Synthesis of α,α-diaryl nitriles by radical nucleophilic substitution

Article abstract of DOI:10.1039/c1nj20699k

The present study shows that the anion of 2-naphthylacetonitrile is substituted selectively at its C_α by aromatic halides, through a radical nucleophilic substitution mechanism, to give the corresponding α,α-diaryl nitriles in good yields. The regioselectivity of this ambident nucleophile changes with the steric hindrance at the radical centre from the aromatic substrate. The selectivity observed was investigated through a computational model of the key reaction step. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2012.

Full text of DOI:10.1039/c1nj20699k

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PAPER
Synthesis of a,a-diaryl nitriles by radical nucleophilic substitutionw
Tomas C. Tempesti, Adriana B. Pierini and Maria T. Baumgartner*
Received (in Gainesville, FL, USA) 10th August 2011, Accepted 6th November 2011
DOI: 10.1039/c1nj20699k
The present study shows that the anion of 2-naphthylacetonitrile is substituted selectively at its
Ca by aromatic halides, through a radical nucleophilic substitution mechanism, to give the
corresponding a,a-diaryl nitriles in good yields. The regioselectivity of this ambident nucleophile
changes with the steric hindrance at the radical centre from the aromatic substrate. The selectivity
observed was investigated through a computational model of the key reaction step.
stabilized aromatic radicals, such as naphthyl and quinolyl
moieties.9 Only one arylnitrile, the anion of phenylacetonitrile,
Introduction
The importance of a-aryl-substituted nitriles lies in their
potential as building blocks to synthesize amides, carboxylic
was studied in this reaction type. This anion reacts with
heteroaryl halides to afford good yields of the substitution
acids, primary amines, ketones, heterocycles and biologically
product at Ca (eqn (1)). The substitution at the phenyl moiety
active compounds with or without the nitrile group.1 In
of the anion is not observed.
contrast to a-alkylation of nitriles with alkyl halides,2 the
direct a-arylation of nitriles appears to be quite difficult to
accomplish, and consequently, the chemistry related to this
ð1Þ
transformation is much less developed. It has been reported
that the anions of diphenylacetonitrile, phenylacetonitrile
and ethyl cyanoacetate can couple with aryl fluorides under
Excellent yields have been obtained with 2-chloropyrazine but
uncatalyzed a-arylations.3
probably by dual radical chain and addition–elimination
mechanisms.10
The palladium-catalyzed a-arylation of nitriles has recently
emerged as a major advancement; the secondary nitriles afford
monoarylation products with aryl halides possessing electron-rich,
electron-poor and electron neutral groups.4 The reactions of
benzyl nitriles take place selectively to form the product of
monoarylation in good yields.5 The selective monoarylation
of acetonitrile and primary nitriles has been achieved using
a-silyl nitriles in the presence of ZnF2.6
On the other hand, a special regiochemistry has been
determined in the reactions of radicals with anions able to
show ambident behavior.11 The anions of the 2-naphthyl
system (Z = O, NH, S) have been reported to react with aryl
radicals to give C1-substitution at their naphthyl moiety. A
preference for heteroatom-arylation has been reported in the
reaction of 2-naphthalenethiolate anion 1 (eqn (2)).12
The application of substitution radical nucleophilic reactions
to C–C forming processes is a subject of continued interest. The
aromatic radical nucleophilic substitution, or SRN1 reaction,7
has been shown to be an excellent route to perform the
nucleophilic substitution of unactivated aromatic compounds
with suitable leaving groups. The main feature of the SRN1
reaction of nitrile anions centers on the fact that depending on
the aryl halides involved, straightforward substitution products
with or without retention of the CN group can be formed.8
However, a-arylated nitriles are almost exclusively formed by
reaction of the alkylnitrile ions (ꢀCHRCN, R = H, Me) with
ð2Þ
In this paper, we present the study of the reaction and
regioselectivity of the ambident nucleophile, 2-naphthylaceto-
nitrile anion, with aryl halides. In this anion, all the positions
that can be substituted correspond to C atoms. We were
interested to inspect the scope of this anion toward the
synthesis of a,a-diaryl nitriles.
INFIQC, Departamento de Quı´mica Orga´nica, Facultad de Ciencias
´
´
Quımicas, Universidad Nacional de Cordoba, Ciudad Universitaria,
5000 Cordoba, Argentina. E-mail: tere@fcq.unc.edu.ar;
Fax: +54-351-4333030/4334170; Tel: +54-351-4334170/73
w Electronic supplementary information (ESI) available: 1H NMR
and 13C NMR spectra of compounds 3a–g and 4d–f. See DOI:
10.1039/c1nj20699k
´
Results and discussion
The photoinitiated reaction of 1 with 2-iodoanisole (2a) in
liquid ammonia (nucleophile : substrate ratio = 3) afforded
c
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Table 1 Photoinitiated reactions of aryl halides 2a–c with the anion
of 2-naphthylacetonitrile (1) in DMSOa
Productsc (% yields)
1
Substrate Base
M ꢁ 103 M ꢁ 103 M ꢁ 103
Exp.
ꢀb (%)
ArH Substitution
X
1d
2
3
4
21
75
65
74
68
70
75
74
70
2a, 7
42
142
148
140
130
133
150
146
151
43
100
85
81
76
5
90
46
42
o5
100
95
95
—
6
8
10
—
—
6
3a, 96
3a, 76
3a, 65
3a, 53
—
3a, 65
3a, 25
3a, 27
Scheme 1
2a, 24
2a, 32
2a, 72
2a, 32
2a, 34
2a, 73
2a, 26
2a, 31
2b, 6
the reduction product 2-methoxynaphthalene (10%) in the
latter solvent (Table 1, exp. 10 and 11).
5e
6f
7g
8h
9i
High yields of the expected substitution product were
obtained by reaction with 9-bromoanthracene (2c) (80%)
(Table 1, exp. 12). In all cases, the reduction product (ArH)
formed is ascribed to hydrogen atom abstraction from the
solvent by the radicals.
4
10d 20
11
12
—
10
19
3b, 90
3b, 84
3c, 80
77
75
2b, 26
2c, 25
142
143
Based on the results found, we extended our study to
4-iodoanisole (2d), a phenyl halide unsubstituted at its ortho
position. This substrate reacts with anion of 1 to afford two
substitution products, the products corresponding to substitution
at the Ca (3) and at the C1 of the naphthyl cycle (4) in 47% and
22% yields respectively (eqn (8), Table 2, exp 1). Similar results
were obtained in DMSO.
a
Photoinitiated reactions (unless indicated), carried out under
b
nitrogen. Reaction time = 180 min. Determined potentiometrically
c
on the basis of the ArX concentration. Determined by GLC and the
internal standard method on the basis of the ArX concentration.
d
e
Solvent = NH3(l). T = ꢀ33 1C. Reaction carried out in the dark.
f
g
mmol%). Di-tert-butylnitroxide
Di-tert-butylnitroxide
h
(44
(64 mmol%). p-Dinitrobenzene (36 mmol%). Reaction carried
i
out in the dark with FeBr2 (80 mmol%).
100% yield of iodide ion, and only the product corresponding
to substitution at Ca of the acetonitrile moiety, 2-(2-anisyl)-
2-(2-naphthyl)acetonitrile 3a (96%) (eqn (3), Table 1, exp. 1).
ð3Þ
ð8Þ
The percentages of products do not increase by changing the
nucleophile/substrate ratio to 5 (Table 1, exp. 3). No reaction
was observed in the absence of light.
By changing the solvent from NH3 to DMSO accompanied by
a three-fold increase in the concentration of the reactants, 3a
was the main product formed (76%) accompanied by the
reduction product anisole (6%) (Table 1, exp. 2). The percentage
of substitution product decreased and that of anisole increased
with a nucleophile : substrate ratio of 2 or 1 (Table 1, exp. 3 and 4).
No reaction was observed in this solvent in the absence of
light (Table 1, exp. 5). When the relation nucleophile :
substrate is 2 or 3 the reaction is not inhibited by the addition
of di-tert-butylnitroxide (DTBN), a radical scavenger (Table 1,
exp. 6). Changing the relation nucleophile : substrate to 1, the
reaction is inhibited by DTBN or by the addition of a good
electron–acceptor such as p-dinitrobenzene (p-DNB) (Table 1,
exp. 7 and 8). The dark reaction in the presence of Fe(II) salt as
initiator did not occur.7 These facts indicate that a photo-
induced nucleophilic substitution with radicals and radical
anions as intermediates is in play (Scheme 1).
Compounds 3e and 4e were obtained by reaction of the
anion of 1 with 1-iodonaphthalene (2e), in 85% and 13%
yields, respectively, in NH3(l) (Table 2, exp. 5).
We observed that both compounds, 3f and 4f, were formed
in the reaction with 9-bromophenanthrene (2f). In both
Table 2 Photoinitiated reactions of aryl halides 2d–f with the anion
of 2-naphthylacetonitrile (1) in DMSOa
Productsc (% yields)
NuH
Substrate Base
M ꢁ 103 M ꢁ 103 M ꢁ 103
Exp.
ꢀb (%)
ArH Substitution
X
1d
2
10
75
120
83
15
78
15
73
2d, 3
25.3
146
243
194
30
153
32
146
100
93
90
1
95
90
98
100
4
3d, 47 4d, 22
3d, 47 4d, 21
3d, 53 4d, 23
2d, 28
2d, 26
2d, 32
2e, 5
2e, 28
2f, 5
2f, 24
11
nc
—
2
6
—
10
3
4e
5d
6
—
—
3e, 85 4e, 13
3e, 68 4e, 16
3f, 79 4f, 18
3f, 76 4f, 15
7d
8
To examine the scope of this procedure to obtain naphthyl-
acetonitrile derivatives, the reaction with other aryl halides
was studied.
a
Photoinitiated reactions (unless indicated), carried out under
b
nitrogen. Reaction time = 180 min. Determined potentiometrically
c
on the basis of the ArX concentration. Determined by GLC and the
In the reaction of 1 with 1-iodo-2-methoxynaphthalene (2b),
compound 3b was the main product formed, 90% and 84% yields
in liquid ammonia and in DMSO, respectively, accompanied by
internal standard method on the basis of the ArX concentration.
d
e
Solvent = NH3(l). T = ꢀ33 1C. Reaction carried out in the dark.
c
598 New J. Chem., 2012, 36, 597–602
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Table 3 Photoinitiated reactions of aryl halide 2g with the anion of
2-naphthylacetonitrile (1) in DMSOa
NuH
Substrate Base
Substitution
product (3g)c
M ꢁ 103 M ꢁ 103
M ꢁ 103
Exp.
Xꢀb (%) (% yields)
1d
77
75
75
74
76
53
201
2g, 27
2g, 26
2g, 27
2g, 28
2g, 28
2g, 26
2g, 101
152
153
155
156
153
110
408
100
97
83
66
82
56
60
93
95
74
51
76
29
50i
2
3e
4e,f
5e,g
6e,g
7e,h
Scheme 2
a
Photoinitiated reactions (unless indicated), carried out under
b
nitrogen. Reaction time = 30 min. Determined potentiometrically
In this context, the intermolecular addition of the aryl
radicals (Arꢂ) can take place at two different positions of the
anion of 1, C1 of the naphthyl moiety, or Ca of the substituent
(Scheme 2). The reaction at the C1 forms the radical anion
intermediate 4ꢂꢀ, which gives the biaryl system. Attack at the
Ca produces the three substituted asymmetric carbons.
c
on the basis of the ArX concentration. Determined by GLC and the
internal standard method on the basis of the ArX concentration.
d
e
Reaction time = 120 min. Reaction carried out in the dark.
f
g
p-Dinitrobenzene (44 mmol% to substrate). Di-tert-butylnitroxide
h
(46 mmol%). Reaction time = 60 min. Isolated product.
i
The potential energy surfaces (PESs) for the coupling step
were calculated. The PESs were inspected from the most stable
solvents, compound 3f was the main product (76%) (Table 2,
exp. 7 and 8).
ꢀ
conformer of the radical anions (3ꢂ and 4ꢂꢀ). The optimized
These results show that the regioselectivity of the reaction of
the anion of 1 is sensitive to the substitution of the aryl radical.
The approach of the radical to the naphthyl-C1 position is
more constrained when the hindrance at the radical centre
increases (2a, 2b, 2c). In these reactions only substitution at
Ca was observed. Recently, we informed that the rate of
a radical–ambident nucleophile coupling is sensitive to steric
hindrance.13 However, the marked changes in the regioselectivity
of the reaction with the nature of the substrate have not been
previously shown in the reactions of aryl halides with ambident
nucleophiles; this being the first report to show that the steric
hindrance increases the selectivity of the coupling.
geometries of radical anions and the transition states corres-
ponding to their formation were calculated by the unrestricted
Density Functional Theory (DFT) with the B3LYP functional
and the 6-31G(d) basis set, as implemented in Gaussian 03.15
Vibrational frequencies were computed for the stationary
points.
The change in hybridization from sp2 (in the anion of 1) to
sp3 occurs by the coupling at either position (C1 and Ca) to
form the radical anions of the corresponding substitution
products (Fig. 1). The TSs of these couplings are located early
along the reaction coordinates; the hybridization changes at
the C1 and Ca take place at shorter C–C distances than those
of the localized TSs (Fig. 2).
In DMSO, anion 1 reacts with 2g to give 3g (93%) and
traces of 4g after 120 minutes of irradiation (eqn (8), Table 3,
exp. 1). Similar results were found after 30 min of reaction.
When the above reaction was conducted with no illumination,
74% of 3g was formed but this was significantly inhibited in
the presence of p-dinitrobenzene (p-DNB) (Table 3, exp. 3 and 4).
The reaction was not inhibited by the addition of DTBN. In all
previous cases, the relation 1/2g was 3; when this relation
decreased to 2, we obtained 29% of product in the reaction with
DTBN (Table 3, exp. 6). This would indicate that radicals and
radical anions are present in the dark reaction. The synthetic
protocol was optimized and 3g was obtained in good yield.
The radical 2g reacts only at the Ca position. This behaviour
is in contrast with the one shown by 2d, and may be due to the
more electrophilic character of the radical, that directs the
reaction to the slightly more nucleophilic part of the ambident
nucleophile.
Table 4 shows the difference in energy between the critical
structures located along the PESs.
The radicals combine exothermically with the anion to form
the radical anion of the product.
In the gas phase, the reactions take place without energy
barriers (negative DEa) evaluated as the energy difference
Fig. 1 B3LYP/6-31G* calculated 3e and 4e radical anions.
Theoretical calculations
In order to complement the experimental results, quantum
mechanical calculations could be of use to explain the regio-
chemistry observed.
We have demonstrated that the carbon vs. heteroatom
regioselectivity of the reactions of the aryl radicals toward
ambident nucleophiles is kinetically controlled.14
Fig. 2 B3LYP/6-31G* calculated TSs for formation of 3e and 4e
radical anions.
c
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Table 4 Energy differences between PES relevant points of the
reaction of the 2-naphthylacetonitrile anion with different aryl radicals
68% of 3d and 16% of 4d, and the ratio 3/4 observed is 4.25.
In contrast with this behavior, 3g is the only product formed
with 2g radical, in agreement with the theoretical results.
Gas phase
Continuum solvente
DG#d DEr DEa DGf
DEra
DEa
DGc
DG#f
b
Ar
Conclusions
2b C1 ꢀ31.95 ꢀ5.83 ꢀ17.91 6.75 ꢀ25.49 4.68 ꢀ11.44 17.26
Ca ꢀ36.47 ꢀ10.80 ꢀ22.59 2.11 ꢀ24.55 ꢀ2.70 ꢀ10.67 10.21
2d C1 ꢀ37.26 ꢀ4.65 ꢀ23.23 6.33 ꢀ33.02 0.44 ꢀ18.99 11.42
Ca ꢀ32.34 ꢀ7.59 ꢀ19.51 3.41 ꢀ25.92 ꢀ0.37 ꢀ13.10 10.63
2g C1 ꢀ44.72 ꢀ11.49 ꢀ30.24 ꢀ0.77 ꢀ34.70 1.70 ꢀ20.22 12.42
Ca ꢀ46.34 ꢀ17.81 ꢀ32.62 ꢀ5.92 ꢀ34.70 ꢀ5.49 ꢀ20.97 6.40
In summary, the photoinduced reaction of the 2-naphthyl-
acetonitrile anion with radicals gives the Ca substitution
selectively. We have developed a simple and versatile system
for the synthesis of a,a-diarylsubstituted nitriles. It should be
noted that product yields are better with hindered radicals.
The key reaction step has been modeled and is predicted to
be under kinetic control, with the observed regioselectivity
resulting mainly from the steric factors within the TSs. The
theoretical calculations show that the activation energy by C1
substitution is higher than that by Ca substitution and the energy
difference order is 2-methoxy-1-naphthyl 4 4-benzonitryl c
4-anisyl, in agreement with the experimental results.
a
DEr (kcal molꢀ1) = energy difference between radical anions and
b
reactants (anion of 1 + radical). DEa (kcal molꢀ1) = energy
difference between transition states and reactants (anion of 1 +
c
radical). DG (kcal molꢀ1) = free energy difference between radical
d
anions and reactants. DG# (kcal molꢀ1) = free energy difference
between transition states and reactants. Continuum solvent model
for DMSO, without geometry optimization. Differences in the total
e
f
solution phase energies informed. The energy correction was taken
to be the same as in the gas phase.
Experimental section
General experimental methods
1H and 13C NMR spectra were recorded on a 200 or a 400
nuclear magnetic resonance spectrometer. All NMR spectra
were measured in CDCl3 or DMSO-d6 using tetramethylsilane
as a reference. High-resolution mass spectra (HRMS) for all
compounds were measured using electron impact ionization
mode. Irradiation was performed in a reactor equipped with
two water-cooled lamps. Gas chromatographic analyses were
performed on a chromatograph with a flame-ionization detector
and using a HP-1 capillary column (methyl silicone, 10 m ꢁ
0.53 mm ꢁ 2.65 mm film thickness). The GS/MS analyses were
carried out employing a column of 30 metres packed with 5%
diphenyl and 95% dimethylpolysiloxane of 0.53 mm ꢁ 2.65 nm
film thickness using electron impact ionization mode. Potentio-
metric titration of halide ions was performed in a pH meter
using an Ag/Ag+ electrode. Melting points were not corrected.
Silica gel (70–270 mesh ASTM) was used for chromatographic
purifications. Radial chromatographic separations used a silica
gel 60 PF-254 with gypsum. Solvents were purified by distillation.
All reagents obtained from commercial suppliers were used
without further purification. DMSO was stored under molecular
sieves (4 A). 1-Iodo-2-methoxynaphthalene (2b) was prepared by
reaction of 1-iodo-2-naphthol, potassium tert-butoxide in DMSO
with methyl iodide. 1-Iodo-2-naphthol was prepared by reaction
of 2-naphthol, iodide and H2O2 in ethanol.17
Fig. 3 B3LYP/6-31G* calculated 3b and 4b radical anions.
between the TS and the reactants. Different results are
obtained for DG# at 298 K.
The different regioselectivity of radicals 2a, 2b and 2c
compared with p-substituted radicals 2d can be explained in
terms of the steric hindrance to the coupling at the radical
centre to form the radical anion intermediates 4. The C1
radical anion (4ꢂꢀꢀ) has a more rigid structure than that of
radical anion 3ꢂ (Scheme 2). Moreover, in radical 2b, the
ortho substituents beside the radical centre (MeO group and
the aryl moiety) increased the steric compression (Fig. 3). As a
consequence, the energy barrier for C1-coupling is higher than
the barrier for Ca-coupling (Table 4) and the reactivity of this
position is smaller in agreement with the experimental results.
Radical 2g reacts without activation energy, while radical 2d
coupled at both positions of the nucleophile with activation
energy. For radicals 2d and 2g, the energy barriers for
C1-coupling (Table 4) are higher than those for Ca-coupling.
The solvent effect was taken into consideration with the
Tomasi’s polarized continuum model (PCM).16 In the
presence of DMSO, the solvent of the experimental reactions,
the PESs were similar to those calculated in the gas phase. The
solvent affects the energies of TSs in a similar way for all
radicals and the barriers ordering determined in the gas phase
Photoinduced reaction of the anion of 2-naphthylacetonitrile (1)
with 2b in liquid ammonia
is maintained under a continuum; the DG# are higher than
The following procedure is representative of these reactions.
The reactions were carried out in a 250 mL three-neck round-
bottom flask equipped with a nitrogen inlet and a magnetic
stirrer. Potassium tert-butoxide 4.3 mmol (490 mg) was added
to distilled ammonia (100 mL) under nitrogen and 2-naphthyl-
acetonitrile 2 mmol (332 mg) was added following 5 minutes.
After 15 min 1-iodo-2-methoxynaphthalene 0.6 mmol (166.8 mg)
was added and the reaction mixture was irradiated for 120 min.
The reaction was quenched with an excess of ammonium nitrate.
C1
the corresponding DG#Ca. These results show that the C1
substitution is more likely to be found for radical 2d than
for radical 2g. For this radical, the Ca substitution has the
lowest activation energy compared with all previous results.
The relation of k3(2d)/k4(2d) is given by: k3(2d)/k4(2d) p e(DDG#/RT)
.
Considering that TS3(2d) is 0.79 kcal molꢀ1 more stable than
TS4(2d), the calculated ratio of constants is 3.9. For 2b and 2g, the
calculated ratio is 43 ꢁ 104. Experimentally, radical 2d gives
c
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The ammonia was allowed to evaporate and water (50 mL)
was added to the residue and extracted twice with CH2Cl2
(20 mL). The iodide ions in the aqueous solution were determined
potentiometrically. The organic extract was dried (MgSO4),
filtered and quantified by GLC. The reduction products (ArH)
were compared by CGL with authentic commercial samples. The
solvent was removed under reduced pressure. The crude residue
was then purified by column chromatography.
(m, 4H); 7.86–7.90 (m, 3H); 7.99 (s, 1H); 8.22–8.25 (m, 2H);
8.46–8.48 (m, 2H); 8.82 (s, 1H). 13C NMR dC 35.09; 119.65(q);
123.95; 124.33; 125.30; 125.37 (2q); 125.96 (q); 126.45; 126.76;
127.22; 127.63; 127.90; 128.98; 129.65 (2q); 129.81; 130.03;
131.92 (2q); 132.67 (q); 133.41 (q); 133.98 (q). m/z = 344 (27);
343 (100); 342 (48); 341 (13); 340 (9); 328 (11); 316 (13); 315
(31); 313 (9); 216 (23); 214 (10); 189 (10); 178 (11); 176 (11); 158
(40); 157 (16). Exact mass calcd for C26H17N: 343.13610;
found: 343.13610.
Photoinduced reaction of the anion of 2-naphthylacetonitrile (1)
with 2b in DMSO
a-(4-Methoxyphenyl)-2-naphthylacetonitrile
(3d).
Mp
1
136–137 1C. HNMR dH 3.80 (s, 3H); 5.25 (s, 1H); 6.87–6.91
(m, 2H); 7.26–7.37 (m, 3H); 7.48–7.53 (m, 2H); 7.80–7.85
(m, 4H). 13CNMR dC 42.01; 55.36; 114.60 (q); 125.19;
126.56; 126.62; 126.75; 127.72; 127.99; 129.04; 129.18 (q);
133.44(q); 161.41(q). m/z 274 (20); 273 (100); 272 (26); 258
(22); 245 (9); 242 (20); 241 (11); 240 (11); 231 (10); 230 (10); 215
(20); 203 (12); 202 (18); 146 (10). Exact mass calcd for
C19H15NO: 273.11536; found: 273.11551.
By way of example, the technique followed for the reaction of
1-iodo-2-methoxynaphthalene with the anion of 2-naphthyl-
acetonitrile is described. In a 50 mL three-neck ball, to 10 mL
of dry and degassed DMSO under nitrogen was added
14.2 mmol (1590 mg) of potassium tert-butoxide, followed
by 7.7 mmol (1278 mg) of 2-naphthylacetonitrile 5 minutes
later. After 15 minutes 2.6 mmol (722 mg) of 1-iodo-2-methoxy-
naphthalene were added and irradiated for 180 minutes in a
photochemical reactor. After the irradiation time the reaction
was stopped by the addition of ammonium nitrate and water.
The extraction of the reaction was carried out with 60 mL of
water and three fractions of 20 mL of methylene chloride. The
organic extract was subsequently washed with two fractions of
20 mL of water. Finally, the extract was dried with anhydrous
MgSO4 and analyzed by GC. Halide ions in water were
determined by potentiometric titration with AgNO3 solution.
In general, the products were isolated using the following
method: the solvent of the organic extract was removed. The
crude residue was distilled under reduced pressure in the
1-(4-Methoxyphenyl)-2-naphthylacetonitrile
(4d).
Mp
143–144 1C. 1H NMR dH 3.62 (s, 2H); 3.19 (s, 3H);
7.05–7.09 (m, 2H); 7.19–7.24 (m, 3H); 7.40–7.53 (m, 3H);
7.61 (d, 1H); 7.87–7.93 (m, 2H). 13C NMR dC 22.53; 55.36;
14.38; 118.34 (q); 125.78; 126.18; 126.56; 126.67; 127.91;
128.53; 129.04 (q); 129.63 (q); 131.04; 133.00 (q); 133.22 (q);
138.99 (q); 159.39 (q). m/z 274 (24); 273 (100); 258 (12); 231
(21); 230 (50); 215 (11); 203 (18); 202 (27); 190 (10); 189 (18).
Exact mass calcd for C19H15NO: 273.11536; found: 273.11556.
a-(1-Naphthyl)-2-naphthylacetonitrile (3e). Mp 104–105 1C.
1H NMR dH 5.99 (s, 1H); 7.36–7.41 (dd,1H); 7.45–7.55
(m, 5H); 7.64–7.68 (dd, 1H); 7.79–7.98 (m, 7H). 13C NMR
dC 40.04; 119.63 (q); 123.03; 125.19; 125.46; 126.24; 126.67;
126.75; 126.94; 127.10; 127.37; 127.69; 128.04; 129.18; 129.64;
130.44 (q); 130.79 (q); 132.60 (q); 132.87 (q); 133.30 (q); 134.22
(q). m/z = 294 (22); 293 (100); 292 (67); 291 (15); 290 (13); 278
(21); 277 (11); 266 (20); 265 (50); 166 (11); 140 (12); 139 (16);
133 (25); 132 (16). Exact mass calcd for C22H15N: 293.12045;
found: 293.12018.
Kugelrohl (o100 1C) and most of the nucleophile (in excess)
¨
was removed. The remaining solid was purified by column or
radial chromatography (petroleum ether : acetone, 98 : 2).
a-(2-Methoxyphenyl)-2-naphthylacetonitrile
(3a).
Mp
141–142 1C. 1H NMR dH 3.81 (s, 3H); 5.66 (s, 1H);
6.48–6.94 (m, 2H); 7.19–7.45 (m, 5H); 7.72–7.86 (m, 4H).
13C NMR dC 36.32; 55.62, 111.04; 119.88 (q); 121.09; 124.43;
125.43; 126.37; 126.51; 126.56; 127.61; 127.94; 128.74; 129.04;
129.74; 132.68 (q); 132.89 (q); 133.24 (q); 156.18 (q). m/z =
274 (21); 273 (100); 272 (22); 258 (41); 257 (10); 243 (10); 242
(43); 241 (13); 240 (24); 231 (36); 230 (20); 215 (17); 203 (15);
202 (25); 115 (10); 101 (19). Exact mass calcd for C19H15NO:
273.11536; found: 273.11540.
1-(1-Naphthyl)-2-naphthylacetonitrile (4e). 1H NMR dH 5.99
(s, 1H); 7.20–8.21 (m, 13H). m/z = 294 (22); 293 (100); 292
(37); 291 (12); 290 (9); 277 (12); 276 (12); 267 (9); 266 (47); 265
(70); 264 (17); 263 (26); 253 (41); 252 (47); 250 (20); 239 (11);
133 (17); 132 (91); 131 (34); 127 (12); 126 (37); 125 (27); 120 (9);
119 (18); 118 (10); 113 (13); 112 (10). MS m/z: 293 (M+, 100).
Exact mass calcd for C22H15N: 293.12045; found: 293.12018.
a-(2-Methoxynaphthyl)-2-naphthylacetonitrile (3b). Mp
137–138 1C. 1H NMR dH 4.02 (s, 3H); 6.58 (s, 1H);
7.32–7.50 (m, 6H); 7.72–7.99 (m, 8H). 13C NMR dC 32.26;
56.76; 113.03; 119.74 (q); 123.30; 123.92; 124.54; 125.59;
126.18; 126.46; 127.43; 127.56; 127.94; 128.69; 128.85; 129.61
(q); 131.28; 131.60 (q); 132.52 (q); 132.76 (q); 133.22 (q);
154.81 (q). m/z = 324 (26); 323 (100); 322 (33); 309 (9); 308
(27); 307 (10); 293 (17); 292 (55); 291 (13); 290 (22); 281 (15);
280 (20); 279 (9); 278 (10); 277 (11); 266 (10); 265 (16); 250 (9);
153 (10); 148 (21); 141 (16); 140 (15); 139 (19); 132 (9); 127 (12);
126 (21); 113 (11). Exact mass calcd for C23H17NO: 323.13101;
found: 323.13102.
a-(9-Phenanthryl)-2-naphthylacetonitrile (3f). 1H NMR dH
6.04 (s, 1H); 7.46–7.58 (m, 4H); 7.63–7.69 (t, 2H); 7.72–7.75
(t, 1H); 7.76–7.89 (m, 3H); 7.95–7.99 (m, 3H); 8.02 (s, 1H);
8.72 (d, 1H); 8.78 (d, 1H). 13C NMR dC 40.61; 119.63 (q);
122.60; 123.57; 124.07; 125.25; 126.73; 126.77; 127.16; 127.24;
127.70; 127.74; 128.08; 128.74; 128.95 (q); 129.05; 129.29;
130.64 (q); 130.97 (q); 131.24 (q); 132.32 (q); 132.98 (q);
133.36 (q). m/z = 343 (100); 327 (16); 316 (11); 315 (9); 157
(11). MS m/z: 343 (M+, 100). Exact mass calcd for C26H17N:
343.13610; found: 343.13575.
a-(9-Anthracenyl)-2-naphthylacetonitrile (3c). 1H NMR dH
7.29–7.32 (dd,1H); 7.36 (s,1H); 7.51–754 (m, 2H); 7.58–7.61
c
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1-(9-Phenanthryl)-2-naphthylacetonitrile (4f). 1H NMR dH
3.57 (c, 2H); 7.18–7.21 (dd, 1H); 7.27–7.33 (m, 3H); 7.40–7.43
(cd, 1H); 7.48–752 (cd, 1H); 7.66–7.70 (m, 2H); 7.75–7.79
(m, 2H); 7.92 (d, 1H); 7.96 (d, 1H); 8.06 (d, 1H); 8.82
(t, 2H). 13C NMR dC 22.33; 118.12 (q); 122.71; 123.18; 125.68;
126.25; 126.44; 126.64 (q); 126.74; 126.88; 127.17; 127.20; 127.32;
127.34; 128.05; 129.03; 129.13; 130.44 (q); 130.70 (q); 131.11 (q);
131.40 (q); 133.02 (q); 133.28 (q); 133.64 (q); 136.95 (q). m/z =
344 (40); 343 (60); 316 (100); 304 (11); 303 (15); 302 (14); 157 (18);
151 (26). MS m/z: 343 (M+, 100). Exact mass calcd for C26H17N:
343.13610; found: 343.13639.
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a-(4-Cyanophenyl)-2-naphthylacetonitrile (3g). H NMR dH
2812–2815 (Chem. Abstr., 1982, 96, 104049r); Ya. L. Gol’dfarb,
´
5.35 (s, 1H); 7.31 (d, 1H), 7.52–7.56 (m, 4H); 7.68 (d, 2H);
7.85–7.86 (m, 4H). 13C NMR dC 42.74; 112.63 (q); 118.05 (q);
118.52 (q); 124.79; 127.06; 127.15; 127.18; 127.83; 128.01;
128.67; 129.76; 131.63 (q); 133.00 (q); 133.04 (q); 133.25 (q);
140.84 (q). m/z = 269 (19); 268 (100); 267 (54); 241 (15); 240
(50); 166 (21); 140 (11); 139 (13); 127 (11); 120 (13); 107 (15);
106 (11); 77 (10); 63 (9). MS m/z: 268 (M+, 100). Exact mass
calcd for C19H12N2: 268.10004; found: 268.10004.
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Acknowledgements
15 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, T. Vreven,
Jr., K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara,
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H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo,
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J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford,
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I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill,
B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople,
GAUSSIAN 03 (Revision B.04), Gaussian, Inc., Pittsburgh, PA,
2003.
16 The solvent effect was modelled with Tomasi’s polarised conti-
nuum model (PCM) [S. Miertus, E. Scrocco and J. Tomasi, Chem.
Phys., 1981, 55, 117; S. Miertus and J. Tomasi, Chem. Phys., 1982,
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single point PCM calculations on the gas-phase optimized geome-
tries at the B3LYP/6-31G* theory level, electrostatic and non-
electrostatic contributions being considered. In the PCM model the
solvent is represented as a polarizable continuum (with dielectric
constant e) surrounding the molecular complex at an interface
constructed by combining atomic van der Waals radii with the
effective probe radius of the solvent. Charges are allowed to
develop on this interface according to the electrostatic potential
of the solute and e, then the polarized reaction field of the solvent
acts back on the quantum mechanical description of the solute.
The wave function of the complex is relaxed self-consistently with
the reaction field to solve the Poisson–Boltzmann (PB) equations.
The solvent was represented with the following parameters: di-
electric constant and probe radius.
This work was supported by Agencia Co
Consejo Nacional de Investigaciones Cientı
(CONICET) and SECyT, Universidad Nacional de Co
´
rdoba Ciencia (ACC),
ficas y Tecnicas
rdoba,
´
´
´
Argentina.
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