New method for the preparation of 3-diazo-1,3-dihydroindol-2-ones

Article abstract of DOI:10.1007/s11172-011-0359-5

A new method for the preparation of diazo compounds of 2-indolinone series by oxidation of isatin hydrazones with polyhaloalkanes in the presence of copper salts in catalytic amounts was developed.

Full text of DOI:10.1007/s11172-011-0359-5

Russian Chemical Bulletin, International Edition, Vol. 60, No. 11, pp. 2343—2346, November, 2011
2343
New method for the preparation of 3ꢀdiazoꢀ1,3ꢀdihydroindolꢀ2ꢀones*
a
a
b
c
V. M. Muzalevskiy, E. S. Balenkova, A. V. Shastin, A. M. Magerramov,
c
a
N. G. Shikhaliev, and V. G. Nenajdenko
aM. V. Lomonosov Moscow State University, Department of Chemistry,
str. 3, 1 Leninskie gory, 119991 Moscow, Russian Federation.
Fax: +7 (495) 932 8846. Eꢀmail: nen@acylium.chem.msu.ru
Institute of Problems of Chemical Physics, Russian Academy of Sciences,
b
1
prosp. Akad. Semenova, 142432 Chernogolovka, Moskovskaya obl., Russian Federation.
c
Baku State University, Department of Chemistry,
2
3 ul. Akad. Z. Khalilova, AZ1148 Baku, Azerbaijan
A new method for the preparation of diazo compounds of 2ꢀindolinone series by oxidation
of isatin hydrazones with polyhaloalkanes in the presence of copper salts in catalytic amounts
was developed.
Key words: catalytic olefination reaction, polyhaloalkanes, copper salts, isatin, oxidation,
catalysis, diazo compounds.
1
Earlier, we have found and extensively studied a new
develop an approach to the synthesis of the corresponding
dihaloalkenes 2, which have several reaction centers and
are of high interest in the synthesis of isatin derivatives.4
However, when carbon tetrachloride was used in the olefiꢀ
nation of isatin hydrazone under standard conditions
(DMSO, aqueous ammonia, 2% CuCl), diazo amide 3a
was obtained in 85% yield instead of the expected dichloroꢀ
alkene 2 (Scheme 2). Similar result was also obtained in
reaction allowing us to form a C=C double bond, viz., the
catalytic olefination reaction. This reaction of polyhaloꢀ
alkanes with Nꢀunsubstituted hydrazones catalyzed with
copper salts allows one to efficiently obtain a wide range
of different alkenes (Scheme 1).
Scheme 1
Scheme 2
1
R
R
= Ar, Alk; Hal = Cl, Br; X = F, Cl, Br, H
2
= Alk, H; Y = F, Cl, Br, CN, CO Et, CF , CF Cl, CF Br
2
3
2
2
The reaction has a general character, hydrazones of
aliphatic, aromatic, and heteroaromatic aldehydes and
1
ketones and a wide range of polyhaloalkanes can be used.
In some cases, the reaction followed an abnormal route
leading to the formation of saturated compounds (without
2
3
a formation of olefination products ).
In the present work, we studied another unusual
transformation occurring under conditions of the catalytic
olefination reaction, viz., the formation of the correspondꢀ
ing diazo alkanes from hydrazones of isatin and its derꢀ
ivatives.
Introducing the isatin hydrazone obtained from isatin
1
a into the catalytic olefination reaction, we expected to
i. EtOH, reflux; ii. NH , DMSO, 2% CuCl.
3
PHA
CCl4
CHBr3
Yield of 3a (%)
PHA
CBr4
Yield of 3a (%)
*
Dedicated to Academician of the Russian Academy of Sciences
85
83
72
69
O. M. Nefedov on the occasion of his 80th birthday.
CF CBr3
3
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2298—2301, November, 2011.
066ꢀ5285/11/6011ꢀ2343 © 2011 Springer Science+Business Media, Inc.
1

2344
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011
Muzalevskiy et al.
the case of other polyhaloalkanes (PHA), however, the
Scheme 4
use of CCl has proved to be the most effective for isolaꢀ
4
tion and purification of the desired reaction products.
In order to study the scope and limitations of this method,
we have used other substrates of the isatin series 1 containꢀ
ing substituents at the nitrogen atom or functional groups
of different nature at position 5. It turned out that this
method has a general character, and the corresponding
diazo compounds 3 can be obtained under mild condiꢀ
tions and in high yields (Scheme 3). To sum up, the polyꢀ
haloalkane—copper chloride—ammonia system serves as
an efficient oxidant of hydrazones into diazo compounds.
i. Cu(acac) , 10%, Et O, 0—5 °C, 20—45 min, O .
2
2
2
X = H, Me, Cl, MeO
Scheme 3
of a ligand and acceptor of the liberated hydrogen halide.
It should be noted that the mild oxidation conditions conꢀ
tribute to high yields of the corresponding diazo comꢀ
pounds even in the presence of copper salts.
Scheme 5
Comꢀ
pound
R
R´
Yield 3
(%)
85
86
71
52
53
73
46
a
b
c
d
e
f
H
Me
Bn
H
H
H
H
H
H
F
Cl
NO2
MeO
g
H
h
H
H
69
47
i
L = NH3
5
Earlier, diazo compounds of the 2ꢀindolinone series 3
have been obtained by oxidation of unsubstituted hydrꢀ
Earlier, unsubstituted hydrazones of carbonyl comꢀ
pounds were oxidized into diazo alkanes with mercury
oxide, lead tetraacetate, iodonium salts, and iodoso comꢀ
pounds, as well as with other inorganic and organic oxiꢀ
dants. Copper salts (like many transition metal salts) efꢀ
fectively catalyze decomposition of diazo alkanes with libꢀ
8
9
azones with mercury oxide or lead tetraacetate, by the
1
0
reaction of 2ꢀindolone (oxyindole) with sulfonylazides,
however, the most widely used method is decomposition of
isatin tosylhydrazones upon the action of aqueous alkali.
1
1
6
The results obtained are the second example of the
copper salt catalyzed oxidation of unsubstituted hydrazone
to diazo compound, providing preparative yields. This
method of the synthesis of diazo compounds is likely to
have a great potential and opens wide synthetic possibiliꢀ
ties, and we are planning further, more detailed studies of
this interesting oxidation system.
eration of the nitrogen molecule. There was only one
work , where copper(II) acetylacetonate was used as a catꢀ
alyst in oxidation of a number of keto hydrazones to the
corresponding diazo ketones with air oxygen at 0—5 °C
7
(
Scheme 4).
Mechanism of the reaction was not discussed in this
work, however, it can be suggested that a divalent copper
is the true oxidant, air oxygen is the cooxidant. Apparentꢀ
ly, in our case a divalent copper is also the true oxidant of
hydrazone to diazoamide (Scheme 5). The role of polyꢀ
Experimental
2
+
haloalkane consists in the regular regeneration of Cu
,
1H and 13C NMR spectra were recorded on a Bruker AMX
i.e., it plays the role of cooxidant in this reaction. Ammoꢀ
nia, as in the catalytic olefination reaction, plays the role
400 spectrometer (400.1 MHz and 100.6 MHz, respectively) in
CDCl3 and DMSOꢀd6 using SiMe4 as an internal standard.

New 3ꢀdiazoꢀ1,3ꢀdihydroindolꢀ2ꢀones synthesis
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 11, November, 2011 2345
NH). 13C NMR (DMSOꢀd ), δ: 55.9 (MeO); 61.1 (C=N );
IR spectra were recorded on an URꢀ20 spectrophotometer for
neat samples. TLC analysis was performed on Silufol UVꢀ254
6
2
105.7, 110.9, 111.8, 118.5, 126.8, 155.1, 168.3 (NHC=O).
Found (%): C, 57.14; H, 3.73; N, 22.21. C H N O . Calculatꢀ
plates, visualizing in acidified aqueous KMnO , in iodine vapor,
4
9
7
3
2
or under the UV light. Column chromatography was performed
on Merck silica gel (63—200 mesh). The starting compounds
ed (%): C, 56.87; H, 3.91; N, 21.98.
3ꢀDiazoꢀ5ꢀpiperidinosulfonylꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone
(3h). The yield was 1.063 g (69%), a brownish yellow powder,
1
b,c (see Ref. 12) and 1d—i (see Ref. 13) were obtained accordꢀ
1
13
–1
ing to the procedures described earlier. The H and C NMR
spectra of compounds 3a (see Ref. 14) and 3b,c (see Ref. 15)
agree with those given in the literature.
m.p. 190—191 °C. IR, ν/cm : 1680 (NHC=O); 2120 (C=N ).
2
1
H NMR (DMSOꢀd ), δ: 1.29—1.38 (m, 2 H, CH ); 1.48—1.58
6
2
(m, 4 H, 2 NCH CH ); 2.81—2.90 (m, 4 H, 2 NCH CH ); 7.09
2
2
2
2
Synthesis of 3ꢀdiazoꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀones 3 (general
procedure). A hot solution of the corresponding isatin 1 (5 mmol)
in ethanol (50 mL) was poured to hydrazine hydrate (0.275 mg,
(d, 1 H, J = 8.3 Hz); 7.43 (dd, 1 H, J = 8.3 Hz, J = 1.6 Hz); 7.88
13
(d, 1 H, J = 1.6 Hz); 11.14 (s, 1 H, NH). C NMR (DMSOꢀd ),
6
δ: 23.4 (CH ); 25.2 (NCH CH ); 47.1 (NCH CH ); 61.7 (C=N );
2
2
2
2
2
2
5
.5 mmol) in ethanol (10 mL). The reaction mixture was reꢀ
110.1, 118.6, 119.1, 125.3, 128.3, 136.5, 168.0 (NHC=O).
Found (%): C, 50.81; H, 4.68; N, 17.99. C H N O S. Calcuꢀ
lated (%): C, 50.97; H, 4.61; N, 18.29.
fluxed for 1—3 h (TLC monitoring), followed by evaporation of
ethanol in vacuo. Then, dimethyl sulfoxide (20 mL), 25% aq.
ammonia (2 mL, ~25 mmol), and CuCl (10 mg, 2 mol.%) were
added, and after stirring the mixture for 5 min, CCl (2.5 mL,
2
ture was stirred for 1 day, poured into water (300 mL), extracted
with dichloromethane (3×50 mL), and dried with magnesium
sulfate. Dichloromethane was evaporated in vacuo on rotary
evaporator, the residue was purified by passing through a filter
with silica gel, using dichloromethane or the dichloroꢀ
methane—methanol (50 : 1) mixture as an eluent.
13
14
4
3
3ꢀDiazoꢀ5ꢀmorpholinosulfonylꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone
(3i). The yield was 0.717 g (47%), a brownish yellow powder,
4
–
1
5 mmol) was poured at room temperature. This reaction mixꢀ
m.p. 245—247 °C. IR, ν/cm : 1680 (NHC=O); 2120 (C=N ).
2
1
H NMR (DMSOꢀd ), δ: 2.81—2.90 (m, 4 H, 2 NCH );
6
2
3.60—3.67 (m, 4 H, 2 OCH ); 7.11 (d, 1 H, J = 8.2 Hz); 7.45
2
(dd, 1 H, J = 8.2 Hz, J = 1.7 Hz); 7.89 (d, 1 H, J = 1.7 Hz); 11.17
13
(s, 1 H, NH). C NMR (DMSOꢀd ), δ: 46.4 (NCH ); 61.8
6
2
(C=N ); 65.8 (OCH ); 110.2, 118.8, 119.3, 125.6, 127.1, 136.8,
2
2
168.0 (NHC=O). Found (%): C, 46.79; H, 3.89; N, 18.07.
C H N O S. Calculated (%): C, 46.75; H, 3.92; N, 18.17.
3
ꢀDiazoꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3a). The yield was
12
12
4
4
0
.676 g (85%), a red powder, m.p. 166—168 °C (Ref. 16: 168 °C).
–
1
IR, ν/cm : 1680 (NHC=O), 2089 (C=N ).
This work was financially supported by the Russian
2
3
ꢀDiazoꢀ1ꢀmethylꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3b). The
yield was 0.749 g (86%), a reddish orange powder, m.p. 88—89 °C
Ref. 15: 88—90 °C).
ꢀDiazoꢀ1ꢀbenzylꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3c). The
yield was 0.878 g (71%), an orange powder, m.p. 85—87 °C
Ref. 15: 84—86 °C). IR, ν/cm–1: 1672 (NHC=O), 2120 (C=N ).
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00897ꢀa)
and the Ministry of Education and Science of the Russian
Federation (State Contract P962).
(
3
References
(
2
3
ꢀDiazoꢀ5ꢀfluoroꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3d). The
yield was 0.464 g (52 %), a brownish yellow powder, m.p.
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–1
2
2
7
06—207 °C (Ref. 17: 209—210 °C). IR, ν/cm : 1687 (NHC=O),
1
096 (C=N ). H NMR (DMSOꢀd ), δ: 6.81—6.92 (m, 2 H);
2
6
13
.34—7.38 (m, 1 H); 10.66 (s, 1 H, NH). C NMR (DMSOꢀd6)
δ: 61.6 (C=N ); 107.1 (d, J = 27.8 Hz); 110.9 (d, J = 8.8 Hz);
2
1
(
12.0 (d, J = 24.2 Hz); 119.0 (d, J = 11.3 Hz); 129.4, 158.1
d, J = 234.9 Hz); 168.1 (NHC=O).
ꢀChloroꢀ3ꢀdiazoꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3e). The
yield was 0.507 g (53%), a brownish yellow powder, m.p.
89—191 °C. IR, ν/cm–1: 1710 (NHC=O); 2120 (C=N ).
5
1
2
1
H NMR (DMSOꢀd ), δ: 6.87 (d, 1 H, J = 8.4 Hz); 7.08 (dd,
6
1
H, J = 8.4 Hz, J = 2.1 Hz); 7.53 (d, 1 H, J = 2.1 Hz); 10.75
13
(
s, 1 H, NH). C NMR (DMSOꢀd ), δ: 60.7 (C=N ); 111.0, 119.0,
6 2
1
19.1, 124.7, 125.2, 131.4, 167.4 (NHC=O). Found (%):
C, 49.54; H, 2.04; N, 21.78. C H ClN O. Calculated (%):
8
4
3
C, 49.63; H, 2.08; N, 21.71.
ꢀDiazoꢀ5ꢀnitroꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3f). The yield
was 0.749 g (73%), a yellow powder, m.p. 237—239 °C (Ref. 18:
3
–
1
2
2
8
1
38—240 °C). IR, ν/cm : 1355, 1520 (NO ); 1710 (NHC=O);
2
1
155 (C=N ). H NMR (DMSOꢀd ), δ: 7.08 (d, 1 H, J = 8.7 Hz);
.04 (dd, 1 H, J = 8.7 Hz, J = 2.3 Hz); 8.50 (d, 1 H, J = 2.3 Hz);
2
6
1.38 (s, 1 H, NH).
3
ꢀDiazoꢀ5ꢀmethoxyꢀ1,3ꢀdihydroꢀ2Hꢀindolꢀ2ꢀone (3g). The
yield was 0.250 g (46%), a red powder, m.p. 137—138 °C. IR,
–
1
1
ν/cm : 1700 (NHC=O); 2110 (C=N ). H NMR (DMSOꢀd ),
2
6
δ: 3.72 (s, 3 H, MeO); 6.66 (dd, 1 H, J = 8.4 Hz, J = 2.4 Hz);
.80 (d, 1 H, J = 8.4 Hz); 7.10 (d, 1 H, J = 2.4 Hz); 10.46 (s, 1 H,
6

2346
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5
(
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Received May 20, 2011;
in revised form July 12, 2011