Practical and chemoselective reduction of acyl chloride to alcohol by borohydride in aqueous dichloromethane

Article abstract of DOI:10.1080/00397910903340645

A simple methodology for the reduction of acid chlorides to their corresponding alcohols has been developed. Various carboxylic acids were converted to alcohols in excellent yields using NaBH4-K2CO3 in a mixed solvent system of dichloromethane and water (1:1) in the presence of a phase-transfer catalyst at low temperature. The importance of the work is its simplicity, selectivity, excellent yield, and very short reaction time. This new reduction condition has proved to be an excellent chemoselective method for a range of acid chlorides in the presence of various functional groups.

Full text of DOI:10.1080/00397910903340645

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Practical and Chemoselective
Reduction of Acyl Chloride to
Alcohol by Borohydride in Aqueous
Dichloromethane
Ramya Rajan a , Sachin Badgujar a , Kamaljit Kaur a , Yashwardhan
Malpani a & Pranab R. Kanjilal a
a Syngenta Research and Technology Centre, Santa Monica Works,
Corlim, Ilhas, Goa, India
Version of record first published: 25 Aug 2010.
To cite this article: Ramya Rajan , Sachin Badgujar , Kamaljit Kaur , Yashwardhan Malpani &
Pranab R. Kanjilal (2010): Practical and Chemoselective Reduction of Acyl Chloride to Alcohol by
Borohydride in Aqueous Dichloromethane, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 40:19, 2897-2907
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Synthetic Communications1, 40: 2897–2907, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903340645
PRACTICAL AND CHEMOSELECTIVE REDUCTION OF
ACYL CHLORIDE TO ALCOHOL BY BOROHYDRIDE IN
AQUEOUS DICHLOROMETHANE
Ramya Rajan, Sachin Badgujar, Kamaljit Kaur,
Yashwardhan Malpani, and Pranab R. Kanjilal
Syngenta Research and Technology Centre, Santa Monica Works, Corlim,
Ilhas, Goa, India
A simple methodology for the reduction of acid chlorides to their corresponding alcohols has
been developed. Various carboxylic acids were converted to alcohols in excellent yields
using NaBH4-K2CO3 in a mixed solvent system of dichloromethane and water (1:1) in
the presence of a phase-transfer catalyst at low temperature. The importance of the work
is its simplicity, selectivity, excellent yield, and very short reaction time. This new reduction
condition has proved to be an excellent chemoselective method for a range of acid chlorides
in the presence of various functional groups.
Keywords: Acyl chloride; alcohol; aqueous dichloromethane; base; borohydride; phase-transfer catalyst
INTRODUCTION
Methodologies for functional group transformation are extremely important
for the continued evolution of organic synthesis. While working on the preparation
of potential agrochemicals, we were searching for efficient and chemoselective
methods to prepare primary alcohols from carboxylic acids and their derivatives.
In literature, a limited number of such methods is reported. These methods[1]
describe the use of sodium borohydride alone or in combination with different Lewis
acids or additives, or use of zinc borohydride or borane complexes for reduction of
carboxylic acids or their different derivatives to the corresponding alcohols.
Recently, Qiu and Zhang[2] reported preparation of alcohols from carboxylic acids
and their derivatives using a combination of potassium borohydride and magnesium
chloride. The methods reported in the literature suffer from one or more of the
following limitations: long reaction times, high reaction temperatures, and use of
either a large excess or expensive reagent. Moreover, these methods generally lack
selectivity and reduce other functional groups in the substrate. Our literature
search[3,4] revealed that carboxylic esters, acid chlorides, alkyl halides, and sulfonate
esters can effectively be reduced by using a combination of sodium borohydride and
Received June 5, 2009.
Address correspondence to Pranab R. Kanjilal, Syngenta Research and Technology Centre, Santa
Monica Works, Corlim, Ilhas, Goa 401 110, India. E-mail: Pranab.kanjilal@syngenta.com
2897

2898
R. RAJAN ET AL.
polyethylene glycol (PEG)-400. The reactions needed high temperatures and long
reaction times to complete. An isolated example of reduction of 6-chloronicotinoyl
chloride to the corresponding alcohol was reported by Sivasankaran et al.[5]
They used borohydride in aqueous dichloromethane in the presence of a carbonate
base. However, the report does not offer a detailed study of the method, which
required long reaction times. There are reports of borohydride reductions using
different phase-transfer catalysts. Yadav and Lande,[6] in their studies of the kinetics
of chemoselective reduction of citronellal, used sodium borohydride and tetraalkyl
ammonium salts as phase-transfer catalysts in biphasic medium and reported
that the rate of reduction with borohydride under phase-transfer catalytic conditions
is very fast. They also explained the mechanism of reduction in the biphasic
medium. PEGs are known as ‘‘poor chemist’s crowns.’’[7] Recently, Cao et al.[8]
reported reduction of aldehydes, ketones, and imines using sodium borohydride
and PEG-400 as phase-transfer catalyst under solvent-free conditions. In another
case, PEG-400 was used as phase-transfer catalyst in combination with PdCl2
as cocatalyst for reduction of the acetylenic bond with borohydride.[9] Freedman[10]
cited a large number of studies in which PEG had been used as a phase-transfer
catalyst and that had industrial applications. Among the different phase-transfer
catalysts, PEG-400 by far was much better, as reported by Cao et al.,[8] because of
its low cost, stability, ready availability, and apparent lack of significant toxicologi-
cal properties. In addition, compared with other phase-transfer catalysts, it has
the most ability to solubilize inorganic salts because of its terminal polar hydroxyl
groups.
RESULTS AND DISCUSSION
Present Work
To make intermediates for our agrochemical research, we required a mild
and selective method for reduction of acid chlorides to the corresponding alcohols.
We wanted to explore the phase-transfer catalytic effect of PEG-400 in our studies
using borohydride as the reducing agent in a biphasic medium (Scheme 1). In this
work, the mechanistic considerations were not our primary interest; rather, we
report a simple, selective, and efficient method that has been successfully scaled up
to 200 g.
Thus, acid chloride and sodium borohydride were added simultaneously to a
mixture of potassium carbonate and PEG-400 in a 1:1 mixture of dichloromethane
and water at low temperature, and the corresponding alcohol was formed in
excellent yield within 15 min. Table 1 shows the results of our explorations.
In our work, we studied different parameters, such as the effects of different
molar ratios of reducing agent, different bases, and different solvents.
Scheme 1. Reduction of acid chloride to alcohol.

CHEMOSELECTIVE REDUCTION OF ACYL CHLORIDE
2899
Table 1. Reduction of acid chlorides with NaBH4-PEG 400 in the presence of K2CO3 in CH2Cl2: H2O (1:1)
Product yields
Substrate
(1 mol equiv)
Mp (ꢀC)
(of product)
Reaction
time
Temp.
(ꢀC)
Entry
1
a
b
C
—
15 min
15 min
0–15
86%
—
—
2
117
0–15
0–15
96%
—
—
3
4
5
—
—
—
15 min
95–98%a–d
—
—
—
—
—
—
16 he
rt
93%
>30 min
0–15
98%f
6
7
8
—
55
45
8 h
15 min
15 min
0–15
0–15
0–15
0–15
18%
94%
95%
95%
38%
—
8%g
—
—
—
9
75
—
15 min
15 min
—
—
10
0–15 77% (volatile)
(Continued )

2900
R. RAJAN ET AL.
Table 1. Continued
Product yields
b
Substrate
(1 mol equiv)
Mp (ꢀC)
(of product)
Reaction
time
Temp.
(ꢀC)
Entry
11
a
C
—
15 min
15 min
0–15
70%
—
—
—
12
13
90
—
0–15
0–15
56%
20%
15 min
Quant.h
14
15
—
—
15 min
15 min
0–15
0–15
91%
97%
—
—
—
—
16
17
18
—
—
—
15 min
15 min
15 min
0–15
0–15
78%
55%
—
—
10%
40%
0–15 Phthalic acid
19
20
—
—
15 min
15 min
0–15
0–15
51%
40%
—
(Continued )

CHEMOSELECTIVE REDUCTION OF ACYL CHLORIDE
2901
Table 1. Continued
Product yields
b
Substrate
(1 mol equiv)
Mp (ꢀC)
(of product)
Reaction
time
Temp.
(ꢀC)
Entry
21
a
C
—
—
15 min
15 min
0–15
70%
—
—
—
—
22
0–15
93%
23
24
—
—
15 min
15 min
0–15
0–15
—
—
—
Recovered
—
93%
O
`
25
26
—
—
8 hi 15 Cart
25%
60%
—
—
60%
—
15 min
0–15
aYield 98% (PTC-PEG-400).
bYield 95% (PTC-TBAF).
cYield 97% (PTC-TBAB).
dYield 95% (PTC-18-Crown-6).
eDry THF was used as solvent.
fKBH4 was used as reducing agent.
gReaction was carried out without using any base, and along with the mixture of products the ester (d)
derived from the starting acyl chloride and alcohol (a) was isolated in 35%.
hThe desired alcohol was isolated along with the lactone in a ratio of 1:2. The lactone was derived from
the intramolecular reaction of the reduced alcohol with the adjacent ester, thus proving that the ester func-
tionality does not get reduced under this reaction condition.
iReaction was carried out in toluene=water (1:1) as the solvent, keeping the rest of the conditions
unchanged (11% starting acid chloride also was recovered along with the corresponding alcohol and acid).
Effect of Reducing Agent
The effects of different quantities of borohydride on the reaction rate and
conversion are shown in Fig. 1. A portion of borohydride was added at the
beginning to the reaction mixture, followed by simultaneous addition of the rest
of the reagent along with acid chloride; otherwise, a substantial amount of the start-
ing acid chloride was hydrolyzed to the starting acid. Our attempt to use potassium

2902
R. RAJAN ET AL.
Figure 1. Effect of the concentration of NaBH4 on the reduction of acid chloride.
borohydride in place of sodium borohydride (entry 5 in Table 1) did not prove to be
beneficial because the reaction required longer time for completion and potassium
borohydride is much more expensive.
Effect of Phase-Transfer Catalyst
Santaniello et al.[4] used 6 mL of PEG-400 and 1 mmol of substrate and reported
the formation of NaB(PEG)2H2 as the reducing agent by reaction of borohydride and
PEG-400 at 65–80 ꢀC. In our case, we used a catalytic amount (20 mol%) of PEG-400
at low temperature. We assume that PEG-400, in our case, played the role of a
phase-transfer catalyst like the tetraalkylammonium salts played in Yadav et al.’s work.[6]
In our case, use of other phase-transfer catalysts like 18-C-6, tetrabutylammonium bro-
mide (TBAB), or tetrabutylammonium fluoride (TBAF) gave similar results (entry 3) to
PEG-400, and an attempt to carry out the reduction without use of any phase-transfer
catalyst resulted in complete hydrolysis of acid chloride to the corresponding acid.
PEG-400 was preferred over the other phase-transfer catalysts for the same reasons.
Effect of Base
Presence of a base is required for the reaction, and potassium carbonate was
found to be the best. The effects of different quantities of potassium carbonate on
the reaction rate and conversion are shown in Fig. 2. Other bases were also tried but
found to be inferior (see Table 2). In the absence of the base, the reaction gave a
Table 2. Effects of different bases on reaction time, temperature, and product composition
Base
Reaction temperature
Reaction time
Product(s)
K2CO3
Cs2CO3
Na2CO3
TEA
0–15 ꢀC
RT
RT
15 min
9 h
a (exclusively)
a (exclusively)
Overnight
Overnight
15 min
Mixture of a, b, c, and d (ester)
Mixture of a, b, c, and d (ester)
Mixture of a, b, c, and d (ester)
RT
0–15 ꢀC
Nil

CHEMOSELECTIVE REDUCTION OF ACYL CHLORIDE
2903
Figure 2. Effect of concentration of K2CO3 on the reduction of acid chloride.
mixture of the desired alcohol (a), the corresponding aldehyde (b), the starting acid (c),
and an ester (d) derived from the reaction of the generated alcohol and the substrate
(entry 6). At pH 11–12, as in our case, borohydride is stable for a couple of days.[11]
We assume that in our case the base gives the stability to borohydride in aqueous
solution in addition to quenching the hydrochloric acid generated from the reaction.
Effect of Solvent
Different solvents were also tried. The reaction did not proceed at all in
CH2Cl2 alone, in tetrahydrofuran (THF) it required a very long time at rt (entry
4), and in a 1:1 mixture of toluene and water it gave rise to a mixture of products
(entry 25). We proved by the titrimetric analysis that the borohydride–PEG complex
is much more soluble in dichloromethane than in toluene.
Effect on Other Reducible Groups
Finally, we studied the effect of our reduction condition on other reducible
functional groups in the substrates. Different acid chlorides were studied, and the
borohydride–PEG combination under this reaction condition selectively reduces
the acid chloride in the presence of other reducible functional groups as evident from
entries 1–3 and 7–26. Anhydrides and imides were the exceptions. The anhydride was
completely hydrolyzed to diacid (entry 18), whereas only one carbonyl group was
reduced to methylene in imide (entry 19). Other combinations of borohydride with
activators reduce other functional groups as well.[12–21]
CONCLUSION
In conclusion, our report describes a simple, rapid, and selective method to
reduce acid chlorides to alcohols in excellent yields employing sodium borohydride
and polyethylene glycol.

2904
R. RAJAN ET AL.
EXPERIMENTAL
All yields reported are isolated yields. The products were characterized by their
melting points, wherever possible, and spectral and analytical data. 1H NMR spectra
were taken in CDCl3 solution (for few cases in dimethylsulfoxide, DMSO) at ambi-
ent temperature in a 400-MHz multinuclear Bruker machine, and the chemical shift
values are mentioned in d. Purities of all the products were ꢁ96% and were checked
by high-performance liquid chromatography (HPLC) in an Agilent-1200 series
machine in a reverse-phase manner. They were also cross-checked in some cases
by gas chromatography–mass spectrometry (GC-MS) on a Trace GC Ultra with
DSQ on a Thermo Finnigan machine and in some cases by liquid chromatography–
mass spectrometry (LC-MS) on a Surveyor HPLC with MSQ on a Thermo Finnigan
machine. Infrared (IR) spectra were taken on a Shimadzu Prestige 21 machine with
DRS 8000 in KBr. All experiments were carried out on a 0.5-g scale unless otherwise
mentioned.
General Procedure for the Preparation of 4-hydroxymethyl-2-
nitrobenzonitrile (15a)
A solution of 4-cyano-3-nitrobenzoic acid (0.5 g, 2.6 mmol) in dichloromethane
(10 mL) was boiled with thionyl chloride (2.8 ml, 3.91 mmol) for 3 h. The reaction
mixture turned to a dark solution. Excess thionyl chloride was distilled out under
reduced pressure along with dichloromethane on a rotary evaporator. The resulting
acid chloride was dissolved again in fresh and dry dichloromethane (2.5 mL) and was
added dropwise to a precooled (0–15 ꢀC) and stirred mixture of dichloromethane
(2.5 mL) and water (2.5 mL) containing potassium carbonate (0.71 g, 5.2 mmol),
PEG-400 (20 mol%), and a portion of sodium borohydride (0.2 eq.). The rest of
the borohydride (2 eq.) was added simultaneously with the acid chloride solution
over a period of 5 min. Stirring continued at the same temperature for another
10 min. The reaction mixture was diluted with water (25 mL) and extracted with
dichloromethane (3 ꢂ 20 mL). The combined organic extracts were washed with
brine (1 ꢂ 20 mL) and dried (Na2SO4). Evaporation of solvent afforded the desired
alcohol (15a) as a gummy mass. Purification on a short column of silica gel provided
1
the pure alcohol (0.45 g, 97%). Yield 97%; gummy mass; H NMR (CDCl3): 4.9 (s,
2H); 7.79 (d, J ¼ 8 Hz, 1H), 7.88 (d, J ¼ 8 Hz, 1H), 8.35 (s, 1H); (Mþ ¼ 178.0).
Exactly the same result was obtained when the reaction was carried out on a
200-g scale.
Selected Data
2-(300-Bromophenyl) ethanol (1a). Yield 86%; gummy mass; 1H NMR
(CDCl3): 2.84 (t, J ¼ 8 Hz, 2H), 3.86 (t, J ¼ 8 Hz, 2H), 7.16–7.18 (m, 2H),
7.35–7.39 (m, 2H).
(500-Methoxy-2’-nitrophenyl) methanol (2a). Yield 96%; mp 117 ꢀC; 1H
NMR (CDCl3): 2.19 (br s, 1H), 3.91 (s, 3H), 4.99 (s, 2H), 6.89 (dd, J ¼ 9.2 and
2.7 Hz, 1H), 7.22 (d, J ¼ 2.7 Hz, 1H), 8.17 (d, J ¼ 9.2 Hz, 1H); (Mþ ¼ 183.1).

CHEMOSELECTIVE REDUCTION OF ACYL CHLORIDE
2905
(4-Methoxyphenyl) methanol (3a). Yield 98%; gummy mass; 1H NMR
(CDCl3): 3.8 (s, 3H), 4.6 (s, 2H), 6.89 (d, J ¼ 8 Hz, 2H), 7.29 (d, J ¼ 8 Hz, 2H);
(Mþ ¼ 138.1).
3-(2’,4’,6’-Trichlorophenyl) propan-1-ol (7a). Yield 94%; mp 55 ꢀC; 1H
NMR (CDCl3): 1.79–1.86 (m, 2H), 2.96–3.0 (m, J ¼ 8 Hz, 2H), 3.73 (t, J ¼ 6 Hz,
2H), 7.30 (s, 2H); (Mþ ¼ 238.1).
(1-Methyl-4-trifluoromethyl-1H-pyrrol-3-yl) methanol (8a). Yield 95%;
1
mp 45 ꢀC; H NMR (CDCl3): 3.63 (s, 3H), 4.55 (s, 2H), 6.64 (s, 1H), 6.88 (s, 1H).
(2-Methyl-5-trifluoromethylthiazol-4-yl) methanol (9a). Yield 95%; mp
1
75 ꢀC; HNMR (CDCl3): 2.17 (br s, 1H), 2.70 (s, 3H), 4.97 (s, 2H).
2,2,2-Trichloroethanol (10a). Yield 77% (volatile colorless liquid); 1H NMR
(CDCl3) 2.85–3.15(br s, 1H), 4.15 (s, 2H); (Mþ ¼ 148.8).
3-(2,4,6-Trichlorophenyl) prop-2-en-1-ol (11a). Yield 70%; gummy mass;
1H NMR (CDCl3): 4.39 (dd, J ¼ 1.6 and 4.8 Hz, 2H), 6.39 (dt, J ¼ 16 and 4.8 Hz,
1H), 6.57 (dt, J ¼ 16 and 2 Hz, 1H), 7.34 (s, 2H); (Mþ ¼ 238.9).
5-(2,4,6-Trichlorophenyl)-pent-2,4-dien-1-ol (12a). Yield 56%; mp 90 ꢀC;
1H NMR (CDCl3): 1.43 (br s, 1H), 4.285 (d, J ¼ 5 Hz, 2H), 6.03 (dt, J ¼ 15.6 and
5 Hz, 1H), 6.463 (dd, J ¼ 10.8 and 15.6 Hz, 1H), 6.53 (d, J ¼ 16 Hz, 1H), 6.85 (dd,
J ¼ 10.8, 16 Hz, 1H), 7.33 (s, 2H); (Mþ ¼ 261.9).
2-Hydroxymethylbenzoic acid methyl ester (13a). Yield (quantitative);
1
gummy mass; H NMR (CDCl3): 3.89 (s, 3H), 5.09 (s, 2H), 7.57–7.61 (m, 3H),
7.89 (dd, J ¼ 4 and 7.2 Hz, 1H).
2-(4-Chlorophenoxy)-2-methylsulfanylethanol (14a). Yield 91%; gummy
1
mass; H NMR (CDCl3): 2.04 (s, 3H), 2.13 (t, J ¼ 7.6 Hz, 1H), 3.85 (ddd, J ¼ 5.6,
7.6, and 9.4 Hz, 1H), 4.03 (ddd, J ¼ 5.6, 7.6, and 9.4 Hz, 1H), 5.18 (dd, J ¼ 5.6
and 7.6 Hz, 1H), 6.98 (dd, J ¼ 5.6 Hz, 2H), 7.28 (dd, J ¼ 5.6 Hz, 2H).
Acetic acid-2-hydroxymethylphenyl ester (16a). Yield 78%; gummy mass;
1H NMR (CDCl3): 2.11 (s, 3H), 5.12 (s, 2H), 6.91–6.95 (m, 2H), 7.25–7.28 (m, 2H),
7.75 (s, 1H).
N-(2-Hydroxymethylphenyl)acetamide (17a). Yield 55%; gummy mass;
1H NMR (DMSO): 2.45 (s, 3H), 3.52 (s, 2H), 7.63–7.66 (m, 2H), 7.96 (dd, J ¼
8 Hz, 1H), 8.16 (d, J ¼ 8 Hz, 1H), (Mþ ¼ 166.13).
2,3-Dihydroisoindol-1-one (19a). Yield (quantitative); gummy mass; 1H
NMR (DMSO): 5.42 (s, 2H), 7.59 (dd, J ¼ 8 Hz, 1H), 7.69 (d, J ¼ 8 Hz, 1H), 7.78
(dd, J ¼ 8 Hz, 1H), 7.85 (d, J ¼ 8 Hz, 1H).
1
(4-Ethynyl-2-methylphenyl) methanol (20a). Yield 46%; gummy mass; H
NMR (DMSO): 2.2 (s, 3H), 4.08 (s, 1H), 4.48 (d, J ¼ 5.2 Hz, 2H), 5.15–5.18 (m, 1H),
7.25 (s, 1H), 7.30 (d, J ¼ 7.6 Hz, 1H), 7.35 (d, J ¼ 7.6 Hz, 1H).
2-(4-Triisopropylsilanyloxyphenoxy) propan-1-ol (21a). Yield 70%;
1
gummy mass; H NMR (CDCl3): 1.09 (d, J ¼ 7.2 Hz, 18H), 1.22 (d, J ¼ 6 Hz,

2906
R. RAJAN ET AL.
3H), 1.21–1.29 (m, 3H), 2.03 (br s, 1H), 3.64–3.75 (m, 2H), 4.33–4.37 (m, 1H), 6.79
(s, 4H).
1
Benzo[1,3]dioxol-4-yl-methanol (22a). Yield 93%; gummy mass; H NMR
(CDCl3): 1.99 (br s, 1H), 4.68 (s, 2H), 5.96 (s, 2H), 6.76–6.86 (m, 3H).
1
(2-Trifluoromethylphenyl) methanol (24a). Yield 93%; gummy mass; H
NMR (DMSO): 4.67 (s, 2H), 5.47 (br s, 1H), 7.45 (dd, J ¼ 7.6 Hz, 1H), 7.68 (dd,
J ¼ 7.6 Hz, 2H), 7.77 (d, J ¼ 7.6 Hz, 1H).
2,2,2-Trichloro-N-(2-hydroxyethyl) acetamide (25a). Yield 60%; gummy
1
mass; H NMR (DMSO): 3.23–3.27 (m, 2H), 3.45–3.50 (m, 2H), 4.78 (t, J ¼ 4 Hz,
1H), 8.88 (br s, 1H).
ACKNOWLEDGMENTS
We gratefully acknowledge the management of Syngenta for their support and
encouragement for this work. We thank Dr. C. S. Prasanna for some technical sug-
gestions and also Saikat Banerjee and Naresh Koneru for recording the spectral and
analytical data.
REFERENCES
1. (a) Chaikin, S. W.; Brown, W. G. Reduction of aldehydes, ketones, and acid chlorides by
sodium borohydride. J. Am. Chem. Soc. 1949, 71, 122–125; (b) Brown, M. S.; Rapoport,
H. The reduction of esters with sodium borohydride. J. Org. Chem. 1963, 28, 3261–3263;
(c) Brown, H. C.; Rao, B. C. S. A new powerful reducing agent—Sodium borohydride in
the presence of aluminum chloride and other polyvalent metal halides. J. Am. Chem. Soc.
1956, 78, 2582–2588; (d) Saeed, A.; Ashraf, Z. Sodium borohydride reduction of aromatic
carboxylic acids via methyl esters. J. Chem. Soc. 2006, 118, 419–423; (e) Haldar, P.;
Barman, G.; Ray, J. K. Sodium borohydride–iodine–mediated reduction of c-lactam car-
boxylic acids followed by DDQ-mediated oxidative aromatization: A simple approach
towards N-aryl-formylpyrroles and 1,3-diaryl-formylpyrroles. Tetrahedron 2007, 63,
3049–3056; (f) Kotsuki, H.; Ushio, Y.; Yoshimura, N.; Ochi, M. Efficient reduction of
acyl chlorides with zinc borohydride=N,N,N,N tetramethylethylenediamine. Tetrahedron
Lett. 1986, 27, 4213–4214; (g) Suzuki, N.; Kaneko, Y.; Tsukanaka, T.; Nomoto, T.;
Ayaguchi, Y.; Izawa, Y. Effective hydrogenation of carbon–carbon triple bonds by
NaBH4=PdCl2 in polyethylene glycol=CH2Cl2: Usefulness of PEG in synthetic reactions.
Tetrahedron 1985, 41, 2387–2392.
2. Qiu, Y.-C.; Zhang, F.-L.; Zhang, C.-N. A practical and efficient procedure for reduction
of carboxylic acids and their derivatives: Use of KBH4–MgCl2. Tetrahedron Lett. 2007,
48, 7595–7598.
3. Santaniello, P. F. E.; Sozzani, P. Reduction of esters to alcohols by means of sodium
borohydride in polyethylene glycols. J. Org. Chem. 1981, 46, 4584–4585.
4. Santaniello, A. F. E.; Manzocchi, A.; Ferraboschi, P. Reductions of esters, acyl halides,
alkyl halides, and sulfonate esters with sodium borohydride in polyethylene glycols: Scope
and limitation of the reaction. J. Org. Chem. 1983, 48, 3074–3077.
5. Sivasankaran, K. R.; Sundarraja, K.; Ratnam, K. R. Ind. Patent App. 181755, A1
19980912, 1998.

CHEMOSELECTIVE REDUCTION OF ACYL CHLORIDE
2907
6. Yadav, G. D.; Lande, S. V. Novelties of kinetics of chemoselective reduction of citronellal
to citronellol by sodium borohydride under liquid–liquid phase transfer catalysis. J. Mol.
Catal. A: Chem. 2006, 247, 253–259.
7. Balasubramanian, D.; Chandani, B. Polyethylene glycol. J. Chem. Ed. 1983, 60, 77.
8. Cao, Y.-Z. D.; Chen, B.-H.; Liu, R. Sodium borohydride reduction of ketones, aldehydes,
and imines using PEG400 as catalyst without solvent. J. Chem. Tech. Biotech. 2005, 80,
834–836.
9. Goldberg, Y. Phase-Transfer Catalysis: Selected Problems and Applications; Gordon
Breach, Amsterdam, 1992.
10. Freedman, H. H. Industrial applications of phase-transfer catalysis (PTC): Past, present,
and future. Pure Appl. Chem. 1986, 58, 857–868.
11. Gervasio, D.; Xu, M.; Thomas, E. Presentation at the Fuel Cell Design, Fabrication, and
Materials Selection Workshop, University of Illinois at Urbana–Champaign, July 26–27,
2005.
12. Encyclopedia of Reagents for Organic Synthesis; Wiley, Chichester, UK, 1999; vol. 7,
pp. 4522–4526.
13. Brown, H.-C.; Yoon, N. M. The borohydride-catalyzed reaction of diborane with epox-
ides: The anti-Markovnikov opening of trisubstituted epoxides. J. Am. Chem. Soc.
1968, 90, 2686.
14. Giannis, K. S. A. LiBH4(NaBH4)=Me3SiCl, an unusually strong and versatile reducing
agent. Angew. Chem. Int. Ed. 1989, 28, 218.
15. Yanada, K. Y. R.; Meguri, H. Promoting effect of sodium selenite (Na2SeO3) on the
activity of molybdenum oxide (MoO3) catalyst for nitroarenes reduction to amines with
sodium borohydride. Tetrahedron Lett. 1992, 33, 1463–1464.
16. Yoo, S. E. L.; Hee, S. Reduction of organic compounds with sodium borohydride–
copper(II) sulfate system. Synlett 1990, 7, 419–420.
17. Lalancette, J. M. F. A.; Brindel, J. R.; Laliberte, M. Reductions of functional groups with
sulfurated borohydrides: Application to steroidal ketones. Synthesis 1972, 10, 526–532.
18. Cowan, J. A. Cupric–borohydride reduction system: Synthetic utility and mode of action.
Tetrahedron Lett. 1986, 27, 1205–1208.
19. Itsuno, S. S.; Yoshiki, S.; Ito, K. Reduction of some functional groups with zirconium
tetrachloride=sodium borohydride. Synthesis 1988, 12, 995–996.
20. Akabori, S. T.; Yoshinori, T. Novel borane–selenium complex: Highly selective reduction
of tertiary amides and nitriles to the corresponding amines with sodium borohydride–
dialkylselenium dibromide. J. Chem. Soc., Perkin Trans. 1 1991, 2, 479–482.
21. Prasad, A. S. B. K.; Bhaskar, J. V.; Periasamy, M. Convenient methods for the reduction
of amides, nitriles, carboxylic esters, acids, and hydroboration of alkenes using the sodium
borohydride–iodine system. Tetrahedron 1992, 48, 4623–4628.