, 818; ESI–MS m/z (%): 1131 [(2M+1)+, 100]; Elemen-
tal analysis: Found (%):C, 69.99; H, 8.34; N, 7.47 Calcd. For
C33H47N3O3S: C, 70.05; H, 8.37; N, 7.43.
4.3.1. Methyl (5ꢀ)-3-[2-[(phenylamino)thioxomethyl]hydr-
azinylidene]-12-oxocholan-24-oate (4a)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +180.01 (c 0.12,
yield 91%; Mp
:
175-176 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.22 (dd, 1H, J = 7.2, 7.6 Hz, ArH),
7.38 (dd, 2H, J = 8.0, 7.6 Hz, ArH), 7.66 (d, 2H, J = 8.0 Hz,
ArH), 8.57 (d, 1H, J = 10.8 Hz, NH), 9.27 (s, 1H, NH); IR
(KBr, cm-1): 3286, 2937, 2872, 1717, 1697, 1594, 1528,
1490, 1439, 1352, 1265, 1178, 1040, 750; ESI–MS m/z (%):
1103 [(2M+1)+, 100]; Elemental analysis: Found (%): C,
4.3.3. Methyl (5ꢀ)-3-[2-[[(4-fluorophenyl)amino]thioxome-
thyl]hydrazinylidene]-12-oxocholan-24-oate (4c)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +135.14 (c 0.12,
yield 84%; Mp
:
198-199 ˚C.

518 Letters in Organic Chemistry, 2011, Vol. 8, No. 7
Shi et al.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.07 (dd, 2H, J = 8.4, 8.4 Hz, ArH),
7.55-7.59 (m, 2H, ArH), 8.57 (d, 1H, J = 10.4 Hz, NH), 9.17
(s, 1H, NH); IR (KBr, cm-1): 3271, 2931, 2867, 1738, 1699,
1519, 1380, 1330, 1268, 1197, 1053, 847; ESI–MS m/z (%):
570 [(M+1)+, 100]; Elemental analysis: Found (%):C, 67.47;
H, 7.71; N, 7.42 Calcd. For C32H44FN3O3S: C, 67.46; H,
7.78; N, 7.37.
NH), 9.28 (s, 1H, NH); IR (KBr, cm-1): 3277, 2935, 2867,
1736, 1706, 1598, 1546, 1456, 1378, 1295, 1162, 1038, 779;
ESI–MS m/z (%): 604 [(M+23)+, 100]; Elemental analysis:
Found (%):C, 68.04; H, 8.11; N, 7.27 Calcd. For
C33H47N3O4S: C, 68.12; H, 8.14; N, 7.22.
4.3.8. Methyl (5ꢀ)-3-[2-[[(2-methylphenyl)amino]thioxome-
thyl]hydrazinylidene]-12-oxocholan-24-oate (4h)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +67.27 (c 0.12,
yield 90%; Mp
:
190-191 ˚C.
4.3.4. Methyl (5ꢀ)-3-[2-[[(4-chlorophenyl)amino]thioxome-
thyl]hydrazinylidene]-12-oxocholan-24-oate (4d)
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
2.37 (s, 3H, Ar-CH3), 3.67 (s, 3H, COOCH3), 7.03 (d, 1H, J
= 7.6 Hz, ArH), 7.26 (dd, 1H, J = 7.6, 4.0 Hz, ArH), 7.46
(dd, 2H, J = 7.6, 6.4 Hz, ArH), 8.56 (d, 1H, J = 8.8 Hz, NH),
9.22 (s, 1H, NH); IR (KBr, cm-1): 3274, 2924, 2867, 1736,
1699, 1587, 1521, 1444, 1379, 1329, 1274, 1168, 1061, 732;
ESI–MS m/z (%): 1131 [(2M+1)+, 100]; Elemental analysis:
Found (%): C, 69.97; H, 8.35; N, 7.46 Calcd. For
C33H47N3O3S: C, 70.05; H, 8.37; N, 7.43.
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +62.09 (c 0.16,
yield 91%; Mp
:
206-207 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.34 (d, 2H, J = 8.4 Hz, ArH), 7.62
(dd, 2H, J = 6.4, 2.0 Hz, ArH), 8.57 (d, 1H, J = 10.8 Hz,
NH), 9.23 (s, 1H, NH); IR (KBr, cm-1): 3269, 2931, 2867,
1735, 1699, 1585, 1518, 1381, 1329, 1267, 1176, 1084,
1013, 827; ESI–MS m/z (%): 1171 [(2M+1)+, 100]; Elemen-
tal analysis: Found (%):C, 65.46; H, 7.53; N, 7.21 Calcd. For
C32H44ClN3O3S: C, 65.56; H, 7.57; N, 7.17.
4.3.9. Methyl (5ꢀ)-3-[2-[[(2,4-dimethylphenyl)amino]thio-
xomethyl]hydrazinylidene]-12-oxocholan-24-oate (4i)
Obtained according to the MWI method as a white solid;
4.3.5. Methyl (5ꢀ)-3-[2-[[(4-bromophenyl)amino]thioxome-
thyl]hydrazinylidene]-12-oxocholan-24-oate (4e)
[ꢀ]2D0
= +60.67 (c 0.14,
yield 85%; Mp
:
166-167 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.10 (s, 3H, 19-CH3),
2.27 (s, 3H, Ar-CH3), 2.32 (s, 3H, Ar-CH3), 3.67 (s, 3H,
COOCH3), 7.05 (d, 2H, J = 10.4 Hz, ArH), 7.43 (d, 1H, J =
8.0 Hz, ArH), 8.62 (dd, 1H, J = 5.6, 5.2 Hz, NH), 8.91 (s,
1H, NH); IR (KBr, cm-1): 3279, 2927, 2867, 1738, 1706,
1594, 1550, 1493, 1452, 1379, 1275, 1187, 1043, 821; ESI–
MS m/z (%): 580 [(M+1)+, 100]; Elemental analysis: Found
(%): C, 70.38; H, 8.49; N, 7.31 Calcd. For C34H49N3O3S: C,
70.43; H, 8.52; N, 7.25.
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +54.55 (c 0.10,
yield 94%; Mp
:
196-197 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.48 (dd, 2H, J = 7.2, 1.6 Hz, ArH),
7.56-7.59 (m, 2H, ArH), 8.64 (d, 1H, J = 10.0 Hz, NH), 9.24
(s, 1H, NH); IR (KBr, cm-1): 3270, 2931, 2867, 1735, 1699,
1582, 1519, 1488, 1383, 1328, 1267, 1175, 1061, 1009, 763;
ESI–MS m/z (%): 1261 [(2M+3)+, 100]; Elemental analysis:
Found (%):C, 60.78; H, 7.01; N, 6.70 Calcd. For
C32H44BrN3O3S: C, 60.94; H, 7.03; N, 6.66.
4.3.10. Methyl (5ꢀ)-3-[2-[[(3-fluorophenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4j)
4.3.6. Methyl (5ꢀ)-3-[2-[[(4-methoxyphenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4f)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +135.29 (c 0.12,
yield 92%; Mp
:
174-175 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 6.90 (dd, 1H, J = 8.0, 8.0 Hz, ArH),
7.28-7.34 (m, 1H, ArH), 7.67 (dd, 1H, J = 10.4, 8.8 Hz,
ArH), 8.58 (d, 1H, J = 8.4 Hz, NH), 9.32 (s, 1H, NH); IR
(KBr, cm-1): 3274, 2933, 2867, 1739, 1699, 1600, 1521,
1442, 1379, 1329, 1273, 1168, 1055, 737; ESI–MS m/z (%):
570 [(M+1)+, 100]; Elemental analysis: Found (%): C, 67.42;
H, 7.75; N, 7.42 Calcd. For C32H44FN3O3S: C, 67.46; H,
7.78; N, 7.37.
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +111.36 (c 0.12,
yield 89%; Mp
:
198-199 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 3.82 (s, 3H, Ar-OCH3), 6.91 (d, 2H,
J = 8.4 Hz, ArH), 7.46-7.49 (m, 2H, ArH), 8.56 (d, 1H, J =
11.2 Hz, NH), 9.09 (s, 1H, NH); IR (KBr, cm-1): 3285, 2931,
2866, 1734, 1699, 1589, 1522, 1379, 1329, 1238, 1174,
1036, 840; ESI–MS m/z (%): 604 [(M+23)+, 100]; Elemental
analysis: Found (%):C, 68.01; H, 8.10; N, 7.25 Calcd. For
C33H47N3O4S: C, 68.12; H, 8.14; N, 7.22.
4.3.11. Methyl (5ꢀ)-3-[2-[[(3-chlorophenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4k)
4.3.7. Methyl (5ꢀ)-3-[2-[[(2-methoxyphenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4g)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +91.07 (c 0.10,
Obtained according to the MWI method as a white solid;
yield 90%; Mp
:
187-188 ˚C.
[ꢀ]2D0
= +128.19 (c 0.14,
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.10 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.18 (d, 1H, J = 7.2 Hz, ArH), 7.29
(dd, 1H, J = 8.0, 11.6 Hz, ArH), 7.60 (dd, 1H, J = 6.8, 7.2
Hz, ArH), 7.76 (d, 1H, J = 11.2 Hz, ArH), 8.60 (d, 1H, J =
9.2 Hz, NH), 9.28 (s, 1H, NH); IR (KBr, cm-1): 3270, 2933,
yield 86%; Mp
:
141-142 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.8
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 3.83 (s, 3H, Ar-OCH3), 6.76 (d, 1H,
J = 8.0 Hz, ArH), 7.14 (d, 1H, J = 5.6 Hz, ArH), 7.24-7.28
(m, 1H, ArH), 7.47 (s, 1H, ArH), 8.55 (d, 1H, J = 9.6 Hz,

Rapid and Efficient Synthesis of New Deoxycholic Acid
Letters in Organic Chemistry, 2011, Vol. 8, No. 7
519
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2866, 1734, 1699, 1592, 1521, 1486, 1378, 1269, 1172,
1055, 713; ESI–MS m/z (%): 586 [(M+1)+, 100]; Elemental
analysis: Found (%): C, 65.4; H, 7.53; N, 7.24 Calcd. For
C32H44ClN3O3S: C, 65.56; H, 7.57; N, 7.17.
[4]
[5]
4.3.12. Methyl (5ꢀ)-3-[2-[[(3-bromophenyl)amino]thioxo-
methyl]hydrazinylidene]-12-oxocholan-24-oate (4l)
Obtained according to the MWI method as a white solid;
[ꢀ]2D0
= +81.63 (c 0.12,
yield 92%; Mp
:
195-196 ˚C.
CH2Cl2). 1H NMR (400 MHz, CDCl3) ꢀ 0.86 (d, 3H, J = 6.4
Hz, 21-CH3), 1.05 (s, 3H, 18-CH3), 1.09 (s, 3H, 19-CH3),
3.67 (s, 3H, COOCH3), 7.23 (dd, 1H, J = 8.0, 8.0 Hz, ArH),
7.33 (d, 1H, J = 7.2 Hz, ArH), 7.66 (dd, 1H, J = 8.0, 8.0 Hz,
ArH), 7.89 (d, 1H, J = 12.0 Hz, ArH), 8.63 (d, 1H, J = 4.0
Hz, NH), 9.28 (s, 1H, NH); IR (KBr, cm-1): 3268, 2934,
2866, 1733, 1700, 1585, 1520, 1483, 1379, 1268, 1173,
1059, 707; ESI–MS m/z (%): 1262 [(2M+4)+, 100]; Elemen-
tal analysis: Found (%): C, 60.87; H, 7.07; N, 6.61 Calcd.
For C32H44BrN3O3S: C, 60.94; H, 7.03; N, 6.66.
[6]
[7]
[8]
[9]
4.4. Conventional Procedure for the Preparation of Ster-
oidal Thiosemicarbazones 4a-l
[10]
[11]
The steroidal diketone 2 (1 mmol) and the thiosemicar-
bazides 3a-l (1 mmol) were dissolved in ethanol (20 ml).
After completely dissolving, two drops of acetic acid were
added. The mixture was stirred for 300-500 min at 80 ˚C.
After cooling, the products were filtered, recrystallized from
ethanol and obtained 51-64% yields.
[12]
[13]
ACKNOWLEDGEMENTS
[14]
[15]
We greatly thank the Innovative Research Program for
Graduates of Southwest University for Nationalities (No.
CX201102) and Special Financial Project of Central Chinese
University (No. 11NZYQN05) for the financial support.
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SUPPLEMENTARY MATERIAL
Supplementary material is available on the publishers
Web site along with the published article.
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