On the reaction of isatin with cyanomethylene(triphenyl)phosphorane. A nucleophilic attack of alkyl phosphites on the carbon-carbon double bond of (E)-oxindolylideneacetonitrile

Article abstract of DOI:10.1016/S0040-4020(99)01065-0

The reaction of cyanomethylene(triphenyl)phosphorane (2) with isatin (1) in dry benzene at room temperature for 1 h led to the formation of (1,2- dihydro-2-oxo-3H-indol-3-yl)acetonitrile as a mixture of E- and Z-stereo isomers 3 and 4. Trialkyl phosphites 7 reacted with (E)-nitrile 3 in dry benzene at 70°C for about 10 h to give the phosphonates 8 as two isomers together with the unexpected spiro products of isomers 9. When the (E)- nitrile 3 was allowed to react with dialkyl phosphites (11) without solvents at 100°C for about 30 h, a mixture of the phosphonate derivatives 8 and one isomer of the dimeric structure 9 were obtained. The reaction mechanisms are considered and the structural assignments of the new compounds are based on chemical and spectroscopic evidence. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01065-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1863–1871
On the Reaction of Isatin with Cyanomethylene(triphenyl)-
phosphorane. A Nucleophilic Attack of Alkyl Phosphites on the
Carbon–Carbon Double Bond of (E)-Oxindolylideneacetonitrile
*
Fayez H. Osman and Fatma A. El-Samahy
Department of Pesticide Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt
Received 8 June 1999; revised 17 November 1999; accepted 2 December 1999
Abstract—The reaction of cyanomethylene(triphenyl)phosphorane (2) with isatin (1) in dry benzene at room temperature for 1 h led to the
formation of (1,2-dihydro-2-oxo-3H-indol-3-yl)acetonitrile as a mixture of E- and Z-stereo isomers 3 and 4. Trialkyl phosphites 7 reacted
with (E)-nitrile 3 in dry benzene at 70ЊC for about 10 h to give the phosphonates 8 as two isomers together with the unexpected spiro products
of isomers 9. When the (E)-nitrile 3 was allowed to react with dialkyl phosphites (11) without solvents at 100ЊC for about 30 h, a mixture of
the phosphonate derivatives 8 and one isomer of the dimeric structure 9 were obtained. The reaction mechanisms are considered and the
structural assignments of the new compounds are based on chemical and spectroscopic evidence. ᭧ 2000 Elsevier Science Ltd. All rights
reserved.
Introduction
(triphenyl)phosphorane (2). Also, our studies include the
reaction of alkyl phosphites with (E)-oxindolylideneaceto-
nitrile (3).
1
Pietra reported that the reaction of isatin (1) with cyano-
acetic acid afforded oxindolylidenecyanoacetic acid, which
upon heating with pyridine, lost carbon dioxide with the
formation of oxindolylideneacetonitrile. This product was2
separated as two isomers (E)-(3) and (Z)-(4) by Long et al.
Now, we report the one-step synthesis of the two forms via
Wittig reaction between isatin (1) and cyanomethylene-
Results and Discussion
The reaction of isatin (1) with cyanomethylene(triphenyl)-
phosphorane (2) in dry benzene at room temperature for 1 h
Scheme 1.
Keywords: isatin; cyanomethylene(triphenyl)phosphorane; (E)-oxindolylideneacetonitrile.
*
Corresponding author. E-mail: osman_f@hotmail.com
0
040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01065-0

1
864
F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
Scheme 2.
led to the formation of orange yellow crystals of (E)-(1,2-
dihydro-2-oxo-3H-indol-3-yl)acetonitrile (3) (79%) and
Reaction of compound 5 with methyl iodide in presence of
acetone and anhydrous potassium carbonate afforded an oily
product could not be solidified of (2,3-dihydro-1,3-
dimethyl-2-oxo-1H-indol-3-yl)acetonitrile (6) (Scheme 1).
The structure of compound 6 was elucidated by correct
elemental analyses, molecular weight determination (MS)
and compatible spectroscopic results. Its IR spectrum
disclosed the absence of absorption band of NH group.
(
(
Z)-(1,2-dihydro-2-oxo-3H-indol-3-yl)acetonitrile (4) (3%)
Scheme 1). These two isomers were separated by column
chromatography on silica gel and identified by spectral data
and elemental analyses. The H NMR spectra of the two
1
isomers in DMSO-d showed the resonance of the olefinic
6
proton of 3 (d 6.51) at higher field than of 4 (d 6.94). The
aromatic proton at C-4 in compound 3 (d 7.85) is deshielded
more than that of compound 4 (d 7.70) due to the nitrile
1
The H NMR spectrum, of 6 showed two singlets for the
C-Me and N-Me groups and AB pattern for the CH group
2
3
1
5
group. H NMR measurements showed equilibration of the
(JABˆ16.8 Hz). Also, further evidence supporting structure
13
pure (Z)-nitrile 4 in DMSO-d to a mixture of both isomers 4
6 is C NMR spectral data (cf. Experimental).
6
and 3 in 44/56 ratio after about two weeks.
Trialkyl phosphites (7) reacted with (E)-nitrile (3) in dry
benzene at 70ЊC for about 10 h to give dialkyl [cyano(2,3-
dihydro-2-oxo-1H-indol-3-yl)methyl]phosphonate (8) as
two isomers together with the unexpected product of
isomers 9A and 9B (Scheme 2). These compounds were
separated by column chromatography using silica gel with
n-hexane/acetone as eluent. The colourless crystalline
product 8 was found to be a mixture of two diastereomeric
forms 8 and 8 . We separated small amounts of one isomer
The double bond of 3 is reduced with zinc dust in boiling
acetic acid to give (2,3-dihydro-2-oxo-1H-indol-3-yl)aceto-
nitrile (5) in quantitative yield (Scheme 1). The H NMR
1
spectrum of 5 (CDCl ϩdrop DMSO-d ) included three
3
6
doublets of doublets for ABX system of the CH CH side
2
4
chain (JABˆ17 Hz, J ˆ8.4 Hz, J ˆ5.0 Hz). Also its
AX
BX
1
3
structure was supported by C NMR results (cf. Experi-
mental).
A
B

F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
1865
Scheme 3.
1
0
by column chromatography with identification by H NMR,
whereas the other isomer 8B could not be isolated. The
suggested structures of the phosphonates 8 and 8 were
displacement of R in the intermediate 12 (Arbuzov-type
reaction).
A
B
1
13
1
supported by H and C NMR chemical shifts. The H
The two isomers 9 and 9 were separated as colourless
A
B
NMR spectrum of isomer 8a showed two doublets of
crystals and their structures were established by spectro-
scopic techniques as well as elemental analyses and molec-
A
3
doublets at d 4.17 ( J ˆ25.4 Hz, J ˆ3.4 Hz) and d
HP
HH
2
4
.49 ( J ˆ23.6 Hz, J ˆ3.4 Hz) for H-3 and H-8, respec-
ular weight determination (MS). Their IR spectra showed
HP
HH
Ϫ1
tively, whereas these two protons in the other isomer 8a
two absorption bands near 3419 and 3316 cm
for
B
3
6
appeared at d 4.05 ( J ˆ16.6 Hz, J ˆ2.4 Hz) and d 4.43
asymmetric and symmetric NH stretching frequencies.
The H NMR spectra of both isomers 9 and 9 contained
HP
HH
2
1
(
J ˆ24.6 Hz, J ˆ2.6 Hz) as two doublets of doublets.
HP
HH
A
B
1
3
Moreover, C NMR spectrum of 8a exhibited a doublet
a singlet at d 6.30 corresponding to the ϪNH group and
A
2
1
at d 28.9 ( J ˆ141.6 Hz) corresponding to C-8 and for the
another two singlets at d 10.69, 11.03 for the two indole
PC
1
other isomer 8a a doublet at d 29.2 ( J ˆ145.3 Hz).
N–H protons, which are exchangeable with D O. By
B
PC
2
1
comparison of the H NMR spectra of the two isomers the
chemical shift of H-4 in 9a (d 8.21) is downfield about
1
0
The H NMR spectrum of the pure isomer 8 in DMSO-d
A
6
A
changed with time, showing after about 3 h the two equi-
0.59 ppm from that of 9aB (d 7.62). This reflects the
deshielding effect of the nitrile group on H-4 . Also, H-8
0
3
librating species 8 and 8 in a 67/33 ratio, which became
A
B
57/43 ratio after 24 h.
in 9 and 9 is a singlet at d 3.94, 4.27, respectively. The
A
B
downfield effect of H-8 in case of 9 than 9 can be attri-
B
A
The proposed mechanism for the formation of phosphonates
from the reaction of (E)-nitrile 3 with trialkyl phosphites 7
is depicted in Scheme 3. This involves primary nucleophilic
attack by phosphite-phosphorus on the exocyclic methide
carbon in 3 to yield the dipolar species 12. The intermediate
buted mainly to the effect of neighboring carbonyl functions
0
13
8
(C-2 and C-2). These data were supported by C NMR
results (cf. Experimental) which showed the appearance
1
7,8
C-10 as a doublet at d 86.1 ( J ˆ199.0 Hz) for the
PC
isomer 9a and for the other isomer 9a , the doublet at d
A
B
1
12 undergoes addition of water due to the non-avoidable
87.1 ( J ˆ195.3 Hz).
PC
moisture to give 13, which eliminates alcohol to form the
phosphonate structure 8. Another proposed pathway
for formation of 8 could take place via nucleophilic
The postulated mechanism for the formation of the spiro-
products 9A,B illustrated in Scheme 4 shows the reaction of

1
866
F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
Scheme 4.
the phosphonate 8 with (E)-nitrile 3 involving the spiro-
intermediate 15. The latter collapses to the final isolable
isomers 9 and 9 .
A
B
Treatment of the major isomers 9a and 9b with methyl
B
B
iodide in presence of acetone and anhydrous potassium
carbonate led to the formation of colourless crystals of
compounds 10a and 10b, respectively, as shown in Scheme
2
. The structure of compounds 10a and 10b was elucidated
by correct elemental analyses, molecular weight determi-
nation (MS) and compatible spectroscopic results. The IR
spectra of these adducts exhibited strong absorption bands
around 3462 and 3315 cm , corresponding to NH group.
Their H NMR spectra revealed the presence of two singlets
The formation of the phosphonates 8A,B from the reaction of
(E)-nitrile 3 with phosphites (11) can be explained in
Scheme 3 by initial nucleophilic attack of the phosphite-
phosphorus on the exocyclic methide-carbon in 3 to yield
the phosphonium species 14, which afforded the phospho-
Ϫ1
2
1
at d 3.20, 3.23, for the two N-Me groups, which appeared in
nates 8 and 8 as two isomers.
A B
13
C NMR spectra at d 26.7 and 27.0.
Methylation of the isomeric mixture 8bA and 8bB with
methyl iodide in presence of acetone and anhydrous
potassium carbonate led to the formation of a mixture
of diethyl [1-cyano-1-(2,3-dihydro-1,3-dimethyl-2-oxo-
1H-indol-3-yl)ethyl]phosphonate (16a) and diethyl [cyano
(2,3-dihydro-1,3-dimethyl-2-oxo-1H-indol-3-yl)methyl]-
phosphonate (16b). The colourless crystals of compounds
16a and 16b were separated by column chromatography
on silica gel and their structures were established by
When the (E)-nitrile 3 was allowed to react with dialkyl
phosphites (11) without solvents at 100ЊC for about 30 h,
a mixture of the phosphonate derivatives 8A,B (as two
isomers) and only one isomer of the dimeric structure 9B
were obtained. These products were separated by column
chromatography as colourless crystals. The structures were
1
verified by mp, mixed mp and comparison of IR and H
NMR spectra with authentic samples (vide supra).
Scheme 5.

F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
1867
Scheme 6.
1
spectroscopic results. The H NMR spectrum of the adduct
6a showed two singlets at d 1.62, 3.19, corresponding to
the Me at C-3 and at d 3.31, due to the N-Me. Two doublets
1
at d 3.81, 3.89 (J ˆ11.0 Hz) correspond to the methoxyl
HP
Me at C-3 and N-Me, respectively, whereas the Me at C-8
groups attached to phosphorus atom.
appeared as a doublet at d 1.95 (J ˆ15.4 Hz but in case of
HP
1
product 16b, the H NMR spectum revealed the presence of
Also, the phosphonate 19b was obtained from the reaction
of compound 17b with methyl iodide under the same experi-
mental conditions described above for 17a. Its H NMR
spectrum is compatible with structure 19b and shows the
presence of singlets, for the Me at C-3 and the N-Me.
a singlet at d 3.22, due to N-Me and two doubletes at d 1.57
4
2
1
(
J ˆ2.0 Hz) and d 3.64 ( J ˆ23.0 Hz), for Me at C-3
HP
HP
13
and H-8, respectively. These data were supported by
C
NMR results (cf. Experimental). The observed transfor-
mation of 8 to 8 in DMSO-d explains the highly pre-
B
A
6
dominant stability of the latter species. This may indicate
that the formation of 16a and 16b via thermal methylation
reaction of the corresponding diastereoisomeric mixture of
Conclusion
8
must originate from the more stable isomer 8 (Scheme 5).
The above results demonstrate a convenient new route and
direct approach for preparing oxindolylideneacetonitrile (3)
and (4) from the reaction of isatin (1) with cyanomethylene-
(triphenyl)phosphorane (2). Also, the reaction of (E)-nitrile
(3) with alkyl phosphites gave the phosphonates 8 as two
isomers with unexpected spiro products 9.
A
9
Recently, it has been reported that the methylation of
dimethyl [dicyano(2,3-dihydro-2-oxo-1H-indol-3-yl)methyl]-
phosphonate (17a) with methyl iodide in presence of
acetone and anhydrous potassium carbonate gave a product
of structure 18a (Scheme 6). On repetition of the same experi-
ment, we have found the reaction was over after about
30 min (examined by TLC) to give dimethyl [dicyano(2,3-
Experimental
dihydro-1,3-dimethyl-2-oxo-1H-indol-3-yl)methyl]phospho-
nate (19a) and not the reported structure 18a (Scheme 6).
On increasing the reaction time, compound 19a in solution
is transformed into a product insoluble in acetone and
agglomerated with potassium carbonate. For this reason,
we could not isolate it in the pure form. The assigned struc-
ture of 19a was established from elemental analyses and
spectral properties. The IR spectrum shows a strong absorp-
Melting points were determined on electrical digital-
melting-point apparatus and are uncorrected. The IR spectra
were recorded in KBr disks, on a Jasco Fourier Transform
Infrared spectrophotometer Model FT/IR-3000E. The NMR
spectra were recorded on a Varian Gemini 200 spectrometer
1
for H operating at 200 MHz and on a Jeol Ex-270 spectro-
13
meter for C operating at 67.5 MHz. Chemical shifts are
given in positive values downfield from internal tetra-
methylsilane (TMS). The mass spectra (MS) were deter-
mined at 70 eV on a Finnigan MAT SSQ 7000 spectrometer.
Ϫ1
tion band characteristic for the amidic carbonyl at 1718 cm
Ϫ1
and other two bands at 1267, 1031 cm , corresponding to
6
PvO and P-O-Alkyl, respectively. However, the spectrum
Ϫ1
does not exhibit the expected band around 2200 cm , due
to the nitrile stretching absorption. This observation is not
unusual and similar to other previously reported compounds
(E)- and (Z)-(1,2-Dihydro-2-oxo-3H-indol-3-yl)aceto-
nitriles (3 and 4). A mixture of isatin (1) (1.47 g, 10
mmol) and cyanomethylene(triphenyl)phosphorane (2)
10–13
14
containing cyano group attached to saturated carbon.
1
The H NMR spectrum shows two singlets at d 1.90, for
(3.06 g, 10.2 mmol) in dry benzene (15 mL) was stirred at

1
868
F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
room temperature. After 5 min, the isatin dissolved due to
the exothermic reaction with the formation of orange yellow
precipitate. Stirring was continued for 1 h. Then, the solid
product was filtered off, washed with dry benzene and
ganic residue, the solution was evaporated under reduced
pressure to give an oily product 6 (0.66 g, 83%), purified by
column chromatography using 10% acetone/n-hexane as
eluent. [Found C, 71.91; H, 6.10; N, 14.04. C H N O
requires C, 71.98; H, 6.04; N, 13.99%], nmax cm (thin
film): 2249 (CuN); 1714 (CvO). 1614 (CvC), dH
12
12
2
Ϫ1
crystallized from benzene to give the (E)-nitrile (3)
2
(
0.50 g), mp 206–207ЊC (lit. 202–203ЊC), [Found C,
7
3
1
6
0.50; H, 3.63; N, 16.52. C H N O requires C, 70.58; H,
(270 MHz, CDCl ) 1.45 (s, Me at C-3); 2.50, 2.78 (2d,
1
0
6
2
3
Ϫ1
a
b
.56; N, 16.46%], nmax cm 3160 (NH); 2218 (CuN);
718 (CvO); 1610 (CvC), dH (200 MHz, DMSO-d6)
.51 (s, vCH); 6.92 (d, JHHˆ7.6 Hz, H-7); 7.10, 7.43 (2t,
J
a
b
ˆ16.8 Hz, H , H ); 3.17 (s, N-Me); 6.84 (d,
H H
JHHˆ7.6 Hz, H-7); 7.06, 7.29 (2t, J ˆ7.8 Hz, H-5, H-6);
HH
7.40 (d, J ˆ7.3 Hz, H-4), d (67.5 MHz, CDCl ) 22.0 (Me
HH
C
3
JHHˆ7.6 Hz, H-5, H-6); 7.85 (d, J ˆ7.6 Hz, H-4); 10.88
at C-3); 26.1 (CH ); 26.3 (N-Me); 44.7 (C-3); 108.6 (C-7);
HH
2
ϩ
(
(
s, NH), m/z 170 (M , 100%), 142 (36), 115 (29), 88 (5), 75
2), 63 (3) and 52 (4).
116.5 (CN); 122.9 (C-5); 123.1 (C-4); 129.0 (C-6); 130.8
ϩ
(C-3a); 142.5 (C-7a); 177.3 (CvO), m/z 200 (M , 57%),
1
94 (7), 160 (100), 145 (4), 130 (9), 117 (9), 115 (4), 89 (3),
The benzene filtrate was evaporated to dryness on silica gel
and separated on column chromatography using n-hexane
and acetone as eluent. The first fraction (87–85% n-hexane)
gave an additional amount of 3 (0.85 g) (total yield 1.35 g,
77 (3) and 51 (2).
Reaction of (E)-nitrile (3) with trimethyl phosphite (7a).
To a suspension of compound 3 (1.40 g, 8.0 mmol) in dry
benzene (30 mL), freshly distilled trimethyl phosphite (7a)
(4 mL) was added. The mixture was heated under reflux at
70ЊC for about 10 h. Then, the solvent was evaporated under
reduced pressure and the residue was chromatographed on
silica gel with n-hexane and acetone (increasing amounts) as
eluent to give four fractions. The first fraction (65–60%
n-hexane) afforded a small amount of colourless crystalline
7
9%). The second fraction (85–80% n-hexane) afforded
orange yellow crystals of (Z)-nitrile (4) (0.05 g, 3%), recrys-
tallized from acetone/n-hexane, mp 193–194ЊC (lit. 170–
2
1
71ЊC), [Found C, 70.65; H, 3.51; N, 16.39. C H N O
10 6 2
Ϫ1
requires C, 70.58; H, 3.56; N, 16.46%], nmax cm 3220
(
(
NH); 2212 (CuN): 1720 (CvO); 1618 (CvC), dH
200 MHz, DMSO-d ) 6.87 (d, J ˆ7.6 Hz, H-7); 6.94 (s,
6
HH
vCH); 7.02, 7.39 (2t, JHHˆ7.6 Hz, H-5, H-6); 7.70 (d,
product of dimethyl [cyano(2,3-dihydro-2-oxo-1H-indol-3-
yl)methyl]phosphonate (isomer 8a ), examined by H NMR
spectrum, mp 164–165ЊC, [Found C, 51.35; H, 4.59; N,
ϩ
1
JHHˆ7.6 Hz, H-4); 10.87 (s, NH), m/z 170 (M , 100%),
A
1
42 (43), 115 (30), 99 (2), 88 (9), 75 (4), 63 (6) and 52
(
6). The third fraction (75–70% n-hexane) yielded a colour-
10.08; P, 11.12. C H N O P requires C, 51.43; H, 4.68;
12
13
2
4
Ϫ1
less crystals of triphenylphosphine oxide (2.5 g, 90%), mp
and mixed mp with an authentic sample.
N, 10.00; P, 11.05%], nmax cm 3209 (NH); 2241 (CuN):
1724 (CvO); 1622 (CvC); 1240 (PvO); 1028 (P-O-Me),
dH (200 MHz, DMSO-d ) 3.51, 3.68 [2d, J ˆ11.2 Hz,
6
HP
(
2,3-Dihydro-2-oxo-1H-indol-3-yl)acetonitrile (5). The
P(OMe) ]; 4.17 (dd, J ˆ25.4 Hz, J ˆ3.4 Hz, H-3); 4.49
2
HP
HH
orange solution of (E)-nitrile (3) (0.68 g, 4.0 mmol) in
(dd, J ˆ23.6 Hz, J ˆ3.4 Hz, H-8); 6.89 (d, J ˆ7.6 Hz,
HP HH HH
acetic acid (10 mL) was heated under reflux. Zinc dust
H-7); 7.04, 7.27 (2t, J ˆ7.6 Hz, H-5, H-6); 7.49 (d,
HH
(
0.5 g) was added in small portions and the mixture was
JHHˆ7.6 Hz, H-4); 10.67 (s, NH), d (67.5 MHz, DMSO-
C
1
refluxed for about 1 h. After removal of the inorganic
residue by filtration, the filtrate was concentrated followed
by addition of water (10 mL) and extracted with ethyl
acetate. The extract was dried over anhydrous sodium
sulfate and concentrated under reduced pressure. Then,
n-hexane was added to give colourless crystalline product
d ) 28.9 (d, J ˆ141.6 Hz, C-8); 43.1 (C-3); 53.4, 53.8 [2d,
6
PC
2
2
J ˆ7.4 Hz, P(OMe) ]; 109.7 (C-7); 116.1 (d, J ˆ
PC
2
PC
8.6 Hz, CuN); 121.4 (C-5); 124.7 (C-4); 125.5 (d,
3
J ˆ8.5 Hz, C-3a); 128.8 (C-6); 142.97 (C-7a); 175.2 (d,
PC
3
ϩ
J ˆ14.6 Hz, CvO), m/z 280 (M , 100%), 252 (3), 233
PC
(2), 185 (2), 170 (91), 154 (13), 145 (50), 132 (29), 110 (90),
95 (10), 80 (20), 77 (12) and 51 (5). The second fraction
contained a mixture of the two isomers 8a and 8a (0.43 g,
5
(0.58 g, 84%), recrystallized from ethyl acetate/n-hexane,
mp 164–165ЊC, [Found C, 69.69; H, 4.75; N, 16.34.
C H N O requires C, 69.76; H, 4.68; N, 16.27%], n
A
B
23%). The isomer 8aB could not be isolated by either
10
8
2
max
Ϫ1
cm
(
J
1
J
(
3136 (NH); 2248 (CuN); 1707 (CvO); 1620
column chromatography or fractional crystallization. The
1
13
CvC), dH (200 MHz, CDCl ϩdrop DMSO-d ) 2.77 (dd,
H NMR and C NMR spectra of 8a were taken from
3
6
B
a
a
b
ˆ17.0 Hz, J
HaHx
ˆ8.4 Hz, H ); 3.08 (dd, J
b
a
ˆ
the isomeric mixture, d (200 MHz, DMSO-d ) 3.81, 3.84
H 6
H H
H H
b
7.0 Hz, J
b
x
5.0 Hz, H ); 3.65 (dd, J
x
a
ˆ8.4 Hz,
[2d, J ˆ11.2 Hz, P(OMe) ]; 4.05 (dd, J ˆ16.6 Hz,
H H
H H
HP
2
HP
x
x
b
ˆ5.0 Hz, H ); 6.94 (d, J ˆ7.6 Hz, H-7); 7.05, 7.27
J
ˆ2.4 Hz, H-3); 4.43 (dd, J ˆ24.6 Hz, J ˆ2.6 Hz,
H H
HH
HH HP HH
2t, J ˆ7.6 Hz, H-5, H-6); 7.43 (d, J ˆ7.8 Hz, H-4);
H-8); 6.91 (d,
J
ˆ7.6 Hz, H-7); 7.04, 7.29 (2t,
HH
HH
HH
1
0.09 (s, NH), d (67.5 MHz, DMSO-d ) 17.6 (CH ); 41.3
JHHˆ7.6 Hz, H-5, H-6); 7.59 (d, J ˆ7.6 Hz, H-4); 10.80
C
6
2
HH
1
(C-3); 109.6 (C-7); 118.3 (CN); 121.7 (C-5); 124.3 (C-4);
(s, NH), d (67.5 MHz, DMSO-d ) 29.2 (d, J ˆ145.3 Hz,
C
6
PC
2
1
1
(
27.2 (C-3a); 128.7 (C-6); 142.8 (C-7a); 176.5 (CvO), m/z
C-8); 43.0 (C-3); 53.1, 54.4 [2d, J ˆ7.4 Hz, P(OMe) ];
PC
2
ϩ
2
72 (M , 69%), 146 (3), 132 (100), 117 (14), 104 (16), 89
109.7 (C-7); 114.4 (d, J ˆ7.3 Hz, CuN); 121.6 (C-5);
PC
10), 77 (11), 63 (7) and 51 (10).
124.6 (C-3a); 125.9 (C-4); 129.0 (C-6); 143.0 (C-7a);
1
74.3 (CvO). The third fraction (40–35% n-hexane gave
(
2,3-Dihydro-1,3-dimethyl-2-oxo-1H-indol-3-yl)aceto-
colourless crystals of the dimeric structure 9aA (0.23 g,
12%), recrystallized from acetone/n-hexane, mp 263-
264ЊC, [Found C, 58.63; H, 4.28; N, 12.50; P, 6.93.
C H N O P requires C, 58.67; H, 4.25; N, 12.44; P,
nitrile (6). To a solution of compound 5 (0.69 g, 4.0 mmol)
in dry acetone (20 mL), anhydrous potassium carbonate
(
3 g) was added. The mixture was heated under reflux.
22
19
4
5
Ϫ1
Then, freshly distilled methyl iodide (4 mL) was added
6.88%], nmax cm 3419, 3318 (NH ); 3185 (NH); 2254
2
with continuous heating for 6 h. After removal of the inor-
(CuN); 1730, 1702 (CvO); 1635 (CvC); 1213 (PvO);

F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
1869
1
13
1
057, 1018 (P-O-Me), d (200 MHz, DMSO-d ) 3.26, 3.43
in the pure form. The H and C NMR spectra of 8b were
H
6
B
[
2d, J ˆ11.2 Hz, P(OMe) ]; 3.94 (s, H-8); 6.27 (s, NH );
taken from the isomeric mixture. d (200 MHz, DMSO-d )
HP
2
2
H
6
0
6
.88, 6.97 (2d, J ˆ7.8 Hz, H-7, H-7 ); 7.09, 7.12 (2t,
1.29 [t, JHHˆ7.2 Hz, P(OCH Me) ]; 3.60–4.50 [m,
HH
2
2
0
JHHˆ7.6 Hz, H-5, H-5 ); 7.26 (d, J ˆ7.2 Hz, H-4); 7.28,
{P(OCH Me) , H-3 and H-8}]; 6.90 (d, J ˆ7.4 Hz, H-7);
HH
2 2 HH
0
7
.35 (2t, J ˆ7.8 Hz, H-6, H-6 ); 8.21 (d, J ˆ7.6 Hz,
7.02, 7.26 (2t, JHHˆ7.4 Hz, H-5, H-6); 7.62 (d, J ˆ7.4 Hz,
HH
HH
HH
0
H-4 ); 10.69, 11.03 (2s, 2NH), d (67.5 MHz, DMSO-d )
H-4); 10.77 (s, NH), d (67.5 MHz, DMSO-d ) 15.9, 16.0
C
6
C
6
3
2
3
1
4
5.2 (d, J ˆ13.4 Hz, C-8); 51.3, 51.9 [2d, J ˆ4.9 Hz,
[2d, J ˆ7.4, 6.1 Hz, P(OCH Me) ]; 29.9 (d, J ˆ
PC
PC
PC
2
2
PC
3
0
2
P(OMe) ]; 61.4 (d, J ˆ14.6 Hz, C-3 ); 63.6 (d,
145.3 Hz, C-8); 43.1 (C-3); 63.7, 63.9 [2d, J ˆ7.4,
2
PC
PC
2
1
J ˆ17.1 Hz, C-3); 86.1 (d, J ˆ199.0 Hz, C-10);
8.9 Hz, P(OCH Me) ]. 109.7 (C-7); 114.5 (d,
PC
PC
2
2
0
2
1
(
09.7, 110.4 (C-7, C-7 ); 116.0 (CuN); 122.1, 122.3
J ˆ7.3 Hz, CuN); 121.6 (C-5); 125.4 (C-3a); 126.0
PC
0
0
C-5, C-5 ); 124.0, 126.8 (C-4, C-4 ); 127.0, 129.3 (C-3a,
(C-4); 129.0 (C-6); 143.0 (C-7a); 174.3 (CvO). The third
0
0
0
C-3 a); 129.9, 130.9 (C-6, C-6 ); 141.8, 142.9 (C-7a, C-7 a);
1
4
fraction (40–35% petroleum ether) afforded colourless
2
63.1 (d, J ˆ17.1 Hz, C-9); 176.0, 177.8 (2 CvO), m/z
crystals of isomer 9b (13%), recrystallized from acetone/
PC
A
ϩ
50 (M , 100%), 422 (15), 358 (3), 355 (8), 341 (69); 313
n-hexane, mp 293–294ЊC, [Found C, 60.29; H, 4.79; N,
(
15), 296 (9); 270 (3), 142 (4), 110 (5) and 79 (2). The fourth
11.76; P, 6.51. C H N O P requires C, 60.25; H, 4.85;
24
23
4
5
Ϫ1
fraction (35–30% n-hexane) yielded colourless crystalline
isomer 9aB (0.55 g, 29%), recrystallized from acetone/
n-hexane, mp 249–250ЊC, [Found C, 58.73; H, 4.18; N,
N, 11.71; P, 6.47%], nmax cm : 3417, 3323 (NH ); 3240
2
(NH); 2245 (CuN, very weak); 1728 (CvO); 1635
(CvC); 1200 (PvO); 1024 (P-O-Et), dH (200 MHz,
DMSO-d ) 0.93, 1.12 [2t, J ˆ7.0 Hz, P(OCH Me) ];
1
2.39; P, 6.95. C H N O P requires C, 58.67; H, 4.25;
22 19 4 5
Ϫ1
6
HH
2
2
N, 12.44; P, 6.88%], nmax cm 3411, 3316 (NH ); 3240
3.57–3.82 [m, P(OCH Me) ]; 3.94 (s, H-8); 6.23 (s, NH );
2 2 2
2
0
(
NH); 1726 (CvO); 1620 (CvC); 1213 (PvO); 1026
6.88, 6.98 (2d, JHHˆ7.6 Hz, H-7, H-7 ); 7.09-7.13 (2t,
0
(P-O-Me), dH (200 MHz, DMSO-d ) 3.16, 3.46 [2d,
JHHˆ7.8 Hz, H-5, H-5 ); 7.26 (d, J ˆ7.4 Hz, H-4); 7.28,
6
HH
0
J ˆ11.2 Hz, P(OMe) ]; 4.27 (s, H-8); 6.32 (s, NH );
7.36 (2t, J ˆ7.8 Hz, H-6, H-6 ); 8.22 (d, J ˆ7.8 Hz,
HP
2
2
HH
HH
0
0
6
.89, 7.01 (2d, J ˆ7.6 Hz, H-7, H-7 ); 7.12, 7.20 (2t,
H-4 ); 10.69, 11.04 (2s, 2NH), d (67.5 MHz, DMSO-d )
HH
C
6
0
3
JHHˆ7.8 Hz, H-5, H-5 ); 7.30, 7.40 (2t, J ˆ7.8 Hz, H-6,
15.6, 15.8 [2d, J ˆ7.3 Hz, P(OCH Me) ]; 45.2 (d,
2
PC PC
HH
PC
2
2
0
0
3
H-6 ); 7.56, 7.62 (2d, J ˆ7.2 Hz, H-4, H-4 ); 10.69, 11.01
J ˆ14.6 Hz, C-8); 60.3, 61.0 [2d, J ˆ4.9 Hz,
0
2 2 PC
HH
3
3
(
2s, 2NH), dC (67.5 MHz, DMSO-d ) 45.3 (d, J ˆ
P(OCH Me) ]; 61.5 (d, J ˆ14.6 Hz, C-3 ); 63.5 (d,
6
PC
2
2
1
1
6
8
1
4.7 Hz, C-8); 51.5, 51.6 [2d, J ˆ4.9 Hz, P(OMe) ];
J ˆ18.3 Hz, C-3); 87.4 (d, J ˆ197.8 Hz, C-10);
PC
2
PC PC
3
0
2
0
1.3 (d, J ˆ14.6 Hz, C-3 ); 64.0 (d, J ˆ17.1 Hz, C-3);
109.6, 110.3 (C-7, C-7 ); 116.0 (CuN); 122.0, 122.2
PC
PC
1
0
0
0
7.1 (d, J ˆ195.3 Hz, C-10); 109.8, 110.7 (C-7, C-7 );
(C-5, C-5 ); 124.2, 126.8 (C-4, C-4 ); 127.0, 129.2 (C-3a,
C-3 a); 129.8, 130,8 (C-6, C-6 ); 142.0, 142.9 (C-7a, C-7 a);
PC
0
0
0
0
15.5 (CuN); 121.7, 122.4 (C-5, C-5 ); 125.1, 125.6
0
0
2
(
C-4, C-4 ); 126.9, 129.3 (C-3a, C-3 a); 129.6, 130.2 (C-6,
162.5 (d, J ˆ15.9 Hz, C-9); 176.0, 177.8 (2 CvO), m/z
PC
0
0
2
ϩ
C-6 ); 142.0, 143.1 (C-7a, C-7 a); 162.1 (d, J ˆ17.1 Hz,
478 (M , 95%), 450 (10), 405 (2), 376 (4), 341 (100), 314
PC
ϩ
C-9); 175.8, 178.5 (2CvO), m/z 450 (M , 26%), 422 (11),
(17), 233 (3), 171 (7), 111 (3) and 82 (2). The fourth fraction
(35–25% petroleum ether) yielded colourless crystalline
4
08 (4), 390 (3), 355 (23), 341 (100), 296 (22), 270 (11), 247
(
4), 203 (2), 184 (4), 170 (28), 142 (28), 109 (72), 79 (31)
product of the dimeric structure, isomer 9b (33%), recrys-
tallized from acetone/n-hexane, mp 279–280ЊC, [Found C,
B
and 77 (4).
6
0.31; H, 4.76; N, 11.79; P, 6.50. C H N O P requires C,
24 23 4 5
Ϫ1
Reaction of (E)-nitrile (3) with triethyl phosphite (7b).
Carrying out the same experimental procedure as described
above gave also four fractions. The first fraction [70–65%
petroleum ether (bp 60–80ЊC)] afforded a small amount of
colourless crystals of diethyl [cyano(2,3-dihydro-2-oxo-1H-
60.25; H, 4.85; N, 11.71; P, 6.47%], nmax cm 3423, 3320
(NH ); 3253 (NH); 1737, 1706 (CvO); 1624 (CvC); 1190
(PvO); 1026 (P-O-Et), dH (200 MHz, DMSO-d ), 0,82,
2
6
1.16 [2t, JHHˆ7.2 Hz, 6H, P(OCH Me) ]; 3.38–3.87 [m,
2
2
4H, P(OCH Me) ]; 4.27 (s, H-8); 6.28 (s, NH ); 6.88, 7.00
2
2
2
0
indol-3-yl)methyl]phosphonate (isomer 8b ), examined by
(2d, JHHˆ7.6 Hz, H-7, H-7 ); 7.11, 7.20 (2t, J ˆ7.6 Hz,
A
HH
1
0
0
H NMR spectrum, mp 154–155ЊC, [Found C, 54.62; H,
H-5, H-5 ); 7.29, 7.39 (2t, J ˆ7.6 Hz, H-6, H-6 ); 7.52,
HH
0
5
.51; N, 9.02; P, 10.11. C H N O P requires C, 54.54;
7.59 (2d, JHHˆ7.6 Hz, H-4, H-4 ); 10.67, 10.99 (2s, 2NH),
1
4
17
2
4
Ϫ1
3
H, 5.56; N, 9.09; P, 10.05%], nmax cm 3192 (NH); 2239
dC (67.5 MHz, DMSO-d ) 15.6, 15.8 [2d, J ˆ7.4 Hz,
6
3
PC
(
CuN); 1724 (CvO); 1620 (CvC): 1280 (PvO); 1014
P(OCH Me) ]; 45.3 (d, J ˆ14.7 Hz, C-8); 60.3, 60.9
2
2
PC
2
3
(P-O-Et), dH (200 MHz, DMSO-d ) 1.13, 1.19 [2t,
[2d, J ˆ4.9 Hz, P(OCH Me) ]; 61.4 (d, J ˆ14.7 Hz,
0
PC PC
6
PC 2 2 PC
2
1
JHHˆ7.0 Hz, P(OCH Me) ]; 3.69–4.08 [m, P(OCH Me) ];
C-3 ); 64.0 (d, J ˆ17.1 Hz, C-3); 88.1 (d, J ˆ
2
2
2
2
0
4
.16 (dd, J ˆ27.0 Hz, J ˆ3.4 Hz, H-3); 4.36 (dd,
195.3 Hz, C-10); 109.7, 110.7 (C-7, C-7 ); 115.6 (CuN);
HP
HH
0 0
121.6, 122.3 (C-5, C-5 ); 125.0, 125.7 (C-4, C-4 ); 127.0,
J ˆ23.4 Hz, J ˆ3.4 Hz, H-8); 6.87 (d, J ˆ7.6 Hz,
HP
HH
HH
0 0
129.1 (C-3a, C-3 a); 129.1, 130.1 (C-6, C-6 ); 142.1, 143.0
2
H-7); 7.02, 7.26 (2t, J ˆ7.6 Hz, H-5, H-6); 7.47 (d,
HH
0
JHHˆ7.8 Hz, H-4); 10.63 (s, NH), d (67.5 MHz, DMSO-
(C-7a, C-7 a); 161.6 (d, J ˆ15.8 Hz, C-9); 175.8, 178.5 (2
C
PC
3
ϩ
d ) 15.9, 16.0 [2d, J ˆ7.4, 6.1 Hz, P(OCH Me) ]; 29.2 (d,
CvO), m/z 478 (M , 40%), 450 (10), 376 (8), 369 (15), 341
6
PC
2
2
1
2
J ˆ141.6 Hz, C-8); 43.1 (C-3); 63.0, 63.2 [2d, J ˆ7.4,
(100), 296 (26), 233 (9), 229 (3), 199 (2), 170 (24), 142 (15),
115 (12), 82 (6) and 69 (12).
PC
PC
2
6
.1 Hz, P(OCH Me) ]; 109.6 (C-7); 116.4 (d, J ˆ7.3 Hz,
2
2
PC
CuN); 121.3 (C-5); 124.7 (C-4); 125.5 (C-3a); 128.7 (C-6);
1
1
3
ϩ
43.0 (C-7a); 175.3 (d, J ˆ14.6 Hz, CvO), m/z 308 (M ,
Reaction of methyl iodide with 9a . A mixture of
9a (0.23 g, 0.5 mmol), freshly distilled methyl iodide
PC
B
00%), 263 (11), 208 (5), 199 (3), 171 (74), 170 (45), 138
B
(
63), 111 (77), 82 (47), 81 (39), 77 (33) and 65 (17). The
(1.5 mL) and anhydrous powdered potassium carbonate
(1 g) in dry acetone (15 mL) was gently heated, under reflux
for about 5 h. After removal of the inorganic residue and
second fraction contained a mixture of the two isomers 8bA
and 8b (20%). The other isomer 8b could not be isolated
B
B

1
870
F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
volatile materials, the solid product (0.20 g, 83%) was crys-
tallized from acetone–diethyl ether to give 10a as colourless
crystals, mp 259–260ЊC, [Found C, 60.31; H, 4.78; N,
NMR spectrum compared with an authentic sample
previously reported).
1
1.66; P, 6.54. C H N O P requires C, 60.25; H, 4.85;
Similarly, compounds 8b (as a mixture of the two isomers
8b , 8b ) and isomer 9b were formed from the reaction of
2
4
23
4
5
Ϫ1
N, 11.71; P, 6.47%], nmax cm 3462, 3315 (NH ); 2245
2
A
B
B
(
CuN, very weak); 1736, 1707 (CvO); 1628 (CvC);
240 (PvO); 1012 (P-O-Me), dH (270 MHz, DMSO-d6)
3 with diethyl phosphite (11b) under the same experimental
conditions described above. The first fraction yielded a
colourless crystals of the phosphonate 8b (34%) as a
1
3
2
.17, 3.43 [2d, J ˆ11.6 Hz, P(OMe) ]; 3.20, 3.23 (2s,
HP
2
1
N-Me); 4.31 (s, H-8); 6.34 (s, NH ); 7.09, 7.20 (2d,
mixture of the two isomers 8b and 8b (shown by its H
2
A
B
0
JHHˆ7.8 Hz, H-7, H-7 ); 7.21, 7.29 (2t, J ˆ7.4 Hz, H-5,
NMR spectrum). The second fraction afforded a colourless
HH
0
0
H-5 ); 7.41, 7.50 (2t, J ˆ7.6 Hz, H-6, H-6 ); 7.62, 7.68
crystals of the isomer 9bB (25%) (identified by its mp,
HH
0
1
(
2d, JHHˆ7.3 Hz, H-4, H-4 ), d (67.5 MHz, DMSO-d )
mixed mp and comparative H NMR spectrum with an
C
6
3
2
5
6.7, 27.0 (2 N-Me); 44.7 (d, J ˆ14.6 Hz, C-8); 51.4,
authentic sample previously reported).
PC
2
3
1.9 [2d, J ˆ3.7 Hz, P(OMe) ]; 60.9 (d, J ˆ13.4 Hz,
PC
2
PC
0
2
1
C-3 ); 63.5 (d, J ˆ17.1 Hz, C-3); 87.1 (d, J ˆ
Reaction of methyl iodide with the phosphonate 8b as a
PC
PC
0
1
1
1
96.5 Hz, C-10); 108.7, 109.7 (C-7, C-7 ); 115.6 (CuN);
mixture of the two isomers 8b and 8b . To a solution of
A
B
0
0
22.3, 122.9 (C-5, C-5 ); 124.6, 125.4 (C-4, C-4 ); 126.4,
the mixture 8b (0.93 g, 3 mmol) in dry acetone (30 mL),
anhydrous potassium carbonate (2 g) and freshly distilled
methyl iodide (4 mL) were added. The mixture was gently
heated under reflux for about 8 h. Then, the inorganic
residue and volatile materials were removed and the
residual substance was chromatographed on silica gel
using n-hexane and acetone as eluent to give two fractions.
The first fraction (80–75% n-hexane) gave colourless crystals
of diethyl [1-cyano-1-(2,3-dihydro-1,3-dimethyl-2-oxo-1H-
indol-3-yl)ethyl]phosphonate (16a) (0.34 g, 33%), recrystal-
lized from benzene/n-hexane, mp 89–90ЊC, [Found 58.23; H,
6.59; N, 8.04; P 8.79. C H N O P requires C, 58.28; H,
0
0
28.8 (C-3a, C-3 a); 129.4, 130.2 (C-6, C-6 ); 143.5, 144.6
0
2
(
C-7a, C-7 a); 161.8 (d, J ˆ15.9 Hz, C-9); 174.0, 176.9 (2
PC
ϩ
CvO). m/z 478 (M , 100%), 450 (5), 383 (6), 369 (96), 341
(
1
26), 324 (40), 294 (84), 261 (9), 247 (5), 194 (3), 184 (61),
55 (27), 130 (10) and 79 (3).
Similarly, compound 10b was obtained as colourless crys-
tals from the reaction of 9b with methyl iodide under the
same experimental conditions described above.
B
Compound 10b (88%), crystallized from chloroform–
petroleum ether (bp 60–80ЊC), mp 256–257ЊC, [Found C,
6
6
(
(
17
23
2
4
Ϫ1
6.62; N, 8.00; P, 8.84%], nmax cm 2237 (CuN); 1711
(CvO); 1612 (CvC); 1261 (PvO); 1049 (P-O-Et), dH
(200 MHz, CDCl3) 1.05, 1.18 [2t, JHHˆ7.2 Hz,
P(OCH Me) ]; 1.62 (s, Me at C-3); 1.95 (d, J ˆ15.4 Hz,
1.71; H, 5.45; N, 11.01; P, 6.08. C H N O P requires C,
26 27 4 5
Ϫ1
1.66; H, 5.37; N, 11.06; P, 6.12%], nmax cm 3411, 3313
NH ); 2240 (CuN, very weak); 1728 (CvO); 1635, 1612
2
2
2
HP
CvC); 1209 (PvO); 1049, 1018 (P-O-Et), d (270 MHz,
Me at C-8); 3.19 (s, N-Me); 3.39–4.15 [m, P(OCH Me) ];
2 2
H
CDCl ) 0.75, 1.20 [2t, J ˆ7.0 Hz, P(OCH Me) ]; 3.21,
6.83 (d, JHHˆ 7.6 Hz, H-7); 7.07, 7.31 (2t, J ˆ7.6 Hz, H-5,
3
HH
2
2
HH
3
.23 (2s, 2 N-Me); 3.35–4.10 [m, P(OCH Me) ]; 4.46 (s,
H-6); 7.72 (d, J ˆ7.4 Hz, H-4), d (67.5 MHz, CDCl )
2
2
HH
C
3
0
2
H-8); 5.16 (s, NH ); 6.84, 6.92 (2d, J ˆ7.6 Hz, H-7, H-7 );
16.0 (d, J ˆ6.1 Hz, Me at C-8); 16.1, 16.4 [2d,
2
HH
PC
0
3
3
7
.15, 7.21 (2t, JHHˆ7.4 Hz, H-5, H-5 ), 7.32, 7.40 (2t,
J ˆ4.9, 3.6 Hz, P(OCH Me) ]; 21.3 (d, J ˆ9.8 Hz,
PC
2
2
PC
0
1
JHHˆ7.8 Hz, H-6, H-6 ); 7.49, 7.59 (2d, J ˆ7.6 Hz, H-4,
Me at C-3); 26.3 (N-Me); 43.1 (d, J ˆ144.1 Hz, C-8);
HH
PC
0
3
2
H-4 ), d (67.5 MHz, CDCl ) 15.5, 15.8 [2d, J ˆ7.4 Hz,
47.0 (C-3); 63.7, 63.8 [2d,
J ˆ7.3, 8.5 Hz,
C
3
PC
PC
3
2
P(OCH Me) ; 26.7, 27.1 (2 N-Me); 44.5 (d, J ˆ13.5 Hz,
P(OCH Me) ]; 108.0 (C-7); 118.8 (d, J ˆ8.5 Hz,
2
2
PC
2
2
PC
2
C-8); 60.9, 62.0 [2d, J ˆ4.9 Hz, P(OCH Me) ]; 61.3 (d,
CuN); 122.3 (C-5); 124.6 (C-4); 128.8 (C-6); 130.7
PC
2
2
3
0
2
ϩ
J ˆ14.7 Hz, C-3 ); 63.9 (d, J ˆ18.3 Hz, C-3); 91.3 (d,
(C-3a); 142.2 (C-7a); 175.7 (CvO), m/z 350 (M , 36%),
PC
PC
1
0
J ˆ192.8 Hz, C-10); 108.3, 109.2 (C-7, C-7 ); 115.4
305 (1), 249 (1), 213 (1), 191 (2), 160 (100) and 132 (3). The
second fraction (75–72% n-hexane) afforded colourless
crystals of diethyl [cyano(2,3-dihydro-1,3-dimethyl-2-oxo-
1H-indol-3-yl)methyl]phosphonate (16b) (0.39 g, 38%),
recrystallized from benzene/n-hexane, mp 132–133ЊC,
[Found C, 57.20; H, 6.33; N, 8.27; P, 9.28, C H N O P
PC
0
(
CuN); 122.5, 123.5 (C-5, C-5 ); 125.1, 125.3 (C-4,
0
0
0
C-4 ); 125.4, 128.9 (C-3a, C-3 a); 129.5, 130.6 (C-6,
0
2
C-6 ); 143.6, 143.9 (C-7a, C-7 a); 160.6 (d, J ˆ15.8 Hz,
PC
ϩ
C-9); 174.3, 176.5 (2 CvO), m/s 506 (M , 100%), 478 (4),
4
04 (3), 397 (13), 369 (85), 324 (26), 322 (44), 310 (13), 265
16
21
2
4
Ϫ1
(4), 247 (16), 225 (3), 184 (36), 155 (25), 138 (11) and 111 (6).
requires C, 57.14; H, 6.29; N, 8.33; P, 9.21%]. nmax cm
2
241 (CuN); 1709 (CvO); 1614 (CvC); 1265 (PvO);
Reaction of (E)-nitrile (3) with dimethyl phosphite (11a).
A mixture of compound 3 (2.55 g, 15 mmol) and freshly
distilled dimethyl phosphite (11a) (4 mL) was heated with-
out solvent at 100–105ЊC. After 30 h, the excess dimethyl
phosphite was removed under reduced pressure and the oily
residue was chromatographed on silica gel, using acetone
and n-hexane as eluent to give two fractions. The first frac-
tion (65–60% n-hexane) yielded colourless crystalline
product (1.31 g, 36%), proved to be the phosphonate 8a
1020 (P-O-Et), dH (200 MHz, CDCl ) 1.02, 1.23 [2t,
3
4
JHHˆ7.2 Hz, P(OCH Me) ]; 1.57 (d, J ˆ2.0 Hz, Me at
2
2
HP
C-3); 3.22 (s, N-Me); 3.23–4.09 (m, P(OCH Me) ]; 3.64
2
2
2
(d overlaped, J ˆ23.0 Hz, H-8); 6.88 (d, J ˆ7.8 Hz,
HP
HH
H-7); 7.09, 7.33 (2t, J ˆ7.6 Hz, H-5, H-6); 7.58 (d,
HH
J
ˆ7.6 Hz, H-4), d (67.5 MHz, CDCl ) 15.9, 16.0 [2d,
HH
C
3
3
3
J ˆ2.4 Hz, P(OCH Me) ]; 24.6 (d, J ˆ13.5 Hz, Me at
PC
2 2 PC
1
C-3); 26.6 (N-Me); 37.2 (d, J ˆ141.6 Hz, C-8); 45.8 (d,
PC
2
2
J ˆ2.4 Hz, C-3); 63.2, 63.4 [2d, J ˆ7.3, 6.1 Hz,
PC
PC
2
containing a mixture of the two isomers 8a and 8aB
P(OCH Me) ]; 108.5 (C-7); 115.0 (d, J ˆ9.8 Hz,
A
2
2
PC
1
examined by its H NMR spectrum. The second fraction
CuN); 122.4 (C-5); 123.9 (C-4); 129.1 (C-6); 129.4
ϩ
(
40–35% n-hexane) gave a colourless crystalline product
(C-3a); 143.3 (C-7a); 176.6 (CvO), m/z 336 (M , 36%),
183 (3), 160 (100) and 130 (4).
1
(1.12 g, 31%) proved to be 9a (mp, mixed mp and H
B

F. H. Osman, F. A. El-Samahy / Tetrahedron 56 (2000) 1863–1871
1871
Preparation of 3-dicyanomethylene-2-oxindole.
mixture of isatin (1) (1.47 g, 10 mmol) and malononitrile
0.73 g, 11 mmol) in absolute ethanol (30 mL) was stirred at
A
amide); 1267 (PvO); 1031 (P-O-Me), dH (200 MHz,
CDCl ) 1.90 (s, Me at C-3); 3.31 (s, 3H, N-Me); 3.81,
3
(
3.89 [2d, JHHˆ11.0 Hz, P(OMe) ]; 6.96 (d, J ˆ8.0 Hz,
2
HH
room temperature for about 15 min. During this time, the
isatin dissolved and a deep red precipitate was formed. It
was filtered off and crystallized from absolute ethanol to
give 1.71 g of 3-dicyanomethylene-2-oxindole, mp 237–
H-7); 7.22, 7.49 (2t, J ˆ7.8 Hz, H-5, H-6) 7.85 (d,
HH
3
JHHˆ7.6 Hz, H-4), d (67.5 MHz, CDCl ) 22.2 (d, J ˆ
C
3
PC
2
4.9 Hz, Me at C-3); 27.1 (N-Me); 35.4 (d, J ˆ2.9 Hz,
PC
2
C-3); 54.4, 56.1 [2d, J ˆ7.8 Hz, P(OMe) ]; 55.7 (d,
PC
2
1
5
1
2
38ЊC (lit. 235ЊC). The filtrate afforded upon concen-
J ˆ140.4 Hz, C-8); 109.3 (C-7); 113.6, 113.9 (2d,
PC
2
3
tration an additional amount of 0.14 g (total yield 1.85 g,
J ˆ4.9, 7.8 Hz, 2 CuN); 120.3 (d, J ˆ5.9 Hz, C-3a);
PC
PC
Ϫ1
4
9
1
5%), nmax cm 3261 (NH); 2240 (CuN, very weak);
730, 1716 (CvO); 1620, 1585 (CvC).
123.8 (C-5); 126.7 (d, J ˆ3.9 Hz, C-4); 131.3 (d,
PC
6
4
J ˆ2.0 Hz, C-6): 144.4 (d, J ˆ6.8 Hz, C-7a); 168.5
PC
PC
ϩ
(
CvO), m/z 333 (M , 77%), 318 (2), 254 (100), 224 (20),
Preparation of dimethyl [dicyano(2,3-dihydro-2-oxo-
198 (25), 171 (20), 146 (35), 117 (11); 109 (25), 93 (83), 79
(10) and 63 (7).
1
H-indol-3-yl)methyl]phosphonate (17a). A mixture of
3
-dicyanomethylene-2-oxindole (3.0 g, 15.4 mmol) and
freshly distilled dimethyl phosphite (3 mL) was heated
under reflux at 100–105ЊC. After about 2 h, the reaction
mixture was allowed to stand overnight. The colourless
crystals, thus formed, was filtered off and washed with dry
ether. Recrystallization from ethyl methyl ketone afforded9
the phosphonate 17a (3.2 g, 66%), mp 226–227ЊC (lit.
The phosphonate 19b was also obtained as colourless
crystals when 17b reacted with methyl iodide under the
same experimental conditions described above.
Diethyl
[dicyano(2,3-dihydro-1,3-dimethyl-2-oxo-1H-
indol-3-yl)methyl]phosphonate (19b) (72%), crystallized
from benzene/n-hexane, mp 136–137ЊC, [Found C, 56.43;
H, 5.62; N, 11.58; P, 8.65. C H N O P requires C, 56.51;
2
22ЊC), [Found C, 51.24; H, 3.90; N, 13.74; P, 10.21.
C H N O P requires C, 51.15; H, 3.96; N, 13.77; P,
13
12
3
4
17 20
3
4
Ϫ1
Ϫ1
1
1
0.15%], nmax cm 3151 (NH); 1724 (CvO, amide);
255 (PvO); 1026 (P-O-Me), dH (200 MHz,
H, 5.58; N, 11.63; P, 8.57%], nmax cm 1720 (CvO,
amide); 1263 (PvO); 1018 (P-O-Et), dH (200 MHz,
CDCl ) 1.222, 1.689 [2dt, J ˆ7.0 Hz, J ˆ0.8 Hz,
CDCl ϩDMSO-d ) 3.66, 3.69 [2d, J ˆ11.0 Hz,
3
6
HP
3
HH
HP
P(OMe) ]; 4.81 (d, J ˆ6.8 Hz, H-3); 6.88 (d, J
ˆ
HH
P(OCH Me) ]; 1.92 (s, Me at C-3); 3.29 (s, N-Me); 4.19
2 2
2
HP
8
.0 Hz, H-7); 7.00, 7.25 (2t, J ˆ7.8 Hz, H-5, H-6); 7.53
[m, P(OCH Me) ]; 6.94 (d, J ˆ7.8 Hz, H-7); 7.20, 7.47
HH
2
2
HH
(
d, JHHˆ7.8 Hz, H-4); 10.90 (s, NH), d (67.5 MHz,
(2t, JHHˆ7.8 Hz, H-5, H-6); 7.82 (d, J ˆ7.6 Hz, H-4). m/z
C
HH
1
ϩ
DMSO-d ) 27.0 (C-3); 52.9 (d, J ˆ139.2 Hz, C-8); 55.5,
361 (M , 100%), 346 (4), 282 (92), 254 (6), 224 (7), 210
6
PC
2
5
7.7 [2d, J ˆ7.3 Hz, P(OMe) ]; 110.9 (C-7); 111.1, 111.5
(25), 198 (72), 171 (11), 146 (42), 109 (7) and 58 (13).
PC
2
2
3
(
2d, J ˆ14.6, 8.6 Hz, 2 CuN); 121.4 (d, J ˆ5.1 Hz,
PC
PC
5
C-3a); 122.8 (d,
J ˆ2.5 Hz, C-5); 125.8 (d,
PC
4
6
J ˆ2.4 Hz, C-4); 131.2 (d, J ˆ2.4 Hz, C-6); 143.0 (d,
PC
PC
4
3
J ˆ7.4 Hz, C-7a); 170.6 (d, J ˆ2.5 Hz, CvO).
References
PC
PC
Diethyl [dicyano(2,3-dihydro-2-oxo-1H-indol-3-yl)methyl]-
phosphonate (17b) (69%) was obtained similarly from
1. Pietra, S. Farmaco, Ed. Sci. 1957, 12, 946; Chem. Abstr. 1958,
52, 12841f.
2. Long, D. R.; Richards, C. G.; Ross, M. S. F. J. Heterocycl.
Chem. 1978, 15, 633.
3. Jones, G.; Rae, W. J. Tetrahedron 1966, 22, 3021.
4. Mathieson, D. W. Nuclear Magnetic Resonance for Organic
Chemists, Academic Press: London, 1967 (Chapter 3, p 38).
5. Kemp, W. Organic Spectroscopy, 3rd ed.; Macmillan: Hamp-
shire, 1991 (pp 152 and 158).
6. Colthup, N. B.; Daly, L. H.; Wiberley, S. E. Introduction to
Infrared and Raman Spectroscopy, Academic Press: New York,
1964 (Chapter 11, p 278, Chapter 12, pp 299–301).
3
-dicyanomethylene-2-oxindole and diethyl phosphite,
recrystallized from ethyl methyl ketone, mp 175–176ЊC
9
(lit. 164ЊC), [Found C, 53.97; H, 4.92; N, 12.55; P, 9.38.
C H N O P requires C, 54.06; H, 4.84; N, 12.61; P,
1
5
16
3
4
Ϫ1
9
.29%], nmax cm 3124 (NH); 1726 (CvO, amide); 1248
(PvO); 1020 (P-O-Et), d (200 MHz, CDCl ) 1.35, 1.39 [2t
H
3
overlaped, JHHˆ7.2 Hz, P(OCH Me) ]; 4.25 [m,
2
2
P(OCH Me) ]; 4.77 (d, J ˆ6.6 Hz, H-3); 6.82 (d,
2
2
HP
J
7
ˆ7.8 Hz, H-7); 7.18 7.35 (2t, J ˆ7.6 Hz, H-5, H-6);
HH
HH
.71 (d, J ˆ7.6 Hz, H-4); 9.00 (s, NH).
HH
7
. McClure, C. K.; Grote, C. W.; Lockett, B. A. J. Org. Chem.
Dimethyl [dicyano(2,3-dihydro-1,3-dimethyl-2-oxo-1H-
indol-3-yl)methyl]phosphonate (19a). To a solution of
1992, 57, 5195.
8. Bottin-Strzalko, T.; Seyden-Penne, J.; Pouet, M. J.; Simonnin,
M. P. Organic Magnetic Resonance 1982, 19, 69.
9. Mahran, M. R.; Abdou, W. M.; Abd El-Rahman, N. M.; Sidky,
M. M. Phosphorus, Sulfur and Silicon 1989, 45, 47.
10. Bellamy, L. J. The Infra-red Spectra of Complex Molecules,
3rd ed.; Chapman & Hall: London, 1978 (p 297).
11. Latif, N.; Mishriky, N. Can. J. Chem. 1966, 44, 1271.
12. Mirck, J. Chem. Scripta 1988, 28, 295.
13. Mishriky, N.; Asaad, F. M.; Ibrahim, Y. A.; Girgis, A. S. Rec.
Trav. Chim. Pays-Bas 1994, 113, 35.
14. Trippett, S.; Walker, D. M. J. Chem. Soc. 1959, 3874.
15. Walter, W. Chem. Ber. 1902, 35, 1320.
1
7a (0.31 g, 1 mmol) in dry acetone (20 mL), anhydrous
potassium carbonate (2 g) was added. The mixture was
gently heated at 70ЊC. Then, freshly distilled methyl iodide
(
1 mL) was added with continuous heating for about 30 min.
After the reaction has been completed (examined by TLC),
the inorganic and volatile materials were removed. The
residual substance triturated with n-hexane to give colour-
less crystalline product of 19a (0.25 g, 76%), recrystallized
from benzene/n-hexane, mp 142–143ЊC, [Found C, 54.14;
H, 4.76; N, 12.51; P, 9.35. C H N O P requires C, 54.05;
1
5
16
3
4
Ϫ1
H, 4.84; N, 12.60; P, 9.29%], nmax cm 1718 (CvO,