Transformations of N-(2-acylaryl)benzamides and their analogs under the Camps cyclization conditions

Article abstract of DOI:10.1134/S107042801607006X

N-(2-Acylaryl)benzamides and analogous N-substituted furan-2-, thiophene-2-, and cyclopropane-carboxamides in the systems EtONa–EtOH, EtONa–THF, and t-BuOK–t-BuOH undergo Camps cyclization to 2-aryl-, 2-hetaryl-, and 2-cyclopropylquinolin-4(1H)-ones with

Full text of DOI:10.1134/S107042801607006X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 7, pp. 956–969. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © S.S. Mochalov, A.N. Fedotov, E.V. Trofimova, N.S. Zefirov, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 7,
pp. 964–976.
Transformations of N-(2-Acylaryl)benzamides and Their Analogs
under the Camps Cyclization Conditions
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 15, 2016
Abstract—N-(2-Acylaryl)benzamides and analogous N-substituted furan-2-, thiophene-2-, and cyclopropane-
carboxamides in the systems EtONa–EtOH, EtONa–THF, and t-BuOK–t-BuOH undergo Camps cyclization to
2-aryl-, 2-hetaryl-, and 2-cyclopropylquinolin-4(1H)-ones with high yields. The same substrates in the system
t-BuOK (5 equiv)–THF are converted mainly to the corresponding N-(2-hydroxyaryl) amides as a result of
oxidative transformation of the acyl fragment into hydroxy group.
DOI: 10.1134/S107042801607006X
Biological activity of 2-phenylquinolin-4(1H)-one
derivatives has been extensively studied over the past
20–25 years. As a result of these studied, many com-
pounds of this series have been found to exhibit high
cytotoxic [1–10], antibacterial [11–13], immuno-
stimulating [14], antihepres [15], anti-HIV [16], and
antibiotic activities [17, 18], so that a large series of
new drugs have been designed and implemented in
modern therapeutic practice.
because of some difficulties related to the synthesis of
initial 2-acylanilines.
We previously succeeded in developing methods
for the synthesis of a number of difficultly accessible
2-acylanilines. For example, 2-propanoylanilines can
be obtained from the corresponding (2-nitroaryl)cyclo-
propanes [24, 25], whereas 2-acylanilines containing
various alkyl groups in the acyl fragment are available
via Friedel–Crafts acylation and nitration of 1,2-di-
alkoxybenzenes with subsequent reduction of the cor-
responding 2-nitro-1-acylbenzenes [26–28]. Following
the developed procedures, we have synthesized
a variety of substituted quinolin-2-ones by intramolec-
ular Knoevenagel condensation [29–31]. As we noted
in [30], if the initial N-(2-acylaryl)amide contained two
types of methylene components so that both Camps
and Knoevenagel condensations were possible, only
the latter occurred (Scheme 1). Taking this into
account, we presumed that the Camps cyclization
would be feasible if the amide part of initial N-(2-acyl-
aryl)amide lacked active methylene group. In order to
verify this assumption, we synthesized a large series of
anilides containing an active methylene group only in
the 2-acyl substituent (most of these compounds were
not described previously) and studied their behavior
under conditions of base-catalyzed Camps cyclization.
The results obtained in the field of biological and
medical studies stimulated further research aimed at
synthesizing new derivatives of 2-phenylquinolin-
4(1H)-ones with a view to revealing new kinds of their
biological activity and improving therapeutic prop-
erties of drugs based on known 2-phenylquinolinones.
Nowadays, there are two synthetic approaches to
2-phenylquinolin-4(1H)-one derivatives, which are
used most frequently by synthetic chemists. The first
approach is based on the condensation of anilines with
aroylacetic acid esters, followed by high-temperature
cyclization (Conrad–Limpach synthesis), and the
second one implies the synthesis of N-(2-acylaryl)-
substituted carboxylic acid amides and their base-
catalyzed cyclization (Camps cyclization). The scope
of the Conrad–Limpach synthesis of 2-phenylquinoli-
nones has been studied in sufficient detail [1, 6, 7,
19–21], whereas the scope of the Camps cyclization is
limited to base-catalyzed cyclization of only
(2-acetylaryl)benzamides [4, 5, 22, 23], presumably
Initial 2-acetylanilides 1a, 1b, and 2a–2h, 2-pro-
panoylanilides 3a–3g, 4, 5a, 5b, and 6a–6i, 2-buta-
noylanilides 7a–7c, and 2-(phenylacetyl)anilides 8a–
956

TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
957
Scheme 1.
O
O
Me
O
O
N
H
CH2Ph
EtO–/EtOH, ∆
O
O
Et
Et
NHC(O)CH2Ph
O
O
Ph
O
N
H
8c were synthesized by acylation of 2-acylanilines
with the corresponding carboxylic acid chlorides ac-
cording to the procedure reported in [30] (Scheme 2).
but weaker than sodium or potassium tert-butoxide.
We anticipated that analogous conditions could be ap-
propriate for the cyclization of N-(2-acylaryl)benz-
amides containing an active methylene group in the
acyl substituent.
Analysis of published data on the synthesis of
2-arylquinolin-4-ones from N-(2-acetylaryl)benz-
amides showed that base-catalyzed Camps cyclization
of the latter can be accomplished by the action of
sodium or potassium tert-butoxide [2, 4, 5, 22, 23] or
weaker bases, sodium or potassium hydroxides
[32, 33]. As we found previously [30, 31], N-(2-acyl-
aryl)acetamides are readily converted to the corre-
sponding quinolin-2-ones in the presence of sodium
ethoxide which is a stronger base than NaOH or KOH
In fact, benzamides 3a–3g, 4, 5a, 5b, 6a–6d, 6f–6i,
7a, and 8a–8c possessing a propanoyl-, butanoyl-, or
phenylacetyl substituent in the ortho position with
respect to the amide fragment readily underwent
cyclization to quinolin-4(1H)-ones 9a–9v by the action
of sodium ethoxide in ethanol (Scheme 3, Table 1).
However, none of N-(2-acetylaryl)benzamides 1a, 1b,
and 2a–2h was converted into 2-arylquinolinones
Scheme 2.
O
O
R4C(O)Cl, 3 N NaOH
dioxane
R2
R3
R1
R2
R3
R1
C(O)R4
NH2
N
H
1a, 1b, 2a–2h, 3a–3g, 4, 5a, 5b
6a–6i, 7a–7c, 8a–8c
1, R1 = R2 = H, R3 = t-Bu, R4 = 4-ClC6H4 (a), 4-BrC6H4 (b); 2, R1 = H, R2R3 = OCH2CH2O, R4 = cyclopropyl (a), 4-MeC6H4 (b),
3-FC6H4 (c), 4-FC6H4 (d), 2-ClC6H4 (e), 4-ClC6H4 (f), 3-BrC6H4 (g), 3-IC6H4 (h); 3, R1 = Me, R2 = R3 = H, R4 = cyclopropyl (a),
3-MeOC6H4 (b), 4-FC6H4 (c), 4-ClC6H4 (d), 2-BrC6H4 (e), 4-BrC6H4 (f), thiophen-2-yl (g); 4, R1 = Me, R2 = H, R3 = Br, R4 =
cyclopropyl; 5, R1 = Me, R2 = Cl, R3 = H, R4 = 4-ClC6H4 (a), 4-BrC6H4 (b); 6, R1 = Me, R2R3 = OCH2CH2O, R4 = 4-MeC6H4 (a),
cyclopropyl (b), 2-FC6H4 (c), 2-BrC6H4 (d), 3-BrC6H4 (e), 4-BrC6H4 (f), 3-IC6H4 (g), furan-2-yl (h), thiophen-2-yl (i); 7, R1 = Et,
R2R3 = OCH2CH2O, R4 = 4-MeC6H4 (a), 3-BrC6H4 (b), 4-O2NC6H4 (c); 8, R1 = Ph, R2R3 = OCH2CH2O, R4 = cyclopropyl (a),
4-MeC6H4 (b), 4-ClC6H4 (c).
Scheme 3.
O
O
R2
R3
R1
R2
R3
R1
R4
EtONa, EtOH, 78°C
C(O)R4
N
H
N
H
3a–3g, 4, 5a, 5b, 6a–6d
6f–6i, 7a–7c, 8a–8c
9a–9v
9, R1 = Me, R2 = R3 = H, R4 = cyclopropyl (a), 3-MeOC6H4 (b), 4-FC6H4 (c), 4-ClC6H4 (d), 2-BrC6H4 (e), 4-BrC6H4 (f), thiophen-
2-yl (g); R2 = H, R3 = Br, R4 = cyclopropyl (h); R2 = Cl, R3 = H, R4 = 4-ClC6H4 (i), 4-BrC6H4 (j); R2R3 = OCH2CH2O, R4 =
4-MeC6H4 (k), cyclopropyl (l), 2-FC6H4 (m), 2-BrC6H4 (n), 4-BrC6H4 (o), 3-IC6H4 (p), furan-2-yl (q), thiophen-2-yl (r); R1 = Et,
R2R3 = OCH2CH2O, R4 = 4-MeC6H4 (s); R1 = Ph, R2R3 = OCH2CH2O, R4 = cyclopropyl (t), 4-MeOC6H4 (u), 4-ClC6H4 (v).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

MOCHALOV et al.
958
Table 1. Yields of 2-aryl(hetaryl-, cyclopropyl)quinolin-4(1H)-ones 9a–9v in the Camps cyclization of N-(2-acylaryl) amides
Initial
amide
Reaction
time, h
Initial
amide
Reaction
time, h
Quinolin-4(1H)-one Yield, %
Quinolin-4(1H)-one Yield, %
3a
3b
3c
3d
3e
3f
07
07
07
17
17
17
10
07
07
10
10
9a
9b
9c
9d
9e
9f
93
98
6b
6c
6d
6f
17
17
17
17
17
05
10
17
05
05
05
9l
088
088
093
086
084
098
092
d048d
100
100
100
9m
9n
9o
9p
9q
9r
9s
86
91
a77a
6g
6h
6i
87
3g
4
9g
9h
9i
85
b46b
c83c
81
7a
8a
8b
8c
5a
5b
6a
9t
9j
9u
9v
9k
92
a
b
c
d
Calculated on the reacted amide.
Apart from quinolin-4(1H)-one, 54% of 5-bromo-2-propanoylaniline was formed as a result of amide bond cleavage.
The reaction was carried out using 2 equiv of EtONa.
52% of the initial amide was recovered.
under these conditions, and the initial compounds were
quantitatively recovered from the reaction mixtures.
5-bromo-2-propanoylaniline, the latter resulting from
cleavage of the amide bond (Scheme 4).
As follows from the data in Table 1, the cyclization
of phenylacetyl derivatives 8a–8c was much easier
than the cyclization of propanoyl-substituted analogs,
while the latter were more reactive in the Camps
cyclization than N-(2-butanoylphenyl)benzamides (cf.
the data for 6a and 7a).
While studying the behavior of N-(2-acylaryl)-
benzamides under standard cyclization conditions, we
found that the cyclization of some substrates was
accompanied by some other transformations. For
example, the treatment of 4 with sodium ethoxide in
ethanol gave a mixture of quinolinone 9h and
Dichloro-substituted benzamide 5a was converted
into quinolinone 9i together with an appreciable
amount of a product in which one chlorine atom was
replaced by ethoxy group. This undesirable side
reaction can be avoided by carrying out the cyclization
of 5a with the use of 2 equiv of EtONa (Table 1). We
failed to obtain the corresponding quinolin-4-one from
2-butanoyl-substituted 4-nitrobenzamide 7c. The
reaction at elevated temperature led to the formation of
a complex mixture of products, presumably due to
reduction of the nitro group), whereas no reaction
occurred at 20°C for at least 30 h.
Scheme 4.
O
O
Me
Me
O
O
Br
Br
N
H
N
H
Me
9h
EtO–/EtOH
O
Br
N
H
O
O
Me
OEt
Me
4
–
COOEt
Br
Br
NH2
N
H
O–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
959
Scheme 5.
O
O
t-BuOK (5 equiv)
THF, 65°C, 5–20 h
R2
R3
R1
R2
R3
R1
R4
R2
R3
OH
O
+
C(O)R4
N
H
N
H
N
H
R4
1a, 1b, 2c, 2g, 2h, 6e, 6g, 6i, 7b
10a–10e
11a–11f
10, R1 = R2 = H, R3 = t-Bu, R4 = 4-ClC6H4 (a), 4-BrC6H4 (b); R1 = H, R2R3 = OCH2CH2O, R4 = 3-FC6H4 (c), 3-BrC6H4 (d),
3-IC6H4 (e); 11, R2 = H, R3 = t-Bu, R4 = 4-ClC6H4 (a), 4-BrC6H4 (b); R2R3 = OCH2CH2O, R4 = 3-FC6H4 (c), 3-BrC6H4 (d),
3-IC6H4 (e), thiophen-2-yl (f).
Since N-(2-acetylaryl)benzamides 1a, 1b, and 2a–
2h neither cyclized nor changed under the above
conditions, we tried to effect their cyclization under
the conditions reported in [22]. According to [22],
N-(2-acetyl-4,6-dimethoxyphenyl)benzamide was con-
verted to the corresponding 3-unsubstituted 2-phenyl-
quinolin-4(1H)-one by the action of 5 equiv of potas-
sium tert-butoxide in THF. In fact, by treatment of 1a,
1b, 2c, 2g, and 2h with 5 equiv of t-BuOK in THF we
obtained 3-unsubstituted quinolinones 10a–10e, but in
all cases their yields were lower than the yields of
compounds 11a–11e resulting from the transformation
of the acetyl group in the initial benzamide into
hydroxy group (Scheme 5, Table 2). Propanoyl deriv-
atives 6e, 6g, and 6i and butanoyl analog 7b almost
failed to undergo Camps cyclization under the same
conditions, whereas oxidative transformation products
11d, 11e, and 11f were formed in high yields
(Scheme 5, Table 2). These findings indicated that the
newly observed transformation of N-(2-acylaryl)benz-
amides into N-(2-hydroxylaryl)benzamides 11a–11f is
general and that this reaction is facilitated for sub-
strates in which the acyl-substituted benzene ring also
bears alkoxy groups.
action of 5 equiv of EtONa in THF (a), 5 equiv of
t-BuOK in t-BuOH (b), and 2 equiv of t-BuOK in THF
(c). N-(2-Acetylaryl)benzamide 2e in systems a and b
was converted only to the Camps cyclization product
10f (Scheme 7). Propanoyl derivatives 3d, 6c, 6f, and
6h behaved similarly, and the corresponding 2-aryl-
quinolin-4(1H)-ones were formed (Table 3). By con-
trast, N-(2-acetylaryl)benzamide 2e remained un-
changed in the presence of 2 equiv of t-BuOK in THF
(c), whereas propanoylanilides 6f and 6h in the same
system were converted into quinolinones as easily as in
systems a and b (Table 3).
Thus, the examined N-(2-acylaryl)benzamides in
the systems EtONa–EtOH, EtONa–THF, t-BuOK–t-
BuOH, and t-BuOK–THF (substrate-to-base ratio 1:2)
readily undergo Camps cyclization to the correspond-
ing quinolinones, while potassium tert-butoxide
(5 equiv) in THF promotes mainly oxidative elimina-
tion of the 2-acyl group. Obviously, in the latter case,
due to steric hindrances in N-(2-acylaryl)benzamides
Table 2. Cyclization of N-(2-acylaryl) amides by the action
of potassium tert-butoxide in THF
Yield, %
Reaction
The structure of 11a–11f was confirmed by spectral
data (see Experimental), as well as by alkylation of
11d with diazomethane, which afforded 3-bromo-(7-
methoxy-2,3-dihydro-1,4-benzodioxin-6-yl)benzamide
(12) (Scheme 6).
Initial amide
time, h
quinolinone
amidophenol
1a
1b
2c
2g
2h
6e
6g
6i
20
10a, 40
10b, 44
10c, 10a
10d, 8a
10e, 36
9w, traces
9p, traces
9r, traces
–
11a, 59
11b, 55
11c, 86
11d, 81
11e, 48b
11d, 82b
11e, 74b
11f, 95
20
10
We also studied the effects of the base, solvent, and
reactant ratio on the formation of N-(2-hydroxylaryl)-
benzamides 11. For this purpose, we compared the
behavior of some N-(2-acylaryl)benzamides under the
10
20
07.5
07.5
05
Scheme 6.
7b
07.5
11d, 84b
R2
OMe
O
CH2N2, Et2O
a
Identified by the 3-H, 5-H, and 8-H signals of the quinoline
fragment in the 1H NMR spectra of the reaction mixture.
6-[(Arylcarbonyl)amino]-2,3-dihydro-1,4-benzodioxine was
11d
R3
N
H
C6H4Br-3
b
12
isolated in addition to N-(2-hydroxyaryl)benzamide.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

MOCHALOV et al.
960
Scheme 7.
O
O
EtONa (5 equiv), THF, 65°C or
t-BuOK (5 equiv), t-BuOH, 80°C
O
O
O
O
Me
NHC(O)C6H4Cl-2
Cl
N
H
2e
10f
Scheme 8.
R1
–O
H
O
Me
R1
R2
R3
R1
R2
R3
R2
O
t-BuO–, THF
O
Me
C(O)R4
O
C(O)R4
NHC(O)R4
N
H
N
R3
H
1a, 1b, 2e, 2g, 2i, 7b
A
R2
R3
O–
R2
R3
OH
H+/H2O
H2O, OH–
–R1CH2COO–
O
N
H
R4
NHC(O)R4
11a–11g
and high concentration of potassium tert-butoxide in
the reaction medium, the addition of tert-butoxide ion
to the acyl carbonyl group becomes preferred. Interme-
diate adduct A (Scheme 8) is likely to be responsible
for the transformation of 1a, 1b, 2e, 2g, 2i, and 7b into
N-(2-hydroxyaryl) amides 11a–11f.
and acylbenzenes were oxidized to phenols with
peroxy acids (Scheme 10; Baeyer–Villiger oxidation
[37–39]). It is seen that that adducts B and C
mediating the formation of phenols from 4-hydroxy-
benzaldehyde and acetophenone (Schemes 9, 10) are
structurally similar to those assumed as intermediates
in the transformation of acylanilides by the action of
t-BuOK in THF (adducts A; Scheme 8). Presumably,
migration of the aryl residue in A to the oxygen atom
linked to the tert-butyl group is energetically favor-
able; therefore, the described transformation of the
acyl group in N-(2-acylaryl) amides to hydroxy group
The transformations of aldehyde group in benzal-
dehydes and of acyl group in acylbenzenes into
hydroxy group have been reported. For example,
benzaldehydes were converted into the corresponding
phenols by treatment with hydrogen peroxide in
alkaline medium (Scheme 9, Dakin reaction [34–36]),
Table 3. Cyclization of N-(2-acylaryl)benzamides 2e, 3d, 6c, 6f, and 6h by the action of bases
Initial amide
Reaction conditions
Reaction time, h
2-Arylquinolin-4(1H)-one
Yield, %
2e
3d
6h
2e
6c
6f
a: EtONa (5 equiv), THF, 65°C
12
12
10
21
07
07
10
08
08
10f
081
100
a
09d
09q
10f
a
095
b: t-BuOK (5 equiv), t-BuOH, 80°C
092
b
09m
09o
10f
098
b
091
2e
6f
c: t-BuOK (2 equiv), THF, 65°C
Traces
088
c
c
09o
09g
6h
098
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TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
961
Scheme 9.
O–
H
(1) H2O, OH–
(2) H2O, H+
CHO
OH
O
H
OH
H2O2, NaOH
O
O
HO
HO
HO
HO
B
Scheme 10.
O–
O
Me
O
Me
O
Me
OH
CF3CO3H
H+/H2O
Me
O
O
O
C
Scheme 11.
–O
R
O
Bu-t
O
O
O
O
H+
O
O
–t-BuOC(O)R
O
NHC(O)Ar
NHC(O)Ar
N
Ar
H
A
can be regarded as a process analogous to the Dakin
reaction of aldehydes and Baeyer–Villiger oxidation of
acylbenzenes.
recorded in mineral oil on a UR-20 spectrometer. The
elemental analyses were obtained on a Vario-11 CHN
analyzer. The melting points were determined on
an Electrothermal Model 1A9100 digital melting point
apparatus.
Possible intermediacy of adducts A (Scheme 8) in
the oxidative reactions of N-(2-acylaryl)benzamides is
confirmed by the formation of N-(2,3-dihydro-1,4-
benzodioxin-6-yl) amides from 2h, 6e, 6g, and 7b
(Table 2). Apart from migration of the aryl anion in A
to the oxygen atom, leading to the formation of
N-(2-hydroxyaryl) amides 11e–11f, heterolytic disso-
ciation of the Carom–Cα bond in A can occur with
elimination of the corresponding neutral tert-butyl car-
boxylate molecule (Scheme 11).
Initial 2-acylanilines were synthesized as described
in [24–28].
N-(2-Acylaryl) amides 1a, 1b, 2a–2h, 3a–3g, 4,
5a, 5b, 6a–6i, 7a–7c, and 8a–8c (general procedure).
2-acylaniline, 0.01 mol, was dissolved in 25 mL of
dioxane, 0.01 mol of the corresponding acid chloride
(solid acid chlorides were dissolved in anhydrous
dioxane) and 0.01 mol of sodium hydroxide (a 3 N so-
lution) were simultaneously added dropwise. The mix-
ture was stirred for 1–1.5 h at 20°C and poured into
150 mL of water, and the precipitate was filtered off,
washed with water, dried in air, and recrystallized.
Compounds 2a [40], 3e, 6a, 6c, and 6h [27] were
Thus, the systems EtONa–EtOH, EtONa–THF,
t-BuOK–t-BuOH (substrate-to-base ratio 1:5), and
t-BuOK–THF (substrate-to-base ratio 1:2) ensure suc-
cessful cyclization of N-(2-acylaryl)benzamides and
analogous N-substituted hetarene- and cyclopropane-
carboxamides to 2-aryl-, 2-hetaryl-, and 2-cyclopropyl-
quinolin-4(1H)-ones. Unlike the above systems,
N-(2-acylaryl)benzamides react with 5 equiv of t-BuOK
in THF to give mainly N-(2-hydroxyaryl)benzamides.
1
described previously. The H NMR spectra of 1a, 1b,
2b–2h, 3b, 3c, 3g, 5a, 5b, 6d–6g, 6i, and 7a–7c were
recorded in DMSO-d6, and of 3a, 3d, 3f, 4, 6b, and
8a–8c, in CDCl3.
N-(5-tert-Butyl-2-propanoylphenyl)-4-chloro-
benzamide (1a). Yield 81%, mp 163–164°C (from
EtOH). H NMR spectrum, δ, ppm: 1.33 s [9H,
EXPERIMENTAL
1
1
The H NMR spectra were recorded on a Varian
C(CH3)3], 2.67 s (3H, CH3), 7.31 d.d (1H, Harom, J =
1.7, 8.0 Hz), 7.69 d (2H, Harom, J = 8.2 Hz), 7.96 d
(2H, Harom, J = 8.2 Hz), 8.04 d (1H, Harom, J = 8.0 Hz),
8.77 d (1H, Harom, J = 1.7 Hz), 12.44 s (1H, NH).
VXR-400 spectrometer at 400 MHz; the chemical
shifts were measured relative to the residual proton
signal of the deuterated solvent. The IR spectra were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

MOCHALOV et al.
962
1
Found, %: C 68.79, 68.87; H 5.85, 5.92; N 4.26, 4.38.
C19H20ClNO2. Calculated, %: C 69.18; H 6.11; N 4.25.
(from EtOH). H NMR spectrum, δ, ppm: 2.61 s (3H,
CH3), 4.28 m and 4.35 m (2H each, OCH2CH2O),
7.62 s (1H, Harom), 7.65 d (2H, Harom, J = 8.2 Hz),
7.93 d (2H, Harom, J = 8.2 Hz), 8.24 s (1H, Harom),
12.53 s (1H, NH). Found, %: C 61.22, 61.31; H 4.12,
4.18; N 4.13, 4.21. C17H14ClNO4. Calculated, %:
C 61.55; H 4.25; N 4.22.
4-Bromo-N-(5-tert-butyl-2-propanoylphenyl)-
benzamide (1b). Yield 77%, mp 148–149°C (from
1
EtOH). H NMR spectrum, δ, ppm: 1.32 s [9H,
C(CH3)3], 2.67 s (3H, CH3), 7.30 d.d (1H, Harom, J =
1.7, 8.0 Hz), 7.82 d (2H, Harom, J = 8.2 Hz), 7.88 d
(2H, Harom, J = 8.2 Hz), 8.03 d (1H, Harom, J = 8.0 Hz),
8.77 d (1H, Harom, J = 1.7 Hz), 12.43 s (1H, NH).
Found, %: C 60.38, 60.58; H 5.09, 5.18; N 3.68, 3.81.
C19H20BrNO2. Calculated, %: C 60.97; H 5.39; N 3.74.
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
3-bromobenzamide (2g). Yield 92%, mp 154–155°C
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
2.62 s (3H, CH3), 4.30 m and 4.37 m (2H each,
OCH2CH2O), 7.56 t (1H, Harom, J = 8.1 Hz), 7.62 s
(1H, Harom), 7.84 d.d (1H, Harom, J = 1.3, 8.1 Hz),
1
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
4-methylbenzamide (2b). Yield 89%, mp 181–182°C
7.91 d.d (1H, Harom, J = 1.3, 8.1 Hz), 8.05 d (1H, Harom
,
1
(from EtOH). H NMR spectrum, δ, ppm: 2.39 s (3H,
J = 1.3 Hz), 8.20 s (1H, Harom), 12.49 s (1H, NH).
Found, %: C 53.88, 53.94; H 3.41, 3.52; N 3.69, 3.75.
C17H14BrNO4. Calculated, %: C 54.26; H 3.75; N 3.72.
CH3), 2.61 s (3H, CH3), 4.29 m and 4.36 m (2H each,
OCH2CH2O), 7.38 d (2H, Harom, J = 8.0 Hz), 7.60 s
(1H, Harom), 7.82 d (2H, Harom, J = 8.0 Hz), 8.30 s (1H,
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
3-iodobenzamide (2h). Yield 73%, mp 184–185°C
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
2.60 s (3H, CH3), 4.28 m and 4.36 m (2H each,
OCH2CH2O), 7.39 t (1H, Harom, J = 8.0 Hz), 7.59 s
(1H, Harom), 7.89 d.d (1H, Harom, J = 1.6, 8.0 Hz),
7.98 d.d (1H, Harom, J = 1.6, 8.0 Hz), 8.19 s (1H,
Harom), 12.52 s (1H, NH). Found, %: C 68.98, 69.21;
H 5.19, 5.32; N 4.32, 4.51. C18H17NO4. Calculated, %:
C 69.44; H 5.51; N 4.50.
1
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
3-fluorobenzamide (2c). Yield 83%, mp 163–164°C
1
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
2.62 s (3H, CH3), 4.30 m and 4.37 m (2H each,
OCH2CH2O), 7.49 d.t (1H, Harom, J = 1.7, 8.0 Hz),
7.62 s (1H, Harom), 7.63–7.69 m (2H, Harom), 7.76 d
(1H, Harom, J = 7.2 Hz), 8.22 s (1H, Harom), 12.51 s
(1H, NH). Found, %: C 64.31, 64.53; H 4.14, 4.26;
N 4.27, 4.38. C17H14FNO4. Calculated, %: C 64.76;
H 4.48; N 4.44.
H
arom), 8.21 t (1H, Harom, J = 1.6 Hz), 12.48 s (1H,
NH). Found, %: C 47.68, 47.77; H 3.01, 3.11; N 3.28,
3.40. C17H14INO4. Calculated, %: C 48.24; H 3.33;
N 3.31.
N-(2-Propanoylphenyl)cyclopropanamide (3a).
1
Yield 71%, mp 56–57°C (from EtOH). H NMR spec-
trum, δ, ppm: 0.87 m (2H), 1.08 m (2H), and 1.67 m
(1H) (C3H5), 1.24 t (3H, CH2CH3, J = 7.3 Hz), 3.08 q
(2H, CH2CH3, J = 7.3 Hz), 7.09 d.t (1H, Harom, J = 1.3,
8.1 Hz), 7.52 d.t (1H, Harom, J = 1.6, 8.2 Hz), 7.91 d
(1H, Harom, J = 8.2 Hz), 8.74 d (1H, Harom, J = 8.1 Hz),
12.02 s (1H, NH). Found, %: C 71.53, 71.68; H 6.68,
6.81; N 6.34, 6.48. C13H15NO2. Calculated, %:
C 71.86; H 6.96; N 6.45.
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
4-fluorobenzamide (2d). Yield 87%, mp 205–206°C
1
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
2.61 s (3H, CH3), 4.29 m and 4.36 m (2H each,
OCH2CH2O), 7.43 d.d (2H, Harom, J = 7.5, 7.6 Hz),
7.62 s (1H, Harom), 7.99 d.d (2H, Harom, J = 4.1,
7.6 Hz), 8.23 s (1H, Harom), 12.51 s (1H, NH). Found,
%: C 64.26, 64.39; H 4.21, 4.31; N 4.19, 4.41.
C17H14FNO4. Calculated, %: C 64.76; H 4.48; N 4.44.
3-Methoxy-N-(2-propanoylphenyl)benzamide
1
(3b). Yield 79%, mp 91–92°C (from EtOH). H NMR
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
2-chlorobenzamide (2e). Yield 91%, mp 193–194°C
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
2.55 s (3H, CH3), 4.31 m and 4.38 m (2H each,
OCH2CH2O), 7.40–7.51 m (5H, Harom), 8.32 s (1H,
spectrum, δ, ppm: 1.12 t (3H, CH2CH3, J = 6.8 Hz),
3.18 q (2H, CH2CH3, J = 6.8 Hz), 3.88 s (3H, OCH3),
1
7.18 d.d (1H, Harom, J = 1.5, 8.0 Hz), 7.22 t (1H, Harom
J = 8.0 Hz), 7.49–7.58 m (3H, Harom), 7.65 t (1H, Harom
,
,
J = 8.0 Hz), 8.11 d (1H, Harom, J = 8.0 Hz), 8.69 d (1H,
arom, J = 8.0 Hz), 12.46 s (1H, NH). Found, %:
Harom), 12.11 s (1H, NH). Found, %: C 61.03, 61.21;
H
H 3.98, 4.11; N 4.18, 4.27. C17H14ClNO4. Calculated,
%: C 61.55; H 4.25; N 4.22.
C 71.67, 71.81; H 5.74, 5.82; N 4.79, 4.88. C17H17NO3.
Calculated, %: C 72.06; H 6.05; N 4.94.
N-(7-Acetyl-2,3-dihydro-1,4-benzodioxin-6-yl)-
4-chlorobenzamide (2f). Yield 78%, mp 190–191°C
4-Fluoro-N-(2-propanoylphenyl)benzamide (3c).
Yield 76%, mp 126–127°C (from EtOH). H NMR
1
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TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
963
4-Chloro-N-(4-chloro-2-propanoylphenyl)benz-
amide (5a). Yield 89%, mp 147–148°C (from EtOH).
1H NMR spectrum, δ, ppm: 1.07 t (3H, CH2CH3, J =
7.4 Hz), 3.12 q (2H, CH2CH3, J = 7.4 Hz), 7.67 d
(2H, Harom, J = 8.2 Hz), 7.70 d.d (1H, Harom, J = 2.1,
7.9 Hz), 7.93 d (2H, Harom, J = 8.2 Hz), 8.06 d (1H,
spectrum, δ, ppm: 1.12 t (3H, CH2CH3, J = 6.6 Hz),
3.26 q (2H, CH2CH3, J = 6.6 Hz), 7.26 t (1H, Harom
,
J = 8.0 Hz), 7.46 d.d (2H, Harom, J = 8.1, 8.1 Hz), 7.67 t
(1H, Harom, J = 8.0 Hz), 8.04 d.d (2H, Harom, J = 4.8,
8.1 Hz), 8.25 d (1H, Harom, J = 8.0 Hz), 8.64 d (1H,
Harom, J = 8.0 Hz), 12.29 s (1H, NH). Found, %:
C 70.32, 70.54; H 4.89, 5.01; N 5.14, 5.21.
C16H14FNO2. Calculated, %: C 70.83; H 5.20; N 5.16.
H
arom, J = 2.1 Hz), 8.42 d (1H, Harom, J = 7.9 Hz),
11.98 s (1H, NH). Found, %: C 59.22, 59.34; H 3.81,
3.91; N 3.98, 4.16. C16H13ClN2O2. Calculated, %:
C 59.64; H 4.07; N 4.35.
4-Chloro-N-(2-propanoylphenyl)benzamide (3d).
1
Yield 78%, mp 112–113°C (from EtOH). H NMR
4-Bromo-N-(4-chloro-2-propanoylphenyl)benz-
amide (5b). Yield 81%, mp 156–157°C (from EtOH–
spectrum, δ, ppm: 1.28 t (3H, CH2CH3, J = 6.8 Hz),
3.14 q (2H, CH2CH3, J = 6.8 Hz), 7.18 d.t (1H, Harom
,
1
CHCl3). H NMR spectrum, δ, ppm: 1.14 t (3H,
J = 1.3, 8.2 Hz), 7.52 d (2H, Harom, J = 8.4 Hz), 7.63 d.t
(1H, Harom, J = 1.4, 8.2 Hz), 8.01 d.d (1H, Harom, J =
1.4, 8.2 Hz), 8.04 d (2H, Harom, J = 8.4 Hz), 8.94 d.d
(1H, Harom, J = 1.3, 8.2 Hz), 12.79 s (1H, NH). Found,
%: C 66.12, 66.31; H 4.65, 4.72; N 4.77, 4.85.
C16H14ClNO2. Calculated, %: C 66.78; H 4.90; N 4.87.
CH2CH3, J = 6.8 Hz), 3.11 q (2H, CH2CH3, J =
6.8 Hz), 7.57 d.d (1H, Harom, J = 2.1, 8.2 Hz), 7.69 d
(2H, Harom, J = 7.8 Hz), 7.85 d (2H, Harom, J = 7.8 Hz),
8.00 d (1H, Harom, J = 2.1 Hz), 8.67 d (1H, Harom, J =
8.2 Hz), 12.34 s (1H, NH). Found, %: C 51.83, 51.96;
H 3.27, 3.34; N 3.70, 3.83. C16H13BrClNO2. Calculat-
ed, %: C 52.41; H 3.57; N 3.82.
4-Bromo-N-(2-propanoylphenyl)benzamide (3f).
1
Yield 84%, mp 117–118°C (from EtOH). H NMR
N-(7-Propanoyl-2,3-dihydro-1,4-benzodioxin-
6-yl)cyclopropanecarboxamide (6b). Yield 79%,
spectrum, δ, ppm: 1.24 t (3H, CH2CH3, J = 7.2 Hz),
3.11 q (2H, CH2CH3, J = 7.2 Hz), 7.15 t (1H, Harom, J =
7.8 Hz), 7.60 t (1H, Harom, J = 7.8 Hz), 7.65 d (2H,
Harom, J = 8.1 Hz), 7.93 d (2H, Harom, J = 8.1 Hz),
7.98 d (1H, Harom, J = 7.8 Hz), 8.92 d (1H, Harom, J =
7.8 Hz), 12.76 s (1H, NH). Found, %: C 57.31, 57.42;
H 3.95, 4.02; N 4.14, 4.23. C16H14BrNO2. Calculated,
%: C 57.84; H 4.25; N 4.22.
1
mp 147–148°C (from EtOH). H NMR spectrum, δ,
ppm: 0.84 m (2H), 1.06 m (2H), 1.63 m (1H) (C3H5);
1.21 t (3H, CH2CH3, J = 7.5 Hz), 2.96 q (2H, CH2CH3,
J = 7. 5 Hz), 4. 25 m and 4. 31 m (2H each,
OCH2CH2O), 7.42 s (1H, Harom), 8.30 s (1H, Harom),
12.01 s (1H, NH). Found, %: C 65.01, 65.16; H 5.88,
6.03; N 4.94, 5.06. C15H17NO4. Calculated, %:
C 65.44; H 6.23; N 5.09.
N-(2-Propanoylphenyl)thiophene-2-carboxamide
(3g). Yield 81%, mp 103–104°C (from EtOH).
1H NMR spectrum, δ, ppm: 1.12 t (3H, CH2CH3, J =
7.2 Hz), 3.15 q (2H, CH2CH3, J = 7.2 Hz), 7.24 t (1H,
2-Bromo-N-(7-propanoyl-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (6d). Yield 88%, mp 215–
1
217°C (from EtOH–CHCl3). H NMR spectrum, δ,
Harom, J = 8.0 Hz), 7.31 d.d (1H, HTh, J = 3.4, 4.8 Hz),
ppm: 1.01 t (3H, CH2CH3, J = 6.6 Hz), 3.03 q (2H,
CH2CH3, J = 6.6 Hz), 4.31 m and 4.38 m (2H each,
OCH2CH2O), 7.46 d.t (1H, Harom, J = 1.7, 8.0 Hz),
7.54 d.t (1H, Harom, J = 1.1, 7.9 Hz), 7.61 s (1H, Harom),
7.62 d.d (1H, Harom, J = 1.7, 7.9 Hz), 7.75 d.d (1H,
Harom, J = 1.1, 8.0 Hz), 8.13 s (1H, Harom), 11.88 s
(1H, NH). Found, %: C 55.02, 55.21; H 3.91, 4.02;
N 3.43, 3.56. C18H16BrNO4. Calculated, %: C 55.40;
H 4.13; N 3.59.
7.66 t (1H, Harom, J = 8.0 Hz), 7.84 d (1H, HTh, J =
3.4 Hz), 7.95 d (1H, HTh, J = 4.8 Hz), 8.12 d (1H,
Harom, J = 8.0 Hz), 8.48 d (1H, Harom, J = 8.0 Hz),
12.32 s (1H, NH). Found, %: C 64.48, 64.62; H 4.82,
4.88; N 5.26, 5.38. C14H13NO2S. Calculated, %:
C 64.84; H 5.05; N 5.40.
N-(5-Bromo-2-propanoylphenyl)cyclopropane-
carboxamide (4). Yield 77%, mp 104–105°C (from
1
EtOH). H NMR spectrum, δ, ppm: 0.91 m (2H),
3-Bromo-N-(7-propanoyl-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (6e). Yield 92%, mp 188–
1.09 m (2H), and 1.67 m (1H) (C3H5); 1.23 t (3H,
CH2CH3, J = 7.2 Hz), 3.05 q (2H, CH2CH3, J =
7.2 Hz), 7.21 d.d (1H, Harom, J = 2.0, 8.1 Hz), 7.77 d
(1H, Harom, J = 8.1 Hz), 9.01 d (1H, Harom, J = 2.0 Hz),
12.07 s (1H, NH). Found, %: C 52.32, 52.41; H 4.38,
4.56; N 4.64, 4.72. C13H14BrNO2. Calculated, %:
C 52.72; H 4.76; N 4.73.
1
189°C (from EtOH–CHCl3). H NMR spectrum, δ,
ppm: 1.08 t (3H, CH2CH3, J = 6.8 Hz), 3.07 q (2H,
CH2CH3, J = 6.8 Hz), 4.30 m and 4.37 m (2H each,
OCH2CH2O), 7.58 t (1H, Harom, J = 7.8 Hz), 7.64 s
(1H, Harom), 7.85 d (1H, Harom, J = 7.8 Hz), 7.92 d (1H,
H
arom, J = 7.8 Hz), 8.06 s (1H, Harom), 8.19 s (1H,
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MOCHALOV et al.
964
Harom), 12.48 s (1H, NH). Found, %: C 54.92, 55.11;
H 3.84, 3.91; N 3.35, 3.47. C18H16BrNO4. Calculated,
%: C 55.40; H 4.13; N 3.59.
ppm: 0.93 t (3H, CH2CH3, J = 7.1 Hz), 1.63 sext (2H,
CH2CH3, J = 7.1 Hz), 2.99 t (2H, CH2CH2CH3, J =
7.1 Hz), 4.29 m and 4.36 m (2H each, OCH2CH2O),
7.57 t (1H, Harom, J = 8.0 Hz), 7.61 s (1H, Harom),
7.82 d (1H, Harom, J = 8.0 Hz), 7.89 d (1H, Harom, J =
8.0 Hz), 8.04 s (1H, Harom), 8.18 s (1H, Harom), 12.48 s
(1H, NH). Found, %: C 55.92, 56.17; H 4.15, 4.26;
N 3.28, 3.41. C19H18BrNO4. Calculated, %: C 56.45;
H 4.49; N 3.47.
4-Bromo-N-(7-propanoyl-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (6f). Yield 94%, mp 224–
1
225°C (from EtOH–CHCl3). H NMR spectrum, δ,
ppm: 1.07 t (3H, CH2CH3, J = 6.7 Hz), 3.08 q (2H,
CH2CH3, J = 6.7 Hz), 4.31 m and 4.38 m (2H each,
OCH2CH2O), 7.65 s (1H, Harom), 7.82 d (2H, Harom, J =
8.4 Hz), 7.87 d (2H, Harom, J = 8.4 Hz), 8.23 s (1H,
Harom), 12.63 s (1H, NH). Found, %: C 54.96, 55.18;
H 3.81, 4.03; N 3.46, 3.61. C18H16BrNO4. Calculated,
%: C 55.40; H 4.13; N 3.59.
N-(7-Butanoyl-2,3-dihydro-1,4-benzodioxin-6-
yl)-4-nitrobenzamide (7c). Yield 78%, mp 210–211°C
1
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
1.02 t (3H, CH2CH3, J = 6.7 Hz), 1.72 sext (2H,
CH2CH3, J = 6.7 Hz), 3.01 t (2H, CH2CH2CH3, J =
6.7 Hz), 4.30 m and 4.38 m (2H each, OCH2CH2O),
7.52 s (1H, Harom), 8.21 d (2H, Harom, J = 8.4 Hz),
8.38 s (1H, Harom), 8.40 d (2H, Harom, J = 8.4 Hz),
12.85 s (1H, NH). Found, %: C 61.06, 61.32; H 4.63,
4.78; N 7.31, 7.45. C19H18N2O6. Calculated, %:
C 61.61; H 4.90; N 7.57.
3-Iodo-N-(7-propanoyl-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (6g). Yield 83%, mp 181–
1
182°C (from EtOH–CHCl3). H NMR spectrum, δ,
ppm: 1.08 t (3H, CH2CH3, J = 6.8 Hz), 3.05 q (2H,
CH2CH3, J = 6.8 Hz), 4.29 m and 4.36 m (2H each,
OCH2CH2O), 7.41 t (1H, Harom, J = 8.1 Hz), 7.62 s
(1H, Harom), 7.92 d (1H, Harom, J = 8.1 Hz), 7.99 d (1H,
Harom, J = 8.1 Hz), 8.18 s (1H, Harom), 8.24 s (1H,
Harom), 12.45 s (1H, NH). Found, %: C 48.83, 49.06;
H 3.31, 3.48; N 2.96, 3.11. C18H16INO4. Calculated, %:
C 49.44; H 3.69; N 3.20.
N-[7-(Phenylacetyl)-2,3-dihydro-1,4-benzodiox-
in-6-yl]cyclopropanamide (8a). Yield 81%, mp 130–
1
131°C (from EtOH). H NMR spectrum, δ, ppm:
0.81 m (2H), 1.03 m (2H), 1.59 m (1H) (C3H5); 4.23 m
and 4.31 m (2H each, OCH2CH2O), 4.25 s (2H,
CH2Ph), 7.24–7.38 m (5H, Harom), 7.53 s (1H, Harom),
8.33 s (1H, Harom), 11.92 s (1H, NH). Found, %:
C 70.81, 70.93; H 5.43, 5.48; N 3.96, 4.11. C20H19NO4.
Calculated, %: C 71.20; H 5.68; N 4.15.
N-(7-Propanoyl-2,3-dihydro-1,4-benzodioxin-
6-yl)thiophene-2-carboxamide (6i). Yield 91%,
1
mp 168–169°C (from EtOH–CHCl3). H NMR spec-
trum, δ, ppm: 1.24 t (3H, CH2CH3, J = 6.5 Hz), 2.99 q
(2H, CH2CH3, J = 6.5 Hz), 4.27 m and 4.35 m (2H
each, OCH2CH2O), 7.15 d.d (1H, HTh, J = 3.5, 4.9 Hz),
7.46 s (1H, Harom), 7.51 d (1H, HTh, J = 4.9 Hz), 7.82 d
(1H, HTh, J = 3.5 Hz), 8.43 s (1H, Harom), 12.75 s
(1H, NH). Found, %: C 60.22, 60.31; H 4.51, 4.56;
N 4.29, 4.38. C16H15NO4S. Calculated, %: C 60.55;
H 4.76; N 4.41.
4-Methoxy-N-[7-(phenylacetyl)-2,3-dihydro-
1,4-benzodioxin-6-yl]benzamide (8b). Yield 92%,
1
mp 211–212°C (from EtOH–CHCl3). H NMR spec-
trum, δ, ppm: 3.87 s (3H, OCH3), 4.26 m and 4.34 m
(2H each, OCH2CH2O), 4.28 s (2H, CH2Ph), 6.98 d
(2H, Harom, J = 8.8 Hz), 7.28–7.31 m (3H, Harom), 7.34–
7.39 m (2H, Harom), 7.58 s (1H, Harom), 8.02 d (2H,
N-(7-Butanoyl-2,3-dihydro-1,4-benzodioxin-
6-yl)-4-methylbenzamide (7a). Yield 84%, mp 199–
200°C (from EtOH–CHCl3). H NMR spectrum, δ,
H
arom, J = 8.8 Hz), 8.57 s (1H, Harom), 12.57 s
(1H, NH). Found, %: C 71.03, 71.21; H 4.98, 5.11;
N 3.33, 3.41. C24H21NO5. Calculated, %: C 71.45;
H 5.25; N 3.47.
1
ppm: 0.96 t (3H, CH2CH3, J = 7.2 Hz), 1.67 sext (2H,
CH2CH3, J = 7.2 Hz), 2.40 s (3H, CH3), 2.96 t (2H,
CH2CH2CH3, J = 7.2 Hz), 4.27 m and 4.34 m (2H
each, OCH2CH2O), 7.34 d (2H, Harom, J = 7.8 Hz),
7.55 s (1H, Harom), 7.83 d (2H, Harom, J = 7.8 Hz),
8.34 s (1H, Harom), 12.57 s (1H, NH). Found, %:
C 70.34, 70.41; H 6.03, 6.11; N 3.98, 4.07. C20H21NO4.
Calculated, %: C 70.78; H 6.24; N 4.13.
4-Chloro-N-[7-(phenylacetyl)-2,3-dihydro-
1,4-benzodioxin-6-yl]benzamide (8c). Yield 95%,
mp 193–194°C (from EtOH–CHCl3). H NMR spec-
trum, δ, ppm: 4.27 m and 4.36 m (2H each,
OCH2CH2O), 4.28 s (2H, CH2Ph), 7.27–7.33 m (3H,
1
Harom), 7.35–7.39 m (2H, Harom), 7.46 d (2H, Harom, J =
8.3 Hz), 7.59 s (1H, Harom), 7.98 d (2H, Harom, J =
8.3 Hz), 8.54 s (1H, Harom), 12.67 s (1H, NH). Found,
%: C 67.21, 67.42; H 4.09, 4.26; N 3.27, 3.38.
C23H18ClNO4. Calculated, %: C 67.73; H 4.45; N 3.44.
3-Bromo-N-(7-butanoyl-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (7b). Yield 93%, mp 150–
1
151°C (from EtOH–CHCl3). H NMR spectrum, δ,
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TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
965
Cyclization of N-(2-acylaryl) amides 1a, 1b,
2a–2h, 3a–3g, 4, 5a, 5b, 6a–6i, 7a, 7b, and 8a–8c to
2-aryl-, 2-hetaryl-, and 2-cyclopropylquinolin-
4(1H)-ones (general procedure). Amide 1–8, 1 mmol,
was added to a solution of 5 mmol of sodium ethoxide
in 30 mL of ethanol or anhydrous THF (a), 5 mmol of
potassium tert-butoxide in 30 mL of tert-butyl alcohol
(b), or 2 mmol of potassium tert-butoxide in 30 mL of
anhydrous THF (c). The mixture was refluxed for
a time indicated in Tables 1 and 3, cooled to 20°C, and
poured into 180 mL of cold water. The precipitate was
filtered off, washed with water until neutral washings,
dried, and recrystallized. The cyclization conditions
2-(2-Bromophenyl)-3-methylquinolin-4(1H)-one
(9e). mp 281–282°C (from EtOH–CHCl3). IR spec-
trum, ν, cm–1: 2935, 1632, 1580, 1545, 1481. 1H NMR
spectrum, δ, ppm: 1.72 s (3H, CH3), 7.31 t (1H, Harom
,
J = 8.0 Hz), 7.48–7.64 m (5H, Harom), 7.85 d (1H,
Harom, J = 8.0 Hz), 8.14 d (1H, Harom, J = 8.0 Hz),
11.76 s (1H, NH). Found, %: C 60.68, 60.84; H 3.52,
3.70; N 4.29, 4.36. C16H12BrNO. Calculated, %:
C 61.17; H 3.85; N 4.46.
2-(4-Bromophenyl)-3-methylquinolin-4(1H)-one
1
(9f). mp 267–268°C (from EtOH). H NMR spectrum,
δ, ppm: 1.87 s (3H, CH3), 7.29 t (1H, Harom, J =
8.0 Hz), 7.53 d (2H, Harom, J = 8.2 Hz), 7.57–7.68 m
(2H, Harom), 7.78 d (2H, Harom, J = 8.2 Hz), 8.12 d
(1H, Harom, J = 8.0 Hz), 11.60 s (1H, NH). Found, %:
C 60.58, 60.72; H 3.53, 3.66; N 4.31, 4.46.
C16H12BrNO. Calculated, %: C 61.17; H 3.85; N 4.46.
1
and yields are given in Tables 1 and 3. The H NMR
spectra of the products were recorded from solutions in
DMSO-d6.
2-Cyclopropyl-3-methylquinolin-4(1H)-one (9a).
1
mp 314–316°C (from EtOH). H NMR spectrum, δ,
3-Methyl-2-(thiophen-2-yl)quinolin-4(1H)-one
(9g). mp 221–222°C (from EtOH). IR spectrum, ν,
ppm: 0.99 m (2H), 1.06 m (2H), 2.15 m (1H) (C3H5);
2.11 s (3H, CH3), 7.22 d.t (1H, Harom, J = 1.2, 7.8 Hz),
1
cm–1: 3278, 2936, 1638, 1610, 1580, 1469. H NMR
7.54 d.t (1H, Harom, J = 1.2, 7.8 Hz), 7.65 d (1H, Harom
,
spectrum, δ, ppm: 2.05 s (3H, CH3), 7.29 d.d (1H, HTh,
J = 3.7, 5.2 Hz), 7.51 d.d (1H, HTh, J = 1.1, 3.9 Hz),
J = 7.8 Hz), 8.04 d (1H, Harom, J = 7.8 Hz), 10.59 s
(1H, NH). Found, %: C 77.98, 78.06; H 6.28, 6.36;
N 6.87, 6.97. C13H13NO. Calculated, %: C 78.36;
H 6.57; N 7.03.
7.87 d.d (1H, HHt, J = 1.1, 5.2 Hz), 7.31 d.t (1H, Harom
,
J = 1.4, 8.0 Hz), 7.61 d.t (1H, Harom, J = 1.4, 8.0 Hz),
7.63 d.d (1H, Harom, J = 1.4, 8.0 Hz), 8.11 d.d (1H,
2-(3-Methoxyphenyl)-3-methylquinolin-4(1H)-
one (9b). mp 226–228°C (from EtOH). IR spectrum, ν,
Harom, J = 1.4, 8.0 Hz), 11.58 s (1H, NH). Found, %:
C 69.31, 69.54; H 4.32, 4.69; N 5.67, 5.72.
C14H11NOS. Calculated, %: C 69.68; H 4.60; N 5.81.
1
cm–1: 2944, 1639, 1585, 1540, 1472. H NMR spec-
trum, δ, ppm: 1.91 s (3H, CH3), 3.83 s (3H, OCH3),
7.10–7.13 m (3H, Harom), 7.29 m (1H, Harom), 7.48 t
(1H, Harom, J = 8.0 Hz), 7.59–7.62 m (2H, Harom),
8.12 d (1H, Harom, J = 8.0 Hz), 11.59 s (1H, NH).
Found, %: C 76.62, 76.80; H 5.41, 5.52; N 5.14, 5.26.
C17H15NO2. Calculated, %: C 76.96; H 5.70; N 5.28.
2-Cyclopropyl-7-bromo-3-methylquinolin-
4(1H)-one (9h). mp 307–309°C (from EtOH–CHCl3).
IR spectrum, ν, cm–1: 3270, 2930, 1638, 1590, 1550,
1
1472. H NMR spectrum, δ, ppm: 0.97 m (2H), 1.08 m
(2H), 2.16 m (1H) (C3H5), 2.09 s (3H, CH3), 7.35 d.d
(1H, Harom, J = 1.7, 8.4 Hz), 7.89 d (1H, Harom, J =
1.7 Hz), 7.94 d (1H, Harom, J = 8.4 Hz), 10.57 s
(1H, NH). Found, %: C 55.76, 55.83; H 4.09, 4.16;
N 4.86, 5.01. C13H12BrNO. Calculated, %: C 56.13;
H 4.35; N 5.04.
2-(4-Fluorophenyl)-3-methylquinolin-4(1H)-one
(9c). mp 312–314°C (from EtOH). IR spectrum, ν,
1
cm–1: 2938, 1637, 1588, 1548, 1478. H NMR spec-
trum, δ, ppm: 1.88 s (3H, CH3), 7.27–7.32 m (1H,
H
arom), 7.41 d.t (2H, Harom, J = 2.4, 8.1 Hz), 7.59–
6-Chloro-2-(4-chlorophenyl)-3-methylquinolin-
4(1H)-one (9i). mp 287–289°C (from EtOH). IR spec-
trum, ν, cm–1: 2942, 1635, 1610, 1578, 1475. 1H NMR
7.65 m (4H, Harom), 8.12 d (1H, Harom, J = 8.0 Hz),
11.59 s (1H, NH). Found, %: C 75.64, 75.79; H 4.63,
4.80; N 5.31, 5.46. C16H12FNO. Calculated, %:
C 75.87; H 4.78; N 5.53.
spectrum, δ, ppm: 1.87 s (3H, CH3), 7.60 d (2H, Harom
J = 8.2 Hz), 7.62–7.68 m (4H, Harom), 8.05 d (1H,
arom, J = 1.7 Hz), 11.75 br.s (1H, NH). Found, %:
,
2-(4-Chlorophenyl)-3-methylquinolin-4(1H)-one
(9d). mp 258–261°C (from EtOH). IR spectrum, ν,
H
1
cm–1: 3288, 2935, 1630, 1610, 1515, 1469. H NMR
C 62.71, 62.92; H 3.42, 3.48; N 4.43, 4.52.
C16H11ClN2O. Calculated, %: C 63.18; H 3.65; N 4.61.
spectrum, δ, ppm: 1.86 s (3H, CH3), 7.29 m (1H,
Harom), 7.54–7.67 m (6H, Harom), 8.11 d (1H, Harom, J =
8.1 Hz), 11.63 s (1H, NH). Found, %: C 70.78, 70.91;
H 4.31, 4.41; N 4.99, 5.08. C16H12ClNO. Calculated,
%: C 71.24; H 4.49; N 5.19.
2-(4-Bromophenyl)-6-chloro-3-methylquinolin-
4(1H)-one (9j). mp 308–310°C (from EtOH–CHCl3).
IR spectrum, ν, cm–1: 3340, 2948, 1630, 1608, 1560,
1
1471. H NMR spectrum, δ, ppm: 1.90 s (3H, CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

MOCHALOV et al.
966
7.43 d (2H, Harom, J = 8.3 Hz), 7.48 d.d (1H, Harom, J =
2.4, 8.4 Hz), 7.68 d (2H, Harom, J = 8.3 Hz), 7.83 d
(1H, Harom, J = 8.4 Hz), 8.07 d (1H, Harom, J = 2.4 Hz),
11.66 s (1H, NH). Found, %: C 54.79, 54.89; H 2.95,
3.16; N 3.91, 3.98. C16H11BrClNO. Calculated, %:
C 55.12; H 3.18; N 4.02.
8.0 Hz), 11.31 s (1H, NH). Found, %: C 57.69, 57.78;
H 3.42, 3.58; N 3.58, 3.71. C18H14BrNO3. Calculated,
%: C 58.08; H 3.79; N 3.76.
7-(3-Iodophenyl)-8-methyl-2,3-dihydro[1,4]di-
oxino[2,3-g]quinolin-9(6H)-one (9p). mp 325–326°C
1
(from EtOH). H NMR spectrum, δ, ppm: 1.83 s (3H,
CH3), 4.29 m and 4.34 m (2H each, OCH2CH2O),
7.01 s (1H, Harom), 7.35 t (1H, Harom, J = 8.1 Hz), 7.45 s
(1H, Harom), 7.55 d (1H, Harom, J = 8.1 Hz), 7.88 m
(1H, Harom), 7.91 d (1H, Harom, J = 8.1 Hz), 11.32 s
(1H, NH). Found, %: C 51.12, 51.31; H 3.06, 3.16;
N 3.28, 3.31. C18H14INO3. Calculated, %: C 51.57;
H 3.37; N 3.34.
8-Methyl-7-(4-methylphenyl)-2,3-dihydro[1,4]-
dioxino[2,3-g]quinoline-9(6H)-one (9k). mp 310–
311°C (from EtOH). IR spectrum, ν, cm–1: 3380, 2940,
1636, 1600, 1472. H NMR spectrum, δ, ppm: 1.85 s
(3H, CH3), 2.40 s (3H, CH3), 4.28 m and 4.33 m (2H
each, OCH2CH2O), 7.03 s (1H, Harom), 7.36 d (2H,
1
H
arom, J = 8.1 Hz), 7.40 d (2H, Harom, J = 8.1 Hz),
7.45 s (1H, Harom), 11.23 s (1H, NH). Found, %:
C 73.92, 74.26; H 5.41, 5.63; N 4.41, 4.52. C19H17NO3.
Calculated, %: C 74.25; H 5.57; N 4.56.
7-(Furan-2-yl)-8-methyl-2,3-dihydro[1,4]dioxino-
[2,3-g]quinolin-9(6H)-one (9q). mp 317–318°C (from
EtOH). IR spectrum, ν, cm–1: 3376, 2935, 1638, 1590,
1
1520, 1468. H NMR spectrum, δ, ppm: 2.15 s (3H,
7-Cyclopropyl-8-methyl-2,3-dihydro[1,4]dioxino-
[2,3-g]quinolin-9(6H)-one (9l). mp >340°C (from
EtOH–CHCl3). H NMR spectrum, δ, ppm: 0.92 m
CH3), 4.22 m and 4.34 m (2H each, OCH2CH2O),
6.77 d.d (1H, HFu, J = 2.1, 3.6 Hz), 7.05 d (1H, HFu,
J = 3.6 Hz), 7.98 d (1H, HFu, J = 2.1 Hz), 7.21 s (1H,
1
(2H), 1.01 m (2H), and 2.06 m (1H) (C3H5); 2.05 s
(3H, CH3), 4.26 m and 4.30 m (2H each, OCH2CH2O),
7.09 s (1H, Harom), 7.37 s (1H, Harom), 10.31 s
(1H, NH). Found, %: C 69.39, 69.64; H 5.56, 5.65;
N 5.21, 5.36. C15H15NO3. Calculated, %: C 70.02;
H 5.88; N 5.45.
Harom), 7.45 s (1H, Harom), 11.12 s (1H, NH). Found, %:
C 67.52, 67.81; H 4.33, 4.67; N 4.76, 4.93. C16H13NO4.
Calculated, %: C 67.84; H 4.62; N 4.95.
8-Methyl-7-(thiophen-2-yl)-2,3-dihydro[1,4]di-
oxino[2,3-g]quinolin-9(6H)-one (9r). mp 298–299°C
(from EtOH). IR spectrum, ν, cm–1: 3246, 2942, 1648,
7-(2-Fluorophenyl)-8-methyl-2,3-dihydro[1,4]-
dioxino[2,3-g]quinolin-9(6H)-one (9m). mp 315–
317°C (from EtOH–CHCl3). IR spectrum, ν, cm–1:
1
1608, 1540, 1471. H NMR spectrum, δ, ppm: 2.00 s
(3H, CH3), 4.29 m and 4.34 m (2H each, OCH2CH2O),
7.06 s (1H, Harom), 7.44 s (1H, Harom), 7.27 d.d (1H,
HTh, J = 3.9, 5.4 Hz), 7.46 d (1H, HTh, J = 3.9 Hz),
7.85 d (1H, HHt, J = 5.4 Hz), 11.28 s (1H, NH). Found,
%: C 63.85, 64.05; H 4.15, 4.30; N 4.51, 4.62.
C16H13NO3S. Calculated, %: C 64.21; H 4.38; N 4.68.
1
3368, 2926, 1645, 1622, 1593, 1486. H NMR spec-
trum, δ, ppm: 1.78 s (3H, CH3), 4.30 m and 4.34 m
(2H each, OCH2CH2O), 7.01 s (1H, Harom), 7.39–7.46 m
(2H, Harom), 7.51 s (1H, Harom), 7.53–7.57 m (1H,
Harom), 7.60–7.65 m (1H, Harom), 11.72 s (1H, NH).
Found, %: C 69.01, 69.22; H 4.27, 4.35; N 4.44, 4.48.
C18H14FNO3. Calculated, %: C 69.45; H 4.53; N 4.50.
8-Ethyl-7-(4-methylphenyl)-2,3-dihydro[1,4]di-
oxino[2,3-g]quinolin-9(6H)-one (9s). mp 286–287°C
1
7-(2-Bromophenyl)-8-methyl-2,3-dihydro[1,4]di-
(from EtOH). H NMR spectrum, δ, ppm: 0.92 t (3H,
oxino[2,3-g]quinolin-9(6H)-one (9n). mp 329–331°C
(from EtOH). H NMR spectrum, δ, ppm: 1.67 s (3H,
CH2CH3, J = 7.4 Hz), 2.28 q (2H, CH2CH3, J =
7.4 Hz), 2.40 s (3H, CH3), 4.28 m and 4.32 m (2H
each, OCH2CH2O), 7.01 s (1H, Harom), 7.34 s (4H,
1
CH3), 4.30 m and 4.33 m (2H each, OCH2CH2O),
6.95 s (1H, Harom), 7.47 s (1H, Harom), 7.48–7.63 m
(3H, Harom), 7.82 d (1H, Harom, J = 8.1 Hz), 11.46 s
(1H, NH). Found, %: C 57.58, 57.76; H 3.51, 3.62;
N 3.48, 3.56. C18H14BrNO3. Calculated, %: C 58.08;
H 3.79; N 3.76.
Harom), 7.45 s (1H, Harom), 11.20 s (1H, NH). Found, %:
C 74.38, 74.51; H 5.71, 5.82; N 4.28, 4.34. C20H19NO3.
Calculated, %: C 74.75; H 5.96; N 4.36.
7-Cyclopropyl-8-phenyl-2,3-dihydro[1,4]dioxino-
[2,3-g]quinolin-9(6H)-one (9t). mp 383–385°C
(sublimes). IR spectrum, ν, cm–1: 3260, 2945, 1645,
7-(4-Bromophenyl)-8-methyl-2,3-dihydro[1,4]di-
1
oxino[2,3-g]quinolin-9(6H)-one (9o). mp 362–364°C
1610, 1590, 1470. H NMR spectrum, δ, ppm: 0.85 m
1
(from EtOH–CHCl3). H NMR spectrum, δ, ppm:
(2H), 0.96 m (2H), and 1.83 m (1H) (C3H5), 4.28 m
and 4.32 m (2H each, OCH2CH2O), 7.17 s (1H, Harom),
7.24–7.30 m (3H, Harom), 7.34–7.39 m (2H, Harom),
7.40 s (1H, Harom), 10.22 s (1H, NH). Found, %:
1.83 s (3H, CH3), 4.30 m and 4.32 m (2H each,
OCH2CH2O), 7.01 s (1H, Harom), 7.45 s (1H, Harom),
7.48 d (2H, Harom, J = 8.0 Hz), 7.75 d (2H, Harom, J =
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TRANSFORMATIONS OF N-(2-ACYLARYL)BENZAMIDES
967
1
C 74.62, 74.81; H 5.16, 5.33; N 4.21, 4.37. C20H17NO3.
Calculated, %: C 75.22; H 5.36; N 4.39.
cm–1: 3224, 2965, 1632, 1606, 1592, 1481. H NMR
spectrum, δ, ppm: 4.37 m and 4.41 m (2H each,
OCH2CH2O), 6.26 s (1H, Harom), 7.18 s (1H, Harom),
7.55–7.72 m (5H, Harom), 11.83 s (1H, NH). Found, %:
C 64.71, 64.88; H 3.51, 3.67; N 4.32, 4.41.
C17H12ClNO3. Calculated, %: C 65.08; H 3.86; N 4.47.
7-(4-Methoxyphenyl)-8-phenyl-2,3-dihydro[1,4]-
dioxino[2,3-g]quinolin-9(6H)-one (9u). mp 318–
319°C (from EtOH). IR spectrum, ν, cm–1: 2934, 1635,
1
1610, 1572, 1471. H NMR spectrum, δ, ppm: 3.73 s
Reaction of N-(2-acylaryl) amides 1a, 1b, 2c, 2g,
2h, 6e, 6g, 6i, and 7b with 5 equiv of potassium
tert-butoxide in THF (general procedure). Amide 1a,
1b, 2c, 2g, 2h, 6e, 6g, 6i, or 7b, 1 mmol, was added to
a suspension of 5 mmol of potassium tert-butoxide in
30 mL of anhydrous THF. The mixture was refluxed
for a time indicated in Table 2, cooled to 20°C, and
poured into 180 mL of water. In the reactions with 1a,
1b, 2e, 2g, and 2h, the precipitate was filtered off,
washed with water, dried, and recrystallized to isolate
compounds 10a–10c. The filtrate was acidified with
2 N aqueous HCl to pH 4–5, and the amorphous solid
was filtered off, washed with water, dried, and purified
by reprecipitation from a 2% solution of potassium
hydroxide. We thus isolated compounds 11a–11e. In
the reactions with 6e, 6g, 6i, and 7b, the solution
obtained after pouring the reaction mixture into water
was acidified with 2 N aqueous HCl, and the amor-
phous solid (11d, 11e, or 11f) was separated, washed,
(3H, OCH3), 4. 30 m and 4. 35 m (2H each,
OCH2CH2O), 6.85 d (2H, Harom, J = 8.4 Hz), 7.03 m
(2H, Harom), 7.09–7.21 m (6H, Harom), 7.48 s (1H,
Harom), 11.40 s (1H, NH). Found, %: C 74.62, 74.78;
H 4.81, 4.97; N 3.48, 3.69. C24H19NO4. Calculated, %:
C 74.79; H 4.97; N 3.63.
7-(4-Chlorophenyl)-8-phenyl-2,3-dihydro[1,4]di-
oxino[2,3-g]quinolin-9(6H)-one (9v). mp 327–328°C
(from EtOH). IR spectrum, ν, cm–1: 2943, 1644, 1609,
1
1585, 1472. H NMR spectrum, δ, ppm: 4.31 m and
4.35 m (2H each, OCH2CH2O), 7.01–7.04 m (2H,
Harom), 7.10 s (1H, Harom), 7.11–7.19 m (3H, Harom),
7.28 d (2H, Harom, J = 7.8 Hz) 7.37 d (2H, Harom, J =
7.8 Hz), 7.49 s (1H, Harom), 11.56 s (1H, NH). Found,
%: C 70.44, 70.61; H 3.91, 4.06; N 3.44, 3.51.
C23H16ClNO3. Calculated, %: C 70.86; H 4.14; N 3.59.
7-tert-Butyl-2-(4-chlorophenyl)quinolin-4(1H)-
1
one (10a). H NMR spectrum, δ, ppm: 1.35 s [9H,
1
C(CH3)3], 6.36 s (1H, Harom), 7.42 d (1H, Harom, J =
8.3 Hz), 7.58 d (1H, Harom, J = 8.3 Hz), 7.63 d (2H,
and purified as described above. The H NMR spectra
of 11a–11f were recorded from solutions in DMSO-d6,
and the spectrum of 12 was measured in CDCl3.
H
H
arom, J = 8.2 Hz), 7.76 s (1H, Harom), 8.03 d (2H,
arom, J = 8.2 Hz), 11.70 s (1H, NH). Found, %:
N-(5-tert-Butyl-2-hydroxyphenyl)-4-chlorobenz-
C 72.63, 72.81; H 5.52, 5.71; N 4.24, 4.36.
C19H18ClNO. Calculated, %: C 73.19; H 5.82; N 4.49.
1
amide (11a). mp 251–252°C (from EtOH). H NMR
spectrum, δ, ppm: 1.31 s [9H, C(CH3)3], 7.24 d (1H,
Harom, J = 8.3 Hz), 7.67 d (2H, Harom, J = 8.0 Hz),
7.94 d (1H, Harom, J = 8.3 Hz), 7.97 d (2H, Harom, J =
8.0 Hz), 8.80 s (1H, Harom), 12.17 s (1H, NH). Found,
%: C 70.51, 70.69; H 6.11, 6.17; N 4.63, 4.78.
C17H18ClNO2. Calculated, %: C 70.95; H 6.30; N 4.87.
2-(4-Bromophenyl)-7-tert-butylquinolin-4(1H)-
1
one (10b). mp 253–255°C (from EtOH). H NMR
spectrum, δ, ppm: 1.35 s [9H, C(CH3)3], 6.33 s (1H,
H
arom), 7.43 d.d (1H, Harom, J = 1.2, 8.3 Hz), 7.75–
7.83 m (5H, Harom), 8.02 d (1H, Harom, J = 8.3 Hz),
11.69 s (1H, NH). Found, %: C 63.56, 63.71; H 4.81,
4.93; N 3.82, 3.88. C19H18BrNO. Calculated, %:
C 64.05; H 5.09; N 3.93.
4-Bromo-N-(5-tert-butyl-2-hydroxyphenyl)benz-
amide (11b). mp 266–267°C (from EtOH). IR spec-
1
trum: ν 3411 cm–1 (OH). H NMR spectrum, δ, ppm:
7-(3-Iodophenyl)-2,3-dihydro[1,4]dioxino[2,3-g]-
quinolin-9(6H)-one (10e). mp 319–321°C (from
EtOH–CHCl3). 1H NMR spectrum, δ, ppm: 4.32 m and
4.35 m (2H each, OCH2CH2O), 6.19 s (1H, Harom),
7.18 s (1H, Harom), 7.35 t (1H, Harom, J = 7.9 Hz), 7.43 s
(1H, Harom), 7.79 d.d (1H, Harom, J = 1.4, 7.9 Hz),
7.92 d (1H, Harom, J = 7.9 Hz), 8.13 d (1H, Harom, J =
1.4 Hz), 11.47 s (1H, NH). Found, %: C 54.10, 54.28;
H 3.06, 3.14; N 3.35, 3.56. C17H12INO3. Calculated, %:
C 54.71; H 3.24; N 3.75.
1.32 s [9H, C(CH3)3], 7.24 d.d (1H, Harom, J = 1.8,
8.3 Hz), 7.79 d (2H, Harom, J = 8.4 Hz), 7.87 d (2H,
Harom, J = 8.4 Hz), 7.98 d (1H, Harom, J = 8.3 Hz),
8.80 d (1H, Harom, J = 1.8 Hz), 12.24 s (1H, NH).
Found, %: C 58.17, 58.26; H 5.01, 5.07; N 3.79, 3.93.
C17H18BrNO2. Calculated, %: C 58.63; H 5.21; N 4.02.
3-Fluoro-N-(7-hydroxy-2,3-dihydro-1,4-benzodi-
oxin-6-yl)benzamide (11c). mp 231–233°C (from
1
EtOH). IR spectrum: ν 3392 cm–1 (OH). H NMR
spectrum, δ, ppm: 4.27 m and 4.34 m (2H each,
OCH2CH2O), 7.47–7.52 m (2H, Harom), 7.60–7.68 m
(2H, Harom), 7.73 d (1H, Harom, J = 8.0 Hz), 8.21 s (1H,
7-(2-Chlorophenyl)-2,3-dihydro[1,4]dioxino-
[2,3-g]quinolin-9(6H)-one (10f). IR spectrum, ν,
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MOCHALOV et al.
968
3. Li, L., Wang, H.K., Kuo, S.C., Wu, T.S., Lednicer, D.,
Lin, C.M., Hamel, E., and Lee, K.H., J. Med. Chem.,
1994, vol. 37, p. 3400.
4. Xia, Y., Yang, Z.-Y., Xia, P., Hacke, T., Hamel, E.,
Mauger, A., Wu, J.-H., and Lee, K.-H., J. Med. Chem.,
2001, vol. 44, p. 3932.
5. Hadjeri, M., Peiller, E.-L., Beney, Ch., Deka, N.,
Lawson, M.A., Dumontet, Ch., and Boumendjel, A.,
J. Med. Chem., 2004, vol. 47, p. 4964.
Harom), 12.11 s (1H, NH). Found, %: C 61.79, 61.92;
H 3.92, 4.01; N 4.72, 4.78. C15H12FNO4. Calculated,
%: C 62.28; H 4.18; N 4.84.
3-Bromo-N-(7-hydroxy-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (11d). mp 248–249°C (from
1
EtOH). IR spectrum: ν 3408 cm–1 (OH). H NMR
spectrum, δ, ppm: 4.28 m and 4.35 m (2H each,
OCH2CH2O), 7.47 s (1H, Harom), 7.54 t (1H, Harom, J =
8.0 Hz), 7.83 d.d (1H, Harom, J = 1.1, 8.0 Hz), 7.89 d
(1H, Harom, J = 8.0 Hz), 8.05 s (1H, Harom), 8.20 s (1H,
6. Pain, Ch., Celanire, S., Guillaumet, G., and Joseph, B.,
Tetrahedron, 2003, vol. 59, p. 9627.
Harom), 12.14 s (1H, NH). Found, %: C 50.88, 51.12;
7. Nakamura, S., Kozuka, M., Bastow, K.F., Tokuda, H.,
Nishino, H., Suzuki, M., Tatsuzaki, J., Morris
Natschke, S.L., Kuo, S.-C., and Lee, K.-H., Bioorg.
Med. Chem., 2005, vol. 13, p. 4396.
8. Chen, Y.-C., Lu, P.-N., Pan, S.-L., Teng, C.-M.,
Kuo, S.-C., Lin, T.P., Ho, Y.-F., Huang, Y.-C., and
Guh, J.-H., Biochem. Pharmacol., 2007, vol. 74, p. 10.
9. Wang, S.-W., Pan, S.-L., Huang, Y.-C., Guh, J.-H.,
Chiang, P.-C., Huang, D.-Y., Kuo, S.-C., Lee, K.-H., and
Teng, C.-M., Mol. Cancer Ther., 2008, vol. 7, p. 350.
10. Soural, M., Hlavac, J., Hradil, P., and Hajduch, M., Eur.
J. Org. Chem., 2009, p. 3867.
H 3.19, 3.28; N 3.86, 3.94. C15H12BrNO4. Calculated,
%: C 51.45; H 3.45; N 4.00.
N-(7-Hydroxy-2,3-dihydro-1,4-benzodioxin-
6-yl)-3-iodobenzamide (11e). mp 217–219°C (from
1
EtOH). IR spectrum: ν 3340 cm–1 (OH). H NMR
spectrum, δ, ppm: 4.27 m and 4.34 m (2H each,
OCH2CH2O), 7.37 t (1H, Harom, J = 8.0 Hz), 7.47 s
(1H, Harom), 7.91 d.d (1H, Harom, J = 1.5, 8.0 Hz),
7.97 d (1H, Harom, J = 8.0 Hz), 8.20 s (1H, Harom),
8.23 d (1H, Harom, J = 1.5 Hz), 12.32 s (1H, NH).
Found, %: C 44.81, 45.06; H 2.92, 2.98; N 3.41, 3.52.
C15H12INO4. Calculated, %: C 45.36; H 3.04; N 3.53.
11. Gootz, T.D. and Brighty, K.E., Med. Res. Rev., 1996,
vol. 16, p. 433.
N-(7-Hydroxy-2,3-dihydro-1,4-benzodioxin-6-
yl)thiophene-2-carboxamide (11f). mp 242–243°C
(from EtOH). IR spectrum: ν 3420 cm–1 (OH).
1H NMR spectrum, δ, ppm: 4.26 m and 4.34 m (2H
each, OCH2CH2O), 7.24 m (1H, HTh), 7.68 d (1H, HTh,
J = 3.9 Hz), 7.90 d (1H, HTh, J = 4.6 Hz), 7.47 s (1H,
12. Mitscher, L.A., Chem. Rev., 2005, vol. 105, p. 559.
13. Boteva, A.A. and Krasnykh, O.P., Chem. Heterocycl.
Compd., 2009, vol. 45, p. 757.
14. Moyer, M.P., Weber, F.H., and Gross, J.L., J. Med.
Chem., 1992, vol. 35, p. 4595.
15. d’A. Lucero, B., Gomes, C.P.B., de P.P. Frugu-
lhetti, I.C., Faro, L.V., Alvarenga, L., de Souza, M.C.,
de Souza, T.M.L., and Ferreira, V.F., Bioorg. Med.
Chem. Lett., 2006, vol. 16, p. 1010.
Harom), 8.14 s (1H, Harom), 12.08 s (1H, NH). Found, %:
C 55.92, 56.11; H 3.71, 3.81; N 4.95, 5.01.
C13H11NO4S. Calculated, %: C 56.31; H 4.00; N 5.05.
16. Di Santo, R., Costi, R., Roux, A., Artico, M., Lave-
cchia, A., Marinelli, L., Novellino, E., Palmisano, L.,
Andreotti, M., Amici, R., Galluzzo, C.M., Nencioni, L.,
Palamara, A.T., Pommier, Y., and Marchand, Ch.,
J. Med. Chem., 2006, vol. 49, p. 1939.
17. Volmer, D.A., Mansoori, B., and Locke, S.J., Anal.
Chem., 1997, vol. 69, p. 4143.
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Perkin Trans. 1, 2002, p. 1232.
3-Bromo-N-(7-methoxy-2,3-dihydro-1,4-benzo-
dioxin-6-yl)benzamide (12). mp 187–188°C (from
EtOH). 1H NMR spectrum, δ, ppm: 3.94 s (3H, OCH3),
4.28 m and 4.34 m (2H each, OCH2CH2O), 7.39 t (1H,
Harom, J = 8.0 Hz), 7.60 s (1H, Harom), 7.68 m (1H,
H
arom), 7.94 m (1H, Harom), 8.19 t (1H, Harom, J =
1.8 Hz), 8.47 s (1H, Harom), 11.94 s (1H, NH). Found,
%: C 52.41, 52.58; H 3.64, 3.76; N 3.71, 3.82.
C16H14BrNO4. Calculated, %: C 52.77; H 3.87; N 3.85.
19. Casey, A.C., J. Med. Chem., 1974, vol. 17, p. 255.
20. Xia, Y., Yang, Z.-Y., Xia, P., Bastow, K.F., Naka-
nishi, Y., Nampoothiri, P., Hamel, E., Brossi, A., and
Lee, K.-H., Bioorg. Med. Chem. Lett., 2003, vol. 13,
p. 2891.
21. Brunet, M.L., Bailey, M.D., Ghiro, E., Gorys, V.,
Halmos, T., Poirier, M., Rancourt, J., and Goudreau, N.,
J. Med. Chem., 2004, vol. 47, p. 6584.
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