Selective 1,4-reduction of chalcones with Zn/NH4Cl/C 2H5OH/H2O

Article abstract of DOI:10.1002/jccs.200800057

In this paper, the Zn/NH₄Cl/C₂H₅OH/H ₂O system was applied for the selective 1,4-reduction of chalcones undermild conditions with high selectivity. Themerit lies in inexpensive reagent, simple operation and envi

Full text of DOI:10.1002/jccs.200800057

390
Journal of the Chinese Chemical Society, 2008, 55, 390-393
Selective 1,4-Reduction of Chalcones with Zn/NH4Cl/C2H5OH/H2O
Jian-Ping Li* (
), Yong-Xia Zhang (
) and Yan Ji (
)
College of Chemical and Environmental Science, The Key Laboratory of Environmental Pollution Control
Technology of Henan Province, Henan Normal University, Xinxiang, 453007, P. R. China
In this paper, the Zn/NH4Cl/C2H5OH/H2O system was applied for the selective 1,4-reduction of
chalcones under mild conditions with high selectivity. The merit lies in inexpensive reagent, simple opera-
tion and environmental friendliness. The structures of the products were characterized by IR, 1H NMR,
MS spectra and elemental analysis. A possible mechanism is also suggested.
Keywords: Selective 1,4-reduction; Zinc powder; Ammonium chloride; Chalcones.
INTRODUCTION
Chemoselective reduction of conjugated carbonyl
and poor yields of the desired product. Therefore, the de-
velopment of a mild and selective reducing agent for the
conjugate reduction of a,b-unsaturated carbonyl com-
pounds still attracts a great deal of attention from organic
chemists.
compounds is a useful functional group transformation in
organic synthesis. Many useful methodologies for selective
1,2-reduction of a,b-unsaturated carbonyl compounds
have been developed through metal hydride mediated re-
duction1-3 or hydrogenation reactions.4 On the other hand,
selective 1,4-reduction of a,b-unsaturated carbonyl com-
pounds have not been developed as much. It has always
been a challenging problem in organic synthesis.5 Numer-
ous methodologies have been reported in the literature, for
example, Pd, Rh, Pt, Ni, Ir, Co and their complexes,6-9 hy-
drides of Sn, Se, Te, B;10,11 sodium dithionite12,13 and so-
dium borohydride14-16 have also been reported to be useful
for the hydrogenation of a,b-unsaturated carbonyl com-
pounds. However, some of these systems suffer from their
own limitations: handling of reagents, strict reaction condi-
tions, temperature maintenance, long reaction time, cost
RESULTS AND DISCUSSION
Chalcones are typical a,b-unsaturated carbonyl com-
pounds. More recently, the Zn/CH3COONH4/C2H5OH/H2O
system has been reported to reduce carbon-carbon double
bonds of chalcones at room temperature.17 However, an ex-
cess of ammonium acetate (50 mmol) had to be added in
small portions to the substrate (0.5 mmol) in ethanol. The
Zn/NH4Cl/C2H5OH/H2O system has also been reported to
reduce nitrophenols.18 Recently, we have studied the char-
acteristics of the Zn/NH4Cl/C2H5OH/H2O system (Scheme
I).
Chalcone (1a) was chosen as a model substrate to in-
Scheme I
* Corresponding author. E-mail: jplig@163.com

A New Method for Selective Reduction of a,b-Unsaturated Ketones
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 391
vestigate the appropriate conditions for selective conjugate
reduction in chalcones; the molar ratio of substrate to zinc
powder to ammonium chloride was varied, and reactions
were attempted in different solvents such as dichloro-
methane, ethyl acetate, THF, DMF, methanol and ethanol.
While the reactions of 1a in dichloromethane, ethyl ace-
tate, THF, and DMF were incomplete, reactions in metha-
nol and ethanol showed the predominant formation of
dihydrochalcones. Therefore, we chose ethanol as solvent
because of its non-toxicity. When water was not added to
the reaction system, the yield of product was poor. The
amount of water plays a crucial role in the selective reduc-
tion. We have also investigated NH4Br and NH4I instead of
NH4Cl in the same conditions; however, we found a long
reaction time was required. Additionally, NH4Cl is less ex-
pensive. Therefore, NH4Cl is the best choice in this system.
The way zinc powder is added is also important. When zinc
powder was added in the reaction solution all at once, the
reaction is incomplete even with a long reaction time. How-
ever, zinc powder added in small increments can cause the
experimental operation to become complicated. Numerous
trials have indicated that adding zinc powder in three equal
portions is the best choice. Remarkable chemoselective
carbon-carbon double bond reductions were observed in all
of these cases, and labile functionality like ketone was
unaffected under these conditions.
(2) was formed. Thirdly, (2) accepted an electron from the
zinc to form the enol anion (3). Finally, the enol anion be-
came the saturated alkone by passing an proton from am-
monia ion.
We also investigated cyclohexenone, cyclopenten-
one, b-ionone and carvone under the same conditions.
They could not be selectively reduced, as their reactions
did not take place and b-ionone showed the formation of a
mixture of compounds. Further, we extended the scope of
this reagent to achieve chemoselective reduction of a,b-
unsaturated aldehydes and ester. Unfortunately, the reac-
tion did not happen as we expected. In the case of Cinna-
maldehyde, the sole product was cinnamyl alcohol. a,b-
unsaturated ester, namely Cinnamic acid ethylester, had no
reaction at all.
EXPERIMENTAL SECTION
Melting points were determined with a XRC-1 micro
melting point apparatus and were uncorrected. IR spectra
were recorded on a FTS-40 spectrophotometer using KBr
pellets. 1H NMR spectra were measured on a Bruker DPX-
400 spectrometer at 400 MHz, using TMS as internal stan-
dard and CDCl3 as solvent. MS spectra were taken on a
KRTOS-AEI-MS50 (U.K) spectrometer. Elemental analy-
ses were performed on a PE-2400 elemental analyzer.
General Procedure
According to the fact that when ammonium chloride
was not added to the reaction system there is no reaction
sign, a possible mechanism was suggested (Scheme II):
Firstly, chalcone accepted an electron from the zinc to form
the anion free radical (1). Secondly, the anion free radical
abstracted a proton from the solution of the reaction, then
Chalcone (0.5 mmol) in ethanol (50 mL) was added to
water solution (8 mL) containing 1.07 g (20 mmol) ammo-
nium chloride at room temperature and stirred vigorously
with 0.195 g (3 mmol) zinc powder added in three equal
portions at intervals of 15min. Stirring was continued for
15 min. The progress of the reaction was monitored by
Scheme II

392 J. Chin. Chem. Soc., Vol. 55, No. 2, 2008
Li et al.
TLC using petroleum ether : ethyl acetate (90:10; v/v). The
suspended material was removed by filtration and the fil-
trate was evaporated under reduced pressure then ice-cold
water was added to the residual material. After filtration,
the crude product was recrystallised from 95% ethanol. By
this method, we have successfully synthesized fifteen satu-
rated alkones in excellent yields (85-95%) under mild con-
ditions. The structures of the products were characterized
by IR, 1H NMR, MS spectra and elemental analysis. The re-
sults indicated that this system was an economical method
for the selective reduction of chalcones because of its se-
lectivity, simple work-up procedure, inexpensive reagents
and environmental friendliness.
for C16H16O: C, 85.71; H, 7.14. Found: C, 85.99; H, 7.21.
Compound 2f: White tabular; mp. 75-76 °C, Lit16:
75-76 °C; yield 90%; IR (KBr) n: 3060, 3027 (Ar-H), 2951,
2863 (CH2), 1683 (C=O), 1604, 1587, 1571 cm-1; 1H NMR
(CDCl3): d 3.06 (t, J = 7.6 Hz, 2H, CH2), 3.27 (t, J = 7.6 Hz,
2H, CH2), 7.19-7.90 (m, 9H, Ar-H); MS (m/z): 244 (M+),
139 (100), 111, 91; Anal. Calcd. for C15H13ClO: C, 73.62;
H, 5.32. Found: C, 73.48; H, 5.40.
Compound 2g: White sticks; mp. 74-76 °C; yield
85%; IR (KBr) n: 3056, 3035 (Ar-H), 2942, 2868 (CH2),
1682 (C=O), 1601, 1581, 1519 cm-1; 1H NMR (CDCl3): d
2.32 (s, 3H, CH3), 3.07 (t, J = 7.6 Hz, 2H, CH2), 3.27 (t, J =
7.6 Hz, 2H, CH2), 7.19-7.91 (m, 8H, Ar-H); Anal. Calcd.
for C16H15ClO: C, 74.27; H, 5.80. Found: C, 74.10; H, 5.96.
Compound 2h: White sticks; mp. 69-70 °C; yield
88%; IR (KBr) n: 3059, 3038 (Ar-H), 2941, 2863 (CH2),
1680 (C=O), 1599, 1581, 1521 cm-1; 1H NMR (CDCl3): d
2.39 (s, 3H, CH3), 3.02 (t, J = 7.2 Hz, 2H, CH2), 3.23 (t, J =
7.2 Hz, 2H, CH2), 6.94-7.85 (m, 8H, Ar-H); Anal. Calcd.
for C16H15FO: C, 79.34; H, 6.20. Found: C, 79.49; H, 6.07.
Compound 2i: White sticks; mp. 49-50 °C; yield
86%; IR (KBr) n: 3020 (Ar-H), 2939, 2841 (CH2), 1672
(C=O), 1605, 1575, 1511 cm-1; 1H NMR (CDCl3): d 2.31 (s,
3H, CH3), 3.03 (t, J = 7.2 Hz, 2H, CH2), 3.28 (t, J = 7.2 Hz,
2H, CH2), 7.13-7.95 (m, 8H, Ar-H); Anal. Calcd. for
C16H15BrO: C, 63.37; H, 4.95. Found: C, 63.44; H, 5.19.
Compound 2j: White tabular; mp. 79-81 °C; yield
92%; IR (KBr) n: 3030 (Ar-H), 2920, 2876 (CH2), 1676
(C=O), 1600, 1521, 1477 cm-1; 1H NMR (CDCl3): d 3.03 (t,
J = 7.2 Hz, 2H, CH2), 3.28 (t, J = 7.2 Hz, 2H, CH2),
7.13-7.95 (m, 9H, Ar-H); Anal. Calcd. for C15H13BrO: C,
62.28; H, 4.50. Found: C, 62.43; H, 4.37.
Physical properties and spectral data
Compound 2a: White tabular; mp. 68-69 °C, Lit16:
68-69.5 °C; yield 95%; IR (KBr) n: 3062, 3025 (Ar-H),
2922, 2865 (CH2), 1682 (C=O), 1596, 1581, 1493 cm-1; 1H
NMR (CDCl3): d 3.06 (t, J = 8.0 Hz, 2H, CH2), 3.30 (t, J =
8.0 Hz, 2H, CH2), 7.18-7.96 (m, 10H, Ar-H); MS (m/z):
210 (M+), 105 (100), 91, 77, 51; Anal. Calcd. for C15H14O:
C, 85.71; H, 6.67. Found: C, 85.55; H, 6.79.
Compound 2b: White tabular; mp. 64-65 °C, Lit16:
64-65 °C; yield 90%; IR (KBr) n: 3003 (Ar-H), 2960, 2932,
2836 (CH2), 1682 (C=O), 1604, 1592, 1580 cm-1; 1H NMR
(CDCl3): d 3.03 (t, J = 7.6 Hz, 2H, CH2), 3.25 (t, J = 7.6 Hz,
2H, CH2), 3.79 (s, 3H, OCH3), 6.85-7.98 (m, 9H, Ar-H);
MS (m/z): 240 (M+), 121 (100), 135, 105, 91, 77; Anal.
Calcd. for C16H16O2: C, 80.00; H, 6.67. Found: C, 80.17; H,
6.74.
Compound 2c: White sticks; mp. 54-56 °C, Lit16:
53-54 °C; yield 92%; IR (KBr) n: 3032 (Ar-H), 2918, 2879
1
(CH2), 1670 (C=O), 1598, 1582, 1495 cm-1; H NMR
(CDCl3): d 3.04 (t, J = 7.2 Hz, 2H, CH2), 3.26 (t, J = 7.2 Hz,
2H, CH2), 7.12-7.93 (m, 9H, Ar-H); MS (m/z): 244 (M+),
105 (100), 125, 77, 51; Anal.Calcd. for C15H13ClO: C,
73.62; H, 5.32. Found: C, 73.78; H, 5.26.
Compound 2k: White tabular; mp. 68-70 °C, Lit16:
68-70 °C; yield 89%; IR (KBr) n: 3019 (Ar-H), 2970, 2929,
2840 (CH2), 1680 (C=O), 1604, 1577, 1508 cm-1; 1H NMR
(CDCl3): d 3.01 (t, J = 7.2 Hz, 2H, CH2), 3.21 (t, J = 7.2 Hz,
2H, CH2), 3.85 (s, 3H, OCH3), 6.90-7.92 (m, 8H, Ar-H);
MS (m/z): 274 (M+), 135 (100), 107, 92, 77; Anal. Calcd.
for C16H15ClO2: C, 69.95; H, 5.46. Found: C, 70.11; H,
5.37.
Compound 2d: White needles; mp. 66-67 °C; yield
91.5%; IR (KBr) n: 3034 (Ar-H), 2916, 2882 (CH2), 1670
(C=O), 1595, 1586, 1493 cm-1; 1H NMR (CDCl3): d 3.03 (t,
J = 7.6 Hz, 2H, CH2), 3.24 (t, J = 7.6 Hz, 2H, CH2),
7.11-7.94 (m, 9H, Ar-H); Anal. Calcd. for C15H13BrO: C,
62.28; H, 4.50. Found: C, 62.40; H, 4.43.
Compound 2l: White tabular; mp. 72-73 °C; yield
90%; IR (KBr) n: 3028 (Ar-H), 2972, 2931, 2847 (CH2),
1678 (C=O), 1609, 1587, 1501 cm-1; 1H NMR (CDCl3): d
3.03 (t, J = 7.2 Hz, 2H, CH2), 3.27 (t, J = 7.2 Hz, 2H, CH2),
3.84 (s, 3H, OCH3), 6.95-7.91 (m, 8H, Ar-H); Anal. Calcd.
for C16H15FO2: C, 74.41; H, 5.81. Found: C, 74.29; H, 5.98.
Compound 2m: White tabular; mp. 58-59 °C; yield:
Compound 2e: White tabular; mp. 62-64 °C; yield
90%; IR (KBr) n: 3058 (Ar-H), 2947, 2921, 2860 (CH2),
1681 (C=O), 1602, 1588, 1569 cm-1; 1H NMR (CDCl3): d
2.32 (s, 3H, CH3), 3.05 (t, J = 7.2 Hz, 2H, CH2), 3.26 (t, J =
7.2 Hz, 2H, CH2), 7.12-7.99 (m, 9H, Ar-H); Anal. Calcd.

A New Method for Selective Reduction of a,b-Unsaturated Ketones
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 393
90%; IR (KBr) n: 3031 (Ar-H), 2947, 2869 (CH2), 1683
(C=O), 1599, 1579, 1560 cm-1; 1H NMR (CDCl3): d 3.07 (t,
J = 7.2 Hz, 2H, CH2), 3.26 (t, J = 7.2 Hz, 2H, CH2),
7.19-7.91 (m, 8H, Ar-H); Anal. Calcd. for C15H12FClO: C,
68.57; H, 4.57. Found: C, 68.70; H, 4.51.
Compound 2n: White tabular; mp. 62-64 °C, Lit16:
59.5-61.5 °C; yield 87%; IR (KBr) n: 3003 (Ar-H), 2964,
2938, 2838 (CH2), 1677 (C=O), 1611, 1587, 1571 cm-1; 1H
NMR (CDCl3): d 3.01 (t, J = 7.6 Hz, 2H, CH2), 3.23 (t, J =
7.6 Hz, 2H, CH2), 3.79 (s, 3H, OCH3), 6.83-7.89 (m, 8H,
Ar-H); MS (m/z): 274 (M+), 121 (100), 139, 108, 91, 77;
Anal. Calcd. for C16H15ClO: C, 69.95; H, 5.46. Found: C,
70.17; H, 5.36.
REFERENCES
1. Singh, J.; Sharma, M.; Kaur, I.; Kad, G. L. Synth. Commun.
2000, 30, 1515.
2. Kawakami, T.; Miyatake, M.; Shibata, I.; Baba, A. J. Org.
Chem. 1996, 61, 376.
3. Zeynizadeh, B.; Setamdideh, D. J. Chin. Chem. Soc. 2005,
52, 1179.
4. Chen, J.-X.; Daeuble, J. F.; Brestensky, D. M.; Stryker, J. M.
Tetrahedron 2000, 56, 2153.
5. Lee, H. Y.; An, M. Tetrahedron Lett. 2003, 44, 2775.
6. Yu, H.-T.; Kang, R.-H.; Ou Yang, X.-M. Chin. J. Org. Chem.
2000, 20, 441.
7. McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809.
8. Sakaguchi, S.; Yamaga, T.; Ishii, Y. J. Org. Chem. 2001, 66,
4710.
9. Sonavane, S. U.; Jagaram, R. V. Synlett. 2004, 146.
10. Yamashita, M.; Tanaka, Y.; Arita, A.; Nishida, M. J. Org.
Chem. 1994, 59, 3500.
Compound 2o: White tabular; mp. 53-54 °C; yield
88%; IR (KBr) n: 3060, 3027 (Ar-H), 2951, 2863 (CH2),
1683 (C=O), 1604, 1587, 1571 cm-1; 1H NMR (CDCl3): d
3.06 (t, J = 7.2 Hz, 2H, CH2), 3.27 (t, J = 7.2 Hz, 2H, CH2),
3.80 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 7.19-7.91 (m, 8H,
Ar-H); Anal. Calcd. for C17H18O3: C, 75.56; H, 6.67. Found:
C, 75.39; H, 6.76.
11. Leonard, N. M.; Wieland, L. C.; Mohan, R. S. Tetrahedron
2002, 58, 8373.
12. Dhillon, R. S.; Singh, R. P.; Kaur, D. Tetrahedron Lett. 1995,
36, 1107.
13. Akamanchi, K. G.; Patel, H. C.; Meenakshi, R. Synth.
Commun. 1992, 22, 1655.
14. Khurana, J. M.; Sharma, P. Bull Chem. Soc. Jpn. 2004, 77,
549.
ACKNOWLEDGMENTS
We are grateful for the financial support from the
Natural Science Foundation of Technology Commission
(0611021700) and the Natural Science Foundation of Edu-
cation of Commission of Henan Province (2007150024).
15. Ren, P.-D.; Pan, S.-F.; Dong, T.-W.; Wu, S.-H. Chin. Chem.
Lett. 1996, 7, 788.
16. Ranu, B. C.; Samanta, S. J. Org. Chem. 2003, 68, 7130.
17. Zhou, Y.-B.; Wang, Y.-L.; Wang, J.-Y. J. Chem. Res. 2004,
118.
18. Sridharam, V.; karpagavalli, M.; Muthsnbramaniam, S.;
Sivasubramanian, S. Indian J. Chem. 2004, 43(B), 2243.
Received April 30, 2007.