Dehydration of aldoximes to nitriles using trichloroacetonitrile without catalyst

Article abstract of DOI:10.1080/00397911.2021.1943752

Trichloroacetonitrile has been found to be an efficient dehydrating agent for a range of aldoximes including aromatic and heterocyclic aldoxime yielding the corresponding nitriles in moderate to good yields. The dehydration reactions can take place in non-acetonitrile media without the aid of a metal catalyst. In addition, it has been confirmed that trichloroacetonitrile was converted into trichloroacetamide in the reaction.

Full text of DOI:10.1080/00397911.2021.1943752

Synthetic Communications
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Dehydration of aldoximes to nitriles using
trichloroacetonitrile without catalyst
Xiaoyun Ma, Dan Liu & Zhengjian Chen
To cite this article: Xiaoyun Ma, Dan Liu & Zhengjian Chen (2021): Dehydration of aldoximes
to nitriles using trichloroacetonitrile without catalyst, Synthetic Communications, DOI:
10.1080/00397911.2021.1943752
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https://doi.org/10.1080/00397911.2021.1943752
Dehydration of aldoximes to nitriles using
trichloroacetonitrile without catalyst
Xiaoyun Ma, Dan Liu, and Zhengjian Chen
School of Chemistry and Materials Science, Guizhou Education University, Guiyang, China
ABSTRACT
ARTICLE HISTORY
Received 3 May 2021
Trichloroacetonitrile has been found to be an efficient dehydrating
agent for a range of aldoximes including aromatic and heterocyclic
aldoxime yielding the corresponding nitriles in moderate to good
yields. The dehydration reactions can take place in non-acetonitrile
media without the aid of a metal catalyst. In addition, it has been
confirmed that trichloroacetonitrile was converted into trichloroace-
tamide in the reaction.
KEYWORDS
Nitrile; aldoxime;
trichloroacetonitrile; tolu-
ene; trichloroacetamide
GRAPHICAL ABSTRACT
Introduction
Dehydration of aldoximes is a common method for the preparation of nitriles. There
are many reports on the dehydration of aldoximes to nitriles, numerous reagents and
various conditions have been developed. Among these, the metal-catalysed conversion
of aldoximes to nitriles in acetonitrile or propionitrile has attracted the attention of
many researchers over the last twenty years. To our knowledge, more than thirteen
kinds of catalysts such as copper salts,[1] SnCl2,[2] GaCl3,[2] osmium-guanidinate com-
plexes,[3] PhSeOH,[4] Pd(OAc)2,[5] Palladium(II) complexes,[6] nickel catalysts,[7]
Ga(OTf)3,[8] [RuCl2(pcymene)],[9] InCl3,[10] AlI3,[11] and [(CH3CH2CN)2PtCl4][12] have
been reported for dehydration of aldoximes. Interestingly, these catalytic reactions
should perform in a solvent containing the nitrile group such as CH3CN, and the use
of a catalyst is necessary.
Recently we reported the preparation of aromatic and heterocyclic nitriles by treating
aldoximes with malononitrile and Cu(OAc)2 in water, theses dehydration reactions can
take place in non-acetonitrile media with loading stoichiometric malononitrile.[13] We
now report an improved method in which the aldoximes react with trichloroacetonitrile
in toluene to provide the corresponding nitriles, and no catalyst is required.
CONTACT Xiaoyun Ma
maxiaoyun821215@163.com
School of Chemistry and Materials Science, Guizhou
Education University, Guiyang, China.
ß 2021 Taylor & Francis Group, LLC

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X. MA ET AL.
Table 1. Optimization of the reaction conditions (solvent, dehydration reagent) for the dehydration
of benzaldoxime to benzonitrile.a
Entry
Reagent(equiv.)
Solvent
toluene
Time (h)
yieldb/%
81(80)c
–
10
–
88
–
–
1
2
3
4
5
6
7
8
CCl3CN (1.0)
CCl3CN (1.0)
CCl3CN (1.0)
–
CCl3CN (1.5)
CH3CN (1.5)
CH3(CH2)3CN
6
6
6
6
4
4
4
4
acetone
acetonitrile
toluene
toluene
toluene
toluene
toluene
–
9
10
11
ClCH2CH2CN
CH2ClCN (1.5)
CHCl2CN (1.5)
toluene
toluene
toluene
4
4
4
trace
16
67
aReaction conditions: a stirred mixture of benzaldoxime (2 mmol) and a dehydration reagent in different solvent (6 mL)
was reacted for various times.
bIsolated yield.
c0.1 mmol Cu(OAc)2 was added, the mixture was stirred for 24 h at room temperature.
Results and discussion
For our optimization studies, we selected benzaldoxime as a model substrate to
investigate the influence of reaction solvent and dehydration reagents on the yields
of the reaction. The results are listed in Table 1. As shown in the table, we found
that benzaldoxime was easily converted to benzonitrile by the action of trichloroace-
tonitrile in refluxing toluene, benzonitrile was obtained in 81% yield without the aid
of a catalyst (Table 1, entry 1). The combination use of trichloroacetonitrile and a
metal catalyst, which is similar to our previous work,[13] can lower the required
reaction temperature. Benzaldoxime was easily converted to benzonitrile in presence
of trichloroacetonitrile and cupric acetate at room temperature, and benzonitrile was
obtained in 80% yield (Table 1, entry 1). Although a catalyst can reduce the activa-
tion energy of the reaction, we did not intend to explore the combination use of tri-
chloroacetonitrile and a metal catalyst in this reaction because a number of methods
have been published for the aldoxime – nitrile transformation in the presence of
transition metals and nitrile such as acetonitrile, propionitrile and malononitrile.
Being a nitrile, trichloroacetonitrile should have the same role in these transforma-
tions. Thus, we only explored the dehydration of aldoximes under non-catalytic con-
ditions in this paper. Use of acetone instead of toluene resulted in no product
(Table 1, entry 2). When acetonitrile was used in place of toluene as solvent, the
yield of benzonitrile was only 10% (Table 1, entry 3). On the basis of the results
obtained, toluene is suitable solvent for the dehydration reaction without a catalyst.
It is worth noting that a higher boiling point solvents such as paraxylene are also
an effective solvent, they were not selected as reaction media in this paper because
they are not easy to remove by distillation.

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Table 2. Yields of a series of nitriles prepared by reaction of an aldoxime with trichloroacetonitrile
in toluenea.
Entry
Substrate (R)
3-NO2-C6H4
4- NO2-C6H4
2-Cl-C6H4
4- N(CH3)2-C6H4
4-OH-C6H4
4-CH3O-C6H4
3-MeO-4-MeO-C6H3
4-CH3-C6H5
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
5
5
5
1
2
2
2
6
4
4
3
2
80
90c
83
87
84
83
86
62c
76
85
91
90
9
9-Anthryl
1-Naphthyl
10
11
12
(E)-C6H5-CH ¼ CH
2-Thienyl
aReaction conditions: aldoxime (2 mmol), trichloroacetonitrile (3 mmol), toluene (6 mL), reflux.
bIsolated yield.
c2.0 equiv. trichloroacetonitrile was used.
Trichloroacetonitrile was necessary, no product formation was detected in the
absence of trichloroacetonitrile (Table 1, entry 4). Increasing the amount of trichlor-
oacetonitrile to 1.5 equiv. shortened the reaction time and raised the yield slightly,
and benzaldoxime was dehydrated to the corresponding nitrile with complete conver-
sion (Table 1, entry 5). In addition, we investigated the reactivities of acetonitrile,
pentanenitrile, cyclopropanecarbonitrile, 3-chloropropanenitrile, chloroacetonitrile and
dichloroacetonitrile. No product was detected when acetonitrile, pentanenitrile or
cyclopropanecarbonitrile was used as a dehydrating agent (Table 1, entries 6–8). In
the case of 3-chloropropanenitrile, a trace amount of benzonitrile was detected by
TLC. However, the yield of benzonitrile was very low and it was difficult to separate
by column chromatography (Table 1, entry 9). Chloroacetonitrile and dichloroaceto-
nitrile exhibited relatively high reactivities, and the reaction of benzaldoxime with
chloroacetonitrile and dichloroacetonitrile gave benzonitrile in 16% and 67% yields,
respectively (Table 1, entries 10–11). In general, trichloroacetonitrile show the high-
est reactivity in the dehydration reaction. We thought that the strong negative
inductive effect of the trichloromethyl group enhance electrophilicity of the nitrile
carbon, which facilitating the nucleophilic addition of aldoxime.
On the basis of the above results, we can conclude that using trichloroacetonitrile in
refluxing toluene is the optimal condition for the dehydration of aldoximes to nitriles.
This optimum method was then applied to other aldoximes and the yields of the cor-
responding nitriles are shown in Table 2. Compared with benzaldoxime, substrates bear-
ing electron-withdrawing group showed relatively low reactivity and longer reaction
time was needed (Table 2, entries 1–3). The yields of 4-nitrobenzonitrile, 3-nitrobenzo-
nitrile and 2-chlorobenzonitrile are not less than 80%, in the case of 4-nitrobenzalde-
hyde oxime, 2 equiv. trichloroacetonitrile was used and the yield of 4-nitrobenzonitrile
went up to 90% (Table 2, entry 2).

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Scheme 1. Proposed mechanism for the preparation of nitriles from aldoximes
Aldoximes bearing strong electron-donating groups show relatively high reactivity
and the reaction could be completed within 2 h, the corresponding nitriles were
obtained in good yield (Table 2, entries 4–7). In the case of 4-methylbenzaldehyde
oxime, although it has a weak electron-donating methyl group at the 4th position, the
conversion rate was found to be relatively lower. Increasing the amount of trichloroace-
tonitrile and extending reaction time cannot effectively improve the conversion of 4-
methylbenzaldehyde oxime to 4-methylbenzonitrile, the yield of the reaction was only
62% (Table 2, entries 8).
In the case of polycyclic aromatic aldoxime, cinnamaldehyde oxime and heterocyclic
aldoxime the reaction process were similar to the aldoxime mentioned above, and they
were smoothly converted to the corresponding nitriles in good yields under the
employed reaction conditions (Table 2, 9–12). In addition, it should be noted that ali-
phatic aldoximes could not effectively be converted to the corresponding nitriles in this
reaction system, various by-products were formed and separation was difficult.
A possible reaction mechanism is proposed in Scheme 1. We thought that the reac-
tion mechanism is similar to that reported in the literatures.[1a,1b,3,5a,12], which explained
metal-catalysed conversion of aldoximes to nitriles in acetonitrile or propionitrile solv-
ent. As shown in Scheme 1, unlike the mechanism reported in the literatures,
3,4-dimethoxybenzaldehyde oxime react with trichloroacetonitrile to provide 3,4-dime-
thoxybenzonitrile without the aid of a catalyst, the strong negative inductive effect of
the trichloromethyl group results in an enhanced electrophilicity of the nitrile carbon
facilitating the nucleophilic addition of 3,4-dimethoxybenzaldehyde oxime, the resulting
complex disproportionating to give 3,4-dimethoxybenzonitrile and trichloroacetamide.
Trichloroacetamide can be separated easily by a simple method: 3,4-dimethoxybenzal-
dehyde oxime react with trichloroacetonitrile in refluxing toluene for 2 h, then the
resulted mixture was cooled to room temperature and kept for 2 h, the precipitated solid
was filtered off and washed with carbon tetrachloride, petroleum ether/ethyl acetate
1
(15:1) and water to give pure trichloroacetamide and it has been characterized by H
NMR and melting point determination.
Conclusions
In conclusion, we disclosed a method for the dehydration of aldoximes to nitriles using
trichloroacetonitrile as a dehydrating agent in reflux toluene. Using this method aldox-
imes, including aromatic aldoximes and heterocyclic aldoxime, were converted into the
corresponding nitriles in moderate to high yield. A possible reaction mechanism was

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5
proposed and it was confirmed that trichloroacetonitrile was transformed into trichlor-
oacetamide in the dehydration reaction.
Experimental
Melting points were determined on a Thomas Hoover capillary apparatus and were
1
uncorrected. HNMR spectra were obtained from a Bruker Avance NEO 600 spectrom-
eter. Analytical thin layer chromatography (TLC) was performed on precoated silica gel
60 F254 plates. Yields refer to the isolated yields of the products after purification by
silica-gel column chromatography (300 mesh). Aldoximes were synthesized according to
the method reported in the literature.[14] All the nitriles products and 2,2,2-trichloroace-
1
tamide are known compounds and they were characterized by H NMR spectra.
General procedure for the synthesis of nitriles
To a 25 mL round-bottom flask equipped with magnetic stirrer were added aldoxime
(2 mmol), trichloroacetonitrile (3 mmol) and toluene (6 mL). The mixture was heated to
reflux for 1–6 h. After cooling to room temperature, the solution was directly evapo-
rated to dryness and the residue was purified by column chromatography on silica gel
(ethyl acetate/petroleum ether) to give the corresponding nitriles.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This work was supported by the Construction Project of Key Laboratories from the Education
Department of Guizhou Province [Grant No. QJHKY[2018]001] and the Construction Project of
First-class Courses from Guizhou Education University [Grant No. GSYF[2018]100].
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