A new reaction of 1,2-di- and 1,2,3-trialkyldiaziridines: Ring expansion under the action of diethyl acetylenedicarboxylate in ionic liquids

Article abstract of DOI:10.1002/jhet.204

(Chemical Equation Presented) New reaction of diaziridine ring expansion resulting in diethyl 1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate derivatives was discovered under the action of diethyl acetylenedicarboxylate on 1,2-di- and 1,2,3-trialkyldiaziri

Full text of DOI:10.1002/jhet.204

November 2009
A New Reaction of 1,2-Di- and 1,2,3-Trialkyldiaziridines: Ring
Expansion under the Action of Diethyl Acetylenedicarboxylate
in Ionic Liquids
1195
Yuliya S. Syroeshkina, Vladimir V. Kuznetsov, Vadim V. Kachala,
and Nina N. Makhova*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation
*E-mail: mnn@ioc.ac.ru
Received April 16, 2009
DOI 10.1002/jhet.204
Published online 5 November 2009 in Wiley InterScience (www.interscience.wiley.com).
New reaction of diaziridine ring expansion resulting in diethyl 1,2,3,6-tetrahydropyrimidine-4,5-dicar-
boxylate derivatives was discovered under the action of diethyl acetylenedicarboxylate on 1,2-di- and
1,2,3-trialkyldiaziridines in ionic liquids.
J. Heterocyclic Chem., 46, 1195 (2009).
INTRODUCTION
[8–11]. Moreover, absolutely unexpected heterocyclic
structures were built in those solvents in some cases.
For example, derivatives of earlier unknown infused
1,2,4,6-tetrazepan-5-thione were obtained in one prepa-
rative step by an interaction of 1,2-dialkyldiaziridines 1
with benzoylisothiocyanate in 1-butyl-3-methylimidazi-
lium tetrafluoroborate ([bmim][BF4]) or hexafluorophos-
phate ([bmim][PF6]) [8].
Over a few last years, new simple approaches to the
construction of different nitrogen-containing heterocyclic
systems have been developed in our laboratory. These
are based on the strained diaziridine ring transformation
in readily available [1,2] 1,2-dialkyldiaziridines 1 and
1,5-diazabicyclo[3.1.0]hexanes 2 under the action of
electrophilic reagents, in particular, dipolarophiles.
Herein, the diaziridine ring is capable of opening on the
CAN or NAN bonds to generate dipolar intermediates
prone to cycloaddition reactions (so-called ring expan-
sion reactions) resulting in other heterocyclic structures
[3–10].
We continued examining ring expansion reactions of
monocyclic 1,2-dialkyldiaziridines 1 with dipolarophiles
in ionic liquids within this research effort. As a dipolar-
ophile dialkyl esters of acetylenedicarboxylic acid were
selected. The reaction between 1,2-dialkyldiaziridine
derivatives and dimethyl acetylenedicarboxylate in ben-
zene had been described in literature [12]. The authors
of this study have found out that the interaction of these
compounds resulted in only linear products 7 and 8 and
the diaziridine ring opening occurred on the NAN bond.
The research on this reaction mechanism was assisted
by labeled atoms (D). On the basis of the obtained com-
pounds structure authors of the work [12] assumed that
the first reaction step was the formation of dipolar inter-
mediates 9. Where one of the substituents at nitrogen
atoms of initial diaziridine 1a was benzyl, intermediate
9a was stabilized by a proton split-off from the CH2
group of the benzyl fragment followed by the generation
of enamine 7. If one of the substituents at nitrogen
atoms was Ph (1b), intermediate 9b was stabilized by
proton breaking from the C(3)-carbon atom of the
Arylketenes [3–6], aroyliso- and aroylisothiocyanates
[7,8], carbon disulfide [9,10], and activated nitriles
[10,11] were investigated as dipolarophiles. Thus, the
reaction of arylketenes with 1,2-dialkyldiaziridines 1
resulted in 5-aryl-1,3-dialkylimidazolidin-4-ones 3 and
with 1,5-diazabicyclo[3.1.0]hexanes 2—in heterocyclic
compounds of two kinds—1-(arylacetyl)pyrazolidines 4
and 1,5-diazabicyclo[3.3.0]octan-2-ones 5 (Scheme 1).
However, these researches showed that new heterocy-
clic systems in common organic solvents could only be
achieved in reactions with highly reactive reagents—
arylketenes [3–6] and aroylisocyanates [7]. A reaction
between diaziridines 1 and 2 and the other foresaid
reagents was also performed successfully though only
with ionic liquids (ILs) used as a reaction medium
C
V
2009 HeteroCorporation

1196
Y. S. Syroeshkina, V. V. Kuznetsov, V. V. Kachala, and N. N. Makhova
Vol 46
Scheme 1
diaziridines 1 and diethyl acetylenedicarboxylate 12 as a
dipolarophyle. From a large number of ILs we picked
1-butyl-3-methylimidazolium tetrafluoroborate or hexa-
fluorophosphate ([bmim][BF4] or [bmim][PF6]). These
ionic liquids relate to room temperature ionic liquids
group (RTIL) and are one of the most accessible ones.
Note that during the reaction the reaction mixture is col-
ored orange at first and then red at reaction end.
The investigations were started with 1,2-dibutyldiazir-
idine 1c in [bmim][BF4]. At first, the equimolar quantity
of the reagents was added to the reaction. In about
30 min at 20ꢀC, the reaction was completed (as shown
by TLC) and a new compound, diethyl 1-[3-ethoxy-1-
(ethoxycarbonyl)-3-oxoprop-1-enyl]-3-buthyl-6-propyl-
1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate 13c, was
obtained in 37% yield. According to mass spectra this
contained one molecule of diaziridine 1c and two mole-
cules of diethyl acetylenedicarboxylate 12. After adding
one mole of diaziridine 1c and two moles of dipolaro-
phile 12 to the reaction, the yield of 13c became higher
ꢁ69%. This reaction was found to have a general char-
acter—compounds 13d–f were synthesized from diaziri-
dines 1d–f and dipolarophile 12 in close yields. The
reaction ran in ionic liquid [bmim][PF6] as well as in
[bmim][BF4]. Reaction rate depended on solubility of
initial diaziridines 1c–f in Ils—the shorter alkyl substitu-
ents at nitrogen atoms the higher their solubility and
rate of reaction.
diaziridine ring with further generation of product 8
(Scheme 2) [12].
Originating from the data obtained in [8–11] we
hoped that ILs as a reaction medium would change the
stabilization pathways of intermediates 9 and result in
heterocyclic structures 10 or 11 depending on CAN- or
NAN-positioned opening of the diaziridine ring in the
interaction of 1,2-dialkyldiaziridines 1 with dialkyl
esters of acetylenedicarboxylic acid (Scheme 3).
Ionic liquids have been widely used over the past years
as a potential replacement of conventional solvents for a
variety of chemical processes [13,14]. ILs have consider-
able advantages over available organic solvents—they
are fire-resistant and have limited vapor pressure thus
allowing efficient recovery of organic products. In addi-
tion, they are recyclable and can be used several times in
the same reactions. Moreover, many reactions gain accel-
eration in ILs due to stabilization of charged intermedi-
ates or ions [15–17]. The realization of different reactions
in ILs pertains to a new prospective field of organic
chemistry—‘‘green chemistry.’’
Further on, it was found that, apart from 1,2-dia-
lkyldiaziridines 1c–f, 1,2,3-trialkyldiaziridines 1g–i
were also capable of entering the reaction with diethyl
acetylenedicarboxylate 12 to produce corresponding
tetrahydropyrimidine derivatives 13g–i. However,
the latter are formed only at the replacement of
ionic liquids [bmim][BF4] or [bmim][PF6] with
[emim][HSO4] being herein both a reaction medium
and an acidic catalyst. Yields of compounds 13g–i
were also increased as affected by lengthening of the
alkyl substituents both at N and at C(3) atoms of
initial diaziridines 1g–i.
RESULTS AND DISCUSSION
1,2-Dibutyl-(1c), 1,2-dipropyl-(1d), 1,2-diethyl-(1e), 1,2-
dimethyl-(1f), 1,2,3-triethyl-(1g), 1,2-diethyl-3-methyl-(1h),
1,2-dipropyl-3-ethyl-(1i), and 3-benzyl-1,2-di(2-phenyl-
ethyl)- (1j) diaziridines were examined as initial dialkyl-
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
A New Reaction of 1,2-Di- and 1,2,3-Trialkyldiaziridines: Ring Expansion
under the Action of Diethyl Acetylenedicarboxylate in Ionic Liquids
1197
Scheme 3
Figure 1. The molecule 13d structure.
atoms. The proposed molecular structure was tetrahydro-
pyrimidine ring with substituents (Fig. 1)
The structures of compounds 13c–i were established
by aggregating elemental analysis data and spectral
characteristics (mass-spectra, IR-, NMR 1H, 13C, 15N-
spectra with use of COSY, NOESY, 1H-13C HSQC,
1
The H-13C HMBC correlations of the compound 13d
are shown in Figure 2.
The 1H-15N HMBC spectrum revealed two sp3 N-
atoms with chemical shifts of ꢁ295.1 and ꢁ291.9 ppm
(with an external reference CH3NO2, d ¼ 0.0 ppm) and
connectivity between both N-atoms and protons, which
is shown in Figure 3.
1
1H-13C HMBC, and H-15N HMBC methods). The proof
of compounds 13 structure was demonstrated on exam-
ple of compound 13d. 13C APT spectrum revealed 6
CH3 groups, 8 CH2 groups, 2 CH groups, and 7 quater-
nary carbon atoms, four of them were in the region of
The most important NOE interactions in the molecule
13d revealed in NOESY experiment (Fig. 4)
1
carboxylic carbon resonance. H spectrum was assigned
with COSY, NOESY, and HSQC 2D spectra. The inves-
tigation of these spectra showed that molecule contained
four carboethoxy, one N-propyl-, one 1-substituted N-
propyl group, one CH2 group which had no interactions
with other protons, and one sp2-CH group. 1H-13C
HMBC 2D spectral correlations allowed us to approve
the structure of these fragments and interconnections
between them, as well as positions of quaternary carbon
Cis-configuration of two carboethoxy groups near
double bond at N-1 was proved by NOE interactions H-
8/H-2 and H-6/H-12 in NOESY spectrum. Another im-
portant NOE correlation was between H-2 and H-9 also
proved the structure of this molecule.
Initial 1,2-dialkyldiaziridines 1c–i are chiral com-
pounds but they were introduced to the reaction with
diethyl acetylenedicarboxylate 12 in a racemic form.
Figure 2. 1H-13C HMBC correlations of the compound 13d.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1198
Y. S. Syroeshkina, V. V. Kuznetsov, V. V. Kachala, and N. N. Makhova
Vol 46
Figure 3. 1H-15N HMBC correlations of the compound 13d.
And the reaction evidently proceeds not stereoselec-
tively. The synthesized compounds (13c–i) contain chi-
ral carbon atoms (C(6) in 13c–f and C(2) and C(6) in
13g–i), however, 13c–f are racemates and, as seen from
the spectral characteristics, no diastereomers were fixed
in 13g–i prepared from 1,2,3-trialkyldiaziridines 1g–i.
The chemical shifts of signals NMR 1H, 13C, 15N
spectra by the example of compounds 13c, 13d, 13h are
presented in Table 1. The atom numeration is shown on
Figure 5.
new method for preparing tetrahydropyrimidine deriva-
tives and is a valuable supplement to the known syn-
thetic methods for such kind of compounds. Pyrimidines
and their analogs represent an important class of nitro-
gen heterocycles, which are components both of various
biologically active natural compounds and of diverse
drugs [18(a)]. They display antiviral [18(b)], antibacte-
rial [18(b,c)], anti-inflammatory [18(a,b)], and anti-HIV
(HIV Integrase inhibitors) activities [18(d)] and are use-
ful as inflammatory mediators in Parkinson’s disease
therapy [18(e)].
This result is in agreement with the assumed mecha-
nism of the reaction. The first step (as in ref. [12]) is
the formation of dipolar intermediate 9, however, its life
time evidently increases in ionic liquids able to solvate
both positively and negatively charged particles or mole-
cule moieties [15–17]. Therefore, the second molecule
of diethyl acetylenedicarboxylate 12 has time to enter a
reaction with intermediate 9, generating the second in-
termediate 14, which is transformed to final compound
13. Generally, the formation of compounds 13 can be
presented as two-step condensation of one molecule of
initial diaziridine 1 and two molecules of compound 12
according to Scheme 4. Unlike the transformation of in-
termediate 9 in benzene (Scheme 2), the anion of inter-
mediate 9 in ILs evidently attacks the proton of the CH2
group bound to same nitrogen atom to generate a new
anion, which in turn attacks the second molecule of
diethyl acetylenedicarboxylate 12 (Scheme 4).
The expected five-member heterocyclic compound,
i.e., diethyl 5-benzyl-1,2-bis(2-phenylethyl)-2,5-dihydro-
1H-pyrazole-3,4-dicarboxylate 15, was obtained only in
one case by the interaction of 1,2-di(2-phenylethyl)-3-
phenylmethyldiaziridine 1j with diethyl acetylenedicar-
boxylate 12 in ionic liquid [emim][HSO4] (Scheme 5).
Evidently, here, the attack of the second molecule of
dipolarophile 12 on intermediate 9j was sterically
hindered.
EXPERIMENTAL
Elemental analysis was performed by the CHN Analyzer
Perkin–Elmer 2400. The IR spectra (m, cmꢁ1) were measured
using a SPECORD-M82 spectrometer. Mass spectra were
measured using a Finnigan MAT INCOS-50 instrument. The
NMR spectra of compound 15 were recorded using a Bruker
1
AM-300 spectrometer at 300 MHz for H and 75.47 MHz for
13C Spectra in CDCl3. The NMR spectra of all compounds
13c–i were measured on Bruker AV-600 instrument with the
frequencies 600.13, 150.90, and 60.81 MHz for 1H, 13C, and
15N, correspondingly. The chemical shifts of the signals of
CDCl3 residual proton (7.27 ppm) and carbon (77.0 ppm) were
used as the internal standard. The 15N spectra were measured
with CH3NO2 (d ¼ 0.0 ppm) as the external standard. All
15N
2D-spectra were recorded using standard Bruker methods with
Z-gradient. The spectra were measured at 30ꢀC. Analytical
thin-layer chromatography (TLC) was conducted on silica gel
plates (Silufol UV-254). New compounds were purified by
flash-chromatography (column chromatography for 15) on
Thus a new unexpected transformation of 1,2-dialkyl-
diaziridines 1 under the action of diethyl acetylenedicar-
boxylate 12 in ionic liquids resulting in tetrahydropyri-
midine derivatives 13 was discovered. The reaction is a
Figure 4. The most important NOE interactions in the molecule
revealed in NOESY experiment.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
A New Reaction of 1,2-Di- and 1,2,3-Trialkyldiaziridines: Ring Expansion
under the Action of Diethyl Acetylenedicarboxylate in Ionic Liquids
1199
Table 1
Chemical shifts of 13c, 13d, 13h NMR 1H, 13C, 15N spectra.
Compounds
13c
13d
13h
Atom numbers
(Fig. 5)
1H
13C/15
N
1H
13C/15
N
1H
13C/15
N
1
2
–
4.24; 4.45
ꢁ292.2
59.1
ꢁ293.8
148.8
99.3
53.4
154.9
91.8
52.3
32.4
21.3
15.2
39.3
20.2
15.2
–
–
4.25; 4.43
ꢁ291.9
57.6
ꢁ295.2
147.5
97.9
55.0
153.6
90.2
52.7
22.1
10.9
–
–
4.48
–
–
67.5
–
3
4
–
–
–
–
–
–
146.0
106.3
47.1
150.1
91.0
45.6
14.4
–
5
–
–
6
7
4.33
–
4.22
–
4.22
–
8
9
10
11
12
4.94
3.03; 3.07
1.52
1.26
0.89
1.51; 1.76
1.34; 1.41
0.89
–
4.94
2.98; 3.04
1.55
0.85
–
4.99
3.03; 3.19
1.18
–
–
–
13
14
1.51; 1.85
0.91
–
28.6
10.1
–
1.42
–
20.0
–
15
16
–
1.36
–
4.09
1.25
–
4.32
1.33
–
–
–
–
16.9
167.2
59.6
14.2
164.5
61.9
14.3
164.7
60.2
14.4
165.5
62.1
14.2
4-COOEt
–
168.5
61.1
15.3
165.7
63.4
15.3
166.6
61.3
15.7
166.6
63.7
15.7
–
167.0
59.5
13.7
164.2
61.9
13.7
165.1
59.8
14.2
165.1
62.2
14.2
4.06
1.23
–
4.31
1.35
–
4.07
1.22
–
4.30
1.32
–
5-COOEt
7-COOEt
8-COOEt
4.14
1.22
–
4.12
1.22
–
4.17
1.27
–
4.36
1.33
4.36
1.35
4.43
1.39
Silicagel, 0.060–0.200 mm, 60 A (ACROS). Rf of all com-
pounds 13 and 15 was measured with the usage of eluent [n-
hexane-ethyl acetate, 2:1 (v/v)].
pounds (TLC-control), the reaction mixture color was changed
through the time from orange to red. After that the resulting
substituted 1,2,3,6-tetrahydropyrimidine 13 was extracted from
ionic liquid by mixture of solvents hexane and ethyl acetate
(5:1, 4–5 times by 7 mL), then the solvent was evaporated.
Final substituted 1,2,3,6-tetrahydropyrimidine 13 was purified
by the method of flash-chromatography on Silicagel with the
solvent of n-hexane and ethyl acetate (2:1).
General procedure for the synthesis of substituted
1,2,3,6-tetrahydropyrimidines by the reaction of 1,2-di- and
1,2,3-trialkyldiaziridines 1c-i with diethyl acetylenedicar-
boxylate 12 in ionic liquid. To a stirred mixture (20ꢀC) of
diaziridine 1c–i (1.0 mmol) and ionic liquid ([bmim][BF4]
or [bmim][PF6] for 1,2-dialkyldiaziridines 1c–f and
[emim][HSO4] for 1,2,3-trialkyldiaziridines 1g–i) (0.4 g),
diethyl acetylenedicarboxylate 12 (2.0 mmol) was added drop-
wise for about 1 min and the reaction mixture was stirred for
an additional 30 min to the full conversion of initial com-
Synthesis of diethyl 5-benzyl-1,2-bis(2-phenylethyl)-2,5-
dihydro-1H-pyrazole-3,4-dicarboxylate (15). To
a stirred
mixture (20ꢀC) of diaziridine 1j (1.0 mmol) and ionic liquid
([bmim][BF4] or [bmim][PF6]) (0.4 g), diethyl acetylenedicar-
boxylate 12 (1.0 mmol) was added dropwise for about 1 min
Figure 5. Atom numeration of compounds 13c, 13d, and 13h.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1200
Y. S. Syroeshkina, V. V. Kuznetsov, V. V. Kachala, and N. N. Makhova
Vol 46
Scheme 4
and the reaction mixture was stirred for an additional 48 h to
the full conversion of initial compounds (TLC-control), the
reaction mixture color was changed through the time from or-
ange to red. After that the resulting compound 15 was
extracted from ionic liquid by mixture of solvents hexane and
ethyl acetate (5:1, 6 times by 7 mL), then the solvent was
evaporated. Final compound 15 was purified by the method of
column chromatography on Silicagel with the solvent of n-hex-
ane and ethyl acetate (3:1).
(C2ringH2), 61.08 (CH3CH2OOCC4ring), 61.28 (CH3CH2OOC-
CchainN), 63.44 (CH3CH2OOCC5ring), 63.73 (CH3CH2OOC-
C
chainH), 91.79 (EtOOCCchainH), 99.26 (EtOOCC5ring), 148.85
(EtOOCC4ring), 154.90 (EtOOCCchainN), 165.72 (EtOOCCr5ing),
166.58 (EtOOCCchainH), 166.61 (EtOOCCchainN), 168.51 ppm
(EtOOCC4ring); 15N NMR: d ꢁ292.2 ppm (N1), ꢁ293.8 (N3);
ms: m/z (I, %) 496 (3, M), 467 (23, M – C2H5), 451 (5, M –
C3H7 – 2H), 438 (4, M – 2C2H5), 323 (13, M – CO2C2H5),
350 (6, M – 2CO2C2H5), 168 (15, diethyl acetilenedicarboxy-
late – 2H), 155 (71, 1,2-dibutyl diaziridine – H), 43 (100,
C3H7). Anal. Calcd for C25H40N2O8 (496.59): C, 60.47; H,
8.12; N, 5.64. Found: C, 60.44; H, 8.15; N, 5.63.
The physical and spectral data of compounds 13c–i and 15
are as follows.
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-buthyl-6-propyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarbo-
xylate (13c). This compound was obtained as yellow nondis-
tilled oil, 69% yield, Rf 0.37; IR: 668, 772, 864, 924, 1024,
1044, 1096, 1152, 1172, 1220, 1248, 1372, 1444, 1456, 1580,
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-propyl-6-ethyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxy-
late (13d). This compound was obtained as yellow nondistilled
oil, 77% yield, Rf 0.37; IR: 666, 748, 774, 864, 1024, 1046,
1098, 1154, 1222, 1246, 1372, 1446, 1462, 1580, 1700, 1738,
1
1652, 1700, 1740, 2876, 2936, 2960, 2970 cmꢁ1; H NMR: d
3
0.89 (t, 6H, CH3(CH2)3N þ CH3(CH2)2N, J ¼ 7.1 Hz), 1.22
2876, 2922, 2950, 2984 cmꢁ1
;
1H NMR: d 0.85 (t, 3H,
(t, 3H, CH3CH2OOCCchainN, 3J ¼ 7.2 Hz), 1.23 (t, 3H,
CH3(CH2)2N, J ¼ 7.2 Hz), 0.91 (t, 3H, CH3CH2C6ringH, J ¼
3
3
CH3CH2OOCC4ring
,
3J
¼
7.2 Hz), 1.26 (m, 2H,
7.3 Hz), 1.22 (t, 6H, CH3CH2OOCC4ring þ CH3CH2OOC-
3
3
CH3CH2(CH2)2N, J ¼ 7.2), 1.33 (t, 3H, CH3CH2OOCCchainH,
CchainN, J ¼ 7.2 Hz), 1.32 (t, 3H, CH3CH2OOCCr5ing
,
3J ¼
3J ¼ 7.2 Hz), 1.34, 1.41 (2m, 2H, CH3CH2CH2C6ring), 1.35 (t,
7.2 Hz), 1.35 (t, 3H, CH3CH2OOCCchainH, J ¼ 7.2 Hz), 1.51,
1.85 (2m, 2H, CH3CH2C6ring), 1.55 (m, 2H, CH3CH2CH2N),
2.98, 3.04 (2m, 2H, CH3CH2CH2N), 4.07 (m, 2H,
3
3H, CH3CH2OOCCr5ing
,
3J ¼ 7.2 Hz), 1.51, 1.76 (2m, 2H,
CH3CH2CH2C6ring), 1.52 (m, 2H, CH3CH2CH2CH2N), 3.03,
3.07 (2m, 2H, CH3(CH2)2CH2N), 4.06 (m, 2H,
CH3CH2OOCC4ring
,
3J
¼
7.2 Hz), 4.12 (m, 2H,
3
CH3CH2OOCC4ring
,
3J
¼
7.2 Hz), 4.14 (m, 2H,
CH3CH2OOCCchainN, J ¼ 7.2 Hz), 4.22 (m, 2H, C6ringH),
CH3CH2OOCCchainN, 3J ¼ 7.2 Hz), 4.24, 4.45 (dd, 2H,
4.25, 4.43 (dd, 2H, C2ringH2), 4.30 (m, 2H, CH3CH2OOCC6ring
,
C2ringH2), 4.31 (m, 2H, CH3CH2OOCC5ring
,
3J ¼ 7.2 Hz), 4.33
3J ¼ 7.2 Hz), 4.36 (m, 2H, CH3CH2OOCCchainH, 3J ¼ 7.2
3
(m, 2H, C6ringH), 4.36 (m, 2H, CH3CH2OOCCchainH, J ¼ 7.2
Hz), 4.94 ppm (s, 1H, EtOOCCchainH); 13C NMR: 15.25
(CH3(CH2)3N and CH3(CH2)2C6ring), 15.26 (CH3CH2OOCC4ring),
15.29 (CH3CH2OOCC5ring), 15.68 (CH3CH2OOCCchainN),
15.74 (CH3CH2OOCCchainH), 20.24 (CH3CH2CH2C6ring), 21.27
(CH3CH2CH2CH2N), 32.39 (CH3CH2CH2CH2N), 39.32
(C6ringCH2), 52.27 (CH3CH2CH2CH2N), 53.36 (C6ringH), 59.11
Hz), 4.94 ppm (s, 1H, EtOOCCchainH); 13C NMR:
d
10.12 (CH3CH2Cr6ing), 10.86 (CH3CH2CH2N), 13.72
(CH3CH2OOCC4ring),
13.76
(CH3CH2OOCC5ring),
14.18
(CH3CH2OOCCchainN), 14.23 (CH3CH2OOCCchainH), 22.09
(CH3CH2CH2N), 28.56 (C6ringCH2CH3), 52.67 (CH3CH2CH2N),
55.02 (C6ringH), 57.55 (Cr2ingH2), 59.51 (CH3CH2OOCCr4ing),
59.77 (CH3CH2OOCCchainN), 61.93 (CH3CH2OOCC5ring),
Scheme 5
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
A New Reaction of 1,2-Di- and 1,2,3-Trialkyldiaziridines: Ring Expansion
under the Action of Diethyl Acetylenedicarboxylate in Ionic Liquids
1201
62.16 (CH3CH2OOCCchainH), 90.23 (EtOOCCchainH), 97.90
(EtOOCC5ring), 147.46 (EtOOCCr4ing), 153.60 (EtOOCCchainN),
164.17 (EtOOCCr5ing), 165.10 (EtOOCCchainN and EtOOC-
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
2,3-diethyl-6-methyl-1,2,3,6-tetrahydropyrimidine-4,5-dicar-
boxylate (13g). This compound was obtained as yellow non-
distilled oil, 57% yield, Rf 0.38; IR: 664, 748, 782, 810, 866,
974, 1042, 1110, 1160, 1234, 1282, 1366, 1442, 1588, 1710,
C
chainH), 167.01 ppm (EtOOCC4ringN); 15N NMR: d ꢁ291.9
ppm (N1), ꢁ295.2 (N3); ms: m/z (I, %) 468 (5, M), 439 (30, M
– C2H5), 423 (4, M – C3H7 – 2H), 410 (3, M – 2C2H5), 395
(7, M – CO2C2H5), 322 (3, M – 2CO2C2H5), 168 (17, diethyl
acetilenedicarboxylate – 2H), 126 (60, 1,2-dipropyl diaziridine
– 2H), 43 (100, C3H7). Anal. Calcd for C23H36N2O8 (468.54):
C, 58.96; H, 7.74; N, 5.98. Found: C, 59.00; H, 8.11; N, 5.96.
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-ethyl-6-methyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxy-
late (13e). This compound was obtained as yellow nondistilled
oil, 65% yield, Rf 0.36; IR: 664, 752, 776, 804, 864, 1024,
1048, 1100, 1156, 1224, 1244, 1300, 1372, 1384, 1448, 1468,
1738, 2868, 2910, 2940, 2974, 2986 cmꢁ1 1H NMR: d 0.82
;
(t, 3H, CH3CH2Cr2ing
,
3J ¼ 6.35 Hz), 1.20, 1.28 (2t, 12H,
CH3CH2COO, 3J ¼ 7.33 Hz), 1.49 (m, 3H, NCH2CH3, 3J ¼
3
6.84 Hz), 1.59, 1.97 (2m, 3H, CH3C6ring, J ¼ 5.86 Hz), 1.86,
2.22 (2m, 2H, CH3CH2Cr2ing
,
3J ¼ 5.37 Hz), 3.01, 3.22 (2m,
3
2H, NCH2CH3, J ¼ 6.83 Hz), 4.11, 4.26 (2m, 10H, C6ringH,
C2ringH, 4 CH3CH2OOC), 4.79 ppm (s, 1H, EtOOCCchainH);
13C NMR:
d
10.36 (CH3CH2C2ring), 13.91, 14.27
(CH3CH2COO), 14.73 (NCH2CH3), 20.24 (C6ringCH3), 24.63
(CH3CH2C2ring), 47.34 (NCH2CH3), 63.03 (C2ringH), 59.70,
60.36, 61.99, 62.22 (CH3CH2COO), 73.57 (C6ringH), 91.10
1580, 1700, 1736, 2876, 2908, 2940, 2984 cmꢁ1; H NMR: d
1
3
1.06 (t, 3H, CH3CH2N, J ¼ 7.3 Hz), 1.13 (t, 3H, CH3Cr6ing
,
þ
(EtOOCCchainH),
108.28
(EtOOCCchainN),
145.55
3J
¼
7.5 Hz), 1.21 (t, 6H, CH3CH2OOCCchain
H
(EtOOCC4ring), 150.67 (EtOOCCr5ing), 164.78, 164.86, 165.61,
167.15 ppm (COOEt). Anal. Calcd for C23H36N2O8 (468.54):
C, 58.96; H, 7.74; N, 5.98. Found: C, 58.96; H, 7.77; N, 5.98.
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-ethyl-2,6-dimethyl-1,2,3,6-tetrahydropyrimidine-4,5-dicar-
boxylate (13h). This compound was obtained as yellow non-
distilled oil, 35% yield, Rf 0.39; IR: 668, 756, 864, 1032,
1040, 1040, 1152, 1296, 1368, 1444, 1464, 1588, 1736, 2880,
CH3CH2OOCC4ring
,
3J ¼ 7.3 Hz), 1.34 (t, 6H, CH3CH2OOC-
C5ring þ CH3CH2OOCCchainN, 3J ¼ 7.3 Hz), 3.15, 3.25 (2m, 2H,
CH3CH2N), 4.06 (m, 2H, CH3CH2OOCC4ring, 3J ¼ 7.3 Hz), 4.11
(m, 2H, CH3CH2OOCCchainH, 3J ¼ 7.3 Hz), 4.28 (m, 2H,
3
CH3CH2OOCC5ring, J ¼ 7.3 Hz), 4.35, 4.46 (dd, 2H, C2ringH2),
3
4.36 (m, 2H, CH3CH2OOCCchainN, J ¼ 7.3 Hz), 4.82 (m, 2H,
C6ringHMe), 4.83 ppm (s, 1H, EtOOCCchainH); 13C NMR: 10.33
(CH3CH2N), 13.65 (CH3CH2OOCC5ring and CH3CH2OOC-
CchainN), 13.92 (CH3CH2OOCCchainH and CH3CH2OOCC4ring),
16.02 (C6ringCH3), 41.22 (CH3CH2N), 48.97 (C6ringH), 59.41
(CH3CH2OOCC4ring), 59.55 (CH3CH2OOCCchainH), 61.32
(CH3CH2OOCC5ring), 62.31 (CH3CH2OOCCchainN), 63.98
(C2ringH2), 88.45 (EtOOCCchainH), 112.33 (EtOOCC5ring), 149.43
(EtOOCC4ringN), 151.95 (EtOOCCchainN), 163.65 (EtOOCC-
chainH), 165.16 (EtOOCCchainN), 166.78 (EtOOCC4ringN), 167.01
ppm (EtOOCC5ring); 15N NMR: d ꢁ280.3 (N1), ꢁ288.0 ppm
(N3). Anal. Calcd for C21H32N2O8 (440.49): C, 57.26; H, 7.32;
N, 6.36. Found: C, 57.30; H, 7.29; N, 6.33.
2940, 2984 cmꢁ1
;
1H NMR: d 1.18 (t, 3H, CH3CH2N, 3J ¼
3
5.37 Hz), 1.25 (t, 3H, CH3CH2OOCC4ring, J ¼ 6.35 Hz), 1.27
(t, 3H, CH3CH2OOCCchainN, 3J ¼ 6.35 Hz), 1.33 (t, 3H,
3
3
CH3CH2OOCC5ring, J ¼ 6.35 Hz), 1.36 (t, 3H, CH3C2ring, J ¼
5.86 Hz), 1.39 (t, 3H, CH3CH2OOCCchainH, 3J ¼ 6.35 Hz),
1.42 (d, 3H, CH3Cr6ing
,
3J ¼ 4.88 Hz), 3.03, 3.19 (2m, 2H,
3
CH3CH2N, J ¼ 6.84 Hz), 4.09 (qv, 2H, CH3CH2OOCCr4ing
,
3J ¼ 6.35 Hz), 4.17 (qv, 2H, CH3CH2OOCCchainN, J ¼ 6.35
Hz), 4.22 (qv, 1H, C6ringH, 3J ¼ 4.88 Hz), 4.32 (m, 2H,
3
CH3CH2OOCC5ring
,
3J
¼
6.35 Hz), 4.43 (m, 2H,
CH3CH2OOCCchainH, 3J ¼ 6.35 Hz), 4.48 (qv, 1H, C2ringH, 3J ¼
5.86 Hz), 4.99 ppm (s, 1H, EtOOCCchainH); 13C NMR: d 14.18
(CH3CH2OOCC4ring), 14.22 (CH3CH2OOCCchainH), 14.30
(CH3CH2OOCC5ring), 14.38 (CH3CH2OOCCchainN), 14.39
(CH3CH2N), 16.94 (CH3C2), 19.98 (CH3Cr6ing), 45.64
(NCH2CH3), 47.10 (C6ringH), 59.57 (CH3CH2OOCCr4ing),
60.16 (CH3CH2OOCCchainN), 61.91 (CH3CH2OOCC5ring), 62.13
(CH3CH2OOCCchainH), 67.50 (C2ringH), 91.03 (EtOOCCchainH),
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-methyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate
(13f). This compound was obtained as yellow nondistilled oil,
34% yield, Rf 0.36; IR: 664, 756, 860, 1028, 1096, 1144,
1252, 1372, 1448, 1560, 1696, 1736, 2872, 2940, 2984 cmꢁ1
;
1H NMR: d 1.06 (t, 3H, CH3CH2N, 3J ¼ 7.34 Hz), 1.13 (t,
3H, CH3CringHN, 3J ¼ 6.61 Hz), 1.21 (t, 6H, CH3CH2OOC-
CchainH, CH3CH2OOCCringNEt, 3J ¼ 5.14 Hz), 1.34 (t, 6H,
106.32
(EtOOCC5ring),
145.99
(EtOOCC4ring),
150.11
CH3CH2OOCCringCHMe, CH3CH2OOCCchainN, 3J
¼
5.87
(EtOOCCchainN), 164.52 (EtOOCC5ring), 164.75 (EtOOCCchainN),
165.53 (EtOOCCchainH), 167.17 ppm (EtOOCC4ring); ms: m/z (I,
%) 423 (3, M – OC2H5 – 2H), 381 (7, M – CO2C2H5), 366
(3, M – OC2H5 – C2H5 – 2 CH3), 243 (36, M – 2 CO2C2H5 – 2 C
– CH – CH3), 168 (100, pyrimidine þ 2 CO2), 138 (23, pyrimi-
dine þ 2 H þ2 CH3) þ C2H5), 94 (37, pyrimidine þ H þ CH3),
45 (46, C2H5). Anal. Calcd for C22H34N2O8 (454.51): C, 58.14;
H, 7.54; N, 6.16. Found: C, 58.17; H, 7.53; N, 6.16.
Diethyl 1-[3-ethoxy-1-(ethoxycarbonyl)-3-oxoprop-1-enyl]-
3-propyl-2,6-diethyl-1,2,3,6-tetrahydropyrimidine-4,5-dicar-
boxylate (13i). This compound was obtained as yellow nondis-
tilled oil, 62% yield, Rf 0.38; IR: 668, 748, 780, 808, 864, 976,
1048, 1100, 1156, 1232, 1280, 1368, 1448, 1584, 1700, 1736,
Hz), 3.15, 3.25 (2m, 2H, CH3CH2N), 4.06 (m, 2H,
CH3CH2OOCCringNEt), 4.11 (m, 2H, CH3CH2OOCCchainH),
4.28 (m, 2H, CH3CH2OOCCringCHMe), 4.35, 4.46 (dd, 2H,
C2ringH2, 2J ¼ 5.87 Hz), 4.36 (m, 2H, CH3CH2OOCCchainN),
4.82 (m, 1H, CHMe), 4.83 ppm (s, 1H, CH3CH2OOCCchainH);
13C NMR: 13.77 (CH3 in EtOOCCringCHMe and EtOOCC-
chainN), 14.23 (CH3 in EtOOCCchainH and EtOOCCringN),
16.02 (NCringHCH3), 41.22 (CH3CH2N), 48.97 (NCringHMe),
59.41 (CH2 in EtOOCCringN), 59.55 (CH2 in EtOOCCchainH),
61.32 (CH2 in EtOOCCringCHN), 62.31 (CH2 in EtOOCC-
chainN), 63.98 (NCH2N), 88.45 (EtOOCCchainH), 112.33
(EtOOCCringCHN), 149.43 (EtOOCCringN), 151.95 (EtOOCC-
chainN), 163.65 (EtOOCCchainH), 165.16 (EtOOCCchainN),
166.78 (EtOOCCringN), 167.01 ppm (EtOOCCringCHN). Anal.
Calcd for C19H28N2O8 (412.43): C, 55.33; H, 6.84; N, 6.79.
Found: C, 55.35; H, 6.84; N, 6.76.
2876, 2908, 2936, 2980 cmꢁ1
;
1H NMR: d 0.64 (t, 3H,
3
CH3CH2C2ring, J ¼ 6.84 Hz), 0.77 (t, 3H, CH3CH2CH2N), 0.79
(t, 3H, CH3CH2C6ringH), 1.16, 1.28 (2t, 12H, CH3CH2COO, 3J ¼
6.35 Hz), 1.44 (m, 2H, NCH2CH2CH3, 3J ¼ 6.84 Hz), 1.51,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1202
Y. S. Syroeshkina, V. V. Kuznetsov, V. V. Kachala, and N. N. Makhova
Vol 46
3
1.86 (2m, 2H, CH3CH2Cr6ingH, J ¼ 7.32 Hz), 1.62, 2.09 (2m,
[2] Kuznetsov, V. V.; Syroeshkina, Y. S.; Moskvin, D. I.;
Struchkova, M. I.; Makhova, N. N.; Zharov, A. A. J Heterocycl Chem
2008, 45, 497.
2H, CH3CH2C2ring
,
3J ¼ 7.33 Hz), 2.81, 3.07 (2m, 2H,
NCH2CH2, 3J ¼ 6.35 Hz), 4.11 (m, 1H, Cr6ingH), 4.24, 4.32 (2m,
3
8H, CH3CH2OOC, J ¼ 6.35 Hz), 4.27 (m, 1H, C2ringH), 4.82
[3] Shevtsov, A. V.; Petukhova, V. Y.; Strelenko, Y. A.; Lys-
senko, K. A.; Fedyanin, I. V.; Makhova, N. N. Mendeleev Commun
2003, 221.
13
ppm (s, 1H, EtOOCCchainH); C NMR: d 7.45 (CH3CH2C2ring),
10.38 (CH3CH2Cr6ing), 11.46 (CH3CH2CH2N), 14.18, 14.63
(CH3CH2COO), 22.18 (CH3CH2C2ring), 23.12 (NCH2CH2CH3),
24.22 (CH3CH2Cr6ing), 51.44 (Cr2ingH), 54.46 (NCH2CH2CH3),
59.32, 59.78, 61.94, 62.36 (CH3CH2COO), 73.94 (C6ringH),
92.16 (EtOOCCchainH), 102.96 (EtOOCCchainN), 147.94
(EtOOCC4ring), 150.08 (EtOOCCr5ing), 164.56, 167.22
[4] Shevtsov, A. V.; Petukhova, V. Y.; Strelenko, Y. A. Men-
deleev Commun 2005, 29.
[5] Shevtsov, A. V.; Petukhova, V. Y.; Strelenko, Y. A.;
Lyssenko, K. A.; Makhova, N. N.; Tartakovski, V. A. Izv Acad
Nauk Ser Khim 2005, 997 (Russ Chem Bull Int Ed 2005, 54,
1021).
(EtOOCC4ring
,
EtOOCC5ring
,
EtOOCCchainN), 165.28 ppm
[6] Shevtsov, A. V.; Kuznetsov, V. V.; Kislukhin, A. A.; Petu-
khova, V. Y.; Strelenko, Y. A.; Makhova, N. N. J Heterocycl Chem
2006, 43, 881.
(EtOOCCchainH). Anal. Calcd for C25H40N2O8 (496.59): C,
60.47; H, 8.12; N, 5.64. Found: C, 60.46; H, 8.14; N, 5.62.
Diethyl 5-benzyl-1,2-bis(2-phenylethyl)-2,5-dihydro-1H-
pyrazole-3,4-dicarboxylate (15). This compound was obtained
as yellow nondistilled oil, 47% yield, Rf 0.41; IR: 700, 752, 860,
1028, 1096, 1180, 1240, 1372, 1456, 1500, 1604, 1740, 2876,
[7] Shevtsov, A. V.; Kuznetsov, V. V.; Molotov, S. I.; Lys-
senko, K. A.; Makhova, N. N. Izv Acad Nauk Ser Khim 2006, 534
(Russ Chem Bull Int Ed 2006, 55, 554).
2940, 2984, 3028, 3064 cmꢁ1
;
1H NMR: d 1.31 (t, 6H, 2
[8] Shevtsov, A. V.; Kuznetsov, V. V.; Kislukhin, A. A.; Petu-
khova, V. Y.; Strelenko, Y. A.; Makhova, N. N. Mendeleev Commun
2006, 218.
3
3
CH3CH2OOC, J ¼ 6.33 Hz), 2.92 (m, 6H, 3 C6H5CH2, J ¼
7.34 Hz), 4.24 (m, 5H, C5ringH, 2 NCH2, 3J ¼ 6.61 Hz), 4.30 (qv,
[9] Syroeshkina, Y. S.; Kuznetsov, V. V.; Lyssenko, K. A.;
Makhova, N. N. Mendeleev Commun 2008, 18, 42.
[10] Syroeshkina, Y. S.; Kuznetsov, V. V.; Lyssenko, K. A.;
Makhova, N. N. Izv Acad Nauk Ser Khim 2009, 534 (Russ Chem Bull
Int Ed 2009, 58, 554).
3
4H, 2 CH3CH2OOC, J ¼ 6.35 Hz), 7.27 ppm (m, 15H, H in
C6H5); 13C NMR: d 14.06 (CH3CH2OOC), 33.17, 35.13, 36.04
(C6H5CH2), 54.44, 63.02 (NCH2), 60.44, 61.84 (CH3CH2OOC),
66.30 (C5ringH), 126.62, 127.74, 128.02, 128.13, 128.39, 128.48,
128.66, 128.83 (o-, m-, p-C in C6H5), 137.56, 139.65, 139.82
ppm (ipso- C in C6H5); ms: m/z 481 (5, M – CH2CH3 – 2H), 445
(6, M – CH3CH2OO – 2H), 346 (8, M – 2C6H5 – CH2), 329 (10,
M – 2C6H5CH2), 301 (16, M – 2C6H5CH2CH2), 226 (14, M –
[11] Syroeshkina, Y. S.; Kuznetsov, V. V.; Struchkova, M. I.;
Epishina, M. A.; Makhova, N. N. Mendeleev Commun 2008, 18,
207.
[12] Carbony, B.; Toupet, L.; Carrie, R. Tetrahedron 1987, 43,
2293.
3C6H5
– 2CH2CH2), 105 (100, C6H5CH2CH2), 91 (88,
C6H5CH2), 77 (64, C6H5), 65 (35, pyrazole), 43 (36, NCH2CH2
þ H). Anal. Calcd for C19H28N2O8 (512.43): C, 74.97; H, 7.08;
N, 5.46. Found: C, 74.95; H, 7.10; N, 5.48.
[13] Welton, T. Chem Rev 1999, 99, 2071.
[14] Wasserscheid, P.; Kein, W. Angew Chem Int Ed Engl
2000, 39, 3772.
[15] Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis;
Wiley-VCH: New York, 2003; p 380.
Acknowledgment. These investigations were partially sup-
ported by Russian Foundation for Basic Research (09-03-01-091-
a) and the program of Presidium of the Russian Academy of Sci-
ences ‘‘Development of methods for synthesizing chemical com-
pounds and creating new materials.’’
[16] D’Anna, F.; Noto, R. Tetrahedron 2007, 63, 11681.
[17] Astolfi, D. L.; Mayville, F. C., Jr. Tetrahedron Lett 2003,
44, 9223.
[18] (a) Niedballa, U.; Vorbruggen, H. J Org Chem 1974, 39,
3660; (b) Zhang, M.; Jiang, H.; Liu, H.; Zhu, Q. Org Lett 2007, 9,
4111; (c) Weston Hurst, E.; Hull, R. J Med Pharm Chem 1961, 3,
215; (d) Nair, V.; Chi, G.; Ptak, R.; Neamati, N. J Med Chem 2006,
49, 445; (e) Pattarini, R.; Smeyne, R. J.; Morgan, J. I. Neuroscience
2007, 145, 654.
REFERENCES AND NOTES
[1] Makhova, N. N.; Petukhova, V. Y.; Kuznetsov, V. V.
ARKIVOC 2008, i, 128.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet