o-Acylbenzonitriles: Synthesis and Heterocyclization under Acid Hydrolysis of the Cyano Group

Article abstract of DOI:10.1134/S1070428018030065

2-Cyanobenzophenones were synthesized by reaction of 2-bromobenzophenones with copper(I) cyanide in DMF, and their transformations involving acid hydrolysis of the cyano group were studied. Reactions of o-benzoylbenzonitriles with trifluoroacetic acid in

Full text of DOI:10.1134/S1070428018030065

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 3, pp. 403–413. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © S.S. Mochalov, A.N. Fedotov, E.V. Trofimova, N.S. Zefirov, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 3,
pp. 399–408.
o-Acylbenzonitriles: Synthesis and Heterocyclization
under Acid Hydrolysis of the Cyano Group
S. S. Mochalov, A. N. Fedotov,* E. V. Trofimova, and N. S. Zefirov†
Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia
*e-mail: fed@org.chem.msu.ru
Received April 12, 2017
Abstract—2-Cyanobenzophenones were synthesized by reaction of 2-bromobenzophenones with copper(I)
cyanide in DMF, and their transformations involving acid hydrolysis of the cyano group were studied.
Reactions of o-benzoylbenzonitriles with trifluoroacetic acid in the presence or in the absence of sulfuric acid
afforded 3-hydroxyphthalimidines in high yields. Under analogous conditions, benzonitriles having no acyl
group in the ortho position were converted to the corresponding benzamides. 2-Cyanobenzophenones reacted
with sulfuric acid in the absence of trifluoroacetic acid to give only substituted anthraquinones.
DOI: 10.1134/S1070428018030065
We previously showed [1–3] that 2-cyclopropyl-
and 2-(prop-1-en-1-yl)benzamides under the condi-
tions ensuring generation of benzylic carbenium ions
from alkyl substituents are quantitatively converted to
3-ethylphthtalimidines (3-ethyl-2,3-dihydro-1H-isoin-
dol-1-ones). The latter are heterocyclic compounds
used as subjects for biological studies and intermediate
products for the synthesis of polyamides, pigments,
and dyes (Scheme 1).
cyano group to aminocarbonyl and of the acyl carbonyl
to hydroxy group. It is known that the reduction of
carbonyl compounds with NaBH4 does not affect
amide groups.
There are very scarce published data on o-acyl-
benzonitriles, and no general efficient methods for
their synthesis have been reported so far. We succeed-
ed in obtaining a series of 2-acylbenzonitriles by acyla-
tion of 6-bromo-1,4-benzodioxane (1) and 4-bromo-
1,2-dimethoxybenzene (2) or by benzoylation of
monosubstituted benzenes and 1,4-benzodioxane with
2-bromobenzoyl chloride (Schemes 2, 3), followed by
nucleophilic substitution of bromine by the action of
copper(I) cyanide in DMF (Rosenmund–von Braun
reaction; Scheme 4).
In order to extend the synthetic potential of this
heterocyclization of ortho-substituted benzamides, it
seemed important to develop approaches to benz-
amides containing other than cyclopropyl or propenyl
substituents in the ortho position, capable of generat-
ing benzylic carbenium ions under acidic conditions.
We believed that 2-carbamoyl-substituted benzyl
alcohols and benzhydrols would meet these require-
ments. Such benzamides can be synthesized, e.g., from
2-cyanoacylbenzenes by successive reduction of the
While studying the reaction of 2-bromo-substituted
acylbenzenes with CuCN in DMF, it was found that
nucleophilic substitution of the bromine atom was rela-
tively successful only for substrates lacking hydrogen
Scheme 1.
Et
Et
R
O
Me
NH2
H+
H2O
–H+
NH2
NH
NH2
X
X
X
X
O
O
O
R = cyclo-C3H5, MeCH=CH; X = H, Br, Et.
† Deceased.
403

MOCHALOV et al.
404
Scheme 2.
R3COCl
AlCl3, CCl4
R1
R2
Br
R1
Br
O
R3
R2
1, 2
3a–3g, 4
1, 3, R1R2 = OCH2CH2O; 3, R3 = Me (a), PhCH2 (b), cyclo-C3H5 (c), thiophen-2-yl (d), Ph (e), 4-MeC6H4 (f), 2-ClC6H4 (g);
2, 4, R1 = R2 = MeO; 4, R3 = 4-MeC6H4.
Scheme 3.
O
Br
R1
R2
COCl
Br
R1
R2
AlCl3, CCl4
+
5a–5e
6a–6e
R1 = R2 = H (a); R1 = H, R2 = Me (b), MeO (c), Br (d); R1R2 = OCH2CH2O (e).
Scheme 4.
O
O
R1
R2
R1
R2
CuCN, DMF
110°C, 12 h
R3
R3
Br
CN
3c–3g, 4, 6a–6e
7a–7k
7, R1R2 = OCH2CH2O, R3 = cyclo-C3H5 (a), thiophen-2-yl (b), Ph (c), 4-MeC6H4 (d), 2-ClC6H4 (e); R1 = R2 = MeO, R3 =
4-MeC6H4 (f); R1 = R2 = H, R3 = Ph (g), 4-MeC6H4 (h), 4-MeOC6H4 (i), 4-BrC6H4 (j), 1,4-benzodioxan-6-yl (k).
atoms in the α-position with respect to the carbonyl
group, namely for 2-bromobenzophenones 3d–3h, 4,
and 6a–6e and 2-bromophenyl(cyclopropyl)methanone
(3c). No desired benzonitriles were obtained under
these conditions from 7-acetyl- and 7-phenacyl-6-
bromo-1,4-benzodioxanes 3a and 3b, but only poly-
merization products were formed. Analogous result
was reported by Helberger [4] who attempted to syn-
thesize 2-cyanoacetophenone.
carbonyl group. Presumably, under the given condi-
tions cyanide ion acts as both nucleophile and base.
The mobility of the α-hydrogen atoms in 3a and 3b is
likely to be sufficient for cyanide ion to initiate
intermolecular condensation rather than nucleophilic
substitution of bromine. However, it cannot be ruled
out that the condensation processes initiated by
cyanide ions occur after the substitution of bromine by
cyano group. In this case, the condensation of cyano-
substituted acylbenzenes should be even more facile
than with bromides 3a and 3b since the cyano group in
the ortho position activates the α-hydrogen atoms to
The anomalous behavior of 3a and 3b in the
reaction with CuCN in DMF may be related to the
presence of hydrogen atoms in the α-position to the
Scheme 5.
CuCN, DMF
153°C, 12 h
O
O
O
Br
O
O
CN
1
8
O
CuCN, DMF
153°C, 12 h
O
O
Br
O
CN
O
9
10
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 3 2018

o-ACYLBENZONITRILES: SYNTHESIS AND HETEROCYCLIZATION
405
Scheme 6.
OC(O)CF3
O
H+
CF3COOH
–H+
H2O
R
CN
R
C
NH
R
R
–H+
–CF3COOH
NH
NH2
A
Scheme 7.
O
(1) CF3COOH–H2SO4 (4:1), 5 h, reflux
(2) H2O
O
CN
CN
O
O
NH2
O
O
8
11, 74%
O
O
(1) CF3COOH–H2SO4 (4:1), 5 h, reflux
(2) H2O
O
O
O
O
NH2
10
12, 70%
a greater extent than does bromine atom. Cyclopropyl
ketone 3c possesses a hydrogen atom in the α-position
with respect to the carbonyl group, but nevertheless
the bromine atom in 3c is replaced by cyano group.
Obviously, the acidity of the α-hydrogen atom in 3c
is insufficient to allow cyanide ion to initiate side
reactions.
reaction mixture was treated with water, so that the
hydrolysis to carboxylic acid was inhibited.
Taking into account the data of [5], we initially
studied the behavior of nitriles 8 and 10 containing no
acyl substituent in the ortho position with respect to
the cyano group and found that, in fact, compounds 8
and 10 under the given conditions were converted in
good yields to the corresponding amides 11 and 12
(Scheme 7). However, unlike nitriles 8 and 10,
2-cyanobenzophenones 7c and 7d reacted with
CF3COOH–H2SO4 (1:1) under reflux to give with high
yields 3-hydroxyphthalimidines 13b and 13c rather
than expected benzamides. Moreover, 2-cyanobenzo-
phenones 7b–7k readily underwent heterocyclization
to 13a–13j by the action of trifluoroacetic acid alone,
and (what is most important), this transformation
required no heating (Scheme 8, Table 1).
It was quite important that nucleophilic substitution
of the bromine atom in 2-bromobenzophenones 3c–3h,
4, and 6a–6e was significantly easier than in bromo-
benzenes having no carbonyl group in the ortho
position with respect to the bromine atom (Scheme 5).
Thus, the substitution of bromine by cyano group in 1
and 9 required elevated temperature (boiling DMF) as
compared to 2-acyl-1-bromobenzenes 3c–3h, 4, and
6a–6e (Schemes 4, 5); furthermore, in the reaction
with dibromo derivative 6d, only the bromine atom
neighboring to the benzoyl substituent was replaced by
cyano group.
As follows from the data in Table 1, the rate of
heterocyclization of 2-cyanobenzophenones strongly
depended on the substituents in the aromatic rings. The
Various benzamides are commonly synthesized by
hydrolysis of the cyano group in the corresponding
benzonitriles. This reaction generally requires careful
control of the conditions since the amide group is
prone to further hydrolysis to carboxy, especially under
acidic conditions. Moorthy and Singhal [5] reported
a convenient and efficient procedure for acid hydrol-
ysis of aliphatic and aromatic nitriles to amides by the
action of a mixture of trifluoroacetic and concentrated
sulfuric acids at a ratio of 4:1. The key stage in this
reaction was presumed to be the formation of a stable
product of addition of CF3COOH to the cyano group
(intermediate A in Scheme 6), which existed until the
Scheme 8.
OH
R3
R1
7b–7k
NH
R2
O
13a–13j
13, R1R2 = OCH2CH2O, R3 = thiophen-2-yl (a), Ph (b),
4-MeC6H4 (c), 2-ClC6H4 (d); R1 = R2 = MeO, R3
=
4-MeC6H4 (e); R1 = R2 = H, R3 = Ph (f), 4-Tol (g),
4-MeOC6H4 (h), 4-BrC6H4 (i), 1,4-benzodioxan-6-yl (j).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 3 2018

MOCHALOV et al.
406
Table 1. Yields of phthalimidines 13a–13j in the hetero-
cyclization of 2-cyanobenzofenones 7b–7k by the action of
trifluoroacetic acid
electron-donating substituents required a considerably
longer time to achieve even satisfactory yield of
3-hydroxyphthalimidines 13 (run nos. 4, 6, 9). These
findings, as well as milder conditions for the hydrol-
ysis of benzonitriles containing an acyl group in the
ortho position, may be rationalized by nucleophilic
assistance of the carbonyl fragment to the protonation
of the cyano group. This assumption makes clear why
nucleophilic assistance of the carbonyl group in benzo-
nitriles with electron-donating substituents is stronger
than in those containing no electron-donating groups.
Run no. Compound no. Reaction time, h
Yield, %
01
02
03
04
05
06
07
08
09
10
13a
13b
13c
13d
13e
13f
13g
13h
13i
01
01
01
16
01
16
05
01
16
01
96
82
86
44
87
59
76
92
64
71
Attempted hydrolysis of 2-cyanobenzophenones 7d
and 7k in concentrated sulfuric acid (without trifluoro-
acetic acid) afforded neither 3-hydroxyphthalimidines
nor benzamides, while the major products were the
corresponding anthraquinones 14 and 15 (Scheme 9).
It is quite obvious that in these reactions the initially
formed amide group is then converted to carboxy, and
o-benzoylbenzoic acid thus formed readily undergoes
cyclization by the action of concentrated sulfuric acid.
13j
reactions of alkoxy-substituted 2-acylbenzonitriles 7b–
7d, 7f, 7i, and 7k with CF3COOH were complete in
1 h to afford heterocyclization products in high yields
(run nos. 1–3, 5, 8, 10), whereas analogous transforma-
tion of benzonitriles 7e, 7g, and 7j lacking strong
Taking into consideration that the “hydrolysis–
heterocyclization” of 2-cyanobenzophenones requires
Scheme 9.
O
O
(1) H2SO4, 100–120°C
(2) H2O
O
O
O
O
CN
Me
Me
O
14
O
7d
O
(1) H2SO4, 100–120°C
(2) H2O
O
O
O
O
NC
O
7h
15
Scheme 10.
R3
C
O
R3
R1
R2
R1
R1
R2
:
R3
NH
CF3COOH
O
O
R2
CF3COO–
NH
N
OCOCF3
A
B
C
HO
HO
R3
N
R3
NH
R1
R2
R1
~H+
H2O
–CF3COOH
R2
OCOCF3
O
D
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o-ACYLBENZONITRILES: SYNTHESIS AND HETEROCYCLIZATION
407
Scheme 11.
O
O
O
O
O
O
R2OH, H+
NH
NH
HO
R2O
R1
R1
13b, 13c
16a, 16b, 17a, 17b
16, R1 = H, R2 = Et (a), i-Pr (b); 17, R1 = Me, R2 = Et (a), PhCH2 (b).
Scheme 12.
O
:
O
O
O
O
O
O
HCOOH
O
O
NH
C
HCOO–
N
NH
OC(O)H
7a
E
F
HO
HO
O
O
O
O
O
O
H+
–H+
H+
H2O
–HCOOH
N
NH
NH
–H2O
OC(O)H
O
O
G
18
H
O
H
O
O
HCOOH
NH
O
O
19, 68%
the presence of trifluoroacetic acid, as well as the data
of [5], a probable scheme of the formation of 3-hy-
droxyphthalimidines from o-acylbenzonitriles is out-
lined in Scheme 10. This scheme rationalizes both low
reactivity of 7e and relatively low yield of 13d (run
no. 4). Presumably, the reason is difficult formation of
cyclic intermediate D from adduct C due to steric
effect of the ortho-chlorine atom in the R3 substituent
on the interaction of the imino nitrogen atom with the
carbonyl group in C.
The structure of previously unknown 3-hydroxy-
phthalimidines was confirmed by physicochemical
methods, as well as by alkylation of the hydroxy group
in 13b and 13c (Scheme 11).
Under the above conditions, cyclopropyl ketone 7a
was converted to a complex mixture of products
resulting from transformations of the cyano group and
cyclopropane fragment, and we failed to isolate indi-
vidual compounds from that mixture. On the other
hand, nitrile 7a underwent heterocyclization to phthal-
imidine derivative by the action of formic acid (reflux,
1 h) which is weaker than trifluoroacetic acid. In this
case, the final product was not 3-hydroxy-3-cyclo-
propylphthalimidine 18 (Scheme 12) but compound 19
which was formed via subsequent acid-catalyzed open-
ing of the cyclopropane ring. Since the transformation
of 7a in formic acid was as facile as the reactions of
7b–7k with trifluoroacetic acid, it should be assumed
that formic acid is also capable of adding to cyano
group with formation of stable adduct F (Scheme 12)
which is analogous to adduct C with CF3COOH
(Scheme 10) responsible for the formation of amide
fragment.
The acid-catalyzed transformation of compound 18
is likely to be facilitated by easy generation therefrom
of carbenium ion H (Scheme 12); the small ring in the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 3 2018

MOCHALOV et al.
CHN analyzer. The melting points were measured on
408
2.3%
10.0%
3.9%
an Electrothermal model 1A9100 digital melting point
apparatus. The products were isolated, and their purity
was checked, by column and thin-layer chromatog-
raphy on Al2O3 (Brockmann activity grade II) using
diethyl ether–methylene chloride–petroleum ether at
different ratios as eluent.
4.1%
7.0%
O
H
H
H2
C
O
H
H
C
H2
2.8%
3.5%
O
O
7.4%
NH
2-Bromoacylbenzenes 3a–3g, 4, and 9 were synthe-
sized by acylation of 6-bromo-1,4-benzodioxane (1)
and 4-bromo-1,2-dimethoxybenzene (2) with the corre-
sponding carboxylic acid chlorides. Compounds 6a–6e
were prepared by benzoylation of benzene, toluene,
anisole, bromobenzene, and 1,4-benzodioxane 5a–5e
according to the procedure described in [9]. Com-
pounds 3a (yield 69%) [10], 3c (74%), 3f (76%) [11],
6b (71%) [12, 13], 6c (82%) [14], and 6e (81%) [15]
were reported previously.
O
19
Fig. 1. Nuclear Overhauser effects in the molecule of phthal-
imidine 19.
latter readily isomerizes to open-chain structure which
takes up an external nucleophile in the final stage.
Analogous isomerizations have been reported previ-
ously [6, 7]. The Z configuration of the exocyclic C=C
double bond in 19 was confirmed by measuring
nuclear Overhauser effects (Fig. 1).
1-(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)-
2-phenylethanone (3b). Yield 84%, mp 145–146°C
1
(from EtOH–CHCl3). H NMR spectrum (CDCl3), δ,
Due to ring–chain tautomerism, 2-acylbenzamides
and 3-hydroxyphthalimidines can exist as individual
tautomers or their equilibrium mixtures. According to
the 1H NMR data (see Experimental), compounds 13a–
13j in solution are individual 3-hydroxyphthal-
imidines. The structure of 5,6-ethylenedioxy-3-hy-
droxy-3-phenylphthalimidine 13b in crystal was
determined by X-ray analysis [8]. Thus, it was found
that compound 13b has cyclic structure both in crystal
and in solution.
ppm: 4.24–4.29 m (6H, CH2Ph, OCH2CH2O), 7.05 s
(1H, Harom), 7.13 s (1H, Harom), 7.27 m (3H, Harom),
7.33 m (2H, Harom). Found, %: C 57.73, 57.64; H 3.88,
3.76. C16H13BrO3. Calculated, %: C 57.68; H 3.93.
(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)-
cyclopropylmethanone (3c). Yield 72%, mp 61–62°C
1
(purified by chromatography). H NMR spectrum
(CDCl3), δ, ppm: 1.08 m (2H), 1.28 m (2H), and
2.47 m (1H) (C3H5); 4.29 m (4H, OCH2CH2O), 7.13 s
(2H, Harom). Found, %: C 51.13, 51.21; H 3.71, 3.77.
C12H11BrO3. Calculated, %: C 50.91; H 3.92.
The obtained results allowed us to draw two main
conclusions. First, 2-acylbenzonitriles cannot be con-
verted into the corresponding 2-acylbenzamides despite
favorable acid hydrolysis conditions [5]. Second, the
observed heterocyclization of 2-cyanobenzophenones
in trifluoroacetic or formic acid can be regarded as
a new effective method of synthesis of 3-hydroxy-
phthalimidines.
(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)-
(thiophen-2-yl)methanone (3d). Yield 76%, mp 111–
112°C (from EtOH). 1H NMR spectrum (DMSO-d6), δ,
ppm: 4.32 m (4H, OCH2CH2O), 7.13 s (1H, Harom),
7.25 m (2H, Harom, HTh), 7.48 d (1H, HTh, J = 4.2 Hz),
8.14 d (1H, HTh, J = 4.6 Hz). Found, %: C 47.74,
47.86; H 2.61, 2.74. C13H9BrO3S. Calculated, %:
C 48.02; H 2.79.
EXPERIMENTAL
(7-Bromo-2,3-dihydro-1,4-benzodioxin-6-yl)-
The NMR spectra were recorded on Bruker DRX-
500 (500.13 MHz, 1H) and Varian VXR-400 spectrom-
eters [400.13 (1H), 100.61 MHz (13C)] using CDCl3 as
solvent and reference or DMSO-d6 as solvent and
tetramethylsilane as internal standard. The IR spectra
were recorded on a UR-20 instrument from samples
dispersed in mineral oil or hexachlorobutadiene. The
mass spectra (electron impact, 70 eV) were obtained
on a Finnigan MAT INCOS-50 instrument. The ele-
mental compositions were determined with a Varian-11
(2-chlorophenyl)methanone (3g). Yield 79%,
1
mp 106–108°C (from EtOH–CHCl3). H NMR spec-
trum (DMSO-d6), δ, ppm: 4.33 m (4H, OCH2CH2O),
6.98 s (1H, Harom), 7.26 s (1H, Harom), 7.48 m (2H,
Harom), 7.53 m (2H, Harom). Found, %: C 51.12, 51.23;
H 2.67, 2.74. C15H10BrClO3. Calculated, %: C 50.95;
H 2.85.
(2-Bromo-4,5-dimethoxyphenyl)(4-methyl-
phenyl)methanone (4). Yield 52%, mp 90–91°C
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o-ACYLBENZONITRILES: SYNTHESIS AND HETEROCYCLIZATION
409
1
(from EtOH). H NMR spectrum (CDCl3), δ, ppm:
7-Benzoyl-2,3-dihydro-1,4-benzodioxine-6-
carbonitrile (7c). Yield 62%, mp 208–209°C (from
DMF). IR spectrum, ν, cm–1: 2240 (CN), 1660 (C=O).
1H NMR spectrum (DMSO-d6), δ, ppm: 4.38 m (4H,
OCH2CH2O), 7.16 s (1H, Harom), 7.53–7.59 m (2H,
Harom), 7.60 s (1H, Harom), 7.68–7.76 m (3H, Harom).
Found, %: C 72.07, 72.16; H 4.18, 4.21; N 5.16, 5.28.
C16H11NO3. Calculated, %: C 72.45; H 4.46; N 5.18.
2.44 s (3H, CH3), 3.86 s (3H, OCH3), 3.95 s (3H,
OCH3), 6.89 s (1H, Harom), 7.09 s (1H, Harom), 7.28 d
(2H, Harom, J = 8.2 Hz), 7.73 d (2H, Harom, J = 8.2 Hz).
Found, %: C 57.02, 57.09; H 4.31, 4.43. C16H15BrO3.
Calculated, %: C 57.33; H 4.51.
(2-Bromophenyl)(4-bromophenyl)methanone
(6d). Yield 74%, mp 66°C (from EtOH). 1H NMR spec-
trum (CDCl3), δ, ppm: 7.34–7.47 m (3H, Harom), 7.61–
7.70 m (5H, Harom). Found, %: C 45.63, 45.76; H 2.17,
2.24. C13H8Br2O. Calculated, %: C 45.92; H 2.37.
7-(4-Methylbenzoyl)-2,3-dihydro-1,4-benzodi-
oxine-6-carbonitrile (7d). Yield 63%, mp 195–196°C
(from EtOH–DMF). IR spectrum, ν, cm–1: 2240 (CN),
1
1662 (C=O). H NMR spectrum (DMSO-d6), δ, ppm:
Benzonitriles 7a–7k and 10 (general procedure).
A mixture of 0.01 mol bromo derivative 3c–3g, 4, 6a–
6e, or 9 and 0.015 mol of CuCN in 5 mL of DMF was
heated to 110–120°C (or 153°C) and was stirred for
12 h. The mixture was cooled and poured into a solu-
tion of 6 g of FeCl3·6H2O and 1.5 mL of aqueous HCl
in 10 mL of water, the resulting mixture was stirred for
0.5 h at 70–90°C and cooled to room temperature, and
the precipitate was filtered off, washed with water, and
recrystallized from appropriate solvent. Oily com-
pounds were extracted with chloroform, the extract
was evaporated, and the residue was purified by
chromatography on an Al2O3 plate. Compounds 7g
(yield 36%) and 8 (yield 62%) were described
previously [16, 17].
2.41 s (3H, CH3), 4.39 m (4H, OCH2CH2O), 7.15 s
(1H, Harom), 7.38 d (2H, Harom, J = 8.1 Hz), 7.60 s (1H,
Harom), 7.66 d (2H, Harom, J = 8.1 Hz). Found, %:
C 72.86, 73.01; H 4.51, 4.68; N 4.74, 4.88. C17H13NO3.
Calculated, %: C 73.11; H 4.69; N 5.01.
7-(2-Chlorobenzoyl)-2,3-dihydro-1,4-benzodi-
oxine-6-carbonitrile (7e). Yield 78%, mp 143–144°C
(from EtOH–DMF). IR spectrum: ν 2244 cm–1 (CN).
1H NMR spectrum (DMSO-d6), δ, ppm: 4.38 m (4H,
OCH2CH2O), 6.97 s (1H, Harom), 7.49–7.64 m (5H,
H
arom). Found, %: C 63.91, 64.03; H 3.15, 3.26;
N 4.42, 4.55. C16H10ClNO3. Calculated, %: C 64.12;
H 3.36; N 4.67.
4,5-Dimethoxy-2-(4-methylbenzoyl)benzonitrile
(7f). Yield 54%, mp 102–103°C (from EtOH).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.41 s (3H,
CH3), 3.83 s (3H, OCH3), 3.91 s (3H, OCH3), 7.22 s
(1H, Harom), 7.39 d (2H, Harom, J = 8.1 Hz), 7.60 s (1H,
7-(Cyclopropylcarbonyl)-2,3-dihydro-1,4-benzo-
dioxine-6-carbonitrile (7a). Yield 34%, mp 184–
1
185°C (from EtOH). H NMR spectrum (DMSO-d6),
δ, ppm: 1.06 m (4H) and 2.51 m (1H) (C3H5), 4.40 m
H
arom), 7.70 d (2H, Harom, J = 8.1 Hz). Mass spectrum,
(4H, OCH2CH2O), 7.52 s (1H, Harom), 7.82 s (1H,
m/z (Irel, %): 281 (30) [M]+, 266 (10), 250 (12), 190
(16), 119 (100), 104 (10), 91 (61), 76 (9), 65 (31), 51
(8), 39 (18). Found, %: C 72.21, 72.33; H 5.11, 5.22;
N 4.78, 4.90. C17H15NO3. Calculated, %: C 72.58;
H 5.37; N 4.98. M 281.32.
H
arom). Mass spectrum, m/z (Irel, %): 229 (75) [M]+, 200
(6), 188 (100), 162 (11), 160 (6), 145 (11), 132 (22),
117 (7), 104 (29), 88 (13), 76 (34), 69 (33), 50 (15), 41
(49), 39 (49). Found, %: C 67.81, 67.92; H 4.65, 4.71;
N 5.88, 6.03. C13H11NO3. Calculated, %: C 68.11;
H 4.84; N 6.11. M 229.24.
2-(4-Methylbenzoyl)benzonitrile (7h). Yield 42%,
1
mp 110–111°C (from EtOH). H NMR spectrum
7-(Thiophen-2-ylcarbonyl)-2,3-dihydro-1,4-ben-
(CDCl3), δ, ppm: 2.46 s (3H, CH3), 7.31 d (2H, Harom
,
zodioxine-6-carbonitrile (7b). Yield 52%, mp 198–
1
J = 7.9 Hz), 7.64–7.74 m (5H, Harom), 7.81 d (1H,
199°C (from EtOH–CHCl3). H NMR spectrum
H
arom, J = 7.3 Hz). Mass spectrum, m/z (Irel, %): 221
(DMSO-d6), δ, ppm: 4.41 m (4H, OCH2CH2O),
7.33 d.d (1H, HTh, J = 4.9, 3.8 Hz), 7.42 s (1H, Harom),
7.62 s (1H, Harom), 7.67 d.d (1H, HTh, J = 3.8, 1.1 Hz),
8.20 d.d (1H, HTh, J = 4.9, 1.1 Hz). Mass spectrum,
m/z (Irel, %): 271 (55) [M]+, 243 (22), 229 (31), 215
(12), 188 (23), 162 (17), 159 (10), 134 (14), 132 (11),
111 (100), 104 (14), 88 (10), 83 (22), 50 (15), 45 (13),
39 (84). Found, %: C 61.71, 61.96; H 3.28, 3.38;
N 5.02, 5.11. C14H9NO3S. Calculated, %: C 61.98;
H 3.34; N 5.16. M 271.30.
(18) [M]+, 206 (19), 130 (19), 119 (100), 102 (40), 91
(74), 75 (28), 65 (70), 51 (35), 39 (48). Found, %:
C 81.54, 81.66; H 5.13, 5.24; N 6.09, 6.17. C15H11NO.
Calculated, %: C 81.43; H 5.01; N 6.33. M 221.25.
2-(4-Methoxybenzoyl)benzonitrile (7i). Yield
46%, mp 63–64°C (from EtOH). IR spectrum, ν, cm–1:
1
2235 (CN), 1660 (C=O). H NMR spectrum (CDCl3),
δ, ppm: 3.98 s (3H, OCH3), 6.08 d (2H, Harom, J =
8.6 Hz), 7.62–7.72 m (3H, Harom), 7.81–7.84 m (3H,
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MOCHALOV et al.
7.3, 4J = 1.3 Hz), 7.24–7.27 m (2H, Harom), 7.57 m (1H,
410
Harom). Found, %: C 75.63, 75.78; H 4.92, 5.11;
N 5.78, 5.93. C15H11NO2. Calculated, %: C 75.93;
H 4.67; N 5.91.
Harom), 7.78 m (1H, Harom), 8.12 m (2H, Harom),
7.40 br.s and 8.18 br.s (1H each, NH2). Mass spectrum,
m/z (Irel, %): 283 (47) [M]+, 239 (6), 163 (100), 148
(14), 135 (20), 126 (9), 107 (25), 92 (11), 79 (23), 65
(12), 51 (36), 44 (23). Found, %: C 67.61, 67.76;
H 4.32, 4.45; N 4.69, 4.72. C16H13NO4. Calculated, %:
C 67.84; H 4.63; N 4.94. M 283.29.
2-(4-Bromobenzoyl)benzonitrile (7j). Yield 45%,
mp 140–141°C (from EtOH). IR spectrum, ν, cm–1:
2238 (CN), 1660 (C=O). Mass spectrum, m/z (Irel, %):
285 (7) [M]+, 206 (45), 183 (44), 155 (33), 130 (48),
102 (66), 89 (9), 75 (100), 62 (11), 50 (78), 39 (18).
Found, %: C 58.51, 58.62; H 2.63, 2.78; N 4.66, 4.74.
C14H8BrNO. Calculated, %: C 58.77; H 2.82; N 4.90.
M 286.12.
8-Hydroxy-8-phenyl-2,3,7,8-tetrahydro-6H-
[1,4]dioxino[2,3-f]isoindol-6-one (13b). mp 212–
213°C (from acetone). 1H NMR spectrum (DMSO-d6),
δ, ppm: 4.24 m (4H, OCH2CH2O), 6.70 s (1H, Harom),
2-[(2,3-Dihydro-1,4-benzodioxin-6-yl)carbonyl]-
benzonitrile (7k). Yield 47%, mp 139–140°C (from
6.80 s (1H, OH), 7.05 s (1H, Harom), 7.27 t (1H, Harom
,
1
J = 7.2 Hz), 7.33 t (2H, Harom, J = 7.2 Hz), 7.45 d (2H,
Harom, J = 7.4 Hz), 9.07 s (1H, NH). Mass spectrum,
m/z (Irel, %): 283 (7) [M]+, 265 (100), 237 (49), 223
(42), 209 (15), 206 (18), 188 (25), 181 (16), 162 (70),
153 (21), 149 (7), 134 (92), 119 (10), 105 (21), 77
(28), 62 (12), 58 (8), 50 (80), 43 (36), 39 (8). Found,
%: C 67.55, 67.69; H 4.41, 4.48; N 4.72, 4.81.
C16H13NO4. Calculated, %: C 67.84; H 4.63; N 4.94.
M 283.26.
EtOH–CHCl3). H NMR spectrum (CDCl3), δ, ppm:
4.34 m (4H, OCH2CH2O), 7.04 d (1H, Harom, J =
8.2 Hz), 7.24–7.28 m (2H, Harom), 7.70 d.d (1H, Harom
,
3J = 7.6, J = 1.2 Hz). 7.77–7.86 m (2H, Harom),
4
3
4
8.05 d.d (1H, Harom, J = 7.7, J = 1.3 Hz). Mass spec-
trum, m/z (Irel, %): 265 (70) [M]+, 223 (31), 163 (100),
153 (8), 135 (10), 130 (14), 107 (12), 102 (15), 79
(13), 75 (7), 51 (20). Found, %: C 72.31, 72.46;
H 4.28, 4.34; N 5.17, 5.08. C16H11NO3. Calculated, %:
C 72.45; H 4.18; N 5.28. M 265.28.
8-Hydroxy-8-(4-methylphenyl)-2,3,7,8-tetra-
hydro-6H-[1,4]dioxino[2,3-f]isoindol-6-one (13c).
mp 172–174°C (from acetone–petroleum ether).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.27 s (3H,
CH3), 4.24 m (4H, OCH2CH2O), 6.67 s (1H, Harom),
3-[(2,3-Dihydro-1,4-benzodioxin-6-yl)carbonyl]-
benzonitrile (10). Yield 57%, mp 106–107°C (from
EtOH–CHCl3). H NMR spectrum (DMSO-d6), δ,
1
ppm: 4.34 m (4H, OCH2CH2O), 7.04 d.d (1H, Harom
,
3J = 7.8, J = 1.8 Hz), 7.28 m (2H, Harom), 7.75 t (1H,
4
6.72 s (1H, OH), 7.03 s (1H, Harom), 7.13 d (2H, Harom
,
J = 7.9 Hz), 7.32 d (2H, Harom, J = 7.9 Hz), 9.01 s (1H,
NH). Mass spectrum, m/z (Irel, %): 297 (19) [M]+, 279
(100), 264 (78), 251 (35), 237 (47), 223 (11), 206 (35),
195 (14), 188 (40), 162 (52), 139 (10), 134 (75), 119
(66), 104 (9), 91 (25), 78 (21), 65 (15), 50 (58), 39
(12). Found, %: C 68.18, 68.32; H 5.14, 5.21; N 4.54,
4.61. C17H15NO4. Calculated, %: C 68.67; H 5.09;
N 4.71. M 297.30.
H
arom, J = 7.8 Hz), 7.97 m (1H, Harom), 8.08 m (1H,
arom), 8.11 m (1H, Harom). Mass spectrum, m/z
H
(Irel, %): 265 (33) [M]+, 163 (100), 153 (10), 130 (15),
107 (18), 102 (28), 79 (21), 75 (15), 63 (8), 51 (42).
Found, %: C 72.41, 72.61; H 4.11, 4.32; N 5.04, 5.16.
C16H11NO3. Calculated, %: C 72.45; H 4.18; N 5.28.
M 265.28.
Transformations of benzonitriles 7c, 7d, 8, and
10 in CF3COOH–H2SO4 (general procedure). A solu-
tion of 3.5 mmol of 7c, 7d, 8, or 10 in a mixture of
1 mL of concentrated sulfuric acid and 4 mL of
trifluoroacetic acid was refluxed for 5 h. The mixture
was poured into a mixture of 35 mL of water and 35 g
of ice, and the precipitate was filtered off, washed with
water, and dried in air. If necessary, the product was
recrystallized from an appropriate solvent. Compound
11 was described previously [17]. The yields of 13b
and 13c are given in Table 1.
Transformations of 2-acylbenzonitriles 7b–7k in
trifluoroacetic acid (general procedure). A solution of
3.5 mmol of nitrile 7b–7k in 5 mL of trifluoroacetic
acid was stirred at 20°C for a time indicated in Table 1.
The mixture was poured into a mixture of 35 mL of
water and 35 g of ice, and the precipitate was filtered
off, washed with water until neutral washings, and
recrystallized from an appropriate solvent. The yields
of 13a–13j are given in Table 1. Compound 13f was
1
described in [18]. The H NMR spectra of 3-hydroxy-
phthalimidines 13a–13j were recorded in DMSO-d6.
All compounds 13a–13j melted with decomposition.
3-[(2,3-Dihydro-1,4-benzodioxin-6-yl)carbonyl]-
benzamide (12). mp 133–134°C (from toluene–
1
CHCl3). H NMR spectrum (DMSO-d6), δ, ppm:
8-Hydroxy-8-(thiophen-2-yl)-2,3,7,8-tetrahydro-
6H-[1,4]dioxino[2,3-f]isoindol-6-one (13a). mp 185–
3
4.29 m (4H, OCH2CH2O), 6.98 d.d (1H, Harom, J =
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o-ACYLBENZONITRILES: SYNTHESIS AND HETEROCYCLIZATION
411
1
186°C (from acetone). H NMR spectrum, δ, ppm:
4.26 m (4H, OCH2CH2O), 6.83 s (1H, Harom), 6.94 m
(1H, HTh), 6.97 d.d (1H, HTh, J = 3.6, 1.3 Hz), 7.01 br.s
(1H, OH), 7.04 s (1H, Harom), 7.42 d.d (1H, HTh, J =
5.0, 1.3 Hz), 9.24 s (1H, NH). Mass spectrum, m/z
(Irel, %): 289 (93) [M]+, 272 (100), 256 (30), 206 (18),
188 (40), 162 (13), 134 (32), 111 (98), 104 (10), 83
(22), 78 (18), 69 (13), 62 (18), 57 (19), 50 (98), 44
(58), 39 (95). Found, %: C 57.93, 58.05; H 3.48, 3.56;
N 4.57, 4.71. C14H11NO4S. Calculated, %: C 58.12;
H 3.83; N 4.84. M 289.04.
C15H13NO3. Calculated, %: C 70.58; H 5.13; N 5.49.
M 255.09.
3-(4-Bromophenyl)-3-hydroxy-2,3-dihydro-1H-
isoindol-1-one (13i). mp 214–215°C (from benzene).
1H NMR spectrum, δ, ppm: 7.01 s (1H, OH), 7.39 d
3
(1H, Harom, J = 7.5 Hz), 7.41 m (2H, Harom), 7.49 m
(1H, Harom), 7.52–7.56 m (3H, Harom), 7.63 d (1H,
3
H
arom, J = 7.4 Hz), 9.28 s (1H, NH). Mass spectrum,
m/z (Irel, %): 305 (16) [M]+, 285 (18), 183 (10), 155
(12), 148 (100), 130 (86), 102 (37), 76 (80), 65 (14),
50 (68), 44 (16), 39 (13). Found, %: C 54.98, 55.11;
H 3.12, 3.16; N 4.69, 4.52. C14H10BrNO2. Calculated,
%: C 55.29; H 3.31; N 4.61. M 304.14.
8-(2-Chlorophenyl)-8-hydroxy-2,3,7,8-tetrahy-
dro-6H-[1,4]dioxino[2,3-f]isoindol-6-one (13d).
1
mp 197–199°C (from MeCN). H NMR spectrum, δ,
3-(1,4-Benzodioxin-6-yl)-3-hydroxy-2,3-dihydro-
ppm: 4.26 m (4H, OCH2CH2O), 6.53 s (1H, OH),
6.90 s (1H, Harom), 7.06 s (1H, Harom), 7.31 d.d (1H,
1H-isoindol-1-one (13j). mp 150–152°C (from ben-
1
zene). H NMR spectrum, δ, ppm: 4.21 m (4H,
3
4
OCH2CH2O), 6.19 d (1H, Harom, 3J = 8.5 Hz), 6.82 br.s
H
arom, J = 7.8, J = 1.5 Hz), 7.35 m (1H, Har4om),
3
3
4
7.42 m (1H, Harom), 8.16 d.d (1H, Harom, J = 7.9, J =
1.6 Hz), 8.89 s (1H, NH). Mass spectrum, m/z (Irel, %):
317 (48) [M]+, 300 (100), 282 (33), 206 (57), 188 (56),
162 (10), 139 (18), 111 (19), 75 (27), 50 (41), 44 (15).
Found, %: C 60.21, 60.38; H 3.62, 3.74; N 4.32, 4.55.
C16H12ClNO4. Calculated, %: C 60.48; H 3.51; N 4.41.
M 317.72.
(1H, OH), 6.86 d.d (1H, Harom, J = 8.5, J = 2.1 Hz),
6.94 d (1H, Harom, 4J = 2.1 Hz), 7.31 d (1H, Harom, 3J =
7.5 Hz), 7.44–7.55 m (2H, Harom), 7.62 d (1H, Harom
,
3J = 7.4 Hz), 9.88 s (1H, NH). Mass spectrum, m/z
(Irel, %): 283 (41) [M]+, 266 (68), 223 (49), 163 (93),
153 (29), 148 (17), 135 (14), 130 (77), 126 (18), 107
(26), 102 (44), 76 (100), 63 (26), 51 (93), 44 (20), 40
(21). Found, %: C 67.68, 67.56; H 4.42, 4.51; N 5.03,
5.11. C16H13NO4. Calculated, %: C 67.84; H 4.63;
N 4.94. M 283.29.
3-Hydroxy-5,6-dimethoxy-3-(4-methylphenyl)-
2,3-dihydro-1H-isoindol-1-one (13e). mp 198–199°C
(from MeCN). 1H NMR spectrum, δ, ppm: 2.27 s (3H,
CH3), 3.72 s (3H, OCH3), 3.82 s (3H, OCH3), 6.69 br.s
(1H, OH), 6.77 s (1H, Harom), 7.13 m (3H, Harom),
Transformations of 2-acylbenzonitriles 7d and
7k by the action of sulfuric acid (general procedure).
A solution of 3.5 mmol of 7d or 7k in 5 mL of
concentrated sulfuric acid was stirred for 5 h at 110–
120°C. The mixture was cooled and poured into
a mixture of 35 mL of water and 35 g of ice, and the
precipitate was filtered off, washed with water until
neutral washings, dried in air, and recrystallized from
chloroform.
3
7.34 d (2H, Harom, J = 7.9 Hz), 8.92 s (1H, NH).
Found, %: C 68.04, 68.21; H 5.58, 5.70; N 4.61, 4.68.
C17H17NO4. Calculated, %: C 68.21; H 5.72; N 4.51.
3-Hydroxy-3-(4-methylphenyl)-2,3-dihydro-1H-
isoindol-1-one (13g). mp 177–178°C (from MeCN).
1H NMR spectrum, δ, ppm: 2.32 m (3H, CH3), 6.63 s
3
(1H, OH), 7.09 d (2H, Harom, J = 7.8 Hz), 7.25 d (1H,
3
H
arom, J = 7.2 Hz), 7.37–7.49 m (4H, Harom), 7.61 d
8-Methyl-2,3-dihydroanthra[2,3-b][1,4]dioxine-
6,11-dione (14). Yield 62%, mp 253–254°C. H NMR
spectrum (CDCl3), δ, ppm: 2.53 s (3H, CH3), 4.40 m
3
1
(1H, Harom, J = 7.2 Hz), 8.97 s (1H, NH). Found, %:
C 75.03, 75.31; H 5.27, 5.33. C15H13NO2. Calculated,
%: C 75.30; H 5.48.
3
4
(4H, OCH2CH2O), 7.56 d.d (1H, Harom, J = 7.7, J =
0.8 Hz), 7.76 s (2H, Harom), 8.07 d (1H, Harom, J =
0.8 Hz), 8.17 d (1H, Harom, J = 7.7 Hz). Mass spectrum,
m/z (Irel, %): 280 (75) [M]+, 265 (6), 224 (16), 196
(15), 181 (10), 168 (61), 152 (10), 139 (100), 126 (15),
113 (8), 89 (77), 75 (19), 63 (67), 50 (69), 44 (18),
39 (36). Found, %: C 72.56, 72.68; H 4.16, 4.29.
C17H12O4. Calculated, %: C 72.85; H 4.32. M 280.28.
3-Hydroxy-3-(4-methylphenyl)-2,3-dihydro-1H-
isoindol-1-one (13h). mp 162–163°C (from benzene).
1H NMR spectrum, δ, ppm: 3.76 s (3H, OCH3), 6.61 s
3
(1H, OH), 6.82 d (2H, Harom, J = 8.6 Hz), 7.26 d (1H,
3
Harom, J = 7.6 Hz), 7.39–7.49 m (4H, Harom), 7.61 d
3
(1H, Harom, J = 7.4 Hz), 8.97 s (1H, NH). Mass spec-
trum, m/z (Irel, %): 255 (30) [M]+, 238 (58), 195 (12),
148 (28), 139 (12), 135 (100), 130 (84), 102 (33), 92
(28), 77 (59), 63 (31), 50 (40), 44 (27), 39 (24). Found,
%: C 70.65, 70.31; H 5.35, 5.21; N 5.08, 5.21.
2,3-Dihydroanthra[2,3-b][1,4]dioxine-6,11-dione
(15). Yield 56%, mp 298–299°C (from CDCl3).
1H NMR spectrum (CDCl3), δ, ppm: 4.41 m (4H,
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MOCHALOV et al.
412
OCH2CH2O), 7.77 m (4H, Harom), 8.28 m (2H, Harom).
Mass spectrum, m/z (Irel, %): 266 (100) [M]+, 251 (14),
238 (9), 210 (32), 182 (27), 154 (51), 138 (10), 126
(76), 104 (40), 99 (10), 87 (12), 76 (63), 62 (19), 50
(84), 43 (15), 39 (14). Found, %: C 71.98, 72.06;
H 3.61, 3.82. C16H10O4. Calculated, %: C 72.12;
H 3.79. M 266.26.
133 (16), 119 (7), 91 (13), 65 (7), 50 (9). Found, %:
C 69.91, 70.08; H 5.68, 5.82; N 4.13, 4.19. C19H19NO4.
Calculated, %: C 70.14; H 5.89; N 4.30. M 325.37.
8-(Benzyloxy)-8-(4-methylphenyl)-2,3,7,8-tetra-
hydro-6H-[1,4]dioxino[2,3-f]isoindol-6-one (17b).
Yield 61%, mp 174–175°C (from PhCH2OH).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.30 s (3H,
CH3), 4.10 d and 4.40 d (1H each, PhCH2, J =
11.6 Hz); 4.26 m (4H, OCH2CH2O), 6.85 s (1H, Harom),
7.13 s (1H, Harom), 7.19 d (2H, Harom, J = 8.0 Hz),
7.25–7.35 m (5H, Harom), 7.43 d (2H, Harom, J =
8.0 Hz), 9.24 s (1H, NH). Mass spectrum, m/z (Irel, %):
387 (18) [M]+, 280 (100), 266 (9), 253 (7), 224 (18),
188 (50), 162 (12), 144 (11), 134 (15), 119 (19), 108
(23), 91 (96), 77 (40), 65 (25), 50 (27), 39 (15).
Found, %: C 74.24, 74.46; H 5.12, 5.33; N 3.43,
3.51. C24H21NO4. Calculated, %: C 74.40; H 5.46;
N 3.62. M 387.44.
3-Alkoxyphthalimidines 16a, 16b, 17a, and 17b
(general procedure). A 0.1-mL portion of 10 M
aqueous HCl and 1 mol of 3-hydroxyphthalimidine
13b or 13c were added to 5 mL of ethanol, propan-
2-ol, or benzyl alcohol, and the mixture was refluxed
for 5 min. The mixture was cooled to room tempera-
ture, and the precipitate was filtered off, washed with
diethyl ether, and dried in air.
8-Ethoxy-8-phenyl-2,3,7,8-tetrahydro-6H-
[1,4]dioxino[2,3-f]isoindol-6-one (16a). Yield 58%,
1
mp 240–241°C (from EtOH). H NMR spectrum
(3Z)-3-(8-Oxo-2,3,7,8-tetrahydro-6H-[1,4]di-
oxino[2,3-f]isoindol-6-ylidene)propyl formate (19).
A solution of 0.8 g (3.5 mmol) of benzonitrile 7a in
10 mL of formic acid was refluxed for 1 h. The
mixture was cooled and poured into a mixture of
35 mL of water and 35 g of ice, and the precipitate was
filtered off, washed with water until neutral washings,
dried in air, and recrystallized from ethanol. Yield
(DMSO-d6), δ, ppm: 1.14 t (3H, CH3, J = 7.0 Hz),
3.07 m and 3.36 m (1H each, CH2CH3), 4.29 m (4H,
OCH2CH2O), 6.77 s (1H, Harom), 7.09 s (1H, Harom),
7.34 m (3H, Harom), 7.45 m (2H, Harom), 9.13 s (1H,
NH). Mass spectrum, m/z (Irel, %): 311 (5) [M]+, 266
(100), 237 (11), 223 (7), 210 (6), 188 (16), 162 (11),
134 (18), 126 (9), 104 (8), 77 (13), 50 (5). Found, %:
C 69.22, 69.54; H 5.56, 5.64; N 4.20, 4.36. C18H17NO4.
Calculated, %: C 69.44; H 5.50; N 4.50. M 311.34.
1
0.65 g (68%), mp 201–202°C. H NMR spectrum
(DMSO-d6), δ, ppm: 2.65 m (2H, C=CHCH2), 4.17 t
(2H, HCOOCH2, J = 6.7 Hz), 4.30 m (4H,
OCH2CH2O), 5.51 t (1H, C=CH, J = 7.9 Hz), 7.08 s
(1H, Harom), 7.33 s (1H, Harom), 8.23 s [1H, OC(O)H],
10.36 s (1H, NH). 13C NMR spectrum (DMSO-d6), δC,
ppm: 26.60, 63.16, 64.41, 64.70, 101.49, 108.98,
110.84, 123.37, 131.62, 135.31, 145.06, 147.83,
162.64, 168.03. Mass spectrum, m/z (Irel, %): [M]+ 275
(10), 229 (48), 216 (100), 201 (12), 170 (10), 160 (27),
145 (18), 132 (13), 117 (18), 104 (48), 89 (35), 77
(90), 63 (37), 55 (70), 50 (82), 39 (43). Found, %:
C 61.01, 61.25; H 4.52, 4.78; N 4.88, 4.92. C14H13NO5.
Calculated, %: C 61.09; H 4.76; N 5.09. M 275.26.
8-(1-Methylethoxy)-8-phenyl-2,3,7,8-tetrahydro-
6H-[1,4]dioxino[2,3-f]isoindol-6-one (16b). Yield
1
51%, mp 235–236°C (from i-PrOH). H NMR spec-
trum (CDCl3), δ, ppm: 1.09 d and 1.22 d [3H each,
CH(CH3)2, J = 5.6 Hz], 3.65 m [1H, CH(CH3)2],
4.27 m (4H, OCH2CH2O), 6.47 s (1H, NH), 6.78 s
(1H, Harom), 7.32 s (4H, Harom), 7.53 m (2H, Harom).
Mass spectrum, m/z (Irel, %): 325 (6) [M]+, 266 (100),
237 (10), 223 (7), 210 (16), 188 (13), 162 (11), 153
(6), 134 (17), 127 (6), 105 (7), 77 (13), 50 (14), 45
(17). Found, %: C 69.97, 70.03; H 5.68, 5.89; N 4.06,
4.14. C19H19NO4. Calculated, %: C 70.14; H 5.89;
N 4.30. M 325.37.
This study was performed under financial support
by the Council for Grants at the President of the
Russian Foundation (project no. 10268.2016.3).
8-Ethoxy-8-(4-methylphenyl)-2,3,7,8-tetrahydro-
6H-[1,4]dioxino[2,3-f]isoindol-6-one (17a). Yield
87%, mp 202–203°C (from EtOH). 1H NMR spectrum
(CDCl3), δ, ppm: 1.21 t (3H, CH2CH3, J = 7.0 Hz),
2.33 s (3H), 3.15 m and 3.50 m (1H each, CH2CH3),
4.26 m (4H, OCH2CH2O), 6.34 s (1H, NH), 6.74 s
(1H, Harom), 7.14 d (2H, Harom, J = 7.9 Hz), 7.30 s (1H,
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