Reduction of carbonyl compounds to the corresponding alcohols with isopropanol on dehydrated alumina under microwave irradiation

Article abstract of DOI:10.1081/SCC-120005436

The reduction of different types of aldehydes and ketones were performed in the presence of isopropylalcohol (as solvent and hydride source) under microwave irradiation. It is proved that dehydrated Woelm chromatographic alumina supported KOH catalyses these transformations. Regioselectivity was observed in the reduction of cinnamaldehyde and chemoselectivity was observed in the reduction of carbonyl in the presence of nitro group.

Full text of DOI:10.1081/SCC-120005436

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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REDUCTION OF CARBONYL COMPOUNDS TO THE
CORRESPONDING ALCOHOLS WITH ISOPROPANOL
ON DEHYDRATED ALUMINA UNDER MICROWAVE
IRRADIATION
F. Kazemi & A. R. Kiasat
To cite this article: F. Kazemi & A. R. Kiasat (2002) REDUCTION OF CARBONYL COMPOUNDS TO
THE CORRESPONDING ALCOHOLS WITH ISOPROPANOL ON DEHYDRATED ALUMINA UNDER
MICROWAVE IRRADIATION, Synthetic Communications, 32:14, 2255-2260, DOI: 10.1081/
SCC-120005436
To link to this article: http://dx.doi.org/10.1081/SCC-120005436
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 14, pp. 2255–2260, 2002
REDUCTION OF CARBONYL
COMPOUNDS TO THE CORRESPONDING
ALCOHOLS WITH ISOPROPANOL ON
DEHYDRATED ALUMINA UNDER
MICROWAVE IRRADIATION
F. Kazemi and A. R. Kiasat
Chemistry Department, College of Science, Shahid
Chamran University, Ahvaz, Iran
E-mail: fkazemi_2000@yahoo.com
ABSTRACT
The reduction of different types of aldehydes and ketones
were performed in the presence of isopropylalcohol (as sol-
vent and hydride source) under microwave irradiation. It is
proved that dehydrated Woelm chromatographic alumina
supported KOH catalyses these transformations. Regio-
selectivity was observed in the reduction of cinnamaldehyde
and chemoselectivity was observed in the reduction
of carbonyl in the presence of nitro group.
The reduction of carbonyl compounds to the corresponding alcohols is
an important transformation in organic synthesis[1] and because of its
significant role the development of newer reductive protocols continues to
receive attention in spite of the availability of numerous reagents.
2255
DOI: 10.1081/SCC-120005436
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

2256
KAZEMI AND KIASAT
Hydrogenation of carbonyl compounds by hydrogen donors catalyzed
by metal alkoxides[2] (especially aluminum alkoxide, Meerwein-Poundrof-
Verley reduction, MPV) is a method that was very often used before the
advent of metal hydrides as reducing agents. This method has real advantages
over the hydride transfer agents and catalytic hydrogenation using molecular
hydrogen, since it can be carried out on a large scale and under atmospheric
pressure.
The use of alumina as catalyst and reagent in organic synthesis is
increasingly widespread due to improved efficiency of many surface bound
reagents.[3,4] Horner et al[5] have used chlorinated ꢀ-Al2O3 in combination
with a small amount of Al(iso-PrO)3 as catalyst in the MPV reduction of
benzaldehyde, cyclohexanone, and acetophenone by isopropanol. In the
absence of Al(iso-PrO)3, no reaction occurred. A large reaction rate
enhancement was found by the addition of a strong base. Posner et al[6,7]
reasoned that dehydration of alumina and then introduction of 2-propanol
as hydride source in place of the removed water would produce novel alu-
mina which is weaker reducing agent than sodium borohydride and which is
at least as selective as sodium cyanoborohydrides and 9-borabicyclo [3.3.1]
nonane. The four most serious drawbacks to general use of this reagent as a
reducing agent are: 1) the high temperature (400ꢀC) required for the alumina
activation, 2) the relatively large amount of alumina (3–5 g/mmol of carbo-
nyl substrate) required for effective substrate reduction, 3) the crude alcohol
products (before purification) indicates a small amount of conjugated
carbonyl absorption due to aldol condensation and 4) unlike aldehydes,
reduction of ketones was achieved in low yields and in long reaction times.
Microwave heating and its application in organic chemistry for a variety
of reactions have been developed successfully, and in the past few years
there have been a tremendous amount of interest in this area. Remarkable
decrease in reaction times and, in some cases, clean reaction and better
yields have been reported with microwave irradiation.[8,9]
According to the above facts, the design of new systems for
hydrogenation of carbonyl compounds by hydrogen donors in a mild and
selective manner is a challenging and rewarding undertaking in organic
synthesis and numerous catalysts have been reported.[10] We now wish to
report that dehydrated Woelm chromatographic alumina supported KOH

REDUCTION OF CARBONYL COMPOUNDS
2257
can be used as an effective catalyst for this goal in the presence of isopropyl
alcohol as a source of active hydride and solvent under microwave
irradiation.
Alumina was activated by two different methods: by heating it in a
quartz vessel at 400ꢀC for 24 h[7] or by microwave irradiation in a commer-
cial microwave oven (800W) for 5 min. The two kinds of activated alumina
obtain show almost the same catalytic activity in the reduction reactions.
The reducing system was easily prepared by addition of activated alumina to
a suspension of KOH in isopropyl alcohol. Several reduction reactions were
performed, at various powers and with different amount of potassium
hydroxide and activated alumina, in order to find the most adequate con-
dition for this reaction under microwave irradiation. The required mole
ratio of KOH to substrate 0.5 : 1, weight ratio of activated alumina to sub-
strate 2.5 : 1, and the maximum power output of 200W were found to be the
optimal conditions.
The alumina/KOH system was cleanly and rapidly applied to the
reduction of variety of ketones and aldehydes in isopropyl alcohol with a
short time of microwave irradiation. The results are shown in Table 1. Thus
the reduction of aromatic, alicyclic, and aliphatic ketones (Entries 1–13),
aromatic and aliphatic aldehydes (Entries 14–26) afforded the correspond-
ing alcohols in excellent yields. Position and electronic properties of sub-
stituents on the benzene ring do not influence appreciably the reactivities of
aromatic aldehydes and ketones.
The successful reduction of acyloins (Entry 27) to their diols might
extend the utility of the present simple procedure. By this method absolute
selectivity is observed for the reduction of carbonyl functionality in the
presence of a nitro group (Entries 15,16).
Selective 1,2reduction of ꢁ,ꢂ-unsaturated carbonyl compound vs. 1,4
reduction is an important achievement for the synthesis of allyl alcohols
from easily available ꢁ,ꢂ-unsaturated carbonyl compounds. Posner
et al.[6,10] have applied ꢀ-Al2O3 in the MPV reduction of unsaturated
carbonyl compounds by isopropyl alcohol. However, rather high tempera-
tures were needed (up to 300ꢀC) and only low yields of alcohol were
obtained due to the occurrence of several side reactions. We have studied
the reduction of cinnamaldehyde with our system. The reduction is highly
regioselective and only cinnamyl alcohol is isolated with high yield (Entry
28).
It is previously proved that strong bases are frequently added as pro-
moters in H-transfer reactions since often they exert a beneficial effect on
reaction rates.[11,12] Also, in our experiments, it was found that the presence
of KOH in reaction media is essential, since the reaction in the absence of
KOH, furnished only a trace of the product.

2258
KAZEMI AND KIASAT
Table 1. Reduction of Ketones and Aldehydes to Alcohols with Isopropanol in the
Presence of Activated Alumina in Basic Media Under Microwave Irradiation
Time Yield
(min) (%)
Entry
Substrate
PhCOCH3
p-ClC6H4COCH3
PhCOCH2Br
PhCOPh
PhCH2COCH3
PhCH2COCH2Ph
Cyclohexanone
Cycloheptanone
CH3COCH2CH3
Product
PhCHOHCH3
p-ClC6H4CHOHCH3
PhCHOHCH2Br
PhCHOHPh
PhCH2CHOHCH3
PhCH2CHOHCH2Ph
Cyclohexanol
Cycloheptanol
CH3CHOHCH2CH3
1
2
3
4
5
6
7
8
9
13
90
1291
11
13
15
92
87
87
85
16
1288
13
13
14
13
13
13
87
89
86
90
90
89
10
11
12CH
13
14
15
16
17
18
19
20
21
22
23
24
25
2
CH3COCH2CH(CH3)CH3 CH3CHOHCH2CH(CH3)CH3
CH3(CH2)5COCH3
3CH2CO(CH2)2CH3
CH3COCH2COCH3
PhCHO
m-NO2C6H4CHO
p-NO2C6H4CHO
o-ClC6H4CHO
CH3(CH2)5CHOHCH3
CH3CH2CHOH(CH2)2CH3
CH3CHOHCH2COCH3
PhCH2OH
m-NO2C6H4CH2OH
p-NO2C6H4CH2OH
o-ClC6H4CH2OH
1288
9
10
11
93
92
92
90
p-ClC6H4CHO
p-BrC6H4CHO
p-ClC6H4CH2OH
p-BrC6H4CH2OH
11
1291
14
13
13
m-CH3C6H4CHO
p-CH3C6H4CHO
o-CH3OC6H4CHO
m-CH3OC6H4CHO
p-CH3OC6H4CHO
2-Naphthaldehyde
m-CH3C6H4CH2OH
p-CH3C6H4CH2OH
o-CH3OC6H4CH2OH
m-CH3OC6H4CH2OH
p-CH3OC6H4CH2OH
2-Naphthylmethanol
CH3(CH2)6CH2OH
PhCHOHCHOHPh
PhCH¼CHCH2OH
88
90
90
87
13
1289
14
13
13
88
88
91
6
3(CCHH) CHO
2 6
27
28
PhCOCHOHPh
PhCH¼CHCHO
1288
a) Yields referred to isolated yields; b) Products were characterized by comparison of
their physical data, IR NMR spectra with known samples.
To show the dramatic acceleration in the rate of reduction due to micro-
wave irradiation, under the same experimental condition several aldehydes
and ketones were heated just by conventional heating (82ꢀC). However, only
low yields of alcohols were obtained in comparably very long time. e.g.,
1-phenyl ethanol was isolated from acetophenone at (10–12%, reflux, 24 h).
Transformation of benzaldehyde was performed also on a 100 mmol
(10.6 g) scale to illustrate application of this method to preparation of gram

REDUCTION OF CARBONYL COMPOUNDS
2259
quantities of alcohols. Benzyl alcohol is obtained without appreciable
decrease in the yield as compared to that obtained by the small scale
experiment.
Although, the MPV reduction of aldehydes using aluminum alkoxide
often gives significant amounts of aldol, Tishchenko, and Cannizaro con-
densation products[11] and in the application on dried Woelm alumina, the
product is contaminated by conjugated carbonyl compounds due presum-
ably to aldol condensation.[6] In our method, infrared analysis of the
obtained products does not indicates any conjugated carbonyl by-product
adsorption due to aldol condensations.
Compared to some previously reported reagents with major or minor
drawbacks, several noteworthy features of this reagent are apparent: easy
work-up procedure, availability of the reagent, operational simplicity, selec-
tivity, use of inexpensive reagent, and high yields of products in consider-
ably short reaction time. Therefore, we feel that it may be a suitable addition
to the currently available methodology.
EXPERIMENTAL
General: IR spectra were recorded on a Shimadzo 450 spectropho-
1
tometer, H NMR spectra in CDCl3 on a Bruker Avance DPX instrument
(250 MHz). Required carbonyl compounds were purchased from Fluka and
Merck. Alumina 60 G neutral (Type E, Art. 1090) was purchased from
Merck. Products were characterized by comparison of their physical data,
1
IR and H NMR spectra with known samples. The purity determination of
the products and reaction monitoring were accomplished by TLC on silica
gel polygram SILG/ UV 254 plates.
Dehydration of Alumina and General Procedure for the
Reduction of Carbonyl Compounds
Alumina (1.5 g) was taken in a Pyrex Erlenmeyer flask (25 mL) and
irradiated in a commercial microwave oven (800W) for 5 min. It was then
allowed to reach room temperature. Fine powdered potassium hydroxide
(0.14g, 2.5 mmol) was thoroughly mixed with the activated alumina (1.33 g)
and the resulting powder was taken in a Pyrex round bottomed flask
(25 mL) equipped with a reflux condenser (reflux condenser was outside
the microwave oven) containing 15 mL of isopropyl alcohol. Carbonyl
compound (5 mmol) was added to the resulting mixture and then irradiated
in a commercial microwave oven (200W) for 9–16 min. The progress of the

2260
KAZEMI AND KIASAT
reaction was monitored by TLC. The reaction mixture was then allowed to
reach room temperature and neutralized with HCl (5%). The reaction mix-
ture was filtered and the combined filtrate was extracted with dichlomethane
(2 ꢁ 15 mL). The organic layer was dried over anhydrous sodium sulfate and
solvent evaporated under reduced pressure to afford the TLC and 1HNMR
pure products in 85–93% isolated yields.
ACKNOWLEDGMENT
We would like to acknowledge the partial support of this work by
Shahid Chamran Ahvaz University Research Council.
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5. Horner, L.; Kaps, U.B. Liebrge Ann. Chem. 1980, 192.
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Received in the UK May 22, 2001