Borontrifluoride etherate promoted one-pot conversion of nitriles to esters

Article abstract of DOI:10.1081/SCC-120024013

One-pot borontrifluoride etherate promoted transformation of nitriles to esters was achieved by heating in corresponding alcohol as a reactant and solvent.

Full text of DOI:10.1081/SCC-120024013

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Borontrifluoride Etherate Promoted One-Pot
Conversion of Nitriles to Esters
G. Jayachitra a , N. Yasmeen a , K. Srinivasa Rao a , Samuel L. Ralte a , R. Srinivasan a & A.
K. Singh a
a Fine Chemicals Laboratory, Division of Organic Chemistry–III, Indian Institute of Chemical
Technology, Hyderabad, India
Version of record first published: 15 Aug 2006.
To cite this article: G. Jayachitra, N. Yasmeen, K. Srinivasa Rao, Samuel L. Ralte, R. Srinivasan & A. K. Singh (2003):
Borontrifluoride Etherate Promoted One-Pot Conversion of Nitriles to Esters, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:19, 3461-3466
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 19, pp. 3461–3466, 2003
Borontrifluoride Etherate Promoted One-Pot
Conversion of Nitriles to Esters#
G. Jayachitra, N. Yasmeen, K. Srinivasa Rao, Samuel L. Ralte,
*
R. Srinivasan, and A. K. Singh
Fine Chemicals Laboratory, Division of Organic
Chemistry–III, Indian Institute of Chemical
Technology, Hyderabad, India
ABSTRACT
One-pot borontrifluoride etherate promoted transformation of
nitriles to esters was achieved by heating in corresponding alcohol
as a reactant and solvent.
Key Words: Borontrifluoride; One-pot conversion; Nitriles; Esters;
Alcohols.
#IICT Communication No. 020805.
*Correspondence: A. K. Singh, Fine Chemicals Laboratory, Division of Organic
Chemistry–III, Indian Institute of Chemical Technology, Hyderabad 500 007,
India; E-mail: aksingh@iict.ap.nic.in.
3461
DOI: 10.1081/SCC-120024013
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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3462
Jayachitra et al.
The extensive uses of BF3.OEt2 in many organic transformations like
acetylation,[1] alkylation, cyclization,[2] polymerization,[3] cleavage of
ethers[4] & epoxides[5] and dehydration are well known in literature.
BF3.OEt2 catalyzed hydration and condensation of nitriles,[6] and the
conversion of nitrile to ester via hydrolysis to carboxylic acid have
been reported in the literature.[1,7] Using mineral acids in a dry alcohol[1,7]
and polyphosphate esters in methanol[8] for the transformation of nitriles
to esters are known in literature. In this report, we described the usage of
BF3.OEt2 in an alcohol for the direct, simple and clean conversion of
nitriles to the variety of corresponding esters (Sch. 1).
While we have been engaged with BF3.OEt2 catalyzed functional
group transformations, the usage of BF3.OEt2 was found in the forma-
tion of esters directly from the corresponding nitriles and alcohols. It was
confirmed by conducting the experiments on the reaction of benzonitrile
with refluxing ethyl alcohol and water separately in presence of BF3.OEt2,
which lead to ethyl benzoate and benzamide respectively. When we
performed the same reaction of benzonitrile in refluxing ethyl alcohol
in the absence of BF3.OEt2 for seven days, we did not observe any
change in staring material and it was recovered quantitatively. Apart
from the advantage of one-pot conversion of nitriles to esters, this
conversion has the possibility of desired ester formation by selecting
the appropriate alcohol as reactant and solvent. To generalize these
observations, several experiments were conducted by utilizing various
substituted aromatic nitriles, and aliphatic alcohols like methanol,
ethanol, and iso-propanol and the results were tabulated based on
some variants (Table 1).
The study was extended to the aliphatic substrate (malononitrile),
which is more reactive than the aromatic substrates. To generalize our
findings on this conversion, the catalytic studies were done on malono-
nitrile withvarious alcoohls under similar conditions for converting
the aliphatic nitirile to aliphatic monoesters and diesters (Sch. 2). For
example, malononitrile was heated in refluxing ethanol in presence of
BF3.OEt2 to obtain ethyl cyanoacetate as major and ethyl malonate as
minor products. The results of other reactions were tabulated as above
(Table 2). Spectral data of all compounds are satisfied as in literature.
BF3.OEt2
RCN
RCOOR'
R = Aryl
R'OH, Reflux
R' = Alkyl
Scheme 1.

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Borontrifluoride Etherate
3463
Table 1.
Ratio
Time Substrate: BF3.OEt2 Yielda (%)
Substrate
[solvent]
S. no.
Product
CN
COOR
[9a]
1
2
3
23 hb
1:4.0
82
91
76
13, R = CH3
[CH3OH]
[C2H5OH]
[(CH3)2CHOH]
[9b]
20 h1:4.0
62 h1:4.0
14, R = C2H5
15, R = iPr[10a]
CN
Cl
COOR
Cl
4
5
6
6.5db
8.0d
1:4.0
1:6.7
43
67
83
16, R = CH3[10b]
17, R = C2H5[10b]
18, R = iPr
[CH3OH]
[C2H5OH]
[(CH3)2CHOH]
23 h1:6.5
COOR
CN
N
N
[9c]
7
8
7.0d
6.0d
1:6.0
1:6.0
43
67
19, R = CH3
[CH3OH]
[C2H5OH]
[9d]
20, R = C2H5
CN
COOR
N
N
9
10
11
4.5d
5.0d
3.5d
1:4.0
1:4.0
1:4.0
63
40
54
[9e]
[CH3OH]
21, R = CH3
[9f]
[C2H5OH]
[(CH3)2CHOH]
22, R = C2H5
23, R = iPr
CN
COOEt
12
3.6d
1:4.4
54
F
F
F
F
[C2H5OH]
24[10c]
aIsolated yields.
bd ¼ days; h ¼ hours.
In conclusion, the borontrifluoride etherate complex promoted
direct conversion of nitriles to the corresponding esters (alkyl/aryl–
alkyl) had been successfully achieved by using excess of an appropriate
alcohol. The step-wise process through acids or amides to esters was

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3464
Jayachitra et al.
CN
CN
CN
COOR'
COOR'
BF3.OEt2
H2C
H2C
H2C
+
R'OH, Reflux
COOR'
Major
Minor
R' = Alkyl
Scheme 2.
Table 2. Reaction of malononitrile and alcohol.
COOR'
COOR'
CN
Ratio
H2C
H2C
S.
no. Alcohol
Time
(h)
COOR '
Mono estera
Diesterb
Substrate: BF3.OEt2
1
2
3
4
EtOH
EtOH
MeOH
90%; R0 ¼ Et[11a]
4%[11b]
Not formed
24
36
68
21
1:2.1
1:1.3
1:2.1
1:2.0
100%; R0 ¼ Et
68%; R0 ¼ Me[11c] 28%[11d]
n-BuOH 75%; R0 ¼ Bu[11e] 20%[12]
aIsolated yields.
avoided by adopting this direct conversion of nitriles. Malononitrile
was selectively converted into monoester (major) and diester (minor) by
varying the molarity of BF3.OEt2 and reaction time (Table 2). The studies
for finding a more efficient catalyst for the above transformation and the
scope of utilization of this observation i.e., desymmetrization by selective
functional group transformation in dinitriles are under progress.
EXPERIMENTAL
General Procedure
In a round bottom flask (50 mL) fitted witha reflux condenser was
taken benzonitrile (1 g, 9.71 mmol) in ethanol (10 mL). A freshly distilled
BF3.OEt2 (5.51 g, 38.82 mmol) was introduced into the reaction vessel and
then the resulting mixture was refluxed under N2 atm for 20 h. The solvent
was removed under reduced pressure, washed with water (2 ꢀ 15 mL) and
extracted withDCM (3 ꢀ 30 mL). DCM layer was dried over anhy.
Na2SO4, the solvent was removed in vacuo and the crude product was
purified through silica gel column using Petroleum ether–Ethyl acetate
(9.8:0.2) as eluent to obtain compound 14 as a colorless liquid.

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Borontrifluoride Etherate
3465
Compound15.Rf ¼ 0.70(EtOAc–Pet.ether,1:49);IR(Neat,ꢀmax)cmÀ1
:
1715; 1H NMR (200 MHz, CDCl3/TMS) ppm: ꢁ 1.40 (d, J ¼ 6.75 Hz, 6H,
-(CH3)2), 5.25 (p, J ¼ 6.75 Hz, 1H, -CH-), 7.50 (d, J ¼ 6.75 Hz, 2H, ArH),
7.55 (dd, J ¼ 6.75 Hz, 1H, ArH), 7.85 (d, J ¼ 6.75 Hz, 2H, ArH); MS (m/e):
164 (Mþ).
Compound 18. Rf ¼ 0.81 (EtOAc–Pet.ether, 1:4); IR (neat, ꢀmax) cmÀ1
:
1
1720; H NMR (400 MHz, CDCl3/TMS) ppm: ꢁ 1.25 (d, J ¼ 8.7 Hz, 6H,
-(CH3)2), 4.25 (p, J ¼ 8.7 Hz, 1H, -CH-), 7.25–7.35 (m, 3H, ArH), 7.65
(d, J ¼ 8.7 Hz, 1H, ArH); MS (m/e): 198, 200 (Mþ).
Compound 20. Rf ¼ 0.56 (EtOAc–Pet.ether, 1:3); IR (Neat, ꢀmax
)
cmÀ1: 1718; 1H NMR (200 MHz, CDCl3/TMS) ppm: ꢁ 1.40 (t, J ¼
8.1 Hz, 3H, COOCH2CH3), 4.40 (q, J ¼ 8.1 Hz, 2H, COOCH2CH3),
7.40 (dd, J ¼ 10.8 Hz, 1H, ArH), 8.30 (d, J ¼ 10.8 Hz, 1H, ArH), 8.75
(d, J ¼ 10.8 Hz, 1H, ArH), 9.20 (s, 1H, ArH); MS (m/e): 151 (Mþ).
Compound 23. Rf ¼ 0.40 (EtOAc-Pet.ether, 1:4); IR (Neat, ꢀmax) cmÀ1
:
1
1717; H NMR (400 MHz, CDCl3/TMS) ppm: ꢁ 1.45 (d, J ¼ 6.6 Hz, 6H,
-(CH3)2), 5.30 (p, J ¼ 6.6 Hz, 1H, -CH-), 7.85 (d, J ¼ 8.8 Hz, 2H, ArH),
8.80 (d, J ¼ 8.8 Hz, 2H, ArH); MS (m/e): 165 (Mþ).
ACKNOWLEDGMENT
Authors thank Dr. K. V. Raghavan, Director, IICT and CSIR,
New Delhi for allowing us to work on this project and for financial support.
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