Copper(II)-mediated intramolecular cyclization of (Z)-chalcogenoenynes: Synthesis of 3-halochalcogenophene derivatives

Article abstract of DOI:10.1002/ejoc.201100992

We present our results on the cyclization of (Z)-chalcogenoenynes mediated by copper(II) salts to afford 3-halochalcogenophenes in satisfactory yields through an intramolecular 5-endo-dig cyclization. The methodology was carried out using CuCl₂

Full text of DOI:10.1002/ejoc.201100992

FULL PAPER
DOI: 10.1002/ejoc.201100992
Copper(II)-Mediated Intramolecular Cyclization of (Z)-Chalcogenoenynes:
Synthesis of 3-Halochalcogenophene Derivatives
Daniela A. Barancelli,[a] Ricardo F. Schumacher,[a] Marlon R. Leite,[a] and Gilson Zeni*[a]
Keywords: Heterocycles / Selenium / Sulfur / Copper / Halides / Cyclization
We present our results on the cyclization of (Z)-chalcogeno-
enynes mediated by copper(II) salts to afford 3-halochalcog-
enophenes in satisfactory yields through an intramolecular 5-
endo-dig cyclization. The methodology was carried out using
CuCl2 at 50 °C or CuBr2 at room temperature under an ambi-
ent atmosphere. The reaction took place under very mild re-
action conditions and tolerated considerable functionality.
One 3-bromo-selenophene derivative was applied as a sub-
strate in the palladium-catalyzed cross-coupling reaction
with a boronic acid to give the Suzuki type product in good
yield.
Chalcogenophene derivatives play an important role in
organic synthesis and many of them show biological activi-
ties. In this context, selenophenes are widely studied agents
that display a diverse array of biological effects. These in-
clude antioxidant,[12] antitumoral,[13] anticonvulsant,[14,15]
hepatoprotective,[16] antinociceptive,[17] antihypertensive,[18]
and fungicidal properties.[19] In addition, these compounds
are very useful synthetic intermediates and can function as
building blocks in the synthesis of other biologically active
compounds, including natural products.[20]
In a continuation of our efforts to develop a simple and
economical methodology for the cyclization of function-
alized alkynes,[21] we planned to examine whether 3-halo-
chalcogenophenes 2 could be generated from (Z)-seleno-
and thioenynes 1 through intramolecular cyclization reac-
tions using CuII as the cyclizing agent (Scheme 1).
Introduction
Heterocycles are an important class of compounds that
are found in nature and also in pharmaceutical products,
and they have attracted the attention of medicinal chemists
due to their wide-ranging biological activities and interest-
ing structural variations.[1] This broad range of applications
has resulted in the development of several strategies for the
preparation of single and more complex heterocycles.[2] Im-
portant contributions have come from transition-metal-cat-
alyzed cyclization reactions using acyclic precursors.[3]
These approaches include the use of palladium, which is
one of the most employed transition metals.[4] The innov-
ative use of halocyclization reactions of appropriately sub-
stituted alkynes is also a notable achievement in the synthe-
sis of heterocycle derivatives.[5] The main advantage of this
methodology is that when bromine or iodine is used as the
electrophilic source, the product has a halogen atom in the
final structure, which becomes a synthetic handle for fur-
ther reactions, such as palladium-catalyzed cross-coupling
reactions.[6]
In recent years, the importance of sustainable chemistry
in the preparation of heterocycles has become apparent,
and the use of green, mild, and less expensive methods has
increased significantly.[7] Thus, copper salts have appeared
as a versatile alternative to palladium compounds due to
their low price and reduced toxicity. To date, nitrogen,[8]
oxygen,[8a,8c,9] sulfur,[10] and carbon heterocycles[11] have all
been successfully synthesized through the use of copper
salts.
Scheme 1. Copper(II)-mediated intramolecular cyclization of (Z)-
chalcogenoenynes.
Results and Discussion
The required starting chalcogenenynes 1 were prepared
through the hydrochalcogenation of alkynes according to a
reported procedure.[22] The cyclization of chalcogenoenyne
1a was initially examined under the influence of a copper
salt. Unfortunately, the reaction of 1a (0.5 mmol) with Cu-
(OTf)2, CuCN, or CuBr (2 equiv.), in acetonitrile (3 mL) at
room temperature failed to give the target selenophene 2a
(Table 1, entries 1–3). The use of CuCl2 provided the cy-
clized product; however, under these conditions we found
[a] Laboratório de Síntese, Reatividade, Avaliação Farmacológica
e Toxicológica de Organochalcogênios, CCNE, UFSM,
Santa Maria, Rio Grande do Sul, CEP 97105-900, Brazil
Fax: +55-55-32208978
E-mail: gzeni@pq.cnpq.br
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100992.
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G. Zeni et al.
FULL PAPER
that the yield of 2a did not exceed 55% (Table 1, entry 4). mixture of (Z)-selenoenyne 1a (0.5 mmol), CuBr2 (2 equiv.)
Heating to 50 °C significantly improved the yield of the re- in THF at room temperature. It is important to point out
action to 70% (Table 1, entry 5). Moreover, the combina- that both reactions were carried out under an ambient at-
tion of CuCl2 with other solvents such as MeOH, tetra- mosphere.
hydrofuran (THF), N,N-dimethylformamide (DMF), or
The methodology was extended to the synthesis of a
CH2Cl2 at 50 °C did not improve the yield. This indicated range of 3-chloro/bromo-chalcogenophenes (Table 2). We
that the reaction proceeded effectively with CuCl2 only in were pleased to observe excellent reactivity for a variety of
acetonitrile.
neutral (Table 2, entry 1), electron-rich (Table 2, entries 2
and 3), electron-deficient (Table 2, entry 4), and bulky (Z)-
selenoenynes (Table 2, entry 6) with good to excellent yields
of 3-haloselenophenes. The reaction was tolerant of alterna-
tive alkyl groups directly bonded to the alkyne, producing
moderate yields of the subsequent selenophenes (Table 2,
entries 7–9). Because thiophene derivatives exhibit a broad
range of biological activities[23] and have applications as in-
termediates in organic synthesis,[24] the next phase of this
study involved the use of this newly developed procedure
for the preparation of thiophenes. Under the standard con-
ditions, we tested copper in the cyclization of a series of
(Z)-thioenynes. As shown in Table 2, treatment of (Z)-thio-
enynes 1j–m containing neutral, or moderately electron-do-
nating or electron-attracting groups under standard condi-
tions, provided 3-halothiophenes 2j–m in 44–79% isolated
yields (Table 2, entries 10–13).
Table 1. Optimization of cyclization conditions.[a]
Entry
Cu salt
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
Cu(OTf)2
CuCN
CuBr
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
MeCN
MeOH
DMF
THF
n.r
n.r.
n.r.
55
CuCl2
CuCl2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2[d]
CuBr2[e]
CuBr2
CuBr2
70[c]
56
78
42
n.r.
81
45
9
10
11
12
13
To complete our investigation and to further demon-
strate the potential of 3-halo-selenophene derivatives as pre-
cursors for compounds with increasing molecular complex-
ity, we tested the reactivity of these compounds in palla-
THF
THF
THF
66
45[c]
[a] Reaction preformed using 1a (0.5 mmol), [Cu] (2 equiv.), solvent
(3 mL) at room temperature in an open atmosphere. [b] Yield of
isolated product. [c] The reaction was carried out at 50 °C. [d]
1.2 equiv. of CuBr2 was used. [e] 1.5 equiv. of CuBr2 was used.
Considering the difference in the reactivity of the aryl
chloride and bromide, an important goal would be to intro-
duce these halogen substituents into the same substrate by
changing only the halogen source. For this purpose, we re-
acted chalcogenoenyne 1a and CuBr2 in a range of solvents
at different temperatures. An examination of the impor-
tance of the solvent in this reaction (Table 1, entries 6–10)
revealed that THF was significantly better than CH2Cl2,
MeCN, MeOH and DMF. Attempts to further optimize the
conditions by changing the amount of CuBr2 (Table 1, en-
tries 11–12) or altering the temperature (Table 1, entry 13)
were unsuccessful. This indicated that the copper(II) species
are acting not only to activate the triple bond to promote
the cyclization, but also as a halogen source. It is important
to note that the reaction time was 15 h; additional time did
not improve the yields, whereas running the reaction for
shorter periods resulted in incomplete consumption of the
starting material. To make our methodology more attract-
ive from an economic standpoint, we tested the reaction in
the absence of an inert atmosphere. For this purpose, all
reactions were carried out in an open atmosphere and the
yields were not affected. We concluded that the reaction of
the (Z)-selenoenyne 1a (0.5 mmol), CuCl2 (2 equiv.) in
MeCN at 50 °C was highly effective for obtaining 3-chloro-
selenophene. On the other hand, when the aim was to pre-
Scheme 2. Synthesis of 2,3,5-triarylselenophenes by palladium-cat-
alyzed Suzuki cross-coupling reaction.
Scheme 3. Proposed mechanism for the copper(II)-mediated intra-
pare 3-bromoselenophene, the best conditions involved a molecular cyclization of (Z)-chalcogenoenynes.
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Copper(II)-Mediated Synthesis of 3-Halochalcogenophenes
Table 2. Cu-promoted cyclization of chalcogenoenynes to form 3-halo-chalcogenophenes.[a]
[a] Reactions were performed using 1 (0.5 mmol) and CuX2 (2 equiv.) in solvent (3 mL; THF for X = Br and MeCN for X = Cl).
dium-catalyzed Suzuki cross-coupling reactions. The reac- erate an intermediate A; (ii) anti attack of the selenium/
tion of 2a with aryl boronic acids gave the corresponding sulfur atom on the activated triple bond of the intermediate
Suzuki products 3a–d in 56–80% yields (Scheme 2).
A to produce the salt B, and (iii) reductive elimination of B
On the basis of the current results, and in agreement with to provide the 3-halo-chalcogenophene derivative 2, Cu0
the literature,[25] we believe that the mechanism of this cycli- and 1-halobutane as a co-product. The formed Cu0 can be
zation reaction involves the following: (i) coordination of oxidized by CuX2 to produce CuX,[26] which explains the
the carbon–carbon triple bond to the CuX2 species to gen- need for two equivalents of CuX2 in this reaction
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G. Zeni et al.
FULL PAPER
50 MHz): δ = 149.05, 141.94, 134.98, 134.65, 129.63, 129.08,
129.03, 128.49, 128.27, 128.22, 125.85, 108.24 ppm. MS: m/z (%) =
362 (59), 282 (18), 202 (100), 126 (10), 101 (34), 89 (19). HRMS
calcd. for C16H11BrSe 361.9209; found 361.9245.
(Scheme 3). Because this reaction probably proceeds
through SN2 displacement of the group directly linked to
the chalcogen atom by the halide anion present in the reac-
tion, this cyclization reaction occurs only with selenoenynes
having a Se–Csp3 bond.
3-Bromo-2,5-di(p-tolyl)selenophene (2b): Yield 0.144 g (74%). 1H
NMR (CDCl3, 200 MHz): δ = 7.56–7.48 (m, 2 H, ArH), 7.46–7.35
(m, 3 H, ArH), 7.27–7.12 (m, 4 H, ArH), 2.38 (s, 3 H, CH3), 2.36
(s, 3 H, CH3) ppm. 13C NMR (CDCl3, 50 MHz): δ = 148.76,
141.44, 138.21, 138.13, 132.29, 131.83, 129.66, 129.17, 129.01,
128.90, 125.67, 107.84, 21.29, 21.19 ppm. MS: m/z (%) = 390 (100),
296 (20), 230 (37), 215 (55), 115 (51), 101 (25). C18H15BrSe
(390.18): calcd. C 55.41, H 3.87; found C 55.62, H 3.93.
Conclusions
We have developed an alternative and efficient method
with which to synthesize 3-halo-chalcogenophene deriva-
tives through intramolecular 5-endo-dig cyclization of (Z)-
chalcogenoenynes. The reactions were carried out under an
ambient atmosphere using CuCl2 at 50 °C or CuBr2 at
room temperature, which is a relatively economic and eco-
friendly protocol. 3-Bromo-selenophene derivatives were
applied as substrates in palladium catalyzed cross-coupling
reactions with boronic acids, to give the Suzuki type prod-
ucts in good yields. To the best of our knowledge, this is
the first example of chalcogenophene synthesis using a cop-
per(II) salt. There are some advantages to the use of cop-
1
3-Bromo-2-butyl-5-phenylselenophene (2g): Yield 0.111 g (65%). H
NMR (CDCl3, 200 MHz): δ = 7.63–7.52 (m, 2 H, ArH), 7.45–7.22
(m, 3 H, ArH), 6.93 (s, 1 H, ArH), 2.83 (t, J = 7.93 Hz, 2 H,
CH2CH2), 1.65 (quint, J = 7.49 Hz, 2 H, CH2CH2CH2), 1.41 (sext.,
J = 7.49 Hz, 2 H, CH2CH2CH3), 0.94 (t, J = 7.20 Hz, 3 H,
CH2CH3) ppm. 13C NMR (CDCl3, 50 MHz): δ = 152.24, 139.98,
135.08, 130.89, 129.06, 128.34, 127.81, 106.45, 34.08, 32.24, 22.08,
13.77 ppm. MS: m/z (%) = 341 (48), 298 (100), 218 (30), 138 (49),
115 (19). HRMS: calcd. for C14H15BrSe [M + Na]+ 364.9420;
found 364.9444.
per(II) instead of copper(I), such as the possibility of cycliz- 3-Bromo-2,5-dibutylselenophene (2h): Yield 0.090 g (56%). 1H
NMR (CDCl3, 200 MHz): δ = 6.74 (s, 1 H, ArH), 2.84–2.65 [m, 4
H, 2ϫ (CH2CH2)], 1.60 [quint, 7.45 Hz, H, 2ϫ
ing and introducing a halogen atom into the product struc-
ture, which are quite useful in synthesis, not least because
there are many ways to transform the resulting halogen
functionalities into other substituents.
J
=
4
(CH2CH2CH2)], 1.42 [sext, J = 7.45 Hz, 4 H, 2ϫ (CH2CH2CH3)],
1.01–0.84 [m, 6 H, 2ϫ (CH3)] ppm. 13C NMR (CDCl3, 50 MHz):
δ = 149.52, 142.70, 128.73, 107.29, 34.11, 33.77, 32.24, 31.31, 22.17,
22.05, 13.83, 13.77 ppm. MS: m/z (%) = 321 (36), 278 (100), 243
(45), 222 (34), 157 (15), 91 (32). C12H19BrSe (322.15) calcd. C
44.74, H 5.94; found C 44.91, H 6.01.
Experimental Section
1
3-Bromo-2,5-diphenylthiophene (2j): Yield 0.113 g (72%). H NMR
General Remarks: 1H NMR spectra were obtained at 200 MHz
with a DPX-200 NMR spectrometer or at 400 MHz with a DPX-
400 NMR spectrometer. Spectra were recorded in CDCl3 solutions.
13C NMR spectra were obtained either at 50 MHz with a DPX-
200 NMR spectrometer or at 100 MHz with a DPX-400 NMR
spectrometer. Spectra were recorded in CDCl3 solutions. Column
chromatography was performed using Merck Silica Gel (230–
400 mesh). Thin layer chromatography (TLC) was performed using
Merck Silica Gel GF254 (0.25 mm thickness). For visualization,
TLC plates were either placed under UV light, or stained with
iodine vapor, or acidic vanillin. Most reactions were monitored by
TLC for disappearance of starting material. MS spectra were re-
corded with a Shimadzu GC-MS-2010P. Elemental analyses were
performed with a Vario EL III elemental analysis instrument.
HRMS were recorded with a Shimadzu LC-MS-IT-TOF spectrom-
eter.
(CDCl3, 200 MHz): δ = 7.74–7.64 (m, 2 H, ArH), 7.62–7.53 (m, 2
H, ArH), 7.47–7.27 (m, 7 H, ArH) ppm. 13C NMR (CDCl3,
50 MHz): δ = 143.16, 137.24, 133.06, 132.75, 128.98, 128.80,
128.50, 128.23, 128.15, 127.34, 125.43, 107.85 ppm. MS: m/z (%) =
315 (100), 234 (38), 202 (25), 189 (15), 120 (30), 77 (10). C16H11BrS
(315.23) calcd. C 60.96, H 3.52; found C 61.15, H 3.60.
General Procedure for the CuCl2-Mediated Cyclization: To a solu-
tion of the appropriate (Z)-chalcogenenyne 1 (0.5 mmol) in MeCN
(3 mL) was added copper(II) chloride (2 equiv.). The reaction mix-
ture was stirred at 50 °C for the desired time, then the reaction was
quenched with saturated aq. NH4Cl. The mixture was extracted
with ethyl acetate (3ϫ10 mL) and the combined organic layers
were dried with anhydrous MgSO4 and concentrated under vacuum
to yield the crude product, which was purified by flash chromatog-
raphy on silica gel using ethyl acetate/hexane as the eluent.
General Procedure for the CuBr2-Mediated Cyclization: To a solu-
tion of the appropriate (Z)-chalcogenenyne 1 (0.5 mmol) in THF
(3 mL) was added copper(II) bromide (2 equiv.). The reaction mix-
ture was stirred at room temperature for the desired time, then the
reaction was quenched with saturated aq. NH4Cl. The mixture was
3-Chloro-2,5-diphenylselenophene (2aЈ): Yield 0.111 g (70%). 1H
NMR (CDCl3, 200 MHz): δ = 7.69–7.60 (m, 2 H, ArH), 7.55–7.46
(m, 2 H, ArH), 7.45–7.27 (m, 7 H, ArH) ppm. 13C NMR (CDCl3,
50 MHz): δ = 147.58, 140.19, 135.04, 133.89, 129.01, 128.85,
128.55, 128.26, 128.08, 127.30, 125.72, 121.78 ppm. MS: m/z (%) =
then extracted with ethyl acetate (3ϫ10 mL) and the combined 317 (100), 281 (13), 202 (81), 158 (10), 100 (24). C16H11ClSe
organic layers were dried with anhydrous MgSO4 and concentrated
under vacuum to yield the crude product, which was purified by
flash chromatography on silica gel using ethyl acetate/hexane as the
eluent.
(317.68) calcd. C 60.49, H 3.49; found C 60.71, H 3.56.
3-Chloro-2,5-di(p-tolyl)selenophene (2bЈ): Yield 0.089 g (52%). 1H
NMR (CDCl3, 200 MHz): δ = 7.59–7.49 (m, 2 H, ArH), 7.42–7.33
(m, 3 H, ArH), 7.28–7.14 (m, 4 H, ArH), 2.38 (s, 3 H, CH3), 2.36 (s,
3 H, CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 147.26, 139.72,
138.20, 138.00, 132.40, 131.11, 129.65, 129.24, 128.69, 126.70,
125.58, 121.34, 21.23, 21.18 ppm. MS: m/z (%) = 346 (100), 230
3-Bromo-2,5-diphenylselenophene (2a): Yield 0.146 g (81%). 1H
NMR (CDCl3, 200 MHz): δ = 7.67–7.61 (m, 2 H, ArH), 7.57–7.48
(m, 2 H, ArH), 7.47–7.27 (m, 7 H, ArH) ppm. 13C NMR (CDCl3,
6716
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Copper(II)-Mediated Synthesis of 3-Halochalcogenophenes
(12), 215 (26), 173 (13), 115 (21), 101 (11). C18H15ClSe (345.73)
calcd. C 62.53, H 4.37; found C 62.60, H 4.41.
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2-Butyl-3-chloro-5-phenylselenophene (2gЈ): Yield 0.059 g (40%). 1H
NMR (CDCl3, 200 MHz): δ = 7.64–7.50 (m, 2 H, ArH), 7.45–7.17
(m, 3 H, ArH), 6.90 (s, 1 H, ArH), 2.82 (t, J = 7.82 Hz, 2 H,
CH2CH2), 1.65 (quint, J = 7.45 Hz, 2 H, CH2CH2CH2), 1.42 (sext,
J = 7.45 Hz, 2 H, CH2CH2CH3), 0.94 (t, J = 7.21 Hz, 3 H,
CH2CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 150.87, 138.21,
134.36, 128.83, 128.63, 128.42, 127.68, 119.99, 34.02, 32.32, 22.06,
13.74 ppm. MS: m/z (%) = 297 (43), 254 (100), 218 (13), 174 (28),
138 (42). C14H15ClSe (297.69) calcd. C 56.49, H 5.08; found C
56.61, H 5.11.
2,5-Dibutyl-3-chloroselenophene (2hЈ): Yield 0.055 g (40%). 1H
NMR (CDCl3, 200 MHz): δ = 6.74 (s, 1 H, ArH), 2.84–2.65 [m, 4
H, 2ϫ (CH2CH2)], 1.60 [quint, J = 7.45 Hz, 4 H, 2ϫ (CH2CH2-
CH2)], 1.42 [sext, J = 7.45 Hz, 4 H, 2ϫ (CH2CH2CH3)], 1.01–0.84
[m, 6 H, 2ϫ (CH2CH3)] ppm. 13C NMR (CDCl3, 50 MHz): δ =
148.38, 140.90, 126.50, 120.42, 34.07, 33.75, 32.30, 29.44, 22.18,
22.04, 13.83, 13.79 ppm. MS: m/z (%) = 278 (32), 243 (40), 234
(100), 176 (26), 112 (24), 91 (19), 77 (17). HRMS: calcd. for
C12H19ClSe 278.0341; found 278.0349.
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3-Chloro-2,5-diphenylthiophene (2jЈ): Yield 0.087 g (65%). 1H NMR
(CDCl3, 200 MHz): δ = 7.72–7.63 (m, 2 H, ArH), 7.58–7.48 (m, 2
H, ArH), 7.44–7.24 (m, 6 H, ArH), 7.16 (s, 1 H, ArH) ppm. 13C
NMR (CDCl3, 50 MHz): δ = 141.89, 135.22, 133.10, 132.10,
128.97, 128.57, 128.42, 128.13, 128.07, 125.31, 124.95, 121.52 ppm.
MS: m/z (%) = 269 (100), 233 (21), 202 (16), 134 (11), 120 (16).
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General Procedure for the Palladium-Catalyzed Coupling Reaction
of 6a with Arylboronic Acids:[27] To a Schlenk tube, under argon,
containing a solution of 3-bromo-2,5-diphenylselenophene (2a;
0.144 g, 0.40 mmol) in toluene/dioxane (1:1, 3.2 mL), was added
[Pd(PPh3)4] (0.023 g, 0.02 mmol). The resulting solution was stirred
for 30 min at room temperature, then the appropriate arylboronic
acid (0.6 mmol) and a solution of K3PO4 (0.211 g, 1 mmol) in H2O
(0.5 mL) were added. The mixture was stirred at 90 °C for 3 h, then
diluted with ethyl acetate (20 mL) and washed with brine
(3ϫ20 mL). The organic phase was separated, dried with MgSO4,
and concentrated under vacuum. The residue was purified by flash
chromatography on silica gel using ethyl acetate/hexane as the elu-
ent.
2,5-Diphenyl-3-(p-tolyl)selenophene (4a): Yield 0.116 g (78%). 1H
NMR (CDCl3, 400 MHz): δ = 7.59–7.57 (m, 3 H, ArH), 7.39–7.35
(m, 2 H, ArH), 7.30–7.19 (m, 8 H, ArH), 7.10–7.08 (m, 2 H, ArH),
2.33 (s, 3 H, CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 148.25,
140.84, 136.57, 136.32, 136.17, 134.71, 129.58, 129.25, 129.21,
129.05, 129.01, 128.92, 128.38, 127.64, 127.19, 126.02, 21.19 ppm.
MS: m/z (%) = 373 (100), 281 (65), 296 (45), 220 (42), 128 (72), 91
(65). HRMS: Calcd. C23H18Se 374.0574; found 374.0580.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and analytical data for compounds
2a–m and 2aЈ–mЈ.
Acknowledgments
We are grateful to Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior, Fundação de Amparo à Pesquisa do Estado do Rio
Grande do Sul (grant number PRONEX-10/0005-1) and Conselho
Nacional de Desenvolvimento Científico e Tecnológico (INCT-
catalise) for the fellowships.
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Received: July 7, 2011
Published Online: September 19, 2011
6718
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Eur. J. Org. Chem. 2011, 6713–6718