Synthesis of tetrasubstituted pyridazines via cascade reactions of diazocarbonyl compounds with pyridinium ylides

Article abstract of DOI:10.1007/s11172-008-0160-2

Reactions of pyridinium ylides with diazocarbonyl compounds involve the formation of functionalized azine intermediates that can undergo intramolecular cyclocondensation into tetrasubstituted pyridazines provided the starting reagents contain carbonyl groups. Reactions of pyridinium ylides with diazo compounds were studied for various substituents in both the substrates.

Full text of DOI:10.1007/s11172-008-0160-2

Russian Chemical Bulletin, International Edition, Vol. 57, No. 6, pp. 1252—1256, June, 2008
1252
Synthesis of tetrasubstituted pyridazines via cascade reactions
of diazocarbonyl compounds with pyridinium ylides
Yu. V. Tomilov, D. N. Platonov, D. V. Dorokhov, and A. A. Zhalnina
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
Reactions of pyridinium ylides with diazocarbonyl compounds involve the formation
of functionalized azine intermediates that can undergo intramolecular cyclocondensation into
tetrasubstituted pyridazines provided the starting reagents contain carbonyl groups. Reactions of
pyridinium ylides with diazo compounds were studied for various substituents in both the substrates.
Key words: methyl diazoacetate, pyridinium ylides, pyridazines, addition and elimination reꢀ
actions.
Pyridinium and triphenylphosphonium ylides conꢀ
condensation.3 In both cases, the overall "one pot" proꢀ
cess results in the formation of one C–N bond and three
new carbon—carbon bonds.
taining a carbonyl or carboxyl group at the ylide C atom
react with diazo esters to give polysubstituted pyrazoles or
pyridazines.1,2 Such reactions are of cascade character
and involve sequential interactions of two molecules of
phosphorus ylide (or three molecules of nitrogen ylide) with
a molecule of diazo ester with simultaneous elimination
of the ylideꢀforming molecule.3 For pyridinium ylides 1
containing a carboxyl or carbonyl group, these processes
usually differ in the final step, namely, heterocyclization
(Scheme 1). In the case of an azine containing four ester
groups, cyclization leads, through the corresponding ene
hydrazone,1 to tetrahydropyridazinetetracarboxylate 2;
for an azine containing a conjugated carbonyl group,
cyclization gives tetrasubstituted pyridazine 3 via aldol
Results and Discussion
As noted above, reactions of pyridinium ylides conꢀ
taining a carbonyl or carboxyl group at the ylide C atom
have been investigated only with diazo esters. To extend
the scope of this reaction and obtain new heterocyclic
compounds, here we studied a reaction of pyridinium
benzoylmethylide with methyl diazoacetate and, for
the first time, reactions of carbonylꢀ and methoxycarbonꢀ
ylꢀcontaining pyridinium ylides with diazo ketones.
In contrast to ylides 1a,b, pyridinium benzoylmethꢀ
ylide (1c) is stable under normal conditions4 and thus can
be both used in the individual state and generated from
appropriate pyridinium salts under the action of bases.
It turned out that ylide 1c reacts with methyl diazoacetate
like ylide 1b, regardless of the way of its preparation (use
of a specially prepared ylide for the reaction in CH2Cl2
or in situ generation of the ylide from phenacylpyridiniꢀ
um bromide and K2CO3 in acetonitrile). A series of casꢀ
cade transformations give substituted pyridazine 4 in
64—71% yield (Scheme 2). Essentially, a diazo acetate
molecule adds through its terminal N atom to the ylide
molecule with elimination of pyridine and formation of
a reactive azine. Then two more ylide molecules add
sequentially to the azine with elimination of two pyridine
molecules. The final step of the process involves aldol
cyclocondensation of tetrasubstituted azine 5 into pyꢀ
ridazine 4.
Scheme 1
As in the case of methylpyridazine 3, phenylpyridazine
4 exists in solution in the ketone and enol forms. Accordꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1228—1232, June, 2008.
1066ꢀ5285/08/5706ꢀ01252 © 2008 Springer Science+Business Media, Inc.

Synthesis of tetrasubstituted pyridazines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 6, June, 2008
1253
Scheme 2
ing to the 1H and 13C NMR spectra, the enol form is vastly
dominant in chloroform, while in DMSO, the ratio of
both forms approximates to 1 : 1 (Table 1).
Scheme 3
Like diazoacetates, diazo ketones (e.g., diazoacetone
(6a) or diazoacetophenone (6b)) react with pyridiniꢀ
um (methoxycarbonyl)methylide (1a) generated by
K2CO3ꢀpromoted decomposition of methoxycarbonylꢀ
methylpyridinium bromide to give, through a series of
cascade transformations and cyclocondensation of funcꢀ
tionalized azine intermediates 7, tetrasubstituted pyꢀ
ridazines 8a,b containing three ester groups (Scheme 3).
Despite the moderate yields of pyridazines (50—57%),
their "one pot" synthesis from relatively simple reagents
makes this method sufficiently convenient and efficient.
The structures of pyridazines 8a,b were determined
from their 1H and 13C NMR and mass spectra (see Experꢀ
imental).
In contrast to methyl diazoacetate, pyridinium acetylꢀ
methylide 1b improperly reacted with both diazoacetone
and diazoacetophenone. In both cases, a base added to
the reaction mixture for in situ generation of the ylide
initiates various side transformations of the resulting
polyketones, thus causing resinification of the reaction
mixture. However, specially prepared stable ylide 1c can
be successfully used in reactions with diazo ketones 6a,b
to give the expected pyridazines in 60—68% yields
(Scheme 4). In the case of diazoacetophenone, intermeꢀ
diate azine 9b is symmetrical and hence the product is
individual pyridazine 10. With diazoacetone, azine 9a
contains different substituents at reactive carbonyl
groups, which leads to a mixture of pyridazines 11 and 12
in the ratio ~2.6 : 1. The isomers were assigned from the
1H and 13C NMR chemical shifts of the signals for the
methyl groups: δH 2.1—2.2 and δC 15—16 for MeC(5)
and δH 2.6—2.9 and δC 25—27 for MeCOC(3). It should
also be noted that each of the pyridazines 10—12, like
pyridazines 3 and 4, exists in solution in the ketone and
R = Me (a), Ph (b)
enol forms: their H and 13C NMR spectra show characꢀ
teristic signals for the methylene and olefinic protons
(see Table 1).
1
The character of the substituents in both diazo comꢀ
pound and ylide substantially influences the pathway of
the reactions under discussion. This influence is possible
in any step of the process. For instance, diazomethane
and phenyldiazomethane do not react noticeably with
pyridinium ylides 1a—c even in the first step. Nor does
in situ generated unsubstituted pyridinium methylide reꢀ
act with either diazoacetone or methyl diazoacetate. That
is why the presence of electronꢀwithdrawing substituents
in an ylide and a diazo compound is important for sucꢀ
cessful implementation of both the first and subsequent
steps of the reaction. However, this criterion has some
limitations. For instance, a bulky substituent in a diazoꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 6, June, 2008
Tomilov et al.
Table 1. Ratio of the ketone and enol forms in pyridazines 4 and 10—12 and the chemical shifts δ of the key signals in the 1H and
13C NMR spectra
Comꢀ
pound
Solvent
Ketone :
enol
1H NMR
13C NMR
Ketone, Enol,
CH2 =CH
Ketone
CH2 C(6)
Enol
C(6)
C=O
=CH =C(OH)
C=O
at С(6)
at С(3) and С(4)
3 (see Ref. 3) CDCl3
1 : 1.6
4.29 5.30 49.0 163.3
4.45 5.58 47.8 160.6
4.68 5.77 44.5 159.7
4.78 5.65 44.2 160.0
4.72 5.83 44.4 158.8
4.68 5.73 44.5 159.3
202.7
203.6
196.1
195.9
196.0
196.0
*
89.0
88.6
89.2
88.3
88.9
89.1
86.1
189.7
186.1
178.7
177.5
182.0
182.5
185.1
153.8
154.1
157.0
156.5
154.9
155.3
156.1
164.5, 200.6
159.0, 200.0
163.2, 192.2
162.7, 192.0
189.6, 193.4
192.6, 195.5
192.2, 195.9
DMSOꢀd6 13 : 1
CDCl3 1 : 4
DMSOꢀd6 1.1 : 1
4
10
11
12
CDCl3
CDCl3
CDCl3
1 : 6
1 : 5.1
1 : 5
4.94
6.10
44.4
*
* These signals cannot be identified unambiguously because of the low concentration of isomer kꢀ12 in the mixture (11 : 12 = 2.6 : 1).
Scheme 4
diazoacetone (6a), while 1ꢀadamantanoyldiazomethane
does not react with pyridinium ylides at all, including
specially prepared ylide 1c. Surprisingly, neither methyl
diazomalonate nor ethyl diazopyruvate reacts with ylides.
Apparently, the assumption that the ylide C atom is diꢀ
rectly attacked by the terminal N atom of the diazo comꢀ
pound is insufficient. In fact, for the formation of a new
C—N bond, a certain orientation of the molecule of the
diazo compound relative to the polarized C—N bond of
the ylide can be important (e.g., the transition state forꢀ
mally close to 1,3ꢀdipolar addition reactions).
The behavior of disubstituted pyridinium ylides 13
and monosubstituted analogs in reactions with diazo
compounds differ substantially. First of all, it should be
noted that only reactions with diazo esters provided
a sufficiently informative result. Earlier,2 we found that
a reaction of methyl diazoacetate with pyridinium
(methoxycarbonyl)phenylmethylide (13a) stops after the
addition of two ylide molecules to the diazo compound.
Ene hydrazone 14a was isolated as a stable reaction prodꢀ
uct (Scheme 5). It turned out that ylide 13b containing
two ester groups at the ylide C atom reacts with methyl
diazoacetate in a similar way leading to individual ene
hydrazone 14b bearing five ester groups (see Scheme 5).
The yield of compound 14b was 46%. At the same time,
methyl diazoacetate does not react with ylide 13c conꢀ
taining an electronꢀdonating ethyl group as a second subꢀ
stituent at the ylide C atom.
The resulting diaza dienes 14a,b are not CH acids
since their double bonds are fully substituted. Because of
this, they are very stable and resist cyclization in the
presence of bases or on heating (e.g., in boiling toluene).
Hence, like diazo esters, sterically unhindered diazo
ketones can react with pyridinium ylides containing an
electronꢀwithdrawing substituent (acyl or ester group)
at the ylide C atom. Sequential addition of three ylide
molecules followed by cyclocondensation lead to tetraꢀ
carbonyl compound lowers the reaction rate: the formaꢀ
tion of pyridazine derivatives from diazoacetophenone
(6b) takes twice as much time as in the reaction with

Synthesis of tetrasubstituted pyridazines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 6, June, 2008
1255
Scheme 5
(s, 2 H, CH2), 7.10—7.87 (m, 3 Ph of both tautomers). 1H NMR
(200 MHz, DMSOꢀd6), δ: enol form (47%), 3.74 (s, 3 H, OMe),
5.65 (s, 1 H, =CH), 16.0 (OH); ketone form (53%), 3.80 (s, 3 H,
OMe), 4.78 (s, 2 H, CH2), 7.05—7.85 (m, 3 Ph of both tautomers).
13C NMR (50 MHz, DMSOꢀd6), δ: enol form (47%), 52.3 (OMe),
88.3 (=CH), 156.5, 158.0 (C(6) and iꢀC(Ph) at C(5)), 162.7
(COO), 177.5 (=COH), 192.0 (CO); ketone form (53%), 44.2
(CH2), 52.5 (OMe), 160.0 (C(6)), 163.9 (COO), 191.5 (CO), 195.9
(CO in the side chain), 125—129 (CH of the benzene rings in both
tautomers), 131—139 (quaternary C atoms of the pyridazine ring
and three benzene rings in both tautomers). Selected key signals for
both tautomers are given in Table 1.
R1 = Ph, R2 = Me (a); R1 = CO2Et, R2 = Et (b); R1 = Et, R2 = Me (c)
substituted pyridazines. In the case of disubstituted pyriꢀ
dinium ylides, the reaction involves two ylide molecules
and the final products are stable (under the reaction conꢀ
ditions) diazaalkadienes (ene hydrazones) bearing up to
five ester groups. The compounds obtained can be of
interest as polyfunctional synthons for various chemical
processes.
B. Methyl diazoacetate (1.00 g, 0.01 mol) was added to a solution
of pyridinium benzoylmethylide (1c) (5.92 g, 0.03 mol) in CH2Cl2
(60 mL). The mixture was left at 5 °C for 24 h. Then the solvent was
removed in vacuo and the residue was crystallized from methanol
(30 mL) (see method A) to give an orange crystalline solid (2.83 g,
64%), which was identical with compound 4 obtained above.
Methyl 3,4ꢀdimethoxycarbonylꢀ5ꢀmethylpyridazinꢀ6ꢀylacetate
(8a). Potassium carbonate dihydrate (10.4 g, ~0.06 mol) was added
to a mixture of diazoacetone (6a) (0.84 g, 0.01 mol) and
Nꢀ(methoxycarbonylmethyl)pyridinium bromide (6.96 g, 0.03 mol)
in acetonitrile (40 mL). The reaction mixture was stirred at ~20 °C
for 15 h. The precipitate that formed was filtered off and the solvent
was removed in vacuo. The resinous residue was dissolved in water
(120 mL) and the product was extracted with ethyl acetate (3×50 mL).
The extract was dried with anhydrous Na2SO4 and concentrated
in vacuo. The residue was chromatographed on SiO2 with benꢀ
zene—AcOEt (1 : 1) as an eluent. The yield of pyridazine 8a was 1.60 g
(57%), light yellow crystals, m.p. 68—70 °C. Found (%): C, 51.32;
H, 5.12; N, 9.67. C12H14N2O6. Calculated (%): C, 51.07; H, 5.00;
N, 9.93. MS, m/z (Irel (%)): 282 [M]+ (10), 251 [M – OMe]+ (22),
223 [M – CO2Me]+ (13), 209 [M – CH2CO2Me]+ (13), 194
[M – CH2CO2Me – Me]+ (32), 166 (100). 1H NMR (CDCl3), δ:
2.32 (s, 3 H, Me); 3.71 (s, 3 H, CO2Me in the side chain); 3.97, 4.03
(both s, 3 H each, 2 CO2Me); 4.31 (s, 2 H, CH2). 13C NMR (50 MHz,
CDCl3), δ: 15.2 (Me), 40.1 (CH2), 52.6, 53.3, 53.6 (3 OMe),
128.3, 135.1 (C(4) and C(5)), 146.7 (C(3)), 159.4 (C(6)), 164.2
(COO at C(3)), 165.7 (COO at C(4)), 169.0 (COO in the side chain).
Methyl 3,4ꢀdimethoxycarbonylꢀ5ꢀphenylpyridazinꢀ6ꢀylacetate
(8b). Potassium carbonate (8.70 g, 0.05 mol) and Nꢀ(methoxyꢀ
carbonylmethyl)pyridinium chloride (5.11 g, 22 mmol) were added
to a solution of diazoacetophenone (6b) (1.02 g, 7 mmol) in acetoꢀ
nitrile (45 mL). The reaction mixture was stirred at ~20 °C for 18 h.
The precipitate that formed was filtered off and the filtrate was
concentrated in vacuo. The resinous residue was dissolved in water
(100 mL) and the product was extracted with ethyl acetate
(3×50 mL). The organic fractions were combined, dried with anhyꢀ
drous Na2SO4, and concentrated in vacuo. Then the residue was left
in diethyl ether (30 mL) at ~20 °C for ~14 h. The undissolved
precipitate was filtered off and the solvent was removed in vacuo.
The yield of pyridazine 8b was 1.20 g (~50%), a light yellow, highly
viscous liquid. MS, m/z (Irel (%)): 344 [M]+ (10), 314 [M – CH2O]+
(20), 313 [M – OMe]+ (22), 285 [M – CO2Me]+ (13), 271
[M – CH2CO2Me]+ (13), 256 (32), 228 (48), 168 (45), 59 (100).
1H NMR (CDCl3), δ: 3.61, 3.66, 4.09 (all s, 3 H each, 3 CO2Me);
4.05 (s, 2 H, CH2); 7.23, 7.48 (both m, 2 H + 3 H, Ph). 13C NMR
(CDCl3), δ: 40.1 (CH2), 52.4, 52.9, 53.6 (3 OMe), 128.3, 128.8
(Co, Cm, Ph), 129.7 (Cp, Ph), 131.9, 133.8 (C(4), C(5)), 138.4
(Cipso, Ph), 146.6 (C(3)), 158,3 (C(6)), 164.1, 164.9 (2 COO),
169.3 (COO in the side chain).
Experimental
1
H and 13C NMR spectra were recorded on Bruker ACꢀ200
(200.13 and 50.3 MHz, respectively) and Bruker ACꢀ300 specꢀ
trometers (300.13 and 75.36 MHz, respectively) in CDCl3 or
DMSOꢀd6 with 0.05% Me4Si as the internal standard. Mass spectra
were recorded on a Finnigan MAT INCOSꢀ50 instrument (EI, 70 eV).
For column chromatography, silica gel 60 (0.063—0.200 mm,
Merck) was used. The water content of potassium carbonate (reꢀ
agent grade) upon drying was ~20%. Its molecular formula is close
to K2CO3•2H2O. Solvents were distilled before use.
Diazo ketones 6a,b and adamantanoyldiazomethane were preꢀ
pared according to a standard procedure from diazomethane and
acetyl, benzoyl, or adamantanecarbonyl chlorides.5,6 Quaternary
pyridinium salts were prepared by quaternization of pyridine with
αꢀhalo carbonyl compounds in acetone.7 Pyridinium benzoylmeꢀ
thylide (1c) and pyridinium bis(ethoxycarbonyl)methylide (13b)
were prepared by deprotonation of appropriate quaternary Nꢀ(pheꢀ
nacyl)pyridinium and Nꢀ(methoxycarbonylmethyl)pyridazinium
salts under the action of potassium carbonate and triethylamine,
respectively.4,8
Methyl 4ꢀbenzoylꢀ6ꢀphenacylꢀ5ꢀphenylpyridazineꢀ3ꢀcarboxyꢀ
late (4). A. Potassium carbonate dihydrate (10.4 g, ~0.06 mol) was
added to a mixture of Nꢀphenacylpyridinium bromide (8.34 g,
0.03 mol) and methyl diazoacetate (1.00 g, 0.01 mol) in acetonitrile
(70 mL). The reaction mixture was stirred at ~20 °C for 12 h and
filtered. The filtrate was concentrated in vacuo and water (40 mL)
was added to the residue. The product was extracted with CH2Cl2
(3×30 mL). The extract was dried with anhydrous MgSO4 and
concentrated in vacuo. A nearly black residue was diluted with
methanol (30 mL). The crystalline precipitate that formed was
filtered off. The filtrate was concentrated to 1/3 of the initial volume
and cooled to 5 °C. Another crop of the precipitate was filtered off
and combined with the main crop. The yield of pyridazine 4 was
3.10 g (71%), small yellowꢀorange crystals, m.p. 185—187 °C.
Found (%): C, 74.02; H, 4.50; N, 6.22. C27H20N2O4. Calculated
(%): C, 74.30; H 4.62; N, 6.42. MS, m/z (Irel (%)): 436 [M]+ (29),
435 [M – H]+ (30), 407 [M – HCO]+ (38), 331 [M – COPh]+
(32), 105 [COPh]+ (100), 77 [Ph]+ (90). 1H NMR (200 MHz,
CDCl3), δ: enol form (80%), 3.88 (s, 3 H, OMe), 5.77 (s, 1 H,
=CH), 15.9 (OH); ketone form (20%), 3.91 (s, 3 H, OMe), 4.68

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Tomilov et al.
3,4ꢀDibenzoylꢀ6ꢀphenacylꢀ5ꢀphenylpyridazine (10). Diazoaceꢀ
tophenone (6b) (1.46 g, 10 mmol) was added to a solution of pyridinꢀ
ium benzoylmethylide (1c) (6.51 g, 33 mmol) in CH2Cl2 (50 mL).
The reaction mixture was kept at –5 °C for two days. The solvent
was removed in vacuo and the residue was recrystallized from methꢀ
the residue was treated with benzene (30 mL). The undissolved part
was filtered off. The filtrate was concentrated in vacuo and the
residue was chromatographed on SiO2 with benzene as an eluent.
The yield of compound 14b was 0.96 g (46%), an orange oil.
Found (%): C, 49.68; H, 6.07; N, 6.51. C17H24N2O10. Calculatꢀ
ed (%): C, 49.04; H, 5.81; N, 6.73. MS, m/z (Irel (%)): 416 [M]+
(30), 370 [M – EtOH]+ (62), 59 [CO2Me]+ (100). 1H NMR
(CDCl3), δ: 1.25, 1.28 (both t, 6 H each, 4 Me, J = 7.3 Hz); 3.87
(s, 3 H, OMe); 4.14—4.43 (m, 8 H, 4 OCH2); 14.06 (s, 1 H, NH).
13C NMR (CDCl3), δ: 13.9 and 14.0 (2 Me each), 52.8 (OMe),
61.5, 61.7, 61.9, 62.7 (4 OCH2), 99.6 (C(6)), 130.0 (C(5)), 153.8
(C(2)), 160.0, 161.6, 162.3, 164.1, 166.1 (5 COO).
anol (20 mL). The yield of compound 10 was 3.29
g
(68%), an orange fine crystalline solid, m.p. 190—192 °C. Found (%):
C, 79.30; H, 4.42; N, 5.59. C32H22N2O3. Calculated (%):
C, 79.65; H, 4.60; N, 5.81. 1H NMR (CDCl3), δ: ketone form (15%),
4.77 (s, 2 H, CH2), 7.10—7.79 (m, 4 Ph of both tautomers), 7.86
and 8.18 (both br.d, 2 H each, Ho (2 Ph), 3J = 8.0 Hz); enol form
(85%), 5.89 (s, 1 H, CH), 7.10—7.79 (m, 4 Ph of both tautomers),
8.09 (br.d, 2 H, Ho, Ph, 3J = 8.2 Hz), 11.9 (br.s, 1 H, OH).
13C NMR (CDCl3), δ: ketone form, 44.4 (CH2), 127.0—139.4
(C atoms of the pyridazine ring and the phenyl groups), 158.8
(C(6)), 191.8, 193.8, 196.0 (3 C=O); enol form, 88.9 (=CH),
127.0—139.4 (C atoms of the pyridazine ring and the phenyl
groups), 147.6 (Cipso, Ph at C(5)), 154.9 (C(6)), 182.0 (=C(OH)),
189.6, 193.4 (2 C=O). Selected key signals for both tautomers are
given in Table 1.
3ꢀAcetylꢀ4ꢀbenzoylꢀ6ꢀphenacylꢀ5ꢀphenylpyridazine (11) and
3,4ꢀdibenzoylꢀ5ꢀmethylꢀ6ꢀphenacylpyridazine (12). A reaction of
diazoacetone (6a) (0.42 g, 5 mmol) with pyridinium benzoylmethꢀ
ylide (1c) (3.16 g, 16 mmol) was carried out as described for
pyridazine 10. Recrystallization from methanol gave dark yellow
crystals (1.26 g, 60%), m.p. 174—177 °C. According to 1H NMR
data, the crystals were a mixture of regioisomers 11 and 12 (~2.6 : 1),
each of which exists in solution in the ketone and enol forms
(see Table 1). Found (%): C, 77.01; H, 4.52; N, 6.49. C27H20N2O3.
Calculated (%): C, 77.13; H, 4.79; N, 6.66. MS, m/z (Irel (%)): 420
[M]+ (22), 419 [M – H]+ (16), 392 (11), 391 (15), 315
[M – COPh]+ (22), 105 [COPh]+ (100), 77 [Ph]+ (85). 1H NMR
(CDCl3), δ: compound kꢀ11, 2.90 (s, 3 H, COMe), 4.63 (s, 2 H,
CH2); compound eꢀ11, 2.62 (s, 3 H, COMe), 5.74 (s, 1 H, =CH),
16.05 (br.s, 1 H, OH); compound kꢀ12, 2.19 (s, 3 H, Me at C(5)),
4.94 (s, 2 H, CH2); compound eꢀ12, 2.08 (s, 3 H, Me at C(5)), 6.01
(s, 1 H, =CH), 16.30 (br.s, 1 H, OH), 7.0—8.1 (m, 3 Ph of all four
isomers). 13C NMR (CDCl3), δ: 15.3 (Me in eꢀ12), 15.5 (Me in kꢀ12),
25.5 (Me in eꢀ11), 26.8 (Me in kꢀ11). The rest of the signals
appeared approximately in the same regions as for compound 10;
the interpreted signals for the ketone and enol forms of regioisomers
11 and 12 are given in Table 1.
This work was financially supported by the Presidium
of the Russian Academy of Sciences (Basic Research Proꢀ
gram "Development of the Methods for the Synthesis of
Chemical Compounds and Creation of Novel Materiꢀ
als", Subprogram "Development of the Methodology of
Organic Synthesis and Creation of Compounds with Valuꢀ
able Practical Properties") and the Council on Grants of
the President of the Russian Federation (Program for
State Support of Leading Scientific Schools of the Rusꢀ
sian Federation, Grant NShꢀ3237.2008.3).
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8. R. G. Kostyanovsky, V. F. Rudchenko, V. G. Shtamburg, I. I.
Chervin, S. H. Nasibov, Tetrahedron, 1981, 37, 4245.
Diethyl 2,6ꢀdiethoxycarbonylꢀ5ꢀmethoxycarbonylꢀ3,4ꢀdiazaꢀ
heptaꢀ2,5ꢀdieneꢀ1,7ꢀdioate (14b). Methyl diazoacetate (0.50 g,
5 mmol) was added to a suspension of ylide 13b (2.37 g, 10 mmol)
in acetonitrile (25 mL). The reaction mixture was refluxed with
stirring for 18 h. Then the solvent was removed in vacuo and
Received February 6, 2008;
in revised form April 11, 2008