Unusual formation of hydroperoxides in the reactions of substituted spiro[pyrazolinecyclopropanes]

Article abstract of DOI:10.1007/s11172-005-0110-1

3-Cyano- and 3-(alkoxycarbonyl)spiro[2-pyrazoline-5,1'-cyclopropane] and 5-phenylspiro[1-pyrazoline-3,1'-cyclopropane] undergo unusual transformations into 3(5)-substituted 5(3)-(2-hydroperoxyethyl)pyrazoles in the presence of atmospheric oxygen. The cond

Full text of DOI:10.1007/s11172-005-0110-1

Russian Chemical Bulletin, International Edition, Vol. 53, No. 10, pp. 2257—2261, October, 2004
2257
✾
Unusual formation of hydroperoxides in the reactions of
substituted spiro[pyrazolinecyclopropanes]
I. V. Kostyuchenko, G. P. Okonnishnikova, E. V. Shulishov, and Yu. V. Tomilovꢀ
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 6390. Eꢀmail: tom@ioc.ac.ru
3ꢀCyanoꢀ and 3ꢀ(alkoxycarbonyl)spiro[2ꢀpyrazolineꢀ5,1´ꢀcyclopropane] and 5ꢀphenylꢀ
spiro[1ꢀpyrazolineꢀ3,1´ꢀcyclopropane] undergo unusual transformations into 3(5)ꢀsubstituted
5(3)ꢀ(2ꢀhydroperoxyethyl)pyrazoles in the presence of atmospheric oxygen. The conditions for
the formation of hydroperoxides (e.g., in oxygenꢀsaturated solutions of spiro[2ꢀpyrazolineꢀ
5,1´ꢀcyclopropanes] in CHCl3) and their conversion into (2ꢀhydroxyethyl)pyrazoles or the
corresponding nitrates under the action of nitrosating reagents were considered.
Key words: spiro[1ꢀ and 2ꢀpyrazolinecyclopropanes], hydroperoxides, opening of the cycloꢀ
propane ring, organic nitrates.
Earlier, we showed1,2 that the generation and [3+2]
spectrum in CD3OD contains two triplets at δ 4.16
cycloaddition of diazocyclopropane to acrylonitrile or
methyl acrylate affords 3ꢀcyanoꢀ (1a) or 3ꢀmethoxyꢀ
carbonylspiro[2ꢀpyrazolineꢀ5,1´ꢀcyclopropanes] (1b). It
turned out that these pyrazolines are most conveniently
obtained from diazocyclopropane generated by decomꢀ
position of NꢀcyclopropylꢀNꢀnitrosourea at 5 to 10 °C in
the presence of K2CO3 containing water (~20%). The
yields of pyrazolines 1a,b were 70 to 75%. However, in
some cases, byꢀproducts were obtained as a result of the
opening of the cyclopropane ring (e.g., in the synthesis of
pyrazoline 1a with access for air or when keeping pyrazoꢀ
lines 1a,b in CDCl3 for several hours). The 1H NMR
spectra of these compounds in CDCl3 contain characterꢀ
istic sets of signals: two triplets at δ 4.1 and 2.9 (J =
6.9 Hz) and a singlet at δ 6.5. Tentatively, these specꢀ
tra could belong to 4ꢀunsubstituted pyrazoles with an
OCH2CH2 fragment formed as a result of the opening of
the cyclopropane ring.
and 3.09 and a broadened lowꢀfield singlet at δ 6.69. Note
that without access for atmospheric oxygen, LiCl has no
noticeable effect on cyanopyrazoline 1a. Nor did attempts
at oxidation of pyrazoline 1a with such reagents as
mꢀchloroperbenzoic acid or lead tetraacetate afford hydroꢀ
peroxide 2a.
With the aim of studying possible ways of formation of
suggested βꢀoxyethylpyrazoles and determining their
structures, we investigated some chemical transformaꢀ
tions of 2ꢀpyrazolines 1a—c and 5ꢀphenylspiro[1ꢀpyrazoꢀ
lineꢀ3,1´ꢀcyclopropane],3 which can yield, under certain
conditions, products with the above characteristic set of
signals in their 1H NMR spectra.
Prolonged (48 h) stirring of pyrazoline 1a in CH2Cl2
in the presence of 10 mol. % LiCl in air gave a compound
containing no cyclopropane fragment. The major product
isolated with a satisfactory purity by preparative TLC on
silica gel was identified as 3ꢀcyanoꢀ5ꢀ(2ꢀhydroperoxyꢀ
ethyl)pyrazole (2a) (~55% yield). This compound is poorly
soluble in CDCl3 but well soluble in CD3OD. Its 1H NMR
Y = CN (a), COOMe (b), COOBut (c)
Later, we found that pyrazoline 1a can be efficiently
oxidized in oxygenꢀsaturated CHCl3 (5 °C, 12 h) to give
pure hydroperoxide 2a in virtually stoichiometric yield.
Its 1H NMR spectrum in (CD3)2SO shows, along with the
aforementioned two triplets and singlet, distinct separate
signals for the NH and OH protons at δ 11.8 and 13.7,
respectively. 13C NMR spectroscopy revealed the presꢀ
ence of the pyrazole ring containing two quaternary
C atoms and two CH2 groups. One of them is manifested
as a lowꢀfield signal (δC 75.4) because of its bond to the
hydroperoxide fragment. The composition of compound
2a was also confirmed by MS and elemental analysis data.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2160—2164, October, 2004.
1066ꢀ5285/04/5310ꢀ2257 © 2004 Springer Science+Business Media, Inc.

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Kostyuchenko et al.
It should be noted that iodometric titration gave an acꢀ
ceptable result (~96%) for a sample refluxed in CHCl3
for 5 min.
ditions, the direct reaction of butyl nitrite with pyrazoline
1a in air affords nitrate 4 in 42% yield. Its 1H NMR
spectrum, as well as the spectrum of hydroperoxide 2a,
contains two triplets at δ 4.70 and 3.23 and a singlet at
δ 6.65; its mass spectrum shows the molecular ion peak
with m/z 182.
The relatively high chemical and thermal stability
of (peroxyethyl)pyrazole 2a (m.p. 56—58 °C, without
decomp.) can be associated with intramolecular hydroꢀ
gen bonding, which prevents its radical decomposition.
Under analogous conditions (oxygenꢀsaturated
CHCl3, 5 °C, 12 h), pyrazoline 1b oxidizes nonselectively
to give a mixture of compounds (1H NMR spectrum conꢀ
tains several signals for methoxy groups). According to
the integral intensities of the characteristic signals for the
2ꢀhydroperoxyethyl substituent, the yield of hydroperꢀ
oxide 2b does not exceed 20%; compound 2b was not
isolated in the individual state. Unlike methoxycarboꢀ
nylpyrazoline 1b, its tertꢀbutyl analog 1c was converted
under the same conditions into the corresponding hydroꢀ
peroxide 2c in up to 85% yield.
Obviously,5 nitrate 4 is formed in the reaction of hydroꢀ
peroxide 2a (obtained through the oxidation of pyrazoline
1a with atmospheric oxygen) with alkyl nitrite used to
nitrosate cyclopropylamine. Indeed, the same reaction of
acrylonitrile, cyclopropylamine, and isoamyl nitrite in the
presence of 10 mol. % PhCOOH (see Ref. 4) without
access for atmospheric oxygen yields only pyrazoline 1a
and no hydroperoxide 2a and, accordingly, nitrate 4.
So far, we cannot unambiguously judge the reaction of
cyanopyrazoline 1a with an oxygen molecule. However,
the easy formation of hydroperoxide 2a in some cases
suggests a possible preꢀinitiation of the pyrazoline molꢀ
ecule and a generation of radical intermediates (e.g., comꢀ
pounds 5a,b). At the same time, it was experimentally
found that hydroperoxide obtained by the oxidation of
pyrazoline 1a with atmospheric oxygen in CDCl3 conꢀ
tains no deuterium. For instance, the 1H NMR spectrum
of the product in (CD3)2SO after the removal of the chloꢀ
roform retains the fullꢀproton signals for the NH and OH
groups at δ 11.8 and 13.7, which suggests a concerted
rather than freeꢀradical mechanism of the formation of
hydroperoxides 2.
When stored for several days, hydroperoxides 2a,c
slowly decompose, which is evident from a second set of
1
signals in their H NMR spectra (in particular, two tripꢀ
lets appear at δ ≈ 3.8 and 2.9). As expected, the decompoꢀ
sition products are substituted (2ꢀhydroxyethyl)pyrazoles
3a,c (13C NMR and MS data). Treatment of hydroperꢀ
oxide 2a with Na2S2O5 in aqueous methanol for 40 h
affords 3ꢀcyanoꢀ5ꢀ(2ꢀhydroxyethyl)pyrazole (3a) in 84%
yield.
As noted above, hydroperoxide 2a can also form durꢀ
ing the synthesis of pyrazoline 1a itself in air. Byꢀproduct
2a is obtained not only when diazocyclopropane is generꢀ
ated from NꢀcyclopropylꢀNꢀnitrosourea in the presence
of K2CO3, but also in the direct nitrosation of cycloꢀ
propylamine with alkyl nitrites.4 For instance, when kept
in air at 5 °C for 5 days, equimolar amounts of acryloniꢀ
trile, cyclopropylamine, and butyl nitrite in the presence
of 10 mol. % PhCOOH give a mixture of pyrazoline 1a,
hydroperoxide 2a, and 2ꢀ(3ꢀcyanopyrazolꢀ5ꢀyl)ethyl niꢀ
trate (4) in a molar ratio of 1 : 6.8 : 2.2, respectively
(1H NMR data). Only nitrate 4 was isolated in the pure
state (18%) from the final reaction mixture by preparative
TLC (SiO2, hexane—Et2O, 3 : 1). Under analogous conꢀ
It is also worth noting that the formation of hydroperꢀ
oxides 2 under the aforesaid conditions is characteristic of
2ꢀpyrazolines rather than isomeric 1ꢀpyrazolines 6, which
can be identified under certain conditions, despite the
presence of electronꢀwithdrawing substituents and a reacꢀ
tive αꢀH atom, from the 1H and 13C NMR spectra of the
reaction mixtures obtained by addition of in situ generꢀ
ated diazocyclopropane to acrylonitrile or tertꢀbutyl acryꢀ
late. For instance, a reduction in K2CO3 from its double
excess to an equimolar amount, as well as a reduction in
the reaction time from 2.5 to 1.5 h (when Nꢀcyclopropylꢀ
Nꢀnitrosourea is not yet decomposed completely), gives
both 2ꢀ (1a,c) and 1ꢀpyrazolines 6a,c. In the case of

Oxidation of spiro[pyrazolinecyclopropanes]
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
2259
acrylonitrile, 2ꢀpyrazoline 1a is dominant (isomer ratio
~4 : 1); in contrast, in the reaction of tertꢀbutyl acrylate
with diazocyclopropane under these conditions, the maꢀ
jor product is 1ꢀpyrazoline (ratio between isomers 1c and
6c is ~1 : 3; total yield is ~70%). The 1H NMR spectra of
1ꢀpyrazolines 6a,c show a characteristic ABX system, the
X part of which (δ ~5.2, dd) corresponds to the proton of
the CH—N=N fragment. In the absence of acids or bases,
1ꢀpyrazolines are rather stable; however, attempts at their
isolation by TLC on SiO2 or neutral Al2O3, as well as the
treatment of K2CO3 in CH2Cl2 in an inert atmosphere,
causes complete isomerization of 1ꢀpyrazolines 6a,c into
2ꢀpyrazolines 1a,c. For instance, in oxygenꢀsaturated soꢀ
lutions of the resulting 1ꢀ and 2ꢀpyrazolines in CHCl3
(5 °C, 12 h), 2ꢀpyrazolines 1a,c are converted into the
corresponding hydroperoxides 2a,c, while 1ꢀpyrazolines
6a,c remain virtually unchanged (1H NMR data).
of 5ꢀ(2ꢀhydroperoxyethyl)ꢀ3ꢀphenylpyrazole (9). The
1H NMR spectrum of compound 9 contains two triplets
at δ 4.08 and 2.92 (J = 6.9 Hz) and a singlet at δ 6.51,
while its 13C NMR spectrum shows signals characteristic
of an oxyethyl (δ 79.0 and 29.0), phenyl, and 3,5ꢀdisubꢀ
stituted pyrazole fragments. Of course, the same reaction
in an argon atmosphere yields no noticeable amounts of
peroxyethylpyrazole 9.
Hydroperoxide 9 decomposes with time to give a
complex mixture of compounds; however, in the presꢀ
ence of KOH (~50 h), the major decomposition product
is 5(3)ꢀ(2ꢀhydroxyethyl)ꢀ3(5)ꢀphenylpyrazole (10). Its
1H NMR spectrum also contains two triplets at δ 3.84
and 2.88 and a singlet at δ 6.48. As expected, the triplet
signals are slightly shifted upfield compared to those for
hydroperoxide 9.
The reaction of hydroperoxide 9 with butyl nitrite in
CHCl3 in the presence of 10 mol. % PhCOOH (5 °C,
40 h) gave, as in the case of hydroperoxide 2a, the correꢀ
sponding 2ꢀpyrazolylethyl nitrate 11 in ~80% yield.
In our opinion, the unexpected formation of hydroꢀ
peroxide 9 from 1ꢀpyrazoline 7 in the reaction in air is
difficult to imagine without generation of radical interꢀ
mediates similar to structures 5a,b, which seem to be
highly reactive toward atmospheric oxygen.
Y = CN (a), COOBut (c)
Thus, we discovered the selective formation of
(2ꢀhydroxyethyl)pyrazoles in the oxidation of some
spiro[pyrazolinecyclopropanes] with molecular oxygen.
Their sensitivity to atmospheric oxygen under certain conꢀ
ditions points to a possible generation of radical intermeꢀ
diates responsible for the formation of the corresponding
hydroperoxides, which is favored by the opening of the
spiroꢀconnected cyclopropane ring.
Unexpectedly, a structurally analogous hydroperoxide
was obtained on attempted reduction of 5ꢀphenylspiꢀ
ro[1ꢀpyrazolineꢀ3,1´ꢀcyclopropane] (7) with lithium in
EtOH in air. The previously described 5(3)ꢀethylꢀ3(5)ꢀ
phenylpyrazole (8)6 was also identified (~18%) among
the reaction products. This compound is formed as a reꢀ
sult of baseꢀinduced partial isomerization of the starting
pyrazoline 7. A second compound, which is poorly soluble
in CHCl3, was isolated in ~60% yield as a colorless finely
crystalline powder (m.p. 110—113 °C). According to MS,
1H and 13C NMR, elemental analysis, and iodometric
titration data, this compound was assigned the structure
Experimental
1
H and 13C NMR spectra were recorded on Bruker ACꢀ200
(200 and 50.3 MHz) and Bruker AMꢀ300 spectrometers (300 and
75.5 MHz) in CDCl3, CD3OD, or (CD3)2SO with 0.05% Me4Si
as the internal standard. Mass spectra were recorded on a
Finnigan MAT INCOSꢀ50 instrument (EI, 70 eV, direct inlet
probe). IR spectra were recorded on a Bruker IFSꢀ113v specꢀ
trometer in CCl4. The starting pyrazolines 1a,b and 7 were preꢀ
pared according to known procedures.1—3 nꢀButyl nitrite (97%,
Merck) and tertꢀbutyl acrylate (98%, Aldrich) were used withꢀ
out additional purification. Thinꢀlayer chromatography was carꢀ
ried out on Merck silica gel 60 (0.040—0.063 mm).
6ꢀtertꢀButoxycarbonylꢀ4,5ꢀdiazaspiro[2.4]heptꢀ5ꢀene (1c)
was synthesized as described for pyrazolines 1a,b 1,2 by the reacꢀ
tion of NꢀcyclopropylꢀNꢀnitrosourea7 (130 mg, 1 mmol) with
K2CO3 (400 mg, 2.3 mmol) containing water (~20%) and
tertꢀbutyl acrylate (280 mg, 2.2 mmol) in CH2Cl2 at 5 °C. The
reaction mixture was stirred for 2 h, filtered through a dense
filter, and concentrated in vacuo to give pyrazoline 1c (190 mg,
75%) as a viscous liquid. 1H NMR (CDCl3), δ: 0.80 and 0.88
(both m, 2 H each, CH2CH2); 1.55 (s, 9 H, CMe3); 2.98 (s, 2 H,

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Kostyuchenko et al.
CH2); 5.75 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 13.0
(CH2CH2); 28.2 (3 Me); 38.2 (C(4)); 45.5 (C(5)); 81.7 (C—O);
143.8 (C(3)); 162.2 (C=O). Partial MS, m/z (Irel (%)): 196 (15)
[M]+, 140 (15), 95 (50) [M—COOBut]+, 57 (100) [But]+.
3(5)ꢀCyanoꢀ5(3)ꢀ(2ꢀhydroperoxyethyl)pyrazole (2a). A. Oxyꢀ
gen was passed at 5 °C for 40 min through a solution of
cyanopyrazoline 1a (0.18 g, 1.5 mmol) in 4 mL of CHCl3 at a
rate of no higher than 1 mL min–1. The solution was kept at this
temperature for 16 h. The layer of peroxide was separated and
washed with 1 mL of CHCl3. The residual solvent was removed
in vacuo. The yield of compound 2a was 0.22 g (96%), colorless
crystals, m.p. 56—58 °C. Found (%): C, 46.72; H, 4.58; N, 27.22.
C8H12N2O2. Calculated (%): C, 47.06; H, 4.61; N, 27.44.
1H NMR (DMSOꢀd6), δ: 2.98 (t, 2 H, 3J = 6.5 Hz); 4.08 (t, 2 H,
3J = 6.5 Hz); 6.75 (s, 1 H); 11.75 and 13.69 (both br.s, 1 H each,
NH and OH). 1H NMR (CD3OD), δ: 3.09 (t, 2 H, J = 6.6 Hz);
4.16 (t, 2 H, J = 6.6 Hz); 6.69 (s, 1 H). 13C NMR (CDCl3), δ:
24.9 (CH2); 75.4 (CH2O); 110.3 (C(4)); 115.3 (CN); 126.2 and
143.6 (C(3) and C(5)). Partial MS, m/z (Irel (%)): 153 (15) [M]+,
135 (18) [M – H2O]+, 106 (100). IR, ν/cm–1: 3500—3150 (OH,
NH), 2923 s (CH2), 2854 m (CH2), 2243 m (CN), 994 m (OO).
B. Lithium chloride (4 mg, 0.094 mmol) was added at 20 °C
to a solution of pyrazoline 1a (68 mg, 0.56 mmol) in 3 mL of
CH2Cl2. The reaction mixture was stirred with free access for air
for 4 days and concentrated in vacuo. Hydroperoxide 2a (49 mg,
49%) was isolated as colorless crystals from the residue by preꢀ
parative TLC (SiO2, benzene—AcOEt, 1 : 1), Rf 0.54. The comꢀ
pound obtained was identical with hydroperoxide 2a in proceꢀ
dure A.
3(5)ꢀtertꢀButoxycarbonylꢀ5(3)ꢀ(2ꢀhydroperoxyethyl)pyrazole
(2c) was obtained as described for hydroperoxide 2a (see proceꢀ
dure A) from 6ꢀtertꢀbutoxycarbonylꢀ4,5ꢀdiazaspiro[2.4]heptꢀ5ꢀ
ene (1c) (0.29 g, 1.5 mmol). The yield of compound 2c was
0.29 g (85%). 1H NMR (DMSOꢀd6), δ: 1.48 (s, 9 H, CMe3);
2.91 (br.t, 2 H, 3J = 6.5 Hz); 4.09 (t, 2 H, 3J = 6.5 Hz); 6.50 (s,
1 H); 11.70 and 13.10 (both br.s, 1 H each, NH and OH).
13C NMR (CD2Cl2), δ: 24.9 (CH2); 27.4 (CMe3); 74.5 (CH2O);
81.7 (CMe3); 106.4 (C(4)); 140.0 and 146.2 (C(3) and C(5));
160.0 (C=O).
3(5)ꢀCyanoꢀ5(3)ꢀ(2ꢀhydroxyethyl)pyrazole (3a). Sodium
pyrosulfite (40 mg, 0.21 mmol) in 4 mL of water was added to a
solution of hydroperoxide 2a (54 mg, 0.35 mmol) in 5 mL of
MeOH. The reaction mixture was kept for ~40 h and concenꢀ
trated. The residue was treated with MeOH and the solution was
filtered and concentrated. Alcohol 3a (40 mg, 84%) was isolated
as a lowꢀmelting waxy mass from the residue by preparative
TLC (SiO2, benzene—AcOEt, 1.3 : 1), Rf 0.55. 1H NMR
(CD3OD), δ: 2.94 (t, 2 H, CH2, J = 6.5 Hz); 3.82 (t, 2 H,
CH2O, J = 6.5 Hz); 6.67 (s, 1 H). Partial MS, m/z (Irel (%)): 137
(36) [M]+, 119 (6) [M – H2O]+, 107 (100).
(C(4)); 113.7 (CN); 125.1 and 141.0 (C(3) and C(5)). Partial
MS, m/z (Irel (%)): 182 (10) [M]+, 136 (5) [M – NO2]+, 119 (8),
106 (100), 76 (25), 46 (55).
B. nꢀButyl nitrite (36 mg, 0.35 mmol) and then PhCOOH
(4.3 mg, 0.035 mmol) and cyclopropylamine (20 mg, 0.35 mmol)
were added at 5 °C to a stirred solution of acrylonitrile (19 mg,
0.35 mmol) in 4 mL of CHCl3. The reaction mixture was kept at
5 °C for 5 days. The final mixture contained pyrazoline 1a,
hydroperoxide 2a, and nitrate 4 in a molar ratio of 1 : 6.8 : 2.2
(1H NMR data). The solvent was removed in vacuo and nitrate 4
(11.5 mg, 18%) was isolated from the residue by TLC.
5(3)ꢀ(2ꢀHydroperoxyethyl)ꢀ3(5)ꢀphenylpyrazole (9). Lithium
metal (56 mg, 8.0 mmol) was added in two portions to a solution
of pyrazoline 7 (0.95 g, 5.5 mmol) in 10 mL of EtOH with free
access for air. Thirty minutes after the metal was dissolved, the
solution was diluted with water (20 mL) and organic material
was extracted with CH2Cl2 (35 mL). The organic layer was
separated, dried with anhydrous Na2SO4 and concentrated in
vacuo to give a compound (0.17 g, 18%) identical with 5(3)ꢀethylꢀ
3(5)ꢀphenylpyrazole (8) 6 (1H and 13C NMR data). The aqueꢀ
ous layer was acidified with 3% HCl (~15 mL) to pH 2 and
organic material was extracted with CH2Cl2. The extract
was dried with anhydrous Na2SO4 and concentrated in vacuo
to give hydroperoxide 9 (0.67 g, 60%) as colorless crystals,
m.p. 110—113 °C. Found (%): C, 64.15; H, 5.58; N, 13.27.
C8H12N2O2. Calculated (%): C, 64.69; H, 5.92; N, 13.72.
1H NMR (DMSOꢀd6), δ: 2.92 (t, 2 H, CH2, J = 6.9 Hz); 4.08 (t,
2 H, CH2O, J = 6.9 Hz); 6.51 (s, 1 H, H(4)); 7.38 and 7.71
(both m, 3+2 H, Ph); 11.71 (s, OOH); 12.62 (br.s, NH).
13C NMR (DMSOꢀd6), δ: 29.0 (CH2); 79.00 (CH2O); 105.2
(C(4)); 129.1, 131.5, 132.3 (Ph); 136.1 and 149.6 (C(3) and
C(5)). Partial MS, m/z (Irel (%)): 204 (16) [M]+, 186 (19)
[M – H2O]+, 157 (100). IR, ν/cm–1: 3256 (OH), 2935 s (CH2),
2764 m (CH2), 968 m (OO).
5(3)ꢀ(2ꢀHydroxyethyl)ꢀ3(5)ꢀphenylpyrazole (10). A solution
of KOH (28 mg, 0.5 mmol) in 0.3 mL of water was added to a
solution of hydroperoxide 2d (98 mg, 0.48 mmol) in 3 mL of
EtOH. The reaction mixture was stirred at 20 °C for 50 h and
then neutralized with 3% HCl and concentrated to a half volꢀ
ume in vacuo. The product was extracted with CH2Cl2. The
organic layer was dried with anhydrous Na2SO4 and concenꢀ
trated. (Hydroxyethyl)pyrazole 10 (57 mg, 63%) as colorless
crystals was isolated from the residue by TLC on silica gel (benꢀ
zene—AcOEt, 4 : 1), m.p. 158—160 °C, Rf 0.65. Found (%):
C, 70.58; H, 6.18; N, 15.06. C11H12N2O. Calculated (%):
1
C, 70.19; H, 6.43; N, 14.88. H NMR (DMSOꢀd6), δ: 2.81 (t,
2 H, CH2, J = 6.7 Hz); 3.69 (t, 2 H, CH2O, J = 6.7 Hz); 4.82
(br.s, OH); 6.51 (s, 1 H, H(4)); 7.32 and 7.76 (both m, 2+3 H,
Ph); 12.62 (br.s, NH). 13C NMR (DMSOꢀd6), δ: 28.7 (CH2);
60.0 (CH2O); 100.3 (C(4)); 124.5, 126.7, 128.1 and 133.7 (Ph),
141.5 and 149.8 (C(3) and C(5)). Partial MS, m/z (Irel (%)): 188
(88) [M]+, 171 (25) [M – H2O]+, 158 (100).
5(3)ꢀ(2ꢀNitrooxyethyl)ꢀ3(5)ꢀphenylpyrazole (11). A solution
of BunONO (10 mg, 0.1 mmol) in 0.1 mL of CHCl3 was added
to a suspension of hydroperoxide 9 (20 mg, 0.1 mmol) in 0.5 mL
of CHCl3. The reaction mixture was stirred at 5 °C for 40 h and
then concentrated in vacuo. Nitrate 11 (18 mg, 80%) was isoꢀ
lated from the residue by TLC on silica gel (benzene—AcOEt,
3 : 1), Rf 0.62. 1H NMR (CDCl3), δ: 3.05 (t, 2 H, CH2, J =
6.2 Hz); 4.65 (t, 2 H, CH2O, J = 6.2 Hz); 6.42 (s, 1 H, H(4));
7.35 and 7.65 (both m, 2+3 H, Ph); 9.18 (br.s, 1 H, NH).
3(5)ꢀCyanoꢀ5(3)ꢀ(2ꢀnitrooxyethyl)pyrazole (4). A. Benzoic
acid (0.10 g, 0.89 mmol) and then BunONO (0.92 g, 8.9 mmol)
were added at 5 °C to a stirred solution of pyrazoline 1a (0.90 g,
7.4 mmol) in 15 mL of CHCl3. The reaction mixture was stirred
at 5 °C for 3 h, filtered through a dense porous filter, and conꢀ
centrated in vacuo. Nitrate 4 (0.55 g, 42%) was isolated from the
residue by preparative TLC on silica gel (benzene—AcOEt, 3 : 1),
Rf 0.70. IR, ν/cm–1: 3430 (NH); 2252 (CN); 1648, 1280 (NO2).
1H NMR (CDCl3), δ: 3.23 (t, 2 H, CH2, J = 6.4 Hz); 4.70 (t,
2 H, CH2O, J = 6.4 Hz); 6.65 (s, 1 H, CH); 12.0 (br.s, 1 H,
NH). 13C NMR (CDCl3), δ: 23.7 (CH2); 70.5 (CH2O); 110.4

Oxidation of spiro[pyrazolinecyclopropanes]
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
2261
13C NMR (CDCl3), δ: 25.1 (CH2); 71.5 (OCH2); 102.5 (C(4));
125.8 (oꢀPh); 128.3 (pꢀPh); 128.8 (mꢀPh); 130.1 (iꢀPh); 145.4
and 147.6 (C(3) and C(5)). Partial MS, m/z (Irel (%)): 233 [M]+
(19), 157 [M – CH2ONO2]+ (100).
above mixture of pyrazolines 1c and 6c ((20 mg, 0.1 mmol,
ratio 1 : 3) in 0.5 mL of CH2Cl2. The reaction mixture was
stirred for 4 h, filtered, and concentrated to give pure pyrazoꢀ
line 1c (1H NMR data).
Spectroscopic detection of 1ꢀpyrazolines 6a,c (general proꢀ
cedure). NꢀCyclopropylꢀNꢀnitrosourea (64 mg, 0.5 mmol) and
K2CO3 (69 mg, 0.4 mmol) containing water (~20%) were added
at 5 °C in an argon atmosphere to a solution of acrylonitrile or
tertꢀbutyl acrylate (1 mmol) in 5 mL of CH2Cl2. The mixture
was stirred at 5 °C for 1.5 h and filtered. The filtrate was concenꢀ
trated, and C6H6 (2 mL) was added. The unreacted Nꢀcycloꢀ
propylꢀNꢀnitrosourea was filtered off. The filtrate was concenꢀ
trated to give a residue (45—55 mg) containing compounds 1a
and 6a (molar ratio ~4 : 1) or compounds 1c and 6c (ratio ~1 : 3)
in a total yield of ~70% (1H NMR data).
6ꢀCyanoꢀ4,5ꢀdiazaspiro[2.4]heptꢀ4ꢀene (6a). 1H NMR
(CDCl3), δ: 1.27 (m, 2 H, H(1) and H(2), directed from the
N atom of the heterocycle); 1.82—1.95 (m, 2 H, H(1) and H(2),
directed toward the N atom of the heterocycle); 2.11 (dd, 1 H,
Ha(7), 2J = 12.6 Hz, 3J = 8.0 Hz); 2.21 (dd, 1 H, Hb(7), 2J =
12.6 Hz, 3J = 10.5 Hz); 5.22 (dd, 1 H, H(6), 3J = 10.5 Hz,
3J = 8.0 Hz).
6ꢀtertꢀButoxycarbonylꢀ4,5ꢀdiazaspiro[2.4]heptꢀ5ꢀene (6c).
1H NMR (CD2Cl2), δ: 1.15 (m, 2 H, H(1) and H(2), directed
from the N atom of the heterocycle); 1,48 (s, 9 H, CMe3);
1.63—1.81 (m, 2 H, H(1) and H(2), directed toward the N atom
of the heterocycle); 1.89 (dd, 1 H, Ha(7), 2J = 12.5 Hz, 3J =
7.8 Hz); 2.02 (dd, 1 H, Hb(7), 2J = 12.5 Hz, 3J = 10.3 Hz); 5.18
(dd, 1 H, H(6), 3J = 10.3 Hz, 3J = 7.8 Hz). 13C NMR (CD2Cl2),
δ: 13.6 and 13.8 (CH2CH2); 26.9 (C(7)); 37.3 (Me3C); 69.8
(C(3)); 81.7 (Me3C); 89.5 (C(6)); 167.4 (C=O).
References
1. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, and
O. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 1997, 532 [Russ.
Chem. Bull., 1997, 46, 511 (Engl. Transl.)].
2. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, and
O. M. Nefedov, In Modern Problems of Aliphatic Diazo Comꢀ
pounds Chemistry, Abstrs, S.ꢀPetersburg, 2000, p. 68.
3. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, B. B.
Averkiev, M. Yu. Antipin, and O. M. Nefedov, Izv. Akad.
Nauk, Ser. Khim., 1999, 1328 [Russ. Chem. Bull., 1999, 48,
1316 (Engl. Transl.)].
4. Yu. V. Tomilov, G. P. Okonnishnikova, E. V. Shulishov, and
O. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 2004, 639 [Russ.
Chem. Bull., Int. Ed., 2004, 53, 671].
5. R. Criegee and W. Schnorrenberg, Leib. Ann. Chem., 1949,
563, 93.
6. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, B. B.
Averkiev, M. Yu. Antipin, and O. M. Nefedov, Izv. Akad.
Nauk, Ser. Khim., 1999, 1328 [Russ. Chem. Bull., 1999, 48,
1316 (Engl. Transl.)].
7. W. Kirmse and H. Schutte, Chem. Ber., 1968, 101, 1674;
Yu. V. Tomilov, E. V. Shulishov, and O. M. Nefedov, Izv.
Akad. Nauk SSSR, Ser. Khim., 1991, 1057 [Bull. Acad. Sci.
USSR, Div. Chem. Sci., 1991, 40, 939 (Engl. Transl.)].
Isomerization of 1ꢀpyrazoline 6c into 2ꢀpyrazoline 1c. Potasꢀ
sium carbonate (17 mg, 0.1 mmol) containing water (~20%) was
added at 5 °C in an argon atmosphere to a solution of the
Received July 16, 2004