Reaction of 1-arylmethylidenepyrazolidin-1-azomethine imines with aryl ketenes

Article abstract of DOI:10.1007/s11172-010-0259-0

A reaction of aryl ketenes with 1-arylmethylidenepyrazolidin-1-azomethine imines, generated by the diaziridine ring opening in 6-aryl-1,5-diazabicyclo[3. 1.0]hexanes catalyzed with Et2O?BF3, leads to 1,2-bis(phenylacetyl) pyrazolidine, 2-arylacetyl-1-arylidenepyrazolidin-1-ium chlorides, or a representative of 1,5-diazabicyclo[3.3.0]octan-2-ones, viz., 4-(4-eth-oxyphenyl)-3,3-diphenyl-1,5-diazabicyclo[3.3.0]octan-2-one, depending on the reaction conditions and the structure of the starting compounds. A mechanism suggested earlier for the transformation of 1,5-diazabicyclo[3.1.0] hexanes in the reaction with ketenes was confirmed.

Full text of DOI:10.1007/s11172-010-0259-0

Russian Chemical Bulletin, International Edition, Vol. 59, No. 7, pp. 1433—1441, July, 2010
1433
Reaction of 1ꢀarylmethylidenepyrazolidinꢀ1ꢀazomethine imines
with aryl ketenes
Yu. S. Syroeshkina,a V. Yu. Petukhova,a V. V. Kachala,a Yu. V. Nelyubina,b and N. N. Makhovaa
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: mnn@ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: unelya@xrlab.ineos.ac.ru
A reaction of aryl ketenes with 1ꢀarylmethylidenepyrazolidinꢀ1ꢀazomethine imines, genꢀ
erated by the diaziridine ring opening in 6ꢀarylꢀ1,5ꢀdiazabicyclo[3.1.0]hexanes catalyzed with
Et2O•BF3, leads to 1,2ꢀbis(phenylacetyl)pyrazolidine, 2ꢀarylacetylꢀ1ꢀarylidenepyrazolidinꢀ1ꢀ
ium chlorides, or a representative of 1,5ꢀdiazabicyclo[3.3.0]octanꢀ2ꢀones, viz., 4ꢀ(4ꢀethꢀ
oxyphenyl)ꢀ3,3ꢀdiphenylꢀ1,5ꢀdiazabicyclo[3.3.0]octanꢀ2ꢀone, depending on the reaction conꢀ
ditions and the structure of the starting compounds. A mechanism suggested earlier for the
transformation of 1,5ꢀdiazabicyclo[3.1.0]hexanes in the reaction with ketenes was confirmed.
Key words: 6ꢀarylꢀ1,5ꢀdiazabicyclo[3.1.0]hexanes, 1ꢀarylmethylidenepyrazolidinꢀ1ꢀ
azomethine imines, ring expansion, ionic liquids, BF3·Et2O, aryl ketenes, 1,2ꢀbis(phenylꢀ
acetyl)pyrazolidine, 2ꢀarylacetylꢀ1ꢀarylidenepyrazolidinꢀ1ꢀium chlorides, 1ꢀ(phenylacetyl)ꢀ
pyrazolidine, 1ꢀ(phenylacetyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrazole, 2,2ꢀdiphenylꢀ3ꢀ(4ꢀethoxyphenyl)ꢀ
tetrahydroꢀ1H,5Hꢀpyrazolo[1,2ꢀa]pyrazolꢀ1ꢀone.
Azomethine imines are extremely reactive structures,
which are widely used for the formation of nitrogenꢀconꢀ
taining heterocyclic systems based on [3+2] or [3+3] diꢀ
polar cycloaddition reactions to various dipolarophiles or
1,3ꢀdipoles, respectively.1—4 Especially intensive studies
were devoted to azomethine imines derived from pyrazolꢀ
idines, in particular, 1ꢀarylmethylidenepyrazolidinꢀ1ꢀ
azomethine imines 1, since they are used for the synꢀ
thesis of biologically active γꢀlactams derivatives, i.e.,
1,5ꢀdiazabicyclo[3.3.0]octanꢀ2ꢀones.5—7 For obtaining
stable azomethine imines of this type, for example, comꢀ
pounds 2, an aromatic substituent is incorporated into the
molecule of 1 for the stabilization of the positively charged
C=N+ fragment and a C=О group for the stabilization of
the negatively charged nitrogen atom. Structures 2 are
obtained by the condensation of pyrazolidinꢀ3ꢀone 3 with
aromatic aldehydes.8,9 For the in situ generation of unstable
under usual conditions azomethine imines 1 unsubstiꢀ
tuted in the pyrazolidine ring, thermolysis of 6ꢀarylꢀ1,5ꢀ
diazabicyclo[3.1.0]hexanes 4 in the presence of highly reꢀ
active dipolarophiles, for example, Nꢀarylmaleimides 5, is
used at 130—140 °C (reflux in xylene).10—14 In the work15
of the same authors, it was shown that azomethine imines
1 can also be generated in situ from compounds 4 already
at 20 °C using catalysis with Lewis acids (BF3•Et2O,
In(OTf)3) in acetonitrile. The reactions with compounds
5 in both cases led to the condensed heterocyclic systems
6 (Scheme 1).
Scheme 1
i. 130—140 °C/xylene, (BF3•Et2O/MeCN), 20 °C
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1401—1408, July, 2010.
1066ꢀ5285/10/5907ꢀ1433 © 2010 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
Syroeshkina et al.
Scheme 2
i. [bmim][X] (X = BF4–, PF6–), BF3•Et2O, 20 °C
Ar = 4ꢀMeOC6H4, 4ꢀEtOC6H4, 4ꢀPriOC6H4, 4ꢀMeC6H4; Ar´ = 3ꢀNO2C6H4; R = CCl , CO2Et; [bmim] =
3
Studying behavior of azomethine imines 1 generated
from bicyclic diaziridines 4 in common organic solvents
in the presence of BF3•Et2O as a catalyst at 20 °C, we
showed16—19 that under these conditions azomethine imiꢀ
nes 1 do not react with less active dipolarophiles, such as
carbon disulfide, nitriles, or other activated olefins, for
example, βꢀnitrostyrenes. These reactions were successꢀ
fully accomplished only in ionic liquids, that allowed us to
develop simple methods for the preparation of a number of
bicyclic structures 7—10 (Scheme 2).16—19
Scheme 3
The present work is devoted to the study of a possibility
of condensation of azomethine imines 1, generated in situ
from 6ꢀarylꢀ1,5ꢀdiazabicyclo[3.1.0]hexanes 4 under conꢀ
ditions found earlier,15—19 with aryl ketenes 11 in order to
obtain 3,4ꢀdiaryl(3,3,4ꢀtriaryl)ꢀ1,5ꢀdiazabicyclo[3.3.0]ꢀ
octanꢀ2ꢀones 12, new γꢀlactam azaanalogs (Scheme 3).
We expected that preliminary preparation of azomeꢀ
thine imines 1 from 6ꢀarylꢀ1,5ꢀdiazabicyclo[3.1.0]hexanes
4 using BF3•Et2O as a catalyst either in organic solvents
or in ionic liquid under conditions developed by us earlier
would allow us to accomplish their condensation with aryl
ketenes 11 to form di(tri)arylꢀsubstituted 1,5ꢀdiazaꢀ
bicyclo[3.3.0]octanꢀ2ꢀones 12. Aryl ketenes, as earlier,
were supposed to be generated in situ from arylacetyl chlorꢀ
ides and Et3N.
Earlier,20 we have studied the reaction of other repreꢀ
sentatives of 1,5ꢀdiazabicyclo[3.1.0]hexanes, viz., 6Hꢀ,
6ꢀAlkꢀ, and 6,6ꢀAlk2ꢀderivatives 13, with aryl ketenes 11
generated in situ from arylacetyl chlorides and Et3N in
benzene or diethyl ether at reduced temperature and
showed that in this case the reaction proceeds with the
formation of 1ꢀacylpyrazolidines 14 in moderate yields.
The following mechanism was suggested for this direction
of the reaction: aryl ketene 11 attacks the starting bicycle
13 to form zwitterionic intermediate 15, which is opened
at the C—N bond of the diaziridine fragment to yield the
second dipolar intermediate 16. Being a stronger base than
Et3N, the enolate ion of intermediate 16 combines with
HCl from Et3N•HCl, formed in the process of generation
of ketene 11, that leads to intermediate 17. The contact of
compound 17 with water in the process of isolation on
a SiO2 column resulted in its hydrolysis to 1ꢀacylpyrazolꢀ

Reaction of azomethine imines with aryl ketenes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
1435
O(1)
C(7)
idines 14 and the corresponding carbonyl compounds. The
cyclization of intermediate 16 to bicyclic system 18 is
restricted by the Baldwin´s rules and was successfully acꢀ
complished only for two examples on heating in low yields
(Scheme 4).
C(8)
C(6)
C(3)
C(9)
N(1)
C(1)
C(5)
N(1A)
C(2)
In order to find conditions for the preparation of desꢀ
ired bicyclic compounds 12, the reaction was initialꢀ
ly performed in MeCN under conditions described in
the work,15 using 6ꢀ(4ꢀmethylphenyl)ꢀ1,5ꢀdiazabicycloꢀ
[3.1.0]hexane 4a and phenyl ketene 11a (Ar = Ph, R3 = H)
as an example. However, the reaction was complicated
and resulted in the formation of a mixture of products
including polymeric, from which 1,2ꢀbis(phenylacetyl)ꢀ
pyrazolidine 19 was isolated by column chromatography
in 12% yield instead of expected bicyclic compound 12
(Ar = 4ꢀMeC6H4). Its structure was confirmed by a combiꢀ
nation of the elemental analysis data, spectral characterisꢀ
tics (Scheme 5, Tables 1—4), and Xꢀray diffraction study.
The latter showed that molecule 19 in the crystal is symꢀ
metric with respect to the axis going through the middle of
the N—N bond (Fig. 1). The pyrazolidine ring has the
twistꢀconformation; its geometrical parameters are within
the range of the values characteristic of this class of comꢀ
pounds (see, for example, Refs 21—23).
Since, as it turned out, the reaction outcome does not
depend on the bicyclic diaziridine used (in all the cases,
1,2ꢀbis(phenylacetyl)pyrazolidine 19 was isolated in low
yield), we decided to generate azomethine imine 1a in
ionic liquids [bmim][BF4] and [bmim][PF6] under condiꢀ
tions described in the works.16—19 Azomethine imine 1a
was generated upon the action of BF3•Et2O in catalytꢀ
ic amounts (0.1 mmol) on the starting compound 4a
C(4)
O(1A)
C(10)
Fig. 1. General view of compound 19 in representation of atoms
by probability ellipsoids of thermal vibrations (p = 50%).
(0.3 mmol) in MeCN or ionic liquid (IL), then phenylꢀ
acetyl chloride and Et3N were added simultaneously dropꢀ
wise at reduced temperature. However, in this case too the
reaction took similar direction only at considerably higher
rate, and 1,2ꢀbis(phenylacetyl)pyrazolidine 19 was isolatꢀ
ed in low yield as the reaction product independent on the
structure of compound 4a—c involved into the reaction.
It may be supposed that in both MeCN and ionic liqꢀ
uids, phenyl ketene 11a in the first step of the reaction
attacks the negatively charged nitrogen atom of azomeꢀ
thine imines 1a—c to form intermediates 20a—c, close in
their structure to intermediates 16. Then, as in the reacꢀ
tion in Scheme 3, the enolate ions of intermediates 20
remove HCl from Et3N•HCl to yield new intermediates
21, analogs of intermediates 17. But, since both MeCN
and ionic liquids could contain certain amount of water,
intermediates 21 were apparently hydrolyzed under the
reaction conditions to 1ꢀphenylacetylpyrazolidine 14a,
which reacted with the second molecule of ketene 11a
leading to 1,2ꢀbis(phenylacetyl)pyrazolidine 19. In all the
Scheme 4
13: R1, R2 = H, Alk
18: R1 = R2 = H; Ar = R3 = Ph (a) (35%); Ar = 4ꢀClC6H4, R3 = H (b) (14%)

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
Syroeshkina et al.
Table 1. Some physicoꢀchemical characteristics of compounds obtained
Compound
M.p./°C
Rf*
Found
Calculated
Molecular
formula
(%)
C
H
N
Cl
—
12a
14a
19
152.0—152.5
Orange oil
85.5—86.0
Orange oil
Orange oil
0.17
0.11
0.36
—
78.35
78.36
69.40
69.45
74.05
74.00
66.98
66.94
70.21
70.19
6.59
6.58
7.49
7.42
6.51
6.54
6.51
6.46
6.41
6.43
7.01
7.03
14.76
14.73
9.03
9.08
7.83
7.81
14.84
14.88
С26H26N2O2
С11H14N2O
С19H20N2O2
С20H23ClN2O2
С11H12N2O
—
—
21с
23
9.83
9.88
—
0.23
* nꢀHexane—ethyl acetate (1 : 1 (v/v)) is the eluent, visualization with diphenylamine and under
the UV light.
cases, the corresponding aromatic aldehydes were either
isolated or characterized by NMR (see Scheme 5).
a fragment ion corresponding to [M+ – Cl], the rest of the
molecule fragmentation completely corresponded to the
structure 21c. The presence of the absorption band at
840 cm–1 in the IR spectrum is apparently due to the fact
that, as it is known, αꢀchloromethylamines exist in the
equilibrium mixture of the salts of the type 21 and coꢀ
valent compounds of the type 22. In our case, this equilibꢀ
rium, by all accounts, is shifted to the side of the salt
structures 21. The NMR spectral data obtained using the
{1H—1H}gNOESY, {1H—13C}HMBC, {1H—15N}HMBC,
and {1H—13C}HSQC procedures on the 1H, 13C, 15N nuꢀ
clei were the most informative. Compound 21c in its
1H NMR spectrum is characterized by a lowꢀfield singlet
at δ 9.86 (in the 13C NMR spectrum, at δ 190.87) related
to the CH=N+ group, as well as by a broad singlet for the
CH2 group of the CОCH2Ph fragment at δ 3.77 (in the
To avoid formation of compounds of the type 19 and
synthesize desired bicyclic compounds 12, we carried out
the reaction of azomethine imine 1c with phenyl ketene
11a in anhydrous benzene in the flow of argon. In this
case, after evaporation of benzene, by extraction with hot
hexane, 1ꢀ(4ꢀethoxybenzylidene)ꢀ2ꢀ(phenylacetyl)pyrꢀ
azolidinꢀ1ꢀium chloride 21c (analog of intermediates 17
in Scheme 4; Scheme 6) was isolated, which proved stable
under usual conditions and, hence, was characterized by
IR and NMR spectroscopy and mass spectrometry (see
Tables 1—4). The IR spectrum exhibited an absorption
band at 840 cm–1 corresponding to the stretching vibraꢀ
tions of the C—Cl bond, the mass spectrum contained
1
13C NMR spectrum, at δ 40.01). The H and 13C NMR
Table 2. IR spectra of compounds obtained
spectroscopic data for the reactions of azomethine imine
1c with ketenes 11b,c and azomethine imine 1b with ketene
11a showed formation of compounds 21b—e in a mixture
with other products (Table 5), however, we failed in their
isolation in pure form (see Scheme 6).
Compound
IR, ν/cm–1
12a
640, 692, 700, 740, 840, 920, 1004, 1052,
1116, 1184, 1248, 1308, 1392, 1436, 1512,
1584, 1612, 1684, 2840, 2900, 2984, 3052
668, 696, 720, 840, 892, 912, 972, 972, 1032,
1076, 1128, 1216, 1256, 1292, 1332, 1432,
1452, 1496, 1632, 1720, 2884, 2932, 2980,
3028, 3060, 3228
14a
Table 3. Massꢀspectra of compounds 12a and 21c
Compound
MS, m/z (I (%))
19
664, 700, 720, 752, 928, 1004, 1032, 1164,
1232, 1288, 1436, 1456, 1500, 1604, 1668,
1712, 2896, 2924, 2988, 3032, 3064, 3332
520, 616, 696, 720, 808, 840, 920, 1044,
1116, 1160, 1256, 1304, 1396, 1432, 1472,
1496, 1508, 1576, 1600, 1680, 1700, 2744,
2932, 2980, 3028, 3060, 3240, 3448
668, 696, 720, 744, 928, 1032, 1076, 1124,
1176, 1288, 1432, 1456, 1496, 1512, 1600,
1652, 1728, 2856, 2928, 2960, 3028, 3064
12a
398 [М] (6), 327 [М – pyrazolidine] (2),
204 [М — Ph2CCO] (100), 194 [Ph2CCO] (9),
165 [Ph2C] (43), 147 [NCHC6H4OEt] (14),
121 [C6H4OEt] (11), 77 [Ph] (15),
21с
70 [pyrazolidine] (7)
21с
322 [М – Сl – Н] (7), 282 [М – (СН2)3 +
+ Н – Сl] (3), 203 [М – PhCH2CO – Сl] (18),
190 [M – EtOC6H4CH – Сl] (9), 91 [PhCH2]
(100), 77 [Ph] (14), 70 [pyrazolidine] (72)
23

Reaction of azomethine imines with aryl ketenes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
1437
Scheme 5
i. BF3•Et2O, MeCN or ionic liquid
Ar = 4ꢀMeC6H4 (a), 4ꢀMeOC6H4 (b), 4ꢀEtOC6H4 (c)
To sum up, we succeeded in obtaining compounds 21,
analogs of αꢀchlorobenzylamines, whose structure is close
to the intermediates 17 suggested earlier (see Scheme 4),
which undergo hydrolysis during isolation to yield 1ꢀarylꢀ
acetylpyrazolidine 14. The higher stability of compounds
21 as compared to the intermediates 17 is apparently due
Table 4. 1H and 13C NMR spectra of compounds obtained*
Comꢀ
δ, J/Hz (CDCl3)
pound
1H NMR
13C NMR
12a
1.38 (t, 3 Н, CH3CH2O, 3J = 6.00); 2.47 (br.m, 2 Н,
NCH2CH2); 2.48, 3.23 (both br.m, 2 Н, СНNCH2, Δν = 150 Hz);
3.64, 3.91 (both br.m, 2 Н, СОNCH2, Δν = 54); 3.96 (q, 2 Н,
CH3CH2O, 3J = 6.00); 4.84 (br.s, 1 Н, С6Н4СНN); 6.65, 7.55
(both d, 4 Н, EtOC6H4, 3J = 7.00); 6.84, 7.29 (both m, 10 Н, Ph)
(Ar); 158.91 (СО)
14.78 (CH3CH2O); 27.16 (NCH2CH2); 39.72
(СНNCH2); 53.12 (СОNCH2); 63.36
(CH3CH2O); 78.50 (С6Н4СНN); 113.71 (СPh2),
126.68, 126.95, 127.15, 127.48, 127.87, 128.39,
129.11, 129.22, 130.11, 130.25, 138.92, 165.38
14a
19
1.96 (m, 2 Н, NCH2CH2, 3J = 8.00, 3J = 6.00); 2.90 (t, 2 Н,
НNCH2, 3J = 6.00); 3.46 (t, 2 Н, СОNCH2, 3J = 8.00); 3.84
(s, 2 Н, СОCH2Ph); 4.37 (br.m, 1 Н, NH); 7.26 (m, 5 Н, Ph)
1.80 (m, 2 Н, NCH2CH2, 3J = 6.88); 2.56, 4.13 (both br.m,
4 Н, NCH2CH2); 3.64 (q, 4 Н, СОCH2Ph, 2JАВ = 12.79);
7.26 (m, 10 Н, Ph)
1.36 (t, 3 Н, CH3CH2O, 3J = 6.00); 1.93 (m, 2 Н, NCH2CH2,
3J = 12.00); 2.82 (br.m, 2 Н, СНN+CH2); 3.33 (br.m, 2 Н,
СОNCH2); 3.77 (br.s, 2 Н, СОCH2Ph); 4.14 (q, 2 Н,
CH3CH2O, 3J = 6.00); 7.10, 7.85 (both d, 4 Н, EtOC6H4,
3J = 6.00); 7.19 (t, 1 Н, pꢀСН in Ph, 3J = 6.00); 7.23 (t, 2 Н,
mꢀСН in Ph, 3J = 6.00); 7.26, 7.28 (both d, оꢀСН in Ph,
3J = 6.00); 9.86 (s, 1 Н, СНN+CH2)
27.17 (NCH2CH2); 40.92 (НNCH2); 43.91
(СОNCH2); 47.83 (СОCH2Ph); 126.19,
128.16, 128.99, 135.88 (Ph); 171.34 (СО)
24.95 (NCH2CH2); 40.63 (СОCH2Ph); 41.04,
45.36 (both br, NCH2CH2); 127.16, 128.57,
128.78, 129.09, 129.37, 139.66, 143.66 (Ph)
14.36 (CH3CH2O); 26.78 (NCH2CH2);
40.01 (СОCH2Ph); 43.61 (СНN+CH2);
47.26 (СОNCH2); 63.68 (CH3CH2O);
114.80, 129.47, 131.73, 169.98
21s
(С6Н4OEt); 126.00, 127.73, 128.10, 129.09,
136.52 (Ph); 163.48 (СО); 190.87 (СH=N+)
23
2.81 (td, 2 Н, NCH2CH2, 3J = 10.10, 3J = 1.50); 3.76 (t, 2 Н,
NCH2, 3J = 10.10); 3.92 (s, 2 Н, СОCH2Ph); 6.88 (t, 1 Н, NCH,
3J = 1.50); 7.14 (t, 1 Н, pꢀСН in Ph, 3J = 8.31); 7.23 (t, 2 Н,
mꢀСН in Ph, 3J = 8.31); 7.29 (d, 2 Н, оꢀСН in Ph, 3J = 8.31)
33.32 (NCH2CH2); 40.81 (СОCH2); 42.02
(СОNCH2); 126.75, 128.48, 129.52, 135.47
(Ph); 147.72 (NCH); 169.69 (СО)
* The 15N NMR spectrum of compound 21c: –53 (CHN+); –220 (CОNCH2).

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Syroeshkina et al.
Table 5. The most characteristic signals in the 1H and 13C NMR spectra of compounds 21b—f
Group
1H/13C NMR
1H NMR
b
c
d
f
e
NCH2CH2
СНN+CH2
СОNCH2
СОHXAr´*
СНN+CH2
1.80/24.98
2.90/43.64
3.62/51.83
3.97/40.23
9.89/190.89
1.93/26.78
2.82/43.61
3.33/47.26
3.77/40.01
9.86/190.87
1.88/29.38
3.15/44.03
3.64/52.20
4.15/40.37
9.90/190.78
1.96/27.01
2.87/44.18
3.54/47.96
3.89/39.57
9.88/190.60
1.91
2.85
3.42
3.77
9.79
* X = H (b—e), Ph (f).
Scheme 7
to the replacement of aliphatic substituents on the imine
fragment of these structures by the aromatic fragments
with electronꢀdonating substituents at position 4, which
stabilize a positive charge in compounds 21. To verify the
mechanism suggested in Schemes 4 and 5 for the transforꢀ
mation of 1,5ꢀdiazabicyclo[3.1.0]hexane derivatives to
1ꢀarylacetylpyrazolidines 14, we treated compound 21c
with water in the twoꢀphase system benzene—water at 20 °C
and in fact obtained desired 1ꢀphenylacetylpyrazolidine
14a, that confirmed the reaction mechanism suggested
in the work.20 However, in addition to compound 14a,
1ꢀphenylacetylpyrazoline 23 was isolated as the reaction
product as well, which is formed, by all accounts, through
the oxidation of pyrazolidine 14a with air oxygen under
conditions of isolation. Such reactions are very characterꢀ
istic of 1ꢀsubstituted pyrazolidines.24—26 Compounds 14a
and 23 were isolated by column chromatography on SiO2.
Their structures are confirmed by a combination of eleꢀ
mental analysis data and spectral characteristics (see Taꢀ
bles 1—4). 4ꢀEthoxybenzaldehyde was isolated in high
yield as well (Scheme 7).
Ar = 4ꢀEtOC6H4
case the enolate ion in the intermediate 20f is stabilized
much stronger due to the conjugation with two phenyl
groups than in the reactions with other aryl ketenes studꢀ
ied and, therefore, is predominantly involved into intramoꢀ
lecular cyclization to form 4ꢀ(4ꢀethoxyphenyl)ꢀ3,3ꢀdipheꢀ
nylꢀ1,5ꢀdiazabicyclo[3.3.0]octanꢀ2ꢀone 12a (see Table 1—4),
however, the spectra showed the presence of compound
21f in small amount as well (no more than 15%) (Scheme 8).
The synthesis of representative of compounds 12 based
on the condensation of azomethine imines 1 and aryl
ketenes 11 was successfully accomplished only for one
example under the same conditions as the reaction of
azomethine imine 1c with diphenyl ketene 11d in benzene
and catalysis with BF3•Et2O at 20 °C. Apparently, in this
Scheme 6
Comꢀ
pound
1b
1c
4b
Ar
Comꢀ
pound
11a
11b
11c
Ar´
Comꢀ
pound
20b, 21b
20c, 21c
20d, 21d
20e, 21e
Ar
Ar´
4ꢀMeOC6H4
4ꢀEtOC6H4
4ꢀMeOC6H4
4ꢀEtOC6H4
Ph
4ꢀMeOC6H4
4ꢀEtOC6H4
4ꢀEtOC6H4
4ꢀEtOC6H4
Ph
Ph
4ꢀMeC6H4
2,4ꢀ(NO2)2C6H3
4ꢀMeC6H4
2,4ꢀ(NO2)2C6H3
4c

Reaction of azomethine imines with aryl ketenes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
1439
Scheme 8
21f
Ar = 4ꢀEtOC6H4
measured on a Gallenkamp (Sanyo). Mass spectra (EI) were
measured on a Finnigan MAT INCOSꢀ50 spectrometer. TLC
monitoring of the reaction course was performed on Silufol
UVꢀ254 plates. The Rf values were determined in the nꢀhexꢀ
ane—ethyl acetate, 1 : 1 (v/v) solvent system.
The most characteristic chemical shifts in the NMR
spectra of compounds 21b—f are given in Table 5.
In conclusion, the synthesis of representatives of
1,5ꢀdiazabicyclo[3.3.0]octanꢀ2ꢀones by the reaction of
6ꢀarylꢀ1,5ꢀdiazabicyclo[3.1.0]hexanes with aryl ketenes,
proceeding through the Et2O•BF3ꢀcatalyzed intermediꢀ
ate formation of azomethine imines, was successfully acꢀ
complished only for diphenyl ketene by carrying out the
reaction in anhydrous benzene. Analogous reaction with
monoaryl ketenes in ionic liquids led to 1,2ꢀbis(arylꢀ
acetyl)pyrazolidines, whereas in benzene, to 1ꢀarylideneꢀ
2ꢀ(arylacetyl)pyrazolidinꢀ1ꢀium chlorides, one of which,
viz., 1ꢀ(4ꢀethoxyphenyl)ꢀ2ꢀ(phenylacetyl)pyrazolidinꢀ1ꢀ
ium chloride, was isolated and fully characterized. Hyꢀ
drolysis of the latter during isolation yielded 1ꢀphenylꢀ
acetylpyrazolidine and its oxidation product with air oxyꢀ
gen, viz., 1ꢀphenylacetylpyrazoline, that confirmed the
mechanism suggested earlier20 for the transformation of
1,5ꢀdiazabicyclo[3.1.0]hexanes in the reactions with aryl
ketenes.
Xꢀray diffraction data. Crystals of compound 19 (C19H20N2O2,
M = 308.37) are orthorhombic, the space group is Pbcn at 120 K:
a = 14.0802(8), b = 11.5168(7), c = 10.1006(6) Å, V =
3
= 1637.90(17) Å , Z = 4 (Z´ = 1/2), dcalc = 1.251 g cm–3
,
μ(MoꢀKα) = 0.82 cm–1, F(000) = 656. Intensities of 16824 reꢀ
flections were measured on a Bruker SMART 1000 CCD difꢀ
fractometer (λ(MoꢀKα) = 0.71072 Å, ωꢀscanning, 2θ < 58°),
and 2180 independent reflections (Rint = 0.0281) were used in
further refinement. The structure was solved by the direct methꢀ
od and refined by the fullꢀmatrix least squares method on F2 in
anisotropicꢀisotropic approximation. Positions of hydrogen atꢀ
oms were calculated geometrically. The final values of unreliꢀ
ability factors for 19: wR2 = 0.1400 and GOOF = 1.006 for
all the independent reflections (R1 = 0.0530 were calculated on
F for 1568 observed reflections with I > 2σ(I)). All the calꢀ
culations were performed using the SHELXTL PLUS 5.0 proꢀ
gram package.
1,2ꢀBis(phenylacetyl)pyrazolidine (19). A. Solutions of phenꢀ
ylacetyl chloride (0.69 g, 4.5 mmol) obtained by a standard
procedure27,28 in anhydrous MeCN (3 mL) and anhydrous Et3N
(0.32 g, 3.0 mmol) in MeCN (5 mL) were added dropwise simulꢀ
taneously with the addition of 2 drops (0.1 mmol) of boron triꢀ
fluoride diethyl etherate to a solution of 6ꢀ(4ꢀmethylphenyl)ꢀ
1,5ꢀdiazabicyclo[3.1.0]hexane (4a) (0.52 g, 3.0 mmol) obtained
by a standard procedure29 in anhydrous MeCN (10 mL) at
0÷–4 °C in the flow of Ar, the stirring at this temperature was
continued for 30 min, then the reaction mixture was spontaneꢀ
ously heated to 44 °C and kept at this temperature for 2 h. The
solvent was evaporated in vacuo of a waterꢀjet pump. Compound 19
was isolated by column chromatography on SiO2 (0.060—0.200 mm,
60 A, ACROS) using hexane—ethyl acetate = (2 : 1) → (0.3 : 5)
as an eluent. The yield of 1,2ꢀbis(phenylacetyl)pyrazolidine (19)
was 0.11 g (12%).
Experimental
IR spectra were recorded on a URꢀ20 spectrometer in KBr
pellets or for neat samples; 1H and 13C NMR spectra were reꢀ
corded on a Bruker AM 300 spectrometer (75.5 MHz for
13C NMR) in CDCl3. The 13C NMR spectra were obtained with
proton decoupling. To confirm the structure of compound 21c,
its 1H, 13C, 15N NMR spectra were recorded on a Bruker AVꢀ600
spectrometer (600.13, 150.90, and 60.81 MHz for H, 13C, and
1
15N, respectively). Nitromethane (δ
= 0) was used as an exꢀ
15N
ternal standard for recording 15N NMR spectra. Assignment of
signals in the NMR spectra of compound 21c was performed
using {1H—1H}gNOESY, {1H—13C}HMBC, {1H—15N}HMBC,
and {1H—13C}HSQC techniques. All the 2Dꢀspectra were obꢀ
tained using the Bruker standard procedures with the Zꢀgradiꢀ
ent. The spectra were recorded at 30 °C. Melting points were
Compound 19 was obtained similarly from 6ꢀ(4ꢀmethoxyꢀ
phenyl)ꢀ1,5ꢀdiazabicyclo[3.1.0]hexane (4b) and 6ꢀ(4ꢀethoxyꢀ

1440
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 7, July, 2010
Syroeshkina et al.
phenyl)ꢀ1,5ꢀdiazabicyclo[3.1.0]hexane (4c) in 8 and 13% yields,
respectively.
the yield was 0.1 g (10%). Concentration of the mother liquor
gave the residue, which according to the 1H and 13C NMR specꢀ
tral data contained 2ꢀ(diphenylacetyl)ꢀ1ꢀ(4ꢀethoxybenzylidene)ꢀ
pyrazolidinꢀ1ꢀium chloride 21f in the mixture with 12a.
B. Phenylacetyl chloride (0.35 g, 2.3 mmol) and anhydrous
Et3N (0.16 g, 1.5 mmol) were added dropwise simultaneously
with the addition of 1 drop (0.05 mmol) of boron trifluoride
diethyl etherate to a solution of 6ꢀ(4ꢀmethylphenyl)ꢀ1,5ꢀdiazaꢀ
bicyclo[3.1.0]hexane (4a) (0.26 g, 1.5 mmol) in ionic liquid
[bmim][BF4] at 18 °C, the stirring at this temperature was conꢀ
tinued until the color of the reaction mixture stopped to change
(from light yellow to bright orange), for about 30 min. The ionic
liquid was three times extracted with the hexane—ethyl acetate
(4 : 1) mixture, the extract was concentrated on a rotary evapoꢀ
rator at ~35—40 °C using a water bath. The residue was subjectꢀ
ed to separation on a column similarly to method A yielding 19
(0.5 g, 16%).
The authors are grateful to M. I. Struchkova for reꢀ
cording NMR spectra.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ01091ꢀa)
and the Russian Academy of Sciences (program of the
Presidium of RAS, PRANꢀ18).
References
Synthesis of 1ꢀarylideneꢀ2ꢀ(arylacetyl)pyrazolidinꢀ1ꢀium
chlorides 21b—e (general procedure). Solutions of arylacetyl chloꢀ
ride (2.5 mmol) in anhydrous benzene (3 mL) and anhydrous
Et3N (2.7 mmol) in anhydrous benzene (5 mL) were added dropꢀ
wise simultaneously with addition of 2 drops (0.1 mmol) of boꢀ
ron trifluoride diethyl etherate to a solution of compounds 4
(2.5 mmol) in anhydrous benzene (10 mL) at 18 °C in the flow of
Ar, the stirring at this temperature was continued for 40 h. The
solvent was evaporated in vacuo of a waterꢀjet pump. Compounds
21 were isolated by extraction with boiling hexane for 30 min.
The solvent was evaporated in vacuo of a waterꢀjet pump to
obtain 1ꢀ(4ꢀethoxybenzylidene)ꢀ2ꢀ(phenylacetyl)pyrazolidinꢀ1ꢀ
ium chloride (21c) (0.4 g, 42%). 1ꢀ(4ꢀMethoxybenzylidene)ꢀ2ꢀ
(phenylacetyl)pyrazolidinꢀ1ꢀium chloride (21b) (0.17 g, 18%),
1ꢀ(4ꢀethoxybenzylidene)ꢀ2ꢀ(4ꢀmethylphenylacetyl)pyrazolidinꢀ
1ꢀium chloride (21d) (0.14 g, 16%), and 1ꢀ(4ꢀethoxybenzylꢀ
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(21e) (0.16 g, 14%) were obtained similarly, but failed to be
isolated in pure form and were characterized only with spectral
data (see Table 5).
Hydrolysis of 1ꢀ(4ꢀethoxybenzylidene)ꢀ2ꢀ(phenylacetyl)pyrꢀ
azolidinꢀ1ꢀium chloride (21c). Water (5 mL) was added to a soꢀ
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mixture was stirred for 2 h, followed by addition of 10% aq.
NaHCO3 (10 mL), and the stirring was continued for 2 h. The
organic layer was separated, dried with MgSO4. The residue was
subjected to column chromatography on SiO2 (0.060—0.200 mm,
60 A, ACROS) using ethyl acetate—hexane (2 : 1) → (1 : 0) as an
eluent to obtain 1ꢀphenylacetylpyrazolidine 14a (0.08 g, 12%) as
a yellow oil, 1ꢀphenylacetylꢀ4,5ꢀdihydropyrazole (23) (0.24 g,
38%), and 4ꢀethoxybenzaldehyde (0.3 g, 60%).
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Reaction of azomethine imines with aryl ketenes
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Received June 25, 2009;
in revised form December 23, 2009