P(RNCH2CH2)3N-catalyzed α,β-dimerization of unsaturated nitriles: Formation of 2-alkylidene-3-alkylglutaronitriles

Full text of DOI:10.1021/jo981513f

J . Org. Chem. 1998, 63, 10057-10059
10057
giving a low concentration13,14 of the -CH2CN anion. It
P (RNCH2CH2)3N-Ca ta lyzed
r,â-Dim er iza tion of Un sa tu r a ted Nitr iles:
F or m a tion of
2-Alk ylid en e-3-a lk ylglu ta r on itr iles
Philip Kisanga, Bosco D’Sa, and J ohn Verkade*
Department of Chemistry, Iowa State University,
Ames, Iowa 50011 USA
Received J uly 30, 1998
has also been demonstrated that this anion adds to
carbonyl compounds to form R,â-unsaturated nitriles13
or â-hydroxynitriles.14 In the formation of R,â-unsatur-
ated nitriles we reported that aldehydes lacking an
R-hydrogen (e.g., trimethylacetaldehyde and aromatic
aldehydes) react to form R,â-unsaturated nitriles while
primary aldehydes form the aldol products.13 Here we
show that secondary aldehydes in the presence of 1a or
1b afford 2-alkylidene-3-alkylglutaronitriles (2) which are
R,â-dimers of the R,â-unsaturated nitriles we expected
originally. We observed no â,â-dimer in our reaction (a
product that accompanies the copper(I) oxide-isocyanide
process4).
Furthermore, only the R-carbon atom of the delocalized
anion Michael adds to a second molecule of the unsatur-
ated nitrile. We believe that this is due to the stability
of MeCHdCHChHCN relative to MeChHCHdCHCN since
the negative charge in the former can be stabilized by
the nitrile group.
In tr od u ction
The oligomerization and polymerization of olefins has
been of interest to researchers for decades. Of specific
interest are processes that lead to the formation of dimers
that can be utilized in copolymerization reactions. Such
dimers are often observed as byproducts in Michael
addition reactions. Dimerization reactions for unsatur-
ated nitriles include electrolytic processes1,2 and those
catalyzed by transition metal complexes,3,4 trialkyl phos-
phines,4 isocyanide-copper(I) oxide binary systems,4-6
and bases.7 Reactions catalyzed by trialkyl phosphines
or transition metal complexes suffer from the major
drawback that they are restricted to the dimerization of
â-unsubstituted-R,â-unsaturated acrylonitrile and the
corresponding acrylates. Moreover, the isocyanide-cop-
per(I) system requires a lengthy reaction time and a high
temperature, and the conversion ratio is disappointing.
Electrolytic reactions produce glutaronitriles as a minor
product and are therefore inefficient routes to this class
of compounds. Reports of the use of ionic bases in the
dimerization of nitriles are scanty. The report by White7
et al. describes a rapid reaction that is catalytic in R4-
NCN but provides very low to modest yields (15-54%)
along with several byproducts. Shabtai8 and co-workers
reported on the dimerization of crotononitrile and allyl
cyanide using a catalyst system consisting of potassium/
benzylpotassium. However, these reactions produce the
corresponding dimers in apparently very low (unreported)
yields along with other products including trimers. The
method reported by Daweal9 utilizes a condensation
between propionaldehyde and cyanoacetic acid to produce
3-ethyl-2-propylideneglutaronitrile in low yield.
Commercially available 3-6 are converted in high
yields to the corresponding glutaronitriles 7-10, respec-
tively (Table 1). These products are assumed to form via
the corresponding R,â-unsaturated nitriles (eq 1), which
Resu lts a n d Discu ssion s
We have shown previously that acetonitrile can be
deprotonated by the nonionic bases 1a ,10 1b,11 and 1c,12
(1) Baizer, M.; Anderson, J . D. J . Org. Chem. 1965, 30, 1357.
(2) Baizer, M.; Chruma, L.; White, A. Tetrahedron Lett. 1973, 52,
5209.
(3) Misorro, A.; Uchida, Y.; Tamai, K.; Hidai, M. Bull. Chem. Soc.
J pn. 1967, 40, 931.
(4) Saegusa, T.; Ito, Y.; Tomita, S.; Kinoshita, H. J . Org. Chem. 1970,
35, 670.
(5) Saegusa, T.; Ito, Y.; Tomita, S. J . Am. Chem. Soc. 1971, 93, 5656.
(6) Saegusa, T.; Ito, Y.; Tomita, S. Bull. Chem. Soc. J pn. 1972, 45,
830.
(7) White, A.; Baizer, M. M. J . Chem. Soc., Perkins Trans. 1 1973,
2231.
(8) Shabtai, J .; Ney-Igner, E.; Pines, H. J . Org. Chem. 1975, 40,
1158.
are subsequently deprotonated by 1a or 1b to form an
allylic anion that can then undergo Michael addition to
a second molecule of the R,â-unsaturated nitrile. This
process is depicted in Scheme 1. The isomerization of the
double bond as shown in this scheme is consistent with
our previous observation that 1a and 1b are capable of
conjugating methylene-interrupted double bonds.14 In
accord with this finding, we expected nonionic bases of
type 1 to be able to produce Michael addition products
(9) Dewael, A. Bull. Soc. Chim. Belg. 1932, 324.
(10) Schmidt, H.; Lensink, C.; Xi, S. K.; Verkade, J . G. Z. Anorg.
Allg. Chem. 1989, 578, 75.
(11) D’Sa, B.; Verkade, J . G. Phosphrus, Sulfur Silicon Relat. Elem.
1997, 123, 301.
(12) Wroblewski, A. E.; Pinkas, J .; Verkade, J . G. Main Group Chem.
1995, 1, 69.
(13) D’Sa, B.; Kisanga, P.; Verkade, J . G. J . Org. Chem. 1998, 63,
3961.
(14) Kisanga, P.; McLeod, D.; D’Sa, B.; Verkade, J . G. In press.
10.1021/jo981513f CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/10/1998

10058 J . Org. Chem., Vol. 63, No. 26, 1998
Notes
Ta ble 1. Con d ition s a n d Yield s for th e P r ep a r a tion of
Glu ta r on itr ilesa
slower, however, requiring up to 12 h to achieve yields
similar to those obtained with reactions carried out in
benzene that require only 1-3 h. This may be attributed
to solvation of the anions in the more polar acetonitrile.
substrate
solvent
T (°C)
catalystb
product (yield %)
3
4
5
CH3CN
CH3CN
CH3CN
CH3CN
C6H6
30
30
30
30
40
40
50
30
40
25
25
1a or b
1a or b
1a or b
1a or b
1a or b
1b
7 (98)c
8 (81)c
9 (85)c
10 (95)c
17 (98)d
19 (90)e
19 (90)e
18 (94)d
0
As shown in Table 1, both 1a and 1b function as
catalysts for these Michael addition reactions. Likewise,
1c catalyzes reactions of 3 and 4 with acetonitrile to
produce the corresponding glutaronitriles 7 and 8 in 97
and 93% conversions, respectively (estimated by 1H NMR
integration), in 2.5 h. As postulated in Scheme 1, the γ-
rather than the R-hydrogen is deprotonated by nonionic
bases at the R,â-unsaturated nitrile stage of these
Michael additions. This assumption receives support from
the lack of reaction in Table 1 of substrates 14 and 16,
which both lack a γ-hydrogen. Substrate 1515 on the other
hand produces the dimer in excellent yield. The reaction
of the methylene interrupted unsaturated nitrile 12 in
the presence of catalytic amounts of 1a or 1b produces
the dimer 19 in 90% yield in addition to the isomerized
monomer 20 in 10% yield. Evidence for the isomerization
of the â,γ-unsaturated glutaronitrile produced in the
penultimate step of Scheme 1 to the more stable R,â-
unsaturated isomeric final product is therefore provided
by the formation of product 19. The failure of 19 to
undergo conjugation may be due to the sterically hin-
dered environment of the R-hydrogen owing to the
presence of the two six-membered rings. The formation
of compound 19 also serves as evidence for the postulated
reaction pathway shown in Scheme 1. The isolation of
product 20 on the other hand supports our previous
observation that 1b is capable of isomerizing double
bonds. In a similar way, the production of the glutaroni-
triles 17 and 18 from the substrates 11 and 13, respec-
tively, using 1a , 1b, or 1c as bases indicate that all these
bases are capable of isomerizing double bonds.
6
11
12
12
13
14
15
16
C6H6
MeOHf
C6H6
1a
1b or 1c
1a or 1b
1b
g,h
C6H6
C6H6
C6H6
8 (96)
0
1b
a
b
The time was 2.5 h unless stated otherwise. Present in 10
mol % concentration unless stated otherwise. c The amount of base
d
used was 30 mol %. The reaction time was 1 h in the presence
of 10 mol % of 1a or 1c. e In addition to the glutaronitrile 19, 10%
of isomerized substrate was isolated (see text). f The reaction time
g
was 10 min. Several solvents were tried (MeOH, CH3CN, THF,
Et2O). The reaction was also attempted at room temperature.
h
Sch em e 1
from substrates possessing double bonds poised to con-
jugate (11-13). The results of the experiments for these
substrates in addition to the R,â-unsaturated nitriles 14-
16 are shown in Table 1.
Although further experiments along the above lines are
underway, we have thus far recovered only starting
materials in attempted dimerizations of methylene-
interrupted â,γ-unsaturated esters or ketones. Diphenyl
acetaldehyde and 2-phenylpronionaldehyde have so far
also failed to give the glutaronitriles under the reaction
conditions used here for secondary aldehydes. Primary
aldehydes undergo aldol condensation as we previously
reported.13
Exp er im en ta l Section
The aldehydes and nitriles (Aldrich Chemical Co.) were used
as received. Acetonitrile was distilled from calcium hydride and
stored over 4 Å molecular sieves. All reactions were carried out
under nitrogen. The bases 1a ,10 1b,11 and 1c12 were prepared
according to our previously reported procedures,10-12 although
1a is commercially available (Strem).
Gen er a l P r oced u r e for th e P r ep a r a tion of Glu ta r on i-
tr iles fr om Ald eh yd es. In a typical experiment, 30 mg (0.12
mmol) of 1b was weighed under nitrogen in a 10 mL round-
bottomed flask containing a magnetic stirring bar. Dry aceto-
nitrile (2 mL) was then added, and the solution was warmed to
40 °C in an oil bath. The aldehyde (0.40 mmol) was added in
one portion, and the reaction mixture was stirred for 2.5 h. After
the volatiles were removed under vacuum, the glutaronitriles
were eluted on a silica gel column with Et2O in hexane. The
ratio of Et2O was gradually increased from 0 to 60% in 5%
increments. The dinitriles eluted with 40% Et2O in hexane to
afford a mixture of diastereomers in 98, 81, 85, and 95% yield
Scheme 1 further suggests that -CH2CN may act as a
base in catalyzing the formation of the glutaronitriles.
This was substantiated in reactions in which the sub-
strates 11-13 were reacted separately with 10 mol % of
1b in CD3CN. The 31P NMR of the reaction mixture
revealed the existence of 1b, 1bH+, and 1bD+. The 13C
NMR spectrum of the reaction mixture showed the
existence of CD3CN and a substantial amount of CD2-
HCN which can be formed if the -CD2CN produced by
the deprotonation of CD3CN deprotonates the substrate
or 1b H+. Reactions in the presence of acetonitrile are
(15) Palomo, C.; Aizpuruo, J .; Garcia, J .; Ganboa, I.; Cossio, F. B.;
Leua, B.; Lopez, C. J . Org. Chem. 1990, 55, 2498.

Notes
J . Org. Chem., Vol. 63, No. 26, 1998 10059
for 7-10, respectively.16 Attempts to isolate the E-isomer from
the mixture by column chromatography failed.
Ack n ow led gm en t. The authors thank the donors
of the Petroleum Research Fund, administered by the
American Chemical Society, and the Iowa State Center
for Advanced Technology Development for grant support
of this work.
Gen er a l P r oced u r e for th e P r ep a r a tion of Glu ta r on i-
tr iles fr om Nitr iles. This reaction was carried out by weighing
25 mg (0.12 mmol) of 1a or 30 mg of 1b (0.12 mmol) under
nitrogen in a 10 mL round-bottomed flask containing a magnetic
stirring bar. To this was added 2 mL of the solvent, and the
resulting solution was warmed to the required temperature
(Table 1). The nitrile was then added (1.2 mmol), and the
mixture was stirred for the time shown in Table 1. Removal of
the volatiles under vacuum followed by column chromatography
using ether and hexane as mentioned above afforded the
corresopnding glutaronitriles as products.16
Su p p or tin g In for m a tion Ava ila ble: Text and tables of
1H and 13C NMR data and mass spectral molecular weights
figures of NMR spectra (23 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
(16) See Supporting Information for spectral data recorded for these
compounds.
J O981513F