A novel reductive cyclization of arylmethylidenemalononitrile promoted by low-valent titanium

Article abstract of DOI:10.1081/SCC-120014037

The intermolecular and intramolecular reductive coupling reactions of arylmethylidenemalononitriles induced by low-valent titanium have been studied. A possible reaction mechanism is proposed.

Full text of DOI:10.1081/SCC-120014037

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A NOVEL REDUCTIVE CYCLIZATION OF
ARYLMETHYLIDENEMALONONITRILE PROMOTED BY
LOW-VALENT TITANIUM
Daqing Shi a , Hong Zhao a , Xiangshan Wang a , Changsheng Yao a & Longhu Zhou a
a Department of Chemistry , Xuzhou Normal University , Xuzhou, 221009, P.R. China
Published online: 16 Aug 2006.
To cite this article: Daqing Shi , Hong Zhao , Xiangshan Wang , Changsheng Yao & Longhu Zhou (2002) A NOVEL REDUCTIVE
CYCLIZATION OF ARYLMETHYLIDENEMALONONITRILE PROMOTED BY LOW-VALENT TITANIUM, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:21, 3311-3317, DOI: 10.1081/
SCC-120014037
To link to this article: http://dx.doi.org/10.1081/SCC-120014037
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 21, pp. 3311–3317, 2002
A NOVEL REDUCTIVE CYCLIZATION OF
ARYLMETHYLIDENEMALONONITRILE
PROMOTED BY LOW-VALENT
TITANIUM
*
Daqing Shi, Hong Zhao, Xiangshan Wang,
Changsheng Yao, and Longhu Zhou
Department of Chemistry, Xuzhou Normal University,
Xuzhou, 221009, P.R. China
ABSTRACT
The intermolecular and intramolecular reductive coupling
reactions of arylmethylidenemalononitriles induced by low-
valent titanium have been studied. A possible reaction
mechanism is proposed.
Key Words: Low-valent titanium; Reductive cyclization;
Arylmethylidenemalononitrile
Low-valent titanium reagents have an exceedingly high ability to pro-
mote the reductive coupling of carbonyl compounds and are attracting
increasing interest in organic synthesis. A lot of other functional groups
can also be coupled.[1,2] Although several results have been reported
on saturated carbonyl compounds, only a few studies on the coupling
*Corresponding author. E-mail: wxs2001z@sina.com.cn
3311
DOI: 10.1081/SCC-120014037
Copyright & 2002 by Marcel Dekker, Inc.
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3312
SHI ET AL.
Scheme 1.
a,b-unsaturated cabonyl compounds have been published.[3,4] Recently, we
have reported the cyclodimerization of a,b-unsaturated ketones promoted
by this reagent to yield cyclopentane derivatives.[5] It has been known that
a,b-unsaturated carboxylic acid derivatives are reduced with samarium diio-
dide to the corresponding saturated compounds,[6] but there is no report on
such a reaction using low-valent titanium. Here, we wish to report the novel
reductive cyclization of arylmethylidenemalononitriles promoted by treat-
ment with titanium tetrachloride/zinc in anhydrous tetrahydrofuran (THF).
It has been known that the cyano group is relatively more stable to
low-valent titanium reagents than the carbonyl group and could not be
reduced unless the reaction mixture was refluxed for a long time and only
with low yield.[7,8] We considered that the conjugated carbon–carbon double
bond could perhaps influence the reactivity of the cyano group. Therefore,
we studied the behavior of the cyano group in a,b-unsaturated nitrile deri-
vatives when treated with titanium tetrachloride and zinc in anhydrous THF.
When arylmethylidenemalononitriles 1 were treated with low-valent
titanium in THF, the intermolecularly (and reductively) coupled cyclization
products, the trans-2-amino-1,3,3-tricyano-4,5-diarylcyclopentenes 2, were
formed (Sch. 1).
Table 1 summarizes our results of the cyclodimerization of a number
of substrates. In the reactions the cleavage takes place at the carbon–
nitrogen triple bond and the carbon–carbon double bond. The chloro and
alkoxy groups of the substrates could not be reduced under the reaction
conditions and have no influence on the rate of cyclodimerization.
Though the detailed mechanism of the above cyclodimerization has
not been clarified yet, the cyclopentene formation can be explained by the
possible mechanism depicted in Sch. 2.
In the initial step, an electron is transferred from low-valent titanium
to substrate (1) to form a radical anion which then reacts with another one
to produce a dianion. Moreover, the intramolecular nucleophilic addition of
the dianion can occur automatically to afford a five-membered ring product
due to the stability of the five-membered ring. Considering the stability of

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ARYLMETHYLIDENEMALONONITRILE
3313
Table 1. Cyclodimerization of Arylmethylidene-
malononitriles Induced by Low-Valent Titanium
Entry
Ar
4-ClC6H4
4-CH3C6H4
C6H5
4-CH3OC6H4
3,4-OCH2O-C6H3
2-Furyl
Isolated Yield (%)
A
B
C
D
E
F
78
73
67
72
60
64
Scheme 2.
the dianion and product, it is obvious that the trans-isomer is easy to form.
In support of the mechanism, only the tans-isomer was obtained in this
reaction. The relative configuration for C(4)/C(5) in product was determined
by analysis of the coupling constrant between H(5)/H(4)(J ¼ 9–10 Hz,
trans).[9,10]
However, treatment of ( p-nitrobenzylidene)malononitrile (3) with
titanium tetrachloride and zinc in anhydrous THF under the same reaction
conditions was found to afforded only product (4) formed by reduction of
the nitro group in (3) (Sch. 3).
On the other hand, when (o-nitrobenzylidene) mlononitrile derivatives
(5) were subjected to the above procedure, neither products (3) nor (4) were
detected. However, the intramolecular reductive cyclization products,
2-aminoquinoline derivatives (6) (Sch. 4), were found in good yields.

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3314
SHI ET AL.
Scheme 3.
Scheme 4.
In summary, the intermolecular cyclodimerization of arylmethylidene-
malononitrile induced by low-valent titanium took place to afford trans-2-
amino-1,3,3-tricyano-4,5-diarylcyclopentene, while under the same reaction
conditions the intramolecular reductive cyclization of o-nitrobenzylidene
malononitrile derivatives was found, which allowed a facile synthesis of
2-aminoquinoline derivatives.
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a FTIR-8101 spectrometer.
1H NMR spectra were measured on a R-1500A spectrometer using TMS
as internal standard. Elemental analysis were determined using
Perkin-Elmer 240C elemental analysers.
Cyclopentenes2: General Procedure
TiCl4 (2.2 mL, 20 mmol) was added dropwise using a syringe to a stirred
suspension of Zn powder (2.6 g, 40 mmol) in freshly distilled anhydrous THF
(20 mL) at r.t. under N2. On completion of the addition, the mixture was

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ARYLMETHYLIDENEMALONONITRILE
3315
refluxed for 2 h. The black suspension of the low-valent titanium reagent
formed was allowed to cool to r.t. and a solution of arylmethylidenemalono-
nitrile (10 mmol) in THF (10 mL) was added dropwise over ca.20 min. The
mixture was stirred at r.t. under N2. When the reaction was complete, the
reaction was quenched with 3% HCl (50 mL) and extracted with
CH2ClCH2Cl (3 ꢀ 50 mL). The combined organic layers were washed with
water (2 ꢀ 30 mL), dried (Na2SO4), and the solvent was removed in vacuum
to give the crude product, which was further purified by column chromatog-
raphy [silica gel, EtOAc/petroleum ether (b.p. 60–90ꢁC), 1 : 2].
2a: M.p. 158–160ꢁC (Lit.[10] m.p. 158–160ꢁC); IR (KBr, ꢀ, cmꢂ1): 3375,
1
3190, 2220, 1670, 1625, 1495, 1090, 1015; H NMR (CDCl3, ꢁ, ppm): 3.74
(1H, d, J ¼ 10 Hz, ArCH), 4.50 (1H, d, J ¼ 10 Hz, ArCH), 5.32 (2H, s, NH2),
6.85–7.40 (8H, m, ArH).
2b: M.p. 186–188ꢁC; (Lit.[10] m.p. 190–192ꢁC); IR (KBr, ꢀ, cmꢂ1):
3375, 3240, 2220, 1670, 1660, 1630, 1515, 1095, 1075, 825; 1H NMR
(CDCl3, ꢁ, ppm): 2.24 (3H, s, CH3), 2.30 (3H, s, CH3), 3.77 (1H, d,
J ¼ 10 Hz, ArCH), 4.50 (1H, d, J ¼ 10 Hz, ArCH), 5.32 (2H, s, NH2),
6.93–7.38 (8H, m, ArH).
2c: M.p. 130–132ꢁC; (Lit.[10] m.p. 128–130ꢁC); IR (KBr, ꢀ, cmꢂ1):
3375, 3175, 2210, 1675, 1625, 1500, 1450, 1380, 1100, 700; 1H NMR
(CDCl3, ꢁ, ppm): 3.82 (1H, d, J ¼ 9 Hz, ArCH), 4.58 (1H, d, J ¼ 9 Hz,
ArCH), 5.21 (2H, s, NH2), 7.10–7.74 (10H, m, ArH).
2d: M.p. 98–100ꢁC; (Lit.[10] m.p. 95–97ꢁC); IR (KBr, ꢀ, cmꢂ1): 3375,
3240, 2220, 1670, 1630, 1610, 1515, 1260, 1250, 1180, 1035, 830, 810;
1H NMR (CDCl3, ꢁ, ppm): 3.65 (3H, s, OCH3), 3.76 (3H, s, OCH3), 4.15
(1H, d, J ¼ 10 Hz, ArCH), 4.53 (1H, d, J ¼ 10 Hz, ArCH), 5.38 (2H, s, NH2),
6.71–7.51 (8H, m, ArH).
2e: M.p. 163–165ꢁC; (Lit.[10] m.p. 166–168ꢁC); IR (KBr, ꢀ, cmꢂ1):
3380, 3240, 2220, 1670, 1620, 1505, 1490, 1450, 1380, 1040, 940, 930;
1H NMR (CDCl3, ꢁ, ppm): 4.24 (1H, d, J ¼ 9 Hz, ArCH), 4.45 (1H, d,
J ¼ 9 Hz, ArCH), 5.30 (2H, s, NH2), 5.97 (4H, s, 2 ꢀ OCH2O), 6.30–6.94
(6H, m, ArH).
2f: M.p. 126–128ꢁC; (Lit.[10] m.p. 125–127ꢁC); IR (KBr, ꢀ, cmꢂ1):
3360, 3240, 2220, 1680, 1630, 1510; 1H NMR (CDCl3, ꢁ, ppm): 4.25 (1H, d,
J ¼ 9 Hz, ArCH), 4.62 (1H, d, J ¼ 9 Hz, ArCH), 5.61 (2H, s, NH2), 6.25–7.52
(6H, m, ArH).
Product 4 and 2-Aminoquinolines7: General Procedure
A black suspension of low-valent titanium reagents was prepared with
TiCl4 (40 mmol) and Zn powder (80 mmol) in THF (40 mL) using the same

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3316
SHI ET AL.
procedure mentioned above. A solution of 3 or 5 (10 mmol) in THF (20 mL)
was added carefully to the suspension at r.t. When the reaction was
complete (at r.t. under N2), most of the solvent was removed in vacuo.
The residue was poured into 10% K2CO3 (200 mL), and extracted with
CH2ClCH2Cl (4 ꢀ 50 mL). The combined organic layers were washed with
water (2 ꢀ 30 mL), dried (Na2SO4), and the solvent was removed in vacuum
to give the crude product, which was further purified by recrystallization
from 95% EtOH.
4: M.p. 202–204ꢁC; yield 88%; IR (KBr, ꢀ, cmꢂ1): 3350, 3250,
2220, 1650, 1610, 1580, 1550, 1520, 1460, 1370, 1350, 1330, 1250,
1175, 820; 1H NMR (CDCl3, ꢁ, ppm): 6.69 (2H, d, J ¼ 10 Hz, ArH),
7.63 (2H, d, J ¼ 10 Hz, ArH), 7.86 (1H, s, –CH¼). Anal. calcd.
for C10H7N3: C, 70.99; H, 4.17; N, 24.84. Found: C, 71.15; H, 4.06;
N, 24.78.
6a: M.p. 230–232ꢁC; (Lit.[10] m.p. 226–227ꢁC yield 81%; IR (KBr, ꢀ,
1
cmꢂ1): 3400, 3160, 2230, 1650, 1620, 750; H NMR (CDCl3, ꢁ, ppm): 5.45
(2H, s, NH2), 7.30–7.75 (4H, m, ArH), 8.31 (1H, s, ArH).
6b: M.p. 275–277ꢁC; (Lit.[10] m.p. 280ꢁC); yield 76%; IR (KBr, ꢀ,
cmꢂ1): 3400, 3200, 2230, 1650; 1H NMR (CDCl3, ꢁ ppm): 6.14 (2H, s,
OCH2O), 6.65 (2H, s, NH2), 6.90 (1H, s, ArH), 7.12 (1H, s, ArH), 8.37
(1H, s, ArH).
ACKNOWLEDGMENT
We are grateful to the Foundation of the ‘‘333 Project’’ of Jiangsu
Province and the Key Laboratory of Organic Synthesis, Suzhou University
for financial support.
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3317
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Received in Japan April 16, 2001

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