Reductive activation of arenes 21. Reaction of products of two-electron reduction of arenecarbonitriles by alkali metals in liquid ammonia with bromo-and dibromoalkanes

Article abstract of DOI:10.1007/s11172-006-0366-0

Reductive alkylation of benzonitrile, ortho-, meta-, para-tolunitriles, and 1-naphthonitrile by sequential action of alkali metal and alkyl bromide in liquid ammonia results in corresponding alkylarenes and 1-alkyl-1- cyanocyclohexa-2,5-dienes. The experimental conditions for target synthesis of the specified products are found. A method of synthesis of 1-(ω- bromoalkyl)-1-cyanocyclohexa-2,5-dienes based on the interaction of two-electronic reduction products of aromatic nitriles with α,ω- dibromoalkanes Br(CH₂)_nBr (_n = 3-5) is developed.

Full text of DOI:10.1007/s11172-006-0366-0

Russian Chemical Bulletin, International Edition, Vol. 55, No. 6, pp. 981—986, June, 2006
981
Reductive activation of arenes
21.* Reaction of products of twoꢀelectron reduction of arenecarbonitriles
by alkali metals in liquid ammonia with bromoꢀ and dibromoalkanes**
T. A. Vaganova,a E. V. Panteleeva,a,b P. S. Yuferov,b Yu. V. Rebitva,a,c and V. D. Shteingartsa,bꢀ
aN. N. Vorozhtsov Novosibirsk Iinstitute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9752. Eꢀmail: shtein@nioch.nsc.ru
bNovosibirsk State University,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation
cNovosibirsk State Pedagogical University,
28 ul. Vilyujskaya, 630126 Novosibirsk, Russian Federation
Reductive alkylation of benzonitrile, orthoꢀ, metaꢀ, paraꢀtolunitriles, and 1ꢀnaphthonitrile
by sequential action of alkali metal and alkyl bromide in liquid ammonia results in correspondꢀ
ing alkylarenes and 1ꢀalkylꢀ1ꢀcyanocyclohexaꢀ2,5ꢀdienes. The experimental conditions for
target synthesis of the specified products are found. A method of synthesis of 1ꢀ(ωꢀbromoalkyl)ꢀ
1ꢀcyanocyclohexaꢀ2,5ꢀdienes based on the interaction of twoꢀelectronic reduction products of
aromatic nitriles with α,ωꢀdibromoalkanes Br(CH2)nBr (n = 3—5) is developed.
Key words: aromatic nitriles, reductive alkylation, cyanocyclohexadienyl anions, 1ꢀalkylꢀ
1ꢀcyanocyclohexaꢀ2,5ꢀdienes, 1ꢀ(ωꢀbromoalkyl)ꢀ1ꢀcyanocyclohexaꢀ2,5ꢀdienes.
Twoꢀelectron reduction of arenecarbonitriles, namely,
benzonitrile, naphthonitrile, cyanoanthracene,2 and
orthoꢀ, metaꢀ, and paraꢀtolunitriles1 by alkali metals in
liquid NH3 allows one to generate preparative amounts of
stable cyclohexadienyl anions that are highly reactive in
the reactions with electrophilic reagents, in particular,
alkyl halides.3 The primary products of such reactions,
namely, dihydroarenes alkylated at the saturated carbon
atom possess a versatile reactivity. Therefore, they can be
used as initial compounds in fine organic synthesis, e.g.,
as building blocks4 in the design of analogs of natural
biologically active compounds, such as fungicides and
insecticides, reagents for generation of free radicals, etc.
Production of cyclohexadienyl anions as mentioned
above is accompanied by the formation of an equivalent
amount of amide ions. Under the action of amide ions the
primary alkylation products of anions, that is, alkylꢀ
cyanodihydroarenes undergo dehydrocyanation to give
alkylarenes (Scheme 1).
ment by phenyl one5 and introduction of Me group at
paraꢀposition of the substrate,5—7 which seems to be due
to a decrease in the CHꢀacidity of the primary dihydroꢀ
arene. Besides, the percentage of dihydroarene depends
on the nature of alkyl halide and increases on going from
chlorides to iodides.5 It also increases upon branching of
the alkyl fragment6 probably owing to more efficient neuꢀ
tralization of amide ion by alkyl halides or products of
their ammonolysis. It should be emphasized that the maꢀ
jor reaction product is always the alkylarene.
The aim of this work was to establish the experimental
conditions suitable for minimization of the yields of
dehydrocyanation products and for the use of products of
twoꢀelectron reduction of cyanoarenes in liquid NH3 as
synthons for cyanodihydroarylation of alkyl halides. With
this purpose we studied the effects of the nature of alkali
metal, protonꢀdonor additives and cosolvent, the reagent
ratio, and the order of mixing of reagents on the ratio of
the products of reductive alkylation of aromatic nitriles.
Additionally, we studied the interaction of cyclohexaꢀ
dienyl anions with α,ωꢀdibromoalkanes. This is the first
example of alkylation of such anions using dihalogenides.
The overall yield of alkylation products is 55 to 90%,
and the dihydroarene/alkylarene ratio varies in the range
0.1—0.5 depending on the nature of the substrate and
alkyl halide. For instance, the proportion of dihydroarene
increases both upon replacement of the naphthyl fragꢀ
Results and Discussion
* For Part 20, see Ref. 1.
** Dedicated to the memory of Academician V. A. Koptyug on
the occasion of the 75th anniversary of his birth.
Cyclohexadienyl anions were generated from benzoꢀ
nitrile (1), its methyl derivatives, namely, orthoꢀ (2),
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 945—950, June, 2006.
1066ꢀ5285/06/5506ꢀ0981 © 2006 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 6, June, 2006
Vaganova et al.
Scheme 1
X = H (1, 6a,b, 11a,b), oꢀMe (2, 7a,b, 12a,b), mꢀMe (3, 8a—f, 13a—f), pꢀMe (4, 9a,b, 14a,b);
M = Li, Na, K; BH = ButOH, NH4Cl, ButCl; Hal = Br, I;
R = Bu (6a, 7a, 9a—12a, 14a, 15a), (CH2)5Br (6b, 7b, 9b—12b, 14b, 15b);
8, 13: R = Bu (a), Bui (b), Me (c), (CH2)3Br (d), (CH2)4Br (e), (CH2)5Br (f)
metaꢀ (3), and paraꢀtolunitriles (4), and 1ꢀnaphthoꢀ
nitrile (5). As was found earlier for anions 1ꢀH–,
3ꢀH–—5ꢀH– (see Scheme 1) and established in this work
for anion 2ꢀH–, 1ꢀalkylꢀ1ꢀcyanoꢀ1,4ꢀdihydroarenes 6—10
formed after adding a primary alkyl halide to sodium salts
of cyclohexadienyl anions in liquid NH3 (procedure A)
undergo almost complete dehydrocyanation and transꢀ
form into alkylarenes 11—15 (see Scheme 1 and Table 1).
The conditions for reductive alkylation of aromatic niꢀ
triles were optimized in order to obtain compounds 6—10
taking the reactions of anion 3ꢀH– with primary alkyl
halides as an example. We studied the effect of protonꢀ
donor additives, cosolvent, nature of alkali metal, and
order of mixing of the reagents on the extent of dehydroꢀ
cyanation of alkylcyanodihydroarenes 8. The reagents used
and the reagent ratios are listed in the Experimental and
Table 1. Effect of reaction conditions on the ratio of products of the reductive alkylation of nitriles 1—5 in liquid NH3
(see Scheme 1)
Nitrꢀ
ile
M
Cosolvꢀ
ent
Protonating
agent
RHal
Alkylation
procedure*
Product yield (mol.%)**
Diene/Arene
Diene
Arene
1 5
1
2
K
Li
Na
Li
Na
Na
Na
Na
Na
Li
Na
Na
Li
—
THF
—
THF
—
—
—
—
THF
THF
—
—
THF
—
THF
—
THF
—
ButOH
—
BuBr
BuBr
BuBr
BuBr
BuBr
BuiBr
BuiBr
BuiBr
BuiBr
BuiBr
BuiBr
MeI
BuBr
BuBr
BuBr
BuBr
BuBr
A
B
A
B
A
A
A
A
A
A
B
B
B
A
B
A
B
13 (6a)
88 (6a)
1 (7a)
93 (7a)
1 (8a)
10 (8b)
28 (8b)
35 (8b)
28 (8b)
47 (8b)
1 (8b)
45 (8c)
88 (8a)
27 (9a)
73 (9a)
2 (10a)
79 (10a)
42 (11a)
1 (11a)
54 (12a)
3 (12a)
83 (13a)
63 (13b)
34 (13b)
27 (13b)
51 (13b)
27 (13b)
53 (13b)
3 (13c)
7 (13a)
61 (14a)
1 (14a)
68 (15a)
2 (15a)
0.3
88
0.02
31
0.01
0.2
0.8
1.3
0.6
1.7
0.02
15
13
0.4
73
0.03
39
2
ButOH
—
3 6
3 6
3
—
NH4Cl
ButCl
ButOH
ButOH
—
3
3
3
3
3
3
4 7
4
5 5
5
—
ButOH
—
Na
Li
K
ButOH
—
Li
ButOH
* A and B denote the conventional and reverse order of mixing of reagents (see Experimental).
1
** According to GLC/MS and H NMR spectroscopy data.

Reductive activation of arenecarbonitriles
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 6, June, 2006
983
the reaction product yields are given in Table 1. The
previously unknown alkylation products were isolated from
the reaction mixtures and characterized spectroscopically
(see Experimental).
showed that alkylation of the sodium salts of anions 1ꢀH–
and 5ꢀH– with a large excess of MeI allows one to reduce
the extent of dehydrocyanation of the primary reaction
product to 10%. However, from our experiments carried
out in this study it follows that the result of alkylation
performed using the reverse order of reagent mixing
strongly depends on both the reactivity of the alkyl halide
and the conditions for generation of cyclohexadienyl
anion. For instance, as with conventional mixing of reꢀ
agents, the interaction of the sodium salt of anion 3ꢀH–
with an excess of BuiBr results in isobutyltoluene 13b as
the major product. The extent of dehydrocyanation conꢀ
siderably decreases only in the reaction with a more reacꢀ
tive methyl iodide (ammonolysis rates for MeI and BuiBr
differ by several orders of magnitude10), namely, the
dihydroarene/alkylarene ratio is 15 and the yield of the
major reaction product (8c) reaches a value of 45%. Thereꢀ
fore, the effect of the reverse order of reagent mixing in
the alkylation of sodium salt of anion 3ꢀH– in the presꢀ
ence of sodium amide manifests itself only when using
those alkyl halides that are comparable with MeI in reacꢀ
tivity. Reduction of nitrile 3 under lowerꢀbasicity condiꢀ
tions, that is, by lithium in a NH3/THF mixture in the
presence of ButOH followed by slow addition of the soluꢀ
tion of the salt of anion 3ꢀH– thus generated to an excess
of BuBr leads to preferred formation of cyclohexadiene
8a in 88% yield (8a/13a ratio is ~13).
Amide ions were neutralized using NH4Cl, ButOH,
and ButCl. tertꢀButyl chloride acting as protonating agent
undergoes elimination and transforms into isobutylene.
These reagents were added to solutions of the reduction
products of nitrile 3 prior to treatment with alkyl halide.
Then, alkylation was performed and the reaction mixꢀ
tures were neutralized with an excess of ammonium chloꢀ
ride. Neutralization of amideꢀion with NH4Cl and ButCl
causes the 8b/13b ratio to increase to 0.8 and 1.3, respecꢀ
tively. Adding an equivalent amount of ButOH to the
solution of sodium salt of anion 3ꢀH– in ammonia causes
no decrease in the contribution of the secondary transforꢀ
mations. Reduction of nitrile 3 by sodium in the presence
of ButOH with THF as cosolvent (THF : ammonia =
1 : 5 v/v) leads to a decrease in the yield of the deꢀ
hydrocyanation product (8b/13b ratio equals 0.6). When
sodium is replaced by lithium, the 8b/13b ratio increases
to 1.7. A decrease in the extent of dehydrocyanation on
going from sodium to lithium is likely due to lower basicꢀ
ity of lithium salts in liquid ammonia compared to soꢀ
dium salts.8
The reaction of twoꢀelectron reduction products of
benzonitrile and orthoꢀmethoxybenzonitrile by lithium in
the NH3/THF/ButOH system with benzyl bromide and
3ꢀbromoꢀ1ꢀchloropropane results in 65—80% yields of
substituted cyanocyclohexadienes.9 Dehydrocyanation of
these compounds is efficiently inhibited by neutralizing
the reaction mixture with NH4Cl after alkylation.9 In conꢀ
trast to this, the highest yield of diene 8b achieved in this
work under similar conditions is at most 50%, the deꢀ
hydrocyanation product 13b being also formed in nearly
30% yield.
The results obtained suggest that alkylation of cycloꢀ
hexadienyl anion on slow addition of the alkylating agent
to the solution of the twoꢀelectron reduction product of
nitrile is accompanied by the dehydrocyanation of diene.
Cyanocyclohexadienes 6—10 formed as a result of protoꢀ
nation of cyclohexadienyl anions are oxidized to initial
nitriles upon treatment of the reaction mixture or unꢀ
dergo transformation into cyclohexadienyl anions under
the action of bases followed by alkylation.
In this connection one could expect that dehydroꢀ
cyanation will be most efficiently inhibited by reversing
the order of reagent mixing, i.e., on slow addition of the
solution of cyclohexadienyl anion salt to an excess alkyl
halide (procedure B). Here, alkylcyanocyclohexadiene is
formed in the presence of minimum amounts of bases
(cyclohexadienyl anion and amide ion) that are neutralꢀ
ized faster than in conventional mixing due to the presꢀ
ence of excess alkyl halide and ammonium ion produced
as a result of ammonolysis of the alkyl halide. Earlier,5 we
In order to check the general character of the proceꢀ
dure employed, we carried out a series of experiments
with nitriles 1, 2, 4, and 5 and established that the reacꢀ
tions of anions 1ꢀH–, 2ꢀH–, 4ꢀH– and 5ꢀH– generated
under these conditions with BuBr in all cases result in
preferred formation of the corresponding alkylcyanoꢀ
dihydroarenes 6a, 7a, 9a, and 10a in ~70—90% yields.
This makes it possible to consider the proposed procedure
for reductive alkylation of aromatic mononitriles synthetiꢀ
cally valuable.
In order to extend the field of application of this
method for synthesis of functionalized cyanocyclohexaꢀ
dienyl compounds, it was appropriate to extend the specꢀ
trum of the alkylating agents by involving dihaloalkanes
in the reactions with cyclohexadienyl anions. We studied
the interaction of anions 1ꢀH–—5ꢀH– with α,ωꢀdibromoꢀ
alkanes including three to five carbon atoms in the main
chain. ωꢀHaloalkylated products can be obtained in the
reactions of the anions formed in the reduction of
monocyanobenzenes,9 nitrobenzene,11 naphthalene,12
and 3,4ꢀdiphenylcinnoline13 with α,ωꢀdihaloalkanes. Broꢀ
mide reagents were chosen because other alkyl halides are
prone to involvement in side reactions, in particular, subꢀ
stitution of both halogen atoms in diiodoalkanes or protoꢀ
nation of anionic reduced forms of nitriles by chloroꢀ
alkanes that possess the properties of CHꢀacids.5
We established that the reactions of anion 3ꢀH– genꢀ
erated by reduction of nitrile 3 by lithium in NH3/THF

984
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 6, June, 2006
Vaganova et al.
Table 2. Reaction of products of twoꢀelectron reduction of aroꢀ
matic nitriles 1—5 by lithium in NH3/THF/ButOH mixture
with Br(CH2)nBr (procedure B)
The following conclusions can be drawn. The results
of the reaction of cyanodihydroaryl anions 1ꢀH–—5ꢀH–
(twoꢀelectron reduction products of aromatic mononitriles
in liquid ammonia) with alkyl halides strongly depend on
the reaction conditions, namely, the nature of the counterꢀ
ion, protonating agents, cosolvent, reagent ratio, and the
order of mixing of reagents. By varying these factors it is
possible to carry out target synthesis of alkylcyanoꢀ
cyclohexadienes or alkylarenes.
Nitrꢀ
ile
n
Yield of reaction products (mol.%)*
Dihydroarene
Bromoalkylarene
3
3
3
3 **
1
2
4
5
3
4
5
5
5
5
5
5
92 (8d)
71 (8e)
75 (8f)
50 (8f)
72 (6b)
75 (7b)
67 (9b)
54 (10b)
3 (13d)
—
9 (13f)
11 (13f)
18 (11b)
2 (12b)
7 (14b)
11 (15b)
We established specific conditions for reductive alkyꢀ
lation of nitriles 1—5 (lithium as reducing agent, equivaꢀ
lent amount of ButOH, THF as cosolvent, reverse order
of mixing of reagents) under which one can almost comꢀ
pletely inhibit the side transformations initiated by bases
and obtain 1ꢀalkylꢀ1ꢀcyanoꢀ1,4ꢀdihydroarenes in high
yields. In addition to alkyl halides, α,ωꢀdibromoalkanes
are also involved in the reaction with the reduced forms
of cyanoarenes. This made it possible to elaborate a
method for the synthesis of 1ꢀ(ωꢀbromoalkyl)ꢀ1ꢀcyanoꢀ
1,4ꢀdihydroarenes. The synthesis of such compounds is
of great value because cyclohexadienes functionalized at
the saturated carbon atom are potential synthons for the
synthesis of analogs of natural biologically active comꢀ
pounds.4 The method of synthesis of alkylꢀ and diꢀ
alkylarenes also seems to be quite valuable. Traditionally,
the most common method of alkylation of the aromatic
nucleus is the Friedel—Krafts reaction.15 However, this
reaction is inappropriate for obtaining a broad spectrum
of individual dialkylbenzenes. Other methods of alkylaꢀ
tion of the aromatic nucleus, mainly involving organoꢀ
metallic reagents, are intensively developing.16 Alternaꢀ
tive methods also include the reductive alkylation of availꢀ
able aromatic nitriles employed in this work, which
can be used to obtain alkylbenzenes, ꢀtoluenes, and
ꢀnaphthalenes.
* According to GLC/MS and 1H NMR spectroscopy data.
** Experiment was carried out following procedure A; the mixture
of products also contained compounds 16 (18%) and 17 (7%).
mixture in the presence of ButOH with 1,3ꢀdibromoꢀ
propane, 1,4ꢀdibromobutane, and 1,5ꢀdibromopentane
carried out using the reverse order of the addition of the
reagents result in the corresponding 1ꢀ(ωꢀbromoalkyl)ꢀ1ꢀ
cyanoꢀ3ꢀmethylcyclohexaꢀ2,5ꢀdienes 8d—f (see Scheme 1
and Table 2) as the major products. Here, the extent
of dehydrocyanation of compounds 8d—f to give
3ꢀ(ωꢀbromoalkyl)toluenes 13d—f is low. Taking the inꢀ
teraction of anion 3ꢀH– with 1,5ꢀdibromopentane as an
example, we studied the possibility of the synthesis of
substituted dienes using a conventional order mixing of
reagents, which does not require a large excess of alkyl
halide. This results in diene 8f and toluene 13f in a 4.5 : 1
ratio. Additionally, considerable amounts of the substituꢀ
tion products of the second bromine atom, namely,
1,5ꢀdi(1ꢀcyanoꢀ3ꢀmethylcyclohexaꢀ2,5ꢀdienyl)pentane
(16) and 1ꢀcyanoꢀ3ꢀmethylꢀ1ꢀ[5ꢀ(3ꢀmethylphenyl)penꢀ
tyl]cyclohexaꢀ2,5ꢀdiene (17) are formed. Compounds 16
and 17 were not isolated in individual form, but they were
detected in the mixtures of reaction products (see Table 2)
by GLC/MS and 1H NMR spectroscopy. Therefore, a
slow addition of dibromoalkane to a solution of the salt of
anion 3ꢀH– is accompanied by the formation of rather
large amounts of secondary products corresponding to
both dehydrocyanation of diene 8f and replacement of a
bromine atom in 8f or in toluene 13f, whereas the proceꢀ
dure involving the reverse order of reagent mixing permits
almost complete inhibition of side processes.
Experimental
1
H NMR spectra were recorded with a Bruker ACꢀ200 specꢀ
trometer in CDCl3. IR spectra were recorded with a Bruker
Vectorꢀ22 instrument for slice measurements. The precise moꢀ
lecular weights of ions were determined by high resolution mass
spectrometry with a Finnigan MATꢀ8200 instrument. GLC/MS
identification of mixture components was performed using a
Hewlett Packard G1081A setup comprising an HP 5890 Series II
gas chromatograph and an HP5971 mass selective detector; elecꢀ
tron ionization energy of 70 eV; HP5 column (5% of diphenyl
and 95% of dimethylsiloxane), 30 m × 0.25 mm × 0.25 µm; with
helium as carrier gas, flow rate 1 mL min–1; column temperaꢀ
ture programming from 50 °C (2 min) at an increment of
10 deg min–1 to 280 °C (5 min); injector temperature 280 °C;
ion source temperature 173 °C; data acquisition rate 1.2 scan s–1
in the mass range 30 to 650 amu.
Reactions of anions 1ꢀH–, 2ꢀH–, 4ꢀH–, and 5ꢀH–
with 1,5ꢀdibromopentane under similar conditions also
result in 5ꢀbromopentylcyanodihydroarenes 6b, 7b, 9b,
and 10b as the major products (yields 55—75%). The
minor reaction products, bromoalkylarenes 11—15,
were reported earlier.14 Their content in the mixtures
was estimated based on 1H NMR spectroscopy and
GLC/MS data.
Liquid NH3 was purified by dissolving metallic sodium folꢀ
lowed by distillation to a reaction vessel cooled to –70 °C; THF
was purified by boiling over benzophenone ketyl followed by
distillation in argon atmosphere. The oxide films were removed

Reductive activation of arenecarbonitriles
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 6, June, 2006
985
from alkali metals under an anhydrous hexane layer. Alkyl haꢀ
lides and dihaloalkanes were purified by passing through aluꢀ
mina followed by distillation. Nitriles 1—5 were distilled
over P2O5.
Generation of twoꢀelectron reduction products of nitriles 1—5
(general procedure). 1). To a solution of 2.5 mmol of nitrile 1, 3,
or 5 in liquid NH3 (50 to 55 mL, concentration ~5•10–2
mol L–1), alkali metal (5.2 mmol) was added with stirring in
inert atmosphere at –35 °C and the reaction mass was kept for 5
to 10 min under the same conditions.
2). To a solution of alkali metal (5.2 mmol) in liquid NH3
(50 mL), a solution of nitrile 2 or 4 (2.5 mmol) in abs. THF
(5 mL) was added with stirring at –35 °C and the reaction mass
was kept for 5 to 10 min under the same conditions.
When generating the reduced forms using the protonating
agents, ButCl or NH4Cl (2.5 mmol) was added to the solution of
the nitrile reduction products and ButOH (2.5 mmol) was added
to the nitrile solution in NH3/THF (5 : 1, v/v) mixture prior to
adding metal, and the solutions of the reduction products were
allowed to stay for 15 to 20 min.
2.53—2.64 (m, 2 H, H(4)); 5.50 (dt, 1 H, H(6), J = 10.0 Hz, J =
2.0 Hz); 5.57—5.65 (m, 1 H, H(3)); 5.88 (dtd, 1 H, H(5), J =
10.0 Hz, J = 3.0 Hz, J = 1.0 Hz). IR, ν/cm–1: 2229 (C≡N).
Found: m/z 175.13586 [M]+. C12H17N. Calculated:
M = 175.13609.
1ꢀ(5ꢀBromopentyl)ꢀ1ꢀcyanoꢀ2ꢀmethylcyclohexaꢀ2,5ꢀdiene
1
(7b). H NMR, δ: 1.01—1.25, 1.26—1.43 (both m, 2 H, CH2);
1.59—1.90 (m, 4 H, 2 CH2); 1.77—1.79 (m, 3 H, Me); 2.53—2.64
(m, 2 H, H(4)); 3.29 (t, 2 H, CH2, J = 9.0); 5.50 (dt, 1 H, H(6),
J = 10.0 Hz, J = 2.0 Hz); 5.57—5.65 (m, 1 H, H(3)); 5.88 (dtd,
1 H, H(5), J = 10.0 Hz, J = 3.0 Hz, J = 1.0 Hz). IR, ν/cm–1
:
2229 (C≡N). Found: m/z 267.06202 [M]+. C13H18BrN. Calcuꢀ
lated: M = 267.06231.
1ꢀCyanoꢀ1,3ꢀdimethylcyclohexaꢀ2,5ꢀdiene (8c). 1H NMR,
δ: 1.43 (s, 3 H, C(1)Me); 1.71 (s, 3 H, C(3)Me); 2.50—2.59 (m,
2 H, H(4)); 5.32—5.39 (m, 1 H, H(2)); 5.64 (dq, 1 H, H(6),
J =10.0 Hz, J = 2.0 Hz); 5.84 (dt, 1 H, H(5), J = 10.0 Hz, J =
3.6 Hz). IR, ν/cm–1: 2228 (C≡N). Found: m/z 133.0872 [M]+.
C9H11N. Calculated: M = 133.0891.
1ꢀ(3ꢀBromopropyl)ꢀ1ꢀcyanoꢀ3ꢀmethylcyclohexaꢀ2,5ꢀdiene
(8d). 1H NMR, δ: 1.73 (s, 3 H, Me); 1.74—2.00 (m, 4 H, 2 CH2);
2.52—2.61 (m, 2 H, H(4)); 3.37 (t, 2 H, CH2, J = 9.0 Hz);
5.27—5.34 (m, 1 H, H(2)); 5.59 (dq, 1 H, H(6), J = 10.0 Hz, J =
2.0 Hz); 5.94 (dt, 1 H, H(5), J = 10.0 Hz, J = 3.5 Hz). IR,
ν/cm–1: 2228 (C≡N). Found: M = 239 (GLC/MS). C11H14BrN.
Found: m/z 238.0238 [M – 1]+. C11H13BrN. Calculated:
M – 1 = 238.0232.
Reaction of products of twoꢀelectron reduction of nitriles 1—5
with alkyl halides (general procedure). A. To a solution of the
reduction product, alkyl halide (6 mmol) was added dropwise
with stirring at –35 °C. The reaction mixture was kept for 30 min
under the same conditions and then an excess of NH4Cl (~5 g)
and Et2O (50 mL) were added sequentially. The mass obtained
was stirred until complete evaporation of NH3 and water (50 mL)
was added to the residue. The ethereal layer was separated and
the aqueous layer was extracted with ether (2×50 mL). The
combined organic extracts were washed with water and dried
with MgSO4. The compositions of the mixtures of the reaction
products were determined based on the 1H NMR spectroscopy,
GLC, and GLC/MS data; the values averaged over the results of
at least two runs (deviation was at most 5%) are listed in Tables 1
and 2. Individual compounds were separated by column chromaꢀ
tography or TLC (with silica gel as sorbent and hexane—diethyl
ether mixture (9 : 1, v/v) as eluent). The separation process was
monitored visually upon exposure of Silufol plates to UV light.
The yields of the target products were at least 80% of their
content in the mixtures. The structures of the compounds isoꢀ
1ꢀ(4ꢀBromobutyl)ꢀ1ꢀcyanoꢀ3ꢀmethylcyclohexaꢀ2,5ꢀdiene
1
(8e). H NMR, δ: 1.35—1.53, 1.59—1.77 (both m, 2 H, CH2);
1.75 (s, 3 H, Me); 1.77—1.95 (m, 2 H, CH2); 2.52—2.59 (m,
2 H, H(4)); 3.36 (t, 2 H, CH2, J = 9.0 Hz); 5.27—5.33 (m, 1 H,
H(2)); 5.59 (dq, 1 H, H(6), J = 10.0 Hz, J = 2.0 Hz); 5.92 (dt,
1 H, H(5), J = 10.0 Hz, J = 3.4 Hz). IR, ν/cm–1: 2228
(C≡N). Found: m/z 253.0467 [M]+. C12H16BrN. Calculated:
M = 253.0432.
1ꢀ(5ꢀBromopentyl)ꢀ1ꢀcyanoꢀ3ꢀmethylcyclohexaꢀ2,5ꢀdiene
1
(8f). H NMR, δ: 1.25—1.54 (m, 4 H, 2 CH2); 1.57—1.75 (m,
2 H, CH2); 1.76 (s, 3 H, Me); 1.77—1.95 (m, 2 H, CH2);
2.51—2.59 (m, 2 H, H(4)); 3.38 (t, 2 H, CH2, J = 9.0); 5.29—5.36
(m, 1 H, H(2)); 5.61 (dq, 1 H, H(6), J = 10.0, J = 2.0 Hz); 5.92
(dt, 1 H, H(5), J = 10.0 Hz, J = 3.4 Hz). IR, ν/cm–1: 2227
(C≡N). Found: m/z 267.0631 [M]+. C13H18BrN. Calculated:
M = 267.0623.
1ꢀ(5ꢀBromopentyl)ꢀ1ꢀcyanoꢀ4ꢀmethylcyclohexaꢀ2,5ꢀdiene
(9b). 1H NMR, δ: 1.05, 1.09 (both d, 3 H, Me, J = 6.0);
1.25—1.50 (m, 4 H, 2 CH2); 1.59—1.76, 1.77—1.94 (both m,
2 H, CH2); 2.67—2.74 (m, 1 H, H(4)); 3.35 (t, 2 H, CH2, J =
9.0 Hz); 5.56, 5.58 (both dd, 2 H, H(2), H(6), J = 10.0 Hz, J =
2.0 Hz); 5.82 (dd, 2 H, H(3), H(5), J = 10.0 Hz, J = 3.0 Hz). IR,
ν/cm–1: 2231 (C≡N). Found: m/z 267.0630 [M]+. C13H18BrN.
Calculated: M = 267.0623.
1ꢀ(5ꢀBromopentyl)ꢀ1ꢀcyanoꢀ1,4ꢀdihydronaphthalene (10b).
1H NMR, δ: 1.26—1.53 (m, 4 H, 2 CH2); 1.58—1.77, 1.70—1.89
(both m, 2 H, CH2); 3.21—3.38 (m, 2 H, H(4)); 3.36 (t, 2 H,
CH2, J = 9.0 Hz); 5.88 (dt, 1 H, H(2), J = 10.0 Hz, J = 2.0 Hz);
6.21 (dt, 1 H, H(3), J = 10.0 Hz, J = 3.5 Hz); 7.18—7.54
(m, 4 H, H(5)—H(8)). IR, ν/cm–1: 2227 (C≡N). Found:
m/z 304.2321 [M]+. C16H18BrN. Calculated: M = 304.2313.
1
lated were established by H NMR and IR spectroscopy and by
high resolution mass spectrometry.
B (Reverse order of mixing of reagents). To a solution of
alkyl halide (25—30 mmol) in THF (1 : 1, v/v) cooled to
–10—0 °C, a solution of the reduction product was added with
stirring over a period of 20 to 30 min. The reaction mixture was
stirred for 10 min and then an excess of NH4Cl (~5 g) and 50 mL
of diethyl ether was added sequentially. Subsequent treatment
and analysis of the mixtures of the reaction products were perꢀ
formed as described above.
1ꢀ(5ꢀBromopentyl)ꢀ1ꢀcyanocyclohexaꢀ2,5ꢀdiene
(6b).
1H NMR, δ: 1.20—1.45 (m, 4 H, 2 CH2); 1.52—1.71, 1.73—1.90
(both m, 2 H, CH2); 2.61—2.70 (m, 2 H, H(4)); 3.36 (t, 2 H,
CH2); 5.60 (dt, 2 H, H(2), H(6), J = 10.0 Hz, J = 2.0 Hz); 5.91
(dt, 2 H, H(3), H(5), J = 10.0 Hz, J = 3.5 Hz). IR, ν/cm–1
:
2230 (C≡N). Found: M = 253 (GLC/MS). C12H16BrN.
Found: m/z 252.0493 [M – 1]+. C12H15BrN. Calculated:
M – 1 = 252.0388.
1ꢀButylꢀ1ꢀcyanoꢀ2ꢀmethylcyclohexaꢀ2,5ꢀdiene
(7a).
1H NMR, δ: 0.82 (t, 3 H, Me, J = 9.0 Hz); 1.00—1.31 (m, 4 H,
This work was financially supported by the Chemistry
and Materials Science Division of the Russian Academy
2 CH2); 1.58—1.91 (m, 2 H, CH2); 1.77—1.79 (m, 3 H, Me);

986
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 6, June, 2006
Vaganova et al.
8. A. J. Birch and S. G. Rao, Reduction by MetalꢀAmmonia
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istry. Methods and Results, Ed. E. C. Taylor, Wiley, New
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of Sciences (Grant 4.1.9) and the Russian Foundation for
Basic Research (Project No. 05ꢀ03ꢀ32309a).
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Received March 20, 2006;
in revised form May 22, 2006