Self-Condensation of Enaminodiones as a Method for Benzene Ring Construction: Synthesis of Diacyl-Substituted Phenols and Catechols

Article abstract of DOI:10.1021/acs.joc.9b00623

A novel transition metal-free approach for the construction of the benzene core has been developed through self-condensation of available enaminodiones. Functionalized acyl-substituted phenols and catechols were obtained in 29-97% yields with high chemoselectivity under mild conditions. This base-promoted formal [4+2] annulation proceeds via cyclohexanone formation and involves the cascade transformation based on double Michael addition and aromatization (retro-Claisen cleavage and amine elimination).

Full text of DOI:10.1021/acs.joc.9b00623

Subscriber access provided by University of Otago Library
Note
Self-Condensation of Enaminodiones as a Method for the Benzene Ring
Construction: Synthesis of Diacyl-Substituted Phenols and Catechols
Dmitrii L'vovich Obydennov, Elena Vladimirovna Chernyshova, and Vyacheslav Y. Sosnovskikh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00623 • Publication Date (Web): 18 Apr 2019
Downloaded from http://pubs.acs.org on April 22, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 14
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Self-Condensation of Enaminodiones as a Method for the Benzene Ring
Construction: Synthesis of Diacyl-Substituted Phenols and Catechols
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dmitrii L. Obydennov,* Elena V. Chernyshova, and Vyacheslav Y. Sosnovskikh
Institute of Natural Sciences and Mathematics, Ural Federal University, 620000 Ekaterinburg, Russian Federation.
Supporting Information Placeholder
O
O
R2
R1
OH
O
O
O
R2
R2
R1
Me2N
R1
Me2N
LiH, Si(OEt)4
NMe2
O
+
, DME
O
O
O
O
R1
R2
R1
R1
R2
23 examples
yields up to 97%
Me2N
R1 = Ar, Het, OEt, Alk; R2 = H, Me, MeO, BnO, PhO
ABSTRACT: A novel transition metal-free approach for the construction of the benzene core has been developed through self-
condensation of available enaminodiones. Functionalized acyl-substituted phenols and catechols were obtained in 29–97% yields
and with high chemoselectivity under mild conditions. This base-promoted formal [4+2] annulation proceeds via cyclohexanone
formation and involves the cascade transformation based on double Michael addition and aromatization (retro-Claisen cleavage,
amine elimination).
Benzene derivatives are an important class of molecules that
are widely used in human life, including bioactive
compounds1a–c and modern materials.1d,e Therefore, efficient
methods for the preparation of polysubstituted benzenes have
always been paid a lot of attention. The most popular and
convenient methods include CH-functionalization2 of
preexisting arenes, such as electrophilic (Friedel-Crafts
reaction2a,b) and nucleophilic substitution transformations, as
well as interactions with organometallic reagents.2c,d However,
there are often difficulties related to the selectivity because of
substituent influence, as a result, the use of multistage
sequential manipulation of functional groups is necessary.
Therefore, straightforward and efficient de novo syntheses of
highly functionalized benzenes on the basis of easily
accessible precursors are highly attractive, moreover, these
approaches are also important for sustainable chemistry.3 The
well-explored strategies include Reppe trimerization of
alkynes, Diels−Alder reaction, Bergman cyclization,
Danheiser annulation, ring-closing metathesis, Dötz [3+2+1]
reaction and Wulff [5+1] ortho-benzannulation.4 In recent
time, selective transformations for the construction of
substituted benzenes have been developed on the basis of
diketones and enones,5 which are usually used as valuable
building blocks, including multicomponent,5f carbene-
catalyzed,5g,h and transition metal-free5i reactions. Since
enaminones can be related to enones and hidden diketones,
this structural feature allows to consider them as convenient
intermediates for the synthesis of arenes.6 There are several
transition metal-free approaches in the literature (Scheme 1)
based on enaminones, such as the acid-promoted [2+2+2]
trimerization,7a the catalyst-free [3+3] reaction with 3-
formylchromones,7b and the acid-promoted formal [4+2]
cycloaddition with dienals.7c Besides, Rh- and In-catalyzed
benzannulations have also been actively developed with the
use of enaminones.8
We envisaged to introduce an additional nucleophilic center
into the enaminone structure, which could be used for
designing a domino transformation to obtain cyclohexanones
based on the double Michael addition.9 Subsequent
aromatization including dimethylamine elimination and retro-
Claisen reaction10 should lead to the formation of acyl-
substituted phenols and catechols (R2
=
OR). This
transformation will open access to an important class of
compounds, such as hydroxy-substituted benzophenones,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
which are used as UV filters,11a,b biologically active
the Claisen condensation of acetates
Page 2 of 14
with various
1
compounds,11c–e and intermediates for organic synthesis.11f
Although de novo approaches for the construction of phenols
have been described in the literature,5a methods for the
preparation of catechols derivatives are a little-studied area. In
addition, such self-condensation is of interest because it allows
to develop a convenient method for the synthesis of
asymmetric benzene derivatives.
acetophenones 2 in the presence of NaH in Et2O at 0 °C
(Scheme 2, see SI, Table S1). With obtained 1,3-diketones 3,
the enamination reaction was performed with DMA-DMF.
The transformation proceeded at only one methylene group,
and previously unknown enaminodiones 4a–l were obtained in
40–95% yields.16
1
2
3
4
5
6
7
8
Scheme 2. Synthesis of RO-Substituted Enaminodiones 4
Scheme 1. Transition Metal-Free Reactions of Benzene
Ring Formation Based on Enaminones
9
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
RO
O
O
OMe
1
O
OH
Ar
RO
Known approaches
1) NaH, Et2O
2) H+
O
O
DMA-DMF
Ar
+
RO
O
C6H6, 
H+
R
R
[2+2+2]
Me2N
O
3
Me2N
O
R
4a-l
ref. 7a
3a-l
Me
Ar
2
O
R
O
O
R1
R1
R2
Having a number of enaminodiones 4 in our hands, we tried
to carry out the condensation of enaminodione 4a with diethyl
oxalate to prepare 5-acyl-3-hydroxy-4-pyrone 5 according to
the known methods (Table 1).13 To our surprise,
O
NR2
MeCN
O
[3+3]
+
+

R2
ref. 7b
Me
O
OH
NR2
R1
R2
O
O
AcOH/EtOH
[4+2]
diaroylbenzene 6a as
a self-condensation product was
Me2N
R1
R
2
O
80 o
C
ref. 7c
obtained in the presence of NaH or LiH in 15% and 55%,
respectively (entries 1 and 2). Interestingly, when we decided
to carry out this transformation without diethyl oxalate using
LiH as the base of choice in various solvents (entries 3–5),
product 6a was obtained in extremely low yields. Thus, the
presence of diethyl oxalate is important for increasing the
outcome of the reaction, and this fact can be probably
connected with the formation of the ethoxide anion. Next, we
added EtOH and t-BuOH to prepare in situ LiOEt and LiOt-
Bu, respectively, but benzophenone 6a was obtained in low
yields (15–20%, entries 6 and 7). When Ti(Oi-Bu)4 (0.5
equiv.) was used as an additive with LiH in THF, the reaction
gave the desired product in only 22% yield (entry 8). To our
delight, the reaction in the presence of Si(OEt)4 (0.5 equiv.)
and LiH (1.2 equiv.) in THF led to compound 6a in 59% yield
(entry 9).
CHO
This work
[4+2]
OH
O
O
O
R2
R1
R2
LiH, Si(OEt)4
DME
2
R1
NMe2
R2 = H, Me, OR
O
R1
On the other hand, enaminodiones have been described to be
multifunctional building blocks for organic synthesis and are
usually used as 1,3-bielectrophiles for the preparation of
pyrazoles,12a,b isoxazoles,12c and 2-pyridones.12d The
application of enaminodiones as 1,4-ambiphiles has been
actively developed in recent times to obtain highly reactive 3-
acyl-4-pyrones.13 To the best of our knowledge, in the
chemistry of enaminodiones there is only one fact of the
benzene formation as a by-product based on ethyl 2-
((dimethylamino)methylene)-3-oxobutanoate.14
Although changing amounts of Si(OEt)4 (entries 10 and 11)
did not allow to improve the reaction outcome, solvent
screening with the use of Si(OEt)4 as the additive of choice
(0.5 equiv.) made it possible to achieve a higher yield of 6a
(entries 12 and 13). Thus, refluxing of enaminodione 4a in
glyme for 5 h in the presence of Si(OEt)4 (0.5 equiv.) with LiH
(1.2 equiv.) turned out to be the best conditions for the self-
condensation resulting in benzophenone 6a in 71% yield.
When Si(OMe)4 was used as an additive, benzophenone 6a
was obtained in a lower yield (63%, entry 14). Enaminodione
4a did not give the product in the absence of a base (entry 15)
and was recovered without changing. Our attempts to use
CaH2 as a base (entry 16) or acid catalysts did not lead to the
formation of compound 6a (entry 17, Table 1).
It should also be noted that aminomethylidene derivatives of
4-hydroxyacetoacetic esters are the starting molecules for the
preparation of modern HIV integrase inhibitors, such as
dolutegravir and bictegravir.15 On this point, we were
especially interested in RO-substituted enaminodiones, which
may be the core structure for introducing the moiety of
diketobutanoic acid into various compounds. Here, we
describe a transition metal-free and general approach for the
synthesis of acyl-substituted phenols and catechols with the
use of the base-promoted self-condensation of easily
accessible enaminodiones.
We started this study with the synthesis of alkoxy- and
phenoxy-substituted enaminodiones 4 because this class of
compounds has not been previously reported in the literature,
excepting
aminomethylidene
derivatives
of
4-
Table 1. Optimization of the Reaction Conditions for the Self-
Condensation of Enaminodione 4aa
hydroxyacetoacetic ester. 4-Alkoxy- and 4-phenoxy-
substituted 1,3-diketones 3a–l were obtained in 54–85% by
ACS Paragon Plus Environment

Page 3 of 14
The Journal of Organic Chemistry
substituted benzophenones 6i,j were obtained in 46–52%
O
O
1
2
3
4
5
6
7
8
9
BnO
yields, while in the case of methoxy derivative 4k, the
outcome decreased to 29% because of the formation of a
complex mixture of products. This fact can be connected with
demethylation process, which proceeds more readily than
debenzylation.
Ph
Me2N
4a
(CO2Et)2
NaH, THF, 
Table 2. Synthesis of Catechols 6 Based on Self-Condensation
of Enaminodiones 4a
O
O
O
O
O
OBn
CO2Et
Ph
Ph
OH
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
O
O
O
LiH, Si(OEt)4
RO
5
6a
OBn
DME, 
Ar
Ar
Ar
2
-ROCH2CONMe2
OH
Me2N
7
Entr Base
Solvent
Time,
h, Δ
Additive
(equiv.)
Yield
6a, %
4a-k
6a-k
OR
y
1
2
3
4
5
(equiv.)
NaH (1.2) THF
LiH (1.2) THF
NaH (1.2) THF
Catechol 6
R
Ar
Yield, %
71
4
(CO2Et)2 (1.2)
15
55
9
a
b
c
d
e
f
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Ph
Ph
Me
Ph
8
(CO2Et)2 (1.2)
4-MeOC6H4
4-MeC6H4
4-PhC6H4
4-ClC6H4
2-Naphthyl
1-Naphthyl
2-Thienyl
Ph
56
1
–
–
–
66
LiH (1.2)
LiH (1.2)
THF
12
2
5
63
dioxane
10
52
6
7
8
LiH (1.2)
LiH (1.2)
LiH (1.2)
THF
8
5
8
EtOH (4.0)
15
13
22
63
glyme
THF
t-BuOH (1.0)
g
h
i
49
Ti(Oi-Bu)4
(0.5)
73
46
9
LiH (1.2)
LiH (1.2)
LiH (1.2)
THF
THF
THF
8
8
2
Si(OEt)4 (0.5)
Si(OEt)4 (1.0)
59
50
22
j
2-Thienyl
Ph
52
10
11
k
29
Si(OEt)4
(0.25)
a Unless otherwise noted, enaminodione 4 (0.607 mmol), Si(OEt)4
(63.1 mg, 0.303 mmol), and LiH (5.8 mg, 0.729 mmol) were
refluxed in glyme (1 mL) for 5 h.
12
LiH (1.2)
dioxane
8
Si(OEt)4 (0.5)
48
13
14
15
16
17
LiH (1.2)
glyme
glyme
glyme
glyme
EtOAc
5
5
–
5
1
Si(OEt)4 (0.5)
71
Products
6
were isolated without using column
LiH (1.2)
Si(OMe)4 (0.5) 63
chromatography by simple recrystallization from ethanol,
which is a convenient solvent to separate products 6 from
–
Si(OEt)4 (0.5)
Si(OEt)4 (0.5)
–
–
–
CaH2
–
dimethylacetamides
7
and plausible by-products, 1,3-
diketones 3. The latter could be generated during incomplete
conversion of enaminodiones 4 or their reaction with water.
For benzyloxy derivatives, we could observe the second
product, dimethylamide of benzyloxyacetic acid (7a), by
NMR spectroscopy in the filtrate after the recrystallization of
products 6 from ethanol (see SI).
LiCl (0.5),
HCl
a Enaminodione 4a (196 mg, 0.607 mmol) was refluxed in a
solvent (1 mL).
The optimized conditions were extended to a variety of RO-
substituted enaminodiones 4 (Table 2). As a result, self-
condensation products 6a–k were obtained in 29–73% yields.
In the case of benzyloxy derivatives, the nature of the aromatic
substituent has almost no effect on this transformation, and
benzenes 6a–h were prepared in 49–73% yields, but 3-
methoxyphenyl substituted enaminodione 4l did not give the
desired product leading to a mixture of unidentified aromatic
compounds. The nature of the RO-substituent has a strong
influence on the formation of compounds 6. Thus, phenoxy
The structure of the products 6 was assigned on the basis of
1H and 13C NMR spectra, and the data of elemental analysis.
In the 1H NMR spectra of benzophenones 6 in CDCl3, a
characteristic downfield doublet of the H-2 proton of the
benzene ring was observed at δ 7.68–8.42 ppm with J = 1.6–
2.0 Hz, and the OH group appeared at δ 12.19–12.74 ppm as
the result of the formation of the intramolecular hydrogen
bond.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 14
A possible mechanism (Scheme 3) of this transformation Next, we decided to extend this transformation to the
1
2
3
4
5
6
7
8
includes deprotonation (anion A), Michael addition
(intermediate B) followed by cyclization to cyclohexadienone
C. This transformation including the double Michael addition
can be considered as Rauhut − Currier reaction.9 The
aromatization of cyclohexadienone C gives more stable
intermediate D as the result of the elimination of NHMe2 and
the retro-Claisen reaction leading to the cleavage of
dimethylacetamide 7. Our attempts to isolate or detect any
cyclohexane intermediates by NMR spectroscopy were
simplest enaminodiones (without the RO group) for the
synthesis of 2,4-diacylsubstituted phenols (Table 3). We
thought that enaminodiones 8 should be deprotonated under
more severe conditions due to their lower CH acidity.
However, it was observed that the reaction under the same
conditions (in glyme or dioxane) led to the substituted phenols
9a–i in 51–97% yields. Although in most cases, glyme was a
convenient solvent for this transformation, in the case of
compounds 9e,f,h, the use of higher boiling dioxane as a
solvent allowed to increase the outcome by 16–38%. For
compounds 8j,k bearing the propionyl moiety, the
transformation was carried out in dioxane and the yield
decreased to 36–37%, which is in good agreement with the
steric and electron-donating effects of the methyl group, which
lowers the CH acidity of the enaminodiones. It should be
noted that diacyl-substituted phenols 9a–k are hard-to-reach
compounds because of low selectivity of the direct double
acylation of phenols, and in the literature, only benzophenone
9a has been described.19 Interestingly, this reaction was also
extended to the carboethoxy derivative 8l, which led to diethyl
4-hydroxyisophthalate (9l, 92% yield), an important
intermediate for the preparation of natural compounds.20
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
unsuccessful. In the H NMR spectra of the reaction mixture,
only
the
starting
compounds,
corresponding
dimethylacetamide 7, and phenolate D were observed.
Apparently, upon heating the aromatization proceeds much
faster than the double Michael reaction. An important feature
of the aromatization is selectivity of the retro-Claisen reaction
(intermediate C). The cleavage occurs only at the RO-acetyl
moiety, which is confirmed by the formation of only one
benzophenone 6, while the other possible benzophenone was
not even detected. The explanation of this selectivity is
associated with a higher reactivity of the carbonyl group of the
acetyl moiety compared to the aroyl moiety.
Scheme 3. Possible Mechanism of Enaminodione Self-
Condensation
Table 3. Synthesis of Phenols 9 Based on Self-Condensation
of Enaminodiones 8a
O
O
O
O
O
O
LiH, Si(OEt)4
O
O
RO
R
Ar
Ar
Ar
Ar
DME,

LiH
RO
4
2
4
Ar
NMe2
Me2N
Ar
NMe2
OR
-RCH2CONMe2
or LiOEt
Michael
addition
OH
9a-l
R
Me2N
A
8a-l
O
O
B
Phenol 9
R
Ar
Yield, %
62
Michael
addition
a
b
c
d
e
f
H
Ph
O
O
O
O
H
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-MeC6H4
4-ClC6H4
4-NO2C6H4
2-Naphthyl
2-Thienyl
Ph
91
RO
RO
H+
Ar
aromatization
Ar
H
94
6
Me2N
Ar
NMe2
OR
-NHMe2
-ROCH2CONMe2
H
82
O
Ar
H
80b
51b
53
O
O
D
C
H
In the literature the application of Si(OR)4/CsF mixture has
g
h
i
H
been previously described as the catalyst and the source of
alkoxide anions for the reaction of ketones with aldehydes or
Michael acceptors.17 The use of Si(OEt)4 as an additive in our
transformation can probably have several functions: (a)
activation of LiH, which has low solubility in organic
solvents, as the result of formation of LiOEt or
H
97b
53
H
j
Me
Me
H
37b
36b
92
k
l
2-Thienyl
OEt
hydroethoxysilicates;17
(b)
coordination
with
the
a
Unless otherwise noted, enaminodione 1a (1.214 mmol), Si(OEt)4
enaminodione molecules and the formation of intermediate
triethoxysilylenolates,18a which make it possible to bring
together two molecules and to promote the Michael
addition;18b,c (c) fixation of small amounts of water, which
may be present in reactants and initiates side-processes, such
as destruction and hydrolysis.
(126.2 mg, 0.606 mmol), and LiH (11.6 mg, 1.458 mmol) were
refluxed in glyme (2 mL) for 5 h.
b Refluxing in dioxane for 8 h.
In the case of enaminodione 8m, which was obtained from
acetylacetone and bears two reactive methyl groups, the self-
condensation was observed to proceed with the participation
ACS Paragon Plus Environment

Page 5 of 14
The Journal of Organic Chemistry
of three molecules, as a result, compound 10 was formed in rise to ambient temperature, and the reaction mixture was
1
2
3
4
5
6
7
8
32% yield (Scheme 4). A possible mechanism involves the
formation of 2,4-diacetylphenolate 9m, which then reacts with
another molecule of enaminodione 8m.
stirred overnight. Then the resulting mixture was treated wth
AcOH (4 mL) and H2O (4 mL) at 0 ºC and stirred for 30 min.
The product was extracted with EtOAc (3 × 10 mL). The
combined extracts were washed with saturated sodium
bicarbonate solution (10 mL), water (10 mL), and brine (10
mL). The organic phase was dried with anhydrous Na2SO4 and
evaporated under reduced pressure. The residue was boiled in
n-hexane, and after cooling n-hexane was decanted if the
product is liquid. For solid products, the product was isolated
by filtration.
Scheme 4. Self-condensation of enaminodione 8m
O
O
O
O
LiH, Si(OEt)4
Me
Me
Me
Me
2
dioxane, 
9
Me2N
OLi
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8m
9m
1) LiH
8m
2) H+
4-(Benzyloxy)-1-phenylbutane-1,3-dione (3a).
Yield 72% (4.46 g), yellow liquid. IR (ATR): 3064, 3032,
2864, 1602, 1573, 1266, 1108, 696 cm−1; 1H NMR (400 MHz,
DMSO-d6, ppm) δ 4.18 (s, 2H, CH2), 4.22 (s, 2H, CH2), 6.57
(s, 1H, =СH), 7.24–7.40 (m, 5H, Bn), 7.49 (t, J = 7.5 Hz, 2Н,
Н-3, Н-5 Ph), 7.57 (tt, J = 7.2 Hz, J = 1.2 Hz, 1Н, Н-4 Ph),
7.90 (d, J = 8.0 Hz, 2Н, Н-2, H-6 Ph), 15.95 (s, 1H, OH). The
analytical data are in accordance with those reported in the
literature.22
Me
O
O
O
Me
OH
HO
Me
10
In summary, we have developed a selective de novo
synthesis of diverse acyl-substituted phenols and catechols
based on enaminodione self-condensation, which exhibits both
the broad substrate scope and a good functional group
tolerance. This cascade transformation includes the double
Michael addition followed by the subsequent aromatization as
the result of NHMe2 elimination and retro-Claisen reaction.
The obtained benzophenones are of further interest as
bioactive compounds and UV filters.
4-(Benzyloxy)-1-(4-methoxyphenyl)butane-1,3-dione
(3b).
Yield 55% (3.79 g), orange liquid. IR (ATR): 3031, 2934,
1
2840, 1601, 1509, 1256, 1173, 1107, 788, 696 cm−1; H NMR
(400 MHz, CDCl3, ppm) δ 3.87 (s, 3H, Me), 4.17 (s, 2H, CH2),
4.65 (s, 2H, CH2), 6.48 (s, 1H, =СH), 6.94 (d, J = 9.0 Hz, 2Н,
Н-3, H-5 Ar), 7.25–7.40 (m, 5H, Bn), 7.89 (d, J = 9.0 Hz, 2Н,
Н-2, H-6 Ar), 16.11 (s, 1H, OH); 13C{1H} NMR (100 MHz,
CDCl3, ppm) δ 55.5, 71.5, 73.5, 92.7, 114.0, 127.1, 127.9,
128.0, 128.6, 129.4, 137.8, 163.4, 183.9, 192.4; HRMS
(ESI/Q-TOF) m/z: [M+Na]+ Calcd for C18H18NaO4 321.1103;
Found 321.1113.
EXPERIMENTAL SECTION
1H NMR spectra were recorded on 400 and 500 MHz
instruments, 13C NMR spectra were recorded on 100 and 126
MHz instruments in DMSO-d6 or CDCl3. Chemical shifts are
reported relative to TMS, CHCl3 (δ = 7.26 ppm, H NMR),
DMSO-d6 (δ = 2.50 ppm, H NMR), CDCl3 (δ = 77.16 ppm,
1
4-(Benzyloxy)-1-p-tolylbutane-1,3-dione (3c).
1
13C NMR) and DMSO-d6 (δ = 39.52 ppm, 13C NMR). IR
spectra were recorded on a FTIR spectrometer with ATR
accessory. High-resolution mass spectra (HRMS) were carried
out at a instrument for HRMS-ESI-QTOF. All solvents used
were dried and distilled by standard procedures. Methyl 2-
(benzyloxy)acetate, methyl 2-methoxyacetate, and methyl 2-
phenoxyacetate were prepared based on the reported
procedures.21a,b Enaminodiones 8a,b,e–i,l,m were prepared
according to the literature procedure.13
Yield 75% (4.89 g), yellow powder, mp 34–35 °С. IR
1
(ATR): 3029, 2913, 2863, 1727, 1607, 1104, 696 cm−1; H
NMR (400 MHz, CDCl3, ppm) δ 2.41 (s, 3H, Me), 4.17 (s, 2H,
CH2), 4.65 (s, 2H, CH2), 6.52 (s, 1H, =СH), 7.26 (d, J = 8.1
Hz, 2Н, Н-3, H-5 Ar), 7.27–7.42 (m, 5H, Bn), 7.81 (d, J = 8.1
Hz, 2Н, Н-2, H-6 Ar), 15.99 (s, 1H, OH); 13C{1H} NMR (100
MHz, CDCl3, ppm) δ 21.7, 71.7, 73.5, 93.2, 127.3, 128.0,
128.1, 128.6, 129.4, 131.8, 137.4, 143.5, 183.6, 193.9; HRMS
(ESI/Q-TOF) m/z: [M+Na]+ Calcd for C18H18NaO3 305.1154;
Found 305.1147.
4-(Benzyloxy)-1-(biphenyl-4-yl)butane-1,3-dione (3d).
General method for the preparation of 4-benzyloxy-1,3-
diketones 3a–h,l and 4-methoxy-1,3-diketone 3i.
Yield 85% (6.67 g), light-yellow powder, mp 81–83 °С. IR
(ATR): 3060, 3035, 2863, 1605, 1433, 1119, 763 cm−1; H
1
In cooled in a ice bath a 50 mL-flask with a reflux
condenser equipped with a calcium chloride drying tube, NaH
(60%-suspension in oil) (1.11 g, 27.7 mmol) was slowly added
to a stirred solution of acetophenone (23.1 mmol) and methyl
2-(benzyloxy)acetate (5.00 g, 27.7 mmol) or methyl 2-
methoxyacetate (2.88 g, 27.7 mmol) in dry Et2O (15 mL) (in
the case of 3i, the reaction mixture was heated for initiating
the condensation). The reaction temperature was allowed to
NMR (400 MHz, CDCl3, ppm) δ 4.19 (s, 2H, CH2), 4.66 (s,
2H, CH2), 6.59 (s, 1H, =СH), 7.26–7.43 (m, 6H, Bn, Ph), 7.47
(t, J = 7.5 Hz, 2Н, Н-3, H-5 Ph), 7.63 (t, J = 8.1 Hz, 2Н, Ph),
7.68 (d, J = 8.4 Hz, 2Н, Ph), 7.98 (d, J = 8.4 Hz, 2Н, Ph),
15.96 (s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ
71.8, 73.5, 93.4, 127.2, 127.3, 127.7, 127.9, 128.0, 128.2,
128.6, 128.9, 133.2, 137.2, 139.9, 145.3, 182.6, 194.5. Anal.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 14
Calcd for C23H20O3: C, 80.21; H, 5.85. Found: C, 80.12; H,
5.81.
4-(Benzyloxy)-1-(4-chlorophenyl)butane-1,3-dione (3e).
Ph), 7.54 (tt, 1H, J = 7.3 Hz, J = 1.0 Hz, H-4 Ph), 7.97 (dd, J =
1
2
3
4
5
6
7
8
7.8 Hz, J = 1.0 Hz,2Н, H-2, H-6 Ph), 15.87 (s, 1H, OH). The
analytical data are in accordance with those reported in the
literature.22
Yield 76% (5.32 g), yellow crystals, mp 63–66 °С. IR
(ATR): 3059, 3029, 2862, 1591, 1531, 1454, 1087, 778 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 4.17 (s, 2H, CH2), 4.65 (s,
2H, CH2), 6.51 (s, 1H, =СH), 7.28–7.40 (m, 5H, Bn), 7.43 (d,
J = 8.6 Hz, 2Н, Н-3, H-5 Ar), 7.87 (d, J = 8.6 Hz, 2Н, Н-2, H-
6 Ar), 15.88 (s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 71.8, 73.6, 93.5, 128.0, 128.2, 128.6, 128.7, 129.1,
133.1, 137.3, 138.9, 182.0, 194.6. Anal. Calcd for C17H15ClO3:
C, 67.44; H, 4.99. Found: C, 67.24; H, 4.96.
4-(Benzyloxy)-1-(3-methoxyphenyl)butane-1,3-dione (3l).
Yield 71% (4.89 g), yellow liquid. IR (ATR): 3031, 2936,
1
1729, 1578, 1455, 1273, 1108, 1041, 782, 736, 697 cm−1; H
NMR (400 MHz, CDCl3, ppm) δ 3.86 (s, 3H, Me), 4.18 (s, 2H,
CH2), 4.65 (s, 2H, CH2), 6.53 (s, 1H, =СH), 7.08 (ddd, J = 8.2
Hz, J = 2.6 Hz, J = 0.9 Hz, 1Н, Ar), 7.27–7.41 (m, 6H, Bn,
Ar), 7.44 (dd, J = 2.6 Hz, J = 1.6 Hz, 1Н, H-2 Ar), 7.08 (ddd,
J = 7.7 Hz, J = 1.5 Hz, J = 1.1 Hz, 1Н, Ar), 15.88 (s, 1H, OH);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 55.4, 71.7, 73.5,
93.7, 111.9, 118.8, 119.7, 127.9, 128.1, 128.6, 129.7, 136.0,
137.3, 159.9, 183.2, 194.2; HRMS (ESI/Q-TOF) m/z: [M+H]+
Calcd for C18H19O4 299.1283; Found 299.1297.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-(Benzyloxy)-1-(naphthalen-2-yl)butane-1,3-dione (3f).
Yield 84% (6.18 g), yellow powder, mp 20–21 °С. IR
(ATR): 3061, 3031, 2864, 1604, 1570, 1232, 1106, 736, 696
1
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 4.22 (s, 2H, CH2),
General method for the preparation of 4-phenoxy-1,3-
diketones 3i,j
4.68 (s, 2H, CH2), 6.69 (s, 1H, =СH), 7.30–7.45 (m, 5H, Bn),
7.54 (td, J = 7.0 Hz, J = 1.1 Hz, 1Н, Naph), 7.58 (td, J = 7.0
Hz, J = 1.1 Hz, 1Н, Naph), 7.85–7.92 (m, 3H, Naph), 7.95 (d,
J = 8.0 Hz, 1Н, H-3 Naph), 8.47 (d, J = 0.8 Hz, 1Н, H-1
Naph), 15.99 (s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 71.8, 73.6, 93.9, 123.1, 126.8, 127.8, 128.0, 128.1,
128.2, 128.5, 128.6, 129.4, 131.7, 132.7, 135.4, 137.3, 182.9,
194.6 (1C was not observed); HRMS (ESI/Q-TOF) m/z:
[M+Na]+ Calcd for C21H18NaO3 341.1154; Found 341.1155.
In cooled in a ice bath a 50 mL-flask with a reflux
condenser equipped with a calcium chloride drying tube, NaH
(60%-suspension in oil) (1.11 g, 27.7 mmol) was slowly added
to a stirred solution of acetophenone (23.1 mmol) and methyl
2-(phenoxy)acetate (4.60 g, 27.7 mmol) in dry Et2O (15 mL).
The reaction temperature was allowed to rise to ambient
temperature, and the reaction mixture was stirred overnight.
Then a paticipate formed was filtered off and washed with
toluene. To a suspension of the sodium salt in Et2O (20 mL), a
solution of hydrochloric acid (1 : 2) was added until the salt
dissolved completely. The ether layer was separated, and
additional quantity of Et2O (10 mL) was used for extraction of
the product. The combined extracts were washed with
saturated sodium bicarbonate solution (10 mL), water (10
mL), and brine (10 mL). The organic phase was dried with
anhydrous Na2SO4 and evaporated under reduced pressure.
The residue was crystallized from n-heptane.
4-(Benzyloxy)-1-(naphthalen-1-yl)butane-1,3-dione (3g).
Yield 54% (3.97 g), yellow powder, mp 37–39 °С. IR
(ATR): 3061, 3032, 2864, 1728, 1601, 1105, 776, 696 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 4.22 (s, 2H, CH2), 4.65 (s,
2H, CH2), 6.41 (s, 1H, =СH), 7.23–7.66 (m, 8H, Bn), 7.77 (d,
J = 7.0 Hz, 1Н, Naph), 7.90 (d, J = 7.0 Hz, 1Н, Naph), 7.98 (d,
J = 8.0 Hz, 1Н, Naph), 8.49 (d, J = 8.3 Hz, 1Н, Naph), 15.91
(s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 71.6,
73.6, 98.7, 124.9, 125.6, 126.5, 127.4, 127.5, 127.9, 128.1,
128.6, 130.2, 132.0, 137.3, 133.8, 133.9, 188.1, 193.1 (1C was
not observed). Anal. Calcd for C21H18O3: C, 79.22; H, 5.70.
Found: C, 79.18; H, 5.86.
4-Phenoxy-1-phenylbutane-1,3-dione (3i).
Yield 62% (3.64 g), white powder, mp 69–71 °С. IR (ATR):
3064, 3032, 2864, 1602, 1573, 1266, 1108, 696 cm−1; 1H NMR
(400 MHz, CDCl3, ppm) δ 4.69 (s, 2H, CH2), 6.58 (s, 1H,
=СH), 6.90–7.07 (m, 3H, Ph), 7.32 (t, J = 7.7 Hz, 2Н, H-3, H-
5 Ph), 7.45 (t, J = 7.5 Hz, 2Н, H-3, H-5 Ph), 7.54 (t, J = 7.5
Hz, 1Н, H-4 Ph), 7.89 (d, J = 8.0 Hz, 2Н, H-2, H-6 Ph), 15.91
(s, 1H, OH). The analytical data are in accordance with those
reported in the literature.23
4-(Benzyloxy)-1-(thiophen-2-yl)butane-1,3-dione (3h).
Yield 75% (4.75 g), yellow liquid. IR (ATR): 3090, 2865,
1756, 1659, 1453, 1310, 1109, 726 cm−1; 1H NMR (400 MHz,
CDCl3, ppm) δ 4.16 (s, 2H, CH2), 4.64 (s, 2H, CH2), 6.38 (s,
1H, =СH), 7.14 (d, J = 5.0 Hz, J = 3.8 Hz,1Н, Н-4 Th), 7.27–
7.42 (m, 5H, Bn), 7.62 (dd, J = 5.0 Hz, J = 1.1 Hz, 1Н, Н-5
Th), 7.73 (dd, J = 3.8 Hz, J = 1.1 Hz, 1Н, Н-3 Th), 15.50 (s,
1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 70.4, 73.5,
93.8, 127.9, 128.1, 128.3, 128.6, 130.8, 132.8, 137.2, 141.2,
181.6, 187.6. Anal. Calcd for C15H14O3S: C, 65.67; H, 5.14.
Found: C, 65.27; H, 5.49.
4-Phenoxy-1-(thiophen-2-yl)butane-1,3-dione (3j).
Yield 58% (3.49 g), light yellow powder, mp 51–53 °С. IR
(ATR): 3093, 2892, 2577, 1583, 1226, 1066, 780, 750, 687,
1
605 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 4.67 (s, 2H,
CH2), 6.41 (s, 1H, =СH), 6.90–7.06 (m, 3H, Ph), 7.13 (dd, J =
5.0 Hz, J = 3.9 Hz, 1Н, H-4 Th), 7.27–7.36 (m, 2H, Ph), 7.62
(dd, J = 5.0 Hz, J = 1.1 Hz, 1Н, H-5 Th), 7.72 (dd, J = 3.9 Hz,
J = 1.1 Hz, 1Н, H-3 Th), 15.56 (s, 1H, OH); 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 64.8, 93.8, 114.8, 121.8, 128.4,
4-Methoxy-1-phenylbutane-1,3-dione (3k).
Yield 63% (2.80 g), yellow liquid. IR (ATR): 2934, 2825,
1713, 1600, 1569, 1449, 1265, 1114, 772 cm−1; 1H NMR (500
MHz, CDCl3, ppm) δ 3.49 (s, 3H, Me), 4.11 (s, 2H, CH2), 6.49
(s, 1H, =СH), 7.46 (dd, J = 7.8 Hz, J = 7.3 Hz, 2Н, H-3, H-5
ACS Paragon Plus Environment

Page 7 of 14
The Journal of Organic Chemistry
129.7, 131.0, 133.0, 133.0, 140.7, 157.9, 181.1, 187.0. Anal. 4-(Benzyloxy)-1-(biphenyl-4-yl)-2-
1
2
3
4
5
6
7
8
Calcd for C14H12O3S: C, 64.60; H, 4.65. Found: C, 64.67; H,
4.66.
((dimethylamino)methylene)butane-1,3-dione (4d).
Yield 78% (3.12 g), light yellow powder, mp 47–50 °С. IR
(ATR): 3061, 3030, 2925, 1657, 1574, 1448, 1120, 747 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 2.49–3.45 (br m, 6Н,
2Me), 4.05 (s, 2H, CH2), 4.33 (s, 2H, CH2), 7.12–7.29 (m, 5H,
Bn), 7.39 (t, J = 7.3 Hz, 1Н, Н-4 Ph), 7.47 (t, J = 7.5 Hz, 2Н,
H-3, Н-5 Ph), 7.58–7.67 (m, 4H, Ph), 7.77 (s, 1H, =CH), 7.85
(d, J = 8.1 Hz, 2Н, H-2, Н-6 Ph); 13C{1H} NMR (126 MHz,
CDCl3, ppm) δ 42.1, 47.3, 72.9, 74.6, 109.4, 127.1, 127.2,
127.5, 127.7, 128.1, 128.2, 128.9, 129.6, 137.5, 139.3, 139.9,
144.8, 156.9, 194.1, 195.4. Anal. Calcd for C26H25NO3: C,
78.17; H, 6.31; N, 3.51. Found: C, 78.22; H, 6.60; N, 3.75.
General method for the preparation enaminodiones 4
and 8.
Dimethylformamide dimethyl acetal (1.55 g, 13.0 mmol)
was added to the corresponding 1,3-diketone (10.0 mmol) in
anhydrous benzene (4.6 mL), the reaction mixture was stirred
for 24 h at room temperature and then refluxed for 1 h using a
reflux condenser equipped with a calcium chloride drying
tube. Then the solvent and an excess of DMF-DMA were
removed at reduced pressure, the residue was diluted with n-
hexane or Et2O. The resulting mixture was maintained at –20
ºC for several hours (sometimes crystallization should be
induced by rubbing the inside surface of the crystallization
vessel), and the precipitate that formed was filtered off. Liquid
product 4k was isolated by decantation.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-(Benzyloxy)-1-(4-chlorophenyl)-2-
((dimethylamino)methylene)butane-1,3-dione (4e).
Yield 95% (3.40 g), yellow powder, mp 71–74 °С. IR
(ATR): 3056, 2961, 2882, 1649, 1575, 1087, 759 cm−1; H
1
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-
phenylbutane-1,3-dione (4a).
NMR (400 MHz, CDCl3, ppm) δ 2.41–3.40 (br m, 6Н, 2Me),
3.99 (s, 2H, CH2), 4.30 (s, 2H, CH2), 7.14–7.20 (m, 2H, Bn),
7.22–7.31 (m, 3H, Bn), 7.35 (d, J = 8.5 Hz, 2Н, Н-3, Н-5 Ar),
7.69 (d, J = 8.5 Hz, 2Н, Н-2, H-6 Ph), 7.72 (s, 1Н, =CH);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 42.3, 47.5, 73.0,
74.7, 109.1, 127.7, 128.3, 128.7, 130.4, 137.3, 138.4, 139.0,
157.2, 193.1, 195.4 (1С was not observed). Anal. Calcd for
C20H20ClNO3: C, 67.13; H, 5.63; N, 3.91. Found: C, 66.96; H,
5.77; N, 3.77.
Yield 88% (2.85 g), yellow powder, mp 85–87 °С. IR
(ATR): 3032, 2925, 2882, 1651, 1573, 1085, 780 cm−1; H
1
NMR (400 MHz, CDCl3, ppm) δ 2.40 –3.40 (br m, 6Н, 2Me),
4.01 (s, 2H, CH2), 4.30 (s, 2H, CH2), 7.16–7.32 (m, 5H, Bn),
7.40 (t, J = 7.5 Hz, 2Н, Н-3, Н-5 Ph), 7.50 (t, J = 7.3 Hz, 1Н,
Н-4 Ph), 7.73–7.83 (m, 3Н, =CH, Н-2, H-6 Ph); 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 42.0, 47.3, 72.9, 74.6, 109.3,
127.5, 127.7, 128.2, 128.4, 129.0, 132.1, 137.5, 140.6, 157.1,
194.5, 195.4. Anal. Calcd for C20H21NO3: C, 74.28; H, 6.55;
N, 4.33. Found: C, 73.97; H, 6.78; N, 4.61.
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-
(naphthalen-2-yl)butane-1,3-dione (4f).
Yellow 65% (2.43 g), light yellow powder, mp 74–75 °С.
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-(4-
methoxyphenyl)butane-1,3-dione (4b).
IR (ATR): 3055, 2924, 2838, 1630, 1557, 1310, 1099, 833
1
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.53–3.47 (br m,
6Н, 2Me), 4.00 (s, 2H, CH2), 4.26 (s, 2H, CH2), 7.09–7.21 (m,
5H, Bn), 7.50–7.62 (m, 2H, Naph), 7.82 (s, 1H, =CH), 7.83–
7.93 (m, 4H, Naph), 8.23 (s, 1Н, H-1 Naph); 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 41.8, 47.2, 73.0, 74.8, 109.6, 125.0,
126.8, 127.6, 127.8, 127.9, 128.2, 128.3, 128.7, 130.7, 132.6,
135.4, 137.5, 138.2, 157.1, 194.7, 195.8 (1С was not
observed); HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C24H24NO3 374.1756; Found 374.1765.
Yield 84% (2.97 g), yellow powder, mp 55–58 °С. IR
(ATR): 3001, 2911, 2842, 1597, 1567, 1420, 1299, 1252, 838
1
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.37–3.50 (br m,
6Н, 2Me), 3.85 (s, 3H, MeO), 4.02 (s, 2H, CH2), 4.33 (s, 2H,
CH2), 6.88 (d, J = 8.5 Hz, 2Н, Н-3, Н-5 Ar), 7.16–7.30 (m,
5H, Bn), 7.70–7.81 (m, 3H, =CH, H-2, H-6 Ar); 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 42.0, 47.2, 55.6, 73.1, 74.6,
109.4, 113.9, 127.6, 127.9, 128.4, 131.5, 133.6, 137.8, 156.2,
163.2, 193.9, 195.0. Anal. Calcd for C21H23NO4: C, 71.37; H,
6.56; N, 3.96. Found: C, 71.06; H, 6.57; N, 4.19.
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-
(naphthalen-1-yl)butane-1,3-dione (4g).
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-p-
tolylbutane-1,3-dione (4c).
Yield 80% (2.99 g), yellow powder, mp 72–75 °С. IR
(ATR): 3029, 2841, 1653, 1567, 1305, 1091, 786 cm−1; H
1
NMR (400 MHz, CDCl3, ppm) δ 2.57–3.47 (br m, 6Н, 2Me),
4.09 (s, 2H, CH2), 4.29 (s, 2H, CH2), 7.10–7.21 (m, 5H, Bn),
7.41 (dd, J = 8.1 Hz, J = 7.2 Hz, 1Н, Naph), 7.43–7.54 (m, 2H,
Naph), 7.57 (s, 1H, =CH), 7.61 (d, J = 6.9 Hz, 1Н, Naph), 7.86
(d, J = 7.8 Hz, 1Н, Naph), 7.91 (d, J = 8.2 Hz, 1Н, Naph), 8.38
(d, J = 7.6 Hz, 1Н, Naph); 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 42.7, 48.1, 73.3, 75.5, 112.4, 124.6, 126.2, 126.6,
127.6, 127.7, 127.9, 128.1, 128.4, 130.8, 131.4, 134.1, 137.7,
138.9, 159.3, 194.9, 197.3 (1С was not observed); HRMS
Yield 94% (3.17 g), light yellow powder, mp 65–67 °С. IR
(ATR): 3060, 3028, 2923, 2834, 1659, 1557, 1370, 1112, 954,
1
736 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.88 (s, 3H,
Me), 2.49–3.43 (br m, 6Н, 2Me), 4.01 (s, 2H, CH2), 4.31 (s,
2H, CH2), 7.17–7.29 (m, 7H, Bn, Ar), 7.68 (d, J = 7.9 Hz, 2Н,
Н-2, Н-6 Ar), 7.74 (s, 1H, =CH); 13C{1H} NMR (100 MHz,
CDCl3, ppm) δ 21.6, 42.0, 47.4, 72.9, 74.5, 109.4, 127.5,
127.7, 128.2, 129.2, 137.5, 138.0, 143.0, 156.7, 194.4, 195.2.
Anal. Calcd for C21H23NO3: C, 74.75; H, 6.87; N, 4.15. Found:
C, 74.54; H, 7.05; N, 4.31.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 14
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C24H24NO3 374.1756;
Found 374.1761.
74.2, 109.1, 127.09, 128.5, 128.9, 132.2, 157.0, 194.5, 195.4;
HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C14H18NO3
248.1281; Found 248.1285.
1
2
3
4
5
6
7
8
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-
(thiophen-2-yl)butane-1,3-dione (4h).
4-(Benzyloxy)-2-((dimethylamino)methylene)-1-(3-
methoxyphenyl)butane-1,3-dione (4l).
Yield 84% (2.62 g), yellow powder, mp 73–77 °С. IR
(ATR): 3106, 3093, 2927, 2839, 1652, 1601, 1563, 1422,
Yield 40% (1.41 g), light yellow powder, mp 46–48 °С. IR
(ATR): 3005, 2920, 1655, 1554, 1421, 1261, 1120, 767 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 2.55–2.80 (br s, 3Н, Me),
3.11–3.36 (br s, 3Н, Me), 3.75 (s, 3H, MeO), 4.02 (s, 2H,
CH2), 4.29 (s, 2H, CH2), 7.04 (ddd, J = 7.7 Hz, J = 2.7 Hz, J =
1.5 Hz, 1Н, Ph), 7.18–7.34 (m, 8H, Bn, Ar), 7.78 (s, 1Н,
=CH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 42.1, 47.6,
55.3, 72.9, 74.7, 109.5, 112.7, 119.0, 121.9, 127.5, 127.6,
128.2, 129.4, 137.6, 142.0, 157.0, 159.8, 194.3, 195.3. Anal.
Calcd for C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C,
71.55; H, 6.72; N, 4.01.
1
1106, 726 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.59–
3.41 (br m, 6Н, 2Me), 4.15 (s, 2H, CH2), 4.39 (s, 2H, CH2),
7.06 (dd, 1H, J = 4.9 Hz, J = 3.8 Hz, H-4 Th), 7.20–7.39 (m,
5H, Bn), 7.48 (dd, J = 3.8 Hz, J = 1.1 Hz, 1Н, Н-3 Th), 7.60
(dd, J = 4.9 Hz, J = 1.1 Hz, 1Н, Н-5 Th), 7.73 (s, 1H, =CH);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 73.1, 74.3, 109.3,
127.5, 127.7, 127.9, 128.2, 128.6, 132.6, 133.4, 137.6, 147.5,
155.8, 186.7, 194.5. Anal. Calcd for C18H19NO3S: C, 65.63; H,
5.81; N, 4.25. Found: C, 65.73; H, 6.09; N, 4.47.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-((Dimethylamino)methylene)-4-phenoxy-1-
phenylbutane-1,3-dione (4i).
2-((Dimethylamino)methylene)-1-(3-
methoxyphenyl)butane-1,3-dione (8c).
Yield 85% (2.62 g), light yellow powder, mp 113–115 °С.
IR (ATR): 3060, 2975, 2929, 1650, 1587, 1492, 1319, 1204,
Yield 90% (2.23 g), yellow powder, mp 57–59 °С. IR
1
983, 800, 689 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.66
(ATR): 3030, 2973, 2930, 1647, 1584, 1480, 1281, 940, 868
1
(br s, 3H, Me), 3.24 (br s, 3H, Me), 4.55 (s, 2H, CH2), 6.70 (d,
J = 8.0 Hz, 2H, H-2, H-6 Ph), 6.89 (t, J = 7.5 Hz, 1H, H-4 Ph),
7.18 (t, J = 7.6 Hz, 2H, H-3, H-5 Ph), 7.39 (t, J = 7.6 Hz, 2H,
H-3, H-5 Ph), 7.49 (t, J = 7.3 Hz, 1H, H-4 Ph), 7.72–7.81 (3H,
m, Ph, =CH). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 42.3,
47.6, 71.8, 114.4, 121.1, 128.5, 129.0, 129.26, 129.3, 132.3,
140.6, 157.8, 193.7, 194.6 (1С was not observed); HRMS
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C19H20NO3 310.1443;
Found 310.1447.
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.04 (s, 3H, Me),
2.37–3.48 (br s, 6H, NMe2), 3.86 (s, 3H, MeO), 7.09 (ddd, J =
8.0 Hz, J = 2.6 Hz, J = 1.5 Hz, 1H, Ar), 7.32–7.43 (m, 3H,
Ar), 7.86 (s, 1H, =CH). Anal. Calcd for C14H17NO3: C, 68.00;
H, 6.93; N, 5.66. Found: C, 67.83; H, 6.91; N, 5.46.
2-((Dimethylamino)methylene)-1-(2-
methoxyphenyl)butane-1,3-dione (8d).
Yield 86% (2.13 g), yellow powder, mp 70–72 °С. IR
(ATR): 3067, 2927, 2840, 1643, 1581, 1387, 1107, 925, 747
2-((Dimethylamino)methylene)-4-phenoxy-1-(thiophen-
2-yl)butane-1,3-dione (4j).
1
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.10 (s, 3H, Me),
2.70–3.33 (br s, 6H, NMe2), 3.84 (s, 3H, MeO), 6.94 (d, J =
8.4 Hz, 1H, H-3 Ar), 7.00 (td, J = 7.6 Hz, J = 0.7 Hz, 1H, H-5
Ar), 7.43 (ddd, J = 8.4 Hz, J = 7.6 Hz, J = 1.7 Hz, 1H, H-4
Ar), 7.49 (dd, J = 7.5 Hz, J = 1.7 Hz, 1H, H-6 Ar), 7.79 (s, 1H,
=CH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 29.8, 44.9 (br
s, Me2N), 55.7, 111.5, 115.0, 120.6, 130.2, 131.5, 132.1,
157.3, 158.3, 192.6, 197.1. Anal. Calcd for C14H17NO3: C,
68.00; H, 6.93; N, 5.66. Found: C, 67.78; H, 6.95; N, 5.53.
Yield 83% (2.61 g), yellow crystals, mp 81–83 °С. IR
(ATR): 3079, 2925, 1657, 1574, 1494, 1412, 1270, 1175, 944,
1
744 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.71 (br s, 3H,
Me), 3.22 (br s, 3H, Me), 4.68 (s, 2H, CH2), 6.75 (dd, J = 8.7
Hz, J = 0.9 Hz, 2H, H-2, H-6 Ph), 6.90 (tt, J = 7.3 Hz, J = 0.9
Hz, 1H, H-4 Ph), 7.05 (dd, J = 4.9 Hz, J = 3.8 Hz, 1H, H-4
Th), 7.16–7.22 (m, 2H, H-3, H-5 Ph), 7.45 (dd, J = 3.8 Hz, J =
1.1 Hz, 1H, H-3 Th), 7.60 (dd, J = 4.9 Hz, J = 1.1 Hz, 1H, H-5
Th), 7.79 (s, 1H, =CH); 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 41.4, 47.8, 71.5, 108.9, 114.4, 121.0, 127.9, 129.3,
132.6, 133.6, 147.4, 156.3, 157.9, 186.7, 192.7. Anal. Calcd
for C17H17NO3S: C, 64.74; H, 5.43; N, 4.44. Found: C, 64.85;
H, 5.40; N, 4.43.
2-((Dimethylamino)methylene)-1-phenylpentane-1,3-
dione (8j).
Yield 88% (2.04 g), yellow powder, mp 82–83 °С. IR
1
(ATR): 2924, 1648, 1575, 1369, 1122, 782 cm−1; H NMR
(400 MHz, CDCl3, ppm) δ 0.98 (t, J = 7.4 Hz, 3H, Me), 2.31
(q, J = 7.4 Hz, 2H, CH2), 2.45–3.35 (br s, 6H, NMe2), 7.45
(dd, J = 7.8 Hz, J = 7.2 Hz, 2H, H-3, H-5 Ph), 7.54 (tt, J = 7.4
Hz, J = 1.6 Hz, 1H, H-4 Ph), 7.83 (d, J = 7.8 Hz, 2H, H-2, H-6
Ph), 7.86 (s, 1H, =CH); 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 9.5, 34.2, 44.4 (br s, Me2N), 111.2, 128.6, 129.2,
132.4, 140.7, 155.6, 196.2, 198.7. Anal. Calcd for C14H17NO2:
C, 72.70; H, 7.41; N, 6.06. Found: C, 72.77; H, 7.34; N, 6.01.
2-((Dimethylamino)methylene)-4-methoxy-1-
phenylbutane-1,3-dione (4k).
Yield 81% (2.00 g), yellow liquid. IR (ATR): 3060, 2972,
2821, 1658, 1568, 1369, 1116, 803 cm−1; 1H NMR (400 MHz,
CDCl3, ppm)  2.49–2.81 (br s, 3Н, Me), 3.15 (s, 3H, MeO),
3.17–3.36 (br s, 3Н, Me), 3.94 (s, 2H, CH2), 7.44 (t, 2H, J =
7.5 Hz, H-3, H-5 Ph), 7.52 (tt, J = 7.4 Hz, J = 1.0 Hz, 1Н, Н-3,
H-5 Ph), 7.76 (s, 1H, =CH), 7.79 (d, J = 7.4 Hz, H-2, H-6 Ph);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 42.0, 47.4, 58.6,
2-((Dimethylamino)methylene)-1-(thiophen-2-
yl)pentane-1,3-dione (8k).
ACS Paragon Plus Environment

Page 9 of 14
The Journal of Organic Chemistry
Yield 77% (1.83 g), yellow powder, mp 59–60 °С. IR
1H, H-4 Bn), 7.40 (t, J = 7.5 Hz, 2Н, Н-3, H-5 Bn), 7.47 (d, J
= 7.6 Hz, 2Н, Н-2, H-6 Bn), 7.57 (d, J = 1.8 Hz, 1Н, Н-6 Ar),
7.67 (d, J = 8.9 Hz, 2Н, Н-2, H-6 Ar), 7.74 (d, J = 8.9 Hz, 2Н,
Н-2, H-6 Ar), 7.74–7.77 (m, 1Н, H-2 Ar), 12.47 (s, 1H, OH);
13C{1H} NMR (100 MHz, DMSO-d6, ppm) δ 55.5, 55.6, 70.2,
113.8, 113.9, 116.3, 124.5, 125.3, 127.6, 127.9, 128.2, 128.4,
129.59, 129.62, 131.8, 131.9, 136.5, 146.6, 150.1, 162.5,
163.3, 192.4, 194.4; HRMS (ESI/Q-TOF) m/z: [M+Na]+
Calcd for C29H24NaO6 491.1471; Found 491.1452.
1
(ATR): 2973, 2923, 2807, 1634, 1571, 1516, 1406, 1350,
1189, 858 cm−1; 1H NMR (400 MHz, CDCl3, ppm) δ 1.04 (t, J
= 7.4 Hz, 3H, Me), 2.42 (q, J = 7.4 Hz, 2H, CH2), 2.51–3.44
(br s, 6H, NMe2), 7.11 (dd, J = 4.8 Hz, J = 3.8 Hz, 1H, H-4
Th), 7.54 (dd, J = 3.8 Hz, J = 0.8 Hz, 1H, H-3 Th), 7.66 (dd, J
= 4.8 Hz, J = 0.8 Hz, 1H, H-5 Th), 7.75 (s, 1H, =CH); 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 9.6, 33.5, 42.4, 46.1, 110.9,
128.1, 133.2, 133.9, 147.7, 154.0, 188.6, 197.6. Anal. Calcd
for C12H15NO2S: C, 60.73; H, 6.37; N, 5.90. Found: C, 60.81;
H, 6.39; N, 6.11.
2
3
4
5
6
7
8
9
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis(p-
tolylmethanone) (6c).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General method for the preparation of diacyl-
substituted catechols 6.
Yield 66% (87 mg), light yellow powder, mp 175–176 °С.
IR (ATR): 3066, 2923, 1649, 1626, 1604, 1498, 1275, 744
1
A mixture of the corresponding enaminodione 4 (0.607
mmol), Si(OEt)4 (63.1 mg, 0.303 mmol), and LiH (5.8 mg,
0.729 mmol) was refluxed in 1,2-dimethoxyethane (1 mL) for
5 h using a reflux condenser equipped with a calcium chloride
drying tube. After that, (in the case of enaminodiones 4b–e)
lithium salt of phenols 6b–e formed as a solid, was filtered off,
and washed with cold toluene. Then the salt was quenched
with HCl (1 : 2) (2 mL) at 0 ºC and stirred for 30 min. The
precipitate was filtered off and recrystallized from EtOH. In
the case of enaminodiones 4a,f–k, the reaction mixture was
quenched with HCl (1 : 2) to pH = 2 at 0 ºC and stirred for 30
min. The reaction mixture was diluted with H2O (3 mL), and
the product was extracted with EtOAc (3 × 5 mL). The
combined extracts were washed with water (5 mL) and brine
(5 mL). The organic phase was dried with anhydrous Na2SO4
and evaporated under reduced pressure. The residue was
diluted with EtOH (2 mL) and maintained at –20 ºC for 24 h.
The precipitate that formed was filtered off.
cm−1; H NMR (400 MHz, CDCl3, ppm) δ 2.43 (s, 6H, 2Me),
5.25 (s, 2H, CH2), 7.22 (d, J = 7.9 Hz, 2Н, Н-3, H-5 Ar), 7.28
(d, J = 7.9 Hz, 2Н, Н-3, H-5 Ar), 7.32–7.43 (m, 3H, Bn), 7.47
(d, J = 7.1 Hz, 2Н, Н-2, H-6 Bn), 7.58 (d, J = 7.9 Hz, 2Н, Н-2,
H-6 Ar), 7.60–7.62 (m, 1Н, H-6 Ar), 7.63 (d, J = 7.9 Hz, 2Н,
Н-2, H-6 Ar), 7.77 (d, J = 1.9 Hz, 1Н, Н-2 Ar), 12.64 (s, 1H,
OH); 13C{1H} NMR (100 MHz, DMSO-d6, ppm) δ 21.1, 21.2,
70.2, 116.4, 124.9, 127.5, 127.6, 127.8, 127.9, 128.2, 128.4,
128.9, 129.2, 129.5, 134.3, 134.6, 136.5, 142.5, 143.7, 146.7,
150.7, 193.3, 195.7. Anal. Calcd for C29H24O4: C, 79.80; H,
5.54. Found: C, 79.57; H, 5.51.
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis(biphenyl-4-
ylmethanone) (6d).
Yield 63% (107 mg), light yellow powder, mp 193–195 °С.
IR (ATR): 3056, 3031, 1649, 1618, 1602, 1302, 1277, 745,
1
694 cm−1; H NMR (400 MHz, CDCl3, ppm) δ 5.29 (s, 2H,
CH2), 7.32–7.52 (m, 11H, 3Ph), 7.58 (ddd, J = 7.8 Hz, J = 7.2
Hz, J = 1.1 Hz, 4Н, Н-3, H-5 2Ph), 7.64 (d, J = 8.3 Hz, 2Н, Н-
3, H-5 Ar), 7.69 (d, J = 8.3 Hz, 2Н, Н-3, H-5 Ar), 7.70 (d, J =
1.8 Hz, 1Н, H-6 Ar), 7.74 (d, J = 8.3 Hz, 2Н, Н-2, H-6 Ar),
7.80 (d, J = 8.3 Hz, 2Н, Н-2, H-6 Ar), 7.84 (d, J = 1.8 Hz, 1Н,
Н-2 Ar), 12.55 (s, 1H, OH); 13C{1H} NMR (100 MHz,
DMSO-d6, ppm) δ 70.4, 116.4, 124.8, 126.0, 126.8, 126.9,
127.0, 127.6, 127.7, 127.9, 128.4, 129.1, 130.07, 130.11,
135.8, 136.1, 136.5, 138.8, 138.9, 143.6, 144.6, 146.9, 151.1,
193.2, 195.7 (4C were not observed); HRMS (ESI/Q-TOF)
m/z: [M+H]+ Calcd for C39H29O4 561.2066; Found 561.2042.
(5-(Benzyloxy)-4-hydroxy-1,3-
phenylene)bis(phenylmethanone) (6a).
Yield 71% (88 mg), yellow powder, mp 137–138 °С. IR
1
(ATR): 3033, 1645, 1622, 1594, 1572, 1278, 713 cm−1; H
NMR (400 MHz, CDCl3, ppm) δ 5.27 (s, 2H, CH2), 7.30–7.44
(m, 5H, Ph), 7.44–7.51 (m, 4H, Ph), 7.54 (tt, J = 7.5 Hz, J =
1.1 Hz, 1Н, Н-4 Ph), 7.57 (tt, J = 7.5 Hz, J = 1.1 Hz, 1Н, Н-4
Ph), 7.63–7.67 (м, 1Н, H-6 Ar), 7.65 (dd, J = 8.7 Hz, J = 1.3
Hz, 2Н, Н-2, H-6 Ph), 7.70 (dd, J = 8.3 Hz, J = 1.3 Hz, 2Н, Н-
2, H-6 Ph), 7.76 (d, J = 2.0 Hz, 1Н, H-2 Ar), 12.68 (s, 1H,
OH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 71.5, 118.8,
120.0, 127.6, 127.7, 128.35, 128.39, 128.6, 128.9, 129.2,
129.4, 129.7, 132.3, 132.7, 136.3, 137.3, 137.5, 147.9, 158.0,
194.4, 201.4; HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C27H21O4 409.1440; Found 409.1432.
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis((4-
chlorophenyl)methanone) (6e).
Yield 57% (83 mg), yellow powder, mp 133–135 °С. IR
(ATR): 3036, 2962, 1646, 1617, 1584, 1296, 840, 696 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 5.26 (s, 2H, CH2), 7.33–
7.45 (m, 7H, Ph, Ar), 7.47 (d, J = 8.5 Hz, 2Н, Н-3, H-5 Ar),
7.54–7.56 (m, 1H, H-6 Ar), 7.56 (d, J = 8.6 Hz, 2Н, Н-2, H-6
Ar), 7.65 (d, J = 8.5 Hz, 2Н, Н-2, H-6 Ar), 7.68 (d, J = 1.9 Hz,
1Н, H-2 Ar), 12.36 (s, 1H, OH); 13C{1H} NMR (100 MHz,
DMSO-d6, ppm) δ 70.3, 116.5, 124.9, 125.1, 127.4, 127.6,
127.9, 128.4, 128.6, 128.7, 131.1, 131.2, 135.7, 136.0, 136.4,
137.1, 138.1, 146.9, 150.8, 192.6, 194.6; HRMS (ESI/Q-TOF)
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis((4-
methoxyphenyl)methanone) (6b).
Yield 56% (80 mg), yellow powder, mp 158–160 °С. IR
(ATR): 3065, 3033, 2929, 2839, 1646, 1625, 1599, 1256,
1168, 847, 699 cm−1; 1H NMR (400 MHz, CDCl3, ppm) δ 3.88
(s, 6H, 2Me), 5.26 (s, 2H, CH2), 6.90 (d, J = 8.9 Hz, 2Н, Н-3,
H-5 Ar), 6.96 (d, J = 8.9 Hz, 2Н, Н-3, H-5 Ar), 7.31–7.37 (m,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 14
m/z: [M+H]+ Calcd for C27H19Cl2O4 477.0660; Found
477.0670.
Н-4 Ph), 7.70–7.75 (m, 4H, 2Ph), 7.75 (d, J = 1.9 Hz, 1Н, Н-6
1
2
3
4
5
6
7
8
Ph), 7.99 (d, J = 1.9 Hz, 1Н, Н-2 Ph), 12.65 (s, 1H, OH);
13C{1H} NMR (100 MHz, CDCl3, ppm)  117.6, 119.7, 123.6,
127.3, 128.0, 128.4, 128.6, 129.4, 129.7, 129.9, 131.7, 132.5,
132.8, 137.1, 146.3, 157.0, 159.0, 193.9, 201.2 (1C was not
observed); HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C26H19O4 395.1283; Found 395.1268.
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis(naphthalen-
2-ylmethanone) (6f).
Yield 63% (97 mg), yellow powder, mp 166–168 °С. IR
(ATR): 3058, 2963, 1650, 1623, 1591, 1259, 1016, 793 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 5.29 (s, 2H, CH2), 7.32–
7.43 (m, 3H, Bn), 7.47–7.62 (m, 6H, Bn, Naph), 7.75–7.91 (m,
10H, Ar, Naph), 8.18 (d, J = 1.0 Hz, 1Н, Н-1 Naph), 8.22 (d, J
= 1.0 Hz, 1Н, Н-1 Naph), 12.68 (s, 1H, OH); 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 71.5, 119.0, 119.8, 125.2, 125.7,
127.0, 127.2, 127.7, 128.0, 128.2, 128.40, 128.43, 128.49,
128.7, 128.9, 129.1, 129.5, 131.0, 131.2, 132.27, 132.34,
134.6, 134.9, 135.2, 136.3, 148.2, 157.9, 194.7, 201.2 (3C
were not observed). Anal. Calcd for C35H24O4: C, 82.66; H,
4.76. Found: C, 82.87; H, 4.83.
(5-(Phenoxy)-4-hydroxy-1,3-phenylene)bis(thiophen-2-
ylmethanone) (6j).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yield 52% (64 mg), yellow powder, mp 120–122 °C. IR
(ATR): 3081, 2675, 1615, 1582, 1488, 1410, 1281, 1106, 864
cm–1; 1H NMR (500 MHz, CDCl3, ppm)  7.06 (d, J = 8.0 Hz,
2Н, Н-2, Н-6 Ph), 7.13 (t, J = 7.2 Hz, 1Н, Н-4 Ph), 7.15 (t, J =
4.3 Hz, 1Н, Н-4 Th), 7.23 (t, J = 4.5 Hz, 1Н, Н-4 Th), 7.36 (t,
J = 7.9 Hz, 2Н, Н-3, H-5 Ph), 7.64 (d, J = 3.5 Hz, 1Н, H-3
Th), 7.71 (d, J = 4.8 Hz, 1Н, H-5 Th), 7.80 (d, J = 1.6 Hz, 1Н,
Н-4 Ph), 7.81 (d, J = 4.9 Hz, 1Н, Н-5 Th), 7.86 (d, J = 3.5 Hz,
1Н, Н-3 Th), 8.42 (d, J = 1.6 Hz, 1Н, Н-2 Ph), 12.19 (s, 1H,
OH); 13C{1H} NMR (100 MHz, CDCl3, ppm)  117.7, 120.4,
123.6, 126.3, 128.1, 128.5, 128.6, 128.9, 129.9, 134.2, 134.3,
135.3, 141.5, 142.8, 146.4, 156.9, 158.0, 185.3, 190.5. Anal.
Calcd for C22H14O4S2: C, 65.01; H, 3.47. Found: C, 65.04; H,
3.50.
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis(naphthalen-
1-ylmethanone) (6g).
Yield 49% (76 mg), yellow powder, mp 104–106 °С. IR
1
(ATR): 1629, 1578, 1456, 1280, 1027, 959 cm−1; H NMR
(400 MHz, CDCl3, ppm) δ 5.26 (s, 2H, CH2), 7.32–7.43 (m,
21H, 2Naph, Ar, Bn), 13.22 (s, 1H, OH); 13C{1H} NMR (100
MHz, CDCl3, ppm) δ 71.4, 119.3, 119.5, 124.1, 125.1, 125.5,
126.4, 126.6, 127.05, 127.07, 127.3, 127.4, 127.6, 128.1,
128.3, 128.4, 128.5, 128.8, 130.2, 130.5, 130.7, 131.0, 131.6,
133.6, 134.3, 135.5, 136.0, 148.3, 158.9, 195.3, 203.4 (2C
were not observed). Anal. Calcd for C35H24O4: C, 82.66; H,
4.76. Found: C, 82.53; H, 4.61.
(5-(Methoxy)-4-hydroxy-1,3-
phenylene)bis(phenylmethanone) (6k).
Yield 29% (29 mg), grey powder, mp 140–142 °C. IR
(ATR): 3068, 2980, 2933, 1654, 1622, 1597, 1448, 1305,
1273, 1128, 978, 724 cm–1; 1H NMR (400 MHz, CDCl3, ppm)
 4.02 (s, 3H, Me), 7.42–7.50 (m, 4H, Ph), 7.53–7.61 (m, 2H,
Ph), 7.67–7.72 (m, 4H, Ph), 7.72–7.77 (m, 2H, Ph), 12.74 (s,
1H, OH). 13C{1H} NMR (100 MHz, CDCl3, ppm)  55.5,
115.8, 117.0, 126.6, 127.3, 127.4, 127.8, 128.3, 128.6, 131.3,
131.6, 136.1, 136.5, 148.3, 156.4, 193.6, 200.3; HRMS
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C21H17O4 333.1127;
Found 333.1129.
(5-(Benzyloxy)-4-hydroxy-1,3-phenylene)bis(thiophen-2-
ylmethanone) (6h).
Yield 73% (103 mg), yellow powder, mp 133–135 °С. IR
(ATR): 3100, 3080, 1615, 1585, 1408, 1301, 1251, 728 cm−1;
1H NMR (400 MHz, CDCl3, ppm) δ 5.29 (s, 2H, CH2), 7.09
(dd, J = 4.9 Hz, J = 3.8 Hz, 1Н, Н-4 Th), 7.19 (dd, J = 4.9 Hz,
J = 3.8 Hz, 1Н, Н-4 Th), 7.32–7.44 (m, 4H, Bn, Th), 7.48 (d, J
= 7.0 Hz, 2Н, Н-2, H-6 Bn), 7.66 (d, J = 1.9 Hz, 1Н, Н-6 Ar),
7.69 (dd, J = 4.9 Hz, J = 1.0 Hz, 1Н, Н-5 Th), 7.77 (dd, J =
4.9 Hz, J = 1.0 Hz, 1Н, Н-5 Th), 7.80 (dd, J = 3.8 Hz, J = 1.0
Hz, 1Н, Н-3 Th), 8.21 (d, J = 1.9 Hz, 1Н, Н-2 Ar), 12.19 (s,
1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 71.3,
119.3, 125.9, 127.5, 128.0, 128.3, 128.4, 128.5, 128.8, 134.0,
134.1, 134.9, 135.2, 136.2, 141.7, 143.0, 147.7, 156.9, 185.8,
190.7 (1C were not observed). Anal. Calcd for C27H24O4S2: C,
68.04; H, 5.08. Found: C, 68.40; H, 4.95.
General method for the preparation of diacyl-
substituted phenoles 9.
A mixture of the corresponding enaminodione 8 (1.214
mmol), Si(OEt)4 (126.5 mg, 0.607 mmol), and LiH (11.6 mg,
1.458 mmol) was refluxed in 1,2-dimethoxyethane (2 mL) for
5 h or dioxane (2 mL) (for enaminodiones 8e,f,h,j,k) for 8 h
using a reflux condenser equipped with a calcium chloride
drying tube. After that (in the case of enaminodiones
8b,d,e,h,i,l), the reaction mixture was quenched with HCl (1 :
2) to pH = 2 at 0 ºC and stirred for 30 min. The precipitate was
filtered and recrystallized from EtOH or aq. EtOH (for 9l). If
the participate did not form (in the case of enaminodiones
8a,c,f,g,j,k) after the acidification, the reaction mixture was
diluted with H2O (6 mL) and the product was extracted with
EtOAc (3 × 10 mL). The combined extracts were washed with
water (10 mL) and brine (10 mL). The organic phase was
dried with anhydrous Na2SO4 and evaporated under reduced
pressure. The residue was diluted with EtOH (2 mL) and
(5-(Phenoxy)-4-hydroxy-1,3-
phenylene)bis(phenylmethanone) (6i).
Yield 46% (55 mg), yellow powder, mp 163–165 °C. IR
(ATR): 3062, 2960, 1631, 1573, 1287, 1120, 1021, 879, 694
cm–1; 1H NMR (400 MHz, CDCl3, ppm)  7.05 (d, J = 8.0 Hz,
2Н, Н-2, Н-6 Ph), 7.12 (t, J = 7.4 Hz, 1Н, Н-4 Ph), 7.36 (t, J =
8.0 Hz, 2Н, Н-3, H-5 Ph), 7.44 (t, J = 7.7 Hz, 2Н, Н-3, H-5
Ph), 7.51 (t, J = 7.7 Hz, 2Н, Н-3, H-5 Ph), 7.55 (tt, J = 7.5 Hz,
J = 1.1 Hz, 1Н, Н-4 Ph), 7.61 (tt, J = 7.5 Hz, J = 1.0 Hz, 1Н,
ACS Paragon Plus Environment

Page 11 of 14
The Journal of Organic Chemistry
maintained at –20 ºC for 24 h. The precipitate that formed was 55.5, 111.3, 111.6, 180.0, 119.4, 120.6, 120.7, 127.0, 128.5,
1
2
3
4
5
6
7
8
filtered off.
128.9, 129.1, 129.3, 131.8, 132.5, 137.2, 137.7, 156.6, 156.9,
166.6, 194.0, 202.0; HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd
for C22H19O5 363.1232; Found 363.1229.
(4-Hydroxy-1,3-phenylene)bis(phenylmethanone) (9a).
Yield 62% (114 mg), grey solid, mp 91–92 °C (lit.19 mp 101
°C). IR (ATR): 3055, 2966, 1621, 1477, 1339, 1250, 987, 795,
695 cm–1; 1H NMR (400 MHz, CDCl3, ppm)  7.16 (d, J = 8.7
Hz, 1Н, Н-5 Ph), 7.44–7.53 (m, 4H, Ph), 7.54–7.63 (m, 2H,
Ph), 7.69–7.77 (m, 4H, Ph), 8.02 (dd, J = 8.7 Hz, J = 2.2 Hz,
1Н, Н-6 Ph), 8.20 (d, J = 2.2 Hz, 1Н, Н-2 Ph), 12.49 (s, 1H,
OH); 13C{1H} NMR (126 MHz, CDCl3, ppm) δ 118.5, 128.3,
128.4, 128.5, 129.3, 129.6, 132.3, 132.6, 136.6, 137.0, 137.4,
137.8, 166.6, 194.4, 201.3 (1С was not observed); HRMS
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C20H15O3 303.1021;
Found 303.1019.
(4-Hydroxy-1,3-phenylene)bis(p-tolylmethanone) (9e).
Yield 80% (160 mg), yellow powder, mp 80–82 °С. IR
(ATR): 3325, 2924, 1648, 1627, 1600, 1560, 1155, 914, 790
1
cm–1; H NMR (400 MHz, CDCl3, ppm)  2.43 (s, 3H, Me),
9
2.44 (s, 3H, Me), 7.13 (d, J = 8.7 Hz, 1Н, H-5 Ar), 7.24–7.33
(m, 4H, Ar); 7.63 (d, J = 8.2 Hz, 2Н, H-2, H-6 Ar), 7.67 (d, J
= 8.2 Hz, 2Н, H-2, H-6 Ar), 7.97 (dd, J = 8.7 Hz, J = 2.2 Hz,
1Н, H-6 Ar), 8.20 (d, J = 2.2 Hz, 1Н, H-2 Ar), 12.46 (s, 1H,
OH); 13C{1H} NMR (100 MHz, CDCl3, ppm)  21.64, 21.66,
118.3, 118.7, 128.7, 129.0, 129.3, 129.6, 129.9, 134.5, 134.8,
136.3, 137.6, 143.2, 143.5, 166.4, 194.3, 201.0. Anal. Calcd
for C22H18O3: C, 79.98; H, 5.49. Found: C, 79.62; H, 5.49.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4-Hydroxy-1,3-phenylene)bis((4-
methoxyphenyl)methanone) (9b).
(4-Hydroxy-1,3-phenylene)bis((4-
chlorophenyl)methanone) (9f).
Yield 91% (200 mg), yellow powder, mp 108–110 °С. IR
(ATR): 3000, 2838, 1646, 1598, 1506, 1246, 1026, 765 cm–1;
1H NMR (400 MHz, CDCl3, ppm)  3.89 (s, 6H, Me), 6.96 (d,
J = 8.8 Hz, 2Н, H-3, H-5 Ar), 6.99 (d, J = 8.8 Hz, 2Н, H-3, H-
5 Ar), 7.13 (d, J = 8.7 Hz, 1Н, H-5 Ar), 7.75 (d, J = 8.8 Hz,
2Н, H-2, H-6 Ar), 7.78 (d, J = 8.8 Hz, 2Н, H-2, H-6 Ar), 7.95
(dd, J = 8.7 Hz, J = 2.1 Hz, 1Н, H-6 Ar), 8.18 (d, J = 2.1 Hz,
1Н, H-2 Ar), 12.38 (s, 1H, OH); 13C{1H} NMR (100 MHz,
CDCl3, ppm)  55.5, 55.6, 113.7, 113.9, 118.2, 118.8, 128.9,
129.7, 130.1, 132.0, 132.2, 135.8, 137.2, 163.2, 163.4, 166.0,
193.5, 199.6. Anal. Calcd for C22H18O5: C, 72.92; H, 5.01.
Found: C, 72.64; H, 5.07.
Yield 51% (114 mg), brown powder, mp 92–94 °С. IR
(ATR): 3300, 1647, 1627, 1584, 1276, 1090, 777 cm–1; H
1
NMR (400 MHz, CDCl3, ppm)  7.16 (d, J = 8.7 Hz, 1Н, Н-5
Ph), 7.46 (d, J = 8.5 Hz, 2Н, H-3, H-5 Ar), 7.50 (d, J = 8.5 Hz,
2Н, H-3, H-5 Ar), 7.66 (d, J = 8.5 Hz, 2Н, H-2, H-6 Ar), 7.69
(d, J = 8.5 Hz, 2Н, H-2, H-6 Ar), 7.96 (dd, J = 8.7 Hz, J = 2.1
Hz, 1Н, H-6 Ar), 8.13 (d, J = 2.1 Hz, 1Н, H-2 Ar), 12.32 (s,
1H, OH). 13C{1H} NMR (100 MHz, CDCl3, ppm)  118.5,
118.7, 128.2, 128.8, 129.0, 130.7, 131.1, 135.3, 135.6, 135.9,
137.8, 139.0, 139.3, 166.6, 193.1, 199.9. Anal. Calcd for
C20H12Cl2O3: C, 64.71; H, 3.26. Found: C, 64.82; H, 3.41.
(4-Hydroxy-1,3-phenylene)bis((3-
methoxyphenyl)methanone) (9c).
(4-Hydroxy-1,3-phenylene)bis((4-
nitrophenyl)methanone) (9g).
Yield 94% (207 mg), yellow liquid. IR (ATR): 3068, 2936,
2834, 1716, 1623, 1576, 1425, 1256, 1039, 882 cm–1; 1H NMR
(400 MHz, CDCl3, ppm)  3.85 (s, 3H, MeO), 3.86 (s, 3H,
MeO), 7.08–7.14 (m, 2H, Ar), 7.15 (d, J = 8.7 Hz, 1Н, H-5
Ar), 7.23–7.31 (m, 4H, Ar), 7.33–7.43 (m, 2H, Ar), 8.03 (dd, J
= 8.7 Hz, J = 2.2 Hz, 1Н, H-6 Ar), 8.22 (d, J = 2.2 Hz, 1Н, H-
2 Ar), 12.45 (s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3,
ppm)  55.4, 55.5, 114.1, 114.2, 118.4, 118.5, 118.6, 118.7,
121.8, 122.2, 128.4, 129.3, 129.5, 136.7, 137.8, 138.3, 138.8,
159.6, 159.7, 166.7, 194.2, 201.1; HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C22H19O5 363.1232; Found 363.1231.
Yield 53% (252 mg), brown powder, mp 131–133 °С. IR
(ATR): 3106, 1630, 1514, 1343, 1103, 850 cm–1; H NMR
1
(500 MHz, CDCl3, ppm)  7.22 (d, J = 8.6 Hz, 1Н, H-5 Ar),
7.91 (s, 1Н, H-2 Ar), 7.95–8.08 (m, 6H, Ar), 8.34–8.52 (m,
1
3H, Ar), 12.25 (s, 1H, OH); H NMR (400 MHz, DMSO-d6,
ppm)  7.22 (d, J = 8.7 Hz, 1Н, H-5 Ar), 7.63–8.54 (m, 10H,
Ar), 11.48 (s, 1H, OH); 13C{1H} NMR (100 MHz, DMSO-d6,
ppm)  117.1, 123.6, 123.7, 124.9, 127.2, 130.3, 130.4, 133.2,
135.4, 142.1, 143.0, 149.2, 149.8, 161.0, 192.5, 194.3. Anal.
Calcd for C20H12N2O7: C, 61.23; H, 3.08; N, 7.14. Found: C,
61.05; H, 3.21; N, 6.82.
(4-Hydroxy-1,3-phenylene)bis((2-
methoxyphenyl)methanone) (9d).
(4-Hydroxy-1,3-phenylene)bis(naphthalen-2-
ylmethanone) (9h).
Yield 82% (180 mg), brown powder, mp 81–83 °С. IR
(ATR): 3063, 3011, 2965, 1656, 1624, 1596, 1429, 1014, 907,
Yield 97% (237 mg), brown powder, mp 168–170 °С. IR
(ATR): 3056, 2964, 1645, 1618, 1466, 1220, 906, 776 cm–1;
1H NMR (400 MHz, CDCl3, ppm) δ 7.22 (d, J = 8.7 Hz, 1Н,
Н-5 Ar), 7.49–7.64 (m, 4H, Naph), 7.80 (dd, J = 8.5 Hz, J =
1.7 Hz, 1Н, Naph), 7.83–7.95 (m, 7H, Naph), 8.10 (dd, J = 8.7
Hz, J = 2.2 Hz, 1Н, Н-6 Ar), 8.23 (s, 2Н, H-1 2Naph), 8.32 (d,
J = 2.2 Hz, 1Н, Н-2 Ar), 12.53 (s, 1H, OH); 13C{1H} NMR
(100 MHz, CDCl3, ppm)  118.7, 118.8, 125.1, 125.6, 126.9,
1
769 cm–1; H NMR (400 MHz, CDCl3, ppm)  3.63 (s, 3H,
MeO), 3.69 (s, 3H, MeO), 6.89 (d, J = 8.4 Hz, 1Н, Ar), 6.94
(d, J = 8.4 Hz, 1Н, Ar), 6.99 (td, J = 7.5 Hz, J = 0.6 Hz, 1Н,
Ar), 7.02–7.07 (m, 2H, Ar), 7.25–7.32 (m, 2H, Ar), 7.41 (ddd,
J = 8.3 Hz, J = 7.5 Hz, J = 1.7 Hz, 1Н, Ar), 7.47 (ddd, J = 8.3
Hz, J = 7.5 Hz, J = 1.7 Hz, 1Н, Ar), 7.91 (dd, J = 8.7 Hz, J =
2.2 Hz, 1Н, H-6 Ar), 7.94 (d, J = 2.1 Hz, 1Н, H-2 Ar), 12.67
(s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm)  55.4,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
127.1, 127.8, 127.9, 128.3, 128.4, 128.5, 128.6, 128.9, 129.28,
Page 12 of 14
2.2 Hz, 1Н, H-2 Ar), 11.31 (s, 1H, OH). The analytical data
are in accordance with those reported in the literature.14
1
2
3
4
5
6
7
8
129.32, 130.8, 131.2, 132.2, 132.3, 134.4, 134.8, 135.1, 135.2,
136.6, 137.8, 166.7, 194.6, 201.2; HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C28H19O3 403.1334; Found 403.1352.
(2E,4Z)-1-(3-Acetyl-4-hydroxyphenyl)-4-(1-
hydroxyethylidene)hex-2-ene-1,5-dione (10).
(4-Hydroxy-1,3-phenylene)bis(thiophen-2-ylmethanone)
(9i).
A mixture of 3-((dimethylamino)methylene)pentane-2,4-
dione (8m) (0.40 g, 2.58 mmol), Si(OEt)4 (0.27 g, 1.29 mmol),
and LiH (24.6 mg, 3.09 mmol) was refluxed in dioxane (2 mL)
for 1 h using a reflux condenser equipped with a calcium
chloride drying tube. After that, the reaction mixture was
quenched with HCl (1 : 2) to pH = 2 at 0 ºC and stirred for 30
min. The reaction mixture was diluted with H2O (6 mL), and
the product was extracted with EtOAc (3 × 10 mL). The
combined extracts were washed with water (10 mL) and brine
(10 mL). The organic phase was dried with anhydrous Na2SO4
and evaporated under reduced pressure. The residue was
diluted with EtOH (2 mL) and maintained at –20 ºC for 24 h.
The precipitate that formed was filtered off. Yield 32% (79
mg), red powder, mp 125–128 ºС. IR (ATR): 2917, 1668,
Yield 53% (102 mg), grey powder, mp 97–99 °С. IR
1
(ATR): 1630, 1605, 1565, 1415, 1282, 1091, 862 cm–1; H
9
NMR (500 MHz, CDCl3, ppm) δ 7.17 (d, J = 8.6 Hz, 1Н, Н-5
Ar), 7.19 (dd, J = 5.0 Hz, J = 3.8 Hz, 1Н, H-4 Th), 7.21 (dd, J
= 5.0 Hz, J = 3.8 Hz, 1Н, H-4 Th), 7.67 (dd, J = 3.8 Hz, J =
1.1 Hz, 1Н, H-3 Th), 7.73 (dd, J = 5.0 Hz, J = 1.1 Hz, 1Н, H-5
Th), 7.79 (dd, J = 5.0 Hz, J = 1.1 Hz, 1Н, H-5 Th), 7.82 (dd, J
= 3.8 Hz, J = 1.1 Hz, 1Н, H-3 Th), 8.11 (dd, J = 8.6 Hz, J =
2.2 Hz, 1Н, H-6 Ar), 8.61 (d, J = 2.2 Hz, 1Н, H-2 Ar), 12.08
(s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm)  118.6,
119.1, 128.0, 128.4, 129.3, 133.9, 134.07, 134.11, 134.8,
135.1, 136.7, 141.5, 143.1, 165.9, 185.8, 190.7. Anal. Calcd
for C16H10O3S2: C, 61.13; H, 3.21. Found: C, 61.04; H, 3.14.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1635, 1531, 1330, 1176, 983, 834 cm–1; H NMR (400 MHz,
1
CDCl3, ppm) δ 2.45 (s, 6Н, 2Me), 7.06 (d, J = 8.7 Hz, 1Н, H-5
Ar), 8.07 (dd, J = 8.7 Hz, J = 2.1 Hz, 1Н, H-6 Ar), 7.09 (d, J =
15.4 Hz, 1Н, CH), 7.95 (d, J = 15.4 Hz, 1Н, CH), 8.48 (d, J =
2.1 Hz, 1Н, H-2 Ar), 13.33 (s, 1H, OH), the ОН proton was
not observed due to broadening; 13C{1H} NMR (100 MHz,
CDCl3, ppm)  25.3, 26.3, 110.4, 118.7, 119.4, 119.5, 128.5,
130.3, 136.1, 141.5, 167.2, 193.1, 195.2, 195.7. Anal. Calcd
for C16H16O5: C, 66.66; H, 5.59. Found: C, 66.50; H, 5.59.
(4-Hydroxy-5-methyl-1,3-
phenylene)bis(phenylmethanone) (9j).
Yield 37% (72 mg), yellow powder, mp 86–88 °С. IR
(ATR): 3061, 2918, 1650, 1669, 1598, 1444, 1278, 1183, 821
1
cm–1; H NMR (400 MHz, CDCl3, ppm) δ 2.38 (s, 3Н, CH3),
7.43–7.51 (m, 4H, H-3, H-5, H-3', H-5' 2Ph), 7.53–7.61 (m,
2H, H-4, H-4' 2Ph), 7.66–7.76 (m, 4H, H-2, H-6, H-2', H-6'
2Ph), 7.89–7.94 (m, 1H, H-6 Ar), 8.01 (d, J = 2.1 Hz, 1H, H-2
Ar), 12.80 (s, 1H, OH); 13C{1H} NMR (100 MHz, CDCl3,
ppm)  15.7, 117.6, 127.6, 128.0, 128.3, 128.5, 129.3, 126.6,
132.2, 132.4, 134.6, 137.4, 137.7, 138.1, 165.3, 194.8, 201.6.
Anal. Calcd for C21H16O3: C, 79.73; H, 5.10. Found: C, 79.72;
H, 4.88.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
1H and 13C NMR spectra for compounds 3a–l, 4a–l, 6a–k,
(4-Hydroxy-5-methyl-1,3-phenylene)bis(thiophen-2-
ylmethanone) (9k).
8c,d,j.k, 9a–l, 10 (PDF)
Yield 36% (72 mg), grey powder, mp 104–105 °С. IR
(ATR): 3072, 2916, 1618, 1557, 1512, 1408, 1231, 1112,
AUTHOR INFORMATION
Corresponding Author
1
1055, 768 cm–1; H NMR (400 MHz, CDCl3, ppm) δ 2.38 (s,
3Н, Me), 7.16–7.22 (m, 2Н, H-4, H-4' 2Th), 7.67 (dd, J = 3.8
Hz, J = 1.0 Hz, 1Н, H-3 Th), 7.72 (dd, J = 4.9 Hz, J = 1.0 Hz,
1Н, H-5 Th), 7.77 (dd, J = 5.0 Hz, J = 1.0 Hz, 1Н, H-5 Th),
7.79 (dd, J = 3.8 Hz, J = 1.0 Hz, 1Н, H-3 Th), 7.95 (d, J = 1.9
Hz, 1Н, H-6 Ar), 8.45 (d, J = 1.9 Hz, 1Н, H-2 Ar), 12.38 (s,
1H, OH); 13C{1H} NMR (100 MHz, CDCl3, ppm)  15.8,
118.1, 128.0, 128.1, 128.3, 128.5, 131.7, 133.9, 134.0, 134.6,
135.0, 137.1, 141.7, 143.2, 164.5, 186.1, 191.1. Anal. Calcd
for C17H12S2O3: C, 62.17; H, 3.68. Found: C, 61.94; H, 3.62.
*E-mail: dobydennov@mail.ru.
Dmitrii L. Obydennov: 0000-0002-6659-9832
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was financially supported by the Russian Science
Foundation (Grant 18-73-00186). Analytical studies were carried
out using equipment of the Center for Joint Use “Spectroscopy
and Analysis of Organic Compounds” at the Postovsky Institute
of Organic Synthesis of the Russian Academy of Sciences (Ural
Branch) and the Laboratory of Complex Investigations and Expert
Evaluation of Organic Materials of the Center for Joint Use at the
Ural Federal University.
Diethyl 4-hydroxyisophthalate (9l).
1
Yield 92% (134 mg), yellow powder, mp 49–51 °С. H
NMR (500 MHz, CDCl3, ppm) δ 1.40 (t, J = 7.1 Hz, 3Н, Me),
1.45 (t, J = 7.1 Hz, 3Н, Me), 4.37 (q, J = 7.1 Hz, 2Н, CH2),
4.45 (q, J = 7.1 Hz, 2Н, CH2), 7.01 (d, J = 8.7 Hz, 1Н, H-5
Ar), 8.12 (dd, J = 8.7 Hz, J = 2.2 Hz, 1Н, H-6 Ar), 8.56 (d, J =
ACS Paragon Plus Environment

Page 13 of 14
The Journal of Organic Chemistry
Transformations of Diethyl 2-Ethoxymethylenemalonate and Diethyl
Polyfluorobenzoylmalonates in Water. Tetrahedron Lett. 2012, 53,
1961–1963.
REFERENCES
1
2
3
4
5
6
7
8
1. (a) Taylor, R. D.; MacCoss, M.; Lawson A. D. G. Rings in
Drugs. J. Med. Chem. 2014, 57, 5845−5859. (b) Boström, J.; Brown,
D. G.; Young, R. J.; Keserü, G. M. Expanding the Medicinal
Chemistry Synthetic Toolbox. Nat. Rev. Drug Discov. 2018, 17, 709–
727. (c) The Chemistry of Phenols; Z. Rappoport, Ed.; Wiley-VCH,
New York, 2003. (d) Dormán, G.; Nakamura, H.; Pulsipher, A.;
Prestwich, G. D. The Life of Pi Star: Exploring the Exciting and
Forbidden Worlds of the Benzophenone Photophore. Chem. Rev.
2016, 116, 15284−15398. (e) Ye, Q.; Chi, C. Recent Highlights and
Perspectives on Acene Based Molecules and Materials. Chem. Mater.
2014, 26, 4046−4056.
2. (a) Poulsen, T.; Jørgensen, K. A. Catalytic Asymmetric Friedel-
Crafts Alkylation Reactions – Copper Showed the Way. Chem. Rev.
2008, 108, 2903−2915. (b) You, S.-L.; Cai, Q.; Zeng, M. Chiral
Brønsted acid catalyzed Friedel–Crafts alkylation reactions. Chem.
Soc. Rev. 2009, 38, 2190−2201. (c) Yang, J. Transition Metal
Catalyzed meta-C–H Functionalization of Aromatic Compounds.
Org. Biomol. Chem. 2015, 13, 1930–1941. (d) Davies, H. M. L.;
Morton, D. Recent Advances in C−H Functionalization. J. Org.
Chem. 2016, 81, 343–350.
6. For enaminones, see reviews: (a) Greenhill, J. V. Enaminones.
Chem. Soc. Rev. 1977, 6, 277−294. (b) Elassar, A. A.; El-Khair, A. A.
Recent Developments in the Chemistry of Enaminones. Tetrahedron
2003, 59, 8463 − 8480. (c) Stanovnik, B.; Svete, J. Synthesis of
Heterocycles from Alkyl 3-(Dimethylamino)propenoates and Related
Enaminones.Chem. Rev. 2004, 104, 2433 − 2480. (d) Negri, G.;
Kascheres, C.; Kascheres, A. J. Recent Development in Preparation
Reactivity and Biological Activity of Enaminoketones and
Enaminothiones and Their Utilization to Prepare Heterocyclic
Compounds. J. Heterocycl. Chem. 2004, 41, 461−491. (e) Dar’in, D.
V.; Lobanov, P. S. Push-Pull Enamines in the Synthesis of Fused
Azaheterocycles. Russ. Chem. Rev. 2015, 84, 601−633.
7. (a) Wan, J.-P.; Lin, Y.; Hua, K.; Liu, Y. Metal-Free Synthesis of
1,3,5-Trisubstituted Benzenes by the Cyclotrimerization of
Enaminones or Alkynes in Water. RSC Adv. 2014, 4, 20499–20505.
(b) Barkov, A. Y.; Korotaev, V. Y.; Kutyashev, I. B.; Sosnovskikh, V.
Y. Synthesis of Polyfunctionalized Benzophenones via the Reaction
of 3-Formylchromones with Tertiary Push-Pull Enamines.
Tetrahedron 2016, 72, 2026−2033. (c) Yang, L.; Wei, L.; Wan, J.-P.
Redox Neutral [4+2] Benzannulation of Dienals and Tertiary
Enaminones for Benzaldehyde Synthesis. Chem. Commun. 2018, 54,
7475−7478.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3. Pfennig, T.; Johnson, R. L.; Shanks, B. H. The Formation of p-
Toluic Acid from Coumalic Acid: a Reaction Network Analysis.
Green Chem. 2017, 19, 3263–3271.
4. See reviews about the de novo benzene formation: (a) Serra, S.;
Fuganti, C.; Brenna, E. Recent Advances in the Benzannulation of
Substituted 3-Alkoxycarbonyl-3,5-hexadienoic Acids and 3-
Alkoxycarbonylhex-3-en-5-ynoic Acids to Polysubstituted Aromatics.
Chem. Eur. J. 2007, 13, 6782–6791. (b) Kotha, S.; Misra, S.; Halder,
S. Benzannulation. Tetrahedron 2008, 64, 10775–10790. (c)
Mohamed, R. K.; Peterson, P. W.; Alabugin, I. V. Concerted
Reactions That Produce Diradicals and Zwitterions: Electronic, Steric,
Conformational, and Kinetic Control of Cycloaromatization
Processes. Chem. Rev. 2013, 113, 7089–7129.
5. (a) Poudel, T. N.; Tamargo, R. J. I.; Cai, H.; Lee, Y. R. Recent
Progress in Transition-Metal-Free, Base-Mediated Benzannulation
Reactions for the Synthesis of a Diverse Range of Aromatic and
Heteroaromatic Compounds. Asian J. Org. Chem. 2018, 7, 985–1005.
(b) Poudel, T. N.; Lee, Y. R. Transition-Metal-Free Benzannulation
for Diverse and Polyfunctionalized Biaryl Formation. Org. Lett. 2015,
17, 2050 − 2053. (c) Chen, H.; Xie, F.; Gong, J.; Hu, Y. Domino
Reaction to Functionalized 2-Hydroxybenzophenones from Electron-
Deficient Chromones and 1,3-Dicarbonyl Compounds. J. Org. Chem.
2011, 76, 8495–8500. (d) Maezono, S. M. B.; Poudel, T. N.; Lee, Y.
R. One-Pot Construction of Sterically Challenging and Diverse
Polyarylphenols via Transition-Metal-Free Benzannulation and Their
Potent in vitro Antioxidant Activity. Org. Biomol. Chem. 2017, 15,
2052–2062. (e) Gao, Q.; Tan, X.-c.; Pan, Y.-m.; Wang, H.-s.; Liang,
Y. Palladium-Catalyzed Formation of Phenolic Compounds by
Reaction of Carbonyl Compounds with Carbon Dioxide. Chem.
Commun. 2012, 48, 12080–12081. (f) Shu, W.-M.; Zheng, K.-L.; Ma,
8. (a) Cai, H.; Xia, L.; Lee, Y. R. Regioselective Construction of
Diverse and Multifunctionalized 2-Hydroxybenzophenones for Sun
Protection by Indium(III)-Catalyzed Benzannulation. Chem.
Commun. 2016, 52, 7661−7664. (b) Zhao, Y.; Zheng, Q.; Yu, C.; Liu,
Z.; Wang, D.; You, J.; Gao, G. Rh(III)-Catalyzed Regioselective C–H
[4+2] C-annulation of Vinyl Enaminones with Alkynes to Form
Polysubstituted Salicylaldehydes. Org. Chem. Front. 2018, 5, 2875−
2879. (c) Liang, G.; Rong, J.; Sun, W.; Chen, G.; Jiang, Y.; Loh, T.-P.
Synthesis of Polyaromatic Rings: Rh(III)-Catalyzed [5+1] Annulation
of Enaminones with Vinyl Esters through C−H Bond
Functionalization. Org. Lett. 2018, 20, 7326−7331.
9. (a) Xie, P.; Huang Y. Domino Cyclization Initiated by Cross-
Rauhut–Currier Reactions. Eur. J. Org. Chem. 2013, 28, 6213−6226.
(b) Jeon, S.; Han, S. An Accelerated Intermolecular Rauhut−Currier
Reaction Enables the Total Synthesis of (−)-Flueggenine C. J. Am.
Chem. Soc. 2017, 139, 6302−6305.
10. (a) Theobald, D. W. Bromo-Derivatives of Dimethyl 4-Oxo-
trans-2,6-diphenylcyclohexane-1,1-dicarboxylate
and
Their
Dehydrobromination. J. Chem. Soc., Perkin Trans. 1 1982, 101−105.
(b) Marshall, L. J.; Cable, K. M.; Botting, N. P. The Synthesis of
Substituted Phenols from Pyranone Precursors. Tetrahedron 2009, 65,
8165–8170.
11. (a) Appel, B.; Rotzoll, S.; Kranich, R.; Reinke, H.; Langer, P.
Domino Michael/Retro-Michael/Mukaiyama-Aldol Reactions of 1,3-
Bis-Silyl Enol Ethers with 3-Acyl- and 3-Formylbenzopyrylium
Triflates – Synthesis of Functionalised 2,4-Dihydroxybenzophenones.
Eur. J. Org. Chem. 2006, 3638–3644. (b) Kim, S.; Choi, K.
Occurrences, Toxicities, and Ecological Risks of Benzophenone-3, a
Common Component of Organic Sunscreen Products: A Mini-review.
Environ. Int. 2014, 70, 143–157. (c) Álvarez, C.; Álvarez, R.;
Corchete, P.; Pérez-Melero, C.; Peláeza, R.; Medarde, M. Synthesis
and Biological Activity of Naphthalene Analogues of Phenstatins:
Naphthylphenstatins. Bioorg. Med. Chem. Lett. 2007, 17, 3417–3420.
(d) Khanum, S. A.; Venu, T. D; Shashikantha, S.; Firdouse, A.
Synthesis of Some Newer Analogues of Substituted Dibenzoylphenol
as Potent Anti-inflammatory Agents. Bioorg. Med. Chem. Lett. 2004,
J.-R.;
Wu,
A.-X.
Transition-Metal-Free
Multicomponent
Benzannulation Reactions for the Construction of Polysubstituted
Benzene Derivatives. Org. Lett. 2015, 17, 5216–5219. (g) Zhu, T.;
Mou, C.; Li, B.; Smetankova, M.; Song, B.-A.; Chi, Y. R. N ‑
Heterocyclic Carbene-Catalyzed δ ‑ Carbon LUMO Activation of
Unsaturated Aldehydes. J. Am. Chem. Soc. 2015, 137, 5658−5661. (h)
Zhu, T.; Zheng, P.; Mou, C.; Yang, S.; Song, B.-A.; Chi, Y. R.
Benzene Construction via Organocatalytic Formal [3+3]
Cycloaddition Reaction. Nature Commun. 2014, 5, 5027. (i) Bazhin,
D. N.; Kudyakova, Y. S.; Burgart, Y. V.; Saloutin, V. I. Catalyst-Free
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 14
14, 5351–5355. (e) Tang, G.; Nikolovska-Coleska, Z.; Qiu, S.; Yang,
16. The double bond of enaminodiones have a push−pull and
1
2
3
4
5
6
7
8
C.-Y.; Guo, J.; Wang, S. Acylpyrogallols as Inhibitors of
Antiapoptotic Bcl-2 Proteins. J. Med. Chem. 2008, 51, 717–720. (f)
Dam, J.; Bode, M. L.; De Koning, C. B. Ceric Ammonium Sulfate
(CAS) Mediated Oxidations of Benzophenones Possessing a Phenolic
Substituent for the Synthesis of Xanthones and Related Products. J.
Org. Chem. 2019, 84, 150–160.
12. (a) Souza, T. F.; Silva, M. J. V.; Silva, R. G. M.; Gonçalves, D.
S.; Simon, P. A.; Jacomini, A. P.; Basso, E. A.; Moura, S.; Martins,
M. A. P.; Back, D. F.; Rosa F. A. Regiochemical Control of Pyrazoles
by Solvent and β‐Enamino Diketone Structure: Regioselective
Synthesis of 4,5‐Disubstituted N‐Phenylpyrazoles. Asian J. Org.
Chem. 2017, 6, 627–633. (b) Silva, M. J. V.; Poletto, J.; Jacomini, A.
P.; Pianoski, K. E.; Goncalves, D. S.; Ribeiro, G. M.; S. Melo, S. M.;
Back, D. F.; Moura, S., Rosa, F. A. Unconventional Method for
partially unsaturated character,thus allowing for hindered rotation. For
details, see reference 13.
17. Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Reactlvlty of
Penta- and Hexacoordinate Silicon Compounds and Their Role as
Reaction Intermediates. Chem. Rev. 1993, 93, 1371–1448.
18. (a) Nakajima, M.; Orito, Y.; Ishizuka, T.; Hashimoto, S.
Enantioselective Aldol Reaction of Trimethoxysilyl Enol Ether
Catalyzed by Lithium Binaphtholate. Org. Lett. 2004, 6, 3763–376.
(b) Dede, R.; Langer, P. Synthesis of Functionalized Acetophenones
by [3 + 3] Cyclizations of 1,3-Bis-silyl Enol Ethers with 2-Acetyl-3-
silyloxyalk-2-en-1-ones. Tetrahedron Lett. 2004, 45, 9177–9179. (c)
Rashid, M. A.; Rasool, N.; Adeel, M.; Reinke, H.; Spannenberg, A.;
Fischer, C.; Langer, P. Regioselective Synthesis of Sterically
Encumbered Diaryl Ehers Based on One-pot Cyclizations of 4-
Aryloxy-1,3-bis(trimethylsilyloxy)-1,3-dienes. Tetrahedron. 2008, 64,
529–535.
19. Martin, R.; Coton, G. Transposition des propionate et benzoate
de tertiobutyl-4 Phenyles. Bull. Soc. Chim. Fr. 1973, 1442–1445.
20. Ma, D.; Xia, C.; Jiang, J.; Zhang, J.; Tang, W. Aromatic
Nucleophilic Substitution or CuI-Catalyzed Coupling Route to
Martinellic Acid. J. Org. Chem. 2003, 68, 442–445.
21. (a) Niederl, J. B.; Lederer, S. J. Carboxymethyl Ether of
Epinephrine. J. Org. Chem. 1952, 17, 1617–1620. (b) Harbeson, S.
L.; Tung, R, D.; Liu, J. F.; Masse, C. E. Hydroxyethylamino
Sulfonomide Derivatives. Patent WO 2010127272, 2010.
22. Karapetyan, V.; Mkrtchyan, S.; Hefner, J.; Fischer, C.; Langer,
P. Chelation Control in the [3+3] Annulation Reaction of Alkoxy-
Substituted 1,1-Diacylcyclopropanes with 1,3-Bis(trimethylsilyloxy)-
1,3-butadienes. Diversity-Oriented Synthesis of Isochromanes. J. Org.
Chem. 2010, 75, 809–814.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of 3
arylpyrazoles. J. Org. Chem. 2017, 82, 12590−12602. (с) Menozzi,
G.; Schenone, P.; Mosti, L. Reaction of
2‐Dimethylaminomethylene‐1,3‐diones with Dinucleophiles. II.
Synthesis of 5‐(Alkyl)(phenyl)‐4‐acylisoxazoles and
‑Carboxyethyl-4-formyl(hydroxy)-5-aryl-N-
6,7‐Dihydro‐1,2‐benzisoxazol‐4(5H)‐ones. J. Heterocyclic Chem.
1983, 20, 645–648. (d) Jones, W. D., Jr.; Schnettler, R. A.; Huber, E.
W.
A.
Convenient
Synthesis
of
5‐Acyl‐6‐substituted
3‐cyano‐2(1H)‐pyridinones. J. Heterocycl. Chem. 1990, 27, 511–518.
13. Obydennov, D. L.; Goncharov, A. O.; Sosnovskikh, V. Y.
Preparative synthesis of ethyl 5-acyl-4-pyrone-2-carboxylates and 6-
aryl-, 6-alkyl-, and 5-acylcomanic acids on their basis. Russ. Chem.
Bull., Int. Ed. 2016, 65, 2233–2242.
14. Shu, L.; Gu, C.; Dong, Y.; Brinkman, R. Efficient Large-Scale
Synthesis of a 2,4,5-Triarylimidazoline MDM2 Antagonist. Org.
Proc. Res. Dev. 2012, 16, 1940–1946.
23. Dulenko, V. I.; Tolkunov, S. V. Synthesis and Reactions of
Benzo[b]furo[2,3-c]pyrylium Salts. Chem. Heterocycl. Compd. 1987,
27, 730–733
15. (a) Schreiner, E.; Richter F.; Nerdinger, S. Development of
Synthetic Routes to Dolutegravir. Top. Heterocycl. Chem. 2016, 44,
187–208. (b) Ziegler, R. E.; Desai, B. K.; Jee, J.-A.; Gupton, B. F.;
Roper, T. D.; Jamison, T. F. 7-Step Flow Synthesis of the HIV
Integrase Inhibitor Dolutegravir. Angew. Chem. Int. Ed. 2018, 57,
7181–7185.
ACS Paragon Plus Environment