Ethers Haloethers

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)... 

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. 

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. 

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). 

Starting with the knowledge of carbenium ion stability and the understanding that it is necessary to decrease this stability enabling the reaction of these ions with nitriles102 (Section III.B.l), it should be assumed that acetals 209, oc-haloethers 211, enols 217 and vinyl ethers 218 are ineffective precursors since they are the sources of the highly stable hydroxy- (223) and alkoxycarbenium ions 224. In contrast, the carbonyl compound derivatives, which can produce destabilized ions (in comparison to ions 223 and 224) are the most interesting for reactions with nitriles. This includes acyloxycarbocations 225 (see Section III.B.3), halocarbocations 226, A-acyliminium ions 228 and vinyl cations 229. 

Reactions of a-haloethers in aqueous medium has been reviewed recently . The reactions in water are extremely rapid and in general precise kinetic data is not available. For example, it is estimated that methyl chloromethyl ether undergoes hydrolysis 10 times faster than n-propyl chloride . The rapidity of the reactions of a-haloethers is attributed to resonance stabilization of the transition state according to the structures... 

This mechanism for -elimination is supported by the fact that other processes which would be expected to produce carbanions beta to groups easily displaced also cause elimination to occur. It is well known that Grignard and Wurtz reactions of 0-haloethers lead to olefins. Tetra-hydrofurfuryl chloride, for example, gives 4-pentene-l-ol on treatment with sodium,8 and 0-bromoethyl phenyl ether yields phenol and ethylene4 when it is allowed to react with magnesium in dry ether. Presumably the mechanisms are ... 

Hal... C—OR <- Hal... C=OR). Although in the case of 1-haloethers (e.g. C1CH20CH3, compare Chap. V, Exp. 33) both lithium- and Grignard compounds give good results, the results with 1,2-dibromoethers are much better when the substitution reaction is carried out with the Grignard-derivatives. 1,2-Dibromotetrahydrofuran and 1,2-dibromotetrahydropyran seem to be less reactive than the open-chain ethers, but also in these cases specific displacement of... 

The flammable characteristics of haloethers are very much different from those of the ether class of componnds. Halogen substitntions... 

The explosion hazards of low aliphatic ethers caused by peroxide formation are not manifested by the haloethers. The halogens inhibit the ether oxidation to peroxides. 

O—CH2—Cl, a chloro-substituted aliphatic ether, the first member of a homologous series of haloethers... 

GC and GC/MS are the most widely used techniques for the analysis of bis(2-chloro-ethyl)ether. Methods for analysis of this compound in wastewaters and soils and solid wastes along with other haloethers are described in EPA procedures (U.S. EPA 1992, Methods 611, 625 1986, Methods 8010 and 8270). 

An aliphatic haloether containing two chloroisopropyl groups Synonyms 2,2 -dichloroisopropyl ether di-chlorodiisopropyl ether bis(/l-chloroiso-propyl) ether bis(2-chloro-l-methylethyl) ether... 

Haloethers [chlorophenylphenyl ether, bro-mophenylphenyl ether, bis(dichloroisopro-pyl)ether, bis(chloroethoxy)methane, and polychlorinated diphenyl ethers] Halomethanes (methylene chloride, methyl chloride, methyl bromide, bromoform, di-chlorobromomethane, trichlorofluorometh-ane, and dichlorodifluoromethane) Heptachlor and metabolites Hexachlorobutadiene Hexachlorocyclohexane (all isomers) Hexachlorocyclopentadiene Isophorone Naphthalene Nitrobenzene... 

A valuable group of Wittig reagents is derived from a-haloethers. They react with aldehydes or ketones to form vinyl ethers, which on acid hydrolysis are converted into aldehydes containing one more carbon atom. Thus cyclohexanone is converted into cyclohexane carboxaldehyde (2.75). The addition of an aldehyde... 

Haloethers = Compounds that contain an ether moiety (R-O-R) and halogen atoms attached to the aryl or alkyl groups (e.g., bis(2-chloroethyl) ether bis(2-chloroethoxy)methane bis(2-chloroi-sopropyl) ether 4-bromophenyl phenyl ether 4-chlorophenyl phenyl ether). 

Depending on the mole ratio of reactants used, the polyacetals have either both terminal vinyl groups, both terminal hydroxyl groups, or one vinyl ether and one hydroxyl group. The reaction can be run at -10° to 20°C using acid salts of strong acids, e,g, alkali metal bisulfate or a-haloethers. Organic acids with dissociation constants of 10 to 10 are used if a reaction temperature of 20°-180°C is desired. 

Although secondary alkyl halides are generally unsatisfactory in the phase transfer catalyzed Williamson ether synthesis, the more reactive a-haloethers are as useful as, and more reactive than, simple alkyl halides. Thus the Koenigs-Knorr reaction has been successfully executed under phase transfer conditions [10]. a-2-Bromo-3,4,5,6-... 

Acetals can also be used to protect alcohols. In these cases, an enol ether such as ethyl vinyl ether or dihydropyran is used in place of the aldehyde as in Equation 6.34 [57]. Under basic conditions an a-haloether will convert an alcohol to an acetal as in Equation 6.35 [58]. 

Haloetherification (Table 43.6) Considering the abundance of bioactive haloethers in nature, one may assume that the catalytic enantioselective haloetherification of alkenyl alcohols would be a desirable tool to secure such natural products. Although the practical application of this method to the total synthesis of halogenated ethers remains unexplored, it is relevant to briefly mention recent progress in this area. 

Double bonds, internal triple bonds, ether and tertiary amino groups are tolerated, with the exception of ether groups /3 to the hahde, which undergo elimination upon reaction with magnesium. Grignard compounds from a-haloethers (e.g., 3) are stable, at least... 

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