Magnesium ethoxide as an effective catalyst in the synthesis of dicayanomethylendihydrofurans

Article abstract of DOI:10.1080/00397910500522066

Magnesium ethoxide was used for the first time in the synthesis of the titled compounds. In these preparations, product yields were significantly improved compared with similar synthesis catalyzed by other metal ethoxides. The effectiveness of magnesium e

Full text of DOI:10.1080/00397910500522066

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Magnesium Ethoxide as an Effective
Catalyst in the Synthesis of
Dicayanomethylendihydrofurans
Tao Zhang a , Kun Peng Guo a , Ling Qiu a & Yuquan Shen a
a Technical Institute of Physics and Chemistry, Chinese Academy of Sciences,
Beijing, China
Published online: 16 Aug 2006.
To cite this article: Tao Zhang , Kun Peng Guo , Ling Qiu & Yuquan Shen (2006) Magnesium Ethoxide as
an Effective Catalyst in the Synthesis of Dicayanomethylendihydrofurans, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:10, 1367-1372
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Synthetic Communicationsw, 36: 1367–1372, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500522066
Magnesium Ethoxide as an Effective
Catalyst in the Synthesis of
Dicayanomethylendihydrofurans
Tao Zhang, Kun Peng Guo, Ling Qiu, and Yuquan Shen
Technical Institute of Physics and Chemistry, Chinese Academy
of Sciences, Beijing, China
Abstract: Magnesium ethoxide was used for the first time in the synthesis of the titled
compounds. In these preparations, product yields were significantly improved
compared with similar synthesis catalyzed by other metal ethoxides. The effectiveness
of magnesium ethoxide as catalyst was tentatively rationalized.
Keywords: Dicayanomethylendihydrofurans, electron acceptors, magnesium ethoxide
Chromophores with push–pull p-electron-conjugated systems constitute the
basic class of organic nonlinear optical materials (NLO), and electron
acceptors are the key chemical structural units. 3-Cyano-2-dicayanomethylen-
dihydrofuran and its derivatives are recognized as one of the best sorts of
electron acceptors and have attracted extensive attention since their
discovery,[1–3] particularly after the first successful use of this class of
compound as an electron acceptor in an NLO chromophore in 1998.[4] In
addition, these dihydrofurans may be also be used to synthesize compounds
for labeling and visualizing biomolecules and biological structures.[5] Unfor-
tunately, the yields of these acceptors are not ideal, especially for steric
hindrance substituted derivatives; however, it is important to introduce
hindered substituents at the 5-position of the dihydrofuran ring to inhibit
Received in China February 1, 2006
Address correspondence to Yuquan Shen, Technical Institute of Physics and
Chemistry, Chinese Academy of Sciences, Beijing 100101, China. E-mail: shenyq@
mail.ipc.ac.cn
1367

1368
T. Zhang et al.
some unwanted dipole–dipole interactions between the NLO chromophore
themselves. In this article, we report that magnesium ethoxide, as an
effective catalyst, could improve product yields of titled compounds signifi-
cantly and therefore make the synthesis of the steric hindrance substituted
derivatives possible.
The synthesis of compound A to E catalyzed by lithum ethoxide[6] and
sodium ethoxide[7] as well as by magnesium ethoxide were conducted in
our laboratory. The results are shown in Table 1 and Table 2. There is no
product yield data available for the compounds in Table 1 in literature
except that product A has a reported yield of 75%[7] or 36%[8] and 88%
under microwave-assisted conditions[9] when catalyzed by sodium ethoxide.
As shown in Table 2, magnesium ethoxide is the base or catalyst that offers
the highest product yield. The tentative explanation is given later. Steric
hindrance obviously plays an important role in determining product yields.
The order of steric hindrance of the substituents at 5-position basically corre-
sponds to the order of the product yields. Compound A has highest yield of
91%, whereas a yield of only 33% is achieved for the most hindered
compound E.
The mechanism of the condensation of a-hydroxy ketone with malonon-
trile is suggested in Scheme 1. a-Hydroxy ketone reacts with malononitrile
through a Knoevenagel condensation (1), followed by intramolecular attack
of the OH group on the nitrile group in 1 to form iminolactone 2. Then, 2
reacts through an another type of Knoevenagel condensation (2) with a
second malononitrile molecule to form product A to E while releasing NH3.
He and his coworkers[6] believe the Pinner reaction indicated in Scheme 1
is the crucial step in forming the desired product. They found that when the
Table 1. Synthesis of the dicayanomethylendihydrofurans catalyzed by the
magnesium ethoxide
Product
R1
R2
Reaction time (h) Isolated yield (%)
A
B
C
D
E
Methyl Methyl
Methyl Butyl
8
24
24
24
72
91
70
65
60
33
Methyl Cyclohexyl
Methyl 2-Ethylhexyl
Butyl
Butyl

Dicayanomethylendihydrofuran Synthesis
1369
Table 2. Comparasion of the catalyst effect of magnesium ethoxide with commonly
used compounds
Isolated product yield (%)
Product
Magnisium ethoxide
Lithium ethoxidea
Sodium ethoxideb
A
B
C
D
E
91
70
65
60
33
80
—
30 (75[6] or 36 [7])
—
—
—
Poor
Poor
Poor
Poor
aThe procedure was performed according to Ref. 6.
bThe procedure was performed according to Ref. 7.
base is changed to LiOC2H5, the ring-closure reaction is more successful
compared to the case of NaOC2H5 because of a tentatively presumed
stronger Li-N intermediate complex between the nitrile nitrogen and the
base. Our result is in agreement with this mechanism. It is reasonable to
believe that an even stronger interaction between the bivalent ion Mg2þ and
the nitrogen atom of the nitrile group in 1, as in our case, facilitates the
ring-closure reaction, and a higher product yield is expected.
In conclusion, magnesium ethoxide was used for the first time as a
catalyst in the synthesis of dicayanomethylendihydrofurans, and five deriva-
tives have been prepared in clearly higher yields compared with the cases
catalyzed by ethoxides of monovalent metal ion. It may be worthwhile to
note that in this preparation, highly steric hindered derivatives such as
compound E could also be obtained in an acceptable product yield.
EXPERIMENTAL
Reagents were purchased and used as received unless otherwise stated. Mal-
ononitrile was freshly distilled prior to use. Magnesium ethoxide was prepared
according to this procedure: activated magnesium turning (4.8 g, 0.2 mol) was
added to absolute ethanol (50 mL), and ethanol was kept refluxing until
magnesium turning disappeared. Ethanol was evaporated, and magnesium
Scheme 1. Steps involved in the TCF ring synthesis.

1370
T. Zhang et al.
ethoxde was collected as white powder. Alternatively, magnesium ethoxide
could be prepared and used as catalyst without isolation for the synthesis
of dicayanomethyldihydrofurans. The a-hydroxy ketones used in this
work were obtained as follows: 3-hydroxy-3-methyl-2-butanone was
purchased from Aldrich and used as received; 3-butyl-3-hydroxy-2-
heptanone was synthesized according to a known procedure.[10] The other
three a-hydroxy ketones were synthesized in this laboratory; the detailed pro-
cedures together with other work will be published later. FR-IR spectrum was
determined on a BIO-RAD FTS-165 spectrometer; MS spectrum was deter-
1
mined on a TRIO-2000 spectrometer. H NMR spectrum was determined
1
on a Varian Gemini 300 (300 MHz) H NMR spectrometer (with CDCl3 as
solvent and tetramethylsilane as internal reference). All melting points are
uncorrected.
The general procedure: 1 molar part of a-hydroxy ketones, 2 to 3 molar
parts of malononitrile, 1 to 1.5 molar parts of magnesium ethoxide, and 20 to
30 molar parts of absolute of ethanol were mixed. The reactant solution was
kept at 608C for 8–72 h and then concentrated by rotary evaporation. The
residue was dissolved with methylene chloride, and the solution was
filtrated. The solvent was evaporated, and the residue was collected and
washed with 20–30 mL of deionized water. Then, the residue was recrystal-
lized from ethanol to give products A–E.
2-(3-Cyano-4,5,5-trimethyl-5H-furan-2-ylidene)malononitrile
(A):
According to the general procedure, a mixture of malononitrile (3 g,
45 mmol), 3-hydroxy-3-methyl-2-butonone (1.53 g, 15 mmol), magnesium
ethoxide (1.94 g, 17 mmol), and absolute ethanol (15 mL) was stirred effec-
tively at 608C for 8 h. Product A (3.17 g, 15.9 mmol) was obtained as light
yellow crystal, yield 91%, mp 197–1988C, lit.[7] 1998C, IR (KBr):
n
max(cm21): 2995, 2235, 2222, 1619, 1591.
2-(3-Cyano-4,5-dimethyl-5-butyl-5H-furan-2-ylidene)malononitrile (B):
A mixture of malonontrile (3 g, 45 mmol), 3-butyl-3-hydroxy-2-butaone
(2.16 g, 15 mmol), magnesium ethoxide (1.94 g, 17 mmol), and absolute
ethanol (15 mL) was stirred effectively at 608C for 24 h. Compound B
(2.53 g, 10.5 mmol) was obtained as a colorless crystal, yield 70%, mp:
1048C, IR (KBr): nmax(cm21): 2958, 2933, 2228.5, 1620, 1596.7; MS, m/s
(%): 241 (Mþ, 100), 184 (52), 57 (50); 1H NMR (d, ppm, JH-H, Hz),
2.3303 (s, 3H, C4-CH3), 2.0384 (m, 2H), 1.7958 (m, 2H), 1.5998 (s, 3H,
C5-CH3), 1.3271 (m, 2H, JH-H ¼ 7), 0.9232 (t, 3H, JH-H ¼ 7.2).
2-(3-Cyano-4,5,-dimethyl-5-cyclohexyl-5H-furan-2-ylidene)malononitrile
(C): A mixture of malonontrile (3 g, 45 mmol), 3-cyclohexyl-3-hydroxy-2-
butaone (2.55 g, 15 mmol), magnesium ethoxide (1.94 g, 17 mmol), and
absolute ethanol (15 mL) was stirred effectively at 608C for 24 h. Product C
(2.6 g, 9.75 mmol) was obtained as a colorless crystal, yield 65%, mp:
2108C, IR (KBr): nmax(cm21): 2931, 2857, 2228.5, 1616.25, 1592.21, MS,

Dicayanomethylendihydrofuran Synthesis
1371
m/z (%): 267 (Mþ, 30), 185 (42), 83 (100); 1H NMR (d, ppm): 2.3350 (s, 3H,
C4-CH3), 1.8270 (m, 5H), 1.5743 (s, 3H, C5-CH3), 1.2482 (m, 6H).
2-[3-Cyano-4,5-dimethyl-5-(2-ethylhexyl)-5H-furan-2-ylidene]malononi-
trile (D): A mixture of malonontrile (3 g, 45 mmol), 5-ethyl-3-hydroxy-3-
methyl-2-nonanone (3 g, 15 mmol), magnesium ethoxide (1.94 g, 17 mmol),
and absolute ethanol (15 mL) was stirred effectively at 608C for 24 h.
Product D (2.68 g, 9 mmol) was obtained as a colorless crystal, yield 60%,
mp: 1188C; IR (KBr): nmax(cm21): 2963, 2931, 2862, 2227, 1617, 1587,
1
MS, m/z (%): 298 (Mþ, 100), 184 (15), 71 (15.70), 57 (16.74); H NMR
(d ppm): 2.3447 (s, 3H, C4-CH3), 1.9549 (m, 1H), 1.8251 (m, 2H), 1.5968
(s, 3H, C5-CH3), 1.3002–1.200 (m, 8H), 0.9056 (t, 3H, CH3), 0.8928 (t, 3H,
CH3).
2-(3-Cyano-4-methyl-5,5-dibutyl-5H-furan-2-ylidene)malononitrile (E):
A mixture of malononitrile (3 g, 45 mmol), 3-butyl-3-hydroxy-2-heptanone
(2.8 g, 15 mmol), magnesium ethoxide (1.94 g, 17 mmol), and absolute
ethanol (15 mL) was stirred effectively at 608C for 72 h. Product E (1.49 g,
5.2 mmol) was obtained as a colorless crystal, yield 33%, mp: 928C, IR
(KBr): nmax(cm21): 2926, 2970, 2221, 1619, 1595, 1465, MS: m/z (%):
1
284 (Mþ, 21), 227 (49), 184 (62), 57 (100), 41 (79); H NMR (d, ppm, JH-
H, Hz): 2.2962 (s, 3H, C4-CH3), 2.0558 (m, 2H), 1.8057 (m, 2H), 1.3326
(t, JH-H ¼ 7.4 H), 1.1871 (m, 4H), 0.9141 (t, JH-H ¼ 7.44, 6H, 2 ꢀ CH3).
ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of
China under contract number 60237010.
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