Isomerization of 3-unsubstituted 4,5-dihydroisoxazoles over alumina. A new synthesis of β-hydroxy nitriles

Article abstract of DOI:10.1134/S1070428016030179

3-Unsubstituted 4,5-dihydroisoxazoles obtained by nitrosation of arylcyclopropanes are capable of undergoing efficient isomerization into 3-aryl-3-hydroxypropanenitriles during chromatography on alumina.

Full text of DOI:10.1134/S1070428016030179

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 3, pp. 397–403. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © S.S. Mochalov, A.N. Fedotov, E.V. Trofimova, R.A. Gazzaeva, N.S. Zefirov, 2016, published in Zhurnal Organicheskoi Khimii,
2016, Vol. 52, No. 3, pp. 417–423.
Isomerization of 3-Unsubstituted 4,5-dihydroisoxazoles
over Alumina. A New Synthesis of β-Hydroxy Nitriles
S. S. Mochalova, A. N. Fedotova, E. V. Trofimovaa, R. A. Gazzaevab, and N. S. Zefirova
a Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia
e-mail: fed@org.chem.msu.ru
b Khetagurov North Ossetian State University, ul. Vatutina 44–46, Vladikavkaz, 362025 Russia
Received November 9, 2015
Abstract—3-Unsubstituted 4,5-dihydroisoxazoles obtained by nitrosation of arylcyclopropanes are capable of
undergoing efficient isomerization into 3-aryl-3-hydroxypropanenitriles during chromatography on alumina.
DOI: 10.1134/S1070428016030179
Five-membered heterocyclic 4,5-dihydroisoxazole
systems, which may be regarded as cyclic form of
O-alkyl oximes, are structural units of many biologi-
cally active molecules [1], including natural alkaloids
[2–5]. Therefore, systematic studies are performed
with the goal of obtaining medicinal agents on the
basis of dihydroisoxazole substrates. However, apart
from medical purposes, the possibility of using dihy-
droisoxazole derivatives in synthetic organic chemistry
is equally important. Due to the ability of 4,5-dihydro-
isoxazole structures to be converted into β-hydroxy
nitriles, β-hydroxy ketones, γ-amino alcohols, and
α,β-unsaturated ketones and acids, these compounds
were referred to as those possessing latent bifunc-
tionality [6–8].
initiated through elimination of the 3-substituent. On
the other hand, Huisgen and Christl [16] showed that
β-hydroxy nitriles can readily be obtained by treatment
of 3-unsubstituted 4,5-dihydroisoxazoles with triethyl-
amine on heating (Scheme 1).
It is quite obvious that the synthesis of β-hydroxy
nitriles from 3-unsubstituted 4,5-dihydroisoxazoles is
more advantageous than their synthesis from 3-substi-
tuted analogs. However, no due attention has been paid
for a long time to the Huisgen synthesis of β-hydroxy
nitriles, presumably because of the lack of efficient
procedures for preparation of 3-unsubstituted 4,5-dihy-
droisoxazoles. In recent years, extensive studies have
been performed on the synthesis of 3-unsubstituted
4,5-dihydroisoxazoles, and reliable and efficient meth-
ods for their synthesis have been developed [8, 17–30].
The possibility for synthesizing β-hydroxy nitriles in
moderate to high yields according to Huisgen was
subsequently confirmed in [31–33]. While continuing
studies on the base-catalyzed isomerization of 3-un-
substituted 4,5-dihydroisoxazoles into β-hydroxy ni-
triles, it was shown that, apart from triethylamine, this
reaction can be initiated by other bases, such as sodium
methoxide, potassium tert-butoxide, and 1,8-diazabi-
cycloundec-7-ene (DBU) [8, 34].
From the viewpoint of synthetic potential, the trans-
formation of 4,5-dihydroisoxazoles into β-hydroxy
nitriles seems to be the most important, since these
transformation products are quite useful building
blocks for the synthesis of β-hydroxy carboxylic acids
and their derivatives and γ-amino alcohols and are
often used to assemble complex biologically active
molecules [7, 9]. Up to now, syntheses of β-hydroxy
nitriles from 3-bromo- [10, 11], 3-carboxy- [12], 3-tri-
methylsilyl- [13], and 3-(benzenesulfonyl)-4,5-dihy-
droisoxazoles [14, 15] have been well documented;
in these reactions, the formation of cyano group is
In this study we have shown that the isomerization
of 3-unsubstituted 4,5-dihydroisoxazoles into β-hy-
droxy nitriles can be efficiently catalyzed by alumina.
The process can be performed in a one-pot mode; it
includes reaction of arylcyclopropanes with nitrous
acid (synthesis of 3-unsubstituted 4,5-dihydroisoxa-
Scheme 1.
OH
Et3N, ∆
N
CN
Ph
O
Ph
397

MOCHALOV et al.
398
Scheme 2.
NaNO2, CF3COOH
CHCl3, 0–5°C, 0.5 h
R
R
R
N +
CHO
O
Ar
Ar
Ar
1a–1k
2a–2k
3a–3f, 3h, 3i
R = H, Ar = Ph (a), 4-BrC6H4 (b), 3-BrC6H4 (c), 5,6,7,8-tetrahydronaphthalen-2-yl (d), fluoren-2-yl (e), 4-AllC6H4 (f), 4-(cyclo-
propylmethyl)phenyl (g), 4-(2,2-dichlorocyclopropylmethyl)phenyl (h), 3-(2,2-dichlorocyclopropylmethyl)phenyl (i), PhCH2 (j);
R = Me, Ar = 4-i-PrC6H4 (k).
zoles) and subsequent isomerization of the resulting
heterocyclic compounds into β-hydroxy nitriles by the
action of Al2O3.
atom (run nos. 2, 3) or 2,2-dichlorocyclopropyl sub-
stituent (run nos. 8, 10). Despite the use of 2 equiv of
NaNO2, complete conversion of 1h was not attained,
and a considerable amount of the initial arylcyclo-
propane remained unchanged (run no. 9). Analogous
relation between the nature of substituents in aryl-
cyclopropanes and the yield of 4,5-dihydroisoxazoles
was noted in [30] where the behavior of arylcyclo-
propanes with electron-donating and electron-with-
drawing substituents in the benzene ring was studied in
the reaction with nitrosyl chloride in the presence of
sulfur(VI) oxide.
It should be emphasized that substrates 1f and 1g
containing allyl or cyclopropylmethyl group capable of
competing with the conjugated cyclopropyl substituent
in the electrophilic addition reaction reacted with
nitrous acid only through the cyclopropane fragment
conjugated with the benzene ring.
1
According to the H NMR data, the reaction
mixtures obtained by reactions of arylcyclopropanes
1a–1k with an equimolar amount of sodium nitrite in
acid medium contained the corresponding 3-unsubsti-
tuted 4,5-dihydroisoxazoles 2a–2k and cinnamalde-
hydes 3a–3h together with unreacted initial com-
pounds (Table 1, Scheme 2). The data in Table 1 show
that each arylcyclopropane 1a–1k gives rise mainly to
3-unsubstituted dihydroisoxazole and that cinnamalde-
hydes either are not formed (run nos. 7, 8, 11, 12) or
are formed as minor products. An exception was the
reaction with m-bromophenylcyclopropane (run no. 3).
Under the nitrosation conditions, arylcyclopropanes
having no electron-withdrawing substituents are con-
verted into 3-unsubstituted dihydroisoxazoles in higher
yields (run nos. 1, 4, 5, 11, 12) than are those contain-
ing even weakly acceptor groups, namely a bromine
By chromatographic separation of the reaction
mixtures from run nos. 1–8 and 10–12 on alumina
Table 1. Composition of the reaction mixtures in the reactions of arylcyclopropanes 1a–1k with an equimolar amount of
nitrous acid
Composition of the reaction mixture,a %
Run no.
Initial arylcyclopropane
dihydroisoxazole
cinnamaldehyde
unreacted arylcyclopropane
01
02
03
04
05
06
07
08
09
10
11
12
1a
1b
1c
1d
1e
1f
2a (79.5)
2b (70.5)
2c (42.2)
2d (91.5)
2e (94.0)
2f (68.1)
2g (55.5)
2h (50.2)
2h (75.1)
2i (56.3)
2j (72.2)
2k (93.0)
3a (8.3)
3b (8.1)
3c (20.3)
3d (~2.0)
3e (~3.0)
3f (4.6)
–
1a (12.5)
1b (21.3)
1c (36.6)
1d (6.5)
1e (4.0)
1f (26.5)
1g (44.3)
1h (49.3)
1h (22.7)
1i (41.5)
1j (26.3)
1k (~3.0)
1g
1h
1hb
1i
–
3g (2.1)
3h (~2.0)
–
1j
1k
–
a
According to the 1H NMR data.
2 equiv of HNO2.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

ISOMERIZATION OF 3-UNSUBSTITUTED 4,5-DIHYDROISOXAZOLES OVER ALUMINA.
399
Table 2. Yields of compounds 1–4 (%) after chromatographic separation on Al2O3 of the reaction mixtures obtained in run
nos. 1–8 and 10–12
Run no.
Dihydroisoxazolea
Cinnamaldehyde
Unreacted arylcyclopropane
β-Hydroxy nitrilea
01
02
03
04
05
06
07
08
10
11
12
2a, 10.5 (7.5)
2b, 9.5 (12.7)
2c, 6.8 (15.8)
2d, 21.8 (20.7)
2e, 9.4 (11.5)
2f, 14.5 (20.4)
2g, 19.5 (30.8)
2h, 5.3 (11.2)
2i, 8.7 (16.3)
2j, 17.5 (24.1)
2k, 53.0
3a, 6.5
1a, 10.4
1b, 18.2
1c, 36.7
1d, 3.9
1e, 5.5
4a, 69.0 (82.5)
4b, 67.1 (87.5)
4c, 46.1 (84.2)
4d, 66.8 (71.5)
4e, 71.0 (88.5)
4f, 56.7 (79.3)
4g, 45.4 (69.2)
4h, 42.5 (88.8)
4i, 44.5 (83.7)
4j, 55.0 (75.9)
4k, 47
3b, 8.3
3c, 10.2
3d, 1.6
3e, 4.3
3f, 5.1
1f, 17.5
1g, 35.5
1h, 52.2
1i, 46.7
1j, 27.5
1k, –
–
–
–
–
–
a
In parentheses are given the concentrations (%) of 2a–2k and 4a–4k after a single chromatographic separation, which indicate the degree
of isomerization of 2 over Al2O3.
(Table 2) we isolated both components of the initial
mixture and (major products) β-hydroxy nitriles 4a–4k
resulting from isomerization of 3-unsubstituted 4,5-di-
hydroisoxazoles 2a–2k (Scheme 3).
on Al2O3; as a result, β-hydroxy nitrile 4l was obtained
in high yield (Scheme 4). These findings allow us to
believe that 3-unsubstituted 4,5-dihydroisoxazoles syn-
thesized by any other method (not only by reaction of
1 with HNO2) should undergo efficient Al2O3-cata-
lyzed isomerization into the corresponding 3-hydroxy-
alkanenitriles. The transformation sequence including
nitrosation of arylcyclopropanes followed by chroma-
tography of the resulting 3-unsubstituted 4,5-dihydro-
isoxazoles on Al2O3 may be regarded as a one-pot syn-
thesis of β-hydroxy nitriles from arylcyclopropanes.
Scheme 3.
R
Al2O3, 20°C
R
N
CN
O
Ar
Ar
OH
2a–2k
4a–4k
The efficiency of the Al2O3-catalyzed isomerization
may be estimated by comparing the amounts of dihy-
droisoxazoles 2a–2k isolated by chromatography and
the corresponding β-hydroxy nitriles 4a–4k (Table 2,
in parentheses), calculated on 2a–2k taken for chro-
matography.
EXPERIMENTAL
1
The H NMR spectra were recorded from solutions
in CDCl3 on a Varian VXR-400 spectrometer
(400 MHz) using the residual proton signal of the
solvent as reference. The IR spectra were measured on
a UR-20 spectrometer from samples prepared as thin
films or Nujol mulls (solids). The mass spectrum of 4i
(electron impact, 70 eV) was obtained on a Finnigan
SSQ 7000 GC/MS instrument (DB-1 capillary column,
30 m×0.2 mm; carrier gas helium; oven temperature
programming from 50 to 300°C at a rate of 10 deg ×
In order to demonstrate that the presence of unre-
acted initial arylcyclopropanes 1a–1k and cinnamalde-
hydes (by-products) in the reaction mixtures does not
affect the isomerization process, 5-aryldihydroisoxa-
zole 2l was specially isolated by crystallization from
the reaction mixture obtained in the nitrosation of 1l
and subjected to isomerization upon chromatography
Scheme 4.
H
H
H
N
N
N
HNO2, 0–5°C
Al2O3, 20°C
71%
CN
O
Cl
O
Cl
O
Cl
O
N
OH
1l
2l
4l
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

MOCHALOV et al.
400
min–1). The elemental compositions were determined
using a Vario-11 CHN analyzer. The melting points
were measured on an Electrothermal 1A9100 digital
melting point apparatus.
(1H, J = 6.8, 15.4 Hz) and 3.02 d.d (1H, J = 7.6,
15.4 Hz) (3-CH2), 6.99 d (1H, Harom, J = 7.6 Hz),
7.05 s (1H, Harom), 7.11 d (1H, Harom, J = 7.6 Hz),
7.26 t (1H, Harom). Found, %: C 64.22, 64.41; H 5.68,
5.77. C13H14Cl2. Calculated, %: C 64.75; H 5.85.
The products were isolated from the reactions mix-
tures by column chromatography on Al2O3 (Brock-
mann activity grade II) using diethyl ether, diethyl
ether–chloroform (1:3, 1:2), and chloroform–metha-
nol (1:1) as eluents.
1-(1-Methylcyclopropyl)-4-(propan-2-yl)benzene
(1k) was synthesized by reduction of 1-(2,2-dichloro-
1-methylcyclopropyl)-4-(propan-2-yl)benzene accord-
ing to [40]. Yield 69%, bp 126–127°C (30 mm), nD20 =
1
1.5082. H NMR spectrum, δ, ppm: 0.78 m (2H) and
Arylcyclopropanes 1a, 1b [35], 1c [36], 1e [37], 1f
[38], 1j [39], and 1l [28] were synthesized according to
known procedures.
0.93 m (2H, CH2) (C3H4), 1.32 d [6H, CH(CH3)2, J =
7.4 Hz], 1.48 s (3H, CH3), 2.96 sept [1H, CH(CH3)2],
7.22 d and 7.26 d (2H each, Harom, J = 7.8 Hz). Found,
%: C 89.21, 89.32; H 10.14, 10.21. C13H18. Calculated,
%: C 89.59; H 10.41.
2-Cyclopropyl-5,6,7,8-tetrahydronaphthalene
(1d) was synthesized by catalytic decomposition of
3-(5,6,7,8-tetrahydronaphthalen-2-yl)-4,5-dihydro-1H-
pyrazole according to Kischner. Yield 69%, bp 173–
Reaction of arylcyclopropanes 1a–1l with
nitrous acid generated in situ (general procedure).
Sodium nitrite, 0.69 g (0.01 mol), was added in
portions over a period of 10–15 min to a mixture of
0.01 mol of arylcyclopropane 1a–1l, 5.2 g of trifluoro-
acetic acid, and 15 mL of chloroform, cooled to 0–5°C.
The mixture was allowed to warm up to 20°C, kept for
1 h at that temperature, and poured into 100 mL of
cold water. The organic phase was separated, the aque-
ous phase was extracted with chloroform (2×10 mL),
the extracts were combined with the organic phase,
washed with water (2×30 mL), and dried over MgSO4,
the solvent was removed, and the residue was analyzed
by 1H NMR. Compound 2l was isolated by crystalliza-
tion. The compositions of the reaction mixtures are
given in Table 1. The physical constants and spectral
characteristics of 2a [16], 2b [30], and 2l [28] coin-
cided with published data.
174°C (45 mm), nD20 = 1.5544. H NMR spectrum, δ,
1
ppm: 0.73 m (2H), 0.99 m (2H), and 1.92 m (1H,
C3H5), 1.82 m (4H, 6-H, 7-H), 2.82 m (4H, 5-H, 8-H),
6.88–6.91 m (2H) and 7.05 d (1H, J = 8.1 Hz) (1-H,
3-H, 4-H). Found, %: C 90.28, 90.37; H 9.12, 9.19.
C13H16. Calculated, %: C 90.64; H 9.36.
1-Cyclopropyl-4-(cyclopropylmethyl)benzene
(1g) was synthesized by reduction of 1-cyclopropyl-4-
(2,2-dichlorocyclopropylmethyl)benzene as described
in [40]. Yield 72%, bp 151–153°C (20 mm), nD20
=
1
1.5395. H NMR spectrum, δ, ppm: 0.27 m (2H),
0.58 m (2H), and 1.06 m (1H) (C3H5CH2); 0.75 m
(2H), 1.01 m (2H), and 1.95 m (1H) (1-C3H5); 2.58 d
(2H, 4-CH2, J = 6.2 Hz), 7.08 d and 7.23 d (2H each,
Harom, J = 8.0 Hz). Found, %: C 90.31, 90.46; H 9.14,
9.22. C13H16. Calculated, %: C 90.64; H 9.36.
1-Cyclopropyl-4-(2,2-dichlorocyclopropyl-
methyl)benzene (1h) was synthesized by dichloro-
cyclopropanation of 1-allyl-4-cyclopropylbenzene as
described in [40]. Yield 81%, bp 199–201°C (12 mm),
nD20 = 1.5522. 1H NMR spectrum, δ, ppm: 0.73 m (2H)
and 1.01 m (2H, CH2) (C3H5), 1.26 m (1H) and 1.71 m
(1H, CH2, Cl2C3H3), 1.93 m (2H, CH), 2.79 d.d (1H,
J = 6.6, 14.7 Hz) and 3.01 d.d (1H, J = 7.8, 14.7 Hz)
(4-CH2), 7.09 d and 7.21 d (2H each, Harom, J =
8.1 Hz). Found, %: C 64.31, 64.52; H 5.63, 5.73.
C13H14Cl2. Calculated, %: C 64.75; H 5.85.
5-(3-Bromophenyl)-4,5-dihydro-1,2-oxazole (2c).
Viscous oily material. H NMR spectrum, δ, ppm:
1
2.98 d.d.d (1H, 4-H, J = 2.0, 7.4, 17.8 Hz) and
3.46 d.d.d (1H, 4-H, J = 2.0, 10.5, 17.8 Hz), 5.51 d.d
(1H, 5-H, J = 7.4, 10.5 Hz), 7.23 s (1H, 3-H), 7.23–
7.28 m (3H, Harom), 7.49 m (1H, Harom). Found, %:
C 47.33, 47.51; H 3.36, 3.42; N 5.91, 6.02. C9H8BrNO.
Calculated, %: C 47.82; H 3.57; N 6.20.
5-(5,6,7,8-Tetrahydronaphthalen-2-yl)-4,5-dihy-
1
dro-1,2-oxazole (2d). Viscous oily material. H NMR
spectrum, δ, ppm: 1.82 m (4H, 6′-H, 7′-H), 2.78 m
(4H, 5′-H, 8′-H), 3.02 d.d (1H, 4-H, J = 8.0, 17.2),
3.41 d.d (1H, 4-H, J = 11.2, 17.2 Hz), 5.56 d.d (1H,
5-H, J = 7.8, 11.2 Hz), 7.05–7.10 m (3H, Harom), 7.24 s
(1H, 3-H). Found, %: C 77.43, 77.61; H 7.41, 7.56;
N 7.04, 7.12. C13H15NO. Calculated, %: C 77.58;
H 7.51; N 6.96.
1-Cyclopropyl-3-(2,2-dichlorocyclopropyl-
methyl)benzene (1i) was synthesized in a similar way.
Yield 64%, bp 214–215°C (23 mm), nD20 = 1.5541.
1H NMR spectrum, δ, ppm: 0.75 m (2H) and 1.01 m
(2H, CH2) (C3H5), 1.25 m (1H) and 1.72 m (1H, CH2)
(Cl2C3H3), 1.94 m (2H, CH in C3H5, Cl2C3H3), 2.78 d.d
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ISOMERIZATION OF 3-UNSUBSTITUTED 4,5-DIHYDROISOXAZOLES OVER ALUMINA.
401
5-(9H-Fluoren-2-yl)-4,5-dihydro-1,2-oxazole
(2e). mp 111–112°C (from Et2O). H NMR spectrum,
5-Benzyl-4,5-dihydro-1,2-oxazole (2j). Oily mate-
rial. H NMR spectrum, δ, ppm: 2.73 d.d.d (1H, 4-H,
1
1
δ, ppm: 3.07 d.d.d (1H, 4-H, J = 1.7, 8.2, 17.6 Hz),
3.50 d.d.d (1H, 4-H, J = 1.7, 11.2, 17.6 Hz), 3.91 s
(2H, 9′-H), 5.62 d.d (1H, 5-H, J = 8.2, 11.2 Hz), 7.28 s
J = 1.9, 7.4, 17.5 Hz), 2.99 d.d.d (1H, 4-H, J = 1.9,
10.4, 17.5 Hz), 2.82 d.d (1H, J = 7.2, 13.6 Hz) and
3.06 d.d (1H, J = 6.4, 13.6 Hz) (5-CH2), 4.82 m (1H,
5-H), 7.12 s (1H, 3-H), 7.22–7.35 m (5H, Harom).
Found, %: C 74.42, 74.56; H 6.56, 6.71; N 8.71, 8.78.
C10H11NO. Calculated, %: C 74.51; H 6.88; N 8.69.
(1H, 3-H), 7.31–7.42 m (3H, Harom), 7.55 m (2H,
3
H
arom), 7.79 t (2H, Harom, J = 7.8 Hz). Found, %:
C 81.16, 81.37; H 5.35, 5.60; N 5.88, 6.01. C16H13NO.
Calculated, %: C 81.68; H 5.57; N 5.95.
5-Methyl-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-
1
5-[4-(2-Prop-2-en-1-yl)phenyl]-4,5-dihydro-1,2-
oxazole (2f). Viscous oily material. 1H NMR spectrum,
δ, ppm: 2.98 d.d.d (1H, 4-H, J = 1.8, 8.4, 17.7 Hz),
3.43 d.d.d (1H, 4-H, J = 1.8, 10.6, 17.7 Hz), 3.40 d
(2H, 4′-CH2, J = 7.1 Hz), 5.08–5.12 m (2H, CH=CH2),
5.52 d.d (1H, 5-H, J = 8.4, 10.6 Hz), 5.92–6.02 m (1H,
1,2-oxazole (2k). Oily material. H NMR spectrum, δ,
ppm: 1.26 d [6H, CH(CH3)2, J = 6.4 Hz], 1.73 s (3H,
CH3), 2.93 sept [1H, CH(CH3)2], 3.14 d and 3.17 d
(1H each, 4-H, J = 15.2 Hz), 7.19 s (1H, 3-H), 7.23 d
(2H, Harom, J = 8.2 Hz), 7.35 d (2H, Harom, J = 8.2 Hz).
Found, %: C 76.27, 76.45; H 8.11, 8.20; N 6.92, 7.02.
C13H17NO. Calculated, %: C 76.81; H 8.43; N 6.89.
3
CH=CH2), 7.20 s (1H, 3-H), 7.21 d (2H, Harom, J =
3
8.0 Hz), 7.28 d (2H, Harom, J = 8.0 Hz). Found, %:
Chromatographic separation of the reaction
mixtures on Al2O3. A column, 2.5 cm in diameter and
18 cm in height, was charged with 25–30 g of Al2O3
(Brockmann activity grade II) and wetted with petro-
leum ether (40–70°C), 0.5–0.6 g of the reaction mix-
ture obtained by nitrosation of 1a–1l was applied on
the top, and the column was eluted in succession with
diethyl ether, diethyl ether–chloroform (1:3, 1:2), and
chloroform–methanol (1:1). The product yields are
given in Table 2.
C 76.62, 76.73; H 6.76, 6.82; N 7.16, 7.31. C12H13NO.
Calculated, %: C 76.98; H 7.00; N 7.48.
5-[4-(Cyclopropylmethyl)phenyl]-4,5-dihydro-
1,2-oxazole (2g). Viscous oily material. 1H NMR spec-
trum, δ, ppm: 0.21 m (2H), 0.53 m (2H), and 0.99 m
(1H) (C3H5); 2.56 d (2H, 4′-CH2, J = 6.4 Hz), 2.99 d.d
(1H, 4-H, J = 8.2, 17.6 Hz), 3.42 d.d (1H, 4-H, J =
11.6, 17.6 Hz), 5.51 d.d (1H, 5-H, J = 8.2, 11.6 Hz),
3
7.21 s (1H, 3-H), 7.30 d (2H, Harom, J = 7.8 Hz),
3
7.33 d (2H, Harom, J = 7.8 Hz). Found, %: C 77.21,
3-Hydroxy-3-phenylpropanenitrile (4a). Viscous
77.38; H 7.27, 7.39; N 6.93, 7.06. C13H15NO. Calculat-
ed, %: C 77.58; H 7.51; N 6.96.
oily material. IR spectrum, ν, cm–1 (film): 3465 (OH),
1
2278 (CN). H NMR spectrum, δ, ppm: 2.78 d (2H,
5-{4-[(2,2-Dichlorocyclopropyl)methyl]phenyl}-
4,5-dihydro-1,2-oxazole (2h). Viscous oily material.
1H NMR spectrum, δ, ppm: 1.26 m (1H), 1.71 m (1H),
and 1.88 m (1H) (Cl2C3H3); 2.82 d.d (1H, J = 6.7,
15.6 Hz) and 2.98 d.d (1H, J = 7.8, 15.6 Hz) (4′-CH2),
3.03 d.d.d (1H, 4-H, J = 1.4, 8.0, 17.6 Hz), 3.45 d.d.d
(1H, 4-H, J = 1.4, 10.7, 17.6 Hz), 5.55 d.d (1H, 5-H,
J = 8.0, 10.7 Hz), 7.24 d (1H, 3-H, J = 1.4 Hz), 7.31 s
(4H, Harom). Found, %: C 57.23, 57.36; H 4.56, 4.62;
N 5.26, 5.31. C13H13Cl2NO. Calculated, %: C 57.80;
H 4.85; N 5.19.
CH2CN, J = 5.9 Hz), 2.95 br.s (1H, OH), 5.05 t (1H,
CHOH, J = 5.9 Hz), 7.35–7.39 m (5H, Harom). Found,
%: C 73.24, 73.31; H 5.98, 6.07; N 9.31, 9.42.
C9H9NO. Calculated, %: C 73.45; H 6.16; N 9.52.
3-(4-Bromophenyl)-3-hydroxypropanenitrile
(4b). Viscous oily material. IR spectrum, ν, cm–1: 3450
(OH), 2276 (CN). 1H NMR spectrum, δ, ppm: 2.51 br.s
(1H, OH), 2.75 d (2H, CH2CN, J = 6.2 Hz), 5.02 t (1H,
3
CHOH, J = 6.2 Hz), 7.29 d (2H, Harom, J = 8.2 Hz),
3
7.54 d (2H, Harom, J = 8.2 Hz). Found, %: C 47.53,
47.69; H 3.28, 3.41; N 5.93, 6.03. C9H8BrNO. Calcu-
lated, %: C 47.82; H 3.57; N 6.20.
5-{3-[(2,2-Dichlorocyclopropyl)methyl]phenyl}-
4,5-dihydro-1,2-oxazole (2i). Viscous oily material.
1H NMR spectrum, δ, ppm: 1.26 m (1H), 1.70 m (1H),
and 1.91 m (1H) (Cl2C3H3); 2.84 d.d (1H, J = 6.6,
15.4 Hz) and 2.98 d.d (1H, J = 7.4, 15.4 Hz) (3′-CH2),
3.05 d.d.d (1H, 4-H, J = 1.4, 8.2, 17.6 Hz), 3.46 d.d.d
(1H, 4-H, J = 1.4, 10.7, 17.6 Hz), 5.54 d.d (1H, 5-H,
J = 8.2, 10.7 Hz), 7.22 s (1H, 3-H), 7.23–7.29 m (4H,
Harom). Found, %: C 57.31, 57.53; H 4.61, 4.73;
N 4.88, 5.01. C13H13Cl2NO. Calculated, %: C 57.80;
H 4.85; N 5.19.
3-(3-Bromophenyl)-3-hydroxypropanenitrile
(4c). Viscous oily material. IR spectrum, ν, cm–1: 3450
1
(OH), 2270 (CN). H NMR spectrum, δ, ppm: 2.73 d
(2H, CH2CN, J = 5.6 Hz), 3.78 br.s (1H, OH), 4.98 t
3
(1H, CHOH, J = 5.6 Hz), 7.25 t (1H, Harom, J =
3
7.8 Hz), 7.31 d (1H, Harom, J = 7.8 Hz), 7.45 d.d
4
3
(1H, Harom, J = 1.1, J = 7.8 Hz), 7.54 s (1H, Harom).
Found, %: C 47.38, 47.51; H 3.33, 3.44; N 6.17, 6.34.
C9H8BrNO. Calculated, %: C 47.82; H 3.57; N 6.20.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

MOCHALOV et al.
402
3-Hydroxy-3-(5,6,7,8-tetrahydronaphthalen-2-
117.1, 125.9, 128.8, 139.3, 141.2. Found, %: C 57.48,
57.57; H 4.61, 4.75; N 4.92, 5.03. C13H13Cl2NO. Cal-
culated, %: C 57.80; H 4.85; N 5.19.
yl)propanenitrile (4d). Viscous oily material. IR spec-
1
trum, ν, cm–1: 3465 (OH), 2273 (CN). H NMR spec-
trum, δ, ppm: 1.81 m (4H, 6′-H, 7′-H), 2.65 br.s (1H,
OH), 2.76 d (2H, CH2CN, J = 6.2 Hz), 2.78 m (4H,
5′-H, 8′-H), 4.98 t (1H, CHOH, J = 6.2 Hz), 7.08–
7.13 m (3H, Harom). Found, %: C 77.21, 77.36; H 7.19,
7.31; N 6.68, 6.87. C13H15NO. Calculated, %: C 77.58;
H 7.51; N 6.96.
3-{3-[(2,2-Dichlorocyclopropyl)methyl]phenyl}-
3-hydroxypropanenitrile (4i). Viscous oily material.
IR spectrum, ν, cm–1: 3455 (OH), 2278 (CN). 1H NMR
spectrum, δ, ppm: 1.28 m (1H), 1.71 m (1H), and
1.91 m (1H) (Cl2C3H3); 2.75 br.s (1H, OH), 2.77 d
(2H, CH2CN, J = 6.2 Hz), 2.84 d.d (1H, J = 6.6,
15.4 Hz) and 3.01 d.d (1H, J = 7.7, 15.4 Hz) (3′-CH2),
5.04 t (1H, CHOH, J = 6.2 Hz), 7.28 d (1H, Harom, 3J =
3-(9H-Fluoren-2-yl)-3-hydroxypropanenitrile
(4e). mp 118–119°C. IR spectrum, ν, cm–1: 3440 (OH),
3
1
7.6 Hz), 7.30 d (1H, Harom, J = 7.6 Hz), 7.33 s (1H,
2280 (CN). H NMR spectrum, δ, ppm: 2.54 br.s (1H,
3
H
arom), 7.38 t (1H, Harom, J = 7.8 Hz). Mass spectrum,
OH), 2.82 d.d (1H, J = 5.8, 11.2 Hz) and 2.84 d.d (1H,
J = 5.8, 11.2 Hz) (CH2CN), 3.92 s (2H, 9′-H), 5.13 t
(1H, CHOH, J = 5.8 Hz), 7.34 d.t (1H, Harom, 4J = 1.2,
m/z (Irel, %): 229 (4) [270 – CH3CN], 160 (84), 133
(100), 129 (32), 105 (67), 77 (34), 51 (26).
C13H13Cl2NO. Calculated: M 270.15.
3
3J = 7.8 Hz), 7.41 t (2H, Harom, J = 8.0 Hz), 7.57 d
(1H, Harom, 3J = 7.8 Hz), 7.60 s (1H, Harom), 7.80 d (2H,
Harom, 3J = 8.0 Hz). Found, %: C 81.11, 81.32; H 5.24,
5.34; N 5.52, 5.69. C16H13NO. Calculated, %: C 81.68;
H 5.57; N 5.95.
3-Hydroxy-4-phenylbutanenitrile (4j). Viscous
oily material. IR spectrum, ν, cm–1: 3450 (OH), 2275
1
(CN). H NMR spectrum, δ, ppm: 2.48 d.d (1H, J =
6.3, 16.6 Hz) and 2.54 d.d (1H, J = 4.9, 16.6 Hz)
(CH2CN), 2.70 br.s (1H, OH), 2.89 d (2H, CH2Ph, J =
3-Hydroxy-3-[4-(prop-2-en-1-yl)phenyl]propane-
3
6.7 Hz), 4.14 m (1H, CHOH), 7.23 d (2H, Harom, J =
nitrile (4f). Viscous oily material. IR spectrum, ν,
1
cm–1: 3460 (OH), 2276 (CN). H NMR spectrum, δ,
8.2 Hz), 7.26 m (1H, Harom), 7.34 m (2H, Harom).
Found, %: C 74.23, 74.34; H 6.69, 6.75; N 8.28, 8.44.
C10H11NO. Calculated, %: C 74.51; H 6.88; N 8.69.
ppm: 2.58 br.s (1H, OH), 2.77 d (2H, CH2CN, J =
5.8 Hz), 3.41 d (2H, CH2CH=CH2, J = 6.8 Hz), 5.03 t
(1H, CHOH, J = 5.8 Hz), 5.12 m (2H, CH=CH2),
3-Hydroxy-3-[4-(propan-2-yl)phenyl]butaneni-
3
trile (4k). Viscous oily material. IR spectrum, ν, cm–1:
5.91–6.01 m (1H, CH=CH2), 7.23 d (2H, Harom, J =
3
1
8.0 Hz), 7.34 d (2H, Harom, J = 8.0 Hz). Found, %:
3470 (OH), 2276 (CN). H NMR spectrum, δ, ppm:
C 76.63, 76.77; H 6.78, 6.83; N 7.19, 7.31. C12H13NO.
Calculated, %: C 76.98; H 7.00; N 7.48.
1.25 d [6H, CH(CH3)2, J = 7.2 Hz], 1.75 s (3H, CH3),
2.28 br.s (1H, OH), 2.78 d and 2.83 d (1H each,
CH2CN, J = 12.6 Hz), 2.91 sept [1H, CH(CH3)2],
7.24 d (2H, Harom, 3J = 7.8 Hz), 7.39 d (2H, Harom, 3J =
7.8 Hz). Found, %: C 76.48, 76.57; H 8.18, 8.31;
N 6.57, 6.81. C13H17NO. Calculated, %: C 76.81;
H 8.43; N 6.89.
3-[4-(Cyclopropylmethyl)phenyl]-3-hydroxypro-
panenitrile (4g). Viscous oily material. IR spectrum,
ν, cm–1: 3470 (OH), 2275 (CN). 1H NMR spectrum, δ,
ppm: 0.22 m (2H), 0.54 m (2H), and 0.99 m (1H)
(C3H5); 2.56 d (2H, 4′-CH2, J = 6.8 Hz), 2.67 br.s (1H,
OH), 2.75 d (1H, J = 6.2 Hz) and 2.77 d (1H, J =
6.6 Hz) (CH2CN), 5.02 d.d (1H, CHOH, J = 6.2,
2-Chloro-N-[4-(2-cyano-1-hydroxyethyl)phenyl]-
benzamide (4l). mp 116–118°C (from EtOH). IR spec-
6.6 Hz), 7.30 d (2H, Harom, J = 8.0 Hz), 7.32 d (2H,
trum, ν, cm–1: 3470 (OH), 2281 (CN). H NMR spec-
3
1
Harom, 3J = 8.0 Hz). Found, %: C 77.24, 77.33; H 7.22,
7.44; N 6.58, 6.76. C13H15NO. Calculated, %: C 77.58;
H 7.51; N 6.96.
trum, δ, ppm: 2.60 br.s (1H, OH), 2.79 d (2H, CH2CN,
J = 4.7 Hz), 5.06 t (1H, CHOH, J = 4.7 Hz), 7.41–
3
7.48 m (5H, Harom), 7.68 d (2H, Harom, J = 8.1 Hz),
3
7.76 d (1H, Harom, J = 7.8 Hz), 8.01 br.s (1H, NH).
3-{4-[(2,2-Dichlorocyclopropyl)methyl]phenyl}-
3-hydroxypropanenitrile (4h). Viscous oily material.
IR spectrum (film), ν, cm–1: 3437 (OH), 2253 (CN).
1H NMR spectrum, δ, ppm: 1.27 m (1H), 1.71 m (1H),
and 1.88 m (1H) (Cl2C3H3); 2.59 br.s (1H, OH), 2.77 d
(2H, CH2CN, J = 6.2 Hz), 2.84 d.d (1H, J = 6.2,
15.6 Hz) and 2.98 d.d (1H, J = 7.6, 15.6 Hz) (4′-CH2),
5.04 t (1H, CHOH, J = 6.2 Hz), 7.34 d (2H, Harom, 3J =
Found, %: C 64.21, 64.30; H 4.51, 4.54; N 9.25, 9.40.
C16H13ClN2O2. Calculated, %: C 63.90; H 4.36; N 9.31.
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