Reactions of 4-phenyl-1,2,4-triazoline-3,5-dione with 2-pyrazolines

Article abstract of DOI:10.1007/s11172-011-0252-2

4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) acts as an efficient Michael acceptor in reactions with 1-unsubstituted 2-pyrazolines, giving substituted (3,5-dioxo-4-phenyl-1,2,4-triazol-idin-1-yl)-1-pyrazolines in quantitative yields. Through elimination of molecular nitrogen, the latter are easily transformed into the corresponding cyclopropanes. A reaction of methyl 5-methyl-2-pyrazoline-5-carboxylate with a twofold excess of PTAD leads to an intermediate bisadduct, which undergoes dediazotization to form a 1,3,5-triazabicyclo[3.3.0]octane-2,4-dione derivative. 1-Substituted 2-pyrazolines also add to PTAD with the exception that the 2-pyrazoline structure is retained in the product because of the migration of the C(3)H proton to PTAD.

Full text of DOI:10.1007/s11172-011-0252-2

Russian Chemical Bulletin, International Edition, Vol. 60, No. 8, pp. 1685—1693, August, 2011
1685
Reactions of 4ꢀphenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione with 2ꢀpyrazolines
R. A. Novikov, V. A. Korolev, and Yu. V. Tomilov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Eꢀmail: tom@ioc.ac.ru
4ꢀPhenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione (PTAD) acts as an efficient Michael acceptor in reacꢀ
tions with 1ꢀunsubstituted 2ꢀpyrazolines, giving substituted (3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolꢀ
idinꢀ1ꢀyl)ꢀ1ꢀpyrazolines in quantitative yields. Through elimination of molecular nitrogen, the
latter are easily transformed into the corresponding cyclopropanes. A reaction of methyl
5ꢀmethylꢀ2ꢀpyrazolineꢀ5ꢀcarboxylate with a twofold excess of PTAD leads to an intermediate
bisadduct, which undergoes dediazotization to form a 1,3,5ꢀtriazabicyclo[3.3.0]octaneꢀ2,4ꢀ
dione derivative. 1ꢀSubstituted 2ꢀpyrazolines also add to PTAD with the exception that the
2ꢀpyrazoline structure is retained in the product because of the migration of the C(3)H proton
to PTAD.
Key words: 4ꢀphenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione, ene reaction, pyrazoline, cyclopropane,
dediazotization, stereoselectivity, NMR spectra.
4ꢀPhenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione (PTAD) contains
a highly reactive N=N bond and readily enters into the
Diels—Alder reactions with various carboꢀ and heteroꢀ
dienes1—6 and into ene reactions with substrates containꢀ
ing an allylic H atom7—11 (Scheme 1). These reactions
are of both synthetic2—6,10,11 and mechanistic interꢀ
est.8—10,12,13 The wide use of PTAD in organic synthesis is
due to a variety of accessible substrates, easily occurring
and selective reactions, and high yields of reaction prodꢀ
ucts.2—6,10,11,14—18
taining the C=N or N=N bond have not been described
hitherto. However, the study of such reactions could result
in developing new approaches to the synthesis of various
azaheterocycles. In connection with this, we studied reacꢀ
tions of PTAD with 2ꢀ and 1ꢀpyrazolines containing the
C=N and N=N bonds, respectively, and some transforꢀ
mations of the reaction products, out of which dediazotiꢀ
zation to the corresponding cyclopropanes proved to be
important.
Results and Discussion
Scheme 1
We found that 1ꢀunsubstituted 2ꢀpyrazolines 1a—f
react with PTAD very rapidly even at 0 °C. The reaction
was completed in less than 1 min, the bright red (because
of PTAD) initial solution turning colorless. The firstꢀstep
reaction products are substituted 1ꢀpyrazolines 2a—f,
which were detected from the 1H and 13C NMR spectra of
the reaction mixtures. The solutions of 1ꢀpyrazolines 2 are
stable at 0 °C for several hours. However, they eliminate
molecular nitrogen even at room temperature, selectively
giving cyclopropanes 3a—f (Scheme 2). The dediazotizaꢀ
tion process largely depends on the substituents in the
starting 2ꢀpyrazolines and is substantially promoted in
boiling chloroform or dichloroethane. No further purifiꢀ
cation of the resulting cyclopropanes is usually required;
should the need arise, however, they can be recrystallized
from diethyl ether or diethyl ether—hexane.
i. [2+4] cycloaddition; ii. ene reaction.
We studied reactions of PTAD with 2ꢀpyrazolines conꢀ
taining the ester and phenyl groups in different positions
of the heterocycle, as well as with a pyrazoline fused to a
Although much research has dealt with PTADꢀinvolvꢀ
ing transformations, its reactions with compounds conꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1660—1668, August, 2011.
1066ꢀ5285/11/6008ꢀ1685 © 2011 Springer Science+Business Media, Inc.

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Novikov et al.
Scheme 2
i. 0 °C, 1 min; ii. 20—60 °C.
Comꢀ
pound
a
R1
R2
R3
R4
Comꢀ
pound
d
e
R1
R2
R3
R4
CO2Me
H
H
H
H
H
Me
H
H
Ph
H
CO2Me CO2Me
Ph
b
CO2Me
Ph
H
c
CO2Me
H
CO2Me
H
f
CO2Me
norbornane fragment. A reaction of PTAD with disubstiꢀ
tuted pyrazoline 1b gives stereoisomeric pyrazolines
Eꢀ and Zꢀ2b in a ratio of ~3 : 1. The spatial arrangement of
the substituents in these products was determined by 2D
NOESY NMR spectroscopy. For the minor isomer, the
spectrum shows a distinct coupling between the methyl
protons and the C(3)H proton, which corresponds to
isomer Zꢀ2b.
pyrazoline ring. This effect is especially pronounced in
pyrazolines 1d and 1f: their reactions with PTAD proceed
stereospecifically to give stereoisomers Eꢀ2d and antiꢀ2f
only. Steric hindrances presented by the phenyl subꢀ
stituent and the norbornane framework preclude PTAD
from approaching the pyrazoline ring on the side of
these substituents, which allow its addition to the C(3)
atom only from the less shielded side of the heterocycle
(Scheme 3).
As noted above, the dediazotization of pyrazolines 2
smoothly occurs when they are kept at 20 °C for several
hours or refluxed in chloroform, though variation in the
reaction conditions for some of them leads to somewhat
different outcomes (Table 1).
For instance, the dediazotization of pyrazoline 2a conꢀ
taining no substituents in positions 4 and 5 of the pyrazolꢀ
ine ring at 40 °C gives gemꢀdisubstituted cyclopropane 3a
in a quantitative yield. However, this reaction in boiling
1,2ꢀdichloroethane is nonselective, producing cycloꢀ
The stereochemistry of the addition of PTAD to the
C=N bond of pyrazolines 1 is appreciably affected by sterꢀ
ic factors due to the presence of the substituents in the
Scheme 3

Reactions of PTAD with 2ꢀpyrazolines
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1687
Table 1. Reactions of 4ꢀphenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione (PTAD) with 2ꢀpyrazolinesa
Starting
pyrazoline
Solvent
Step 1,b
product
Step 2c
T/°C
t/min
Product
Yieldd (%)
1a
1a
CH2Cl2
(CH2Cl)2
2a
2a
40
83
150
15
3a
3a + Eꢀ4 + Zꢀ4
(~10 : 4 : 1)
Eꢀ3b + Zꢀ3b
(2.9 : 1)
Eꢀ3c + Zꢀ3c
(4.9 : 1)
Eꢀ3c + Zꢀ3c
(2.6 : 1)
98
98
1b
1c
1c
CHCl3
CHCl3
CHCl3
Eꢀ2b + Zꢀ2b
(3 : 1)
60
25
60
15
180
15
96
95
97
Eꢀ2c + Zꢀ2c
(2.8 : 1)
Eꢀ2c + Zꢀ2c
(2.8 : 1)
Eꢀ2d
1d
1e
1f
CHCl3
CHCl3
(CH2Cl)2
60
60
83
15
15
30
Eꢀ3d
3e
antiꢀ3f
92
96
98
2e
antiꢀ2f
a The molar ratio is 1 : 1.
b The first step (0 °C, 1—2 min) is the formation of 1ꢀpyrazolines 2 in >95% yields. Their yields were
determined from the 1H NMR spectra of the reaction mixtures.
c The second step is dediazotization to cyclopropanes 3.
d The yields of cyclopropanes 3 and unsaturated compounds 4 are given with respect to the gross amount of
the dediazotization products isolated.
propane 3a (up to 33% yield) and unsaturated compounds
4 as a ~4 : 1 mixture of Eꢀ and Zꢀisomers (Scheme 4).
conversion of fused pyrazoline 2f can be attained only
under more drastic conditions (dichloroethane, reflux,
30 min). The spatial arrangement of the substituents in
cyclopropane 3f was determined by 2D NMR experiments
(1H,13C HOESY: Heteronuclear Overhauser Effect Spectroꢀ
scopy). The C atoms of the ester group show a characterꢀ
istic 1H,13C NOE peak with the C(8)H proton of the norꢀ
bornane framework (see Scheme 3).
Scheme 4
At the same time, the stereoselectivity of the dediazoꢀ
tization of isomeric pyrazolines 2c varies with the reaction
conditions. For instance, a mixture of pyrazolines Eꢀ and
Zꢀ2c (2.8 : 1) in boiling chloroform is completely transꢀ
formed into a mixture of cyclopropanes Eꢀ and Zꢀ3c
(~2.6 : 1), while the same pyrazolines at 20 °C (complete
conversion in 3 h) yield cyclopropanes 3c with E : Z =
= 4.9 : 1 (see Table 1).
Apparently, the dediazotization of the 1ꢀpyrazolines
studied proceeds through a biradical transition state in
which the configuration of the substituents can be partialꢀ
ly changed by rotation about the single C—C bond. The
stereochemical outcome of these transformations depends
in a complicated manner19 on the electronic and steric
effects of the substituents in the transition state.
The Eꢀ and Zꢀisomers of cyclopropane 3b were identiꢀ
fied from 2D NOESY data. The presence of a coupling
between the methyl protons and the C(1)H proton was
indicative of the minor isomer. In the case of cycloproꢀ
panes 3c, 1H,1HꢀNOESY and 1H,13CꢀHOESY NMR exꢀ
periments revealed couplings of the C atoms of both ester
groups with the same cisꢀvicinal proton of the cycloproꢀ
pane ring in the major isomer Eꢀ3c.
i. 83 °C, 15 min.
Isomeric pyrazolines 2b (E : Z = 3 : 1) are transformed
into cyclopropanes Eꢀ and Zꢀ3b, regardless of the dediazoꢀ
tization conditions. The stereochemistry of the substituꢀ
ents remains nearly the same (2.9 : 1) as that in the startꢀ
ing pyrazolines 2b. Likewise, isomerically pure pyrazolꢀ
ines Eꢀ2d and antiꢀ2f with substantial steric effects of the
substituents undergo dediazotization to the corresponding
isomerically pure cyclopropanes Eꢀ3d and antiꢀ3f in high
yields. In contrast to other pyrazolines 2, the complete

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Novikov et al.
anism proposed above (see Scheme 5), according to which
the elimination of N2 follows the addition of the second
PTAD molecule, is confirmed by the absence of isomeric
cyclopropanes 3b.
In contrast to pyrazoline 1b, pyrazolines 1a and 1c
react with two equivalents of PTAD (60 °C, 30 min) to
yield no products resulting from double addition of PTAD
(like triazabicyclooctane 5). Under these conditions, as
with one equivalent of PTAD, the reaction products are
compounds 3a and 4 or cyclopropane 3c; the second equiꢀ
valent of PTAD remains intact. Obviously, the resulting
pyrazolines 2a and 2c tend to undergo intramolecular
transformations (ring closure into cyclopropanes 3a and
3c or formation of isomeric olefins 4) rather than react
with PTAD. It should be noted that 1ꢀpyrazolines 6a,b
(see Refs 20—22) deprived of the 3,5ꢀdioxoꢀ4ꢀphenylꢀ
1,2,4ꢀtriazolidine substituent do not react with PTAD in
such a way as to produce compounds like triazabicycloꢀ
octane 5. Below 130 °C, the reaction does not occur at all;
at higher temperatures, either starting component decomꢀ
poses independently. Pyrazolines 6a,b are mainly transꢀ
formed into cyclopropanes and isomeric alkenes (similar
transformations have been described earlier22,23), while
PTAD yields a 1,3,5,7ꢀtetraazabicyclo[3.3.0]octane deꢀ
rivative.24
A reaction of 2ꢀpyrazoline 1b with a twofold excess of
PTAD gives 1,3,5ꢀtriazabicyclo[3.3.0]octaneꢀ2,4ꢀdione 5
through an intermediate bisadduct (Scheme 5). The reacꢀ
tion occurs in boiling CHCl3 for 30 min. Recrystallization
from diethyl ether gives functionalized triazabicycloꢀ
octanes Eꢀ and Zꢀ5 (~10 : 1) in 82% yield. Their strucꢀ
tures were determined from 2D NOESY experiments. As
expected, the major product is isomer Eꢀ5, which is steriꢀ
cally least hindered.
When the reaction temperature is lowered to 30 °C and
the reaction time is extended to 2 h, the formation of
triazabicyclooctane Eꢀ5 becomes less selective. The ratio
Eꢀ5 : Zꢀ5 is nearly the same (~3 : 1) as that for isomeric
pyrazolines Eꢀ and Zꢀ2b. It should be noted that a specialꢀ
ly prepared mixture of cyclopropanes Eꢀ and Zꢀ3b does
not react with PTAD in boiling CHCl3, nor yielding biꢀ
cyclic products of the type 5. Apparently, the first step
involves a rapid reaction of 2ꢀpyrazoline 1b with PTAD
followed by addition of a second PTAD molecule to
1ꢀpyrazoline 2b (in the form of a biradical intermediate),
which leads to compounds Eꢀ and Zꢀ5. The reaction mechꢀ
Strange as it may seem, PTAD also reacts with Nꢀsubꢀ
stituted 2ꢀpyrazolines to give, in high yields, products forꢀ
Scheme 5
i. 60 °C, 30 min.

Reactions of PTAD with 2ꢀpyrazolines
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1689
Scheme 6
R = CHPhCH2CH(CO2Me)2 (a), COPh (b)
Reaction conditions and products: i. 20 °C, 30 min, 8a; ii. 35 °C, 90 h, 8b.
mally derived by addition of PTAD to the H—C(3) bond
of 2ꢀpyrazolines 7a,b (Scheme 6). Since the formation of
the 1ꢀpyrazoline structure is impossible, the C—N bond
formation is followed by proton transfer from the pyrazolꢀ
ine fragment to the triazoline one and thus the 2ꢀpyrazolꢀ
ine structure is retained in the reaction product.
thyl 3ꢀmethylꢀ1ꢀpyrazolineꢀ3ꢀcarboxylate in the presence of
scandium triflate,25 the reaction occurs at room temperaꢀ
ture and is completed in about 30 min, giving substituted
2ꢀpyrazoline 8a. The presence of the electronꢀwithdrawing
benzoyl substituent at the N atom in pyrazoline 7b makes
this compound appreciably less reactive: its reaction with
PTAD at 35 °C takes 4 days and a twofold excess of PTAD
is required for complete conversion of compound 7b.
In the case of Nꢀalkylpyrazoline 7a prepared from diꢀ
methyl 2ꢀphenylcyclopropaneꢀ1,1ꢀdicarboxylate and meꢀ
Scheme 7
i. 20 °C, 30 min.

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Novikov et al.
3
3
2.40 (ddd, 1 H, Hb(4), 2J = 14.0 Hz, J = 8.5 Hz, J = 7.5 Hz);
3.79 (s, 3 H, OMe), 4.66 (ddd, 1 H, Ha(5), 2J = 18.2 Hz, 3J = 8.4 Hz,
3J = 7.5 Hz); 5.01 (ddd, 1 H, Hb(5), 2J = 18.2 Hz, 3J = 8.5 Hz,
3J = 4.3 Hz); 7.34—7.50 (m, 5 H, Ph); 8.05 (br.s, 1 H, NH).
13C NMR (CDCl3), δ: 27.4 (C(4)); 53.9 (OMe); 79.8 (C(5));
106.5 (C(3)); 126.0 (Co); 128.8 (Cp); 129.3 (Cm); 130.7 (Cipso);
154.0, 154.6 (C=O); 166.1 (COO).
Replacement of the proton in position 3 of the pyrazolꢀ
ine ring by a methoxycarbonyl group (as in, e.g., 2ꢀpyrꢀ
azoline 7c (see Ref. 25)) causes its reaction with PTAD to
follow a redox pattern. As a result, 1,3,5ꢀtrisubstituted
pyrazole 9 and 4ꢀphenylꢀ1,2,4ꢀtriazolidineꢀ3,5ꢀdione
(10),26,27 which is insoluble in dichloromethane, are obꢀ
tained in quantitative yields (Scheme 7). Apparently, in
this case too, the first step involves addition of PTAD to
the double bond of 2ꢀpyrazoline 7c, which is followed by
double proton transfer from the pyrazoline ring in a biꢀ
polar intermediate to the N=N bond of PTAD and the
formation of pyrazole 9.
To sum up, 4ꢀphenylꢀ1,2,4ꢀtriazolineꢀ3,5ꢀdione show
high efficiency in reactions with various substituted
2ꢀpyrazolines. Under slight heating, the resulting 1ꢀpyrꢀ
azolines can be smoothly transformed into dioxotriazolidꢀ
inylcyclopropanes. After an appropriate transformation of
the triazolidine ring (reduction or hydrolysis),3—6,10 the
latter can be of interest for the synthesis of substituted
aminocyclopropanes or cyclopropylhydrazines.
Methyl 5ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ3ꢀmeꢀ
thylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazoleꢀ3ꢀcarboxylate (2b). A 3 : 1 mixꢀ
ture of Eꢀ and Zꢀisomers. Eꢀisomer. 1H NMR (CD2Cl2), δ: 1.55
(s, 3 H, Me); 1.95 (dd, 1 H, Ha(4), J = 13.7 Hz, 3J = 8.8 Hz);
2
2
3
2.18 (dd, 1 H, Hb(4), J = 13.7 Hz, J = 7.9 Hz); 3.80 (s, 3 H,
OMe); 6.67 (dd, 1 H, H(5), 3J = 8.8 Hz, 3J = 7.9 Hz); 7.34—7.53
(m, 5 H, Ph); 7.80 (br.s, 1 H, NH). Zꢀisomer. 1H NMR
(CD2Cl2), δ: 1.58 (s, 3 H, Me); 1.42 (dd, 1 H, Ha(4), 2J = 13.7 Hz,
3J = 8.8 Hz); 2.51 (dd, 1 H, Hb(4), J = 13.7 Hz, J = 8.8 Hz);
2
3
3.79 (s, 3 H, OMe); 6.58 (dd, 1 H, H(5), 3J1
≈
3J2 = 8.8 Hz);
7.35—7.51 (m, 5 H, Ph); 7.80 (br.s, 1 H, NH).
Dimethyl 3ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ4,5ꢀ
dihydroꢀ3Hꢀpyrazoleꢀ3,5ꢀdicarboxylate (2c). A 2.8 : 1 mixture
of Eꢀ and Zꢀisomers. Eꢀisomer. 1H NMR (CD2Cl2), δ: 2.56 (dd,
1 H, Ha(4), 2J = 14.5 Hz, 3J = 5.6 Hz); 2.83 (dd, 1 H, Hb(4),
2J = 14.5 Hz, 3J = 9.4 Hz); 3.82, 3.84 (both s, 3 H each, 2 OMe);
5.77 (dd, 1 H, H(5), 3J = 9.4 Hz, 3J = 5.6 Hz); 7.39—7.54 (m, 5 H,
Ph); 8.45 (br.s, 1 H, NH). 13C NMR (CD2Cl2), δ: 30.3 (C(4));
54.7, 55.6 (OMe); 94.9 (C(5)); 108.9 (C(3)); 127.5 (Co); 130.4
(Cp); 130.8 (Cm); 132.2 (Cipso); 155.4, 155.8 (C=O); 167.4, 168.3
Experimental
1
H, 13C, and 15N NMR spectra were recorded on a Bruker
1
AMXꢀ400 spectrometer (400.1, 100.6, and 40.5 MHz, respecꢀ
tively) for solutions in CDCl3 or CD2Cl2 containing 0.05% Me4Si
as the internal standard. For 15N NMR spectra, CD3NO2 was
used as the standard. The signals were assigned and the isomers
of the compounds obtained were distinguished by homoꢀ and
heteronuclear 2D correlation techniques (DEPT, COSY, NOESY,
HSQC, HMBC, and HOESY). 13C,1HꢀHOESY NMR spectra
(COO). Zꢀisomer. H NMR (CD2Cl2), δ: 2.58 (dd, 1 H, Ha(4),
2J = 14.1 Hz, J = 9.1 Hz); 2.77 (dd, 1 H, Hb(4), J = 14.1 Hz,
3
2
3J = 8.3 Hz); 3.79, 3.88 (both s, 3 H each, 2 OMe); 5.47 (dd,
1 H, H(5), 3J = 9.1 Hz, J = 8.3 Hz); 7.39—7.54 (m, 5 H, Ph);
3
8.45 (br.s, 1 H, NH). 13C NMR (CD2Cl2), δ: 32.4 (C(4));
54.2, 55.7 (OMe); 94.5 (C(5)); 109.4 (C(3)); 127.6 (Co);
130.4 (Cp); 130.8 (Cm); 132.4 (Cipso); 155.6, 156.2 (C=O); 166.6,
168.8 (COO).
were recorded using a pulse "hoesy" program (AMX version28
)
for Bruker spectrometers with a mixing time of 2.0 s. Mass specꢀ
tra were measured on a Finnigan MAT INCOSꢀ50 instrument
(EI, 70 eV, direct inlet probe). Pyrazolines 1a,29 1b,30,31 1c,32
1d,33 1e,34 and 1f (see Ref. 35) were prepared by 1,3ꢀdipolar
cycloaddition reactions of diazo compounds with alkenes as deꢀ
scribed earlier; Nꢀsubstituted pyrazolines 7a—c were prepared
according to our own procedures.25 4ꢀPhenylꢀ1,2,4ꢀtriazolineꢀ
3,5ꢀdione (PTAD) was purchased from Aldrich. Solvents (reꢀ
agent grade, >99.5%) were used without further purification.
Synthesis of (3,5ꢀdioxotriazolidinyl)ꢀ1ꢀpyrazolines 2a—f (genꢀ
eral procedure). Powdery PTAD (105 mg, 0.6 mmol) was added
in one portion at 0 °C to a solution of 2ꢀpyrazoline 1 (0.6 mmol)
in CH2Cl2 (5—7 mL). The reaction mixture was stirred for
~1 min to complete homogenization and decoloration. The reꢀ
sulting solutions of virtually pure pyrazolines 2a—f are stable at
0 °C for several hours and can be used for further chemical
transformations. For recording 1H and 13C NMR spectra, analꢀ
ogous reactions were carried out in an NMR tube by adding
powdery PTAD (0.1 mmol) in one portion at 0 °C to a solution
of 2ꢀpyrazolines 1a—f (0.1 mmol) in CD2Cl2 or CDCl3 (0.5 mL).
The reaction mixture was stirred at 0 °C for ~1 min and NMR
spectra were recorded at the same temperature. The yields of
1ꢀpyrazolines 2a—f were >95%.
Dimethyl (E)ꢀ5ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ
4ꢀphenylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazoleꢀ3,3ꢀdicarboxylate (2d).
1H NMR (CDCl3), δ: 3.40, 3.85 (both s, 3 H each, 2 OMe); 4.20
(d, 1 H, H(4), 3J = 10.4 Hz); 6.90 (d, 1 H, H(5), 3J = 10.4 Hz);
7.03—7.65 (m, 11 H, 2 Ph, NH).
5ꢀ(3,5ꢀDioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ3,3ꢀdiphenylꢀ
4,5ꢀdihydroꢀ3Hꢀpyrazole (2e). 1H NMR (CDCl3), δ: 2.18 (dd, 1 H,
Ha(4), 2J = 13.2 Hz, 3J = 10.1 Hz); 2.93 (dd, 1 H, Hb(4),
3
3
2J = 13.2 Hz, J = 7.3 Hz); 6.30 (dd, 1 H, H(5), J = 10.1 Hz,
3J = 7.3 Hz); 7.21—7.53 (m, 15 H, Ph); 7.60 (br.s, 1 H, NH).
13C NMR (CDCl3), δ: 34.1 (C(4)); 95.7 (C(5)); 100.3 (C(3));
125.7 (Co, Ph—N); 126.6, 126.8 (Co, Ph—C); 128.0, 128.3
(Cp, Ph—C); 128.7 (Cp, Ph—N), 128.8, 129.0 (Cm, Ph—C); 129.3
(Cm, Ph—N); 130.9 (Cipso, Ph—N); 139.8, 143.7 (Cipso, Ph—C);
153.1, 154.3 (C=O).
Methyl 5ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀexoꢀ
3,4ꢀdiazatricyclo[5.2.1.02,6]decꢀ3ꢀeneꢀ5ꢀcarboxylate (2f).
1H NMR (CD2Cl2), δ: 0.77, 0.97 (both m, 1 H each, H2C(10),
2J = 11.1 Hz); 1.15, 1.26, 1.48, 1.62 (all m, 1 H each, H2C(8),
H2C(9)); 2.01, 2.93 (both m, 1 H each, H(1), H(7)); 2.46 (m, 1 H,
H(6), J2,6 = 5.9 Hz); 3.75 (s, 3 H, OMe); 4.85 (m, 1 H, H(2),
J2,6 = 5.9 Hz); 7.32—7.51 (m, 5 H, Ph); 8.85 (br.s, 1 H, NH).
13C NMR (CD2Cl2), δ: 25.2, 28.7, 32.7 (C(8), C(9), C(10));
37.8, 38.0, 44.6 (C(1), C(6), C(7)); 53.2 (OMe); 99.3 (C(2));
107.2 (C(5)); 125.7 (Co); 128.7 (Cp); 129.2 (Cm); 130.6 (Cipso);
153.8, 154.2 (C=O); 165.7 (COO).
Methyl 3ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ4,5ꢀ
1
dihydroꢀ3Hꢀpyrazoleꢀ3ꢀcarboxylate (2a). H NMR (CDCl3), δ:
3
2.35 (ddd, 1 H, Ha(4), 2J = 14.0 Hz, 3J = 8.4 Hz, J = 4.3 Hz);

Reactions of PTAD with 2ꢀpyrazolines
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1691
Synthesis of (3,5ꢀdioxotriazolidinyl)cyclopropanes 3a—f (genꢀ
eral procedure). Powdery PTAD (105 mg, 0.6 mmol) was added
at 20 °C to a solution of 2ꢀpyrazoline 1 (0.6 mmol) in chloroform
(7 mL). The reaction mixture was stirred for ~1 min to complete
homogenization and decoloration and then refluxed for 15 min
(~60 °C) until gas evolution ceased. For compound 1a, the reacꢀ
tion was carried out at 40 °C for 2.5 h; in specific cases, the
reaction medium was boiling dichloroethane (see Table 1). Then
the reaction mixture was filtered through a cotton plug and conꢀ
centrated in vacuo. If required, the residue was recrystallized
from diethyl ether or Et2O—hexane (2 : 1) and dried in vacuo
(0.01 Torr). The yields of cyclopropanes 3a—f were 92—98%,
colorless crystals.
Methyl 1ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)cycloꢀ
propaneꢀ1ꢀcarboxylate (3a), m.p. 138—140 °C. Found (%):
C, 56.73; H, 4.76; N, 15.07. C13H13N3O4. Calculated (%):
C, 56.25; H, 4.72; N, 14.71. MS, m/z (Irel (%)): 275 (15) [M]+,
260 (1) [M – Me]+, 243 (7) [M – OMe]+, 232 (35), 216 (13)
[M – CO2Me]+, 200 (13) [M – Ph]+, 177 (12), 172 (21), 156 (12),
145 (26), 141 (50), 134 (14), 127 (9), 119 (100), 96 (19), 91 (31),
84 (13), 77 (13), 69 (11), 64 (18), 59 (17). 1H NMR (CDCl3), δ:
1.45 (m, 2 H, Ha(2), Ha(3)); 1.58 (m, 2 H, Hb(2), Hb(3)); 3.69
(s, 3 H, OMe), 7.32—7.55 (m, 5 H, Ph); 8.3 (br.s, 1 H, NH).
13C NMR (CDCl3), δ: 16.4 (CH2CH2); 39.7 (C(1)); 53.0 (OMe);
126.0 (Co); 128.5 (Cp); 129.2 (Cm); 131.2 (Cipso); 154.2, 154.3
(C=O); 170.6 (COO).
(CDCl3), δ: 19.2 (C(3)); 30.5 (C(2)); 44.7 (C(1)); 52.8, 53.3
(OMe); 125.8 (Co); 128.6 (Cp); 129.2 (Cm); 131.0 (Cipso); 154.0,
154.4 (C=O); 167.5, 167.9 (COO). 15N NMR (CDCl3), δ:
–254.54 (1 N); –254.59 (2 N). Zꢀisomer. 1H NMR (CDCl3), δ:
2.02 (dd, 1 H, Ha(3), J = 6.1 Hz, J = 9.1 Hz), 2.29 (dd, 1 H,
Hb(3), 2J = 6.1 Hz, 3J = 7.9 Hz), 2.77 (dd, 1 H, H(2), 3J = 9.1 Hz,
3J = 7.9 Hz); 3.70, 3.75 (both s, 3 H each, 2 OMe); 7.35—7.51
(m, 5 H, Ph); 8.95 (br.s, 1 H, NH). 13C NMR (CDCl3), δ:
20.6 (C(3)); 28.8 (C(2)); 44.7 (C(1)); 53.0, 53.6 (OMe); 126.0
(Co); 128.6 (Cp); 129.2 (Cm); 131.1 (Cipso); 154.0, 154.4 (C=O);
168.5, 168.8 (COO). 15N NMR (CDCl3), δ: –254.54 (1 N);
–254.59 (2 N).
2
3
Dimethyl (E)ꢀ2ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ
3ꢀphenylcyclopropaneꢀ1,1ꢀdicarboxylate (3d), m.p. 68—69 °C.
Found (%): C, 61.25; H, 4.88; N, 10.65. C21H19N3O6. Calculatꢀ
ed (%): C, 61.61; H, 4.68; N, 10.26. MS, m/z (Irel (%)): 409 (1)
[M]+, 377 (3) [M – MeOH]+, 345 (31), 318 (11), 279 (43),
232 (40), 219 (28), 187 (31), 173 (40), 159 (33), 145 (21),
131 (33), 119 (100), 116 (66), 103 (50), 91 (100), 77 (60), 59 (56).
1H NMR (CDCl3), δ: 3.50, 3.84 (both s, 3 H each, 2 OMe); 3.96
3
(d, 1 H, H(3), J = 6.1 Hz); 4.27 (d, 1 H, H(2), 3J = 6.1 Hz);
7.15—7.55 (m, 11 H, 2 Ph, NH). 13C NMR (CDCl3), δ: 36.7
(C(3)); 42.1 (C(1)); 45.0 (C(2)); 52.8, 53.8 (OMe); 125.7
(Co, Ph—N); 128.1, 128.3 (Cp); 128.6, 128.7, 129.2 (Co, Ph—C,
both Cm); 131.0, 132.0 (Cipso); 153.5, 154.0 (C=O); 165.4,
167.3 (COO).
Methyl 2ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ1ꢀmeꢀ
thylcyclopropaneꢀ1ꢀcarboxylate (3b). A 2.9 : 1 mixture of Eꢀ and
Zꢀisomers, m.p. 53—54 °C. Found (%): C, 57.69; H, 5.12;
N, 14.67. C14H15N3O4. Calculated (%): C, 58.13; H, 5.23; N, 14.53.
MS, m/z (Irel (%)): 289 (19) [M]+, 257 (26) [M – MeOH]+, 230
(7) [M – CO2Me]+, 214 (12), 187 (11), 177 (24), 154 (21), 138
1ꢀ(3,5ꢀDioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ2,2ꢀdiphenylꢀ
cyclopropane (3e), m.p. 87—89 °C. MS, m/z (Irel (%)): 250 (2)
[M – PhNCO]+, 249 (3), 219 (2), 183 (36), 177 (28), 165 (17),
152 (9), 119 (34) [PhNCO]+, 105 (93), 77 (100), 51 (53). HRMS:
found m/z 368.1381; calculated for C23H19N3O2: [M – H]+
368.1394. 1H NMR (CDCl3), δ: 1.71 (dd, 1 H, Ha(3), 2J = 6.6 Hz,
1
2
3
(25), 119 (100), 112 (97), 91 (39), 69 (35). Eꢀisomer. H NMR
3J = 8.2 Hz); 2.33 (dd, 1 H, Hb(3), J = 6.6 Hz, J = 4.3 Hz);
3.64 (dd, 1 H, H(1), 3J = 6.6 Hz, 3J = 4.3 Hz), 7.18—7.51 (m, 15 H,
3 Ph), 7.61 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 18.4 (C(3));
37.1 (C(2)); 41.5 (C(3)); 125.6 (Co, Ph—N); 127.2, 127.5
(Co, Ph—C); 128.4 (Cp, Ph—N); 128.83, 128.85, 129.1, 129.2,
(CD2Cl2), δ: 1.37 (s, 3 H, Me); 1.37 (dd, 1 H, Ha(3), 2J = 5.8 Hz,
3
3J = 4.9 Hz); 1.70 (dd, 1 H, Hb(3), 2J = 5.8 Hz, J = 8.3 Hz);
3.66 (dd, 1 H, H(2), 3J = 8.3 Hz, 3J = 4.9 Hz); 3.67 (s, 3 H,
OMe); 7.33—7.51 (m, 5 H, Ph); 8.40 (br.s, 1 H, NH). 13C NMR
(CDCl3), δ: 13.6 (Me); 20.9 (C(3)); 25.2 (C(1)); 40.6 (C(2));
52.4 (OMe); 125.7 (Co); 128.5 (Cp); 129.2 (Cm); 131.1 (Cipso);
153.2, 153.5 (C=O); 173.5 (COO). Zꢀisomer. 1H NMR (CD2Cl2),
129.4 (Cp, Ph—C, Cm); 131.1 (Cipso, Ph—N); 138.8, 143.2 (Cipso
Ph—C); 153.6, 154.0 (C=O).
,
Methyl 3ꢀantiꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)ꢀ
exoꢀtricyclo[3.2.1.02,4]octaneꢀ3ꢀcarboxylate (3f), m.p. 65—66 °C.
Found (%): C, 63.31; H, 5.85; N, 12.55. C18H19N3O4. Calculatꢀ
ed (%): C, 63.33; H, 5.61; N, 12.31. MS, m/z (Irel (%)): 341 (30)
[M]+, 309 (4) [M – MeOH]+, 298 (6) [M – CO2Me]+, 282 (4),
268 (3), 255 (4), 239 (8), 207 (14), 179 (9), 177 (9), 163 (12), 119
(100), 105 (22), 91 (59), 77 (45), 66 (32), 59 (26). 1H NMR
(CDCl3), δ: 0.83, 0.87 (both m, 1 H each, H2C(8), 2J = 13.0 Hz);
1.30 (m, 2 H, Hendo(6), Hendo(7)); 1.52 (m, 2 H, Hendo(6),
Hendo(7)); 1.82 (m, 2 H, H(1), H(5)); 2.68 (m, 2 H, H(2), H(4));
3.75 (s, 3 H, OMe); 7.33—7.54 (m, 5 H, Ph); 8.40 (br.s, 1 H,
NH). 13C NMR (CDCl3), δ: 28.7 (C(6), C(7)); 30.3 (C(8)); 30.7
(C(2), C(4)); 35.9 (C(1), C(5)); 43.6 (C(3)); 52.9 (OMe); 125.7
(Co); 128.3 (Cp); 129.1 (Cm); 131.2 (Cipso); 151.4, 152.9 (C=O);
168.3 (COO).
Synthesis of methyl (E)ꢀ and (Z)ꢀ2ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ
1,2,4ꢀtriazolidinꢀ1ꢀyl)butꢀ2ꢀenoates (Eꢀ and Zꢀ4) in a mixture
with cyclopropane 3a. Powdery PTAD (105 mg, 0.6 mmol) was
added in one portion at 20 °C to a solution of 2ꢀpyrazoline 1a
(77 mg, 0.6 mmol) in dichloroethane (7 mL). The reaction mixꢀ
ture was stirred for ~1 min to complete homogenization and
decoloration and refluxed until gas evolution ceased (83 °C,
3
δ: 1.25 (dd, 1 H, Ha(3), 2J = 6.3 Hz, J = 7.9 Hz); 1.35 (s, 3 H,
Me); 2.10 (dd, 1 H, Hb(3), 2J = 6.3 Hz, 3J = 5.1 Hz); 3.13 (dd, 1 H,
H(2), 3J = 7.9 Hz, 3J = 5.1 Hz); 3.68 (s, 3 H, OMe); 7.33—7.51
(m, 5 H, Ph); 8.40 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 18.7
(Me); 20.9 (C(3)); 26.2 (C(1)); 42.2 (C(2)); 52.8 (OMe); 125.7
(Co); 128.4 (Cp); 129.2 (Cm); 131.2 (Cipso); 152.6, 154.5 (C=O);
172.7 (COO).
Dimethyl 1ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀyl)cycloꢀ
propaneꢀ1,2ꢀdicarboxylate (3c). The ratio of Eꢀ and Zꢀisomers
in the product was 2.6 : 1 (60 °C, 15 min; m.p. 45—46 °C) or
4.9 : 1 (20 °C, 3 h (see Table 1); m.p. 51—52 °C). Found (%):
C, 53.89; H, 4.69; N, 12.75. C15H15N3O6. Calculated (%): C, 54.06;
H, 4.54; N, 12.61. MS, m/z (Irel (%)): 333 (16) [M]+, 302 (6)
[M – OMe]+, 290 (6), 274 (6) [M – CO2Me]+, 258 (2), 231 (5),
215 (2), 199 (3), 183 (11), 177 (12), 157 (86), 156 (70), 119 (100),
91 (55), 59 (80). IR, ν/cm–1 (CHCl3): 3360 (NH), 1784, 1728
1
(O=CO, NC=O), 1600, 1504, 1440, 1428. Eꢀisomer. H NMR
(CDCl3), δ: 1.83 (dd, 1 H, Ha(3), 2J = 6.1 Hz, 3J = 10.0 Hz);
2
3
2.15 (dd, 1 H, Hb(3), J = 6.1 Hz, J = 8.5 Hz); 2.71 (dd, 1 H,
3
3
H(2), J = 10.0 Hz, J = 8.5 Hz); 3.71, 3.73 (both s, 3 H each,
2 OMe); 7.35—7.51 (m, 5 H, Ph); 8.95 (br.s, 1 H, NH). 13C NMR

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
Novikov et al.
~30 min). After cooling, the mixture was filtered through a cotꢀ
ton plug, concentrated in vacuo, and dried (0.01 Torr). The yield
of the product was 161 mg (98%), colorless powdery solid, m.p.
1 H each, H2C(4″), 2J = 17.3 Hz); 3.56 (dd, 1 H, H(2´), 3J = 8.4 Hz,
3J = 6.2 Hz); 3.73, 3.74 (both s, 3 H each, 2 OMe); 4.13 (dd, 1 H,
H(2´); 3J = 9.3 Hz, 3J = 5.7 Hz); 7.20—7.55 (m, 2 Ph and NH).
Isomer R*,R*ꢀ8a. 1H NMR (CDCl3), δ: 1.09 (s, 3 H, Me); 2.31
(ddd, 1 H, Ha(1´), 2J = 14.4 Hz, 3J = 9.5 Hz, 3J = 4.9 Hz); 2.67
(ddd, 1 H, Hb(1´), 2J = 14.4 Hz, 3J = 9.9 Hz, 3J = 5.1 Hz); 3.22,
1
146—149 °C. According to H and 13C NMR data, the product
consists of cyclopropane 3a and unsaturated compounds Eꢀ and
Zꢀ4 in a ratio of ~10 : 4 : 1. These compounds are inseparable by
chromatography on SiO2 or crystallization. Isomer Eꢀ4. 1H NMR
(CDCl3), δ: 2.16 (d, 3 H, Me, 3J = 7.5 Hz); 3.80 (s, 3 H, OMe);
6.72 (q, 1 H, H(3), 3J = 7.5 Hz); 7.36—7.53 (m, Ph); 8.40 (br.s,
NH). 13C NMR (CDCl3), δ: 14.8 (Me); 52.5 (OMe); 125.9 (Co);
127.0 (C(2)); 128.6 (Cp); 129.3 (Cm); 131.2 (Cipso); 145.7 (C(3));
154.1, 154.5 (C=O); 162.9 (COO). Isomer Zꢀ4. 1H NMR
(CDCl3), δ: 1.94 (d, 3 H, Me, 3J = 7.1 Hz); 3.91 (s, 3 H, OMe);
7.21 (q, 1 H, H(3), 3J = 7.1 Hz); 7.36—7.53 (m, Ph); 8.40 (br.s,
NH). 13C NMR (CDCl3), δ: 14.2 (Me); 52.2 (OMe); 125.8 (Co);
126.9 (C(2)); 128.6 (Cp); 129.3 (Cm); 131.2 (Cipso); 145.4 (C(3));
154.0, 154.4 (C=O); 163.0 (COO).
2
3.84 (both d, 1 H each, H2C(4″), J = 17.6 Hz); 3.70 (dd, 1 H,
H(2´), 3J = 9.5 Hz, 3J = 5.1 Hz); 3.71, 3.75, 3.80 (all s, 3 H each,
3 OMe); 4.32 (dd, 1 H, H(2´), 3J = 9.9 Hz, 3J = 4.9 Hz);
7.20—7.55 (m, 2 Ph, NH).
Methyl 1ꢀbenzoylꢀ3ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀ
yl)ꢀ5ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylate (8b). Powꢀ
dery PTAD (52 mg, 0.3 mmol) was added to a solution of
2ꢀpyrazoline 7b (74 mg, 0.3 mmol) in CH2Cl2 (5 mL). The
reaction mixture was stirred under argon at room temperature
for ~90 h, while adding PTAD as rapidly as it was being conꢀ
sumed (decoloration of the solution); the total amount of PTAD
added was 122 mg (0.7 mmol). The reaction mixture was filtered
through a cotton plug and concentrated in vacuo. The residue
was dissolved in diethyl ether—hexane (1 : 1) and the product
was precipitated with hexane and dried in vacuo (0.01 Torr).
The yield of compound 8b was 113 mg (90%), colorless crystals,
m.p. 110—113 °C. Found (%): C, 59.36; H, 4.64; N, 16.16.
C21H19N5O5. Calculated (%): C, 59.85; H, 4.54; N, 16.62. MS,
m/z (Irel (%)): 421 (1) [M]+, 362 (1) [M – CO2Me]+, 177 (4),
141 (1), 119 (14), 105 (100), 91 (9), 77 (37). 1H NMR (CDCl3),
δ: 1.87 (s, 3 H, Me); 3.46, 3.79 (both d, 1 H each, H2C(4),
2J = 18.4 Hz); 3.81 (s, 3 H, OMe); 7.28—7.56 (m, 9 H, Ph, Cm,
Cp, Bz, NH); 7.82 (m, 2 H, Co, Bz). 13C NMR (CDCl3), δ: 22.0
(Me); 44.3 (C(4)); 55.2 (OMe); 68.3 (C(5)); 125.8 (Co, Bz);
127.9 (Co); 129.1 (Cp); 129.5, 129.6 (Cm); 130.3 (Cipso); 131.2
(Cp, Bz); 133.7 (Cipso, Bz); 144.0, 147.4 (C=O); 150.8 (C(3));
166.2 (C=O); 171.3 (COO).
Dimethyl 2ꢀ(3,5ꢀdimethoxycarbonylꢀ1Hꢀpyrazolꢀ1ꢀyl)ꢀ2ꢀ
phenylethylmalonate (9). Powdery PTAD (42 mg, 0.24 mmol)
was added to a solution of Nꢀsubstituted pyrazolineꢀ3,5ꢀdicarbꢀ
oxylate 7c (R*,R*ꢀdiastereomer;25 100 mg, 0.24 mmol) in chloꢀ
roform (5 mL). The reaction mixture was stirred at room temꢀ
perature for 15 min. The precipitate of 4ꢀphenylꢀ1,2,4ꢀtriazolꢀ
idineꢀ3,5ꢀdione (10) that formed was filtered off (m.p. 206—207 °C;
the 1H and 13C NMR spectra agree with the literature data34,35).
The mother liquor was concentrated in vacuo and the residue
was dried (0.01 Torr). The yield of pyrazole 9 was 100 mg
(~100%), colorless oil. Found (%): C, 57.18; H, 5.33; N, 6.88.
C20H22N2O8. Calculated (%): C, 57.40; H, 5.30; N, 6.70. MS,
m/z (Irel (%)): 418 (7) [M]+, 387 (2) [M – OMe]+, 319 (1),
295 (2), 287 (70), 273 (85), 255 (16), 235 (12), 213 (21), 203 (14),
185 (44), 171 (28), 153 (17), 121 (65), 115 (100), 103 (26),
91 (27), 77 (27), 59 (82). 1H NMR (CDCl3), δ: 2.82—2.91 (m, 1 H,
Ha(1´)); 3.13—3.25 (m, 2 H, Hb(1´), H(2)); 3.70, 3.72, 3.85,
3.93 (all s, 3 H each, 4 OMe); 6.60 (m, 1 H, H(2´)); 7.26 (m, 1 H,
HCp); 7.30 (m, 2 H, HCm); 7.34 (s, 1 H, H(4″)); 7.41 (m, 2 H,
HCo). 13C NMR (CDCl3), δ: 34.4 (C(1´)); 48.9 (C(2)); 52.15,
52.23, 52.67, 52.71 (4 OMe); 61.8 (C(2´)); 114.6 (C(4″));
127.3 (Co); 128.4 (Cp); 128.7 (Cm); 133.9 (C(5″)); 138.9 (C(3″));
142.6 (Cipso); 159.5 (C(5″) COO); 162.1 (C(3″) COO); 168.9,
169.1 (2 COO).
Methyl (E)ꢀ and (Z)ꢀ6ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ
1ꢀyl)ꢀ8ꢀmethylꢀ2,4ꢀdioxoꢀ3ꢀphenylꢀ1,3,5ꢀtriazabicyclo[3.3.0]ꢀ
octaneꢀ8ꢀcarboxylate (5). Powdery PTAD (123 mg, 0.7 mmol)
was added at 20 °C to a solution of 2ꢀpyrazoline 1a (50 mg,
0.35 mmol) in chloroform (7 mL). The reaction mixture was
stirred for 1 min to complete homogenization and then refluxed
for 30 min until gas evolution ceased. The solvent was removed
in vacuo and the product was recrystallized from diethyl ether.
The yield of triazabicyclo[3.3.0]octane 5 as a ~10 : 1 mixture of
Eꢀ and Zꢀisomers was 134 mg (82%), colorless crystals, m.p.
111—112 °C. Found (%): C, 56.97; H, 4.52; N, 18.06. C22H20N6O6.
Calculated (%): C, 56.89; H, 4.34; N, 18.10. MS, m/z (Irel (%)):
288 (47) [M – PhC2HN3O2]+, 230 (15), 177 (23) [PhC2H2N3O2]+,
169 (13), 141 (100), 119 (84), 109 (18), 97 (21), 91 (44), 77 (26),
64 (27). IR, ν/cm–1 (CHCl3): 3352 (NH), 1772, 1728 (O=C),
1600, 1504, 1412. Eꢀisomer. 1H NMR (CD2Cl2), δ: 1.73 (s, 3 H,
Me); 2.95 (dd, 1 H, Ha(7), 2J = 13.8 Hz, 3J = 7.1 Hz); 3.04 (dd,
1 H, Hb(7), 2J = 13.8 Hz, 3J = 9.0 Hz); 3.73 (s, 3 H, OMe); 6.16
3
3
(dd, 1 H, H(6), J = 9.0 Hz, J = 7.1 Hz); 7.30—7.52 (m, Ph);
8.55 (br.s, NH). 13C NMR (CDCl3), δ: 21.9 (Me); 42.4 (C(7));
53.9 (OMe); 67.1 (C(6)); 67.5 (C(8)); 125.9, 126.0 (Co); 128.77,
128.82 (Cp); 129.4 (Cm); 130.7, 131.2 (Cipso); 152.9, 153.2, 153.8,
155.3 (C=O); 171.3 (COO). Zꢀisomer. 1H NMR (CD2Cl2), δ:
1.76 (s, 3 H, Me); 2.80 (dd, 1 H, Ha(7), 2J = 13.7 Hz, 3J = 3.2 Hz);
2
3
3.59 (dd, 1 H, Hb(7), J = 13.7 Hz, J = 8.3 Hz); 3.77 (s, 3 H,
OMe); 6.25 (dd, 1 H, H(6), 3J = 8.3 Hz, 3J = 3.2 Hz); 7.30—7.52
(m, Ph); 8.55 (br.s, NH). 13C NMR (CDCl3), δ: 22.6 (Me); 45.8
(C(7)); 54.3 (OMe); 64.5 (C(8)); 67.1 (C(6)); 125.69, 125.74
(Co); 128.6, 128.7 (Cp); 129.4 (Cm); 130.8, 131.2 (Cipso); 153.75,
153.76, 154.98, 154.99 (C=O); 172.2 (COO).
Dimethyl 2ꢀ{2ꢀ[3ꢀ(3,5ꢀdioxoꢀ4ꢀphenylꢀ1,2,4ꢀtriazolidinꢀ1ꢀ
yl)ꢀ5ꢀmethoxycarbonylꢀ5ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazolꢀ1ꢀyl]ꢀ
2ꢀphenylethyl}malonate (8a). Powdery PTAD (35 mg, 0.2 mmol)
was added at 20 °C to a solution of 2ꢀpyrazoline 7a (a ~1 : 1
mixture of two diastereomers;25 75 mg, 0.2 mmol) in CH2Cl2
(5 mL). The reaction mixture was stirred for 30 min, filtered
through a cotton plug, concentrated in vacuo, and dried (0.01 Torr).
The yield of compound 8a as a ~1 : 1 mixture of two diastereoꢀ
mers (90—94% purity, 1H NMR) was 110 mg, colorless oil.
Attempted purification by preparative TLC on SiO2 only conꢀ
taminated the product. Isomer S*,R*ꢀ8a. 1H NMR (CDCl3), δ:
1.51 (s, 3 H, Me); 2.34 (ddd, 1 H, Ha(1´), 2J = 14.3 Hz,
3J = 8.4 Hz, 3J = 5.7 Hz); 2.71 (ddd, 1 H, Hb(1´), 2J = 14.3 Hz,
3J = 9.3 Hz, 3J = 6.2 Hz); 2.98 (s, 3 H, OMe); 3.21, 3.85 (both d,
This work was financially supported by the Ministry of
Education and Science of the Russian Federation (State
Contract No. 02.740.11.0258).

Reactions of PTAD with 2ꢀpyrazolines
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1693
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Received December 28, 2010;
in revised form April 8, 2011