Advancements in Ether Synthesis: From Organic Solvents to Water, Exercises of Effective CV Writing

Download Advancements in Ether Synthesis: From Organic Solvents to Water and more Exercises Effective CV Writing in PDF only on Docsity! RSC Advances REVIEW Pu bl is he d on 2 1 Ju ly 2 01 6. D ow nl oa de d on 6 /7 /2 02 2 2: 11 :3 5 PM . View Article Online View Journal | View IssueA review on theaHomogeneous Catalysis Laboratory, Depa Burdwan, Golapbag, Burdwan, 713104, W com; Fax: +91-342-2530452; Tel: +91-94763 bDepartment of Chemistry, TDB College R India S K p U a i N i i d Cite this: RSC Adv., 2016, 6, 69605 Received 18th May 2016 Accepted 1st July 2016 DOI: 10.1039/c6ra12914e www.rsc.org/advances This journal is © The Royal Society of Cadvancement of ether synthesis from organic solvent to water Sangita Mandal,a Swagata Mandal,a Sumanta K. Ghosh,a Pintu Sar,a Aniruddha Ghosh,a Rumpa Sahab and Bidyut Saha*a Ethers have been synthesized by the different protocols such as Williamson ether synthesis, the Mitsunobu reaction, bimolecular dehydration, the Ullmann method, a transition metal-free coupling reaction between aliphatic alcohols and unsymmetric diaryliodonium salts, room temperature ionic liquid promoted synthesis, Cu(II) catalyzed synthesis, microwave assisted synthesis, and synthesis under solvent free micellar conditions. A good number of homogeneous Bronsted acids and Lewis acid based transition metals have also been reported as catalysts in the etherification of alcohols. The above mentioned pathway has exhibited some drawbacks including their deactivation through decomposition caused by the water formed during the course of the reaction. In many cases these methods also reveal the accumulation of a significant amount of acid at the end of the reaction due to the hydrolysis of Lewis acid catalysts such as metal oxides, which upon neutralization give a considerable amount of salts. A literature survey shows some reports on the use of phase transfer and polymer and clay supported catalysts for the synthesis of symmetrical and unsymmetrical ethers. To a synthetic chemist, an aqueous micellar solution is a good choice as a reaction medium for synthesizing several organic compounds. Micellar conditions are a new direction of study for ether synthesis as they are simple, efficient, economical and environmentally friendly.1. Introduction Ethers are a class of organic compounds characterized by an oxygen atom bonded to two alkyl or aryl groups (e.g. R–O–R0). Generally ethers may be categorized as aryl ether, allyl ether,rtment of Chemistry, The University of B, India. E-mail: b_saha31@rediffmail. 41691; +91-342-2533913 aniganj, Raniganj, West Bengal 713383, angita Mandal was born in hatra, Bankura in 1991. She assed her M.Sc degree from The niversity of Burdwan in 2013 nd got a UGC-RGNF fellowship n 2015. She also cleared the ET exam in Chemical Sciences n 2012. She is working in a lab n the “Homogeneous Catalysis” ivision. hemistry 2016phenolic ether, phenacyl ether, and polyether. They have different structures depending upon the groups that are con- nected to the ether oxygen. Crown ethers are special type of cyclic ether. These types of ethers are low molecular polyethers.1 The compounds containing an ether oxygen with a phenyl group on one end and aryl, alkyl, benzyl, allyl, vinyl, etc. on the other end are called phenolic ethers or aromatic ethers. These ethers have a wide range of applications. The uses of phenolic ethers depend upon the nature of the group attached to the other end of the phenolic oxygen. For example, diphenyl ether and its halo derivatives have agrochemical applications such asSwagata Mandal was born in Bankura in 1991. She passed her M.Sc degree from The University of Burdwan in 2013 and got a UGC-RGNF fellowship in 2015. She is working in a lab in the “Homogeneous Catalysis” division. RSC Adv., 2016, 6, 69605–69614 | 69605 RSC Advances Review Pu bl is he d on 2 1 Ju ly 2 01 6. D ow nl oa de d on 6 /7 /2 02 2 2: 11 :3 5 PM . View Article Onlineherbicides and fungicides.2,3 Similarly phenolic ethers nd applications in chemical engineering,4 pharmaceuticals, and food.5 The preparation of ethers is an important synthetic reaction for which a wide variety of procedures have been developed during the last hundred years. The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical as well as symmetrical ethers.6–10 Williamson ether synthesis is an organic reaction, forming ether from an organic halide and an alcohol. The discovery, development and identication of biologically active compounds has gained a lot of importance in recent years. EvenSumanta K. Ghosh was born in Burdwan in 1974. He passed his M.Sc degree from Visva-Bharati in 2010 and got a NET-CSIR fellowship in 2001. He was awarded a Ph.D. degree from the University of Burdwan in 2013. He is now working as a Post Doc. Pintu Sar was born in Hooghly, in 1989. He passed his M.Sc degree from Visva-Bharati in 2011 and got a NET-UGC fellowship in 2012. He is presently working in the lab. He is working in the “Homogeneous Catalysis” divi- sion. Aniruddha Ghosh was born in Raniganj, in 1988. He passed his M.Sc degree from The University of Burdwan in 2010 and got a NET-UGC fellowship in 2010. He is working as a SRF in the lab. He is working in the “Homoge- neous Catalysis” division. 69606 | RSC Adv., 2016, 6, 69605–69614though there are a considerable number of adverse effects, chemists have always tried to design a drug possessing maximum therapeutic application and minimum toxicity.11 Organic ethers are one of the most important classes of chem- icals which have signicant applications as herbicides, disin- fectants, pharmaceuticals, plasticizers, solvents, drug intermediates and as solvents in organic synthesis. They are also used as important precursors for polymers and fragrances.12,13 A good number of homogeneous Bronsted acids and Lewis acid catalysts are commonly used in the preparation of unsymmetrical substituted ethers.14 There are few available procedures for the conversion of phenols or alcohols into ethers: Mitsunobu-type rections,15 reductive condensation of ketones and esters,16 hydroalkonylation of alkynes,17 and oxidative C–H alkoxylation of arenes.18 The methods above can be considered as a general method for the preparation of ethers. Another general root for the synthesis of aryl ethers is typi- cally achieved via a nucleophilic aromatic substitution (NAS) process or transition metal catalyzed Ullmann type reaction.19,20 Remarkable drawbacks encountered in many conventional methods necessitated the search for an appropriate reaction system to enhance reaction conversion and lessen environ- mental pollution. Combinatorial synthesis has brought about a lot of changes in the recent trends of ether synthesis in aqueous micellar media. Many chemical reactions with organicRumpa Saha was born in Burd- wan, 1987. She passed her M.Sc. degree from the University of Burdwan, 2009 and got a CSIR NET fellowship in 2009. She was awarded a Ph.D. degree from the University of Burdwan in 2015. Dr Rumpa Saha is presently working as an Assistant Professor in the Department of Chemistry, TDB College, Raniganj, Burdwan, India. Bidyut Saha was born in Birb- hum, WB, India in 1975. He ob- tained his Ph.D degree from Visva Bharati University, India in 2007. He was a visiting scientist for the year 2009–2010 in the Department of Chemistry, UBC, Vancouver, Canada. Dr Saha is presently working as an Associate Professor in the Department of Chemistry, The University of Burdwan, India. His area of interests is bioremediation of toxic metals, micellar catalysis and chemical kinetics. He has already published 90 papers in international journals. This journal is © The Royal Society of Chemistry 2016 Scheme 6 Copper catalyzed ether synthesis. Scheme 8 Etherification in aqueous micellar media. Review RSC Advances Pu bl is he d on 2 1 Ju ly 2 01 6. D ow nl oa de d on 6 /7 /2 02 2 2: 11 :3 5 PM . View Article Onlineimportance. Diaryloxymethanes are synthetically important compounds used as fungicides,60 parasiticides,61 in the treatment of liver uke infection in mammals,62 and in the preparation of condensation polymers.63,64 Diaryloxymethanes were used in the preparation of various catalysts such as cavitations65 and crown ethers66 and in the preparation of diols such as 2,2-o-dihydroxy-6,6- o-dimethoxy-1,10-biphenyl. Diaryloxymethanes were prepared through methylation of the appropriate phenol with diiodo- methane, bromochloromethane, and dichloromethane using different inorganic bases, such as Cs2CO3, KOH, and NaH.63–67 The reactions of alkali metal phenolates with methylating agents were generally carried out in several polar solvents such as DMSO and DMF. An ionic liquid was used for regioselective O-alkylation of naphthols, although C-alkylation also occurs with this method which requires a prolonged time period and harsh reaction conditions.65 Recently room-temperature ionic liquids as “green solvents” in organic synthesis have gained considerable impor- tance because of their solvating ability, negligible vapor pressure, and easy recyclability and reusability.68 These unique properties of ionic liquids make them a strong alternative to conventional solvents. Herein we used the ionic liquid 1-methyl-3-butylimidazolium bromide [bmim]Br for the reaction of phenoxides with alkyldihalides. The ionic liquid [bmim]Br was prepared as per the literature method.69–72 Substituted phenoxide ions react with dichloromethane in the presence of the ionic liquid [bmim]Br at 60 C without any added catalyst (Scheme 5). The synthesized diaryloxymethanes were fully characterized by IR, 1H-NMR, and 13C-NMR, and physical constants were assigned with their reported values in the literature. The ionic liquid was recovered (almost 100%) and reused at least three times (Table 1) for the reaction of p- methoxyphenoxide with dichloromethane without any consid- erable loss in yield.67 5. Catalysis in ether synthesis 5.1. Copper(II)-catalyzed ether synthesis from aliphatic alcohols and potassium organotriuoroborate salts The formation of carbon–heteroatom bonds using metal catal- ysis is emerging as one of the most signicant classes of cross-Scheme 7 Microwave-assisted synthesis without catalyst. This journal is © The Royal Society of Chemistry 2016coupling reactions. In the area of C–O ether bond formation, there has been a resurgence of interest in Cu mediated reac- tions beyond that of the classical Ullmann ether synthesis.73,74 A protocol for the Cu(II) catalyzed etherication of aliphatic alcohols undermild and essentially neutral conditions has been described. Air and moisture stable potassium alkenyl and aryl triuoroborate salts undergo cross-coupling with a variety of aliphatic primary and secondary alcohols and phenols, and are tolerant of a range of functional groups. The optimized condi- tions utilize catalytic copper(II)acetate with 4-dimethylamino pyridine as a ligand in the presence of 4 Å molecular sieves under an atmosphere of oxygen (Scheme 6).755.2. Microwave-assisted synthesis of diaryl ethers without a catalyst Diaryl ether motifs are known to be present in a variety of natural products and biologically interesting compounds.76 We have also reported that microwave-assisted coupling of phenols, including those having a strong electron withdrawing group, with aryl halides in the presence of potassium carbonate provide diverse diaryl ethers within a few minutes.77 A range of phenols were employed to couple with the electron decient aryl halides (Scheme 7) such as mono-halogen substituted benzonitrile and 1-chloro-4-nitrobenzene in the presence of 2 equiv. of potassium carbonate under microwave irradiation in a DMSO medium and the results were obtained.785.3. Ether synthesis under solvent-free micellar condition A good number of homogeneous Bronsted acids and Lewis acid based transition metals have also been reported as catalysts in the etherication of alcohols. However, these systems exhibited some drawbacks including their deactivation through decom- position by the water formed during the course of reaction. In many cases these methods also reveal the accumulation of a signicant amount of acid at the end of the reaction due to the hydrolysis of Lewis acid catalysts such as metal oxides, which upon neutralization give a considerable amount of salts. The acid waste, residual catalyst and salt material may cause severalRSC Adv., 2016, 6, 69605–69614 | 69609 Scheme 9 Localization of reactant molecules in micellar media. RSC Advances Review Pu bl is he d on 2 1 Ju ly 2 01 6. D ow nl oa de d on 6 /7 /2 02 2 2: 11 :3 5 PM . View Article Onlineenvironmental problems when they are disposed off, and some of them may be toxic. Difficulties such as catalyst recovery for reuse and neutralization of the reaction mixture also make the process tedious. A literature survey shows some reports on the use of phase transfer, and polymer and clay supported catalysts for the synthesis of symmetrical and unsymmetrical ethers.79–85 Another general root for the synthesis of organic ethers is the Mitsunobu reaction in which PPh3 or polymer bound PPh3 is used as the catalyst.15 Triphenylphosphene is highly sensi- tive86,87 to water and toxic in nature and the reaction83 demands inert and dry conditions.88,89 A literature survey indicated that surfactants have been used to promote a variety of synthetic organic reactions. It is believed that surfactants form micelles in protic solvents such as water which act as micro reactors90,91 to enhance the reaction rates and afford very good to excellent yields of end products.92–94 One of the main areas for achieving this target is the exploration of alternative reaction conditions and reaction media to accom- plish the desired chemical transformations with minimized byproducts or waste as well as eliminating the use of conven- tional organic solvents, wherever possible. Consequently, several newer strategies have appeared such as solvent free reactions (grinding), multi-component reactions under solvent free conditions could enhance the efficiency from an economic as well as an ecological point of view and so the solid state organic reactions are gaining signicance both from mecha- nistic and synthetic points of view.95,96 Synthesis of naphthol ethers under Williamson conditions requires several hours ($20 h) at relatively high temperature. Although there are some reports to modify the drastic conditions of these reactions, many of them exhibited long reaction times and accumulation of unwanted byproducts, which ultimately involved tedious work-up procedures. Encouraged by this aspect, we conducted an O-alkylation of aromatic and heteroaromatic alcohol97 reac- tion in a micellar medium under acid-free conditions.11 The literature also indicated11 that etherication of phenols and hydroxy pyridine can be performed using two methods; one is acidic conditions and the other is replacing H2SO4 with a variety of micelle forming surfactants (acid-free conditions) such as sodium dodecylsulphate (SDS), cetyl- trimethylammonium bromide (CTAB), and Triton X-100 (TX-69610 | RSC Adv., 2016, 6, 69605–69614100). When b-naphthol reacts with methanol in acidic condi- tions, the time required is 20 hours, yield 91%, but in acid free conditions when CTAB is used the time required is only 1.1 hours, yield 96%, in the case of SDS the time required is 2.0 hours, yield 86% and for TX-100 the time required is 3.0 hours, yield 91%. The results indicated that the catalytic activity of different micelles in etherication is in the order: CTAB > SDS > TX-100 (Scheme 8). The catalytic effect of the micellar solution of CTAB may be attributed to the hydrophobic nature of organic substrates (Scheme 9).6. Comparison of experimental details for etherification of b-naphthols 6.1. Experimental procedure for etherication of b- naphthols under conventional conditions Substituted b-naphthol (1.44 g, 10 mmol) was added to a stirred solution of methanol (0.64 g, 20 mmol) and 0.1 M micellar solution (10 mL) and then heated up to reux. The progress of the reaction was monitored by TLC. Aer the completion of the reaction, the reaction mixture was diluted with dichloro- methane (10 mL), and separated from the aqueous layer. The organic layer was then washed with water (3 5 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude product was puried by column chromatography (silica gel, 100–200 mesh) using EtOAc–hexane (1 : 9) as an eluent to obtain the desired product.116.2. Experimental procedure for etherication of b- naphthols by ultrasonically assisted etherication (USAS) Substituted b-naphthol (1.44 g, 10 mmol) was added to a solu- tion of methanol (0.64 g, 20 mmol) and 0.1 M micellar solution (10 mL) at room temperature, which was then sonicated at 40 C using an ultrasonic bath. The ultrasonic bath had a frequency of 33 kHz and an electric power rating of 100 W. The reaction was carried out in a round bottom ask of 50 mL capacity equipped with a mechanical agitator and the ask was suspended at the centre of the ultrasonic bath. The nal products were isolated by absorbing the reaction mixture into silica gel and purifying it by column chromatography using an ethyl acetate/hexane gradient.116.3. Experimental procedure for etherication of b- naphthols by microwave irradiated etherication (MWAR) Substituted b-naphthol (1.44 g, 10 mmol) was added to a solu- tion of methanol (0.64 g, 20 mmol) and 0.1 M micellar solution (10 mL) and these mixtures were heated using a controlled microwave synthesizer (Biotage Initiator + SP Wave model, 0– 200 W at 2.45 GHz, capped at 60 W during steady state) for a few minutes (attains a temperature of 120 C and 1 bar pressure). The nal products were isolated by absorbing the reaction mixture into silica gel and purifying it by column chromatog- raphy using an ethyl acetate/hexane gradient.11This journal is © The Royal Society of Chemistry 2016 Fig. 1 Several uses of ether. Chart 1 World consumption of ethyl ether. Review RSC Advances Pu bl is he d on 2 1 Ju ly 2 01 6. D ow nl oa de d on 6 /7 /2 02 2 2: 11 :3 5 PM . View Article Online7. Disadvantages of conventional method and advantages of aqueous method The disadvantages of this method are the very dilute solutions (3 to 12% strength aqueous solutions), the sometimes long reaction times of up to 24 hours and the associated low yield. The low selectivities are likewise disadvantageous with the platinum catalysts used;98 the yields are only ca. 68 to 89% following workup by distillation. The Williamson reaction oen competes with the base catalyzed elimination of the alkylating agent, and the nature of the leaving group as well as the reaction conditions (particularly the temperature and solvent) can have a strong effect on which is favored. In particular, some struc- tures of alkylating agent can be particularly prone to elimina- tion. When the nucleophile is an aroxide ion, the Williamson reaction can also compete with alkylation on the ring since aroxide is an ambident nucleophile.99 The reaction times were drastically reduced to one to two hours under sonication and few minutes under microwave conditions from the several hour timescales of classical reac- tions. Thus, the present protocols show rate acceleration asso- ciated with high product yields, when compared with similar reactions performed under classical conditions.11 Water is notThis journal is © The Royal Society of Chemistry 2016only an inexpensive and environmentally benign solvent, but also plays an important role in reactivity and selectivity. Surfactants catalyze the reaction efficiently with short reaction times without using any harmful organic reagents and solvents. 8. Industrial advances and future prospects 8.1. Solvent Ethers are quite unreactive and therefore desirable solvents for fats, oils, waxes, perfumes, resins, dyes, gums, and hydrocar- bons. In addition, vapours of certain ethers are used as insec- ticides and fumigants for top soil.100 8.2. Medicinal purposes Ethers also play an important role in pharmacology and medi- cine, especially for the use of anesthetics101 (Fig. 1a). Methoxy- methane otherwise known as codeine is an effective pain- relieving drug, and is the primary ingredient in morphine. Ethyl ether (or just ether) was one of the rst anesthetics replaced by other less-ammable anesthetics, such as nitrous oxide and halothane used for surgical procedures during the 1800s. A mixture of alcohol and ether was known as "Spirit of ether" or Hoffman's drops though it is ammable. 8.3. Industrial purposes Ethoxy ethane (ethyl ether) is quite volatile and therefore used as a starter uid for diesel engines (Fig. 1b) and gasoline engines in cold weather. Dimethyl ether is used as a spray propellant and refrigerant; ethers of ethylene glycol are used as solvents and plasticizers. Methyl t-butyl ether (MTBE) is a gasoline stabilizer which increases octane concentration and reduces pollutants.102 8.4. Dimethyl ether use, production, and application Most of the above fundamental studies were performed on a laboratory scale, whereas outstanding development for DME synthesis has also been completed on an industrial scale in recent years. Regarded as a clean fuel103 for the 21st century, DME has remarkable market and industrial potential, forRSC Adv., 2016, 6, 69605–69614 | 69611