Use of isopropyl alcohol as a solvent in Ti(O-i-Pr)4-catalyzed Kn?evenagel reactions

Article abstract of DOI:10.1016/j.tet.2005.06.008

Kn?evenagel reactions of aldehydes and ketones with malononitrile, isopropyl cyanoacetate and diisopropyl malonate catalyzed by Ti(O-i-Pr) ₄ proceeded smoothly in i-PrOH to give the corresponding reaction products in good to high yield. 3-Substituted coumarins were prepared by the present method.

Full text of DOI:10.1016/j.tet.2005.06.008

Tetrahedron 61 (2005) 7981–7985
Use of isopropyl alcohol as a solvent in Ti(O-i-Pr)4-catalyzed
¨
Knoevenagel reactions
*
Kohei Yamashita, Takanori Tanaka and Masahiko Hayashi
Department of Chemistry, Faculty of Science, Kobe University, Nada, Kobe 657-8501, Japan
Received 2 May 2005; revised 3 June 2005; accepted 3 June 2005
Available online 23 June 2005
¨
Abstract—Knoevenagel reactions of aldehydes and ketones with malononitrile, isopropyl cyanoacetate and diisopropyl malonate catalyzed
by Ti(O-i-Pr)4 proceeded smoothly in i-PrOH to give the corresponding reaction products in good to high yield. 3-Substituted coumarins
were prepared by the present method.
q 2005 Elsevier Ltd. All rights reserved.
Table 1. Solvent effect in the reaction of benzaldehyde with malononitrile
1. Introduction
¨
The Knoevenagel reaction is a well-known classical
reaction as a condensation between carbonyl compounds
and activated methylene compounds catalyzed by amines.1
As activated methylene compounds, alkyl acetoacetates and
dialkyl malonates have often been used.
Entry
Solvent
Product (% yielda)
1
2
3
4
i-PrOH
CH3CN
CH2Cl2
Toluene
93
72
¨
Recently, on the other hand, Knoevenagel reactions
66b
24b
catalyzed by Lewis acids have been reported. The
Venkataratnam2 and Sandhu3,4 groups reported reactions
catalyzed by ZnCl2, BiCl3, and CdI2, respectively.
However, all of them required a high temperature (75–
100 8C) under solvent-free conditions. Furthermore, the
reaction in an ionic liquid was also reported.5
a Isolated yield by fractional recrystallizations unless otherwise noted.
b Isolated yield by silica-gel column chromatography.
As shown in Table 1, we found that the reaction using
i-PrOH as a solvent was accelerated by 0.05 equiv of Ti(O-i-
Pr)4 to produce 2-(phenylmethylene)malononitrile in 93%
yield at 25 8C for 11 h. Under identical conditions, a variety
of aldehydes were reacted with malononitrile to afford
2-(arylidene)malononitrile in good to high yield (Table 2,
entries 1–9). In the cases of ketones, larger amounts of
Ti(O-i-Pr)4 were required (0.5–1 equiv) to obtain the
products in satisfactory yield (entries 10 and 11).
¨
We recently reported Ti(O-i-Pr)4-promoted Knoevenagel
reaction of aldehydes with diketene.6 During the course of
this study, we observed that Ti(O-i-Pr)4 promoted the
reaction of aldehydes with isopropyl acetoacetate. There-
fore, we examined the scope of Ti(O-i-Pr)4-promoted
¨
Knoevegenal reaction of carbonyl compounds with acti-
vated methylene compounds.
As for the reaction mechanism, the carboanion of malonate
will attack the electrophilic carbonyl carbon coordinated by
Ti(O-i-Pr)4. The carboanionic character of malononitrile
might be enhanced by the alcoholic solvent producing a
keteneimine intermediate.5a After addition to carbonyl
compounds, some kind of an elimination process may
occur to produce 2-substituted methylenemalononitrile and
to regenerate the Ti species those activate aldehydes.
2. Results and discussion
We first examined the reaction of benzaldehyde with
malononitrile in the presence of Ti(O-i-Pr)4 in a variety of
solvents (Table 1).
¨
Keywords: Knoevenagel reaction; Titanium alkoxide; Isopropyl alcohol.
Corresponding author. Tel.: C81 78 803 5687; fax: C81 78 803 5688;
*
e-mail: mhayashi@kobe-u.ac.jp
We then examined the reactions of some aldehydes with
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.008

7982
K. Yamashita et al. / Tetrahedron 61 (2005) 7981–7985
Table 2. Reactions of a variety of aldehydes and ketones with malononitrile promoted by Ti(O-i-Pr)4
Entry
R1
R2
Ti(O-i-Pr)4/equiv
Conditions
Temperature/8C
Product (% yielda)
Time/h
1
2
3
4
5
6
7
8
Ph
H
H
H
H
H
H
H
H
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
1.0
25
22
21
21
20
20
22
20
20
70
70
11
12
12
13
25
3
11
12
24
18
52
93 (1a)
97 (1b)
92 (1c)
98 (1d)
92b (1e)
74b (1f)
64 (1g)
63b (1h)
60b (1i)
61b (1j)
86 (1k)
p-ClC6H4
p-MeOC6H4
p-BrC6H4
c-C6H11
Ph(CH2)2
(E)-PhCH]CH
CH3(CH2)2
t-Bu
9
10
11
H
Me
Ph
Ph
Ph
1.0
a Isolated yield by fractional recrystallizations unless otherwise noted.
b Isolated yield by silica-gel column chromatography.
isopropyl cyanoacetate and diisopropyl malonate with the
aid of Ti(O-i-Pr)4 in i-PrOH (Table 3). The reactions of
isopropyl cyanoacetate and diisopropyl malonate with
aldehydes were carried out with the aid of 0.2–1.0 equiv
of Ti(O-i-Pr)4 in i-PrOH.
two methods, one is the so-called Pechmann condensation,
that is, acid-mediated condensation of phenol with
b-ketoesters to produce coumarins.7 In these reactions,
strong acids such as H2SO4 and AlCl3 have been used. The
¨
other method is the Knoevenagel reaction between
salicylaldehydes and dialkyl malonate. For example,
solvent-free synthesis,8 Montmorillonite KSF-catalyzed
synthesis9 and a solid-phase synthesis10 for substituted
coumarin-3-carboxylic acids derivatives have been recently
reported.
While 0.05 equiv of Ti(O-i-Pr)4 was enough for the reaction
of aldehydes with malononitrile, it was found that 0.2 equiv
and 1 equiv of Ti(O-i-Pr)4 were necessary in the cases of
isopropyl cyanoacetate and diisopropyl malonate, respect-
ively, for the completion of the reaction, probably due to the
lower reactivity of activated methylene compounds. In the
cases of entry 1 and 2, only (E)-isomers (2a and 2b) were
obtained, that was consistent with the results of the reported
methods.2,3,5
We first examined the reaction of salicylaldehyde with
malononitrile in the presence of 0.1 equiv of Ti(O-i-Pr)4 in
i-PrOH (Scheme 1). The reaction proceeded smoothly at
room temperature to afford 3-cyanocoumarin (4) in 70%
yield. The introduction of isopropyl carboxylate to the
3-position of coumarin was performed by using isopropyl
cyanoacetate in the presence of 1 equiv of Ti(O-i-Pr)4 in
i-PrOH to give 3-isopropoxycarbonylcoumarin (5). The
reaction of diisopropyl malonate was so sluggish that the
yield of 5 was only moderate (37%). It should be mentioned
that the reaction of salicylaldehyde with diketene in the
We applied our method to the synthesis coumarin
derivatives. Coumarins (2H-1-benzopyran-2-one) are
important compounds found in natural and artificial
compounds such as perfume, agricultural and pharmaceu-
tical products. So far, there have been many reports for the
synthesis of coumarin frameworks. There are fundamentally
Table 3. Reactions of some aldehydes with isopropyl cyanoacetate and diisopropyl malonate promoted by Ti(O-i-Pr)4
Entry
R1
R2
R3
Ti(O-i-Pr)4/equiv
Conditions
Temperature/8C
Product (% yielda)
Time/h
1
2
3
4
Ph
CN
CN
CO2-i-Pr
CO2-i-Pr
CO2-i-Pr
CO2-i-Pr
CO2-i-Pr
CO2-i-Pr
0.2
0.2
1.0
1.0
70
70
22
20
25
24
50
51
78b (2a)
63b,c (2b)
93 (3a)
(E)-PhCH]CH
Ph
c-C6H11
97 (3b)
a Isolated yield by silica-gel column chromatography unless otherwise noted.
b Only (E)-isomer was obtained (determined by NOE experiments).
c Isolated yield by fractional recrystallizations.

K. Yamashita et al. / Tetrahedron 61 (2005) 7981–7985
7983
Scheme 1.
presence of 2 equiv of Ti(O-i-Pr)4 at 25 8C proceeded
smoothly to produce 3-acetylcoumarin in 76% yield in
CH2Cl2 and 59% yield in i-PrOH, respectively.
3.1.3. 2-[(4-Methoxyphenyl)methylene]malononitrile
(1c). RfZ0.47 (2:1 hexane–ethyl acetate); mp 116–118 8C
(lit.2 119 8C); IR (KBr, nmax (cmK1)): 2225 (CN), 1560
(C]C); 1H NMR: d 7.91 (d, 2H, JZ8.8 Hz), 7.65 (s, 1H,),
7.01 (d, 2H, JZ8.8 Hz), 3.92 (s, 3H); 13C NMR: d 164.8,
158.8, 133.4, 124.0, 115.1, 114.4, 113.3, 78.7, 55.8; MS m/z
(relative intensity): 184 (MC, 100%), 169 (13%), 141
(28%), 114 (45%).
The present method has the following characteristic
¨
features: (1) Ti(O-i-Pr)4-catalyzed Knoevegenal reaction
of aldehydes and ketones is performed in non-toxic i-PrOH.
(2) In the case of aldehydes, only a catalytic amount
(0.05 equiv) of Ti(O-i-Pr)4 was required for smooth
reaction. (3) Coumarin derivatives are synthesized when
salicylaldehyde is used.
3.1.4. 2-[(4-Bromophenyl)methylene]malononitrile (1d).
RfZ0.61 (3:1 hexane–ethyl acetate); mp 165–166 8C (lit.11
164 8C); IR (KBr, nmax (cmK1)): 2225 (CN), 1558 (C]C);
1H NMR: d 7.77 (d, 2H, JZ8.2 Hz), 7.72 (s, 1H), 7.69 (d,
2H, JZ8.2 Hz); 13C NMR: d 158.4, 133.0, 131.8, 130.0,
129.6, 113.4, 112.3, 83.5; MS m/z (relative intensity): 235
(81Br-MC, 11%), 234 (88%), 233 (79Br-MC, 13%), 232
(89%), 153 (100%), 126 (79%), 100 (34%).
3. Experimental
3.1. General procedure for Ti(O-i-Pr)4-promoted
¨
Knoevenagel reaction
Malononitrile (330 mg, 5 mmol) and i-PrOH (Wako
dehydrated grade) 6 mL were placed in a Schlenk tube
under argon atmosphere. To this solution, aldehydes
(5 mmol) then Ti(O-i-Pr)4 0.08 mL (0.025 mmol) were
added and stirred at room temperature (20–25 8C) for
3–25 h. After confirmation of the completion of the
reaction, the reaction mixture was poured into 1 N HCl
and vigorously stirred at 0 8C for 0.5 h. It was extracted by
ethyl acetate and the extract was washed with sodium
bicarbonate and brine solution. The organic layer was dried
with anhydrous sodium sulfate and evaporated. Purification
of the residues by recrystallization or silica-gel column
3.1.5. 2-(Cyclohexylmethylene)malononitrile (1e). RfZ
0.54 (4:1 hexane–ethyl acetate); IR (KBr, nmax (cmK1)):
2235 (CN), 1608 (C]C); H NMR: d 7.15 (d, 1H, JZ
10.4 Hz), 2.78–2.68 (m, 1H), 1.83–1.71 (m, 4H), 1.43–1.18
(m, 6H); 13C NMR: d 173.6, 112.2, 110.6, 87.8, 42.1, 30.9,
25.1, 24.6; MS m/z (relative intensity): 160 (MC, 3%), 159
(9%), 145 (11%), 132 (14%), 118 (7%), 105 (18%), 82
(19%), 67 (52%), 56 (78%), 41 (100%). Anal. Calcd for
C10H12N2: C, 74.97; H, 7.55; N, 17.48. Found: C, 74.89; H,
7.59; N, 17.32.
1
3.1.6. 2-(3-Phenylpropylidene)malononitrile (1f). RfZ
0.54 (3:1 hexane–ethyl acetate); IR (KBr, nmax (cmK1)):
¨
chromatography afforded Knoevenagel reaction products.
1
2236 (CN), 1601 (C]C); H NMR: d 7.34 (t, 2H, JZ
3.1.1. 2-(Phenylmethylene)malononitrile (1a). RfZ0.56
(3:1 hexane–ethyl acetate); mp 84–85 8C (lit.11 83 8C); IR
(KBr, nmax (cmK1)): 2223 (CN), 1591 (C]C); 1H NMR: d
7.91 (d, 2H, JZ7.2 Hz), 7.78 (s, 1H), 7.64 (t, 1H, JZ
7.2 Hz), 7.55 (t, 2H, JZ7.2 Hz); 13C NMR: d 160.1, 134.6,
131.0, 130.7, 129.6, 113.8, 112.7, 82.6; MS m/z (relative
intensity): 154 (MC, 100%), 127 (94%), 103 (70%), 76
(23%).
7.2 Hz), 7.30–7.27 (m, 2H), 7.17 (d, 2H, JZ7.2 Hz), 2.96–
2.86 (m, 4H); 13C NMR: d 168.3, 138.2, 136.9, 129.0, 128.3,
127.1, 114.9, 112.0, 110.4, 90.5, 34.2, 33.5; MS m/z
(relative intensity): 182 (MC, 40%), 91 (100%), 77
(25%), 65 (100%), 51 (59%). Anal. Calcd for C12H10N2:
C, 79.10; H, 5.53; N, 15.37. Found: C, 79.10; H, 5.56; N,
15.22.
3.1.2. 2-[(4-Chlorophenyl)methylene]malononitrile (1b).
RfZ0.54 (3:1 hexane–ethyl acetate); mp 167–168 8C (lit.2
165 8C); IR (KBr, nmax (cmK1)): 2228 (CN), 1584 (C]C);
1H NMR: d 7.85 (d, 2H, JZ8.4 Hz), 7.73 (s, 1H), 7.52 (d,
2H, JZ8.4 Hz); 13C NMR: d 158.2, 141.2, 131.8, 130.1,
129.3, 113.4, 112.3, 83.4; MS m/z (relative intensity): 190
(37Cl-MC, 26%), 188 (35Cl-MC, 75%), 161 (29%), 153
(100%), 137 (22%), 126 (19%), 100 (12%), 75 (21%).
3.1.7. 2-[(E)-3-Phenyl-2-propenylidene]malononitrile
(1g). RfZ0.53 (3:1 hexane–ethyl acetate); mp 126–128 8C
(lit.12 126 8C); IR (KBr, nmax (cmK1)): 2224 (CN), 1609
(C]C), 1560 (C]C); 1H NMR: d 7.61–7.59 (m, 3H), 7.48–
7.42 (m, 3H), 7.27 (d, 2H, JZ10.4 Hz); 13C NMR: d 159.9,
150.3, 134.0, 132.1, 129.3, 128.9, 122.3, 113.5, 111.6; MS
m/z (relative intensity): 180 (MC, 99%), 179 (41%), 153
(100%), 115 (97%), 51 (40%).

7984
K. Yamashita et al. / Tetrahedron 61 (2005) 7981–7985
3.1.8. 2-(Butylidene)malononitrile (1h). RfZ0.54 (3:1
hexane–ethyl acetate); IR (KBr, nmax (cmK1)): 2239 (CN),
1607 (C]C); H NMR: d 7.33 (t, 1H, JZ7.6 Hz), 2.58 (q,
2H, JZ7.6 Hz), 1.62 (sextet, 2H, JZ7.6 Hz), 1.02 (t, 3H,
JZ7.6 Hz); 13C NMR: d 169.4, 112.1, 90.2, 34.6, 21.1,
19.6, 13.5; MS m/z (relative intensity): 120 (MC, 19%), 119
(21%), 105 (31%), 92 (33%), 79 (28%), 67 (46%), 55
(59%), 42 (100%), 41 (73%). Anal. Calcd for C7H8N2: C,
69.97; H, 6.71; N, 23.32. Found: C, 69.93; H, 6.65; N, 23.23.
RfZ0.41 (7:1 hexane–ethyl acetate); IR (KBr, nmax (cmK1)):
1724 (C]O), 1631 (C]C); H NMR: d 7.69 (s, 1H), 7.48
1
1
(dd, 2H, JZ6.8, 2.4 Hz), 7.41–7.34 (m, 3H), 5.29–5.21 (m,
1H), 5.19–5.11 (m, 1H), 1.31 (d, 6H, JZ6.4 Hz), 1.29 (d,
6H, JZ6.4 Hz); 13C NMR: d 166.3, 163.7, 141.4, 133.0,
130.4, 129.5, 128.7, 127.1, 69.3, 69.2, 21.8, 21.5; MS m/z
(relative intensity): 276 (MC, 9%), 217 (20%), 175 (66%),
174 (100%), 158 (27%), 146 (29%), 130 (24%), 102 (28%),
43 (98%). Anal. Calcd for C10H6N2: C, 69.54; H, 7.30.
Found: C, 69.54; H, 7.31.
3.1.9. 2-(2,2-Dimethylpropylidene)malononitrile (1i).
RfZ0.53 (3:1 hexane–ethyl acetate); mp 64–65 8C; IR
(KBr, nmax (cmK1)): 2233 (CN), 1606 (C]C); 1H NMR: d
7.26 (s, 1H), 1.32 (s, 9H); 13C NMR: d 177.4, 113.1, 111.1,
86.9, 37.0, 28.5; MS m/z (relative intensity): 133 (MC-1,
8%), 119 (29%), 92 (63%), 73 (38%), 65 (53%), 57 (35%),
42 (100%). Anal. Calcd for C8H10N2: C, 71.61; H, 7.51; N,
20.88. Found: C, 71.40; H, 7.47; N, 20.76.
3.1.15. Diisopropyl 2-(cyclohexylmethylene)malonate
(3b). RfZ0.54 (6:1 hexane–ethyl acetate); IR (KBr, nmax
1
(cmK1)): 1718 (C]O), 1646 (C]C); H NMR: d 6.73 (d,
1H, JZ10.8 Hz), 5.24–5.14 (m, 1H), 5.13–5.03 (m, 1H),
2.42–2.33 (m, 1H), 1.74–1.66 (m, 4H), 1.31 (d, 6H, JZ
6.4 Hz), 1.27 (d, 6H, JZ6.8 Hz), 1.23–1.10 (m, 6H); 13C
NMR: d 165.4, 163.8, 152.5, 127.6, 68.7, 68.6, 38.9, 31.7,
25.6, 25.2, 21.7; MS m/z (relative intensity): 180 (49%), 163
(55%), 162 (100%), 95 (33%), 43 (89%), 41 (72%). Anal.
Calcd for C10H6N2: C, 68.06; H, 9.28. Found: C, 68.13; H,
9.37.
3.1.10. 2-(1-Phenylethylidene)malononitrile (1j). RfZ
0.42 (3:1 hexane–ethyl acetate); mp 94–96 8C (lit.13
92 8C); IR (KBr, nmax (cmK1)): 2228 (CN), 1585 (C]C);
1H NMR: d 7.58–7.48 (m, 5H), 2.64 (s, 3H); 13C NMR: d
175.4, 135.9, 132.2, 129.1, 127.3, 112.7, 84.7, 24.2; MS m/z
(relative intensity): 168 (MC, 100%), 141 (64%), 140
(67%), 128 (58%), 114 (37%), 103 (30%), 77 (33%), 51
(49%).
3.1.16. 3-Cyanocoumarin (4). RfZ0.30 (2:1 hexane–ethyl
acetate); mp 184–186 8C (lit.15 182–184 8C); IR (KBr, nmax
(cmK1)): 2229 (CN), 1728 (C]O), 1604 (C]C); 1H NMR:
d 8.28 (s, 1H), 7.73 (t, 1H, JZ8.0 Hz), 7.62 (dd, 1H, JZ8.0,
1.6 Hz), 7.43 (t, 1H, JZ8.0 Hz), 7.42 (t, 1H, JZ8.0 Hz);
13C NMR: d 155.5, 154.0, 136.5, 130.8, 126.5, 118.5, 118.3,
117.9, 115.2, 103.8; MS m/z (relative intensity): 171 (MC,
100%), 143 (99%), 115 (50%), 88 (27%), 63 (24%), 62
(23%). Anal. Calcd for C10H6N2: C, 70.18; H, 2.94; N, 8.18.
Found: C, 70.30; H, 2.94; N, 8.35.
3.1.11. 2-(Diphenylmethylene)malononitrile (1k). RfZ
0.51 (3:1 hexane–ethyl acetate); mp 143–144 8C (lit.14
138 8C); IR (KBr, nmax (cmK1)): 2223 (CN), 1530 (C]C);
1H NMR: d 7.58 (t, 2H, JZ7.2 Hz), 7.51–7.42 (m, 8H); 13
C
NMR: d 175.0, 136.1, 132.7, 130.4, 128.9, 113.9, 81.7; MS
m/z (relative intensity): 230 (MC, 96%), 229 (75%), 203
(64%), 165 (100%), 88 (29%).
3.1.17. 3-Isopropoxycarboxycoumarin (5). RfZ0.62 (3:1
hexane–ethyl acetate); mp 89–90 8C (lit.16 84–86 8C); IR
(KBr, nmax (cmK1)): 1750 (C]O), 1606 (C]C); 1H NMR:
d 8.47 (s, 1H), 7.64 (t, 1H, JZ8.0 Hz), 7.61 (dd, 1H, JZ8.0,
1.6 Hz), 7.36 (d, 1H, JZ8.0 Hz), 7.34 (t, 1H, JZ8.0 Hz),
5.32–5.23 (m, 1H), 1.4 (d, 6H, JZ6.0 Hz); 13C NMR: d
162.4, 156.7, 155.1, 148.0, 134.2, 129.4, 124.8, 118.7,
117.9, 116.8, 69.7, 21.8. MS m/z (relative intensity): 232
(MC, 26%), 174 (35%), 173 (98%), 146 (100%), 118 (41%),
101 (22%), 89 (41%), 43 (49%). Anal. Calcd for C13H12O2:
C, 67.23; H, 5.21. Found: C, 67.23; H, 5.12.
3.1.12. Isopropyl (E)-2-cyano-3-phenyl-2-propenoate
(2a). RfZ0.63 (3:1 hexane–ethyl acetate); mp 76–79 8C;
IR (KBr, nmax (cmK1)): 2219 (CN), 1717 (C]O), 1607
1
(C]C); H NMR: d 8.24 (s, 1H), 7.99 (d, 2H, JZ6.8 Hz),
7.58–7.48 (m, 3H), 5.26–5.16 (m, 1H), 1.38 (d, 6H, JZ
6.4 Hz); 13C NMR: d 161.9, 154.7, 133.1, 131.5, 130.9,
129.2, 115.4, 103.5, 70.7, 21.7; MS m/z (relative intensity):
215 (MC, 32%), 173 (100%), 172 (100%), 156 (85%), 129
(78%), 128 (63%), 102 (58%), 101 (33%), 77 (57%), 43
(88%). Anal. Calcd for C10H6N2: C, 72.54; H, 6.09; N, 6.51.
Found: C, 72.52; H, 6.11; N, 6.46.
Acknowledgements
3.1.13. Isopropyl (2E,4E)-2-cyano-5-phenyl-2,4-penta-
dienoate (2b). RfZ0.69 (3:1 hexane–ethyl acetate); mp
104–106 8C; IR (KBr, nmax (cmK1)): 2220 (CN), 1712
We thank Dr. Hideki Amii for helpful discussions. This
research was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
1
(C]O), 1612 (C]C), 1582 (C]C); H NMR: d 8.00 (dd,
1H, JZ8.0, 2.4 Hz), 7.59 (dd, 2H, JZ6.8, 2.4 Hz), 7.44–
7.42 (m, 3H), 7.28 (d, 1H, JZ8.0 Hz), 7.27 (d, 1H, JZ
2.4 Hz), 5.22–5.12 (m, 1H), 1.35 (d, 6H, JZ6.0 Hz); 13C
NMR: d 161.8, 155.1, 148.5, 134.7, 131.1, 129.1, 128.5,
123.1, 114.6, 105.2, 70.3, 21.7; MS m/z (relative intensity):
241 (MC, 20%), 199 (74%), 182 (27%), 171 (58%), 155
(64%), 154 (100%), 127 (64%), 115 (55%), 77 (33%), 43
(69%). Anal. Calcd for C10H6N2: C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.51; H, 6.28; N, 5.75.
References and notes
1. Jones, G. Org. React. 1967, 15, 204–599.
2. Rao, P. S.; Venkataratnam, R. V. Tetrahedron Lett. 1991, 32,
5821–5822.
3.1.14. Diisopropyl 2-(phenylmethylene)malonate (3a).
3. Prajapati, D.; Sandhu, J. S. Chem. Lett. 1992, 1945–1946.

K. Yamashita et al. / Tetrahedron 61 (2005) 7981–7985
7985
4. Prajapati, D.; Sandhu, J. S. J. Chem. Soc., Perkin Trans. 1
1993, 739–740.
5. (a) Su, C.; Chen, Z. C.; Zheng, Q. G. Synthesis 2003, 4,
9. Bigi, F.; Chesini, L.; Maggi, R.; Sartori, G. J. Org. Chem.
1999, 64, 1033–1035.
10. Watson, B. T.; Christiansen, G. E. Tetrahedron Lett. 1998, 39,
6087–6090.
¨
555–559. See also for recently reported Knoevenagel reaction:
(b) Bigi, F.; Conforti, M. L.; Maggi, R.; Piccinno, A.; Satori,
G. Green Chem. 2000, 2, 101–103. (c) Amantini, D.;
Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro, L. Green
Chem. 2001, 3, 229–232. (d) Hangarge, R. V.; Sonwane, S. A.;
Jarikote, D. V.; Shingare, M. S. Green Chem. 2001, 3,
310–312.
11. Zabicky, J. J. Chem. Soc. 1961, 683–687.
12. Angeletti, E.; Canepa, C.; Martinetti, G.; Venturello, P.
J. Chem. Soc., Perkin Trans. 1 1989, 105–107.
13. Texier-Boullet, F.; Foucaud, A. Tetrahedron Lett. 1982, 23,
4927–4928.
´
14. Cruz, P. D. L.; Dıez-Barra, E.; Loupy, A.; Langa, F.
6. Hayashi, M.; Nakamura, N.; Yamashita, K. Tetrahedron 2004,
60, 6777–6783.
Tetrahedron Lett. 1996, 37, 1113–1116.
15. Jose, A. C.; Juan, M. C.; Angel, G.; Luna, D.; Jose, M. M.
J. Org. Chem. 1984, 49, 5195–5197.
7. Pechmann, H.; Duisberg, C. Ber. Dtsch. Chem. Ges. 1883, 16,
2119.
8. Sugino, T.; Tanaka, K. Chem. Lett. 2001, 110–111.
16. Kadaba, P. K. Synthesis 1972, 628–630.