An Efficient Synthesis of Dinitrile Derivatives by the Reaction of Oxime Esters or Acid Anhydrides with Cyanotrimethylsilane Catalyzed by La(OiPr)3

Article abstract of DOI:10.1021/jo0055281

The reaction of oxime esters with cyanotrimethylsilane (Me₃SiCN) under the influence of a catalytic amount of lanthanide compounds produced α-trimethylsilyloxydinitrile derivatives in excellent yields accompanied with the formation of trimethylsilyl oxime ethers. Among the lanthanoid catalysts examined, La(OⁱPr)₃ was found to be the best catalyst. The reaction seems to proceed through the formation of acyl cyanides as intermediates, followed by the addition of Me₃SiCN to them. Additionally, the reaction of acetic anhydride with Me₃SiCN catalyzed by La(OⁱPr)₃ gave 1-trimethylsilyloxyethane dinitrile. Thus, various α-trimethylsilyloxydinitriles were synthesized in good yields by allowing oxime esters or acid anhydrides to react with Me₃SiCN in the presence of a catalytic amount of La(OⁱPr)₃.

Full text of DOI:10.1021/jo0055281

J . Org. Chem. 2000, 65, 6209-6212
6209
An Efficien t Syn th esis of Din itr ile Der iva tives by th e Rea ction of
Oxim e Ester s or Acid An h yd r id es w ith Cya n otr im eth ylsila n e
Ca ta lyzed by La (OiP r )3
Akiko Fujii, Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology, Research Center,
Kansai University, Suita, Osaka 564-8680, J apan
ishii@ipcku.kansai-u.ac.jp
Received May 29, 2000
The reaction of oxime esters with cyanotrimethylsilane (Me3SiCN) under the influence of a catalytic
amount of lanthanide compounds produced R-trimethylsilyloxydinitrile derivatives in excellent yields
accompanied with the formation of trimethylsilyl oxime ethers. Among the lanthanoid catalysts
examined, La(OiPr)3 was found to be the best catalyst. The reaction seems to proceed through the
formation of acyl cyanides as intermediates, followed by the addition of Me3SiCN to them.
Additionally, the reaction of acetic anhydride with Me3SiCN catalyzed by La(OiPr)3 gave 1-tri-
methylsilyloxyethane dinitrile. Thus, various R-trimethylsilyloxydinitriles were synthesized in good
yields by allowing oxime esters or acid anhydrides to react with Me3SiCN in the presence of a
catalytic amount of La(OiPr)3.
Introduction of a cyano group to carbonyl compounds
through a catalytic or noncatalytic process has been often
used as a synthetic tool. Among many cyanating re-
agents, cyanotrimethylsilane (Me3SiCN) is recognized as
a useful reagent.1-6 It has been reported that the reaction
of carbonyl compounds such as ketones and aldehydes
with Me3SiCN catalyzed by Yb(CN)3 affords R-trimeth-
ylsilyloxycyanides.4 In addition, acid chlorides react with
Me3SiCN without any catalyst to give carbonitrile de-
rivatives.5 However, there are few papers on the synthe-
sis of dinitrile derivatives which are precursors of R-hy-
droxy carboxylic acids or malnonitiriles. Classically, the
dinitrile compounds were prepared by the reaction of acyl
chlorides with Me3SiCN in the presence of pyridine at
120 °C.6 Recently, Shioiri et al. showed that dicyano-
phosphates can be prepared by the reaction of carboxylic
acids with diethyl phosphorocyanidate in the presence
of triethylamine.7
In a previous paper, we have reported the efficient
acetylcyanation of aldehydes in the presence of acetone-
cyanohydrin and isopropenyl acetate under the influence
of a lanthanide compound such as Cp*Sm(thf)2 as a
catalyst.8 Now, we find that the reaction of oxime esters
or acid anhydrides with Me3SiCN catalyzed by La(OiPr)3
affords the corresponding R-trimethylsilyloxydinitriles in
high yields (eq 1). To our best knowledge, this is the first
catalytic method for the synthesis of R-trimethylsilyloxy-
dinitrile derivatives.
(1) (a) March, J . Advanced Organic Chemistry, 4th ed.; Wiley: New
York, 1992; pp 964-965. (b) Groutas, W. C.; Felker, D. Synthesis 1980,
861.
(2) (a) Matsubara, S.; Kodama, T.; Utimoto, K. Tetrahedron Lett.
1990, 31, 6379. (b) Sassaman, M. B.; Surya Prakash, G. K.; Olah, G.
A. J . Org. Chem. 1990, 55, 2016. (c) Imi, K.; Yanagihara, N.; Utimoto,
K. J . Org. Chem. 1987, 52, 1013.
Cyclohexanoneoxime acetate (1) was chosen as a model
substrate and allowed to react with Me3SiCN (2) under
the influence of a catalytic amount of various lanthanide
compounds (Table 1). The reaction of 1 with 2 (2.5 equiv
with respect to 1) catalyzed by Cp*Sm(thf)2 in toluene
at room temperature gave 1-trimethylsilyloxyethane
dinitrile (3) in 88% yield at 92% conversion (run 1). In
this reaction, trimethylsilyl oxime ether (4) was formed
in 92% yield along with 3 (eq 1). Previously, we showed
that the reaction of 1 with acetonecyanohydrin catalyzed
by Cp*Sm(thf)2 produced 1-cyano-N-cyclohexylhydroxy-
amine O-acetate (eq 2).8 Thus, different types of cyano
compounds were prepared by the reaction of 1 with Me3-
(3) (a) Kobayashi, S.; Tsuchiya, Y.; Mukaiyama, T. Chem. Lett. 1991,
537. (b) Reetz, M. T.; Drewes, M. W.; Harms, K.; Reif, W. Tetrahedron
Lett. 1988, 29, 3295. (c) Vougioukas, A. E.; Kagan, H. B. Tetrahedron
Lett. 1987, 28, 5513. (d) Comber, R. N.; Hosmer, C. A.; Brouillette, W.
J . J . Org. Chem. 1985, 50, 3627. (e) Greenlee, W. J .; Hangauer, D. G.
Tetrahedron Lett. 1983, 24, 4559. (f) Utimoto, K.; Wakabayashi, Y.;
Horiie, T.; Inoue, M.; Shishiyama, Y.; Obayashi, M.; Nozaki, H.
Tetrahedron 1983, 39, 967. (g) Noyori, R.; Murata, S.; Suzuki, M.
Tetrahedron 1981, 37, 3899. (h) Gassman, P. G.; Talley, J . J . Tetra-
hedron Lett. 1978, 3773. (i) Evans, D. A.; Carroll, G. L.; Truesdale, L.
K. J . Org. Chem. 1974, 39, 914. (j) Lidy, W.; Sundermeyer, W. Chem.
Ber. 1973, 106, 587.
(4) Matsubara, S.; Takai, T.; Utimoto, K. Chem. Lett. 1991, 1447.
(5) Herrmann, K.; Simchen, G. Synthesis 1979, 204.
(6) (a) Yamaguchi, S.; Araki, H.; Hanafusa, T. Chem. Lett. 1985,
685. (b) Lidy, W.; Sundermeyer, W. Tetrahedron Lett. 1973, 14, 1449.
(7) (a) Mizuno, M.; Shioiri, T. Tetrahedron Lett. 1998, 39, 9209. (b)
Tanaka, M. Tetrahedron Lett. 1980, 21, 2959.
(8) Kawasaki, Y.; Fujii, A.; Nakano, Y.; Sakaguchi, S.; Ishii, Y. J .
Org. Chem. 1999, 64, 4214.
10.1021/jo0055281 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/24/2000

6210 J . Org. Chem., Vol. 65, No. 19, 2000
Fujii et al.
Sch em e 1. A P ossible Rea ction P a th
Ta ble 1. Rea ction of 1 w ith 2 u n d er th e In flu en ce of
Va r iou s Ca ta lystsa
run
catalyst
convn (%)
yield (%)
1b
2
3
4
5
6
7
8
Cp*2Sm(thf)2
SmI2
SmI3
92
>99
96
79
>99
>99
88
61
48
64
56c
86
SmCl3
Sm(OiPr)3
La(OiPr)3
Al(OiPr)3
Zr(OiPr)3
no reaction
no reaction
a
1 (1 mmol) was allowed to react with 2 (2.5 mmol) in the
presence of catalyst (0.1 mmol) in THF (1 mL) at room temperature
b
for 15 h. Toluene (1 mL) was used as a solvent. c Acetyl cyanide
was obtained in 35% yield.
Ta ble 2. Rea ction of Va r iou s Oxim eester s w ith 2
a
Ca ta lyzed by La (OiP r )3
La(OiPr)3, the excess amount of concentrated HCl was
added to the reaction mixture, followed by stirring at
refluxing temperature to form 2-hydroxyphenyl acetic
acid in 50% yield (eq 3).
Treatment of 5 with 1 equiv of 2 in the presence of
La(OiPr)3 for 0.5 h produced benzoyl cyanide (7) as a
major product (30%) along with dinitrile compound 6 (4%)
at 48% conversion (eq 4). This fact shows that R-tri-
methylsilyloxy dinitriles are formed via stepwise reac-
tions: the substitution of the oxime moiety by a cyanide
group, giving a mono cyanated compound like 7, and the
addition of 2 to the resulting 7 to form dinitrile compound
like 6.
SiCN or acetonecyanohydrin as the cyanating agent
under the influence of Cp*Sm(thf)2.
Other samarium compounds such as SmI2, SmI3, and
SmCl3 afforded 3 in low yields (runs 2-4). It was found
that La(OiPr)3 produced 3 in high yield (86%), while the
Sm(OiPr)3-catalyzed reaction showed lower selectivity to
form 3 in 56% yield (runs 5 and 6). Al(OiPr) and
A possible reaction path is shown in Scheme 1. The
reaction may be initiated by the reaction of La(OiPr)3
with Me3SiCN to form La(CN)3 whose formation is
confirmed by the observation of a strong absorption band
at 1986 cm-1. Utimoto et al. reported that Yb(CN) 3 was
obtained by the reaction of Yb(OiPr)3 with 3 equiv of Me3-
SiCN.4 Thus, it is reasonable to assume that La(CN)3 (A),
generated in situ from La(OiPr)3 and Me3SiCN, was
reacted with 1, followed by 2 to form a lanthanide
alkoxide D together with 4. The alkoxide D is attacked
by another 2 to give 3, and the A is regenerated.
In the present cyanation reaction, the formation of
trimethylsilyl oxime ether 4 from oxime acetate 1 seems
to be favorable to promote the reaction.
3
Zr(OiPr)4 were inert in this reaction (runs 7 and 8). It is
interesting that the present reaction is catalyzed only by
lanthanide compounds.
Table 2 shows the reaction of various types of oxime
esters with 2 in the presence of La(OiPr)3 catalyst. All
oxime esters used were successfully converted into the
corresponding R-trimethylsilyloxy dinitrile compounds in
good yields. The reaction of the sterically hindered
acetoneoxime pivaloate with 2.5 equiv of 2 catalyzed by
La(OiPr)3 for 15 h produced 2,2-dimethyl-1-trimethyl-
silyloxypropane dinitrile in 97% yield (run 3). Similarly,
cyclohexanoneoxime benzoate (5) under these reaction
conditions gave the corresponding dinitirile, 1-phenyl-1-
trimethylsilyloxymethane dinitrile (6) (90%) (run 4).
The dinitrile 6 could be converted into R-hydroxycar-
boxylic acid. After the reaction of 5 and 2 catalyzed by
Recently, we have shown that the reaction of alcohol
with 1 by La(OiPr)3 under neutral conditions produces
the corresponding acetate and oxime in almost quantita-

Efficient Synthesis of Dinitrile Derivatives
J . Org. Chem., Vol. 65, No. 19, 2000 6211
Ta ble 3. Rea ction of Acyl Com p ou n d s w ith 2 Ca ta lyzed
esters with Me3SiCN in the presence of a catalytic
amount of La(OiPr)3. In addition, the reaction of acid
anhydrides with Me3SiCN catalyzed by La(OiPr)3 at 50
°C produced the corresponding dinitrile compounds in
satisfactory yields.
a
by La (OiP r )3
Exp er im en ta l Section
1
Gen er a l P r oced u r e. H and 13C NMR spectra were mea-
sured at 270 and 67.5 MHz, respectively, in CDCl3 with TMS
as the internal standard. IR spectra were measured as films
on NaCl plates. GLC analysis was performed with a flame
ionization detector using a 1 mm × 30 m capillary column (OV-
1). Oxime esters were synthesized by the reaction of the
corresponding oximes with acid chlorides or acid anhydrides
in THF at room temperature and were purified by distillation
or recrystallization. Other starting materials were commer-
cially available and used after distillation or recrystallization.
Cp*Sm(thf)2,11 SmI2,12 and SmI313 were prepared according to
the literature procedures. Sm(OiPr)3 and La(OiPr)3 were
purchased from High Purify Chemical Laboratory Co. Ltd.
Gen er a l P r od u r e for th e Rea ction of Oxim eester w ith
2 Ca ta lyzed by La (OiP r )3. To a Schlenk tube containing a
THF solution (1.0 mL) of La(OiPr)3 (0.1 mmol) were added Me3-
SiCN (2.5 mmol) and oxime ester (1.0 mmol). The reaction
mixture was stirred at room temperature for 15 h under Ar.
After the reaction, wet diisopropyl ether was added to the
solution, and the catalyst precipitated was removed by simple
filtration. The products were purified by the use of HPLC and
identified by the NMR and IR measurements and were
obtained as oil. Benzoyl cyanide (7) was commercially available
and identified through comparison of the isolated product with
an authentic sample.
Ta ble 4. Rea ction of Sever a l Acid An h yd r id es w ith 2
Ca ta lyzed by La (OiP r )3
a
1-Tr im et h ylsilyloxyet h a n e d in it r ile (3):6b 1H NMR
(CDCl3/TMS) δ 1.94 (s, 3H), 0.29 (s, 9H); 13C NMR (CDCl3/
TMS) δ 115.6, 59.1, 30.4, 0.3; IR (neat) 2964, 1261, 1167, 993,
853 cm-1
.
Tr im eth ylsilyloxim e ester (4):14 1H NMR (CDCl3/TMS)
δ 2.31 (m, 2H), 2.24-2.20 (m, 2H), 1.52-1.32 (m, 6H), 0.19 (s,
9H); 13C NMR (CDCl3/TMS) δ 164.4, 32.3, 27.1, 26.0, 25.8, 25.0,
tive yield.9 Although it is known that acyl chloride and
acid anhydride can be used as acylating reagents, 1 could
be used as an efficient acylating reagent, which reaction
can be carried out under neutral conditions. Thus, we
next examined the reaction of several acetyl compounds
with Me3 SiCN in the presence of a catalytic amount of
La(OiPr)3 (Table 3).
-0.7; IR (neat) 2971, 1746, 1463, 1377, 1250 cm-1
.
1-Tr im eth ylsilyloxyp en ta n e d in itr ile: 1H NMR (CDCl3/
TMS) δ 2.16-2.08 (m, 2H), 1.66-1.52 (m, 2H), 1.50-1.37 (m,
2H), 0.97 (t, J ) 7.2 Hz, 3H), 0.36 (s, 9H); 13C NMR (CDCl3/
TMS) δ 115.3, 63.3, 42.2, 25.5, 21.7, 13.6; IR (neat) 2963, 1258,
1139, 852, 760 cm-1
.
2-Met h yl-1-t r im et h ylsilyloxyp r op a n e d in it r ile:15 1H
NMR (CDCl3/TMS) δ 2.03 (heptet, J ) 6.6 Hz, 1H), 0.96 (d, J
) 6.6 Hz, 6H), 0.13 (s, 9H); 13C NMR (CDCl3/TMS) δ 114.7,
68.4, 39.9, 16.3, 0.2.
The reaction of isopropenyl acetate (8) with 2 catalyzed
by La(OiPr)3 gave 3 in 12% yield (run 2). Similarly, acyl
chloride (9) resulted in 3 in 13% yield under these
reaction conditions (run 3).10 The low yield of the product
3 from 8 and 2 may be due to the difficulty of the
formation of isopropenyl silyl ether. Similarly, the dif-
ficulty of the formation of 3 from 9 and 2 is attributed to
the difficulty of the generation of Me3SiCl. However, it
was found that the reaction of acetic anhydride (10) with
2.5 equiv of 2 under the influence of La(OiPr)3 in THF
produced 3 in 60% yield along with trimethylsilyl acetate
(run 4). When this reaction was carried out at 50 °C, the
yield of 3 was improved to 74% (run 5). Hence, various
acid anhydrides were allowed to react with Me3SiCN in
the presence of La(OiPr)3 at 50 °C (Table 4). The reaction
took place smoothly to give the corresponding dinitrile
compounds in good yields (runs 1 and 5).
2,2-Dim eth yl-1-tr im eth ylsilyloxyp r op a n e d in itr ile:6b
1H NMR (CDCl3/TMS) δ 0.95 (s, 9H), 0.13 (s, 9H); 13C NMR
(CDCl3/TMS) δ 120.5, 114.8, 71.9, 41.5, 23.7; IR (neat) 2972,
2243, 1258, 1134, 851 cm-1
.
1-P h en yl-1-tr im eth ylsilyloxym eth a n e d in itr ile (6):6 1
H
NMR (CDCl3/TMS) δ 7.71-7.50 (m, 5H), 2.36-2.23 (m, 4H),
0.36 (s, 9H); 13C NMR (CDCl3/TMS) δ 134.5, 131.0, 129.4,
125.5, 115.0, 65.1, 0.5; IR (neat) 2963, 2243, 1682, 1453, 1258,
1198, 1103 cm-1
.
P r oced u r e for th e Syn th esis of 2-Hyd r oxyp h en yla ce-
tic Acid fr om 5. To a Schlenk tube containing a THF solution
(1.0 mL) of La(OiPr)3 (0.1 mmol) were added Me3SiCN (2.5
mmol) and 5 (1.0 mmol). The reaction mixture was stirred at
room temperature for 15 h under Ar. Then, 3.0 mL of
concentrated HCl was added, and the mixture was stirred at
In conclusion, a new route to R-trimethylsiloxy dinitrile
derivatives has been developed by the reaction of oxime
(11) Evans, W. J .; Bloom, I.; Hunter, W. E.; Atwood, J . L. J . Am.
Chem. Soc. 1981, 103, 6507.
(12) Girard, P.; Namy, J . L.; Kagan, H. B. J . Am. Chem. Soc. 1980,
102, 2693.
(9) Tashiro, D.; Kawasaki, Y.; Sakaguchi, S.; Ishii, Y. J . Org. Chem.
1997, 62, 8141.
(13) Yu, Y.; Lin, R.; Zhang, Y. Tetrahedron Lett. 1993, 34, 4547.
(14) Hoffman, R. V.; Buntain, G. A. Synthesis 1987, 831.
(15) Hertenstein, U.; Huenig, S. Reichelt, H.; Schaller, R. Chem. Ber.
1982, 115, 261.
(10) It has been reported that the reaction of propionyl chloride with
2 at 60 °C for 2 h gave propionyl cyanide in 40% yield.5

6212 J . Org. Chem., Vol. 65, No. 19, 2000
Fujii et al.
refluxing temperature for 12 h. After the reaction, the mixture
was extracted with Et2O (10 mL × 3), and dried over
anhydrous MgSO4. After removal of the solvent in vacuo, the
product was purified by recrystallization from ethanol, and
identified through comparison of the isolated product with an
authentic sample which was purchased from Aldrich (mp 147-
149 °C). The isolated yield is shown.
Priority Areas (No. 283, “Innovative Synthetic Reac-
tions” from Monbusho).
Su p p or tin g In for m a tion Ava ila ble: Copies of 13C and
1H NMR and IR spectra for the compounds 3, 4, 1-trimethyl-
silyloxypentane dinitrile, 2-methyl-1-trimethylsilyloxypropane
dinitrile, 2,2-dimethyl-1-trimethylsilyloxypropane dinitrile, 6,
and 2-phenyl-2-hydroxyactetic acid. This information available
free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work is supported by a
Grant-in-Aid for Scientific Research (No. 1119268) on
J O0055281