Nucleophilic substitution reactions ether synthesis

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Intramolecular nucleophilic substitution reactions of phenol ether derivatives induced by activated iodine(III) reagents such as PIFA-TMSOTf and PIFA-BF3 Et20 [Eq. (7) - (11)] have been applied to total or formal synthesis of various types of bioactive natural products. 

When substitution or elimination reactions are used in synthesis, care must be taken to choose reactants and reaction conditions that will maximize the yield of the desired product. In Section 10.4, you saw that nucleophilic substitution reactions of alkyl halides can lead to a wide variety of orgaiuc compounds. For example, ethers are synthesized by the reaction of an alkyl halide with an alkoxide ion. This reaction, discovered by Alexander Williamson in 1850, is still considered one of the best ways to synthesize an ether. 

The Williamson ether synthesis is a nucleophilic substitution reaction. It is an Sn2 reaction because it requires a high concentration of a good nucleophile. If you want to synthesize an ether such as butyl propyl ether, you have a choice of starting materials You can use either a propyl halide and butoxide ion or a butyl halide and propoxide ion. 

Nucleophilic substitution reactions involving molten salts are well known. A number of esamples of molten pyridinium hydrochloride (mp 144 °C) being used in chemical synthesis, dating back to the 1940s, are known. Pyridinium chloride can act as both an acid and as a nucleophilic source of chloride. These properties are exploited in the dealkylation reactions of aromatic ethers [85]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.2-51 and a mechanistic explanation is given in Scheme 5.2-52. 

An important route to unsymmetrical ethers is a nucleophilic substitution reaction known as the Williamson ether synthesis. 

Alkyl halides readily undergo nucleophilic substitution reactions with alkoxides to give ethers (the Williamson ether synthesis). In this case, the reaction would be an Intramolecular... 

Nucleophilic aromatic substitution reactions of haloarenes complexed to transition metal moieties with oxygen-, sulfin-, and nitrogen-containing nucleophiles allows for the synthesis of a wide variety of aryl ethers, thioethers, and amines. These metal-mediated reactions proceed under very mild conditions and allow for the incorporation of a number of different functional groups. Nucleophilic substitution reactions of chloroarenes complexed to the cyclopentadienyliron moiety have been the focus of many studies directed toward the design of functionalized organic monomers. ... 

The Williamson ether synthesis is a nucleophilic substitution reaction. It requires a high concentration of a good nucleophile, which indicates that it is an Sn2 reaction. 

Scheme 10.10 outlines the synthesis of polyfaryl ether ketone) s copolymers derived from different molar ratio of TFPOPH and hydroquinone with 4,4 -difluorobenzophenone by the nucleophilic substitution reaction method. 

Gas-liquid phase-transfer catalysis (GL-PTC) is a new synthetic organic method that has similarities both with phase-transfer catalysis (PTC) and with gas-liquid chromatography (GLC) in that anion transfer processes and partition equilibria between gaseous and liquid phases both take place and affect the synthesis. Using GL-PTC, nucleophilic substitution reactions have been so far carried out under operative conditions and with synthetic results, making this method different from the well known liquid-liquid (LL-) and solid-liquid (SL-) phase-transfer catalysis. As regards these latter, phase-transfer catalysts (onium salts, crown ethers and cryptands) transfer the reactive anion from an aqueous liquid (LL-PTC) or a solid salt (SL-PTC) phase into the organic one in which the substitution reaction occurs. In the case of GL-PTC, where no solvent is used, the catalyst always acts as an anion transfer (between solid and liquid phases) but, as it works in the molten state it also constitutes the medium in which the reaction proceeds. 

A similar method was used by Zhai [77] for the synthesis of BAPBDS and 4,4 -bis(4-aminophenylthio)benzophenone-3,3 -disulfonic acid (BAPTBPDS), as well as by Shobha et al. [78] for the synthesis of sulfonated bis(3-aminophenyl)phenyl phosphine oxide (SBAPPO). Because of the aromatic nucleophilic substitution reaction, this procedure leads to the incorporation of two ether bridges in the corresponding sulfonated diamines. This structure... 

Nucleophilic substitution reaction is another class of important transformations that organosilicon reagents play key roles in organic synthesis. Electrophiles such as acyl and alkyl halides activated by a Lewis acid in a stoichiometric amount readily react with silyl enol ethers, allylsilanes, and alkenylsilanes. ... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Hydroxyl Group. Reactions of the phenohc hydroxyl group iaclude the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl hahde (WiUiamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

The nucleophilic aromatic substitution reaction for the synthesis of poly(arylene ether ketone)s is similar to that of polysulfone, involving aromatic dihalides and aromatic diphenolates. Since carbonyl is a weaker electron-withdrawing group titan sulfonyl, in most cases, difluorides need to be used to afford high-molecular-weight polymers. Typically potassium carbonate is used as a base to avoid the... 

Smith, Jason A., 431 Sn2+ compounds, 233 Sn4+ compounds, 232 SNAr reaction. See also Nucleophilic aromatic substitution reaction poly(arylene ether sulfone) synthesis via, 336-340... 

This is not a new reaction. This is just an Sn2 reaction. We are simply using the alkoxide ion (ethoxide in this case) to function as the attacking nucleophile. But notice the net result of this reaction we have combined an alcohol and an alkyl halide to form an ether. This process has a special name. It is called the Williamson Ether Synthesis. This process relies on an Sn2 reaction as the main step, and therefore, we must be careful to obey the restrictions of Sn2 reactions. It is best to use a primary alkyl halide. Secondary alkyl halides cannot be used because elimination will predominate over substitution (as seen in Sections 10.9), and tertiary alkyl halides certainly cannot be used. 

The Williamson ether synthesis remains the most practical method for the preparation of tetrahydrofurans, as can be exemplified by the two examples shown in the following schemes. A simple synthesis of 2-substituted tetrahydrofuran-3-carbonitriles 84 is achieved by generating the alkoxide under a phase transfer condition via reaction between 4-chlorobutyronitrile and non-enolizable aldehydes <00SL1773>. A synthesis of 2-alkylidene-tetrahydrofuran 85 was recorded, in which a dianion can be generated through treatment of the amide shown below with an excess of LDA, and is followed by addition of l-bromo-2-chloroethane. In this way, the more basic y-carbon is alkylated and leads eventually to the nucleophilic cyclization <00SL743>. 

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