Practical synthesis of β-isothiocyanato ketones from chalcones

Article abstract of DOI:10.1080/00397911.2016.1167221

Practical synthesis of 1,3-diaryl-substituted 3-isothiocyanatopropan-1-ones based on the reaction of chalcones with thiocyanic acid generated in situ by treatment of thiocyanate ammonium with dilute sulfuric acid has been developed.

Full text of DOI:10.1080/00397911.2016.1167221

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Practical Synthesis of β-isothiocyanato Ketones
From Chalcones
Anastasia A. Fesenko, Pavel A. Solovyev & Anatoly D. Shutalev
To cite this article: Anastasia A. Fesenko, Pavel A. Solovyev & Anatoly D. Shutalev (2016):
Practical Synthesis of β-isothiocyanato Ketones From Chalcones, Synthetic Communications,
DOI: 10.1080/00397911.2016.1167221
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Date: 01 April 2016, At: 13:23

Practical Synthesis of -Isothiocyanato Ketones From Chalcones
1
1
1
Anastasia A. Fesenko , Pavel A. Solovyev , Anatoly D. Shutalev
1
Department of Organic Chemistry, Moscow Technological University, Moscow,
Russian Federation
Address correspondence to prof. Anatoly D. Shutalev, Department of Organic Chemistry,
Moscow Technological University, 86 Vernadsky Avenue, 119571 Moscow, Russian
Federation. E-mail: anatshu@gmail.com
Abstract
Practical synthesis of 1,3-diaryl-substituted 3-isothiocyanatopropan-1-ones based on the
reaction of chalcones with thiocyanic acid generated in situ by treatment of thiocyanate
ammonium with dilute sulfuric acid has been developed.
KEYWORDS: Chalcones; isothiocyanates; ketones; thiocyanic acid; addition
INTRODUCTION
-Isothiocyanato aldehydes and ketones 1 (Fig. 1) with two highly reactive functional
groups are valuable starting materials for the synthesis of a large number of nitrogen-
containing acyclic and heterocyclic compounds.
[
1]
The first representatives of 1 were described in 1946. Since then these compounds have
[
2]
been the focus of considerable attention. Isothiocyanates 1 were used in synthesis of
[
3]
[4]
[5]
[6]
[7]
pyrimidines, 1,3-oxazines, 1,3-thiazines, 1,2,4-triazepines, pyridines, various
[
8]
[9]
fused heterocycles, nucleosides, etc. Commonly, compounds 1 were prepared by the
addition of thiocyanic acid generated by treatment of thiocyanate salts with strong
1

[
10,11]
mineral acids to , -unsaturated aldehydes and ketones in water.
However, success
of this reaction is highly dependent on the substrate structure, particularly on the nature
of substituents. For example, the presence of aryl group(s) due to conjugation would
cause significant hindrance for the addition of HNCS. Indeed, the synthesis of some
isothiocyanates 1 starting from alkyl-substituted unsaturated carbonyl compounds was
described in the literature; however, there are only few reports on preparation of aryl
substituted isothiocyanates 1. Benzylidene acetone, p-anisylidene acetone, and
benzylidene acetophenone (chalcone) failed to give any adducts with HNCS under a wide
[10]
variety of reaction conditions. In contrast, Sammour et al. described the reaction of
chalcone with HNCS affording 3-isothiocyanato-1,3-diphenylpropan-1-one (2) in 54%
[
12]
yield. The structure of this compound was established by elemental analysis and some
chemical transformations. Later, Weber et al. prepared isothiocyanate 2 from chalcone
1
under Sammour’s conditions and provided selected IR and H NMR spectroscopic data
[
13]
for the product. To date there are no reports describing the addition of HNCS to other
chalcones.
[
14]
In continuation of our research in the synthesis of cyclic (thio)semicarbazones we were
interested in preparation of 1,3-diaryl-substituted 3-isothiocyanatopropan-1-ones. First,
we attempted to obtain isothiocyanate 2 from unsubstituted chalcone under the described
[
12]
conditions (chalcone/H SO /NH NCS molar ratio = 1:1:3.3, water, rt, 3 h). However,
2
4
4
1
according to H NMR spectroscopic data, the crude product contained 95% of the starting
material and only 5% of isothiocyanate 2.
2

Thus, the reaction of chalcones with HNCS had to be reinvestigated to develop simple
and general procedure for the preparation of 1,3-diaryl-3-isothiocyanatopropan-1-ones.
Here, we report the results of this reinvestigation.
RESULTS AND DISCUSSION
Chalcones 3a-i which were readily prepared by base-catalyzed condensation of the
[
15]
corresponding acetophenones and aromatic aldehydes were used as starting materials.
They reacted with aqueous thiocyanic acid generated in situ by treatment of thiocyanate
ammonium with dilute sulfuric acid to give the target 1,3-diaryl-3-isothiocyanatopropan-
1
-ones 4a-i (Scheme 1). This reaction proceeded under heterogeneous conditions, and its
result (yield and purity of 4a-i) depended on a number of factors, including molar ratio of
reagents, concentration, temperature, and reaction time (Table 1). It should be noted that
small amounts of byproducts identified as 3,4-dihydro-2H-1,3-oxazine-2-thiones 5a-i
formed in this reaction.
Our initial experiments showed that reaction of 3b with HNCS did not proceed when the
reaction mixture was a suspension [H O, 3b/NH NCS/H SO in a ratio of 1.00:5.11:2.59
2
4
2
4
or 1.00:5.05:5.07, 24 h, rt; H O, 3b/NH NCS/H SO in a ratio of 1.00:3.02:1.40 or
2
4
2
4
1
1
.00:6.16:3.12, 3 h, 70 °C; H O/AcOH (1:1, v/v), 3b/NH NCS/H SO in a ratio of
2 4 2 4
.00:3.08:1.58, 3 h, 70 °C]. Based on the experience in preparation of some other 3-
isothiocyanatoketones which proceeded with emulsion of starting ketone in aqueous
media, we attempted to obtain the reaction mixture with 3b as an emulsion. To achieve
this we increased the reaction temperature to 70 °C (H O, 3b/NH NCS/H SO in a ratio
2
4
2
4
3

of 1.00:3.02:1.40 or 1.00:6.16:3.12, 3 h), but no emulsion formed. We applied AcOH as a
co-solvent, and only with more than 6 equivalents of HNCS emulsions were obtained
(entries 5, 6, and 7); however, the reaction proceeded in a small extent. The use of two-
phase systems (Et O/H O, 3b/NH NCS/H SO in a ratio of 1.00:10.31:5.21, 3 h, rt;
2
2
4
2
4
CHCl /H O, 3b/NH NCS/H SO in a ratio of 1.00:3.15:1.61, 3 h, reflux) gave no
3
2
4
2
4
products.
With low-melting chalcone 3a (mp 56–57 °C) emulsion was obtained by heating the
reaction mixture at 50 °C without addition of AcOH, but still only trace amount of
isothiocyanate 4a formed (entry 2). A decrease in the volume of water in this reaction led
to formation of the desired product in considerable amounts (entry 3). Thus,
isothiocyanate 4a was prepared from chalcone 3a in 59% isolated yield. It is noteworthily
that neutralization of the reaction mixture with aqueous NaHCO during the extractive
3
1
work-up did not cause decomposition of the product. Otherwise, H NMR spectroscopic
data always showed the presence of acid in the crude product regardless the number of
washings of the extract with H O.
2
Under conditions described for 3a, chalcones 3b-d,g gave the corresponding
isothiocyanates 4b-d,g in 42–45% isolated yields (entries 8, 16, 19, and 25). Then, we
attempted to optimize the reaction conditions. With chalcone 3b a twelvefold excess of
HNCS (entry 10) or further decrease in the volume of water in the reaction mixture (entry
1
7
1) had no effect on the isolated yield of 4b. An increase in the reaction temperature to
0 °C (entry 8 vs entry 13) caused a decrease in the yield of 4b from 45 to 30%, while a
4

decrease in the reaction time at 70 °C led to an increase in the yield of 4b (entry 13 vs
entry 12). From comparison of entries 8 and 9 it was clear that further increase in the
reaction time at 50 °C would not lead to any increase in the yield of 4b. We suppose that
some kind of equilibrium between chalcone 3b and isothiocyanate 4b was reached in the
reaction mixture at 50 °C after 3 hours. Since aqueous solutions of HNCS were reported
[
16]
to be unstable at high concentrations, with chalcone 3c we tried the addition of
NH NCS to the reaction mixture in portions (entry 17), but this had no effect on the
4
isolated yield of 4c (entry 17 vs entry 16). At room temperature the addition of HNCS to
chalcone 3b proceeded slower than at heating (entry 14 vs entry 8); however, an increase
in the reaction time from 3 to 24 h led to a considerable increase in the isolated yield of
isothiocyanate 4b (entry 14 vs entry 15). With chalcone 3g, further increase in the
reaction time (from 24 h to 48 h) had no effect on the yield of product 4g (entry 26 vs
entry 27).
At room temperature chalcones 3a-c,e-g formed emulsions under conditions applied
(
entries 4, 15, 18, 22, 24, 26); however, under similar conditions for chalcones 3d,h,i the
reaction mixtures were suspensions. Therefore, the reaction mixtures were heated at 50
C. Emulsions formed in all cases but with chalcone 3i six equivalents of H SO were
°
2
4
used to obtain emulsion. For chalcone 3d a decrease in the reaction time and the use of
six equivalents of H SO led to a slight increase in the yield of 4d (entry 19 vs entry 21).
2
4
Though the reaction of 3h with HNCS could be performed at room temperature, but
presumably because of great excess of H SO which could cause some side reactions, the
2
4
isolated yield of isothiocyanate 4h did not differ significantly from that obtained under
5

heating (entry 29 and entry 30). The same effect of temperature was observed for
compound 3i (entry 31 vs entry 33); heating for 5 minutes at the beginning of the reaction
(entry 31) was used to obtain emulsion which retained at room temperature. A decrease
in the reaction time under heating (entry 32 vs entry 33) led to a slight increase in the
yield of isothiocyanate 4i.
The differences between the isolated yields and the amount of isothiocyanates in the
1
crude products determined by H NMR spectroscopy (Table 1) can be explained by
resinification of organic materials which proceeded in some extent under the action of
strong acids during the reactions. Partial destruction of organic materials under acidic
conditions could be seen from the comparison of entries 29 and 30 (for 3h), entries 16,
1
7, and 18 (for 3c). In all cases the mixtures transformed from fine light orange
emulsions into dense brown oils; with methoxy-derivatives 3c,d,h,i they became dark
brown. All isothiocyanates 4a-i were isolated using silica gel column chromatography. In
all cases isolation was not tedious since the products cleanly left the columns before all
other components of the mixture. It should be noted that purification of the crude product
using crystallization can be performed only with isothiocyanate 4a but it does not remove
the coloring of product.
The data obtained show that the reaction of chalcones 3a-i with HNCS was always
accompanied by formation of the corresponding dihydro-1,3-oxazine-2-thiones 5a-i
(Table 1) whose structure was assigned on the basis of NMR spectroscopic data. The
amount of oxazines increased with an increase in the amount of H SO in the reaction
2
4
6

mixtures (entry 8 vs entry 10; entry 19 vs entry 21). Further increase in the acidity of
reaction media (2 additional equivalents of H SO over NH NCS, entry 20) had only a
2
4
4
slight effect on the amount of oxazine (entry 20 vs entry 21). Prolongation of the reaction
had a negligible effect on the amount of oxazines (entry 32 vs entry 33; entry 14 vs entry
1
1
5). Under all test conditions the amount of oxazines 5a-i did not exceed 13 mol% ( H
NMR spectroscopic data). We suppose that these compounds formed via the enol forms
of isothiocyanato ketones 4a-i followed by their intramolecular cyclization.
CONCLUSION
Practical synthesis of 1,3-diaryl-substituted 3-isothiocyanatopropan-1-ones based on the
reaction of chalcones with thiocyanic acid generated in situ by treatment of thiocyanate
ammonium with dilute sulfuric acid has been developed. Principal condition for
successful proceeding of the reaction is the formation of emulsion in the reaction mixture.
It should be stressed that its formation does not depend on the melting point of the
starting chalcone as evidenced by our data. The optimal overall volume of H O was
2
found to be 0.38 mL per 1 mmol of chalcone, and the chalcone/NH NCS/H SO molar
4
2
4
ratio was found to be 1:6:3. If emulsion did not form at room temperature under these
conditions, first, slight heating at 50 °C for 1.5 h should be applied, second, 3 equivalents
of H SO should be added.
2
4
We hope that this research will be helpful in the preparation of a large variety of 1,3-
diaryl-3-isothiocyanatopropan-1-ones from readily available chalcones. These
isothiocyanato ketones could serve as a versatile starting material in organic synthesis.
7

The use of these compounds in heterocyclic synthesis will be the subject of our
forthcoming publications.
EXPERIMENTAL SECTION
[
15]
Chalcones 3a-i were prepared following the literature procedure and recrystallized
from EtOH prior to use. Concentrated H SO (94 wt%, d = 1.831 g/mL) was used.
2
4
CH Cl and petroleum ether (bp 40–60 ºC) were distilled. All other reagents and solvents
2
2
were purchased from commercial sources and used without additional purification. FTIR
spectra were recorded using a Bruker Vector 22 spectrophotometer in Nujol for solid
samples or in neat for oil samples. Band characteristics in the IR spectra are defined as
1
very strong (vs), strong (s), medium (m), weak (w), shoulder (sh), and broad (br). H
1
3
NMR and proton-decoupled C NMR spectra (solutions in DMSO-d ) were acquired
6
1
13
1
using a Bruker DPX 300 spectrometer at 300.13 MHz ( H) and 75.48 MHz ( C). H
NMR chemical shifts are referenced to the residual proton signal in DMSO-d (2.50
6
1
3
ppm). In C NMR spectra, central signals of DMSO-d (39.50 ppm) were used as
6
references. Multiplicities are reported as singlet (s), doublet (d), triplet (t), quartet (q), and
1
1
some combinations of these, multiplet (m). Selective H– H decoupling and DEPT-135
1
13
experiments were used to aid in the assignment of H and C NMR signals. Elemental
analyses (CHN) were performed by using a Thermo Finnigan Flash EA1112 apparatus.
High-resolution mass spectra (HRMS) were obtain using a Bruker mikrOTOF II focus
spectrometer (ESI, solutions in MeCN). Thin-layer chromatography was carried out on
Aldrich silica gel 60 F254 aluminum backed plates in CH Cl /petroleum ether (1:1, v/v) as
2
2
solvent system. Spots were visualized with UV light. Column chromatography was
8

performed with Macherey–Nagel silica gel 60 (0.063–0.200 mm). Isothiocyanates 4a-i
left columns before all other components of the mixture. All yields refer to isolated,
spectroscopically and TLC pure compounds. The color of substances was white, if not
otherwise mentioned.
3
-Isothiocyanato-1,3-Diphenylpropan-1-One (4a) (Typical Procedure)
To a stirred mixture of compound 3a (1.089 g, 5.22 mmol) and NH NCS (2.415 g, 31.73
4
mmol) in H O (0.98 mL) was added a solution of H SO (0.95 mL, 16.67 mmol) in H O
2
2
4
2
(1 mL). The obtained emulsion was stirred at room temperature for 24 h 20 min. The
resulting material was triturated with a mixture of ether (20 mL) and CH Cl (10 mL) and
2
2
transferred to the separatory funnel. Saturated aqueous solution of NaHCO (10 mL) was
3
added and then solid NaHCO was added in small portions until neutralization was
3
completed (pH 8 of aqueous layer, universal indicator paper). Two liquid layers with
some foam and solid material were obtained and filtered through cotton wool giving
almost clear liquids. The aqueous layer (lower) was separated, organic layer was washed
with saturated aqueous solution of NaHCO (2 × 10 mL), H O (3 × 20 mL), brine (2 × 10
3
2
mL), and dried over Na SO . The drying agent was filtered, the solvent was removed in
2
4
vacuum, and the residue was purified by column chromatography on silica gel 60 (20.23
g) eluting with petroleum ether–CH Cl (from 80:20 to 70:30). The main fraction was
2
2
concentrated, the obtained solid was triturated with petroleum ether, the suspension was
cooled (–10 °C), the precipitate was filtered, washed with petroleum ether, and dried to
[12]
give 4a (1.033 g, 74%) as a white solid. Mp 91.5 92.5 °C (EtOH) [lit. mp 90 °C
–
1
(
benzene)]. IR (Nujol) ν, cm : 3060 (w), 3055 (w), 3030 (w) (CHarom), 2181 (vs), 2138
9

(vs), 2102 (vs) (NCS), 1678 (s) (C=O), 1595 (m), 1578 (m), 1496 (m) (CCarom), 770 (s),
1
7
53 (s), 699 (s), 685 (s) (CHarom); H NMR (300.13 MHz, DMSO-d ) δ: 8.00–8.05 (2H,
6
m, ArH), 7.63–7.70 (1H, m, ArH), 7.50–7.57 (4H, m, ArH), 7.33–7.47 (3H, m, ArH),
3
3
2
3
5
.60 (1H, dd, J = 9.1, J = 4.2 Hz, CHN), 4.03 (1H, dd, J = 18.0, J = 9.1 Hz, H in
A
2
3
13
CH ), 3.67 (1H, dd, J = 18.0, J = 4.2 Hz, H in CH ); C NMR (75.48 MHz, DMSO-
2
B
2
d6) δ: 196.04 (C=O), 138.46 (C), 135.94 (C), 133.68 (CH), 130.41 (br) (NCS), 128.80
(
2CH), 128.78 (2CH), 128.38 (CH), 128.18 (2CH), 126.59 (2CH), 56.51 (CHN), 45.48
CH ). Anal. Calcd for C H NOS: C, 71.88; H, 4.90; N, 5.24. Found: C, 71.98; H, 5.04;
(
2
16 13
N, 5.11.
ACKNOWLEDGMENTS
This research was financially supported by the Ministry of Education and Science of the
Russian Federation (project part of government order, 4.1849.2014/K) and Russian
Foundation for Basic Research (Grant No. 15-03-07564).
SUPPLEMENTAL MATERIAL
1
Full experimental details and characteristics for all compounds and copies of IR, H
1
3
NMR and C NMR spectra for this article can be accessed on the publisher’s website.
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1
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1
0

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1
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1
4
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Heterocycl Compd. 1996, 32, 732–736; Unkovskii, B. V.; Ignatova L. A. Chem
Heterocycl Compd. 1969, 5, 667–669.
6
4
5
7
1
8
. (a) Danilkina, N. A.; Mikhaylov, L. E.; Ivin, B. A. Chem. Heterocycl. Compd. 2011,
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Fuchsgruber, A. Monatsh. Chem. 1976, 107, 183–193; (c) Singh, H.; Kumar, S.
Tetrahedron 1987, 43, 2177–2180.
1
1

9
. Shutalev, A. D.; Zavodnik, V. E.; Gurskaya, G. V. Nucleosides, Nucleotides Nucleic
Acids 2000, 19, 1831–1846; (b) Shutalev, A. D.; Ignatova, L. A.; Unkovskii, B. V. Chem.
Heterocycl. Compd. 1984, 20, 201–203.
1
1
0. Bhanot, O. S.; Ralhan, N. K.; Narang, K. S. Indian J. Chem. 1964, 2, 238–239.
1. (a) Ignatova, L. A.; Shutalev, A. D.; Shingareeva, A. G.; Dymova, S. F.; Unkovskii,
B. V. Chem. Heterocycl. Compd. 1985, 21, 218–224; (b) Peretokin, A. V.; Shutalev, A.
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1
2. Sammour, A.; Selim, M. I. B.; Nonr El-Reen, M. M.; Abd-El-Halim, M. U. A. R. J.
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1
3. Weber, F. G.; Pusch, U.; Brauer, B. Pharmazie 1979, 34, 443–444.
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1
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1
2

Table 1. Synthesis of -isothiocyanato ketones 4a-i by reaction of chalcones 3a-i with
NH NCS and H SO in water.
4
Entr
y
2
4
1
2
3
R
R
R
Conc. 3/NH NCS/H2 Reaction
4
Products
Yield
a
of 3
mol/
L)
SO molar ratio conditions
distribution
of 4
4
b
(
(%)
4
5
0
0
4
2
2
0
0
4
2
3
c
1
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3c
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1.338 1.00:3.31:1.00 3 h, rt
5
95
98
17
2
-
2
3
4
H
0.249 1.00:6.15:3.17 1 h, 50 °C
2.636 1.00:6.03:3.07 3 h, 50 °C
2.637 1.00:6.09:3.19 24.33 h, rt
0.241 1.00:12.08:6.09 3 h, 70 °C
0.249 1.00:5.99:3.01 6 h, 70 °C
0.228 1.00:6.00:3.04 3 h, 70 °C
2.636 1.00:6.02:3.18 3 h, 50 °C
2.645 1.00:6.08:3.21 1 h, 50 °C
2.639 1.00:12.03:6.06 3 h, 50 °C
5.269 1.00:6.06:3.43 3 h, 50 °C
2.634 1.00:6.09:3.19 1 h, 70 °C
2.635 1.00:6.14:3.24 3 h, 70 °C
2.643 1.00:6.09:3.03 3 h, rt
2
-
H
79
96
19
14
13
63
52
59
74
-
H
d
5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
79
86
87
33
46
d
6
-
d
7
-
8
9
45
40
42
45
38
30
28
62
45
1
1
1
1
1
1
1
0
1
2
3
4
5
6
62 12 26
66
49
49
37
81
50
8
3
4
0
3
3
26
48
47
63
16
47
2.634 1.00:6.17:3.26 24 h, rt
2.644 1.00:6.09:3.18 3 h, 50 °C
OMe H
1
3

e
1
1
1
2
2
2
2
2
2
2
2
2
7
8
9
0
1
2
3
4
5
6
7
8
3c
3c
H
H
OMe H
OMe H
2.639 1.00:6.29 :6.06 2 h, 50 °C
69
65
60
9
3
4
22
32
36
42
55
42
-
2.637 1.00:6.09:3.25 24 h, rt
2.648 1.00:6.54:3.20 3 h, 50 °C
2.635 1.00:6.13:8.36 3 h, 50 °C
3d OMe OMe H
3d OMe OMe H
3d OMe OMe H
63 13 24
2.643 1.00:6.17:6.34 1.5 h, 50 °C 66 11 23
44
64
58
66
44
60
61
49
3e
3f
H
H
H
H
H
H
H
t-Bu
H
H
2.634 1.00:6.14:3.05 24 h, rt
76
79
93
68
82
83
69
3
3
1
3
4
5
4
21
18
6
Me 2.627 1.00:6.03:3.15 3 h, 50 °C
Me 2.633 1.00:6.03:3.18 23 h, rt
Me 2.641 1.00:6.12:3.17 3 h, 50 °C
Me 2.645 1.00:6.18:3.28 24 h, rt
Me 2.640 1.00:6.15:3.30 48 h, rt
3f
H
3g
3g
3g
3h
Me
Me
Me
29
14
12
27
OMe Me 2.637 1.00:6.15:3.29 2 h, 50-35
°
°
C; 22 h, 35
C
2
3
3
9
0
1
3h
3h
3i
H
H
OMe Me 2.637 1.00:6.13:6.28 22.5 h, rt
OMe Me 2.644 1.00:6.19:3.74 1.5 h, 50 °C 58
72 10 18
76 12 12
41
45
45
2
40
OMe OMe Me 2.643 1.00:6.13:6.34 5 min, 50
C;
2.5 h, rt
OMe OMe Me 2.637 1.00:6.15:6.53 3 h, 50 °C
°
2
3
2
3
3i
3i
64 11 25
40
44
3
OMe OMe Me 2.646 1.00:6.18:6.63 1.5 h, 50 °C 68 10 22
a
1
According to H NMR spectroscopic data for the crude product.
b
Yield after purification of the crude product using column chromatography.
1
4

c
[12]
This experiment was carried out under the described conditions.
d
A mixture of H O/AcOH (1:1, v/v) was used as a solvent.
2
e
3
.02 equivalents of NH NCS were added at the beginning of the reaction then 1.06, 1.09,
4
and 1.12 equivalents were subsequently added after 30, 40, and 50 min.
1
5

Scheme 1. Synthesis of -isothiocyanato ketones 4a-i from chalcones 3a-i.
1
6

Figure 1. General formula of -isothiocyanato aldehydes and ketones 1.
1
7