Electrophiles ethers

The crucial questions are really three does any one of the ethers really stand out from the others as having a particularly high o p-ratio does such a high 0 p-ratio require a specific o-interaction between the ether and the electrophile to account for it does the identification of a specific o-interaction require the intervention of dinitrogen pentoxide ... 

F.N. Tebbe (1978 [footnote 20]) and R.R. Schrock (1976) have shown that electrophilic titanium or tantalum ylides can alkylidenate the carbonyl group of esters. Vinyl ethers are obtained in high yields with Tebbe s reagent, p-chlorobis(ri -2,4-cyclopentadien-l-ylXdime-thylaluminum)- 4-methylenetitanium (S.H. Pine, 1980 A.G.M. Barrett, 1989). 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Other Synthesis Routes. Several alternative routes to the nucleopbilic substitution synthesis of polysulfones are possible. Polyethersulfone can be synthesized by the electrophilic Eriedel-Crafts reaction of bis(4-chlorosulfonylphen5l)ether [121 -63-1] with diphenyl ether [101-84-8] (11—13). 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

Like other aromatic compounds, aromatic ethers can undergo substitution in the aromatic ring with electrophilic reagents, eg, nitration, halogenation, and sulfonation. They also undergo Eriedel-Crafts (qv) alkylation and acylation. 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The classical structures of pyrrole, furan and thiophene (31) suggest that these compounds might show chemical reactions similar to those of amines, ethers and thioethers (32) respectively. On this basis, the initial attack of the electrophile would be expected to take place at the heteroatom and lead to products such as quaternary ammonium and oxonium salts, sulfoxides and sulfones. Products of this type from the heteroaromatic compounds under consideration are relatively rare. 

These compounds typically react with electrophiles on carbon and in this respect they resemble enamines, enol ethers and enol thioethers. For example, both pyrrole and 1-pyrrolidinocyclohexene can be C-acetylated (Scheme 4). 

The high reactivity of pyrroles to electrophiles is similar to that of arylamines and is a reflection of the mesomeric release of electrons from nitrogen to ring carbons. Reactions with electrophilic reagents may result in addition rather than substitution. Thus furan reacts with acetyl nitrate to give a 2,5-adduct (33) and in a similar fashion an adduct (34) is obtained from the reaction of ethyl vinyl ether with hydrogen bromide. 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

Oxadiazoles, 6, 365-391 aldol condensation, 6, 383 bond lengths, 6, 378 catalytic hydrogenation, 5, 75 chemotherapy, 6, 391 dipole moments, 6, 378 electron densities, 6, 378 electrophilic substitution, 6, 382 ethers... 

The six-position may be functionalized by electrophilic aromatic substitution. Either bromination (Br2/CH2Cl2/-5°) acetylation (acetyl chloride, aluminum chloride, nitrobenzene) " or chloromethylation (chloromethyl methyl ether, stannic chloride, -60°) " affords the 6,6 -disubstituted product. It should also be noted that treatment of the acetyl derivative with KOBr in THF affords the carboxylic acid in 84% yield. The brominated crown may then be metallated (n-BuLi) and treated with an electrophile to form a chain-extender. To this end, Cram has utilized both ethylene oxide " and dichlorodimethyl-silane in the conversion of bis-binaphthyl crowns into polymer-bound resolving agents. The acetylation/oxidation sequence is illustrated in Eq. (3.54). 

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Most of the compounds in this class have been prepared from preexisting crown ether units. By far, the most common approach is to use a benzo-substituted crown and an electrophilic condensation polymerization. A patent issued to Takekoshi, Scotia and Webb (General Electric) in 1974 which covered the formation of glyoxal and chloral type copolymers with dibenzo-18-crown-6. The latter were prepared by stirring the crown with an equivalent of chloral in chloroform solution. Boron trifluoride was catalyst in this reaction. The polymer which resulted was obtained in about 95% yield. The reaction is illustrated in Eq. (6.22). 

Enol ethers are readily attacked in buffered medium by electrophilic reagents such as halogens, A -haloamides, perchloryl fluoride and organic peracids to give a-substituted ketones. Similarly, electrophilic attack on... 

Alkyl silyl ethers are cleaved by a variety of reagents Whether the silicon-oxygen or the carbon-oxygen bond is cleaved depends on the nature of the reagent used Treatment of alkoxysilanes with electrophilic reagents like antimony tri-fluonde, 40% hydrofluonc acid, or a boron tnfluonde-ether complex results in the cleavage of the silicon-oxygen bond to form mono-, di-, and tnfluorosiloxanes or silanes [19, 20, 21) (equations 18-20)... 

Nitrated fluoro compounds are synthesized by electrophilic (NOz+), radical (NO2 ), or nucleophilic (NO2-) methods Indirect nitration routes can suppress the side reactions associated with severe reaction conditions and some nitration reagents Novel fluoronitro compounds, unobtainable by direct nitration, can also be pre pared For example, the nitration of (2-fluoro-2,2-dinitroethoxy)acetaldoxime followed by oxidation of the nitroso intermediate with hydrogen peroxide yields 2-fluoro-2,2-dinitioethyl 2,2-dinitroethyl ether [f] (equation 1)... 

Fluoroalkyl ketones may be used as the electrophilic partners in condensation reactions with other carbonyl compounds The highly electrophilic hexafluo-roacetone has been used in selective hexafluoroisopropyhdenation reactions with enol silyl ethers and dienolsilyl ethers [f] (equation 1)... 

Bis(trifluoromethyl)trioxide, CF3OOOCF3, adds to only one equivalent of octafluorocyclopentene to give cis and trans isomers of a mixed tnfluoromethyl ether-tnfluoromethylperoxide (equation 13) A radical rnechamsm is involved [J/, unlike in the electrophilic reacuons of CF3OOCI [32]... 

Bu3SnSMe, BF3-Et20, toluene, -20° 0°, 1.5 h H30, 70-97% yield. When treated with various electrophiles, the intermediate stannanes from this reaction form benzyl and MEM ethers, benzoates, and tosylates, and when treated with PCC, they form aldehydes." " ... 

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