Azo-coupling and reduction of cyclopropanediazonium ions in the reactions with polyhydroxyarenes and aminophenols

Article abstract of DOI:10.1007/s11172-008-0225-2

A reaction of cyclopropanediazonium ion, generated by decomposition of N-cyclopropyl-N-nitrosourea upon treatment with potassium or cesium carbonates, with various poly-hydroxyarenes and aminophenols has been studied. The reaction of azo-coupling proceeds with phloroglucinol, resorcinol, 3-methoxy- and 3-aminophenol giving rise to mono-, bis-, and tris(cyclopropylazo)arenes as the major products. Oxidizable phenols such as hydro-quinone, 2-methoxy-, 4-amino-, and 2-aminophenol give products of radical transformations with participation of cyclopropyl radical.

Full text of DOI:10.1007/s11172-008-0225-2

Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1703—1711, August, 2008
1703
Azoꢀcoupling and reduction of cyclopropanediazonium ions
in the reactions with polyhydroxyarenes and aminophenols
E. V. Shulishov, I. P. Klimenko, V. A. Korolev, I. V. Kostyuchenko,†
G. P. Okonnishnikova, 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
A reaction of cyclopropanediazonium ion, generated by decomposition of Nꢀcyclopropylꢀ
Nꢀnitrosourea upon treatment with potassium or cesium carbonates, with various polyꢀ
hydroxyarenes and aminophenols has been studied. The reaction of azoꢀcoupling proceeds
with phloroglucinol, resorcinol, 3ꢀmethoxyꢀ and 3ꢀaminophenol giving rise to monoꢀ, bisꢀ,
and tris(cyclopropylazo)arenes as the major products. Oxidizable phenols such as hydroꢀ
quinone, 2ꢀmethoxyꢀ, 4ꢀaminoꢀ, and 2ꢀaminophenol give products of radical transformations
with participation of cyclopropyl radical.
Key words: NꢀcyclopropylꢀNꢀnitrosourea, cyclopropylazoarenes, cyclopropanes, NMR
spectra, phenols, diazo compounds, azo compounds.
One of the most important intermediates arising
during decomposition of NꢀcyclopropylꢀNꢀnitrosourea
(1a) under action of bases is cyclopropanediazonium ion
(2),* able to enter into the reaction of azoꢀcoupling with
CHꢀacids and naphthols.1,2 However, in a number of
cases, the formation of azo adducts is complicated by side
processes, that is especially pronounced in the case of azo
component with lower activity, for example, phenol.3 In
this case, cyclopropanediazonium has time to eliminate a
nitrogen molecule with the formation of cyclopropyl or
allyl cation, which further react with suitable substrates
present in the reaction mixture.
Recently, we showed4 that diazonium ion 2 similarly
to arenediazonium ions is able to generate cyclopropyl
radical. This process proceeds readily enough when a
suitable reducing agents is present in the reaction mixꢀ
ture, for example, hydroquinone or its monomethyl ether.
This paper demonstrates a dependence of transformation
routes of cyclopropanediazonium ion 2, generated by
alkaline decomposition of nitrosourea (1a), on the nature
of phenols used.
Thus it is known that phloroglucinol, symmetrical
1,3,5ꢀtrihydroxybenzene, readily enter into the azoꢀcouꢀ
pling with benzenediazonium ion, giving rise to diꢀ and
triazo adducts.5 It turned out that cyclopropanediazonium
ion 2, generated by decomposition of nitrosourea 1a upon
treatment with potassium carbonate in CH2Cl2 at 5 °C,
also undergoes the azoꢀcoupling with phloroglucinol, with
activity of the latter being so high that the product of
triple azoꢀcoupling 3 is exclusively obtained (Scheme 1).
In this case, when even equimolar amounts of nitrosourea
1a and phloroglucinol were used, we failed to detect forꢀ
mation of the products of its monoꢀ and bisazoꢀcoupling
with ion 2. According to the spectral data, the trisadduct 3
formed, similarly to trisꢀphenylazophloroglucinol,6 exists
in tautomeric form of trihydrazone. In the IR spectrum,
intensive absorption bands are observed at 1588 and 1480 cm–1
characteristic of the conjugate C=O and C=N bonds, whereas
in the 13C NMR spectrum, a lowꢀfield signal at δC 178 is
present. It should be noted that trihydrazone obtained
is stable to acid hydrolysis and is recovered unchanged
after heating in dilute hydrochloric acid at 60 °C.
First, for our research we have chosen phenols
that are not prone to the oxidation reactions, but readily
undergo electrophilic substitution reactions.
Under similar conditions, resorcinol first forms with
one equivalent of nitrosourea 1a monoadduct 4 (~64%
yield on isolated product), whereas, after addition of
another 1.5 equivalents of nitrosourea 1a, predominantly
gives diadduct 5 in 68% yield (Scheme 2). In contrast to
phloroglucinol, this reaction proceeds less selectively. In
the 1H NMR spectrum of the reaction mixture, impurities
of the Oꢀ and Cꢀallyl derivatives are present, resulting
from the attack of allylic cation at the aromatic ring and
†
Deceased.
* It should be noted that the term cyclopropanediazonium is a
simplified form for representation of the reactive intermediate,
which under these conditions can also exist as cyclopropyldiazo
hydrate. Further, we will use the term cyclopropanediazonium
without additional explanations.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1671—1679, August, 2008.
1066ꢀ5285/08/5708ꢀ1703 © 2008 Springer Science+Business Media, Inc.

1704
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Shulishov et al.
Scheme 1
Scheme 2
H
N
N
O
N
OAII
OAII
OH
a
a
O
H
O
N
K2CO3
H
N
1a
+
+
+
+
b
CH2Cl2, 5—7 °C
c
O
H
AII
b
OH
OH
N
OH
N
N
4
5
hydroxy group; their total amount is 10—15%. It should
be noted that in the 13C NMR spectra of both azoꢀcouꢀ
pling products 4 and 5, the signals for the C atoms bearing
hydroxy groups are observed in the characteristic region
δC 155—159 (Table 1), which indicates the retention of
the dihydroxybenzene structure.
Table 1. 13C NMR spectra of cyclopropylazoarenes 3—14 (CDCl3, δ)
Comꢀ
pound
C–O
CN=
C(a)
C(b)
C(c)
CH2
CH
OMe
3
4
177.9
154.9,
158.9
156.1
(2 C)
155.7,
159.9
154.7,
162.3
156.2,
158.2
155.8,
157.4
155.2
127.8
131.9
—
103.7
—
133.2
—
107.8
7.5
10.2
35.7
48.2
—
—
5a
6
130.8
(2 C)
134.6
103.6
99.6
117.5
118.6
132.7
120.0
119.1
133.2
9.3
9.8
49.0
50.6
48.2
—
108.0
106.8
55.7
55.5
56.4
56.2
—
7
131.7
101.5
100.3
100.3
101.6
10.1
8
130.5,
134.9
135.4
9.7
10.5
9.6
51.2
48.3
51.1
9b
12
117.1
106.9
130.5,
150.1
(CNH2)
131.8,
144.1
(CNH2)
129.6,
130.4,
146.1
9.8
9.6
47.7
49.8
13
14
158.0
156.3
102.1
101.7
127.9
130.5
105.7
—
—
—
9.7
10.0
50.0
48.0
(CNH2)
a DMSOꢀd6 was the solvent. b Allyl substituent: δ 34.9 (CH2), 116.9 (=CH2), 136.4 (CH).

Reactions of cyclopropanediazonium ions
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1705
1
Table 2. H NMR and mass spectra of cyclopropylazoarenes 3—14
1H NMR in CDCl3, δ (J/Hz)
Comꢀ
pound H(a)
MS (EI, 70 eV),
m/z (Iотн (%))
H(b)
H(c)
(dd)
CH2CH2
(m)
CH
(m)
OMe
OH (NHx)
(br.s)
(s, 3H)
3a
4
—
—
7.59 (d,
—
6.45
(J = 8.5,
J = 2.6)
1.10
1.26, 1.36
(2 H each)
3.45
3.60
(1 Н)
—
15.1
5.40, 12.3
(1 Н each)
—
6.35 (d,
4J = 2.6) 3J = 8.5)
178 (84) [M]+,
150 (27), 136 (100),
109(42), 95 (80),
81 (56), 69 (46)
246 (18) [M]+,
192 (84), 177 (62),
164 (30), 136 (49),
95 (40), 67 (53),
56 (71), 39 (100)
192 (100) [M]+,
177 (33), 150 (37),
136 (66), 122 (35),
108 (90), 93 (45)
192 (55) [M]+,
5
6.45
(s, 1 H)
7.49
(s, 1 H)
—
1.26, 1.39
(4 H each)
3.69
(2 Н)
—
11.2
(2 Н)
6
7
8
6.49 (d,
4J = 2.5) 3J = 8.5)
7.31 (d,
6.35
(J = 8.5,
J = 2.5)
1.21, 1.46
(2 Н each)
3.73
(1 Н)
3.88
3.80
4.00
6.05
(1 Н)
6.53 (d,
4J = 2.5) 3J = 8.6)
7.61 (d,
6.40
(J = 8.6,
J = 2.5)
1.25, 1.37
(2 Н each)
3.62
(1 Н)
12.2
(1 Н)
164 (12), 150 (100),
109 (31), 95 (29),
80 (22), 69 (28)
260 (10) [M]+,
6.51
(s, 1 H)
7.81
(s, 1 H)
—
—
—
1.26 (4 H),
1.39, 1.51
(2 H each)
3.66,
3.77
(1 Н each)
12.3
(1 Н)
233 (23), 218 (68),
191 (38), 178 (19),
163 (21), 150 (20),
69 (54), 39 (100)
232 (100) [M]+,
217 (44), 190 (25),
176 (37), 148 (22),
120 (23), 103 (16),
91 (51), 69 (26)
—
9b
6.51
(s, 1 H)
7.20
(s, 1 H)
1.21, 1.47
(2 H each)
3.74
(1 Н)
3.91
5.61
(1 Н)
10c
11d
6.38
7.47
(s, 1 H)
7.36 (d,
1.24, 1.35
(2 H each)
1.20, 1.31
(2 Н each)
3.60
(1 Н)
3.80
3.83
3.89
12.2
(1 Н)
(s, 1 H)
6.58 (d,
4J = 2.4) 3J = 8.9)
6.46
—
(J = 8.9,
J = 2.4)
6.25
(J = 8.5,
J = 2.4)
(1 Н)
12
13
14
6.11 (d,
4J = 2.4) 3J = 8.5)
7.47 (d,
1.20, 1.30
(2 Н each)
3.54
(1 Н)
—
—
—
12.4
(4.03)
177 (48) [M]+,
149 (29), 135 (100),
122 (21), 108 (28),
94 (23), 80 (28),
68 (26)
177 (87) [M]+,
149 (24), 135 (100),
121 (23), 108 (14),
94 (73), 80 (51),
67 (33)
245 (24) [M]+,
218 (18), 190 (41),
176 (100), 163 (50),
149 (41), 135 (76),
121 (23), 94 (47)
6.11 (d,
4J = 2.5) 3J = 8.5)
7.44 (d,
6.21
(J = 8.5,
J = 2.5)
1.17, 1.34
(2 Н each)
3.57
(1 Н)
5.40
(3 Н)
6.07
(s, 1 H)
7.95
(s, 1 H)
—
1.23, 1.36
(4 H each)
3.60
(2 Н)
12.4
(5.84)
a The ratio integral intensities of the signals observed is 4 : 1 : 1.
b Allyl substituent: δ 3.34 (dt, 2 H, CH2, 3J = 6.2 Hz, 4J = 1.5 Hz); 5.13—5.22 (m, 2 H, =CH2); 5.98 (m, 1 H, =CH).
c Allyl substituent: δ 3.33 (dt, 2 H, CH2, 3J = 6.5 Hz, 4J = 1.5 Hz); 5.03—5.11 (m, 2 H, =CH2); 6.00 (m, 1 H, =CH).
d Allyl substituent: δ 4.56 (dt, 2 H, OCH2, 3J = 6.0 Hz, 4J = 1.5 Hz); 5.31 (д.к, 1 H, =CH(cis), 3J = 10.6 Hz, 4J = 1.5 Hz);
5.43 (dq, 1 H, = CH(trans), 3J = 17.4 Hz, 4J = 1.5 Hz); 6.06 (m, 1 H, =CH).

1706
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Shulishov et al.
Decomposition of nitrosourea 1a under action of
K2CO3 in the presence of equimolar amount of 3ꢀmethoxyꢀ
phenol leads to the formation of two monoadducts,
differing in the position of cyclopropyldiazene fragment
relatively to the OH group (Scheme 3). Assignment of the
the same adduct of double azoꢀcoupling, viz., compound
8 (Scheme 4). The latter can easily be isolated from the
reaction mixture by crystallization in 30—32% yield with
a total yield of monoadducts 6 and 7 being no more than
23%. The relatively low yield of azoꢀcoupling products
6—8 can be explained by the proceeding of side allylation
of the benzene ring and hydroxy group. Using methods
of crystallization and chromatographic separation, we
succeded, in particular, in isolation of two isomeric comꢀ
pounds 9 and 10 containing both the cyclopropyldiazene
fragment and the allylic group in the aromatic ring. The
mass spectra of both isomers have intensive peaks of
molecular ions (m/z 232), while the 1H NMR spectra the
characteristic signals of four substituents and two isolated
protons of the aromatic ring (see Table 2). It should be also
noted that the chemical shifts for the CH2 fragment of the
allylic substituent appears at δ ~3.3, rather than in the region
δ ~4.6 characteristic of the OCH2 fragment. The strucꢀ
tures of the major reaction products of 3ꢀmethoxyphenol
1
isomers was made on the basis of the H NMR spectra
of azo adducts 6 and 7 isolated in the individual state.
Compound 6 was isolated from the reaction mixture by
crystallization from chloroform—light petroleum, whereas
isomer 7, being liquid at room temperature, by column
1
chromatography on SiO2. The H NMR spectra of azo
adducts 6 and 7 differ mainly in position of the signal for
the proton of the hydroxy group, which in chelate 7
appears at δ ∼ 12, while in compound 6 (free hydroxyl) at
δ ∼ 6 (Table 2). A difference in position of the signals for
the C(b), which in azo compound 7 are shifted upfield by
~14 ppm in comparison with isomer 6, should be noted,
too, and this tendency caused, apparently, by the presꢀ
ence of the intramolecular hydrogen bond is also
observed for other similar structures (see Table 2).
1
with excess 1a inferred from the H NMR data for the
reaction mixture are given in Scheme 4.
1
A comparison of the H NMR spectra of the starting
Scheme 3
reaction mixture, the intermediate fractions, and the comꢀ
pounds isolated showed that allyl ether 11 was one of the
components of the reaction mixture, however, we failed
in its isolation in the individual state. The most probable
pathway for the formation of this particular isomer conꢀ
sists in allylation of monoadduct 6 containing free OH
group. This hypothesis is indirectly confirmed by the fact
that the methylation of 4ꢀcyclopropylazoresorcinol 4 upon
treatment with CH2N2/HBF4 proceeds with exclusive
alkylation of the free hydroxy group.7
On the whole, it should be noted that the observed
formation of insertion products of the allyl fragment into
the aromatic ring can result either from the direct electroꢀ
philic attack at the aromatic ring by the allylic cation
(dediazoniation of ion 2 and the cyclopropane ring openꢀ
ing), or through the intermediate formation of allyl ethers
with subsequent rearrangement.
Reagents and conditions: K CO , CH Cl , 5 °C,
2
3
2
2
1a : MeOC H OH = 1 : 1.
6
4
When excess nitrosourea 1a (2.5 equiv.) is used, both
monoadducts 6 and 7 further react with the forming
cyclopropanediazonium 2 and partially are converted into
Scheme 4
Reagents and conditions: K CO , CH Cl , 5 °C, 1a : MeOC H OH = 2.5 : 1.
2
3
2
2
6 4
Product ratios: 6 : 7 : 8 : 9 : 10 : 11 = 2.7 : 2.3 : 7.0 : 3.0 : 1 : 3.5.

Reactions of cyclopropanediazonium ions
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1707
Scheme 5
1a:H2NC6H4OH
12
13
14
1
2
:
:
1
1
35%
17%
37%
1%
<2%
55%
It is known that aniline and its derivatives undergo the
of nitrosourea 1a under action of cesium carbonate in the
presence of 4ꢀmethoxyphenol leads to the formation
of three major compounds, viz., 2ꢀ(cyclopropylazo)ꢀ
4ꢀmethoxyphenol, cyclopropane, and allene in the molar
ratio of ~1.6 : 1.8 : 1.0.
azoꢀcoupling reaction with the aromatic diazonium ions,
as a rule, in weakly acidic media. It is no wonder, thereꢀ
fore, that decomposition of nitrosourea 1a under action
of K2CO3 or Cs2CO3 in the presence of aniline did not
lead to its azoꢀcoupling with ion 2, with allyl alcohol
being the major product of the decomposition of Nꢀcycloꢀ
propylꢀNꢀnitrosourea in this case.
Using this approach, we have studied decomposition
of nitrosourea 1a under action of Cs2CO3 in CD2Cl2 at
10 °C in the presence of other hydroxyarenes, possessing
reducing properties. It turned out that 1,2ꢀdihydroxyꢀ,
1,2,3ꢀ and 1,2,4ꢀtrihydroxybenzenes, as well as 2ꢀ and
4ꢀaminophenols behave similarly, giving rise to cycloproꢀ
pane itself and a small amount of allene. The major differꢀ
ence between these phenols consists in the amount of
products of the allylic cyclopropane ring opening (Table 3).
Virtually in none of the experiments, the adducts of azoꢀ
coupling or products of formal insertion of the cyclopropyl
fragment into the benzene ring or into the O—H and
N—H bonds were observed. The use of γꢀterpinene or
1,4ꢀcyclohexadiene, having properties of the spin trapꢀ
ping agents,8 did not lead to the trapping of the cyclopropyl
radicals either, which, apparently, is caused by the high
disposition of the latter to the abstraction of a hydrogen
atom from the medium or the substrates used with the
formation of cyclopropane.
In contrast to aniline itself, 3ꢀaminophenol readily
undergoes the azoꢀcoupling with cyclopropanediazonium
2, and the amino group no longer has a retarding influꢀ
ence on the target reaction. Monoadducts 12 and 13,
which differ in position of the cyclopropyldiazene fragꢀ
ment, are the products of the reaction when equimolar
amounts of reagents are used. These compounds, similarly
to azo adducts 6 and 7, can be easily distinguished by their
1H NMR spectra, in which chemical shifts for the proton
of the OH group appear at δ 12.4 and 5.4, respectively
(see Table 2). In this case, the yields of the side products,
resulting from the small ring opening, are not high (~2%).
Addition of the second equivalent of nitrosourea 1a and
K2CO3 to the reaction mixture leads to the virtually comꢀ
plete transformation of isomer 13 into bisadduct 14 with
considerable retention of isomer 12 (Scheme 5). This result
indicates the difference in reactivity of monoadducts 12
and 13. In this case, isomer 13 containing no the chelate
ring undergoes the azoꢀcoupling reaction with ion 2 easier
than the isomer with intramolecular hydrogen bond.
Earlier, we have shown4 that decomposition of
NꢀcyclopropylꢀNꢀnitrosourea 1a under action of bases
in the presence of compounds able to display reducing
properties such as, for example, 1ꢀphenylpyrazolidinꢀ
3ꢀone, hydroquinone or its monomethyl ether, considerꢀ
ably changes the character of occuring transformations.
An ability to reduce diazonium ion 2 (or other related
intermediate) into cyclopropyl radical is a specific feature
of these substrates. This process was confirmed not only
by the formation of the trapped products of this species
(cyclopropane, cyclopropyl bromide, etc.), but also by
the direct observation of the chemical nuclear polarizaꢀ
tion effect for the signal of cyclopropane when the reaction
was carried out directly in the detector of an NMR specꢀ
trometer.4 In particular, it was found that decomposition
Sterically hindered 2,6ꢀdiꢀtertꢀbutylcresol (ionol),
widely used as the antioxidant, is also able to reduce
Table 3. Molar ratios of cyclopropane, allene, and products of
allylic cyclopropane ring opening, formed during decomposition
of nitrosourea 1a under action of Cs2CO3 in the presence of the
oxidizable phenols (according to the 1H NMR spectra of the
reaction mixtures)
Substrate
Cycloꢀ
Allene
Allylic
propane
derivatives
Hydroquinone
Pyrocatechol
Ionol
4ꢀMethoxyphenol (lit.4)
2ꢀAminophenol
4ꢀAminophenol
1,2,4ꢀTrihydroxybenzene
1,2,3ꢀTrihydroxybenzene
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.09
—
0.12
2.4
0.07
0.02
0.02
0.02
1.2
12.5
0.08
1.2
3.7*
0.2
3.1*
—
* Allylic alcohol predominates.

1708
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Shulishov et al.
Scheme 6
OH
t
t
t
Bu
Bu
t
t
Bu
Bu
Me
HO
Me
Cs2CO3
H2C
C CH2
1a
+
+
+
+
O
O
CD2Cl2, 5—7 °C
O
t
Bu
Bu
Me
1 : 1
15
16
cyclopropanediazonium generated in situ with the presꢀ
ence of relatively low amount of allylic derivatives (see
Table 3). Thus, decomposition of nitrosourea 1a with
cesium carbonate in the presence of equimolar amount of
ionol leads, from the one hand, to the formation of cycloꢀ
propane, and from the other hand, to the oxidation prodꢀ
ucts of ionol, compound 15 described earlier9 and its
cyclopropyl ether 16 (Scheme 6).
no formation of the azoꢀcoupling products was observed
at all. Formation of butatriene was the main direction of
decomposition of 1e (together with its partial denitrosaꢀ
tion, ~10%).12
Scheme 7
1
According to the H NMR spectrum of the reaction
mixture, the ratio of cyclopropane and compounds 15
and 16 is ~8.3 : 9.3 : 1. When the reaction is carried out in
the detector of an ESR spectrometer, the intensive signal
of the radical species was recorded as the quartet of
triplets, stable at 10 °C for several minutes, which correꢀ
sponded to the known radical of ionol.10
It turned out that the formation of cyclopropane (and,
consiquently, generation of cyclopropyl radical) can sucꢀ
cessfully take place when much lower amount of ionol is
used (10—12 mol.%). For this, it is sufficient to carry out
the reaction, for example, in the presence of γꢀterpinene,
which does not react with intermediates of the alkaline
decomposition of NꢀcyclopropylꢀNꢀnitrosourea, however,
is able to regenerate the molecule of ionol by reduction of
the intermediately formed diꢀtertꢀbutylphenoxyl radical,
being oxidized into 4ꢀisopropyltoluene.
Further, we have studied the effect of substituents in
the small ring on a possibility of generation of correꢀ
sponding diazonium ions and cyclopropyl radicals during
alkaline decomposition of substituted Nꢀcyclopropylꢀ
Nꢀnitrosourea 1b—f in the presence of 2ꢀnaphthol and
4ꢀmethoxyphenol.
R = H (a); Me (b); Cl (c); Ph (d)
Reagents and conditions: K CO , 2ꢀnaphthol, CH Cl , 5 °C.
2
3
2
2
Product yields (%): 90 (17a); 55 (17b); 27 (17c); 79 (17d).
Decomposition of substituted NꢀcyclopropylꢀNꢀnitrosoꢀ
ureas in the presence of 4ꢀmethoxyphenol as the
substrate, allowing one to generate cyclopropyl radicals,
considerably differs from the alkaline decomposition of
nitrosourea 1a. In this case, their decomposition pathway
with generation of the corresponding radicals plays
significantly lesser role. Thus, in the presence of
4ꢀmethoxyphenol considerable amount of cyclopropane
is formed only during decomposition of nitrosoureas 1b
and 1f (Scheme 8). Rather, the formation of substituted
Scheme 8
Earlier, we have shown11 that the introduction of
geminal methyl groups or two chlorine atoms into the
threeꢀmembered ring of nitrosocyclopropylureas 1b,c
allows one to generate the corresponding diazonium ions,
however, their trapping with 2ꢀnaphthol proceeds with
lower efficiency than in the case of unsubstituted cycloꢀ
propanediazonium ion 2 (Scheme 7). In the present work,
in addition to this series we have studied decomposition
of gemꢀdiphenylcyclopropylꢀ (1d) and Nꢀ(methylideneꢀ
cyclopropyl)ꢀNꢀnitrosourea (1e) under action of K2CO3
in the presence of 2ꢀnaphthol. It turned out that, if in the
first case the generation and azoꢀcoupling of diphenylꢀ
cyclopropanediazonium proceeds highly efficient and gives
azoꢀcoupling adduct 17d in 79% yield, in the case of 1,
Product ratios:
b: R = Me
d: R = Ph
2.4 : 1
9 : 1
1 : —
3 : 1
e: RR = H C
2
f: RR = CH CH
2
2
Reagents and conditions: K CO , CH Cl , 5—7 °C.
2
3
2
2

Reactions of cyclopropanediazonium ions
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1709
allenes becomes the main direction of the decomposition
of substituted NꢀcyclopropylꢀNꢀnitrosoureas, as in the
case when the substrate is absent.
or cesium carbonates in the presence of various hydroxyꢀ
arenes depends on the nature of the substrates used and
leads to the azoꢀcoupling products of diazonium ion 2
with active azo components (resorcinol, 3ꢀmethoxyphenol,
3ꢀaminophenol, phloroglucinol), as well as to the prodꢀ
ucts of the allylic type resulting from the generation
and isomerization of the cyclopropyl cation. Oxidizable
phenols (1,2ꢀdihydroxyꢀ, 1,2,3ꢀ and 1,2,4ꢀtrihydroxyꢀ
benzenes, ionol, and 2ꢀ and 4ꢀaminophenols) are able to
reduce diazonium ion 2 into cyclopropyl radical with its
subsequent conversion into cyclopropane. The ability to
form cyclopropanediazonium ions sharply decreases when
substituents are introduced into the cyclopropane ring;
the formation of the corresponding allenes, the products
of dediazoniation of diazocyclopropanes and isomerizaꢀ
tion of the cyclopropylidenes formed, become the main
direction of decomposition of substituted nitrosocycloꢀ
propylureas under action of potassium carbonate, rather than
the azoꢀcoupling or generation of cyclopropyl radicals.
It should also be noted that 2ꢀnaphthol easily gives
the azoꢀcoupling product with 2,2ꢀdiphenylcyclopropaneꢀ
diazonium ion (compound 17d), whereas 4ꢀmethoxyphenol
practically does not form the azo adducts with it. The
predominant formation of diphenylallene in this reaction
indicates that the equilibrium in the system diphenylꢀ
cyclopropanediazonium—diazodiphenylcyclopropane is
driven far toward the diazo compound, which can easily be
converted into diphenylallene, whereas the reactivity of
the diazonium ion turned out to be insufficient for its
efficient azoꢀcoupling with 4ꢀmethoxyphenol. We supꢀ
posed that a decrease in the basicity of the medium during
decomposition of nitrosourea 1d can change the ratio of
the intermediates formed. To increase the protonating
strength of the medium, we used an equimolar mixture of
potassium carbonate with KHCO3 instead of potassium
carbonate alone. Decomposition of nitrosourea 1d under
these conditions in the presence of 4ꢀmethoxyphenol
allowed us to identify 2ꢀ(2,2ꢀdiphenylcyclopropylazo)ꢀ
4ꢀmethoxyphenol (18) and 3,3ꢀdiphenylallyl alcohol in
the 1H NMR spectrum of the reaction mixture, though, as
before, diphenylallene was the major reaction product:
the molar ratio was ~1 : 1 : 11 (Scheme 9). Further
increase in acidity of the medium only owing to the use
of potassium bicarbonate turned out to be unsuccessful
since it does not lead to decomposition of nitrosourea 1d.
In conclusion, the direction of decomposition of
NꢀcyclopropylꢀNꢀnitrosourea under action of potassium
Experimental
1H and 13C NMR spectra were recorded on a Bruker AMꢀ300
spectrometer (300 and 75.5 MHz, respectively) for solutions in
CDCl3, CD3OD, or CD2Cl2 containing 0.05% of Me4Si as the
internal standard. Mass spectra were recorded on a Finnigan
MAT INCOSꢀ50 instrument (EI, 70 eV, direct inlet). IR spectra
were recorded on a Specord M82 spectrophotometer in KBr pellets.
The ESR spectrum was recorded by A. V. Lalov (Institute of Organic
Chemistry, Russian Academy of Sciences) on a Bruker EMXꢀEPR
ESR spectrometer. Silica gel 60 (0.040—0.063 mm, Merck)
was used for thinꢀlayer chromatography. Preparative isolation was
performed on a column with silica gel 60 (0.063—0.200 mm,
Merck) or on a Gilson liquid chromatograph equipped with an
Alltime C18 column with the phase size of 5 micron and a UV
detector with detection at λ = 254 nm. The starting compounds,
viz., 3ꢀ and 4ꢀmethoxyphenols, phloroglucinol, 1,2,3ꢀ and 1,2,4ꢀtriꢀ
hydroxybenzenes, resorcinol, 2ꢀ, 3ꢀ and 4ꢀaminophenols, 2,6ꢀdiꢀ
tertꢀbutylcresol (ionol), γꢀterpinene, and cyclohexaꢀ1,4ꢀdiene
(Merck), were used as purchased. NꢀCyclopropylꢀNꢀnitrosourea
(1a),13 Nꢀ(2,2ꢀdimethylcyclopropyl)ꢀNꢀnitrosourea (1b),14 Nꢀnitrosoꢀ
Nꢀ(2,2ꢀdiphenylcyclopropyl)urea (1d),15 Nꢀ(methylidenecycloꢀ
propyl)ꢀNꢀnitrosourea (1e),12 and NꢀnitrosoꢀNꢀspiropentylurea
(1f)16 were obtained according to the described procedures.
Azoꢀcoupling of cyclopropanediazonium ion with hydroxyꢀ and
aminophenols (general procedure). An equivalent amount of the
corresponding hydroxyarene was added to a solution of Nꢀcycloꢀ
propylꢀNꢀnitrosourea in dichloromethane followed by the portionꢀ
wise addition of the powdered K2CO3•2H2O or Cs2CO3 (2 eq.
relative to nitrosourea) with stirring and cooling down to 5—7 °C.
The reaction mixture was stirred at the indicated temperature
for 1—1.5 h in the case of K2CO3 and for 15 min in the case of
Cs2CO3 until complete decomposition of the starting nitrosourea,
then it was filtered through a thick glass filter. To raise the yields
of target products, in a number of cases a precipitate of salts
from the filter was dissolved in dilute hydrochloric acid and
extracted with CH2Cl2, the organic layer and the filtrate were
combined, concentrated and the residue was recrystallized from
suitable solvent or purified by column chromatography on SiO2.
Scheme 9
Ph
Ph
Ph
Ph
H2C
C C
–N2
N2
– H+
Ph
K2CO3
KHCO3
H
Ph
H2O
–N2
Ph
Ph
OH
1d
+
N2
CH2Cl2, 5 °C
4-MeOC6H4OH
Ph
Ph
MeO
N
O
N
H
18

1710
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Shulishov et al.
2,4,6ꢀTris(cyclopropylhydrazono)cyclohexaneꢀ1,3,5ꢀtrione
(3) was synthesized from nitrosourea 1a (2.32 g, 18 mmol),
phloroglucinol (as the dihydrate) (0.94 g, 5.8 mmol), and
K2CO3•2H2O (6.26 g, 36 mmol) in CH2Cl2 (20 mL). Compound
3 (1.51 g, 79%) was obtained after recrystallization from chloroꢀ
form as yellowish green crystals, m.p. 178—179 °C. Found (%):
C, 54.17; H, 5.69; N, 24.71. C15H18N6O3. Calculated (%): C,
54.54; H, 5.49; N, 25.44. IR, ν/cm–1: 3400—3425 (NH), 3076 and
3068 (cycloꢀC3H5), 1588 (C=O), 1480 (C=N), 1024 (cycloꢀC3H5).
The 1H and 13C NMR spectra are given in Tables 1 and 2.
4ꢀ(Cyclopropylazo)resorcinol (4) was synthesized from nitrosoꢀ
urea 1a (1.16 g, 9 mmol), resorcinol (0.99 g, 9 mmol), and
K2CO3•2H2O (3.13 g, 18 mmol) in CH2Cl2 (15 mL). A solid
mass (1.46 g) was obtained after evaporation of the solvent,
which according to the 1H NMR spectrum contained ~85% of
azo adduct 4. Pure azo adduct 4 (1.02 g, 64%) was isolated by
column chromatography on SiO2 (eluent, toluene—AcOEt,
35 : 1) as yellow crystals, m.p. 154—156 °C (decomp.). Found
(%): C, 60.36; H, 5.84; N, 15.32. C9H10N2O2. Calculated (%):
C, 60.66; H, 5.66; N, 15.72. The 1H and 13C NMR and mass
spectra are given in Tables 1 and 2.
SiO2 (eluent, toluene—AcOEt, 35 : 1) collecting fractions
enriched with monoadducts 6 and 7 (the total yield no more
than 23%), as well as with compounds 9 and 10. The latter were
isolated in the individual state by HPLC using a mixture of
acetonitrile with water in the ratio of 1 : 1 and the flow rate
of 5 mL min–1 to obtain compound 9 (0.21 g, 11%, the purity
~96%) as a dark yellow crystalline mass and compound 10
(0.07 g, 4%, the purity ~93%) as a yellowish brown viscous
liquid. The 1H and 13C NMR spectra of azoallylphenols 9 and
10 and mass spectrum of 9 are given in Tables 1 and 2.
2ꢀ(Cyclopropylazo)ꢀ5ꢀaminophenol (12) and 4ꢀ(cyclopropylꢀ
azo)ꢀ3ꢀaminophenol (13) was synthesized from nitrosourea 1a
(1.16 g, 9 mmol), 3ꢀaminophenol (0.98 g, 9 mmol), and
K2CO3•2H2O (3.13 g, 18 mmol) in CH2Cl2 (20 mL). After
evaporation of the solvent, a solid residue (1.17 g) was obtained,
from which compound 12 (0.56 g, 35%) was isolated by column
chromatography on SiO2 (eluent, light petroleum—Et2O, 1 : 2) as
yellow crystals, m.p. 130—132 °C (decomp.), as well as isomer 13
(0.59 g, 37%) as yellow crystals too, m.p. 134—135 °C (decomp.).
Compound 13: found (%): C, 60.72; H, 6.30; N, 23.22. C9H11N3O.
Calculated (%): C, 61.00; H, 6.26; N, 23.71. The 1H and
13C NMR and mass spectra are given in Tables 1 and 2.
2,4ꢀBis(cyclopropylazo)ꢀ5ꢀaminophenol (14) was synthesized
from nitrosourea 1a (1.29 g, 10 mmol), 3ꢀaminophenol (0.54 g,
5 mmol), and K2CO3•2H2O (3.48 g, 20 mmol) in CH2Cl2
(17 mL). After evaporation of the solvent, a solid residue
(0.91 g) was obtained, from which monoadduct 12 (0.15 g, 17%)
was isolated by column chromatography on SiO2 (eluent, light
petroleum—Et2O, 1 : 2) similar to the described above, as
well as compound 14 (0.67 g, 55%) as yellowish orange crystals,
m.p. 160—161 °C (decomp.). Found (%): C, 58.64; H, 6.30;
N, 28.37. C12H15N5O. Calculated (%): C, 58.76; H, 6.16;
N, 28.55. The 1H and 13C NMR and mass spectra are given in
Tables 1 and 2.
4,6ꢀBis(cyclopropylazo)resorcinol (5) was synthesized from
nitrosourea 1a (2.58 g, 20 mmol), resorcinol (0.88 g, 8 mmol),
and K2CO3•2H2O (6.96 g, 40 mmol) in CH2Cl2 (25 mL).
Diadduct 5 (1.34 g, 68%) was obtained after evaporation of the
solvent, recrystallization from chloroform, and column chroꢀ
matography on SiO2 (eluent, toluene—AcOEt, 35 : 1) as orange
crystals, m.p. 194—195 °C. Found (%): C, 58.74; H, 5.70; N, 22.32.
C12H14N4O2. Calculated (%): C, 58.53; H, 5.73; N, 22.75. The
1H and 13C NMR and mass spectra are given in Tables 1 and 2.
4ꢀCyclopropylazoꢀ3ꢀmethoxyphenol (6) and 2ꢀcyclopropylꢀ
azoꢀ5ꢀmethoxyphenol (7). A mixture of nitrosourea 1a (1.16 g,
9 mmol), 3ꢀmethoxyphenol (1.12 g, 9 mmol), and K2CO3•2H2O
(3.13 g, 18 mmol) in CH2Cl2 (15 mL) was dissolved in minimum
chloroform and azo compound 6 was precipitated by the addiꢀ
tion of light petroleum to obtain yellow crystalline compound
(0.71 g, 41%) with m.p. 122—123 °C (decomp.). Found (%): C,
62.27; H, 6.32; N, 14.54. C10H12N2O2. Calculated (%): C, 62.49;
1ꢀ(2,2ꢀDiphenylcyclopropylazo)ꢀ2ꢀnaphthol (17d). Potassium
carbonate dihydrate (0.17 g, ~1 mmol) was added to a solution
of nitrosourea 1d (56.3 mg, 0.2 mmol) and 2ꢀnaphthol (28.8 mg,
0.2 mmol) in CH2Cl2 (1.5 mL) and this was stirred at 5 °C for
2 h. The reaction mixture was filtered, washed with CH2Cl2,
dried with anhydrous MgSO4 and the solvent was removed
in vacuo to obtain a solid yellow residue (~80 mg) containing
mainly azonaphthol 17d and 1,1ꢀdiphenylallene (molar ratio
~4.9 : 1) according to the 1H NMR spectrum. Analytically pure
azo compound (57.6 mg, 79%) was isolated as yellow needleꢀ
like crystals by column chromatography on SiO2 (eluent, light
petroleum—Et2O, 1 : 2), m.p. 122—124 °C (decomp.). Found
(%): C, 81.96; H, 5.90; N, 7.43. C25H20N2O. Calculated (%):
C, 82.39; H, 5.53; N, 7.69. MS, m/z (Irel (%)): 364 (52) [M]+,
1
H, 6.29; N, 14.57. The H and 13C NMR and mass spectra are
given in Tables 1 and 2. The residue left after isolation of azo
compound 6 was separated by column chromatography on SiO2
(eluent, toluene—AcOEt, 35 : 1) to obtain azo compound 7
(0.57 g, 33%) as a yellow mass crystallizing at 7—9 °C. The
1H and 13C NMR and mass spectra are given in Tables 1 and 2.
2,4ꢀBis(cyclopropylazo)ꢀ5ꢀmethoxyphenol (8). A mixture
of nitrosourea 1a (2.58 g, 20 mmol), 3ꢀmethoxyphenol (0.99 g,
8 mmol), and K2CO3•2H2O (6.96 g, 40 mmol) in CH2Cl2
(25 mL) was dissolved in chloroform and azo compound 8
was precipitated by addition of a mixture of light petroleum
and benzene in the ratio of 9 : 1 to obtain yellowish orange
crystalline compound (0.66 g, 31%) with m.p. 135—136 °C
(decomp.). Found (%): C, 60.08; H, 6.29; N, 21.20. C13H16N4O2.
Calculated (%): C, 59.99; H, 6.20; N, 21.52. The 1H and 13C
NMR and mass spectra are given in Tables 1 and 2. Signals for
4ꢀallyloxyꢀ1ꢀ(cyclopropylazo)ꢀ2ꢀmethoxybenzene (11) were also
1
206 (100), 184 (61) [M – Ph2C=CH2]+. H NMR (CDCl3), δ:
2.16 (dd, 1 H, H(3´a), Jcis = 7.8 Hz, 2J = 5.7 Hz); 2.54 (dd, 1 H,
H(3´b), Jtrans = 4.3 Hz, 2J = 5.7 Hz); 4.45 (dd, 1 H, H(1´),
Jcis = 7.8 Hz, Jtrans = 4.3 Hz); 6.97 (d, 1 H, H(3), J = 9.2 Hz);
7.18—7.40 (m, 11 H, 2 Ph and H(6)); 7.56 (ddd, 1 H, H(7),
J = 8.4 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.69 (br.d, 1 H, H(4),
J = 9.2 Hz); 7.71 (br.d, 1 H, H(5), J = 8.0 Hz); 8.73 (br.d, 1 H,
H(8), J = 8.4 Hz); 12.6 (br.s, OH). 13C NMR (CDCl3), δ: 24.4
(C(3´)); 41.6 (C(2´)); 60.6 (C(1´)); 120.1 (C(3)); 121.6 (C(8));
124.2 (C(6)); 126.8, 127.3, 127.7 and 128.0 (C(5), C(7) and
2 Cp); 127.8 (2 CH); 128.7 (4 CH); 130.3 (2 CH); 128.1, 128.6
and 132.6 (C(1), C(4a) and C(8a); 134.0 (C(4)); 139.8 and
144.0 (2 Ci); 152.5 (C(2)).
1
observed in the H NMR spectrum of the reaction mixture (see
Table 2).
2ꢀAllylꢀ4ꢀ(cyclopropylazo)ꢀ5ꢀmethoxyphenol (9) and 4ꢀallylꢀ
2ꢀ(cyclopropylazo)ꢀ5ꢀmethoxyphenol (10). The residue left after
isolation of the major amount of bisadduct 8 (the preceding
experiment) was first separated by column chromatography on

Reactions of cyclopropanediazonium ions
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1711
NMR study of decomposition reactions of Nꢀcyclopropylꢀ
Nꢀnitrosourea in the presence of the oxidizable phenols.
In order to identify and to determine relative content of comꢀ
pounds formed, first of all allene and cyclopropane, the reactions
was carried out in the NMR tube. For this, Cs2CO3 (42—43 mg,
0.13 mmol) was added in one portion to a solution containing
equimolar amounts (~0.07 mmol) of NꢀcyclopropylꢀNꢀnitrosoꢀ
urea 1a and the corresponding phenol (1,2ꢀdihydroxyꢀ, 1,2,3ꢀ
or 1,2,4ꢀtrihydroxybenzene, 2ꢀ or 4ꢀaminophenol) in CD2Cl2
(0.45 mL) at 0 °C, the tube was shaken at 5—7 °C for 12—15 min
and the 1H NMR spectra were recorded. The molar ratios of
cyclopropane, allene, and the products of allylic opening of the
cyclopropane ring are given in Table 3.
2. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, O. M.
Nefedov, Mendeleev Commun., 2002, 104.
3. I. P. Klimenko, V. A. Korolev, Yu. V. Tomilov, O. M.
Nefedov, Zh. Org. Khim., 2006, 42, 1320 [Russ. J. Org. Chem.,
2006, 42, 1299 (Engl. Transl.)].
4. Yu. V. Tomilov, I. V. Kostyuchenko, G. P. Okonnishnikova,
I. P. Klimenko, E. V. Shulishov, Izv. Akad. Nauk, Ser. Khim.,
2006, 1934 [Russ. Chem. Bull., Int. Ed., 2006, 55, 2008].
5. (a) A. G. Perkin, J. Chem. Soc., 1897, 1154; (b) S. Li, A. Gupta,
O. Vogl, Monatsh. Chem., 1983, 114, 937.
6. R. M. Ageeva, I. V. Gudvylsich, A. A. Berlin, Izv. Akad.
Nauk SSSR, Ser. Khim., 1967, 2635 [Bull. Acad. Sci. USSR.
Div. Chem. Sci., 1967, 16 (Engl. Transl.)].
When the reaction was carried out with ionol under similar
conditions, the signals of cyclopropane, allene, compound 15
(see Ref. 9), and 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀ(cyclopropyloxy)ꢀ4ꢀmethylꢀ
cyclohexaꢀ2,5ꢀdienꢀ1ꢀone (16) in the ratio ∼8 : 1 : 9 : 1 were
recorded in the 1H NMR spectrum of the reaction mixture.
1H NMR for compound 16 (CD2Cl2), δ: 0.91 (m, 4 H, CH2CH2);
1.23 (s, 18 H, 2 But); 1.41 (s, 3 H, Me); 3.69 (m, 1 H, CH); 6.38
(s, 2 H, H(3) and H(5).
7. R. A. Novikov, I. P. Klimenko, E. V. Shulishov, V. A.
Korolev, Yu. V. Tomilov, Izv. Akad. Nauk, Ser. Khim., 2008,
№8, 1686 [Russ. Chem. Bull., Int. Ed., 2008, 57, 1718].
8. V. P. Ananikov, D. A. Malyshev, I. P. Beletskaya, G. G.
Aleksandrov, I. L. Eremenko, Adv. Synth. Catal., 2005, 347,
1993.
9. B. M. Benjamin, V. F. Raaen, E. W. Hagaman, L. L. Brown,
J. Org. Chem., 1978, 43, 2989.
Decomposition of substituted NꢀcyclopropylꢀNꢀnitrosoureas
1b and 1d—f in the presence of 4ꢀmethoxyphenol was performed
similarly. The ratio of substituted cyclopropanes and allenes
10. R. S. Macomber, J. Org. Chem., 1982, 47, 2481.
11. I. P. Klimenko, Yu. V. Tomilov, O. M. Nefedov, Izv. Akad.
Nauk, Ser. Khim., 2004, 226 [Russ. Chem. Bull., Int. Ed.,
2004, 53, 236].
1
according to the H NMR spectra are given on Scheme 8.
Decomposition of nitrosourea 1d upon treatment with
equimolar mixture of K2CO3 and KHCO3 in the presence of
4ꢀmethoxyphenol allowed us to identify 2ꢀ(2,2ꢀdiphenylcycloꢀ
12. Yu. V. Tomilov, I. P. Klimenko, E. V. Shulishov, O. M.
Nefedov, Izv. Akad. Nauk, Ser. Khim., 2000, 1210 [Russ.
Chem. Bull., 2000, 49, 1207 (Engl. Transl.)].
13. V. P. Golmov, Zh. Obshch. Khim, 1935, 5, 1562 [J. Gen.
Chem., 1936, 107 (II), 1905].
14. Yu. V. Tomilov, E. V. Shulishov, I. P. Klimenko, O. M.
Nefedov, Izv. Akad. Nauk, Ser. Khim., 1996, 2698 [Russ.
Chem. Bull., 1996, 45, 2557 (Engl. Transl.)].
1
propylazo)ꢀ4ꢀmethoxyphenol. H NMR (CD2Cl2), δ: 2.15 (dd,
Jcis = 7.8 Hz, 2J = 5.4 Hz); 2.54 (dd, Jtrans = 4.3 Hz, 2J = 5.4 Hz);
3.80 (s, OMe); 4.29 (dd, N—CH, Jcis = 7.8 Hz, Jtrans = 4.3 Hz);
10.2 (br.s, OH); 7.15—7.60 (m, the signals overlap with the
aromatic protons of other compounds).
15. W. M. Jones, D. L. Muck, J. Am. Chem. Soc., 1966, 88,
3798.
16. Y. V. Tomilov, E. V. Shulishov, G. P. Okonnishnikova,
O. M. Nefedov, Mendeleev Commun., 1997, 200.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ33149).
References
1. Yu. V. Tomilov, I. V. Kostyuchenko, E. V. Shulishov, G. P.
Okonnishnikova, Izv. Akad. Nauk, Ser. Khim., 2003, 941
[Russ. Chem. Bull., Int. Ed., 2003, 52, 993].
Received March 26, 2008