Formation and reactions of substituted diazocyclopropanes and cyclopropyldiazonium ions

Article abstract of DOI:10.1023/B:RUCB.0000024855.62916.80

Decomposition of N-nitroso-N-cyclopropylureas at 5-7°C on treatment with K₂CO₃ containing 15-20% H₂O allows simultaneous generation of both substituted diazocyclopropanes and cyclopropyldiazonium ions, which can react according to 1,3-dipolar cycloaddition or azo-coupling pattern with appropriate substrates. The nature of substituents in the cyclopropyl ring have a pronounced influence on the product ratio (and, probably, on the equilibrium between the diazo compound and the diazonium ion). Thus, on treatment with a base in the presence of equimolar amounts of methyl metacrylate as a trap for the diazo compound and 2-naphthol as a trap for the diazonium ion, N-cyclopropyl- and N-(2,2-dimethylcyclopropyl)-N- nitrosourea azo coupling products predominate. Conversely, N-(2,2- dichlorocyclopropyl)-N-nitrosourea is transformed predominantly into 1,3-cycloaddition products. A rationalization for the experimental data is proposed.

Full text of DOI:10.1023/B:RUCB.0000024855.62916.80

236
Russian Chemical Bulletin, International Edition, Vol. 53, No. 1, pp. 236—241, January, 2004
Formation and reactions of substituted diazocyclopropanes
and cyclopropyldiazonium ions
I. P. Klimenko, Yu. V. Tomilov,ꢀ and O. M. Nefedov
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
Decomposition of NꢀnitrosoꢀNꢀcyclopropylureas at 5—7 °C on treatment with K2CO3
containing 15—20% H2O allows simultaneous generation of both substituted diazocyclopropanes
and cyclopropyldiazonium ions, which can react according to 1,3ꢀdipolar cycloaddition or
azoꢀcoupling pattern with appropriate substrates. The nature of substituents in the cyclopropyl
ring have a pronounced influence on the product ratio (and, probably, on the equilibrium
between the diazo compound and the diazonium ion). Thus, on treatment with a base in the
presence of equimolar amounts of methyl metacrylate as a trap for the diazo compound and
2ꢀnaphthol as a trap for the diazonium ion, Nꢀcyclopropylꢀ and Nꢀ(2,2ꢀdimethylcyclopropyl)ꢀ
Nꢀnitrosourea azo coupling products predominate. Conversely, Nꢀ(2,2ꢀdichlorocyclopropyl)ꢀ
Nꢀnitrosourea is transformed predominantly into 1,3ꢀcycloaddition products. A rationalizaꢀ
tion for the experimental data is proposed.
Key words: nitrosocyclopropylureas, diazocyclopropanes, cyclopropyldiazonium ions, azo
compounds, spiro[4,5ꢀdihydropyrazoleꢀ5,1´ꢀcyclopropanes], competitive reactions.
Scheme 1
Baseꢀinduced decomposition of NꢀcyclopropylꢀNꢀ
nitrosourea (1a) is a convenient method for generation of
diazocyclopropane (2a), which enters into 1,3ꢀdipolar
cycloaddition with some unsaturated compounds, giving
rise to spirocyclopropaneꢀcontaining 1ꢀ and 2ꢀpyrazoꢀ
lines.1 Recently, we have shown2,3 that by using active
aromatic compounds and aliphatic CHꢀacids as substrates,
it is possible to trap also the cyclopropyldiazonium ion
(3a) with the formation of azo coupling products. Moreꢀ
over, both intermediates, 2a and 3a, can be trapped siꢀ
multaneously under the same conditions. Decomposition
of nitrosourea 1a induced by K2CO3 carried out at +5 °C
in the presence of equimolar amounts of methyl methꢀ
acrylate and pentaneꢀ2,4ꢀdione yields both pyrazoline 4a,
formed upon 1,3ꢀdipolar cycloaddition of 2a to methyl
methacrylate, and cyclopropylhydrazone 5a, resulting
from the addition of ion 3a to the reactive methylene
group of the diketone. The 4a to 5a ratio equals3 2.2 : 1
(Scheme 1).
This study deals with reactions of substituted diazoꢀ
cyclopropanes and the related cyclopropyldiazonium ions,
formed from Nꢀ(2,2ꢀdichlorocyclopropyl)ꢀ (1b) and
Nꢀ(2,2ꢀdimethylcyclopropyl)ꢀNꢀnitrosourea (1c).4 The
influence of substituents in the cyclopropane ring on the
equilibrium between diazocyclopropanes and the cycloꢀ
propyldiazonium ions was studied. In addition, the proꢀ
cedure for the preparation of nitrosourea 1b was conꢀ
siderably improved. First, the nitrosation of starting
Nꢀ(2,2ꢀdichlorocyclopropyl)urea with N2O3 was carried
out in the presence of AcONa for binding HNO2. Secꢀ
ond, after the reaction, the product was precipitated by
diluting the reaction mixture with light petroleum, the
precipitate was extracted with CHCl3, and the resulting
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 226—231, January, 2004.
1066ꢀ5285/04/5301ꢀ0236 © 2004 Plenum Publishing Corporation

Diazocyclopropanes and cyclopropyldiazonium ions Russ.Chem.Bull., Int.Ed., Vol. 53, No. 1, January, 2004
237
solution of nitrosourea 1b was washed with a 1% solution
of NaHCO3 (see Experimental). All workꢀup was carried
out rather rapidly at a temperature of 0—5 °C. This alꢀ
lowed us to prepare pure nitrosourea 1b (yield ∼30%),
formed as pale yellow crystals slowly decomposing at
110 °C (previously,4 it was reported that this nitrosourea
decomposes above 35 °C). The relatively low yield of
product 1b can be due to either partial nitrosation of the
starting urea at the NH2 group or to the fact that a subꢀ
stantial portion of nitrosourea decomposes in the acid
medium to give 2,2ꢀdichlorocyclopropyl isocyanate.
Unlike nitrosourea 1b, this compound is soluble in a
CH2Cl2—light petroleum mixture and, thus, it can be
separated. The formation of the isocyanate on decompoꢀ
sition of 1b is confirmed by the fact that treatment with an
excess of dry NH3 of the filtrate obtained after precipitaꢀ
tion of nitrosourea 1b with light petroleum affords the
starting Nꢀ(2,2ꢀdichlorocyclopropyl)urea in a yield of
up to 25%. In another run, the treatment of this filtrate
with MeOH gave rise to methyl Nꢀ(2,2ꢀdichlorocycloꢀ
propyl)carbamate (yield 20%). The formation of isocyanꢀ
ates on decomposition of nitrosoureas has been noted
previously, for example, for NꢀmethylꢀNꢀnitrosourea.5
However, in this case, decomposition proceeds apparꢀ
ently even at –10 °C and is catalyzed by the acid present,
because nitrosourea 1b that has been isolated from the
reaction mixture is quite stable.
ester group, whereas the Hb(7) signal is in higher field
(δ 1.62). In the antiꢀisomer, the discordant action of these
groups results in a smaller distance between the signals of
Ha(7) and Hb(7), which occur at δ 2.26 and 2.03, respecꢀ
tively. The deshielding effect of the diaza group leads to a
downfield shift of the signals of the Ha(2) protons oppoꢀ
site to this group by 0.83 ppm compared to the Hb(2)
signal.
Scheme 2
Baseꢀinduced decomposition of nitrosoureas 1b,c alꢀ
lowed us to generate diazocyclopropanes 2b,c and diazoꢀ
nium ions 3b,c both with donor and with acceptor subꢀ
stituents in the cyclopropane ring and to compare their
reactivities in the competing reactions with appropriate
substrates, by analogy with unsubstituted parent comꢀ
pounds 2a and 3a.3
R = Cl (b), Me (c)
1
Diazocyclopropanes 2b,c were trapped by methyl
methacrylate, which is a fairly reactive dipolarophile and
normally gives stable 1ꢀpyrazoline derivatives in reactions
with various aliphatic diazo compounds, including diꢀ
azocyclopropane (2a) generated under various condiꢀ
tions.6 The reactions were carried out at +5 °C in CH2Cl2
using K2CO3 as a base. In both cases, after the yellow
color inherent in starting nitrosoureas 1b,c disappeared,
the reaction mixture was filtered through SiO2 and the
filtrate was concentrated to give pure 1ꢀpyrazolines 4b,c
in 74 and 32% yields, respectively (Scheme 2). Each prodꢀ
uct was a mixture of antiꢀ and synꢀisomers; in the case of
4b, the antiꢀisomer predominated, while for 4c, the
synꢀisomer was the major product. In the 1H NMR specꢀ
trum, each of the H(2) and H(7) protons of isomeric
pyrazolines 4b forms two isolated ABꢀsystems with spinꢀ
spin coupling constants of 8.3 and 13.8 Hz, correspondꢀ
ing to the geminal protons of threeꢀ and fiveꢀmembered
rings. It is characteristic that the Ha(7) proton in the
synꢀisomer appeared in a lower field (δ 2.61), due to the
simultaneous deshielding influence of the Cl atoms of the
The H NMR spectrum of a mixture of pyrazoline 4c
isomers is more complex. Besides eight doublets due to
the H(2) and H(7) protons of synꢀ and antiꢀisomers, the
highꢀfield region contains six separate signals for the
Me groups. The use of NOESY and {C,H}ꢀcorrelation
2D techniques provided full assignment of the H and
13C NMR signals of antiꢀ and synꢀisomers of pyrazoꢀ
lines 4b,c.
1
The cyclopropyldiazonium ions 3b,c were trapped usꢀ
ing 2ꢀnaphthol and acetylacetone as azo components
(Scheme 3). It was found that decomposition of nitrosoꢀ
urea 1b on treatment with moist K2CO3 in the presence of
2ꢀnaphthol results in cyclopropylazoarene 6b in 27% yield,
whereas with acetylacetone, no azo coupling product (5b)
was detected even by direct NMR monitoring of the reacꢀ
1
tion mixture. According to the H NMR spectrum, the
only identifiable product formed in decomposition of
compound 1b was 1,1ꢀdichloroallene, responsible for a
singlet at δ 5.39.7 It should be noted that under identical
conditions in the presence of K2CO3, substituted nitrosoꢀ
ureas 1b,c decompose much more slowly than the unꢀ

238
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 1, January, 2004
Klimenko et al.
substituted analog 1a, their complete decomposition reꢀ
quiring at least 12 h instead of 2—3 h.
tive NHꢀproton decoupling, this signal degenerates into a
doublet of doublets with spinꢀspin coupling constants of
7.5 and 4.4 Hz, which is consistent with the expected
structure of the trisubstituted cyclopropane fragment. In
the 1H NMR spectrum of azoarene 6c, the lowꢀfield douꢀ
blet at δ 8.76 is due to the H(8) proton, as in azoarenes
6a,b. It is noteworthy that on going from 6b to 6c, the
signal of the methine proton of the cyclopropane ring
markedly shifts upfield (∆δ 0.67).
Scheme 3
These results show that intermediate 3b is the least
stable* among the cyclopropyldiazonium ions studied and
is fairly sensitive to the nature of the trapping reagent. It
adds only to highly reactive azo components, for example,
to 2ꢀnaphthol to give products in moderate yields. Conꢀ
versely, the diazonium cation 3c, having two Me substituꢀ
ents in the cyclopropane ring, is less sensitive to the naꢀ
ture of the azo component and can react with a larger
number of such compounds. The lower yields of adducts
5c and 6c compared to the yields of unsubstituted comꢀ
pounds 5a and 6a are probably due to steric factors, i.e.,
to the presence of Me substituents.
1
The data of the H NMR spectra of pyrazolines 4b,c
and azoarenes 6b,c were further used to determine the
ratio of the products of competitive reactions between
substituted diazocyclopropanes and cyclopropyldiazonium
ions in 1,3ꢀdipolar cycloaddition and azo coupling, reꢀ
spectively. The reactions (Scheme 4) were carried out by
a standard procedure using cyclopropylnitrosoureas 1a—c,
K2CO3, methyl methacrylate, and 2ꢀnaphthol in
1 : 2 : 4 : 4 molar ratio. The yields and the ratios of the
resulting adducts are summarized in Table 1.
Since an equimolar ratio of methyl methacrylate and
2ꢀnaphthol gave a fairly low yield of pyrazoline 4a (≤4%),
to determine the relative reactivities of the substrates more
accurately, we repeated the experiment taking 4 moles of
2ꢀnaphthol and 12 moles of methyl methacrylate per mole
of nitrosourea 1a. The yields of adducts 4a and 6a were
∼11 and 78%; thus, 2ꢀnaphthol has actually proved to be a
∼20 times more active trapping agent than methyl methꢀ
acrylate.
It can be seen from Table 1 that the introduction of
two Cl atoms into the cyclopropane ring inverts the ratio
of the trapping products of (dichlorocyclopropyl)diꢀ
azonium 3b and diazodichlorocyclopropane 2b. In this
case, the presence of even mediumꢀstrength electronꢀ
withdrawing substituents (such as Cl atoms) seems to inꢀ
duce a substantial shift of equilibrium in the system of
intermediates 3b—2b toward diazocyclopropane due to
the easier proton abstraction from the diazonium ion.
The magnitude of such shift was fairly difficult to predict.
R = H (a), Cl (b), Me (c)
Azoarene 6b was isolated using preparative TLC and
characterized by 1H and 13C NMR spectra. The 1H NMR
spectrum contains a threeꢀspin system of protons of the
cyclopropane ring as a doublet of doublets for each signal
at δ 2.34, 2.42, and 4.27 and a lowꢀfield broadened doublet
at δ 8.68, typical of the H(8) proton of the naphthalene
ring (the analogous signal for unsubstituted 1ꢀ(cycloꢀ
propylazo)ꢀ2ꢀnaphthol2 occurs at δ 8.72).
For estimating the reactivity of 2ꢀnaphthol and acetylꢀ
acetone toward azo coupling with the cyclopropylꢀ
diazonium ions, we carried out their competing reaction
with ion 3a. This was done using nitrosourea 1a, K2CO3,
2ꢀnaphthol, and acetylacetone in 1 : 2 : 4 : 4 molar ratio.
1
According to H NMR data, the reaction mixture conꢀ
tained compounds 6a and 5a in 6.3 : 1 ratio, respectively.
Thus, 2ꢀnaphthol is actually more reactive in this reacꢀ
tion than acetylacetone. This difference seems to be even
more pronounced in trapping of ion 3b.
Unlike the (dichlorocyclopropyl)diazonium ion 3b,
the dimethyl analog 3c forms azo coupling products both
with 2ꢀnaphthol and with acetylacetone. The yields of
adducts 6c and 5c amount to 55 and 29%, respectively.
The generation of ion 3c in the competitive reaction beꢀ
tween 2ꢀnaphthol and acetylacetone results in adducts 6c
and 5c in ∼1.4 : 1 ratio. In the 1H NMR spectrum, the Ac
groups of cyclopropylhydrazone 5c are responsible for
two separate singlets with δ 2.33 and 2.51, due to their
different positions with respect to the C=N bond. The
signal with δ 2.95 for the methine proton of the cycloproꢀ
pane fragment resembles a quintet; however, with selecꢀ
* The high selectivity of the diazonium cation 3b and the low
yield of azo coupling products could be due to low current
concentration of ion 3b caused by a substantial shift of the
equilibrium toward diazocyclopropane 2b.

Diazocyclopropanes and cyclopropyldiazonium ions Russ.Chem.Bull., Int.Ed., Vol. 53, No. 1, January, 2004
239
Scheme 4
composition of nitrosourea 1a easily proceeds at 5 °C on
treatment with dry potassium naphtholate in CH2Cl2 (reꢀ
actant molar ratio 1 : 3). The mixture immediately acꢀ
quires a bright yellow color and, after vigorous stirring for
∼15 min, it does not contain the starting nitrosourea any
longer. Pure azo adduct 6a was isolated from the reaction
mixture in 66% yield by preparative TLC. Apparently,
potassium naphtholate not only decomposes nitrosourea
1a at least 8 times as fast as K2CO3 does, but is simultaꢀ
neously azo coupled with the cyclopropyldiazonium catꢀ
ion 3a generated in situ.
Thus, we demonstrated the possibility of simultaneous
generation and trapping of substituted diazocyclopropanes
and the corresponding cyclopropyldiazonium ions by deꢀ
composition of NꢀcyclopropylꢀNꢀnitrosoureas by moist
K2CO3 in the presence of appropriate trapping agents.
The type of substituents has a great influence on the equiꢀ
librium between the diazo compound and the diazonium
ion. The generation of unsubstituted (2a) or gemꢀdiꢀ
methylꢀsibstituted diazocyclopropanes (2c) and cycloꢀ
propyldiazonium ions 3a,c in the presence of methyl
methacrylate and 2ꢀnaphthol results in the azo coupling
products prevailing over the 1,3ꢀdipolar addition prodꢀ
ucts. The introduction of two Cl atoms into the cycloproꢀ
pane ring results in an opposite ratio of the reaction prodꢀ
ucts. In addition, in the case of generation of dimethyl
derivatives 2c and 3c, the overall yield of trapping prodꢀ
ucts of both diazocyclopropane 2c and the cyclopropylꢀ
diazonium 3c considerably decreases. Apparently, this is
due to the lower reactivity of these intermediates caused
by the steric effects of substituents in the cycloproꢀ
pane ring.
In the case of dimethyl derivatives 2c and 3c, the azo
coupling product prevails once again over the 1,3ꢀdipolar
cycloaddition product, although to a lesser extent than in
the case of unsubstituted cyclopropyldiazonium. This is
accompanied by a decrease in the overall yield of the
trapping products of both diazo compound 2c and diazoꢀ
nium ion 3c, related apparently to the decrease in the
reactivity due to steric factors and to a higher contribuꢀ
tion of side processes, in particular, dediazotization.
The efficiency of 2ꢀnaphthol in the azo coupling with
cyclopropyldiazonium ions 3a—c is apparently provided,
among other factors, by an optimal combination of the
basic and nucleophilic properties of the naphtholate anꢀ
ions formed in the naphthol—K2CO3 system (for 2ꢀnaphꢀ
thol, pKa equals ∼9.5)8. The naphtholate anions can act
themselves as counterꢀions for intermediates 3a—c, which
makes the azo coupling preferable. We showed that deꢀ
Experimental
1
H and 13C NMR spectra were recorded on a Bruker AMꢀ300
spectrometer (300 and 75.5 МHz) for solutions in CDCl3 conꢀ
taining 0.05% Me4Si as the internal standard; 2D NOESY exꢀ
periments were performed on a Bruker DRXꢀ500 spectromꢀ
eter (500 МHz). Mass spectra were recorded on a Finnigan
MAT INCOSꢀ50 instrument (EI, 70 eV, direct injection).
UV spectrum was measured on a Specord Mꢀ40 spectrophotomꢀ
eter. Nꢀ(2,2ꢀDimethylcyclopropyl)ꢀNꢀnitrosourea (1c) was synꢀ
thesized by a previously reported procedure.4 Chemically
pure grade K2CO3 containing ∼20% H2O was used. TLC was
done using Merck silica gel 60 (0.040—0.063 mm). Potassium
2ꢀnaphtholate was obtained by the reaction of potassium with
2ꢀnaphthol in toluene.
Nꢀ(2,2ꢀDichlorocyclopropyl)ꢀNꢀnitrosourea (1b). A ∼20ꢀfold
excess of N2O3 (prepared from KNO2 and 80% H2SO4) was
passed through a suspension of Nꢀ(2,2ꢀdichlorocyclopropyl)urea
(340 mg, 2 mmol) and AcONa (246 mg, 3 mmol) in 12 mL of
dry CH2Cl2 at –10 °C for 30 min. After a persistent greenꢀblue
color has appeared, the reaction mixture was cooled to –30 °C,
20 mL of light petroleum was added, and excess N2O3 was
removed by passing a stream of argon through the suspension
formed. The reaction mixture was filtered off at a temperature
Table 1. Yields and ratios of pyrazolines 4a—c and azonaphtholes
6a—c under conditions of competitive reactions (molar ratio
1a—c : methyl methacrylate : 2ꢀnaphthol = 1 : 4 : 4)
Nitrosourea
Yield (%)
Ratio
4 : 6
pyrazoline 4
azoarene 6
1a
1b
1c
≤4
78
16
86
12
48
∼1 : 22
6.5 : 1
1 : 3

240
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 1, January, 2004
Klimenko et al.
not higher than –10 °C and the precipitate was washed with
30 mL of a light petroleum—CH2Cl2 mixture (2 : 1). The filtrate
containing 2,2ꢀdichlorocyclopropyl isocyanate was stored in a
refrigerator and the precipitate collected on the filter was exꢀ
tracted with CHCl3 at –10 °C (10×5 mL). The extract was
quickly washed with a 1% solution of NaHCO3 (2×10 mL) and
H2O (10 mL) and dried with Na2SO4 for 3 h at 5 °C. The
removal of the solvents gave 118 mg (30%) of nitrosourea 1b as
small pale yellow crystals that slowly decompose starting from
N, 14.43. C10H16N2O2. Calculated (%): C, 61.20; H, 8.22;
N, 14.27. MS, m/z (Irel (%)): 196 [M]+ (1), 168 [M – N2]+ (2),
153 [M – Pr]+ (28), 137 [M – COOMe]+ (61), 125 [M – N2 –
Pr]+ (13), 109 [M – COOMe – N2]+ (73), 67 (100). Pyrazoline
antiꢀ4c. 1H NMR (CDCl3), δ: 0.94 (d, 1 H, Hb(2), Jgem
=
5.3 Hz); 1.13 (s, 3 H, Meb); 1.49 (s, 3 H, Mea); 1.57 (s, 3 H,
Me); 1.65 (d, 1 H, Hb(7), Jgem = 12.9 Hz); 1.81 (d, 1 H, Ha(2),
Jgem = 5.3 Hz); 2.12 (d, 1 H, Ha(7), Jgem = 12.9 Hz); 3.78 (s,
3 H, OMe). 13C NMR (CDCl3) δ: 21.6 (Mea); 22.6 (Me); 23.5
(Meb); 26.4 (C(1)); 28.6 (C(2)); 33.2 (C(7)); 52.8 (OMe); 78.05
1
110 °C and melt at 120—124 °C. The H and 13C NMR spectra
correspond to those described previously.4
(C(3)); 91.9 (C(6)); 171.9 (C=O). Pyrazoline synꢀ4c. H NMR
1
An excess of dry NH3 was passed into the resulting solution
of 2,2ꢀdichlorocyclopropyl isocyanate in a mixture of light peꢀ
troleum and CH2Cl2 (see above), the precipitate was filtered off,
dried in vacuo at 0.1 Torr, and recrystallized from CHCl3 to give
85 mg (25%) of Nꢀ(2,2ꢀdichlorocyclopropyl)urea analogous to
an authentic sample.
In another similar experiment, excess MeOH was added to
the obtained solution of 2,2ꢀdichlorocyclopropyl isocyanate, the
solution was kept for 0.5 h and concentrated, and the residue
was dried in vacuo (0.1 Torr) and recrystallized from an
ether—pentane mixture (2 : 1) to give 74 mg (20%) of methyl
Nꢀ(2,2ꢀdichlorocyclopropyl)carbamate as colorless crystals,
m.p. 69—70 °C. 1H NMR (DMSOꢀd6), δ: 1.57 (br.dd, 1 H,
Jgem = 8.3 Hz, Jtrans = 6.6 Hz); 1.93 (dd, 1 H, Jcis = 9.9 Hz,
Jgem = 8.3 Hz); 3.22 (br.ddd, 1 H, Jcis = 9.9 Hz, Jtrans = 6.6 Hz,
JCH—NH = 4.3 Hz); 3.59 (br.s, 3 H, OMe); 7.92 (br.d, 1 H, NH,
J = 4.3 Hz). 13C NMR (CDCl3), δ: 27.9 (CH2); 38.4 (CH); 52.8
(OMe); 58.9 (CCl2); 157.1 (CO). MS, m/z (Irel (%)): 182
[M(2 35Cl) – H]+ (1); 172 (1), 170 (8), 168 (12) [M – Me]+; 150
(37), 148 (100) [M – Cl]+.
(CDCl3), δ: 0.92 (d, 1 H, Hb(2), Jgem = 5.1 Hz); 1.14 (s, 3 H,
Meb); 1.45 (d, 1 H, Hb(7), Jgem = 12.8 Hz); 1.51 (s, 3 H, Mea);
1.58 (s, 3 H, Me); 1.76 (d, 1 H, Ha(2), Jgem = 5.1 Hz); 2.31 (d,
1 H, Ha(7), Jgem = 12.8); 3.79 (s, 3 H, OMe). 13C NMR (CDCl3),
δ: 21.6 (Mea); 22.3 (Me); 23.2 (Meb); 25.9 (C(1)); 28.8 (C(2));
33.5 (C(7)); 52.8 (OMe); 78.01 (C(3)); 92.0 (C(6));
171.9 (C=O).
Azoarenes 6b,c (general procedure). 2ꢀNaphthol (28.8 mg,
0.2 mmol) and K2CO3 (69 mg, 0.4 mmol) were added succesꢀ
sively to a solution of nitrosourea 1b (0.2 mmol, 39.6 mg) or 1c
(31.4 mg) in 1 mL of CH2Cl2 cooled to 5—7 °C and the mixture
was vigorously stirred for 12 h. The resulting suspension was
filtered, the precipitate was washed with CHCl3 (3×0.3 mL),
and the combined organic extracts were concentrated. The resiꢀ
due, which consisted of 2ꢀnaphthol and azo adducts 6b or 6c
(1H NMR data), was separated by preparative TLC (SiO2, light
petroleum—AcOEt as the eluent, 8 : 1), collecting a brightꢀyelꢀ
low zone with Rf 0.5. The product was additionally purified by
crystallization from hexane at –18 °C.
1ꢀ(2,2ꢀDichlorocyclopropylazo)ꢀ2ꢀnaphthol (6b). Yield
15.1 mg (27%), yellow needle crystals, m.p. 90—91 °C.
Found (%): C, 55.31; H, 3.57; N, 9.70. C13H10Cl2N2O. Calcuꢀ
lated (%): C, 55.54; H, 3.59; N, 9.96. 1H NMR (CDCl3), δ: 2.34
(dd, 1 H, Hc, Jcis = 9.1 Hz, Jgem = 8.1 Hz); 2.42 (dd, 1 H, Hc,
Jtrans = 6.1 Hz, Jgem = 8.1 Hz); 4.27 (dd, 1 H, Ha, Jcis = 9.1 Hz,
Jtrans = 6.1 Hz); 7.11 (d, 1 H, H(3), J = 9.1 Hz); 7.43 (ddd, 1 H,
H(6), J = 8.0 Hz, J = 6.9 Hz, J = 1.2 Hz); 7.60 (ddd, 1 H, H(7),
J = 8.5 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.75 (br.d, 1 H, H(5), J =
8.0 Hz); 7.83 (br.d, 1 H, H(4), J = 9.1 Hz); 8.68 (br.d, 1 H,
H(8), J = 8.5 Hz); 13.41 (br.s, 1 H, OH). 13C NMR (CDCl3), δ:
29.9 (Cc); 59.0 (Ca); 59.7 (Cb); 120.4 (C(3)); 121.5 (C(8));
124.8 (C(6)); 128.2 (C(7)); 128.3 (C(5)); 128.3, 129.5, 132.8
(C(1), C(9), C(10)); 136.1 (C(4)); 154.6 (C(2)). MS,
m/z (Irel (%)): 246 (14), 244 (44) [M – HCl]+; 217 (27), 215
(81) [M – HCl – HCO]+; 209 [M – HCl – Cl]+ (100).
UV (hexane), λmax/nm (ε): 227 (34900) (+ 206 sh (17100)), 254
(10400), 262 (9700) (+ 280 sh (3100)), 344 (5800), 386 (5900)
(+ 418 sh (4600)).
Pyrazolines 4b,c (general procedure). Potassium carbonate
(69 mg, 0.4 mmol) was added at 5—7 °C to a solution of methyl
methacrylate (30 mg, 0.3 mmol) and nitrosourea 1b (0.2 mmol,
39.6 mg) or 1c (0.2 mmol, 31.4 mg) in 1 mL of CH2Cl2. The
mixture was vigorously stirred for 12 h. The resulting suspension
was centrifuged, the solution was concentrated, the precipitate
was washed with CHCl3 (2×0.3 mL), and the combined organic
extracts were passed through a short SiO2 layer. Evaporation
gave pyrazolines 4b,c as lightꢀyellow oils.
1,1ꢀDichloroꢀ6ꢀmethoxycarbonylꢀ6ꢀmethylꢀ4,5ꢀdiazaꢀ
spiro[2.4]heptꢀ4ꢀene (4b). Yield 35 mg (74%), a mixture of
antiꢀ and synꢀisomers (1.6 : 1). Found (%): C, 40.27; H, 4.37;
N, 11.98. C8H10Cl2N2O2. Calculated (%): C, 40.53; H, 4.25;
N, 11.82. MS, m/z (Irel (%)): 236 [M(2 35Cl)]+ (1); 181 (1),
179 (6), 177 (13) [M – COOMe]+; 115 (12), 113 (37) [M –
COOMe – HCl – N2]+; 41 (100). Pyrazoline antiꢀ4b. 1H NMR
(CDCl3), δ: 1.66 (s, 3 H, Me); 1.90 (d, 1 H, Hb(2), Jgem
=
8.4 Hz); 2.03 (d, 1 H, Hb(7), Jgem = 13.8 Hz); 2.26 (d, 1 H,
Ha(7), Jgem = 13.8 Hz); 2.71 (d, 1 H, Ha(2), Jgem = 8.4 Hz); 3.74
(s, 3 H, OMe). 13C NMR (CD3OD), δ: 22.2 (Me); 33.1 (C(2));
35.1 (C(7)); 53.5 (OMe); 62.1 (C(1)); 79.1 (C(3)); 95.8 (C(6));
171.4 (C=O). Pyrazoline synꢀ4b. 1H NMR (CDCl3), δ: 1.62 (d,
1 H, Hb(7), Jgem = 13.8 Hz); 1.65 (s, 3 H, Me); 1.88 (d, 1 H,
Hb(2), Jgem = 8.3 Hz); 2.61 (d, 1 H, Ha(7), Jgem = 13.8 Hz); 2.72
(d, 1 H, Ha(2), Jgem = 8.3 Hz); 3.75 (s, 3 H, OMe). 13C NMR
(CD3OD), δ: 21.9 (Me); 33.2 (C(2)); 35.2 (C(7)); 53.5 (OMe);
62.2 (C(1)); 79.0 (C(3)); 95.8 (C(6)); 171.6 (C=O).
1ꢀ(2,2ꢀDimethylcyclopropylazo)ꢀ2ꢀnaphthol (6c). Yield
26.3 mg (55%), yellow needle crystals, m.p. 38—40 °C.
Found (%): C, 74.69; H, 6.64; N, 11.39. C15H16N2O. Calcuꢀ
1
lated (%): C, 74.97; H, 6.71; N, 11.66. H NMR (CDCl3), δ:
1.28 (s, 3 H, Me); 1.38 (dd, 1 H, Hc, Jcis = 7.6 Hz, Jgem
=
5.3 Hz); 1.43 (s, 3 H, Me); 1.49 (dd, 1 H, Hc, Jtrans = 3.9 Hz,
Jgem = 5.3 Hz); 3.60 (dd, 1 H, Ha, Jcis = 7.6 Hz, Jtrans = 3.9 Hz);
7.11 (d, 1 H, H(3), J = 9.0 Hz); 7.40 (ddd, 1 H, H(6), J =
8.1 Hz, J = 6.9 Hz, J = 1.2 Hz); 7.57 (ddd, 1 H, H(7), J =
8.5 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.75 (br.d, 1 H, H(5), J =
8.1 Hz); 7.76 (br.d, 1 H, H(4), J = 9.0 Hz); 8.76 (br.d, 1 H,
H(8), J = 8.5 Hz); 13.80 (br.s, 1 H, OH). 13C NMR (CDCl3), δ:
6ꢀMethoxycarbonylꢀ1, 1, 6ꢀtrimethylꢀ4, 5ꢀdiazaꢀ
spiro[2.4]heptꢀ4ꢀene (4c). Yield 12.6 mg (32%) as a mixture of
antiꢀ and synꢀisomers (1 : 1.2). Found (%): C, 61.06; H, 8.54;

Diazocyclopropanes and cyclopropyldiazonium ions Russ.Chem.Bull., Int.Ed., Vol. 53, No. 1, January, 2004
241
20.8 (Me); 24.6 (Cb); 25.3 (Me); 25.9 (Cc); 60.3 (Ca); 120.1
(C(3)); 121.6 (C(8)); 124.2 (C(6)); 127.7 (C(7)); 128.0 (C(5));
128.1, 128.6, 132.5 (C(1), C(9), C(10)); 133.7 (C(4)); 152.9
(C(2)). MS, m/z (Irel (%)): 240 [M]+ (23), 225 [M – Me]+ (18),
184 [M – N2 – CO]+ (17), 158 (54), 144 (33), 129 (78), 115
(68), 41 (100).
The brightꢀyellow filtrate was concentrated and the residue was
separated by preparative TLC (SiO2, elution with light petroꢀ
leum—AcOEt (8 : 1)), collecting the brightꢀyellow zone of the
azo compound with Rf 0.5. The yield of azo compound 6a was
1
7 mg (66%). The H and 13C NMR spectra correspond to those
described previously.2
3ꢀ(2,2ꢀDimethylcyclopropyl)hydrazonopentaneꢀ2,4ꢀdione
(5c). Potassium carbonate (104 mg, 0.6 mmol) was added with
stirring to a solution of nitrosourea 1c (31.4 mg, 0.2 mmol) and
acetylacetone (23.3 mg, 0.24 mmol) in 1.2 mL of CH2Cl2 cooled
to 5—7 °C, and the mixture was vigorously stirred for 12 h. The
resulting suspension was filtered, the precipitate was washed
with CH2Cl2 (2×0.5 mL), the combined organic extracts were
concentrated, and the residue was dried in vacuo (1 Torr). Hexꢀ
ane (1 mL) was added to the residue and the resulting suspenꢀ
sion was centrifuged. Decanting and concentrating of the soluꢀ
tion gave 11.3 mg (29%) of hydrazone 5c as a lightꢀyellow oil.
Found (%): C, 61.34; H, 7.72; N, 14.48. C10H15N2O2. Calcuꢀ
The authors are grateful to Yu. A. Strelenko (N. D.
Zelinsky Institute of Organic Chemistry, RAS) for meꢀ
thodical help in recording and interpretation of the NMR
spectra on a Bruker DRXꢀ500 spectrometer.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
33365), the Program for the Support of Leading Scienꢀ
tific Schools of the Russian Federation (Grant
NShꢀ1987.2003.03), and the Fundamental Research Proꢀ
gram of the Division of Chemistry and Materials Sciences
of the RAS "Theoretical and Experimental Study of the
Nature of the Chemical Bond and Mechanisms of Most
Important Chemical Reactions and Processes."
1
lated (%): C, 61.52; H, 7.74; N, 14.35. H NMR (CDCl3), δ:
0.90 (dd, 1 H, Hc, Jcis = 7.5 Hz, Jgem = 5.8 Hz); 0.93 (dd, 1 H,
H
c, Jtrans = 4.4 Hz, Jgem = 5.8 Hz); 1.10, 1.16 (both s, each 3 H,
Me); 2.33, 2.51 (both s, each 3 H, COMe); 2.95 (m, 1 H, Ha,
Jcis = 7.5 Hz, Jtrans = 4.4 Hz, JCH—NH = 3.75 Hz); 13.68 (br.s,
1 H, NH). 13C NMR (CDCl3), δ: 19.0 (Cc); 19.3 (Me); 20.0
(Cb); 24.9 (Me); 26.5, 31.3 (C(1), C(5)); 45.3 (Ca); 133.4 (C(3));
196.8, 197.0 (C(2), C(4)). MS, m/z (Irel (%)): 196 [M]+ (2), 153
[M – COMe]+ (11), 43 [COMe]+ (100).
References
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organicheskoi khimii [Modern Problems of Organic Chemistry],
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O. M. Nefedov, Mendeleev Commun., 2002, 104.
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Competitive reactions (general procedure). 2ꢀNaphthol
(28.8 mg, 0.2 mmol) and K2CO3 (17.3 mg, 0.1 mmol) were
successively added with stirring at 5—7 °C to a solution of
nitrosourea 1a—c (0.05 mmol) and acetylacetone (19.4 mg,
0.2 mmol) or methyl methacrylate (20 mg, 0.2 mmol) in 1 mL of
CH2Cl2. The vigorous stirring was continued for 5 h at 5—7 °C
and the reaction mixture was kept for ∼12 h at the same temꢀ
perature. The resulting suspension was filtered, the precipitate
was washed with CH2Cl2 until the filtrate discolored (3×1 mL),
and the combined organic extracts were concentrated and dried
in vacuo (1 Torr). The yellow crystalline precipitate was comꢀ
1
pletely dissolved in CDCl3 and analyzed by H NMR spectroꢀ
scopy.
Reaction of NꢀcyclopropylꢀNꢀnitrosourea (1a) with potasꢀ
sium 2ꢀnaphtholate. Potassium 2ꢀnaphtholate (27.3 mg,
0.15 mmol) was added with stirring at 4 °C to a solution of
nitrosourea 1a (6.5 mg, 0.05 mmol) in 1 mL of CH2Cl2. An
intense yellow color appeared immediately. The vigorous stirꢀ
ring was continued for an additional 15 min at 4—5 °C, the
reaction mixture was quickly filtered at a temperature not higher
than 5 °C, and the precipitate was washed with 1 mL of CH2Cl2.
7. W. E. Billups and R. E. Bachman, Tetrahedron Lett., 1992,
33, 1825.
8. E. Pines, B. Magnes, M. J. Lang, and G. R. Fleming, Chem.
Phys. Lett., 1997, 281, 413.
Received November 17, 2003;
in revised form December 25, 2003