Ethyl ethers, Substituted

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

Broxton and Bunnett (1979) determined the products of the reaction of 4-chloro-3-nitrobenzenediazonium ions with ethoxide ion in ethanol, which is exactly analogous to the reaction in methanol discussed earlier in this section. These authors found 12.8% 4-chloro-3-nitrophenetole, 83% 2-chloronitrobenzene, and 0.8% 2-nitrophenetole. When the reaction was carried out in C2H5OD, the first- and second-mentioned products contained 99% D and 69% D respectively. Dediazoniation in basic ethanol therefore results in a higher yield of hydro-de-diazoniation with this diazonium salt compared with the reaction in methanol. This is probably due to the slightly higher basicity of the ethoxide ion and to the more facile formation of the radical CH3-CHOH (Packer and Richardson, 1975). Broxton and McLeish (1983 c) measured the rates of (Z) — (E) interconversion for some substituted 2-chlorophenylazo ethyl ethers in ethanol. 

Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, -butyl vinyl ether, when reacted at 50° for 10 hours, gives -butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, -butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 horns of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). 

Substitution of methanol by another alcohol such as propanol would not be expected to radically change selectivity because in both cases a proton donor solvent is present. However, a greater change in selectivity can be expected by using ethyl ether (proton acceptor) or methylene chloride (large dipole moment). 

Substituted anilines were reacted with EMME in diphenyl ether by heating to 185°C, with distillation of the ethanol formed. The temperature of the reaction mixture was then raised to 245°C and the reaction mixture was heated at 245°C for 1 hr to give ethyl 6-substituted quinoline-3-carboxylates in good yields (85USP4560692). 

Numerous further examples of protonation of variously substituted hydroxy- and alkoxy-benzenes in several acid solvent mixtures have been reported more recently and show a bewildering variety of behaviour. Several hydroxy- or alkoxy-groups favour C-protonation. Thus, 1,3,5-trihydroxybenzene and its ethers have been known for some time to be C-protonated at moderate acid concentrations (35-65% perchloric acid) (Kresge et al., 1962). In partial methyl and ethyl ethers of 1,3,5-trihydroxybenzene, there is a preference for protonation para to the hydroxy- rather than the alkoxy-group (Kresge et al., 1971a). 1,3-Dihydroxybenzene and its methyl ethers are also C-protonated in perchloric and sulphuric acid, whereas C-protonation of anisole would be expected only in >70%... 

Ethyl ether was purchased from Mallinckrodt Inc. (analytical grade) methylene chloride may be substituted, but the monomethyl ester is more soluble in ether. At least two other extractions will be necessary to optimize the yield when methylene chloride is used. 

Ethyl ether may be substituted, but its greater water solubility is a disadvantage. Evaporation of the combined organic layers at reduced pressure below 40° leaves a residue of about 5% (based on sulfur trioxide) of 2,4-diphenylbutane-l,4-sultone, which may be purified (60% recovery) by recrystallization from... 

Desflurane is a fluorinated methyl ethyl ether identical to isoflurane except for the substitution of a chlorine by a fluorine atom (Figure 3.2). It is the least soluble of all the volatile anaesthetics with a similar blood/gas solubility to nitrous oxide (0.42). It is non-flammable under all clinical conditions. The vapour pressure of desflurane approaches 1 atm at 23°C making controlled administration impossible with a conventional vaporiser. A desflurane vaporiser is an electronically controlled pressurised device that delivers an accurately metered dose of vaporised desflurane into a stream of fresh gases passing through it. The MAC of desflurane (6.5% in adults) is the highest of any modern fluorinated agent but in common with these the value decreases in the elderly and in other circumstances (see below). 

Nevertheless, chiral propargylic amines remain interesting substrates for achieving the diastereoselective addition of substituted allylic organozinc compounds to metallated alkynes. Besides crotylzincation, one example of diastereoselective addition of zincated allyl ethyl ether to 328 has also been reported183. 

Another very important ring substitution reaction of ferrocene is its ability to undergo metalation with organolithium and organosodium compounds. Metalation with n-butyllithium in ethyl ether, first reported by Nesmeyanov and coworkers (63) and independently by Benkeser, Goggin, and Schroll (3),"leads to rather low yields of ferrocenyllithium (XXXI, M = Li) and l,l -ferrocenylenedi-lithium (XXXII, M = Li). It was subsequently shown by Mayo, Shaw, and... 

Substitution of hydrogen by fluorine also occurs, albeit with difficulty, in the formyl group of formates ethyl formate reacts with sulfur tetrafluoride in the presence of potassium fluoride to give a mixture of difluoromethyl ethyl ether (14) and ethyl trifluoromethyl ether (15).175... 

With this intent, the acetates (R = COCH3, 78a), carbamates (R = CONH2, 78b), sulfamates (R = S02NH2, 78c), and ethyl ethers (R = C2H5,78d) of isosorbide 2- and 5-nitrate were investigated, and found to be similar in activity to the parent compounds.146 Several isohexide nitrates further substituted by purine bases 154 were prepared as potential cardiovascular agents.143... 

Conversion of phenols into their methyl or ethyl ethers by reaction with the corresponding alkyl sulphates in the presence of aqueous sodium hydroxide affords a method which avoids the use of the more expensive alkyl halides (e.g. the synthesis of methyl 2-naphthyl ether and veratraldehyde, Expt 6.111). Also included in Expt 6.111 is a general procedure for the alkylation of phenols under PTC conditions.38,39 The method is suitable for 2,6-dialkylphenols, naphthols and various functionally substituted phenols. The alkylating agents include dimethyl sulphate, diethyl sulphate, methyl iodide, allyl bromide, epichlorohy-drin, butyl bromide and benzyl chloride. 

Rates are thus expected to show the first-order dependence on the concentration ofT added, and the rate enhancement (RE, Equation 9.8) for a given concentration of T is easily shown to be the corresponding product ratio [Q] / [P ]. Behaviour of this kind occurs, for example, in the solvolysis of2-propyl tosylate in aqueous ethanol [22]. Products are those of nucleophilic substitution - a mixture of 2-propanol and 2-propyl ethyl ether. When the reaction is rim in the presence of sodium azide, an excellent nucleophile, rates of disappearance of the tosylate are enhanced and 2-propyl azide is also formed. The relationships between amounts of azide product and rate enhancements for a series of different azide concentrations were accurately described by Equations 9.5-9.8. 

Notice that for SN2 substitution, the alkyl halide came from the less sterically hindered group. For SN1 type reactions, the alkyl halide forms from the fragment of the original molecule that forms the more stable cation. Thus, the reaction of t-butyl ethyl ether with HI gives t-butyl iodide and ethyl alcohol. The following mechanism occurs ... 

As an alternative method of procedure, the following may be substituted for Steps 4 to 7 inclusive of the above process. After distilling the benzol, the tarry mass may be stirred directly with 2000 mL of hot 0.3 N NaOH with a mechanical stirrer. The suspension is chilled and the supernatant Liquid poured or siphoned off. Repetition of the extraction two or three times is advisable. The alkaline aqueous solution is then extracted five or six times with 400 mL portions of sulfuric ether, thus transferring the hormone to ether solution. After distillation of the ether the residue is steam distilled as long as a distillate other than water is obtained. The condensed water is removed by vacuum distillation and the small amount of dark tarry residue leached 5 times with 50 mL of hot 0.3 N NaOH. This solution is filtered and the filtrate extracted with sulfuric ether (100 mL, 6 times). The ether solution is distilled and the residue leached with cold 0.3 N NaOH using 20 mL five times. This alkaline solution is filtered and extracted with 50 mL of sulfuric ether five times. Upon distillation of the ether and solution of the residue in a small quantity of hot ethyl alcohol, the hormone separates in semi-crystalline balls which may be filtered off. A further quantity is obtained by adding 3 volumes of water to the alcoholic solution. It may be recrystallized from 25% aqueous ethyl alcohol or from 25% aqueous acetone or from any of the following chloroform, benzol, ethyl acetate, ethyl ether or petroleum ether. The final product consists of colorless crystals which, when crystallized from dilute alcohol, possess a distinct rhomboid outline. The crystals melt at 242-243°C (248-249°C corrected) with some decomposition. 

The high electron density in the double bond system of ethylenes makes nucleophilic attack unfavorable unless the system is substituted with one or more electron withdrawing groups such as -N02, -CN, -COR. When these substituents are present, attack by alcohols or alkoxide ions occurs at the beta-carbon predominantly. For example, researchers have found (12) that sodium methoxide or sodium ethoxide added rapidly at room temperature to beta-nitrostyrene leads to the alkoxide formation of the derivative (Reaction VIII). This reaction is generally not only for arylnitroalkenes (13) but also for other activated double bonds (14). Another example of alcohol addition to an activated double bond includes the reaction of alcohols with acrylonitrile to produce a cyano-ethylated ether (14A). 

Grease-proof pulp, a bleached sulfite pulp from spruce, with high hemi-cellulose content, from Billerud-Uddeholm AB, Saffle, Sweden. Ethyl cellulose, three samples prepared from alkali cellulose and ethyl chloride to low degrees of substitution (DS) about 0.25, 0.4 and 0.6 ethyl ether groups per glucose unit. 

The degree of substitution (DS) of the EC substrate has a pronounced effect (Table III). At high DS values, conversion of monomer increases from about 70 to the level 80%, but the grafting efficiency decreases at DS=0.60. This may be a blocking effect of the ethyl ether groups and to some extent an effect of increased water solubility of the substrate after grafting. The intermediate DS-level (0.40) is most favorable for grafting. 

For NPLC, the three solvents selected were the same as those recommended by Snyder, except that methyl-r-butyl ether is substituted for ethyl ether. The (nonpolar) carrier solvent recommended is hexane, and the stationary phase is silica. 

Thiazole itself can be obtained by condensing chloroacetaldehyde and thioformamide (Scheme 159). The reaction is explosive and proceeds in low yield because of the instability of the thioformamide under acid conditions. Higher thioamides are more stable and react under milder conditions with chloroacetaldehyde, affording 2-substituted thiazoles in moderate yields. It is possible, and often preferable, to prepare the thioamide in situ in dioxane solution by the action of phosphorus pentasulfide on the corresponding amide and in the presence of solid MgC03 (Scheme 160). With arylthioamides, except for some nitrothiobenzamides, yields are usually higher and the cyclization is carried out over several hours in boiling absolute alcohol. Chloroacetaldehyde can be replaced in these reaction by derivatives such as 1,2-dichloro- or dibromo-ethyl methyl or ethyl ether, 1,2-dichloro- or dibromo-ethyl acetate, 2-chloro- or dibromo-ethyl acetate, and 2-chloro or bromo-diethyl-acetal. 

The first study of a nucleophilic aromatic substitution in which formation of a Meisenheimer-type complex and its subsequent decomposition were separately observable was reported by Orvik and Bunnett (1970). The study involved the reaction of 2,4-dinitro-l-naphthyl ethyl ether [7] with n-butyl- and t-butylamine in DMSO. The use of DMSO in this kinetic study enabled the rate behaviour to be unambiguously interpreted by avoiding complications due to aggregation phenomena, while stabilizing any a-complexes which are formed. The reaction sequence is given in equation (28). In this OEt... 

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