Ether reactions that form

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

Classification and Organization of Reactions Forming Difunctional Compounds. This chapter considers all possible difunctional compounds formed from the groups acetylene, carboxylic acid, alcohol, thiol, aldehyde, amide, amine, ester, ether, epoxide, thioether, halide, ketone, nitrile, and olefin. Reactions that form difunctional compounds are classified into sections on the basis of the two functional groups of the product. The relative positions... 

Alternative reaction pathways exploring different synthetic possibilities have been studied. For instance, electron-rich dihydroazines also react with isocyanides in the presence of an electrophile, generating reactive iminium species that can then be trapped by the isocyanide. In this case, coordination of the electrophile with the isocyanide must be kinetically bypassed or reversible, to enable productive processes. Examples of this chemistry include the hydro-, halo- and seleno-carba-moylation of the DHPs 270, as well as analogous reactions of cyclic enol ethers (Scheme 42a) [223, 224]. p-Toluenesulfonic acid (as proton source), bromine and phenylselenyl chloride have reacted as electrophilic inputs, with DHPs and isocyanides to prepare the corresponding a-carbamoyl-(3-substituted tetrahydro-pyridines 272-274 (Scheme 42b). Wanner has recently, implemented a related and useful process that exploits M-silyl DHPs (275) to promote interesting MCRs. These substrates are reacted with a carboxylic acid and an isocyanide in an Ugi-Reissert-type reaction, that forms the polysubstituted tetrahydropyridines 276 with good diasteroselectivity (Scheme 42c) [225]. The mechanism involves initial protiodesilylation to form the dihydropyridinum salt S, which is then attacked by the isocyanide, en route to the final adducts. 

Fig. 4. Ether phospholipid synthesis from dihydroxyacetone-phosphate. (A) Dihydroxyacetone-P acyl transferase (DHAPAT). The first step of ether phospholipid synthesis is catalyzed by peroxisomal DHAPAT. This enzyme is a required component of complex ether lipid biosynthesis and its role cannot be assumed by a cytosolic enzyme that also forms acyldihydroxyacetone-P. (B) Ether bond formation by alkyl-DHAP synthase. The reaction that forms the 0-alkyl bond is catalyzed by alkyl-DHAP synthase and is thought to proceed via a ping-pong mechanism. Upon binding of acyl-DHAP to the enzyme alkyl-DHAP synthase, the pro-f hydrogen at carbon atom 1 is exchanged by enolization of the ketone, followed by release of the acyl moiety to form an activated enzyme-DHAP complex. The carbon atom at the 1-position of DHAP in the enzyme complex is thought to carry a positive charge that may be stabilized by an essential sulfhydryl group of the enzyme thus, the incoming alkox-ide ion reacts with carbon atom 1 to form the ether bond of alkyl-DHAP. It has been proposed that a nucleophilic cofactor at the active site covalently binds the DHAP portion of the substrate.

In Chapter 11, several different nucleophiles reacted with alkyl halides or sulfonate esters via both S l and Sn2 conditions. Alkoxides (RO ) are important nucleophiles, and the 8 2 reaction of an alkoxide with an alkyl halide was the basis of the Williamson ether synthesis in Chapter 11, Section 11.3.2. Based on the poor reactivity of tertiary halides with nucleophiles in the 8 2 reaction, reading Chapter 11 may lead to the conclusion that an alkoxide such as sodium ethoxide will give no reaction when mixed with a tertiary halide. This is incorrect. A reaction that forms the basis of this chapter occurs because alkoxides such as sodium ethoxide are strong bases as well as nucleophiles. 

Pell and Pilcher have tabulated the strain energies of cyclic alkanes, ethers, imines, and sulfides (Table 12), which all decrease with ring size in the order 3 > 4 > 5 > 6. Thus if the same fraction of the strain energy is always developed in the transition state, it would be expected that if this were the only controlling factor the rates of reactions that form rings of this type would be in the order 6 > 5 > 4 > 3. 

Draw a stepwise, detailed mechanism for the following intramolecular reaction that forms a cyclic ether. 

Finally, a homogeneous heterobimetallic Pd(COD)Cl-SnCl3 catalyst for the 5 reactions that form a new C-C bond between primary and secondary allylic alcohols and nucleophiles such as arenes, heteroarenes, active methylene-, and organometallic compounds has been reported. Yields range from 60 to 92%. The Sf 2/Sj 2 ratio is usually high, even up to 100/0, although exceptions occur. The reaction is successful when ben-zylic and propargylic alcohols or symmetric and unsymmetric allyl ethers are used in place of allylic alcohols. 

Ethers form Lewis acid Lewis base complexes with metal ions Certain cyclic polyethers called crown ethers, are particularly effective m coor dinatmg with Na" and K" and salts of these cations can be dissolved m nonpolar solvents when crown ethers are present Under these conditions the rates of many reactions that involve anions are accelerated... 

Acetophenone. Acetophenone [98-86-2] (methyl phenyl ketone) is a colorless Hquid that forms laminar crystals at low temperature (mp 20°C). It has a characteristic sweet orange blossom odor, and is soluble in alcohols and ethers. It is found in nature in oil of casatoreum, obtained from beavers oil of labdanum, recovered from plants and in buds of balsam poplar. It can be prepared by the Friedel-Crafts reaction (qv) of acetyl chloride with benzene in the presence of aluminum chloride however, this route is of Htde commercial significance. 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

In the presence of cationic initiators, the possibiUty for loss of pendant ether groups to form free alcohol is another side reaction that usually results in color formation because of the highly conjugated products formed. 

This reaction is the cause of a widely recognized laboratory hazard. The peroxides formed from several commonly used ethers, such as diethyl ether and tetrahydrofuran, are explosive. Appreciable amounts of such peroxides can build up in ether samples that have been exposed to the atmosphere. Because the hydroperoxides are less volatile than the ethers, they are concentrated by evaporation or distillation, and the concentrated peroxide solutions may explode. For this reason, extended storage of ethers that have been exposed to oxygen is extremely hazardous. 

Poloxamers are used primarily in aqueous solution and may be quantified in the aqueous phase by the use of compleximetric methods. However, a major limitation is that these techniques are essentially only capable of quantifying alkylene oxide groups and are by no means selective for poloxamers. The basis of these methods is the formation of a complex between a metal ion and the oxygen atoms that form the ether linkages. Reaction of this complex with an anion leads to the formation of a salt that, after precipitation or extraction, may be used for quantitation. A method reported to be rapid, simple, and consistently reproducible [18] involves a two-phase titration, which eliminates interferences from anionic surfactants. The poloxamer is complexed with potassium ions in an alkaline aqueous solution and extracted into dichloromethane as an ion pair with the titrant, tet-rakis (4-fluorophenyl) borate. The end point is defined by a color change resulting from the complexation of the indicator, Victoria Blue B, with excess titrant. The Wickbold [19] method, widely used to determine nonionic surfactants, has been applied to poloxamer type surfactants 120]. Essentially the method involves the formation in the presence of barium ions of a complex be-... 

To 2 mmol of freshly prepared ethereal LiCu(C.H3), are added 154 mg (1 mmol) of ( — )-m-5-melhyl-2-cyclo-hexenyl acetate (3a). [a]25 —2.7 (c = 3, CHC1,), in a centrifuge tube at 0°C. The mixture is kept at 0 °C for 8 h after which 1 mL of water is added. Methane is evolved and a reddish precipitate forms. After centrifuging, the supernatant liquid is decanted and concentrated, and the product trims-4 is isolated by preparative GC. Isolated yields range from 30% and 40%. However, it was reported in a similar reaction that the yields range from 90% and 95% 5. Analysis by capillary GC shows the product to be 99.5% trans-4 and 0.5% t -4. Capillary GC of the starting 3a shows the acetate 3a to be homogeneous except for a trace ( — 1.0%) of the trans-isomers. 

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