A Synthesis of Novel Perinaphthenones from Acetylenic Esters and Acenaphthoquinone-Malononitrile Adduct in the Presence of Triphenylphosphine

Article abstract of DOI:10.1055/s-0037-1610253

A facile protocol involving Tebby zwitterions (PPh ₃ -acetylenic esters) and the Knoevenagel condensation product of acenaphthylene-1,2-dione with malononitrile or ethyl cyanoacetate for the selective synthesis of a new series of perinaphthenone derivatives is described. Triphenylphosphine plays a catalytic role in these transformations. The structure of a typical product was confirmed by X-ray crystallography. The merits of this method include high yields of products, good atom economy, and a metal-free catalyst.

Full text of DOI:10.1055/s-0037-1610253

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2018, 29, A–D
letter
A
en
Synlett
I. Yavari et al.
Letter
A Synthesis of Novel Perinaphthenones from Acetylenic Esters
and Acenaphthoquinone–Malononitrile Adduct in the Presence of
Triphenylphosphine
Issa Yavari*a
Aliyeh Khajeh-Khezria
Mohammad Reza Halvagarb
X
X
1
2
CO R
NC
O
O
R2
CO2R1
PPh3 (10 mol%)
CN
a
Department of Chemistry, Tarbiat Modares University,
PO Box 14115-175, Tehran, Iran
yavarisa@modares.ac.ir
+
CH2Cl2
0 °C to r.t.
R2
b
Department of Inorganic Chemistry, Chemistry and
Chemical Engineering Research Center of Iran,
PO Box 14335-186, Tehran, Iran
X = CN, CO2Et
10 Examples, 75–88% yield
Regioselective
Mild reaction conditions
Metal-free catalyst
1
t
R
R
= Me, Et, Bu
= H, CO2Me, CO2Et, CO2 Bu
2
t
Received: 16.06.2018
OH
OCH3
R
Accepted after revision: 25.07.2018
Published online: 23.08.2018
O
O
O
O
DOI: 10.1055/s-0037-1610253; Art ID: st-2018-b0264-l
OH
Ph
Abstract A facile protocol involving Tebby zwitterions (PPh -acetylen-
3
ic esters) and the Knoevenagel condensation product of acenaphth-
ylene-1,2-dione with malononitrile or ethyl cyanoacetate for the selec-
tive synthesis of a new series of perinaphthenone derivatives is
described. Triphenylphosphine plays a catalytic role in these transfor-
mations. The structure of a typical product was confirmed by X-ray
crystallography. The merits of this method include high yields of prod-
ucts, good atom economy, and a metal-free catalyst.
Perinaphthenone (A)
B
C
D R = OH
E R = OMe
Figure 1 Perinaphthenone (A) and some natural perinaphthenone
derivatives B–E
lenic esters and the Knoevenagel condensation product of
acenaphthylene-1,2-dione13 with malononitrile or ethyl cy-
anoacetate (1 and 2, respectively) in the presence of triph-
enylphosphine as a catalyst in dry CH Cl at 0 °C to room
Key words perinaphthenones, acenaphthylenedione, alkynoate esters,
triphenylphosphine, malononitrile
2
2
The yellow dye perinaphthenone (A; 1H-phenalen-1-
temperature, which led to a new series of perinaphthe-
one) is an aromatic ketone used as a singlet oxygen sensi-
nones in moderate to good yields.14
1
tizer in photochemistry and photobiology. Some natural
Initially, we studied the effects of the amount of PPh3,
the temperature, and various solvents on the reaction of
DMAD (3a) with adduct 1 as a model reaction. First, the ef-
fects of various amounts of PPh in CH Cl at 0 °C to room
perinaphthenone derivatives, for example B–E (Figure 1),
have been reported and their photodynamic fungicidal ac-
2–4
tivity has been demonstrated. The synthesis of novel fun-
gicides based on the structures of perinaphthenone-type
natural products is considered to be a promising strategy.4
The α,β-unsaturated carbonyl group in perinaphthe-
none is responsible for its remarkable photophysical and
photochemical properties. The nature of the lowest singlet
and triplet excited states of aromatic ketones (n, π*) or (π,
π*) is highly dependent on the interaction between the car-
3
2
2
temperature were investigated (Table 1, entries 1–7). The
use of 10 mol% of PPh gave product 4a in 84% yield (entry
3
2). We then tested the effects of EtOH, MeCN, THF, and tolu-
ene as solvents (entries 8–16), but none gave an improved
yield of the product. Therefore, the best reaction conditions
for this transformation are CH Cl as solvent in the presence
2
2
of 10 mol% of PPh at 0 °C to room temperature.
3
5–7
bonyl group and the arene system.
With the optimal reaction conditions in hand, we pro-
ceeded to explore the substrate scope of this reaction. The
Knoevenagel condensation products of acenaphthylene-
1,2-dione with malononitrile or ethyl cyanoacetate (1 and
2, respectively) were successfully applied in the reaction to
give perinaphthenone derivatives 4a–j in satisfactory yields
(Table 2).14
Some derivatives of 1-oxo-1H-phenalene-2,3-dicarbo-
nitrile have important applications as molecular fluores-
8
cent sensors and as anticancer drugs. The synthesis these
derivatives has some similarities to that of the new com-
pounds described in this letter.
During our previous studies on applications of trivalent
phosphorus nucleophiles in syntheses of organic com-
9–12
pounds,
we discovered a novel reaction between acety-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

B
Synlett
I. Yavari et al.
Letter
Table 1 Optimization of the Reaction Conditions for the Preparation
of Perinaphthenone Derivative 4a
Table 2 Synthesis of Perinaphthenone Derivatives 4a–ja
a
X
CO2R1
X
NC
O
CN
+
R2
O
CN
CO2Me
CO2Me
1
O
CN
CO R
2
O
CN
CO2Me
PPh3 (10 mol%)
CH Cl
PPh3 (mol%)
CN
+
R2
2
2
solvent
0 °C to r.t.
temperature
CO2Me
1: X = CN
: X = CO2Et
3
4
2
1
3a
4a
Entry
X
R1
R2
Product
Yield (%)
b
b
Entry
PPh
3
(mol%) Solvent
Temp (°C)
Yield (%)
1
2
3
4
5
6
7
8
9
CN
Me
Et
CO
CO
CO
H
2
2
2
Me
4a
4b
4c
4d
4e
4f
84
80
75
85
88
86
83
81
88
86
1
2
3
4
5
6
7
8
9
5
10
20
30
40
50
100
10
10
10
10
10
10
10
10
10
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
0 to r.t
0 to r.t
0 to r.t
0 to r.t
0 to r.t
0 to r.t
0 to r.t
0 to r.t
72
84
67
61
58
64
78
75
69
68
60
74
69
72
69
76
CN
CN
CN
CN
CO
CO
CO
CO
CO
Et
tBu
Me
Et
-t-Bu
H
2
2
2
2
2
Et
Et
Et
Et
Et
Me
Et
CO
CO
CO
H
2
2
2
Me
Et
4g
4h
4i
t-Bu
Me
Et
-t-Bu
EtOH
EtOH
THF
0 to r.t then reflux
0 to r.t
10
H
4j
10
11
12
13
14
15
16
a
2 2
Reaction conditions: 1 or 2 (1 mmol), 3 (1 mmol), CH Cl (5 mL), 12 h.
Isolated yield.
THF
0 to r.t then reflux
0 to r.t
b
MeCN
MeCN
0 to r.t then reflux
0 to r.t
reaction path involving cyclization to provide intermediate
. This intermediate, is converted into 9 by ring expansion
and elimination of a cyanide ion. This cyanide ion then un-
dergoes Michael addition to intermediate 9 to afford adduct
0, which is converted into product 4 by a retro-Michael
Toluene
Toluene
7
0 to r.t then reflux
0 to r.t then 40
2 2
CH Cl
a
Reaction conditions: 1 (1 mmol), 3a (1 mmol), solvent (5 mL), 12 h.
Isolated yield.
1
b
elimination of PPh3.
In conclusion, we succeeded in regioselective syntheses
of perinaphthenone derivatives through the reaction of
acetylenic esters with the Knoevenagel condensation prod-
ucts of acenaphthylene-1,2-dione with malononitrile or
The structures of products 4a–j were fully assigned
from their IR, H NMR, C NMR, and mass spectra. The IR
1
13
spectrum of 4a revealed the presence of carbonyl (1728 and
–1
–1
1
1
654 cm ) and nitrile groups (2194 cm ). The H NMR
ethyl cyanoacetate in the presence of PPh (10 mol%) as a
3
spectrum of 4a showed signals for two methoxy groups at
δ = 3.94 and 4.02 ppm. The C NMR spectra clearly showed
catalyst at 0 °C to room temperature in dry CH Cl . The syn-
thesis is simple and versatile, and the new compounds have
potential applications as dyes or drug precursors. The pres-
2
2
13
signals for CN, CO R, and C=O groups in the appropriate re-
2
gions of the spectrum.
The structure of compound 4c was also confirmed by
15
single-crystal X-ray analysis (Figure 2). Similar structures
were assumed for derivatives 4a, 4b, and 4f–h on the basis
of the similarities of their NMR spectra. The olefinic pro-
tons of compounds 4d, 4e, 4i, and 4j appeared at about
δ = 7.10–7.43 ppm, which is consistent with an E-geometry
16
of the double bond.
A plausible mechanism for the formation of perinaph-
thenone derivatives 4a–j is shown in Scheme 1. It is con-
ceivable that the initial addition of PPh to the acetylenic
3
ester 3 affords the reactive zwitterionic intermediate 5.
Next, addition of intermediate 5 to the Knoevenagel con-
densation product 1 or 2 gives intermediate 6. On the basis
Figure 2 X-ray crystal structure of compound 4c
17
of a mechanism reported in the literature, we propose a
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

C
Synlett
I. Yavari et al.
Letter
R2
X
R2
X
Ph3P
R1O
Ph3P
CN
O
CN
O
OR1
1
R O
O
O
O
1
or 2
cyclization
ring expansion
Ph3P
+
3
R2
PPh3
5
6
7
X
X
X
X
CN
O
R2
O
Ph3P
NC
Michael addition
O
Ph3P
O
Ph3P
CN
R2
R2
R2
CN
–
PPh3
+
8
9
10
4a–j
Scheme 1 Plausible mechanism for the formation of products 4a–j
ent method has the advantage that the reaction is carried
out under mild and metal-free conditions. The reported
method might serve as a convenient strategy for preparing
a variety of perinaphthenone derivatives.
(14) 1H-Phenalen-1-one Derivatives 4a–j; General Procedure
A mixture of PPh (0.026 g, 0.1 mmol) and CH Cl (5 mL) at 0 °C
3
2
2
was added dropwise over 10 min to a stirred solution of the
appropriate Knoevenagel adduct 1 or 2 (1 mmol) and acetylenic
ester 3 (1 mmol) in CH Cl (5 mL). The mixture was then
2
2
allowed to warm to r.t. and stirred for 12 h. The solvent was
removed under reduced pressure, and the residue was purified
by column chromatography [silica gel, hexane–EtOAc (2:1)].
Dimethyl 2-Cyano-3-(2-cyano-1-oxo-1H-phenalen-3-yl)but-
Funding Information
We gratefully acknowledge the financial support from the Research
Council of Tarbiat Modares University.
2-enedioate (4a)
Yellow solid; yield: 0.31 g (84%); mp 185–190 °C. IR (KBr): 3057,
2
952, 2194 (CN), 1728 (C=O), 1654 (C=O), 1571, 1437 (C=CAr),
–1 1
1255, 1008, 778 cm . H NMR (500 MHz, CDCl ): δ = 3.94 (s, 3
Supporting Information
3
3
H, MeO), 4.02 (s, 3 H, MeO), 7.77 (t, J = 7.5 Hz, 1 H Ar-H), 7.92 (t,
3
3
3
Supporting information for this article is available online at
J = 7.5 Hz, 1 H Ar-H), 8.13 (d, J = 7.5 Hz, 1 H, Ar-H), 8.26 (d, J =
3
3
https://doi.org/10.1055/s-0037-1610253.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
8.0 Hz, 1 H Ar-H), 8.30 (d, J = 8.0 Hz, 1 H Ar-H), 8.78 (d, J = 7.5
Hz, 1 H Ar-H). C NMR (125 MHz, CDCl ): δ = 53.9 (2 × MeO),
13
3
111.1 (CN), 111.8 (CN), 112.3 (C), 113.0 (C), 122.5 (C), 126.7
References and Notes
(CH), 126.8 (C), 127.9 (CH), 131.2 (C), 131.9 (C), 132.5 (CH),
1
33.6 (CH), 136.3 (CH), 136.7 (CH), 150.5 (C), 153.1 (C), 158.6
(1) Schmidt, R.; Tanielian, C.; Dunsbach, R.; Wol, C. J. Photochem.
+
(C=O), 162.1 (C=O), 177.7 (C=O). EI-MS: m/z (%) = 372 (M , 82),
Photobiol., A 1994, 79, 11.
313 (53), 299 (48), 272 (51), 255 (100), 226 (50), 200 (32). Anal.
(
2) Otálvaro, F.; Nanclares, J.; Vásquez, L. E.; Quiñones, W.;
Echeverri, F.; Arango, R.; Schneider, B. J. Nat. Prod. 2007, 70, 887.
3) Hölscher, D.; Schneider, B. J. Nat. Prod. 2000, 63, 1027.
4) Hidalgo, W.; Duque, L.; Saez, J.; Arango, R.; Gil, J.; Rojano, B.;
Schneider, B.; Otálvaro, F. J. Agric. Food Chem. 2009, 57, 7417.
5) Turro, N. J. Modern Molecular Photochemistry; University
Science Books: Sausalito, 1991.
Calcd for C21H12N O (372.34): C, 67.74; H, 3.25; N, 7.52. Found:
2
5
C, 67.95; H, 3.32; N, 7.61.
(
(
Dimethyl
2-Cyano-3-[2-(ethoxycarbonyl)-1-oxo-1H-phe-
nalen-3-yl]but-2-enedioate (4f)
Yellow solid; yield: 0.36 g (86%); mp 180–185 °C. IR (KBr): 3055,
(
2
988, 2214 (CN), 1727 (C=O), 1625 (C=O), 1588, 1370 (C=CAr),
–1
1
1
269, 780 cm . H NMR (500 MHz, DMSO-d ): δ = 1.25 (t,
6
(
(
6) Darmanyan, A. P.; Foote, C. S. J. Phys. Chem. 1993, 97, 5032.
7) Redmond, R. W.; Braslavsky, S. E. Chem. Phys. Lett. 1988, 148,
3
J = 7.0 Hz, 3 H Me), 3.28 (s, 3 H, MeO), 3.52 (s, 3 H, MeO), 4.48
3
3
(
q, J = 7.0 Hz, 2 H, CH O), 7.73 (t, J = 7.5 Hz, 1 H Ar-H), 7.88 (t,
J = 7.5 Hz, 1 H Ar-H), 8.10 (d, J = 8.0 Hz, 1 H, Ar-H), 8.31 (d,
J = 8.0 Hz, 1 H Ar-H), 8.33 (d, J = 8.0 Hz, 1 H Ar-H), 8.64 (d,
J = 7.5 Hz, 1 H Ar-H). C NMR (125 MHz, CDCl ): δ = 13.8 (Me),
2
523.
3
3
(8) Xiao, Y.; Liu, F.; Chen, Z.; Zhu, M.; Xu, Y.; Qian, X. Chem.
Commun. 2015, 51, 6480; and citations therein.
3
3
3
13
3
(9) Yavari, I.; Khalili, G. Synlett 2010, 1862.
5
2.0, 52.7 (2 × MeO), 64.6 (CH O), 114.6 (CN), 122.9 (C), 126.1
2
(
(
10) Yavari, I.; Khalili, G.; Mirzaei, A. Helv. Chim. Acta 2010, 93, 277.
11) Yavari, I.; Azad, L.; Sanaeishoar, T. Monatsh. Chem. 2011, 142,
(CH), 126.5 (CH), 127.1 (C), 127.6 (C), 128.4 (C), 128.5 (CH),
128.7 (CH), 129.2 (C), 131.3 (C), 131.9 (CH), 133.6 (CH), 149.1
177.
(
C), 150.7 (C), 158.3 (C=O), 161.8 (C=O), 162.3 (C=O), 187.2
(
(
12) Yavari, I.; Nematpour, M. Tetrahedron Lett. 2013, 54, 5061.
13) For a recent review, see: Yavari, I.; Khajeh-Khezri, A. Synthesis
+
(C=O). EI-MS: m/z (%) = 419 (M , 91), 360 (62), 345 (53), 318
2018, DOI: 10.1055/s-0037-1610209.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

D
Synlett
I. Yavari et al.
Letter
(
52), 301 (100), 275 (42), 246 (25), 202 (34). Anal. Calcd for
refined as riding atoms with relative isotropic displacement
parameters. All refinements were performed by using the X-
STEP32, SHELXL-2014, and WinGX-2013.3 programs.19 CCDC
1502615 contains the supplementary crystallographic data
for compound 4c. The data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
C23H17NO (419.10): C, 65.87; H, 4.09; N, 3.34. Found: C, 65.99;
H, 4.16; N, 3.41.
7
(
15) X-Ray Crystal-Structure Determination of 4c
The X-ray diffraction measurements were carried out on STOE
IPDS 2T diffractometer with graphite-monochromated Mo Kα
radiation. A single crystal suitable for X-ray analysis was grown
from DMSO solution, mounted on a glass fiber, and used for
data collection. Compound 4c crystallizes in the monoclinic
(16) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
Wiley: Chichester, 1994, Chap. 9 569.
crystal system with a = 1062.8(2) pm, b = 1862.6(4) pm, c =
(17) Lenk, R.; Tessier, A.; Lefranc, P.; Silvestre, V.; Planchat, A.; Blot,
V.; Dubreuil, D.; Lebreton, J. J. Org. Chem. 2014, 79, 9754.
(18) X-AREA: Program for the Acquisition and Analysis of Data,
Version 1.30; Stoe & Cie GmbH: Darmstadt, 2005.
(19) (a) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837. (b) Spek, A. L.
J. Appl. Crystallogr. 2003, 36, 7. (c) Allen, F. H.; Johnson, O.;
Shields, G. P.; Smith, B. R.; Towler, M. J. Appl. Crystallogr. 2004,
37, 335. (d) Macrae, C. F.; Edgington, P. R.; McCabe, P.; Pidcock,
E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl.
Crystallogr. 2006, 39, 453. (e) Burnett, M. N.; Johnson, C. K.
ORTEP-III Report ORNL-6895; Oak Ridge National Laboratory:
Oak Ridge, 1996. (f) Sheldrick, G. M. Acta Crystallogr., Sect. A
2008, 64, 112.
3
1278.5(3) pm, β = 109.11(3)°; cell volume = 2.3914(10) nm .
Orientation matrices for data collection were obtained by least-
square refinement of 12379 diffraction data for compound 4c.
The diffraction data were collected in a series of ω scans with 1°
oscillations and were integrated by using the Stoe X-AREA soft-
18
ware package. A numerical absorption correction was applied
by using X-Red32 software. The structure was solved by direct
methods and subsequent difference Fourier maps and then
2
refined on F by a full-matrix least-squares procedure using
anisotropic displacement parameters. Atomic factors are from
the International Tables for X-ray Crystallography. All non-
hydrogen atoms were refined with anisotropic displacement
parameters. Hydrogen atoms were placed in ideal positions and
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D