Direct synthesis of 2,3-diaryloxirane-2,3-dicarbonitriles from aroyl chlorides using potassium hexacyanoferrate(II) as an eco-friendly cyanide source

Article abstract of DOI:10.1016/j.tet.2012.08.042

A direct synthetic method for 2,3-diaryloxirane-2,3-dicarbonitriles from aroyl chlorides using potassium hexacyanoferrate(II) as an eco-friendly cyanide source, triphenylphosphine as a promoter, and triethylamine as a catalyst is described. This protocol has the features of no use of strong toxic cyanating agents, high yield, and simple work-up procedure.

Full text of DOI:10.1016/j.tet.2012.08.042

Tetrahedron 68 (2012) 8880e8883
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Direct synthesis of 2,3-diaryloxirane-2,3-dicarbonitriles from aroyl chlorides
using potassium hexacyanoferrate(II) as an eco-friendly cyanide source
*
Zheng Li , Jun Xu, Pengxian Niu, Chenhui Liu, Jingya Yang
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A direct synthetic method for 2,3-diaryloxirane-2,3-dicarbonitriles from aroyl chlorides using potassium
hexacyanoferrate(II) as an eco-friendly cyanide source, triphenylphosphine as a promoter, and triethyl-
amine as a catalyst is described. This protocol has the features of no use of strong toxic cyanating agents,
high yield, and simple work-up procedure.
Received 12 February 2012
Received in revised form 10 July 2012
Accepted 14 August 2012
Available online 21 August 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
2,3-Diphenyloxirane-2,3-dicarbonitrile
Potassium hexacyanoferrate(II)
Triphenylphosphine
Triethylamine
Eco-friendly cyanide source
1. Introduction
Herein, we report the direct synthesis of 2,3-diaryloxirane-2,3-
dicarbonitriles from aroyl chlorides using potassium hex-
2,3-Diaryloxirane-2,3-dicarbonitriles are well known as impor-
tant synthetic intermediates.1 The reported synthetic methods for
2,3-diaryloxirane-2,3-dicarbonitriles utilized aroyl cyanides as cy-
anide sources.2 However, the commercially available aroyl cyanides
are limited and comparatively expensive. Especially, synthesis of
aroyl cyanides also had to use strong toxic reagents as original
cyanide sources, such as HgCN,3 NaCN,4 CuCN,5 KCN,6 and TMSCN,7
which render the reactions unsafe and environmentally unfriendly.
Therefore, there is a need to explore environmentally benign
cyanating agents and simple procedure for the synthesis of 2,3-
diaryloxirane-2,3-dicarbonitriles.
acyanoferrate(II) as an environmentally benign cyanide source,
triphenylphosphine as a promoter, and triethylamine as a catalyst.
2. Results and discussion
Initially, the direct synthesis of 2,3-diaryloxirane-2,3-
dicarbonitriles was attempted using benzoyl chloride and potas-
sium hexacyanoferrate(II) as typical substrates. It was found that no
corresponding product was observed in the absence of a promoter
and a catalyst (Table 1, entry 1). The later research was found that
the reaction could not proceed using either a promoter, such as
trimethylphosphine, tributylphosphine, and triphenylphosphine,
or a catalyst, such as trimethylamine, triethylamine, pyridine, 1,4-
diazabicyclo-[2.2.2]octane (DABCO), and N,N-dimethylaminopyr-
idine (DMAP) (Table 1, entries 2e9). Fortunately, in the presence of
both a promoter and a catalyst the reaction could be taken place
efficiently (Table 1, entries 10e24). Among them, the combination
of triphenylphosphine and triethylamine gave the corresponding
product in highest yield (Table 1, entry 15).
The further research showed that solvents also played an im-
portant role in the reaction. It was found that no 2,3-
diphenyloxirane-2,3-dicarbonitrile was observed in some solvents
such as Et2O and DMF. However, the reactions in THF, MeCN,
PhMe, MeOH, EtOH, and CH2Cl2 could give the desired product
in moderate to high yield. Especially the reaction in CH2Cl2 afforded
2,3-diphenyloxirane-2,3-dicarbonitrile in highest yield (Table 2).
Potassium hexacyanoferrate(II), K4[Fe(CN)6], is non-toxic and is
even used in the food industry for metal precipitation. In addition,
it has been described as an antiagglutinating auxiliary for table salt
(NaCl). K4[Fe(CN)6] is commercially available on a ton scale and is
even cheaper than KCN. Very recently, K4[Fe(CN)6] has been proved
to be an efficient cyanide source for the cyanation of aryl halides,8
benzyl chlorides,9 and indoles10 to corresponding nitriles, the
cyanation of aroyl chlorides to aroyl cyanides,11 the cyanoaroylation
of aldehydes to cyanohydrin esters,12 the Strecker reactions to
a
-aminonitriles,13 the arylcyanation of internal alkynes to
lalkenylnitriles,8d and the nucleophilic additioneelimination of
-dibromoacetophenones to 2-aryl-3,3-dibromoacrylonitriles.14
b-ary-
a,a
* Corresponding author. Fax: þ86 931 7971989; e-mail address: lizheng@
nwnu.edu.cn (Z. Li).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.042

Z. Li et al. / Tetrahedron 68 (2012) 8880e8883
8881
Table 1
reactions to afford the desired 2,3-diaryloxirane-2,3-dicarbonitriles
in high yield. The substituents on the aryl rings have no obvious
effect on the yield of reactions. The heteroaroyl chloride, such as
furoyl chloride, was also available for the synthetic reaction.
However, the tests for aroyl chlorides bearing nitro, bromo, 2,4-
dichloro, and methoxy groups were not succeeded presumably
because of strong electronic properties. In addition, some aliphatic
acid chlorides such as acetyl chloride, propionyl chloride, and
butyryl chloride instead of aroyl chlorides were also tested for the
similar reactions for the direct synthesis of 2,3-dialkyloxirane-2,3-
dicarbonitriles using potassium hexacyanoferrate(II) as an eco-
friendly cyanide source. However it was found that no corre-
sponding products were observed. The promoter, triphenylphos-
phine, was transformed into triphenylphosphine oxide in the
reactions, which could be easily recovered from the reaction
system.
A plausible mechanism for the synthesis of 2,3-diaryloxirane-
2,3-dicarbonitriles is shown in Scheme 2. Aroyl chlorides reacted
with potassium hexacyanoferrate(II) to afford aroyl cyanides first.
Then aroyl cyanides were, respectively, attacked by triphenyl-
phosphine and triethylamine to give intermediates A and B. The
similar intermediates were also reported by Shi.15 Intermediates B
were nucleophilic substituted by oxygen ions of intermediates A to
yield intermediates C after loss of triethylamine. Intermediates C
underwent transient states D, followed by releasing triphenyl-
phosphine oxide to give the final products, 2,3-diaryloxirane-2,3-
dicarbonitriles.
The effect of promoters and catalysts on the yield of 2,3-diphenyloxirane-2,3-
dicarbonitrilea
O
NC
Promoter, catalyst
CH2Cl2
Cl
+
K4[Fe(CN)6]
CN
O
Entry
Promoter
Catalyst
Yieldb (%)
1
2
3
4
5
6
7
8
d
d
0
0
0
0
0
0
0
0
0
51
60
73
58
67
80
45
49
56
52
31
35
40
58
43
PMe3
PnBu3
PPh3
d
d
d
d
NMe3
NEt3
d
d
Pyridine
DABCO
DMAP
NMe3
NMe3
NMe3
NEt3
d
9
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
PMe3
PnBu3
PPh3
PMe3
PnBu3
PPh3
PMe3
PnBu3
PPh3
PMe3
PnBu3
PPh3
PMe3
PnBu3
PPh3
NEt3
NEt3
Pyridine
Pyridine
Pyridine
DABCO
DABCO
DABCO
DMAP
DMAP
DMAP
3. Conclusion
a
Reaction condition: benzoyl chloride (1 mmol), potassium hexacyanoferrate(II)
A
direct synthetic method for 2,3-diaryloxirane-2,3-
(0.2 mmol), promoter (0.5 mmol), and catalyst (0.02 mmol) in 10 mL of CH2Cl2 for
8 h.
dicarbonitriles from aroyl chlorides using potassium hex-
acyanoferrate(II) as an eco-friendly cyanide source, triphenyl-
phosphine as a promoter, and triethylamine as a catalyst has
developed. This protocol has the features of no use of strong toxic
cyanide sources, high yield, and simple work-up procedure.
b
The isolated yield.
Table 2
The effect of solvents on the yield of 2,3-diphenyloxirane-2,3-dicarbonitrilea
O
NC
4. Experimental
PPh3-Et3N
Solvent
Cl
+
K4[Fe(CN)6]
CN
O
4.1. General information
IR spectra were recorded using KBr pellets on an Alpha Centauri
FTIR spectrophotometer. 1H NMR and 13C NMR spectra on a Mer-
cury-400BB instrument using CDCl3 as solvent and Me4Si as in-
ternal standard. Melting points were observed in an electrothermal
melting point apparatus. Potassium hexacyanoferrate(II) was dried
at 80 ꢀC under vacuum for 24 h and finely powdered prior to use.
Entry
Solvent
Reaction time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Et2O
DMF
16
16
8
8
8
8
8
8
0
0
PhMe
THF
MeCN
CH2Cl2
MeOH
EtOH
35
20
25
80
58
64
4.2. Typical procedure for the synthesis of 2,3-diaryloxirane-
2,3-dicarbonitriles
a
Reaction condition: benzoyl chloride (1 mmol), potassium hexacyanoferrate(II)
(0.2 mmol), triphenylphosphine (0.5 mmol), and triethylamine (0.02 mmol) in
10 mL of solvent for 8 h.
The mixture of K4[Fe(CN)6] (0.2 mmol) and aroyl chloride
(1 mmol) was heated at 160 ꢀC for 3 h. Then the reaction mixture
was cooled to room temperature, and triphenylphosphine
(0.5 mmol) and triethylamine (0.02 mmol) in 10 mL of CH2Cl2 were
added. The resulting mixture was stirred at room temperature for
appropriate time indicated in Table 3. After completion of the re-
action, monitored by TLC, the resulting mixture was evaporated off
b
The isolated yield.
Base on these promising findings, a series of 2,3-diaryloxirane-
2,3-dicarbonitriles were synthesized under the similar conditions
(Scheme 1). Aroyl chlorides bearing both electron-donating (CH3)
and electron-withdrawing (Cl, F) groups could participate in
O
R
NC
PPh3-Et3N
CH2Cl2
Cl
+
R
K4[Fe(CN)6]
CN
R
O
Scheme 1. Synthesis of 2,3-diaryloxirane-2,3-dicarbonitriles using K4[Fe(CN)6] as cyanide source.

8882
Z. Li et al. / Tetrahedron 68 (2012) 8880e8883
O
CN
1/6 FeCl2
R
CN
1/6 K4[Fe(CN)6]
4/6 KCl
PPh3
O
O
NEt3
O
Cl
CN
R
R
R
PPh3
CN
A
O
R
NEt3
B
NEt3
NC
O
O
R
R
R
NC
NC
O
CN
R
R
CN
CN
R
O
PPh3
O
Ph3P
Ph3P=O
D
C
Scheme 2. Proposed mechanism for the synthesis of 2,3-diaryloxirane-2,3-dicarbonitriles using K4[Fe(CN)6] as a cyanide source.
the solvent, and the residue was subjected to column chromatog-
raphy to give pure product. The analytical data for products are
given below.
Table 3
Synthesis of 2,3-diaryloxirane-2,3-dicarbonitriles using K4[Fe(CN)6] as cyanide
source
O
R
NC
4.2.1. 2,3-Diphenyloxirane-2,3-dicarbonitrile (Table 3, entry 1).
White solid, mp 112e114 ꢀC (known compound);1 IR (KBr): 3067,
2925, 2232, 1556, 1491, 1447, 771 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
PPh3-Et3N
CH2Cl2
Cl
+
R
K4[Fe(CN)6]
CN
R
O
d
8.11e8.13 (m, 2H), 8.03e8.05 (m, 2H) 7.53e7.56 (m, 6H); 13C NMR
Entry
Aroyl chloride
Reaction time (h)
Yielda (%)
Mp (ꢀC)
(CDCl3, 100 MHz):
d 161.0, 157.6, 131.7, 131.1, 129.4, 129.1, 126.9,
125.7, 125.7, 125.3, 113.9. Anal. Calcd for C16H10N2O: C, 78.03; H,
4.09; N, 11.38. Found: C, 77.94; H, 4.08; N, 11.35.
O
1
2
8
80
112e114
133e135
Cl
4.2.2. 2,3-Bis(2-chlorophenyl)oxirane-2,3-dicarbonitrile (Table 3, en-
try 2). White solid, mp 133e135 ꢀC; IR (KBr): 3070, 2925, 2239, 1532,
O
1465,1438, 768 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
8.07e8.10 (m,1H),
7.75e7.78 (m, 1H), 7.41e7.61 (m, 6H); 13C NMR (CDCl3, 100 MHz):
160.0, 155.9, 133.2, 133.0, 132.4, 132.3, 131.4, 131.2, 131.0, 130.9, 127.2,
Cl
12
75
d
Cl
O
127.0,124.4,124.2,113.5,112.6. Anal. Calcd for C16H8Cl2N2O: C, 60.98; H,
2.56; N, 8.89. Found: C, 61.05; H, 2.56; N, 8.87.
Cl
3
4
5
10
8
70
68
76
168e169
193e195
185e186
4.2.3. 2,3-Bis(3-chlorophenyl)oxirane-2,3-dicarbonitrile (Table 3, en-
try 3). White solid, mp 168e169 ꢀC; IR (KBr): 3070, 2923, 2233, 1556,
1477,1413, 792 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
8.10e8.11 (m, 1H),
7.95e8.02 (m, 3H), 7.46e7.55 (m, 4H); 13C NMR (CDCl3, 100 MHz):
160.0,153.1,135.6,135.3,132.0,131.3,130.8,130.5,126.9,126.9,126.5,
Cl
O
Cl
d
125.6, 125.0, 123.8, 113.2, 110.5. Anal. Calcd for C16H8Cl2N2O: C, 60.98;
H, 2.56; N, 8.89. Found: C, 60.88; H, 2.55; N, 8.91.
Cl
O
4.2.4. 2,3-Bis(4-chlorophenyl)oxirane-2,3-dicarbonitrile (Table 3, en-
Cl
8
try 4). White solid, mp 193e195 ꢀC; IR (KBr): 2963, 2925, 2232,
1604, 1554, 1485, 837 cmꢁ1 1H NMR (CDCl3, 400 MHz):
; d 8.04 (d,
F
2H J¼8.0 Hz), 7.96 (d, 2H J¼8.0 Hz), 7.50e7.55 (m, 4H); 13C NMR
O
(CDCl3, 100 MHz):
d 156.7, 138.3, 137.5, 129.8, 129.5, 128.1, 127.0,
Cl
6
7
10
73
105e107
124.0, 123.6, 113.8, 107.3. Anal. Calcd for C16H8Cl2N2O: C, 60.98; H,
2.56; N, 8.89. Found: C, 60.92; H, 2.57; N, 8.86.
CH3
O
4.2.5. 2,3-Bis(4-fluorophenyl)oxirane-2,3-dicarbonitrile (Table 3, en-
try 5). White solid, mp 185e186 ꢀC; IR (KBr): 3074, 2921, 2229,
Cl
10
10
77
65
136e137
145e146
1607, 1504, 1414, 839 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
8.09e8.12
(m, 2H), 8.01e8.05 (m, 2H), 7.24e7.28 (m, 4H); 13C NMR (CDCl3,
100 MHz): 166.1, 165.4, 163.6, 162.9, 160.0, 156.8, 129.2, 129.1,
H3C
O
O
d
8
Cl
128.0, 127.9, 121.9, 121.5, 116.9, 116.7, 116.6, 116.4, 113.7, 109.7. Anal.
Calcd for C16H8F2N2O: C, 68.09; H, 2.86; N, 9.93. Found: C, 68.20; H,
2.87; N, 9.95.
a
Yields refer to the isolated products.

Z. Li et al. / Tetrahedron 68 (2012) 8880e8883
8883
4.2.6. 2,3-Bis(3-tolyl)oxirane-2,3-dicarbonitrile (Table 3, entry 6).
White solid, mp 105e107 ꢀC; IR (KBr): 3056, 2919, 2231, 1593, 1556,
1479, 795 cmꢁ1 1H NMR (CDCl3, 400 MHz): 7.89e7.92 (m, 2H),
7.82e7.85 (m, 2H), 7.31e7.45 (m, 4H), 2.47 (s, 3H), 2.46 (s, 3H); 13C
NMR (CDCl3,100 MHz): 161.0,157.7,139.2,139.0,132.5,131.9,129.2,
Supplementary data
;
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.08.042.
d
129.0, 127.3, 126.1, 125.6, 125.2, 124.0, 122.9, 114.0, 109.2, 21.5, 21.4.
Anal. Calcd for C18H14N2O: C, 78.81; H, 5.14; N,10.21. Found: C, 78.93;
H, 5.13; N, 10.23.
References and notes
1. Muller, A. J.; Nishiyama, K.; Griffin, G. W.; Ishikawa, K.; Gibson, D. M. J. Org.
Chem. 1982, 47, 2342.
2. (a) Konovalova, I. V.; Ofitserova, E. K.; Mironov, V. F.; Ofitserov, E. N.; Os-
tanina, I. L.; Pudovik, A. N. J. Gen. Chem. USSR (Engl. Transl.) 1982, 52, 2715;
(b) Konovalova, I. V.; Burnaeva, L. A.; Khusnutdinova, E. K.; Khafizova, G. S.;
Pudovik, A. N. J. Gen. Chem. USSR (Engl. Transl.) 1985, 55, 2189.
3. Haase, K.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. Engl. 1982, 21, 83.
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Dlouhy, M. Org. Prep. Proced. Int. 2011, 43, 285.
4.2.7. 2,3-Bis(4-tolyl)oxirane-2,3-dicarbonitrile (Table 3, entry 7).
White solid, mp 136e137 ꢀC; IR (KBr): 2921, 2852, 2230, 1615, 1500,
816 cmꢁ1; 1H NMR (CDCl3, 400 MHz): 7.98 (d, 2H, J¼8.0 Hz), 7.91 (d,
2H J¼8.0 Hz), 7.31e7.35 (m, 4H), 2.44 (s, 3H), 2.43 (s, 3H); 13C NMR
(CDCl3, 100 MHz):
d 160.9, 157.7, 142.2, 141.6, 130.0, 129.8, 126.8,
125.7, 123.1, 122.7, 114.1, 108.7, 21.6. Anal. Calcd for C18H14N2O: C,
78.81; H, 5.14; N, 10.21. Found: C, 78.75; H, 5.12; N, 10.18.
5. Macias-Ruvalcaba, N. A.; Evans, D. H. J. Org. Chem. 2007, 72, 589.
6. (a) Patrocinio, A. F.; Moran, P. J. S. J. Braz. Chem. Soc. 2001, 12, 7; (b) Cao, Y. Q.;
Du, Y. F.; Chen, B. H.; Li, J. T. Synth. Commun. 2004, 34, 2951.
7. (a) Wei, Z.; Yang, J. Y.; Meng, B.; Zhang, B.; Jiang, M. Z.; Chen, F. X. Lett. Org.
Chem. 2009, 6, 637; (b) Duplais, C.; Bures, F.; Sapountzis, I.; Korn, T. J.; Cahiez,
G.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 2968.
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Weissman, S. A.; Zewge, D.; Chen, C. J. Org. Chem. 2005, 70, 1508; (c) Grossman,
O.; Gelman, D. Org. Lett. 2006, 8, 1189; (d) Cheng, Y. N.; Duan, Z.; Yu, L. J.; Li, Z.
X.; Zhu, Y.; Wu, Y. J. Org. Lett. 2008, 10, 901; (e) Jia, X. F.; Yang, D. P.; Wang, W. H.;
Luo, F.; Cheng, J. J. Org. Chem. 2009, 74, 9470; (f) Kim, J.; Chang, S. J. Am. Chem.
Soc. 2010, 132, 10272; (g) Yeung, P. Y.; Tsang, C. P.; Kwong, F. Y. Tetrahedron Lett.
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4.2.8. 2,3-Di(furan-2-yl)oxirane-2,3-dicarbonitrile (Table 3, entry 8).
White solid, mp 136e137 ꢀC; IR (KBr): 3120, 2924, 2234, 1622, 1539,
1481, 758 cmꢁ1; 1H NMR (CDCl3, 400 MHz): 7.65 (d, 2H, J¼12.0 Hz),
7.17 (d, 1H, J¼4.0 Hz), 7.10 (d, 1H, J¼4.0 Hz), 6.60e6.63 (m, 2H); 13C
NMR (CDCl3, 100 MHz):
d 152.9, 149.2, 145.8, 145.5, 140.9, 140.7,
114.2, 112.8, 112.5, 112.3, 108.3. Anal. Calcd for C12H6N2O3: C, 63.72;
H, 2.67; N, 12.39. Found: C, 63.66; H, 2.68; N, 12.35.
9. Ren, Y. L.; Yan, M. J.; Zhao, S.; Sun, Y. P.; Wang, J. J.; Yin, W. P.; Liu, Z. F. Tetra-
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Acknowledgements
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14. (a) Zhao, Z. X.; Li, Z. Eur. J. Org. Chem. 2010, 5460; (b) Zhao, Z. X.; Li, Z. J. Braz.
Chem. Soc. 2011, 22, 148.
The authors thank the National Natural Science Foundation of
China (21162024) for the financial support of this work.
15. Zhang, W.; Shi, M. Tetrahedron 2006, 62, 8715.