A green microwave method for synthesizing a more stable phthalazin-1-ol isomer as a good anticancer reagent using chemical plasma organic reactions
2021; Elsevier BV; Volume: 7; Issue: 3 Linguagem: Inglês
10.1016/j.heliyon.2021.e06220
ISSN2405-8440
AutoresSameh A. Rizk, Maher A. El‐Hashash, Amr Youssef, Abdelfattah T. Elgendy,
Tópico(s)Nanomaterials for catalytic reactions
ResumoConventional synthesis of the phthalazine has already allowed affording the phthalazin-1-one phthalazin-1-ol dynamic equilibrium that decreases the anticancer activity due to diminishing the concentration of the phthalazin-1-ol product. Nowadays, pure phthalazin-1-ol (5) can be gaining by using green microwave tools that increase the power of the phthalazine nucleus as an anticancer drug. A microscopic thermal kinetic parameter like activation energy and the pre-exponential factor of the chemical plasma organic reactions affording pure phthalazin-1-ol (5) is calculated by using DFT simulation is obtained. Then we fed these parameters into the exact Arrhenius model to evaluate the distribution of chemical equilibrium conditions for producing phthalazin-1-ol. The proposed novel models that matching between microscopic and macroscopic show that the thermal stability of the equivalent temperature of phthalazin-1-ol is more stable than phthalazinone-1-one (4) in case of using plasma organic effect (green microwave) at 485 K. The structures of the prepared compounds were explained by physical and spectral data like FT-IR, 1H-NMR. Moreover, the theoretical calculations of Gibbs entropy of the phase transfer confirmed the equilibrium state of phthalazin-1-ol with the experimental result is achieved. Briefly, we introduce a good study for obtaining more stable phthalazin-1-ol isomer by using a green microwave method which is considered as good anticancer reagents of phenolic group (OH) and p-propenyl-anisole precursor as anise oil analogous. Conventional synthesis of the phthalazine has already allowed affording the phthalazin-1-one phthalazin-1-ol dynamic equilibrium that decreases the anticancer activity due to diminishing the concentration of the phthalazin-1-ol product. Nowadays, pure phthalazin-1-ol (5) can be gaining by using green microwave tools that increase the power of the phthalazine nucleus as an anticancer drug. A microscopic thermal kinetic parameter like activation energy and the pre-exponential factor of the chemical plasma organic reactions affording pure phthalazin-1-ol (5) is calculated by using DFT simulation is obtained. Then we fed these parameters into the exact Arrhenius model to evaluate the distribution of chemical equilibrium conditions for producing phthalazin-1-ol. The proposed novel models that matching between microscopic and macroscopic show that the thermal stability of the equivalent temperature of phthalazin-1-ol is more stable than phthalazinone-1-one (4) in case of using plasma organic effect (green microwave) at 485 K. The structures of the prepared compounds were explained by physical and spectral data like FT-IR, 1H-NMR. Moreover, the theoretical calculations of Gibbs entropy of the phase transfer confirmed the equilibrium state of phthalazin-1-ol with the experimental result is achieved. Briefly, we introduce a good study for obtaining more stable phthalazin-1-ol isomer by using a green microwave method which is considered as good anticancer reagents of phenolic group (OH) and p-propenyl-anisole precursor as anise oil analogous. 1. IntroductionPhthalazin-1-ol and its substituted derivatives in position 1 were reported to possess anticancer [[1]Wang C. Wu H. Evron T. Vardy E. Han G. Huang X. Hufeisen S. Mangano T. Urban D. Katritch V. Cherezov V. Caron M. Roth B. Stevens R. Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.Nature commun. 2014; Google Scholar, [2]Tsoungas P.G. Searcey M. A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators.Tetrahedron Lett. 2001; 42: 6589-6592Crossref Scopus (33) Google Scholar, [3]Sivakumar R. Gnanasam S.K. Ramachandran S. Leonard J.T. Pharmacological evaluation of some new 1-substituted-4-hydroxy-phthalazines.Eur. J. Med. Chem. 2002; 37: 793-801Crossref PubMed Scopus (54) Google Scholar, [4]Li Juan Zhao Yan-Fang Yuan Xiao-Ye Xu Jing-Xiong Gong Ping Synthesis and anticancer activities of novel 1,4-disubstituted phthalazines.Molecules. 2006 Jul; 11: 574-582Crossref PubMed Scopus (142) Google Scholar, [5]Elmeligie S. Aboul-Magd A. Lasheen D. Ibrahim T. Abdelghany T. Khojah S. Abouzid K. Design and synthesis of phthalazine-basedcompounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition.J. Enzym. Inhib. Med. Chem. 2019; 34: 1347-1367Crossref PubMed Scopus (14) Google Scholar, [6]El-Helby A. Ayyad R. Sakr H. El-Adl K. Ali M. Khedr F. Design, synthesis, molecular docking, and anticancer activity of phthalazine derivatives as VEGFR-2 inhibitors.Arch. Pharmazie. 2017; 350: 1700240Crossref Scopus (38) Google Scholar, [7]Turky A. Bayoumia A. Ghiatya A. El-Azab A. Abdel-Aziz A. Abulkhaira H. Design, synthesis, and antitumor activity of novel compounds based on 1,2,4-triazolophthalazine scaffold: apoptosis-inductive and PCAF-inhibitory effects.Biorg. Chem. 2020; 101: 104019Crossref PubMed Scopus (21) Google Scholar, [8]Rizk S.A. Abdelwahab S.S. El-Badawy A.A. Design, regiospecific green synthesis, chemical computational analysis, and antimicrobial evaluation of novel phthalazine heterocycles.J. Heterocycl. Chem. 2019; 56: 2347-2357Crossref Scopus (9) Google Scholar], anticonvulsant [[9]Haider N. Kabicher T. Käferböck J. Plenk A. Synthesis and in-vitro antitumor activity of 1-[3-(Indol-1-yl)prop-1-yn-1-yl]phthalazines and related compounds.Molecules. 2007; 12: 1900-1909Crossref PubMed Scopus (28) Google Scholar], cardiotonic [[10]Zhang S. Zhao Y. Liu Y. Chen D. Lan W. Zhao Q. Dong C. Xia L. Gong P. Synthesis and antitumor activities of novel 1,4-disubstituted phthalazine derivatives.Eur. J. Med. Chem. 2010; 45: 3504-3510Crossref PubMed Scopus (39) Google Scholar], vasorelaxant activities [[11]El-Hashash M.A. Rizk S.A. El-Bassiouny F.A. Guirguis D.B. Khairy S.M. Guirguis Facile synthesis and structural characterization of some phthalazin-1(2H)-one derivatives as antimicrobial nucleosides and reactive dye.Egypt. J. Chem. 2017; 60: 407Google Scholar] and the canonical Gibbs entropy of residual mass is achieved. Our proposed novel dual system which merges both microscopic (DFT simulation) and macroscopic (kinetic Arrhenius Model) show that phthalazin-1-ol (5) is more stable than phthalzin-1-one (4). The results find a significant equilibrium temperature of the optimized structures of the phthalazine-1-ol inhibitors mounted on the cancer cell [[12]Elgendy A.T. Abdallah T. Cancer therapy system based on gold nanoparticle/cold plasma via stimulated singlet oxygen production.J. Phys.: Conf. Ser. 2019; 1253012003Crossref Scopus (4) Google Scholar, [13]Elgendy A.T. AbdelAty A. Youssef A. Khder M. Lotfy K. Owyed S. Exact solution of Arrhenius equation for non-isothermal kinetics at constant heating rate and n-th order of reaction.J. Math. Chem. 2019; Google Scholar, [14]Elgendy A.T. Youssef A. Rizk S.A. Which energetically favorable sustainable synthesis of 4-amino-8-azacoumarin ester or 4-hydroxy-3-cyano derivative based on new exact kinetic Arrhenius and DFT stimulation.J. Iran. Chem. Soc. 2020; Crossref Scopus (5) Google Scholar, [15]Agrawal M. Kharkar P. Moghe S. Mahajan T. Deka V. Thakkar C. Nair A. Mehta C. Bose J. Kulkarni-Almeida A. Bhedi D. Vishwakarma R.A. Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening.Bioorg. Med. Chem. Lett. 2013; 23: 5740-5743Crossref PubMed Scopus (15) Google Scholar]. Geometry optimization of phthalazine-1-ol and its derivatives inhibitors via plasma organic synthesis loaded on cancer surface via molecular dynamics process yields structures of low energies (i.e., stable structures) without loss byproduct, where the structure stability is expressed in terms of negative values of total energy Figure 1. During the simulation process, phthalazine-1-ol molecules are randomly rotated and translated around the cancer cell [[16]Elagawany M. Ibrahim M.A. Ali Ahmed H.E. El-Etrawy A.S.H. Ghiaty A. Abdel-Samii Z.K. El-Feky S.A. Bajorath J. Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors.Bioorg. Med. Chem. Lett. 2013; 23: 2007-2013Crossref PubMed Scopus (26) Google Scholar, [17]Cho J.Y. Kwon H.C. Williams P.G. Jensen P.R. Fenical W. Azamerone, a terpenoid phthalazinone from a marine-derived bacterium related to the genus Streptomyces (Actinomycetales).Org. Lett. 2006; 8: 2471-2474Crossref PubMed Scopus (97) Google Scholar, [18]Olmo E. Barboza B. Ybarra M.I. López-Pérez J.L. Carrón R. Sevilla M.A. Boselli C. San Feliciano A. Vasorelaxant activity of phthalazinones and related compounds.Bioorg. Med. Chem. Lett. 2006; 16: 2786-2790Crossref PubMed Scopus (71) Google Scholar, [19]Calligaris S. Manzocco L. Conte L.S. Nicolia M.C. Application of a modified Arrhenius equation for the evaluation of oxidation rate of sunflower oil at subzero temperatures.J. Food Sci. 2004; 69: 361-366Crossref Scopus (49) Google Scholar, [20]Schwaab M. Pinto J.C. Optimum reference temperature for reparameterization of the Arrhenius equation. Part 1: problems involving one kinetic constant.Chem. Eng. Sci. 2007; 62: 2750-2764Crossref Scopus (203) Google Scholar]. In our theoretical study we will use the output parameters of DFT simulation then we fed these results as input parameters in the exact analytical solution of kinetic Arrhenius model to find a reliable mechanism of chemical reaction conclusion [[21]Pearce J.A. Relationship between Arrhenius models of thermal damage and the CEM 43 thermal dose.SPIE BiOS: Biomedical Optics. 2009; 15: 718104-718114Google Scholar, [22]He X. Bhowmick S. Bischof J.C. Thermal therapy in urologic systems: a comparison of Arrhenius and thermal isoeffective dose models in predicting hyperthermic injury.J. Biomech. Eng. 2009; 131074507Crossref PubMed Scopus (55) Google Scholar]. The thermal degradation of phthalazin-1-ol at heating rate °K/sec are presented on Figure 2. From the TGA-curve: the first full half reaction at 404 K which is related to 50.8% mass loss of the benzylidenephthalide (1) outlined the thermal stability of the phthalazin-1-one (4) 50.9% than that approximately produced phthalazine-1-ol (5) 40%. This result agreed well with the phenomena of phthalazin-1-one = phthalazin-1-ol dynamic equilibrium. The thermal kinetic control of the phthalazin-1-one (4) is stabilized by 13 kcal/mol and so more yield formed (50.9%) more than yield of phthalazin-1-ol (5) be 40%. It was accompanied by endothermic effect and burning via decarbonylation and decomposition of the phthalzin-1-one (4) that produced from the thermal degradation during the half lifetime of concentration [[23]Yelon A. Movaghar B. Microscopic explanation of the compensation (Meyer-Neldel) rule.Phys. Rev. Lett. 1990; 65: 618-620Crossref PubMed Scopus (233) Google Scholar, [24]Krug R.R. Hunter W.G. Grieger R.A. Enthalpy-entropy compensation. 2. Separation of the chemical from the statistical effect.J. Phys. Chem. 1976; 80: 2341-2351Crossref Scopus (696) Google Scholar, [25]Yelon A. Movaghar B. Crandall R. Multi-excitation entropy: its role in thermodynamics and kinetics.Rep. Prog. Phys. 2006; 69: 1145-1194Crossref Scopus (182) Google Scholar]. In promoted microwave reaction, the thermodynamic phthalazin-1-ol (5) is formed at 413 K that stabilized by 36 kcal/mol due to aromaticity more than phthalazine-1-one (4). Therefore, our proposed novel green synthesis with dual system which combines both microscopic (DFT simulation) and macroscopic (kinetic Arrhenius Model) show that phthalazin-1-ol (5) is more stable than phthalzin-1-one (4). Based on these results we can also calculate the activation energy (E) and pre-exponential factor (A) of phthalazine-1-ol under the influence of promoted plasma organic reaction condition. Therefore, the results find a significant equilibrium temperature of the optimized structures of the phthalazine-1-ol inhibitors mounted on cancer cell [[26]Barrie P.J. The mathematical origins of the kinetic compensation effect: 2. the effect of systematic errors.Phys. Chem. Chem. Phys. 2012; 14: 327-336Crossref PubMed Google Scholar, [27]Barrie P.J. The mathematical origins of the kinetic compensation effect: 1. the effect of random experimental errors.Phys. Chem. Chem. Phys. 2012; 14: 318-326Crossref PubMed Google Scholar, [28]Napoletano M. Norcini G. Pellacini F. Morazzoni G. Ferlenga P. inhibitiors Pradella L. Phthalazine PDE4 Part 2: the synthesis and biological evolution of 6-methoxy-1,4-disubstituted derivatives.Bioorg. Med. Chem. Lett. 2001; 11: 33-37Crossref PubMed Scopus (56) Google Scholar].Figure 2TGA thermal decomposing full half decomposition of benzal phthalide (3) and their capture half minimum phthalazinone production (4) [Red point; 397 K). Plasma treatment (high temperature), saving in afforded the phthalazine-1-ol (5) [Blue point; 413 K].View Large Image Figure ViewerDownload Hi-res image Download (PPT)2. Macroscopic study using theoretical Arrhenius modelIn the macroscopic non-isothermal state, if an arbitrary material ensemble dissolved thermally, then the mass conversion fraction of degradable ensemble could be described in what follows [[29]Rizk S.A. Abdelwahab S.S. Elrazaz E. Synthesis and QSAR study of some novel heterocyclic derivatives as in vitro cytotoxic agents.J. Heterocycl. Chem. 2019; 56: 443Crossref Scopus (4) Google Scholar, [30]Ramtohup Y.K. James M.N.G. Vederas J.C. Synthesis and evaluation of keto-glutamine analogues as inhibitors of hepatitis A virus 3C proteinase.J. Org. Chem. 2002; 67: 3169Crossref PubMed Scopus (73) Google Scholar, [31]Gordillo R. Dudding T. Anderson C.D. Houk K.N. Hydrogen bonding catalysis operates by charge stabilization in highly polar Diels−Alder reactions.Org. Lett. 2007; 9: 501-503Crossref PubMed Scopus (66) Google Scholar, [32]Kissinger H. Variation of peak temperature with heating rate in differential thermal analysis.J. Res. Natl. Bur. Stand. 1956; 57: 217-221Crossref Google Scholar].1−χi=exp[E(T)](1) Where, E(T) is dimensionless function can be calculated as:E(T)=T0−Tλ+ρλln(TT0)+ρ22λTF22(1,1;3,2;−ρT)−ρ22λT0F22(1,1;3,2;−ρT0)(2) Where, χ_i is the mass conversion fraction, 1-χ_iis the residual mass, λ = β∖/A and ρ = Ei ∖/R, R is the gas constant. E_i is the activation energy and the constant heating rate temperature dT/dt = β. With regard to Eq. (1). The residual mass fraction of degradable ensemble represents as follow:dχi/dT=Aexp[E(T)]βexp[−ρT](3) The equilibrium conversion of the rate constant of the Arrhenius equation can be calculated as [[16]Elagawany M. Ibrahim M.A. Ali Ahmed H.E. El-Etrawy A.S.H. Ghiaty A. Abdel-Samii Z.K. El-Feky S.A. Bajorath J. Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors.Bioorg. Med. Chem. Lett. 2013; 23: 2007-2013Crossref PubMed Scopus (26) Google Scholar]:ε=kf(T)1+kf(T)(4) Finally, an important relationship in statistical mechanics, the entropy of canonical ensemble which is the statistical ensemble that represents the possible states of our residual mass of our system in thermal equilibrium with a heat rate of temperature can be evaluated as a canonical Gibbs entropy of residual mass like [[17]Cho J.Y. Kwon H.C. Williams P.G. Jensen P.R. Fenical W. Azamerone, a terpenoid phthalazinone from a marine-derived bacterium related to the genus Streptomyces (Actinomycetales).Org. Lett. 2006; 8: 2471-2474Crossref PubMed Scopus (97) Google Scholar, [18]Olmo E. Barboza B. Ybarra M.I. López-Pérez J.L. Carrón R. Sevilla M.A. Boselli C. San Feliciano A. Vasorelaxant activity of phthalazinones and related compounds.Bioorg. Med. Chem. Lett. 2006; 16: 2786-2790Crossref PubMed Scopus (71) Google Scholar, [19]Calligaris S. Manzocco L. Conte L.S. Nicolia M.C. Application of a modified Arrhenius equation for the evaluation of oxidation rate of sunflower oil at subzero temperatures.J. Food Sci. 2004; 69: 361-366Crossref Scopus (49) Google Scholar]:SGBχ=−KB(1−χi)Log((1−χi))(5) The pervious Gibbs equation of entropy can be used to find the exact temperature of transfer phase through our chemical reaction which get the final component of chemical reaction with very low disorder of state.3. Result and discussion3.1 ChemistryIn chemistry, the thermodynamic stability of phthalazine-1-ol (5) by 36 kcal/mol is available under microwave-plasma reaction conditions due to the aromaticity and stronger of intermolecular hydrogen bond (O–H...O) than the corresponding (N–H…..O=C) of phthalazine-1-one (4) (Scheme 2). Sonication using polar solvent can strongly favor the amide-like structure of phthalazin-1(2H)-one tautomer (4) in polar protic solvent e.g. ethanol solution appears 100%, in polar aprotic solvent e.g. DMSO appears 60% [[2]Tsoungas P.G. Searcey M. A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators.Tetrahedron Lett. 2001; 42: 6589-6592Crossref Scopus (33) Google Scholar, [3]Sivakumar R. Gnanasam S.K. Ramachandran S. Leonard J.T. Pharmacological evaluation of some new 1-substituted-4-hydroxy-phthalazines.Eur. J. Med. Chem. 2002; 37: 793-801Crossref PubMed Scopus (54) Google Scholar]. Otherwise, reaction in nonpolar or less polar solvent e.g. petroleum ether or acetone, it afforded the phthalazin-1-ol lactim-like structure [[20]Schwaab M. Pinto J.C. Optimum reference temperature for reparameterization of the Arrhenius equation. Part 1: problems involving one kinetic constant.Chem. Eng. Sci. 2007; 62: 2750-2764Crossref Scopus (203) Google Scholar, [21]Pearce J.A. Relationship between Arrhenius models of thermal damage and the CEM 43 thermal dose.SPIE BiOS: Biomedical Optics. 2009; 15: 718104-718114Google Scholar, [22]He X. Bhowmick S. Bischof J.C. Thermal therapy in urologic systems: a comparison of Arrhenius and thermal isoeffective dose models in predicting hyperthermic injury.J. Biomech. Eng. 2009; 131074507Crossref PubMed Scopus (55) Google Scholar, [33]Marin G. Yablonsky G.S. Kinetics of Chemical Reactions: Decoding Complexity. Wiley-VCH Verlag, Weinheim2011Google Scholar, [34]Akerblom Ida E. Ojwang Dickson O. Grins Jekabs Svensson Gunnar A thermogravimetric study of thermal dehydration of copper hexacyanoferrate by means of model-free kinetic analysis.J. Therm. Anal. Calorim. 2017; 129: 721-731Crossref Scopus (24) Google Scholar, [35]Huang Chung-Wei Yang Teng-Chun Hung Ke-Chang Jin-Wei Xu Wu Jyh-Horng The effect of maleated polypropylene on the non-isothermal crystallization kinetics of wood fiber-reinforced polypropylene composites.Polymers. 2018; 10: 382Crossref Scopus (22) Google Scholar]. In the absence of effective solvation and at concentration less than 10−5 M to minimize dimeric hydrogen-bonded association, the lactam: lactim ratio is around 2:3 changing even further to 2:1 in the gas phase (Scheme 3) [[23]Yelon A. Movaghar B. Microscopic explanation of the compensation (Meyer-Neldel) rule.Phys. Rev. Lett. 1990; 65: 618-620Crossref PubMed Scopus (233) Google Scholar]. For first-order reactions, the pre-exponential factor (A) can fluctuate from 105 to 106 min−1. In Figure 2, the residual mass decomposition of benzylidene phthalide (1) intersected (red point) with the final product of phthalazin-1-one (4) at 397 K and starting a new product of the phthalazin-1-ol (5) (blue point) at 413 K. The mathematical equation can indicate the typical value of the apparent activation energy(E) and pre-exponential factor(A). The Arrhenius equation is higher for the first stage of the thermal degradation of phthalazin-1-one (Table 1). The high factors are a loose complex [[26]Barrie P.J. The mathematical origins of the kinetic compensation effect: 2. the effect of systematic errors.Phys. Chem. Chem. Phys. 2012; 14: 327-336Crossref PubMed Google Scholar, [27]Barrie P.J. The mathematical origins of the kinetic compensation effect: 1. the effect of random experimental errors.Phys. Chem. Chem. Phys. 2012; 14: 318-326Crossref PubMed Google Scholar]. The concentrations in phthalazinone (4) are not controllable in many cases. It would have been convenient if the magnitude of the pre-exponential factor (A) showed for reaction so called molecularity. This performance is valid for non-surface-controlled reactions are having low (<108 min−1) pre-exponential factors. So, the reactions of elementary can only be bimolecular. The change of entropy ΔS reflected for the activated complex configuration of the starting materials. Therefore, the formation of the phthalazine-2-ol (5) is to its thermodynamic equilibrium. Scheme 2 outlined the stronger intermolecular hydrogen bond in the phthalazine-1-ol (5) i.e. lower the entropy ΔS and spontaneous free energy ΔG pushing toward the phthalazine-1-ol product. The reconstructed structure of the phalazin-1-ol using plasma process afforded a more stable isomer (5) than isomer (4) [[36]Attia S.K. Elgendy A.T. Rizk S.A. Efficient green synthesis of antioxidant azacoumarin dye bearing spiro-pyrrolidine for enhancing electro-optical properties of perovskite solar cells.J. Mol. Struct. 2019; 1184: 583-592Crossref Scopus (17) Google Scholar, [37]El-Hashash M.A. Darwish K.M. Rizk S.A. El-Bassiouny F.A. The uses of 2-ethoxy-(4H)-3,1-benzoxazin-4-one in the synthesis of some quinazolinone derivatives of antimicrobial activity.Pharmaceuticals. 2011; 4: 1032-1051Crossref Scopus (17) Google Scholar, [38]Azab M.E. Rizk S.A. Mahmoud N.F. Facile synthesis, characterization, and antimicrobial evaluation of novel heterocycles, schiff bases, and N-nucleosides bearing phthalazine moiety.Chem. Pharm. Bull. 2016; 64: 439-450Crossref PubMed Scopus (19) Google Scholar]. Using the exact model of Arrhenius model can be confirmed by the DFT simulation. Table 1 outlines that the E and A values for the thermal degradation of phthalazin1-one (4) are higher than the phthalazine-1-ol (5). The value of the activation energy E is approximately 60 kJ mol-1 that may enhance a diffusion-controlled kinetic process. For more presentation of 3D kinetic relation of variable degradation of residual mass of thermal decomposing of phthalic anhydride with phenyl acetic acid afforded benzylidene phthalide (1), the temperature and rate of reaction at constant heat and constant activation energy (53 k j/mole) by pre-exponential factor (1.1 106) Figures 3, 4, and 5. The graph shows growth rate of decomposition of mass residual of reactants 1 and 2 with increasing rate of heat constant. The thermodynamic equilibrium becomes far and yields the activated complex when reactants have higher values of activation entropy. Therefore, we can observe the short reaction times.Table 1Outline activation energy and Entropy of the amide-amidate rearrangement.CompoundActivation energy (KJ)Exponential factor A ∗106EntropyJ/molTo oKTf oK4531.134132885285a603.34852955735b707.1480296531 Open table in a new tab Figure 33D graphical representation between the residual mass, pre-exponential factor and heat constant rate (heat control) up to (350 °K) of phthalic anhydride (1) and phenyl acetic acid (2).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 43D graphical up to (397 °K) of benzykidenephthalic anhydride (1) and 4-chlorobenzaldehyde (2).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 53D graphical representation up to (404 °K) 5 beta decomposing of reactants (1) and (2).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Also, the model shows the relation of heat constant rate and the pre-exponential factor which can give a recommendation for a good mechanism of stable reaction of phthalazin-1-ol. From our study of exact analytical solutions and the results of thermogravimetric analysis outlined in Figure 2. The addition-elimination reaction of the hydrazide (3) afforded the phthalazine-1-one (4) and phthalazine-1-ol (5) products at 413 K and 485 K respectively under plasma organic reaction condition (Scheme 1) (Figures 6, 7, and 8). The amide amidate of the phthalazinone-phthalazin-1-ol dynamic equilibrium occur at 432 K (orange line) (Figure 6). This shows the tautomer's unsolvated to be of approximately equal thermodynamic stability of the phthalazine-1-ol (5). The experimental results of the plasma organic synthesis of phthalazine-1-ol (5) are confirmed and good agreement with 1H-NMR, theoretical and simulation studies. As seen from Figures 3, 4, 5, 6, 7, and 8.Scheme 1Outline synthesis of the phthalazine-1-ol (5) via plasma organic reaction.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6Decomposition of the reactants phthalazinone (4) (blue line), dynamic equilibrium (50-50) (orange line) and phthalazine-1-ol (5) (green line) by plasma temperature control.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 7Outline the formation of the products of pure phthalazinone (4) (blue line), pure phthalazine-1-ol (5) (green line) and dynamic equilibrium (50-50) (orange line) between the compounds 4 and 5 at plasma temperature control.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 8Outline the Gibbs entropy which indicate the phase transfer of pure phthalazinone (4) 413 K (blue line), pure phthalazine-1-ol (5) 485 K (green line) respectively under plasma treatment and dynamic equilibrium (50-50) 432 K (orange line) between the compounds 4 and 5 at plasma temperature control.View Large Image Figure ViewerDownload Hi-res image Download (PPT)4. DFT-characterization based on the thermodynamic aspectsPhthalazin-1(2H)-one is extremely unflavored in the lactam⇌lactim dynamic in particular, the negative values of ΔS would indicate that the formation of activated complex is connected with decrease of entropy, i.e., the activated complex is "more organized" structure compared to the initial substance and such reactions are classified as "slow" [[28]Napoletano M. Norcini G. Pellacini F. Morazzoni G. Ferlenga P. inhibitiors Pradella L. Phthalazine PDE4 Part 2: the synthesis and biological evolution of 6-methoxy-1,4-disubstituted derivatives.Bioorg. Med. Chem. Lett. 2001; 11: 33-37Crossref PubMed Scopus (56) Google Scholar]. From Figures 6 and 7, the authors advice that reaction takes place more effective at lower heat constant flow (β) because the higher β will decrease value of pre-exponential factor (A) which decrease the yield of the phthalazin-1-ol (5). The thermal stability of the phthalazin-1-ol in high energy of ultrasonic medium. The second singlet n-π∗ state has the lowest energy in phthalazine. In this isomer, it is the second singlet excited state, 0.46 eV above the S1 state. The S2 state in phthalazine stems from the HOMO - LUMO. DFT indicated the proposal mechanism of the phthalazine-1-ol via ring-opening of benzylidene phthalide (1) using hydrazine hydrate followed by 4-chlorobenzaldehyde (2) to afford the hydrazide (3) that is confirmed thermodynamic parameters the electrophilicity of the benzylidene phthalide was more than 4-chlorobenzaldehyde (Figure 9). Therefore, we can support the experimental suggestion [[29]Rizk S.A. Abdelwahab S.S. Elrazaz E. Synthesis and QSAR study of some novel heterocyclic derivatives as in vitro cytotoxic agents.J. Heterocycl. Chem. 2019; 56: 443Crossref Scopus (4) Google Scholar] that the second singlet excited state of phthalazine is an np∗ state with a small oscillator strength. Finally, we can give also a good reason for the higher activity of phthalazin-1-ol in the cytotoxicity of anticancer due to this reaction is include the reactive speeches of OH group. The relation of equation 6 of the residual mass Gibbs entropy of the thermal degradation of the lowest disorder of the three components (benzylidene phthalide (1) transition phase at 410 K, phthalazine-1-one (4) 436 K and phthalazine-1-ol (5) 485 K as follow blue, yellow and Green curves respectively in Figure 8. On the other hand, the density function theory (DFT) and differential thermogravimeter DGA (Figure 7) transition phase at 406, 433 and 481 K was also confirmed the mathematical calculation in which ΔE -(EHO-ELU) was corresponding to the activation energy of the phthalazinone-phthalazin-1-ol dynamic equilibrium and the reaction was pushing to the phthalazin-1-ol 70% as major product. 1H-NMR of the microwave product confirmed the presence of the phthalazin-1-ol (5) as a major product δ OH in the phthalazine-1-ol is 10.23 that higher than 6.46 ppm of the phthalazine-1(2H)-one that is approved with dihedral angle. In the phthalazine-1-ol, the dihedral angle in t
Referência(s)