Spectral study of the reaction of functionally substituted enehydrazides with proton donors

Article abstract of DOI:10.1023/A:1021643510974

Reactions of new enehydrazides, N′,N′ -dimethyl-N-vinylpropenohydrazide and N′,N′ -dimethyl-N-vinylbenzohydrazide with chloroform, phenol, and hydrogen chloride in carbon tetrachloride were studied by IR spectroscopy. In the first two cases, molecular complexes are formed between the hydrazide and proton donor. The reaction of N′,N′-dimethyl-N-vinylpropenohydrazide with HCl results in formation of dihydropyrazole derivative which exists as a tautomeric mixture of the major lactam and minor lactim forms. N′,N′ -dimethyl-N-vinylbenzohydrazide reacts with hydrogen chloride to give protonated form in which proton is localized on the amino nitrogen atom. The structure of the initial compounds and the products was analyzed in terms of AM1 quantum-chemical calculations.

Full text of DOI:10.1023/A:1021643510974

Russian Journal of Organic Chemistry, Vol. 38, No. 9, 2002, pp. 1266 1270. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 9, 2002,
pp. 1321 1325.
Original Russian Text Copyright
2002 by Sarapulova, Rozinova, Rozinov, Kolbina.
Spectral Study of the Reaction of Functionally Substituted
Enehydrazides with Proton Donors
G. I. Sarapulova, L. G. Rozinova, V. G. Rozinov, and V. E. Kolbina
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: amedved@irioch.irk.ru
Institute of Petrochemical and Coal-Chemical Synthesis, Irkutsk State University,
ul. Karla Marksa 1, Irkutsk, 664033 Russia
Received January 9, 2002
Abstract Reactions of new enehydrazides, N ,N -dimethyl-N-vinylpropenohydrazide and N ,N -dimethyl-N-
vinylbenzohydrazide with chloroform, phenol, and hydrogen chloride in carbon tetrachloride were studied by
IR spectroscopy. In the first two cases, molecular complexes are formed between the hydrazide and proton
donor. The reaction of N ,N -dimethyl-N-vinylpropenohydrazide with HCl results in formation of dihydro-
pyrazole derivative which exists as a tautomeric mixture of the major lactam and minor lactim forms. N ,N -di-
methyl-N-vinylbenzohydrazide reacts with hydrogen chloride to give protonated form in which proton is
localized on the amino nitrogen atom. The structure of the initial compounds and the products was analyzed
in terms of AM1 quantum-chemical calculations.
Interest in new functionally substituted hydrazine
derivatives, specifically in enehydrazines and ene-
hydrazides, is explained by their high biological
activity (which is responsible for their application
in medicine) and the ability to undergo tautomeric and
conformational transformations [1 5]. Some trans-
formations of enehydrazines (provided that they have
an appropriate structure) are not typical of common
hydrazines, and they involve both nitrogen atoms
simultaneously [2]. Although enehydrazines may be
regarded as aza analogs of extensively studied
enamines, the similarity in stereochemical behavior
of enamines and enhydrazines is sometimes difficult
to reveal since the latter have been studied poorly.
The most typical transformation of enehydrazines
is cyclization to pyrroles or their fused analogs, which
is accompanied by loss of one nitrogen atom. As
a rule, such processes occur on heating or (in the
presence of acids) even in the cold [2]. Acetylation
of arylhydrazones [6] gives acyl derivatives of ene-
hydrazines, which are converted into indoles on treat-
ment with dilute acids or alkalies. Another important
property of enehydrazines is enehydrazine hydrazone
tautomerism, which is formally analogous to keto
enol or imine enamine tautomerism; however, there
are strong differences due to specific electronic struc-
ture of the enehydrazino group [1, 2, 4, 5, 7, 8].
It is also known that, despite the presence of
several basic centers, enehydrazines are protonated
at 70 C at the carbon atom (like enamines) to give
hydrazonium salts which were isolated in the crystal-
line state [9]. However, N-protonated species were
not detected by spectral methods though the results
of enhydrazine transformations in the presence of
acids clearly indicate the existence of such forms.
Presumably, the basicity of the nitrogen atoms is
strongly reduced or the concentration of N-protonated
species is very small.
In the recent years, increased number of studies
were published, where the stereochemistry of hydra-
zine derivatives was examined by both experimental
[1, 4, 10] and theoretical [11] methods. In the present
work we studied by IR spectroscopy reactions with
proton donors of new enehydrazides possessing un-
saturated functional groups of different polarities:
N ,N -dimethyl-N-vinylpropenohydrazide (I) and
N ,N -dimethyl-N-vinylbenzohydrazide (II). As proton
donors we used chloroform (pKa = 15), phenol
(pKa = 9.95) in carbon tetrachloride, and dry hydrogen
chloride (pKa = 7) in carbon tetrachloride. We also
1070-4280/02/3809-1266$27.00 2002 MAIK Nauka/Interperiodica

SPECTRAL STUDY OF THE REACTION OF FUNCTIONALLY
1267
analyzed the electronic and steric structure of the
initial compounds and products of their transforma-
tions in terms of the AM1 quantum-chemical method.
hydrazide and phenol and complete rupture of the
intramolecular hydrogen bond.
On the basis of the set of spectral shifts of the
stretching vibration frequency of free phenolic OH
group, which characterize complex formation with
The IR spectra of dilute solutions of compounds I
and II in carbon tetrachloride contain the following
1
various bases [15], we can conclude that the observed
absorption bands, cm : ( C H) 3030 3120,
1
shifts
OH = 262 and 400 cm correspond to
(C O) 1660 1670, (C C) 1635 1615, (C N)
1315 1305, (N N) 1060, and (CH CH2) 960
970. This pattern is consistent with the enehydrazide
structure [2, 12, 13]. The carbonyl and hydrazine
groups each give a single band, though both hydra-
zides and enone systems in solution can exist as
different conformers or their equilibrium mixtures
(Z and E conformers) due to some degrees of freedom
and restricted rotation about formally single bonds
in conjugated systems, specifically about the amide
C N bond [2, 11]. The carbonyl absorption frequency
is unexpectedly low, as compared to the frequency
a 1:2 molecular complex with C O H O and
N
H O intermolecular hydrogen bonds.
Radically different transformations occur in the
reaction of enehydrazides I and II with dry hydrogen
chloride in CCl4 solution. When a solution of I in
carbon tetrachloride was purged with dry HCl for 2
to 20 min, bands belonging to the vinyl group disap-
peared from the spectrum. Simultaneously, new bands
at 1720 [ (C O)] and 3370 cm 1 [ (NH)] and a series
1
of characteristic bands at 1080, 1250, and 1360 cm
appeared, and their intensity sharply increased. This
pattern should be interpreted as rupture of C C
bonds and formation of five-membered ring [16] with
a secondary amide (lactam) group (the above fre-
quencies are typical of a fixed cis-O C N H
1
region 1680 1700 cm typical of related hydrazides
and enones [12 14].
Heating of solutions of enehydrazides I and II in
decane to 130 C leads to appearance of a high-fre-
1
moiety). In addition, strong amide II (1520 cm ) and
1
quency (C O) band at 1680 cm and increase in
1
amide III bands (1290 cm ) appear [12, 16], which
its intensity. By contrast, the amide (C N) band
shifts to lower frequencies. The absence of concentra-
tion dependence of the carbonyl absorption frequency
and intensity and similarity in the variation of the
(C O), ( CH), and ( CH) bands with rise in
temperature suggest that the corresponding fragments
are involved in intramolecular hydrogen bond like
C O H C , which undergoes rupture as the tem-
perature rises.
are lacking in the spectrum of the initial enhydrazide.
+
+
The bands at +2800 [ (NCH3), 1410 [ (NCH3), and
1
908 cm [ (N N)] [16, 17] can be assigned with
certainty to protonated form in which the positive
charge is localized on the terminal nitrogen atom
of the hydrazine fragment. The possibility for protona-
tio+n of the N atom is ruled out, for in this case the
1
(N H) frequency should be 3000 cm or lower,
as was shown for homoconjugated NH groups [18].
A different pattern of spectral changes is observed
in a proton-donor solvent (chloroform) at room tem-
perature: in addition to the main carbonyl absorption
Elimination of the N-vinyl group from enehydra-
zide I by the action of HCl yields 1,1-dimethyl-4,5-di-
hydropyrazolinium-3-oxide (Ia) which is the major
tautomer. However, the presence of minor tautomer Ib
in solution cannot be excluded: in the IR spectrum we
1
band at 1660 cm , a low-frequency component
1
appears at 1650 cm . Simultaneously, the frequency
and intensity of the (C N) band considerably in-
1
1
observed absorption at 1570 cm due to endocyclic
crease (to 1330 cm ). These data indicate formation
C N bond [16]. Thus the product gives rise to
lactam lactim tautomerism (Scheme 1).
of a new, though weak, intermolecular hydrogen bond
between the carbonyl group and proton-donor solvent
and partial rupture of the intramolecular H-bond.
The geometric structure of initial compounds I
and II was calculated for a large set of possible con-
formations with account taken of rotation about the
C N, C Carom, and N N bonds. The most favorable
conformers were selected on the basis of the lowest
heats of formation, which correspond to cis-orienta-
tion of the hydrazine fragment with respect to the
double bond. Schemes 1 and 2 give the structures,
enthalpies of formation, and dipole moments of the
predominant conformers of enhydrazides I and II and
products of their transformations. It should be noted
In the IR spectra of solutions of enhydrazines I and
II in carbon tetrachloride in the presence of phenol
we observed a new low-frequency carbonyl band at
1
1650 cm and a broad band with two maxima at
1
3340 and 3430 cm which belongs to associated
hydroxy group of phenol. With excess phenol, the
1
low-frequency absorption band at 1650 cm pre-
dominates in the carbonyl region. The observed
spectral changes unambiguously indicate formation
of intermolecular hydrogen bond between the ene-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

1268
SARAPULOVA et al.
Scheme 1.
Hf
=
45.26 kcal/mol
= 3.19 D
Hf
=
38.46 kcal/mol
= 5.6 D
Hf
=
51.50 kcal/mol
= 6.0 D
1
that, according to the H NMR data [2], enehydrazines
are characterized by E configuration of the hydrazine
fragment with respect to symmetrically substituted
double bond [2].
The results of our calculations indicate the exist-
ence in molecules I and II of shortened intramolecular
contacts C O H C 2.068 , which are consider-
ably shorter than the sum of the corresponding van der
Waals radii. These data support the presence of intra-
molecular hydrogen bond which stabilizes the Z
configuration. The assumed orientation of the enone
fragment in I with respect to the N N bond is addi-
tionally stabilized by attractive interaction between
the 1-H atom and hydrogen atom of one of the methyl
Variation of the IR spectrum on reaction of ene-
hydrazide II with HCl in carbon tetrachloride unam-
biguously indicates removal of vinyl group from
the molecule (the corresponding absorption bands
disappear from the spectrum) and formation of secon-
dary acyclic amide group: the observed (NH) and
(C O) frequencies, 3400 and 1690 cm , respec-
tively, are consistent with the spectra of benzohydra-
zides [12]. Amide II (1510 cm ) and amide III bands
(1315 cm ) are also present+. Taking into account
appearance o+f new bands, (NCH3) 2820, (NCH3)
1420, and (N N) 910 cm , the observed IR pattern
indicates protonation of 1,1-dimethyl-2-benzoylhydra-
zine (IIa) at the N atom (Scheme 2). No other tauto-
meric forms were detected.
1
groups at the terminal nitrogen atom (shortened H
contact, 2.02 ).
H
1
Table 1 contains the geometric parameters of com-
pounds I and II, optimized by the AM1 procedure.
It is seen that molecule II is characterized by greater
acoplanarity of the enhydrazine fragment and carbonyl
group. The torsion angle N N C2C1 is 9 , while the
corresponding angle in molecule I is 2 (for atom
numbering, see Scheme 3). The enehydrazine moiety
in both molecules is faily planar: the torsion angle
C6C4N N does not exceed 3 . The fragment involved
in intramolecular hydrogen bond is also flattened
(within 1 5 ), which undoubtedly creates favorable
steric conditions for hydrogen bonding and effective
conjugation.
1
+
1
Scheme 2.
Scheme 3.
Hf
=
45.26 kcal/mol
= 3.19 D
Hf
=
54.29 kcal/mol
= 3.93 D
The results obtained are in agreement with our
previous data for hydrazides derived from carboxylic
and fluorocarboxylic acids, which are protonated at
the amino nitrogen atom [12].
The benzene ring in molecule II is almost ortho-
gonal to the carbonyl group plane (the corresponding
torsion angle is 92 ), while the vinyl group in the
enone fragment of I forms an angle of 38 with
respect to the carbonyl group plane. Analysis of the
geometric parameters shows that steric conditions in
molecule I are more farvorable for formation of
According to the AM1 calculations, lactam form
Ia is more favorable than lactim tautomer by a
H
value of 13.04 kcal/mol. Analogous results ( H =
14 kcal/mol) were obtained by Feshin et al. [19] who
studied protonation of carboxylic acid hydrazides
ab initio.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

SPECTRAL STUDY OF THE REACTION OF FUNCTIONALLY
1269
Table 1. Geometric parameters of molecules I and II, optimized by the AM1 methoda
d,
, deg
, deg
Bond
Angle
Angle
I
II
I
II
I
II
C O
N N
1.24
1.38
1.42
1.48
1.41
1.34
1.24
1.38
1.42
1.49
1.41
1.34
NNC2
117.9
119.9
118.5
127.8
112.0
118.5
117.7
119.8
118.8
127.9
112.1
117.5
N N C2C1
N C2C1C7
OC2N N
4.3
9.0
52.3
171.5
2.9
177.8
1.3
N C2C1
OC2N
155.0
176.0
2.1
177.8
5.1
N
C2
C1 C2
N C4C6
N C4C5
C4N C2
C6C4N N
H5C4N N
H5C4N C2
N
C4
C4 C6
a
For atom numbering, see Scheme 3.
a
p
-type cross-conjugated system with participa-
bond, in contrast, acquires an amide character and
shortens from 1.422 to 1.382 , the latter value being
typical of amides. The geometric parameters are con-
sistent with the spectral data.
tion of multiple bonds surrounding the N N group.
The p, -conjugation in hydrazine derivatives was
studied in most detail using hydrazones as examples
[3]. Only scanty data are available for the other
derivatives. As a result of conjugation, the whole
enehydrazine fragment tends to adopt a planar con-
formation. However, the N atom in the enehydrazides
under study has a pyramidal configuration, the sum
of the bond angles thereat being 337 and 343 for
compounds I and II, respectively; the height of the
nitrogen pyramid is 0.65 0.7 . A conclusion can be
drawn that hybridization of the terminal nitrogen atom
(N ) is closer to sp3. Obviously, these conditions
determine the accessibility of unshared electron pair
on the terminal nitrogen atom to nucleophilic attack
and protonation. The sum of the bond angles at the
N is almost equal to 360 , and the pyramid height
is close to zero; these data indicate the maximal
p-character of the nonhybridized atomic orbital.
The results of calculations revealed a composite
molecular orbital formed by five individual atomic
orbitals with various contributions. For compound I,
these contributions are as follows: N 86.23, C2 6.86,
C4 2.88, C1 1.74, O 1.16%, and for compound II,
N 86.53, C2 6.77, C4 2.76, C1 1.69, O 1.17%. These
values are consistent with formation of a cross-con-
jugated system with maximal localization of electron
density on the N atom.
Comparative analysis of the -orders (P ) of
principal bonds in initial enehydrazide I and pre-
dominant tautomer Ia also indicates a pronounced
amide p, -conjugation (specific delocalization of
the unshared electron pair on the nitrogen over the
-C O bond. This follows from increased -order of
the C N bond (0.288) and reduced -order of the
C O bond (0.766; see Table 2). The -order of the
C2 C1 bond in aromatic enehydrazide II is consider-
ably lower (0.044) than in its analog I (0.059). This
is consistent with rupture of , -conjugation between
the aromatic ring and the carbonyl group, which are
turned apart through an angle of 92 . In addition,
the -order of the N N bond in compound Ia is
considerably reduced (to 0.019) against the value
0.043 for initial compound I and especially relative
to the corresponding value for protonated enhydrazide
IIa (0.06). These data indicate strong differences in
the electron density delocalization in the initial ene-
hydrazides and products of their transformations.
Table 2. -Orders of bonds (P ) in initial compounds I
and II and their protonated forms Ia and IIa, according
to the results of AM1 calculationsa
Bond
I
Ia
II
IIa
The structure of cyclic tautomer Ia, formed by
reaction of compound I with hydrogen chloride, may
be represented as a ring with alternating deviations
of nodal atoms from the plane within a torsion angle
of 2 6 . The N H bond in the ring-fixed amide frag-
ment declines from the C N plane by 15 . The car-
bonyl group deviates insignificantly (by 2 ). The
N N
N
0.043
0.198
0.805
0.059
0.113
0.922
0.019
0.288
0.766
0.043
0.199
0.823
0.046
0.111
0.927
0.06
C2
0.189
0.835
0.044
C O
C2 C1
N
C4
C4 C6
N N bond length increases to 1.51
1.384
relative to
in initial enehydrazide I, while the C2
N
For atom numbering, see Scheme 3.
a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 9 2002

1270
SARAPULOVA et al.
5. Zapevalova, N.N. and Sokolova, T.A., Izv. Akad.
Thus enehydrazides react with proton donors,
Nauk SSSR, Ser. Khim., 1965, no. 8, pp. 1442 1447.
chloroform and phenol, to form intermolecular com-
plexes. The reaction of enehydrazide I with a mineral
acid, HCl, gives a cyclic product protonated at the
N atom, which exists as two tautomers Ia and Ib.
Enehydrazide II reacts with hydrogen chloride with
formation of acyclic product IIa protonated at the
amino nitrogen atom. The spectral parameters of the
initial compounds and products of their transforma-
tions agree well with the results of AM1 quantum-
chemical calculations.
6. Suvorov, N.N., Sorokin, N.P., and Sheinker, Yu.N.,
Dokl. Akad. Nauk SSSR, 1961, vol. 136, pp. 840 842.
7. Bagrov, F.V., Nasakin, O.E., and Skobelev, S.P.,
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EXPERIMENTAL
10. Bagrov, F.V., Russ. J. Org. Chem., 2000, vol. 36,
no. 9, pp. 1316 1320.
Initial compounds were synthesized by the proce-
dures described in [20]. The IR spectra were measured
on a Specord 75IR two-beam spectrophotometer; cells
with a layer thickness of 0.01 to 0.5 cm were used.
In order to eliminate distortions of the shape of the
OH band of phenol in the presence of bases, a cell
of the same thickness containing a solution of the
base was placed in the reference channel. The con-
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12. Sarapulova, G.I., Cand. Sci. (Chem.) Dissertation,
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4
centration of phenol was 5 10 M, and that of the
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2
base, 3 10 M. The temperature measurements were
no. 9, pp. 3425 3430.
performed with the aid of a temperature adapter (Karl
Zeiss, Jena) with a calibrated thermocouple.
15. Zeegers-Huyskens, Th., Bull. Soc. Chim. Belg., 1977,
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Solutions of enehydrazides in dry carbon tetra-
chloride (2 ml) were purged with dry HCl over
a period of 2, 10, and 20 min (in succession), each
time the IR spectrum was recorded.
AM1 calculations were performed using MOPAC.6
software package [21].
16. Physical Methods in Heterocyclic Chemistry, Kat-
ritzky, A.R., Ed., New York: Academic, 1963.
Translated under the title Fizicheskie metody v
khimii geterotsiklicheskikh soedinenii, Moscow:
Khimiya, 1966, p. 657.
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