Theoretical analysis and experimental study of the spatial structure and isomerism of acetone azine and its cyclization to 3,5,5-trimethyl-4,5-dihydro- 1H-pyrazole

Article abstract of DOI:10.1007/s10947-005-0054-1

An ab initio (RHF/6-31G*and MP2/6-31G*) study has been undertaken to investigate the spatial structure and relative stability of the acyclic isomers of acetone azine (acetone N-(1-methylethylidene) hydrazone (CH₃)₂C=N-N=C(CH₃)₂), differing in the position of multiple bonds, and of the cyclic isomer 3,5,5-trimethyl-4,5- dihydro-1H-pyrazole. In the series of structures under study, the latter possesses the greatest thermodynamic stability so that formation of acyclic isomers such as 1-isopropenyl-2-isopropyldiazene, acetone N- isopropenylhydrazone, and 1,2-diisopropenylhydrazine from acetone azine is thermodynamically unfavorable. For each structure, stable conformations have been found, and the internal rotation barriers of molecules relative to the N-N, C-N, and C-C single bonds have been estimated. The noncoplanar goshconformer of acetone azine was found to possess the greatest thermodynamic stability. The acetone azine molecule is considered in comparison with model hydrazine, butadiene, and vinylamine molecules. Acetone azine is conformationally preferable not only because of steric factors, but also due to the interaction of the lone electron pair (LEP) of nitrogen atoms with adjacent N=C multiple bonds.

Full text of DOI:10.1007/s10947-005-0054-1

Journal of Structural Chemistry, Vol. 45, No. 5, pp. 748-755, 2004
Original Russian Text Copyright © 2004 by V. B. Kobychev, N. M. Vitkovskaya, N. V. Pavlova, ȿ. Yu. Schmidt, and B. Ⱥ. Trofimov
THEORETICAL ANALYSIS AND EXPERIMENTAL
STUDY OF THE SPATIAL STRUCTURE AND ISOMERISM
OF ACETONE AZINE AND ITS CYCLIZATION TO
3,5,5-TRIMETHYL-4,5-DIHYDRO-1ɇ-PYRAZOLE
V. B. Kobychev,1 N. M. Vitkovskaya,1 N. V. Pavlova,1
ȿ. Yu. Schmidt,2 and B. Ⱥ. Trofimov2
UDC 539.194+547.314+541.124
An ab initio (RHF/6-31G* and MP2/6-31G*) study has been undertaken to investigate the spatial structure
and relative stability of the acyclic isomers of acetone azine (acetone N-(1-methylethylidene)hydrazone
(CH3)2C=N–N=C(CH3)2), differing in the position of multiple bonds, and of the cyclic isomer 3,5,5-
trimethyl-4,5-dihydro-1ɇ-pyrazole. In the series of structures under study, the latter possesses the greatest
thermodynamic stability so that formation of acyclic isomers such as 1-isopropenyl-2-isopropyldiazene,
acetone N-isopropenylhydrazone, and 1,2-diisopropenylhydrazine from acetone azine is thermodynamically
unfavorable. For each structure, stable conformations have been found, and the internal rotation barriers of
molecules relative to the N–N, C–N, and C–C single bonds have been estimated. The noncoplanar gosh
conformer of acetone azine was found to possess the greatest thermodynamic stability. The acetone azine
molecule is considered in comparison with model hydrazine, butadiene, and vinylamine molecules.
Acetone azine is conformationally preferable not only because of steric factors, but also due to the
interaction of the lone electron pair (LEP) of nitrogen atoms with adjacent N=C multiple bonds.
Keywords: acetone azine, internal rotation, isomerization, cyclization, 3,5,5-trimethyl-4,5-dihydro-1ɇ-
pyrazole, ab initio calculations.
Unsaturated compounds with nitrogen atoms possess a number of interesting properties making them very important
intermediates and structural units in organic chemistry. As examples one can cite imine-enamine tautomerism, triad rearran-
gement of imines, syn–anti isomerization of imines, oximes, hydrazones, and azines, Fischer’s rearrangement of arylhydrazo-
nes to indoles, Piloty–Robinson’s cyclization of azines to pyrroles, Kizhner–Wolff’s reduction of aldehydes and ketones via
hydrazones, etc. Specific problems arise in describing interactions in nitrogen-containing systems with several multiple bonds
and several nitrogen atoms. Unsaturated hydrocarbons form a class of compounds with specific chemical properties and
structural peculiarities caused by conjugation effects. Less attention has been paid to conjugation in systems containing C=N
and N=N bonds along with C=C. Examples of compounds from this class are conjugate 2,3-diazabutadienes-1,3, generally
known as azines, in particular, acetone azine (1) or acetone N-(1-methylethylidene)hydrazone, (CH3)2C=N–N=C(CH3)2. In
superbasic media (of KOBu-t/DMSO and KOH/DMSO types), in which unsaturated heteroatomic systems generally readily
undergo prototropic isomerization [1], one would expect partial isomerization of 1 into 1-isopropenyl-2-isopropyldiazene (2)
as a result of a [1,5]-prototropic rearrangement of 1 or two successive [1,3]-hydrogen shifts (Scheme 1) with acetone N-isopro-
1Irkutsk State University; gimli@cc.isu.ru. 2A. E. Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian
Academy of Sciences. Translated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 5, pp. 792-799, September-October, 2004.
Original article submitted June 26, 2003.
748
0022-4766/04/4505-0748 © 2004 Springer Science+Business Media, Inc.

Scheme 1
penylhydrazone (3) formed as an intermediate. Other forms are assumed to be 1,2-diisopropenylhydrazine (4) and the cyclic
isomer — 3,5,5-trimethyl-4,5-dihydro-1ɇ-pyrazole (5), whose precursors could be Z isomer 2 or the s-cis form of its E
isomer. Azine cyclization with organic acids and hydrogen halides is a known route to dihydropyrazoles [2, 3]. Therefore, ab
initio quantum-chemical studies of multiple bond migration in azines is not merely of theoretical interest; it can prove useful
for developing new methods for the preparation of heterocyclic compounds or elaborating known ones. No publications
dealing with theoretical investigation of the mechanisms of multiple bond migration for these structures have yet appeared in
the literature, while quantum-chemical studies of azines are reduced to analysis at the level of the Hückel method [4].
The aim of the present work is an ab initio study of the relative stability of acetone azine and its possible prototropic
isomerization products. For all compounds under study, the potential curves of internal rotation relative to the N–N, C–N, and
C–C bonds have been studied, and the structure of the conformational isomers (Fig. 1) possessing the minimal energy on the
potential energy surfaces (PESs) has been determined.
Fig. 1. Structure of compounds 1-5. Bond lengths (Å) and bond and torsion angles (MP2/6-31G* data).
749

Fig. 2. Model compounds 6-11.
CALCULATION PROCEDURE
PES sections for acetone azine and model compounds 6-11 (Fig. 2) were obtained within the framework of the
restricted Hartree–Fock (RHF) method and including electron correlation effects in second order Möller–Plesset (MP2)
perturbation theory using the 6-31G* basis set. For compounds 2-5, PES sections were investigated in the RHF
approximation (6-31G* basis set); the energies of the critical points on the PES were further refined with additional full
geometry optimization in the framework of the MP2 method.
To calculate the relative stability of acetone azine isomers, for each isomer we considered conformers possessing the
minimal energy on the PES and applied corrections for zero-point energy (ZPE).
Calculations were accomplished with GAMESS software [5].
DISCUSSION OF RESULTS
The mutual arrangement of the methyl groups of the (CH3)2C=N– fragment was preliminarily studied for the model
compound (CH3)2C=NH (6). The PES minimum corresponds to a structure with C2v local symmetry of the (CH3)2C=N
fragment (Fig. 2). The energy barrier to rotation of methyl groups in 6 is up to 1 kcal/mol. Substitution of the –N=C(CH3)2
group for the hydrogen atom on passing to 1 changes the mutual arrangement of the methyl groups (Fig. 1). The (CH3)2C=N
fragment in 3 is assumed to have a similar structure corresponding to the transition state in 6.
Rotation around the N–N bond in 1 was considered in RHF and MP2 approximations (Fig. 3). The RHF approach
predicts a single minimum for 1ɚ (Fig. 3), for which the internuclear repulsion is minimal, the LEPs of the neighboring
nitrogen atoms are directed oppositely, and the planar s-trans structure of the C=N–N=C fragment provides the best
conditions for the formation of a conjugate system. When electron correlation effects are included in calculations, the
potential curve of internal rotation also has a single minimum, but its structure corresponds to s-gosh structure 1b (Fig. 3)
with a dihedral CNNC angle of 119.5q, but not to the planar s-trans conformation 1a. The s-trans conformation is a transition
750

Fig. 3. Potential curves of internal rotation for acetone azine 1
(RHF/6-31G* and MP2/6-31G* data).
state providing an energy barrier of 1.36 kcal/mol between the two neighboring s-gosh minima. Applying a ZPE correction
yields a barrier of 1.27 kcal/mol.
Rotation relative to the N–N bond through an angle larger than 90q leads to a drastically increased energy due to
increased interatomic repulsion. When the CNNC angle is 75q (1c, Fig. 3), the distance between the hydrogen atoms of the
approaching methyl groups is smaller than the sum of their van der Waals radii; therefore, the synclinal s-gosh and syn-planar
s-cis conformations are impossible for 1.
The results of this study indicate that 1 is a structurally labile compound. Investigation of reasons for structural
lability, in particular, factors contributing to stabilization of the s-gosh conformation is hindered by the presence of
interactions which cannot be separated. Therefore, we performed calculations for a number of model compounds in the stated
approximations.
Hydrazine is the simplest compound which can be analyzed for rotation around the N–N bond; the spatial and
electronic structure of this compound was investigated many times by both experimental [6-8] and theoretical [9-15]
methods. The characteristic conformation of this molecule involves an orthogonal mutual arrangement of the LEPs of the
nitrogen atoms. In the 6-31G* basis set used, this is the most stable conformation in both RHF (‘HNNH 90.4q) and MP2
(‘HNNH 91.1q) approximations, which agrees with experimental data (91.5q) [8]. The fully eclipsed conformation is a
transition state; the barrier between the two s-gosh conformations was estimated at 10.13 kcal/mol (RHF) and 9.36 kcal/mol
(MP2). The energy of the s-trans conformer, which also corresponds to a PES minimum, is 2.34 kcal/mol (RHF) higher than
the energy of the most stable (s-gosh) structure; in the MP2 approximation, the difference decreases to 0.87 kcal/mol.
Therefore, if conformational preference in 1 depended on the interaction between the LEPs of the neighboring nitrogen
atoms, the corresponding effect would show itself as a potential curve obtained in the RHF approach. However, the RHF
method predicted a planar s-trans structure for 1, while MP2 gave a minimum for the s-gosh conformation alone. That is why
the nonplanar structure of 1 can hardly be determined by this type of interaction.
751

TABLE 1. Relative Energies ('E, kcal/mol) and the Sum of Bond Angles (D, deg) at the Nitrogen Atom for
Molecular Conformations of Vinylamine 7 and Formaldehyde Hydrazone 8
RHF
ɆɊ2
Structure
'E
D
'E
D
7a
7b
7c
8a
8b
8c
4.93
6.22
0
327.6
329.6
339.3
314.2
324.2
332.8
5.74
6.95
0
324.5
325.8
337.0
309.3
318.9
332.1
3.38
11.50
0
4.35
11.91
0
Another type of interaction that is possible in molecule 1 is n–ʌ* interaction between the LEP of the nitrogen atom
and the neighboring multiple bond. For the model compound involving an interaction of this kind we considered vinylamine
H2ɋ=ɋ–NH2 (7).
For the vinylamine molecule with fragments rotated around the N–C bond, on the PES section we obtained three
stationary points corresponding to the cis (7ɚ), trans (7b), and orthogonal (7c) gosh orientations of the LEP of the nitrogen
atom relative to the vinyl fragment (Fig. 2). The gosh conformer proved to be much more stable than the cis and trans
conformations, which are transition states (Table 1). Conjugation between the nitrogen LEP and the neighboring C=C bond,
stabilizing gosh conformation 7, shows itself as the increased sum of bond angles at the nitrogen atom (Table 1). The energy
gain of this conjugation obtained in the MP2 approximation was more significant than that in the RHF approach. The least
stable structure was 7b, having maximal repulsion between the electrons of N–H bonds and the S electrons of the vinyl
group. Previously [16, 17], similar data were obtained on the stability of conformers for 1-dimethylamino-1-propene; for the
phosphorus-containing analog, where the LEP of the heteroatom undergoes weaker interaction with the neighboring multiple
bond, the most stable conformer is the one analogous to 7a.
For formaldehyde hydrazone H2C=N–NH2 (8), the relative stability of the gosh form with a mutually orthogonal
arrangement of the nitrogen LEP was expected to increase. Indeed, if molecular fragments are rotated relative to the N–N
bond, the PES section also contains three stationary points corresponding to the cis (8ɚ), trans (8b), and orthogonal (8c) gosh
orientations of the nitrogen LEP relative to the N=C bond (Fig. 2). Mutual repulsion of the LEPs leads to an appreciably
greater destabilization of 8b with respect to 8c compared to the increase in energy from 7ɫ to 7b. At the same time, the
energy difference between 8a and 8c with the trans and gosh arrangements of LEP is smaller than the difference observed for
7. This indicates that n–S* interaction of the nitrogen LEP with the neighboring multiple bond is less pronounced for the N=C
bond compared to the ɋ=ɋ bond. As in the case of 7, the MP2 method predicts slightly greater stabilization by this type of
interaction compared to RHF. In molecule 1, where full n–S* conjugation is hindered by steric factors, the difference between
the RHF and MP2 estimates of the role of this interaction may be responsible for differences in describing the conformational
preference of 1 within the framework of the two approaches.
Because of the different character of the nitrogen LEP involved in conjugation in 1, the n–S* interaction differs in
character from that in 7 and 8. In the latter two compounds, the LEP is more of p character compared to the sp2-hybridized
LEP in 1. For this type of interaction, formaldehyde azine H2C=N–N=CH2 (9) may be taken as a model molecule.
Analysis of the PES sections of internal rotation relative to the N–N bond in 9 (Fig. 4) shows that in RHF (torsion
angle is close to 90q) the curve acquires an inflexion point which in the MP2 calculation including correlation effects is
transformed into the second local minimum (CNNC torsion angle is 88.9q). The energy of the gosh conformer is 1.03 kcal/mol
higher than that of the coplanar trans conformer, and the barrier between the forms is up to 0.1 kcal/mol. In contrast to 1, the
cis conformation is attainable for 9; in both RHF and MP2 approaches, this is a transition state between two trans structures
in RHF and two gosh conformations in MP2. The total barrier to internal rotation around the N–N bond in unsubstituted azine
752

Fig. 4. Potential curves of internal rotation for formal-
dehyde azine 9 and difluoroformaldehyde azine 10 (RHF/6-
31G* and MP2/6-31G* data).
was estimated at 17.97 kcal/mol (RHF) and 16.44 kcal/mol (MP2). As in the case of 7 and 8, inclusion of correlation effects
leads to additional stabilization of the gosh form due to n–S* conjugation.
Although 9 has more favorable conditions for n–S* conjugation (Fig. 2) compared to 1, stabilization of the gosh
form in it is less pronounced. This may be attributed to increased occupancies on the nitrogen atoms caused by the
introduction of the four methyl substituents. Indeed, Mulliken’s charge on these atoms as calculated for the planar trans
structures is –0.28 au for 9 and –0.39 au for 1; it changes little when both compounds have rotation around the N–N bond.
Due to electron density acceptors introduced in its molecule, the model compound F2C=N–N=CF2 (10) does not show a
minimum corresponding to the gosh form (Fig. 4).
In butadiene, the S–S interaction stabilizes the planar s-trans structure; rotation relative to the C–C bond leads to a
barrier estimated at 6.07 kcal/mol and 5.95 kcal/mol on the potential curve (RHF and MP2, respectively). Since internuclear
interaction also affects the form of the internal rotation curve in butadiene, the maximum lies at torsion angles of 102.2q
(RHF/6-31G*) and 101.6q (MP2/6-31G*). A comparison with the potential curves of 9 shows that this conjugation effect is
not realized in the case of the C=N bonds.
For compounds with C=N and N=N bonds along with C=C, the relative stability is determined by the additive effect
of S–S, n–n, and n–S* interactions. For compounds 1-5, we inferred that formation of acyclic isomers 2, 3, and 4 from 1 is
thermodynamically unfavorable (Table 2). The energy of E isomer 2, having a planar structure with s-trans arrangement of
the vinyl fragment relative to the N=N bond (Fig. 1) and oppositely oriented LEPs of nitrogen, is 13.69 kcal/mol higher than
the energy of 1. For the conformer with s-cis orientation of the vinyl group, the energy additionally increases by 4.54 kcal/mol.
Finally, the energy of Z isomer 2 is 15.30 kcal/mol higher than that of E isomer and 28.98 kcal/mol higher than that of 1.
753

TABLE 2. Relative Thermodynamic Stability (kcal/mole) for Acetone Azine Isomers
Structure
RHF/6-31G*
MP2/6-31G*
RHF/6-31G* (ZPE)
MP2/6-31G* (ZPE)
1
2
3
4
5
0
0
0
0
11.90
13.47
24.91
–5.35
13.00
14.15
30.17
–9.73
12.59
14.02
26.19
–2.78
13.69
14.70
31.45
–7.16
TABLE 3. Conditions for Treatment of Azine 1 with Superbasic Systems
Reaction mixture (mass ratio)
Time, h
Ɍ, qC
1/KOH/DMSO (30:2:100)
20
50
7
5
1/KOH/DMSO (5:1:25)
1/KOH/DMSO (3:1:50)
1/KOH/DMSO (10:2:50)
1/KOBu-t/DMSO (3:1:50)
80
0.1
1
100
20
7
This relationship between the energies of 1 and 2 challenges the possibility for 2 to form at the initial stages of
cyclization of 1 to 5. Indeed, after treatment of 1 with superbasic systems in different conditions (Table 3), 1ɇ NMR analysis
(400 MHz, CDCl3, HMDS as internal standard) did not reveal even trace amounts of 2.
Because of S–S conjugation between the C=C and N=N bonds, 2 was expected to be more stable than 3; however,
compounds 2 and 3 proved to be close in energy (Table 2). The energy of 3 is only 1.01 kcal/mol higher than that of 2.
Factors stabilizing compound 3 are considered for the model compound H2C=CH–NH–N=CH2 (11).
When the molecule involves rotation around the C–N and N–N bonds, the PES of 11 contains a stationary point
corresponding to a structure with mutually orthogonal LEPs of the nitrogen atoms. This configuration provides the best
conditions for the interaction of the LEP of the sp3-hybrid nitrogen atom with the S systems of both C=C and N=C bonds.
Rotation through 30q around the N–N bond increases the N–N bond length by 0.015 Å; the C–N bond is lengthened by the
same amount. Similarly, rotation around the C–N bond increases the C–N bond length by 0.009 Å, while the N–N bond
length increases by 0.017 Å. The spatial structure of 11, as well as symbatic variation of the lengths of bonds formed by the
sp3-hybrid nitrogen atom and the results of MO composition analysis, suggest that there is a single conjugate system as the
major stabilizing factor for compound 11 and for compound 3 whose spatial structure is close to that of 11.
If 4 is considered as a substituted acyclic derivative of hydrazine, it would be reasonable to expect the most stable
conformational isomer to be the one with a nearly orthogonal arrangement of the LEPs of the nitrogen atoms. Indeed, among
the numerous thermodynamically stable conformers with rotating molecular fragments around the C–N and N–N bonds, the
minimal-energy conformer is the one whose nitrogen LEP lies at an angle of 75.7q (RHF) and 68.7q (ɆɊ2) (Fig. 1). n–S*
Interaction between the nitrogen LEPs and the adjacent S systems of the vinyl fragments is another factor stabilizing the
energetically preferable conformer. As would be expected, compound 4 is the least stable isomer of all possible acyclic
products of isomerization of 1. The energy of isomerization of 3 to 4 is 11.44 kcal/mol (RHF) and 16.02 kcal/mol (MP2), or
12.17 kcal/mol and 16.75 kcal/mol, respectively, when zero-point energies are taken into account. These values are close to
the energies of isomerization of 1 to 3 and to the energies of transformation of acetoxime and its derivatives (obtained in the
same approximations)
754

TABLE 4. Cyclization of Azine 1 to Pyrazole 5
Reaction mixture (mass ratio)
Time, h
Yield of 5, %
Ɍ, qɋ
–20
–20
20
5
6
7
2
7
3
7
43
1/BF3˜OEt2 (10:0,5)
1/BF3˜OEt2/KOH (10:0.8:1.0)
1/PdCl2/PPh3/ɌɎɆɋɄ (1:0.01:0.01:0.01)
1/PdCl2/PPh3 (5:0.05:0.01)
1/PdCl2/PPh3/CuBr (1:0.01:0.01)
1/Pd(PPh3)4 (1:0.01)
11
11
60
Traces
20
»
Not found
»
20
1/CuBr (50:1)
20
due to which the mean energy of the C–C=N o C=C–N rearrangement is estimated at 12 kcal/mol-15 kcal/mol. Cyclic
isomer 5 is the most stable structure of all structures considered here (Table 2). Previously, it was noted that during
protonation with anhydrous organic acids and certain hydrogen halides, azines cyclize to pyrazolines with good yields at
a100qɋ [2, 3]. According to our experimental data (Table 4), in the presence of boron trifluoride etherate, cyclization 1 o 5
occurs even at –20qɋ and does not stop even in the presence of KOH. It is interesting that the salts and complexes of
catalytically active transition metals show low activity (PdCl2/PPh3), or are altogether inactive (Pd(PPh3)4, CuBr) in this
cyclization. According to MP2 data, the deviation from the planar C–C=N–NH structure in 5 is up to 2q, and the dihedral
angle between this plane and the LEP of the sp3-hybridized nitrogen atom is 96q (Fig. 1), which creates favorable conditions
for n–S* interaction with the neighboring double bond. Thus this type of interaction is one of the major factors that determine
which conformation of an unsaturated nitrogen-containing compound is preferable.
This work was supported by RFBR grant No. 03-03-32312.
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