Perlite-SO3H nanoparticles as an efficient and reusable catalyst for one-pot three-component synthesis of 1,2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one derivatives under both microwave-assisted and thermal solvent-free conditions: Single crystal X-ray structure analysis and theoretical study

INTRODUCTION

       The use of heterogeneous catalysts [1-3]has received considerable importance in organic synthesis because of their ease of handling, enhanced reaction rates, greater selectivity, simple work-up, and recoverability of catalysts. Among the various heterogeneous catalysts, particularly, perlite nanoparticles has advantages of eco-friendly, low cost, ease of preparation and catalyst recycling [4]. Perlite is an amorphous volcanic glass that has relatively high water content, typically formed by the hydration of obsidian. Because of its low density and relatively low price, many commercial applications for perlite have developed In the construction and manufacturing fields, it is used in lightweight plasters and mortars, insulation and ceiling tiles, however there are few reports about using perlite as suitable support for catalytic applications [5-8].

      Multicomponent reactions (MCRs) [9-13] can be defined as convergent chemical processes where three or more reagents are combined in such a way that the final product retains significant portions of all starting materials. Therefore, they lead to the connection of three or more starting materials in a single synthetic operation with high atom economy and bond-forming efficiency, thereby increasing molecular diversity and complexity in a fast and often experimentally simple fashion [14,15]. For this reason, multicomponent reactions are particularly well suited for diversity-oriented synthesis [16-18] and the exploratory   power  arising  from  their  conciseness  makes them also very powerful for library synthesis aimed at carrying out structure-activity relationship (SAR) studies of drug-like compounds, which are an essential part of the research performed in pharmaceutical and agrochemical companies [19,20]. For all these reasons, the development of new multicomponent reactions is rapidly becoming one of the frontiers of organic synthesis.

      Aromatic condensed oxazinone derivatives have received considerable attention due to the attractive pharmacological properties associated with their heterocyclic scaffold [21]. Since many of these heterocyclic systems exhibit biological activities such as anti-inflammatory, antiulcer, antipyretic, antihypertensive and antifungal, these derivatives have become an integral part of pharmacologically important heterocyclic compounds [22-26]. Some of them also act as 5-HT ligands [27], DP receptor antagonists [28], integrin antagonists [29], platelet fibrinogen receptor antagonists [30], calmodulin antagonists [31], inhibitors of the transforming growth factor b (TGF-b) signaling pathway [32], soybean lipoxygenase [33], Janus kinase (JAK) and other protein kinases [34]. Moreover, benzo[1,4]oxazin-3-one analogs act as effective potassium channel openers, immunomodulating reagents, and etc. [35,36]. This class of heterocyclic compounds has been also used as precursors in the synthesis of phosphinic ligands for asymmetric catalysis [37]. Therefore, aromatic condensed oxazinone derivatives scaffold can be viewed as a ‘privileged structure’ among pharmaceutical compounds [38,39]. Inspite of their high potential, there are only few reports which describe the synthesis of naphthalene-condensed oxazinone derivatives [40-43]. In general, all these methods require elevated temperature non recyclable catalyst except those reported by Chaskar et al. [40]. Besides, a multi-step and cumbersome reaction involving the use of harsh conditions is required for the synthesis of starting materials such as amino alkylnaphthol. Therefore, development of simple, robust and safer methodologies for the synthesis of naphthoxazinone derivatives is of the prime interest for obtaining these products under conditions tolerated by sensitive functional groups from both synthetic and environmental points of view [44].

      Microwave chemistry and microwave-assisted organic synthesis (MAOs) are nowadays undeniably effective tools in medicinal chemistry [45]. The availability of safe, single-mode dedicated microwave units has allowed the incorporation of this new technology into accelerating drug-discovery, hit-to-lead, and lead optimization programs. The development of more economical synthetic routes can ameliorate the overall process since drug discovery is a costly exercise with a high attrition rate [45]. The use of MAOs has been shown to dramatically reduce processing times, increase product yields, and enhance the purity of the product when compared to the conventionally processed experiments [45]. Since there are several manufacturers of professional-grade equipment and a plethora of adapted methods, one can conclude that this interest continues to grow [46].

      Motivated by the afore-mentioned findings, and in a continuation of our interest in synthesis of a wide range of heterocyclic systems in our laboratory [47-54], we describe here a facile one-pot three-component synthesis of 1,2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one derivatives (4) from 2-naphthol (1), aldehyde (2) and urea (3) in the presence of perlite-SO₃H nanoparticles as efficient catalyst under both microwave and thermal solvent-free conditions (Scheme 1).

      In recent years, computational chemistry has become an important tool for chemists and a well-accepted partner for experimental chemistry [55-58].Density functional theory (DFT) method has become a major tool in the methodological arsenal of computational organic chemists. In the present work, we investigate the energetic and structural properties of crystal structures of 4i using DFT calculations. The optimized geometry, frontier molecular orbitals (FMO), detail of quantum molecular descriptors, molecular electrostatic potential (MEP), chemical tensors, natural charge and NBO analysis were calculated.

RESULTS AND DISCUSSION

      Recently, it has been reported that multi-component reactions of 2-naphthol (1) with benzaldehyde (2a) and urea (3) in the presence of a number of catalysts and reagents such as H₂NSO₃H [59], HClO₄/SiO₂ [60], 2,4,6-trichloro-1,3,5-triazine [61], InCl₃ [62] and CH₃SO₃H [63] afforded uncyclized product (5a) in good yields, without any formation of cycloadduct (4a) (Scheme 2).

      To optimize the reaction conditions to give cycloadduct 4a, the reaction of 2-naphthol (1) with benzaldehyde (2a) and urea (3) in the presence of various types of perlite as catalyst was used as a model reaction to oxazinone derivatives synthesis. According to the obtained data, using the perlite-SO₃H nanoparticles (0.01 g) under solvent-free conditions for the oxazinone formation represents the best reaction conditions (Table 1).

Scheme 1. Synthesis of 1,2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one derivatives (4a-j)

Scheme 2. Possible cyclized and uncyclized products of the reaction

      Table 1 clearly demonstrates that perlite-SO₃H nanoparticles are an effective catalyst in terms of yield of the obtained product. To find out the optimum quantity of perlite-SO₃H nanoparticles, the model reaction was carried out at 110 °C using different quantities of perlite-SO₃H nanoparticles (Table 2). According to the obtained data, 0.01 g of perlite-SO₃H nanoparticles gave the best yield in 45 min (Table 2, entry 3).

 Table 1. Reaction between 2-Naphthol (1), Benzaldehyde (2a) and Urea (3) in the  Presence  of  Various  Types of  Perlite as Catalyst under Thermal and Solvent-Free Conditions^a

Table 2. Optimization Amount of perlite-SO₃H nanoparticles on the Reaction of  2-Naphthol (1), Benzaldehyde (2a) and Urea (3) under Thermal and Solvent-Free Conditions

      The above reaction was also examined in various solvents (Table 3). The results indicated that different solvents affect the efficiency of the reaction. These solvents required a longer time and gave low to moderate yields, and the best results were obtained when solvent-free conditions were used (Table 3, entry 5).

      Encouraged by this success, we attempted the reaction of 2-naphthol (1) with a range of  other  aromatic  aldehydes (2) and urea under similar conditions (using perlite-SO₃H nanoparticles), furnishing the respective 1,2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one derivatives in good yields. The optimized results are summarized in Table 4. The termal solvent-free conditions are well suited  for either electron-donating or electron-withdrawing substituents on the aromatic aldehydes.

Table 3. Solvent Effect on the Reaction Between 2-Naphthol (1), Benzaldehyde (2a) and Urea (3) under Thermal and Solvent-Free Conditions (0.01 g)

        Table 4. Selected Interatomic Distances and Torsion Angles of 4i

 Crystal Structure of 4i

      Centrosymmetric crystals of 4i (space group P2₁/n) contain racemic 4i compound. The molecular structure of (S)-enantiomer is shown in Fig. 1. A summary of the conditions for the data collection and the structure refinement parameters are given in Experimental Part. The selected geometrical parameters are given in Table 4.

      In 4i molecule, the bond lengths and angles are within normal ranges [64], and the overall conformation of 4i is very similar to those observed in previously reported 1-phenyl, 1-(4-fluorophenyl) and 1-(4-chlorophenyl) derivatives [65-67]. The six-membered ring O(1)/C(1)/N(1)/C(2)/C(3)/C(4) is slightly puckered (Cremer & Pople [68] amplitude Q = 0.280(2) Å). The mutual orientation of the planar regions, i.e. phenyl and naphthalene moieties, is defined by the dihedral angle between them, which is 77.6(1)°,  and by  the  torsion  angle C(13)-C(2)-C(3)-C(12) amounting to -77.21(17)°.

Fig. 1. (a) X-Ray crystal structure of (S)-enantiomer of 4i compound (displacement ellipsoids at 50%  probability  level), (b) Geometrical  structure  of  the  4i compound (optimized at B3LYP/6-311+G* level).

      In the crystal lattice of 4i, the adjacent molecules of the same chirality, related by the action of the 2₁ screw axis, are joined to each other viaN(1)-H(1N)···O(2)ⁱhydrogen bondsand weak C(17)-H(17)···O(1)ⁱⁱ interactions to form homochiralchains running down the b-axis (Fig. 5; geometry and symmetry codes therein). The inter-chain contacts are provided by the weak π···π interactions involving C(3)/C(4)/C(5)/C(6)/C(7)/C(12) rings of the adjacent molecules related by the inversion [centroid···centroidⁱⁱⁱdistance of 3.652(2) Å, centroid···plane perpendicular distance of 3.567(1)Å; symmetry code (iii) -x,-y+1,-z+1)].

      Also in order to decrease the reaction time, microwave irradiation under solvent-free conditions was used. The reaction time decreased from almost 1 h to a few minutes. Moreover, the yields of products increased in all cases examined (Table 5).  

Fig. 2. Molecules of 4i joined to each other via N/C-H···O contacts (dashed lines) to form homochiralchains  running down  the b-axis. [H···A, D···A, and D–H···A for  N(1)-H(1N)···O(2)ⁱ: 2.08(2), 2.807(2) Å and  143(2)°; for C(17)–H(17)···O(1)ⁱⁱ: 2.58, 3.187(2) Å and 122°. Symmetrycodes (i) -x+1/2, y+1/2, -z+3/2; (ii) x, y+1, z].

Table 5. Reaction Between 2-Naphthol (1),  Aromatic  Aldehydes (2)  and   Urea (3)   under  Solvent-Free (I) and Microwave-Assisted^a (II) Conditions Using 0.01 g Perlite-SO₃H NPs as Catalyst

A plausible mechanism for the formation of 2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one  derivatives in  the presence of perlite-SO₃H nanoparticles is shown in Scheme 3. It may be proposed that similar to several classical multi-component condensations, the initial event in this reaction is the condensation of aldehyde and urea to give reactive acylimine intermediate. Subsequently, the resulting acylimine intermediate undergoes a cyclization with 2-naphthol affording the corresponding products and ammonia [69,70].

Scheme 3.Aproposed mechanism for the synthesis of 2-dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3- one derivatives in the presence of perlite-SO₃H nanoparticles.

 Fig. 3. Development of the yield after several recycling cycles of the catalyst.

       In order to explore the recyclability of the catalyst, the perlite-SO₃H nanoparticles in solvent-free conditions were used as a catalyst for the same reaction repeatedly and the change in their catalytic activity was studied. The relation between the number of cycles of the reaction and the catalytic activity in terms of yield of the products is presented in Fig. 3. It was found that perlite-SO₃H nanoparticles could be reused for four cycles with negligible loss of their activity.

Electronic Properties and MEP Analysis

      Quantum chemical methods are important to obtaininformation about molecular structure and electrochemical behavior. The Frontier Molecular Orbitals (FMO) analysis was carried out for 4i compound at B3LYP/6-311+G* level [71].The results of FMO such as E_HOMO, E_HOMO-1, E_LUMO, E_LUMO+1 and HOMO-LUMO energy gap (Eg) of the molecule 4i are summarized in Table 6.

Table 6. Calculated   (B3LYP/6-311+G*) HOMO,  LUMO,  Energy Gaps (HOMO-LUMO) and Related Molecular Properties of 4i Molecule

Fig. 4. Calculated frontier molecular orbitals HOMO (a) and LUMO (b) of structure 4i.

      The energy values  of the highest occupied molecular orbital (E_HOMO) can act as an electron donor and  the  lowest unoccupied molecular orbital (E_LUMO) can act as the electron acceptor and their energy gaps reflect the chemical activity of the molecule [72].As shown in Fig. 4 and Table 6, E_HOMO and E_LUMO of the title compound is -6.3 eV and -1.68 eV, respectively. As seen in Fig. 4, charge transfer takes place within the molecule. The graphic pictures of HOMO and LUMO orbitals show that the HOMO of 4i molecule is localized   mainly  on  naphthalene and  oxazinone  rings, whereas the LUMO is focused mainly on naphthalene ring. The HOMO → LUMO transition implies an electron density transfer from oxazinone to naphthalene ring.

      Also in this work, electronic structure of the 4i compound was studied using total densities of states (DOSs) [73].DOS plot shows population analysis per orbital and demonstrates a simple view of the character of the molecular orbitals in a certain energy range [74]. According to Fig. 5, DOS analysis indicates that the calculated HOMO-LUMO energy gap (Eg) of the 4i molecule is4.62 eV.

      A detail of quantum molecular descriptors of 4i structure such as the ionization potential (I), electron affinity (A), chemical hardness (η), electronic chemical potential (µ) and electrophilicity (ω) are summarized in Table 6. Dipole moment (µ_D) is a good measure for the asymmetric nature of a structure [71]. The size of the dipole moment depends on the composition and dimensionality of the 3D structures. As shown in Table 6, dipole moment of the title structure is 5.567 Debye that the high value of dipole momentis due to its asymmetric character that the atoms are irregularly arranged which gives rise to the increased dipole moment. In addition, the point group of structure is C1 (see Table 6).

 Fig. 5. Calculated DOS plots of 4i structure (usingB3LYP/6-311+G*).

       The molecular electrostatic potential (MEP) was checked out by theoretical calculations at B3LYP/6-311+G* level. Molecular electrostatic potential shows the electronic density and is useful in recognition sites for electrophilic attack and nucleophilic reactions as well as hydrogen bonding interactions [75,76]. The negative areas (red color) of MEP are related to electrophilic reactivity and the positive areas (blue color) to nucleophilic reactivity shown in Fig. 6. Molecular electrostatic potential V(r) [77] value is -8.930e^-2.According to the MEP maps in Fig. 6, negative region of 4i compound is mainly focused over the oxygen in C=O group (more color intensity), therefore it is useful region for nucleophilic activity. In addition, the lowest electron density with the highest intensity blue color is observed for the hydrogen atom in N-H, therefore it is suitable site for electrophilic attraction.

Atomic Charge

      We calculated the charge distributions for the equilibrium geometry of 4i molecule by Natural Bond Orbital (NBO) analysis (natural charge) [71,78]at B3LYP/6-311+G* level. The total charge of the investigated molecule is equal to zero. According to Fig. 7, the results of the NBO analysis reveal that the highest positive charge belongs to C₁₂ atom in the carbonyl group (0.923e), while the highest value of negative charge  is on the  N₁₃  atom  (-0.650e).  In  addition,  oxygen  atoms  have great negative charge (-0.603e and -0.539e). The carbon atoms of the naphthalene ring bear negative charges except C₉ atom (close to oxygen atom) that bear positive charge (0.333e), while the carbon atoms of the phenyl ring bear negative charges. All hydrogen atoms have  positive  charge and the H₃₁ atom in N-H group has the highest positive charge (0.403e).

Fig. 6. Molecular electrostatic potential (MEP) maps of 4i molecule calculated at B3LYP/6-311+G* level.

Fig. 7. Calculated (B3LYP/6-311+G*) natural charges (NBO) of the atoms of 4i molecule. (The Cartesian coordinates of the optimized structure are available in the supplementary material.).

      The NMR parameters of 4i molecule are summarized in Table 7. The C₂₃ and C₂₄ (methyl groups) have the highest σ_iso  value  (158.160  ppm  and  157.488  ppm, respectively), therefore they are shielder than other atoms due to hyperconjugation effect. While O₂₁ has the lowest σ_iso value (15.809 ppm) and the highest σ_aniso value (368.673 ppm) indicating that O₂₁ is deshielder than other atoms. According to Table 7, the σ_iso value of  H₃₁  in N-H  group is 28.024 ppm that it is shielder than other hydrogen atoms. The σ_iso value of C₈, C₉ and C₁₀ in naphthalene ring is 61.439 ppm, 26.227 ppm and 63.745 ppm, respectively. It shows the C₉ atom is deshielder than the C₈ and C₁₀ atoms, because the C₉ atom is close  to the oxygen atom (O₁₁).  The σ_iso values of C₁₅, C₁₆, C₁₇ and C₁₈ atoms in phenyl ring are 34.305 ppm, 51.738 ppm, 49.950 ppm and 26.033 ppm, respectively. As shown, the C₁₆ atom is shielder than other and the C18 atom is deshielder than other carbon atoms of phenyl ring.

   Table 7. The NMR Parameter Values (ppm) of 4i at B3LYP/6-311+G* Level (Atom Labeling Corresponds to Fig. 7)

NBO Analysis

      Natural bond orbital (NBO) analysis is an important method for studying interaction between bonds.^79,80 The results of NBO analysis such as the occupation numbers with their energies for the interacting NBOs and the polarization coefficient  of atoms for 4i structure  at B3LYP/6-311+G* level are summarized in Table 8. The size of polarization coefficients shows the importance of the two hybrids in formation of the bond.In 4i structure, the calculated bonding orbital for the C₁₂-N₁₃ bond is BD(1) = 0.6169sp^1.82 + 0.7870sp^1.89 with high occupancy 1.98987 a.u. and energy -0.85022 a.u.. The polarization coefficients of C₁₂ = 0.6169 and N₁₃ = 0.7870 suggest that N₁₃ is more electron-rich than  the  C₁₂   atom.

Table 8. Calculated Natural Bond orbitals (NBOs) and  Polarization  Coefficient  for Each Hybrid in Selected Bonds of 4i Compound at B3LYP/6-311+G* Level (Atom Labeling Corresponds to Fig. 7)

The   calculated natural charge (NBO) of N₁₃ atom is more negative (-0.650e) than C₁₂ atom (0.923e). Thus more the charge density resides on the N₁₃. The calculated bonding orbital for the C₁₂-O₂₁ is BD(1) = 0.6002sp^1.71 + 0.7999sp^1.53 with high occupancy 1.99197 a.u. and low energy -1.08004a.u.. The polarization coefficient of O₂₁(0.7999) is greater than C₁₂(0.6002)  suggesting that O₂₁ is more electron-rich (-0.603e)  than C₁₂ (0.923e). Also, in the bonding orbital of C₉-O₁₁ [BD(1)= 0.5642sp^1.37 + 0.8256sp^2.05] with high occupancy 1.98802 a.u. and energy -0.91039 a.u., the polarization coefficient of C₉(0.5642) is greater than O₁₁(0.8256) indicating that O₁₁ is more electron-rich (-0.539e)  than C₉(0.333e). From the natural hybrid orbitals C₉-O₁₁ and C₁₂-O₂₁, the BD(1)C₉-O₁₁ occupies a higher energy orbital (-0.91039 a.u.) with low occupation number (1.98802 a.u.) and BD(1)C₁₂-O₂₁ occupies a lower energy orbital (-1.08004 a.u.) with high polarization coefficient (1.99197 a.u.). According to the calculated bondin orbital for the N₁₃-H₃₁, C₁₄-H₃₂ and C₂₂-H₃₇ bonds, the polarization coefficients of N₁₃, C₁₄ and C₂₂ are   greater    than   that   for   H   atoms   indicative of  the importance of N₁₃, C₁₄ and C₂₂ in formation of N₁₃-H₃₁, C₁₄-H₃₂ and C₂₂-H₃₇ bonds compared to H atoms.

      Electron donor orbital, acceptor orbital and the interacting stabilization energy resulting from the second-order micro disturbance theory [81] are reported in Table 9. The electron delocalization from the filled NBOs (donors) to the empty NBOs (acceptors) describes a conjugative electron transfer process between them [82]. For each donor (i) and acceptor (j), the stabilization energy E(2) associated with the delocalization i→j is estimated. The resonance energy (E(2)) detected the quantity of participation of electrons in the resonance between atoms [71]. The results of the NBO analysis, such as resonance energy (E(2)), donor NBO (i) and acceptor NBO (j), for 4i compound at B3LYP/6-311+G* level are listed in Table 9. 

Table 9. Significant Donor-Acceptor Interactions and Second Order  Perturbation  Energies  of  4i Compound Calculated at B3LYP/6-311+G* Level (Atom Labeling Corresponds to Fig. 7)

According to this table, the BD(1)N₁₃-H₃₁ orbital participates as donor and the anti-bonding BD*(1)C₁₀-O₁₄ and BD*(1)O₁₁-C₁₂ orbitals act as acceptor and their resonance energies (E(2)) are 1.57 and 4.91, respectively. These values indicate large charge transfer from the BD(1)N₁₃-H₃₁ to the anti-bonding orbital of BD*(1)O₁₁-C₁₂ [BD(1)N₁₃-H₃₁→BD*(1)O₁₁-C₁₂]. Based on NBO analysis, the LP(1)N₁₃ orbital participates as donor and the anti-bonding BD*(1)C₁₄-C₁₅, BD*(1)C₁₄-H₃₂ and BD*(1)C₁₅-C₁₆ orbitals act as acceptor and their resonance energies (E(2)) are 6.15, 93.29 and 1.54, respectively. These values indicate large charge transfer from the LP(1)N₁₃ to anti-bonding orbital of BD*(1)C₁₄-H₃₂ [LP(1)N₁₃→BD*(1)C₁₄-H₃₂]. Also, the resonance energies (E(2)) for BD(2)C₁₇-C₁₈→BD*(2)C₁₅-C₁₆, BD(2)C₁₇-C₁₈→BD*(1)C₂₂-C₂₃ and BD(2)C₁₇-C₁₈→BD*(1)C₂₂-C₂₄ are 21.71, 2.54 and 2.62 kcal mol^-1, respectively, showing large charge transfer from BD(2)C₁₇-C₁₈ to the anti-bonding orbital of BD*(2)C₁₅-C₁₆.

EXPERIMENTAL

 General

      All reagents were obtained from Merck (Germany) and Fluka (Switzerland) and used without further purification. Infrared spectra were recorded on a Jasco 6300 FTIR spectrometer. Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. The microwave-assisted procedures were carried out in a Milestone Microwave Oven operating at 1600 W. SEM (Philips XL-30 SEM) with an acceleration voltage of 17 kV was used to investigate the size of the nanoparticles.

  Fig. 8. SEM image of the prepared perlite nanoparticles.

Preparation of the Perlite Nanoparticles

      Perlite powder was first broken down to nano size using the ball-milling technique at the frequency of 45 Hz for 20 h under the dry grinding mode. The morphology and grain size of the perlite nanoparticles was investigated by SEM (12 nm) (Fig. 8). The results from X-ray diffraction (XRD) showed that the sample was perlite nanoparticles as indicated by broadened peaks around 2θ = 26^◦(Fig. 9).

Preparation of the Perlite-SO₃H Nanoparticles

      Perlite-SO₃H  nanoparticles,  was  easily  prepared  by  a simple mixing of the perlite nanoparticles and chlorosulfonic acid at room temperature [83] (Scheme 4). A 250 ml suction flask was equipped with a constant pressure dropping funnel containing chlorosulfonic acid (11.6 g, 0.1 mol) and a gas inlet tube for conducting HCl gas over an adsorbing solution, i.e., H₂O. Then, 30.0 g of the perlite nanoparticles was charged into the flask. Chlorosulfonic acid was added drop wise over a period of 30 min at room temperature. After the addition was complete, the mixture was shaken for 30 min. Perlite-SO₃H was obtained as a white   solid.  Surface  morphology  and  particle  size  were obtained using SEM (28 nm) (Fig. 10).

Fig. 9. X-ray diffraction pattern of the prepared perlite nanoparticles.

Scheme 4. Preparation of the perlite-SO₃H NPs via surface modification of the perlite NPs by chlorosulfonic acid.

One-Pot Synthesis of 1,2-Dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one derivatives (4a-j) under Thermal Conditions

      A mixture of β-naphthol (0.5 mmol), an aromatic aldehyde (0.5 mmol) and urea (0.55 mmol) was heated at 110 °C  in the  presence of perlite-SO₃H nanoparticles (0.01 g) for the indicated time (Table 1). After completion of the reaction, boiling ethanol was added to the reaction mixture.

 Fig. 10. SEM image of the synthesized perlite-SO₃H nanoparticles.

 The catalyst was filtered off and the filtrate was then concentrated and cooled to room temperature. The aqueous ethanol 15% was added to the crude product, the precipitate was separated and then recrystallized using aqueous ethanol 15% twice. The desired pure product(s) was characterized by comparison  of  their  spectroscopical  data (FT-IR)  and physical data with those of known oxazine-3-ones (Table 5).

One-Pot Synthesis of 1,2-Dihydro-1-aryl-naphtho[1,2-e][1,3]oxazine-3-one Derivatives (4a-j) under Microwave Irradiation

      The mixture of β-naphthol (0.5 mmol), an aromatic aldehyde (0.5 mmol) and urea (0.55 mmol) and perlite-SO₃H nanoparticles (0.01 g) was taken in a 50 ml Borosil beaker. The reaction mixture was mixed properly with the help of glass rod and then irradiated in a microwave oven operating power (900 W) for 2-10 min. The progress of the reaction was monitored by TLC, after completion of the reaction; the hot ethanol was added to the reaction mixture and the heterogeneous catalyst was isolated from the mixture by a simple filtration. In continuation of work up, the filtrate ethanol solution was concentrated. The aqueous ethanol (15%) was added to the crude product, the precipitate was separated and then recrystallized using aqueous ethanol (15%) twice. The desired pure product(s) was characterized by comparison of their spectroscopical data (FT-IR) and physical data with those of known oxazine-3-ones.

X-Ray Crystal-Structure Determination of 4i (Fig. 8)

      The crystallographic measurement for 4i CCDC 966112 contains the supplementary crystallographic data for 4i (These data can be obtained free of charge via http://www.ccdc.cam.ac.uk.) was performed at 100(2) K on a Kuma KM4-CCD κ‑geometry four-circle diffractometer with graphite-monochromatizedMoKα radiation. Data were corrected for Lorentz and polarization effects. Data collection, cell refinement, and data reduction and analysis were carried out with the KM4-CCD software, CrysAlis CCD and CrysAlis RED, respectively [84].Empirical (multi-scan) absorption correction was applied to the data with the use of CrysAlis RED. The structure was solved by direct methods with the Shelxs-2013 program [68], and refined on F² by a full-matrix least-squares technique using Shelxl-2013 [68], with anisotropic thermal parameters for the non-H atoms. The H atoms were found in difference Fourier maps, and in the final refinement cycles the C-bonded H atoms were repositioned in their calculated positions  and  refined  using  a  riding   model,  with  C-H = 0.95-1.00 Å, and with U_iso(H) = 1.2U_eq(C) for CH, and 1.5U_eq(C) for CH₃. The N-bonded H atom was refined freely. The figures were made using DIAMOND program [85].

Crystal Ddata for 4i

      C₂₁H₁₉NO₂, M = 317.37, yellow plate, crystal size 0.76 ´ 0.45 ´ 0.07 mm, monoclinic, space group P2₁/n (no. 14), a = 11.919(3), b = 8.061(2), c = 17.437(4) Å, β = 102.89(3)°, V = 1633.1(7) ų, T = 100(2) K, Z = 4, ρ_calc = 1.291 g cm^-3, μ = 0.08 mm^-1 (for MoKα, λ = 0.71073 Å), T_min = 0.943, T_max = 1.000, 7272 reflections measured, 3760 unique (R_int = 0.028), 2608 observed (I > 2σ(I)), θ range 3.1-28.7°, parameters = 223, restraints = 0, R₁ = 0.055, wR₂ = 0.142 (observed refl.), GooF = S = 1.00, largest difference in peak and hole, Δρ_max and Δρ_min = 0.30 and -0.25 e Å^-3.

COMPUTATIONAL DETAILS

      In this work, to gain a further insight into the properties of 4i, we have carried out quantum theoretical calculations for this compound at B3LYP/6-311+G* level (DFT) [86-88] by the Gaussian 03W program package [89] . At first, we optimized structure using Gaussian 03W program (see Fig. 1). The electronic properties such as E_HOMO, E_LUMO, HOMO-LUMO energy gap (Eg), E_HOMO-1, E_LUMO+1, natural charges, molecular properties, dipole moment (μ_D) and point group were detected [90]. The optimized molecular structure, HOMO and LUMO surfaces were visualized using Gauss View 03 program. We also calculated NMR parameters such as chemical shift isotropic (CS^I) and chemical shift anisotropic (CS^A) for title structure [79,91].Also, the electronic structure of 4i compound was studied by using Natural Bond Orbital (NBO) analysis at the same level in order to understand various second-order interactions between the filled orbitals of one subsystem and vacant orbitals of another subsystem, which is a measure of the inter-molecular delocalization or hyper conjugation [71,92].

CONCLUSIONS

      In conclusion, it can be said that a simple, eco-friendly, green     and     efficient      procedure   for  the  synthesis  of naphthalene condensed oxazinone derivatives from 2-naphthol, aldehydes with urea is reported for the first time by our research group using inexpensive, easily recyclable, and efficient perlite-SO₃H nanoparticles as catalysts in economical and safe, solvent-free in both thermal and microwave conditions. The method is very efficient, avoids the use of expensive reagents, and leads to improved product yields. To the best our knowledge, this is the first report on perlite-SO₃H nanoparticles catalyzed synthesis of naphthaoxazinone derivatives and this new procedure opens an important chapter in the efficient recyclability of perlite-SO₃H nanoparticles as an important catalyst. The ambient conditions, high reaction rates, excellent product yields and easy work-up procedures not only make this methodology an alternative platform to the conventional acid/base catalyzed thermal process but also bring it under the umbrella of environmentally greener and safer synthetic procedures. Additional applications of this technique are currently under investigation. In the present study also, the electronic properties of 4i compound have been analyzed using DFT calculations (B3LYP/6-311+G*). The FMO analysis suggests that charge transfer takes place within the 4i molecule and the HOMO is localized mainly on naphthalene and oxazinone rings whereas the LUMO resides on the naphthalene ring. According to the results of NBO analysis, the highest positive and negative charge values belong to carbon atom in carbonyl group (C₁₂: 0.923e), and nitrogen atom (N₁₃: -0.650e), respectvely. NBO nalaysis also show that the polarization coefficients of the electronegative atoms in calculated bonding orbital are greater than electropositive atoms.

ACKNOWLEDGEMENTS

      This work was supported by the “Iran National Science Foundation: INSF”.