Generation of 1-aryl-3-methoxycarbonylnitrilimines and their reactions with unsaturated hydrocarbons

Article abstract of DOI:10.1007/s11172-011-0251-3

Thermolysis of 1-(4-methoxyphenyl)- and 1-(4-fluorophenyl) heptamethoxycarbonyl-3a,7a-dihydroindazoles at 135-140 °C resulted in the elimination of hexamethyl benzene-hexacarboxylate and in the generation of 1-aryl-3-methoxycarbonylnitrilimines, which were trapped by alkenes and dienes to give the corresponding (1) pyrazolines via 1,3-dipolar cycloaddition and (2) 2-oxoalken-1-oic acid hydrazones via allylic proton migration to the nitrogen atom. The reaction with tetramethylethene unexpectedly yielded substituted 5-(1-hydroxy-1-methylethyl)- or 5-acetylpyrazolinecarboxylates as the main products. The formation of the latter compounds suggests initial abstraction of the H atom from tetramethylethene and probable participation of a water molecule that supplies one more oxygen atom to the reaction products.

Full text of DOI:10.1007/s11172-011-0251-3

Russian Chemical Bulletin, International Edition, Vol. 60, No. 8, pp. 1677—1684, August, 2011
1677
Generation of 1ꢀarylꢀ3ꢀmethoxycarbonylnitrilimines
and their reactions with unsaturated hydrocarbons
Yu. V. Tomilov, D. N. Platonov, G. P. Okonnishnikova, and O. M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Eꢀmail: tom@ioc.ac.ru
Thermolysis of 1ꢀ(4ꢀmethoxyphenyl)ꢀ and 1ꢀ(4ꢀfluorophenyl)heptamethoxycarbonylꢀ
3a,7aꢀdihydroindazoles at 135—140 °C resulted in the elimination of hexamethyl benzeneꢀ
hexacarboxylate and in the generation of 1ꢀarylꢀ3ꢀmethoxycarbonylnitrilimines, which were
trapped by alkenes and dienes to give the corresponding (1) pyrazolines via 1,3ꢀdipolar cycloꢀ
addition and (2) 2ꢀoxoalkenꢀ1ꢀoic acid hydrazones via allylic proton migration to the nitrogen
atom. The reaction with tetramethylethene unexpectedly yielded substituted 5ꢀ(1ꢀhydroxyꢀ1ꢀ
methylethyl)ꢀ or 5ꢀacetylpyrazolinecarboxylates as the main products. The formation of the
latter compounds suggests initial abstraction of the H atom from tetramethylethene and probable
participation of a water molecule that supplies one more oxygen atom to the reaction products.
Key words: 3a,7aꢀdihydroindazoles, nitrilimines, pyrazolines, hydrazones, 1,3ꢀdipolar
addition, oxidation, thermolysis.
Nitrilimines are highly reactive 1,3ꢀdipoles and, like
aliphatic diazo compounds, are widely used for the synꢀ
thesis of pyrazolines, pyrazoles, and other heterocycles via
1,3ꢀdipolar cycloaddition to unsaturated compounds.1—5
The electronic state of nitrilimines can be represented by
several resonance (propargyl, allene, allyl, carbene, and
biradical) structures, the contribution of each structure
being appreciably varied with the electronic properties of
the substituents.5—8
It is known10—12 that 3ꢀalkoxycarbonylꢀ1ꢀarylnitrilꢀ
imines generated by baseꢀcatalyzed 1,3ꢀdehydrochlorinaꢀ
tion of appropriate hydrazonyl chlorides readily react with
electronꢀdeficient unsaturated compounds and, to a much
lower degree, with electronꢀdonor olefins. In the latter
case, nitrilimines mainly undergo cyclodimerization into
substituted 1,2,4,5ꢀtetrazines. Since the discovered way of
generating nitrilimines differs from those described earliꢀ
er,10—14 it was interesting to study the thermolysis of 3a,7aꢀdiꢀ
hydroindazoles 1 in the presence of electronꢀsaturated
olefins and dienes containing methyl groups at the double
bond. The formation of trapping products from nitrilimines
generated by common methods has not been documented
hitherto for such unsaturated compounds.
Earlier,9 we have discovered that a number of substiꢀ
tuted 3a,7aꢀdihydroindazoles 1 undergo thermolysis at
130—140 °C with elimination of hexamethyl benzeneꢀ
hexacarboxylate and generation of the corresponding nitrilꢀ
imines 2, which are trapped by unsaturated substrates
(methyl acrylate, ethyl vinyl ether, cyclopentene, and
vinylcyclopropane) (Scheme 1). The reaction products inꢀ
cluded the expected pyrazolines and the corresponding
pyrazoles. In the case of ethyl vinyl ether, the formation
of 1ꢀarylpyrazoleꢀ3ꢀcarboxylates can be due to easy elimiꢀ
nation of ethanol, while the formation of pyrazoles in
the reactions with other substrates should involve parꢀ
tial in situ oxidation of pyrazolines, possibly with nitrilꢀ
imine itself.
Results and Discussion
We used heptamethyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ (1a) and
1ꢀ(4ꢀfluorophenyl)ꢀ3a,7aꢀdihydroindazoleheptacarboxyꢀ
lates (1b) as sources of nitrilimines and 2,3ꢀdimethylbutꢀ
1ꢀene (3), 2,3ꢀdimethylbutadiene (4), 2,5ꢀdimethylhexaꢀ
2,4ꢀdiene (5), and 2,3ꢀdimethylbutꢀ2ꢀene (6) as unsaturꢀ
ated compounds. Reactions were carried out in sealed tubes
in an inert atmosphere as follows. Dihydroindazole 1a was
heated at 135—140 °C with a tenfold molar excess of an
unsaturated compound in 1,4ꢀdioxane. It turned out that
the thermolysis of compound 1a in the presence of diꢀ
methylbutene 3 or dimethylbutadiene 4 gives the expected
pyrazoline 7 or 8 in 40 and 76% yields, respectively. Both
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1651—1659, August, 2011.
1066ꢀ5285/11/6008ꢀ1677 © 2011 Springer Science+Business Media, Inc.

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Tomilov et al.
Scheme 1
E = CO2Me; Ar = 4ꢀFC6H4, 4ꢀMeOC6H4
pyrazolines are regioselectively produced via the formaꢀ
tion of a C—C bond between the nitrilimine and the terꢀ
minal C atom of olefin 3 or diene 4 (Scheme 2). Byꢀ
products of these transformations include acyclic hydrꢀ
azones 9—11 and dihydropyridazine 12, which most likeꢀ
ly suggests asynchronous addition of nitrilimines to unsatꢀ
urated compounds because of consecutive cleavage of the
C—C and C—N bonds in the starting dihydroindazole 1a.
The initial C—C bonding to the alkene and the formation
of betaine structure A or B can be followed either by heteroꢀ
cyclization into pyrazoline 7 or 8 or deprotonation of the
alkene fragment during which the proton migrates to the
negatively charged N atom to form unsaturated hydrazones
9—11 (see Scheme 2). The presence of sixꢀmembered heteroꢀ
cycle 12 among the reaction products can be attributed to
the interconversions of betaine intermediates B and C.
Compounds 7, 8, 11, and 12 were isolated in the indiꢀ
vidual state from the reaction mixtures by column chroꢀ
matography on silica gel; their structures were determined
However, the steric effects preclude regioselective addiꢀ
tion of the nitrilimine to the double bond, and the reaction
produces pyrazoline 13a and its regioisomer 14a in a ratio
of ~7.6 : 1. Both isomers (enriched to 95 and 90% either)
were isolated by column chromatography on SiO2. These
regioisomers were distinguished by analyzing the chemiꢀ
cal shifts of the 13C NMR signals for the quaternary and
protonated C atoms bound to the N(1) or C(3) atoms of
the heterocycle. For pyrazoline 13a, these signals appear
at δ 49.9 and 72.1 (C(4) and C(5), respectively). For pyrꢀ
azoline 14a, the chemical shifts of the corresponding sigꢀ
nals are δ 73.1 and 54.4. Apart from pyrazolines 13a and
14a, we isolated from the reaction mixture unsaturated
hydrazone 15a (Scheme 3), which is produced by addition
of nitrilimine 2a to the fragment HC= of diene 5 followed
by migration of a methyl proton to nitrogen.
The 1H and 13C NMR spectra of hydrazone 15a show
signals for the aryl and ester groups, signals for the fragꢀ
ment =CH2 and three methyl groups at the double bonds,
and two signals for the fragments CH, which appear as
broadened doublets at δH 4.3 and 5.5 with JH,H = 9.5 Hz.
According to the HSQC experiment, the latter signals corꢀ
respond to the signals at δC 47.3 and 124.6. In addition,
the 1H NMR spectrum contains a lowꢀfield (δ 12.1) broadꢀ
ened singlet for the proton of the fragment C=N—NH.
1ꢀFluorophenylnitrilimine 2b reacts with diene 5 in
a similar way to give pyrazolines 13b and 14b with a slightꢀ
ly lower regioselectivity (13b : 14b = 5.7 : 1); the yield of
unsaturated hydrazone 15b was nearly three times as high
(see Scheme 3).
1
from H and 13C NMR and mass spectra. Hydrazones 9
and 10 were analyzed as mixtures of isomers. In all the
compounds obtained, the nitrilimine (2a) and hydrocarbon
(3 or 4) fragments are retained.
Interestingly, the yield of unsaturated pyrazoline 8 is
nearly twice as high as that of pyrazoline 7. This fact can
be due to both the higher reactivity of diene 4 (or the
statistical factor reflecting twice as many similar double
bonds in diene 4 compared to olefin 3) and side transforꢀ
mations of the starting compounds and final products in
the case of olefin 3. The latter assumption is supported by
surprisingly much stronger polymerization of the reaction
mixture in the case of the reaction between compounds 1a
and 3 than between compounds 1a and 4 under the same
conditions.
It should be noted that 1,3ꢀdipolar cycloaddition of
nitrilimines to the multiple bonds of unsaturated comꢀ
pounds is not always regioselective, especially with conjuꢀ
gated and electronꢀdeficient dipolarophiles as traps.2,14—16
The formation of hydrazones 15a,b, as well as the formaꢀ
tion of compounds 9—12, suggests a stepwise character of
Formal trapping of nitrilimine 2a by internal diene 5
also mainly gives 1,3ꢀdipolar cycloaddition products.

Reactions of nitrilimines with alkenes
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1679
Scheme 2
Ar = 4ꢀMeOC6H4
the reaction of nitrilimine 2a or 2b with diene 5 and acquiꢀ
sition of a high positive charge by the hydrocarbon fragꢀ
ment upon the formation of the C—C bond. As distinct
from, e.g., the generation of nitrilimines by 1,3ꢀdehydroꢀ
chlorination of hydrazonoyl chlorides in the presence of
alkenes, the thermolysis of dihydroindazoles 1a,b producꢀ
es no 1,2,4,5ꢀtetrazines, which are nitrilimine cyclic
dimers.
In contrast to unsaturated compounds containing diꢀ
and trisubstituted double bonds, reactions of dihydroindꢀ
azoles 1a and 1b with a tenfold molar excess of tetramethylꢀ
ethene (6) in dioxane under the same conditions gave prodꢀ
ucts no analogs of which had been detected in the aforeꢀ
said experiments. The yields of the expected pyrazoline
16a and hydrazones 17a,b were low, while the major reacꢀ
tion products were compounds 18 and 19 containing
additional oxygen atoms (Scheme 4). In the case of
1ꢀ(4ꢀfluorophenyl)ꢀ3a,7aꢀdihydroindazole 1b, pyrazoline
16b was not obtained; instead, pyrazoline 20 and pyrazole
21 were detected, though in low yields (Scheme 5). All
these compounds were isolated by column chromatograꢀ
phy on SiO2, and their structures were determined from
spectroscopic data. For instance, 1H and 13C NMR studꢀ
ies revealed that alcohols 18a,b and ketones 19a,b formalꢀ
ly contain the nitrilimine fragment (2a or 2b) in the fiveꢀ
membered ring and the isolated alicyclic CH2 group, which
is manifested in the 1H NMR spectra as two doublets with
a geminal coupling constant of 18—19 Hz. Because of

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Tomilov et al.
Scheme 3
To this point, we cannot provide a definite explanation
of the formation of oxygenꢀcontaining compounds 18 and
19. Since these products were detected immediately in the
reaction mixture before its separation by column chromaꢀ
tography, one could assume that probable oxygen sources
in an inert atmosphere inside a sealed tube are either ester
groups or small amounts of water present in the reaction
mixture. However, in any of the experiments, we isolated
no compounds implying a transformation of the ester
group. In addition, the amount of hexamethyl benzeneꢀ
hexacarboxylate was as high as in the other reactions of
dihydroindazoles 1a,b. At the same time, small amounts
of water present in the reaction mixture can participate in
relevant transformations. For instance, deliberate addition
of an equimolar amount of water with respect to dihydroꢀ
indazole 1a to its reaction mixture with tetramethylethene
slightly decreased the yields of compounds 16a and 17a but
increased the yield of acetylpyrazoline 19a from 21 to 32%.
Apparently, tetramethylethene 6 with a sterically hinꢀ
dered double bond is a poor dipolarophile in reactions
with nitrilimines, as well as with other 1,3ꢀdipoles. Howꢀ
ever, generated nitrilimine 2 (or its precursor resulting
from heterolytic or homolytic cleavage of a C—C or C—N
Ar = 4ꢀMeOC6H4 (a), 4ꢀFC6H4 (b)
steric hindrances, the 1H and 13C NMR spectra of tertiary
alcohols 18a,b show geminal nonequivalence of the methꢀ
yl groups of the 1ꢀhydroxyꢀ1ꢀmethylethyl fragment.
Scheme 4
Ar = 4ꢀMeOC6H4
Scheme 5
Ar = 4ꢀFC6H4

Reactions of nitrilimines with alkenes
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1681
Scheme 6
bond in the starting dihydroindazole 1) can react with
hydrazone 15 by removal of hydrogen from its methyl
group. The resulting allylic cation (or radical) reacts with
nitrilimine 2 to give heterocyclic intermediate cation (or
radical) 22, which is transformed into 5ꢀ(1ꢀhydroxyꢀ1ꢀ
methylethyl)pyrazoline 18 upon a reaction with water
(Scheme 6). Thus, the reaction of the generated nitrilꢀ
imine with tetramethylethene is accompanied by formal
reduction leading to a mixture of unidentified highꢀmoꢀ
lecularꢀweight compounds.
According to previous data,17—19 the formation of keꢀ
tones from tertiary alcohols of similar structures can arise
from cleavage of the C—C bond in 2ꢀarylꢀ2ꢀpropyloxyl
radicals, which provides explanation for the formation of
acetylpyrazolines 19 as well. For this purpose, we should
only assume that the scheme of transformations in the
system nitrilimines 2a,b—tetramethylethene involves the
generation of 2ꢀ(pyrazolꢀ5ꢀyl)propꢀ2ꢀyloxyl radicals 23,
which seems to be most probable when some of the reacꢀ
tion steps follow the radical mechanism.
Thus, the observed unexpected formation of comꢀ
pounds 18—21 upon the thermolysis of 3a,7aꢀdihydroinꢀ
dazoleheptacarboxylates 1a,b in the presence of tetraꢀ
methylethene suggests a novel pathway of the chemical
transformations of in situ generated 1ꢀarylꢀ3ꢀ(methoxyꢀ
carbonyl)nitrilimines (or their precursors resulting from
cleavage of one bond in compounds 1a,b), which can atꢀ
tack the allylic C—H bond of an alkene. It should be noted
that conventional12 generation of nitrilimine 2a by 1,3ꢀdeꢀ
hydrochlorination of the arylhydrazone EtO2CC(Cl)=N—
NHC6H4OMeꢀ4 with triethylamine (80 °C, 4 h) in the
presence of tetramethylethene yielded no trapping prodꢀ
ucts at all, the main compound isolated being diethyl
1,4ꢀbis(4ꢀmethoxyphenyl)ꢀ1,2,4,5ꢀtetrazineꢀ3,6ꢀdicarbꢀ
oxylate (cyclic nitrilimine dimer).11 Under similar condiꢀ
tions, the yield of pyrazoline 13a from diene 5 was no
higher than 5%. This indicates that nitrilimines generated
from different sources are differently reactive. Apparently, the
thermolysis of substituted 3a,7aꢀdihydroindazoles can involve
homolytic cleavage of the C(3)—C(3a) and N(1)—C(7a)
bonds followed by reactions of the generated nitrilimines
2a,b (in the form of biradicals) with compound 6.
Experimental
1
H and 13C NMR spectra were recorded on Bruker AVANCE
II 300 (300 and 75.5 MHz, respectively) and Bruker DRXꢀ500
spectrometers (500 MHz and 125.3 MHz, respectively) in CDCl3
containing 0.05% Me4Si as the internal standard. The 19F chemꢀ
ical shifts are referenced to CCl3F. Homoꢀ and heteronuclear
2D correlation experiments (COSY, HMBC, and HSQC) were
used to assign NMR signals and distinguish between the isomers
of the compounds obtained. GCꢀMS spectra were recorded on
a Finnigan MAT DSQII instrument (EI, 70 eV, ion source—ion
trap system temperature 200 °C) coupled with a Trace GC Ultra
chromatograph (Thermo TRꢀ5ms SQC column, 15 000×0.25 mm).
Highꢀresolution mass spectra (HRMS) were recorded on a Bruker
micrOTOF II instrument (ESI, positive ion mode, capillary voltꢀ
age 4500 V).20 IR spectra were recorded on a Specord Mꢀ80
instrument in KBr pellets. Thinꢀlayer chromatography was carꢀ
ried out on Silica gel 60 plates (Merck); spots were visualized
under the iodine vapor. For preparative separation, column chroꢀ
matography (silica gel 60, 0.040—0.063 mm, Merck) was used;
the sample—sorbent ratio was ~1 : 100. Melting points were deꢀ
termined on a Nagema PHMKꢀ05 instrument.
1ꢀ(4ꢀMethoxyphenyl)ꢀ (1a) and 1ꢀ(4ꢀfluorophenyl)ꢀ3,3a,
4,5,6,7,7aꢀheptamethoxycarbonylꢀ3a,7aꢀdihydroindazoles (1b)
(≥98% purity) were prepared as described earlier.21 Unsaturated
compounds were distilled in an inert atmosphere before use;
solvents (reagent grade, >99.5%) were used without further puꢀ
rification.
Thermolysis of 3a,7aꢀdihydroindazoles (1a,b) in the presence
of alkenes or dienes (general procedure). A mixture of heptaꢀ
methyl 3a,7aꢀdihydroindazoleheptacarboxylate 1a or 1b (0.5 mmol)
and an unsaturated compound (5 mmol) in 1,4ꢀdioxane (0.4 mL)
was heated in a sealed tube under argon at 135—140 °C for 8 h.
1
The reaction mixture was analyzed using TLC and H NMR
spectroscopy. The main reaction products were isolated by colꢀ
umn chromatography on SiO2 with benzene—EtOAc (gradient

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Tomilov et al.
elution from 10 : 1 to 2 : 1) or CHCl3—EtOAc (5 : 1) as an eluent.
Hexamethyl benzenehexacarboxylate always emerged from the
column behind the corresponding pyrazolines and hydrazones.
Methyl 5ꢀisopropylꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀmethylꢀ4,5ꢀdihyꢀ
droꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (7), methyl 2ꢀ[(4ꢀmethoxyꢀ
phenyl)hydrazono]ꢀ4,5ꢀdimethylhexꢀ4ꢀenoate (9), and methyl
2ꢀ[(4ꢀmethoxyphenyl)hydrazono]ꢀ5ꢀmethylꢀ4ꢀmethylidenehexꢀ
anoate (10). A reaction of dihydroindazole 1a (315 mg) with
2,3ꢀdimethylbutꢀ1ꢀene (3) (0.42 g) gave compound 7 (58 mg, 40%)
and an inseparable (under these conditions) mixture of hydrꢀ
azones 9 and 10 (20 mg, 14%; 1.3 : 1 (1H NMR)), colorless oil.
MS (EI), m/z (Irel (%)): 290 [M]+ (30), 275 [M – Me]+ (2),
247 (10), 231 (10), 215 (30), 122 (100), 108 (14), 95 (20).
117.7 (Co); 135.6, 136.0 (Cipso, C(3)); 147.9 (=C); 155.3 (Cp);
163.6 (COO).
Compound 11, oil. MS (EI), m/z (Irel (%)): 288 [M]+ (20),
215 (5), 200 (8), 152 (5), 137 (35), 122 (100), 107 (22), 95 (16).
HRMS (ESI): [M + H]+, calculated for C16H21N2O3 289.1547,
found: 289.1553. 1H NMR (CDCl3), δ: 1.95 (d, 3 H, Me,
4J = 1.3 Hz); 3.47 (s, 2 H, CH2); 3.77, 3.78 (both s, 3 H each,
2 OMe); 4.92, 5.00 (both m, 1 H each, =C(6)H2); 5.18, 5.22
(both br.s, 1 H each, H2C=C(4)); 6.85 (d, 2 H, Hm, 3J = 9.0 Hz);
7.11 (d, 2 H, Ho, 3J = 9.0 Hz); 12.1 (br.s, 1 H, NH). 13C NMR
(CDCl3), δ: 21.4 (Me); 36.7 (C(3)); 51.4 (CO2Me); 55.7 (OMe);
113.2, 113.8 (H2C=C(4), C(5)); 114.8, 114.9 (Cm, Co); 125.2
(C(2)); 137.5 (Cipso); 142.76, 145.39 (C(4), C(5)); 155.2 (Cp);
164.5 (COO).
Compound 7, colorless oil. Found (%): C, 65.73; H, 7.45;
N, 9.68. C16H22N2O3. Calculated (%): C, 66.18; H, 7.64;
N, 9.65. MS (EI), m/z (Irel (%)): 290 [M]+ (30), 259 [M – OMe]+
(10), 247 (70), 215 (100), 203 (20), 188 (30), 148 (50), 122 (50),
107 (35), 92 (53), 77 (75), 64 (40), 59 (45). IR, ν/cm–1: 2968,
1696 (COO), 1508 (C=N). 1H NMR (CDCl3), δ: 0.93, 0.95
Compound 12, oil. The product was further purified by preꢀ
parative TLC to give an analytically pure sample, Rf 0.75 (benꢀ
zene : EtOAc = 2 : 1). MS (EI), m/z (Irel (%)): 288 [M]+ (10),
273 [M – Me]+ (100), 199 (10), 148 (9), 107 (6), 92 (8), 77 (10).
HRMS (ESI): [M + Na]+, calculated for C16H20N2O3Na
311.1366, found: 311.1364. IR, ν/cm–1: 3004, 2956, 1696 (COO),
3
(both d, 3 H each, 2 Me, J = 7.0 Hz); 1.33 (s, 3 H, Me); 2.25
(septet, 1 H, HCMe2, 3J = 7.0 Hz); 2.70, 3.18 (both d, 1 H each,
1508 (C=N). H NMR (CDCl3), δ: 1.20 (s, 6 H, 2 Me); 1.89
1
2
H2C(4), J = 17.8 Hz); 3.78, 3.84 (both s, 3 H each, 2 OMe);
(d, 3 H, Me, 4J = 1.4 Hz); 3.80, 3.81 (both s, 3 H each, 2 OMe);
6.35 (q, 1 H, =CH, 4J = 1.4 Hz); 6.85 (d, 2 H, Hm, 3J = 9.0 Hz);
7.22 (d, 2 H, Ho, 3J = 9.0 Hz). 13C NMR (CDCl3), δ: 18.8 (Me);
23.5 (2 Me); 52.1 (CO2Me); 55.6 (OMe); 59.3 (C(6)); 113.7
3
3
6.82 (d, 2 H, Hm, J = 9.0 Hz); 7.21 (d, 2 H, Ho, J = 9.0 Hz).
13C NMR (CDCl3), δ: 17.4, 17.5 (2 Me); 25.3 (Me); 34.5 (CH);
39.1 (CH2); 51.7 (CO2Me); 55.3 (OMe); 75.9 (C(5)); 113.9 (Cm);
121.7 (Co); 135.7, 135.8 (Cipso, C(3)); 156.3 (Cp); 163.6 (COO).
Compound 9. 1H NMR (CDCl3), δ: 1.66, 1.70, 1.76 (all br.s,
3 H each, 3 Me); 3.24 (br.s, 2 H, CH2); 3.76, 3.78 (both s,
3 H each, 2 OMe); 6.86 (m, Hm, this signal coincides with
a similar signal for compound 10); 7.11 (d, 2 H, Ho, 3J = 9.0 Hz);
12.0 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 18.2, 20.6, 20.9
(3 Me); 37.4 (CH2); 51.3 (CO2Me); 55.7 (OMe); 114.7, 114.9
(Cm, Co); 124.5, 125.9 (C(4), C(5)); 126.8 (C(2)); 137.8 (Cipso);
155.0 (Cp); 164.5 (COO).
(C(4)); 113.8 (Cm); 130.3 (Co); 133.2 (C(3)); 137.5, 137.8 (Cipso
C(5)); 158.7 (Cp); 164.8 (COO).
,
Methyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ4,4ꢀdimethylꢀ5ꢀ(2ꢀmethylpropꢀ
1ꢀenyl)ꢀ (13a) and methyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ5,5ꢀdimethylꢀ4ꢀ
(2ꢀmethylpropꢀ1ꢀenyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylates
(14a) and methyl 2ꢀ[(4ꢀmethoxyphenyl)hydrazono]ꢀ5ꢀmethylꢀ3ꢀ
(propꢀ1ꢀenꢀ2ꢀyl)hexꢀ4ꢀenoate (15a). A reaction of dihydroindꢀ
azole 1a (315 mg) with 2,5ꢀdimethylhexaꢀ2,4ꢀdiene (5) (0.55 g)
followed by separation of the products by column chromatoꢀ
graphy (SiO2, CHCl3—EtOAc, 5 : 1) gave pyrazoline 13a (72 mg,
46%; the content of isomeric pyrazoline 14a is <5%), pyrazoline
14a (10 mg, 6%; the content of isomeric pyrazoline 13a is <10%),
and hydrazone 15a (12 mg), which was further purified by TLC
(C6H6—EtOAc, 9 : 1). The yield of compound 15a was ~6%.
Compound 13a, colorless oil. Found (%): C, 68.43; H, 8.40;
N, 8.68. C18H24N2O3. Calculated (%): C, 68.33; H, 7.65;
N, 8.85. GCꢀMS (EI), m/z (Irel (%)): 316 [M]+ (70), 301
[M – Me]+ (62), 285 [M – OMe]+ (8), 189 (42), 174 (35), 149
(58), 121 (100). IR, ν/cm–1: 2959, 1696 (COO), 1616 w, 1520 m,
1
Compound 10. H NMR (CDCl3), δ: 1.08 (d, 6 H, 2 Me,
3J = 7.0 Hz); 2.33 (br.septet, 1 H, CH, 3J = 7.0 Hz); 3.21 (t, 2 H,
4
CH2, J = 1.3 Hz); 3.75, 3.77 (both s, 3 H each, 2 OMe); 4.65,
4.80 (both m, 1 H each, =CH2); 6.86 (m, Hm, this signal coinꢀ
cides with a similar signal for compound 9); 7.14 (d, 2 H, Ho,
3J = 9.0 Hz); 12.1 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 21.7
(2 Me); 33.8 (C(5)); 37.8 (C(3)); 51.2 (CO2Me); 55.6 (OMe);
108.0 (=CH2); 114.8, 114.9 (Cm, Co); 125.9 (C(2)); 137.6 (Cipso);
155.1 (Cp); 164.4 (COO).
Methyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀmethylꢀ5ꢀ(propꢀ1ꢀenꢀ2ꢀyl)ꢀ
4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (8), methyl 2ꢀ[(4ꢀmethꢀ
oxyphenyl)hydrazono]ꢀ5ꢀmethylꢀ4ꢀmethylidenehexꢀ5ꢀenoate (11),
and methyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ5,6,6ꢀtrimethylꢀ1,6ꢀdihydroꢀ
pyridazineꢀ3ꢀcarboxylate (12). A reaction of dihydroindazole 1a
(316 mg) with 2,3ꢀdimethylbutadiene (4) (0.41 g) gave comꢀ
pounds 8 (109 mg, 76%), 11 (3 mg, ~2%), and 12 (16 mg, 11%).
Compound 8, colorless oil. Found (%): C, 66.72; H, 7.19;
N, 9.59. C16H20N2O3. Calculated (%): C, 66.65; H, 6.99;
N, 9.72. IR, ν/cm–1: 2952, 1696 (COO), 1508 (C=N). MS (EI),
m/z (Irel (%)): 288 [M]+ (100), 273 [M – Me]+ (12), 247 (22),
241 (20), 215 (45), 122 (66), 107 (45), 92 (22), 77 (30). 1H NMR
(CDCl3), δ: 1.51 (s, 3 H, Me at C(5)); 1.82 (br.s, 3 H, Me); 2.99,
3.20 (both d, 1 H each, H2C(4), 2J = 18.0 Hz); 3.77, 3.87 (both s,
3 H each, 2 OMe); 5.05, 5.11 (both m, 1 H each, =CH2); 6.79
(d, 2 H, Hm, 3J = 9.1 Hz); 7.23 (d, 2 H, Ho, 3J = 9.1 Hz).
13C NMR (CDCl3), δ: 19.2, 22.7 (2 Me); 46.6 (C(4)); 52.1
(CO2Me); 55.5 (OMe); 73.4 (C(5)); 112.4 (=CH2); 114.2 (Cm);
1
1508 (C=N), 1436. H NMR (CDCl3), δ: 1.20, 1.40 (both s,
3 H each, Me2C(4)); 1.77, 1.79 (both d, 3 H each, =CMe2,
4J = 1.4 Hz); 3.78, 3.84 (both s, 3 H each, 2 OMe); 4.54 (d, 1 H,
H(5), 3J = 9.9 Hz); 5.09 (dsp, 1 H, =CH, 3J = 9.9 Hz, 4J = 1.4 Hz);
3
3
6.82 (d, 2 H, Hm, J = 9.2 Hz); 7.10 (d, 2 H, Ho, J = 9.2 Hz).
13C NMR (CDCl3), δ: 18.5, 25.9 (=CMe2); 20.1, 26.0 (Me2C(4));
49.9 (C(4)); 51.7 (CO2Me); 55.5 (OMe); 72.1 (C(5)); 114.3 (Cm);
117.4 (Co); 118.6 (=CH); 137.4 (Cipso); 137.7 (=C); 144.5 (C(3));
155.1 (Cp); 163.0 (COO).
Compound 14a, colorless oil. GCꢀMS (EI), m/z (Irel (%)):
316 [M]+ (65), 301 [M – Me]+ (20), 200 (25), 175 (15), 163
(100), 148 (95), 122 (15), 92 (15), 77 (20). 1H NMR (CDCl3), δ:
1.21, 1.23 (both s, 3 H each, Me2C(5)); 1.76 (d, 3 H, ZꢀMe,
4J = 1.3 Hz); 1.79 (d, 3 H, EꢀMe, 4J = 1.3 Hz); 3.80, 3.82
3
(both s, 3 H each, 2 OMe); 3.83 (d, 1 H, H(4), J = 10.6 Hz);
4
5.11 (dsp, 1 H, =CH, 3J = 10.6 Hz, J = 1.3 Hz); 6.84 (d, 2 H,
3
3
Hm, J = 9.0 Hz); 7.17 (d, 2 H, Ho, J = 9.0 Hz). 13C NMR

Reactions of nitrilimines with alkenes
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1683
(CDCl3), δ: 18.1 (ZꢀMe); 21.6, 25.3 (Me2C(5)); 26.1 (EꢀMe);
51.9 (CO2Me); 54.4 (C(4)); 55.5 (OMe); 73.1 (C(5)); 114.0 (Cm);
118.6 (=CH); 124.5 (Co); 135.7 (Cipso); 136.1 (=C); 141.4 (C(3));
157.3 (Cp); 163.4 (COO).
(Me); 26.1 (EꢀMe); 47.3 (C(3)); 51.6 (CO2Me); 110.8 (=CH2);
3
2
114.7 (Co, JC,F = 7.7 Hz); 115.9 (Cm, JC,F = 23.2 Hz); 124.3
(C(4)); 129.1, 132.6 (C(2´), C(5)); 140.2 (Cipso, 4JC,F = 2.3 Hz);
146.9 (C(2)); 158.3 (Cp, 1JC,F = 240 Hz); 164.2 (COO). 19F NMR
(CDCl3), δ: –123.3 (tt, CF, 3JH,F = 8.7 Hz, 4JH,F = 4.2 Hz).
Reaction of compound 1a with 2,3ꢀdimethylbutꢀ2ꢀene (6). The
products obtained from dihydroindazole 1a (316 mg) and tetꢀ
ramethylethene (6) (0.42 g) were separated by column chromatoꢀ
graphy on SiO2 (CHCl3—EtOAc, 5 : 1). They include methyl
1ꢀ(4ꢀmethoxyphenyl)ꢀ4,4,5,5ꢀtetramethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrꢀ
azoleꢀ3ꢀcarboxylate (16a) (13 mg, 9%), methyl 2ꢀ[(4ꢀmethꢀ
oxyphenyl)hydrazono]ꢀ3,3,4ꢀtrimethylpentꢀ4ꢀenoate (17a) (14 mg,
10%), methyl 5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀ
methylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (18a) (30 mg,
20%), and methyl 5ꢀacetylꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀmethylꢀ4,5ꢀ
dihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (19a) (30 mg, 21%).
Compound 16a, colorless oil. HRMS (ESI): [M + Na]+,
calculated for C16H22N2O3Na 313.1523, found: 313.1523. MS
(EI), m/z (Irel (%)): 290 [M]+ (85), 275 [M – Me]+ (100), 259
[M – OMe]+ (10), 231 [M – COOMe]+ (22), 216 (22), 163 (40),
148 (74), 121 (20), 92 (20). IR, ν/cm–1: 2976, 2958, 1696 (C=O),
1508 (C=N), 1436. 1H NMR (CDCl3), δ: 1.10 (s, 6 H, Me2C(4));
1.23 (s, 6 H, Me2C(5)); 3.80, 3.84 (both s, 3 H each, 2 OMe);
Compound 15a, colorless oil. HRMS (ESI): [M + H]+,
calculated for C18H25N2O3 317.1860, found: 317.1856. 1H NMR
(CDCl3), δ: 1.69, 1.77 (both d, 3 H each, 2 Me at C(5), 4J = 1.5
Hz); 1.75 (t, 3 H, Me, 4J = 1.3 Hz); 3.78, 3.79 (both s, 3 H each,
3
2 OMe); 4.29 (br.d, 1 H, H(3), J = 9.5 Hz); 4.77 (m, 2 H,
3
4
=CH2); 5.51 (dsp, 1 H, H(4), J = 9.5 Hz, J = 1.5 Hz); 6.87
3
3
(d, 2 H, Hm, J = 9.0 Hz); 7.12 (d, 2 H, Ho, J = 9.0 Hz); 12.1
(br.s, 1 H, NH). 13C NMR (CDCl3), δ: 18.1 (ZꢀMe); 21.4 (Me);
26.1 (EꢀMe); 47.3 (C(3)); 51.4 (CO2Me); 55.7 (OMe); 110.6
(=CH2); 114.8, 115.0 (Co, Cm); 124.6 (C(4)); 127.9, 132.3 (C(2´),
C(5)); 137.8 (Cipso); 147.1 (C(2)); 155.1 (Cp); 164.3 (COO).
Methyl 1ꢀ(4ꢀfluorophenyl)ꢀ4,4ꢀdimethylꢀ5ꢀ(2ꢀmethylpropꢀ1ꢀ
enyl)ꢀ (13b) and methyl 1ꢀ(4ꢀfluorophenyl)ꢀ5,5ꢀdimethylꢀ4ꢀ(2ꢀ
methylpropꢀ1ꢀenyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylates
(14b) and methyl 2ꢀ[(4ꢀfluorophenyl)hydrazono]ꢀ5ꢀmethylꢀ3ꢀ
(propꢀ1ꢀenꢀ2ꢀyl)hexꢀ4ꢀenoate (15b). A reaction of dihydroindꢀ
azole 1b (0.31 g) with 2,5ꢀdimethylhexaꢀ2,4ꢀdiene (5) (0.55 g)
gave regioisomeric pyrazolines 13b and 14b (71 mg, 47%) in
a ratio of 5.7 : 1 (1H NMR) and hydrazone 15b (28 mg, 18%).
For the mixture of isomers 13b and 14b, found (%): C, 66.68;
H, 7.10; N, 8.72. C17H21FN2O2. Calculated (%): C, 67.09;
H, 6.95; N, 9.20.
3
3
6.85 (d, 2 H, Hm, J = 9.0 Hz); 7.17 (d, 2 H, Ho, J = 9.0 Hz).
13C NMR (CDCl3), δ: 19.5, 19.8 (Me2C(4), C(5)); 50.6 (C(4));
51.7 (CO2Me); 55.5 (OMe); 74.9 (C(5)); 113.9 (Cm); 125.5 (Co);
135.9 (Cipso); 145.4 (C(3)); 157.6 (Cp); 163.4 (COO).
Compound 13b. GCꢀMS (EI), m/z (Irel (%)): 304 [M]+ (46),
289 [M – Me]+ (100), 273 [M – OMe]+ (4), 257 (5), 245 (5),
229 (5), 177 (24), 176 (28), 162 (16), 161 (8), 136 (8), 122 (8),
110 (16), 109 (20), 95 (40). 1H NMR (CDCl3), δ: 1.23, 1.39 (both s,
3 H each, 2 Me at C(4)); 1.78, 1.80 (both d, 3 H each, =CMe2,
4J = 1.4 Hz); 3.85 (s, 3 H, OMe); 4.54 (d, 1 H, H(5), 3J = 9.8 Hz);
5.07 (dsp, 1 H, =CH, 3J = 9.8 Hz, 4J = 1.4 Hz); 6.92, 7.11 (both m,
2 H each, Ho, Hm). 13C NMR (CDCl3), δ: 18.4, 25.9 (=CMe2);
20.1, 26.0 (2 Me at C(4)); 50.0 (C(4)); 51.7 (CO2Me); 71.8
(C(5)); 115.4 (d, Cm, 2JC,F = 22.5 Hz); 117.1 (d, Co, 3JC,F = 8.0 Hz);
120.3 (=CH); 137.9 (=C); 139.8 (d, Cipso, 4JC,F = 2.4 Hz); 145.5
(C(3)); 158.3 (d, Cp, 1JC,F = 241 Hz); 162.8 (COO).
Compound 17a (~95% purity), oil. MS (EI), m/z (Irel (%)):
290 [M]+ (80), 275 [M – Me]+ (25), 259 [M – OMe]+ (5), 231
[M – COOMe]+ (10), 215 (10), 149 (12), 135 (20), 121 (100),
108 (35), 95 (50), 84 (90). IR, ν/cm–1: 3268 (NH), 3020, 1702
(C=O), 1670, 1542, 1518, 1438. 1H NMR (CDCl3), δ: 1.37 (s, 6 H,
4
Me2C(3)); 1.67 (t, 3 H, Me, J = 1.2 Hz); 3.72, 3.78 (both s,
3 H each, 2 OMe); 4.75 (q, 2 H, =CH2, 4J = 1.2 Hz); 6.87
(d, 2 H, Hm, 3J = 9.1 Hz); 7.13 (d, 2 H, Ho, 3J = 9.1 Hz); 12.0 (NH).
13C NMR (CDCl3), δ: 20.3 (Me); 27.2 (Me2C(3)); 45.2 (C(3));
50.8 (CO2Me); 55.7 (OMe); 108.4 (=CH2); 114.7, 114.8 (Co, Cm);
132.3 (C(4)); 138.1 (Cipso); 152.1 (C(2)); 154.9 (Cp); 164.5 (COO).
Compound 18a, yellowish oil. Found (%): C, 62.52; H, 7.33;
N, 8.67. C16H22N2O4. Calculated (%): C, 62.73; H, 7.24;
N, 9.14. MS (EI), m/z (Irel (%)): 306 [M]+ (5), 275 [M – OMe]+
(3), 247 [M – COOMe]+ (50), 215 (100); 203 (8); 188 (15), 148
(50), 132 (12); 121 (15); 107 (20); 92 (40); 84 (40); 77 (65); 59
(100). IR, ν/cm–1: 3608 (OH), 2980, 2958, 1696 (C=O), 1508
(C=N), 1449. 1H NMR (CDCl3), δ: 1.21, 1.25 (both s, 3 H each,
2 Me); 1.45 (s, 3 H, MeC(5)); 1.76 (br.s, 1 H, OH); 2.90, 3.25
Compound 14b. GCꢀMS (EI), m/z (Irel (%)): 304 [M]+ (34),
289 [M – Me]+ (16), 273 [M – OMe]+ (4), 257 (5), 248 (4), 245
[M – COOMe]+ (5), 229 (5), 152 (34), 151 (86), 136 (100), 110
(16), 109 (18), 95 (50). 1H NMR (CDCl3), δ: 1.24, 1.27 (both s,
3 H each, Me2C(4)); 1.76, 1.79 (both d, 3 H each, =CMe2,
4J = 1.4 Hz); 3.83 (s, 3 H, OMe); 3.84 (d, 1 H, H(5), 3J = 10.0 Hz);
3
4
5.09 (dsp, 1 H, =CH, J = 10.0 Hz, J = 1.4 Hz); 6.97, 7.20
(both m, 2 H each, Ho, Hm). 13C NMR (CDCl3), δ: 18.1, 26.1
(=CMe2); 21.7, 25.3 (Me2C(4)); 51.8 (CO2Me); 54.8 (C(4)); 72.8
(C(5)); 115.9 (d, Co, 3JC,F = 8.0 Hz); 116.2 (d, Cm, 2JC,F = 22.4 Hz);
118.2 (=CH); 136.4 (=C); 138.8 (d, Cipso, 4JC,F = 2.4 Hz); 142.2
(C(3)); 160.1 (d, Cp, 1JC,F = 243 Hz); 163.3 (COO).
2
(both d, H2C(4), J = 18.0 Hz); 3.76, 3.81 (both s, 3 H each,
2 OMe); 6.81 (d, 2 H, Hm, 3J = 9.0 Hz); 7.32 (d, 2 H, Ho,
3J = 9.0 Hz). 13C NMR (CDCl3), δ: 21.5 (MeC(5)); 25.6, 25.7
(2 Me); 43.6 (C(4)); 51.9 (CO2Me); 55.3 (OMe); 75.5 (C(5));
78.4 (C—OH); 113.7 (Cm); 125.8 (Co); 136.8, 136.9 (C(3), Cipso);
157.3 (Cp); 163.3 (COO).
Compound 15b, colorless crystals, m.p. 46—47 °C (CHCl3).
Found (%): C, 66.95; H, 6.86; N, 9.27. C17H21FN2O2. Calculatꢀ
ed (%): C, 67.09; H, 6.95; N, 9.20. MS (EI), m/z (Irel (%)): 304
[M]+ (38), 289 [M – Me]+ (10), 257 (10), 162 (20), 134 (32), 110
(100), 95 (40), 83 (65). IR, ν/cm–1: 3260 (NH), 2972, 2916,
1676 (C=O), 1612, 1544, 1516 (C=N), 1436. 1H NMR (CDCl3),
Compound 19a, colorless crystals, m.p. 101—102 °C (CHCl3).
Found (%): C, 62.12; H, 6.60; N, 9.38. C15H18N2O4. Calculatꢀ
ed (%): C, 62.06; H, 6.25; N, 9.65. MS (EI), m/z (Irel (%)): 290
[M]+ (14), 247 [M – Ac]+ (65), 215 (100), 188 (20), 160 (10),
148 (32), 107 (12), 92 (22), 77 (30). IR, ν/cm–1: 1716 (COO),
4
δ: 1.70, 1.78 (both d, 3 H each, Me2C(5), J = 1.5 Hz); 1.75
4
1
(t, 3 H, Me, J = 1.2 Hz); 3.79 (s, 3 H, OMe); 4.30 (br.d, 1 H,
1700 (C=O), 1652, 1616, 1540, 1508 (C=N), 1464. H NMR
H(3), 3J = 9.6 Hz); 4.78 (m, 2 H, =CH2); 5.48 (dsp, 1 H, H(4),
3J = 9.6 Hz, 4J = 1.5 Hz); 6.99 (m, 2 H, Hm); 7.11 (m, 2 H, Ho);
12.1 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 18.1 (ZꢀMe); 21.5
(CDCl3), δ: 1.48 (s, 3 H, MeC(5)); 2.23 (s, 3 H, Me); 3.09, 3.35
(both d, H2C(4), 2J = 17.9 Hz); 3.77, 3.90 (both s, 3 H each, 2 OMe);
3
3
6.81 (d, 2 H, Hm, J = 9.0 Hz); 6.99 (d, 2 H, Ho, J = 9.0 Hz).

1684
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
Tomilov et al.
13C NMR (CDCl3), δ: 19.9 (MeC(5)); 24.8 (Me); 45.3 (C(4)); 52.3
(CO2Me); 55.6 (OMe); 76.6 (C(5)); 114.7 (Cm); 117.0 (Co);
134.9, 135.7 (C(3), Cipso); 155.6 (Cp); 162.8 (COO); 206.7 (C=O).
Reaction of compound 1b with 2,3ꢀdimethylbutꢀ2ꢀene (6). The
products obtained from dihydroindazole 1b (0.31 g) and tetramꢀ
ethylethene (6) (0.42 g) were separated by column chromatography
on SiO2 (benzene—EtOAc, gradient elution from 9 : 1 to 2 : 1).
They include methyl 2ꢀ(4ꢀfluorophenyl)hydrazonoꢀ3,3,4ꢀtriꢀ
methylpentꢀ4ꢀenoate (17b) (13 mg, 9%), methyl 1ꢀ(4ꢀfluoroꢀ
phenyl)ꢀ5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ5ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrꢀ
azoleꢀ3ꢀcarboxylate (18b) (41 mg, 28%), methyl 5ꢀacetylꢀ1ꢀ(4ꢀ
fluorophenyl)ꢀ5ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylꢀ
ate (19b) (14 mg, 10%), and minor amounts of methyl 1ꢀ(4ꢀfluoroꢀ
phenyl)ꢀ5ꢀmethylꢀ5ꢀ(propꢀ1ꢀenꢀ2ꢀyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ
3ꢀcarboxylate (20) (3.0 mg, 2%) and methyl 1ꢀ(4ꢀfluorophenyl)ꢀ
5ꢀmethylꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (21) (3.6 mg, 3%).
(Irel (%)): 234 [M]+ (78), 219 [M – Me]+ (5), 203 [M – OMe]+
(100), 176 (45), 160 (22), 135 (25), 109 (15), 95 (45). IR, ν/cm–1
:
2956, 2928, 1724 (COO), 1516 (C=N), 1452. 1H NMR (CDCl3),
δ: 2.31 (s, 3 H, Me); 3.94 (s, 3 H, OMe); 6.74 (br.s, 1 H); 7.17
(m, 2 H, Hm); 7.43 (m, 2 H, Ho). 13C NMR (CDCl3), δ: 12.4
(Me); 52.2 (OMe); 109.3 (C(4)); 116.2 (Cm, 2J = 23.2 Hz); 127.5
(Co, 3J = 8.6 Hz); 135.3 (Cipso, 4J = 3.1 Hz); 140.8 (C(5)); 143.7
(C(3)); 162.5 (Cp, 1J = 248 Hz); 163.0 (COO). 19F NMR
(CDCl3), δ: –111.8 (tt, CF, 3JH,F = 9.4 Hz, 4JH,F = 5.7 Hz).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ00636).
References
1. R. Huisgen, Angew. Chem., Int. Ed. (Engl.), 1963, 2, 565, 633.
2. P. Caramella, P. Grünanger, in 1,3ꢀDipolar Cycloaddition
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1984, vol. 1, p. 292.
3. P. K. Claus, in HoubenꢀWeil, Thieme Verlag, Stuttgart, 1990,
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Compound 17b (~93% purity), oil. MS (EI), m/z (Irel (%)):
278 [M]+ (50), 263 [M – Me]+ (55), 231 (100), 203 (15), 177 (8),
150 (10), 136 (14); 123 (18), 110 (90), 95 (30), 83 (70). 1H NMR
(CDCl3), δ: 1.39 (s, 6 H, Me2C(3)); 1.67 (br.s, 3 H, Me); 3.76 (s, 3 H,
OMe); 4.75 (m, 2 H, =CH2); 7.00 (m, 2 H, Hm); 7.13 (m, 2 H, Ho);
11.9 (NH). 13C NMR (CDCl3), δ: 20.3 (Me); 27.1 (Me2C(3));
45.4 (C(3)); 51.0 (CO2Me); 108.7 (=CH2); 114.6 (Co, 3J = 7.5 Hz);
115.9 (Cm, 2J = 22.5 Hz); 133.6 (C(4)); 140.5 (Cipso, 4J = 3.0 Hz);
1
151.8 (C(2)); 156.2 (Cp, J = 242 Hz); 164.4 (COO). 19F NMR
(CDCl3), δ: –123.7 (tt, CF, 3JH,F = 8.6 Hz, 4JH,F = 4.1 Hz).
Compound 18b, yellowish oil. Found (%): C, 60.96; H, 6.54;
N, 9.46. C15H19FN2O3. Calculated (%): C, 61.21; H, 6.51;
N, 9.52. MS (EI), m/z (Irel (%)): 294 [M]+ (6), 263 [M – OMe]+
(5), 235 [M – CO2Me]+ (45), 203 (100), 191 (15), 136 (30),
95 (30). IR, ν/cm–1: 3612 (OH); 2980, 2956, 1704 (C=O), 1560,
1
1508 (C=N), 1448. H NMR (CDCl3), δ: 1.26, 1.28 (both s,
3 H each, 2 Me); 1.49 (s, 3 H, MeC(5)); 1.70 (br.s, 1 H, OH);
2.95, 3.27 (both d, H2C(4), J = 18.0 Hz); 3.86 (s, 3 H, OMe);
8. F. Cargnoni, G. Molteni, D. L. Cooper, M. Raimondi,
A. Ponti, J. Chem. Soc., Chem. Commun., 2006, 1030.
9. Yu. V. Tomilov, D. N. Platonov, G. P. Okonnishnikova,
O. M. Nefedov, Izv. Akad. Nauk, Ser. Khim., 2010, 1357
[Russ. Chem. Bull., Int. Ed., 2010, 59, 1387].
10. G. Broggini, G. Molteni, M. Orlandi, J. Chem. Soc., Perkin
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14. P. D. Buttero, G. Molteni, S. Mondini, A. Ponti, Heteroꢀ
cycles, 2007, 71, 1095.
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20. P. A. Belyakov, V. I. Kadentsev, A. O. Chizhov, N. G. Koloꢀ
tyrkina, A. S. Shashkov, V. P. Ananikov, Mendeleev Comꢀ
mun., 2010, 20, 125.
2
6.97 (m, 2 H, Hm); 7.46 (m, 2 H, Ho). 13C NMR (CDCl3), δ:
21.6 (MeC(5)); 25.8, 26.1 (2 Me); 44.3 (C(4)); 52.2 (CO2Me);
75.9 (C(5)); 78.4 (C—OH); 115.3 (Cm, 2J = 22.3 Hz); 125.0
(Co, 3J = 7.7 Hz); 138.0 (C(3)); 140.0 (Cipso, 4J = 2.9 Hz); 160.1
(Cp, 1J = 244 Hz); 163.3 (COO). 19F NMR (CDCl3), δ: –123.9
(tt, CF, 3JH,F = 8.7 Hz, 4JH,F = 4.1 Hz).
Compound 19b, colorless crystals, m.p. 156—157 °C (CHCl3).
Found (%): C, 60.30; H, 5.36; N, 10.03. C14H15FN2O3. Calcuꢀ
lated (%): C, 60.43; H, 5.43; N, 10.07. MS (EI), m/z (Irel (%)):
278 [M]+ (12), 235 (62), 203 (100); 191 (14), 148 (10), 136 (25),
109 (10), 95 (30). IR, ν/cm–1: 3020, 1720 (COO), 1700 (C=O),
1
1560, 1508 (C=N), 1448. H NMR (CDCl3), δ: 1.51 (s, 3 H,
MeC(5)); 2.25 (s, 3 H, MeCO); 3.12, 3.38 (both d, H2C(4),
2J = 18.1 Hz); 3.90 (s, 3 H, OMe); 7.00 (m, 4 H, Hm, Ho).
13C NMR (CDCl3), δ: 19.7 (MeC(5)); 24.7 (MeCO); 45.5 (C(4));
2
52.5 (CO2Me); 76.3 (C(5)); 116.2 (Cm, J = 22.7 Hz); 116.7
(Co, 3J = 7.7 Hz); 136.8 (C(3)); 137.5 (Cipso, 4J = 2.8 Hz); 158.6
(Cp, 1J = 243 Hz); 162.6 (COO). 19F NMR (CDCl3), δ: –121.8
(tt, CF, 3JH,F = 8.2 Hz, 4JH,F = 4.9 Hz).
Compound 20, enriched to ~80%. GCꢀMS (EI), m/z (Irel (%)):
276 [M]+ (60), 261 [M – Me]+ (10), 235 (38), 229 (25), 203 (98),
191 (15), 176 (10), 136 (25), 109 (58), 95 (100). 1H NMR
(CDCl3), δ: 1.53 (s, 3 H, MeC(5)); 1.80 (Me); 3.02, 3.21 (both d,
H2C(4), 2J = 18.1 Hz); 3.87 (s, 3 H, OMe); 5.07, 5.12 (both m,
1 H each, =CH2); 6.92 (m, 2 H, Hm); 7.24 (m, 2 H, Ho).
Compound 21, oil. HRMS (ESI): [M + Na]+, calculated for
C12H11FN2O2Na 257.0697, found: 257.0691. MS (EI), m/z
21. Yu. V. Tomilov, D. N. Platonov, R. F. Salikov, G. P. Okonꢀ
nishnikova, Tetrahedron, 2008, 64, 10201.
Received September 2, 2010