Stereoselective synthesis of 2-alkylidene-3-iminoindoles by reaction of 1,1-dianions with oxalic acid bis(imidoyl) chlorides

Article abstract of DOI:10.1021/jo991701l

Treatment of dilithiated nitriles and sulfones with oxalic acid bis(imidoyl) chlorides resulted in a new cyclization reaction which provided a variety of (3-imino-2,3-dihydro-1H-indol-2-ylidene)-acetonitriles and - sulfones in good yields. The reactions p

Full text of DOI:10.1021/jo991701l

J . Org. Chem. 2000, 65, 3603-3611
3603
Ster eoselective Syn th esis of 2-Alk ylid en e-3-im in oin d oles by
Rea ction of 1,1-Dia n ion s w ith Oxa lic Acid Bis(im id oyl) Ch lor id es
Peter Langer,*,† J o¨rg Wuckelt,‡ Manfred Do¨ring,‡ and Helmar Go¨rls‡
Institut fu¨r Organische Chemie der Georg-August-Universita¨t Go¨ttingen, Tammannstrasse 2,
37077 Go¨ttingen, Germany, and Institut fu¨r Anorganische und Analytische Chemie der Universita¨t J ena,
August-Bebel-Strasse 2, 07743 J ena, Germany
Received October 29, 1999
Treatment of dilithiated nitriles and sulfones with oxalic acid bis(imidoyl) chlorides resulted in a
new cyclization reaction which provided a variety of (3-imino-2,3-dihydro-1H-indol-2-ylidene)-
acetonitriles and -sulfones in good yields. The reactions proceeded by condensation of the dianions
with the first imidoyl chloride group of the bis(imidoyl) chloride, subsequent intramolecular attack
of the ortho carbon of the arylimino group onto the second imidoyl chloride group, and final
aromatization. Excellent stereoselectivities were observed in most cases.
The 1,2-dione unit represents an important structural
feature of compounds of pharmaceutical interest and of
materials such as NIR dyes.1,2 A formal 1,2-dione unit is
contained in aurones which represent a small group of
2-benzylidenecoumaranone-based yellow pigments. Au-
rones are biogenetically formed by oxidation of chalcones
and include a variety of natural products such as the
pigment aureusidine 1a . 2-Alkylidene-3-oxindoles 1b,
which can be regarded as azaanalogous aurones, have
recently been recognized as powerful dienophiles3,4 in
Diels-Alder reactions of normal electron demand5 for the
construction of the spirocyclic Aristotelia alkaloid frame-
work 1d .6 2-Alkylidene-3-oxindoles have also been used
as heterodienes in hetero-Diels-Alder reactions of in-
verse electron demand for the preparation of the poten-
tially antitumor-active pyrano[3,2-b]indole 1e7 and of
δ-carboline 1f.8 In addition, 2-alkylidene-3-oxindoles
represent useful starting materials for the preparation
of mycotoxin brevianamides.9 Danishefsky recently re-
ported the need for an enamino ester of type 1b (R1 )
CO2R′′) in the synthesis of the anticancer drug camp-
tothecin.10 Stille also used an 2-alkylidene-3-oxindole as
a building block in the synthesis of tashiromine.11
To date, previous syntheses of 2-alkylidene-3-oxindoles
utilized the aldol reaction4,8a of 3-oxindoles or the Heck
reaction of iodoanilines with alkynes in the presence of
CO12 as the key steps. Using the first approach, 3-oxin-
doles 1b (R1 ) CO2R′′) were obtained with good stereo-
selectivities but low yields (12-44% yield).4 The aldoliza-
tion with benzaldehyde derivatives (R1 ) aryl) proceeded
with low stereocontrol.8a Due to the problems associated
with the synthesis of this type of compounds, we envis-
aged that 2-alkylidene-3-iminoindoles 1c, containing a
masked carbonyl group, could be equally useful as
synthons for the synthesis of alkaloids. In addition, these
compounds represent interesting starting materials for
the generation of photochromic spiroindoles13 and of novel
NIR dyes.14 In the course of our interest in the reaction
of oxalic acid bis(imidoyl) chlorides C2Cl2(NAr)2 215 with
carbon nucleophiles,16 we have recently developed a new
cyclization reaction which allows a convenient and ste-
reoselective synthesis of 3-iminoindoles 1c.17 Herein, we
* To whom correspondence should be addressed.
† Institut fu¨r Organische Chemie der Georg-August-Universita¨t
Go¨ttingen.
(10) Shen, W.; Coburn, C. A.; Bornmann, W. G.; Danishefsky, S. J .
J . Org. Chem. 1993, 58, 611.
(11) Paulvannan, K.; Stille, J . R. J . Org. Chem. 1994, 59, 1613.
(12) Brocato, E.; Castagnoli, C.; Catellani, M.; Chiusoli, G. P.
Tetrahedron Lett. 1992, 33, 7433.
‡ Institut fu¨r Anorganische und Analytische Chemie der Universita¨t
J ena.
(1) (a) Chiu, C. C.; J ordan, F. J . Org. Chem. 1994, 59, 5763. (b)
Fabian, J .; Nakazumi, H.; Matsuoka, M. Chem. Rev. 1992, 92, 1197.
(2) Stachel, H.-D.; Schorp, M.; Maier, L.; Dandl, K. Liebigs Ann.
Chem. 1994, 1121. (b) Saalfrank, R. W.; Stark, A.; Bremer, M.;
Hummel, H.-U. Angew. Chem. 1990, 102, 292. Angew. Chem., Int. Ed.
Engl. 1990, 29, 311. (c) Pattenden, G. Prog. Chem. Nat. Prod. 1978,
35, 133.
(3) The reactivity of 2- and 3-vinylindoles as 4π components in the
Diels-Alder reaction has been extensively studied: (a) Blechert, S.;
Knier, R.; Schroers, H.; Wirth, T. Synthesis 1995, 592. (b) Pindur, U.;
Rogge, M.; Rehn, M.; Massa, W.; Peschel, B. J . Heterocycl. Chem. 1994,
31, 981 and references therein. (c) Le´vy, J .; Sapi, J .; Laronze, J .-Y.;
Royer, D.; Toupet, L. Synlett 1992, 601.
(4) Me´rour, J .-Y.; Chichereau, L.; Desarbre, E.; Gadonneix, P.
Synthesis 1996, 519.
(5) Wenkert, E.; Liu, S. Synthesis 1992, 323.
(6) Stahl, R.; Galli, R.; Gu¨ller, R.; Borschberg, H.-J . Helv. Chim. Acta
1994, 77, 2125.
(7) Davion, Y.; J oseph, B.; Me´rour, J .-Y. Synlett 1998, 1051.
(8) (a) Buzas, A.; Me´rour, J . Y. Synthesis 1989, 458. (b) Me´rour, J .
Y.; Me´rour, A. Synthesis 1994, 767.
(13) For recent examples of indole-derived photochromic spiroox-
azines: (a) Malatesta, V.; Millini, R.; Montanari, L. J . Am. Chem. Soc.
1995, 117, 6258. (b) Delbaere, S.; Bochu, C.; Azaroual, N.; Buntinx,
G.; Vermeersch, G. J . Chem. Soc., Perkin Trans. 2 1997, 1499. (c)
Fabian, J .; Nakazumi, H.; Matsuoka, M. Chem. Rev. 1992, 92, 1197.
(14) Push-pull substituted cyclic π-systems are of theoretical inter-
est and of importance in the field of material sciences. For an excellent
review, see: (a) Gompper, R.; Wagner, H.-U. Angew. Chem. 1988, 100,
1492; Angew. Chem., Int. Ed. Engl. 1988, 27, 1437. See also: (b)
Effenberger, F.; Schlosser, H.; Ba¨uerle, P.; Maier, S.; Port, H.; Wolf,
H. C. Angew. Chem. 1988, 100, 274; Angew. Chem., Int. Ed. Engl. 1988,
27, 281.
(15) Lindauer, D.; Beckert, R.; Do¨ring, M.; Fehling, P.; Go¨rls, H. J .
Prakt. Chem. 1995, 337, 143.
(16) (a) Langer, P.; Do¨ring, M.; Go¨rls, H.; Beckert, R. Liebigs Ann./
Receuil 1997, 2553. (b) Langer, P.; Do¨ring, M. Synlett 1998, 399. (c)
Langer, P.; Wuckelt, J .; Do¨ring, M.; Beckert, R. Eur. J . Org. Chem.
1998, 1467. (d) Do¨ring, M.; Wuckelt, J .; Langer, P.; Beckert, R.; Go¨rls,
H. J . Org. Chem. 1999, 64, 365. (e) Langer, P.; Stoll, M. Angew. Chem.
1999, 111, 1919; Angew. Chem., Int. Ed. 1999, 38, 1803. (f) Langer,
P.; Wuckelt, J .; Do¨ring, M. J . Org. Chem. 2000, 65, 729. (g) Langer,
P.; Schneider, T.; Stoll, M. Chem. Eur. J . 2000, in press. (h) Langer,
P.; Holtz, E. Angew. Chem. 2000, in press.
(9) Sanz-Cervera, J . F.; Glinka, T.; Williams, R. M. Tetrahedron
1993, 49, 8471.
10.1021/jo991701l CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/17/2000

3604 J . Org. Chem., Vol. 65, No. 12, 2000
Langer et al.
Sch em e 2. Rea ction of Dilith ia ted
Ch a r t 1
P h en yla ceton itr ile w ith Bis(im id oyl) Ch lor id e 2a
report full details and investigations related to the scope
and the limitations of this new reaction.
could be improved to 75% when the 1,1-dianion18 of 3a
(generated by addition of 2 equiv of n-BuLi to phenylac-
etonitrile) was used.19 It is important to note that the
product was formed with excellent stereoselectivity (E:Z
> 95:5). Similarly, reaction of dilithiated phenylacetoni-
trile with bis(imidoyl) chlorides 2b,c provided the E-
configured (3-imino-2,3-dihydro-1H-indol-2-ylidene)ace-
tonitriles 4b,c in 76 and 67% yields, respectively (Table
1). In all reactions reported herein, LDA rather than
n-BuLi could be equally successfully used.
Formation of the 2-alkylidene-3-iminoindole 4a can be
rationalized by the following mechanism: Initial attack
of the dianion18 on the dielectrophile gives an ambident
anionic intermediate. A 5-exo-trig cyclization subse-
quently occurs from the ortho carbon of the arylimino
group, and rearomatization leads to the final product.
The phenylimino group which does not participate in the
cyclization exerts a stereochemical bias for the enamine
formation (by interaction with the bulky phenyl group).
Therefore, an excellent stereoselectivity in favor of the
E-configured product was observed.
Resu lts a n d Discu ssion
Reaction of oxalic acid bis(imidoyl) chlorides 2 with
dianions can, in principle, result in a simple 2:1 conden-
sation, cyclization, or polymerization. Condensation of
diethyl oxalate with 2 equiv of the monoanion of phenyl-
acetonitrile was reported to give an open-chain product
which could be cyclized by treatment with acid to give
the dilactone 1g of pulvinic acid (Scheme 1).2c Very
recently, we have developed an efficient synthesis of
pyrrolo[3,2-b]pyrrole-2,5-diones by reaction of oxalic acid
bis(imidoyl) chlorides 2 with ester monoanions.16f For
example, reaction of the carbanion of ethyl phenylacetate
with oxalic acid bis(p-tolylimidoyl) chloride 2b afforded
the pyrrolo[3,2-b]pyrrole-2,5-dione 1h . On the basis of
these results, we expected that reaction of lithiated
phenylacetonitrile 3a with bis(phenylimidoyl) chloride 2a
would result in formation of an open-chain product or of
dilactam 1h .
A brief discussion of the spectroscopic data of 4b and
of other 2-alkylidene-3-iminoindoles is appropriate. The
signal of the NH group is located at 6.38 ppm. The singlet
assigned to H4 (1H NMR, CDCl3, δ ) 6.42) is shifted
upfield by ca. 1 ppm relative to 3-oxindoles. This effect
can be explained by the fact that the arylimino group
attached to C3 is twisted out of plane and H4 is located
within the anisotropic cone of the aryl group and thus
resonates at higher field. In the 13C NMR spectrum of
4b and of other 3-iminoindoles, carbon C4 is shifted
Sch em e 1. Rea ction of P h en yl Aceton itr ile w ith
Dieth yl Oxa la te a n d of Eth yl P h en yla ceta te w ith
Oxa lic Acid Bis(p-tolylim id oyl) Ch lor id e
(18) We refer to the reactive species used as nitrile and sulfone 1,1-
dianions, knowing that they may represent base-associated monolithi-
ated reagents or have
a structure different from that of a R,R-
dilithiomethane (see Conclusion section). For preparative aspects,
see: (a) Kaiser, E. M.; Solter, L. E.; Schwarz, R. A.; Beard, R. D.;
Hauser, C. R. J . Am. Chem. Soc. 1971, 93, 4237. (b) Bo¨hme, H.;
Stammberger, W. Liebigs Ann. Chem. 1971, 56. (c) Kondo, K.; Tun-
emoto, D. Tetrahedron Lett. 1975, 17, 1397. (d) Tanaka, K.; Matsui,
S.; Kaji, A. Bull. Chem. Soc. J pn. 1980, 53, 3619. (e) Eisch, J . J .; Dua,
S. K.; Behrooz, M. J . Org. Chem. 1985, 50, 3676. (f) Hendrickson, J .
J .; Boudreaux, G. J .; Palumbo, P. S. J . Am. Chem. Soc. 1986, 108, 2358.
(g) McCrombie, S. W.; Shankar, B. B.; Ganguly, A. K.; Padwa, A.;
Bullock, W. H.; Dyszlewski, A. D. Tetrahedron Lett. 1987, 28, 4127.
(h) Thomson, M. W.; Handwerker, B. M.; Katz, S. A.; Belser, R. B. J .
Org. Chem. 1988, 53, 906, and references therein.
(19) Only a few cyclization reactions of 1,1-dianions with dielectro-
philes have been reported so far. See for example: (a) Mu¨ller, J . F. K.;
Neuburger, M.; Zehnder, M. Helv. Chim. Acta 1997, 80, 2182. (b) Eisch,
J . J .; Dua, S. K.; Behrooz, M. J . Org. Chem. 1985, 50, 3674. (c)
Mussatto, M. C.; Savoia, D.; Trombini, C.; Umani-Ronchi, A. J . Chem.
Soc., Perkin Trans. 1 1980, 260.
Much to our surprise, a completely different product
was formed in this reaction: Addition of a THF solution
of lithiated 3a to a solution of bis(imidoyl) chloride 2a at
-78 °C afforded the (3-imino-2,3-dihydro-1H-indol-2-
ylidene)acetonitrile 4a in 43% yield (Scheme 2). The yield
(17) Langer, P.; Do¨ring, M. Synlett 1998, 396.

Synthesis of 2-Alkylidene-3-iminoindoles
J . Org. Chem., Vol. 65, No. 12, 2000 3605
Sch em e 3. Rea ction of Nitr ile- a n d
Su lfon e-Der ived Ca r ba n ion s w ith Bis(im id oyl)
Ch lor id es
F igu r e 1. X-ray structure of 4b: Selected bond lengths [Å]:
N(1A)-C(1A) 1.281(9), C(1A)-C(2A) 1.501(10), C(10A)-C(11A)
1.411(11), C(2A)-C(17A) 1.398(11), C(10A)-C(15A) 1.389(10),
C(12A)-C(13A) 1.398(11), N(2A)-C(2A) 1.382(9), C(1A)-
C(15A) 1.475(10), C(11A)-C(12A) 1.359(11), C(13A)-C(14A)
1.375(10), C(14A)-C(15A) 1.404(10), N(2A)-C(10A) 1.377(9).
Ta ble 1. P r ep a r a tion of 2-Alk ylid en e-3-im in oin d oles 4
a n d of Bis-En a m in es 5
yield
yield
3
4
5
R1
R2
R3
E:Za
(4) [%]b (5) [%]c
a
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
-
-
-
-
-
-
q
r
a
C6H5
C6H5
C6H5
2-naphthyl
2-naphthyl
4-(CH3)C6H4
4-(CH3O)C6H4
2-(CH3O)C6H4
3,4-(CH3O)2C6H3 CN CH3
2-pyridyl
2-thienyl
2-benzimidazolyl CN CH3
SiMe3
H
NdC(C6H5)2
2-thienylsulfonyl CN CH3
COPh
CO2Et
CN
CN CH3
H
>95:5
>95:5
75
76
67
68
51
73
72
56
67
12
68
84
34
34
21
62
0
7
0
0
0
0
0
10
0
9
53
0
X-ray diffraction of single crystals of 4b (which were
grown from a DMSO solution) unambigiously proved the
E-configuration of the exocyclic double bond (Figure 1).
The alternation of the bond lengths within the indole unit
indicates that the aromaticity of 4b is disturbed. The
p-tolyl group of the imino group is twisted out of the plane
of the indole moiety. Thus, the crystal structure showed
that the hydrogen atom H4 and the methyl group
attached to C5 are indeed located within the anisotropic
cone of the p-tolylimino group as suggested by the NMR
data. The phenyl group attached to the exocyclic double
bond is only slightly twisted out of plane. It is noteworthy
that the geometry of the nitrile group is slightly distorted
by 8° from the expected value of 180°. This can be
explained by electrostatic repulsion of the nitrogen atoms
of the nitrile and of the imine. The solvent DMSO was
incorporated in the crystal lattice and a hydrogen bond
N-H‚‚‚O was observed between the nitrogen atom of the
indole and the oxygen atom of DMSO (H‚‚‚O distance:
1.920 Å).
a
a
b
b
c
d
e
f
g
h
i
j
j
-
-
-
-
-
b
-
c
d
-
-
-
-
-
-
e
f
g
h
i
CN OCH3 >95:5
CN CH3 >95:5
CN OCH3 >95:5
CN
CN
CN
H
H
H
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
5:1
CN CH3
CN CH3
0
0
0
0
CN
CN
CN
H
H
H
5:1
1:6
k
l
<5:95
0
m
n
n
o
p
q
r
r
s
t
CN CH3
CN
CN CH3
CN CH3
CN CH3
-
14
48
72
56
36
44
0
0
0
0
0
H
-
0
0
0
0
CO2Et
-
CO[N(CH2)5]
CO[N(CH2)4O]
2-pyridyl
SO2Ph
SO2Ph
SO2Ph
-
-
j
H
CN
CH3
H
-
0
-
-
-
-
-
<5:95
<5:95
<5:95
1:2
74
77
21
61
58
CN CH3
CH3
s
t
u
H
SO2Ph
SO2Ph
Ph CH3
Ph OCH3
To investigate the scope and the limitations of the new
cyclization reaction, the substituents were systematically
varied (Scheme 3, Table 1). Treatment of 2-naphthyl-
acetonitrile 3b with bis(imidoyl) chlorides 2b,c afforded
the E-configured 2-alkylidene-3-iminoindoles 4d ,e in good
yields. Reaction of methyl- and methoxy-substituted aryl
acetonitriles 3c-f with 2a or 2b gave the indoles 4f-i
in good yields. In contrast, reaction of 2-pyridylacetoni-
trile 3g with 2b gave a complex reaction mixture from
which the indole derivative 4j could be isolated in only
12% yield. The major product of this reaction was the
open-chain bis-enamine 5d . In the reactions of all other
aryl acetonitriles, open-chain products were isolated in
only low yields or not at all. The reactions of 2-thienyl
acetonitrile 3h and 2-benzimidazolyl acetonitrile 3i with
bis(imidoyl) chloride 2b stereoselectively afforded the
deeply red and orange colored indoles 4k and 4l in 68
and 84% yields, respectively. The use of trimethylsilyl
acetonitrile 3j afforded a 1:5 mixture of the indoles 4m
t
1:2
a
b
Stereochemical assignment based on analogy to 4b. Isolated
yields. For 4m ,n : combined yield of 4m and 4n . c Isolated yields.
The yields of 5d -j refer to experiments where 2 rather than only
1 equiv of the nucleophile was used.
upfield. As expected, this effect is not observed for carbon
C7 which is located on the opposite side of the molecule.
The presence of the nitrile-substituted exocyclic double
bond and the presence of the imino group results in a
downfield shift of the signal of carbon atom C2 by 23.2
ppm relative to carbon C2 of indole. In the 1H NMR
spectrum of 4b, a significant difference (0.36 ppm)
between the chemical shifts of the two methyl groups is
observed. This difference is characteristic also for all
other 2-alkylidene-3-iminoindoles 4 derived from bis-
(imidoyl) chlorides 2b,c and can again be explained by
location of the methyl or the methoxy group attached to
carbon C5 within the anisotropic cone of the arylimino
group which results in a shift of the respective signals
to higher field relative to the methyl or methoxy group
attached at the arylimino group.
1
and 4n (34% yield by H NMR). The latter was presum-
ably formed by base-induced desilylation of the initially
formed trimethylsilyl-substituted indole 4m . Reaction of

3606 J . Org. Chem., Vol. 65, No. 12, 2000
Langer et al.
Sch em e 4. Cycliza tion Rea ction s of Su bstitu ted
Ben zim id a zoles w ith 2b
Ph2CdNCH2CN 3k with bis(imidoyl) chloride 2a gave the
corresponding indole 4o. Reaction of thienylsulfonyl
acetonitrile 3l with 2b gave the 2-alkylidene-3-iminoin-
dole 4p in good yield.
Treatment of sodium diethyl malonate with oxalic acid
bis(m-chlorophenylimidoyl) chloride was reported to give
the corresponding open-chain bis-enamine in low yield.20
Reaction of 2 equiv of benzoyl acetonitrile 3m with 2b
gave the bis-enamine 5e and treatment of 2 equiv of ethyl
cyanoacetate 3n with the bis(imidoyl) chlorides 2a and
2b afforded the bis-enamines 5f and 5g rather than the
corresponding 2-alkylidene-3-iminoindoles.16d Likewise,
reaction of N-(cyanoacetyl)piperidine and -morpholine 3o
and 3p afforded the open-chain bis-enamines 5h and 5i.
Reaction of 2 equiv of lithiated 2-picoline 3q with 2a
afforded the open-chain product 5j. The open-chain
products 5e-j were obtained as the major products also
when only one rather than 2 equiv of the nucleophile and
2 equiv of LDA were employed. Again no 2-alkylidene-
3-iminoindoles could be isolated in these reactions. Ac-
cording to the 1H and 13C spectra of all condensation
products 5, symmetrical structures are adopted in solu-
tion. The configuration of the double bonds of the dienes
was proven by NMR: as indicated by the low field shifts
(1H NMR) of the respective N-H hydrogen atoms of 5e-
i, isomers containing intramolecular hydrogen bonds (N-
H‚‚‚O) are present in solution. Similarly, intramolecular
hydrogen bonds (N-H‚‚‚N) involving the pyridine func-
tionality were present for the pyridine-subtituted dienes
5d and 5j. For dienes 5a -c, symmetrical structures are
also adopted. However, the configuration of the double
bonds could not be unambigiously determined. It is
noteworthy, that the resonance of the intramolecular
hydrogen bond (N-H‚‚‚O) of the amide 5h is shifted
upfield relative to the resonances of the esters 5f,g. The
N-H resonances of the esters are shifted upfield relative
to the respective resonance of the ketone 5e. It is
noteworthy that 1,4-diazabutadienes and 2,3-diamino-
butadienes have recently been used as efficient ligands
in transition metal-catalyzed olefin polymerization reac-
tions.21,22
u
Ta ble 2. UV-Vis Da ta of Selected In d oles 4
4
λmax (lg ꢀ) (acetonitrile/nm)
b
g
i
283 (4.26), 309 (4.14), 480 (3.98)
347 (4.15), 484 (3.75)
281 (4.33), 487 (4.05)
l
279 (4.40), 331 (3.97), 481 (3.82)
265 (4.38), 476 (3.91)
279 (4.50), 473 (4.02)
p
q
t
281 (4.32), 465 (3.87)
the 2-alkylidene-3-iminoindoles 4q-u in good yields
(except for 4s): Employment of phenylsulfonyl acetoni-
trile 3r with 2a ,b afforded the indoles 4q,r with very good
stereocontrol. Treatment of bis(imidoyl) chloride 2b with
methyl phenyl sulfone 3s gave the indole 4s in low yield.
Reaction of benzylphenyl sulfone 3t with bis(imidoyl)
chlorides 2b,c resulted in formation of the indoles 4t and
4u in good yields. However, due to the similar steric
demand of the phenylsulfonyl and the phenyl group
attached to the exocyclic double bond, 2-alkylidene-3-
iminoindoles 4t and 4u were obtained as a mixture of
stereoisomers (E:Z ) 1:2).
In the reaction of bis(imidoyl) chloride 2b with 2-(cya-
nomethyl)benzimidazole (3i), the 2-alkylidene-3-iminoin-
dole 4l was formed in 84% yield (s. a.). In contrast,
regioselective cyclization via the nitrogen atom of the
benzimidazole moiety was observed when 2b was treated
with dilithiated 2-methylbenzimidazole 3u to give the
orange-colored 1-(arylimino)-1H-pyrrolo[1,2-a]benzimi-
dazol-2-amine 6a (Scheme 4).16b This type of cyclization
could be induced also for 2-(cyanomethyl)benzimidazole
3i when triethylamine rather than n-BuLi was used as
the base to give the 1H-pyrrolo[1,2-a]benzimidazole 6b
in moderate yield.
The reaction of sulfone-dianions with bis(imidoyl)
chlorides resulted in clean cyclization reactions to give
(20) Price, C. C.; Velzen, B. J . Org. Chem. 1947, 12, 386.
(21) (a) J ohnson, L. K.; Killian, C. M.; Brookhart, M. J . Am. Chem.
Soc. 1995, 117, 6414. (b) J ohnson, L. K.; Mecking, S.; Brookhart, M.
J . Am. Chem. Soc. 1996, 118, 267. (c) Killian, C. M.; Tempel, D. J .;
J ohnson, L. K.; Brookhart, M. J . Am. Chem. Soc. 1996, 118, 11664.
(d) Killian, C. M.; J ohnson, L. K.; Brookhart, M. Organometallics 1997,
16, 2005. (e) Abu-Surrah, A. S.; Rieger, B. Angew. Chem. 1996, 108,
2627; Angew. Chem., Int. Ed. Engl. 1996, 35, 2475.
(22) (a) van Koten, G.; Vrieze, K. Adv. Organomet. Chem. 1982, 21,
151. (b) Vrieze, K. J . Organomet. Chem. 1986, 300, 307. (c) tom Dieck,
H.; Dietrich, J . Chem. Ber. 1984, 117, 694.
(23) For an excellent review to the structure of lithiated and
dilithiated nitriles and sulfones, see: Boche, G. Angew. Chem. 1989,
101, 286; Angew. Chem., Int. Ed. Engl. 1989, 28, 277.
The UV-vis spectra of 2-alkylidene-3-iminoindoles 4
exhibit strong πfp* absorptions λ2 and λ3, and the colors
of the indoles vary from orange (for 4m ) to deep red (for
4k ). The high absorption coefficients can be explained
by the indigo-type electronic structure of the 3-iminoin-
doles 4 which can thus be regarded as heterocyclic mero-
cyanines. It is interesting to compare cyano-substituted
indoles (R2 ) CN) containing different substituents R1
(Table 2): Relative to 4b (R1 ) Ph), bathochromic shifts
are observed for indoles containing electron-donating aryl
groups (4g, 4i). In contrast, hypsochromic effects are
observed for sulfone-substituted indoles (4p , 4q, and 4t).
(24) For the structure of R,ortho-dilithio sulfones, see: (a) Vollhardt,
J .; Gais, H.-J .; Lukas, K. L. Angew. Chem. 1985, 97, 607; Angew.
Chem., Int. Ed. Engl. 1985, 24, 608. (b) Gais, H.-J .; Vollhardt, J .
Tetrahedron Lett. 1988, 29, 1529.
Con clu sion s. To explain the formation of 2-alkyli-
dene-3-iminoindoles 4, open-chain products 5 and pyr-
rolo[3,2-b]pyrrole-2,5-diones it is interesting to compare
representative substrates (Chart 2).
(25) For the structure of a R,R-dilithio sulfone, see: (a) Gais, H.-J .;
Vollhardt, J .; Lukas, K. L. Angew. Chem. 1985, 97, 607; Angew. Chem.,
Int. Ed. Engl. 1985, 24, 608. (b) Gais, H.-J .; Vollhardt, J .; Gu¨nther,
H.; Moskau, D.; Lindner, H. J .; Braun, S. J . Am. Chem. Soc. 1988,
110, 978.
(26) For the structure of monolithio sulfones, see: Gais, H.-J .;
Vollhardt, J .; Lukas, K. L. Angew. Chem. 1986, 98, 916; Angew. Chem.,
Int. Ed. Engl. 1986, 25, 939.
(27) Crowley, P. J .; Leach, M. R.; Meth-Cohn, O.; Wakefield, B. J .
Tetrahedron Lett. 1986, 27, 2909.
(28) For the structure of a true R,R-dilithio nitrile, see: Zarges, W.;
Marsch, M.; Harms, K.; Boche, G. Chem. Ber. 1989, 122, 1307.
(29) For the structure of R-cyanbenzyllithium in the solid state,
see: (a) Boche, G.; Marsch, M.; Harms, K. Angew. Chem. 1986, 98,
373; Angew. Chem., Int. Ed. Engl. 1986, 25, 373. For the structure in
solution, see: (b) Bauer, W.; Seebach, D. Helv. Chim. Acta 1984, 67,
1972. (c) Das, R.; Wilkie, C. A. J . Am. Chem. Soc. 1972, 94, 4555.

Synthesis of 2-Alkylidene-3-iminoindoles
J . Org. Chem., Vol. 65, No. 12, 2000 3607
Ch a r t 2. Rea ction of Selected Su bstr a tes w ith
The use of diethyl malonate, ethyl cyanoacetate 3n ,
or cyano-substituted amides 3o,p, containing two electron-
withdrawing groups, resulted in formation of the open-
chain products 5e-i, respectively. Interestingly, employ-
ment of (phenylsulfonyl)acetonitrile 3r , a sulfone contain-
ing a cyano rather than an aryl substituent, resulted in
clean cyclization reactions to give the 2-alkylidene-3-
iminoindoles 4q,r . The striking difference between sub-
strates 3n -p and 3r can be explained by the fact that,
in contrast to phenyl sulfones, substrates 3n -p cannot
be transformed into 1,1-dianions. In these reactions,
indole formation requires deprotonation of the initially
formed condensation product. However, this reaction
appears to be slow compared to attack of a second equiv-
alent of the nucleophile onto the imidoyl chloride group.
Alternatively, it is possible that the deprotonation does
take place, but does not lead to cyclization. This can be
explained by the fact that for 3n -p the negative charge
is localized at the oxygen atom rather than delocalized
within the aryl group from where the cyclization can
occur. Reaction of ethyl phenylacetate with bis(imidoyl)
chloride 2b resulted in formation of the pyrrolo[3,2-b]-
pyrrole-2,5-dione 1h , due to nucleophilic attack of the
nitrogen atoms onto the electrophilic ester groups.16f
Oxa lic Acid bis(p-tolylim id oyl) Ch lor id e 2ba
aBelow the formulas the numbers and the yields of the main
products are given.
Sch em e 5. F or m a tion a n d Rea ction s of Su lfon e
Dia n ion s
In summary, reaction of lithiated nitriles and sulfones
with oxalic acid bis(imidoyl) chlorides provided an ef-
ficient and stereoselective synthesis of a variety of
2-alkylidene-3-iminoindoles from simple starting materi-
als. Variation of the bis(imidoyl) chloride and the dianion
allowed the introduction of different substituents both
at the indole moiety and at the exocyclic double bond,
respectively. In contrast to known methods for the
preparation of 2-alkylidene-3-oxindoles, protection of the
indole nitrogen is not necessary, since the latter is formed
during the cyclization. Our current work is directed
toward application of the new cyclization reaction to the
synthesis of alkaloids.
Sch em e 6. F or m a tion a n d Rea ction s of Nitr ile
Dia n ion s
Exp er im en ta l Section
Gen er a l Com m en ts. All solvents were dried by standard
methods, and all reactions were carried out under an inert
atmosphere. The oxalic acid bis(imidoyl) dichlorides 2 were
1
prepared according to literature procedures.15 For the H and
2-Alkylidene-3-iminoindoles 4 could be prepared in
good yields exclusively from starting materials which are
known to form “1,1-dianions”. The presence of an aryl
group in the dianionic substrate is advantageous. How-
ever, cyclizations could also be induced employing methyl
phenyl sulfone 3s, cyanomethyl phenyl sulfone 3r and
(trimethylsilyl)acetonitrile 3j.
Sulfones are known to form true dianions: the lithia-
tion occurs at the CH2 group and at the ortho position of
the phenyl group (Scheme 5). At elevated temperature
the R,ortho-dianion rearranges to a R,R-dianion. At low
temperature, the first attack of the R,ortho-dianion onto
the electrophile occurs at the R-carbon atom and subse-
quent rearrangement affords an R-monoanion which
subsequently reacts with the second equivalent of the
electrophile to give a R,R-difunctionalized sulfone. It is
known that treatment of nitriles with 2 equiv of LDA
results in formation of monoanions associated with 1
equiv of the base rather than in formation of a true
dianion (Scheme 6). However, treatment of these re-
agents with 2 equiv of an electrophile gives rise to
formation of R,R-difunctionalized products by deproto-
nation of the initially formed condensation product.
13C NMR spectra (1H NMR: 200, 300, and 400 MHz, 13C
NMR: 50, 75, and 100 MHz), the deuterated solvents indicated
were used. The multiplicity of the 13C NMR signals were
determined with the DEPT 135 technique and quoted as CH3,
CH2, CH, and C for primary, secondary, tertiary, and quater-
nary carbon atoms. Mass spectral data (MS) were obtained
using the electron ionization (70 eV) or the chemical ionization
technique (CI, H2O). For the preparative scale chromatogra-
phy, silica gel (60-200 mesh) was used. Melting points are
uncorrected. Elemental analyses were performed at the mi-
croanalytical laboratories of the Universities of Go¨ttingen and
J ena.
X-r a y Diffr a ction . The crystals were measured on a CAD4
diffractometer using graphite-monochromated Mo KR radia-
tion. Data were corrected for Lorentz and polarization effects,
but not for absorption. The structures were solved by direct
methods (SHELXS) and refined by full-matrix least squares
techniques against F2 (SHELXL-93).
Cr ysta l Da ta for (4b): C24H19N3‚C2H6OS, Mr ) 855.10
gmol-1, red quader, size 0.40 × 0.38 × 0.36 mm3, monoclinic,
space group P2(1) No. 4, a ) 10.059(2), b ) 45.792(9), c )
10.297(2) Å, â ) 108.09(3)°, V ) 4508(1) Å3, Z ) 8, Fcalcd
)
1.26 gcm-3, µ (Mo KR) ) 1.66 cm-1, F(000) ) 1808, 9764
refelctions in (h, -k, -l, measured in the range 19.1° e Θ e
22.1°, 9258 independent reflections, Rint ) 0.068, 1137 param-

3608 J . Org. Chem., Vol. 65, No. 12, 2000
Langer et al.
eters, R ) 0.063, wR2 ) 0.152, GOOF ) 1.18, largest difference
125.72, 126.81, 126.90, 126.95, 127.80, 128.02, 128.13, 129.39,
129.80, 134.06 (CH, Ph, Naph, C-6), 130.52, 131.38, 132.81,
133.49, 135.21 (C, C-5, Naph-C, Tol-C to C), 145.62, 147.90
(C, C-2, Tol-C to N), 156.50 (C, C-7a), 156.54 (C, C-3). IR (KBr,
cm-1): 3300 (br), 3024 (w), 2920 (w), 2198 (m, CN), 1640 (m),
1618 (m), 1586 (s), 1500 (m), 1480 (s); 1328 (m), 1220 (m), 815
(m). MS-FAB: 401 (100, M+ + 2), 400 (65.0, M+ + 1), 399 (75.4,
M+), 398 (76.6, M+ - 1), 309 (32.9), 295 (31.6). Anal. Calcd for
peak: 0.50 eÅ-3
.
Gen er a l P r oced u r e for th e P r ep a r a tion of (3-Im in o-
2,3-d ih yd r o-1H-in d ol-2-ylid en e)a ceton itr iles a n d -su l-
fon es (4). To a THF solution (20 mL) of the nitrile or sulfone
(6 mmol; volume or weight is indicated in each following
section) was added n-BuLi (9.8 mL, 2.2 molar equiv., 1.6 M
solution in hexane) at 0 °C. A clear yellow solution was formed.
After stirring for 60 min at 0 °C, the solution was transferred
within 10 min to a stirred THF solution (80 mL) of the bis-
(imidoyl) chloride 2 at -78 °C. The color of the solution
changed to green. The temperature was allowed to rise to 20
°C within 30 min to give a deep green to black solution. After
stirring for 2 h at 20 °C, the reaction mixture was poured into
100 mL of water. The color of the organic layer changed to
deep red. The aqueous layer was extracted five times with a
mixture of THF and ethyl ether (1:4, 200 mL). The combined
organic layers were dried (MgSO4) and filtered, and the solvent
was removed in vacuo. Addition of ethyl ether (15 mL) to the
crude product resulted in precipitation of intensely red colored
4 which was washed with ethyl ether (50 mL) and dried in
vacuo. In case of the products 4c, 4e-k , 4m -p , and 4s-u ,
purification by chromatography (silica gel, ethyl ether:petro-
leum ethyl ether ) 1:10 f 3:1) was necessary. In all reactions
LDA rather than n-BuLi can be used.
(2E,3E)-[1,3-Dih yd r o-3-(p h en ylim in o)-2H-in d ol-2-ylid e-
n e]p h en yla ceton itr ile (4a ). Starting with 0.69 mL of phenyl
acetonitrile, 1.46 g (76%) of 4a was isolated as deep orange
crystals, mp 153-156 °C. 1H NMR (DMSO-d6, 200 MHz): δ
6.42 (d, J ) 8 Hz, 1 H, H-4), 6.62 (t, J ) 8 Hz, 1 H, H-5), 6.95-
7.75 (m, 12 H, Ar), 10.38 (br, 1 H, NH). 13C NMR (DMSO-d6,
50 MHz): δc 84.36 (C, CCN), 112.20, 117.91 (CH, C-4, C-7),
117.19 (C, CN), 119.77 (C, C-3a), 120.56, 124.59, 125.83,
128.41, 129.02, 129.46, 129.82, 134.07 (CH, Ph, C-5, C-6),
133.84 (C, Ph-C to C), 146.90, 149.34, 150.84 (C, C-2, Tol-C to
N, C-7a), 157.76 (C, C-3). IR (KBr, cm-1): 3300 (w); 3060 (w),
2195 (m, CN), 1642 (m), 1618 (s), 1590 (s), 1464 (s), 1341 (m),
1218 (s), 1148 (m), 1100 (m), 750 (m). MS (FAB): 322 (100,
M+ + 1). Anal. Calcd for C22H15N3: C 82.23, H 4.70, N 13.07.
Found: C 80.94, H 5.26, N 12.20.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-[(4-m eth ylp h en yl)im i-
n o]-2H-in d ol-2-ylid en e]p h en yla ceton itr ile (4b). Starting
with 0.69 mL of phenyl acetonitrile, 1.57 g (75%) of 4b was
isolated as red crystals, mp 155-157 °C. 1H NMR (CDCl3, 200
MHz): δ ) 2.06, 2.42 (s, 6H, Tol-CH3), 6.42 (s, 1H, H-4), 6.71
(d, J ) 8 Hz, 1H, H-7), 6.90-7.70 (m, 10H, Ar). 13C NMR
(DMSO-d6, 50 MHz): δc ) 20.72, 20.78 (Tol-CH3), 83.63 (C,
CCN), 111.89, 118.09 (CH, C-4, C-7), 117.30 (C, CN), 119.93
(C), 120.55, 125.82, 128.95, 129.40, 130.09, 134.64 (CH, Ph,
Tol, C-6), 129.16, 133.67, 134.01 (C, C-5, Ph-C, Tol-C to C),
147.32, 148.13 (C, C-2, Tol-C to N), 157.62 (C, C-7a), 158.64
(C, C-3). IR (KBr, cm-1): 3300 (br), 3025 (w), 2922 (w), 2198
(m, CN), 1643 (m), 1620 (s), 1587 (s), 1502 (m), 1488 (s), 1332
(m), 1220 (s), 815 (m). MS (FAB): 350 (100, M+ + 1). Anal.:
Calcd. for C24H19N3: C 82.50, H 5.48, N 12.02. Found C 81.92,
H 5.88, N 11.60.
(2E,3E)-[1,3-Dih yd r o-5-m eth oxy-3-[(4-m eth oxyp h en yl)-
im in o]-2H-in d ol-2-ylid en e]p h en yla ceton itr ile (4c). Start-
ing with 0.69 mL of phenyl acetonitrile, 1.53 g (67%) of 4c was
isolated as red crystals, mp 160-163 °C. 1H NMR (CDCl3, 200
MHz): δ ) 3.45, 3.80 (s, 6H, OCH3), 6.48 (d, 1 H, H-4), 6.70
(m, 2 H, Ar), 7.00-8.00 (m, 10 H, Ar). 13C NMR (CDCl3, 75
MHz): δc ) 55.47, 55.72 (OCH3), 86.29 (C, CCN), 112.10, 118.02
(CH, C-4, C-11), 117.10 (C, CN), 119.71 (C, C-3a), 120.52,
125.82, 128.95, 129.40, 130.09, 131.64, 132.01 (C, C-13, Ph-C,
Tol-C to C), 141.20, 142.78, 147.32, 148.13, 157.62, 158.64. MS
(FAB): 382 (100, M+ + 1).
C
28H21N3: C 84.19, H 5.30, N 10.51. Found: C 84.01, H 5.35,
N 10.22.
(2E,3E)-[1,3-Dih yd r o-5-m eth oxy-3-[(4-m eth oxyp h en yl)-
im in o]-2H-in d ol-2-ylid en e](2-n a p h th yl)a ceton itr ile (4e).
Starting with 1.00 g of 2-naphthylacetonitrile, 1.31 g (51%) of
4e was isolated as a red solid, mp 170-173 °C. 1H NMR
(CDCl3, 200 MHz): δ ) 3.47, 3.85 (s, 6H, OCH3), 6.45 (d, 1 H,
H-4), 6.78 (m, 2 H, Ar), 6.98 (m, 4 H, Ar), 7.40-8.10 (7 H, Ar).
13C NMR (CDCl3, 75 MHz): δc ) 55.51, 55.60 (OCH3), 85.29
(C, CCN), 110.68, 111.43 (CH, C-4, C-7), 114.50 (CH, Ar),
118.66 (C, CN), 119.53 (C, Ar), 120.21, 120.25, 125.68, 126.85,
126.88, 127.76, 127.96, 128.07, 129.31, 131.35, 132.75, 133.43,
141.82, 143.31, 148.21, 154.06, 156.55, 157.27. MS (FAB): 432
(100, M+ + 1).
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-(p h en ylim in o)-2H-in -
d ol-2-ylid en e](4-m eth ylp h en yl)a ceton itr ile (4f). Starting
with 0.53 g of (4-methylphenyl)acetonitrile, 0.98 g (73%) of 4f
was isolated as orange solid, mp 161-163 °C. 1H NMR (DMSO-
d6, 200 MHz): δ ) 2.39 (s, 3 H, Tol-CH3), 6.39 (d, J ) 8 Hz, 1
H, H-4), 6.60 (t, J ) 8 Hz, 1 H, Ar), 6.90-7.00 (m, 3 H, Ar),
7.15-7.55 (m, 8 H, Ar). 13C NMR (DMSO-d6, 50 MHz): δc )
20.86 (Tol-CH3), 84.31 (C, CCN), 111.96, 116.99, 117.71,
120.27, 124.36, 125.61, 128.70, 129.61, 129.82, 130.66, 133.84,
137.85, 146.39, 149.13, 150.69, 157.49. MS (70 eV): 335 (44,
M+), 334 (100, M+ - 1). Anal. Calcd for C23H17N3: C 82.37, H
5.11, N 12.52. Found: C 82.54, H 5.02, N 12.27.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-(p h en ylim in o)-2H-in -
d ol-2-ylid en e]-(4-m eth oxyp h en yl)a ceton itr ile (4g). Start-
ing with 0.525 g of (4-methoxyphenyl)acetonitrile, 1.01 g (72%)
1
of 4g was isolated as orange solid, mp 157-159 °C. H NMR
(DMSO-d6, 200 MHz): δ ) 3.83 (s, 3 H, OCH3), 6.40 (d, J ) 8
Hz, 1 H, H-4), 6.60 (t, J ) 8 Hz, 1 H, Ar), 7.00 (m, 3 H, Ar),
7.10 (d, J ) 8 Hz, 2 H, Ar), 7.25 (m, 2 H, Ar), 7.50 (m, 2 H,
Ar), 7.55 (d, J ) 8 Hz, 2 H, Ar). 13C NMR (DMSO-d6, 50 MHz):
δc ) 55.37 (OCH3), 84.33 (C, CCN), 111.93, 114.73, 117.04,
117.73, 119.63, 120.18, 124.31, 125.59, 129.61, 130.22, 133.80,
146.02, 149.14, 150.74, 157.44, 159.12. MS (CI, H2O): 352 (100,
M+ - 1). Anal. Calcd for C23H17N3O: C 78.62, H 4.88, N 11.95.
Found: C 78.38, H 5.02, N 11.66.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-(p h en ylim in o)-2H-in -
d ol-2-ylid en e](2-m eth oxyp h en yl)a ceton itr ile (4h ). Start-
ing with 0.525 g of (2-methoxyphenyl)acetonitrile, 785 mg
(56%) of 4h was isolated as an orange solid, mp 149-152 °C.
1H NMR (acetone-d6, 200 MHz): δ ) 3.92 (s, 3 H, OCH3), 6.58
(m, 2 H, Ar), 6.83 (d, J ) 8 Hz, 1 H, Ar), 7.00-7.50 (m, 10 H,
Ar), 8.98 (br, 1 H, NH). 13C NMR (acetone-d6, 50 MHz): δc )
55.16 (OCH3), 82.37 (C, CCN), 111.13, 111.95, 117.67, 117.84,
120.12, 121.02, 122.00, 124.17, 126.23, 129.50, 130.51, 131.16,
133.69, 147.32, 149.00, 151.35, 157.16, 157.20. MS (CI, H2O):
352 (100, M+ - 1). Anal. Calcd for C23H17N3O: C 78.62, H 4.88,
N 11.95. Found: C 78.44, H 5.10, N 11.78.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-[(4-m eth ylp h en yl)im i-
n o]-2H -in d ol-2-ylid en e](3,4-d im et h oxyp h en yl)a cet on i-
tr ile (4i). Starting with 0.8 g of (3,4-dimethoxyphenyl)-
acetonitrile, 1.24 g (67%) of 4i was isolated as an orange solid,
1
mp 155-157 °C. H NMR (CD2Cl2, 400 MHz): δ ) 2.04, 2.42
(2 × s, 2 × 3 H, Tol-CH3), 3.83, 3.86 (2 × s, 2 × 3 H, OCH3),
6.55 (s, 1 H, H-4), 6.71 (d, 1 H, Ar), 6.90-7.20 (m, 7 H, Ar),
7.27 (s, 1 H, NH). 13C NMR (CD2Cl2, 100 MHz): δc ) 20.90,
21.02 (Tol-CH3), 56.22, 56.34 (OCH3), 85.77 (C, CCN), 110.81,
112.15, 112.26, 118.39, 118.69, 119.62, 120.06, 126.65, 127.11,
130.30, 130.69, 134.48, 134.65, 146.11, 147.56, 148.41, 149.78,
150.20, 157.12. IR (Nujol, cm-1): 3324 (m), 3300 (m), 2195 (m,
CN), 1730 (s), 1643 (s), 1618 (s), 1589 (s), 1515 (s), 1464 (s),
1377 (m), 1254 (s), 1207 (s). Anal. Calcd for C26H23N3O2: C
76.27, H 5.66, N 10.26. Found: C 76.48, H 5.40, N 10.54.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-[(4-m eth ylp h en yl)im i-
n o]-2H-in dol-2-yliden e](2-n aph th yl)aceton itr ile (4d). Start-
ing with 1.00 g of 2-naphthylacetonitrile, 1.63 g (68%) of 4d
1
was isolated as a red solid, mp 167-170 °C. H NMR (CDCl3,
400 MHz): δ 2.08, 2.42 (s, 6 H, Tol-CH3), 6.62 (s, 1 H, H-4),
6.72 (d, J ) 8 Hz, 1 H, Ar), 6.90-8.00 (m, 16 H, Ar). 13C NMR
(CDCl3, 100 MHz): δc 20.91, 21.08 (Tol-CH3), 85.44 (C, CCN),
110.78, 118.18 (CH, C-4, C-7), 118.19 (C, CN), 119.38 (C, C-3a),

Synthesis of 2-Alkylidene-3-iminoindoles
J . Org. Chem., Vol. 65, No. 12, 2000 3609
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-[(4-m eth ylp h en yl)im i-
n o]-2H-in d ol-2-ylid en e](2-p yr id yl)a ceton itr ile (4j). Start-
ing with 708 mg of (2-pyridyl)acetonitrile, 252 mg (12%) of 4j
was isolated as a deep red solid. This compound was contami-
nated by ca. 15% of an inseparable impurity. 1H NMR (CDCl3,
200 MHz): δ ) 2.08, 2.40 (2 × s, 2 × 3 H, Tol-CH3), 6.90-
7.80 (m, 11 H, Ar). IR (KBr, cm-1): 3348 (m); 3028 (w), 2920
(w), 2208 (m, CN), 1604 (s), 1560 (s), 1508 (m), 1464 (w), 1332
(w), 1260 (w), 1176 (m). MS (210 °C): 350 (10, M+ + 1), 349
(16, M+), 337 (26.8), 261 (63.8), 234 (64.9).
(2Z,3E )-N -[1,2-Dih yd r o-5-m e t h yl-2-[cya n o(2-t h ia zo-
lylsu lfon yl)m eth ylen e]-3H-in d ol-3-ylid en e]-4-m eth ylben -
zen a m in e (4p ). Starting with 0.9 g of cyanomethyl (2-thiaz-
olyl) sulfone, 1.25 g (62%) of 4p was isolated as a deep orange
solid, mp 158-161 °C. 1H NMR (DMSO-d6, 200 MHz): δ 2.00,
2.31 (2 × s, 2 × 3 H, Tol-CH3), 6.47 (s, 1 H, H-4), 7.00 (d, 2 H,
Ar), 7.10-7.40 (m, 5 H, Ar), 7.97 (d, 1 H, Hetar), 8.16 (d, 1 H,
Hetar), 11.28 (s, 1 H, NH). 13C NMR (DMSO-d6, 50 MHz): δc
20.45, 20.53 (Tol-CH3), 84.02, 113.53, 116.34, 117.91, 125.35,
128.48, 128.55, 129.82, 132.06, 133.75, 134.70, 134.99, 135.83,
141.05, 145.42, 146.28, 151.17, 157.00. IR (Nujol, cm-1): 3324
(m), 2194 (m, CN), 1643 (m), 1603 (m), 1584 (s), 1462 (s), 1377
(m), 1316 (m), 1131 (m). MS (CI, H2O): 420 (M+ + 1).
(2Z,3E)-N-[1,2-Dih yd r o-2-[cya n o(p h en ylsu lfon yl)m eth -
ylen e]-3H-in dol-3-yliden e]ben zen am in e (4q). Starting with
1.09 g of (phenylsulfonyl)acetonitrile, 1.71 g (74%) of 4q was
isolated as a deep orange solid, mp 159-162 °C. 1H NMR
(DMSO-d6, 400 MHz): δ 6.50 (d, J ) 8 Hz, 1 H, H-4), 6.81 (t,
J ) 8 Hz, 1 H, H-5), 7.01 (d, J ) 9 Hz, 2 H, Ar), 7.25-7.65 (m,
8 H, Ar), 7.78 (m, 2 H, Ar), 11.42 (br, 1 H, NH). 13C NMR
(DMSO-d6, 100 MHz): δc 84.12 (C, CCN), 112.65, 117.82 (CH,
C-4, C-7), 114.72 (C, CN), 116.60 (C, C-3a), 120.75, 123.31,
125.72, 125.78, 127.19, 129.91, 130.18, 134.70 (CH, Ph, C-5,
C-6), 140.28 (C, Ph-C to S), 147.92, 149.50 (C, C-2, Ph-C to
N), 157.82 (C, C-7a), 158.92 (C, C-3). IR (KBr, cm-1): 3332
(m), 3060 (m), 2196 (m, CN), 1636 (m), 1620 (m), 1580 (s), 1464
(s); 1344 (m), 1320 (m), 1140 (m), 1080 (m), 1008 (w). MS (190
°C): 386 (7.5, M+ + 1), 385 (4.6, M+), 320 (7.1), 244 (100). Anal.
Calcd for C22H20N3O2S: C 68.56, H 3.92, N 10.90. Found: C
68.13, H 4.32, N 10.38.
(2E,3E)-[1,3-Dih yd r o-5-m eth yl-3-[(4-m eth ylp h en yl)im i-
n o]-2H-in d ol-2-ylid en e](2-th ien yl)a ceton itr ile (4k ). Start-
ing with 492 mg of (2-pyridyl)acetonitrile, 252 mg (68%) of 4k
1
was isolated as a red solid. H NMR (CDCl3, 200 MHz): δ )
2.06, 2.36 (2 × s, 2 × 3 H, Tol-CH3), 6.60-7.60 (m, 10 H, Ar).
IR (KBr, cm-1): 3346 (m); 3032 (w), 2918 (w), 2209 (m, CN),
1600 (s), 1564 (s), 1512 (m), 1332 (w), 1180 (m). MS (CI, H2O):
356 (100, M+ + 1). Anal. Calcd for C22H17N3S: C 74.34, H 4.82,
N 11.82. Found: C 74.45, H 4.60, N 12.04.
P r ep a r a t ion of (2E,3E)-{1,3-Dih yd r o-5-m et h yl-3-[(4-
tolyl)im in o]-2H-in d ol-2-ylid en e}ben zim id a zole-2-a ceto-
n itr ile (4l). To a THF solution (30 mL) of 1.57 g of 2-(cya-
nomethyl)benzimidazole (10 mmol) was added at 0 °C a THF
solution (50 mL) of 33 mmol of LDA which was prepared
starting with 3.3 mL of diisopropylamine and with 21 mL of a
1.6 M solution of n-BuLi in n-hexane. After being stirred for 2
h, the solution was cooled to -20 °C and a THF solution (50
mL) of 3.05 g of 2b (10 mmol) was added. The temperature
was allowed to rise to 20 °C, and the mixture was stirred for
2 h. The solution was poured into 250 mL of a 5 M aqueous
solution of NH4Cl and was extracted three times with a THF/
Et2O mixture (1:1, 200 mL). The combined organic fractions
were dried (MgSO4) and filtered, and the solvent of the filtrate
was removed in vacuo. To the residue was added ethyl ether
(2 mL), and the precipitated deep red solid was recrystalized
from toluene to give 1.64 g (84%) of red crystals, mp 324-327
(2Z,3E)-N-[1,2-Dih yd r o-5-m et h yl-2-[cya n o(p h en ylsu l-
fo n y l)m e t h y le n e ]-3H -in d o l-3-y lid e n e ]-4-m e t h y lb e n -
zen a m in e (4r ). Starting with 1.09 g of (phenylsulfonyl)-
acetonitrile, 1.91 g (77%) of 4r was isolated as a red solid, mp
157-159 °C. 1H NMR (DMSO-d6, 400 MHz): δ 2.00, 2.36 (s, 6
H, Tol-CH3), 6.44 (d, J ) 10 Hz, 2 H, Ar), 6.50 (s, 1 H, H-4),
7.10-7.40 (m, 4 H, Ar), 7.78 (m, 3 H, Ar), 8.10 (m, 2 H, Ar),
11.38 (br, 1 H, NH). 13C NMR (DMSO-d6, 100 MHz): δc 19.02,
21.03 (Tol-CH3), 83.20 (C, CCN), 113.89, 118.11 (CH, C-4, C-7),
114.80 (C, CN), 116.81 (C, C-3a), 120.62, 125.70, 127.11,
129.52, 130.10, 134.98 (CH, Ph, Tol, C-6), 132.31, 135.20 (C,
C-5, Tol-C to C), 141.00 (C, Ph), 145.82, 146.73 (C, C-2, Tol-C
to N), 157.30 (C, C-7a), 158.81 (C, C-3). IR (KBr, cm-1): 3350
(br), 3320 (m), 3022 (s), 2920 (s), 2198 (m, CN), 1641 (m), 1589
(s), 1487 (s); 1340 (s), 1322 (m), 1150 (s), 1138 (s), 1081 (s),
1035 (m). MS (FAB): 414 (100, M+ + 1). Anal. Calcd for
1
°C. H NMR (200 MHz, DMSO-d6): δ ) 2.00 (s, 3 H, Indole-
CH3); 2.29 (s, 3 H, Tol-CH3), 6.48 (s, 1 H, Hetar), 6.95 (d, 2 H,
J ) 8.1 Hz, Ar), 7.23-7.38 (m, 6 H, Ar), 7.54, 7.51 (2 × br, 2
× 1 H, Hetar), 11.89, 12.62 (2 × br, 2 × 1 H, NH). 13C NMR
(50 MHz, DMSO-d6): δ 20.4, 20.5 (Tol-CH3), 71.7, 111.7, 112.8,
116.7, 117.1, 117.9, 122.1, 122.9, 125.2, 125.7, 128.1, 128.8,
129.8, 130.5, 134.1, 134.5, 143.1, 145.8, 147.4, 148.8, 149.3,
157.3. IR (Nujol, cm-1): ν 3319, 3298 (m, νNH), 2211 (s, νCtN),
1692 (s), 1637 (s), 1620 (s), 1606 (s), 1589 (s), 1563 (s), 1524
(s), 1504 (s), 1481 (s). MS [CI (H2O), m/z (%)]: 378 (M+ + 1,
100), 272, 195, 108. Anal. Calcd for C24H19N5 (377.45):
C
C24H19N3O2S: C 69.72, H 4.63, N 10.16. Found: C 68.63, H
76.37%; H 5.07%; N 18.55%. Found: C 76.70%; H 5.09%; N
18.75%.
5.07, N 10.34.
(2Z,3E)-N-[1,2-Dih yd r o-5-m et h yl-2-[(p h en ylsu lfon yl)-
m et h ylen e]-3H -in d ol-3-ylid en e]-4-m et h ylb en zen a m in e
(4s). Starting with 936 mg of methyl phenyl sulfone, 490 mg
(21%) of 4s was isolated as an orange solid, mp 148-151 °C.
1H NMR (DMSO-d6, 200 MHz): δ 1.94, 2.33 (s, 6 H, Tol-CH3),
6.07 (s, 1 H, 6.29 (s, 1 H, H-4), 6.82 (d, J ) 8 Hz, 2 H, Ar),
7.20 (m, 3 H, Ar), 7.69 (m, 4 H, Ar), 8.03 (m, 2 H, Ar). 13C
NMR (DMSO-d6, 50 MHz): δc 20.37, 20.47 (Tol-CH3), 94.65
(CH, CHSO2Ph), 112.20, 117.90 (CH, C-4, C-7), 116.36 (C,
C-3a), 120.28, 125.47, 126.22, 129.46, 129.83 134.82 (CH, Ph,
Tol, C-6), 129.31, 133.80, 135.07 (C, C-5, Ph-C and Tol-C to
C), 147.47, 148.19 (C, C-2, Tol-C to N), 158.34 (C, C-7a), 158.38
(C, C-3). MS-FAB: 389 (68.2, M+ + 1), 247 (100).
(2Z,3E )-N -[1,2-Dih yd r o-5-m e t h yl-2-[p h e n yl(p h e n yl-
su lfon yl)m et h ylen e]-3H -in d ol-3-ylid en e]-4-m et h ylb en -
zen a m in e (4t). Starting with 1.39 g of benzylphenyl sulfone,
1.69 g (61%) of 4t was isolated as an orange solid as an
unseparable mixture of isomers (E:Z ) 1:2), mp 160-163 °C
(refers to the mixture of isomers). Major isomer: 1H NMR
(CDCl3, 400 MHz): δ 1.92, 2.24 (s, 6 H, Tol-CH3), 6.16 (s, 1 H,
H-4), 6.38 (d, J ) 8 Hz, 2 H, Ar), 7.00-7.80 (m, 14 H, Ar),
10.77 (br, 1 H, NH). 13C NMR (CDCl3, 100 MHz): δc 19.91,
20.12 (Tol-CH3), 61.05 (C, CSO2PH), 112.80, 117.02 (CH, C-4,
C-7), 117.76 (C, C-3a), 121.77, 125.69, 127.62, 128.31, 128.48,
128.70, 129.52, 132.40, 134.13 (CH, Ph, Tol, C-6), 133.88, 134.
16, 134.76, (C, C-5, Ph-C and Tol-C to C), 142.02 (C, Ph-C to
S), 146.70, 147.52 (C, C-2, Tol-C to N), 157.86 (C, C-7a), 158.08
(2E,3E)-[1,3-Dih yd r o-3-(p h en ylim in o)-2H -in d ol-2-yli-
d en e](tr im eth ylsilyl)a ceton itr ile (4m ) a n d (2E,3E)-[1,3-
Dih yd r o-3-(p h en ylim in o)-2H -in d ol-2-ylid en e]a cet on i-
tr ile (4n ). Starting with 0.9 g of (trimethylsilyl)acetonitrile,
0.69 g of an inseparable mixture (1:5) of 4m and 4n was
1
obtained (34% by H NMR). Each compound was formed as a
E:Z ) 5:1-mixture of stereoisomers. 4m : 1H NMR (CDCl3, 200
MHz): δ 0.08 (s, 9 H, minor isomer, SiMe3), 0.35 (s, 9 H, major
isomer, SiMe3), 7.00-7.60 (m, 9 H, Ar). 4n : 5.35 (s, 1 H, minor
isomer, dCH), 5.40 (s, 1 H, major isomer, dCH), 6.58 (m, 2 H,
Ar), 6.90 (m, 2 H, Ar), 7.20 (m, 2 H, Ar), 7.45 (m, 2 H, Ar),
7.70 (d, 1 H, Ar), 8.05 (br, 1 H, NH). 4n (major isomer): 13C
NMR (CDCl3, 50 MHz): δc 66.17 (C, CCN), 110.94, 118.00,
118.10, 118.43, 119.91, 121.08, 124.84, 126.75, 129.27, 129.55,
134.02, 148.76, 150.38, 154.11, 155.81.
(2E ,3E )-[1,3-D ih y d r o -3-(p h e n y lim in o )-2H -in d o l-2-
yliden e](diph en yl-1-azaeth yliden e)aceton itr ile (4o). Start-
ing with 0.8 g of (diphenyl-1-azaethylidene)acetonitrile which
was lithiated by LDA, 323 mg (21%) of 4o was isolated as deep
1
orange crystals, mp 154-157 °C. H NMR (CDCl3, 200 MHz):
δ 6.60 (d, 1 H), 6.80-7.50 (m, 18 H, Ar), 8.02 (br, 1 H, NH).
13C NMR (CDCl3, 50 MHz): δc 84.02 (C, CCN), 110.05, 112.55,
114.83, 117.15, 119.96, 120.09, 121.42, 126.48, 127.31, 127.77,
127.85, 128.28, 129.35, 130.20, 133.78, 134.50, 139.51, 142.04,
142.17, 145.26, 147.04, 151.45. MS (70 °C): 424 (M+ + 1, 40),
347 (100).

3610 J . Org. Chem., Vol. 65, No. 12, 2000
Langer et al.
(C, C-3). IR (KBr, cm-1): 3300 (m); 3025 (w), 2920 (w), 1640
(s), 1618 (m), 1584 (s), 1502 (m), 1478 (m), 1326 (m), 1218 (m).
MS (140 °C): 464 (3.19, M+), 463 (7.5, M+ - 1), 323 (100). Anal.
Calcd for C29H24N2O2S: C 74.98, H 5.21, N 6.03. Found: C
74.01, H 5.55, N 6.40.
cyanoacetic derivatives or benzoyl acetonitrile (10 mmol) was
added a THF solution (25 mL) of 10 mL of NaN(SiMe3)2 (1M
solution in THF) or of a THF solution (25 mL) of LDA
(prepared by addition of 10 mmol of n-BuLi to a THF solution
of 10 mmol of diisopropylamine). After stirring for 10 min at
0 °C, the suspension was transferred to a THF solution (25
mL) of the respective oxalic acid bis(imidoyl) dichloride (2a :
1.5 g, 2b: 1.2 g, 5 mmol) at -20 °C. The cooling bath was
removed, and the reaction mixture was stirred at 50 °C for 24
h. After being cooled to room temperature, the reaction mixture
was poured into an aequous solution of 300 mL of NH4Cl which
was extracted with ethyl ether/THF (1:1). The combined
organic layers were dried (Na2SO4) and filtered, and the
solvent was removed in vacuo. To the residue was added 2
mL of methanol. The precipitated product was washed twice
with methanol and was dried in vacuo. Open-chain products
were obtained as the major products also when only 1 rather
than 2 equiv of the nucleophile in the presence of 2 equiv of
LDA were used.
(2Z,3E)-N-[1,2-Dih yd r o-5-m eth yl-2-[4-m eth oxyp h en yl-
(p h en ylsu lfon yl)m eth ylen e]-3H-in d ol-3-ylid en e]-4-m eth -
oxyben zen a m in e (4u ). Starting with 1.39 g of benzyl phenyl
sulfone, 1.61 g (58%) of 4u was isolated as an orange solid as
an unseparable mixture of isomers (E:Z ) 1:2), mp 160-162
°C (refers to the mixture of isomers). 1H NMR (CDCl3, 200
MHz): δ 3.41, 3.73 (s, 6 H, OCH3, major isomer), 3.62, 3.81 (s,
6 H, OCH3, minor isomer), 6.22 (s, 1 H, H-4, major isomer),
6.19 (s, 1 H, H-4, minor isomer), 6.50 (m, 2 H, Ar), 6.70-7.90
(m, 13 H, Ar), 9.55 (br, 1 H, NH). 13C NMR (CDCl3, 50 MHz):
δc 55.48, 55.52, 55.62, 110.67, 111.31, 112.36, 112.40, 114.10,
114.28, 114.39, 115.89, 117.51, 118.93, 120.14, 121.13, 121.27,
122.88, 123.78, 127.84, 128.01, 128.61, 128.75, 128.89, 129.17,
129.59, 129.79, 130.81, 131.32, 132.35, 133.09, 133.69, 133.72,
138.00, 140.38, 141.61, 142.56, 143.27, 143.50, 151.53, 153.47,
156.78, 157.94, 158.48, 159.17, 161.13, 163.37. MS (FAB): 497
(3.19, M+ + 1), MS (140 °C): 464 (3.19, M+).
Isola tion of Bis-En a m in es (5a -c). During the course of
the isolation of the 2-alkylidene-3-iminoindoles 4, open-chain
products 5 could be frequently isolated in low yields. Whereas
the indoles 4 were soluble in ethyl ether/THF, the 1:2-products
5 precipitated out and could be isolated by filtration and
subsequent recrystallization from EtOH.
(E,E)-Bisp h en yl-(Z,Z)-1,4-d icya n o-2,3-b is(4-t olyl)a m i-
n obu ta d ien e (5a ): mp 336-339 °C. 1H NMR (200 MHz,
CDCl3): δ ) 2.28 (s, 6 H, Tol-CH3), 7.00-7.20 (m, 18 H, Ar).
IR (Nujol):ND ν ) 3268 (w), 1618 (m), 1595 (m), 1512 (m), 1461
(s), 1377 (m), 1233 (m), 1101 (m) cm-1. MS [CI (H2O), m/z (%)]:
467 [M+ + 1] (100).
(Z,Z)-1,4-Dicya n o-2,3-d i(p -t olyl)a m in ob u t a d ien e-1,4-
bis(p h en yl k eton e) (5e). Starting with benzoylacetonitrile
(0.5 g, 3.4 mmol) and 2b (0.5 g, 1.7 mmol), 125 mg of 5e (14%)
1
was isolated, yellow crystals, mp 308-310 °C. H NMR (CD2-
Cl2, 200 MHz): δ 2.38 (s, 6 H, Tol-CH3), 6.98 (d, J ) 8.4 Hz, 4
H, Ar), 7.20 (d, J ) 8.3 Hz, 4 H, Ar), 7.56 (m, 6 H, Ar), 7.85 (d,
J ) 8.0 Hz, 4 H, Ar), 13.35 (s, 2 H, NH). 13C NMR (CD2Cl2, 50
MHz): δC 21.2 (Tol-CH3), 85.6 (C, CCN), 118.8 (C, CN), 123.5,
128.7, 130.6, 132.8, 133.9, 138.5, 139.1 (CH, C, Ar), 159.4 (C,
CNHTol), 193.3 (CO). IR (Nujol): ν ) 2199 (s) cm-1, 1612 (s),
1591 (s), 1570 (s), 1514 (s), 1494 (m). MS (CI, H2O); m/z (%):
523 (22) [M+ + 1], 416 (26), 261 (4) [M+/2]. Anal. Calcd for
C
34H26N4O2 (522.6): C 78.14, H 5.01, N 10.72. Found: C 77.71,
H 5.03, N 10.52.
(Z,Z)-1,4-Dicya n o-2,3-d i(p h en yl)a m in ob u t a d ien e-1,4-
d ica r boxylic Acid Dieth yl Ester (5f). Starting with ethyl
cyanoacetate (1.1 mL, 10 mmol) and 2a (1.35 g, 5 mmol), 2.1
g of 5f (48%) was isolated, yellow crystals, mp 206-209 °C.
1H NMR (CD2Cl2, 200 MHz): δ 1.32 (t, J ) 6.9 Hz, 6 H,
CH2CH3), 4.27 (m, J ) 6.9 Hz, 4 H, CH2CH3), 6.97 (m, 4 H,
Ph), 7.32 (m, 6 H, Ph), 11.38 (s, 2 H, NH). 13C NMR (CD2Cl2,
50 MHz): δC 14.2 (CH2CH3), 62.3 (CH2CH3), 77.8 (C, CCN),
115.8 (C, CN), 123.1, 127.9, 129.8 (CH, Ph), 136.2 (C, Ph), 157.4
(C, CNHPh), 167.5 (CO). IR (Nujol): ν ) 3292 (w) cm-1, 3183
(m), 2213 (s), 1670 (s), 1593 (s), 1580 (s), 1497 (m). MS (CI,
H2O); m/z (%): 431 (100) [M+ + 1], 385 (10), 357 (16). Anal.:
Calcd. for C24H22N4O4 (430.46): C 66.97, H 5.15, N 13.02.
Found: C 67.17, H 5.08, N 13.07.
(E,E)-Bis(4-m eth oxyp h en yl)-(Z,Z)-1,4-d icya n o-2,3-bis-
(4-tolyl)a m in obu ta d ien e (5b): mp 244-246 °C. 1H NMR
(200 MHz, CDCl3): δ ) 2.29 (s, 6 H, Tol-CH3), 3.73 (s, 6 H,
OMe), 6.50-6.70 (m, 6 H, Ar), 6.80-7.10 (m, 10 H, Ar). 13C
NMR (50 MHz, CDCl3): δC ) 21.03 (Tol-CH3), 55.24 (OCH3),
113.42, 114.87, 118.42, 122.17, 126.93, 130.91, 132.43, 133.83,
137.04, 144.33, 158.94. IR (Nujol): ν ) 3398 (m, νNH), 2194
(m), 1635 (m), 1622 (s), 1598 (m), 1579 (m), 1510 (s), 1488 (s),
1488 (s), 1464 (s), 1457 (s), 1249 (s), 1223 (m), 1034 (m) cm-1
.
MS [70 °C, m/z (%)]: 526 (M+ + 1).
(E,E)-Bis(3,4-d im eth oxyp h en yl)-(Z,Z)-1,4-d icya n o-2,3-
bis(4-tolyl)a m in obu ta d ien e (5c): mp 244-247 °C. 1H NMR
(200 MHz, CD2Cl2): δ ) 2.32 (s, 6 H, Tol-CH3), 3.39, 3.80 (2 ×
s, 2 × 6 H, OMe), 6.33 (s, 2 H, Ar), 6.70-6.85 (m, 4 H, Ar),
7.05 (m, 8 H, Ar), 7.82 (br, 2 H, NH). 13C NMR (50 MHz, CD2-
Cl2): δC ) 21.14 (Tol-CH3), 55.66, 56.23 (OCH3), 102.20, 111.55,
114.28, 122.51, 123.03, 127.45, 129.54, 133.29, 137.50, 144.50,
148.95, 149.14, 168.59. IR (Nujol): ν ) 3467, 3298 (s, νNH),
1623 (m), 1595 (m), 1518 (s), 1459 (s), 1377 (m), 1225 (m), 1134
(m), 1021 (m) cm-1. MS [CI (H2O), m/z (%)]: 587 (M+ + 1, 100).
P r ep a r a tion of (E,E)-Bis(2-p yr id yl)-(Z,Z)-1,4-d icya n o-
2,3-bis(4-tolyl)a m in obu ta d ien e (5d ). To a THF solution (30
mL) of (2-pyridyl)acetonitrile (1.2 g, 10 mmol) was added a
THF solution of LDA (5.5 mL, 2 M) at 0 °C. To this solution a
THF solution (50 mL) of 2b (1.53 g, 8 mmol) was added slowly
at -78 °C. After stirring for 2 h at 20 °C, the solvent was
removed in vacuo. To the residue was added CH2Cl2, the
precipitated LiCl was removed by filtration (Celite), and the
solvent of the filtrate was removed in vacuo. To the residue
was added ethyl ether, and the precipitated product was
washed with ethyl ether and recrystallized from toluene to give
a yellow-colored solid (1.24 g, 53%), mp 244-247 °C. 1H NMR
(200 MHz, DMSO-d6, 90 °C): δ ) 2.32 (s, 6 H, Tolyl-CH3),
6.37-8.60 (m, 16 H, Ar), 10.08 (s, 2 H, NH). IR (Nujol): ν )
3359, 3323 (s, νNH), 2216 (s, νCtN), 1632 (s), 1604 (s), 1588 (s),
1558 (s), 1532 (s), 1490 (s) cm-1. MS [CI (H2O), m/z (%)]: 469
(M+ + 1, 13), 353 (9), 131 (15), 119 (100), 108 (46). Anal. Calcd
for C30H24N6 (468.56): C 76.90%, H 5.16%, N 17.94%. Found:
C 76.29%, H 5.49%, N 17.67%.
(Z,Z)-1,4-Dicya n o-2,3-d i(p -t olyl)a m in ob u t a d ien e-1,4-
d ica r boxylic Acid Dieth yl Ester (5g). Starting with ethyl
cyanoacetate (1.1 mL, 10 mmol) and 2b (1.5 g, 5 mmol), 3.3 g
1
of 5g (72%) was isolated, yellow crystals, mp 196-199 °C. H
NMR (CD2Cl2, 200 MHz): δ 1.35 (t, J ) 7.2 Hz, 6 H, CH2CH3),
2.34 (s, 6 H, Tol-CH3), 4.27 (m, J ) 7.2 Hz, 4 H, CH2CH3),
6.87, 7.13 (d, J ) 8.5 Hz, 8 H, Tol), 11.29 (s, 2 H, NH). 13C
NMR (CD2Cl2, 50 MHz): δC 14.4 (CH2CH3), 21.1 (Tol-CH3),
62.3 (CH2CH3), 77.4 (C, CCN), 116.0 (C, CN), 123.2, 130.4 (CH,
Tol), 134.0 (C, Tol-C to C), 138.4 (C, Tol-C to N), 157.9 (C,
CNHTol), 167.2 (CO). IR (Nujol): ν ) 3322 (m) cm-1, 2213 (s),
1670 (s), 1595 (s). MS (EI); m/z (%): 458 (19) [M+], 385 (57),
339 (100), 229 [M+/2]. Anal. Calcd for C26H26N4O4 (458.5): C
68.11, H 5.72, N 12.22. Found: C 68.52, H 5.79, N 11.97.
(Z,Z)-1,4-Dicya n o-2,3-d i(p -t olyl)a m in ob u t a d ien e-1,4-
d ica r boxylic Acid P ip er id id e (5h ). Starting with (cy-
anoacetyl)piperidine (0.76 g, 5 mmol) and 2b (0.76 g, 2.5
mmol), 1.5 g of 5h (56%) was isolated, slight yellow solid, mp
285-287 °C. 1H NMR (CD2Cl2, 200 MHz): δ 1.28 (m, 12 H,
CH2), 2.39 (s, 6 H, Tol-CH3), 2.70, 3.31, 3.74 (m, 20 H, NCH2),
7.24 (m, 8 H, Tol), 8.36 (s, 2 H, NH). 13C NMR (CD2Cl2, 50
MHz): δC 21.2 (Tol-CH3), 24.6, 25.5, 26.5, 42.8, 48.2 (CH2), 96.5
(C, CCN), 126.5, 129.7 (CH, Tol), 137.9 (C, Tol-C to C), 145.2
(C, Tol-C to N), 161.7 (C, CNHTol), 165.8 (CO). IR (Nujol): ν
) 3297 (s) cm-1, 1678 (m). MS (CI, H2O); m/z (%): 537 (3) [M+
+ 1], 452 (8), 268 (3) [M+/2], 147 (100). Anal. Calcd for
Gen er a l P r oced u r e for th e P r ep a r a tion of Bis-En a m -
in es (5e-i). To a THF solution (20 mL) of the respective
C
32H36N6O2 (536.68): C 71.62, H 6.76, N 15.66. Found:
C
71.29, H 6.88, N 15.41.

Synthesis of 2-Alkylidene-3-iminoindoles
J . Org. Chem., Vol. 65, No. 12, 2000 3611
(Z,Z)-1,4-Dicya n o-2,3-d i(p -t olyl)a m in ob u t a d ien e-1,4-
d ica r boxylic Acid Mor p h olid e (5i). Starting with (cy-
anoacetyl)morpholine (1.00 g, 6.48 mmol) and 2b (0.99 g, 3.24
mmol), 1.26 g of 5i (36%) was isolated, slight yellow solid, mp
307-308 °C. 1H NMR (DMSO-d6, 200 MHz): δ 2.34 (s, 6 H,
Tol-CH3), 3.28, 3.32 (m, 16 H, CH2), 7.24 (m, 8 H, Tol), 8.73 (s,
2 H, NH). IR (Nujol): ν ) 3475 (m) cm-1, 3445 (s), 3276 (s),
1676 (w), 1635 (s), 1590 (s), 1579 (s), 1515 (m). MS (CI, H2O);
m/z (%): 541 (12) [M+ + 1], 454 (2), 88 (100). Anal. Calcd for
P r ep a r a tion of 3-Cya n o-N-(4-m eth ylp h en yl)-1-[(4-
m eth ylp h en yl)im in o]-1H-p yr r olo[1,2-a ]ben zim id a zol-2-
a m in e (6b). 2-(Cyanomethyl)benzimidazole (1.57 g, 10 mmol),
NEt3 (3.1 mL, 22 mmol), and 2b (3.05 g, 10 mmol) were
dissolved in toluene (100 mL). After being stirred for 24 h at
60 °C, the precipitated HNEt3Cl was removed by filtration and
the solvent of the filtrate was removed in vacuo. The residue
was purified by chromatography (toluene/acetone ) 10/1) to
give 0.98 g of yellow crystals (25%), mp 224-226 °C (from
methanol). 1H NMR (200 MHz, CD2Cl2): δ 2.42, 2.45 (2 × s, 2
× 3 H, Tol-CH3), 5.09 (d, 1 H, J ) 8.1 Hz, Hetar), 6.74 (t, 1 H,
J ) 8.4 Hz, Hetar), 6.94 (d, 2 H, J ) 8.3 Hz, Ar), 7.03 (t, 1 H,
J ) 7.4 Hz, Hetar), 7.18-7.31 (m, 6 H, Ar), 7.43 (d, 1 H, J )
8.1 Hz, Hetar), 8.29 (s, 1 H, NH). 13C NMR (50 MHz, CD2Cl2):
δC 21.2, 21.3 (Tol-CH3), 113.8, 120.1, 121.3, 124.0, 124.3, 124.6,
128.7, 129.2, 130.3, 130.4, 131.3, 133.3, 136.2, 138.3, 144.4,
151.3. IR (Nujol, cm-1): ν 3313 (br, νNH), 2212 (m, νCtN), 1731
(m), 1693m), 1634 (m), 1621 (s), 1606 (s), 1564 (s), 1557 (s),
1525 (m), 1505 (m). MS [CI (H2O), m/z (%)]: 390 (M+ + 1, 100),
279, 253, 205, 198, 149, 93.
C
30H32N6O4 (540.62): C 66.65, H 5.97, N 15.55. Found:
C
66.41, H 6.05, N 15.71.
P r ep a r a tion of tr a n s-(E,E)-1,4-Bis(2-p yr id yl)-(Z,Z)-2,3-
bis(4-tolyl)a m in obu ta d ien e (5j). To a THF solution (50 mL)
of 0.62 mL of 2-picoline (6.25 mmol) was added 10 mL of
n-BuLi (1.6 M solution in hexane). The reaction mixture was
warmed to 20 °C. After being stirred for 2 h, the mixture was
cooled to -78 °C and a THF solution (50 mL) of 2b (0.95 g,
3.12 mmol) was added. The mixture was warmed to 20 °C and
was stirred for 6 h. The solvent was removed in vacuo, and to
the residue was added CH2Cl2. The suspension obtained was
filtered (Celite), and the solvent of the filtrate was removed
in vacuo. The crude product was precipitated by addition of
methanol to the residue. The yellow solid obtained was filtered
and dried in vacuo to give 0.56 g (44%) of 5j as yellow crystals,
Ack n ow led gm en t. P. L. thanks Professor A. de
Meijere for his support, Professor R. Beckert for helpful
discussions, and J . Anders for experimental contribu-
tions. Generous financial support from the Fonds der
Chemischen Industrie e. V. (Liebig-scholarship and
funds for P. L.) and from the Deutsche Forschungsge-
meinschaft (SFB 416) is gratefully acknowledged.
1
mp 247-249 °C. H NMR (200 MHz, CD2Cl2): δ ) 2.23 (s, 6
H, Tolyl-CH3), 5.80 (s, 2 H, dCH), 6.76, 6.89 (2 d, 8 H, Ar, J
) 8.5 Hz), 6.96 (t, 2 H, Hetar, J ) 5.3 Hz), 7.13 (d, 2 H, Hetar,
J ) 8.2 Hz), 7.58 (t, 2 H, Hetar, J ) 7.6 Hz), 8.44 (d, 2 H,
Hetar, J ) 4.6 Hz), 11.28 (s, 2 H, NH). 13C NMR (50 MHz,
CD2Cl2): δC ) 20.8 (Tol-CH3), 101.4, 118.7, 120.3, 123.2, 129.2,
131.3, 136.2, 139.1, 145.6, 147.7, 159.2. IR (Nujol): ν ) 1630
(s, νCdC), 1609 (s), 1589 (s), 1548 (s), 1517 (s) cm-1. MS [CI
(H2O), m/z (%)]: 419 (M+ + 1, 100), 340 (16), 312 (10), 209
(M+/2, 12). Anal. Calcd for C28H26N4 (418.54): C 80.35%, H
6.26%, N 13.39%. Found: C 79.71%, H 6.23%, N 13.15%.
Su p p or tin g In for m a tion Ava ila ble: Details of the struc-
ture determination including atomic coordinates, H-atom
coordinates, bond distances and bond angles. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O991701L