Selective Monohydrocyanation of Diimine using Potassium Hexacyanoferrate(II)-Benzoyl Chloride Reagent System as a Cyanide Source

Article abstract of DOI:10.1007/s12039-016-1191-0

The selective monohydrocyanation of diimines using potassium hexacyanoferrate(II)-benzoyl chloride reagent system as a cyanide source under catalyst-free condition is described. The advantages of this protocol are the non-toxic, non-volatile and inexpensive cyanide source, high yield, and simple work-up procedure. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-016-1191-0

J. Chem. Sci. ꢀc Indian Academy of Sciences.
DOI 10.1007/s12039-016-1191-0
Selective Monohydrocyanation of Diimine using Potassium
Hexacyanoferrate(II)-Benzoyl Chloride Reagent System
as a Cyanide Source
∗
ZHENG LI , FEI WEN and JINGYA YANG
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu 730070, P. R. China
e-mail: lizheng@nwnu.edu.cn
MS received 22 June 2016; revised 26 August 2016; accepted 12 September 2016
Abstract. The selective monohydrocyanation of diimines using potassium hexacyanoferrate(II)-benzoyl
chloride reagent system as a cyanide source under catalyst-free condition is described. The advantages
of this protocol are the non-toxic, non-volatile and inexpensive cyanide source, high yield, and simple
work-up procedure.
Keywords. Aminonitrile; monohydrocyanation; diamine; potassium hexacyanoferrate(II)
1
1 14
15
1
. Introduction
synthesize benzonitriles,
aroyl cyanides, sulfonyl
16
17
18
cyanides, benzyl cyanides, and cinnamonitriles.
Our current research interests focused on the cyana-
Nucleophilic addition of cyanide to imine is an impor-
tant way to access α-aminonitriles. α-Aminonitriles
are very useful building blocks in the construction of
a variety of organic intermediates, such as natural and
unnatural α-amino acids, different nitrogen-containing
heterocycles like imidazoles, thiadiazoles. Over the
past decade, lots of synthetic protocols for the prepara-
tion of α-aminonitriles have been reported. The direct
introduction of cyano groups into molecules which con-
tain unsaturated carbon-nitrogen bonds appears to be
one of the most straightforward methods. However,
some of these approaches use strongly toxic chemi-
cals, such as HCN, NaCN and KCN, as cyanating
agents, which render nucleophilic additions unsafe and
environmentally unfriendly. Recently, some safer cya-
1
tion of unsaturated compounds including C=O, C=N
and/or C=C bonds by nucleophilic addition reactions
19 24
using K [Fe(CN) ] as a cyanide source.
Especially,
4
6
2
our research group recently has reported some exam-
ples for the hydrocyanation of enones,
3
4
25 28
29 31
imines,
32
33
unsaturated esters and unsaturated nitriles by using
K [Fe(CN) ] as a cyanide source. As an extension, in
this work, we report an efficient method for the selective
monohydrocyanation of substrates bearing two C=N
bonds, diimines, using K [Fe(CN) ]-benzoyl chloride
4
6
4
6
reagent system as a cyanide source under catalyst-free
condition.
5
6
7
8
9
nating agents, such as Zn(CN) , TMSCN and acetone
2
2. Experimental
10
cyanohydrin, were also reported. However, the explo-
ration for green cyanide sources still has very important
meaning to the environment.
2
.1 General information
Potassium hexacyanoferrate(II), K [Fe(CN) ], is a IR spectra were recorded using KBr pellets on an
4
6
1
byproduct of the coal chemical industry and commer- Alpha Centauri FTIR spectrophotometer. H NMR and
cially available on a ton scale. It is also used in the
13
C NMR spectra were recorded on a Mercury-400BB
food industry for metal precipitation. In addition, it has instrument using CDCl as solvent and Me Si as inter-
3
4
been described as an anti-agglutinating auxiliary for nal standard. Elemental analyses were performed on a
table salt (NaCl). Recently, K [Fe(CN) ] has been used Vario El Elemental Analysis instrument. Melting points
4
6
as a cyanide source for some substitution reactions to were observed in an electrothermal melting point appa-
◦
ratus. Potassium hexacyanoferrate(II) was dried at 80 C
under vacuum for 24 h and finely powdered prior to
use. Diimines were prepared according to literature
procedure.
∗
34
For correspondence

Zheng Li et al
In order to further confirm the possibility of dihy-
2.2 The general procedure for the monohydrocyanation
of diimines
drocyantion, the isolated product 2a was further reacted
with K [Fe(CN) ]-benzoyl chloride reagent system
4
6
The mixture of K [Fe(CN) ] (0.2 mmol) and benzoyl under similar condition, including the use of an excess
4
6
◦
chloride (1.2 mmol) was heated at 160 C for 3 h, then amount of K [Fe(CN) ], prolonged reaction time and
4
6
the reaction system was cooled to room temperature and elevated reaction temperature (Scheme 2). However, no
diimine (1 mmol) in 20 mL of MeOH was added. The dihydrocyanated product was obtained. This result fur-
mixture was stirred at room temperature for appropri- ther demonstrated the monohydrocyanation selectivity
ate times indicated in Table 2. After completion of the of 1a. The possible reason is that steric hindrance of
reaction monitored by TLC, the resulting mixture was monohydracyanated product 2a efficiently blocked fur-
filtered, and the filtrate was concentrated under reduced ther hydrocyanation of the second C=N bond of 2a with
pressure, and the residue was isolated by column chro- K [Fe(CN) ].
4
6
matography using petroleum ether and ethyl acetate as
an eluent to obtain pure product.
The solvent also played an important role in this reac-
tion. It was found that the model reaction in toluene
could not take place (Table 1, entry 1). The reac-
tion in THF, 1,4-dioxane, CH Cl , MeCN, DMSO and
2
2
3
. Results and Discussion
DMF could give the desired product in moderate yield
Table 1, entries 2–7). In contrast, the reaction in MeOH
and EtOH afforded the desired product in high yield
Table 1, entries 8–9). Among them, MeOH was the
best solvent for the reaction (Table 1, entry 8).
(
Previous work in our group showed that K [Fe(CN) ]
4
6
can abstract cyanide ions when using an efficient
promoter without transition metal catalysts. It was
found that benzoyl chloride could efficiently promote
K [Fe(CN) ] to release cyanide ions and yield an
(
4
6
intermediate, benzoyl cyanide, which could be iden-
tified and isolated from the reaction system.3 In this
paper, we focus on the hydrocyanation of diimines with
K [Fe(CN) ] by a one-pot two-step procedure using
5
4
6
benzoyl chloride as a promoter.
ꢁ
Initially, N,N -diphenylbutane-2,3-diimine (1a)
1
2
(
Scheme 1, R = Ph, R = Me) was selected as a sub- Scheme 2. Further hydrocyanation of monohydrocyanated
strate to examine the feasibility of hydrocyantion with product 2a.
K [Fe(CN) ]. It was found that 1a could be hydrocyana-
4
6
ted smoothly under catalyst-free condition to afford
-methyl-2-(phenylamino)-3-(phenylimino)butanenitrile
2a) as sole product in 91% yield only using benzoyl
Table 1. The effect of solvents on the yield of the mono-
hydrocyanation of 1a with K4[Fe(CN)6] .
a
2
(
chloride as a promoter. This reaction was even con-
ducted using bases, acids or transition metal complexes
as catalysts. However, no improved yield was observed.
In this reaction, it was found that for 1 mol of 1a,
only 0.2 equiv. of K [Fe(CN) ] was required, which
4
6
−
b
indicated that all six CN groups in K [Fe(CN) ] Entry
Solvent
Time (h)
Yield (%)
4
6
could be readily utilized in this reaction. However,
the dihydrocyanated product was not observed under
the studied conditions. This result indicates the high
monohydrocyanating selectivity of 1a to 2a.
1
2
3
4
5
6
7
8
9
toluene
THF
24
24
24
24
24
24
24
10
10
0
26
38
43
48
53
59
91
79
1,4-dioxane
CH Cl
2
2
MeCN
DMSO
DMF
MeOH
EtOH
a
Reaction condition: 1a (1 mmol), potassium hexacyanofer-
rate(II) (0.2 mmol), benzoyl chloride (1.2 mmol) in 20 mL
of solvent.
Isolated yields.
Scheme 1. Selective monohydrocyanation of diimines with
K4[Fe(CN)6].
b

Monohydrocyanation of Diimines
Table 2. Monohydrocyanation of diimines with K4[Fe(CN)6]-benzoyl chloride reagent
a
system .
R1
R2
Product
Time (h)
Yield (%)
b
Entry
1
2
C6H5
CH3
CH3
10
12
91
87
2-CH3C6H4
3
4
3-CH3C6H4
4-CH3C6H4
CH3
CH3
12
10
89
98
5
6
2,3-(CH3)2C6H3
2,3-(CH3)2C6H3
CH3
H
12
12
83
89
7
8
2,4-(CH3)2C6H3
H
H
12
12
87
86
2-CH3OC6H4

Zheng Li et al
Table 2. Continued.
R1
R2
Product
Time (h)
Yield (%)
b
Entry
9
3-CH3OC6H4
4-BrC6H4
CH3
CH3
10
10
87
91
10
1
1
2
3-Cl-4-FC6H3
3-ClC6H4
CH3
CH3
12
24
83
85
1
13
CH3
24
81
a
Reaction conditions: diimine (1 mmol), K4[Fe(CN)6] (0.2 mmol), benzoyl chloride (1.2
mmol), MeOH (20 mL).
b
Isolated yield.
1
2
Based on the above findings, a series of diimines 1 substrate. This indicated that R and R groups had no
were used as substrates to conduct the monohydrocya- selective effect on the monohydrocyanation.
nation in MeOH with K [Fe(CN) ]-benzoyl chloride
A plausible mechanism for the monohydrocyanation
reagent system as a cyanide source under catalyst- of diimines using K [Fe(CN) ]-benzoyl chloride reagent
4
6
4
6
free conditions (Scheme 1 and Table 2). Diimines 1 system as a cyanide source is shown in Scheme 3.
with electron-donating groups on the aromatic rings First, K [Fe(CN) ] reacts with benzoyl chloride to form
4
6
1
of R afforded the products in slightly higher yield benzoyl cyanide as an intermediate, which was con-
than diimines 1 with electron-withdrawing groups. In firmed by its isolation and identification. Then, benzoyl
addition, diimines 1 bearing ortho-substituted aromatic cyanide is attacked by methanol to yield nucleophilic
rings could give slightly lower yields than the meta- and addition intermediate A. Intermediate A undergoes
para-substituted analogues because of the large steric the loss of methyl benzoate to produce hydrogen
hindrance. The monohydrocyanation of unsymmetrical cyanide in situ. Nucleophilic additions of hydrogen
diimines was also investigated under similar conditions. cyanide to diimines 1 yield α-aminonitriles 2 as
However, complex mixtures were observed for each final products.

Monohydrocyanation of Diimines
Scheme 3. The proposed mechanism for the monohydrocyanation of diimines with
K4[Fe(CN)6]-benzoyl chloride reagent system.
4
. Conclusions
8. Marcantonio K M and Frey L F 2004 Org. Lett. 6 3723
. Seayad A M and Chai C L L 2010 Org. Lett. 12 264
9
1
0. Sakai T and Ukaji Y 2013 Org. Lett. 15 2422
1. Gerber R, Oberholzer M and Frech C M 2012 Chem.
Eur. J. 18 2978
In summary, an efficient method has been developed
for the selective monohydrocyanation of diimines to
1
synthesize α-aminonitriles bearing C=N bonds by one- 12. Yeung P Y, Tsang C P and Kwong F Y 2011 Tetrahe-
pot two-step procedure using K [Fe(CN) ] and ben-
dron Lett. 52 7038
4
6
1
3. Anbarasan P, Neumann H and Beller M 2011 Chem.
Eur. J. 17 4217
zoyl chloride reagent system as a cyanide source under
transition metal catalyst-free condition. Non-toxic, non-
volatile and inexpensive cyanide source, high yield
1
4. Yueng P Y, Chau M S and Chak P L 2011 Org. Lett.
13 648
and simple work-up procedures are the advantages of 15. Li Z, Shi S Y and Yang J Y 2006 Synlett 2495
1
1
1
1
6. Li Z and Xu J 2014 Phosphorus, Sulfur Silicon Relat.
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Elem. 189 374
7. Ren Y L, Dong C H, Zhao S, Sun Y P, Wang J J, Ma J Y
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8. Saha D, Adak L, Mukherjee M and Ranu B C 2012 Org.
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Supplementary Information (SI)
1
13
Full set of characterization data (IR, H and C NMR
spectra) and Figures S1–S39 are available at www.ias.
ac.in/chemsci.
9. Zhao Z X and Li Z 2010 Eur. J. Org. Chem. 5460
20. Zhao Z X and Li Z 2011 J. Braz. Chem. Soc. 22 148
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1. Hu X C, Zhao Z X and Li Z 2012 Phosphorus, Sulfur
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Acknowledgements
2. Li Z, Li R Z, Zheng H H, Wen F, Li H B, Yin J J and
Yang J Y 2013 J. Braz. Chem. Soc. 24 1739
The authors thank the National Natural Science Foun-
dation of China (21462038, 21362034) and Key Labo-
ratory of Eco-Environment-Related Polymer Materials,
3. Li Z, Niu P X, Li R Z, Zhang Y P, Ma B and Yang J Y
2
012 J. Chem. Res. 36 709
4. Li Z, Tian G Q and Ma Y H 2010 Synlett 2164
Ministry of Education for the financial support of 25. Li Z, Liu C H, Zhang Y P, Li R Z, Ma B and Yang J Y
this work.
2012 Synlett 23 2567
6. Li Z, Yin J J, Li T P, Wen G, Shen X L and Yang J Y
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014 Tetrahedron 70 5619
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