Fully Selective Synthesis of Spirocyclic-1,2-oxazine N-Oxides via Non-Catalysed Hetero Diels-Alder Reactions with the Participation of Cyanofunctionalysed Conjugated Nitroalkenes
Abstract
:1. Introduction
2. Results and Discussion
- (1)
- During phases, I–V, the topological changes heading to the creation of two pseudoradical centres [49] at C4 and C5 are taking place. At point P1 V(N2) monosynaptic basin representing nonbonding electron density is created, integrating 0.05 e originating from disynaptic basins V(N2,O1) and V(N2,O11). At the next point two disynaptic basins V(C3,C4) and V’(C3,C4) of the double bond merges into one V(C3,C4) basin with a population of 3.51 e. The monosynaptic basin V(N2) disappears at point P3 increasing V(N2,C3) disynaptic basins population to 2.51 e. Phase V starts with two disynaptic basins V(C5,C6) and V’(C5,C6) combining into one V(C5,C6) integrating 3.22 e. These changes contribute 11.2 kcal∙mol−1 of the energetic cost, in contrast, the transition state is only 3.29 kcal∙mol−1 higher.
- (2)
- Phase VI begins at P5 with the appearance of a pseudoradical center at C4 represented by a monosynaptic basin V(C4) with a population of 0.10 e gathered from the V(C4,C3) disynaptic basin. In the next phase VII, another pseudoradical centre is created at C5–the V(C5,C6) disynaptic basin provides electron density for a new monosynaptic basin V(C5) with initial integration of 0.36 e.
- (3)
- The new bond C4-C5 is created at point P7, at a C-C distance of 2.000 Å by merging of V(C4) and V(C5) monosynaptic basins which show a population of 0.09 e and 0.39 e respectively at the last point of phase VII. The new disynaptic basin V(C4,C5) integrates 0.52 e, representing 28% of its final electron population. The TS3c is part of Phase VIII, where the first bond is already established.
- (4)
- At points P8 and P9, a new pseudoradical centre emerges represented by V(C3) and V’(C3) monosynaptic basins with an initial population of 0.52 e and 0.33 e, respectively. Their electron density originating from the V(C4,C3) disynaptic basin of the C4-C3 underpopulated double bond causes its transition into a single bond.
- (5)
- At point P10 the V(C6) monosynaptic basin appears with a marginal population of 0.01 e. At the start of phase XII, it disappears, and a slight increase in the population of V(O1) and V’(O1) monosynaptic basins takes place.
- (6)
- At the beginning of the last phase, the second bond is created, at an O-C distance of 1.778 Å, by a donation of the nonbonding electron density of O1 to C6. The V(O1,C6) disynaptic basin integrates 0.81 e representing a strongly underpopulated O1-C6 single bond.
- (7)
- The formation of the second O1-C6 bond starts while the first C4-C5 single bond is at 97% of its final population. Therefore, the mechanism of the HDA reaction of nitroalkene 1c with alkene 2 proceeds by a two-stage one-step mechanism [50].
- (8)
- The activation energy associated with this HDA reaction, 7.46 kcal·mol−1, can mainly be related to the depopulation of the C3-C4 and C5-C6 regions, formation of C4 and C5 pseudoradical centres and first C4-C5 single bond.
- (9)
- The conducted BET analysis allowed for the determination and examination of the molecular mechanism of the HDA reaction of the (E)-2-phenyl-1-cyano-1-nitroethene 1c and methylenecyclopentane 2 (Scheme 2).
3. Materials and Methods
3.1. Analytical Techniques
3.2. X-ray Crystal Structure Determination
3.3. Synthesis of Conjugated Nitroalkenes
3.4. Synthesis of Methylenecyclopentane (2)
3.5. HDA Reactions between E-2-Aryl-1-cyano-1-nitroethenes and Methylenecyclopentane–General Procedure
3.6. Quantum Chemical Calculations
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Global Properties | Local Properties | ||||||
---|---|---|---|---|---|---|---|
eletronic chemical potential μ [eV] | chemical hardhess η [eV] | electro- philicity ω [eV] | nucleo- philicityN [eV] | ||||
P−1 | N1 [eV] | P−2 | N2 [eV] | ||||
2.87 | 6.95 | 0.59 | 2.77 | 0.636 | 1.76 | 0.266 | 0.74 |
Nitroalkene | Eletronic Chemical Potential [μ eV] | Chemical Hardhess η [eV] | Electro- Philicity [eV] | Nucleo- Philicityn [eV] |
---|---|---|---|---|
1a | −4.82 | 3.69 | 3.14 | 2.45 |
1b | −5.10 | 3.94 | 3.30 | 2.04 |
1c | −5.27 | 4.06 | 3.42 | 1.80 |
1d | −5.28 | 3.98 | 3.50 | 1.84 |
1e | −5.35 | 3.89 | 3.67 | 1.81 |
1f | −5.31 | 3.81 | 3.70 | 1.90 |
1g | −5.49 | 3.96 | 3.80 | 1.64 |
Structure | ΔH | ΔS | ΔG | Imaginary Frequencies |
---|---|---|---|---|
MC3a | –6.1 | –32.6 | 3.7 | - |
TS3a | 10.0 | –46.6 | 23.9 | −425.7 |
3a | –22.2 | –50.6 | –7.1 | - |
MC4a | –7.8 | –37.5 | 3.4 | - |
TS4a | 24.1 | –53.1 | 39.9 | −586.6 |
4a | –15.8 | –52.4 | –0.1 | - |
MC3b | –6.1 | –33.4 | 3.8 | - |
TS3b | 8.3 | –52.9 | 24.1 | −420.3 |
3b | –23.8 | –50.5 | –8.7 | - |
MC4b | –7.9 | –37.3 | 3.2 | - |
TS4b | 23.2 | –49.9 | 38.1 | −581.7 |
4b | –17.3 | –51.9 | –1.8 | - |
MC3c | –6.1 | –34.0 | 4.0 | - |
TS3c | 8.1 | –46.4 | 21.9 | −421.4 |
3c | –24.7 | –50.1 | –9.8 | - |
MC4c | –7.7 | –37.0 | 3.3 | - |
TS4c | 22.8 | –53.6 | 38.7 | −579.5 |
4c | –18.3 | –53.5 | –2.3 | - |
MC3d | –6.1 | –33.8 | 3.9 | - |
TS3d | 8.4 | –47.3 | 22.6 | −422.5 |
3d | –24.5 | –50.3 | –9.5 | - |
MC4d | –7.8 | –36.6 | 3.2 | - |
TS4d | 22.9 | –52.8 | 38.7 | −580.3 |
4d | –18.0 | –52.3 | –2.4 | - |
MC3e | –6.1 | –34.6 | 4.2 | - |
TS3e | 7.9 | –47.7 | 22.1 | −422.2 |
3e | –25.3 | –51.0 | –10.1 | - |
MC4e | –7.9 | –38.6 | 3.6 | - |
TS4e | 22.5 | –53.2 | 38.3 | −578.9 |
4e | –18.8 | –53.0 | –3.0 | - |
MC3f | –6.1 | –36.4 | 4.8 | - |
TS3f | 7.9 | –49.0 | 22.5 | −421.7 |
3f | –25.3 | –52.2 | –9.7 | - |
MC4f | –7.9 | –38.0 | 3.5 | - |
TS4f | 22.4 | –53.5 | 38.3 | −579.3 |
4f | –18.9 | –54.0 | –2.8 | - |
MC3g | –6.3 | –33.7 | 3.8 | - |
TS3g | 7.0 | –46.2 | 20.8 | −421.5 |
3g | –26.2 | –50.9 | –11.0 | - |
MC4g | –8.0 | –37.9 | 3.3 | - |
TS4g | 22.0 | –52.1 | 37.5 | −578.0 |
4g | –19.7 | –53.0 | –3.9 | - |
Structures | 2 | 1c | MC3c | P1 | P2 | P3 | P4 | P5 | P6 | P7 | TS3c | P8 | P9 | P10 | P11 | P12 | 3c | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Phases | I | II | III | IV | V | VI | VII | VIII | IX | X | XI | XII | XIII | ||||||||||||||||
d1(C1-C14) | 3.131 | 3.126 | 2.861 | 2.405 | 2.240 | 2.039 | 2.019 | 2.000 | 1.962 | 1.954 | 1.896 | 1.563 | 1.557 | 1.539 | 1.543 | ||||||||||||||
d2(O9-C15) | 3.467 | 3.454 | 3.189 | 2.946 | 2.896 | 2.850 | 2.846 | 2.842 | 2.834 | 2.831 | 2.818 | 2.098 | 2.022 | 1.778 | 1.478 | ||||||||||||||
IRC | −9.67 | −9.25 | −5.43 | −2.25 | −1.38 | −0.39 | −0.29 | −0.19 | 0.00 | 0.03 | 0.32 | 2.31 | 5.98 | 7.39 | |||||||||||||||
GEDT | 0.01 | 0.01 | 0.03 | 0.11 | 0.20 | 0.36 | 0.38 | 0.40 | 0.42 | 0.44 | 0.50 | 0.61 | 0.59 | 0.52 | |||||||||||||||
dE kcal | −7.03 | −6.98 | −5.35 | 0.96 | 4.17 | 7.15 | 7.29 | 7.38 | 7.46 | 7.46 | 7.25 | −3.66 | −5.61 | −13.70 | −23.48 | ||||||||||||||
V(O1) | 2.83 | 2.84 | 2.83 | 2.84 | 2.86 | 2.85 | 2.87 | 2.87 | 2.87 | 2.88 | 2.88 | 2.89 | 2.96 | 2.88 | 2.48 | 2.60 | |||||||||||||
V’(O1) | 2.80 | 2.82 | 2.82 | 2.82 | 2.83 | 2.88 | 2.90 | 2.91 | 2.91 | 2.91 | 2.91 | 2.93 | 2.91 | 3.05 | 2.76 | 2.39 | |||||||||||||
V(N2.O1) | 1.85 | 1.85 | 1.88 | 1.88 | 1.81 | 1.77 | 1.71 | 1.71 | 1.70 | 1.69 | 1.69 | 1.67 | 1.41 | 1.39 | 1.30 | 1.23 | |||||||||||||
V(N2.O11) | 2.19 | 2.19 | 2.10 | 2.07 | 2.03 | 1.94 | 1.84 | 1.83 | 1.83 | 1.82 | 1.81 | 1.79 | 1.67 | 1.65 | 1.64 | 1.65 | |||||||||||||
V(C3.N2) | 2.29 | 2.31 | 2.32 | 2.32 | 2.51 | 2.62 | 2.76 | 2.77 | 2.78 | 2.80 | 2.80 | 2.84 | 3.29 | 3.35 | 3.50 | 3.60 | |||||||||||||
V(C4.C3) | 1.76 | 1.66 | 1.66 | 3.51 | 3.50 | 3.49 | 3.42 | 3.41 | 3.39 | 3.36 | 2.83 | 2.42 | 2.06 | 2.05 | 2.04 | 2.04 | |||||||||||||
V’(C4.C3) | 1.79 | 1.86 | 1.87 | ||||||||||||||||||||||||||
V(C5.C6) | 1.78 | 1.73 | 1.73 | 1.78 | 1.77 | 3.28 | 3.22 | 2.89 | 2.85 | 2.77 | 2.76 | 2.65 | 2.17 | 2.14 | 2.07 | 2.01 | |||||||||||||
V’(C5.C6) | 1.78 | 1.79 | 1.79 | 1.70 | 1.61 | ||||||||||||||||||||||||
V(O1.C6) | 0.81 | 1.22 | |||||||||||||||||||||||||||
V(C4.C5) | 0.52 | 0.65 | 0.67 | 0.84 | 1.70 | 1.72 | 1.78 | 1.83 | |||||||||||||||||||||
V(N2) | 0.05 | 0.08 | |||||||||||||||||||||||||||
V(C3) | 0.52 | 0.56 | 0.57 | 0.55 | 0.49 | 0.37 | |||||||||||||||||||||||
V’(C3) | 0.33 | 0.32 | 0.31 | 0.26 | 0.30 | ||||||||||||||||||||||||
V(C4) | 0.10 | 0.09 | |||||||||||||||||||||||||||
V(C5) | 0.36 | ||||||||||||||||||||||||||||
V(C6) | 0.01 |
Reaction | Solvent | Temperature [°C] | Time [h] | Yield [%] |
---|---|---|---|---|
1a+2 | Chloroform | 60 | 24 | 22 |
1b+2 | Chloroform | 60 | 24 | 32 |
1c+2 | Chloroform | 0 | 24 | - |
1c+2 | Chloroform | 25 | 24 | trace |
1c+2 | Chloroform | 60 | 12 | 40 |
1c+2 | Chloroform | 60 | 24 | 58 |
1c+2 | Nitromethane | 60 | 24 | 52 |
1d+2 | Chloroform | 60 | 24 | 61 |
1e+2 | Chloroform | 60 | 24 | 60 |
1f+2 | Chloroform | 60 | 24 | 72 |
1g+2 | Chloroform | 60 | 24 | 69 |
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Woliński, P.; Kącka-Zych, A.; Wróblewska, A.; Wielgus, E.; Dolot, R.; Jasiński, R. Fully Selective Synthesis of Spirocyclic-1,2-oxazine N-Oxides via Non-Catalysed Hetero Diels-Alder Reactions with the Participation of Cyanofunctionalysed Conjugated Nitroalkenes. Molecules 2023, 28, 4586. https://doi.org/10.3390/molecules28124586
Woliński P, Kącka-Zych A, Wróblewska A, Wielgus E, Dolot R, Jasiński R. Fully Selective Synthesis of Spirocyclic-1,2-oxazine N-Oxides via Non-Catalysed Hetero Diels-Alder Reactions with the Participation of Cyanofunctionalysed Conjugated Nitroalkenes. Molecules. 2023; 28(12):4586. https://doi.org/10.3390/molecules28124586
Chicago/Turabian StyleWoliński, Przemysław, Agnieszka Kącka-Zych, Aneta Wróblewska, Ewelina Wielgus, Rafał Dolot, and Radomir Jasiński. 2023. "Fully Selective Synthesis of Spirocyclic-1,2-oxazine N-Oxides via Non-Catalysed Hetero Diels-Alder Reactions with the Participation of Cyanofunctionalysed Conjugated Nitroalkenes" Molecules 28, no. 12: 4586. https://doi.org/10.3390/molecules28124586