Iron (III) Phosphate as a Green and Reusable Catalyst Promoted Chemo Selective Acetylation of Alcohols and Phenols with Acetic Anhydride Under Solvent Free Conditions at Room Temperature

친환경 촉매 Iron (III) phosphate: 실온/무용매 반응조건에서 알코올과 페놀의 선택적인 아실화 반응

Abstract

Iron (III) phosphate was employed as an efficient catalyst for the chemo selective acetylation of alcohols and phenols under solvent free condition at room temperature and with high yields. Iron (III) phosphate is also a potential green catalyst due to solid intrinsically, reusable and with high catalytic activity.

알코올과 페놀 계 화합물을 아실화시키는 반응에서, iron (III) phosphate 촉매를 사용했을 때에, 좋은 수율로 아실화 화합물을 얻었다. Iron (III) phosphate 촉매는 또한 친환경 반응에 재사용할 수 있는 친환경 촉매이다.

INTRODUCTION

Iron (III) phosphate, a cheap and safe catalyst, is prepared1 and purchased as commercially. Iron (III) phosphate2 is being petitioned for use as a pesticide (molluscicide) to prevent extensive damage to and/or destruction of vegetables, citrus and non-citrus fruit, berries, field crops, ornamentals, greenhouse and nursery plants, lawns, and gardens for seed production. It is known that iron (III) phosphate lacks toxicity for fish, birds, and non-target insects such as rove beetles, ground beetles and earthworms. It is a stable compound that does not persist or form undesirable products in the environment under normal conditions of use and storage. Using iron (III) phosphate as a mollascicide is very compatible with sustainable agriculture. Not only does ferric phosphate safe-environmental, but also allows organic growers to effectively control a devastating garden pest. Chemically, iron (III) phosphate is very stable and will not dissociate unless in the presence of concentrated acid which is not present in natural surroundings.

So far, iron (III) phosphate has limitedly been employed in transformation of organic compounds such as the selective oxidation of CH4 to CH3OH,3 benzene to phenol,4 one-pot synthesis of dihydropyrimidinones and thiones5 and one-pot three component synthesis of 2,4,5-triarylated imidazoles.6

On the other hand, acetylation of hydroxyl groups is a frequently used transformation method in organic synthesis. Among the various protecting groups used for the hydroxyl function, acetyl is the most convenient group in view of its easy introduction, being stable to the acidic reaction conditions, and also easily removable by mild alkaline hydrolysis.6 Commonly used reagent for this reaction uses acetic anhydride in the presence of an acid or base catalyst.7 Various metal salts such as CoCl2,8 TiCl4-AgClO4,9 Me3SiCl,10 LiClO4,11 Mg(ClO4)2,12 and some metaltriflates such as Se(OTf)3,13 MeSiOTf ,14 In(OTf)3,15 Cu(OTf)2,16 and Bi(OTf)3,17 have been investigated to meet the demands for more efficient and selective methods. In spite of these waves of interest, due to the importance of acetylation, it is necessary to develop inexpensive, ecofriendly and reusable catalyst to promote acetylation process. Therefore, in continuing previously our research to introduce the efficient and green method for the acetylation of hydroxyl groups using eco-friendly catalyst,18 herein iron (III) phosphate is reported as a green, reusable, recyclable, safe-environmentally, inexpensive and commercially catalyst for the acetylation of alcohols and phenols under solventfree conditions at room temperature (Scheme 1).

Scheme 1.Aliphatic and benzylic alcohols and phenols were acetylated by acetic anhydride using FePO4.

 

RESULTS AND DISCUSSION

In order to establish the optimized reaction condition, we have performed study using 1.0 mmol benzyl alcohol as a model substrate in the presence of 2.5 mmol acetic acid without catalyst. The reaction did not proceed for 48 h. Thus 5 mol% FePO4 was added to the reaction mixture. Conversion was 15% after 48 h. Increasing 10 mol% of the catalyst and 10 mmol acetic acid didn't affect on conversion. Ongoing, 2.5 mmol acetic anhydride was subjected as acetylating agent. In this case, the reaction was completed for 10 h and so was chosen as a model reaction. To aim giving generality to reaction model, acetylation of a variety of alcohols and phenols with acetic anhydride was carried out in the presence of FePO4 at room temperature. The results have been listed in Table 1. As can be seen, the yields of the acetylation hydroxyl group compounds with acetic anhydride were excellent.

Accordingly, various primary and secondary benzyl alcohols having electron donating and electron withdrawing substituent undergo acetylation in high yield in most cases (entries 10-15). This indicates that electronic effects of substituent groups don't have influence on the acetylation reaction. In addition to benzylic alcohols, this catalyst is effective for the variety of aliphatic alcohols (entries 1-9). Primary alcohols acetylated within less time than secondary and tertiary alcohols. The longer reaction time could be due to the steric effect exerted by bulky groups. It is very interesting to note that tertiary and secondary alcohols such as tbutanol can also be acetylated with satisfactory yield and there was no elimination product in the reaction mixture.

Also, isoamyl acetate is a kind of flavor reagent with fruit taste. It is traditionally prepared with H2SO4 as catalyst.7 The use of H2SO4 often causes the problems such as corrosion for equipments and pollution for environment. Until now, the tried replaces include FeCl3, CuSO4, ferric tri-dodecane sulfonate, FeCl3/MnO2, KH2PO4, sulfonated polystyrene, TiSiW12O40/TiO2 and so on,8-14 but some shortcomings limit them being widely applied in industry such as higher wastage for materials, lower yield of product or higher cost in catalyst preparation. Based on these reasons, isoamyl alcohol was chosen as a starting material and isoamyl acetate was resulted in 95% yield (entry 5).

This method tolerates other functionalities on the substrate such as double and triple bonds. In fact, allyl, cinnamyl and propargyl alcohols were subjected as unsaturated alcohols. We would have expected to carry out hydration reaction on double and triple bond in acidic media beside acetylation reaction, so far hydrated products didn't observed at all (entries 16-18). Heterocyclic furfuryl alcohol gives corresponding acetate with excellent yield (entries 26). This may recommend that adjacent heterocyclic ring have no influence at all on the reaction.

Interestingly, phenols too underwent acetylation smoothly under the same reaction condition. Phenols with activating and deactivating groups altogether carried out acetylation rapidly with very high yield (entries 19-25). Strongly electron-withdrawing group such as nitro substituent produces 95% yield (entries 22).

In order to investigate further chemo selectivity of this protocol, 3- and 4-hydroxy benzaldehydes were utilized in acetylation reaction (entries 24, 25). It was observed that aldehydic carbonyl group didn’t change at all. In these cases, IR spectra showed wave number; νmax=1699.16, 1703.84 cm-1 for aldehydic carbonyl group of 3- and 4-formylphenyl acetate while 1666.03, and 1667.09 cm-1 were for aldehydic carbonyl group of 3- and 4-hydroxy benzaldehyde. It is depicted that intermolecular hydrogen bonding in substrate has been disappeared after acetylation of hydroxyl group and absorption band of the aldehydic carbonyl group has shifted to higher frequency.

Therefore, this method introduces chemo selective acetylation of hydroxyl group compounds using FePO4 as a green, economically and reusable catalyst which can efficiently promote the acetylation with the advantages of wide scope of substrates such as aliphatic, benzylic, allylic, propargylic alcohols and phenols under solvent free conditions, excellent recyclability, insensitivity to air and water, and extremely convenient from a practical and facile separation work-up point of view.

Table 1.aYields refer to GC analysis.

The plausible duty of the FePO4 may be due to the activation of carbonyl group of acetic anhydride by coordination, triggering the acetylation process with concomitant regeneration of FePO4, followed by the loss of acetic acid (Scheme 2). This mechanism is in adapt to the catalytic nature of FePO4 in this reaction.

Scheme 2.Proposed mechanism for the acetylation of alcohols and phenols using FePO4.

 

EXPERIMENTAL

IR spectra were recorded on Perkin Eilmer FT-IR spectrometer did scanning between 4000-400 cm-1. 1H NMR spectra were obtained on Bucker DRX-400MHZ NMR instrument. All starting materials purchased from Merck Company and used of them without further purification.

Acetylation of benzyl alcohol with acetic anhydride by FePO4. Typical procedure

To mixture of 0.108 g benzyl alcohol (1.0 mmol), 0.50 g acetic anhydride (2.5mmol) and 0.0075 g FePO4 (0.05 mmol) was added. The mixture was stirred at ambient temperature for 10 h. The progress of reaction was monitored by TLC (eluent, n-hexane: ethyl acetate, 4:1). After completion of the reaction, 15 ml CH2Cl2 was added and the catalyst was filtrated off. Liquor moderate was neutralized by 15 ml sodium bicarbonate (10%) and extracted with CH2Cl2. The organic phase was dried by Na2SO4 and evaporated under reduce pressure. Then, benzyl acetate was resulted in 92% yield (entry 10, Table 1). IR (KBr) 3034(m), 2952(w), 1739(s), 1497(m), 1454(m), 1382(m), 1364(m), 1233(s), 1027(s), 750(s) cm-1. 1H NMR (400 MHZ, CDCl3): δ = 2.00 (s, 3H), 5.01 (s, 2H), 7.32-7.37 (m, 5H).

Recycling of the catalyst

At the end of the reaction, the catalyst was removed, washed with dichloromethane and ethyl acetate, dried at 80 for 1 h, and reused in another reaction. The recycled catalyst was subjected to three reactions without appreciable loss in its activity.

 

CONCLUSION

In conclusion we have developed a catalytic and solvent less system for acetylation of alcohols and phenols using available, inexpensive and extremely safe reagent such as iron(III) phosphate for the mild and high yielding acetylation of alcohols and phenols. The salient features of these reactions are, use of 2.5-1.0 equivalent of acetic anhydride to substrate and catalytic amounts of iron(III) phosphate which are concomitant with solvent less and catalytic nature of the reaction. Neither use of solvent nor elevation of reaction temperature makes operations more convenient. The catalyst can be recycled at least three times without significant lose of catalytic activity. We believe iron(III) phosphate is one of the greenest catalyst which has ever been used for acetylation of alcohols and phenols and this heterogeneous catalytic and solvent less acetylation will find many applications in organic synthesis and industry.