Ethers alkyl halide formation

Formation of 2 naphthyl ethers. Alkyl halides and aryl-alkyl halides (e.g. benzyl chloride) are converted into 2-naphthyl ethers thus ... 

Aldehydes, formates, primary, and secondary alcohols, amines, ethers, alkyl halides, compounds of the type Z—CH2—Z, and a few other compounds add to double bonds in the presence of free-radical initiators/ This is formally the addition of RH to a double bond, but the R is not just any carbon but one connected to an oxygen or a nitrogen, a halogen, or to two Z groups (defined as on p. 548). The addition of aldehydes is illustrated above. Formates and formamides " add similarly ... 

Higher alcohols (> C3) react comparatively slowly with sodium because of the slight solubility of the sodium alkoxide in the alcohol a large excess (say, 8 mols) is therefore employed. The mixed ether is distilled off, and the process (formation of alkoxide and its reaction with the alkyl halide) may be repeated several times. The excess of alcohol can be recovered. cj/cloAliphatic alcohols form sodio compounds with difficulty if small pieces... 

The formation of carbon-oxygen single bonds via the attack of an alkoxide on an alkyl halide, (Williamson ether synthesis) is an extremely important reaction that... 

The alkoxide ion reacts with the substrate in an SN2 reaction, with the resulting formation of the ether. The substrate must bear a good leaving group. Typical substrates are alkyl halides, alkyl sulfonates, and dialkyl sulfates, i.e. 

Homoallyl ethers or sulfides.1 gem-Methoxy(phenylthio)alkanes (2), prepared by reaction of 1 with alkyl halides, react with allyltributyltin compounds in the presence of a Lewis acid to form either homoallyl methyl ethers or homoallyl phenyl sulfides. Use of BF3 etherate results in selective cleavage of the phenylthio group to provide homoallyl ethers, whereas TiCl effects cleavage of the methoxy group with formation of homoallyl sulfides. 

Substitution reactions of cyanide with secondary alkyl halides are often accompanied by the formation of elimination products in variable amounts (Cook et al., 1974). The same holds for reactions of metal acetate complexes of crown ethers (Liotta et al., 1974). 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

It is these reactions that are thought to provide some justification for equation (vii) [in Section VI B3] according to which p-phenethylbi-guanide in methanol exists to some extent as biguanidium methoxide. This being so, the reaction with alkyl halides is the nucleophihc displacement of the halogen ion by methoxide with formation of the methyl ether and the salt of the biguanide. 

The reaction of alkyl halides with silver nitrate constitutes an extremely useful method for the synthesis of high purity nitrate esters on a laboratory scale. ° The driving force for these reactions is the formation of the insoluble silver halide. Reactions have been conducted under homogenous and heterogeneous conditions. For the latter a solution of the alkyl halide in an inert solvent like benzene or ether is stirred with finely powdered silver nitrate. However, this method has been outdated and reactions are now commonly conducted under homogeneous conditions using acetonitrile as solvent. 

Hydroxyl Group. Reactions of the phenolic hydroxyl group include the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl halide (Williamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

Formation of Alkyl Halides from Ethers Halo-de-alkoxylation... 

A polymer-bound guanidine base 31 has been used for the formation of aryl ethers from suitable phenols and alkyl halides. In addition to serving as a base to affect deprotonation, reagent 31 also acts as a sequestering agent for excess starting phenol (reaction 11).26... 

Reaction XLIII. (b) Formation of Ethyl Esters by the Action of Ethyl Chloroformate on Magnesium Alkyl Halide in Dry Ethereal Solution (Grignard).—This is another mode of application of the Grignard reaction to the synthesis of esters. It is more direct than the previous method. 

These methods are not always applicable or convenient. A more general method used by Richard and Jencks utilizes HPLC analysis of carbocation formation in alcohol-water mixtures.22 As shown in Scheme 2 for an a-aryl ethyl cation, formation of the ether product from reaction of the carbocation with the alcohol depends on the rate constant for carbocation formation kll and the partition ratio between product formation and the back reaction to form the alcohol kROiiAii2o- This ratio may be determined from the ratio of products formed from reaction of the carbocation generated from a suitable solvolytic precursor such as an alkyl halide. 

Formation of a symmetrical sulphide (a) (e.g. dipropyl sulphide, Expt 5.204), is conveniently effected by boiling an alkyl halide (the source of carbocations) with sodium sulphide in ethanolic solution. Mixed sulphides (b) are prepared by alkylation of a thiolate salt (a mercaptide) with an alkyl halide (cf. Williamson s ether synthesis, Section 5.6.2, p. 583). In the case of an alkyl aryl sulphide (R-S Ar) where the aromatic ring contains activating nitro groups (see Section 6.5.3, p. 900), the aryl halide is used with the alkyl thiolate salt. The alternative alkylation of a substituted thiophenol is described in Section 8.3.4, p. 1160. The former procedure is illustrated by the preparation of isobutyl 2,4-dinitrophenyl sulphide (Expt 5.205) from l-chloro-2,4-dinitrobenzene and 2-methylpropane-1-thiol. 

Partially fluorinated vinyl ethers of fluoroolefins are quite susceptible to the action of Lewis acids. Reaction usually proceeds with ionization of the allylic C-F bond and results in formation of C=0 group and elimination of alkyl halide. Indeed, 3-chloro-2-methoxyhexafluoro-2-butene 82 reacts with A1C13 with formation of trichlorovinyl ketone 83, and cyclic alkoxyfluoroalkenes demonstrate similar behavior in reaction with aluminum or tin(IV) halides [170] ... 

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