Isatin derivatives in the reaction with phosphorous hexaethyltriamide. A new approach to the synthesis of isoindigo derivatives

Full text of DOI:10.1134/S1070363208100277

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 10, pp. 1977–1979. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.V. Bogdanov, V.F. Mironov, L.I. Musin, B.I. Buzykin, A.I. Konovalov, 2008, published in Zhurnal Obshchei Khimii, 2008,
Vol. 78, No. 10, pp. 1741–1743.
LETTERS
TO THE EDITOR
Isatin Derivatives in the Reaction
with Phosphorous Hexaethyltriamide.
A New Approach to the Synthesis of Isoindigo Derivatives
A. V. Bogdanov, V. F. Mironov, L. I. Musin, B. I. Buzykin, and A. I. Konovalov
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
e-mail: bogdanov@iopc.knc.ru
Received June 18, 2008
DOI: 10.1134/S1070363208100277
Isoindigo [1H,1'H-bis(indolyl-3-indeno)-2,2'-dione]
and its 1- and 1,1'-substituted derivatives in the recent
years attract attention of researchers not only as dyes,
but also as the substances with specific biological
activity (antileukemic, enterohemorragic, proliferative,
antiinflammation and others), inhibiting ortho-
monooxygenases or kinases and possessing other
related properties [1–4]. 1-(β-D-glucopyranosyl)
isoindigo and isoindigo glycoside have been proposed
as antileilkemia means [2, 3].
phosphites and trialkyl phosphites react also at the 3
position of isatin affording dimeric spirophospholanes
[6, 8, 9 and refs.].
Recently on an example of acetophenone we have
shown that phosphorous hexaehyltriamide is more
conventional reagent for the generation of keto-
carbenes and related dimers from cyclic α-diketones
[10]; the fact of formation of respective carbenes was
confirmed by trapping them with an active
dipolarophile fullerene С60 [11].
Now we for first time studied reaction of
Synthesis of 1-substituted isoindigo, including
isoindigo glycoside [4], often is a multistep process.
The most prospective pathway for the synthesis of
isoindigo derivatives seems to be the dimerization of
ketocarbenes generated from derivatives of isatin.
Isatin and its derivatives Iа, Ib relate to the highly
reactive cyclic α-diketones that are used in the
syntheses of various heterocyclic compounds such as
1,2,4-triazines, quinolines and others. In [5] has been
assumed that 3-(triphenylphosphoranylidene)-2,3-
dihydro-1Н-indol-2-one mixed with isoindigo (II, R =
H, Ме) is formed at the reaction of triphenylphosphine
with isatin and 1-methylisatin in a moderate yield (44
and 49%) via a step of intermediate formation of
carbene (B, R = H, Ме). Generation of carbines from
heterocyclic α-diketones at the action of trico-
ordinated phosphorus derivatives has not been studied
sufficiently [6, 7]. Unlike triphenylphosphine, dialkyl
phosphites and chlorophosphites do not generate
ketocarbenes but are added to isatin forming
dioxindolephosphonates and 3-(3-chlorooxindolyl)
phosphine oxides, respectively. Dioxaphospholanes,
phosphorous
hexamethyltriamide
with
isatin
substituted at 1 position (Iа, Ib). Reaction proceeds
selectively under mild conditions (СН2Cl2, –60°С) for
5–10 min and leads to formation in almost quantitative
yield
of
1,1'-R,R-3,3'-bis(indolin-3-ylidene)-2,2'-
diones (IIа, IIb). Regiochemistry of the desoxy-
genation just at the С3 carbon atom is revealed
unambiguously by means of NMR spectroscopy. In the
not decoupled 13С NMR spectrum of IIb a singlet at
167.13 ppm corresponding to atom С2 is converted into
a triplet with spin-spin coupling constant 3JНСNС 3.5 Hz
due to coupling with methylene group protons. The С3
carbon atom induces a doublet with the constant 3JНССС
2.4 Hz due to coupling with the proton at the С4 atom.
Taking into account typical change of color in time
we suggest that the first step includes single electron
transfer from phosphorus atom onto isatin heterocyclic
system with formation of ion-radical pair (A) that then
through several intermediate steps generates
ketocarbene (B) with liberation of phosphoric
hexaethyltriamide. Then under the reaction conditions
1977

1978
BOGDANOV et al.
_
O
O
P(NEt2)3
(Et2N)3P+
O
O
O
_O=P(NEt2)3
N
N
N
R
R
R
Ia, Ib
A
B
5
4
6
O
R
N
3a
7
7a
R
1
3
N
2
O
IIa, IIb
10
9
11
8
8
9
R = C
CH3 (a), CH2
OH (b).
12
14
13
O
3
2
the ketocarbene (B) exerts dimerization with formation
of respective isoindigo derivative IIа and IIb.
1JНС 161.7–161.0, JНС3СС 8.4, JНСС 2.2), 133.82 d.d.d
(s) (С6, JНС 160.6, JНССС 7.3–8.4, JНСС 2.2–2.9),
1
2
116.30 d.d (s) (С7, JНС 170.9, JНССС 7.7), 141.90
br.d.d (s) (С7а, 3JНССС 8.8), 170.54 q (s) (С8, 2JНСС 7.1),
27.31 q (s) (С9, 1JНС 130.9).
1
3
Structures of compounds IIа and IIb were
confirmed by the methods of NMR and IR
spectroscopy.
1,1'-Diacetylbis (indolin-3-ylidene)-2,2'-dione (IIа).
To a solution of 0.5 g of 1-acetylisatin Iа in 10 ml of
methylene chloride at –60°С and at bubbling of argon
was added dropwise 0.69 ml of phosphorous hexa-
ethyltriamide. Color of reaction mixture sharply
changed from light brown to dark green, and after
adding whole amount of phosphorous amide to red.
Then the reaction mixture was allowed to warm to 20°С
and the crimson colored precipitate formed was
filtered off and dried in a vacuum 12 mm Hg. 0.4 g
(89%) of compound IIа was obtained, mp 260–263°С
(published 258°С [12]). IR spectrum, cm–1: 1712,
1596, 1548, 1415, 1331, 1290, 1183, 1152, 1104,
1022, 916, 776, 744, 671, 639, 581, 461. The 1Н NMR
spectrum (СDCl3, δ, ppm, J, Hz): 8.32 d.d (Н4, 3JНССН
8.2, 4JНСССН 0.6), 7.25 d.t (Н5, 3JНССН 8.2, 4JНСССН 0.9),
1,1'-[3,5-Di(tert-butyl)-4-hydroxyphenylmethyl]
bis(indolin-3-ylidene)-2,2'-dione (IIb). To a suspend-
sion of 1 g of benzylisatin Ib in 20 ml of methylene
chloride at –60°С and at bubbling of argon was added
dropwise 0.72 ml of phosphorous hexaethyltriamide.
The reaction mixture becomes dark qoickly. After
complete adding of the phosphorous amide the
reaction mixture was allowed to warm to 20°С. After
removing of solvent in a vacuum (0.1 mm Hg) a
viscous dark red mass was obtained that was triturated
in dry hexane, filtered off and dried in vacuum (12 mm
Hg) 0.9 g (95%) of compound IIb was isolated, red
substance, mp 266–267°С. The IR sectrum, cm–1:
3634, 1701, 1606, 1578, 1468, 1435, 1382, 1237,
1187, 1155, 1104, 1077, 1040, 1023, 919, 870, 773,
1
748, 677, 658, 559, 460. The Н NMR spectrum
3
4
3
7.48 d.t (Н6, JНССН 8.2, JНСССН 0.9), 8.86 d.d (Н7,
(DMSO-d6, δ, ppm, J, Hz): 7.09 d (Н4, JНССН 7.6),
4
3
3
3JНССН 8.2, JНСССН 0.6), 2.77 s (H9). The ЯМР 13С
7.03 d.d (Н5, JНССН 7.6, JНССН 7.3), 7.41 d.d (Н6,
3
3
NMR spectrum (СDCl3, δС, ppm, J, Hz) (here and
hereinafter in parentheses is given appearance of the
signal under conditions of 13С–{1H} decoupling):
167.98 s (s) (С2), 132.98 s (overlapping with a
component of С6) (С3), 122.36 m (s) (С3а), 128.82 d.d
3JНССН 7.9, JНССН 7.9), 9.12 d (Н7, JНССН 7.9), 4.89 s
(H8), 7.15 br.s (H10), 1.32 s (H14). 13С NMR spectrum
(DMSO-d6, δС, ppm, J Hz): 167.13 s (t) (С2, JНСNС
3
3.5), 132.75 s (d) (С3, JНССС 2.4), 120.80 s (m) (С3а,
3
3JНССС 6.8–7.2), 129.46 d.d (s) (С4, JНС 166.9, JНССС
1
3
1
3
(s) (С4, JНС 167.4, JНССС 7.9), 124.96 d.d.d (s) (С5,
8.9), 121.84 d.d (s) (С5, 1JНС 162.1, 3JНССС 6.8), 132.75
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008

ISATIN DERIVATIVES IN THE REACTION WITH PHOSPHOROUS HEXAETHYLTRIAMIDE
1979
1
3
d.d (s) (С6, JНС 161.4, JНССС 8.1), 109.16 d.d (s) (С7,
Fabbro, D., Prudhomme, M., and Moreau, P.,
Anticancer Drugs, 2007, vol. 18, no. 9, p. 1069.
1JНС 162.2–162.7, JНССС 7.8–8.2), 144.43 m (s) (С7а),
3
66.30 t.m (s) (С8, JНС 144.4, JНССС 1.9–2.0), 127.18
1
3
3. Rui, L., Reardon, K.F., and Wood, T.K., Appl. Microbiol.
Biotechnol., 2005, vol. 66, no. 4, p. 422.
2
1
m (s) (С9, JНСС 3.5–4.2), 123.79 d.m (s) (С10, JНС
154.7), 139.34 m (s) (С11), 153.11 т (s) (С12, JНССС
3
4. Sassatelli, M., Saab, E., Anizon, F., Prudhomme, M.,
and Moreau, P., Tetrahedron Lett., 2004, vol. 45, no. 25,
p. 4827.
8.6–9.0), 34.37 br.m (s) (С13), 30.73 q.m (s) (С13, JНС
1
125.7, 3JНССС 4.4).
1
The Н (400 МHz), 13С (100.6 МHz) and 31Р
5. Lathourakis, G.E. and Litinas, K.E., J. Chem. Soc.,
Perkin Trans. 1, 1996, no. 6, p. 491.
(162.0 МHz) NMR spectra were taken on a Bruker
Avance-400. The IR spectra were registered from the
suspensions of substances in Vaseline oil in a Bruker
Vector-22 instrument.
6. Osman, F.H. and El-Samahy, F.A., Chem. Rev., 2002,
vol. 102, no. 3, p. 629.
7. Hahn, F.E. and Jahnke, M.C., Angew. Chem., Internat.
Ed., 2008, vol. 47, no. 17, p. 3122.
ACKNOWLEDGMENTS
8. Gurevich, P.A., Akhmetova, G.Z., Gubaidullin, A.T.,
Moskva, V.V., and Litvinov, I.A., Zh. Obshch. Khim.,
1998, vol. 68, no. 9, p. 1501.
This work was carried out in the framework of the
Program no. 1 of Chemistry Division and Material
Science of Russian Academy of Sciences and at the
support of the Concil on the Grants of the President of
Russian Federation (grant MK-2444.2007.3).
9. Riisalu, Kh.I., VasilТev, V.V., and Ionin, B.I., Zh.
Obshch. Khim., 1985, vol. 55, no. 10, p. 2237.
10. Bogdanov, A.V., Mironov, V.F., Buzykin, B.I., and
Konovalov, A.I., Zh. Obshch. Khim., 2005, vol. 75, no. 5,
p. 873.
REFERENCES
11. Romanova, I.P., Doctorate Sci. (Chem.) Dissertation,
1. Lee, J., Bansal, T., Jayaraman, A., Bentley, W.E., and
Wood, T.K., Appl. and Environ. Microbiol., 2007, vol. 73,
no. 13, p. 4100.
Kazan’, 2008.
12. Friedlaender, S., Chem. Ber., 1924, vol. 57, p. 652.
2. Sassatelli, M., Bouchikhi, F., Aboab, B., Anizon, F.,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008