A New Approach to the Ring-Opening of Epoxides under Mild and Green Conditions

Abstract In this research work, we have designed and introduced [Zr-UiO-66-CO2H]Br as a versatile heterogeneous acid catalyst for the ring-opening of epoxides through SN1 and/or SN2 type mechanisms. In addition, the appropriate method for designing an active and efficient Bronsted acid site in metal-organic frameworks is discussed. [Zr-UiO-66-CO2H]Br was applied for the preparation of α-aryloxy alcohols by the condensation reaction of various epoxides with phenol or thiophenols under mild and green conditions. Graphical abstract


Introduction
Nowadays, scientists and researchers are trying to find new mechanisms to help easily understand the concept of organic chemistry.2][3][4][5][6][7][8] With acidic conditions, ring-opening proceeds via the S N 1 mechanism and the more substituted carbon is the site of the attack.Conversely, when an asymmetric epoxide reacts under basic conditions, ringopening occurs by an S N 2 mechanism, and the less substituted carbon is the site of nucleophilic attack 9,10 whereas epoxides with heteroatom oxygen moiety of S N 2 mechanism type are performed under acidic conditions.Besides, various species of nucleophiles have been applied for the ring-opening of epoxide such as phenol, thiophenol, phthalimide, azide, cyanide, thiocyanate, amine, halides, alcohol, etc. [11][12][13][14][15][16][17][18][19] The structure of epoxide was known in the synthesis of drug compounds and pharmacologic structure [20][21][22] (Figure 1).Also, a-aryloxy alcohols such as guaifenesin, mephenesin, chlorphenesin, propranolol, and naftopidil have been considered for the synthesis of natural products and biological materials. 235][26][27] Therefore, the introduction of a new and logical mechanism for the ring-opening of epoxide is an urgent need.][36][37] Lillerud et al. in 2008, introduced the first example of Zr-UiO-66-PDC based on Zr nuclei. 38r metal-based MOFs was used as a catalyst in the preparation of dicyanomethylene pyridines and dihydrobenzo[g]pyrimido [4,5-b]quinoline. 39,40[46][47][48]

Experimental
Preparation of [Zr-UiO-66-CO 2 H]Br as a Bronsted-acid catalyst At first, Zr-UiO-66-PDC and ethyl 2-bromoacetate were synthesized according to the previous work. 35Then, in a 50 mL round bottom flask, a mixture of Zr-UiO-66-PDC (0.5 g) and ethyl 2bromoacetate (6 mmol, 1 g) was stirred under refluxing EtOH.After the completion reaction, the white participate were separated by centrifuge (2 Â 4000 rpm).Then, HBr (0.5 mL, 48%) and H 2 O (0.5 mL) were added to the white participate and stirred under reflux conditions for 60 min.After this time, the solvent was evaporated and the yellow participate was triturated with diethyl ether (2 Â 5 mL) and dried under powerful vacuum at 70 C (Scheme 2).General procedure for the preparation of a-aryloxy alcohols using [Zr-UiO-66-CO 2 H]Br In a 15-mL round-bottomed flask, a mixture of Ar-X (X: OH, SH) (1 mmol) and epoxide derivatives (1 mmol) in the presence of [Zr-UiO-66-CO 2 H]Br (5 mg) was stirred at 90 C under solvent-free condition.After the completion of the reactions that were monitored by the TLC technique, the described catalyst was separated from the reaction mixture by centrifugation (1000 rpm) after adding 10 mL of EtOH as a solvent.Finally, after the evaporation of the solvent at room temperature, the pure product was obtained by thin layer chromatography (Scheme 1).

Results and discussions
In continuation of our investigation on the epoxides, and functionalized MOFs as catalysts in organic reactions, herein we wish to develop of catalytic systems, consisting of MOF and ethyl 2bromoacetate as a novel and efficient catalyst.With this aim, [Zr-UiO-66-CO 2 H]Br was synthesized, characterized and applied in the ring opening of target epoxides (Scheme 2).To determine the structure and morphology of the presented catalyst, it was characterized by FT-IR, XRD, energy dispersive X-ray (EDS), SEM-elemental mapping, SEM, and N 2 adsorption-desorption isotherms techniques.
The FT-IR spectrum of Zr-UiO-66-PDC, Zr-UiO-66-PDC-CH 2 CO 2 Et, and [Zr-UiO-66-CO 2 H]Br as catalysts was compared in Figure 2. The broad peak at 2600-3400 cm À1 in [Zr-UiO-66-CO 2 H]Br indicates the OH of the CO 2 H functional group.The peak in the 1655 cm À1 indicates the CO of the carbonyl group in the catalyst.The adsorption bands at 3087 cm À1 are related to the C-H bond stretching.Also, the absorption band at 668 cm À1 was linked to the stretching vibrational of the Zr-O group.The changes of Zr-UiO-66-PDC, Zr-UiO-66-PDC-CH 2 CO 2 Et, and hydrolysis were the indicator of synthesized catalyst.
To study the morphology of [Zr-UiO-66-CO 2 H]Br, XRD, EDX spectroscopy, and SEM techniques were used.For this purpose, the XRD technique in the range of 5-50 was used to study morphology as well as the particle size and shape of [Zr-UiO-66-CO 2 H]Br (Figure 3).The XRD pattern of the catalyst shows that it has a crystalline nature.Also, the structure and pattern of Zr-UiO-66-PDC are stable after the functionalized. 49n another investigation, the scaffold [Zr-UiO-66-CO 2 H]Br is composed of C, N, O, Zr, and Br according to the energy-dispersive X-ray spectroscopy (EDX) technique (Figure 4).Also, the distribution of elements including C (red), N (blue), O (green), Zr (yellow), and Br (orange) on the surface of the catalyst was investigated and verified by the SEM-elemental technique (Figure 4).Therefore, energy dispersive X-ray spectroscopy (EDX) and SEM-elemental mapping spectroscopy of all the expected elements confirm the uniform distribution of the elements on the surface.
In another study, the scanning electron microscope (SEM) technique was used to determine the morphology and particle size of the [Zr-UiO-66-CO 2 H]Br.As can be seen in Figure 5, the  obtained images are in good agreement and not completely accumulated with Fcu.Therefore, Fcu topological is a network with 12-connected Zr clusters and according to the text source. 49he textural properties of [Zr-UiO-66-CO 2 H]Br were studied by N 2 adsorption-desorption isotherms (Figure 6).The calculated surface areas based on the BET equation and total pore volumes are 1380 m 2 g À1 and 0.651 cm 3 g À1 , respectively.The pore size distribution of [Zr-UiO-66-CO 2 H]Br based on the BJH method is shown in Figure 6.This plot clearly shows the pore diameter of [Zr-UiO-66-CO 2 H]Br is 1.64 nm.After successful synthesis and characterization of the [Zr-UiO-66-CO 2 H]Br, it was used to prepare a-aryloxy alcohols.The above mentioned catalyst was achieved for reaction between [1,1 0 -biphenyl]-2-ol (1 mmol, 0.17 g) and 2-((allyloxy)methyl)oxirane (1 mmol, 0.114 g) as a model reaction.The model reaction was tested using different amounts of catalysts, solvents, and temperatures.The results of the obtained products are summarized in Table 1.The best choice for the ring-opening of epoxide was achieved in the presence of [Zr-UiO-66-CO 2 H]Br (5 mg) at 90 C under the solvent-free condition (Entry 2, Table 1).The model reaction was also tested using different organic solvents such as n-Hexane, EtOAc, EtOH, H 2 O, MeOH, CH 3 CN, Acetone, CHCl 3 , CH 2 Cl 2, and Toluene (5 mL) which is not improve in the results of reactions (Entry 7-16, Table 1).The results show that [Zr-UiO-66-CO 2 H]Br is suitable for the preparation of a-aryloxy alcohol derivatives.
Following the optimal synthesis of a-aryloxy alcohol derivatives by [Zr-UiO-66-CO 2 H]Br, we tested [1,1 0 -biphenyl]-2-ol (1 mmol, 0.145 g) and 2-((allyloxy)methyl)oxirane (1 mmol, 0.120 g) as a model reaction using inorganic and organic catalysts such as basic, sulfonic acid, phosphonic acid, nano-magnetic and ionic liquids.The results are shown in Table 2.According to the obtained results in Table 2, it can be concluded that the [Zr-UiO-66-CO 2 H]Br had the best performance compared to other used catalysts.After the optimization of the reaction conditions, the efficiency and applicability of [Zr-UiO-66-CO 2 H]Br were studied for the preparation of a-aryloxy alcohol derivatives.The results are summarized in Table 3.As Table 3 indicates, starting materials such as phenol or thiophenol derivatives and various epoxides afforded the desired products (A 1 -A 15 ) with excellent yields (92-98%) and short reaction times (4-10 min.).
To propose a logical mechanism, the obtained product by the reaction of phenol and 2-(butoxymethyl)oxirane, was oxidized using PCC in CH 2 Cl 2 .As can be seen in Scheme 3, aldehyde did  not obtain from oxidation of the product of the epoxide ring-opening reaction.The oxidized obtained product is a ketone, which was characterized by FT-IR, 1 H-NMR and 13 C-NMR (S.I).
Recently, we have reviewed the role of the anomeric effect in organic reactions comprehensively. 52he plausible mechanism via supporting homo anomeric effect is not applicable (Scheme 4).Firstly, epoxide was activated by acidic protons of [Zr-UiO-66-CO 2 H]Br.For a-aryloxy epoxides, two routes are proposed.In paths A and B, via a homo anomeric participation of oxygen lone pairs of alkoxy pending group at the activated epoxide three and/or four-member rings as intermediates are produced respectively.Then, nucleophilic attack of Ar-X (X: phenol or thiophenol) with the symmetrical four-member ring intermediate (path B) to give solely one product which according to the Baldwin rules for "endo-tet breaking bond" is inside of the forming cycle and not allowed. 53Therefore, for Scheme 5. Proposed mechanism a-aryloxy alcohol derivatives via homo anomeric participation and/or S N 2 type reaction.Scheme 4. Proposed mechanism a-aryloxy alcohol derivatives via homo anomeric participation and/or S N 2 type reaction is not applicable. 53-aryloxy epoxides, classic S N 2 mechanism is proposed (Scheme 5, path A).For other epoxides, without a-alkoxy pending groups ring-opening proceeded via an S N 1 type reaction (Scheme 5, path C).To explore the logical mechanism, the 1-butoxy-3-phenoxypropan-2-ol (A 15 ) was oxidized in the presence of PCC in CH 2 Cl 2 as a solvent (Scheme 3).
To evaluate the recyclability of catalyst, we tested [1,1 0 -biphenyl]-2-ol (1 mmol, 0.145 g) and 2-((allyloxy)methyl)oxirane (1 mmol, 0.120 g) as a model reaction under the optimal reaction conditions.The results of Figure 7 show that the [Zr-UiO-66-CO 2 H]Br can be reused up to 4 times without a noticeable change in its catalytic activity.This recycled catalyst was also identified by FT-IR spectra after its application which was the same as the fresh [Zr-UiO-66-CO 2 H]Br (Figure 8).

Conclusions
In summary, a novel MOF that has both Lewis and Bronsted-acidic properties is introduced as a regioselective catalyst for the ring-opening of epoxides with phenol and/or thiophenol via S N 1 and/or S N 2 type reaction.According to the obtained evidence, a logical mechanism was proposed for the observed regioselectivity in the ring opening of 2-(phenoxymethyl)oxirane for the first time.The promising points of the presented methodology are efficiency, generality, high yield, relatively short reaction time, low cost, cleaner reaction profile, ease of work-up, and finally compliance with the green chemistry protocols.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Funding
We thank Bu-Ali Sina University and Iran National Science Foundation (INSF) [grant number: 98001912] for financial support to our research group.

Figure 1 .
Figure 1.Structure of epoxide as natural products and biological materials.

Scheme 1 .
Scheme 1. Preparation of a-aryloxy alcohols in the presence of [Zr-UiO-66-CO 2 H]Br as a mesoporous catalyst.

Scheme 3 .
Scheme 3. Preparation of a-aryloxy alcohols in the presence of [Zr-UiO-66-CO 2 H]Br as a mesoporous catalyst.

Table 1 .
The effect of different amounts of catalysts, temperature, and solvents in the synthesis of a-aryloxy alcohol derivatives.

Table 2 .
Evaluation of various catalysts for the synthesis of a-aryloxy alcohol derivatives.

Table 3 .
Preparation of a-aryloxy alcohol derivatives in the presence of [Zr-UiO-66-CO 2 H]Br.