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S. F. Vasilevsky, E. V. Mshvidobadze and J. Elguero
Vol. 39
of the primary product of addition of the terminal amine
group to the triple bond (Scheme 6). Previously we have
described the isomerization of a pyrazolodiazepine (7-mem-
bered ring) with ring-contraction into an N-aminodiazinone
(6-membered ring). Reciprocally, we have found that
N-aminolactams (isoindolinones) are transformed into
diazinones by heating in the presence of copper chloride (in
the literature there are data about ring contraction under the
action of hydrochloric acid [7]).
have used the absence of coupling constants in the CH
2
groups in compounds 4c and 8c. The fact that there is not
an adjacent proton excluded the five membered ring, leav-
ing only the six-membered pyridinones (way 2). The struc-
ture of the remaining compounds, 4a, 4b, 8a and 8b, are
similar and were assigned based on analysis of their ir
spectra (see [7] for a related problem).
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker AM-300 spec-
trometer. IR spectra were recorded on a Bruker IFS 66 spectrom-
eter (potassium bromide). Mass spectra were recorded on a
Finnigan SSQ-710 instrument (direct inlet, EI, 70 eV, ionization
chamber temperature 220-270 °C). Column chromatography was
carried out on KSK silica gel (60-200 mm). Melting points were
determined with a Kofler apparatus.
Preparation of Methyl Esters of Ethynylpyrazolecarboxylic
Acids (2a-c, 6a-c).
Compounds 1 or 5 (0.01 mole) and 0.01 mol of RCº CCu [cop-
per(I) acetylides] in 40 ml pyridine were heated under argon
atmosphere (TLC control: Silufol®). The reaction mixture was
cooled and poured into chloroform and was washed with aqueous
ammonium hydroxide. Chloroform solution was dried over
sodium sulfate and was filtered through silica gel (height/diame-
ter of the column: 2.5 x 4 cm), the solvent was eliminated under
reduced pressure. The products were recrystallized. The reaction
time and the constants of compounds are given in Table 1.
We also investigated other catalysts like copper(I)
phenylacetylide, bis-(triphenylphosphine)palladium(II)
dichloride and nickel(II) bromide trihydrate (at 80 °C). In
all cases, the product of heterocyclization of 7a was the
same N-aminolactam (8a).
The direction of heterocyclization of 3a-c and 7a-c in the
presence of salts of transition metals is different than that of
the hydrazide of 4-phenylethynyl-1-methylpyrazole-5-car-
boxylic acid (formation of pyridazinones, Scheme 1, class
3 and not of N-amino pyridinones, Scheme 2, class a [7]).
This difference could be related to interrupted conjugation
of the groups in the 3 and 4 positions of the pyrazole ring
compared with positions 4 and 5 (more double bond char-
acter) leading to another transition state.
Preparation of Hydrazides of Pyrazolecarboxylic Acides (3a-c,
7a-c).
Methyl esters of ethynylpyrazolecarboxylic acids (2a-c, 6a-c)
(0.01 mole), 5 ml of 80% hydrazine hydrate in 30 ml of butanol
were heated at reflux, cooled and the precipitate was collected by
filtration, products were recrystallized from ethanol. The reaction
time and the constants of compounds are given in Table 2.
Coming back to Scheme 1, it should be noted that in
benzene derivatives, fused (6,5), (6,6) and (6,7) systems
are formed thus covering all possibilities, but in the pyra-
zole series only (5,6)- and (5,7)-systems have been
obtained [7]. (5,5)-Fused systems formed by two 5-mem-
bered rings were not formed from these substrates in the
reported working conditions. This is correlated with our
conclusions in earlier work that, due to ring strain, (5,5)-
systems are much more difficult than (5,6) ones [7,10].
Of the four possible cases depicted in Scheme 2, three
are now known differences showing between case a in one
hand and cases c and d in the other as well as between
pyrazole and benzene.
The compounds were identified according to the data
reported in Tables 1-3. More precisely, the identity of final
compounds, 4 and 8, was established as follows. Of the
four possible structures of Scheme 1, the ways 3 and 4 can
be excluded because, both in ir and nmr, is by the observa-
tion of an amino group. Therefore, the compounds are
N-aminolactams (ways 1 and 2 in Scheme 1). To decide if
they are five- (way 1) or six-membered rings (way 2), we
Cyclization of Hydrazides of Pyrazolecarboxylic Acids with
Potassium Hydroxide (4a-c, 8a-c).
Hydrazides of pyrazolecarboxylic acids (3a-c, 7a-c) (0.01
mole) and 2.5 g of potassium hydroxide were heated in 30 ml of
ethanol (TLC control). The solvent was distilled under reduced
pressure, the precipitate was dissolved in benzene and filtered
through alumina (2.5 x 2 cm), then the benzene was distilled
under reduced pressure. The products were recrystallized from
ethanol. The reaction times and constants of the compounds are
given in Table 3.
Cyclization of Hydrazides of Pyrazolecarboxylic Acids with
Copper(I) Chloride (4a-c, 8a-c).
Hydrazides (3a-c, 7a-c) (0.01 mole), 0.6 g of copper(I) chlo-
ride in 25 ml of dimethylformamide were heated under argon
atmosphere. The reaction mixture was cooled and poured into
chloroformand was washed with aqueous ammonium hydroxide.
The chloroform solution was dried over sodium sulfate and was
filtered through alumina (2.5 x 2 cm), the solvent was evaporated
under reduced pressure. The products were recrystallized from
ethanol. The time of reactions and constants of compounds are
given in Table 3.
Vasilevsky, Sergei F.
