Nitrilation of carboxylic acids with acetonitrile catalyzed by molybdenum and vanadium complexes

Article abstract of DOI:10.1134/S1070428016090050

Various carbonitriles were synthesized by reaction of the corresponding carboxylic acids with acetonitrile in carbon tetrachloride in the presence of VO(acac)₂and Mo(CO)₆in 6 h at 150–170°C.

Full text of DOI:10.1134/S1070428016090050

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 9, pp. 1282–1286. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © R.I. Khusnutdinov, N.A. Shchadneva, A.R. Bayguzina, Yu.Yu. Mayakova, 2016, published in Zhurnal Organicheskoi Khimii, 2016,
Vol. 52, No. 9, pp. 1295–1299.
Nitrilation of Carboxylic Acids with Acetonitrile
Catalyzed by Molybdenum and Vanadium Complexes
R. I. Khusnutdinov,* N. A. Shchadneva, A. R. Bayguzina, and Yu. Yu. Mayakova
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
*e-mail: inklab4@gmail.com
Received May 25, 2016
Abstract—Various carbonitriles were synthesized by reaction of the corresponding carboxylic acids with
acetonitrile in carbon tetrachloride in the presence of VO(acac)2 and Mo(CO)6 in 6 h at 150–170°C.
DOI: 10.1134/S1070428016090050
Nitriles constitute a very important class of organic
compounds. They are used as solvents and interme-
diate products for the synthesis of drugs, pesticides,
and plasticizers. The most important compounds of
the nitrile series are acetonitrile (universal solvent),
acrylonitrile (monomer for synthetic fiber), and adipo-
nitrile (starting compound for the synthesis of capro-
lactam and hexamethylenediamine). The use of aceto-
nitrile and benzonitrile as promoters of manganese
catalysts for the oxidation of toluene increases the
conversion of toluene by a factor of 15 and reduces the
catalyst consumption by a factor of 28. Benzonitrile is
a starting material for the manufacture of formalde-
hyde resins, azeotropic agent for the separation of
naphthalene–alkylnaphthalene mixtures, and solvent
for chlorinated rubber and cellulose nitrates and
acetates [1, 2].
amines in the presence of NiO2 at 300‒350°C, and
graphite- or sodium iodide-catalyzed cyanation of
aldehydes with hydroxylamine hydrochloride [3–7].
Aliphatic C7–C17 nitriles were synthesized in 50–
57% yield by reaction of acetonitrile with the corre-
sponding aliphatic carboxylic acids at 270°C [8]; for
this purpose, 10-fold excess of sulfuric acid was used
as catalyst [9]. Apart from nitriles, the reaction mix-
tures contained the corresponding amide and N-acetyl
amide at a ratio of 3:1:3.
Reactions of carboxylic acids with acetonitrile can
be catalyzed by transition metal complexes such as
Fe(acac)3, Co(acac)3, Cu(acac)2, Pd(acac)2, Mo(CO)6,
Rh(acac)3, and VO(acac)2. Table contains the results of
the reaction of benzoic acid as model substrate with
acetonitrile in the presence of different metal com-
plexes (Scheme 1). It is seen that the best catalysts are
VO(acac)2 and Mo(CO)6. The reaction of benzoic acid
Classical methods for the preparation of nitriles are
based on addition of hydrogen cyanide to olefins and
1,3-dienes, oxidative ammonolysis (400–500°C),
dehydration of carboxylic acid amides and ammonium
salts, radical cyanation of alkyl iodides, oxidation of
Reaction of benzoic acid with acetonitrile in the presence of
different catalysts
Temperature,
°C
Yield of
benzonitrile, %
Catalyst
Time, h
Scheme 1.
COOH
Fe(acac)3
Co(acac)3
Cu(acac)2
Pd(acac)2
Rh(acac)3
VO(acac)2
Mo(CO)6
200
200
200
200
200
170
150
3
3
3
3
3
3
6
030
063
065
085
094
100
100
+
MeCN + CCl4
1a
Catalyst
CN
150–200°C, 3–6 h
1b
1282

NITRILATION OF CARBOXYLIC ACIDS WITH ACETONITRILE
1283
Scheme 2.
COOH
CN
Mo(CO)6, 150°C, 6 h
+
MeCN
+
CCl4
R
R
2a–5a
2b–5b
2, R = Me; 3, R = MeO; 4, R = Br; 5, R = Cl.
Scheme 3.
COOH
CN
VO(acac)2, 150°C, 6 h
+
MeCN + CCl4
HO
Cl
6a, 7a
6b, 7b
6a, o-OH; 7a, m-OH; 6b, 2-Cl; 7b, 3-Cl.
Scheme 4.
Mo(CO)6 or VO(acac)2
150°C, 6 h
COOMe
CN
+
MeCN
MeCN
+ CCl4
Cl
8a
Cl
6b
COOH
CN
Mo(CO)6, 150°C, 6 h
+
+ CCl4
OMe
OMe
9a
9b
(1a) with acetonitrile in the presence of Mo(CO)6 at
a [Mo]–1a–MeCN–CCl4 molar ratio of 1:100:(300–
500):(50–300) was complete in 6 h at 150°C, and
benzonitrile (1b) was formed in quantitative yield. In
all cases, excess acetonitrile was used since it was
simultaneously the reagent and the solvent. A neces-
sary condition for successful nitrilation was the pres-
ence of carbon tetrachloride as co-solvent. Further
experiments were carried out with Mo(CO)6 and
VO(acac)2 as catalysts.
in the reaction catalyzed by Mo(CO)6 was as low as
28%. Methyl 2-methoxybenzoate (9a) was converted
into 2-methoxybenzonitrile (9b, yield 66%) in the
presence of Mo(CO)6 (Scheme 4).
1- and 2-Naphthoic acids 10a and 11a reacted with
acetonitrile in the presence of Mo(CO)6 at a higher
temperature (170°C) to form naphthalene-1-carboni-
trile (10b) and naphthalene-2-carbonitrile (11b) in 77%
and 82% yield, respectively (Scheme 5). The yields of
10b and 11b at 150°C did not exceed 40–50%.
In the series of substituted benzoic acids, the yields
of the corresponding nitriles depended on the nature of
substituents and their position. The effect of the para
substituent on the reaction course was insignificant.
The reactions of acetonitrile with 4-methylbenzoic,
4-methoxybenzoic, 4-bromobenzoic, and 4-chloro-
benzoic acids 2a–5a smoothly afforded substituted
benzonitriles 2b (92%), 3b (88%), 4b (72%), and 5b
(73%) (Scheme 2). Unexpectedly, the reaction of
acetonitrile with salicylic acid (6a) in the presence of
VO(acac)2 led to the formation of 2-chlorobenzonitrile
(6b) due to concurrent replacement of the hydroxy
group by chlorine with participation of carbon tetra-
chloride. 3-Hydroxybenzoic acid (7a) reacted with
acetonitrile in a similar way (Scheme 3).
Adamantane-1-carboxylic acid (12a) vigorously
reacted with acetonitrile in the presence of Mo(CO)6 to
give a mixture of adamantane-1-carbonitrile (12b) and
3-chloroadamantane-1-carbonitrile (12c) at a ratio of
2:1 with a quantitative overall yield. When VO(acac)2
was taken as catalyst, nitrile 12b was formed as the
only product (Scheme 6). Aliphatic carboxylic acids,
specifically propionic (13a), butyric (14a), valeric
(15a), and decanoic (16a) showed high reactivity
toward acetonitrile under catalysis by Mo(CO)6 and
VO(acac)2. Regardless of the carbon chain length, the
corresponding nitriles (13b–16b) were obtained with
high yields (Scheme 7). The reactivity of dicarboxylic
acids depended on the length of the carbon chain
connecting the carboxy groups. Malonic acid failed to
react with acetonitrile, whereas the reaction of adipic
acid (17a) with acetonitrile under catalysis by
VO(acac)2 smoothly afforded adiponitrile (17b)
2-Chlorobenzonitrile (6b) was also obtained in 70%
yield from 2-chlorobenzoic acid (8a) and acetonitrile
in the presence of VO(acac)2, whereas the yield of 6b
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KHUSNUTDINOV et al.
1284
Scheme 5.
COOH
CN
Mo(CO)6, 170°C, 4 h
+
+
MeCN + CCl4
10a
10b
COOH
CN
Mo(CO)6, 170°C, 4 h
MeCN + CCl4
11a
11b
Scheme 6.
CN
CN
Mo(CO)6, 140°C, 4 h
+
COOH
Cl
+
MeCN + CCl4
12b
12b
2:1
12c
VO(acac)2, 150°C, 6 h
12a
Scheme 7.
VO(acac)2, 150°C, 6 h
Me
COOH
Me
CN
+
MeCN + CCl4
( )n
( )n
13a–16a
13b–16b
13, n = 1; 14, n = 2; 15, n = 3; 16, n = 8.
Scheme 8.
O
VO(acac)2, 150°C, 6 h
OH
NC
+
MeCN + CCl4
HO
CN
O
17a
17b
COOH
CN
VO(acac)2, 150°C, 6 h
+
MeCN + CCl4
HOC(O)
NC
18a
18b
(Scheme 8). The reaction of terephthalic acid (18a)
with MeCN in the presence of VO(acac)2 in CCl4 was
very vigorous, while no reaction was observed with
phthalic or isophthalic acid.
a Shimadzu GCMS-QP2010Plus instrument (SPB-5
capillary column, 30 m×0.25 mm; carrier gas helium;
oven temperature programming from 40 to 300°C at
a rate of 8 deg/min; injector temperature 280°C, ion
source temperature 200°C; electron impact, 70 eV).
The elemental compositions were determined with
a Carlo Erba 1106 analyzer.
The yields of nitriles decreased as the reaction time
increased, presumably due to reversibility of the reac-
tion. The yields refer to the isolated product. The prod-
uct structure was determined by spectral methods and
by comparison with authentic samples.
The reactions were carried in sealed ampules or in
a stainless steel high-pressure microreactor. The prog-
ress of reactions and the purity of the isolated com-
pounds were monitored by GLC on Shimadzu GC-9A
and GC-2014 instruments (2 m×3-mm column packed
with 5% of SE-30 on Chromaton N-AW-HMDS; oven
temperature programming from 50 to 270°C at
8 deg/min; carrier gas helium, flow rate 47 mL/min).
EXPERIMENTAL
The 13C NMR spectra were recorded on a Bruker
Avance-400 spectrometer (100.62 MHz) using CDCl3
as solvent. The mass spectra were obtained on
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NITRILATION OF CARBOXYLIC ACIDS WITH ACETONITRILE
1285
(CN), 113.87 (C1), 129.99 (C6), 130.36 (C5), 131.84
(C2), 133.17 (C4), 135.12 (C3).
General procedure for the reaction of aceto-
nitrile with carboxylic acids. A 17-mL stainless-steel
high-pressure microreactor was charged with 1 mmol
of Mo(CO)6 or VO(acac)2, 100 mmol of carboxylic
acid, 500 mmol of acetonitrile, and 50 mmol of carbon
tetrachloride. The reactor was hermetically closed and
heated for 6 h at 150°C. When the reaction was
complete, the reactor was cooled to room temperature
and opened, the mixture was filtered through a layer of
Al2O3, unreacted acetonitrile and carbon tetrachloride
were distilled off, and the residue was distilled under
atmospheric or reduced pressure or recrystallized from
ethanol.
2-Methoxybenzonitrile (9b). Yield 66%,
bp 98.7°C (3 mm). 13C NMR spectrum, δC, ppm:
109.04 (C1), 112.95 (C3), 117.52 (CN), 121.34 (C5),
133.96 (C6), 135.82 (C4), 161.38 (C2). Mass spectrum,
m/z (Irel, %): 133 (100) [M]+, 134 (7), 132 (29), 104
(12), 103 (19), 102 (5), 90 (31), 78 (7), 77 (5), 76 (10),
75 (7), 64 (12), 63 (14), 50 (5), 39 (12).
Naphthalene-1-carbonitrile (10b). Yield 77%,
mp 35.5–36°C (from EtOH); published data [10]:
13
mp 35°C. C NMR spectrum, δC, ppm: 110.11 (C1),
118.12 (CN), 125.23 (C3), 127.37 (C7), 127.80 (C8a),
128.96 (C8), 129.44 (C6), 131.76 (C2), 132.43 (C4a),
132.87 (C5), 133.42 (C4).
Benzonitrile (1b). Yield 98%, bp 95–96°C
(30 mm); published data [10]: bp 191°C. 13C NMR
spectrum, δC, ppm: 111.77 (C1), 118.30 (CN), 128.65
(C3, C5), 131.52 (C2, C6), 132.30 (C4). Mass spectrum,
m/z (Irel, %): 103 (100) [M]+, 104 (7.4), 77 (5.6), 76
(32.5), 75 (7.5), 59 (4), 52 (5.7), 50 (17.2), 43 (12), 39
(6.7), 37 (4.6), 39 (6.7).
Naphthalene-2-carbonitrile (11b). Yield 82%,
mp 66–67°C (from EtOH); published data: mp 66°C.
13C NMR spectrum, δC, ppm: 109.45 (C2), 119.22
(CN), 126.37 (C3), 127.75 (C8), 128.06 (C6), 128.44
(C8a), 129.06 (C7), 129.20 (C4), 132.27 (C4a), 134.06
(C1), 134.65 (C5).
4-Methylbenzonitrile (2b). Yield 92%, mp 37–
37.5°C (from EtOH); published data [10]: mp 38°C.
13C NMR spectrum, δC, ppm: 21.74 (CH3), 109.27
(C1), 119.30 (CN), 129.65 (C3, C5), 132.02 (C2, C6),
143.68 (C4). Found, %: C 82.15; H 6.48; N 11.28.
C8H7N. Calculated, %: C 82.02; H 6.02; N 11.96.
Adamantane-1-carbonitrile (12b). Yield 98%,
mp 193.5–194°C (from MeOH); published data [11]:
mp 193–194°C. Mass spectrum, m/z (Irel, %): 161 (57)
[M]+, 162 (7), 160 (12), 146 (21), 135 12), 134 (100),
133 (5), 132 (5), 120 (5), 119 (10), 118 (7), 107 (7),
106 (7), 105 (15), 104 (14), 95 (19), 94 (21), 93 (48),
92 (10), 91 (14), 81 (4), 80 (4), 79 (19), 78 (7), 77 (14),
69 (19), 68 (7), 67 (10), 66 (5), 65 (7), 55 (7), 54 (7),
53 (7), 51 (5), 41 (19), 39 (19).
4-Methoxybenzonitrile (3b). Yield 88%, mp 62–
63°C (from MeOH); published data [10]: mp 62°C.
13C NMR spectrum, δC, ppm: 55.55 (OCH3), 104.03
(C1), 114.72 (C3, C5), 119.15 (CN), 134.12 (C2, C6),
162.88 (C4).
3-Chloroadamantane-1-carbonitrile (12c). Yield
32%, mp 208–209°C (from MeOH); published data
[12]: mp 208.5–209°C. Mass spectrum, m/z (Irel, %):
195 (12) [M]+, 168 (7.1), 161 (12), 160 (100), 159 (7),
128 (6.5), 118 (10), 105 (6.3), 104 (14), 93 (13.4), 92
(10), 91 (13), 79 (10), 77 (13), 65 (11), 55 (6), 53 (8),
41 (21.5), 39 (25).
4-Bromobenzonitrile (4b). Yield 70%, mp 111–
111.5°C (from hexane–MeOH); published data [10]:
mp 112°C. 13C NMR spectrum, δC, ppm: 111.19 (C1),
117.90 (CN), 127.76 (C4), 132.68 (C3, C5), 133.27
(C2, C6).
4-Chlorobenzonitrile (5b). Yield 73%, mp 90–
91°C (from EtOH); published data [10]: mp 92°C.
13C NMR spectrum, δC, ppm: 110.79 (C1), 117.90
(CN), 129.68 (C3, C5), 133.27 (C2, C6), 139.87 (C4).
Propanenitrile (13b). Yield 82%, bp 96–97°C;
published data [10]: bp 97°C. Mass spectrum, m/z
(Irel, %): 55 (10) [M]+, 54 (62.2), 53 (7.1), 52 (11), 51
(8.7), 28 (100), 27 (18.4), 26 (20.5), 23 (7.5), 15 (8.6).
2-Chlorobenzonitrile (6b). Yield 75%, mp 42.5–
43°C (from EtOH); published data [10]: mp 43°C.
13C NMR spectrum, δC, ppm: 113.42 (C1), 116.98
(CN), 127.35 (C5), 128.99 (C3), 133.12 (C6), 134.71
(C2), 135. 88 (C4).
Butanenitrile (14b). Yield 80%, bp 118–119°C;
published data [10]: bp 118°C. Mass spectrum, m/z
(Irel, %): 42 (4.3), 41 (100), 40 (4), 39 (9.2), 38 (4), 29
(62.4), 28 (10), 27 (33.6), 26 (7.5), 15 (4.1).
Pentanenitrile (15b). Yield 78%, bp 75°C
(70 mm); published data [10]: bp 141°C. 13C NMR
spectrum, δC, ppm: 13.18 (C5), 16.92 (C2), 21.87 (C4),
27.41 (C3), 119.84 (CN).
3-Chlorobenzonitrile (7b). Yield 72%, mp 41–
42°C (from hexane–MeOH); published data [10]:
mp 41°C [10]. 13C NMR spectrum, δC, ppm: 113.42
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KHUSNUTDINOV et al.
2. Mel’nikov, N.N., Khimiya i tekhnologiya pestitsidov
1286
Decanenitrile (16b). Yield 70%, bp 97–98°C
(5 mm); published data [10]: bp 245°C. 13C NMR
spectrum, δC, ppm: 14.08 (C1), 22.69 (C9), 24.99 (C3),
28.82 (C4), 29.12 (C6, C7), 29.33 (C5), 31.97 (C8),
119.82 (CN).
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Hexanedinitrile (17b). Yield 72%, bp 129–130°C
(3 mm); published data [10]: bp 295°C. 13C NMR
spectrum, δC, ppm: 16.45 (C2, C5), 24.28 (C3, C4),
119.29 (CN).
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Benzene-1,4-dicarbonitrile (18b). Yield 80%,
mp 226.5–227°C (from EtOH); published data [10]:
mp 224–227°C. 13C NMR spectrum, δC, ppm: 115.97
(C1, C4), 117.65 (CN), 131.62 (C2, C3, C5, C6).
p. 1841.
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This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 14-03-97029 r_povolzh’e-a). The spectral studies
were performed at the Agidel’ Joint Center at the
Institute of Petrochemistry and Catalysis of the
Russian Academy of Sciences.
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