Butyltriphenylphosphonium tetrahydroborate (BTPPTB) as a selective reducing agent for reduction of organic compounds

Article abstract of DOI:10.1081/SCC-100104001

Butyltriphenylphosphonium tetraborate (BTPPTB) (1) has been found to be a selective and versatile reducing agent. The reagent in dichloromethane solution or under solvent-free conditions is very useful for reduction of aldehydes, ketones, carboxylic acid chlorides, aryl azides, and aroyl azides to the corresponding alcohols, amines and amides, respectively.

Full text of DOI:10.1081/SCC-100104001

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BUTYLTRIPHENYLPHOSPHONIUM
TETRAHYDROBORATE
(BTPPTB) AS A SELECTIVE
REDUCING AGENT FOR
REDUCTION OF ORGANIC
COMPOUNDS
Abdol Reza Hajipour a & Shadpour E. Mallakpour a
a Pharmaceutical Research Laboratory , College
of Chemistry, Isfahan University of Technology ,
Isfahan, IR, Iran
Published online: 09 Nov 2006.
To cite this article: Abdol Reza Hajipour & Shadpour E. Mallakpour (2001)
BUTYLTRIPHENYLPHOSPHONIUM TETRAHYDROBORATE (BTPPTB) AS A SELECTIVE
REDUCING AGENT FOR REDUCTION OF ORGANIC COMPOUNDS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 31:8, 1177-1185, DOI: 10.1081/SCC-100104001
To link to this article: http://dx.doi.org/10.1081/SCC-100104001
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SYNTHETIC COMMUNICATIONS, 31(8), 1177–1185 (2001)
BUTYLTRIPHENYLPHOSPHONIUM
TETRAHYDROBORATE (BTPPTB) AS A
SELECTIVE REDUCING AGENT FOR
REDUCTION OF ORGANIC COMPOUNDS
Abdol Reza Hajipour* and Shadpour E. Mallakpour
Pharmaceutical Research Laboratory, College of
Chemistry, Isfahan University of Technology, Isfahan, IR,
Iran
ABSTRACT
Butyltriphenylphosphonium tetraborate (BTPPTB) (1)
has been found to be a selective and versatile reducing agent.
The reagent in dichloromethane solution or under solvent-free
conditions is very useful for reduction of aldehydes, ketones,
carboxylic acid chlorides, aryl azides, and aroyl azides to the
corresponding alcohols, amines and amides, respectively.
Lithium borohydride and sodium borohydride are two extremes of
nucleophilic hydride transfer agent. Lithium borohydride is a very powerful
reducing agent and can reduce most of the reducible functional groups. On
the other hand, sodium borohydride is a mild reagent, used mostly for the
reduction of aldehydes and ketones in protic solvents.1 In spite of the great
convenience of using NaBH4, certain limitations may be observed with this
reagent. Polar and protic solvents are needed. This reagent is able to reduce
* Corresponding author. E-mail: haji@cc.iut.ac.ir
1177
Copyright & 2001by Marcel Dekker, Inc.
www.dekker.com

1178
HAJIPOUR AND MALLAKPOUR
only a few functional groups, and a long reaction time is required. To
increase or decrease the reactivity of NaBH4, the modification of sodium
borohydride has attracted a great deal of attention recently.2–16
In general, modification of the usual reducing ability of the sodium
borohydride has led to selective reduction of several functional groups that
are otherwise inert to sodium borohydride alone. For instance, the reduc-
tions of acid chlorides to aldehydes,4 and alkenes to saturated hydrocar-
bons5 can be achieved by use of the combination of sodium borohydride
with Cu (I) and Co (II), respectively, while such conversions cannot be
achieved with sodium borohydride alone. Very recently, 1-benzyl-4-aza-1-
azoniabiyclo[2.2.2]octane tetrahydroborate2 has been reported for reduction
of reducible organic compounds.13–16
We report the preparation of butyltriphenylphosphonium tetraborate
(BTPPTB) (1) and reduction of reducible functional groups with this reagent.
This reagent reduces reducible functional groups in CH2Cl2 at room tempera-
ture. It is quite soluble in CH2Cl2 and produces a clear solution that, on
standing at room temperature, does not lose its reducing ability. This obser-
vation is in contrast to what is reported for tetrabutylammonium tetraborate.
(Bu4NBH4), which decomposes to Bu3N, BuH, and BH3 on standing in sol-
ution.17. The stability of this reagent in comparison to Bu4NBH4 is the reflec-
tion of the presence of the phosphonium cation in the reagent that is more
stable than ammonium cation. BTPPTB 1reduces aldehydes, ketones, and
carboxylic acids to their corresponding alcohols in high yield (Scheme 1and
Tab. 1). The reagent reduces benzylic and allylic aldehydes almost immedi-
ately. Reduction of saturated aldehydes and benzylic ketones with this
reagent is much slower than benzylic and allylic aldehydes. ꢀꢁ-Unsaturated
carbonyl compounds are selectively reduced via 1,2-reduction.
Scheme 1.

ORGANIC COMPOUND REDUCTION
1179
Another noteworthy advantage of this reaction lies in its selective
reduction of aldehydes in the presence of other reducible functions such
as ketones and double bonds. When we retreated an equimolar amount of
aldehyde with 1 in the presence of ketone, only the aldehyde was selectively
reduced (Eq. 1). The C¼O groups of ꢀ,ꢁ-unsaturated aldehydes or ꢀ,ꢁ-
unsaturated ketones were selectively reduced to the corresponding alcohols
and the C¼C double bonds remained intact (Tab. 1). To evaluate the
Table 1. Reduction of Carbonyl Compounds and Carboxylic Acid Chlorides to
their Alcohols in CH2Cl2 at Room Temperature
Reaction
Time (min)
M.p. or
b.p.ꢀC/mm Hg
Entry
R1
R2
Yield%a,b
1
2
3
4
5
6
7
8
9
C6H5
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-BrC6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5
5
5
5
7
6
5
7
5
8
5
5
7
94
93
94
92
90
87
89
96
205
245–246/760
130–132/760
257–259/760
78–80
4-BrC6H4
77–79
35–36
59–61
2-MeC6H4
4-MeC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
9169–71
88
90
10
11
12
13
14
15
16
17
18
19
20
21(-CH
22
23
24
25
26
27
235
70–71
69–71
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2,5-(MeO)2C6H3
3,4-(MeO)2C6H3
3,5-(MeO)2C6H3
(-CH2-)5
94
9130–32
93
85
90
94
95
92
88
90
90
94
94
91
93
90
5
92–94
99–101/0.2
135–37/0.2
43–46
22–24
139–40/760
204/745
82–85/10
33–35
142–44/21
202–205
219–21/750
92–93
10
10
7
50
50
40
55
5
45
5
10
5
—
—
CH3
H
(-CH2-)4
C6H5
2-)6
C6H5CH¼CH
C6H5CH¼CH
C6H5
C6H5CH2
4-NO2C6H4
(-CH2-)6
H
Me
Cl
Cl
Cl
Cl
10
82–85/10
aAll yields refer to pure isolated products; bAll of the products were fully
1
characterized by comparing with known compounds and by their IR and H NMR
spectra.

1180
HAJIPOUR AND MALLAKPOUR
chemo- and regioselectivity of reagent 1, another experiment was performed
with equimolar amounts of ꢀ,ꢁ-unsaturated aldehyde or ꢀ,ꢁ-unsaturated
ketone and reagent 1 (Eq. 2).
In recent years, organic reactions on solid supports19,20 under solvent-
free conditions have attracted attention.21,22 The advantage of these
methods over conventional homogenous reactions is that they provide
greater selectivity, enhanced reaction rates, cleaner products, and manipu-
lative simplicity.23–29 Toda has reported the reduction of various ketones
with NaBH4 under solvent-free conditions. In those reports, a ten-fold
molar ratio of NaBH4 was mixed with ketone and kept in a dry box for 5
days.30,31 This method does not show selectivity for the reduction of ꢀ,ꢁ-
unsaturated carbonyl compounds, and also needs large excesses of the redu-
cing agent and long reaction times. Very recently, Varma reported micro-
wave-assisted reduction of carbonyl compounds under solid-state conditions
using supported NaBH4 on Al2O3. In that report, ꢀ,ꢁ-unsaturated carbonyl
compounds were reduced to the corresponding saturated alcohols in 40%
and allyl alcohol in 60% yields using 8 molar ratio of supported NaBH4 on
Al2O3 and microwave irradiation.32
In continuation of our ongoing program to develop environmentally
benign methods using solid supports,23–29 we tried the reduction of alde-
hydes, ketones, and carboxylic acid chlorides to the corresponding alcohols
with reducing reagent 1 under solvent-free conditions. The reduction
proceeded faster than in dichloromethane. The reaction was normally
completed within 5–30 min grinding a mixture of aldehydes, ketones,

ORGANIC COMPOUND REDUCTION
1181
or carboxylic acid chlorides with reagent 1. The process in its entirety
involves a simple mixing of aldehydes, ketones, or carboxylic acid chlorides
with reagent 1. The process in its entirety involves a simple mixing of alde-
hydes, ketones, or carboxylic acid chlorids with reagent 1. The mixture was
ground for the time specified in Table 2 at room temperature. The yields of
the reactions are excellent (90–97%) and the reaction times are exceedingly
short (1–20 min) (Tab. 2).
Table 2. Reduction of Carbonyl Compounds and Carboxylic Acid Chlorides to
Their Alcohols Under Solvent-Free Conditions
Reaction
Time (min)
Entry
R1
R2
Yield%a,b
1
2
3
4
5
6
7
8
9
C6H5
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-BrC6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1
1
1
1
1
1
1
1
1
2
1
1
1
2
1
1
3
1
1
3
5
192
4
193
2
190
2
99
90
96
90
95
93
94
92
90
94
90
98
92
98
98
93
98
0
4-BrC6H4
2-MeC6H4
4-MeC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
10
11
12
13
14
15
16
17
18
19
20
21(-CH
22
23
24
25
26
27
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2,5-(MeO)2C6H3
3,4-(MeO)2C6H3
3,5-(MeO)2C6H3
(-CH2-)5
—
—
CH3
H
90
94
(-CH2-)4
C6H5
2-)6
0
98
93
C6H5CH¼CH
C6H5CH¼CH
C6H5
C6H5CH2
4-NO2C6H4
(-CH2-)6
H
Me
Cl
Cl
Cl
Cl
90
95
96
aAll yields refer to pure isolated products; bAll of the products were fully
1
characterized by comparing with known compounds and by their IR and H NMR
spectra.

1182
HAJIPOUR AND MALLAKPOUR
BTPPTB 1 is a highly selective reagent for the reduction of aryl azides
and aroyl azides in CH2Cl2 at room temperature to the corresponding
amines and amides, respectively (Scheme 2, Tab. 3). Quaternary ammonium
tetraborates do not show such selectivity, e.g., benzyl azide is reduced
with 1-benzyl-4-aza-1-azoniabiyclo[2.2.2]octane tetrahydroborate 2 and
Bu4NBH4 in 10 and 5 h, respectively, with excellent yields.13–18
reagent ð1Þ
ArN3 ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ! ArNH2
dichloromethane
Scheme 2.
In conclusion, we have discovered a new and useful method for the
reduction of aldehydes, ketones, and carboxylic acid chloride to their cor-
responding alcohols with reducing reagent 1 in high yield. The reaction
proceeds in dichloromethane or under solvent-free conditions. Under sol-
vent-free conditions, the yield of the reactions is higher and the reactions are
faster. The reagent also reduces aryl azides and aroyl azides to their corre-
sponding amines and amides, respectively, in high yields.
Table 3. Reduction of Aryl and Aroyl Azides to the in Corresponding Amines and
Amides in CH2CL2 AT Room Temperature
Reaction
Time (min)
Entry
Ar
Yield(%)a,b
M.p.ꢀC
14-NO
2
3
4
5
6
7
8
9
2C6H4
2-ClC6H4
4-NO2-2-Cl-C6H3
4-EtO2CC6H4
4-MeC6H4
C6H4CH2
C6H4CH(OH)CH2
2-ClC6H4CO
1
5
2
10
16
—
—
20
10
8
97
99
98
92
98
147–149
69–71
107–109
88–90
42–46
—
—
167–170
180–182
no reaction
no reaction
97
4-MeC6H4CO
4-NO2C6H4CO
3,4(MeO)2C6H3CH2CO
6H4CH2CCO
91
10
11
1
65–67 811
no reaction
no reaction
—
—
—
—
2
aAll yields refer to pure isolated products; bAll of the products were fully
1
characterized by comparing with known compounds and by their IR and H NMR
spectra.

ORGANIC COMPOUND REDUCTION
EXPERIMENTAL
1183
All products were identified by comparison with an authentic sample
(IR, NMR, m.p. and b.p.). All m.p. were taken on a Gallenkamp melting
apparatus and are uncorrected. Elemental analyses were performed by the
1
Research Institute of Petroleum Industry, Tehran, I. R. Iran. H NMR
spectra were recorded on a Varian EM-390 NMR Spectrometer operating
at 90 MHz, or a Varian Unity 250 Fourier Transform NMR Spectrometer
operating at 250 MHz. 13C NMR spectra were recorded on a Varian
Unity 400 Fourier Transform NMR Spectrometer operating at 100 MHz.
The spectra were measured in CDCl3 unless otherwise stated, relative to
TMS (0.00 ppm) Mass spectra were recorded on a Shimadzu GC-MS-QP
1000PX.
Synthesis of Reducing Agent (1)
To a solution of butyltriphenylphosphonium bromide (19.97 g,
50 mmol, 50 mL H2O), was added sodium borohydride (1.89 g, 50 mmol)
in one portion. The reaction mixture was stirred at room temperature for
90 m. The resulting white solid product was collected, washed with water
(10 mL) and dried in a desiccator under vacuum over calcium chloride to
yield 16.38 g (98%) of white solid product m.p. 270ꢀ–72ꢀC. H NMR: ꢂ
1
7.90–7.50 (m, 15 H), 3.5 (d, J ¼ 25.6 Hz, CH2-P), 1.8 (m, 4 H), 0.98 (t, 3
H). 13C NMR: ꢂ 133.50, 133.20, 130.20, 129.60, 129.40, 128.10, 127.70,
127.2, 108.30 (d, J ¼ 85.5 Hz, P-CH2). IR (KBr): 1298, 1269, 1098, 1060,
700, 658, 590, 546 cmÀ1. MS (CI) m/z 334 (100, Mþ). Anal calc. for
C22H28BP: C, 79.06; H, 8.44%. Found; C, 78.80; H, 8.80%.
Reduction of Aldeydes, Ketones, and Carboxylic Acid Chlorides to
Their Corresponding Alcohols with Reducing Reagent (1)
in Dichloromethane at Room Temperature
Aldehyde, ketone, or carboxylic acid chloride (1mmol) was added to a
stirred solution of reducing agent (1) (1 mmol, 0.33 g) in CH2Cl2 (10 mL).
The mixture was stirred at room temperature until TLC showed complete
disappearance of the starting material, which required 5–60 min, depending
on the substrate, and then the reaction mixture was washed with water
(2ꢁ15 mL). The dichloromethane layer was dried over MgSO4.
Evaporation of the solvent gave the corresponding alcohols. The product
was purified by column chromatography on silica gel using a mixture of
ethyl acetate/n-hexane (10/90) as eluent.

1184
HAJIPOUR AND MALLAKPOUR
Reduction of Aryl Azides and Aroyl Azides with Reducing Reagent
(1) in Dichloromethane at Room Temperature
Azide (1 mmol) was added to a stirred solution of reducing agent (1)
(1mmol, 0.33 g) in CH 2Cl2 (10 mL). The mixture was stirred at room tem-
perature until TLC showed complete disappearence of the starting material,
which required 5–60 m depending on the substrate, and then the reaction
mixture was washed with water (2ꢁ15 mL). The dichloromethane layer was
dried over MgSO4. Evaporation of the solvent gave the corresponding
amines or azides. The product was purified by column chromatography on
natural alumina using a mixture of ethyl acetate/n-hexane (30/70) as eluent.
Reduction of Aldehydes, Ketones, and Carboxylic Acid Chlorides to
Their Corresponding Alcohols with Reducing Reagent (1)
Under Solvent-Free Conditions
A mortar was charged with aldehyde, ketone, or carboxylic acid chlor-
ide and reducing reagent (1) (1mmol, 0.33 g). The mixture was ground at
room temperature with a pestle until TLC showed complete disappearance
of the starting material. The mixture was then extracted with CCl4
(2ꢁ10 mL). Evaporation of the solvent gave the corresponding alcohols.
The product was purified by column chromatography on silica gel using a
mixture of ethyl acetate/n-hexane (10:90) as eluent.
ACKNOWLEDGMENTS
Partial support of this work by the Isfahan University of Technology
Research Council is gratefully acknowledged.
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Received April 24, 2000