Multiple reaction pathways between the carbanions of α-alkoxy- α-phenylacetonitrile and o-chloronitrobenzene

Article abstract of DOI:10.1002/ejoc.201100909

Carbanions of α-methoxy-and α-phenoxy-α- phenylacetonitriles undergo a variety of reactions with o-chloronitrobenzene by initial formation of σ^H adducts and slower formation of σ^Cl adducts. Reversible formation of σ^H adduc

Full text of DOI:10.1002/ejoc.201100909

FULL PAPER
DOI: 10.1002/ejoc.201100909
Multiple Reaction Pathways between the Carbanions of α-Alkoxy-α-
phenylacetonitrile and o-Chloronitrobenzene
Mieczysław Makosza*[a] and Daniel Sulikowski[a]
˛
Dedicated to Professor V. N. Charushin on the occasion of his 60th birthday
Keywords: Carbanions / Nitroarenes / Reaction mechanisms / Vicarious substitution / Reactive intermediates / Oxidative
substitution / SNAr reaction
Carbanions of α-methoxy- and α-phenoxy-α-phenylacetoni-
triles undergo a variety of reactions with o-chloronitrobenz-
ene by initial formation of σH adducts and slower formation
of σCl adducts. Reversible formation of σH adducts followed
by their fast transformation results in the formation of four
different products with high selectivity. Slower addition in a
position occupied by a chlorine atom to form σCl adducts re-
sults in a conventional SNAr reaction. These five reaction
pathways are efficiently controlled by the conditions and ad-
ditional reagents.
Introduction
The formation of two different products in a reaction
between two reactants is a common situation. It is enough
to mention the formation of isomers in electrophilic aro-
matic substitution, two products of O- and C-, C- and C-,
or C- and N-alkylation of ambident anions, and 1,2- or 1,4-
addition of Grignard reagents and carbanions to β-vinyl
ketones. Much less frequent are cases when two reactants
enter three different reactions and form three different
products.
Here we would like to report a peculiar case where two
reactants react along five different pathways to give five dif-
ferent products. Most importantly, we can control the
course of the reaction by selecting conditions (temperature
and solvent) and additional reagents, which make the reac-
tions proceed with high selectivity.
Scheme 1. Reaction of p-chloronitrobenzene with the carbanion of
α-phenylacetonitrile in pyridine and aqueous ethanol.
mation of SNAr products, whereas σH adducts formed in
The carbanion of α-phenylacetonitrile can react with p- protic media were initially converted into nitrosoarenes by
chloronitrobenzene in two entirely different ways. In pyr- the protonation/elimination of water. In strongly basic reac-
idine, a conventional SNAr reaction with chlorine has been tion media, deprotonation of the α-(nitrosoaryl)acetonitrile
observed, whereas in aqueous ethanol, 3-phenylbenzisox- followed by intramolecular addition/elimination of the cyan-
azole (anthranile) has been obtained as presented in ide anion gave the anthranile.
Scheme 1.[1]
Following these observations, we have reported that the
The results presented in Scheme 1 are explained as fol- carbanion of α,α-diphenylacetonitrile generated under vari-
lows: both of the products were obtained by the addition ous conditions can react with o-chloronitrobenzene in three
of the α-phenylacetonitrile carbanion to p-chloronitroben- different ways. When the carbanion was generated in di-
zene in the 4- or 2-position relative to the nitro group to methyl sulfoxide (DMSO), an SNAr reaction of chlorine
form σCl and σH adducts, respectively. The spontaneous de- took place; in methanol, nitrone was generated as a result
parture of Cl– anions from σCl adducts resulted in the for- of initial formation of the nitroso compound, whereas in
benzene single-electron transfer (SET) took place to pro-
duce tetraphenylsuccinonitrile and azoxybenzene.[2] The
[a] Institute of Organic Chemistry, Polish Academy of Sciences,
Ul.Kasprzaka 44/52, 01-224 Warsaw, Poland
two first reactions proceeded by the formation of anionic
Fax: +48-22-632-66-81
E-mail: icho-s@icho.edu.pl
σX and σH adducts, respectively.
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M. Makosza, D. Sulikowski
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Based on these results, we formulated the hypothesis that addition of sterically demanding carbanions of 1 and 2 to
the addition of carbanions and other nucleophiles to ni- 3 proceeded preferentially in the para position.[9] The ad-
troarenes in the positions occupied by a hydrogen atom is dition is a reversible process, however, and – thanks to the
a fast and reversible process, whereas slower addition in po- high nucleophilicity of these carbanions and entropy ef-
sitions occupied by a halogen atom (X) is essentially fects – it proceeds to completion at low temperature. Thus,
irreversible because of the facile departure of the X– anion when equimolar mixtures of 1 or 2 with 3 in tetra-
from the σX adducts.[3] Furthermore, many ways to convert hydrofuran (THF)/N,N-dimethylformamide (DMF) at
the σH adducts into products of nucleophilic substitution –78 °C were treated with an equimolar amount of tBuOK,
of a hydrogen atom have been developed so that this reac- the corresponding σH adducts 13 and 23 were formed quan-
tion has become a general, versatile process.[3,4] The most titatively. The absence of free carbanions in such mixtures
important of these conversions are: oxidation of σH adducts was confirmed by independent experiments.[9a]
with external oxidants,[3b,5,6] vicarious nucleophilic substi-
tution when the carbanions contain a leaving group such
as Cl or RO,[3,6,7] and conversion of the σH adducts into
nitrosoarenes.[3b,6]
Relationships between the rates of conventional nucleo-
philic substitution of halogen SNAr reactions and nucleo-
philic substitution of a hydrogen atom in halonitrobenzenes
and unambiguous proof that the substitution of a hydrogen
atom is the main process have been presented in our recent
reviews.[8]
In this paper we report that the carbanions of α-meth-
oxy- and α-phenoxy-α-phenylacetonitriles (1 and 2, respec-
tively) can react with o-chloronitrobenzene (3) along five
different pathways to give five different products, four of
which are products of the substitution of a hydrogen atom.
The course of the reaction can be controlled by the condi-
tions and additional reagents to ensure high selectivity and
high yields of the products.
The addition of oxidants to solutions of the σH adducts
produced this way resulted in the formation of products
from the oxidative substitution of a hydrogen atom, 1a and
2a. Oxidation of the σH adducts with 2,3-dichloro-5,6-dicy-
ano-1,4-benzoquinone, commonly used for this purpose,
was moderately effective with yields of 65 and 10% for 1a
and 2a, respectively. Oxidation with potassium permangan-
ate was much more efficient and gave yields of 83 and 60%
for 1a and 2a, respectively. In these cases, powdered
KMnO4 was added to the solution of the σH adduct in
THF/DMF followed by addition of liquid ammonia to dis-
solve the inorganic salt. Alternatively, the addition of 1–
and 2– to 3 and the oxidation can be executed in liquid
ammonia as reported earlier.[9]
Oxidation of the σH adducts of the carbanions of α-
phenylalkanenitriles to nitroarenes with dimethyldioxirane
(DMD) proceeded at the negatively charged nitro group to
give substituted phenols.[10] Oxidation of the σH adducts 13
and 23 with DMD proceeded similarly to give 3-chloro-4-
hydroxyphenyl derivatives of 1 and 2, 1b and 2b, respec-
tively. The reactions are presented in Scheme 2.
Results and Discussion
According to the general pathway of reactions between
The carbanions of 1 and 2 contain a leaving group
carbanions and halonitroarenes, the initial, fast process is (methoxy and phenoxy, respectively) at the nucleophilic
addition in the ortho or para position to the nitro group center; thus, treatment of the σH adducts with a strong base
occupied by a hydrogen atom to form σH adducts.[3,8] The should result in β-elimination of methanol or phenol to give
Scheme 2. Conversion of initial σH adducts of carbanions of 1 and 2 with 3.
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Reactions of α-Alkoxy-α-phenylacetonitrile Anions with o-Chloronitrobenzene
products of the vicarious substitution of a hydrogen atom products 1d and 2d. These criteria are met by phase-transfer
(VNS).[3,6] Indeed, when 1 and 2 were treated with 3 in the catalysis (PTC) conditions, i.e. the generation of carbanions
presence of excess tBuOK (3 equiv.), the mixtures turned in a two-phase system by the action of concentrated aque-
deep blue because of the formation of the nitrobenzylic ous NaOH with tetraalkylammonium bromide as the cata-
carbanion of α-(3-chloro-4-nitrophenyl)acetonitrile (1c). lyst on the carbanion precursors located in the organic
Upon acidification, 1c was isolated in high yield. Of course, phase.[11] Low concentration of the carbanions in the or-
in the reaction of both of these carbanions, which differ ganic phase, which cannot exceed the concentration of the
only in the leaving group present, the same product 1c was catalyst, ensures that, at room temp., the initially formed
obtained in excellent yields (99% starting from 2, σH adducts dissociate rapidly, so slower formation of the
Scheme 2).
σCl adduct occured, which was followed by the fast depar-
As mentioned above, the addition of carbanions in the ture of Cl– and resulted in an SNAr reaction. The effective-
positions occupied by a hydrogen atom to form σH adducts ness of PTC conditions for the nitroarylation of carbanions
is a reversible process. Because of the high nucleophilicity has been demonstrated.[2,12]
of the carbanions of 1 and 2 and the entropy effect, at low
Indeed, when equimolar amounts of 1 or 2 with 3 were
temperatures their addition to 3 proceeded to completion. dissolved in a small volume of acetonitrile and stirred with
However, when solutions of the σH adducts 13 and 23 an excess of 50% aqueous NaOH and 5 mol-% tetrabut-
formed at low temperature were slowly warmed, dissoci- ylammonium bromide (TBAB), a fast SNAr reaction of the
ation of the σH adducts liberated free carbanions. These chlorine atom took place to give 1d (85%) and 2d (72%),
carbanions could enter slower addition in the position oc- respectively (Scheme 3). In the latter case, 1c (5%), the
cupied by a chlorine atom to form σCl adducts, which was product of the VNS reaction, was also formed, because eli-
followed by fast spontaneous dissociation of the carbon– mination of phenol from the σH adduct is a relatively fast
chlorine bond to form products of a conventional SNAr process. Since 1c exists in the reaction mixture as a carban-
substitution reaction of a chlorine atom. Alternatively, the ion that forms a lipophilic ion pair with the TBA cation,
liberated carbanion could also act as a base, which pro- the VNS side reaction inhibits the catalytic process.[12]
moted β-elimination of methanol or phenol from the σH
adduct, so VNS took place. Indeed, when solutions of 13
and 23 formed in THF/DMF in the absence of excess of
base at low temperature were slowly warmed to room temp.,
SNAr products 1d and 2d were formed. As expected, base-
induced β-elimination of phenol is much more facile than
Scheme 3. Reactions of the carbanions of 1 and 2 with 3 under
that of methanol; thus, warming of a solution of 23 also
gave some of the VNS product 1c. These results indicate
unambiguously that the SNAr of a halogen atom was the
secondary reaction that proceeded when the initial σH ad-
ducts were not converted into products of the substitution
PTC conditions.
As mentioned above, σH adducts of carbanions with ni-
of a hydrogen atom, and the conditions promoted their troarenes can be transformed into nitrosoarenes in protic
dissociation. Dissociation of the σH adduct and the subse- media by protonation/elimination according to the intra-
quent SNAr reaction by the slower formation of σCl adducts molecular redox stoichiometry.[1,2,6] The nitroso group is a
led to 1d and 2d (Scheme 2).
very active electrophile; hence, nitrosoarenes cannot usually
Under the conditions that ensure fast equilibration of the be isolated, because they enter further reactions with carb-
addition, in the absence of excessive base and oxidants, re- anions or basic agents present in the reaction mixture. Thus,
actions of the carbanions of 1 and 2 with 3 proceeded exclu- when 1 or 2 and 3 were treated with tBuOK in tert-butyl
sively by irreversible addition in the position occupied by a alcohol, the final products were nitrones 1e and 2e, formed
chlorine atom, which was followed by the fast, spontaneous in reasonable yields of 21 and 65%, respectively. The forma-
departure of the chloride anion and formation of SNAr tion of 1e and 2e proceeds according to the pathway shown
Scheme 4. Reaction of carbanions 1 and 2 with 3 in protic media.
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M. Makosza, D. Sulikowski
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FULL PAPER
in Scheme 4. The initially formed σH adducts were con- carbanions of 1 and 2 to 3 should be facile as the alkoxy-
verted into nitrosoarene by protonation/elimination. Ad- cyano radicals produced should enjoy specific capto-dative
dition of the second carbanion to the nitroso group and stabilization.[16]
subsequent elimination of methoxide or phenoxide anions
resulted in the formation of nitrones 1e and 2e, respectively.
Thus, so far we have shown that, by variation of condi-
Conclusions
tions and additional reagents, the reaction of the carban-
ions of 1 and 2 with 3 can proceed along five different path-
ways to give five different products: 1a, 1b, 1c, 1d, 1e, 2a,
2b, 1c, 2d, and 2e, respectively. These five pathways are: two
variants of oxidative nucleophilic substitution of a hydrogen
atom resulting in the formation of substituted nitroarenes
and substituted phenols, VNS, conversion of σH adducts
into nitrosoarenes followed by their reaction with carban-
ions, and conventional nucleophilic substitution of a chlo-
rine atom, SNAr.
The results presented lead to two major conclusions:
1. Reactions of carbanions with nitroarenes can proceed
in a variety of ways and thus offer a valuable tool for or-
ganic synthesis, albeit with some challenging mechanistic
questions.
2. Once again, it was shown that the SNAr nucleophilic
substitution of the halogen atom in halonitrobenzenes,
which proceeds via σX adducts is a slow, secondary process,
whereas the nucleophilic substitution of a hydrogen atom,
which proceeds by fast conversion of the σH adducts
formed initially, is the primary process.
The first four of these pathways were initiated by fast,
reversible addition of the carbanions of 1 and 2 to 3 in
the para position to form the σH adducts 13 and 23, which
subsequently entered four different reactions to form four
different products. As the conversion of the σH adducts into
these products is faster than dissociation, one can consider
that these reactions are kinetically controlled. The fifth
pathway, the conventional SNAr reaction of a chlorine
atom, which requires equilibration of the addition process,
is a secondary, thermodynamically controlled process.[8]
It is well known that nitroarenes are strong electron ac-
ceptors, whereas carbanions are good electron donors; thus,
SET between these reactants proceeded easily to form radi-
cal and nitroaromatic radical anions,[4c,13] which combined
to form σ adducts. In fact the SET mechanism has been
proposed as a pathway for the formation of σ adducts, and
such a concept has often been abused.[14] We have already
shown that the formation of σH adducts, as a pathway for
VNS, proceeds as a direct addition and not by a two-step
SET process.[15] However, when direct addition was hin-
dered by conditions, SET could proceed, which led to other
reactions. Thus, we have shown previously[2] that the so-
dium α,α-diphenylacetonitrile carbanion in DMSO at room
temperature replaces the chlorine atom in o-chloronitro-
benzene, whereas in benzene, when the carbanions exist as
aggregates and their nucleophilicity was decreased, the reac-
tion resulted in dimerization of the carbanion and forma-
tion of azoxybenzene.[2] Apparently, the diphenylcyano-
methyl radical produced by SET reacted with the carbanion
to form the radical anion of tetraphenylsuccinonitrile,
which was subsequently oxidized by the nitroarene to the
succinonitrile.
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded with
Varian 500 MHz or 200 MHz spectrometers in CDCl3 with TMS
as a standard. Chemical shifts are given in ppm relative to TMS,
and coupling constants (J) are given in Hertz (Hz). EI mass spectra
were recorded with an AMD 604 Inectra GmbH spectrometer at
70 eV, and ESI mass spectra were recorded with a MarinerTM spec-
trometer. THF was distilled from potassium/benzophenone ketyl,
and DMF was distilled from CaH2. Silica gel Merck 60 (230–
400 mesh) was used for column chromatography. α-Methoxy- and
α-phenoxy-α-phenylacetonitriles 1 and 2 were obtained from α-
phenyl-α-tosyloxyacetonitrile by solvolysis in methanol or reaction
with sodium phenoxide, respectively.[17]
Oxidative Nucleophilic Substitution of H in 3 with the Carbanion of
1 or 2: To a solution of o-chloronitrobenzene (3) (0.5 mmol, 74 mg)
and α-alkoxy-α-phenylacetonitrile 1 or 2 (0.5 mmol) in THF/DMF
(6 mL, 2:1, v/v) at –78 °C was added a solution of tBuOK in THF
(0.52 mmol, 0.52 mL, 1 m) over 5 min, and the resulting mixture
was stirred at this temperature for further 15 min. After this time,
either (a) or (b) was followed.
(a) Potassium permanganate (158 mg, 1.0 mmol) was added fol-
lowed by liquid ammonia (ca. 10 mL). After 2 min, the reaction
mixture was quenched by the addition of solid ammonium chloride
(ca. 500 mg). The reaction mixture was allowed to reach room tem-
perature and, after the addition of water (10 mL), extracted with
ethyl acetate. The organic phase was dried, the solvents were evapo-
rated, and the residue was purified by column chromatography (tol-
uene) to give 1a or 2a.
We expected that under similar conditions the carban-
ions of 1 or 2 should dimerize. However, mixing of sodium
or lithium salts of the carbanions of 1 or 2 with 3 in ben-
zene or cyclohexane, conditions that usually ensure high ag-
gregation, did not result in dimerization. Even warming
such mixtures for a few hours did not result in the forma-
tion of definite products, and in particular no dimers of 1
or 2 were detected. Upon acidic quenching of such reaction
mixtures, the majority of the starting materials were reco-
(b) A solution of DMD (10 mL, 0.05 m) in acetone was added and
the mixture allowed to reach room temperature. Sodium sulfite (ap-
prox. 50 mg) was added to destroy the excess DMD. The solvents
were evaporated under reduced pressure, and the residue was puri-
fied as described above to give 1b or 2b.
Vicarious Nucleophilic Substitution of H in 3 with the Carbanion of
1 or 2: To a mixture of THF/DMF (6 mL, 2:1, v/v) cooled to
–78 °C was added a solution of tBuOK (2.0 mmol, 2.0 mL, 1 m)
followed by a mixture of 3 (0.5 mmol, 74 mg) and 1 or 2 (0.5 mmol)
vered. This was somewhat surprising, because SET from the in THF (1 mL), which was added dropwise over 5 min. After stir-
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Reactions of α-Alkoxy-α-phenylacetonitrile Anions with o-Chloronitrobenzene
ring for 10 min, the reaction mixture was quenched at –78 °C by
addition of 10% aq. HCl (10 mL) and left to reach room tempera-
ture. The workup was performed as described above. Product 1c
was obtained as a colorless oil that solidified. Analytical data are
identical to those reported.[18]
2230, 1533, 1354 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.88 (dd,
J = 8.0, 1.0 Hz, 1 H), 7.62–7.61 (m, 1 H), 7.53–7.50 (m, 2 H), 7.45–
7.40 (m, 5 H), 3.34 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 148.9, 143.5, 137.5, 135.6, 129.8, 129.3, 128.9, 127.5, 127.4, 125.2,
115.2, 81.7, 53.9 ppm. EI-MS: m/z (%) = 268 (5) [M]+. C15H12N2O3
(268.27): calcd. C 67.16, H 4.51, N 10.44; found C 67.10, H 4.80,
N 10.20.
SNAr Substitution of Cl in 3 with the Carbanion of 1 or 2 under PTC
Conditions: To a solution of 3 (0.5 mmol, 74 mg), 1 or 2 (0.5 mmol),
and TBAB (16 mg, 0.05 mmol) in acetonitrile (0.5 mL) was added
a 50% aqueous solution of NaOH in water (2 mL). The resulting
mixture was stirred vigorously at room temperature for 15 min, fol-
lowed by addition of water (10 mL). The mixture was extracted
with dichloromethane, and the organic phase was dried, concen-
trated, and the products were purified by column chromatography.
Products 1d or 2d were obtained as yellow oils.
α-(2-Nitrophenyl)-α-phenoxy-α-phenylacetonitrile
(2d):
Yield:
119 mg, 72%; yellowish oil. IR (film, CH Cl ): ν = 3095, 3041,
˜
2
2
2230, 1532, 1353, 1217 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.2
(d, J = 7.9 Hz, 1 H), 7.87 (dd, J = 7.5, 1.0 Hz, 1 H), 7.61–7.59
(m, 2 H), 7.47–7.35 (m, 7 H), 7.25–7.10 (m, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 165.1, 156.4, 151.0, 133.6, 132.8, 130.1,
129.9, 129.5, 127.5, 127.3, 126.3, 123.4, 116.4, 80.1 ppm. EI-MS:
m/z (%) = 330 (3) [M]+. C20H14N2O3 (330.34): calcd. C 72.72, H
4.27, N 8.48; found C 72.90, H 4.50, N 8.40.
Nitrone Formation in the Reaction of 3 with the Carbanions of 1 or
2 in tert-Butyl Alcohol: To a solution of tBuOK (56 mg, 0.5 mmol)
in tert-butyl alcohol (4 mL) was added a solution of 3 (0.5 mmol,
74 mg) and 1 or 2 (1.0 mmol) in tert-butyl alcohol (1.0 mL). The
resulting mixture was stirred at 65 °C for 3 h (with 2) or 24 h (with
1). After cooling to room temperature, 10% aq. HCl (10 mL) was
added, and the workup was performed as described above. Prod-
ucts 1a and 2e were obtained as orange solids.
2-Chloro-4-[cyano(methoxy)(phenyl)methyl]-N-[cyano(phenyl)meth-
ylene]aniline N-Oxide (1e): Yield: 38 mg, 21%; solidifying oil. IR
(film, CH Cl ): ν = 3102, 3042, 2231, 2201, 1534, 1349, 1210 cm–1.
˜
2
2
1H NMR (500 MHz, CDCl3): δ = 8.14–8.10 (m, 3 H), 7.61 (m, 1
H), 7.50–7.45 (m, 4 H), 7.38–7.35 (m, 2 H), 7.43–7.40 (m, 3 H),
7.28–7.20 (m, 3 H), 6.95–6.90 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 171.9, 143.6, 138.6, 133.8, 130.2, 129.9, 129.1, 128.7,
128.6, 128.5, 127.7, 127.1, 126.5, 126.2, 119.1, 118.1, 115.5, 81.8,
54.1 ppm. EI-MS: m/z (%) = 401 (2) [M]+. C23H16ClN3O2 (401.85):
calcd. C 68.74, H 4.01, N 10.46; found C 68.86, H 4.11, N 10.01.
Analytical Data for New Compounds
α-(3-Chloro-4-nitrophenyl)-α-methoxy-α-phenylacetonitrile
(1a):
Yield: 125 mg, 83%; oil. IR (film, CH Cl ): ν = 3102, 2938, 2228,
˜
2
2
1532, 1349 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J =
8.0 Hz, 1 H), 7.49 (d, J = 2.0 Hz, 1 H), 7.51 (d, J = 2 Hz, 1 H),
7.50–7.42 (m, 5 H), 3.45 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 147.8, 145.0, 136.4, 130.0, 129.6, 129.4, 127.7, 126.4,
125.9, 125.6, 116.8, 81.3, 54.5 ppm. EI-MS: m/z (%) = 302 (20)
[M]+. C15H11ClN2O3 (302.72): calcd. C 59.52, H 3.66, N 9.25;
found C 59.70, H 3.60, N 9.10.
2-Chloro-4-[cyano(phenoxy)(phenyl)methyl]-N-[cyano(phenyl)meth-
ylene]aniline N-Oxide (2e): Yield: 38 mg, 65%; solidifying oil. IR
(film, CH Cl ): ν = 3103, 3039, 2233, 2209, 1530, 1209 cm–1. 1H
˜
2
2
NMR (200 MHz, CDCl3): δ = 8.14–8.10 (m, 2 H), 7.93–7.90 (m, 1
H), 7.62–7.58 (m, 2 H), 7.58–7.31 (m, 6 H), 7.31–7.19 (m, 4 H),
6.98–6.89 (m, 1 H), 6.86–6.60 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 171.4, 155.6, 137.7, 134.4, 133.7, 131.1, 130.2, 130.1,
130.0, 129.8, 129.6, 129.3, 129.0, 128.7, 128.6, 128.4, 128.2, 127.6,
120.6, 115.3, 118.9, 81.7 ppm. EI-MS: m/z (%) = 463 (3) [M]+.
C28H18ClN3O2 (463.92): calcd. C 72.49, H 3.91, N 9.06; found C
72.61, H 4.20, N 9.43.
α-(3-Chloro-4-nitrophenyl)-α-phenoxy-α-phenylacetonitrile
(2a):
Yield: 109 mg, 60%; solidifying oil. IR (film, CH Cl ): ν = 3101,
˜
2
2
3039, 2229, 1532, 1349, 1209 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.90 (d, J = 8.5 Hz, 1 H), 7.85 (d, J = 1.0 Hz, 1 H), 7.62 (dd,
J = 8.5, 2.0 Hz 1 H), 7.54–7.51 (m, 2 H), 7.43–7.40 (m, 3 H), 7.28–
7.20 (m, 3 H), 6.95–6.90 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 153.8, 147.9, 144.9, 136.7, 133.7, 130.1, 130.0, 129.7,
129.6, 129.3, 126.6, 126.0, 125.5, 120.0, 117.0, 80.6 ppm. EI-MS:
m/z (%) = 364 (6) [M]+. C20H13ClN2O3 (364.79): calcd. C 65.85, H
3.59, N 7.68; found C 66.01, H 4.20, N 7.60.
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α-(3-Chloro-4-hydroxyphenyl)-α-methoxy-α-phenylacetonitrile (1b):
[4] a) V. A. Charushin, O. N. Chupakhin, Mendeleev Commun.
2007, 15, 249; b) O. N. Chupakhin, V. N. Charushin, H. C.
van der Plas, Nucleophilic Aromatic Substitution of Hydrogen,
Academic Press, San Diego, CA, 1994; c) F. Terrier, Nucleo-
philic Aromatic Displacement, VCH, Weinheim, 1991.
Yield: 69 mg, 51%; oil. IR (film, CH Cl ): ν = 3384 (br), 3064,
˜
2
2
2239, 1605, 1498, 1450 cm–1. 1H NMR (500 MHz, CDCl3): δ =
7.47–7.43 (m, 4 H), 7.40–7.35 (m, 4 H), 5.65 (br. s, 1 H), 3.39 (s, 3
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 151.9, 138.1, 132.3,
129.3, 128.9, 128.8, 127.2, 126.9, 126.5, 117.9, 116.4, 81.4, 54.2
ppm. EI-MS: m/z (%) = 273 (31) [M]+. C15H12ClNO2 (273.72):
calcd. C 65.82, H 4.42, N 5.12; found C 65.50, H 4.21, N 5.51.
[5] M. Makosza, M. Paszewski, Pol. J. Chem. 2005, 79, 163.
˛
[6] M. Makosza, K. Wojciechowski, Chem. Rev. 2004, 104, 2631.
˛
[7] M. Makosza, A. Kwast, J. Phys. Org. Chem. 1998, 11, 341.
˛
[8] a) M. Makosza, Chem. Soc. Rev. 2010, 39, 2855; b) M.
˛
α-(3-Chloro-4-hydroxyphenyl)-α-phenoxy-α-phenylacetonitrile (2b):
Makosza, Synthesis 2011, 2341.
˛
Yield: 23 mg, 13%; solidifying oil. IR (film, CH Cl ): ν = 3380,
˜
2
2
[9] a) M. Makosza, K. Stalin´ski, Chem. Eur. J. 1997, 3, 2025; b)
˛
3063, 2243, 1590, 1532 cm–1. 1H NMR (200 MHz, CDCl3): δ =
7.91–7.83 (m, 2 H), 7.61–7.42 (m, 6 H), 7.32–7.21 (m, 3 H), 7.12–
7.06 (m, 2 H), 5.80 (br. s, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 156.3, 144.7, 141.6, 136.6, 133.3, 130.0, 129.9, 129.6, 129.3,
129.2, 127.2, 126.5, 123.3, 121.6, 116.3, 80.6 ppm. EI-MS: m/z (%)
= 355 (2) [M]+. C20H14ClNO2 (335.79): calcd. C 71.54, H 4.20, N
4.17; found C 71.44, H 4.22, N 4.00.
M. Makosza, K. Stalin´ski, Tetrahedron Lett. 1998, 39, 3575.
˛
[10] a) W. Adam, M. Makosza, K. Stalin´ski, C. G. Zhao, J. Org.
˛
Chem. 1998, 63, 4390; b) W. Adam, M. Makosza, C.-G. Zhao,
˛
M. Surowiec, J. Org. Chem. 2000, 65, 1099.
[11] a) M. Makosza, Pure Appl. Chem. 1975, 43, 439; b) M.
˛
Makosza, M. Fedoryn´ski, Catal. Rev. 2003, 45, 321.
[12] M. Makosza, Tetrahedron Lett. 1969, 10, 673.
˛
˛
[13] a) G. A. Russel, E. G. Janzen, E. T. Strom, J. Am. Chem. Soc.
1964, 86, 1807; b) I. I. Bilkis, S. M. Shein, Tetrahedron 1975,
31, 969.
α-Methoxy-α-(2-nitrophenyl)-α-phenylacetonitrile
(1d):
Yield:
115 mg, 86%; yellowish oil. IR (film, CH Cl ): ν = 3094, 2937,
˜
2
2
Eur. J. Org. Chem. 2011, 6887–6892
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6891

M. Makosza, D. Sulikowski
˛
FULL PAPER
[14] X.-M. Zhang, D.-L. Young, Y.-C. Liu, J. Org. Chem. 1993, 58,
224 and rebuttal, M. Ma˛kosza, R. Podraza, A. Kwast, J. Org.
Chem. 1994, 59, 6796.
[15] M. Ma˛kosza, A. Kwast, Eur. J. Org. Chem. 2004, 2125.
[16] L. Stella, Z. Janousek, R. Merenyi, H. G. Viehe, Angew. Chem.
1978, 90, 741; Angew. Chem. Int. Ed. Engl. 1978, 17, 691.
[17] M. Ma˛kosza, T. Goetzen, Rocz. Chem. 1972, 46, 1059.
[18] M. Ma˛kosza, J. Winiarski, J. Org. Chem. 1984, 49, 1494.
Received: June 22, 2011
Published Online: September 27, 2011
6892
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6887–6892