Haloether

Haloethers (other than those listed elsewhere)... 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

In contrast to hydrogen-type ethers, a-haloethers, both linear and cyclic, are relatively easily cleaved by anhydrous hydrogen fluoride. Bis( 1,1 -difluoroalkyl) ethers are converted to 1,1,1 -trifluoroalkanes and alkanoyl fluorides The cleavage temperature depends on the substituents present ethers having no electronegative substituents other than a-fluorines are readily cleaved below 20 °C, 3-halo-1,1-di fluoroethers require approximately 70 °C, but 2-halo-1,1-difluoroethers are prac tically resistant toward hydrogen fluoride [/I (equation 1)... 

Alkylation of phenol 53 with 1,6-dibromohexane gives haloether... 

Sesquiterpene dialdehydes, dimenoic acid glycosides, haloethers Prosobranchia Triterpenes Pulmonata Polyproprionates... 

Van Duuren, B.L., Katz, C., Goldschmidt, M., Frenkel, K., and Sirak, A. Carcinogenicity of haloethers. II. Stmcture-activity relationships of analogs of bis(chloromethyl) ether, J. Nat. Cancer Inst, 48 1431-1439, 1972. 

The pollutants or groups of pollutants likely to be present in raw wastewater include volatile aromatics, halomethanes, cyanides, haloethers, phenols, polynuclear aromatics, heavy... 

Van Duuren BL, Goldschmidt BM, Langseth L, et al a-Haloethers A new type of alkylating carcinogen. Arch Environ Health 16 472-476, 1968... 

A rather distantly related analogue incorporating a e-di-carbonyl moiety as a bioisosteric replacement for a carboxyl, aril done (55), blocks the uncoating of polio virus and herpes simplex virus type I and thus inhibits infection of cells and i,he early stages of virus replication. Thus effective therapy would require careful timing as it does with amantidine. Alkylation of phenol 53 with 1,6-dibromohexane gives haloether... 

Alkylation of enamines requires relatively reactive alkylating agents for good results. Methyl iodide, allylic and benzylic halides, a-haloesters, a-haloethers, and a-haloketones are the most successful alkylating agents. Some typical examples of enamine alkylation reactions are shown in Scheme 1.10. 

Reactions of polar organometallic and Grignard reagents with a-haloethers generally proceed much more easily than the familiar SN2 displacements with alkyl halides. This may be explained by the large extent of Sjql character due to the ionization ... 

Other alkyl hypohalites usually add to carbon-carbon multiple bonds in a free-radical process.155-158 Ionic additions may be promoted by oxygen, BF3, or B(OMe)3.156-160 While the BF3-catalyzed reaction of alkyl hypochlorites and hypo-bromites gives mainly halofluorides,159 haloethers are formed in good yields but nonstereoselectively under other ionic conditions.156-158 160 In contrast, tert-BuOI reacts with alkenes in the presence of a catalytic amount of BF3 to produce 2-iodoethers.161 Since the addition is stereoselective, this suggests the participation of a symmetric iodonium ion intermediate without the involvement of carbocationic intermediates. 

Haloethers (Method 611). Bis(chloromethyl) ether is known to have a very short half-life in water (38 s). Therefore, it was eliminated from the priority pollutant list and from consideration in EMSL-Cincinnati method studies. Some of the other haloethers are very volatile, and care must be taken to prevent their loss during the concentration step. The haloethers are determined by OHD-GC by using a 1.8-m X 2-mm i.d. glass column containing Supelcoport coated with 3% SP-1000. The temperature is held at 60 °C for 2 min and then programmed at 8 °C/min to 230 °C. 

Subsequent work by Bedos,equally applicable to cyclohexene oxide (Eq. 917), which yielded tla-corresponding jS-haloethers on treatment with methyl, ethyl, or n-propyl halides at 160-190 . The stereochemical course of the reaction was of course not explored at the time, but may be supposed to lend t-n a frans-ooufigur tiou. 

The support originally used for solid-phase synthesis was partially chloromethy-lated cross-linked polystyrene, which was prepared by chloromethylation of cross-linked polystyrene with chloromethyl methyl ether and tin(IV) chloride [1-3] or zinc chloride [4] (Figure 6.1). Haloalkylations of this type are usually only used for the functionalization of supports, and not for selective transformation of support-bound intermediates. Because of the mutagenicity of a-haloethers, other methods have been developed for the preparation of chloromethyl polystyrene. These include the chlorination of methoxymethyl polystyrene (Figure 6.1 [5]), the use of a mixture of dimethoxymethane, sulfuryl chloride, and chlorosulfonic acid instead of chloromethyl methyl ether [6], the chlorination of hydroxymethyl polystyrene [7], and the chlorination of cross-linked 4-methylstyrene-styrene copolymer with sodium hypochlorite [8], sulfuryl chloride [8], or cobalt(III) acetate/lithium chloride [9] (Figure 6.1, Table 6.1). 

Alkylcarboxonium ions may be synthesized easily by the dehalogenation of a-haloethers. In Magic Acid, first the oxygen is protonated to oxonium ion 319, which, upon increasing temperature, decomposes to yield alkylcarboxonium ion 320 [Eq. (3.87)].624 In a similar manner, protonation of a-alkoxyacetic chlorides625 or acids626 also leads to carboxonium ions. The latter approach was used to generate cyclic alkylcarboxonium ion 321 [Eq. (3.88)]. 

For instance, the rate of SN2 reaction is greatly enhanced in a-haloethers 62 and in a-haloketones 63. This enhancement should however occur only when the oxygen atom in 62 has an electron pair anti peri planar to the C — Cl bond (cf 64+ 65). Similarly, in an o-haloketone the it system of the carbonyl group must be parallel to the C —Cl bond (cf, 66 67) (20). 

Samples of sand spiked with 36 nitroaromatic compounds, 19 haloethers, and 42 organochlorine pesticides, and a standard reference soil (certified for 13 polynuclear aromatic hydrocarbons, dibenzofuran, and pentachlorophenol) were extracted with supercritical carbon dioxide in a two- or four-vessel supercritical fluid extractor to establish the efficiency of the extraction and the degree of agreement of the parallel extraction recoveries. Furthermore, the many variables that influence the extraction process (e.g., flowrate, pressure, temperature, moisture content, cell volume, sample size, extraction time, modifier type, modifier volume, static versus dynamic extraction, volume of solvent in the collection vessel, and the use of glass beads to fill the void volume) were investigated. 

Gas Chromatograph - A Varian 6500 equipped with two constant-current/pulsed-frequency electron capture detectors, a 30-m x 0.53-mm ID DB-5 fused-silica open-tubular column (0.83-/ m film thickness), and a 30-m x 0.53-mm ID DB-210 fused-silica open-tubular column (1.0-/ m film thickness), both connected to an 8-in injection tee (Supelco, Bellefonte, Pennsylvania), was used to analyze for the haloethers. The columns were temperature-programmed from 180°C (0.5-min hold) to 260°C (1-min hold) at 2°C/min injector temperature 250°C detector temperature 320°C helium carrier gas 6 mL/min nitrogen makeup gas 20 mL/min. 

The extraction of the 19 haloethers from sand spiked at 600 ng/g (per analyte) was performed at 250 atm/70°C/60 min (dynamic) using carbon dioxide only (Experiments 5 through 8 in Figure 4). Sample size was 2.5 g. In Experiments 5 and 6, two sand samples (spiked in an aluminum cup with 150 / L of 10 ng// L spiking solution) were extracted in parallel. In Experiments 7 and 8, two other sand samples (spiked directly in the extraction vessel to avoid losses due to compound volatilization and sample transfer) were extracted in parallel. In Experiments 9 and 10, two soil samples (spiked in an aluminum cup as in Experiments 5 and 6) were extracted in parallel at 150 atm/50°C/60 min (dynamic). 

Figure 4. Percent recoveries of 19 haloethers (compounds 1 through 19 in Table V) extracted from spiked sand (25 g). Tlie experimental conditions are given in the experimental section.

Sample Extraction for Four-Vessel Setup. All extractions were conducted with supercritical carbon dioxide. The extraction of the 19 haloethers from the four spiked sand samples (2.5 g each, spiked at 600 ng/g per compound) was performed at 250 atm/60°C/60 min (dynamic). 

Figure 4 shows the recoveries of the 19 haloethers. Overall, the recoveries were quite good (averaging around 70 percent across the 19 compounds) but the agreement between the duplicate extractions performed in parallel was not as good as in the case of the nitroaromatics, however, it was within 15 percent for most compounds. To determine if the pressure had any effect upon recovery, we compared experiments 5,6 with experiments 9,10 because they were pairs (performed in parallel at different pressures) and they were performed with sand samples spiked under identical conditions. All recoveries were slightly higher when extractions were performed at lower pressures. This seems to be in contradiction with what we obtained for experiments 7,8 however, in this case the sand was spiked directly in the extraction vessel and therefore, the data from experiments 7,8 cannot be compared with the data from experiments 5,6. 

Table V. Average Recoveries and Percent RSDs for 19 Haloethers Extracted from Spiked Sand with Supercritical Carbon Dioxidea...

EPA. 1975. Investigation of selected potential environmental contaminants, haloethers. Washington, DC U.S. Environmental Protection Agency. NTIS PB-246-356... 

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