Synthesis of 1-Substituted Pyrazolines by Reaction of Donor-Acceptor Cyclopropanes with 1,5-Diazabicyclo[3.1.0]hexanes

Article abstract of DOI:10.1002/ejoc.201900579

Substituted pyrazolines were obtained by Ni(ClO₄)₂·6H₂O-catalyzed reaction of 1,5-diazabicyclo[3.1.0]hexanes with donor-acceptor cyclopropanes. The mechanism of this reaction includes alkylation of diaziridine nitrogen wit

Full text of DOI:10.1002/ejoc.201900579

A Journal of
Accepted Article
Title: Synthesis of 1-Substituted Pyrazolines by Reaction of Donor-
Acceptor Cyclopropanes with 1,5-Diazabicyclo[3.1.0]hexanes
Authors: Alexey O. Chagarovskiy, Vladimir V. Kuznetsov, Olga A.
Ivanova, Alexander S. Goloveshkin, Irina I. Levina, Nina N.
Malhova, and Igor V. Trushkov
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900579
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900579
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
Synthesis of 1-Substituted Pyrazolines by Reaction of Donor-
Acceptor Cyclopropanes with 1,5-Diazabicyclo[3.1.0]hexanes
Alexey O. Chagarovskiy,[a,b] Vladimir V. Kuznetsov, Olga A. Ivanova,*[b,c] Alexander S. Goloveshkin,[d]
[b]
[
e]
[b]
[a,b]
Irina I. Levina, Nina N. Makhova and Igor V. Trushkov*
Abstract: Substituted pyrazolines were obtained by Ni(ClO
4
)
2
·6H
2
O-
can be used as starting compounds for the synthesis of
unnatural amino acid azaproline and its derivatives.[
13]
catalyzed reaction of 1,5-diazabicyclo[3.1.0]hexanes with donor-
acceptor cyclopropanes. The mechanism of this reaction includes
alkylation of diaziridine nitrogen with Lewis acid-activated donor-
acceptor cyclopropane followed by hydration of the formed 1,6-
zwitterionic intermediate and oxidation of pyrazolidine with air
oxygen. This pathway is realized when starting bicyclic diaziridines
have bulky alkyl substituent(s) at the C(6) atom preventing (3+3)-
annulation of two three-membered rings.
Introduction
Azaheterocyclic scaffolds are present in more than half of small
molecules approved for the use as pharmaceuticals.[1] Among
them, pyrazolines (2,3-dihydro-1H-pyrazoles) occupy an
important place. In particular, edaravone is used for the
treatment of amyotrophic lateral sclerosis[2] and to assist the
Figure 1. Examples of pyrazoline-based bioactive compounds.
cerebral ishemic stroke,[
3]
recovery of patients after
a
eltrombopag is efficient for the treatment of idiopathic
[
4]
[5]
thrombocytopenic purpura and hepatitis C-induced cirrhosis,
muzolimine is a diuretic,[6] rosonabant, ibipinabant and related
compounds efficiently bind to cannabinoid CB receptor
The most common methods for the synthesis of pyrazolines
derivatives are reactions of hydrazines with α,β-unsaturated
ketones or β-ketoesters affording 2,3-dihydro-1H-pyrazoles and
1
[
7]
[14,15]
providing appetite suppressant effect, some other pyrazolines
were found to demonstrate antimicrobial, anti-inflammatory,
and other bioactivities.
compounds are given in Fig. 1. Pyrazoline-based tartrazine and
pyrazolin-3-ones respectively.
Nevertheless, these methods
[
8]
[9]
cannot be used for the preparation of pyrazolines bearing no
substituents at α-positions to both endocyclic nitrogen atoms
despite the potent importance of such compounds.[
[
10]
[11]
antiamoebic,
Some of these
13,16]
Orange B are food dyes while Mordant red 19 and Sudan Yellow
3
Very recently, we have described the reaction of donor-
G are applied as industrial azo dyes.[ Moreover, pyrazolines
12]
[17,18]
acceptor (D–A) cyclopropanes
1 with bicyclic diaziridines
[
19]
2
affording hexahydropyridazines 3 as a first example of
(
3+3)-annulation of two different three-membered rings
[
[
a]
b]
Dr. A. O. Chagarovskiy, Prof. Dr. I. V. Trushkov
Dmitry Rogachev National Research Center of Pediatric
Hematology, Oncology and Immunology
Samory Mashela 1, Moscow 117997, Russian Federation
Homepage: https://trushkovgroup.com
Dr. A. O. Chagarovskiy, Dr. V. V. Kuznetsov, Dr. O. A. Ivanova,
Prof. Dr. N. N. Makhova, Prof. Dr. I. V. Trushkov
N. D. Zelinsky Institute of Organic Chemistry of Russian Academy of
Sciences
[20]
(Scheme 1a).
However, under the same conditions
spiro[cyclohexane-1,6'-(1,5-diazabicyclo[3.1.0]hexane)] 2a did
not produce the corresponding hexahydropyridazine affording
other product. This stimulated us to investigate the reaction in
more detail to determine the alternative pathway of the reaction
between 1 and 2. During this study we have found that 2a and
some other 1,5-diazabicyclo[3.1.0]hexanes bearing bulky
substituents at the C(3) atom of the diaziridine ring were
converted into 1-alkylated 2,3-dihydropyrazoles in the reaction
with D–A cyclopropanes (Scheme 1b). Nevertheless, the nature
of donor substituent in cyclopropane influences the reaction
chemoselectivity. Here, we report results of this study.
Leninsky pr. 47, Moscow 119991, Russian Federation
E-mail: trush@ioc.ac.ru
Dr. O. A. Ivanova
[
c]
Department of Chemistry
M. V. Lomonosov Moscow State University
Leninskie Gory 1-3, Moscow 119991, Russian Federation
E-mail: iv@kinet.chem.msu.ru
[
[
d]
e]
A. S. Goloveshkin
A. N. Nesmeyanov Institute of Organoelement Compounds of
Russian Academy of Sciences
Vavilova 28, Moscow 119991, Russian Federation
I. I. Levina
N. M. Emanuel Institute of Biochemical Physics Russian Academy
of Sciences
Results and Discussion
We started our investigation by optimization of reaction
conditions for the model reaction between dimethyl 2-(4-
methylphenyl)cyclopropane-1,1-dicarboxylate 1a and bycyclic
diaziridine 2a (Table 1).
Kosygina 4, Moscow 119334, Russian Federation
Supporting information for this article is given via a link at the end of
the document
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
tin(II) and ytterbium(III) catalyzed the studied reaction however
yield of 4a varied from low to moderate when these catalysts
were used. The best yield of pyrazoline 4a was achieved when
4 2 2
reaction was carried out in the presence of Ni(ClO ) ·6H O (20
mol%). Nevertheless, with this catalyst the target transformation
was accompanied by partial decomposition of diaziridine. To
solve this problem, we used portionwise addition of excess of
diaziridine 2a. Using this procedure and 2.5 equiv of 2a in total,
the goal pyrazoline 4a was obtained in 61% yield.
We studied the scope of this transformation under the
optimized reaction conditions varying donor substituent in D–A
cyclopropanes 1. Diaziridine 2a was transformed into 1-
substituted pyrazolines
4
in reaction with all studied
cyclopropanes 1 (Scheme 2).
Scheme 1. The reaction of D–A cyclopropanes 1 with a series of 1,5-
diazabicyclo[3.1.0]hexanes 2. a) (3+3)-Annulation of two three-membered
rings affording hexahydropyridazine derivatives 3.[20] b) 2,3-Dihydro-1H-
pyrazolines 4 formation (this work).
ꢄꢅ ꢇꢈ
ꢆ
ꢁ
ꢂꢃ
ꢀꢠꢡꢄꢊꢅ ꢢ ꢣꢒꢉ ꢅ
ꢘ ꢆ ꢆ
ꢄꢅ ꢇꢈ
ꢆ
ꢡꢆꢛ ꢤꢥꢊꢔꢢ
ꢁ
ꢂꢃ
ꢄꢅ ꢇꢈ
ꢆ
ꢟ
ꢀ
ꢀ
ꢄꢉ ꢄꢊ ꢋ
ꢀ
ꢀ
ꢆ
ꢆ
ꢄꢅ ꢇꢈ
ꢆ
Table 1. Optimization of reaction conditions for the model reaction between
cyclopropane 1a and diaziridine 2a.[a]
ꢀ
ꢂꢃ
ꢁ
ꢌ
ꢌꢍ
ꢄꢅ ꢇꢈ
ꢄꢅ ꢇꢈ
ꢆ
ꢆ
ꢌ
ꢀ
ꢄꢅ ꢇꢈ
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢆ
ꢀ
ꢀ
ꢁ
ꢁ
ꢁ
ꢃꢎ ꢌꢏꢇꢈꢋ ꢐ ꢑꢋ ꢒꢓꢔ
ꢄꢎ ꢌꢏꢉꢋ ꢕ ꢑꢋ ꢒꢖꢔ
ꢁꢆꢎ ꢌꢏꢉꢋ ꢌꢍꢏꢅꢇꢈꢋ ꢖ ꢑꢋ ꢚꢛꢔ
ꢁꢇꢎ ꢌꢏꢌꢍꢏꢅꢇꢈꢋ ꢖ ꢑꢋ ꢒꢐꢔ
ꢁꢈꢎ ꢌꢏꢉꢋ ꢌꢍꢏꢀꢇꢈꢆꢋ ꢘ ꢑꢋ ꢒꢒꢔ
ꢙ
ꢅꢎ ꢌꢏꢗꢋ ꢐ ꢑꢋ ꢘꢒꢔ
2
a/1a
Entry
Lewis acid (mol %)
time, h
Yield of 4a, %[b]
ꢌ
ratio
ꢇꢈꢅ
ꢇꢈꢅ
1
2
3
4
5
6
7
8
9
Sc(OTf)
3
(10 mol%)
(10 mol%)
(10 mol%)
1
3
3
traces[c]
NR[d]
9[e]
ꢄꢅ ꢇꢈ
ꢆ
Sn(OTf)
2
3
1
ꢌꢍ
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢀ
Yb(OTf)
2.5
2.5
2.5
1
3
ꢁ
ꢁ
ꢉꢎ ꢌꢏꢅꢇꢈꢋ ꢌꢍꢏꢉꢋ ꢖ ꢑꢋ ꢐꢘꢔ
ꢊꢎ ꢌꢏꢉꢋ ꢌꢍꢏꢅꢇꢈꢋ ꢖ ꢑꢋ ꢚꢚꢔ
ꢁꢊ
InCl
3
(20 mol%)
(10 mol%)
3
NR[d]
NR[d]
15[f]
Ni(OTf)
2
3
ꢇꢈ
ꢄꢅ ꢇꢈ
ꢆ
ꢜ
ꢄꢅ ꢇꢈ
ꢆ
ꢅ
Ni(ClO
Ni(ClO
Ni(ClO
Ni(ClO
Ni(ClO
4
)
)
)
)
)
2
2
2
2
2
·6H
·6H
·6H
·6H
·6H
2
2
2
2
2
O (20 mol%)
O (20 mol%)
O (20 mol%)
O (20 mol%)
O (20 mol%)
3
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢀ
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢀ
1.5
2.5
2.5
2.5
3
35[g]
23
4
4
4
4
ꢁ
ꢎꢎ ꢜꢏꢝꢋ ꢖ ꢑꢋ ꢚꢞꢔ
ꢁꢏꢎ ꢜꢏꢅꢋ ꢖ ꢑꢋ ꢚꢘꢔ
1[h]
3
ꢁꢋꢎ ꢐ ꢑꢋ ꢖꢚꢔꢙ
ꢇꢈꢅ
47
ꢄꢅ ꢇꢈ
ꢆ
ꢄꢅ ꢇꢈ
[i]
ꢆ
10
5
68 (61 )
ꢀ
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢀ
ꢄꢅ ꢇꢈ
ꢆ
ꢀ
[
a] 0.05 M solution of 1a in CH
2
Cl
2
, Lewis acid, portionwise addition of 2a (0.25
Cl , reflux. [b] NMR yield. [c]
ꢀ
equiv every 15 min), molecular sieves 4Å, CH
2
2
Cyclopropane conversion did not exceed 5%. [d] NR = no reaction. [e]
Cyclopropane conversion was 24%; yield based on reacted starting material
ꢁꢌꢎ ꢘ ꢑꢋ ꢐꢚꢔ
ꢁꢍꢎ ꢖ ꢑꢋ ꢒꢛꢔ
(
brsm) = 38%. [f] Cyclopropane conversion was 27%; brsm yield = 56%. [g]
Scheme 2. Scope of reaction of cyclopropanes 1 with diaziridine 2a. General
reaction conditions: 0.05 M solution of 1, portionwise addition of 2a (1.25–3
equiv.), molecular sieves 4Å, CH Cl , reflux. Yields of isolated products are
2 2
Cyclopropane conversion was 47%; brsm yield = 74%. [h] Reaction was
performed in 1,2-dichloroethane. [i] Isolated yield.
given. [a] Cyclopropane conversion was 61%; brsm yield = 61%.
We found that indium(III) chloride and nickel(II) triflate failed to
induce the reaction between 1a and 2a under reflux in
dichloromethane. Trifluoromethanesulfonates of scandium(III),
Structures of pyrazolines 4 were determined on the basis of
analysis of their 1D and 2D NMR spectra and unambiguously
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
proved by single-crystal X-ray data for compound 4h.[21] This is
the first example of X-ray data for 1-alkylpyrazolines bearing no
other substituents.[
The yield of pyrazolines 4 was found to be dependent on the
electron-donating ability of the cation-stabilizing group in D–A
cyclopropane. Cyclopropane-1,1-diesters with electron-rich 2-
thienyl, 2-furyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl and
It was found that spiro-cyclopentane derivative 2b is equipotent
to compound 2a while the corresponding cycloheptane analogue
2c afforded the target pyrazoline 4d in 28% only. The large
steric demands of seven-membered ring are presumably
responsible for the lower reactivity of 2c and, as a result, for the
drop of the yield of 4d. 6,6-Diethyl-substituted 1,5-
diazabicyclo[3.1.0]hexane 2d produced pyrazoline 4d in lower
yield than diaziridine 2a. This result can be also explained by
larger steric demands of two ethyl groups in comparison with the
cyclohexane moiety. This is similar to higher nucleophilicity of
piperidine vs. diethylamine in reactions with diverse
electrophiles.[ A similar yield of pyrazolines 4d was obtained in
the reaction of 6-ethyl-6-methyl analogue 2e and
monosubstituted 6-ethyl derivative 2f. The latter was highly
unexpected as earlier both 6-aryl-1,5-diazabicyclo[3.1.0]hexanes
and 1,2,3-triethyldiaziridine in the reaction with D–A
22]
2
,3,4-trimethoxyphenyl groups afforded the target products 4d-
f,h-j in 65-79% yield while substrates with electroneutral
aromatic group 1a,b,l produced the corresponding pyrazolines 4
in moderate yields (57–63%). Cyclopropane 1c with electron-
depleted 4- fluorophenyl substituent afforded pyrazolines 4c in
28]
4
6% yield only. This tendency can be explained by Lewis acid-
[
20,23]
induced side reactions of 2a such as its dimerization
and
partial decomposition; the contribution of side reactions
increases with the decrease of D–A cyclopropane reactivity.
Although 3,4,5-trimethoxyphenyl substituent is usually
considered as an efficient donor, the moderate yield of 4g is
consistent with the aforementioned trend. Indeed, positive
mesomeric effect of 4-methoxy group cannot be realized in this
compound as this group is oriented perpendicular to the
benzene ring due to the repulsion from the adjacent
[20]
cyclopropanes produced only products of (3+3)-annulation.
Oppositely, 6,6-dimethyl-substituted diazabicyclohexane 2g
afforded pyrazoline 4d in 18% yield only; the major product of its
reaction with 1d was (3+3)-cycloadduct 3a. At last, product of
(3+3)-annulation 3b was exclusively obtained in the reaction of
2g with 2-phenylcyclopropane-1,1-diester 1b (Scheme 3).
[
24]
substituents.
than 1d or 1e
As a result, cyclopropane 1g is less reactive
[
25]
and the contribution of side reactions of
diaziridine is quite significant.
At the first glance, the formation of 4m in 60% yield only is
inconsistent with the aforementioned trend as 4-methoxystyryl-
substituted cyclopropane 1m demonstrated excellent reactivity
earlier in various processes.[ Presumably, vinylcyclopropane-
to-cyclopentene isomerization[26,27] competes with the studied
process for this substrate, providing the decrease of the yield of
26]
Scheme 3. (3+3)-Annulation of D–A cyclopropane 1b with diaziridines 2g.
4
m. The moderate conversion of 1k is unclear now.
Then we varied diaziridine derivatives to determine the effect
of their structures on the efficiency of the reaction with D–A
cyclopropane 1d selected as model substrate due to its high
reactivity against diaziridine 2a (Table 2).
The variation of substituents at the C(3) atom in 1,5-
diazabicyclo[3.1.0]hexanes 2 did not alter the direction of their
reaction with D–A cyclopropanes but decreased significantly the
yield of pyrazoline 4. Namely, the introduction of two methyl
groups at the C(3) atom of 1,5-diazabicyclo[3.1.0]hexanes
Table 2. Variation of substituents at the C(6) atom in diazabicyclohexanes 2.[a]
decreased
significantly
their
reactivity
against
D–A
cyclopropanes having no effect on the reaction chemoselectivity.
As a result, pyrazolines 4n,o were obtained in very low yield due
to small conversion of starting compounds (Scheme 4).
Entry
2
a
b
c
d
e
f
R1
R2
Yield of 4d, %
1
2
3
4
5
6
7
-(CH
-(CH
-(CH
5
2
2
2
)
)
)
5
4
6
-
-
-
70
66
[
b]
28
C
C
C
2
2
2
H
H
H
C
2
H
5
55
57
44
5
CH
H
CH
3
5
[
c]
g
CH
3
3
18
Scheme 4. Reaction of D–A cyclopropanes 1 with diaziridines 2h,i. [a]
Cyclopropane conversion was 16%; brsm yield = 75%. [b] Cyclopropane
conversion was 25%; brsm yield = 76%.
[
(
a] General reaction conditions: 0.05 M solution of 1d, portionwise addition of 2
1.8–3 equiv.), molecular sieves 4Å, CH Cl , reflux. Yields of isolated product
2
2
are given. [b] Cyclopropane conversion was 39%; brsm yield = 72%. [c]
Product of (3+3)-annulation 3a was also obtained in 43% yield.
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
Scheme 6. Scope of the reaction of cyclopropanes 1 with diaziridine 2j.
General reaction conditions: 0.05 M solution of 1, portionwise addition of 2j
The low reactivity of diaziridines 2h,i can be explained within this
approach by change of their conformation from pseudo-boat to
pseudo-chair due to the repulsion between two flagpole
substituents. However, axial methyl group in pseudo-chair
conformation prevents approach of D–A cyclopropane to
nitrogen atom(s) (Scheme 5).
(
2 2
1.8–3 equiv.), molecular sieves 4Å, CH Cl , reflux. Yields of isolated products
are given.
The first step in the formation of compounds 4 and 5 is
presumably the alkylation of with Lewis acid-activated
2
cyclopropane 1. There are two ways for the further
transformation of the formed 1,6-zwitterion A (Scheme 7). The
first one (path a) is a 1,3-hydride shift leading to the endocyclic
iminium ion B followed by the loss of alkyl group (as an alkene
or alcohol) producing a cyclic hydrazone.[ The second one
32]
(path b) is the hydration of A with water molecule from nickel
perchlorate hexahydrate affording hemiaminal which
C
eliminates a carbonyl compound yielding 1-alkylated saturated
heterocycle D. Its oxidation by air oxygen accomplishes the
formation of the target product 4 (5).
Scheme 5. Deceleration of reactions of 2h,i in comparison with 2a-g.
On the other hand, 1,6-diazabicyclo[4.1.0]heptane 2j which is a
homologue of 2a, reacted with D–A cyclopropanes 1 in a similar
efficiency providing 1,4,5,6-tetrahydropyridazines 5 which can
[
13,29]
be used for the synthesis of piperazic aicd derivatives
[
30]
including total synthesis of piperazimycin
polyoxypeptins A and B.[31]
A
and
It is noteworthy that cyclopropanes 1b,d in this reaction
afforded exclusively tetrahydropyridazines 5 while cyclopropane
1
h yielded both 5c and (3+3)-cycloadduct 3c (Scheme 6).
Scheme 7. Two possible mechanisms for the formation of compounds 4 and 5.
The formation of pyrazolines 4 and tetrahydropyridazines 5 only
in the presence of water as well as the reported isolation of
pyrazolines in the reaction of primary hydrazines with 1,3-
dihalides in alkaline aqueous medium[ support the realization
of path b but cannot be considered as unambiguous proof of the
mechanism. To better understand this process, we performed
GC-MS investigation of the reaction mixture formed in the
reaction between 1d and 2a and found that it contained
cyclohexanone as side product. Moreover, we found that the
reaction of D–A cyclopropanes 1 with diaziridine 2j produced
initially hexahydropyridazines 6 that were further oxidized to
33]
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
products 5 (Scheme 8). All attempts to isolate these side
The structures of synthesized compounds were elucidated with the aid of
1
13
1
1
1
13
1
D NMR ( H, C) and 2D NMR (COSY H- H, HSQC and HMBC H- C,
products being unsuccessful due to the aforementioned
HMBC H-15N, NOESY 1H- H) spectroscopies. The IR spectra were
1
1
[
21]
oxidation.
All the obtained data are consistent with the
recorded on InfraLUM FT-801 and Bruker “Alpha” spectrometers in the
realization of pathway b including hydration of zwitterionic
intermediate A but not with pathway a including hydride shift in
the above intermediate.
-
1
-1
range 400-4000 cm (resolution 2 cm ). High resolution mass spectra
TM
were recorded on
a
Bruker microTOF-Q
spectrometer with
electrospray ionization (ESI). All measurements were performed in a
positive (+MS) ion mode (interface capillary voltage: 4500 V) with scan
range m/z: 50-3000. External calibration of the mass spectrometer was
performed with Electrospray Calibrant Solution (Fluka). A direct syringe
injection was used for all analyzed solutions in MeCN (flow rate: 3 μL
-
1
min ). Nitrogen was used as nebulizer gas (0.4 bar) and dry gas (4.0 L
-
1
o
min ); interface temperature was set at 180 C. All spectra were
processed by using Bruker DataAnalysis 4.0 software package. GS-MS
2
studies were performed using ACQUITY UPC equipment with ACQUITY
UPC QDA mass detector; Positive Scan 40.00-400.00 Da, Centroid,
2
CV=15. Column: Viridis® HSS C18 SB 3.0 mm x 150 mm, 1/pkg, Waters;
eluent: CO /acetonitrile (90:10, v/v), 35 °C, 160 bar, elution rate = 0.6
2
mL/min. Analytical thin-layer chromatography (TLC) was carried out
using Silufol UV 254 TLC silica gel 60 F254 aluminum plates and
Macherey Nagel ALUGRAM Xtra SIL G UV254. The visualization of the
TLC plates was done by UV lamp (365 nm) or by spraying of the plates
with 5% alcoholic solution of diphenylamine followed by heating of plates.
Melting points (mp) were determined using Electrothermal 9100 and
SMP-20 capillary melting point apparatus. X-ray diffraction studies were
performed using Bruker SMART Apex II diffractometer (MoKα radiation,
graphite monochromator, ω-scans, 120K). Using Olex2[ , structure was
solved by the direct method and refined using anisotropic full-matrix
Scheme 8. Formtation of compounds 5 via the intermediate formation of
hexahydropyridazines 6 followed by their oxidation with air oxygen.
34]
Conclusions
2
approximation against F hkl. Column chromatography was performed on
silica gel 60 (230-400 mesh, Merck or Macherey-Nagel). All the reactions
were carried out using freshly distilled and dry solvents from solvent stills.
Thus, we have shown that the Ni(ClO
reaction of donor-acceptor cyclopropanes, containing aryl,
hetaryl or alkenyl group as donor, with 1,5-
4 2 2
) ·6H O-catalyzed
Cyclopropanes
reactions sequence from
1
were prepared by Knoevenagel/Corey-Chaykovsky
35,36]
the
corresponding
aldehydes.[
a
Cyclopropanes 1a-k,m are known compounds but cyclopropanes 1f,g
were not fully characterized previously. 6,6-Dimethyl-1,5-
diazabicyclo[3.1.0]hexanes bearing bulky alkyl substituents at
the C(6) atom affords the corresponding 1-alkyl-2,3-
dihydropyrazoles. Moreover, it was demonstrated that the
corresponding 1,6-diazabicyclo[4.1.0]heptanes react similarly
producing the corresponding 1,4,5,6-tetrahydropyridazine
derivatives. Approaches to the related monosubstituted cyclic
hydrazones are very restricted and usually characterized by low
yields. Bicyclic diaziridines behave here as synthetic equivalents
of difficultly accessible unsubstituted 2,3-dihydropyrazole and
unstable 1,4,5,6-tetrahydropyridazine. The discussed reaction
proceeds via the alkylation of diaziridine derivative with a Lewis
acid-activated cyclopropane followed by hydration of the formed
diazabicyclo[3.1.0]hexane 2g was synthesized according to the
published procedure.[
37]
Spectral data and boiling point are in full
[37,38]
accordance with the published ones.
2
1
. Synthesis and characterization of donor-acceptor cyclopropanes
f,g,l.
2.1.
dicarboxylate (1f): The 60% suspension of NaH in mineral oil (399 mg,
0.0 mmol) and trimethylsulfoxonium iodide (2.30 g, 10.4 mmol) were
Dimethyl
2-[4-(dimethylamino)phenyl]cyclopropane-1,1-
1
added to dry DMSO (20 mL) under argon and stirred for 0.5 h. The
mixture was cooled to 10 °C and solution of dimethyl 2-[4-
(
dimethylamino)benzylidene]malonate (2.50 g, 9.5 mmol) in DMSO (8
mL) was added. After stirring for 1 h at room temperature, the reaction
was quenched with ice-cold aqueous NH Cl, and extracted with diethyl
ether (4×20 mL). The combined organic layer was washed with water
(5×10 mL), brine and dried over anhydrous Na SO . Concentration under
1
,6-zwitterion producing hemiaminal. The elimination of carbonyl
compound and air oxidation of the formed pyrazolidine
accomplishes the synthesis of title products. The process
chemoselectivity was found to depend on the nature of
substituents at the carbon atom of the diaziridine ring and donor-
acceptor cyclopropane applied.
4
2
4
reduced pressure afforded an orange oil, which was purified by silica gel
chromatography (petroleum ether/EtOAc = 3:1) to afford compound 1f.
Yield 1.9 g (59%), pale-yellow solid; R
f
= 0.55 (petroleum ether/EtOAc
1
2
4
:1); mp = 59–60 °C; H NMR (500 MHz, CDCl
3
):
δ
= 1.72 (dd, J = 5.2
Hz, 3J = 9.3 Hz, 1 H, CH
), 2.17 (dd, J = 5.2 Hz, 3J = 8.1 Hz, 1 H, CH
2
2
2
),
Experimental Section
3
3
2
3
.94 (s, 6 H, 2×CH
3
), 3.18 (dd, J = 9.3 Hz, J = 8.1 Hz, 1 H, CH), 3.42 (s,
3
3
H, CH ), 3.80 (s, 3 H, CH
3
3
), 6.65 (d, J = 8.5 Hz, 2 H, Ar), 7.07 (d, J =
): = 18.8 (CH ), 32.2 (CH),
O), 52.1 (CH O), 111.7 (2×CH), 121.4
8.5 Hz, 2 H, Ar); 13C NMR (125 MHz, CDCl
δ
1
. General information: NMR spectra were recorded on Bruker AM-300,
3
2
Bruker Avance 400 and Bruker Avance 500 spectrometers at room
36.6 (C), 40.0 (2×CH
3
N), 51.6 (CH
3
3
temperature; the chemical shifts δ were measured in ppm with respect to
(C), 128.7 (2×CH), 149.3 (C), 166.8 (CO
2
Me), 170.0 (CO
2
Me); HRMS
1
13
+
+
solvent (CDCl
3
:
Н: δ = 7.26 ppm, C: δ = 77.0 ppm). Splitting patterns
(ESI-TOF): m/z calcd for C15
H
20NO
4
: 278.1388 [M+H] ; found: 278.1387;
are designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;
4
elemental analysis calcd (%) for C15H19NO : C 64.97, H 6.91, N 5.05;
dd, double doublet and br (broad). Coupling constants (J) are given in Hz.
found: C 65.09, H 6.89, N 4.88.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
2
.2.
dicarboxylate (1g): The 60% suspension of NaH in mineral oil (868 mg,
1.7 mmol) and trimethylsulfoxonium iodide (5.00 g, 22.7 mmol) were
added to dry DMSO (40 mL) under argon and stirred for 0.5 h. The
mixture was cooled to 10 °C and dimethyl 2-(3,4,5-
Dimethyl
2-(3,4,5-trimethoxyphenyl)cyclopropane-1,1-
3.1. 1,5-Diazaspiro(bicyclo[3.1.0]hexane-6,1'-cyclohexane) (2a) was
synthesized according to the General procedure 1 from cyclohexanone
(1.96 g, 20 mmol) and 1,3-diaminopropane (2.97 g, 40 mmol). Yield 1.98
2
g (65%); colorless liquid; R
f
= 0.48 (CHCl
3
/MeOH 10:1); bp = 75 °C/1 Torr
, 300 MHz): = 1.26–1.41 (m, 6
), 2.00–2.16 (m, 1 H, C(3)Hax),
(lit. 86–87 °C/1 Torr[ ); H NMR (CDCl
40]
1
δ
3
trimethoxybenzylidene)malonate (6.41 g, 20.7 mmol) in DMSO (15 mL)
was added. After stirring for 1.5 h at room temperature, the reaction was
H, 3×CH ), 1.41–1.64 (m, 4 H, 2×CH
2
2
2.30–2.47 (m, 1 H, C(3)Heq), 2.70–2.82 (m, 2 H, C(2)Hax, C(4)Hax), 3.10–
13
quenched with ice-cold aqueous NH
mL). The combined organic layer was washed with water (5×20 mL),
brine and dried over anhydrous Na SO . Concentration under reduced
pressure afforded cream residue, which was purified by
recrystallization from isopropyl alcohol to afford compound 1g. Yield 4.9
g (73%), colorless crystals; R
7
Hz, 1 H, CH
9
4 2
Cl, and extracted with Et O (4×30
3
3.24 (m, 2 H, C(2)Heq, C(4)Heq); C NMR (CDCl , 75 MHz): δ = 24.2,
24.7, 24.9, 25.8, 35.4, 38.3, 47.6 (2 C), 65.7; IR (thin layer): ν = 3405,
2929, 2885, 2855, 1481, 1448, 1382, 1301, 1249, 1220, 1196, 1123,
2
4
-
1
+
a
1019, 985, 963 cm ; MS (70 eV): m/z (%): 152 (67) [М] , 151 (100) [(М–
+
+
+
Н)] , 124 (31) [(М–2×СН
2
)] , 123 (98) [(М–2×СН
2
–Н)] , 111 (18) [(М–
+
)]+; HRMS (ESI-TOF): m/z calcd for
f
= 0.37 (petroleum ether/EtOAc 4:1); mp =
3×СН
2
–Н)] , 98 (9) [(М–4×СН
: 153.1386 [M+H] ; found: 153.1387.
2
1
2
3
+
+
7–78 °C; H NMR (500 MHz, CDCl
3
3
):
δ
= 1.69 (dd, J = 5.2 Hz, J = 9.3
9 17
C H N
2
2
3
2
), 2.11 (dd, J = 5.2 Hz, J = 8.1 Hz, 1 H, CH
2
), 3.15 (dd, J =
3
3.2. 1,5-Diazaspiro(bicyclo[3.1.0]hexane-6,1'-cyclopentane) (2b) was
synthesized according to the General procedure 1 from cyclopentanone
.3 Hz, J = 8.1 Hz, 1 H, CH), 3.42 (s, 3 H, CH
3
), 3.76 (s, 3 H, CH
3
), 3.78
), 6.39 (s, 2 H, Ar); 1 C NMR (125 MHz,
3
(
s, 3 H, CH
3
), 3.80 (s, 6 H, 2×CH
= 19.6 (CH
O), 60.8 (CH
3
(
1.68 g, 20 mmol) and 1,3-diaminopropane (2.97 g, 40 mmol). Yield 1.47
CDCl
5
3
):
δ
2
), 32.8 (CH), 37.2 (C), 52.4 (CH
3 3
O), 52.8 (CH O),
g (53%); colorless liquid; R
f
= 0.43 (CHCl
= 1.32–1.40 (m, 2 H, CH
), 1.68–1.81 (m, 4 H, CH , C(3)Hax), 1.85–1.98 (m, 1 H,
C(3)Heq), 2.87–2.96 (m, 2 H, C(2)Hax, C(4)Hax), 3.08–3.19 (m, 2 H,
3
/MeOH 10:1); bp = 65 °C/1
6.1 (2×CH
3
3
O), 105.6 (2×CH), 130.3 (C), 137.5 (C), 153.0
1
3
Torr; H NMR (CDCl , 300 MHz):
δ
2
), 1.49–1.65
(
2×C), 167.1 (CO
2
Me), 170.2 (CO
: 325.1277 [M+H] ; found: 325.1282; elemental analysis calcd
2
Me); HRMS (ESI-TOF): m/z calcd for
+
+
(m, 3 H, CH
2
2
C
16
H
21
O
7
(
20 7
%) for C16H O : C 59.25, H 6.22; found: C 59.36, H 5.89.
13
C(2)Heq, C(4)Heq); С NMR (CDCl
3
, 75 MHz): δ = 23.4, 24.5, 26.4, 28.8,
2
.3.
dicarboxylate (1l): The 60% suspension of NaH in mineral oil (701 mg,
7.5 mmol) and trimethylsulfoxonium iodide (4.05 g, 18.4 mmol) were
Dimethyl
2-(1-benzyl-1H-indol-4-yl)cyclopropane-1,1-
38.1, 49.2 (2 C), 70.9; IR (thin layer): ν = 3397, 3274, 2955, 2876, 1643,
-
1
1454, 1436, 1356, 1330, 1287, 1267, 1192, 990, 980 cm ; HRMS (ESI –
+
+
1
8 15 2
TOF): m/z calcd for C H N : 139.1230 [M+H] ; found: 139.1235.
added to dry DMSO (30 mL) under argon and stirred for 0.5 h. The
mixture was cooled to 10 °C and solution of dimethyl 2-(1-benzyl-1H-
3
.3. 1,5-Diazaspiro(bicyclo[3.1.0]hexane-6,1'-cycloheptane) (2c) was
synthesized according to the General procedure 1 from cycloheptanone
2.24 g, 20 mmol) and 1,3-diaminopropane (2.97 g, 40 mmol). Yield 1.93
[39]
indol-4-yl)methylidenemalonate
was added. After stirring for 3 h at room temperature, the reaction was
quenched with ice-cold aqueous NH Cl, and extracted with diethyl ether
4×30 mL). The combined organic layer was washed with water (5×20
mL), brine and dried over anhydrous Na SO . Concentration under
(6.13 g, 17.5 mmol) in DMSO (5 mL)
(
g (58%); colorless liquid; R
Torr; H NMR (CDCl
f
= 0.49 (CHCl
= 1.43–1.50 (m, 2 H, CH
), 1.65–1.75 (m, 2 H, CH ), 1.75–1.90 (m, 1 H, C(3)Hax),
.10–2.25 (m, 1 H, C(3)Heq), 2.81–2.91 (m, 2 H, C(2)Hax, C(4)Hax), 3.16–
3
/MeOH 10:1); bp = 89–91 °C/1
4
1
3
, 300 MHz):
δ
2
), 1.50–1.65
(
(
m, 8 H, 4×CH
2
2
2
4
2
3
2
reduced pressure afforded a yellow residue, which was purified by silica
gel chromatography (petroleum ether/EtOAc = 3:1) to afford compound 1l.
13
.30 (m, 2 H, C(2)Heq, C(4)Heq); С NMR (CDCl
3
, 75 MHz): δ = 24.1,
4.8, 25.3, 29.7, 29.9, 32.5, 40.0, 47.9 (2 C), 66.6; IR (thin layer): ν =
Yield 3.8 g (61%), yellow paste; R
f
= 0.63 (petroleum ether/EtOAc 3:1);
1
2
= 1.87 (dd, J = 4.9 Hz, 3J = 9.3 Hz, 1 H,
3385, 2926, 3854, 1644, 1458, 1384, 1285, 1270, 1189, 1148, 1078,
1
167.1543 [M+H] ; found: 167.1543.
H NMR (500 MHz, CDCl
3
):
δ
3
-
1
+
018, 994, 953, 900 cm ; HRMS (ESI-TOF): m/z calcd for C10
19
H N
2
:
2
CH
2
), 2.43 (dd, J = 4.9 Hz, J = 8.1 Hz, 1 H, CH
2
), 3.26 (s, 3 H, CH
3
),
+
3
3
3
.62 (dd, J = 9.3 Hz, J = 8.1 Hz, 1 H, CH), 3.88 (s, 3 H, CH
3
), 5.33 (s, 2
3
H, CH
2
), 6.75 (br. d, J = 3.2 Hz, 1 H, CH), 6.89–6.90 (m, 1 H, Ar), 7.10–
3
.4. 6,6-Diethyl-1,5-diazabicyclo[3.1.0]hexane (2d) was synthesized
3
7
.13 (m, 3 H, Ar), 7.19 (br. d, J = 3.2 Hz, 1 H, CH), 7.22–7.24 (m, 1 H,
according to the General procedure 1 from pentan-3-one (1.72 g, 20
mmol) and 1,3-diaminopropane (2.97 g, 40 mmol). Yield 1.41 g (51%);
colorless liquid; R
13
Ar), 7.28–7.33 (m, 3 H, Ar); C NMR (125 MHz, CDCl
3
):
O), 52.8 (CH
09.2 (CH), 118.0 (CH), 121.4 (CH), 126.7 (2×CH), 126.8 (C), 127.6
δ
= 19.1 (CH
2
),
3
1
2
0.8 (CH), 36.8 (C), 50.2 (CH ), 51.9 (CH
3
3
O), 100.4 (СH),
/MeOH 10:1); bp = 62–63 °C/1 Torr; 1
f
= 0.38 (CHCl
3
H
NMR (CDCl
3
, 300 MHz): δ JH,H = 7.5 Hz, 3 H, CH ), 1.06 (t,
= 0.87 (t, 3
3
(
(
1
C
(
CH), 129.3 (CH), 128.7 (2×CH), 129.5 (C), 136.0 (C), 137.6 (C), 167.4
3
), 1.39 (q, 3JH,H = 7.5 Hz, 2 H, CH ), 1.45 (q, 3JH,H
J
H,H = 7.5 Hz, 3 H, CH
3
2
CO
2
Me), 170.6 (CO
2
Me); IR (Nujol): ν = 3400, 2990, 1740, 1520, 1500,
=
2
7.5 Hz, 2 H, CH ), 2.02–2.20 (m, 1 H, C(3)Hax), 2.30–2.48 (m, 1 H,
-
1
440, 1325, 1300, 1290, 1010 cm ; HRMS (ESI-TOF): m/z calcd for
C(3)Heq), 2.71–2.85 (m, 2 H, C(2)Hax, C(4)Hax), 3.12–3.28 (m, 2 H,
C(2)Heq, C(4)Heq); С NMR (CDCl
3
1
+
+
22
H
22NO
4
364.1543 [M+H] ; found 364.1543; elemental analysis calcd
: C 72.71, H 5.82, N 3.85; found: C 72.89, H 5.89, N
13
3
, 75 MHz):
δ
= 8.4, 9.3, 17.0, 29.6,
%) for C22H21NO
4
5.0, 47.6 (2 С), 67.9; IR (thin layer): ν = 3424, 2968, 2838, 2886, 1729,
3
.88.
-1
647, 1461, 1382, 1288, 1221, 1104, 1084, 1014, 984, 966 cm ; HRMS
+
+
(
ESI –TOF): m/z calcd for C
H N
8 17 2
: 141.1386 [M+H] ; found: 141.1381.
3
. General procedure 1 for the synthesis of 1,5-diazabicyclo[3.1.0]-
3
.5.
6-Ethyl-6-methyl-1,5-diazabicyclo[3.1.0]hexane (2e) was
hexanes and 1,6-diazabicyclo[4.1.0]heptane (2a-j): Solution of t-
BuOCl (2.39 g, 22 mmol) in MeOH (3 mL) was added dropwise to the
magnetically stirred solution of α,ω-diaminoalkane (40 mmol) in MeОН
synthesized according to the General procedure 1 from butan-2-one
1.44 g, 20 mmol) and 1,3-diaminopropane (2.97 g, 40 mmol). The
diaziridine 2e was formed as a mixture of syn- and anti-isomers in 2:1
(
(
(
30 mL) at –5-0 ºС. Then solution of corresponding ketone or aldehyde
20 mmol) in MeOH (4–6 mL) was added and the reaction mixture was
ratio; yield 1.31 g (52%); colorless liquid; R
f
3
= 0.39 (CHCl /MeOH 10:1);
bp = 47–48 °C/1 Torr.
syn-Isomer: 1H NMR (CDCl
C(9)H ), 1.04 (s, 3 H, C(7)H
stirred for 24 h at 0–5 ºС. The solid formed was filtered off, the solvent
was evaporated under reduced pressure and CHCl (60 mL) was added
to the residue. The precipitate was filtered off, the solution was washed
with water (50 mL), dried with К СО and the solvent was evaporated.
Compounds were purified by distillation under reduced pressure.
Spectral data of the known compounds are consistent well with the
described ones.
= 0.86 (t, 3
J
H,H = 7.5 Hz, 3 H,
), 1.78–
3
, 400 MHz):
), 1.36 (q, JH,H = 7.5 Hz, 2 H, C(8)H
δ
3
3
3
3
2
1
.91 (m, 1 H, C(3)Hax), 2.10–2.23 (m, 1 H, C(3)Heq), 2.70–2.80 (m, 2 H,
2
3
13
C(2)Hax, C(4)Hax), 3.10–3.20 (m, 2 H, C(2)Heq, C(4)Heq); С NMR
CDCl , 100 MHz): = 8.6 (C(9)), 9.6 (C(7)), 32.9 (C(3)), 34.3 (C(8)),
8.0 (C(2), C(4)), 64.3 (C(6)).
(
4
3
δ
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
1
= 1.02 (t, 3JH,H = 7.5 Hz, 3 H,
), 1.98–
anti-Isomer: H NMR (CDCl
3
, 400 MHz):
), 1.36 (q, JH,H = 7.5 Hz, 2 H, C(8)H
δ
4. General procedure 2 for the synthesis of pyrazolines 4, 5 and
3
C(9)H
3
), 1.15 (s, 3 H, C(7)H
3
2
bicyclic hydrazines 3: Cyclopropane 1 (0.5–2 mmol) was dissolved in
2
.08 (m, 1 H, C(3)Hax), 2.25–2.37 (m, 1 H, C(3)Heq), 2.70–2.80 (m, 2 H,
CH
molecular sieves 4 Å was added. The mixture was heated to reflux and a
solution of diaziridine 2 (2–3 equiv.) in CH Cl (4–5 mL) was added
portionwise within 2–3 h (0.25 equiv every 15 minutes). The reaction
mixture was stirred under reflux for the time indicated (TLC control). The
reaction mixture was cooled to ambient temperature, diluted with CH Cl
2 2
and quenched with 0.5 M aqueous solution of disodium EDTA. The
organic layer was washed with 0.5 M solution of disodium EDTA (4–5
2 2 4 2 2
Cl to make 0.05 M solution; then Ni(ClO ) ⋅6Н О (20 mol%) and
13
C(2)Hax, C(4)Hax), 3.10–3.20 (m, 2 H, C(2)Heq, C(4)Heq); С NMR
CDCl , 100 MHz): = 10.5 (C(9)), 20.3 (C(8)), 24.3 (C(7), 34.6 (C(3)),
7.5 (C(2), C(4)), 64.7 (C(6)).
IR (thin layer): ν = 3406, 2968, 2938, 2885, 1370, 1644, 1462, 1382,
(
4
3
δ
2
2
-
1
1
356, 1305, 1261, 1119, 1105, 1078, 1004, 943 cm ; HRMS (ESI–TOF):
+
+
m/z calcd for C
H N
7 15 2
: 127.1230 [M+H] ; found: 127.1227.
3
.6. anti-6-Ethyl-1,5-diazabicyclo[3.1.0]hexane (2f) was synthesized
times), brine and dried with anhydrous Na
solvent under reduced pressure, the residue was purified by column
chromatography on silica gel (SiO , eluent – petroleum ether : ethyl
acetate, 10:1 to 1:1) to afford target product.
2 4
SO . After evaporation of
according to the General procedure 1 from propanal (1.16 g, 20 mmol)
and 1,3-diaminopropane (2.97 g, 40 mmol). Yield 1.43 g (65%); colorless
liquid; R
3
1
2
1
f
= 0.44 (CHCl
3
/MeOH 10:1); bp = 76 °C/10 Torr; H NMR (CDCl
3
,
00 MHz):
δ
= 0.88 (t, 3JH,H = 7.5 Hz, 3 H, CH
3
), 1.32–1.44 (m, 2 H, CH
), 2.14 (t, JH,H = 5.4 Hz, 1H, C(6)H), 2.81–2.97
2
),
3
.57–1.80 (m, 2H, C(3)H
2
4.1. Dimethyl 8-(4-methoxyphenyl)-5,5-dimethyltetrahydro-1H-
13
(
m, 2 H, C(2)Hax, C(4)Hax), 3.21–3.32 (m, 2 H, C(2)Heq, C(4)Heq);
NMR (CDCl , 75 MHz): = 9.2, 22.2, 25.3, 51.4 (2 C), 58.2; IR (thin
layer): ν = 3418, 2968, 2938, 2877, 1731, 1645, 1463, 1456, 1416, 1377,
290, 1266, 1241, 1211, 1191, 1178, 1134, 1078, 1032, 963, 917, 900
С
pyrazolo[1,2-a]pyridazine-6,6(5H)-dicarboxylate (3a) was obtained
together with pyrazoline 4a (18% yield) from cyclopropane 1d (150 mg,
0.57 mmol) and diaziridine 2g (159 mg, 1.42 mmol) after 4 h according to
3
δ
1
the General procedure 2. Yield 92 mg (43%); cream solid; R
(petroleum ether/EtOAc 5:1); mp = 95–96 °C; Н NMR (CDCl
f
= 0.40
, 500
),
-
1
+
+
1
cm ; HRMS (ESI-TOF): m/z calcd for C
1
H N
6 13 2
: 113.1073 [M+H] ; found:
3
13.1070.
МHz):
δ
3 3
= 1.36 (s, 3 Н, CH ), 1.55 (s, 3 Н, CH ), 1.69–1.87 (m, 2 H, CH
2
2
CH
1
.10–2.19 (m, 1 H, CH ), 2.28–2.36 (m, 2 H, CH
2
2
), 2.67–2.73 (m, 1 Н,
3
.7. 3,3-Dimethyl-1,5-diazaspiro(bicyclo[3.1.0]hexane-6,1'-cyclohexa-
3
2
), 2.76–2.82 (m, 1 H, CH
2
), 2.97–3.04 (m, 1 H, CH
2
), 3.51 (dd, JH,H
=
ne) (2h) was synthesized according to the General procedure 1 from
cyclohexanone (1.96 g, 20 mmol) and 2,2-dimethyl-1,3-diaminopropane
0.2 Hz, 3
J
H,H = 5.4 Hz, 1 Н, CH), 3.68 (s, 3 Н, CH
3
O), 3.75 (s, 3 Н,
3
CH
3
O), 3.80 (s, 3 Н, CH
H,H = 8.6 Hz, 2 Н, Ar); С NMR (CDCl
3
13
O), 6.86 (d,
J
H,H = 8.6 Hz, 2 Н, Ar), 7.32 (d,
, 125 MHz): = 14.7 (CH ), 21.9
), 45.2 (C), 52.0 (CH O), 52.3 (CH O), 53.5
O), 60.4 (CH ), 61.3 (C), 66.9 (CH), 113.8 (2×CH, Ar),
Me), 170.6
(
(
4.08 g, 40 mmol). Yield 1.91 g (53%); colorless liquid; R
CHCl
f
= 0.40
3
J
3
δ
3
1
3
/MeOH 10:1); bp = 88–90 °C/1 Torr; H NMR (CDCl
3
, 300 MHz):
), 1.45–
H,H = 10.4 Hz,
H,H = 10.4 Hz, 2 H, C(2)Heq, C(4)Heq);
= 23.1, 24.0, 24.1, 24.2, 25.8, 29.7, 38.4,
7.3, 58.8 (2 C), 70.4; IR (thin layer): ν = 3393, 2955, 2928, 2856, 1732,
δ
(
(
CH
CH
3 2
), 25.0 (CH ), 37.9 (CH
2
3
3
=
1
2
1.05 (s, 3 H, CH
.55 (m, 2 H, CH ), 1.55–1.65 (m, 6 H, 3×CH
H, C(2)Hax, C(4)Hax), 2.77 (d, 2
3
), 1.32 (s, 3 H, CH
3
), 1.35–1.45 (m, 2 H, CH
2
2
), 55.3 (CH
3
2
), 2.37 (d, 2
J
2
2
1
28.6 (2×CH, Ar), 135.3 (C, Ar), 159.0 (C, Ar), 170.3 (CO
2
J
(
CO
2
Me); IR (KBr) 2963, 2835, 1740, 1735, 1610, 1585, 1510, 1455,
13
С NMR (CDCl
3
, 75 MHz):
δ
-1
1
435, 1365, 1245, 1175, 1100, 1070, 1040, 915 cm ; HRMS (ESI-TOF):
5
1
+
+
m/z calcd for C20
analysis calcd (%) for C20H N O
28 2 5
6
29
H N
O
2 5
: 377.2071 [M+H] ; found: 377.2063; elemental
: C 63.81, H 7.50, N 7.44; found: C
–1
646, 1465, 1448, 1384, 1271, 1195, 1139, 1114, 1052, 954, 904 cm ;
+
+
2
HRMS (ESI-TOF): m/z calcd for C11H20NaN : 203.1519 [M+Na] ; found:
2
3.58, H 7.48, N 7.26.
03.1516.
4
.2. Dimethyl 5,5-dimethyl-8-phenyltetrahydro-1H-pyrazolo[1,2-
3
.8. 6-Ethyl-3,3-dimethyl-1,5-diazabicyclo[3.1.0]hexane (2i) was
a]pyridazine-6,6(5H)-dicarboxylate
(3b) was obtained from
synthesized according to the General procedure 1 from propanal (1.16
g, 20 mmol) and 2,2-dimethyl-1,3-diaminopropane (4.08 g, 40 mmol).
cyclopropane 1b (115 mg, 0.45 mmol) and diaziridine 2g (110 mg, 0.98
mmol) after 4 h according to the General procedure 2. Yield 97 mg
Yield 1.71 g (61%); colorless liquid; R
f
= 0.55 (CHCl
= 0.95 (t, 3JH,H = 7.5 Hz, 3 H,
), 1.38–1.50 (m, 2 H, CH ),
H,H = 10.3 Hz, 2 H, C(2)Hax
H,H = 10.3 Hz, 2 H, C(2)Heq, C(4)Heq); 13С NMR
= 9.1, 26.7, 26.9, 29.2, 52.9, 67.5 (2 C), 78.5; IR (thin
layer): ν = 3420, 2961, 2936, 2872, 2361, 2342, 1128, 1646, 1464, 1411,
3
/MeOH 10:1); bp =
1
(
57%); yellow oil; R
f
= 0.52 (petroleum ether/EtOAc 5:1); Н NMR (CDCl
3
,
1
4
5 °C/0.5 Torr; H NMR (CDCl
3
, 300 MHz):
), 1.24 (s, 3 H, CH
H,H = 5.4 Hz, 1 H, CH), 2.65 (d, 2
C(4)Hax,), 3.04 (d, 2
CDCl , 75 MHz):
δ
5
CH
H, CH
CH
9
7
00 МHz): = 1.38 (s, 3 Н, CH
δ
3 3
), 1.57 (s, 3 Н, CH ), 1.70–1.79 (m, 1 H,
CH
1
3
), 1.10 (s, 3 H, CH
3
3
2
2
), 1.82–1.89 (m, 1 H, CH
2
), 2.13–2.18 (m, 1 H, CH
2
), 2.33–2.37 (m, 2
.51 (t, 3
J
J
,
2
H,H = 10.4 Hz, 3 H,H = 8.9 Hz, 3JH,H = 7.1 Hz, 1 Н,
J
2
), 2.72 (ddd,
J
J
), 3.58 (dd, 3JH,H
2
), 2.80–2.84 (m, 1 H, CH
2
), 2.99–3.04 (m, 1 H, CH
2
=
(
3
δ
.9 Hz, 3JH,H = 5.8 Hz, 1 Н, CH), 3.69 (s, 3 Н, CH
3
O), 3.77 (s, 3 Н, CH
3
O),
.25–7.28 (m, 1 Н, Ph), 7.31–7.34 (m, 2 Н, Ph), 7.41–7.42 (m, 2 Н, Ph);
–1
1
385, 1368, 1286, 1198, 1122, 1075, 1038, 1005, 947, 903 cm ; HRMS
13
С NMR (CDCl
CH ), 45.1 (C), 52.1 (CH
C), 67.7 (CH), 127.5 (CH, Ph), 127.6 (2×CH, Ph), 128.5 (2×CH, Ph),
3
, 125 MHz):
δ
3 3 2
= 14.7 (CH ), 22.0 (CH ), 25.0 (CH ), 37.9
+
+
(
ESI-TOF): m/z calcd for C
H N
8 17 2
: 141.1386 [M+H] ; found: 141.1390.
(
(
2
3 3 2 2
O), 52.3 (CH O), 53.5 (CH ), 60.4 (CH ), 61.3
3
.9. 1,6-Diazaspiro(bicyclo[4.1.0]heptane-7,1'-cyclohexane) (2j) was
1
2
1
C
2 2
43.1 (C, Ph), 170.3 (CO Me), 170.6 (CO Me); IR (KBr) 3025, 2975,
synthesized according to the General procedure 1 from cyclohexanone
955, 2840, 1750, 1735, 1605, 1495, 1455, 1435, 1365, 1240, 1195,
(
(
1.96 g, 20 mmol) and 1,4-diaminobutane (3.53 g, 40 mmol). Yield 1.16 g
35%); colorless liquid; R
-
1
175, 1100, 1065, 1005, 915 cm ; HRMS (ESI-TOF): m/z calcd for
f
= 0.41 (CHCl
3
/MeOH 10:1); bp = 86–88 °C/1
, 300 MHz): = 1.35–1.45 (m,
), 1.70–1.85 (m, 4 H, 2×CH ), 2.45–
.60 (m, 2 H, C(2)Hax, C(5)Hax), 3.03–3.12 (m, 2 H, C(2)Heq, C(5)Heq);
+
+
[41]
1
19 27 2 4
H N O : 347.1965 [M+H] ; found: 347.1960.
Torr (lit. 66 °C/15 Torr ); H NMR (CDCl
3
δ
2
2
H, CH
2
), 1.45–1.70 (m, 8 H, 4×CH
2
2
4
.3. Dimethyl 4'-(2,3,4-trimethoxyphenyl)hexahydro-2'H-spiro[cyclo-
hexane-1,1'-pyridazino[1,2-a]pyridazine]-2',2'-dicarboxylate (3c).
= 0.41 (petroleum ether/EtOAc 2:1);
), 1.19–1.26 (m, 1
), 151–1.55 (m, 2 H, CH ), 1.64–1.69 (m,
13
3
С NMR (CDCl , 75 MHz): δ = 17.3 (2 C), 23.6, 24.2, 24.7, 26.0, 38.8,
Yield 83 mg (25%); colorless oil; R
f
3
1
9.5 (2 C), 63.4; IR (thin layer): ν = 3355, 2934, 3857, 1658, 1448, 1388,
1
Н NMR (CDCl
), 1.40–1.47 (m, 3 H, CH
H, CH ), 1.77–1.95 (m, 4 H, CH
Hz, 1 Н, CH ), 2.33–2.35 (m, 1 Н, CH
2.2 Hz, 1 Н, CH
.92–2.97 (m, 1 H, CH
.75 (s, 3 Н, CH O), 3.86 (s, 3 Н, CH
O), 4.99 (dd, 3JH,H = 12.2 Hz,
3 2
, 500 МHz): δ = 1.06–1.12 (m, 1 H, CH
–1
314, 1247, 1184, 1122, 1077, 1014, 951, 905 cm ; MS (70 eV): m/z
H, CH
2
2
2
2
+
+
+
(
%): 166 (47) [М] , 165 (30) [М–Н] , 151 (13) [М−CH
2
−H] , 137 (52)
), 2.28 (dd, JH,H = 14.0 Hz, 3JH,H = 2.9
2
2
2
+
+
+
[
[
[
М−2×CH
М−5×CH
N−N−CH] , 97], 28 (100) [N
2
–H] , 123 (22) [М−3×CH
] , 81 (43) [М−6×CH
2
–H] , 110 (39) [М−4×CH
2
] , 96 (20)
), 2.61 (dd, 2JH,H = 14.0 Hz, 3JH,H
2
2
=
+
−H]+, 70 (46) [(CH
]+, 41 (97)
2
] ; HRMS (ESI-TOF): m/z calcd for
2
+
2
+
2 5
)
1
2
3
2
), 2.56–2.61 (m, 1 H, CH
), 3.04–3.10 (m, 1 H, CH
O), 3.89 (s, 3 Н, CH
3
2
), 2.70–2.76 (m, 1 H, CH
), 3.66 (s, 3 Н, CH
O), 3.90 (s, 3
H,H = 2.9 Hz, 1 Н, CH), 6.72 (d,
2
),
3
O),
2
2
18NaN +
: 189.1362 [M+Na] ; found: 189.1368.
+
C
10
H
2
3
3
3
Н, CH
3
J
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
3JH,H = 8.7 Hz, 1 Н, CH, Ar), 7.19 (d, 3
NMR (CDCl , 125 MHz): = 18.9 (CH
), 26.47 (CH ), 30.0 (CH ), 32.5 (CH
CH), 49.5 (CH ), 52.4 (CH O), 52.5 (CH O), 56.2 (CH
CH O), 61.9 (CH O), 63.9 (CH), 108.4 (CH, Ar), 123.2 (CH, Ar), 128.9
C, Ar), 142.2 (C, Ar), 152.2 (C, Ar), 152.3 (C, Ar), 170.9 (CO Me), 171.8
CO Me); IR (KBr): ν = 2920, 2850, 1752, 1735, 1720, 1600, 1495, 1465,
J
H,H = 8.7 Hz, 1 Н, CH, Ar); 13
), 21.6 (CH ), 22.0 (CH ), 26.45
), 37.3 (C), 38.2 (CH ), 42.9
O), 59.0 (C), 61.0
С
the General procedure 2. Yield 105 mg (70%); colorless oil; R
= 0.28
f
1
3
δ
2
2
2
(petroleum ether/EtOAc 2:1); Н NMR (CDCl
3
, 500 МHz):
), 2.78–2.90 (m, 2 H, CH
O), 3.69 (s, 3 Н, CH
O), 3.88 (t, JH,H = 7.3 Hz, 1 Н, CH), 6.69 (br. s, 1 Н, CH=N),
δ
= 2.38–2.53
), 3.52 (t,
O), 3.75
(
(
(
(
(
CH
2
2
2
2
2
(m, 3 Н, CH
2
), 2.70–2.78 (m, 1 H, CH
2
2
3
2
3
3
3
J
H,H = 7.3 Hz, 1 Н, CH), 3.65 (s, 3 Н, CH
3
3
3
3
3
(s, 3 Н, CH
3
3
3
2
6.82 (br. d, J = 7.4 Hz, 2 Н, CH, Ar), 7.16 (br. d, JH,H = 7.4 Hz, 2 Н, CH,
13
2
Ar); С NMR (CDCl
49.6 (CH ), 52.4 (2×CH
129.7 (2×CH, Ar), 130.9 (C, Ar), 142.8 (CH=N), 159.1 (C, Ar), 169.9
3
, 125 MHz):
δ
= 33.3 (CH
2 2
), 33.7 (CH ), 49.3 (CH),
-
1
1
350, 1285, 1225, 1170, 1100, 1020, 970, 910 cm ; HRMS (ESI-TOF):
2
3 3
O), 55.2 (CH O), 65.1 (CH), 113.6 (2×CH, Ar),
+
+
m/z calcd for C26H38KN
O
2 7
: 529.2311 [M+K] ; found: 529.2314.
(
1
CO
2
Me), 170.0 (CO
2
Me); IR (KBr): ν = 3125, 3010, 2955, 2930, 2850,
4
.4. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(p-tolyl)ethyl]malo-
-1
735, 1610, 1510, 1405, 1385, 1275, 1115, 1030, 935 cm ; HRMS (ESI-
nate (4a) was obtained from cyclopropane 1a (150 mg, 0.60 mmol) and
diaziridine 2a (230 mg, 1.50 mmol) after 5 h according to the General
+
+
TOF): m/z calcd for C17
elemental analysis calcd (%) for C17
.16; found: C 59.88, H 7.02, N 8.02.
H N
22 2
NaO
5
: 357.1421 [M+Na] ; found: 357.1420;
H
22
N O
2
5
·0.5H O: C 59.46, H 6.75, N
2
procedure 2. Yield 116 mg (61%); beige oil; R
ether 1:1); 1Н NMR (CDCl
, 500 МHz): = 2.32 (s, 3 Н, CH
+ 2 H, C(4')H ), 2.75–2.82 (m, 1 Н, C(5')H
+ C(3)H H,H = 6.9 Hz, 1 Н,
), 3.55 (dd, 3JH,H = 7.8 Hz, 3
O), 3.72 (s, 3 Н, CH O), 3.91–3.96 (m, 1 Н,
C(4)H), 6.75 (br. s, 1 Н, C3'), 7.11–7.14 (m, 2 Н, C(3'')H + C(5'')H, Ar),
f
= 0.47 (EtOAc/petroleum
), 2.43–2.56
), 2.84–2.94
8
3
δ
3
(
(
m, 1Н, C(3)H
m, 2 Н, C(5')H
2
2
2
4.8. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(3,4-dimethoxy-
phenyl)ethyl]malonate (4e) was obtained from cyclopropane 1e (110
mg, 0.37 mmol) and diaziridine 2a (114 mg, 0.75 mmol) after 3 h
according to the General procedure 2. Yield 88 mg (65%); beige oil; R
0.18 (petroleum ether/EtOAc 4:1); Н NMR (CDCl
2.46 (m, 1 Н, CH
2.83–2.89 (m, 2 Н, CH
3.70 (s, 3 Н, CH
3
2
2
J
C(2)H), 3.68 (s, 3 Н, CH
3
3
f
=
1
3
1
7
2
5
.15–7.18 (m, 2 Н, C(2'')H + C(6'')H, Ar); С NMR (CDCl
1.2 (CH ), 33.5 (C(4')H ), 33.7 (C(3)H ), 49.4 (C(2)H), 49.7 (C(5')H
2.6 (2×CH
3
, 125 MHz):
δ
=
),
3
, 500 МHz):
δ
= 2.40–
3
2
2
2
2
), 2.47–2.51 (m, 2 Н, CH
2
), 2.74–2.79 (m, 1 Н, CH
O),
O), 3.87 (t,
2
),
3
3
O), 65.6 (C(4)H), 128.7 (C(2'')H, C(6'')H), 129.1 (C(3'')H,
Me),
Me); IR (KBr): ν = 2955, 2845, 1750, 1735, 1435, 1285, 1265,
2
), 3.54 (t, JH,H = 7.4 Hz, 1 Н), 3.66 (s, 3 Н, CH
3
C(5'')H), 135.8 (C(1'')), 137.5 (C(4'')), 143.4 (C(3')H), 170.0 (CO
1
1
2
3
O), 3.83 (s, 3 Н, CH
3
O), 3.84 (s, 3 Н, CH
3
3
70.1 (CO
2
J
H,H = 7.4 Hz, 1 Н, CH), 6.72 (br. s, 1 Н, CH=N), 6.76 (dd, JH,H = 8.3 Hz,
-
1
4JH,H = 1.5 Hz, 1 Н, CH, Ar), 6.78 (d, JH,H = 8.3 Hz, 1 Н, CH, Ar), 6.82 (d,
4JH,H = 1.5 Hz, 1 Н, CH, Ar); 13С NMR (CDCl
, 125 MHz): = 33.4 (CH ),
33.8 (CH ), 49.2 (CH), 49.6 (CH ), 52.4 (2×CH O), 55.8 (CH O), 55.9
(CH O), 65.5 (CH), 110.7 (CH), 111.4 (CH), 121.0 (CH), 131.5 (C), 142.8
CH=N), 148.5 (C), 148.9 (C), 169.8 (CO Me), 170.0 (CO Me); IR (KBr):
3
230, 1155, 1020, 935 cm ; HRMS (ESI-TOF): m/z calcd for
NaO +
: 341.1472 [M+Na] ; found: 341.1480; elemental analysis
+
δ
C
17
H
22
N
2
4
3
2
calcd (%) for C17
7
22
H N
2 4
O : C 64.13, H 6.97, N 8.80; found: C 63.84, H
2
2
3
3
.16, N 8.49.
3
(
2
2
4
.5. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethyl]malo-
ν = 3120, 3000, 2955, 2840, 1750, 1735, 1590, 1515, 1435, 1260, 1235,
1
nate (4b) was obtained from cyclopropane 1b (115 mg, 0.49 mmol) and
diaziridine 2a (224 mg, 1.47 mmol) after 8 h according to the General
procedure 2. Yield 94 mg (63%); beige oil; R
-1
+
150 cm ; HRMS (ESI-TOF): m/z calcd for C18
H N
25 2
O
6
: 365.1707
+
[
M+H] ; found: 365.1702; elemental analysis calcd (%) for
f
= 0.52 (EtOAc/petroleum
18 24 2 6 2
C H N O ·H O: C 56.54, H 6.85, N 7.33; found: C 56.74, H 6.62, N
7
1
ether 1:1); Н NMR (CDCl
3
, 500 МHz)
), 2.87–2.97 (m, 2 Н, CH
δ
= 2.48–2.60 (m, 3 Н, CH
2
), 2.79–
.06.
3
2
.84 (m, 1 Н, CH
CH), 3.70 (s, 3 Н, CH
CH), 6.77 (br. s, 1 Н, CH=N), 7.28–7.35 (m, 5 Н, Ph); 13С NMR (CDCl
25 MHz): = 33.6 (CH ), 33.7 (CH ), 49.4 (CH), 49.8 (CH ), 52.6
2×CH O), 65.9 (CH), 127.9 (CH, Ph), 128.4 (2×CH, Ph), 128.8 (2×CH,
Ph), 138.9 (C, Ph), 142.5 (CH=N), 169.9 (CO Me), 170.1 (CO Me); IR
KBr): ν = 2955, 2845, 1750, 1735, 1435, 1285, 1265, 1230, 1155, 1020,
2
2
), 3.60 (t, JH,H = 7.3 Hz, 1 Н,
3
3
O), 3.74 (s, 3 Н, CH
3
O), 3.99 (t, JH,H = 7.5 Hz, 1 Н,
4.9. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(4-dimethylamino-
phenyl)ethyl]malonate (4f) was obtained from cyclopropane 1f (190 mg,
0.69 mmol) and diaziridine 2a (209 mg, 1.37 mmol) after 4 h according to
the General procedure 2. Yield 158 mg (66%); colorless oil, darkens on
standing; R
МHz):
N(CH
Н, CH
3
,
1
(
δ
2
2
2
3
1
2
2
f
= 0.51 (petroleum ether/EtOAc 2:1); Н NMR (CDCl
3
, 500
(
9
δ
= 2.44–2.53 (m, 3 Н, СH
2 2
), 2.79–2.95 (m, 3 H, СH ), 2.94 (s, 6 Н,
-
1
+
3
35 cm ; HRMS (ESI-TOF): m/z calcd for
16 21
C H N
O
2 4
:
305.1496
3
)
2
), 3.58 (t, JH,H = 7.3 Hz, 1 Н, CH), 3.69 (s, 3 Н, CH
3
O), 3.77 (s, 3
H,H = 8.5 Hz, 2 Н,
J
H,H = 8.5 Hz, 2 Н, Ar); 13С NMR
+
3
3
[
M+H] ; found: 305.1501.
3
O), 3.90 (t, JH,H = 7.5 Hz, 1 Н, CH), 6.68 (d,
J
3
Ar), 6.73 (br. s, 1 Н, CH=N), 7.14 (d,
CDCl , 125 MHz): = 33.4 (CH
9.6 (CH ), 52.45 (CH O), 52.46 (CH
C), 129.5 (2×CH), 142.6 (CH), 150.1 (C), 170.0 (CO
4
.6. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(4-fluorophenyl)-
(
4
(
(
1
3
δ
2
), 33.7 (CH
O), 65.2 (CH), 112.3 (2×CH), 126.5
Me), 170.2
Me); IR (KBr) ν = 3100, 3025, 2800, 1750, 1735, 1610, 1525, 1405,
2 3
), 40.6 (2×NCH ), 49.5 (CH),
ethyl]malonate (4c) was obtained from cyclopropane 1c (190 mg, 0.75
mmol) and diaziridine 2a (229 mg, 1.50 mmol) after 5 h according to the
2
3
3
2
General procedure 2. Yield 111 mg (46%); colorless oil; R
f
= 0.59
= 2.40–2.46
), 2.69–2.75 (m, 1 H, CH ), 2.82–
O),
CO
2
(
(
EtOAc/petroleum ether 1:1); 1Н NMR (CDCl
m, 1 Н, CH
3
, 500 МHz):
δ
-1
270, 1155, 1065, 1020, 945 cm ; HRMS (ESI-TOF): m/z calcd for
2
), 2.47–2.55 (m, 2 Н, CH
2
2
+
+
C
18
H
25 3 4
N NaO : 357.1421 [M+Na] ; found: 357.1420.
3
2
3
.89 (m, 2 H, CH
2
), 3.55 (t, JH,H = 7.4 Hz, 1 Н, CH), 3.67 (s, 3 Н, CH
3
3
.70 (s, 3 Н, CH
3
O), 3.94 (t, JH,H = 7.5 Hz, 1 Н, CH), 6.70–6.71 (m, 1 Н,
4.10.
Dimethyl
2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(3,4,5-
(4g) was obtained from
3
3
3
CH=N), 6.98 (dd, J = 8.7 Hz, JH,F = 8.7 Hz, 2 Н, CH, Ar), 7.23 (dd, J =
8
trimethoxyphenyl)ethyl]malonate
.7 Hz, JH,F = 5.5 Hz, 2 Н, CH, Ar); 13С NMR (CDCl
4
δ
= 33.4
cyclopropane 1g (975 mg, 3.00 mmol) and diaziridine 2a (916 mg, 6.01
mmol) after 3 h according to the General procedure 2. Yield 639 mg
3
, 125 MHz):
(
CH
2
), 33.7 (CH
15.2 (d, 2
34.8 (d, 4
2
), 49.2 (CH), 49.7 (CH
2
), 52.5 (2×CH
3
O), 65.0 (CH),
3
= 0.32 (petroleum ether/EtOAc 2:1); 1Н NMR
), 2.52–2.56 (m, 2 Н, CH ),
), 3.56 (t, JH,H = 7.5 Hz, 1 Н, CH), 3.68 (s, 3 Н,
O), 3.81 (s, 3 Н, CH O), 3.82 (s, 6 Н, 2×CH O),
1
1
J
C,F = 21 Hz, 2×CH, Ar), 130.3 (d,
J
C,F = 8 Hz, 2×CH, Ar),
C,F = 246 Hz, C,
Me); IR (KBr): ν = 3120, 3030, 2955,
(54%); light-yellow oil; R
(CDCl , 500 МHz): = 2.40–2.45 (m, 1 Н, CH
2.78–2.92 (m, 3 H, CH
CH O), 3.71 (s, 3 Н, CH
3.85 (t, JH,H = 7.5 Hz, 1 Н, CH), 6.49 (s, 2 Н, CH, Ar), 6.76 (br. s, 1 Н,
CH=N); 13С NMR (CDCl
, 125 MHz): = 33.5 (CH ), 33.9 (CH ), 49.2
(CH), 49.8 (CH ), 52.53 (CH O), 52.54 (CH O), 56.1 (2×CH O), 60.8
O), 66.1 (CH), 105.4 (2×CH, Ar), 134.9 (C, Ar), 137.3 (С, Ar), 143.1
CH=N), 153.1 (2×C, Ar), 169.9 (CO Me), 170.0 (CO Me); IR (thin layer):
f
J
C,F = 3 Hz, C, Ar), 143.0 (CH=N), 162.3 (d, 1
J
3
δ
2
2
3
Ar), 169.8 (CO
2
2
Me), 169.9 (CO
2
2
-
1
845, 1750, 1735, 1605, 1510, 1405, 1270, 1160, 1015 cm ; HRMS
3
3
3
3
+
+
3
(
ESI-TOF): m/z calcd for C16
2
H19FN NaO
4
: 345.1221 [M+Na] ; found:
: C 59.62, H 5.94,
3
45.1223; elemental analysis calcd (%) for C16
H
19FN
2
O
4
3
δ
2
2
N 8.69; found: C 59.72, H 5.66, N 8.64
2
3
3
3
(
(
CH
3
4
.7. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(4-methoxyphe-
nyl)ethyl]malonate (4d) was obtained from cyclopropane 1d (120 mg,
.45 mmol) and diaziridine 2a (173 mg, 1.13 mmol) after 4 h according to
2
2
ν = 2995, 2955, 2840, 1750, 1735, 1590, 1505, 1460, 1435, 1425, 1325,
0
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
-
1
1
1
270, 1240, 1150, 1125, 1045, 1010 cm ; HRMS (ESI-TOF): m/z calcd
(petroleum ether/EtOAc 2:1); Н NMR (CDCl
3
, 500 МHz):
δ
= 2.57–2.61
+
+
2
3
3
for C19
H
26
N
2
NaO
7
: 417.1632 [M+Na] ; found: 417.1635.
(m, 2 Н, CH
2
), 2.86 (ddd, JH,H = 14.0 Hz, JH,H = 7.5 Hz, JH,H = 6.4 Hz, 1
Н, CH
2
), 2.84 (ddd, 2JH,H = 14.0 Hz, 3
J
H,H = 8.9 Hz, 3
), 3.73 (s, 3 Н, CH O), 3.74 (s, 3 Н, CH
3
J
H,H = 7.0 Hz, 1 Н,
O),
4
.11. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(2,3,4-trimethoxy-
CH
2
), 2.99–3.10 (m, 2H, CH
2
3
phenyl)ethyl]malonate (4h) was obtained from cyclopropane 1h (111
mg, 0.34 mmol) and diaziridine 2a (130 mg, 0.86 mmol) after 4 h
according to the General procedure 2. Yield 103 mg (77%); cream solid;
.76 (dd, 3JH,H = 7.5 Hz, JH,H = 7.0 Hz, 1 Н, CH), 4.52 (dd, 3JH,H = 8.9 Hz,
3
3
3
J
H,H = 6.4 Hz, 1 Н, CH), 6.61 (br. s, 1 Н, CH, Ar), 6.77 (br. s, 1 Н, CH=N),
3
7
.19–7.28 (m, 2 H, CH, Ar), 7.47 (br. d, JH,H = 8.1 Hz, 1 Н, CH, Ar), 7.53
1
R
f
= 0.32 (petroleum ether/EtOAc 2:1); mp = 103–104 °C; Н NMR
br. d, JH,H = 7.6 Hz, 1 Н, CH, Ar); 13С NMR (CDCl
3
(
(
3
, 125 MHz):
), 49.0 (CH), 52.7 (2×CH O), 58.8 (CH),
05.5 (CH, Ar), 111.4 (CH, Ar), 121.1 (CH, Ar), 122.8 (CH, Ar), 124.1
CH, Ar), 128.1 (C, Ar), 143.4 (CH=N), 154.8 (C, Ar), 155.5 (C, Ar), 169.7
δ = 31.0
(
CDCl
3
, 500 МHz):
δ
= 2.35–2.41 (m, 1 Н, CН
), 2.84–2.90 (m, 1 Н, CH
), 3.61 (t, JH,H = 7.1 Hz, 1 H, CH), 3.68 (s, 3 Н, CH
3
O), 3.83 (s, 3 Н, CH
.39 (t, 3JH,H = 7.5 Hz, 1 Н, CH), 6.64 (d, 3
2
), 2.46–2.52 (m, 2 Н, CH
), 3.04–3.09 (m, 1 Н,
O), 3.69 (s, 3 Н,
O), 3.84 (s, 3 Н, CH O),
H,H = 8.7 Hz, 1 Н, CH, Ar),
2
),
CH
2
), 33.8 (CH
2
), 48.5 (CH
2
3
2
CH
CH
4
6
.60–2.67 (m, 1 H, CH
2
2
1
3
2
3
(
(
O), 3.82 (s, 3 Н, CH
3
3
3
CO
2
Me), 169.9 (CO
2
Me); IR (KBr): ν = 3110, 3030, 2955, 2930, 2845,
750, 1735, 1580, 1455, 1435, 1275, 1255, 1155, 1060, 1010, 935 cm ;
HRMS (ESI-TOF): m/z calcd for C18
found: 367.1254; elemental analysis calcd (%) for C18
J
-1
1
3
H,H = 8.7 Hz, 1 Н, CH, Ar); 13С NMR
), 33.5 (CH ), 49.3 (CH), 50.3 (CH ),
O), 56.8 (CH), 60.7 (CH O), 61.1
.70 (br. s, 1 Н, CH=N), 7.06 (d,
, 125 MHz): = 33.4 (CH
2.39 (CH O), 52.40 (CH O), 55.9 (CH
O), 107.4 (CH, Ar), 123.4 (CH, Ar), 124.9 (C, Ar), 141.7 (C, Ar),
42.6 (CH=N), 152.4 (C, Ar), 152.8 (C, Ar), 169.96 (CO Me), 170.00
Me); IR (KBr): ν = 3120, 2995, 2955, 2840, 1750, 1735, 1600, 1465,
J
+
+
H
20
N
2
NaO
5
: 367.1264 [M+Na] ;
: C 62.78,
(
CDCl
3
δ
2
2
2
20 2 5
H N O
5
3
3
3
3
H 5.85, N 8.13; found: C 62.69, H 5.87, N 7.98.
(
CH
3
1
2
4.15.
Dimethyl
2-[2-(1-benzyl-1H-indol-4-yl)-2-(4,5-dihydro-1H-
(
CO
2
pyrazol-1-yl)ethyl]malonate (4l) was obtained from cyclopropane 1l
(180 mg, 0.50 mmol) and diaziridine 2a (189 mg, 1.24 mmol) after 4 h
according to the General procedure 2. Yield 124 mg (57%); colorless
-
1
1
for
435, 1290, 1225, 1155, 1095, 1030 cm ; HRMS (ESI-TOF): m/z calcd
+
+
C H N
19 26 2
NaO
7
:
417.1632 [M+Na] ; found: 417.1631; elemental
: C 57.86, H 6.64, N 7.10; found: C
1
analysis calcd (%) for C19
5
H N
26 2
O
7
oil; R
= 2.49–2.57 (m, 2 Н, CH
CH
Н, CH
Н, CH
f
= 0.33 (petroleum ether/EtOAc 2:1); Н NMR (CDCl
3
, 500 МHz):
δ
7.86, H 6.59, N 6.85.
2
), 2.68–2.73 (m, 1 Н, CH
), 3.63 (t, JH,H = 7.3 Hz, 1 Н, CH), 3.66 (s, 3
O), 4.44 (t, JH,H = 7.2 Hz, 1 Н, CH), 5.32 (s, 2
2
), 2.89–2.93 (m, 2 H,
3
2
), 3.09–3.15 (m, 1 Н, CH
2
4
.12. Dimethyl
2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(5-methyl-
3
3
O), 3.71 (s, 3 Н, CH
3
thiophen-2-yl)ethyl]malonate (4i) was obtained from cyclopropane 1i
200 mg, 0.78 mmol) and diaziridine 2a (196 mg, 1.97 mmol) after 3 h
according to the General procedure 2. Yield 200 mg (79%); yellow oil;
= 0.53 (petroleum ether/EtOAc 2:1); 1Н NMR (CDCl
, 500 МHz):
.43 (d, 4JH,H = 1.1 Hz, 3 Н, CH
), 2.47–2.59 (m, 3 Н, CH ), 2.74–2.80 (m,
Н, CH ), 2.84–2.97 (m, 2 Н, CH
), 3.66 (dd, 3 H,H = 7.6 Hz, 3JH,H = 7.0
O), 3.73 (s, 3 Н, CH
O), 4.36 (dd, 3JH,H
3
2
), 6.74 (d,
J
H,H = 3.3 Hz, 1 Н, CH, Ar), 6.79 (br. s, 1 Н, CH=N),
.13–7.18 (m, 4 H, CH, Ar), 7.23–7.25 (m, 1 H, CH, Ar), 7.26–7.34 (m, 4
(
7
13
H, CH, Ar); С NMR (CDCl
CH), 50.3 (CH ), 50.5 (CH
09.1 (CH, Ar), 119.0 (CH, Ar), 121.6 (CH, Ar), 127.0 (2×CH, Ar), 127.7
CH, Ar), 128.1 (CH, Ar), 131.8 (C, Ar), 128.8 (2×CH, Ar), 131.8 (C, Ar),
36.6 (C, Ar), 137.5 (C, Ar), 142.5 (CH=N), 170.0 (CO Me), 170.1
CO Me); IR (KBr): ν = 3030, 2955, 2845, 1750, 1735, 1605, 1510, 1495,
3
, 125 MHz):
δ
= 33.5 (CH
2 2
), 33.6 (CH ), 49.5
R
f
3
δ =
(
2
2
), 52.4 (2×CH
3
O), 63.8 (CH), 100.6 (CH, Ar),
2
1
3
2
1
(
1
2
2
J
Hz, 1 Н, CH), 3.72 (s, 3 Н, CH
8
Н, CH
CH=N); 13С NMR (CDCl
3
3
=
2
.5 Hz, JH,H = 7.0 Hz, 1 Н, CH), 6.58 (dd, 3JH,H = 3.4 Hz, 4JH,H = 1.1 Hz, 1
3
(
1
C
2
Th), 6.67 (d, 3
J
H,H = 3.4 Hz, 1 Н, CH, Th), 6.77–6.78 (m, 1 Н,
, 125 MHz): = 15.4 (CH ), 33.6 (CH ), 34.3
), 49.2 (CH), 52.5 (CH O), 52.6 (CH O), 60.6 (CH),
24.3 (CH, Th), 126.6 (CH, Th), 138.9 (C, Th), 140.0 (C, Th), 143.4
Me), 170.0 (CO Me); IR (KBr): ν = 3060, 3000, 2955,
845, 1750, 1735, 1580, 1435, 1345, 1155, 1045, 935 cm ; HRMS (ESI-
,
-1
435, 1290, 1275, 1155 cm ; HRMS (ESI-TOF): m/z calcd for
3
δ
3
2
+
+
25
H
27
N
3
NaO
4
: 456.1894 [M+Na] ; found: 456.1895; elemental analysis
·0.33 H O: C 68.32, H 6.35; found: C 68.19, H
(
CH
2
), 49.2 (CH
2
3
3
27
calcd (%) for C25H N
O
3 4
2
1
6
.20.
(
CH=N), 169.8 (CO
2
2
-
1
2
4.16.
Dimethyl
(E)-2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-4-(4-
+
+
TOF): m/z calcd for C15
elemental analysis calcd (%) for C15
found: C 55.27, H 6.15, N 8.45.
21
H N
O
2 4
S : 325.1217 [M+H] ; found: 325.1207;
methoxyphenyl)but-3-en-1-yl]malonate (4m) was obtained from
cyclopropane 1m (200 mg, 0.69 mmol) and diaziridine 2a (262 mg, 1.72
mmol) after 4 h according to the General procedure 2. Yield 149 mg
20 2 4
H N O
S: C 55.54, H 6.21, N 8.64;
(
(
2
3
60%); colorless oil; R
CDCl , 500 МHz): = 2.34–2.40 (m, 1 Н, CH
.97–3.07 (m, 2H, CH ), 3.53–3.98 (m, 1 Н, CH), 3.69 (s, 3 Н, CH
.71–3.74 (m, 1 Н, CH), 3.73 (s, 3 Н, CH
f
= 0.20 (petroleum ether/EtOAc 2:1); 1Н NMR
), 2.57–2.66 (m, 3 Н, CH ),
O),
O), 5.94
4
.13. Dimethyl 2-[2-(4,5-dihydro-1H-pyrazol-1-yl)-2-(5-methylfuran-2-
3
δ
2
2
yl)ethyl]malonate (4j) was obtained from cyclopropane 1j (115 mg, 0.48
mmol) and diaziridine 2a (184 mg, 1.21 mmol) after 5 h according to the
General procedure 2. Yield 110 mg (74%); light yellow oil; R
2
3
3
O), 3.80 (s, 3 Н, CH
3
f
= 0.36
= 2.23 (d,
), 2.68 (ddd, 2JH,H = 14.1
), 2.85–2.91 (m, 1 H, CH ),
3
3
3
(
dd, JH,H = 16.0 Hz, JH,H = 8.7 Hz, 1 Н, CH=), 6.42 (d, JH,H = 16.0 Hz, 1
1
(
4
petroleum ether/EtOAc 2:1); Н NMR (CDCl
J
3
, 500 МHz):
δ
3
Н, CH=), 6.78 (br. s, 1 Н, CH=N), 6.85 (br. d, JH,H = 8.7 Hz, 2 Н, CH, Ar),
7
3
(
1
H,H = 1.1 Hz, 3 Н, CH
3
), 2.47–2.57 (m, 3 Н, CH
H,H = 7.3 Hz, 1 Н, CH
2
.30 (br. d, JH,H = 8.7 Hz, 2 Н, CH, Ar); 13С NMR (CDCl
3
3
, 125 MHz):
), 52.5 (2×CH O), 55.4
O), 63.9 (CH), 114.5 (2×CH), 125.4 (CH), 127.7 (2×CH), 129.4 (C),
33.4 (CH), 143.5 (CH), 159.4 (C), 170.0 (CO Me), 170.1 (CO Me); IR
δ =
Hz, 3 H,H = 8.9 Hz, 3
2
J
J
2
2
2.8 (CH
2
), 33.5 (CH
2
), 49.0 (CH), 49.3 (CH
2
3
3
.94–3.00 (m, 1 H, CH
2
), 3.66 (t, JH,H = 7.3 Hz, 1 Н, CH), 3.71 (s, 6 Н,
CH
3
2
×CH
3
O), 4.25 (dd, JH,H = 8.9 Hz, 3
3
J
H,H = 6.8 Hz, 1 Н, CH), 5.86 (dd,
2
2
3
4
3
J
H,H = 3.0 Hz, JH,H = 1.1 Hz, 1 Н, CH, Fu), 6.05 (d, JH,H = 3.0 Hz, 1 Н,
(
1
KBr): ν = 3120, 3000, 2955, 2840, 1735, 1610, 1510, 1435, 1270, 1155,
CH, Fu), 6.73 (br. s, 1 Н, CH=N); 13С NMR (CDCl
, 125 MHz):
), 49.0 (CH), 52.5 (CH
O), 58.4 (CH), 106.0 (CH, Fu), 109.4 (CH, Fu), 143.1 (CH=N), 150.7
Me), 169.9 (CO Me); IR (KBr): ν =
105, 2955, 2845, 1750, 1735, 1555, 1435, 1345, 1310, 1155, 1020,
δ
= 13.7
3
-1
+
030, 975 cm ; HRMS (ESI-TOF) m/z calcd for C19
25
H N
O
2 5
: 361.1758
: C
(
(
(
CH
CH
3
), 31.0 (CH
2
), 33.6 (CH
2
), 48.2 (CH
2
3
O), 52.6
+
[
M+H] ; found: 361.1759; elemental analysis calcd (%) for C19
H
24
N
2
O
5
3
6
3.32, H 6.71, N 7.77; found: C 63.31, H 6.62, N 7.62.
C, Fu), 151.8 (C, Fu), 169.7 (CO
2
2
3
9
3
4.17. Dimethyl
2-[2-(4,4-dimethyl-4,5-dihydro-1H-pyrazol-1-yl)-2-
-
1
+
60, 935 cm ; HRMS (ESI-TOF): m/z calcd for
C
15
H N
20 2
NaO
5
:
phenylethyl]malonate (4n) was obtained from cyclopropane 1b (115 mg,
0.44 mmol) and diaziridine 2h (157 mg, 0.87 mmol) after 4 h according to
+
31.1264 [M+Na] ; found: 331.1272; elemental analysis calcd (%) for
C
15
H
20
N
2
O
5
: C 58.43, H 6.54, N 9.09; found: C 58.30, H 6.31, N 9.09.
the General procedure 2. Yield 18 mg (12%); beige oil; R
f
= 0.49
1
(
petroleum ether/EtOAc 4:1); Н NMR (CDCl
3
, 500 МHz):
δ = 1.04 (s, 3 Н,
4
.14. Dimethyl 2-[2-(benzofuran-2-yl)-2-(4,5-dihydro-1H-pyrazol-1-
yl)ethyl]malonate (4k) was obtained from cyclopropane 1k (230 mg,
.84 mmol) and diaziridine 2a (319 mg, 2.10 mmol) after 5 h according to
the General procedure 2. Yield 107 mg (37%); pale-yellow oil; R = 0.38
), 2.61 (d, 2JH,H = 9.0 Hz,
CH
3
), 1.08 (s, 3 Н, CH
3
), 2.43–2.49 (m, 1 Н, CH
2
2
1
3
3
2
Н, CH ), 2.65 (d, JH,H = 9.0 Hz, 1 Н, CH
2
), 2.87–2.93 (m, 1 Н, CH ),
2
0
3
.58 (t, JH,H = 7.3 Hz, 1 Н, CH), 3.70 (s, 3 Н, CH
3
O), 3.74 (s, 3 Н, CH
3
O),
f
3
.93 (t, JH,H = 7.4 Hz, 1 Н, CH), 6.48 (br. s, 1 Н, CH=N), 7.28–7.29 (m, 3
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
Н, Ph), 7.32–7.35 (m, 2 Н, Ph); 13С NMR (CDCl
, 125 MHz):
δ
= 24.0
O), 63.9
), 65.7 (CH), 127.8 (CH, Ph), 128.4 (2×CH, Ph), 128.6 (2×CH, Ph),
Me), 170.1 (CO Me); IR (KBr): ν
3030, 2955, 2870, 1755, 1740, 1605, 1585, 1495, 1455, 1435, 1265,
1110, 1035, 965, 945 cm ; HRMS (ESI-TOF): m/z calcd for
-1
3
+
+
(
(
CH
3
3 2
), 24.1 (CH ), 33.7 (CH ), 46.3 (C), 49.3 (CH), 52.6 (2×CH
3
18
C H
24
N
2
NaO
5
: 371.1577 [M+Na] ; found: 371.1578.
CH
2
4
.21.
Dimethyl
2-{2-[5,6-dihydropyridazin-1(4H)-yl]-2-(2,3,4-
1
=
1
C
39.3 (C, Ph), 151.4 (CH=N), 170.0 (CO
2
2
trimethoxyphenyl)ethyl}malonate (5c) was obtained from
cyclopropane 1h (220 mg, 0.68 mmol) and diaziridine 2j (226 mg, 1.36
mmol) after 4 h according to the General procedure 2 together with
-
1
235, 1155, 1065, 1030, 910 cm ; HRMS (ESI-TOF): m/z calcd for
+
+
18 2 4
H24KN O : 371.1368 [M+K] ; found: 371.1365.
product of (3+3)-annulation 3c. Yield 133 mg (48%); a light-yellow oil; R
f
1
4
.18. Dimethyl 2-[2-(4,4-dimethyl-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-
methoxyphenyl)ethyl]malonate (4o) was obtained from cyclopropane
d (120 mg, 0.44 mmol) and diaziridine 2h (159 mg, 1.14 mmol) after 4 h
= 0.10 (petroleum ether/EtOAc 1:2); Н NMR (CDCl
3
, 500 МHz):
), 2.31 (ddd, 2JH,H = 14.0
), 2.50–2.55 (m, 1 H, CH ),
), 2.86–
), 3.67 (dd, 3JH,H = 8.2 Hz, 3JH,H = 6.4 Hz, 1 Н, CH), 3.73
δ =
1.76–1.81 (m, 1 H, CH
2
), 1.93–2.02 (m, 3 H, CH
2
3
3
1
Hz,
J
H,H = 8.2 Hz,
J
H,H = 6.0 Hz, 1 Н, CH
2
2
2
3
3
according to the General procedure 2. Yield 30 mg (19%); yellow oil; R
f
2.85 (ddd, JH,H = 14.0 Hz, JH,H = 9.6 Hz, JH,H = 6.4 Hz, 1 Н, CH
2
1
=
0.38 (petroleum ether/EtOAc 4:1); Н NMR (CDCl
3
, 500 МHz):
), 2.61 (d, 2JH,H
), 2.84–2.90 (m, 1 Н,
O), 3.74 (s, 3 Н,
O), 3.89 (t, JH,H = 7.5 Hz, Hz, 1 Н, CH), 6.46 (br.
δ
= 1.04
2.90 (m, 1 H, CH
2
(
s, 3 Н, CH
3
), 1.07 (s, 3 Н, CH
3
), 2.40–2.46 (m, 1 Н, CН
), 2.63 (d, JH,H = 9.0 Hz, 1 Н, CH
2
=
(s, 6 Н, 2×CH
J
3
O), 3.85 (s, 3 Н, CH
H,H = 9.6 Hz, 3JH,H = 6.0 Hz, 1 Н, CH), 6.65 (d, JH,H = 8.7 Hz, 1 Н, CH,
3
O), 3.87 (s, 6 Н, 2×CH
3
O), 4.44 (dd,
2
3
3
9
.0 Hz, 1 Н, CH
2
2
3
3
H,H = 8.7 Hz, 1 Н, CH, Ar); 13
), 23.2 (CH ), 32.2 (CH ), 47.0
O), 58.2 (CH), 60.7 (CH O),
CH
CH
2
), 3.56 (t, JH,H = 7.3 Hz, 1 Н, CH), 3.69 (s, 3 Н, CH
3
Ar), 6.65 (br. s, 1 Н, CH=N), 7.12 (d,
NMR (CDCl , 125 MHz): = 19.9 (CH
(CH ), 49.5 (CH), 52.4 (2×CH O), 55.9 (CH
61.3 (CH O), 107.2 (CH, Ar), 122.8 (CH, Ar), 125.7 (C, Ar), 138.2
(CH=N), 141.7 (C, Ar), 152.0 (C, Ar), 152.7 (C, Ar), 170.1 (CO Me),
170.2 (CO Me); IR (KBr): ν = 2920, 2850, 1750, 1720, 1600, 1490, 1450,
1350, 1290, 1230, 1170, 1100, 1020, 970, 910 cm ; HRMS (ESI-TOF):
J
С
3
3
O), 3.81 (s, 3 Н, CH
3
3
3
δ
2
2
2
s, 1 Н, CH=N), 6.86 (d, JH,H = 8.7 Hz, 2 Н, Ar), 7.20 (d, 3JH,H = 8.7 Hz, 2
2
3
3
3
Н, Ar); 13С NMR (CDCl
, 125 MHz):
), 46.2 (C), 49.4 (CH), 52.5 (CH O), 52.6 (CH
), 65.1 (CH), 113.7 (2×CH, Ar), 129.7 (2×CH, Ar), 131.3 (C, Ar),
Me), 170.1 (CO Me); IR (thin
layer) 2955, 2870, 2840, 1755, 1740, 1610, 1585, 1515, 1460, 1435,
δ
= 24.0 (CH
), 33.7
3
3
), 24.1 (CH
3
3
(
(
CH
CH
2
3
3
O), 55.3 (CH
3
O), 63.8
2
2
2
-
1
1
51.3 (CH=N), 159.1 (C, Ar), 170.0 (CO
2
2
+
+
m/z calcd for C20H N
28 2
NaO
7
: 431.1789 [M+Na] ; found: 431.1786.
-
1
1
345, 1290, 1250, 1205, 1180, 1160, 1035, 910 cm ; HRMS (ESI-TOF):
+
+
4.22. Dimethyl
2-[2-(tetrahydropyridazin-1(2H)-yl)-2-(2,3,4-
m/z calcd for C19
analysis calcd (%) for C19H N O
26 2 5
27
H N
O
2 5
: 363.1914 [M+H] ; found: 363.1923; elemental
: C 62.97, H 7.23, N 7.73; found: C
trimethoxyphenyl)ethyl]malonate (6) was isolated as mixture with 5c in
1
ratio 87:13; Н NMR (CDCl
3
, 500 МHz):
), 1.53–1.79 (m, 3 H, CH
), 2.11 (ddd, JH,H = 13.8 Hz, 3JH,H = 7.5 Hz, JH,H = 6.1 Hz, 1 Н, CH
δ
= 1.06–1.16 (m, 1 H, CH
2
),
6
3.21, H 7.53, N 7.54.
1
CH
.38–1.45 (m, 1 H, CH
2
2
), 1.98–2.09 (m, 1 H,
2
3
4
.19. Dimethyl 2-{2-[5,6-dihydropyridazin-1(4H)-yl]-2-phenylethyl}-
2
2
),
malonate (5а) was obtained from cyclopropane 1b (145 mg, 0.62 mmol)
and diaziridine 2j (206 mg, 1.24 mmol) after 4 h according to the General
1.98–2.09 (m, 1 H, CH
2
), 2.57–2.70 (m, 1 H, CH
2
), 2.74 (ddd, 2JH,H = 13.8
),
O), 3.79
O), 4.05 (dd, 3JH,H
H,H = 8.7 Hz, 1 Н, CH, Ar),
, 125MHz): = 25.2
), 49.7 (CH), 52.4 (CH O), 52.5
O), 58.9 (CH), 60.8 (CH O), 61.2 (CH O),
3
3
Hz,
J
H,H = 9.6 Hz,
J
H,H = 6.6 Hz, 1 Н, CH
O), 3.71 (s, 3 Н, CH
O), 3.85 (s, 3 Н, CH
2 2
), 2.82–2.97 (m, 2H, CH
procedure 2. Yield 87 mg (44%); colorless oil; R
f
= 0.20 (petroleum
3.69–3.71 (m, 1 Н, CH), 3.69 (s, 3 Н, CH
(s, 3 Н, CH
3
3
1
3
ether/EtOAc 2:1); Н NMR (CDCl , 500 МHz):
δ
= 1.79–1.84 (m, 1 H,
3
O), 3.84 (s, 3 Н, CH
3
3
=
2
3
H,H = 5.7 Hz, 1 Н, CH), 6.65 (d, 3
CH
=
2
), 1.89–1.97 (m, 1 H, CH
2
), 1.99–2.03 (m, 2 H, CH
H,H = 5.9 Hz, 1 Н, CH
), 2.59 (ddd, 2
), 2.68 (ddd, 2JH,H = 11.0
H,H = 14.0 Hz,
2
), 2.43 (ddd, JH,H
9.7 Hz,
J
J
14.0 Hz, 3
J
H,H = 7.9 Hz, 3
J
J
=
6.97 (d, JH,H = 8.7 Hz, 1 Н, CH, Ar); 13С NMR (CDCl
3
δ
2
H,H
3
1
1.0 Hz, JH,H = 9.5 Hz, 3JH,H = 3.5 Hz, 1 H, CH
3
2
(CH
2
), 26.5 (CH
O), 55.2 (CH
2
), 31.5 (CH
), 56.0 (CH
2
), 47.1 (CH
2
3
3
H,H = 5.7 Hz, 3
), 2.89 (ddd, 2
Hz,
J
J
H,H = 4.0 Hz, 1 H, CH
H,H = 6.7 Hz, 1 Н, CH
), 3.68 (dd, 3JH,H = 7.9 Hz, 3
O), 3.74 (s, 3 Н, CH
2
J
(CH
3
2
3
3
3
3
H,H = 9.8 Hz, 3
J
J
2
J
H,H
3
=
106.9 (CH, Ar), 122.9 (C, Ar), 123.4 (CH, Ar), 142.1 (C), 152.8 (C, Ar),
152.9 (C, Ar), 170.3 (CO Me), 170.6 (CO Me).
6
=
5
3
.7 Hz, 1 Н, CH), 3.73 (s, 3 Н, CH
3
3
O), 4.05 (dd, JH,H
2
2
3
9.8 Hz, JH,H = 5.9 Hz, 1 Н, CH), 6.67 (br. s, 1 Н, CH=N), 7.27–7.34 (m,
Н, CH, Ph); 13С NMR (CDCl
2.1 (CH ), 46.3 (CH ), 49.5 (CH), 52.5 (2×CH
3
3
, 125 MHz):
δ
= 19.9 (CH
O), 67.2 (CH), 127.6 (CH,
Me),
2
Me); IR (KBr): ν = 2990, 2950, 2850, 1740, 1725, 1605, 1580,
2 2
), 23.3 (CH ),
2
2
Acknowledgments
Ph), 128.2 (4×CH, Ph), 138.3 (CH=N), 139.7 (C, Ph), 170.1 (CO
2
1
1
70.3 (CO
450, 1425, 1290, 1255, 1120, 1050, 940 cm ; elemental analysis calcd
: C 63.13, H 6.97, N 8.80; found: C 63.55, H 7.15, N
-
1
We thank the Russian Science Foundation (grant 17-73-10404)
for financial support of this work.
(
%) for C17
22
H N
2
O
4
8
.41.
4
.20. Dimethyl 2-{2-[5,6-dihydropyridazin-1(4H)-yl]-2-(4-methoxyphe-
Keywords: diaziridines • donor-acceptor cyclopropanes •
nyl)ethyl}malonate (5b) was obtained from cyclopropane 1d (178 mg,
.68 mmol) and diaziridine 2j (224 mg, 1.35 mmol) after 4 h according to
the General procedure 2. Yield 182 mg (77%); colorless oil; R = 0.23
= 1.79–1.84
), 1.99–2.02 (m, 2 H, CH ), 2.41
), 2.56–2.61
H,H = 14.0 Hz, 3
), 3.65 (dd, 3JH,H = 7.6 Hz, 3
H,H = 6.7
O), 3.74 (s, 3 Н, CH O), 3.81 (s, 3 Н,
nitrogen heterocycles • small ring systems
0
f
[
[
[
1]
2]
3]
E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57,
0257-10274.
D. Petrov, C. Mansfield, A. Moussy, O. Hermine, Front. Aging Neurosci.
017, 9, art. 68.
(
(
(
(
EtOAc/petroleum ether 1:1); 1Н NMR (CDCl
, 500 МHz): δ
3
1
m, 1 H, CH
2
), 1.89–1.97 (m, 1 H, CH
2
2
ddd, JH,H = 14.0 Hz, 3JH,H = 7.6 Hz, JH,H = 6.1 Hz, 1 Н, CH
2
3
2
2
m, 1 H, CH
2
), 2.64–2.68 (m, 1 H, CH
2
), 2.85 (ddd, 2
J
J
H,H
Y. Miyaji, S. Yoshimura, N. Sakai, H. Yamagami, Y. Egashira, M.
=
9.5 Hz, 3
J
H,H = 6.7 Hz, 1 Н, CH
2
J
Shirakawa, K. Uchida, H. Kageyama, Y. Tomogane, Neurol. Med.-chir.
Hz, 1 Н, CH), 3.73 (s, 3 Н, CH
3
3
2
015, 55, 241-247.
O), 3.99 (dd, JH,H = 9.5 Hz, 3JH,H = 6.1 Hz, 1 Н, CH), 6.66 (br. s, 1 Н,
3
CH
3
[
[
4]
5]
J. B. Bussel, G. Cheng, M. N. Saleh, B. Psaila, L. Kovaleva, B. Meddeb,
J. Kloczko, H. Hassani, B. Mayer, N. L. Stone, M. Arning, D. Provan, J.
M. Jenkins, New Eng. J. Med. 2007, 357, 2237-2247.
3
3
CH=N), 6.85 (d, JH,H = 8.7 Hz, 2 Н, CH, Ar), 7.23 (d, JH,H = 8.7 Hz, 2 Н,
CH, Ar); 13С NMR (CDCl
, 125 MHz): = 19.9 (CH ), 23.3 (CH ), 32.1
), 49.5 (CH), 52.6 (2×CH O), 55.3 (CH O), 66.6 (CH),
13.5 (2×CH, Ar), 129.3 (2×CH, Ar), 131.6 (C, Ar), 138.5 (CH=N), 159.0
Me), 170.3 (CO Me); IR (KBr): ν = 3000, 2955, 2910,
835, 1750, 1735, 1610, 1585, 1510, 1435, 1325, 1250, 1175, 1155,
3
δ
2
2
(
CH
2
), 46.2 (CH
2
3
3
J. G. McHutchison, G. Dusheiko, M. L. Shiffman, M. Rodriguez-Torres,
S. Sigal, M. Bourliere, T. Berg, S. C. Gordon, F. M. Campbell, D.
Theodore, N. Blackman, J. Jenkins, N. H. Afdhal, New Eng. J. Med.
1
(
C, Ar), 170.2 (CO
2
2
2
2
007, 357, 2227-2236.
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European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
[
[
6]
7]
P. Wangemann, R. Braitsch, R. Greger, Pflügers Arch. 1987, 410, 674-
76.
25, 1-10; e) F. De Nanteuil, F. De Simone, R. Frei, F. Benfatti, E.
Serrano, J. Waser, Chem. Commun. 2014, 50, 10912-10928; f) T. F.
Schneider, J. Kaschel, D. B. Werz, Angew. Chem. 2014, 126, 5608-
5628; Angew. Chem. Int. Ed. 2014, 53, 5504-5523; g) M. A. Cavitt, L. H.
Phun, S. France, Chem. Soc. Rev. 2014, 43, 804-818.
6
a)) M. R. Iyer, R. Cinar, A. Katz, M. Gao, K. Erdelyi, T. Jourdan, N. J.
Coffey, P. Pacher, G. Kunos, J. Med. Chem. 2017, 60, 1126-1141; b) A.
van Loevezijn, J. Venhorst, W. I. I. Bakker, C. G. de Korte, W. de Looff,
S. Verhoog, J.-W. van Wees, M. van Hoeve, R. P. van de Woestijne, M.
A. W. van der Neut, A. J. M. Borst, M. J. P. van Dongen, N. M. W. J. de
Bruin, H. G. Keizer, C. G. Kruse, J. Med. Chem. 2011, 54, 7030-7054;
c) S. R. Donohue, V. W. Pike, S. J. Finnema, P. Truong, J. Andersson,
B. Gulyas, C. Halldin, J. Med. Chem. 2008, 51, 5608-5616.
[18] For the synthesis of D–A cyclopropanes, see: a) Y. V. Tomilov, L. G.
Menchikov, R. A. Novikov, O. A. Ivanova, I. V. Trushkov, Russ. Chem.
Rev. 2018, 87, 201-250; b) b) M. Yu, B. L. Pagenkopf, Tetrahedron
2005, 61, 321-347; c) H.-U. Reissig, R. Zimmer, Chem. Rev. 2003, 103,
1151-1196.
[
[
8]
9]
a) N. S. Rao, A. B. Shaik, S. R. Routhu, S. M. A. Hussaini, S. Sunkari,
A. V. S. Rao, M. Reddi, A. Alarifi, A. Kamal, Chem. Select 2017, 2,
[19] N. N. Makhova, A. V. Shevtsov, V. Yu. Petukhova, Russ. Chem. Rev.
2011, 80, 1035-1066.
2989-2996; b) M. Yusuf, A. Kaur, M. Abid, J. Heterocycl. Chem. 2017,
[20] A. O. Chagarovskiy, V. S. Vasin, V. V. Kuznetsov, O. A. Ivanova, V. B.
Rybakov, A. N. Shumsky, N. N. Makhova, I. V. Trushkov, Angew.
Chem. 2018, 130, 10495-10499; Angew. Chem. Int. Ed. 2018, 57,
10338-10342.
54, 2536-2547; c) A. Özdemir, M. D. Altintop, Z. A. Kaplancikli, G.
Turan-Zitouni, H. Karaca, Y. Tunali, Arch. Pharm. 2013, 346, 463-469;
d) H. Deng, Z.-Y. Yu, G.-Y. Shi, M.-J. Chen, K. Tao, T.-P. Hou, Chem.
Biol. Drug Des. 2012, 79, 279-289.
[21] See Supporting information for details. CCDC 1904821 contains the
supplementary crystallographic data for compound 4h. These data can
be obtained free of charge from The Cambridge Crystallographic Data
Centre.
a) S. Kaur, P. Kumari, G. Singh, R. Bhatti, P. Singh, ACS Omega 2018,
3
, 5825-5845; b) S. Carradori, D. Secci, A. Bolasco, C. De Monte, M.
Yanez, Arch. Pharm. Chem. Life Sci. 2012, 345, 973-979.
10] F. Hayat, A. Salahuddin, S. Umar, A. Azam, Eur. J. Med. Chem. 2010,
5, 4669-4675.
[
[
[22] X-ray data for 1-tert-butyl-2,3-dihydropyrazole p-toluenesulfonate, 1-
tosyl- and 1-(2,4-dinitrophenyl)-2,3-dihydropyrazoles were reported: a)
S. V. Usachev, G. A. Nikiforov, K. A. Lyssenko, Yu. V. Nelyubina, P. A.
Levkin, R. G. Kostyanovsky, Tetrahedron: Asymmetry 2007, 18, 1540-
1547; b) A. V. Shevtsov, A. A. Kislukhin, V. V. Kuznetsov, V. Yu.
Petukhova, V. A. Maslennikov, A. O. Borissova, K. A. Lyssenko, N. N.
Makhova, Mendeleev Commun. 2007, 17, 119-121; c) G. P. A. Yap, I.
Alkorta, N. Jagerovic, J. Elguero, Aust. J. Chem. 2004, 57, 1103-1108.
[23] a) Y. S. Syroeshkina, V. V. Kuznetsov, K. A. Lyssenko, N. N. Makhova,
Russ. Chem. Bull. 2009, 58, 366–379; b) Y. B. Koptelov, Russ. J. Org.
Chem. 2006, 42, 1510–1515.
4
11] a) M. Khambete, H. Kundaikar, A. Raju, S. Lonkar, M. Degani, M. K.
Ray, Chem. Biol. Drug Des. 2019, 93, 84-88; b) U. S. Goksen, S.
Sarigul, P. Bultinck, W. Herrebout, I. Dogan, K. Yelekci, G. Ucar, N. G.
Kelekci, Chirality 2019, 31, 21-33; c) J. Stefaniak, A. M. Lewis, D.
Conole, S. R. G. Galan, C. J. R. Bataille, G. M. Wynne, M. P. Castaldi,
T. Lundbäck, A. J. Russell, K. V. M. Huber, ACS Chem. Biol. 2018, 13,
2849-2854; d) C. Yamali, H. I. Gul, A. Ece, P. Taslimi, I. Gulcin, Chem.
Biol. Drug Des. 2018, 91, 854-866; e) J. Cao, J. Zang, C. Ma, X. Li, J.
Hou, J. Li, Y. Huang, W. Xu, B. Wang, Y. Zhang, ChemMedChem 2018,
1
3, 431-436; f) N. Kahriman, Z. Hasimoglu, V. Serdaroglu, F. S. Beris,
[24] S. Z. Vatsadze, Yu. D. Loginova, G. dos Passos Gomes, I. V. Alabugin,
Chem. Eur. J. 2017, 23, 3225-3245.
B. Barut, N. Yayli, Arch. Pharm. Chem. Life Sci. 2017, 350, 1600285.
12] a) G. Rychen, G. Azimonti, V. Bampidis, M. de Lourdes Bastos, G.
Bories, A. Chesson, P. S. Cocconcelli, G. Flachowsky, J. Gropp, B.
Kolar, M. Kouba, S. Lopez Puente, M. Lopez-Alonso, A. Mantovani, B.
Mayo, F. Ramos, M. Saarela, R. E. Villa, R. J. Wallace, P. Wester, L. G.
Costa, A.-K. Lundebye, D. Renshaw, O. Holczknecht, M. V. Vettori, G.
Aquilina, EFSA J. 2016, 14, e4613; b) K. Hunger, P. Mischke, W.
Rieper, R. Raue, A. Engel, in Azo Dyes. Ullmann’s Encyclopedia of
Industrial Chemistry. Wiley-VCH, 2005, pp. 1-93.
[
[25] a) E. R. Rakhmankulov, K. L. Ivanov, E. M. Budynina, O. A. Ivanova, A.
O. Chagarovskiy, D. A. Skvortsov, G. V. Latyshev, I. V. Trushkov, M.
Ya. Melnikov, Org. Lett. 2015, 17, 770-773; b) H. Xiong, H. Xu, S. Liao,
Z. Xie, Y. Tang, J. Am. Chem. Soc. 2013, 135, 7851-7854.
[26] a) O. A. Ivanova, A. O. Chagarovskiy, A. N. Shumsky, V. D. Krasnobrov,
I. I. Levina, I. V. Trushkov, J. Org. Chem. 2018, 83, 543-560; b) A. O.
Chagarovskiy, O. A. Ivanova, A. N. Shumsky, I. V. Trushkov, Chem.
Heterocycl. Comp. 2017, 53, 1220-1227.
[
[
13] D. K. An, H.-M. Kim, M. S. Kim, S. K. Kang, J. D. Ha, S. S. Kim, J.-K.
Choi, J. H. Anh, Heterocycles 2004, 63, 2379-2383.
[27] R. Talukdar, D. P. Tiwari, A. Saha, M. K. Ghorai, Org. Lett. 2014, 16,
3954-3957.
14] a) C. J. Thomson, D. M. Barber, D. J. Dixon, Angew. Chem. 2019, 131,
[28] T. Kanzian, T. A. Nigst, A. Maier, S. Pichl, H. Mayr, Eur. J. Org. Chem.
2009, 6379-6385.
2491-2495; Angew. Chem. Int. Ed. 2019, 58, 2469-2473; b) Y.-L.
Zhang, B.-Y. Li, R. Yang, L.-Y. Xia, A-L. Fan, Y.-C. Chu, L.-J. Wang, Z.-
[29] E. L. Handy, K. A. Totaro, C. P. Lin, J. K. Sello, Org. Lett. 2014, 16,
3488-3491.
C. Wang, A.-Q. Jiang, H.-L. Zhu, Eur. J. Med. Chem. 2019, 163, 896-
9
10; c) A. C. Tripathi, S. Upadhyay, S. Paliwal, S. K. Saraf, Med. Chem.
[30] J. P. Kennedy, J. T. Brogan, C. W. Lindsley, Tetrahedron Lett. 2008, 49,
4116-4118.
Res. 2018, 27, 1485-1503.
[
15] a) H. Dai, M. Huang, J. Qian, J. Liu, C. Meng, Y. Li, G. Ming, T. Zhang,
S. Wang, Y. Shi, Y. Yao, S. Ge, Y. Zhang, Y. Ling, Eur. J. Med. Chem.
[31] K. Makino, H. Jiang, T. Suzuki, Y. Hamada, Tetrahedron: Asymmetry
2006, 17, 1644-1649.
2
019, 166, 470-479; b) H. Majed, T. Johnston, C. Kelso, E. Monachino,
[32] Yu. B. Koptelov, A. P. Molchanov, R. R. Kostikov, Russ. J. Org. Chem.
2000, 36, 1025-1026.
[33] a) Y. Ju, R. S. Varma, J. Org. Chem. 2006, 71, 135-141; b) Y. Ju, R. S.
Varma, Tetrahedron Lett. 2005, 46, 6011-6014.
S. Jergic, N. E. Dixon, E. Mylonakis, M. J. Kelso, Bioorg. Med. Chem.
Lett. 2018, 28, 3526-3528; c) A. Thupyai, C. Pimpasri, S. Yotphan, Org.
Biomol. Chem. 2018, 16, 424-432.
[
[
16] For synthesis of such pyrazolines, see: a) S. Xiao, J. T. Davis, Chem.
Commun. 2018, 54, 11300-11303; b) J. Zhang, Y. Zhang, X. Liu, J.
Guo, W. Cao, L. Lin, X. Feng, Adv. Synth. Catal. 2014, 356, 3545-3550;
c) K. Weinhardt, M. B. Wallach, M. Marx, J. Med. Chem. 1985, 28, 694-
[34] O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H.
Puschmann, J. Appl. Cryst. 2009, 42, 339-341.
[35] E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc. 1965, 87, 1353-1364.
[36] W. Fraser, C. J. Suckling, H. C. S. Wood J. Chem. Soc., Perkin Trans.
1 1990, 3137-3144.
698; d) J. Hine, W.-S. Li, J. Org. Chem. 1975, 40, 289-292.
17] For selected recent reviews, see: a) B. L. Pagenkopf, N. Vemula, Eur. J.
Org. Chem. 2017, 2561-2567; b) Isr. J. Chem. 2016, 56, № 6-7,
thematic issues devoted to D–A cyclopropanes and cyclobutanes; c) H.
K. Grover, M. R. Emmett, M. A. Kerr, Org. Biomol. Chem. 2015, 13,
[37] Y. V. Vishnevskiy, J. Schwabedissen, A. N. Rykov, V. V. Kuznetsov, N.
N. Makhova, J. Phys. Chem. А, 2015, 119, 10871-10881.
[38] G. V. Shustov, S. N. Denisenko, I. I. Chervin, N. L. Afsandiarov, R. G.
Kostyanovsky, Tetrahedron 1985, 41, 5719-5731.
655-671; d) R. A. Novikov, Y. V. Tomilov, Mendeleev Commun. 2015,
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900579
FULL PAPER
[
39] J.-Q. Chen, Y. Mi, Z.-F. Shi, X.-P. Cao, Org. Biomol. Chem. 2018, 16,
801-3808.
[40] A. N. Terpigorev, V. P. Kuznetsova, N. E. Uvarova, A. G. Bazanov,
3
Russ. J. Appl. Chem. 1999, 72, 2103-2107.
[
41] S. F. Nelsen, P. J. Hintz, J. Am. Chem. Soc. 1972, 94, 7108-7113.
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Nitrogen Heterocycles
A. O. Chagarovskiy, V. V. Kuznetsov, O.
A. Ivanova,* A. S. Goloveshkin, I. I.
Levina, N. N. Makhova, I. V. Trushkov*
Page No. – Page No.
A simple and efficient methodology for the synthesis of 1-alkyl-2,3-dihydropyrazoles
and the corresponding tetrahydropyridazines has been proposed. In this process
bicyclic diaziridines were used as synthetic equivalent of difficultly accessible
unsubstituted 2,3-dihydropyrazole and unstable unsubstituted tetrahydropyridazine.
Synthesis of 1-Substituted
Pyrazolines by Reaction of Donor-
Acceptor Cyclopropanes with 1,5-
Diazabicyclo[3.1.0]hexanes
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